published_papers
"タイトル(日本語)","タイトル(英語)","著者(日本語)","著者(英語)","担当区分","概要(日本語)","概要(英語)","出版者・発行元(日本語)","出版者・発行元(英語)","出版年月","誌名(日本語)","誌名(英語)","巻","号","開始ページ","終了ページ","記述言語","査読の有無","招待の有無","掲載種別","国際・国内誌","国際共著","DOI","ISSN","eISSN","URL","URL2","主要な業績かどうか","公開の有無"
"Histological and immunohistochemical analysis of epithelial cells in epidermoid cysts in intrapancreatic accessory spleen.","Histological and immunohistochemical analysis of epithelial cells in epidermoid cysts in intrapancreatic accessory spleen.","Satoshi Sumida, Mayuko Shimizu, Yuko Miyakami, Takumi Kakimoto, Tomoko Kobayashi, Yasuyo Saijo, Minoru Matsumoto, Hirohisa Ogawa, Takeshi Oya, Yoshimi Bando, Hisanori Uehara, Shu Taira, Mitsuo Shimada, Koichi Tsuneyama","Satoshi Sumida, Mayuko Shimizu, Yuko Miyakami, Takumi Kakimoto, Tomoko Kobayashi, Yasuyo Saijo, Minoru Matsumoto, Hirohisa Ogawa, Takeshi Oya, Yoshimi Bando, Hisanori Uehara, Shu Taira, Mitsuo Shimada, Koichi Tsuneyama","null","Novel histological features of epithelial cells of ECIPAS were indicated. Although more cases need to be evaluated, we propose that the cause of ECIPAS may be different from that of pancreatic ductal origin. J. Med. Invest. 70 : 251-259, February, 2023.","Novel histological features of epithelial cells of ECIPAS were indicated. Although more cases need to be evaluated, we propose that the cause of ECIPAS may be different from that of pancreatic ductal origin. J. Med. Invest. 70 : 251-259, February, 2023.","null","null","2023","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.70","No.1.2","251","259","eng","true","null","scientific_journal","null","null","10.2152/jmi.70.251","1349-6867","null","null","null","null","null"
"Effect of daikenchuto (TU-100) on carcinogenesis in non-alcoholic steatohepatitis.","Effect of daikenchuto (TU-100) on carcinogenesis in non-alcoholic steatohepatitis.","Shinichiro Yamada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Mayuko Shimizu, Koichi Tsuneyama, Mitsue Nishiyama, Shiori Ishizawa, Mitsuo Shimada","Shinichiro Yamada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Mayuko Shimizu, Koichi Tsuneyama, Mitsue Nishiyama, Shiori Ishizawa, Mitsuo Shimada","null","TU-100 regulates the intestinal microbiome and may suppress subsequent hepatocarcinogenesis in the NASH model. J. Med. Invest. 70 : 66-73, February, 2023.","TU-100 regulates the intestinal microbiome and may suppress subsequent hepatocarcinogenesis in the NASH model. J. Med. Invest. 70 : 66-73, February, 2023.","null","null","2023","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.70","No.1.2","66","73","eng","true","null","scientific_journal","null","null","10.2152/jmi.70.66","1349-6867","null","null","null","null","null"
"Inhibitory effect of non-alcoholic steatohepatitis on colon cancer liver metastasis.","Inhibitory effect of non-alcoholic steatohepatitis on colon cancer liver metastasis.","Shinichiro Yamada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Katsuki Miyazaki, Mayuko Shimizu, Koichi Tsuneyama, Mitsuo Shimada","Shinichiro Yamada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Katsuki Miyazaki, Mayuko Shimizu, Koichi Tsuneyama, Mitsuo Shimada","null","Only mice fed a WD for 16 weeks showed hepatic fibrosis. These mice showed significantly higher alanine aminotransferase and total cholesterol levels compared with the control group (p < 0.05). The WD group showed significantly lower tumor number and smaller tumor diameter (p < 0.05). In the WD group, expression of SAA1, IL6, STAT3 and MMP9 mRNA in the liver was significantly lower than in the control group (p < 0.05). Serum amyloid A1 protein expression was also lower in the WD group.","The WD-fed NASH mouse model showed an inhibitory effect on CLM. Suppressed interleukin-6/signal transducer and activator of transcription 3 signaling and serum amyloid A/matrix metalloproteinase 9 expression may affect this phenomenon.","null","null","2022-11-04","EJSO - European Journal of Surgical Oncology","EJSO - European Journal of Surgical Oncology","Vol.49","No.2","410","415","eng","true","null","scientific_journal","null","null","10.1016/j.ejso.2022.11.002","1532-2157","null","null","null","null","null"
"Characteristic submucosal alteration in biliary carcinogenesis of pancreaticobiliary maljunction with a focus on inflammasome activation.","Characteristic submucosal alteration in biliary carcinogenesis of pancreaticobiliary maljunction with a focus on inflammasome activation.","Shoko Yamashita, Chie Takasu, Yuji Morine, Hiroki Ishibashi, Tetsuya Ikemoto, Hiroki Mori, Shinichiro Yamada, Takeshi Oya, Koichi Tsuneyama, Mitsuo Shimada","Shoko Yamashita, Chie Takasu, Yuji Morine, Hiroki Ishibashi, Tetsuya Ikemoto, Hiroki Mori, Shinichiro Yamada, Takeshi Oya, Koichi Tsuneyama, Mitsuo Shimada","null","Compared with the control and cholecystitis groups, αSMA expression was higher in the cancerous part (stroma) of the GB in patients with GB cancer + PBM and in the lamina propria of patients with PBM. The CD204/CD68 ratio in the lamina propria was higher in the PBM group than in the control and cholecystitis groups. NLRP3 and caspase 1 expression in both the lamina propria and epithelium was higher in the PBM than control group. In the PBM group, NLRP3- and caspase 1-positive cells in the lamina propria were located near the epithelium.","Activated fibroblasts and M2 macrophages in the GB lamina propria may be associated with biliary carcinogenesis of PBM, possibly through inflammasome activation.","null","null","2022-11-01","Journal of Hepato-Biliary-Pancreatic Sciences","Journal of Hepato-Biliary-Pancreatic Sciences","Vol.30","No.4","462","472","eng","true","null","scientific_journal","null","null","10.1002/jhbp.1253","1868-6982","null","null","null","null","null"
"Radiographic Study Evaluating Perforator Vessels in the Ischiorectal Fossa for Safe Elevation of Island Flaps","Radiographic Study Evaluating Perforator Vessels in the Ischiorectal Fossa for Safe Elevation of Island Flaps","Shinji Nagasaka, Yoshiro Abe, Yutaro Yamashita, Hiroyuki Yamasaki, Kazuhide Mineda, Mitsuo Shimada, Ichiro Hashimoto","Shinji Nagasaka, Yoshiro Abe, Yutaro Yamashita, Hiroyuki Yamasaki, Kazuhide Mineda, Mitsuo Shimada, Ichiro Hashimoto","null","Perforator flaps based on the ischiorectal fossa (IRF) (ie, internal pudendal artery perforator flaps) are useful for perineal reconstruction. The three-dimensional characterization of perforator arteries in the IRF remains unclear, as the IRF contains thick adipose tissue as well as organs, such as the rectum, vagina, and urethra. This study aimed to evaluate perforators in the IRF to guide the safe elevation of skin flaps designed based on the IRF. IRF vessels were examined in 200 bilateral computed tomography angiography scans performed in 100 patients. We examined branching patterns arising from the internal iliac artery and the origins of the skin perforators in the IRF. The branching patterns of the internal iliac artery were divided into three groups: perforators derived exclusively from the internal pudendal artery (78%), perforators derived from the internal pudendal artery and the inferior gluteal artery (18%), and perforators derived exclusively from the inferior gluteal artery (4%). The average number of perforators in the IRF was 1.5 ± 0.7. The number of perforators was significantly higher in women than in men. The perforator arteries were found exclusively around the medial and dorsal sides of the ischial tuberosity. We found that perforators in the IRF were stable. All cases had more than one skin perforator, which was mainly derived from the internal pudendal artery. Although perforators cannot be identified during flap elevation because the fatty tissue in the IRF is very thick, physicians must focus on preserving the perforator-containing fatty tissue around the ischial tuberosity.","Perforator flaps based on the ischiorectal fossa (IRF) (ie, internal pudendal artery perforator flaps) are useful for perineal reconstruction. The three-dimensional characterization of perforator arteries in the IRF remains unclear, as the IRF contains thick adipose tissue as well as organs, such as the rectum, vagina, and urethra. This study aimed to evaluate perforators in the IRF to guide the safe elevation of skin flaps designed based on the IRF. IRF vessels were examined in 200 bilateral computed tomography angiography scans performed in 100 patients. We examined branching patterns arising from the internal iliac artery and the origins of the skin perforators in the IRF. The branching patterns of the internal iliac artery were divided into three groups: perforators derived exclusively from the internal pudendal artery (78%), perforators derived from the internal pudendal artery and the inferior gluteal artery (18%), and perforators derived exclusively from the inferior gluteal artery (4%). The average number of perforators in the IRF was 1.5 ± 0.7. The number of perforators was significantly higher in women than in men. The perforator arteries were found exclusively around the medial and dorsal sides of the ischial tuberosity. We found that perforators in the IRF were stable. All cases had more than one skin perforator, which was mainly derived from the internal pudendal artery. Although perforators cannot be identified during flap elevation because the fatty tissue in the IRF is very thick, physicians must focus on preserving the perforator-containing fatty tissue around the ischial tuberosity.","null","null","2022-10-11","Plastic and Reconstructive Surgery. Global Open","Plastic and Reconstructive Surgery. Global Open","Vol.10","No.10","e4561","e4561","eng","true","null","scientific_journal","null","null","10.1097/GOX.0000000000004561","2169-7574","null","null","null","null","null"
"【先天性胆道拡張症up-to-date】胆嚢外瘻と手術術式","【先天性胆道拡張症up-to-date】胆嚢外瘻と手術術式","石橋 広樹, 森 大樹, 横田 典子, 島田 光生","Hiroki Ishibashi, Hiroki Mori, Noriko Yokota, Mitsuo Shimada","null","null","null","null","null","2022-09-25","小児外科","Japanese Journal of Pediatric Surgery","Vol.54","No.9","861","864","jpn","true","null","scientific_journal","null","null","10.24479/ps.0000000224","0385-6313","null","https://search.jamas.or.jp/link/ui/2023047277","null","null","null"
"TIMP1 promotes cell proliferation and invasion capability of right-sided colon cancers via the FAK/Akt signaling pathway.","TIMP1 promotes cell proliferation and invasion capability of right-sided colon cancers via the FAK/Akt signaling pathway.","Beibei Ma, Hiroyuki Ueda, Koichi Okamoto, Masahiro Bando, Shota Fujimoto, Yasuyuki Okada, Tomoyuki Kawaguchi, Hironori Wada, Hiroshi Miyamoto, Mitsuo Shimada, Yasushi Sato, Tetsuji Takayama","Beibei Ma, Hiroyuki Ueda, Koichi Okamoto, Masahiro Bando, Shota Fujimoto, Yasuyuki Okada, Tomoyuki Kawaguchi, Hironori Wada, Hiroshi Miyamoto, Mitsuo Shimada, Yasushi Sato, Tetsuji Takayama","null","Although right-sided colorectal cancer (CRC) shows a worse prognosis than left-sided CRC, the underlying mechanism remains unclear. We established patient-derived organoids (PDOs) from left- and right-sided CRCs and directly compared cell proliferation and invasion capability between them. We then analyzed the expression of numerous genes in signal transduction pathways to clarify the mechanism of the differential prognosis. Cell proliferation activity and invasion capability in right-sided cancer PDOs were significantly higher than in left-sided cancer PDOs and normal PDOs, as revealed by Cell Titer Glo and transwell assays, respectively. We then used quantitative RT-PCR to compare 184 genes in 30 pathways among right-sided and left-sided cancer and normal PDOs and found that the TIMP1 mRNA level was highest in right-sided PDOs. TIMP1 protein levels were upregulated in right-sided PDOs compared with normal PDOs but was downregulated in left-sided PDOs. TIMP1 knockdown with shRNA significantly decreased cell proliferation activity and invasion capability in right-sided PDOs but not in left-sided PDOs. Moreover, TIMP1 knockdown significantly decreased pFAK and pAkt expression levels in right-sided PDOs but not in left-sided PDOs. A database analysis of The Cancer Genome Atlas revealed that TIMP1 expression in right-sided CRCs was significantly higher than in left-sided CRCs. Kaplan-Meier survival analysis showed significantly shorter overall survival in high-TIMP1 patients versus low-TIMP1 patients with right-sided CRCs but not left-sided CRCs. Our data suggest that TIMP1 is overexpressed in right-sided CRCs and promotes cell proliferation and invasion capability through the TIMP1/FAK/Akt pathway, leading to a poor prognosis. The TIMP1/FAK/Akt pathway can be a target for therapeutic agents in right-sided CRCs.","Although right-sided colorectal cancer (CRC) shows a worse prognosis than left-sided CRC, the underlying mechanism remains unclear. We established patient-derived organoids (PDOs) from left- and right-sided CRCs and directly compared cell proliferation and invasion capability between them. We then analyzed the expression of numerous genes in signal transduction pathways to clarify the mechanism of the differential prognosis. Cell proliferation activity and invasion capability in right-sided cancer PDOs were significantly higher than in left-sided cancer PDOs and normal PDOs, as revealed by Cell Titer Glo and transwell assays, respectively. We then used quantitative RT-PCR to compare 184 genes in 30 pathways among right-sided and left-sided cancer and normal PDOs and found that the TIMP1 mRNA level was highest in right-sided PDOs. TIMP1 protein levels were upregulated in right-sided PDOs compared with normal PDOs but was downregulated in left-sided PDOs. TIMP1 knockdown with shRNA significantly decreased cell proliferation activity and invasion capability in right-sided PDOs but not in left-sided PDOs. Moreover, TIMP1 knockdown significantly decreased pFAK and pAkt expression levels in right-sided PDOs but not in left-sided PDOs. A database analysis of The Cancer Genome Atlas revealed that TIMP1 expression in right-sided CRCs was significantly higher than in left-sided CRCs. Kaplan-Meier survival analysis showed significantly shorter overall survival in high-TIMP1 patients versus low-TIMP1 patients with right-sided CRCs but not left-sided CRCs. Our data suggest that TIMP1 is overexpressed in right-sided CRCs and promotes cell proliferation and invasion capability through the TIMP1/FAK/Akt pathway, leading to a poor prognosis. The TIMP1/FAK/Akt pathway can be a target for therapeutic agents in right-sided CRCs.","null","null","2022-09-08","Cancer Science","Cancer Science","Vol.113","No.12","4244","4257","eng","true","null","scientific_journal","null","null","10.1111/cas.15567","1349-7006","null","null","null","null","null"
"Muscle strength is a stronger prognostic factor than muscle mass in patients with gastrointestinal and hepatobiliary-pancreatic cancers.","Muscle strength is a stronger prognostic factor than muscle mass in patients with gastrointestinal and hepatobiliary-pancreatic cancers.","Nanami Nasu, Sonoko Yasui-Yamada, Natsumi Kagiya, Mami Takimoto, Yumiko Kurokawa, Yoshiko Suzuki, Hideya Kashihara, Yu Saitou, Masaaki Nishi, Mitsuo Shimada, Yasuhiro Hamada","Nanami Nasu, Sonoko Yasui-Yamada, Natsumi Kagiya, Mami Takimoto, Yumiko Kurokawa, Yoshiko Suzuki, Hideya Kashihara, Yu Saitou, Masaaki Nishi, Mitsuo Shimada, Yasuhiro Hamada","null","Sarcopenia has been reported as a prognostic risk factor in patients with gastrointestinal (GI) and hepatobiliary pancreatic (HBP) cancers. This study aimed to investigate whether the loss of muscle mass or strength is a stronger prognostic factor, and explore the cutoff values of skeletal muscle mass index (SMI) and handgrip strength (HGS) based on the survival outcome in patients with GI and HBP cancers. A total of 480 elderly patients with primary GI and HBP cancers who underwent their first resection surgery were analyzed retrospectively. Patients were divided into four groups: Appropriate SMI and HGS, low SMI alone, low HGS alone, and low SMI and HGS. Low SMI was derived from a bioelectrical impedance analysis, and low HGS was defined according to the Asian Working Group for Sarcopenia 2019 criteria. The multivariate analysis showed that low SMI was a significant risk factor for mortality in men only, but low HGS was significant in both sexes. From the multivariate analysis of the four groups, low HGS alone and low SMI and HGS showed a significantly higher hazard ratio than appropriate SMI and HGS in both sexes. An SMI of 7.21 kg/m and HGS of 28 kg were obtained as cutoff values based on the 3-y survival outcomes in men. Low muscle strength was a stronger prognostic factor than low muscle mass. Therefore, measuring muscle strength in all patients is essential.","Sarcopenia has been reported as a prognostic risk factor in patients with gastrointestinal (GI) and hepatobiliary pancreatic (HBP) cancers. This study aimed to investigate whether the loss of muscle mass or strength is a stronger prognostic factor, and explore the cutoff values of skeletal muscle mass index (SMI) and handgrip strength (HGS) based on the survival outcome in patients with GI and HBP cancers. A total of 480 elderly patients with primary GI and HBP cancers who underwent their first resection surgery were analyzed retrospectively. Patients were divided into four groups: Appropriate SMI and HGS, low SMI alone, low HGS alone, and low SMI and HGS. Low SMI was derived from a bioelectrical impedance analysis, and low HGS was defined according to the Asian Working Group for Sarcopenia 2019 criteria. The multivariate analysis showed that low SMI was a significant risk factor for mortality in men only, but low HGS was significant in both sexes. From the multivariate analysis of the four groups, low HGS alone and low SMI and HGS showed a significantly higher hazard ratio than appropriate SMI and HGS in both sexes. An SMI of 7.21 kg/m and HGS of 28 kg were obtained as cutoff values based on the 3-y survival outcomes in men. Low muscle strength was a stronger prognostic factor than low muscle mass. Therefore, measuring muscle strength in all patients is essential.","null","null","2022-08-18","Nutrition","Nutrition","Vol.103-104","null","111826","111826","eng","true","null","scientific_journal","null","null","10.1016/j.nut.2022.111826","1873-1244","null","null","null","null","null"
"Four cases of gastric adenocarcinoma and proximal polyposis of the stomach treated by robotic total gastrectomy","Four cases of gastric adenocarcinoma and proximal polyposis of the stomach treated by robotic total gastrectomy","Yosuke Iwakawa, Kouzou Yoshikawa, Koichi Okamoto, Tetsuji Takayama, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Yuuma Wada, Toshiaki Yoshimoto, Shoko Yamashita, Mitsuo Shimada","Yosuke Iwakawa, Kouzou Yoshikawa, Koichi Okamoto, Tetsuji Takayama, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Yuuma Wada, Toshiaki Yoshimoto, Shoko Yamashita, Mitsuo Shimada","null","Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare disease and characterized by a unique point mutation in the promoter 1B region of the adenomatous polyposis coli (APC) gene. There are two aims in surgery for GAPPS; the first is prophylactic gastrectomy, and the second is excising concurrent cancer. We performed robotic total gastrectomy (RTG) for four cases of GAPPS. Case 1 was a woman in her 40 s whose sister had died from gastric cancer. Mutational analysis revealed mutation of APC exon 1B. We performed prophylactic gastrectomy. Case 2 was a woman in her 30 s who had a mutation of APC exon 1B, and preoperative biopsy revealed suspected adenocarcinoma. Case 3 was a woman in her 40 s who was diagnosed with gastric cancer with multiple polyps in the stomach and a mutation of APC exon 1B. Case 4 was a woman in her 20 s in whom biopsy revealed low-grade dysplasia of a raised lesion. She had a mutation in APC exon 1B. We performed RTG with D1 + lymphadenectomy in all patients, and there were no intraoperative complications. Patients with GAPPS are mainly followed regularly with repeat biopsy, and tumors are detected in an early stage. As the safety of robotic surgery for the early gastric cancer is reported, RTG is an option for these patients. This is the first report of RTG for GAPPS patients.","Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare disease and characterized by a unique point mutation in the promoter 1B region of the adenomatous polyposis coli (APC) gene. There are two aims in surgery for GAPPS; the first is prophylactic gastrectomy, and the second is excising concurrent cancer. We performed robotic total gastrectomy (RTG) for four cases of GAPPS. Case 1 was a woman in her 40 s whose sister had died from gastric cancer. Mutational analysis revealed mutation of APC exon 1B. We performed prophylactic gastrectomy. Case 2 was a woman in her 30 s who had a mutation of APC exon 1B, and preoperative biopsy revealed suspected adenocarcinoma. Case 3 was a woman in her 40 s who was diagnosed with gastric cancer with multiple polyps in the stomach and a mutation of APC exon 1B. Case 4 was a woman in her 20 s in whom biopsy revealed low-grade dysplasia of a raised lesion. She had a mutation in APC exon 1B. We performed RTG with D1 + lymphadenectomy in all patients, and there were no intraoperative complications. Patients with GAPPS are mainly followed regularly with repeat biopsy, and tumors are detected in an early stage. As the safety of robotic surgery for the early gastric cancer is reported, RTG is an option for these patients. This is the first report of RTG for GAPPS patients.","null","null","2022-04-18","Surgical Case Reports","Surgical Case Reports","Vol.8","No.1","70","70","eng","true","null","scientific_journal","null","null","10.1186/s40792-022-01425-6","2198-7793","null","null","null","null","null"
"Gastric carcinoma with lymphoid stroma derived from hamartomatous inverted polyp with osteoclast-like giant cells: a case report.","Gastric carcinoma with lymphoid stroma derived from hamartomatous inverted polyp with osteoclast-like giant cells: a case report.","Shoko Yamashita, Masaaki Nishi, Kozo Yoshikawa, Toshihiro Nakao, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Yuma Wada, Toshiaki Yoshimoto, Yosuke Iwakawa, Takeshi Oya, Koichi Tsuneyama, Mitsuo Shimada","Shoko Yamashita, Masaaki Nishi, Kozo Yoshikawa, Toshihiro Nakao, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Yuma Wada, Toshiaki Yoshimoto, Yosuke Iwakawa, Takeshi Oya, Koichi Tsuneyama, Mitsuo Shimada","null","Gastric carcinomas with lymphoid stroma (GCLS) are characterized by prominent stromal infiltration of lymphocyte and account for 1-4% of gastric cancers. Although, osteoclast-like giant cells (OGC) have been reported in some GCLS, OGCs in gastric tumors is exceedingly rare. A 60-year-old woman presented to our hospital after the finding of a positive fecal blood test during a routine medical check. Esophagogastroduodenoscopy revealed a Type 0-III + IIc tumor in the middle part of the gastric body. Biopsy revealed a poorly differentiated tumor and she was referred to our department. Early phase computed tomography showed thickening of the wall in the middle of the gastric body and enlargement of nearby lymph nodes. Laparoscopic total gastrectomy was performed. Pathological examination revealed a hamartomatous inverted polyp (HIP) in the submucosal layer with tub2-por1 tumor in the HIP. Prominent lymphocytic infiltration and OGCs were found around the tumor. Immunohistochemical analysis showed that the tumor cells were negative for EBER, MLH-1, and MSH2, 6. These findings suggest that this tumor was a non-microsatellite instability (MSI)-high GCLS without Epstein-Barr virus (EBV) infection. The patient's postoperative course was uneventful and she was discharged 11 days after surgery. She remains well 3 years after surgery.","Gastric carcinomas with lymphoid stroma (GCLS) are characterized by prominent stromal infiltration of lymphocyte and account for 1-4% of gastric cancers. Although, osteoclast-like giant cells (OGC) have been reported in some GCLS, OGCs in gastric tumors is exceedingly rare. A 60-year-old woman presented to our hospital after the finding of a positive fecal blood test during a routine medical check. Esophagogastroduodenoscopy revealed a Type 0-III + IIc tumor in the middle part of the gastric body. Biopsy revealed a poorly differentiated tumor and she was referred to our department. Early phase computed tomography showed thickening of the wall in the middle of the gastric body and enlargement of nearby lymph nodes. Laparoscopic total gastrectomy was performed. Pathological examination revealed a hamartomatous inverted polyp (HIP) in the submucosal layer with tub2-por1 tumor in the HIP. Prominent lymphocytic infiltration and OGCs were found around the tumor. Immunohistochemical analysis showed that the tumor cells were negative for EBER, MLH-1, and MSH2, 6. These findings suggest that this tumor was a non-microsatellite instability (MSI)-high GCLS without Epstein-Barr virus (EBV) infection. The patient's postoperative course was uneventful and she was discharged 11 days after surgery. She remains well 3 years after surgery.","null","null","2022-04-06","International Cancer Conference Journal","International Cancer Conference Journal","Vol.11","No.3","196","200","eng","true","null","scientific_journal","null","null","10.1007/s13691-022-00547-w","2192-3183","null","null","null","null","null"
"Risk factors for metachronous contralateral inguinal hernia after laparoscopic percutaneous extraperitoneal closure for unilateral inguinal hernia in children.","Risk factors for metachronous contralateral inguinal hernia after laparoscopic percutaneous extraperitoneal closure for unilateral inguinal hernia in children.","Hiroki Mori, Hiroki Ishibashi, Noriko Yokota, Mitsuo Shimada","Hiroki Mori, Hiroki Ishibashi, Noriko Yokota, Mitsuo Shimada","null","We use the laparoscopic percutaneous extraperitoneal closure (LPEC) method as the standard procedure for pediatric inguinal hernia. Despite judging there to be no contralateral patent processus vaginalis (PPV) at the time of the first LPEC, we experienced five cases in which metachronous contralateral inguinal hernia (MCH) developed, so we report the characteristics, including the predictors. For pediatric inguinal hernia, the LPEC method was used in 1277 cases from 2005 to 2019 in our department. Of these, 374 patients underwent unilateral LPEC, and we compared the 5 patients with MCH onset and the 369 without MCH onset. The items to be examined were the gender, age, presence of a low birth weight, initial-onset side, and contralateral internal inguinal ring classification. There was no significant difference in the gender, age, initial-onset side, or contralateral internal inguinal ring classification between the two groups. Low-birth-weight infants were significantly more common among those with MCH than among those without MCH. The only predictor of a contralateral onset after LPEC for pediatric inguinal hernia was a low birth weight. Therefore, for the above-mentioned unilateral LPEC cases, the possibility of a contralateral onset after LPEC due to acquired factors rather than congenital factors should be considered.","We use the laparoscopic percutaneous extraperitoneal closure (LPEC) method as the standard procedure for pediatric inguinal hernia. Despite judging there to be no contralateral patent processus vaginalis (PPV) at the time of the first LPEC, we experienced five cases in which metachronous contralateral inguinal hernia (MCH) developed, so we report the characteristics, including the predictors. For pediatric inguinal hernia, the LPEC method was used in 1277 cases from 2005 to 2019 in our department. Of these, 374 patients underwent unilateral LPEC, and we compared the 5 patients with MCH onset and the 369 without MCH onset. The items to be examined were the gender, age, presence of a low birth weight, initial-onset side, and contralateral internal inguinal ring classification. There was no significant difference in the gender, age, initial-onset side, or contralateral internal inguinal ring classification between the two groups. Low-birth-weight infants were significantly more common among those with MCH than among those without MCH. The only predictor of a contralateral onset after LPEC for pediatric inguinal hernia was a low birth weight. Therefore, for the above-mentioned unilateral LPEC cases, the possibility of a contralateral onset after LPEC due to acquired factors rather than congenital factors should be considered.","null","null","2022-02-24","Surgery Today","Surgery Today","Vol.52","No.10","1491","1496","eng","true","null","scientific_journal","null","null","10.1007/s00595-022-02480-0","1436-2813","null","null","null","null","null"
"Development and Validation of Cutoff Value for Reduced Muscle Mass for GLIM Criteria in Patients with Gastrointestinal and HepatobiliaryPancreatic Cancers","Development and Validation of Cutoff Value for Reduced Muscle Mass for GLIM Criteria in Patients with Gastrointestinal and HepatobiliaryPancreatic Cancers","Mami Takimoto, Sonoko Yasui-Yamada, Nanami Nasu, Natsumi Kagiya, Nozomi Aotani, Yumiko Kurokawa, Yoshiko Suzuki, Hideya Kashihara, Yu Saitou, Masaaki Nishi, Mitsuo Shimada, Yasuhiro Hamada","Mami Takimoto, Sonoko Yasui-Yamada, Nanami Nasu, Natsumi Kagiya, Nozomi Aotani, Yumiko Kurokawa, Yoshiko Suzuki, Hideya Kashihara, Yu Saitou, Masaaki Nishi, Mitsuo Shimada, Yasuhiro Hamada","null","The Global Leadership Initiative on Malnutrition (GLIM) criteria recommends using race- and sex-adjusted cutoff values for reduced muscle mass (RMM), but the only cutoff values available for Asians are the skeletal muscle mass index (SMI) established by the Asian Working Group for Sarcopenia (AWGS). This retrospective study aimed to develop and validate cutoff values for the fat-free mass index (FFMI) and arm circumference (AC) of Asians, and to investigate the association between GLIM malnutrition and prognosis. A total of 660 patients with primary gastrointestinal (GI) and hepatobiliary-pancreatic (HBP) cancers who underwent their first resection surgery were recruited and randomly divided into development and validation groups. The FFMI and AC cutoff values were calculated by receiver operating characteristic curve analysis for the AWGS SMI as the gold standard. The cutoff values for each RMM were used to diagnose malnutrition on the basis of GLIM criteria, and the survival rates were compared. The optimal FFMI cutoff values for RMM were 17 kg/m for men and 15 kg/m for women, and for AC were 27 cm for men and 25 cm for women. In the validation group, the accuracy of the FFMI and AC cutoff values to discriminate RMM were 85.2% and 68.8%, respectively. Using any of the three measures of RMM, overall survival rates were significantly lower in the GLIM malnutrition group. In conclusion, the cutoff values for the FFMI and AC in this study could discriminate RMM, and GLIM malnutrition using these cutoff values was associated with decreased survival.","The Global Leadership Initiative on Malnutrition (GLIM) criteria recommends using race- and sex-adjusted cutoff values for reduced muscle mass (RMM), but the only cutoff values available for Asians are the skeletal muscle mass index (SMI) established by the Asian Working Group for Sarcopenia (AWGS). This retrospective study aimed to develop and validate cutoff values for the fat-free mass index (FFMI) and arm circumference (AC) of Asians, and to investigate the association between GLIM malnutrition and prognosis. A total of 660 patients with primary gastrointestinal (GI) and hepatobiliary-pancreatic (HBP) cancers who underwent their first resection surgery were recruited and randomly divided into development and validation groups. The FFMI and AC cutoff values were calculated by receiver operating characteristic curve analysis for the AWGS SMI as the gold standard. The cutoff values for each RMM were used to diagnose malnutrition on the basis of GLIM criteria, and the survival rates were compared. The optimal FFMI cutoff values for RMM were 17 kg/m for men and 15 kg/m for women, and for AC were 27 cm for men and 25 cm for women. In the validation group, the accuracy of the FFMI and AC cutoff values to discriminate RMM were 85.2% and 68.8%, respectively. Using any of the three measures of RMM, overall survival rates were significantly lower in the GLIM malnutrition group. In conclusion, the cutoff values for the FFMI and AC in this study could discriminate RMM, and GLIM malnutrition using these cutoff values was associated with decreased survival.","null","null","2022-02-23","Nutrients","Nutrients","Vol.14","No.943","1","10","eng","true","null","scientific_journal","null","null","10.3390/nu14050943","2072-6643","null","null","null","null","null"
"【小児外科疾患の家族内発生】側頸瘻","【小児外科疾患の家族内発生】側頸瘻","石橋 広樹, 横田 典子, 森 大樹, 島田 光生","Hiroki Ishibashi, Noriko Yokota, Hiroki Mori, Mitsuo Shimada","null","null","null","null","null","2021-12-25","小児外科","Japanese Journal of Pediatric Surgery","Vol.53","No.12","1243","1247","jpn","true","null","scientific_journal","null","null","10.24479/j00645.2022081267","0385-6313","null","https://search.jamas.or.jp/link/ui/2022081267","null","null","null"
"Essential updates 2020/2021: Current topics of simulation and navigation in hepatectomy.","Essential updates 2020/2021: Current topics of simulation and navigation in hepatectomy.","Yu Saitou, Mitsuo Shimada, Yuji Morine, Shin-ichiro Yamada, Maki Sugimoto","Yu Saitou, Mitsuo Shimada, Yuji Morine, Shin-ichiro Yamada, Maki Sugimoto","null","With the development of three-dimensional (3D) simulation software, preoperative simulation technology is almost completely established. The remaining issue is how to recognize anatomy three-dimensionally. Extended reality is a newly developed technology with several merits for surgical application: no requirement for a sterilized display monitor, better spatial awareness, and the ability to share 3D images among all surgeons. Various technology or devices for intraoperative navigation have also been developed to support the safety and certainty of liver surgery. Consensus recommendations regarding indocyanine green fluorescence were determined in 2021. Extended reality has also been applied to intraoperative navigation, and artificial intelligence (AI) is one of the topics of real-time navigation. AI might overcome the problem of liver deformity with automatic registration. Including the issues described above, this article focuses on recent advances in simulation and navigation in liver surgery from 2020 to 2021.","With the development of three-dimensional (3D) simulation software, preoperative simulation technology is almost completely established. The remaining issue is how to recognize anatomy three-dimensionally. Extended reality is a newly developed technology with several merits for surgical application: no requirement for a sterilized display monitor, better spatial awareness, and the ability to share 3D images among all surgeons. Various technology or devices for intraoperative navigation have also been developed to support the safety and certainty of liver surgery. Consensus recommendations regarding indocyanine green fluorescence were determined in 2021. Extended reality has also been applied to intraoperative navigation, and artificial intelligence (AI) is one of the topics of real-time navigation. AI might overcome the problem of liver deformity with automatic registration. Including the issues described above, this article focuses on recent advances in simulation and navigation in liver surgery from 2020 to 2021.","null","null","2021-12-23","Annals of Gastroenterological Surgery","Annals of Gastroenterological Surgery","Vol.6","No.2","190","196","eng","true","null","scientific_journal","null","null","10.1002/ags3.12542","2475-0328","null","null","null","null","null"
"Update on perioperative management of patients undergoing surgery for liver cancer.","Update on perioperative management of patients undergoing surgery for liver cancer.","Masaki Kaibori, Kosuke Matsui, Mitsuo Shimada, Shoji Kubo, Kiyoshi Hasegawa","Masaki Kaibori, Kosuke Matsui, Mitsuo Shimada, Shoji Kubo, Kiyoshi Hasegawa","null","Hepatocellular carcinoma is often accompanied by chronic hepatitis or cirrhosis. Preoperative evaluation of liver function and postoperative nutritional management are critical in patients with hepatocellular carcinoma who undergo liver surgery. Although the incidence of postoperative complications and death has declined in Japan over the last 10 years, postoperative complications have not been fully overcome. Therefore, surgical procedures and perioperative management must be improved. Accurate preoperative evaluations of liver function, nutrition, inflammation, and body skeletal muscle are required. Determination of the optimal surgical procedure should consider not only tumor characteristics but also the physical reserve of the patient. Nutritional management of chronic liver disorders, especially maintaining protein synthesis for postoperative protein/energy, is important. Prophylactic antibiotics are recommended for short-term use within 24 hours after surgery. Abdominal drainage is recommended for patients with cirrhosis who may develop large amounts of ascites, who are at risk of postoperative bleeding, or who may have bile leakage due to a large resection area. Postoperative exercise therapy may improve insulin resistance in patients with chronic liver damage. Implementation of an early/enhanced recovery after surgery program is recommended to reduce biological invasive responses and achieve early independence of physical activity and nutrition intake. We review the latest information on the perioperative management of patients undergoing liver resection for hepatocellular carcinoma.","Hepatocellular carcinoma is often accompanied by chronic hepatitis or cirrhosis. Preoperative evaluation of liver function and postoperative nutritional management are critical in patients with hepatocellular carcinoma who undergo liver surgery. Although the incidence of postoperative complications and death has declined in Japan over the last 10 years, postoperative complications have not been fully overcome. Therefore, surgical procedures and perioperative management must be improved. Accurate preoperative evaluations of liver function, nutrition, inflammation, and body skeletal muscle are required. Determination of the optimal surgical procedure should consider not only tumor characteristics but also the physical reserve of the patient. Nutritional management of chronic liver disorders, especially maintaining protein synthesis for postoperative protein/energy, is important. Prophylactic antibiotics are recommended for short-term use within 24 hours after surgery. Abdominal drainage is recommended for patients with cirrhosis who may develop large amounts of ascites, who are at risk of postoperative bleeding, or who may have bile leakage due to a large resection area. Postoperative exercise therapy may improve insulin resistance in patients with chronic liver damage. Implementation of an early/enhanced recovery after surgery program is recommended to reduce biological invasive responses and achieve early independence of physical activity and nutrition intake. We review the latest information on the perioperative management of patients undergoing liver resection for hepatocellular carcinoma.","null","null","2021-12-15","Annals of Gastroenterological Surgery","Annals of Gastroenterological Surgery","Vol.6","No.3","344","354","eng","true","null","scientific_journal","null","null","10.1002/ags3.12529","2475-0328","null","null","null","null","null"
"Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors.","Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors.","Jun Uemura, Keiichi Okano, Minoru Oshima, Hironobu Suto, Yasuhisa Ando, Kensuke Kumamoto, Kyuichi Kadota, Shuji Ichihara, Yasutaka Kokudo, Takashi Maeba, Yoshihide Nanno, Hirochika Toyama, Yasutsugu Takada, Mitsuo Shimada, Kazuhiro Hanazaki, Tsutomu Masaki, Yasuyuki Suzuki","Jun Uemura, Keiichi Okano, Minoru Oshima, Hironobu Suto, Yasuhisa Ando, Kensuke Kumamoto, Kyuichi Kadota, Shuji Ichihara, Yasutaka Kokudo, Takashi Maeba, Yoshihide Nanno, Hirochika Toyama, Yasutsugu Takada, Mitsuo Shimada, Kazuhiro Hanazaki, Tsutomu Masaki, Yasuyuki Suzuki","null","The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs). The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that 5 genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear. We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings. Kaplan-Meier analysis indicated that loss of TSC2 (n = 58) or PTEN (n = 37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n = 41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n = 31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1-66.9, P = 0.003) in G2 PNETs. Loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior and clinical outcomes of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs. Loss of pairs in ATRX, TSC2, or PTEN would be useful for selecting the candidate for postoperative adjuvant therapy.","The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs). The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that 5 genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear. We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings. Kaplan-Meier analysis indicated that loss of TSC2 (n = 58) or PTEN (n = 37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n = 41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n = 31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1-66.9, P = 0.003) in G2 PNETs. Loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior and clinical outcomes of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs. Loss of pairs in ATRX, TSC2, or PTEN would be useful for selecting the candidate for postoperative adjuvant therapy.","null","null","2021-12-09","Annals of Surgery","Annals of Surgery","Vol.274","No.6","e949","e956","eng","true","null","scientific_journal","null","null","10.1097/SLA.0000000000003624","1528-1140","null","null","null","null","null"
"Stromal tumor-infiltrating lymphocytes level as a prognostic factor for resected intrahepatic cholangiocarcinoma and its prediction by apparent diffusion coefficient.","Stromal tumor-infiltrating lymphocytes level as a prognostic factor for resected intrahepatic cholangiocarcinoma and its prediction by apparent diffusion coefficient.","Katsuki Miyazaki, Yuji Morine, Shin-ichiro Yamada, Yu Saitou, Kazunori Tokuda, Shohei Okikawa, Shoko Yamashita, Takeshi Oya, Tetsuya Ikemoto, Satoru Imura, Haun Hu, Hisayoshi Morioka, Koichi Tsuneyama, Mitsuo Shimada","Katsuki Miyazaki, Yuji Morine, Shin-ichiro Yamada, Yu Saitou, Kazunori Tokuda, Shohei Okikawa, Shoko Yamashita, Takeshi Oya, Tetsuya Ikemoto, Satoru Imura, Haun Hu, Hisayoshi Morioka, Koichi Tsuneyama, Mitsuo Shimada","null","Tumor-infiltrating lymphocytes (TILs) are a prognostic factor or an indicator of chemotherapy response for various malignancies. The aim of this study was to investigate the prognostic impact of TILs in resected intrahepatic cholangiocarcinoma (IHCC). We also investigated the usefulness of the apparent diffusion coefficient (ADC) in diffusion-weighted magnetic resonance imaging (DW-MRI) to predict TILs. We enrolled 23 patients with IHCC who underwent initial hepatic resection in Tokushima University Hospital from 2006 to 2017. We evaluated stromal TILs in the tumor marginal area and central area in surgical specimens. Patients were divided into low vs high stromal TILs groups. We analyzed the patients' clinicopathological factors, including prognosis, according to the degree of stromal TILs. We also analyzed the correlation between stromal TILs and the minimum ADC value. Stromal TILs in the marginal area reflected overall survival more accurately than that in the central area. Additionally, marginal low TILs was significantly associated with lymph node metastasis and portal vein invasion. Both overall- and disease-free survival rates in the marginal low TILs group were significantly worse than those in the marginal high TILs group (P < 0.05). In the multivariate analysis, marginal low TILs were an independent prognostic factor for both overall- and disease-free survival (P < 0.05), and marginal low TILs were significantly associated with lower minimum ADC values (P < 0.02). Stromal TILs, especially in the marginal area, might demonstrate prognostic impact in patients with IHCC. Moreover, the ADC values from MRI may predict TILs in IHCC tumor tissue.","Tumor-infiltrating lymphocytes (TILs) are a prognostic factor or an indicator of chemotherapy response for various malignancies. The aim of this study was to investigate the prognostic impact of TILs in resected intrahepatic cholangiocarcinoma (IHCC). We also investigated the usefulness of the apparent diffusion coefficient (ADC) in diffusion-weighted magnetic resonance imaging (DW-MRI) to predict TILs. We enrolled 23 patients with IHCC who underwent initial hepatic resection in Tokushima University Hospital from 2006 to 2017. We evaluated stromal TILs in the tumor marginal area and central area in surgical specimens. Patients were divided into low vs high stromal TILs groups. We analyzed the patients' clinicopathological factors, including prognosis, according to the degree of stromal TILs. We also analyzed the correlation between stromal TILs and the minimum ADC value. Stromal TILs in the marginal area reflected overall survival more accurately than that in the central area. Additionally, marginal low TILs was significantly associated with lymph node metastasis and portal vein invasion. Both overall- and disease-free survival rates in the marginal low TILs group were significantly worse than those in the marginal high TILs group (P < 0.05). In the multivariate analysis, marginal low TILs were an independent prognostic factor for both overall- and disease-free survival (P < 0.05), and marginal low TILs were significantly associated with lower minimum ADC values (P < 0.02). Stromal TILs, especially in the marginal area, might demonstrate prognostic impact in patients with IHCC. Moreover, the ADC values from MRI may predict TILs in IHCC tumor tissue.","null","null","2021-10-01","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.26","No.12","2265","2274","eng","true","null","scientific_journal","null","null","10.1007/s10147-021-02026-3","1437-7772","null","null","null","null","null"
"【消化管重複症のすべて】腹部食道","【消化管重複症のすべて】腹部食道","石橋 広樹, 横田 典子, 森 大樹, 島田 光生","Hiroki Ishibashi, Noriko Yokota, Hiroki Mori, Mitsuo Shimada","null","null","null","null","null","2021-09-25","小児外科","Japanese Journal of Pediatric Surgery","Vol.53","No.9","924","929","jpn","true","null","scientific_journal","null","null","10.24479/j00645.2022002817","0385-6313","null","https://search.jamas.or.jp/link/ui/2022002817","null","null","null"
"Effective three-dimensional culture of hepatocyte-like cells generated from human adipose-derived mesenchymal stem cells.","Effective three-dimensional culture of hepatocyte-like cells generated from human adipose-derived mesenchymal stem cells.","Yu Saitou, Tetsuya Ikemoto, Kazunori Tokuda, Katsuki Miyazaki, Shin-ichiro Yamada, Satoru Imura, Masato Miyake, Yuji Morine, Seiichi Oyadomari, Mitsuo Shimada","Yu Saitou, Tetsuya Ikemoto, Kazunori Tokuda, Katsuki Miyazaki, Shin-ichiro Yamada, Satoru Imura, Masato Miyake, Yuji Morine, Seiichi Oyadomari, Mitsuo Shimada","null","The aim of this study was to clarify the effectiveness of a new three-dimensional (3D) culture system for hepatocyte-like cells (HLCs) generated from human adipose-derived mesenchymal stem cells (ADSCs). Human ADSCs (2 × 10 ) with or without 0.1 mg/mL human recombinant peptide μ-piece per well were seeded in a 96-well U-bottom plate and then our three-step differentiation protocol was applied for 21 days. At each step, cell morphology and gene expression were investigated. Mature hepatocyte functions were evaluated after HLC differentiation. These parameters were compared between 2D- and 3D-cultured HLCs, and, DNA microarray analysis was also performed. Finally, HLCs were transplanted in to CCl induced acute liver failure model mice. Two-dimensional-cultured HLCs at day 21 did not have a spindle shape and had formed spheroids after day 6, which gradually increased in size for 3D-cultured HLCs. Definitive endoderm, hepatoblast, and hepatocyte genes showed significantly higher expression in the 3D culture group. Three-dimensional-cultured HLCs also had higher albumin expression, CYP3A4 activity, urea synthesis, and ammonium metabolism, and much higher expression of ion transporter, blood coagulation, and cell communication genes. HLC transplantation improved serum liver function, especially in T-Bil levels, and engrafted into immunodeficient mice with HLA class I positive staining. Our new 3D culture protocol is effective to improve hepatocyte functions. Our HLCs might be promising for clinical cell transplantation to treat metabolic disease.","The aim of this study was to clarify the effectiveness of a new three-dimensional (3D) culture system for hepatocyte-like cells (HLCs) generated from human adipose-derived mesenchymal stem cells (ADSCs). Human ADSCs (2 × 10 ) with or without 0.1 mg/mL human recombinant peptide μ-piece per well were seeded in a 96-well U-bottom plate and then our three-step differentiation protocol was applied for 21 days. At each step, cell morphology and gene expression were investigated. Mature hepatocyte functions were evaluated after HLC differentiation. These parameters were compared between 2D- and 3D-cultured HLCs, and, DNA microarray analysis was also performed. Finally, HLCs were transplanted in to CCl induced acute liver failure model mice. Two-dimensional-cultured HLCs at day 21 did not have a spindle shape and had formed spheroids after day 6, which gradually increased in size for 3D-cultured HLCs. Definitive endoderm, hepatoblast, and hepatocyte genes showed significantly higher expression in the 3D culture group. Three-dimensional-cultured HLCs also had higher albumin expression, CYP3A4 activity, urea synthesis, and ammonium metabolism, and much higher expression of ion transporter, blood coagulation, and cell communication genes. HLC transplantation improved serum liver function, especially in T-Bil levels, and engrafted into immunodeficient mice with HLA class I positive staining. Our new 3D culture protocol is effective to improve hepatocyte functions. Our HLCs might be promising for clinical cell transplantation to treat metabolic disease.","null","null","2021-07-28","Journal of Hepato-Biliary-Pancreatic Sciences","Journal of Hepato-Biliary-Pancreatic Sciences","Vol.28","No.9","705","715","eng","true","null","scientific_journal","null","null","10.1002/jhbp.1024","1868-6982","null","null","null","null","null"
"Robot-assisted total gastrectomy for gastric cancer in a patient with amyotrophic lateral sclerosis receiving long-term tracheostomy invasive ventilation","Robot-assisted total gastrectomy for gastric cancer in a patient with amyotrophic lateral sclerosis receiving long-term tracheostomy invasive ventilation","Masaaki Nishi, Ryosuke Miyamoto, Kasane Shima, Hirokazu Miki, Hideo Terasawa, Chie Takasu, Kouzou Yoshikawa, Takuro Oyama, Katsuya Tanaka, Yuishin Izumi, Mitsuo Shimada","Masaaki Nishi, Ryosuke Miyamoto, Kasane Shima, Hirokazu Miki, Hideo Terasawa, Chie Takasu, Kouzou Yoshikawa, Takuro Oyama, Katsuya Tanaka, Yuishin Izumi, Mitsuo Shimada","null","Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Although affected patients may develop cancers, major surgical intervention has been hampered by its questionable overall benefit due to limited prognosis and risk of postoperative respiratory collapse. A recent study, however, showed that tracheostomy invasive ventilation (TIV) prolonged median survival to 11.3 years; thus, patients with ALS receiving TIV might benefit from major surgery. A 66-year-old man with ALS, who had received TIV and enteral tube feeding for 8 years, presented with bloody stool. The patient also had type 2 diabetes mellitus, stage 4 chronic kidney disease, abdominal aortic aneurysm, and anti-phospholipid syndrome, as well as multiple episodes of pneumonia and catheter-related urinary tract infection treated by antibiotics. Medical examination and esophagogastroduodenoscopy revealed a type 3 tumor in the middle part of the stomach. The patient's preoperative diagnosis was gastric cancer (GC), MU, type3, Less-Post, T3(SS), N1, H0, P0, M0, cStage III. The estimated mortality rate was 30.5%, according to the Japanese National Clinical Database. The patient and his family were fully informed of the risk of surgery; the patient clearly requested curative surgery by eye movement. Thus, robot-assisted total gastrectomy (RATG) was performed. The tissues were extremely fragile and hemorrhagic. The surgical time was 7 h 0 min; intraoperative blood loss was 324 ml. Pathological examination revealed GC, MU, type3, T4a(SE), N2, H0, CY0, P0, M0 fStage IIIB. The postoperative course was uneventful. He has remained in stable condition for 3 months. Our findings suggest that patients with ALS who achieve longer survival with TIV can undergo major cancer surgery, including robot-assisted surgery, which may facilitate a better mid-long-term prognosis. The online version contains supplementary material available at 10.1007/s13691-021-00499-7.","Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Although affected patients may develop cancers, major surgical intervention has been hampered by its questionable overall benefit due to limited prognosis and risk of postoperative respiratory collapse. A recent study, however, showed that tracheostomy invasive ventilation (TIV) prolonged median survival to 11.3 years; thus, patients with ALS receiving TIV might benefit from major surgery. A 66-year-old man with ALS, who had received TIV and enteral tube feeding for 8 years, presented with bloody stool. The patient also had type 2 diabetes mellitus, stage 4 chronic kidney disease, abdominal aortic aneurysm, and anti-phospholipid syndrome, as well as multiple episodes of pneumonia and catheter-related urinary tract infection treated by antibiotics. Medical examination and esophagogastroduodenoscopy revealed a type 3 tumor in the middle part of the stomach. The patient's preoperative diagnosis was gastric cancer (GC), MU, type3, Less-Post, T3(SS), N1, H0, P0, M0, cStage III. The estimated mortality rate was 30.5%, according to the Japanese National Clinical Database. The patient and his family were fully informed of the risk of surgery; the patient clearly requested curative surgery by eye movement. Thus, robot-assisted total gastrectomy (RATG) was performed. The tissues were extremely fragile and hemorrhagic. The surgical time was 7 h 0 min; intraoperative blood loss was 324 ml. Pathological examination revealed GC, MU, type3, T4a(SE), N2, H0, CY0, P0, M0 fStage IIIB. The postoperative course was uneventful. He has remained in stable condition for 3 months. Our findings suggest that patients with ALS who achieve longer survival with TIV can undergo major cancer surgery, including robot-assisted surgery, which may facilitate a better mid-long-term prognosis. The online version contains supplementary material available at 10.1007/s13691-021-00499-7.","null","null","2021-07-12","International Cancer Conference Journal","International Cancer Conference Journal","Vol.10","No.4","318","323","eng","true","null","scientific_journal","null","null","10.1007/s13691-021-00499-7","2192-3183","null","null","null","null","null"
"【胆管損傷と(医原性)術後胆管狭窄:回避とリカバリー法】先天性胆道拡張症手術における胆道再建と術後胆管狭窄へのリカバリーショット","【胆管損傷と(医原性)術後胆管狭窄:回避とリカバリー法】先天性胆道拡張症手術における胆道再建と術後胆管狭窄へのリカバリーショット","森根 裕二, 石橋 広樹, 島田 光生","Yuji Morine, Hiroki Ishibashi, Mitsuo Shimada","null","null","null","null","null","2021-07","胆と膵","Journal of Biliary Tract & Pancreas","Vol.42","No.7","631","637","jpn","true","null","scientific_journal","null","null","null","0388-9408","null","null","null","null","null"
"【シミュレーションとナビゲーション】胸腔鏡下肺葉切除術","【シミュレーションとナビゲーション】胸腔鏡下肺葉切除術","石橋 広樹, 横田 典子, 森 大樹, 島田 光生","Hiroki Ishibashi, Noriko Yokota, Hiroki Mori, Mitsuo Shimada","null","null","null","null","null","2021-05-25","小児外科","Japanese Journal of Pediatric Surgery","Vol.53","No.5","520","524","jpn","true","null","scientific_journal","null","null","10.24479/j00645.2021229968","0385-6313","null","https://search.jamas.or.jp/link/ui/2021229968","null","null","null"
"Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update.","Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update.","Masatoshi Kudo, Yusuke Kawamura, Kiyoshi Hasegawa, Ryosuke Tateishi, Kazuya Kariyama, Shuichiro Shiina, Hidenori Toyoda, Yasuharu Imai, Atsushi Hiraoka, Masafumi Ikeda, Namiki Izumi, Michihisa Moriguchi, Sadahisa Ogasawara, Yasunori Minami, Kazuomi Ueshima, Takamichi Murakami, Shiro Miyayama, Osamu Nakashima, Hirohisa Yano, Michiie Sakamoto, Etsuro Hatano, Mitsuo Shimada, Norihiro Kokudo, Satoshi Mochida, Tetsuo Takehara","Masatoshi Kudo, Yusuke Kawamura, Kiyoshi Hasegawa, Ryosuke Tateishi, Kazuya Kariyama, Shuichiro Shiina, Hidenori Toyoda, Yasuharu Imai, Atsushi Hiraoka, Masafumi Ikeda, Namiki Izumi, Michihisa Moriguchi, Sadahisa Ogasawara, Yasunori Minami, Kazuomi Ueshima, Takamichi Murakami, Shiro Miyayama, Osamu Nakashima, Hirohisa Yano, Michiie Sakamoto, Etsuro Hatano, Mitsuo Shimada, Norihiro Kokudo, Satoshi Mochida, Tetsuo Takehara","null","The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other's work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC.","The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other's work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC.","null","null","2021-05-19","Liver Cancer","Liver Cancer","Vol.10","No.3","181","223","eng","true","null","scientific_journal","null","null","10.1159/000514174","2235-1795","null","null","null","null","null"
"A new pathological classification of intrahepatic cholangiocarcinoma according to protein expression of SSTR2 and Bcl2.","A new pathological classification of intrahepatic cholangiocarcinoma according to protein expression of SSTR2 and Bcl2.","Shoko Yamashita, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Chie Takasu, Shinichiro Yamada, Kazunori Tokuda, Shohei Okikawa, Katsuki Miyazaki, Takeshi Oya, Koichi Tsuneyama, Mitsuo Shimada","Shoko Yamashita, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Chie Takasu, Shinichiro Yamada, Kazunori Tokuda, Shohei Okikawa, Katsuki Miyazaki, Takeshi Oya, Koichi Tsuneyama, Mitsuo Shimada","null","This method could be used to classify IHCC into peripheral and perihilar type by embryological expression patterns of SSTR2 and Bcl2.","This method could be used to classify IHCC into peripheral and perihilar type by embryological expression patterns of SSTR2 and Bcl2.","null","null","2021-05-07","World Journal of Surgical Oncology","World Journal of Surgical Oncology","Vol.19","No.1","142","142","eng","true","null","scientific_journal","null","null","10.1186/s12957-021-02216-3","1477-7819","null","null","null","null","null"
"Malnutrition by European Society for Clinical Nutrition and Metabolism criteria predicts prognosis in patients with gastrointestinal and hepatobiliary-pancreatic cancer","Malnutrition by European Society for Clinical Nutrition and Metabolism criteria predicts prognosis in patients with gastrointestinal and hepatobiliary-pancreatic cancer","Nozomi Aotani, Sonoko Yasui-Yamada, Natsumi Kagiya, TAKIMOTO Mami, Yu Ohiwa, Matsubara Atsumi, Sayaka Matsura, Mayu Tanimura, Yoshiko Suzuki, Hideya Kashihara, Yu Saitou, Masaaki Nishi, Mitsuo Shimada, Yasuhiro Hamada","Nozomi Aotani, Sonoko Yasui-Yamada, Natsumi Kagiya, TAKIMOTO Mami, Yu Ohiwa, Matsubara Atsumi, Sayaka Matsura, Mayu Tanimura, Yoshiko Suzuki, Hideya Kashihara, Yu Saitou, Masaaki Nishi, Mitsuo Shimada, Yasuhiro Hamada","null","The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed the ESPEN diagnostic criteria (EDC) for malnutrition in 2015. There is no report on the association between the EDC and prognosis in patients with gastrointestinal (GI) and hepatobiliary-pancreatic (HBP) cancer. This study aimed to (1) determine the prevalence of EDC malnutrition, (2) investigate the validity of the EDC as a nutritional and prognostic indicator, and (3) examine which components of the EDC are most related to long-term prognosis in patients with GI and HBP cancers. A total of 634 patients with primary GI and HBP cancers who underwent their first resection surgery between July 2014 and March 2018 were retrospectively recruited. According to the EDC, patients were divided into malnourished and non-malnourished groups. Clinical parameters and survival between these two groups were compared. The prognostic effects of the EDC and the EDC components were analyzed using Cox proportional hazard models. The prevalence of EDC malnutrition was 22%. Anthropometric data and biochemical data were associated with EDC malnutrition. The 5-year survival rate was lower in the malnourished group (72%) than in the non-malnourished group (73%; P = 0.007). The multivariate analysis demonstrated that the malnourished group was an independent risk factor for mortality (hazard ratio = 1.70 in the malnourished group; 95% confidence interval 1.08-2.63; P = 0.024). Among EDC components, body mass index (BMI) of <18.5 kg/m was an independent poor prognostic factor. EDC malnutrition is associated with poor postoperative long-term prognosis. Among the EDC components, BMI of <18.5 kg/m is most associated with prognosis in patients with preoperative GI and HBP cancers.","The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed the ESPEN diagnostic criteria (EDC) for malnutrition in 2015. There is no report on the association between the EDC and prognosis in patients with gastrointestinal (GI) and hepatobiliary-pancreatic (HBP) cancer. This study aimed to (1) determine the prevalence of EDC malnutrition, (2) investigate the validity of the EDC as a nutritional and prognostic indicator, and (3) examine which components of the EDC are most related to long-term prognosis in patients with GI and HBP cancers. A total of 634 patients with primary GI and HBP cancers who underwent their first resection surgery between July 2014 and March 2018 were retrospectively recruited. According to the EDC, patients were divided into malnourished and non-malnourished groups. Clinical parameters and survival between these two groups were compared. The prognostic effects of the EDC and the EDC components were analyzed using Cox proportional hazard models. The prevalence of EDC malnutrition was 22%. Anthropometric data and biochemical data were associated with EDC malnutrition. The 5-year survival rate was lower in the malnourished group (72%) than in the non-malnourished group (73%; P = 0.007). The multivariate analysis demonstrated that the malnourished group was an independent risk factor for mortality (hazard ratio = 1.70 in the malnourished group; 95% confidence interval 1.08-2.63; P = 0.024). Among EDC components, body mass index (BMI) of <18.5 kg/m was an independent poor prognostic factor. EDC malnutrition is associated with poor postoperative long-term prognosis. Among the EDC components, BMI of <18.5 kg/m is most associated with prognosis in patients with preoperative GI and HBP cancers.","null","null","2021-04","Clinical Nutrition ESPEN","Clinical Nutrition ESPEN","Vol.42","null","265","271","eng","true","null","scientific_journal","null","null","10.1016/j.clnesp.2021.01.023","2405-4577","null","null","null","null","null"
"Value of the fibrinogen-platelet ratio in patients with resectable pancreatic cancer.","Value of the fibrinogen-platelet ratio in patients with resectable pancreatic cancer.","Yusuke Arakawa, Katsuki Miyazaki, Masato Yoshikawa, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Mitsuo Shimada","Yusuke Arakawa, Katsuki Miyazaki, Masato Yoshikawa, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Mitsuo Shimada","null","Background : Several prognostic factors were reported in pancreatic cancer. The fibrinogen-platelet ratio (FPR) was reported as a prognostic factor of resectable gastric cancer. In this report, the FPR was evaluated in patients with resectable pancreatic cancer. Methods : Between 2004 and 2019, 163 patients with curative resection for pancreatic cancer were enrolled. Cases of non-curative resection were excluded. The FPR was calculated using the preoperative plasma fibrinogen and the platelet counts and the cut-off value was determined by receiver operating characteristic (ROC) curve analysis. The patients were divided into high and low FPR groups according to this cut-off value. Results : The cut-off value of FPR was 25.2. Among age, sex, body mass index (BMI), and surgical factors including surgery type, volume of blood loss and surgery time, there was no significant difference between the two groups. Patients in the low FPR group had significantly better overall survival (OS) and relapse-free survival (RFS) compared with the high FPR group (P < 0.05). On multivariate analysis, a high FPR, CA19-9 > 300 U /l, and receipt of adjuvant chemotherapy were independent risk factors for OS and DFS. Conclusions : The FPR might be a prognostic factor for patients with resectable pancreatic cancer. J. Med. Invest. 68 : 342-346, August, 2021.","Background : Several prognostic factors were reported in pancreatic cancer. The fibrinogen-platelet ratio (FPR) was reported as a prognostic factor of resectable gastric cancer. In this report, the FPR was evaluated in patients with resectable pancreatic cancer. Methods : Between 2004 and 2019, 163 patients with curative resection for pancreatic cancer were enrolled. Cases of non-curative resection were excluded. The FPR was calculated using the preoperative plasma fibrinogen and the platelet counts and the cut-off value was determined by receiver operating characteristic (ROC) curve analysis. The patients were divided into high and low FPR groups according to this cut-off value. Results : The cut-off value of FPR was 25.2. Among age, sex, body mass index (BMI), and surgical factors including surgery type, volume of blood loss and surgery time, there was no significant difference between the two groups. Patients in the low FPR group had significantly better overall survival (OS) and relapse-free survival (RFS) compared with the high FPR group (P < 0.05). On multivariate analysis, a high FPR, CA19-9 > 300 U /l, and receipt of adjuvant chemotherapy were independent risk factors for OS and DFS. Conclusions : The FPR might be a prognostic factor for patients with resectable pancreatic cancer. J. Med. Invest. 68 : 342-346, August, 2021.","null","null","2021","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.68","No.3.4","342","346","eng","true","null","scientific_journal","null","null","10.2152/jmi.68.342","1349-6867","null","null","null","null","null"
"Impact of phase angle on postoperative prognosis in patients with gastrointestinal and hepatobiliary-pancreatic cancer","Impact of phase angle on postoperative prognosis in patients with gastrointestinal and hepatobiliary-pancreatic cancer","Sonoko Yasui-Yamada, Yu Oiwa, Yu Saitou, Aotani Nozomi, Matsubara Atsumi, Matsuura Sayaka, Tanimura Mayu, Yoshiko Suzuki, Hideya Kashihara, Masaaki Nishi, Mitsuo Shimada, Yasuhiro Hamada","Sonoko Yasui-Yamada, Yu Oiwa, Yu Saitou, Aotani Nozomi, Matsubara Atsumi, Matsuura Sayaka, Tanimura Mayu, Yoshiko Suzuki, Hideya Kashihara, Masaaki Nishi, Mitsuo Shimada, Yasuhiro Hamada","null","null","null","null","null","2020-11","Nutrition","Nutrition","Vol.79-80","null","110891","110891","eng","true","null","scientific_journal","null","null","10.1016/j.nut.2020.110891","1873-1244","null","null","null","null","null"
"Conversion therapy for unresectable hepatocellular carcinoma after lenvatinib Three case reports.","Conversion therapy for unresectable hepatocellular carcinoma after lenvatinib Three case reports.","Tetsu Tomonari, Yasushi Sato, Hironori Tanaka, Takahiro Tanaka, Tatsuya Taniguchi, Masahiro Sogabe, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma, Yu Saitou, Satoru Imura, Yoshimi Bando, Mitsuo Shimada, Tetsuji Takayama","Tetsu Tomonari, Yasushi Sato, Hironori Tanaka, Takahiro Tanaka, Tatsuya Taniguchi, Masahiro Sogabe, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma, Yu Saitou, Satoru Imura, Yoshimi Bando, Mitsuo Shimada, Tetsuji Takayama","null","Lenvatinib (LEN) is a novel potent multi-tyrosine kinase inhibitor, approved as first-line treatment for unresectable hepatocellular carcinoma (HCC). Considering its high objective response rate, LEN therapy could be expected to achieve downstaging of tumors and lead to conversion therapy with hepatectomy or ablation. However, the feasibility of conversion therapy after LEN treatment in unresectable HCC remains largely unknown. Here, we reported 3 cases of unresectable HCC: case 1, a 69-year-old man diagnosed with ruptured HCC; case 2, a 72-year-old woman with nonalcoholic steatohepatitis-based HCC; and case 3, a 73-year-old man with a history of alcoholic cirrhosis-based HCC. In all cases, cirrhosis was classified as Child-Pugh 5 and modified albumin-bilirubin grade 1 or 2a. HCC was diagnosed as Barcelona Clinic Liver Cancer (BCLC) stage B. In all cases, LEN was initiated after conventional-transcatheter arterial embolization enforcement, while maintaining liver function. In all cases, the main tumor size decreased after 6 months of LEN treatment and no satellite nodes were detected, indicating downstaging of HCC to BCLC stage A. Subsequently, conversion hepatectomy or ablation was performed. After successful conversion therapy, the general condition of the patients was good, without tumor recurrence during the observation period (median 10 months). This study demonstrated that LEN enables downstaging of HCC and thus represents a bridge to successful surgery or ablation therapy. In particular, LEN treatment may facilitate the possibility for conversion therapy of initially unresectable HCC, while maintaining the hepatic functional reserve.","Lenvatinib (LEN) is a novel potent multi-tyrosine kinase inhibitor, approved as first-line treatment for unresectable hepatocellular carcinoma (HCC). Considering its high objective response rate, LEN therapy could be expected to achieve downstaging of tumors and lead to conversion therapy with hepatectomy or ablation. However, the feasibility of conversion therapy after LEN treatment in unresectable HCC remains largely unknown. Here, we reported 3 cases of unresectable HCC: case 1, a 69-year-old man diagnosed with ruptured HCC; case 2, a 72-year-old woman with nonalcoholic steatohepatitis-based HCC; and case 3, a 73-year-old man with a history of alcoholic cirrhosis-based HCC. In all cases, cirrhosis was classified as Child-Pugh 5 and modified albumin-bilirubin grade 1 or 2a. HCC was diagnosed as Barcelona Clinic Liver Cancer (BCLC) stage B. In all cases, LEN was initiated after conventional-transcatheter arterial embolization enforcement, while maintaining liver function. In all cases, the main tumor size decreased after 6 months of LEN treatment and no satellite nodes were detected, indicating downstaging of HCC to BCLC stage A. Subsequently, conversion hepatectomy or ablation was performed. After successful conversion therapy, the general condition of the patients was good, without tumor recurrence during the observation period (median 10 months). This study demonstrated that LEN enables downstaging of HCC and thus represents a bridge to successful surgery or ablation therapy. In particular, LEN treatment may facilitate the possibility for conversion therapy of initially unresectable HCC, while maintaining the hepatic functional reserve.","null","null","2020-09-18","Medicine","Medicine","Vol.99","No.42","e22782","e22782","eng","true","null","scientific_journal","null","null","10.1097/MD.0000000000022782","0025-7974","null","null","null","null","null"
"Cancer-associated Adipocytes Promote Pancreatic Cancer Progression Through SAA1 Expression","Cancer-associated Adipocytes Promote Pancreatic Cancer Progression Through SAA1 Expression","Masanori Takehara, Yasushi Sato, Tetsuo Kimura, Kazuyoshi Noda, Hiroshi Miyamoto, Yasuteru Fujino, Jinsei Miyoshi, Fumika Nakamura, Hironori Wada, Yoshimi Bando, Tetsuya Ikemoto, Mitsuo Shimada, Naoki Muguruma, Tetsuji Takayama","Masanori Takehara, Yasushi Sato, Tetsuo Kimura, Kazuyoshi Noda, Hiroshi Miyamoto, Yasuteru Fujino, Jinsei Miyoshi, Fumika Nakamura, Hironori Wada, Yoshimi Bando, Tetsuya Ikemoto, Mitsuo Shimada, Naoki Muguruma, Tetsuji Takayama","null","Although pancreatic cancer often invades into peripancreatic adipose tissue, little is known about the cancer-adipocyte interaction. We first investigated the ability of adipocytes to de-differentiate to cancer-associated adipocytes (CAAs) by co-culturing with pancreatic cancer cells. We then examined the effects of CAA-conditioned media (CAA-CM) on the malignant characteristics of cancer cells, the mechanism underlying those effects, and their clinical relevance in pancreatic cancer. When 3T3-L1 adipocytes were co-cultured with pancreatic cancer cells (PANC-1) using Transwell system, adipocytes lost their lipid droplets and morphologically changed to fibroblast-like cells (CAA). Adipocyte-specific marker mRNA levels significantly decreased but those of fibroblast-specific markers appeared, characteristic findings of CAA, as revealed by real-time PCR. When PANC-1 cells were cultured with CAA-CM, significantly higher migration/invasion capability, chemoresistance, and epithelial-mesenchymal transition (EMT) properties were observed compared with control cells. To investigate the mechanism underlying these effects, we performed microarray analysis of PANC-1 cells cultured with CAA-CM, and found 78.5-fold higher expression of SAA1 compared with control cells. When SAA1 gene in PANC-1 cells was knocked down with SAA1 siRNA, migration/invasion capability, chemoresistance, and EMT properties were significantly attenuated compared with control cells. Immunohistochemical analysis on human pancreatic cancer tissues revealed positive SAA1 expression in 46/61 (75.4%). Overall survival in the SAA1-positive group was significantly shorter than in the SAA1-negative group (p=0.013). In conclusion, we demonstrated that pancreatic cancer cells induced de-differentiation in adipocytes toward CAA, and CAA promoted malignant characteristics of pancreatic cancer via SAA1 expression, suggesting that SAA1 is a novel therapeutic target in pancreatic cancer.","Although pancreatic cancer often invades into peripancreatic adipose tissue, little is known about the cancer-adipocyte interaction. We first investigated the ability of adipocytes to de-differentiate to cancer-associated adipocytes (CAAs) by co-culturing with pancreatic cancer cells. We then examined the effects of CAA-conditioned media (CAA-CM) on the malignant characteristics of cancer cells, the mechanism underlying those effects, and their clinical relevance in pancreatic cancer. When 3T3-L1 adipocytes were co-cultured with pancreatic cancer cells (PANC-1) using Transwell system, adipocytes lost their lipid droplets and morphologically changed to fibroblast-like cells (CAA). Adipocyte-specific marker mRNA levels significantly decreased but those of fibroblast-specific markers appeared, characteristic findings of CAA, as revealed by real-time PCR. When PANC-1 cells were cultured with CAA-CM, significantly higher migration/invasion capability, chemoresistance, and epithelial-mesenchymal transition (EMT) properties were observed compared with control cells. To investigate the mechanism underlying these effects, we performed microarray analysis of PANC-1 cells cultured with CAA-CM, and found 78.5-fold higher expression of SAA1 compared with control cells. When SAA1 gene in PANC-1 cells was knocked down with SAA1 siRNA, migration/invasion capability, chemoresistance, and EMT properties were significantly attenuated compared with control cells. Immunohistochemical analysis on human pancreatic cancer tissues revealed positive SAA1 expression in 46/61 (75.4%). Overall survival in the SAA1-positive group was significantly shorter than in the SAA1-negative group (p=0.013). In conclusion, we demonstrated that pancreatic cancer cells induced de-differentiation in adipocytes toward CAA, and CAA promoted malignant characteristics of pancreatic cancer via SAA1 expression, suggesting that SAA1 is a novel therapeutic target in pancreatic cancer.","null","null","2020-07-14","Cancer Science","Cancer Science","Vol.111","No.8","2883","2894","eng","true","null","scientific_journal","null","null","10.1111/cas.14527","1349-7006","null","null","null","null","null"
"【膵・胆管合流異常と先天性胆道拡張症】疫学","【膵・胆管合流異常と先天性胆道拡張症】疫学","石橋 広樹, 島田 光生, 森根 裕二","Hiroki Ishibashi, Mitsuo Shimada, Yuji Morine","null","null","null","null","null","2020-03-20","臨床消化器内科","Clinical Gastroenterology","Vol.35","No.4","355","362","jpn","true","null","scientific_journal","null","null","10.19020/cg.0000001104","0911-601X","null","null","null","null","null"
"Bevacizumab-associated intestinal perforation and perioperative complications in patients receiving bevacizumab.","Bevacizumab-associated intestinal perforation and perioperative complications in patients receiving bevacizumab.","Toshiaki Yoshimoto, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Yukako Takehara, Mitsuo Shimada","Toshiaki Yoshimoto, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Yukako Takehara, Mitsuo Shimada","null","The purposes of this study are to present cases of emergency surgery in which gastrointestinal perforation occurred during bevacizumab administration, consider the indications for emergency surgery, and examine the safety of scheduled surgery after a washout period for bevacizumab. (a) We retrospectively investigated seven patients who underwent emergency surgery for bevacizumab-associated intestinal perforation. (b) We investigated 104 patients with advanced colorectal cancer treated with neoadjuvant therapy who underwent surgery from 2008 to 2018, retrospectively. (a) In the seven patients undergoing emergency surgery for gastrointestinal perforation, the median bevacizumab administration and washout periods were 16 weeks and 24 days, respectively. A stoma was created in all patients except in those who were not candidates. Two patients developed postoperative abdominal abscesses, and two patients died from perioperative sepsis and gastrointestinal bleeding, respectively; both of these patients had poor performance status. (b) In patients receiving bevacizumab (n = 45) and patients treated with bevacizumab-free regimens as neoadjuvant therapy (n = 59), 31 and 52 patients received chemoradiotherapy, respectively. We found no correlation with postoperative complications with or without bevacizumab. The surgical indications should be considered carefully in patients with gastrointestinal perforation secondary to bevacizumab administration. Meanwhile, after appropriate cessation time, scheduled surgery following bevacizumab administration is feasible.","The purposes of this study are to present cases of emergency surgery in which gastrointestinal perforation occurred during bevacizumab administration, consider the indications for emergency surgery, and examine the safety of scheduled surgery after a washout period for bevacizumab. (a) We retrospectively investigated seven patients who underwent emergency surgery for bevacizumab-associated intestinal perforation. (b) We investigated 104 patients with advanced colorectal cancer treated with neoadjuvant therapy who underwent surgery from 2008 to 2018, retrospectively. (a) In the seven patients undergoing emergency surgery for gastrointestinal perforation, the median bevacizumab administration and washout periods were 16 weeks and 24 days, respectively. A stoma was created in all patients except in those who were not candidates. Two patients developed postoperative abdominal abscesses, and two patients died from perioperative sepsis and gastrointestinal bleeding, respectively; both of these patients had poor performance status. (b) In patients receiving bevacizumab (n = 45) and patients treated with bevacizumab-free regimens as neoadjuvant therapy (n = 59), 31 and 52 patients received chemoradiotherapy, respectively. We found no correlation with postoperative complications with or without bevacizumab. The surgical indications should be considered carefully in patients with gastrointestinal perforation secondary to bevacizumab administration. Meanwhile, after appropriate cessation time, scheduled surgery following bevacizumab administration is feasible.","null","null","2020-02-12","Annals of Gastroenterological Surgery","Annals of Gastroenterological Surgery","Vol.4","No.2","151","155","eng","true","null","scientific_journal","null","null","10.1002/ags3.12312","2475-0328","null","null","null","null","null"
"Anastomotic recurrence after laparoscopic distal gastrectomy with delta-shaped anastomosis : report of a case.","Anastomotic recurrence after laparoscopic distal gastrectomy with delta-shaped anastomosis : report of a case.","Daichi Ishikawa, Kouzou Yoshikawa, Jun Higashijima, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Mitsuo Shimada","Daichi Ishikawa, Kouzou Yoshikawa, Jun Higashijima, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Mitsuo Shimada","null","Delta-shaped anastomosis is nowadays an increasingly performed reconstruction method in laparoscopic distal gastrectomy for early gastric cancer. To date, anastomotic recurrence at the delta-shaped anastomotic site has not been reported. Surgery for this disease is more complicated than anastomotic recurrence at the site of conventional Billroth-I anastomosis. A 68-year-old female was referred to our institute with early gastric cancer on the posterior wall of the antrum. She underwent laparoscopic distal gastrectomy with delta-shaped Billroth-I anastomosis. Follow-up gastrofiberscopy 16 months after the operation revealed suspected anastomotic recurrence, and gastric biopsy revealed signet-ring cell carcinoma. Open total gastrectomy with reconstruction with the Roux-en-Y method was performed. At the distal part of the previous anastomosis, an adequate length of the duodenum was dissected from the pancreas. Then, the duodenum was transected 3 cm distal to the anastomosis using a linear stapler. The patient recovered well and was discharged on postoperative day 14. The patient is alive without re-recurrence 3 years postoperatively. We successfully treated a patient with anastomotic recurrence of gastric cancer after delta-shaped anastomosis. Adequate resection of the duodenal stump was performed without any residual tumor or injury to the pancreas. J. Med. Invest. 67 : 211-213, February, 2020.","Delta-shaped anastomosis is nowadays an increasingly performed reconstruction method in laparoscopic distal gastrectomy for early gastric cancer. To date, anastomotic recurrence at the delta-shaped anastomotic site has not been reported. Surgery for this disease is more complicated than anastomotic recurrence at the site of conventional Billroth-I anastomosis. A 68-year-old female was referred to our institute with early gastric cancer on the posterior wall of the antrum. She underwent laparoscopic distal gastrectomy with delta-shaped Billroth-I anastomosis. Follow-up gastrofiberscopy 16 months after the operation revealed suspected anastomotic recurrence, and gastric biopsy revealed signet-ring cell carcinoma. Open total gastrectomy with reconstruction with the Roux-en-Y method was performed. At the distal part of the previous anastomosis, an adequate length of the duodenum was dissected from the pancreas. Then, the duodenum was transected 3 cm distal to the anastomosis using a linear stapler. The patient recovered well and was discharged on postoperative day 14. The patient is alive without re-recurrence 3 years postoperatively. We successfully treated a patient with anastomotic recurrence of gastric cancer after delta-shaped anastomosis. Adequate resection of the duodenal stump was performed without any residual tumor or injury to the pancreas. J. Med. Invest. 67 : 211-213, February, 2020.","null","null","2020-02","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.67","No.1.2","211","213","eng","true","null","scientific_journal","null","null","10.2152/jmi.67.211","1349-6867","null","null","null","null","null"
"Hepatic Stellate Cells Contribute to the Tumor Malignancy of Hepatocellular Carcinoma Through the IL-6 Pathway.","Hepatic Stellate Cells Contribute to the Tumor Malignancy of Hepatocellular Carcinoma Through the IL-6 Pathway.","Shuichi Iwahashi, Feng Rui, Yuji Morine, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada","Shuichi Iwahashi, Feng Rui, Yuji Morine, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada","null","The hepatic stellate cells (HSCs) have relationship to cancer progression. The aim of this study is to investigate the effect of HSCs and the role of IL-6/Stat3 pathway on hepatocellular carcinoma (HCC) progression. HCCs were co-cultured with HSCs. The viability and migration ability of cancer cells were detected. Epithelial-mesenchymal transition (EMT) marker (E-cadherin), stem cell marker (CD44) and p-signal transducer and activator of transcription 3 (p-STAT3) of cancer cells were evaluated. Finally, interleukin-6 (IL-6) neutralization was performed. Co-culture of HCCs with HSCs increased cancer cell viability and migration ability. EMT and stemness of cancer cells increased with HSCs. Following IL-6 neutralization, phospho-STAT3 activation, cancer cell viability and migration, as well as EMT, and stemness of cancer cells decreased. HSCs promoted HCC progression through the IL-6/STAT3 pathway.","The hepatic stellate cells (HSCs) have relationship to cancer progression. The aim of this study is to investigate the effect of HSCs and the role of IL-6/Stat3 pathway on hepatocellular carcinoma (HCC) progression. HCCs were co-cultured with HSCs. The viability and migration ability of cancer cells were detected. Epithelial-mesenchymal transition (EMT) marker (E-cadherin), stem cell marker (CD44) and p-signal transducer and activator of transcription 3 (p-STAT3) of cancer cells were evaluated. Finally, interleukin-6 (IL-6) neutralization was performed. Co-culture of HCCs with HSCs increased cancer cell viability and migration ability. EMT and stemness of cancer cells increased with HSCs. Following IL-6 neutralization, phospho-STAT3 activation, cancer cell viability and migration, as well as EMT, and stemness of cancer cells decreased. HSCs promoted HCC progression through the IL-6/STAT3 pathway.","null","null","2020-02","Anticancer Research","Anticancer Research","Vol.40","No.2","743","749","eng","true","null","scientific_journal","null","null","10.21873/anticanres.14005","1791-7530","null","null","null","null","null"
"Expression Level of MicroRNA-449a Predicts the Prognosis of Patients With Gastric Cancer.","Expression Level of MicroRNA-449a Predicts the Prognosis of Patients With Gastric Cancer.","Daichi Ishikawa, Kouzou Yoshikawa, Chie Takasu, Hideya Kashihara, Masaaki Nishi, Takuya Tokunaga, Jun Higashijima, Mitsuo Shimada","Daichi Ishikawa, Kouzou Yoshikawa, Chie Takasu, Hideya Kashihara, Masaaki Nishi, Takuya Tokunaga, Jun Higashijima, Mitsuo Shimada","null","In previous studies, we demonstrated the significant role of microRNA-449a (miR-449a) in colorectal cancer with in vivo and clinical samples. The importance of miR-449a in gastric cancer is still to be elucidated. This study examined the impact of miR-449a expression in tumor tissue and serum and investigated its potential as a prognostic marker in gastric cancer. Sixty-six patients with gastric cancer who underwent surgery were included in the study. miR-449a expression in tumor tissue and serum were investigated by real-time polymerase chain reaction analysis. The association of miR-449a expression with clinicopathological factors and patient prognosis were also investigated. miR-449a expression was lower in tumor tissue than non-tumor tissue. miR-449a in tumor tissue negatively correlated with the malignancy of tumor and clinical stage. Increased carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were seen at significantly higher frequencies in patients with low miR-449a expression. Patients with low miR-449a expression had poorer cancer-specific survival compared to those with high miR-449a expression. The univariate analysis showed that lymphovascular invasion, increased CEA and CA19-9 and a low expression of miR-449a were associated with a poorer 5-year cancer-specific survival. miR-449a expression level in serum correlated to that in tumor tissue and was also associated with tumor malignancy. The miR-449a level in tumor tissue might be useful as a prognostic indicator for patients with gastric cancer and miR-449a in serum appears to reflect its expression in tumor tissue.","In previous studies, we demonstrated the significant role of microRNA-449a (miR-449a) in colorectal cancer with in vivo and clinical samples. The importance of miR-449a in gastric cancer is still to be elucidated. This study examined the impact of miR-449a expression in tumor tissue and serum and investigated its potential as a prognostic marker in gastric cancer. Sixty-six patients with gastric cancer who underwent surgery were included in the study. miR-449a expression in tumor tissue and serum were investigated by real-time polymerase chain reaction analysis. The association of miR-449a expression with clinicopathological factors and patient prognosis were also investigated. miR-449a expression was lower in tumor tissue than non-tumor tissue. miR-449a in tumor tissue negatively correlated with the malignancy of tumor and clinical stage. Increased carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were seen at significantly higher frequencies in patients with low miR-449a expression. Patients with low miR-449a expression had poorer cancer-specific survival compared to those with high miR-449a expression. The univariate analysis showed that lymphovascular invasion, increased CEA and CA19-9 and a low expression of miR-449a were associated with a poorer 5-year cancer-specific survival. miR-449a expression level in serum correlated to that in tumor tissue and was also associated with tumor malignancy. The miR-449a level in tumor tissue might be useful as a prognostic indicator for patients with gastric cancer and miR-449a in serum appears to reflect its expression in tumor tissue.","null","null","2020-01","Anticancer Research","Anticancer Research","Vol.40","No.1","239","244","eng","true","null","scientific_journal","null","null","10.21873/anticanres.13945","1791-7530","null","null","null","null","null"
"Effect of epigenetic modulation on cancer sphere.","Effect of epigenetic modulation on cancer sphere.","Shuichi Iwahashi, Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Shin-ichiro Yamada, Toru Utsunomiya","Shuichi Iwahashi, Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Shin-ichiro Yamada, Toru Utsunomiya","null","Background : Cancer stem cell properties are highly relevant to the biology of treatment-resistant cancers. Epigenetic modification regulates gene expressions by chromatin remodeling during malignant transformation. The aim of this study was to elucidate the possible strategy for cancer stem cells focusing on epigenetic modification. Methods : We made cancer sphere from HepG2 cells, and we added Histone deacetylase (HDAC) inhibitor, valproic acid to cancer sphere. And we compared methylation status and the gene expression between normal HepG2 and cancer sphere groups, and between cancer sphere and sphere with HDAC inhibitor treatment groups. Results : Valproic acid (VPA) cancelled this spheroid formation. In comparison between normal HepG2 and cancer sphere, the number of methylation status changes more than 0.1 of beta level was 826 probes, and we could isolate some epithelial-mesenchymal transition (EMT) related genes. And VPA reduced the expressions of EMT related genes in sphere with RT-PCR. On the other hand, in comparison between cancer sphere and sphere with VPA treatment, we detected 29 probe of methylation status change, and VPA reduced the expressions of Bcl-6 in sphere. Conclusions : HDAC inhibitor affected the methylation status of cancer stem cells. Histone-acetylation might overcome treatmet-resistant cancer through the regulation of cancer stem cell. J. Med. Invest. 67 : 70-74, February, 2020.","Background : Cancer stem cell properties are highly relevant to the biology of treatment-resistant cancers. Epigenetic modification regulates gene expressions by chromatin remodeling during malignant transformation. The aim of this study was to elucidate the possible strategy for cancer stem cells focusing on epigenetic modification. Methods : We made cancer sphere from HepG2 cells, and we added Histone deacetylase (HDAC) inhibitor, valproic acid to cancer sphere. And we compared methylation status and the gene expression between normal HepG2 and cancer sphere groups, and between cancer sphere and sphere with HDAC inhibitor treatment groups. Results : Valproic acid (VPA) cancelled this spheroid formation. In comparison between normal HepG2 and cancer sphere, the number of methylation status changes more than 0.1 of beta level was 826 probes, and we could isolate some epithelial-mesenchymal transition (EMT) related genes. And VPA reduced the expressions of EMT related genes in sphere with RT-PCR. On the other hand, in comparison between cancer sphere and sphere with VPA treatment, we detected 29 probe of methylation status change, and VPA reduced the expressions of Bcl-6 in sphere. Conclusions : HDAC inhibitor affected the methylation status of cancer stem cells. Histone-acetylation might overcome treatmet-resistant cancer through the regulation of cancer stem cell. J. Med. Invest. 67 : 70-74, February, 2020.","null","null","2020","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.67","No.1.2","70","74","eng","true","null","scientific_journal","null","null","10.2152/jmi.67.70","1349-6867","null","null","null","null","null"
"Establishment of an evaluation system for non-technical skills in surgery : Surgeon and paramedical staff assessments.","Establishment of an evaluation system for non-technical skills in surgery : Surgeon and paramedical staff assessments.","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Toshiaki Yoshimoto, Takashi Iwata","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Toshiaki Yoshimoto, Takashi Iwata","null","Purposes : Non-technical skills contribute to safe and efficient team performance. The aim of this study was to clarify the importance of non-technical skills by a questionnaire and the usefulness of feedback to the operator. Method : A questionnaire was administered to the operator and paramedical staff for 404 operations. Total and individual scores were compared, and the effect of feedback was analyzed by comparison between pre-feedback and post-feedback. Results : The total score of the paramedical staff was 100 [full score] [n = 186], 90-99 [n = 133], and 80-89 [n = 47]. In all cases, the score of the paramedical staff was significantly better than that of the operator. After feedback, the rate of a score less than 80 was significantly decreased. In junior doctor cases with laparoscopy, feedback tended to have a positive effect. Conclusions : Questionnaires completed by both surgeons and paramedical staff are useful for identifying problems with non-technical skills. J. Med. Invest. 67 : 83-86, February, 2020.","Purposes : Non-technical skills contribute to safe and efficient team performance. The aim of this study was to clarify the importance of non-technical skills by a questionnaire and the usefulness of feedback to the operator. Method : A questionnaire was administered to the operator and paramedical staff for 404 operations. Total and individual scores were compared, and the effect of feedback was analyzed by comparison between pre-feedback and post-feedback. Results : The total score of the paramedical staff was 100 [full score] [n = 186], 90-99 [n = 133], and 80-89 [n = 47]. In all cases, the score of the paramedical staff was significantly better than that of the operator. After feedback, the rate of a score less than 80 was significantly decreased. In junior doctor cases with laparoscopy, feedback tended to have a positive effect. Conclusions : Questionnaires completed by both surgeons and paramedical staff are useful for identifying problems with non-technical skills. J. Med. Invest. 67 : 83-86, February, 2020.","null","null","2020","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.67","No.1.2","83","86","eng","true","null","scientific_journal","null","null","10.2152/jmi.67.83","1349-6867","null","null","null","null","null"
"A change in the zinc ion concentration reflects the maturation of insulin-producing cells generated from adipose-derived mesenchymal stem cells.","A change in the zinc ion concentration reflects the maturation of insulin-producing cells generated from adipose-derived mesenchymal stem cells.","Shogo Ohta, Tetsuya Ikemoto, Yuma Wada, Yu Saitou, Shin-ichiro Yamada, Satoru Imura, Yuji Morine, Mitsuo Shimada","Shogo Ohta, Tetsuya Ikemoto, Yuma Wada, Yu Saitou, Shin-ichiro Yamada, Satoru Imura, Yuji Morine, Mitsuo Shimada","null","The generation of insulin-producing cells (IPCs) from pluripotent stem cells could be a breakthrough treatment for type 1 diabetes. However, development of new techniques is needed to exclude immature cells for clinical application. Dithizone staining is used to evaluate IPCs by detecting zinc. We hypothesised that zinc ion (Zn) dynamics reflect the IPC maturation status. Human adipose-derived stem cells were differentiated into IPCs by our two-step protocol using two-dimensional (2D) or 3D culture. The stimulation indexes of 2D -and 3D-cultured IPCs on day 21 were 1.21 and 3.64 (P < 0.05), respectively. The 3D-cultured IPCs were stained with dithizone during culture, and its intensity calculated by ImageJ reached the peak on day 17 (P < 0.05). Blood glucose levels of streptozotocin-induced diabetic nude mice were normalised (4/4,100%) after transplantation of 96 3D-cultured IPCs. Zn concentration changes in the medium of 3D cultures had a negative value in the early period and a large positive value in the latter period. This study suggests that Zn dynamics based on our observations and staining of zinc transporters have critical roles in the differentiation of IPCs, and that their measurement might be useful to evaluate IPC maturation as a non-destructive method.","The generation of insulin-producing cells (IPCs) from pluripotent stem cells could be a breakthrough treatment for type 1 diabetes. However, development of new techniques is needed to exclude immature cells for clinical application. Dithizone staining is used to evaluate IPCs by detecting zinc. We hypothesised that zinc ion (Zn) dynamics reflect the IPC maturation status. Human adipose-derived stem cells were differentiated into IPCs by our two-step protocol using two-dimensional (2D) or 3D culture. The stimulation indexes of 2D -and 3D-cultured IPCs on day 21 were 1.21 and 3.64 (P < 0.05), respectively. The 3D-cultured IPCs were stained with dithizone during culture, and its intensity calculated by ImageJ reached the peak on day 17 (P < 0.05). Blood glucose levels of streptozotocin-induced diabetic nude mice were normalised (4/4,100%) after transplantation of 96 3D-cultured IPCs. Zn concentration changes in the medium of 3D cultures had a negative value in the early period and a large positive value in the latter period. This study suggests that Zn dynamics based on our observations and staining of zinc transporters have critical roles in the differentiation of IPCs, and that their measurement might be useful to evaluate IPC maturation as a non-destructive method.","null","null","2019-12-10","Scientific Reports","Scientific Reports","Vol.9","No.1","18731","18731","eng","true","null","scientific_journal","null","null","10.1038/s41598-019-55172-0","2045-2322","null","null","null","null","null"
"腹痛に対して抑肝散加陳皮半夏が著効した1例","A Case of Stomachache Successfully Treated with Yokukansankachinpihange","福島 裕造, 島田 光生, 河合 知則, 藤田 良介, 上野 力敏, 船越 多恵, 三明 淳一朗, 杉原 徳郎","Yuzo FUKUSHIMA, Mitsuo Shimada, Tomonori KAWAI, Ryosuke FUJITA, Rikitoshi UENO, Tae FUNAKOSHI, Junichiro MIAKE, Tokuo SUGIHARA","null","
We report the case of a 36-year-old male who presented with an abdominal complaint after straightening of irregular teeth. He was examined and treated, however, the cause of the abdominal complaint could not be determined and the treatment was ineffective. He was treated in our clinic with yokukansankachinpihange for obvious pulsation in the supraumbilical region following the oral tradition of Kampo medicine, and the symptom gradually disappeared. We discussed the mechanism of the stomachache in Kampo medicine. After treatment, this case was diagnosed as somatoform autonomic dysfunction in psychiatric medicine. Advanced treatment by a psychiatrist was necessary to treat this disease in psychiatric medicine. In this case it is suggested that treatment following the oral tradition of Kampo medicine was effective.
","We report the case of a 36-year-old male who presented with an abdominal complaint after straightening of irregular teeth. He was examined and treated, however, the cause of the abdominal complaint could not be determined and the treatment was ineffective. He was treated in our clinic with yokukansankachinpihange for obvious pulsation in the supraumbilical region following the oral tradition of Kampo medicine, and the symptom gradually disappeared. We discussed the mechanism of the stomachache in Kampo medicine. After treatment, this case was diagnosed as somatoform autonomic dysfunction in psychiatric medicine. Advanced treatment by a psychiatrist was necessary to treat this disease in psychiatric medicine. In this case it is suggested that treatment following the oral tradition of Kampo medicine was effective.
","null","null","2019-10","日本東洋医学雑誌","Kampo Medicine","Vol.70","No.4","361","365","jpn","true","null","scientific_journal","null","null","10.3937/kampomed.70.361","0287-4857","null","https://ci.nii.ac.jp/naid/130007806365/","null","null","null"
"先天性胆道拡張症と膵・胆管合流異常","先天性胆道拡張症と膵・胆管合流異常","石橋 広樹, 森 大樹, 横田 典子, 島田 光生","Hiroki Ishibashi, Hiroki Mori, Noriko Yokota, Mitsuo Shimada","null","null","null","null","null","2019-10","小児内科","Japanese Journal of Pediatric Medicine","Vol.51","No.10","1516","1520","jpn","true","null","scientific_journal","null","null","null","0385-6305","null","null","null","null","null"
"In vitro and in vivo effects of insulin-producing cells generated by xeno-antigen free 3D culture with RCP piece.","In vitro and in vivo effects of insulin-producing cells generated by xeno-antigen free 3D culture with RCP piece.","Tetsuya Ikemoto, Rui Feng, Shuichi Iwahashi, Shin-ichiro Yamada, Yu Saitou, Yuji Morine, Satoru Imura, Munehide Matsuhisa, Mitsuo Shimada","Tetsuya Ikemoto, Rui Feng, Shuichi Iwahashi, Shin-ichiro Yamada, Yu Saitou, Yuji Morine, Satoru Imura, Munehide Matsuhisa, Mitsuo Shimada","null","To establish widespread cell therapy for type 1 diabetes mellitus, we aimed to develop an effective protocol for generating insulin-producing cells (IPCs) from adipose-derived stem cells (ADSCs). We established a 3D culture using a human recombinant peptide (RCP) petaloid μ-piece with xeno-antigen free reagents. Briefly, we employed our two-step protocol to differentiate ADSCs in 96-well dishes and cultured cells in xeno-antigen free reagents with 0.1 mg/mL RCP μ-piece for 7 days (step 1), followed by addition of histone deacetylase inhibitor for 14 days (step 2). Generated IPCs were strongly stained with dithizone, anti-insulin antibody at day 21, and microstructures resembling insulin secretory granules were detected by electron microscopy. Glucose stimulation index (maximum value, 4.9) and MAFA mRNA expression were significantly higher in 3D cultured cells compared with conventionally cultured cells (P < 0.01 and P < 0.05, respectively). The hyperglycaemic state of streptozotocin-induced diabetic nude mice converted to normoglycaemic state around 14 days after transplantation of 96 IPCs under kidney capsule or intra-mesentery. Histological evaluation revealed that insulin and C-peptide positive structures existed at day 120. Our established xeno-antigen free and RCP petaloid μ-piece 3D culture method for generating IPCs may be suitable for clinical application, due to the proven effectiveness in vitro and in vivo.","To establish widespread cell therapy for type 1 diabetes mellitus, we aimed to develop an effective protocol for generating insulin-producing cells (IPCs) from adipose-derived stem cells (ADSCs). We established a 3D culture using a human recombinant peptide (RCP) petaloid μ-piece with xeno-antigen free reagents. Briefly, we employed our two-step protocol to differentiate ADSCs in 96-well dishes and cultured cells in xeno-antigen free reagents with 0.1 mg/mL RCP μ-piece for 7 days (step 1), followed by addition of histone deacetylase inhibitor for 14 days (step 2). Generated IPCs were strongly stained with dithizone, anti-insulin antibody at day 21, and microstructures resembling insulin secretory granules were detected by electron microscopy. Glucose stimulation index (maximum value, 4.9) and MAFA mRNA expression were significantly higher in 3D cultured cells compared with conventionally cultured cells (P < 0.01 and P < 0.05, respectively). The hyperglycaemic state of streptozotocin-induced diabetic nude mice converted to normoglycaemic state around 14 days after transplantation of 96 IPCs under kidney capsule or intra-mesentery. Histological evaluation revealed that insulin and C-peptide positive structures existed at day 120. Our established xeno-antigen free and RCP petaloid μ-piece 3D culture method for generating IPCs may be suitable for clinical application, due to the proven effectiveness in vitro and in vivo.","null","null","2019-07-24","Scientific Reports","Scientific Reports","Vol.9","No.1","null","null","eng","true","null","scientific_journal","null","null","10.1038/s41598-019-47257-7","2045-2322","null","null","null","null","null"
"The Significance of MicroRNA-449a and Its Potential Target HDAC1 in Patients With Colorectal Cancer.","The Significance of MicroRNA-449a and Its Potential Target HDAC1 in Patients With Colorectal Cancer.","Daichi Ishikawa, Chie Takasu, Hideya Kashihara, Masaaki Nishi, Takuya Tokunaga, Jun Higashijima, Kouzou Yoshikawa, Koji Yasutomo, Mitsuo Shimada","Daichi Ishikawa, Chie Takasu, Hideya Kashihara, Masaaki Nishi, Takuya Tokunaga, Jun Higashijima, Kouzou Yoshikawa, Koji Yasutomo, Mitsuo Shimada","null","miR-449a level might be a prognostic indicator for colorectal cancer and miR-449a might regulate HDAC1 expression.","miR-449a level might be a prognostic indicator for colorectal cancer and miR-449a might regulate HDAC1 expression.","null","null","2019-06","Anticancer Research","Anticancer Research","Vol.39","No.6","2855","2860","eng","true","null","scientific_journal","null","null","10.21873/anticanres.13414","1791-7530","null","null","null","null","null"
"Development of monoclonal mouse antibodies that specifically recognize pancreatic polypeptide.","Development of monoclonal mouse antibodies that specifically recognize pancreatic polypeptide.","Akemi Hara, Yuko Nakagawa, Keiko Nakao, Motoyuki Tamaki, Tetsuya Ikemoto, Mitsuo Shimada, Munehide Matsuhisa, Hiroki Mizukami, Nobuhiro Maruyama, Hirotaka Watada, Yoshio Fujitani","Akemi Hara, Yuko Nakagawa, Keiko Nakao, Motoyuki Tamaki, Tetsuya Ikemoto, Mitsuo Shimada, Munehide Matsuhisa, Hiroki Mizukami, Nobuhiro Maruyama, Hirotaka Watada, Yoshio Fujitani","null","Pancreatic polypeptide (PP) is a 36-amino acid peptide encoded by the Ppy gene, which is produced by a small population of cells located in the periphery of the islets of Langerhans. Owing to the high amino acid sequence similarity among neuropeptide Y family members, antibodies against PP that are currently available are not convincingly specific to PP. Here we report the development of mouse monoclonal antibodies that specifically bind to PP. We generated Ppy knockout (Ppy-KO) mice in which the Ppy-coding region was replaced by Cre recombinase. The Ppy-KO mice were immunized with mouse PP peptide, and stable hybridoma cell lines producing anti-PP antibodies were isolated. Firstly, positive clones were selected in an enzyme-linked immunosorbent assay for reactivity with PP coupled to bovine serum albumin. During the screening, hybridoma clones producing antibodies that cross-react to the peptide YY (PYY) were excluded. In the second screening, hybridoma clones in which their culture media produce no signal in Ppy-KO islets but detect specific cells in the peripheral region of wild-type islets, were selected. Further studies demonstrated that the selected monoclonal antibody (23-2D3) specifically recognizes PP-producing cells, not only in mouse, but also in human and rat islets. The monoclonal antibodies with high binding specificity for PP developed in this study will be fundamental for future studies towards elucidating the expression profiles and the physiological roles of PP.","Pancreatic polypeptide (PP) is a 36-amino acid peptide encoded by the Ppy gene, which is produced by a small population of cells located in the periphery of the islets of Langerhans. Owing to the high amino acid sequence similarity among neuropeptide Y family members, antibodies against PP that are currently available are not convincingly specific to PP. Here we report the development of mouse monoclonal antibodies that specifically bind to PP. We generated Ppy knockout (Ppy-KO) mice in which the Ppy-coding region was replaced by Cre recombinase. The Ppy-KO mice were immunized with mouse PP peptide, and stable hybridoma cell lines producing anti-PP antibodies were isolated. Firstly, positive clones were selected in an enzyme-linked immunosorbent assay for reactivity with PP coupled to bovine serum albumin. During the screening, hybridoma clones producing antibodies that cross-react to the peptide YY (PYY) were excluded. In the second screening, hybridoma clones in which their culture media produce no signal in Ppy-KO islets but detect specific cells in the peripheral region of wild-type islets, were selected. Further studies demonstrated that the selected monoclonal antibody (23-2D3) specifically recognizes PP-producing cells, not only in mouse, but also in human and rat islets. The monoclonal antibodies with high binding specificity for PP developed in this study will be fundamental for future studies towards elucidating the expression profiles and the physiological roles of PP.","null","null","2019-03-06","Endocrine Journal","Endocrine Journal","Vol.66","No.5","459","468","eng","true","null","scientific_journal","null","null","10.1507/endocrj.EJ18-0441","1348-4540","null","null","null","null","null"
"消化器外科領域","Gastroenterological, Hepatobiliary and Pancreatic Surgery","齋藤 裕, 居村 暁, 島田 光生","Yu Saitou, Satoru Imura, Mitsuo Shimada","null","null","null","null","null","2019","日本コンピュータ外科学会誌","Journal of Japan Society of Computer Aided Surgery","Vol.21","No.3","150","152","jpn","true","null","scientific_journal","null","null","10.5759/jscas.21.150","1344-9486","null","https://ci.nii.ac.jp/naid/130007706297/","null","null","null"
"Epigallocatechin-3-gallate Enhances Radiation Sensitivity in Colorectal Cancer Cells Through Nrf2 Activation and Autophagy.","Epigallocatechin-3-gallate Enhances Radiation Sensitivity in Colorectal Cancer Cells Through Nrf2 Activation and Autophagy.","Tumenjin Enkhbat, Masaaki Nishi, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Daichi Ishikawa, Masahide Tominaga, Mitsuo Shimada","Tumenjin Enkhbat, Masaaki Nishi, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Daichi Ishikawa, Masahide Tominaga, Mitsuo Shimada","null","Epigallocatechin-3-gallate (EGCG) is a major polyphenolic component of green tea. EGCG plays a potential role in radio-sensitizing cancer cells. The combined effect of EGCG and radiation was investigated in a colorectal cancer cell line, focusing on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) autophagy signalling. HCT-116 cells were treated with 12.5 μM EGCG for different periods of time, 2 Gy radiation, or both. Cell viability was determined with the WST-8 assay. The number of colonies was determined with the colony formation assay. mRNA expression of LC3 and caspase-9 was analyzed with quantitative real-time polymerase chain reaction. Combination treatment with EGCG and radiation significantly decreased the growth of HCT-116 cells. The number of colonies was reduced to 34.2% compared to the control group. Immunofluorescence microscopy images showed that nuclear translocation of Nrf2 was significantly increased when cells were treated with the combination of EGCG and radiation compared to the control and single-treatment groups. Combined treatment with EGCG and radiation significantly induced LC3 and caspase-9 mRNA expression. EGCG increased the sensitivity of colorectal cancer cells to radiation by inhibiting cell proliferation and inducing Nrf2 nuclear translocation and autophagy.","Epigallocatechin-3-gallate (EGCG) is a major polyphenolic component of green tea. EGCG plays a potential role in radio-sensitizing cancer cells. The combined effect of EGCG and radiation was investigated in a colorectal cancer cell line, focusing on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) autophagy signalling. HCT-116 cells were treated with 12.5 μM EGCG for different periods of time, 2 Gy radiation, or both. Cell viability was determined with the WST-8 assay. The number of colonies was determined with the colony formation assay. mRNA expression of LC3 and caspase-9 was analyzed with quantitative real-time polymerase chain reaction. Combination treatment with EGCG and radiation significantly decreased the growth of HCT-116 cells. The number of colonies was reduced to 34.2% compared to the control group. Immunofluorescence microscopy images showed that nuclear translocation of Nrf2 was significantly increased when cells were treated with the combination of EGCG and radiation compared to the control and single-treatment groups. Combined treatment with EGCG and radiation significantly induced LC3 and caspase-9 mRNA expression. EGCG increased the sensitivity of colorectal cancer cells to radiation by inhibiting cell proliferation and inducing Nrf2 nuclear translocation and autophagy.","null","null","2018-11","Anticancer Research","Anticancer Research","Vol.38","No.11","6247","6252","eng","true","null","scientific_journal","null","null","10.21873/anticanres.12980","1791-7530","null","null","null","null","null"
"Photobiomodulation with red light emitting diodes accelerates hepatocytes proliferation through reactive oxygen species / extracellular signal-regulated kinase pathway.","Photobiomodulation with red light emitting diodes accelerates hepatocytes proliferation through reactive oxygen species / extracellular signal-regulated kinase pathway.","Rui Feng, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Shuichi Iwahashi, Yu Saitou, Mitsuo Shimada","Rui Feng, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Shuichi Iwahashi, Yu Saitou, Mitsuo Shimada","null","null","null","null","null","2018-10","Hepatology Research","Hepatology Research","Vol.48","No.11","926","936","eng","true","null","scientific_journal","null","null","10.1111/hepr.13182","1872-034X","null","null","null","null","null"
"Nrf2 activation drive macrophages polarization and cancer cell epithelial-mesenchymal transition during interaction","Nrf2 activation drive macrophages polarization and cancer cell epithelial-mesenchymal transition during interaction","Rui Feng, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Shuichi Iwahashi, Yu Saitou, Mitsuo Shimada","Rui Feng, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Shuichi Iwahashi, Yu Saitou, Mitsuo Shimada","null","The M2 phenotype of tumor-associated macrophages (TAM) inhibits the anti-tumor inflammation, increases angiogenesis and promotes tumor progression. The transcription factor Nuclear Factor (erythroid-derived 2)-Like 2 (Nrf2) not only modulates the angiogenesis but also plays the anti-inflammatory role through inhibiting pro-inflammatory cytokines expression; however, the role of Nrf2 in the cancer cell and macrophages interaction is not clear. Hepatocellular carcinoma cells (Hep G2 and Huh 7) and pancreatic cancer cells (SUIT2 and Panc-1) were co-cultured with monocytes cells (THP-1) or peripheral blood monocytes derived macrophages, then the phenotype changes of macrophages and epithelial-mesenchymal transition of cancer cells were detected. Also, the role of Nrf2 in cancer cells and macrophages interaction were investigated. In this study, we found that cancer cells could induce an M2-like macrophage characterized by up-regulation of CD163 and Arg1, and down-regulation of IL-1b and IL-6 through Nrf2 activation. Also, Nrf2 activation of macrophages promoted VEGF expression. The Nrf2 activation of macrophages correlated with the reactive oxygen species induced by cancer cells derived lactate. Cancer cells educated macrophages could activate Nrf2 of the cancer cells, in turn, to increase cancer cells epithelial-mesenchymal transition (EMT) through paracrine VEGF. These findings suggested that Nrf2 played the important role in the cancer cells and macrophages interaction. Macrophage Nrf2 activation by cancer cell-derived lactate skews macrophages polarization towards an M2-like phenotype and educated macrophages activate Nrf2 of the cancer cells to promote EMT of cancer cells. This study provides a new understanding of the role of Nrf2 in the cancer cell and TAM interaction and suggests a potential therapeutic target.","The M2 phenotype of tumor-associated macrophages (TAM) inhibits the anti-tumor inflammation, increases angiogenesis and promotes tumor progression. The transcription factor Nuclear Factor (erythroid-derived 2)-Like 2 (Nrf2) not only modulates the angiogenesis but also plays the anti-inflammatory role through inhibiting pro-inflammatory cytokines expression; however, the role of Nrf2 in the cancer cell and macrophages interaction is not clear. Hepatocellular carcinoma cells (Hep G2 and Huh 7) and pancreatic cancer cells (SUIT2 and Panc-1) were co-cultured with monocytes cells (THP-1) or peripheral blood monocytes derived macrophages, then the phenotype changes of macrophages and epithelial-mesenchymal transition of cancer cells were detected. Also, the role of Nrf2 in cancer cells and macrophages interaction were investigated. In this study, we found that cancer cells could induce an M2-like macrophage characterized by up-regulation of CD163 and Arg1, and down-regulation of IL-1b and IL-6 through Nrf2 activation. Also, Nrf2 activation of macrophages promoted VEGF expression. The Nrf2 activation of macrophages correlated with the reactive oxygen species induced by cancer cells derived lactate. Cancer cells educated macrophages could activate Nrf2 of the cancer cells, in turn, to increase cancer cells epithelial-mesenchymal transition (EMT) through paracrine VEGF. These findings suggested that Nrf2 played the important role in the cancer cells and macrophages interaction. Macrophage Nrf2 activation by cancer cell-derived lactate skews macrophages polarization towards an M2-like phenotype and educated macrophages activate Nrf2 of the cancer cells to promote EMT of cancer cells. This study provides a new understanding of the role of Nrf2 in the cancer cell and TAM interaction and suggests a potential therapeutic target.","null","null","2018-09-04","Cell Communication & Signaling","Cell Communication & Signaling","Vol.16","No.1","54","54","eng","true","null","scientific_journal","null","null","10.1186/s12964-018-0262-x","1478-811X","null","null","null","null","null"
"肝癌手術エキスパートへの道 (特集 癌手術エキスパートになるための道)","肝癌手術エキスパートへの道 (特集 癌手術エキスパートになるための道)","齋藤 裕, 居村 暁, 池本 哲也, 森根 裕二, 杉本 真樹, 島田 光生","Yu Saitou, Satoru Imura, Tetsuya Ikemoto, Yuji Morine, 杉本 真樹, Mitsuo Shimada","null","null","null","null","null","2018-09","臨床外科","Journal of Clinical Surgery","Vol.73","No.9","1108","1114","jpn","true","null","scientific_journal","null","null","null","0386-9857","null","null","null","null","null"
"【手術で臓器が「どうなる?」から術後後ケアが見える!わかる!イラスト理解 消化器外科の術式・術後ケア】実はこんな臓器も切られている!","【手術で臓器が「どうなる?」から術後後ケアが見える!わかる!イラスト理解 消化器外科の術式・術後ケア】実はこんな臓器も切られている!","吉川 幸造, 島田 光生","Kouzou Yoshikawa, Mitsuo Shimada","null","null","null","null","null","2018-08","消化器外科Nursing","Gastroenterological Surgery Nursing","Vol.23","No.8","681","682","jpn","true","null","scientific_journal","null","null","null","1341-7819","null","null","null","null","null"
"胆道再建を含む肝切除術 (ビギナーズ特集 手術で臓器が「どうなる?」から術後ケアが見える! わかる! イラスト理解 消化器外科の術式・術後ケア)","胆道再建を含む肝切除術 (ビギナーズ特集 手術で臓器が「どうなる?」から術後ケアが見える! わかる! イラスト理解 消化器外科の術式・術後ケア)","齋藤 裕, 山田 眞一郎, 岩橋 衆一, 池本 哲也, 居村 暁, 森根 裕二, 島田 光生","Yu Saitou, Shin-ichiro Yamada, Shuichi Iwahashi, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Mitsuo Shimada","null","null","null","null","null","2018-08","消化器外科Nursing","Gastroenterological Surgery Nursing","Vol.23","No.8","709","714","jpn","true","null","scientific_journal","null","null","null","1341-7819","null","https://ci.nii.ac.jp/naid/40021644777/","null","null","null"
"The Effect of Roux-en-Y Reconstruction on Type 2 Diabetes in the Early Postoperative Period.","The Effect of Roux-en-Y Reconstruction on Type 2 Diabetes in the Early Postoperative Period.","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu","null","The aim of this study was to investigate the effect of Roux-en-Y (RY) reconstruction on type 2 diabetes with gastric cancer in the early postoperative period. A total of 44 patients with gastric cancer with type 2 diabetes who underwent total gastrectomy (TG) or distal gastrectomy (DG) with Roux-en-Y reconstruction or DG with Bilroth I were enrolled. All three groups had their fasting glucose and daily insulin dose recorded preoperatively, on day 2 postoperatively (POD2) and at discharge. The TG group showed low fasting glucose and daily insulin dose on POD2 compared to their preoperative state. On discharge, the fasting glucose and daily insulin dose were significantly lower in both TG and DG Roux-en-Y groups than preoperatively. Roux-en-Y reconstruction showed early improvement of type 2 diabetes regardless of any body weight loss. The effect of Roux-en-Y reconstruction in TG on type 2 diabetes was more remarkable than that of DG.","The aim of this study was to investigate the effect of Roux-en-Y (RY) reconstruction on type 2 diabetes with gastric cancer in the early postoperative period. A total of 44 patients with gastric cancer with type 2 diabetes who underwent total gastrectomy (TG) or distal gastrectomy (DG) with Roux-en-Y reconstruction or DG with Bilroth I were enrolled. All three groups had their fasting glucose and daily insulin dose recorded preoperatively, on day 2 postoperatively (POD2) and at discharge. The TG group showed low fasting glucose and daily insulin dose on POD2 compared to their preoperative state. On discharge, the fasting glucose and daily insulin dose were significantly lower in both TG and DG Roux-en-Y groups than preoperatively. Roux-en-Y reconstruction showed early improvement of type 2 diabetes regardless of any body weight loss. The effect of Roux-en-Y reconstruction in TG on type 2 diabetes was more remarkable than that of DG.","null","null","2018-08","Anticancer Research","Anticancer Research","Vol.38","No.8","4901","4905","eng","true","null","scientific_journal","null","null","10.21873/anticanres.12805","1791-7530","null","null","null","null","null"
"Analysis of gender-based differences among surgeons in Japan: results of a survey conducted by the Japan Surgical Society. Part. 2: personal life.","Analysis of gender-based differences among surgeons in Japan: results of a survey conducted by the Japan Surgical Society. Part. 2: personal life.","Kazumi Kawase, Kyoko Nomura, Ryuji Tominaga, Hirotaka Iwase, Tomoko Ogawa, Ikuko Shibasaki, Mitsuo Shimada, Tomoaki Taguchi, Emiko Takeshita, Yasuko Tomizawa, Sachiyo Nomura, Kazuhiro Hanazaki, Tomoko Hanashi, Hiroko Yamashita, Norihiro Kokudo, Kotaro Maeda","Kazumi Kawase, Kyoko Nomura, Ryuji Tominaga, Hirotaka Iwase, Tomoko Ogawa, Ikuko Shibasaki, Mitsuo Shimada, Tomoaki Taguchi, Emiko Takeshita, Yasuko Tomizawa, Sachiyo Nomura, Kazuhiro Hanazaki, Tomoko Hanashi, Hiroko Yamashita, Norihiro Kokudo, Kotaro Maeda","null","To assess the true conditions and perceptions of the personal lives of men and women working as surgeons in Japan. In 2014, all e-mail subscribed members of the Japan Surgical Society (JSS, n = 29,861) were invited to complete a web-based survey. The questions covered demographic information, work environment, and personal life (including marital status, childcare, and nursing care for adult family members). In total, 6211 surgeons (5586 men and 625 women) returned the questionnaires, representing a response rate of 20.8%. Based on the questionnaire responses, surgeons generally prioritize work and spend most of their time at work, although women with children prioritize their family over work; men spend significantly fewer hours on domestic work/childcare than do their female counterparts (men 0.76 h/day vs. women 2.93 h/day, p < 0.01); and both men and women surgeons, regardless of their age or whether they have children, place more importance on the role of women in the family. The personal lives of Japanese surgeons differed significantly according to gender and whether they have children. The conservative idea that women should bear primary responsibility for the family still pertains for both men and women working as surgeons in Japan.","To assess the true conditions and perceptions of the personal lives of men and women working as surgeons in Japan. In 2014, all e-mail subscribed members of the Japan Surgical Society (JSS, n = 29,861) were invited to complete a web-based survey. The questions covered demographic information, work environment, and personal life (including marital status, childcare, and nursing care for adult family members). In total, 6211 surgeons (5586 men and 625 women) returned the questionnaires, representing a response rate of 20.8%. Based on the questionnaire responses, surgeons generally prioritize work and spend most of their time at work, although women with children prioritize their family over work; men spend significantly fewer hours on domestic work/childcare than do their female counterparts (men 0.76 h/day vs. women 2.93 h/day, p < 0.01); and both men and women surgeons, regardless of their age or whether they have children, place more importance on the role of women in the family. The personal lives of Japanese surgeons differed significantly according to gender and whether they have children. The conservative idea that women should bear primary responsibility for the family still pertains for both men and women working as surgeons in Japan.","null","null","2018-08","Surgery Today","Surgery Today","Vol.48","No.3","308","319","eng","true","null","scientific_journal","null","null","10.1007/s00595-017-1586-7","1436-2813","null","null","null","null","null"
"Current Status of Surgical Incisions Used in Donors During Living Related Liver Transplantation-A Nationwide Survey in Japan.","Current Status of Surgical Incisions Used in Donors During Living Related Liver Transplantation-A Nationwide Survey in Japan.","Ken Shirabe, Susumu Eguchi, Hideaki Okajima, Kiyoshi Hasegawa, Shigeru Marubashi, Koji Umeshita, Seiji Kawasaki, Katsuhiko Yanaga, Mitsuo Shimada, Toshimi Kaido, Naoki Kawagishi, Akinobu Taketomi, Koichi Mizuta, Norihiro Kokudo, Shinji Uemoto, Yoshihiko Maehara","Ken Shirabe, Susumu Eguchi, Hideaki Okajima, Kiyoshi Hasegawa, Shigeru Marubashi, Koji Umeshita, Seiji Kawasaki, Katsuhiko Yanaga, Mitsuo Shimada, Toshimi Kaido, Naoki Kawagishi, Akinobu Taketomi, Koichi Mizuta, Norihiro Kokudo, Shinji Uemoto, Yoshihiko Maehara","null","Smaller surgical incisions have recently been introduced in living donor liver procurement. This study used national data from Japan to clarify the present status of surgical incisions in living donor liver procurement. A nationwide, questionnaire-based survey related to 3121 donors and recipients was used. Donors were divided into 2 groups: left lateral segment graft (LLSG) procurement (n = 690) and other types (n = 2431). Incisions were classified into 6 types: type I, upper midline and bilateral subcostal; type II, upper midline and right subcostal; type III, upper midline and right subcostal to the right lateral margin of the abdominal rectus muscle; type IV, upper midline without laparoscopy; type V, upper midline with laparoscopy; and type VI, lower abdominal using the full laparoscopic technique. Types I, II, and III were regarded as standard, and types IV, V, and VI as small incisions. In LLSGs, blood transfusion and postoperative complication rates were significantly less frequent in the small incision group than in the standard group. In other graft types, there were no significant differences in blood transfusion, postoperative complication, and recipients' graft loss rates. The rates of wound extension during surgery were 2.8% and 2.1% in the small incision group in LLSGs and in other graft types, respectively. A small incision was adapted more frequently and postoperative complications were less common in high-volume centers. Various incisions have been adopted in living donor liver procurement. Donor safety and graft integrity appear to have been retained for donors receiving small incisions.","Smaller surgical incisions have recently been introduced in living donor liver procurement. This study used national data from Japan to clarify the present status of surgical incisions in living donor liver procurement. A nationwide, questionnaire-based survey related to 3121 donors and recipients was used. Donors were divided into 2 groups: left lateral segment graft (LLSG) procurement (n = 690) and other types (n = 2431). Incisions were classified into 6 types: type I, upper midline and bilateral subcostal; type II, upper midline and right subcostal; type III, upper midline and right subcostal to the right lateral margin of the abdominal rectus muscle; type IV, upper midline without laparoscopy; type V, upper midline with laparoscopy; and type VI, lower abdominal using the full laparoscopic technique. Types I, II, and III were regarded as standard, and types IV, V, and VI as small incisions. In LLSGs, blood transfusion and postoperative complication rates were significantly less frequent in the small incision group than in the standard group. In other graft types, there were no significant differences in blood transfusion, postoperative complication, and recipients' graft loss rates. The rates of wound extension during surgery were 2.8% and 2.1% in the small incision group in LLSGs and in other graft types, respectively. A small incision was adapted more frequently and postoperative complications were less common in high-volume centers. Various incisions have been adopted in living donor liver procurement. Donor safety and graft integrity appear to have been retained for donors receiving small incisions.","null","null","2018-08","Transplantation","Transplantation","Vol.102","No.8","1293","1299","eng","true","null","scientific_journal","null","null","10.1097/TP.0000000000002126","1534-6080","null","null","null","null","null"
"Nab-paclitaxel interrupts cancer-stromal interaction through C-X-C motif chemokine 10-mediated interleukin-6 downregulation in vitro.","Nab-paclitaxel interrupts cancer-stromal interaction through C-X-C motif chemokine 10-mediated interleukin-6 downregulation in vitro.","Rui Feng, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Shuichi Iwahashi, Yu Saitou, Mitsuo Shimada","Rui Feng, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Shuichi Iwahashi, Yu Saitou, Mitsuo Shimada","null","Cancer-associated fibroblasts (CAF), derived from stroma of cancer tissues, interact with cancer cells and play an important role in cancer initiation, growth, and metastasis. Nab-paclitaxel (nab-PTX) is a 130 nm albumin-binding paclitaxel and recommended for many types of cancer chemotherapy. The nab-PTX stromal-disrupting effect during pancreatic cancer treatment has been reported. The aim of the present study was to determine the role of nab-PTX in cancer cells and CAF interaction. Cancer cells (MIA PaCa-2 and Panc-1) were cocultured with CAF or treated with CAF conditioned medium, after which their migration and invasion ability, epithelial-mesenchymal transition (EMT)-related marker expression and C-X-C motif chemokine 10 (CXCL10) expression and secretion were detected. Nab-PTX treatment was carried out during the coculture system or during preparation of CAF conditioned medium. Then cancer cell migration and invasion ability, EMT-related marker expression, CXCL10 expression and secretion, and interleukin-6 (IL-6) expression and secretion by CAF were checked After coculture with CAF, migration and invasion ability of cancer cells increased. CAF also downregulated E-cadherin and upregulated N-cadherin and vimentin expression in cancer cells. During coculture or stimulation with cancer cell-cultured medium, CAF significantly increased IL-6 expression and secretion. However, nab-PTX in the coculture system canceled CAF-induced migration and invasion promotion and EMT-related gene changes. Moreover, nab-PTX increased CXCL10 expression of cancer cells which blocked CAF IL-6 expression and secretion. Nab-PTX treatment could increase CXCL10 expression of cancer cells which blocks CAF cancer cell migration and invasion-promoting effect by inhibiting IL-6 expression.","Cancer-associated fibroblasts (CAF), derived from stroma of cancer tissues, interact with cancer cells and play an important role in cancer initiation, growth, and metastasis. Nab-paclitaxel (nab-PTX) is a 130 nm albumin-binding paclitaxel and recommended for many types of cancer chemotherapy. The nab-PTX stromal-disrupting effect during pancreatic cancer treatment has been reported. The aim of the present study was to determine the role of nab-PTX in cancer cells and CAF interaction. Cancer cells (MIA PaCa-2 and Panc-1) were cocultured with CAF or treated with CAF conditioned medium, after which their migration and invasion ability, epithelial-mesenchymal transition (EMT)-related marker expression and C-X-C motif chemokine 10 (CXCL10) expression and secretion were detected. Nab-PTX treatment was carried out during the coculture system or during preparation of CAF conditioned medium. Then cancer cell migration and invasion ability, EMT-related marker expression, CXCL10 expression and secretion, and interleukin-6 (IL-6) expression and secretion by CAF were checked After coculture with CAF, migration and invasion ability of cancer cells increased. CAF also downregulated E-cadherin and upregulated N-cadherin and vimentin expression in cancer cells. During coculture or stimulation with cancer cell-cultured medium, CAF significantly increased IL-6 expression and secretion. However, nab-PTX in the coculture system canceled CAF-induced migration and invasion promotion and EMT-related gene changes. Moreover, nab-PTX increased CXCL10 expression of cancer cells which blocked CAF IL-6 expression and secretion. Nab-PTX treatment could increase CXCL10 expression of cancer cells which blocks CAF cancer cell migration and invasion-promoting effect by inhibiting IL-6 expression.","null","null","2018-08","Cancer Science","Cancer Science","Vol.109","No.8","2509","2519","eng","true","null","scientific_journal","null","null","10.1111/cas.13694","1349-7006","null","null","null","null","null"
"A learning curve for laparoscopic liver resection: an effective training system and standardization of technique.","A learning curve for laparoscopic liver resection: an effective training system and standardization of technique.","Yu Saitou, Shin-ichiro Yamada, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Shuichi Iwahashi, Mitsuo Shimada","Yu Saitou, Shin-ichiro Yamada, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Shuichi Iwahashi, Mitsuo Shimada","null","The incidence of laparoscopic liver resection (LHx) has been increased in the past decade. There have been some reports about some advantages of LHx, in both short and long-term outcomes after operation. The use of a minor LHx was regarded as a standard surgical practice, and some peri-operative complications hindered worldwide increase of LHx in the Second International Consensus Conference on LHx at Morioka. However, no suggestions were described in terms with how to provide the best teaching and training necessary to shorten the learning curve for inexperienced surgeons using a new surgical technique while continuing to maintain a low rate of morbidity from the very beginning. This study includes a literature review of published research which looked at a learning curve for LHx. As well, it proposes a new step-wise training method for inexperienced surgeons and standardization of a technique for LHx focusing especially on laparoscopic left hepatectomy (LLHx).","The incidence of laparoscopic liver resection (LHx) has been increased in the past decade. There have been some reports about some advantages of LHx, in both short and long-term outcomes after operation. The use of a minor LHx was regarded as a standard surgical practice, and some peri-operative complications hindered worldwide increase of LHx in the Second International Consensus Conference on LHx at Morioka. However, no suggestions were described in terms with how to provide the best teaching and training necessary to shorten the learning curve for inexperienced surgeons using a new surgical technique while continuing to maintain a low rate of morbidity from the very beginning. This study includes a literature review of published research which looked at a learning curve for LHx. As well, it proposes a new step-wise training method for inexperienced surgeons and standardization of a technique for LHx focusing especially on laparoscopic left hepatectomy (LLHx).","null","null","2018-07-23","Translational Gastroenterology and Hepatology","Translational Gastroenterology and Hepatology","Vol.3","null","45","45","eng","true","null","scientific_journal","null","null","10.21037/tgh.2018.07.03","2415-1289","null","null","null","null","null"
"Role of heat shock factor 1 expression in the microenvironment of intrahepatic cholangiocarcinomas.","Role of heat shock factor 1 expression in the microenvironment of intrahepatic cholangiocarcinomas.","Youichiro Kawashita, Yuji Morine, Yu Saitou, Chie Takasu, Tetsuya Ikemoto, Shuichi Iwahashi, Hiroki Teraoku, Masato Yoshikawa, Satoru Imura, Toshiyuki Yagi, Mitsuo Shimada","Youichiro Kawashita, Yuji Morine, Yu Saitou, Chie Takasu, Tetsuya Ikemoto, Shuichi Iwahashi, Hiroki Teraoku, Masato Yoshikawa, Satoru Imura, Toshiyuki Yagi, Mitsuo Shimada","null","Heat shock factor 1 (HSF1), a master regulator of heat shock response, has been shown to play a multifaceted role in cancer progression. However, the clinical significance and biological effect of HSF1 expression in intrahepatic cholangiocarcinoma (IHCC) remain unknown. Forty-nine patients with IHCC who underwent hepatic resection were enrolled in this study. HSF1 expression in tumor tissue was determined by immunohistochemistry, and patients were divided into two groups, those with high (n = 20) and low (n = 29) HSF1 expression. Clinicopathological factors including prognosis were compared in these two groups. HSF1 expression was significantly higher in tumors than in normal tissue. The overall survival rate was significantly lower in patients with high than low HSF1. Multivariate analysis showed that high HSF1 expression was a factor independently prognostic of patient survival. High HSF1 expression in tumor tissues may be a prognostic biomarker in patients with IHCC.","Heat shock factor 1 (HSF1), a master regulator of heat shock response, has been shown to play a multifaceted role in cancer progression. However, the clinical significance and biological effect of HSF1 expression in intrahepatic cholangiocarcinoma (IHCC) remain unknown. Forty-nine patients with IHCC who underwent hepatic resection were enrolled in this study. HSF1 expression in tumor tissue was determined by immunohistochemistry, and patients were divided into two groups, those with high (n = 20) and low (n = 29) HSF1 expression. Clinicopathological factors including prognosis were compared in these two groups. HSF1 expression was significantly higher in tumors than in normal tissue. The overall survival rate was significantly lower in patients with high than low HSF1. Multivariate analysis showed that high HSF1 expression was a factor independently prognostic of patient survival. High HSF1 expression in tumor tissues may be a prognostic biomarker in patients with IHCC.","null","null","2018-07","Journal of Gastroenterology and Hepatology","Journal of Gastroenterology and Hepatology","Vol.33","No.7","1407","1412","eng","true","null","scientific_journal","null","null","10.1111/jgh.14078","1440-1746","null","null","null","null","null"
"Programmed Cell Death Ligand 1 Expression Is an Independent Prognostic Factor in Colorectal Cancer.","Programmed Cell Death Ligand 1 Expression Is an Independent Prognostic Factor in Colorectal Cancer.","Tumenjin Enkhbat, Masaaki Nishi, Chie Takasu, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Hideya Kashihara, Daichi Ishikawa, Mitsuo Shimada","Tumenjin Enkhbat, Masaaki Nishi, Chie Takasu, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Hideya Kashihara, Daichi Ishikawa, Mitsuo Shimada","null","Programmed cell death protein 1 (PD-1)/ programmed cell death ligand 1(PD-L1) axis is associated with immune tolerance via inhibition of T cell activation. The aim of this study was to clarify the significance of PD-1 and PD-L1 expressions and analyze the relationships between PD-1, PD-L1, transforming growth factor-β (TGF-β) and Forkhead box P3 (Foxp3) expressions in colorectal cancer (CRC). A total of 116 patients who underwent curative colectomy for stage II/III CRC were included in the study. PD-1, PD-L1, TGF-β, and Foxp3 expressions were examined by immunohistochemistry and related to prognostic factors by Kaplan-Meier. PD-1 expression was correlated with PD-L1, TGF-β, and Foxp3 expressions. Overall survival rates were significantly poorer in the PD-1 and PD-L1-positive groups. Multivariate analysis showed that PD-L1-positive is an independent risk factor. Disease-free survival (DFS) was tended in the PD-L1-positive group. The group with double-positive expression had significantly poorer prognosis. PD-1 and PD-L1 expressions were associated with a poor prognosis and correlated with TGF-β and Foxp3 expressions in patients with CRC.","Programmed cell death protein 1 (PD-1)/ programmed cell death ligand 1(PD-L1) axis is associated with immune tolerance via inhibition of T cell activation. The aim of this study was to clarify the significance of PD-1 and PD-L1 expressions and analyze the relationships between PD-1, PD-L1, transforming growth factor-β (TGF-β) and Forkhead box P3 (Foxp3) expressions in colorectal cancer (CRC). A total of 116 patients who underwent curative colectomy for stage II/III CRC were included in the study. PD-1, PD-L1, TGF-β, and Foxp3 expressions were examined by immunohistochemistry and related to prognostic factors by Kaplan-Meier. PD-1 expression was correlated with PD-L1, TGF-β, and Foxp3 expressions. Overall survival rates were significantly poorer in the PD-1 and PD-L1-positive groups. Multivariate analysis showed that PD-L1-positive is an independent risk factor. Disease-free survival (DFS) was tended in the PD-L1-positive group. The group with double-positive expression had significantly poorer prognosis. PD-1 and PD-L1 expressions were associated with a poor prognosis and correlated with TGF-β and Foxp3 expressions in patients with CRC.","null","null","2018-06","Anticancer Research","Anticancer Research","Vol.38","No.6","3367","3373","eng","true","null","scientific_journal","null","null","10.21873/anticanres.12603","1791-7530","null","null","null","null","null"
"The Impact of Indoleamine 2,3-dioxygenase (IDO) Expression on Stage III Gastric Cancer.","The Impact of Indoleamine 2,3-dioxygenase (IDO) Expression on Stage III Gastric Cancer.","Masaaki Nishi, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Hideya Kashihara, Chie Takasu, Daichi Ishikawa, Yuma Wada, Mitsuo Shimada","Masaaki Nishi, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Hideya Kashihara, Chie Takasu, Daichi Ishikawa, Yuma Wada, Mitsuo Shimada","null","Indoleamine 2,3-dioxygenase (IDO) down-regulates T cell activation, attenuates regulatory T cell (Treg) activation and is related to immune tolerance. The aim of the study was to clarify the significance of IDO expression and analyze the relationships between the expression of IDO, TGF-β, and Foxp3 in gastric cancer (GC). A total of 60 patients who underwent curative gastrectomy for stage III gastric cancer were included in the study. The expression of IDO, TGF-β, and Foxp3 was examined by immunohistochemistry and the relationship of each expression level to several prognostic factors was examined using univariate and multivariate analyses. IDO expression was not positively correlated with any of the factors examined. IDO expression was positively correlated with TGF-β expression (p<0.05), and TGF-β expression was positively correlated with FoxP3 expression (p<0.05). Overall survival (OS) rates were significantly poorer in the IDO-positive group compared to the IDO-negative group (3-year OS, 78.5% vs. 90%, respectively; p<0.05). Multivariate analysis confirmed IDO expression as independent prognostic factors in OS. Disease-free survival (DFS) was significantly poorer in the IDO-positive group compared to the IDO-negative group (3-year DFS, 59.3% vs. 69.3%, respectively; p<0.05). IDO is associated with poor prognosis and immuno-tolerance through attenuation of Treg activation in Stage III GC.","Indoleamine 2,3-dioxygenase (IDO) down-regulates T cell activation, attenuates regulatory T cell (Treg) activation and is related to immune tolerance. The aim of the study was to clarify the significance of IDO expression and analyze the relationships between the expression of IDO, TGF-β, and Foxp3 in gastric cancer (GC). A total of 60 patients who underwent curative gastrectomy for stage III gastric cancer were included in the study. The expression of IDO, TGF-β, and Foxp3 was examined by immunohistochemistry and the relationship of each expression level to several prognostic factors was examined using univariate and multivariate analyses. IDO expression was not positively correlated with any of the factors examined. IDO expression was positively correlated with TGF-β expression (p<0.05), and TGF-β expression was positively correlated with FoxP3 expression (p<0.05). Overall survival (OS) rates were significantly poorer in the IDO-positive group compared to the IDO-negative group (3-year OS, 78.5% vs. 90%, respectively; p<0.05). Multivariate analysis confirmed IDO expression as independent prognostic factors in OS. Disease-free survival (DFS) was significantly poorer in the IDO-positive group compared to the IDO-negative group (3-year DFS, 59.3% vs. 69.3%, respectively; p<0.05). IDO is associated with poor prognosis and immuno-tolerance through attenuation of Treg activation in Stage III GC.","null","null","2018-06","Anticancer Research","Anticancer Research","Vol.38","No.6","3387","3392","eng","true","null","scientific_journal","null","null","10.21873/anticanres.12605","1791-7530","null","null","null","null","null"
"女性外科医総活躍社会を目指して 日本医学会分科会における女性医師支援2015年 : 第3回アンケート調査","CURRENT STATUS OF SUPPORT FOR FEMALE DOCTORS IN THE SPECIALIST MEDICAL SOCIETIES OF THE JAPANESE ASSOCIATION OF MEDICAL SCIENCE IN 2015 : RESULTS OF A QUESTIONNAIRE SURVEY","野村 幸世, 冨澤 康子, 大津 洋, 小川 朋子, 柴崎 郁子, 島田 光生, 竹下 恵美子, 花崎 和弘, 葉梨 智子, 山下 啓子, 明石 定子, 山内 英子, 岩瀬 弘敬, 田口 智章, 前田 耕太郎, 中村 清吾","野村 幸世, 冨澤 康子, 大津 洋, 小川 朋子, 柴崎 郁子, Mitsuo Shimada, 竹下 恵美子, 花崎 和弘, 葉梨 智子, 山下 啓子, 明石 定子, 山内 英子, 岩瀬 弘敬, 田口 智章, 前田 耕太郎, 中村 清吾","null","null","null","null","null","2018-04","日本外科学会雑誌","Journal of Japan Surgical Society","Vol.119","No.1","97","99","jpn","true","null","scientific_journal","null","null","null","0301-4894","null","https://ci.nii.ac.jp/naid/40021573998/","null","null","null"
"Usefulness of the Transoral Anvil Delivery System for Esophagojejunostomy After Laparoscopic Total Gastrectomy: A Single-institution Comparative Study of Transoral Anvil Delivery System and the Overlap Method.","Usefulness of the Transoral Anvil Delivery System for Esophagojejunostomy After Laparoscopic Total Gastrectomy: A Single-institution Comparative Study of Transoral Anvil Delivery System and the Overlap Method.","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Daichi Ishikawa","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Daichi Ishikawa","null","Many reconstruction techniques have been reported after laparoscopic total gastrectomy (LTG), but it is not clear which anastomosis technique is most useful, and no standard methods have been established. This study examined whether LTG using the transoral anvil delivery system (TOADS) is a feasible and safe procedure for gastric cancer. A series of 47 patients underwent the overlap method and 36 underwent the hemi-double-stapling technique with TOADS. Intraoperative and postoperative outcomes were compared between the 2 groups. In the TOADS group, operation time for reconstruction was shorter (16 3 vs. 45 10in, P=0.003), and blood loss was reduced (45 15 vs. 126 13L, P=0.0002). There were no significant differences in intraoperative complications, conversion to open surgery, and intraoperative anastomosis-related complications between the 2 groups. Furthermore, there were no significant differences in the incidence of complications, reoperation, mortality, and postoperative hospital stay. LTG using TOADS for gastric cancer may be a technically feasible surgical procedure with acceptable morbidity.","Many reconstruction techniques have been reported after laparoscopic total gastrectomy (LTG), but it is not clear which anastomosis technique is most useful, and no standard methods have been established. This study examined whether LTG using the transoral anvil delivery system (TOADS) is a feasible and safe procedure for gastric cancer. A series of 47 patients underwent the overlap method and 36 underwent the hemi-double-stapling technique with TOADS. Intraoperative and postoperative outcomes were compared between the 2 groups. In the TOADS group, operation time for reconstruction was shorter (16 3 vs. 45 10in, P=0.003), and blood loss was reduced (45 15 vs. 126 13L, P=0.0002). There were no significant differences in intraoperative complications, conversion to open surgery, and intraoperative anastomosis-related complications between the 2 groups. Furthermore, there were no significant differences in the incidence of complications, reoperation, mortality, and postoperative hospital stay. LTG using TOADS for gastric cancer may be a technically feasible surgical procedure with acceptable morbidity.","null","null","2018-04","Surgical Laparoscopy, Endoscopy & Percutaneous Techniques","Surgical Laparoscopy, Endoscopy & Percutaneous Techniques","Vol.28","No.2","e40","e43","eng","true","null","scientific_journal","null","null","10.1097/SLE.0000000000000495","1534-4908","null","null","null","null","null"
"A new 2-step acceleration protocol using a histone deacetylase inhibitor to generate insulin-producing cells from adipose-derived mesenchymal stem cells","A new 2-step acceleration protocol using a histone deacetylase inhibitor to generate insulin-producing cells from adipose-derived mesenchymal stem cells","Tetsuya Ikemoto, Rui Feng, Mitsuo Shimada, Yu Saitou, Shuichi Iwahashi, Yuji Morine, Satoru Imura","Tetsuya Ikemoto, Rui Feng, Mitsuo Shimada, Yu Saitou, Shuichi Iwahashi, Yuji Morine, Satoru Imura","null","We aimed to develop a simple protocol for deriving insulin-producing cells (IPCs) from adipose-derived mesenchymal stem cells (ADSCs). We established a 2-step creation method and an acceleration strategy with a histone deacetylase inhibitor that promoted a pro-endocrine pancreatic lineage. We seeded ADSCs in 96-well dishes and cultured in Dulbecco's modified Eagle's medium/F12 medium containing 1% fetal bovine serum, 1% B27 supplement, 1% N2 supplement, 50-ng/mL human activin A, and 10-nM exendin-4 for step 1 of differentiation (7 days). Then 10-mM nicotinamide and 50-ng/mL human hepatocyte growth factor, with or without 1 mM histone deacetylase inhibitor, were added for step 2 of differentiation (14 days). After the 2-step differentiation was complete, cell morphology, immunohistochemistry, messenger RNA expression, and function were investigated. Our new differentiation protocol with the histone deacetylase inhibitor significantly accelerated IPC differentiation compared with the conventional protocol without the histone deacetylase inhibitor (median, 21.6 vs 38.8 days; P < 0.05). It also improved the islet morphology score (P < 0.05) and the glucose stimulation index (3.1). By applying our new and easy 2-step protocol using a histone deacetylase inhibitor, ADSCs may be an effective cell source for differentiation of IPCs.","We aimed to develop a simple protocol for deriving insulin-producing cells (IPCs) from adipose-derived mesenchymal stem cells (ADSCs). We established a 2-step creation method and an acceleration strategy with a histone deacetylase inhibitor that promoted a pro-endocrine pancreatic lineage. We seeded ADSCs in 96-well dishes and cultured in Dulbecco's modified Eagle's medium/F12 medium containing 1% fetal bovine serum, 1% B27 supplement, 1% N2 supplement, 50-ng/mL human activin A, and 10-nM exendin-4 for step 1 of differentiation (7 days). Then 10-mM nicotinamide and 50-ng/mL human hepatocyte growth factor, with or without 1 mM histone deacetylase inhibitor, were added for step 2 of differentiation (14 days). After the 2-step differentiation was complete, cell morphology, immunohistochemistry, messenger RNA expression, and function were investigated. Our new differentiation protocol with the histone deacetylase inhibitor significantly accelerated IPC differentiation compared with the conventional protocol without the histone deacetylase inhibitor (median, 21.6 vs 38.8 days; P < 0.05). It also improved the islet morphology score (P < 0.05) and the glucose stimulation index (3.1). By applying our new and easy 2-step protocol using a histone deacetylase inhibitor, ADSCs may be an effective cell source for differentiation of IPCs.","null","null","2018-04","Pancreas","Pancreas","Vol.47","No.4","477","481","eng","true","null","scientific_journal","null","null","10.1097/MPA.0000000000001017","1536-4828","null","null","null","null","null"
"Ki-67 and Survivin as Predictive Factors for Rectal Cancer Treated with Preoperative Chemoradiotherapy.","Ki-67 and Survivin as Predictive Factors for Rectal Cancer Treated with Preoperative Chemoradiotherapy.","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Syohei Eto, Yoshimi Bando","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Syohei Eto, Yoshimi Bando","null","To evaluate the usefulness of Ki-67 index and survivin as predictive prognostic factors for rectal cancer treated with preoperative chemoradiotherapy. The Ki-67 index and survivin expression were examined in patients with stage II/III rectal cancer (n=46) by immunohistochemistry. Patients were divided into a high-group and a low-group for the Ki-67 index, and positive and negative groups for survivin expression. Overall and disease-free survival were compared between the groups, and the correlation between Ki-67 index and survivin expression was assessed. The 5-year disease-free survival rate of the group with high Ki-67 index was significantly lower than that of the group with low Ki-67 index (53% and 88%, p=0.03), as was the 5-year overall survival rate (68% and 100%, p=0.03). Findings for survivin were not significant. Ki-67 index and survivin may be useful biomarkers for rectal cancer with preoperative CRT.","To evaluate the usefulness of Ki-67 index and survivin as predictive prognostic factors for rectal cancer treated with preoperative chemoradiotherapy. The Ki-67 index and survivin expression were examined in patients with stage II/III rectal cancer (n=46) by immunohistochemistry. Patients were divided into a high-group and a low-group for the Ki-67 index, and positive and negative groups for survivin expression. Overall and disease-free survival were compared between the groups, and the correlation between Ki-67 index and survivin expression was assessed. The 5-year disease-free survival rate of the group with high Ki-67 index was significantly lower than that of the group with low Ki-67 index (53% and 88%, p=0.03), as was the 5-year overall survival rate (68% and 100%, p=0.03). Findings for survivin were not significant. Ki-67 index and survivin may be useful biomarkers for rectal cancer with preoperative CRT.","null","null","2018-03","Anticancer Research","Anticancer Research","Vol.38","No.3","1735","1739","eng","true","null","scientific_journal","null","null","10.21873/anticanres.12409","1791-7530","null","null","null","null","null"
"Living donor liver transplantation for biliary atresia: An analysis of 2085 cases in the registry of the Japanese Liver Transplantation Society.","Living donor liver transplantation for biliary atresia: An analysis of 2085 cases in the registry of the Japanese Liver Transplantation Society.","Mureo Kasahara, Koji Umeshita, Seisuke Sakamoto, Akinari Fukuda, Hiroyuki Furukawa, Shotaro Sakisaka, Eiji Kobayashi, Eiji Tanaka, Yukihiro Inomata, Seiji Kawasaki, Mitsuo Shimada, Norihiro Kokudo, Hiroto Egawa, Hideki Ohdan, Shinji Uemoto","Mureo Kasahara, Koji Umeshita, Seisuke Sakamoto, Akinari Fukuda, Hiroyuki Furukawa, Shotaro Sakisaka, Eiji Kobayashi, Eiji Tanaka, Yukihiro Inomata, Seiji Kawasaki, Mitsuo Shimada, Norihiro Kokudo, Hiroto Egawa, Hideki Ohdan, Shinji Uemoto","null","Biliary atresia (BA) is the most common indication for liver transplantation (LT) in pediatric population. This study analyzed the comprehensive factors that might influence the outcomes of patients with BA who undergo living donor LT by evaluating the largest cohort with the longest follow-up in the world. Between November 1989 and December 2015, 2,085 BA patients underwent LDLT in Japan. There were 763 male and 1,322 female recipients with a mean age of 5.9 years and body weight of 18.6 kg. The 1-, 5-, 10-, 15-, and 20-year graft survival rates for the BA patients undergoing LDLT were 90.5%, 90.4%, 84.6%, 82.0%, and 79.9%, respectively. The donor body mass index, ABO incompatibility, graft type, recipient age, center experience, and transplant era were found to be significant predictors of the overall graft survival. Adolescent age (12 to <18 years) was associated with a significantly worse long-term graft survival rate than younger or older ages. We conclude that LDLT for BA is a safe and effective treatment modality that does not compromise living donors. The optimum timing for LT is crucial for a successful outcome, and early referral to transplantation center can improve the short-term outcomes of LT for BA. Further investigation of the major cause of death in liver transplanted recipients with BA in the long-term is essential, especially among adolescents.","Biliary atresia (BA) is the most common indication for liver transplantation (LT) in pediatric population. This study analyzed the comprehensive factors that might influence the outcomes of patients with BA who undergo living donor LT by evaluating the largest cohort with the longest follow-up in the world. Between November 1989 and December 2015, 2,085 BA patients underwent LDLT in Japan. There were 763 male and 1,322 female recipients with a mean age of 5.9 years and body weight of 18.6 kg. The 1-, 5-, 10-, 15-, and 20-year graft survival rates for the BA patients undergoing LDLT were 90.5%, 90.4%, 84.6%, 82.0%, and 79.9%, respectively. The donor body mass index, ABO incompatibility, graft type, recipient age, center experience, and transplant era were found to be significant predictors of the overall graft survival. Adolescent age (12 to <18 years) was associated with a significantly worse long-term graft survival rate than younger or older ages. We conclude that LDLT for BA is a safe and effective treatment modality that does not compromise living donors. The optimum timing for LT is crucial for a successful outcome, and early referral to transplantation center can improve the short-term outcomes of LT for BA. Further investigation of the major cause of death in liver transplanted recipients with BA in the long-term is essential, especially among adolescents.","null","null","2018-03","American Journal of Transplantation","American Journal of Transplantation","Vol.18","No.3","659","668","eng","true","null","scientific_journal","null","null","10.1111/ajt.14489","1600-6143","null","null","null","null","null"
"Potential predictive factors for microvascular invasion in hepatocellular carcinoma classified within the Milan criteria.","Potential predictive factors for microvascular invasion in hepatocellular carcinoma classified within the Milan criteria.","Satoru Imura, Hiroki Teraoku, Masato Yoshikawa, Daichi Ishikawa, Shin-ichiro Yamada, Yu Saitou, Shuichi Iwahashi, Tetsuya Ikemoto, Yuji Morine, Mitsuo Shimada","Satoru Imura, Hiroki Teraoku, Masato Yoshikawa, Daichi Ishikawa, Shin-ichiro Yamada, Yu Saitou, Shuichi Iwahashi, Tetsuya Ikemoto, Yuji Morine, Mitsuo Shimada","null","Microvascular invasion (mvi) is an important risk factor for recurrent hepatocellular carcinoma (HCC), even after curative liver resection or orthotopic liver transplantation. However, mvi is difficult to detect preoperatively. The aim of this study was to clarify the risk factors of postoperative recurrence and investigate predictive factors of mvi before hepatectomy for HCC classified within the Milan criteria. One hundred fifty-nine patients with hepatocellular carcinoma (HCC) classified within the Milan criteria, who underwent hepatectomy, were enrolled in this study. We investigated the risk factors of recurrence. In addition, we divided them into two groups: mvi-negative group and mvi-positive group, based on pathological findings after surgery. We compared the clinicopathological factors between the two groups and determined the risk factors for mvi. Overall survival rate at 1, 3, and 5 years were 91.6%, 80.5%, and 74.9%, and the recurrence-free survival rate at 1, 3, and 5-years were 72.3%, 51.6%, and 37.2%. Risk factor analysis for tumor recurrence revealed that total bilirubin, albumin, ICGR15, AFP-L3, tumor number, mvi, and tumor stage had a significant predictive value. Multivariate analysis revealed that tumor number and mvi were significant independent risk factors for tumor recurrence. Predictive analysis for risk factors of mvi revealed that multiple tumors and AFP-L3 > 10% were significant independent risk factors for mvi in HCC classified within the Milan criteria. The mvi was one of the independent risk factors for tumor recurrence in HCC classified within the Milan criteria. Multiple tumors and high AFP-L3 value were independent predictive factors for mvi.","Microvascular invasion (mvi) is an important risk factor for recurrent hepatocellular carcinoma (HCC), even after curative liver resection or orthotopic liver transplantation. However, mvi is difficult to detect preoperatively. The aim of this study was to clarify the risk factors of postoperative recurrence and investigate predictive factors of mvi before hepatectomy for HCC classified within the Milan criteria. One hundred fifty-nine patients with hepatocellular carcinoma (HCC) classified within the Milan criteria, who underwent hepatectomy, were enrolled in this study. We investigated the risk factors of recurrence. In addition, we divided them into two groups: mvi-negative group and mvi-positive group, based on pathological findings after surgery. We compared the clinicopathological factors between the two groups and determined the risk factors for mvi. Overall survival rate at 1, 3, and 5 years were 91.6%, 80.5%, and 74.9%, and the recurrence-free survival rate at 1, 3, and 5-years were 72.3%, 51.6%, and 37.2%. Risk factor analysis for tumor recurrence revealed that total bilirubin, albumin, ICGR15, AFP-L3, tumor number, mvi, and tumor stage had a significant predictive value. Multivariate analysis revealed that tumor number and mvi were significant independent risk factors for tumor recurrence. Predictive analysis for risk factors of mvi revealed that multiple tumors and AFP-L3 > 10% were significant independent risk factors for mvi in HCC classified within the Milan criteria. The mvi was one of the independent risk factors for tumor recurrence in HCC classified within the Milan criteria. Multiple tumors and high AFP-L3 value were independent predictive factors for mvi.","null","null","2018-02","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.23","No.1","98","103","eng","true","null","scientific_journal","null","null","10.1007/s10147-017-1189-8","1437-7772","null","null","null","null","null"
"The Outcome of Sorafenib Therapy on Unresectable Hepatocellular Carcinoma: Experience of Conversion and Salvage Hepatectomy.","The Outcome of Sorafenib Therapy on Unresectable Hepatocellular Carcinoma: Experience of Conversion and Salvage Hepatectomy.","Toshiaki Yoshimoto, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Yusuke Arakawa, Shuichi Iwahashi, Yu Saitou, Chie Takasu, Daichi Ishikawa, Hiroki Teraoku, Yoshimi Bando, Mitsuo Shimada","Toshiaki Yoshimoto, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Yusuke Arakawa, Shuichi Iwahashi, Yu Saitou, Chie Takasu, Daichi Ishikawa, Hiroki Teraoku, Yoshimi Bando, Mitsuo Shimada","null","We report the outcomes of sorafenib therapy for advanced hepatocellular carcinoma (HCC) in our Department. Thirty-eight patients with unresectable HCC who were administrated sorafenib from 2009 to 2015 were investigated retrospectively. The 1-year overall survival rate was 59.3%. The macroscopic vascular invasion and response rate were independent prognostic factors of survival. Surgical resection after sorafenib achieved long-term survival in two cases. Case 1: A patient with locally unresectable HCC showed significant response induced by sorafenib, which allowed complete surgical resection. This tumor tested positive for FGF4. Case 2: A patient with a history of hepatectomy for HCC had multiple distant metastases. Most lesions were reduced in size after sorafenib therapy and new lesions in the remnant liver and residual lung metastases were resected. The sorafenib-resistant lesions were negative for FGF4. Sorafenib combined with surgical resection is a feasible option in advanced HCC patients, if sorafenib has been effective.","We report the outcomes of sorafenib therapy for advanced hepatocellular carcinoma (HCC) in our Department. Thirty-eight patients with unresectable HCC who were administrated sorafenib from 2009 to 2015 were investigated retrospectively. The 1-year overall survival rate was 59.3%. The macroscopic vascular invasion and response rate were independent prognostic factors of survival. Surgical resection after sorafenib achieved long-term survival in two cases. Case 1: A patient with locally unresectable HCC showed significant response induced by sorafenib, which allowed complete surgical resection. This tumor tested positive for FGF4. Case 2: A patient with a history of hepatectomy for HCC had multiple distant metastases. Most lesions were reduced in size after sorafenib therapy and new lesions in the remnant liver and residual lung metastases were resected. The sorafenib-resistant lesions were negative for FGF4. Sorafenib combined with surgical resection is a feasible option in advanced HCC patients, if sorafenib has been effective.","null","null","2018-01","Anticancer Research","Anticancer Research","Vol.38","No.1","501","507","eng","true","null","scientific_journal","null","null","10.21873/anticanres.12250","1791-7530","null","null","null","null","null"
"【慢性炎症から肝胆膵癌にいたるランドスケープ】膵・胆管合流異常と胆道癌","【慢性炎症から肝胆膵癌にいたるランドスケープ】膵・胆管合流異常と胆道癌","石橋 広樹, 島田 光生, 森 大樹, 森根 裕二, 安藤 久實","Hiroki Ishibashi, Mitsuo Shimada, Hiroki Mori, Yuji Morine, 安藤 久實","null","null","null","null","null","2018","肝·胆·膵","KAN TAN SUI","Vol.77","No.3","659","667","jpn","true","null","scientific_journal","null","null","null","0389-4991","null","null","null","null","null"
"Treatment strategy for successful hepatic resection of icteric liver.","Treatment strategy for successful hepatic resection of icteric liver.","Keigo Yada, Yuji Morine, Hiroki Ishibashi, Hiroki Mori, Mitsuo Shimada","Keigo Yada, Yuji Morine, Hiroki Ishibashi, Hiroki Mori, Mitsuo Shimada","null","The treatment strategy for jaundiced patients with hilar cholangiocarcinoma (HC) is not well established. In this study, we evaluate the feasibility of our perioperative protocol for jaundiced patients with HC. Twenty patients with HC who underwent hepatic resection at our institute were enrolled, and patients were divided into icteric(n=6) and normal(n=14) group. As a perioperative protocol, Oral administration of Inchinkoto(ICKT), steroid and nafamostat mesilate were introduced. The evaluation of functional future remnant liver(FRL) by asiaroscintigraphy, and postoperative outcomes were retrospectively compared. Indocyanine green dye retention rate at 15 minutes was higher, and LHL15 values was lower in icteric group. However, in the functional evaluation of FRL, which was the sum of GSA uptake of the future FRL, there was no significant difference of LHL15 values of the remnant liver functional reserve between the two groups. As results, according to the difference of liver function, serum AST level was not different between two groups. The number of patients with postoperative morbidity in the two groups was comparable. Even in HC patients with icteric liver, accurate assessment of liver functional reserve and effective perioperative treatment may attribute to successful hepatectomy and favorable post-operative outcomes. J. Med. Invest. 65:37-42, February, 2018.","The treatment strategy for jaundiced patients with hilar cholangiocarcinoma (HC) is not well established. In this study, we evaluate the feasibility of our perioperative protocol for jaundiced patients with HC. Twenty patients with HC who underwent hepatic resection at our institute were enrolled, and patients were divided into icteric(n=6) and normal(n=14) group. As a perioperative protocol, Oral administration of Inchinkoto(ICKT), steroid and nafamostat mesilate were introduced. The evaluation of functional future remnant liver(FRL) by asiaroscintigraphy, and postoperative outcomes were retrospectively compared. Indocyanine green dye retention rate at 15 minutes was higher, and LHL15 values was lower in icteric group. However, in the functional evaluation of FRL, which was the sum of GSA uptake of the future FRL, there was no significant difference of LHL15 values of the remnant liver functional reserve between the two groups. As results, according to the difference of liver function, serum AST level was not different between two groups. The number of patients with postoperative morbidity in the two groups was comparable. Even in HC patients with icteric liver, accurate assessment of liver functional reserve and effective perioperative treatment may attribute to successful hepatectomy and favorable post-operative outcomes. J. Med. Invest. 65:37-42, February, 2018.","null","null","2018","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.65","No.1.2","37","42","eng","true","null","scientific_journal","null","null","10.2152/jmi.65.37","1349-6867","null","null","null","null","null"
"Major liver resection reduces nonprotein respiratory quotient and increases nonesterified fatty acid at postoperative day 14 in patients with hepatocellular carcinoma.","Major liver resection reduces nonprotein respiratory quotient and increases nonesterified fatty acid at postoperative day 14 in patients with hepatocellular carcinoma.","Shoko Wada, Hisami Okumura, Takafumi Katayama, Yuji Morine, Satoru Imura, Mitsuo Shimada","Shoko Wada, Hisami Okumura, Takafumi Katayama, Yuji Morine, Satoru Imura, Mitsuo Shimada","null","null","null","null","null","2017-10-20","Clinical Nutrition ESPEN","Clinical Nutrition ESPEN","Vol.23","null","194","199","eng","true","null","scientific_journal","null","null","10.1016/j.clnesp.2017.10.001","2405-4577","null","null","null","null","null"
"MicroRNA-449a deficiency promotes colon carcinogenesis.","MicroRNA-449a deficiency promotes colon carcinogenesis.","Masanori Niki, Kohhei Nakajima, Daichi Ishikawa, Jun Nishida, Chieko Ishifune, Shin-ichi Tsukumo, Mitsuo Shimada, Shinji Nagahiro, Yoshinori Mitamura, Koji Yasutomo","Masanori Niki, Kohhei Nakajima, Daichi Ishikawa, Jun Nishida, Chieko Ishifune, Shin-ichi Tsukumo, Mitsuo Shimada, Shinji Nagahiro, Yoshinori Mitamura, Koji Yasutomo","null","MicroRNAs have broad roles in tumorigenesis and cell differentiation through regulation of target genes. Notch signaling also controls cell differentiation and tumorigenesis. However, the mechanisms through which Notch mediates microRNA expression are still unclear. In this study, we aimed to identify microRNAs regulated by Notch signaling. Our analysis found that microRNA-449a (miR-449a) was indirectly regulated by Notch signaling. Although miR-449a-deficient mice did not show any Notch-dependent defects in immune cell development, treatment of miR-449a-deficient mice with azoxymethane (AOM) or dextran sodium sulfate (DSS) increased the numbers and sizes of colon tumors. These effects were associated with an increase in intestinal epithelial cell proliferation following AOM/DSS treatment. In patients with colon cancer, miR-449a expression was inversely correlated with disease-free survival and histological scores and was positively correlated with the expression of MLH1 for which loss-of function mutations have been shown to be involved in colon cancer. Colon tissues of miR-449a-deficient mice showed reduced Mlh1 expression compared with those of wild-type mice. Thus, these data suggested that miR-449a acted as a key regulator of colon tumorigenesis by controlling the proliferation of intestinal epithelial cells. Additionally, activation of miR-449a may represent an effective therapeutic strategy and prognostic marker in colon cancer.","MicroRNAs have broad roles in tumorigenesis and cell differentiation through regulation of target genes. Notch signaling also controls cell differentiation and tumorigenesis. However, the mechanisms through which Notch mediates microRNA expression are still unclear. In this study, we aimed to identify microRNAs regulated by Notch signaling. Our analysis found that microRNA-449a (miR-449a) was indirectly regulated by Notch signaling. Although miR-449a-deficient mice did not show any Notch-dependent defects in immune cell development, treatment of miR-449a-deficient mice with azoxymethane (AOM) or dextran sodium sulfate (DSS) increased the numbers and sizes of colon tumors. These effects were associated with an increase in intestinal epithelial cell proliferation following AOM/DSS treatment. In patients with colon cancer, miR-449a expression was inversely correlated with disease-free survival and histological scores and was positively correlated with the expression of MLH1 for which loss-of function mutations have been shown to be involved in colon cancer. Colon tissues of miR-449a-deficient mice showed reduced Mlh1 expression compared with those of wild-type mice. Thus, these data suggested that miR-449a acted as a key regulator of colon tumorigenesis by controlling the proliferation of intestinal epithelial cells. Additionally, activation of miR-449a may represent an effective therapeutic strategy and prognostic marker in colon cancer.","null","null","2017-09-06","Scientific Reports","Scientific Reports","Vol.7","No.1","10696","10696","eng","true","null","scientific_journal","null","null","10.1038/s41598-017-10500-0","2045-2322","null","null","null","null","null"
"Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1.","Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1.","Naoki Muguruma, Koichi Okamoto, Tadahiko Nakagawa, Katsutaka Sannomiya, Shota Fujimoto, Yasuhiro Mitsui, Tetsuo Kimura, Hiroshi Miyamoto, Jun Higashijima, Mitsuo Shimada, Yoko Horino, Shinya Matsumoto, Kenjiro Hanaoka, Tetsuo Nagano, Makoto Shibutani, Tetsuji Takayama","Naoki Muguruma, Koichi Okamoto, Tadahiko Nakagawa, Katsutaka Sannomiya, Shota Fujimoto, Yasuhiro Mitsui, Tetsuo Kimura, Hiroshi Miyamoto, Jun Higashijima, Mitsuo Shimada, Yoko Horino, Shinya Matsumoto, Kenjiro Hanaoka, Tetsuo Nagano, Makoto Shibutani, Tetsuji Takayama","null","Aberrant crypt foci (ACF), the earliest precursor lesion of colorectal cancers (CRCs), are a good surrogate marker for CRC risk stratification and chemoprevention. However, the conventional ACF detection method with dye-spraying by magnifying colonoscopy is labor- and skill-intensive. We sought to identify rat and human ACF using a fluorescent imaging technique that targets a molecule specific for ACF. We found that glutathione S-transferase (GST) P1-1 was overexpressed in ACF tissues in a screening experiment. We then synthesized the fluorogenic probe, DNAT-Me, which is fluorescently quenched but is activated by GSTP1-1. A CRC cell line incubated with DNAT-Me showed strong fluorescence in the cytosol. Fluorescence intensities correlated significantly with GST activities in cancer cell lines. When we sprayed DNAT-Me onto colorectal mucosa excised from azoxymethane-treated rats and surgically resected from CRC patients, ACF with strong fluorescent signals were clearly observed. The ACF number determined by postoperative DNAT-Me imaging was almost identical to that determined by preoperative methylene blue staining. The signal-to-noise ratio for ACF in DNAT-Me images was significantly higher than that in methylene blue staining. Thus, we sensitively visualized ACF on rat and human colorectal mucosa by using a GST-activated fluorogenic probe without dye-spraying and magnifying colonoscopy.","Aberrant crypt foci (ACF), the earliest precursor lesion of colorectal cancers (CRCs), are a good surrogate marker for CRC risk stratification and chemoprevention. However, the conventional ACF detection method with dye-spraying by magnifying colonoscopy is labor- and skill-intensive. We sought to identify rat and human ACF using a fluorescent imaging technique that targets a molecule specific for ACF. We found that glutathione S-transferase (GST) P1-1 was overexpressed in ACF tissues in a screening experiment. We then synthesized the fluorogenic probe, DNAT-Me, which is fluorescently quenched but is activated by GSTP1-1. A CRC cell line incubated with DNAT-Me showed strong fluorescence in the cytosol. Fluorescence intensities correlated significantly with GST activities in cancer cell lines. When we sprayed DNAT-Me onto colorectal mucosa excised from azoxymethane-treated rats and surgically resected from CRC patients, ACF with strong fluorescent signals were clearly observed. The ACF number determined by postoperative DNAT-Me imaging was almost identical to that determined by preoperative methylene blue staining. The signal-to-noise ratio for ACF in DNAT-Me images was significantly higher than that in methylene blue staining. Thus, we sensitively visualized ACF on rat and human colorectal mucosa by using a GST-activated fluorogenic probe without dye-spraying and magnifying colonoscopy.","null","null","2017-07-26","Scientific Reports","Scientific Reports","Vol.7","No.1","6536","6536","eng","true","null","scientific_journal","null","null","10.1038/s41598-017-06857-x","2045-2322","null","null","null","null","null"
"Conversion therapy for inoperable advanced gastric cancer patients by docetaxel, cisplatin, and S-1 (DCS) chemotherapy: a multi-institutional retrospective study.","Conversion therapy for inoperable advanced gastric cancer patients by docetaxel, cisplatin, and S-1 (DCS) chemotherapy: a multi-institutional retrospective study.","Yasushi Sato, Hiroyuki Ohnuma, Takayuki Nobuoka, Masahiro Hirakawa, Tamotsu Sagawa, Koshi Fujikawa, Yasuo Takahashi, Shinya Minami, Shinichi Katsuki, Minoru Takahashi, Masahiro Maeda, Yutaka Okagawa, Naoki Uemura, Syouhei Kikuch, Koichi Okamoto, Hiroshi Miyamoto, Mitsuo Shimada, Ichiro Takemasa, Junji Kato, Tetsuji Takayama","Yasushi Sato, Hiroyuki Ohnuma, Takayuki Nobuoka, Masahiro Hirakawa, Tamotsu Sagawa, Koshi Fujikawa, Yasuo Takahashi, Shinya Minami, Shinichi Katsuki, Minoru Takahashi, Masahiro Maeda, Yutaka Okagawa, Naoki Uemura, Syouhei Kikuch, Koichi Okamoto, Hiroshi Miyamoto, Mitsuo Shimada, Ichiro Takemasa, Junji Kato, Tetsuji Takayama","null","Conversion therapy is an option for unresectable metastatic gastric cancer when distant metastases are controlled by chemotherapy; however, the feasibility and efficacy remain unclear. This study aimed to assess the feasibility and efficacy of conversion therapy in patients with initially unresectable gastric cancer treated with docetaxel, cisplatin, and S-1 (DCS) chemotherapy by evaluating clinical outcomes. One hundred unresectable metastatic gastric cancer patients, enrolled in three DCS chemotherapy clinical trials, were retrospectively evaluated. The patients received oral S-1 (40 mg/m2 b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m2) and docetaxel (50-60 mg/m2) on day 8 every 3 weeks. Conversion therapy was defined when the patients could undergo R0 resection post-DCS chemotherapy and were able to tolerate curative surgery. Conversion therapy was achieved in 33/100 patients, with no perioperative mortality. Twenty-eight of the 33 patients (84.8 %) achieved R0 resection, and 78.8 % were defined as histological chemotherapeutic responders. The median overall survival (OS) of patients who underwent conversion therapy was 47.8 months (95 % CI 28.0-88.5 months). Patients who underwent R0 resection had significantly longer OS than those who underwent R1 and R2 resections (P = 0.0002). Of the patients with primarily unresectable metastases, 10 % lived >5 years. Among patients who underwent conversion therapy, multivariate analysis showed that the pathological response was a significant independent predictor for OS. DCS safely induced a high conversion rate, with very high R0 and pathological response rates, and was associated with a good prognosis; these findings warrant further prospective investigations.","Conversion therapy is an option for unresectable metastatic gastric cancer when distant metastases are controlled by chemotherapy; however, the feasibility and efficacy remain unclear. This study aimed to assess the feasibility and efficacy of conversion therapy in patients with initially unresectable gastric cancer treated with docetaxel, cisplatin, and S-1 (DCS) chemotherapy by evaluating clinical outcomes. One hundred unresectable metastatic gastric cancer patients, enrolled in three DCS chemotherapy clinical trials, were retrospectively evaluated. The patients received oral S-1 (40 mg/m2 b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m2) and docetaxel (50-60 mg/m2) on day 8 every 3 weeks. Conversion therapy was defined when the patients could undergo R0 resection post-DCS chemotherapy and were able to tolerate curative surgery. Conversion therapy was achieved in 33/100 patients, with no perioperative mortality. Twenty-eight of the 33 patients (84.8 %) achieved R0 resection, and 78.8 % were defined as histological chemotherapeutic responders. The median overall survival (OS) of patients who underwent conversion therapy was 47.8 months (95 % CI 28.0-88.5 months). Patients who underwent R0 resection had significantly longer OS than those who underwent R1 and R2 resections (P = 0.0002). Of the patients with primarily unresectable metastases, 10 % lived >5 years. Among patients who underwent conversion therapy, multivariate analysis showed that the pathological response was a significant independent predictor for OS. DCS safely induced a high conversion rate, with very high R0 and pathological response rates, and was associated with a good prognosis; these findings warrant further prospective investigations.","null","null","2017-05","Gastric Cancer","Gastric Cancer","Vol.20","No.3","517","526","eng","true","null","scientific_journal","null","null","10.1007/s10120-016-0633-1","1436-3291","null","null","null","null","null"
"Hemosuccus pancreaticus caused by a mucinous cystic neoplasm of the pancreas.","Hemosuccus pancreaticus caused by a mucinous cystic neoplasm of the pancreas.","Yuri Matsumoto, Hiroshi Miyamoto, Akira Fukuya, Fumika Nakamura, Takahiro Goji, Shinji Kitamura, Tetsuo Kimura, Koichi Okamoto, Masahiro Sogabe, Naoki Muguruma, Mitsuo Shimada, Yoshimi Bando, Tetsuji Takayama","Yuri Matsumoto, Hiroshi Miyamoto, Akira Fukuya, Fumika Nakamura, Takahiro Goji, Shinji Kitamura, Tetsuo Kimura, Koichi Okamoto, Masahiro Sogabe, Naoki Muguruma, Mitsuo Shimada, Yoshimi Bando, Tetsuji Takayama","null","Hemosuccus pancreaticus is a gastrointestinal hemorrhage through the main pancreatic duct. Here, we report a rare case of hemosuccus pancreaticus due to a mucinous cystic neoplasm of the pancreas. A 62-year-old woman who had been followed for a branch duct intraductal papillary mucinous neoplasm visited our emergency room due to severe abdominal pain and bloody discharge. Computed tomography revealed that the pancreatic cyst increased the tension of the wall and a high-density area indicative of bleeding into the cyst was observed. Endoscopy showed opening of and hemorrhaging from the papilla of Vater. The patient was diagnosed with hemosuccus pancreaticus caused by hemorrhaging into the cyst from the branch duct intraductal papillary mucinous neoplasm. Based on this diagnosis, elective distal pancreatectomy was performed. The histopathological diagnosis was a mucinous cystic neoplasm with intermediate-grade dysplasia based upon the pathological findings that fibrous ovarian-type stroma existed abundantly and the stroma cells were positive for progesterone receptor and inhibin. Hemosuccus pancreaticus caused by a mucinous cystic neoplasm is extremely rare and there has been only one case reported to date. In conclusion, it should be recognized that pancreatic cystic neoplasms including mucinous cystic neoplasms may cause hemosuccus pancreaticus.","Hemosuccus pancreaticus is a gastrointestinal hemorrhage through the main pancreatic duct. Here, we report a rare case of hemosuccus pancreaticus due to a mucinous cystic neoplasm of the pancreas. A 62-year-old woman who had been followed for a branch duct intraductal papillary mucinous neoplasm visited our emergency room due to severe abdominal pain and bloody discharge. Computed tomography revealed that the pancreatic cyst increased the tension of the wall and a high-density area indicative of bleeding into the cyst was observed. Endoscopy showed opening of and hemorrhaging from the papilla of Vater. The patient was diagnosed with hemosuccus pancreaticus caused by hemorrhaging into the cyst from the branch duct intraductal papillary mucinous neoplasm. Based on this diagnosis, elective distal pancreatectomy was performed. The histopathological diagnosis was a mucinous cystic neoplasm with intermediate-grade dysplasia based upon the pathological findings that fibrous ovarian-type stroma existed abundantly and the stroma cells were positive for progesterone receptor and inhibin. Hemosuccus pancreaticus caused by a mucinous cystic neoplasm is extremely rare and there has been only one case reported to date. In conclusion, it should be recognized that pancreatic cystic neoplasms including mucinous cystic neoplasms may cause hemosuccus pancreaticus.","null","null","2017-04-01","Clinical Journal of Gastroenterology","Clinical Journal of Gastroenterology","Vol.10","No.2","185","190","eng","true","null","scientific_journal","null","null","10.1007/s12328-016-0711-2","1865-7265","null","null","null","null","null"
"Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative acute kidney injury","Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative acute kidney injury","Naoji Mita, Shinji Kawahito, Tomohiro Soga, Kazumi Takaishi, Hiroshi Kitahata, Munehide Matsuhisa, Mitsuo Shimada, Kinoshita Hiroyuki, Yasuo Tsutsumi, Katsuya Tanaka","Naoji Mita, Shinji Kawahito, Tomohiro Soga, Kazumi Takaishi, Hiroshi Kitahata, Munehide Matsuhisa, Mitsuo Shimada, Kinoshita Hiroyuki, Yasuo Tsutsumi, Katsuya Tanaka","null","The aim of the present study was to evaluate the usefulness of a closed-loop system (STG-55; Nikkiso, Tokyo, Japan), a type of artificial endocrine pancreas for the continuous monitoring and control of intraoperative blood glucose, for preventing postoperative acute kidney injury (AKI) in patients undergoing hepatectomy. Thirty-eight patients were enrolled in this study. Glucose concentrations were controlled with either a manual injection of insulin based on a commonly used sliding scale (manual insulin group, n = 19) or the programmed infusion of insulin determined by the control algorithm of the artificial endocrine pancreas (programmed insulin group, n = 19). After the induction of anesthesia, a 20-G intravenous catheter was inserted into the peripheral forearm vein of patients in the programmed insulin group and connected to an artificial endocrine pancreas (STG-55). The target range for glucose concentrations was set to 100-150 mg/dL. The mean serum creatinine concentrations of preoperative, postoperative 24 and 48 h were 0.72, 0.78, and 0.79 mg/dL in the programmed insulin group, and 0.81, 0.95, and 1.03 mg/dL in the manual insulin group, respectively. Elevations in serum creatinine concentrations postoperative 48 h were significantly suppressed in the programmed insulin group. The STG-55 closed-loop system was effective for maintaining strict blood glucose control during hepatectomy with minimal variability in blood glucose concentrations and for suppressing elevations in serum creatinine concentrations. Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative AKI.","The aim of the present study was to evaluate the usefulness of a closed-loop system (STG-55; Nikkiso, Tokyo, Japan), a type of artificial endocrine pancreas for the continuous monitoring and control of intraoperative blood glucose, for preventing postoperative acute kidney injury (AKI) in patients undergoing hepatectomy. Thirty-eight patients were enrolled in this study. Glucose concentrations were controlled with either a manual injection of insulin based on a commonly used sliding scale (manual insulin group, n = 19) or the programmed infusion of insulin determined by the control algorithm of the artificial endocrine pancreas (programmed insulin group, n = 19). After the induction of anesthesia, a 20-G intravenous catheter was inserted into the peripheral forearm vein of patients in the programmed insulin group and connected to an artificial endocrine pancreas (STG-55). The target range for glucose concentrations was set to 100-150 mg/dL. The mean serum creatinine concentrations of preoperative, postoperative 24 and 48 h were 0.72, 0.78, and 0.79 mg/dL in the programmed insulin group, and 0.81, 0.95, and 1.03 mg/dL in the manual insulin group, respectively. Elevations in serum creatinine concentrations postoperative 48 h were significantly suppressed in the programmed insulin group. The STG-55 closed-loop system was effective for maintaining strict blood glucose control during hepatectomy with minimal variability in blood glucose concentrations and for suppressing elevations in serum creatinine concentrations. Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative AKI.","null","null","2017-03","Journal of Artificial Organs","Journal of Artificial Organs","Vol.20","No.1","76","83","eng","true","null","scientific_journal","null","null","10.1007/s10047-016-0925-6","1619-0904","null","null","null","null","null"
"Duodenal cancer in a young patient with Peuts-Jeghers syndrome harboring an entire deletion of the STK11 gene.","Duodenal cancer in a young patient with Peuts-Jeghers syndrome harboring an entire deletion of the STK11 gene.","Satoshi Teramae, Koichi Okamoto, Kumiko Tanaka, Reika Matsumoto, Shinji Kitamura, Tetsuo Kimura, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma, Yoshimi Bando, Mitsuo Shimada, Tetsuji Takayama","Satoshi Teramae, Koichi Okamoto, Kumiko Tanaka, Reika Matsumoto, Shinji Kitamura, Tetsuo Kimura, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma, Yoshimi Bando, Mitsuo Shimada, Tetsuji Takayama","null","null","null","null","null","2017-03","Clinical Journal of Gastroenterology","Clinical Journal of Gastroenterology","Vol.10","No.3","232","239","eng","true","null","scientific_journal","null","null","10.1007/s12328-017-0731-6","1865-7257","null","null","null","null","null"
"Downregulation of miR-100/miR-125b is associated with lymph node metastasis in early colorectal cancer with submucosal invasion.","Downregulation of miR-100/miR-125b is associated with lymph node metastasis in early colorectal cancer with submucosal invasion.","Yasuteru Fujino, Shunsaku Takeishi, Kensei Nishida, Koichi Okamoto, Naoki Muguruma, Tetsuo Kimura, Shinji Kitamura, Hiroshi Miyamoto, Akiko Fujimoto, Jun Higashijima, Mitsuo Shimada, Kazuhito Rokutan, Tetsuji Takayama","Yasuteru Fujino, Shunsaku Takeishi, Kensei Nishida, Koichi Okamoto, Naoki Muguruma, Tetsuo Kimura, Shinji Kitamura, Hiroshi Miyamoto, Akiko Fujimoto, Jun Higashijima, Mitsuo Shimada, Kazuhito Rokutan, Tetsuji Takayama","null","A majority of early colorectal cancers (CRCs) with submucosal invasion undergo surgical operation, despite a very low incidence of lymph node metastasis. Our study aimed to identify microRNAs (miRNAs) specifically responsible for lymph node metastasis in submucosal CRCs. MicroRNA microarray analysis revealed that miR-100 and miR-125b expression levels were significantly lower in CRC tissues with lymph node metastases than in those without metastases. These results were validated by quantitative real-time PCR in a larger set of clinical samples. The transfection of a miR-100 or miR-125b inhibitor into colon cancer HCT116 cells significantly increased cell invasion, migration, and MMP activity. Conversely, overexpression of miR-100 or miR-125b mimics significantly attenuated all these activities but did not affect cell growth. To identify target mRNAs, we undertook a gene expression array analysis of miR-100-silenced HCT116 cells as well as negative control cells. The Ingenuity Pathway Analysis, TargetScan software analyses, and subsequent verification of mRNA expression by real-time PCR identified mammalian target of rapamycin (mTOR) and insulin-like growth factor 1 receptor (IGF1R) as direct, and Fas and X-linked inhibitor-of-apoptosis protein (XIAP) as indirect candidate targets for miR-100 involved in lymph node metastasis. Knockdown of each gene by siRNA significantly reduced the invasiveness of HCT116 cells. These data clearly show that downregulation of miR-100 and miR-125b is closely associated with lymph node metastasis in submucosal CRC through enhancement of invasion, motility, and MMP activity. In particular, miR-100 may promote metastasis by upregulating mTOR, IGF1R, Fas, and XIAP as targets. Thus, miR-100 and miR-125b may be novel biomarkers for lymph node metastasis of early CRCs with submucosal invasion.","A majority of early colorectal cancers (CRCs) with submucosal invasion undergo surgical operation, despite a very low incidence of lymph node metastasis. Our study aimed to identify microRNAs (miRNAs) specifically responsible for lymph node metastasis in submucosal CRCs. MicroRNA microarray analysis revealed that miR-100 and miR-125b expression levels were significantly lower in CRC tissues with lymph node metastases than in those without metastases. These results were validated by quantitative real-time PCR in a larger set of clinical samples. The transfection of a miR-100 or miR-125b inhibitor into colon cancer HCT116 cells significantly increased cell invasion, migration, and MMP activity. Conversely, overexpression of miR-100 or miR-125b mimics significantly attenuated all these activities but did not affect cell growth. To identify target mRNAs, we undertook a gene expression array analysis of miR-100-silenced HCT116 cells as well as negative control cells. The Ingenuity Pathway Analysis, TargetScan software analyses, and subsequent verification of mRNA expression by real-time PCR identified mammalian target of rapamycin (mTOR) and insulin-like growth factor 1 receptor (IGF1R) as direct, and Fas and X-linked inhibitor-of-apoptosis protein (XIAP) as indirect candidate targets for miR-100 involved in lymph node metastasis. Knockdown of each gene by siRNA significantly reduced the invasiveness of HCT116 cells. These data clearly show that downregulation of miR-100 and miR-125b is closely associated with lymph node metastasis in submucosal CRC through enhancement of invasion, motility, and MMP activity. In particular, miR-100 may promote metastasis by upregulating mTOR, IGF1R, Fas, and XIAP as targets. Thus, miR-100 and miR-125b may be novel biomarkers for lymph node metastasis of early CRCs with submucosal invasion.","null","null","2017-03","Cancer Science","Cancer Science","Vol.108","No.3","390","397","eng","true","null","scientific_journal","null","null","10.1111/cas.13152","1349-7006","null","null","null","null","null"
"【先天性胆道拡張症の最前線】 先天性胆道拡張症の診療ガイドライン(ダイジェスト版)","Japanese clinical practice guidelines for congenital biliary dilatation","石橋 広樹, 島田 光生, 矢田 圭吾","Hiroki Ishibashi, Mitsuo Shimada, Keigo Yada","null","先天性胆道拡張症(congenital biliary dilatation;CBD)は,総胆管を含む肝外胆管が限局性に拡張する先天性の形成異常で,膵・胆管合流異常を合併し,胆汁と膵液の流出障害や相互逆流,胆道癌など肝,胆道および膵にさまざまな病態を引きおこす疾患であるが,診療ガイドラインはいまだ策定されていない.今回,CBD診療ガイドラインの作成にあたり,膵・胆管合流異常診療ガイドラインから,抜粋,一部改変し,clinical question作成,引用文献のレベル分類,ステートメントの推奨度決定を行い,科学的根拠に基づいたCBD診療ガイドラインを作成したので,ダイジェスト版として紹介する.
","先天性胆道拡張症(congenital biliary dilatation;CBD)は,総胆管を含む肝外胆管が限局性に拡張する先天性の形成異常で,膵・胆管合流異常を合併し,胆汁と膵液の流出障害や相互逆流,胆道癌など肝,胆道および膵にさまざまな病態を引きおこす疾患であるが,診療ガイドラインはいまだ策定されていない.今回,CBD診療ガイドラインの作成にあたり,膵・胆管合流異常診療ガイドラインから,抜粋,一部改変し,clinical question作成,引用文献のレベル分類,ステートメントの推奨度決定を行い,科学的根拠に基づいたCBD診療ガイドラインを作成したので,ダイジェスト版として紹介する.
","null","null","2016-12","日本消化器病学会雑誌","The Japanese Journal of Gastro-enterology","Vol.113","No.12","2004","2015","jpn","true","null","scientific_journal","null","null","10.11405/nisshoshi.113.2004","1349-7693","null","http://search.jamas.or.jp/link/ui/2017085326","null","null","null"
"Propensity score-matched study of laparoscopic and open surgery for colorectal cancer in rural hospitals.","Propensity score-matched study of laparoscopic and open surgery for colorectal cancer in rural hospitals.","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Ichio Suzuka, Takashi Nishizaki, Hiroshi Okitsu, Toshiyuki Yagi, Hidenori Miyake, Murato Miura, Mitsutoshi Fukuyama, Daisuke Wada, Yoshiaki Bando","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Ichio Suzuka, Takashi Nishizaki, Hiroshi Okitsu, Toshiyuki Yagi, Hidenori Miyake, Murato Miura, Mitsutoshi Fukuyama, Daisuke Wada, Yoshiaki Bando","null","Various randomized clinical studies have suggested that short- and long-term outcomes of laparoscopic surgery (LAP) for colorectal cancer are comparable with those of open surgery (OP). However, these studies were performed in high-volume hospitals. The aim of the present study was to compare the outcomes of LAP versus OP for colorectal cancer in rural hospitals. This was a multicenter retrospective propensity score-matched case-control study of patients who underwent colorectal surgery from January 2004 to April 2009 in 10 hospitals in Japan. All patients underwent curative surgery for pathologically diagnosed stage II or III colorectal cancer. The primary end point was 5-year overall survival (OS). The secondary end points were disease-free survival (DFS) and postoperative complications. In total, 319 patients who underwent LAP and 1020 patients who underwent OP were balanced to 261 pairs. There was no significant difference in the OS and DFS between two groups. The operation time was significantly shorter for OP than for LAP. Blood loss was significantly lower in LAP than in OP. There was no difference in intraoperative morbidity between the two groups. The postoperative morbidity was significantly lower in LAP than in OP. The hospital stay was significantly shorter in LAP than in OP. There was no significant difference in 90-day postoperative mortality. Laparoscopic surgery may be a feasible option for colorectal cancer in rural hospitals.","Various randomized clinical studies have suggested that short- and long-term outcomes of laparoscopic surgery (LAP) for colorectal cancer are comparable with those of open surgery (OP). However, these studies were performed in high-volume hospitals. The aim of the present study was to compare the outcomes of LAP versus OP for colorectal cancer in rural hospitals. This was a multicenter retrospective propensity score-matched case-control study of patients who underwent colorectal surgery from January 2004 to April 2009 in 10 hospitals in Japan. All patients underwent curative surgery for pathologically diagnosed stage II or III colorectal cancer. The primary end point was 5-year overall survival (OS). The secondary end points were disease-free survival (DFS) and postoperative complications. In total, 319 patients who underwent LAP and 1020 patients who underwent OP were balanced to 261 pairs. There was no significant difference in the OS and DFS between two groups. The operation time was significantly shorter for OP than for LAP. Blood loss was significantly lower in LAP than in OP. There was no difference in intraoperative morbidity between the two groups. The postoperative morbidity was significantly lower in LAP than in OP. The hospital stay was significantly shorter in LAP than in OP. There was no significant difference in 90-day postoperative mortality. Laparoscopic surgery may be a feasible option for colorectal cancer in rural hospitals.","null","null","2016-10","Journal of Gastroenterology and Hepatology","Journal of Gastroenterology and Hepatology","Vol.31","No.10","1700","1704","eng","true","null","scientific_journal","null","null","10.1111/jgh.13322","1440-1746","null","null","null","null","null"
"Neuroendocrine carcinoma of the pancreas with similar genetic alterations to invasive ductal adenocarcinoma.","Neuroendocrine carcinoma of the pancreas with similar genetic alterations to invasive ductal adenocarcinoma.","Tetsuo Kimura, Hiroshi Miyamoto, Akira Fukuya, Shinji Kitamura, Koichi Okamoto, Masako Kimura, Naoki Muguruma, Tetsuya Ikemoto, Mitsuo Shimada, Akiko Yoneda, Yoshimi Bando, Makoto Takishita, Tetsuji Takayama","Tetsuo Kimura, Hiroshi Miyamoto, Akira Fukuya, Shinji Kitamura, Koichi Okamoto, Masako Kimura, Naoki Muguruma, Tetsuya Ikemoto, Mitsuo Shimada, Akiko Yoneda, Yoshimi Bando, Makoto Takishita, Tetsuji Takayama","null","Neuroendocrine carcinoma (NEC) of the pancreas is very rare, and its origin is not fully elucidated. Here, we present a case of a small-size NEC of the pancreas that is genetically similar to invasive ductal adenocarcinoma (IDA). A 65-year-old man was referred to our hospital due to obstructive jaundice and found to have a 12-mm solid tumor in the pancreas head. The tumor exhibited low vascularity on enhanced computed tomography, and endoscopic retrograde pancreatographic imaging revealed an irregular obstruction in a branch duct of the pancreas. The patient was thereby diagnosed with a pancreatic ductal cancer, and stomach-preserving pancreaticoduodenectomy with regional lymph node resection was performed. Histochemical analysis of the resected tumor showed that the neoplastic cells with scanty cytoplasm and hyperchromatic nuclei strongly expressed chromogranin A and synaptophysin. The Ki-67 index was 40 % in the most proliferative tumor regions, and the tumor was diagnosed as a NEC of the pancreas. However, in the analysis of genetic alterations of the tumor tissue, the neoplastic cells showed altered KRAS, TP53, and SMAD4/DPC4, suggesting that the NEC in our case is genetically related to IDA. Our data suggest that poorly differentiated IDAs may transform into NECs.","Neuroendocrine carcinoma (NEC) of the pancreas is very rare, and its origin is not fully elucidated. Here, we present a case of a small-size NEC of the pancreas that is genetically similar to invasive ductal adenocarcinoma (IDA). A 65-year-old man was referred to our hospital due to obstructive jaundice and found to have a 12-mm solid tumor in the pancreas head. The tumor exhibited low vascularity on enhanced computed tomography, and endoscopic retrograde pancreatographic imaging revealed an irregular obstruction in a branch duct of the pancreas. The patient was thereby diagnosed with a pancreatic ductal cancer, and stomach-preserving pancreaticoduodenectomy with regional lymph node resection was performed. Histochemical analysis of the resected tumor showed that the neoplastic cells with scanty cytoplasm and hyperchromatic nuclei strongly expressed chromogranin A and synaptophysin. The Ki-67 index was 40 % in the most proliferative tumor regions, and the tumor was diagnosed as a NEC of the pancreas. However, in the analysis of genetic alterations of the tumor tissue, the neoplastic cells showed altered KRAS, TP53, and SMAD4/DPC4, suggesting that the NEC in our case is genetically related to IDA. Our data suggest that poorly differentiated IDAs may transform into NECs.","null","null","2016-08","Clinical Journal of Gastroenterology","Clinical Journal of Gastroenterology","Vol.9","No.4","261","265","eng","true","null","scientific_journal","null","null","10.1007/s12328-016-0655-6","1865-7265","null","null","null","null","null"
"Combined liver mobilization and retraction: A novel technique to obtain the optimal surgical field during laparoscopic total gastrectomy.","Combined liver mobilization and retraction: A novel technique to obtain the optimal surgical field during laparoscopic total gastrectomy.","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Syohei Eto","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Syohei Eto","null","During laparoscopic gastrectomy, it is important to establish a good operative field and ensure an adequate working space. The combined liver mobilization and retraction method is used to get a safe and optimal view. We retrospectively analyzed 32 consecutive patients who underwent laparoscopic total gastrectomy for gastric cancer. The patients were divided into two groups: the mobilization (+) group (n = 12) and the mobilization (-) group (n = 20). Hepatic function tests were performed in all patients. Mobilization provided a satisfactory view of the working field, especially the gastroesophageal junction and the angle of His during laparoscopic total gastrectomy, and no complications were observed during liver retraction. On postoperative hepatic function testing, there was no significant difference between the two groups on any day. Combined liver mobilization and retraction may be helpful in laparoscopic total gastrectomy.","During laparoscopic gastrectomy, it is important to establish a good operative field and ensure an adequate working space. The combined liver mobilization and retraction method is used to get a safe and optimal view. We retrospectively analyzed 32 consecutive patients who underwent laparoscopic total gastrectomy for gastric cancer. The patients were divided into two groups: the mobilization (+) group (n = 12) and the mobilization (-) group (n = 20). Hepatic function tests were performed in all patients. Mobilization provided a satisfactory view of the working field, especially the gastroesophageal junction and the angle of His during laparoscopic total gastrectomy, and no complications were observed during liver retraction. On postoperative hepatic function testing, there was no significant difference between the two groups on any day. Combined liver mobilization and retraction may be helpful in laparoscopic total gastrectomy.","null","null","2016-05-18","Asian Journal of Endoscopic Surgery","Asian Journal of Endoscopic Surgery","Vol.9","No.2","111","115","eng","true","null","scientific_journal","null","null","10.1111/ases.12271","1758-5910","null","null","null","null","null"
"Intrascrotal lipoblastoma: report of a case and the review of literature.","Intrascrotal lipoblastoma: report of a case and the review of literature.","Keigo Yada, Hiroki Ishibashi, Hiroki Mori, Mitsuo Shimada","Keigo Yada, Hiroki Ishibashi, Hiroki Mori, Mitsuo Shimada","null","Intrascrotal lipoblastoma is a rare pediatric benign soft tissue neoplasm, and only 11 cases have been reported. The accurate preoperative diagnosis is difficult because of its rarelity and the similarity with the other soft tissue tumors. Among them, accurate preoperative diagnosis had been made in only one case. Thus, almost all of the cases had required inguinal mass excision (and orchidectomy in one case). In this paper, we discuss the accurate preoperative diagnosis of intrascrotal lipoblastoma and subsequent simple tumorectomy via minimal invasive scrotal skin incision, in 1-year-old boy. On physical examination, intrascrotal extra-testicular lobulated mass was palpated on the right scrotum. An ultrasonography revealed the well-circumscribed, iso-echoic, scant blood-flow, and lobulated tumors with each lobules of 1 to 4 cm in diameter, and the tumor located outside of the tunica vaginalis testis. The serum values of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (b-hCG) were within normal limit. The preoperative diagnosis of intrascrotal lipoblastoma was made, and the mass was excised via minimal scrotal incision. The right testicle and epididymis were normal. The lesion consisted of the distinct two lobulated tumors, and microscopic examination confirmed the diagnosis of intrascrotal lipoblastoma. The postoperative course was uneventful without evidence of recurrence. A rare intrascrotal lipoblastoma is seldom made accurate preoperative diagnosis; however, the accurate preoperative suspicion of this tumor leads to the minimal invasive tumorectomy via scrotal skin incision and favorable postoperative recovery without recurrence.","Intrascrotal lipoblastoma is a rare pediatric benign soft tissue neoplasm, and only 11 cases have been reported. The accurate preoperative diagnosis is difficult because of its rarelity and the similarity with the other soft tissue tumors. Among them, accurate preoperative diagnosis had been made in only one case. Thus, almost all of the cases had required inguinal mass excision (and orchidectomy in one case). In this paper, we discuss the accurate preoperative diagnosis of intrascrotal lipoblastoma and subsequent simple tumorectomy via minimal invasive scrotal skin incision, in 1-year-old boy. On physical examination, intrascrotal extra-testicular lobulated mass was palpated on the right scrotum. An ultrasonography revealed the well-circumscribed, iso-echoic, scant blood-flow, and lobulated tumors with each lobules of 1 to 4 cm in diameter, and the tumor located outside of the tunica vaginalis testis. The serum values of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (b-hCG) were within normal limit. The preoperative diagnosis of intrascrotal lipoblastoma was made, and the mass was excised via minimal scrotal incision. The right testicle and epididymis were normal. The lesion consisted of the distinct two lobulated tumors, and microscopic examination confirmed the diagnosis of intrascrotal lipoblastoma. The postoperative course was uneventful without evidence of recurrence. A rare intrascrotal lipoblastoma is seldom made accurate preoperative diagnosis; however, the accurate preoperative suspicion of this tumor leads to the minimal invasive tumorectomy via scrotal skin incision and favorable postoperative recovery without recurrence.","null","null","2016-04-09","Surgical Case Reports","Surgical Case Reports","Vol.2","No.1","34","34","eng","true","null","scientific_journal","null","null","10.1186/s40792-016-0160-7","2198-7793","null","null","null","null","null"
"The Kampo medicine ""Daikenchuto (TU-100)"" prevents bacterial translocation and hepatic fibrosis in a rat model of biliary atresia.","The Kampo medicine ""Daikenchuto (TU-100)"" prevents bacterial translocation and hepatic fibrosis in a rat model of biliary atresia.","Keigo Yada, Hiroki Ishibashi, Hiroki Mori, Yuji Morine, Chengzhan Zhu, Rui Feng, Toru Kono, Mitsuo Shimada","Keigo Yada, Hiroki Ishibashi, Hiroki Mori, Yuji Morine, Chengzhan Zhu, Rui Feng, Toru Kono, Mitsuo Shimada","null","Biliary atresia is the most common cause of end-stage liver disease in children. It is known that bile duct ligation contributes to liver fibrosis via bacterial translocation (BT) and toll-like receptor 4 (TLR4) signaling of hepatic stellate cells (HSCs). We have reported previously that the traditional Japanese medicine, ""Dai-kenchu-to (TU-100),"" a form of ""Kampo medicine"" prevents BT in rats exposed to the stress of fasting. The aim of this study was to clarify the effect of TU-100 on a rat model of biliary atresia using bile duct ligation. Bile duct ligation and subsequent daily oral administration of TU-100 was performed in 6-week-old rats. The rats were killed at 3, 7, or 14 days after bile duct ligation to evaluate the liver injury, occurrence of BT, and hepatic fibrosis. As an in vitro experiment, we isolated fresh HSCs from the rats undergoing bile duct ligation. After cell attachment, TU-100 and its 3 component herbs (eg, processed ginger, ginseng radix, and Japanese pepper) were added, and the expressions of Alpha actin2 (acta2), Alpha-1 type I collagen (colIa1), and tissue inhibitor of metalloproteinase 1 (timp1) were analyzed. In vivo experiments demonstrated that oral administration of TU-100 decreased liver injury and atrophy of intestinal mucosa BT, hepatic fibrosis, and hepatic expression of alpha smooth muscle actin ( SMA) and TLR4, compared with rats that underwent bile duct ligation only. In vitro experiments showed that administration of TU-100 or the component herbs inhibited the expressions of acta2, colIa1, and timp1 in the HSCs. TU-100 prevented BT, activation of HSCs, and subsequent hepatic fibrosis. TU-100 may prevent progression of hepatic fibrosis in children with biliary atresia and improve prognosis.","Biliary atresia is the most common cause of end-stage liver disease in children. It is known that bile duct ligation contributes to liver fibrosis via bacterial translocation (BT) and toll-like receptor 4 (TLR4) signaling of hepatic stellate cells (HSCs). We have reported previously that the traditional Japanese medicine, ""Dai-kenchu-to (TU-100),"" a form of ""Kampo medicine"" prevents BT in rats exposed to the stress of fasting. The aim of this study was to clarify the effect of TU-100 on a rat model of biliary atresia using bile duct ligation. Bile duct ligation and subsequent daily oral administration of TU-100 was performed in 6-week-old rats. The rats were killed at 3, 7, or 14 days after bile duct ligation to evaluate the liver injury, occurrence of BT, and hepatic fibrosis. As an in vitro experiment, we isolated fresh HSCs from the rats undergoing bile duct ligation. After cell attachment, TU-100 and its 3 component herbs (eg, processed ginger, ginseng radix, and Japanese pepper) were added, and the expressions of Alpha actin2 (acta2), Alpha-1 type I collagen (colIa1), and tissue inhibitor of metalloproteinase 1 (timp1) were analyzed. In vivo experiments demonstrated that oral administration of TU-100 decreased liver injury and atrophy of intestinal mucosa BT, hepatic fibrosis, and hepatic expression of alpha smooth muscle actin ( SMA) and TLR4, compared with rats that underwent bile duct ligation only. In vitro experiments showed that administration of TU-100 or the component herbs inhibited the expressions of acta2, colIa1, and timp1 in the HSCs. TU-100 prevented BT, activation of HSCs, and subsequent hepatic fibrosis. TU-100 may prevent progression of hepatic fibrosis in children with biliary atresia and improve prognosis.","null","null","2016-03-16","Surgery","Surgery","Vol.159","No.6","1600","1611","eng","true","null","scientific_journal","null","null","10.1016/j.surg.2016.02.002","1532-7361","null","null","null","null","null"
"【イラストでみる最新の胆・膵消化管吻合術】 肝管空腸吻合 先天性胆道拡張症,戸谷分類IV-A型","【イラストでみる最新の胆・膵消化管吻合術】 肝管空腸吻合 先天性胆道拡張症,戸谷分類IV-A型","矢田 圭吾, 石橋 広樹, 森 大樹, 森根 裕二, 島田 光生","Keigo Yada, Hiroki Ishibashi, Hiroki Mori, Yuji Morine, Mitsuo Shimada","null","null","null","null","null","2016-03","胆と膵","Journal of Biliary Tract & Pancreas","Vol.37","No.3","215","220","jpn","true","null","scientific_journal","null","null","null","0388-9408","null","http://search.jamas.or.jp/link/ui/2016212098","null","null","null"
"Uracil-Tegafur and Oral Leucovorin Combined With Bevacizumab in Elderly Patients (Aged · 75 Years) With Metastatic Colorectal Cancer: A Multicenter, Phase II Trial (Joint Study of Bevacizumab, Oral Leucovorin, and Uracil-Tegafur in Elderly Patients [J-BLUE] Study).","Uracil-Tegafur and Oral Leucovorin Combined With Bevacizumab in Elderly Patients (Aged · 75 Years) With Metastatic Colorectal Cancer: A Multicenter, Phase II Trial (Joint Study of Bevacizumab, Oral Leucovorin, and Uracil-Tegafur in Elderly Patients [J-BLUE] Study).","Tomohiro Nishina, Toshikazu Moriwaki, Mitsuo Shimada, Jun Higashijima, Yoshinori Sakai, Toshiki Masuishi, Mitsuharu Ozeki, Kenji Amagai, Yuji Negoro, Shunju Indo, Tadamichi Denda, Mikio Sato, Yuji Yamamoto, Go Nakajima, Minoru Mizuta, Ikuo Takahashi, Yoshinori Hiroshima, Hiroyasu Ishida, Takashi Maeba, Ichinosuke Hyodo","Tomohiro Nishina, Toshikazu Moriwaki, Mitsuo Shimada, Jun Higashijima, Yoshinori Sakai, Toshiki Masuishi, Mitsuharu Ozeki, Kenji Amagai, Yuji Negoro, Shunju Indo, Tadamichi Denda, Mikio Sato, Yuji Yamamoto, Go Nakajima, Minoru Mizuta, Ikuo Takahashi, Yoshinori Hiroshima, Hiroyasu Ishida, Takashi Maeba, Ichinosuke Hyodo","null","We previously reported that uracil-tegafur with oral leucovorin (UFT/LV) treatment for elderly patients (aged · 75 years) was well-tolerated in a phase II study. In the present study, the efficacy and safety of a modified (1-week shorter administration period) UFT/LV schedule combined with bevacizumab for a similar population are reported. The present study was a single-arm, open-label, multicenter, cooperative group clinical trial. The key eligibility criteria included age · 75 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ function. Patients received UFT 300 mg/m(2)/d and LV 75 mg/d on days 1 to 21 and intravenous bevacizumab 5 mg/kg on days 1 and 15. Treatment was repeated every 28 days. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), overall survival (OS), and safety. Of the 55 patients enrolled from 15 Japanese institutions, 52 eligible patients were evaluated. Their median age was 80 years (range, 75-87 years), and 73% had an ECOG performance status of 0. The median PFS was 8.2 months (95% confidence interval [CI], 6.2-10 months). The ORR was 40% (95% CI, 27%-55%). The median OS was 23 months (95% CI, 12-33 months). The most common grade 3 and 4 treatment-related adverse events were hypertension (12%), fatigue (8%), anemia (8%), nausea (6%), and diarrhea (6%). Treatment-related death occurred in 2 patients. UFT/LV (3 weeks of therapy and 1 week without) combined with biweekly bevacizumab is a tolerable and effective treatment option for elderly patients (aged · 75 years) with metastatic colorectal cancer.","We previously reported that uracil-tegafur with oral leucovorin (UFT/LV) treatment for elderly patients (aged · 75 years) was well-tolerated in a phase II study. In the present study, the efficacy and safety of a modified (1-week shorter administration period) UFT/LV schedule combined with bevacizumab for a similar population are reported. The present study was a single-arm, open-label, multicenter, cooperative group clinical trial. The key eligibility criteria included age · 75 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ function. Patients received UFT 300 mg/m(2)/d and LV 75 mg/d on days 1 to 21 and intravenous bevacizumab 5 mg/kg on days 1 and 15. Treatment was repeated every 28 days. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), overall survival (OS), and safety. Of the 55 patients enrolled from 15 Japanese institutions, 52 eligible patients were evaluated. Their median age was 80 years (range, 75-87 years), and 73% had an ECOG performance status of 0. The median PFS was 8.2 months (95% confidence interval [CI], 6.2-10 months). The ORR was 40% (95% CI, 27%-55%). The median OS was 23 months (95% CI, 12-33 months). The most common grade 3 and 4 treatment-related adverse events were hypertension (12%), fatigue (8%), anemia (8%), nausea (6%), and diarrhea (6%). Treatment-related death occurred in 2 patients. UFT/LV (3 weeks of therapy and 1 week without) combined with biweekly bevacizumab is a tolerable and effective treatment option for elderly patients (aged · 75 years) with metastatic colorectal cancer.","null","null","2015-12-17","Clinical Colorectal Cancer","Clinical Colorectal Cancer","Vol.15","No.3","236","242","eng","true","null","scientific_journal","null","null","10.1016/j.clcc.2015.12.001","1938-0674","null","null","null","null","null"
"手術手技 合併症から学ぶ腹腔鏡下胃全摘出術R-Y再建の工夫","手術手技 合併症から学ぶ腹腔鏡下胃全摘出術R-Y再建の工夫","吉川 幸造, 島田 光生, 東島 潤, 中尾 寿宏, 西 正暁, 柏原 秀也","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Toshihiro Nakao, Masaaki Nishi, Hideya Kashihara","null","null","null","null","null","2015-12","手術","Operation","Vol.69","No.13","1821","1825","jpn","true","null","scientific_journal","null","null","null","0037-4423","null","null","null","null","null"
"Prediction of response to preoperative chemoradiotherapy and establishment of individualized therapy in advanced rectal cancer.","Prediction of response to preoperative chemoradiotherapy and establishment of individualized therapy in advanced rectal cancer.","Toshihiro Nakao, Takashi Iwata, Masanori Hotchi, Kouzou Yoshikawa, Jun Higashijima, Masaaki Nishi, Chie Takasu, Shohei Eto, Hiroki Teraoku, Mitsuo Shimada","Toshihiro Nakao, Takashi Iwata, Masanori Hotchi, Kouzou Yoshikawa, Jun Higashijima, Masaaki Nishi, Chie Takasu, Shohei Eto, Hiroki Teraoku, Mitsuo Shimada","null","Preoperative chemoradiotherapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer. However, no specific biomarker has been identified to predict a response to preoperative CRT. The aim of the present study was to assess the gene expression patterns of patients with advanced rectal cancer to predict their responses to preoperative CRT. Fifty-nine rectal cancer patients were subjected to preoperative CRT. Patients were randomly assigned to receive CRT with tegafur/gimeracil/oteracil (S-1 group, n=30) or tegafur-uracil (UFT group, n=29). Gene expression changes were studied with cDNA and miRNA microarray. The association between gene expression and response to CRT was evaluated. cDNA microarray showed that 184 genes were significantly differentially expressed between the responders and the non-responders in the S-1 group. Comparatively, 193 genes were significantly differentially expressed in the responders in the UFT group. TBX18 upregulation was common to both groups whereas BTNL8, LOC375010, ADH1B, HRASLS2, LOC284232, GCNT3 and ALDH1A2 were significantly differentially lower in both groups when compared with the non-responders. Using miRNA microarray, we found that 7 and 16 genes were significantly differentially expressed between the responders and non-responders in the S-1 and UFT groups, respectively. miR-223 was significantly higher in the responders in the S-1 group and tended to be higher in the responders in the UFT group. The present study identified several genes likely to be useful for establishing individualized therapies for patients with rectal cancer.","Preoperative chemoradiotherapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer. However, no specific biomarker has been identified to predict a response to preoperative CRT. The aim of the present study was to assess the gene expression patterns of patients with advanced rectal cancer to predict their responses to preoperative CRT. Fifty-nine rectal cancer patients were subjected to preoperative CRT. Patients were randomly assigned to receive CRT with tegafur/gimeracil/oteracil (S-1 group, n=30) or tegafur-uracil (UFT group, n=29). Gene expression changes were studied with cDNA and miRNA microarray. The association between gene expression and response to CRT was evaluated. cDNA microarray showed that 184 genes were significantly differentially expressed between the responders and the non-responders in the S-1 group. Comparatively, 193 genes were significantly differentially expressed in the responders in the UFT group. TBX18 upregulation was common to both groups whereas BTNL8, LOC375010, ADH1B, HRASLS2, LOC284232, GCNT3 and ALDH1A2 were significantly differentially lower in both groups when compared with the non-responders. Using miRNA microarray, we found that 7 and 16 genes were significantly differentially expressed between the responders and non-responders in the S-1 and UFT groups, respectively. miR-223 was significantly higher in the responders in the S-1 group and tended to be higher in the responders in the UFT group. The present study identified several genes likely to be useful for establishing individualized therapies for patients with rectal cancer.","null","null","2015-08-10","Oncology Reports","Oncology Reports","Vol.34","No.4","1961","1967","eng","true","null","scientific_journal","null","null","10.3892/or.2015.4196","1791-2431","null","null","null","null","null"
"Risk Model for Distal Gastrectomy When Treating Gastric Cancer on the Basis of Data From 33,917 Japanese Patients Collected Using a Nationwide Web-based Data Entry System.","Risk Model for Distal Gastrectomy When Treating Gastric Cancer on the Basis of Data From 33,917 Japanese Patients Collected Using a Nationwide Web-based Data Entry System.","Nobuhiro Kurita, Hiroaki Miyata, Mitsukazu Gotoh, Mitsuo Shimada, Satoru Imura, Wataru Kimura, Naohiro Tomita, Hideo Baba, Yukou Kitagawa, Kenichi Sugihara, Masaki Mori","Nobuhiro Kurita, Hiroaki Miyata, Mitsukazu Gotoh, Mitsuo Shimada, Satoru Imura, Wataru Kimura, Naohiro Tomita, Hideo Baba, Yukou Kitagawa, Kenichi Sugihara, Masaki Mori","null","To establish a risk model for distal gastrectomy in Japanese patients with gastric cancer. Risk stratification for distal gastrectomy in Japanese patients with gastric cancer improves surgical outcomes. The National Clinical Database was constructed for risk determination in gastric cancer-related gastrectomy among Japanese individuals. Data from 33,917 gastric cancer cases (1737 hospitals) were used. The primary outcomes were 30-day and operative mortalities. Data were randomly assigned to risk model development (27,220 cases) and test validation (6697 cases) subsets. Stepwise selection was used for constructing 30-day and operative mortality logistic models. The 30-day, in-hospital, and operative mortality rates were 0.52%, 1.16%, and 1.2%, respectively. The morbidity was 18.3%. The 30-day and operative mortality models included 17 and 21 risk factors, respectively. Thirteen variables overlapped: age, need for total assistance in activities of daily living preoperatively or within 30 days after surgery, cerebrovascular disease history, more than 10% weight loss, uncontrolled ascites, American Society of Anesthesiologists score (≥ class 3), white blood cell count more than 12,000/μL or 11,000/μL, anemia (hemoglobin: males, <13.5 g/dL; females, <12.5 g/dL; or hematocrit: males, <37%; females <32%), serum albumin less than 3.5 or 3.8 g/dL, alkaline phosphatase more than 340 IU/L, serum creatinine more than 1.2 mg/dL, serum Na less than 135 mEq/L, and prothrombin time-international normalized ratio more than 1.25 or 1.1. The C-indices for the 30-day and operative mortalities were 0.785 (95% confidence interval, 0.705-0.865; P < 0.001) and 0.798 (95% confidence interval, 0.746-0.851; P < 0.001), respectively. The risk model developed using nationwide Japanese data on distal gastrectomy in gastric cancer can predict surgical outcomes.","To establish a risk model for distal gastrectomy in Japanese patients with gastric cancer. Risk stratification for distal gastrectomy in Japanese patients with gastric cancer improves surgical outcomes. The National Clinical Database was constructed for risk determination in gastric cancer-related gastrectomy among Japanese individuals. Data from 33,917 gastric cancer cases (1737 hospitals) were used. The primary outcomes were 30-day and operative mortalities. Data were randomly assigned to risk model development (27,220 cases) and test validation (6697 cases) subsets. Stepwise selection was used for constructing 30-day and operative mortality logistic models. The 30-day, in-hospital, and operative mortality rates were 0.52%, 1.16%, and 1.2%, respectively. The morbidity was 18.3%. The 30-day and operative mortality models included 17 and 21 risk factors, respectively. Thirteen variables overlapped: age, need for total assistance in activities of daily living preoperatively or within 30 days after surgery, cerebrovascular disease history, more than 10% weight loss, uncontrolled ascites, American Society of Anesthesiologists score (≥ class 3), white blood cell count more than 12,000/μL or 11,000/μL, anemia (hemoglobin: males, <13.5 g/dL; females, <12.5 g/dL; or hematocrit: males, <37%; females <32%), serum albumin less than 3.5 or 3.8 g/dL, alkaline phosphatase more than 340 IU/L, serum creatinine more than 1.2 mg/dL, serum Na less than 135 mEq/L, and prothrombin time-international normalized ratio more than 1.25 or 1.1. The C-indices for the 30-day and operative mortalities were 0.785 (95% confidence interval, 0.705-0.865; P < 0.001) and 0.798 (95% confidence interval, 0.746-0.851; P < 0.001), respectively. The risk model developed using nationwide Japanese data on distal gastrectomy in gastric cancer can predict surgical outcomes.","null","null","2015-08","Annals of Surgery","Annals of Surgery","Vol.262","No.2","295","303","eng","true","null","scientific_journal","null","null","10.1097/SLA.0000000000001127","1528-1140","null","null","null","null","null"
"外科の立場からのキャリアアップ支援と問題点","外科の立場からのキャリアアップ支援と問題点","髙須 千絵, 島田 光生","Chie Takasu, Mitsuo Shimada","null","null","null","null","null","2015-06-18","第40回日本外科系連合学会学術集会","第40回日本外科系連合学会学術集会","null","null","null","null","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"Detection of Lymph Nodes Metastasis in Biliary Carcinomas:Morphological Criteria by MDCT and the Clinical Impact of DEI-MRI","Detection of Lymph Nodes Metastasis in Biliary Carcinomas:Morphological Criteria by MDCT and the Clinical Impact of DEI-MRI","Yuji Morine, Mitsuo Shimada, Satoru Imura, Tetsuya Ikemoto, Jun Hanaoka, Mami Kanamoto, Hiroki Ishibashi, Toru Utsunomiya","Yuji Morine, Mitsuo Shimada, Satoru Imura, Tetsuya Ikemoto, Jun Hanaoka, Mami Kanamoto, Hiroki Ishibashi, Toru Utsunomiya","null","This study was conducted to assess the usefulness of multi-slice CT (MDCT) and diffusion weighted MR images (DWI-MRI) for diagnosis of metastatic lymph nodes (LNs) in biliary carcinomas. Eighteen patients with biliary carcinomas (total 121 LNs) underwent surgical resection were included. In MDCT, the following criteria were measured: the maximum diameter, the enhanced value and the long and short axis (L/S) ratio. In DWI-MRI, the apparent diffusion coefficients (ADCs) were measured from ADC maps. In ROC analysis, the maximum diameter has the highest diagnostic power with area under curves of 0.903. And when the maximum diameter 8 mm and L/S ratio is less than 2, the accuracy was improved with a sensitivity of 81%, positive predictive value (PPV) of 45%. In DWI-MRI, ADCs values of metastatic LNs significantly lower than that of non-metastatic LNs (mean: 1.65 vs. 2.11 x10 3mm2/s). When the ADC value of 1.8 x10(-3) was used as a cut-off value, the best results were obtained with sensitivity of 75%, PPV of 82%. Using MDCT, diagnosis of LNs metastasis should be more than 8mm diameter and less than 2 of L/S ratio. In addition, DWI-MRI is more useful modality for diagnosis of LNs metastasis.","This study was conducted to assess the usefulness of multi-slice CT (MDCT) and diffusion weighted MR images (DWI-MRI) for diagnosis of metastatic lymph nodes (LNs) in biliary carcinomas. Eighteen patients with biliary carcinomas (total 121 LNs) underwent surgical resection were included. In MDCT, the following criteria were measured: the maximum diameter, the enhanced value and the long and short axis (L/S) ratio. In DWI-MRI, the apparent diffusion coefficients (ADCs) were measured from ADC maps. In ROC analysis, the maximum diameter has the highest diagnostic power with area under curves of 0.903. And when the maximum diameter 8 mm and L/S ratio is less than 2, the accuracy was improved with a sensitivity of 81%, positive predictive value (PPV) of 45%. In DWI-MRI, ADCs values of metastatic LNs significantly lower than that of non-metastatic LNs (mean: 1.65 vs. 2.11 x10 3mm2/s). When the ADC value of 1.8 x10(-3) was used as a cut-off value, the best results were obtained with sensitivity of 75%, PPV of 82%. Using MDCT, diagnosis of LNs metastasis should be more than 8mm diameter and less than 2 of L/S ratio. In addition, DWI-MRI is more useful modality for diagnosis of LNs metastasis.","null","null","2015-06","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.62","No.140","777","781","eng","true","null","scientific_journal","null","null","null","0172-6390","null","null","null","null","null"
"The relationship of CD133, histone deacetylase 1 and thrombospondin-1 in gastric cancer.","The relationship of CD133, histone deacetylase 1 and thrombospondin-1 in gastric cancer.","Shohei Eto, Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Horohiko Sato, Nobuhiro Kurita","Shohei Eto, Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Horohiko Sato, Nobuhiro Kurita","null","Gastric cancer is one of the most common types of cancer. Cancer stem cells (CSCs) have been reported to play important roles in multiple cancer types. This study investigated the correlation between cluster of differentiation 133 (CD133), histone deacetylase 1 (HDAC1) and thrombospondin-1 (THBS1) expression in advanced gastric cancer. The study included 65 patients with gastric cancer with recurrence after surgery. Expression of CD133, HDAC1 and THBS1 was examined by immunohistochemistry. Prognostic factors were investigated by multivariate analysis using Cox's proportional hazard model. Clinicopathological variables, including survival, of patients positive for CD133 expression (n=6, 23%), were compared with those without CD133 expression (n=20, 77%). Positive HDAC1 expression and THBS1 expression were observed in 34 (52%) and 17 (26%) patients, respectively. Using univariate analysis, positive expression of CD133 and negative expression of THBS1 predicted significantly worse prognosis. Multivariate analysis revealed CD133-positive and THBS1-negative expression were independent prognostic indicators. CD133 expression and THBS1 expression were prognostic factors, and a negative relationship between HDAC and THBS1 was observed in advanced gastric cancer. These biomarkers may help determine postoperative treatment in patients with gastric cancer.","Gastric cancer is one of the most common types of cancer. Cancer stem cells (CSCs) have been reported to play important roles in multiple cancer types. This study investigated the correlation between cluster of differentiation 133 (CD133), histone deacetylase 1 (HDAC1) and thrombospondin-1 (THBS1) expression in advanced gastric cancer. The study included 65 patients with gastric cancer with recurrence after surgery. Expression of CD133, HDAC1 and THBS1 was examined by immunohistochemistry. Prognostic factors were investigated by multivariate analysis using Cox's proportional hazard model. Clinicopathological variables, including survival, of patients positive for CD133 expression (n=6, 23%), were compared with those without CD133 expression (n=20, 77%). Positive HDAC1 expression and THBS1 expression were observed in 34 (52%) and 17 (26%) patients, respectively. Using univariate analysis, positive expression of CD133 and negative expression of THBS1 predicted significantly worse prognosis. Multivariate analysis revealed CD133-positive and THBS1-negative expression were independent prognostic indicators. CD133 expression and THBS1 expression were prognostic factors, and a negative relationship between HDAC and THBS1 was observed in advanced gastric cancer. These biomarkers may help determine postoperative treatment in patients with gastric cancer.","null","null","2015-04","Anticancer Research","Anticancer Research","Vol.35","No.4","2071","2076","eng","true","null","scientific_journal","null","null","null","1791-7530","null","null","null","null","null"
"Effective use of a vessel-sealing system for laparoscopic unroofing of liver cysts.","Effective use of a vessel-sealing system for laparoscopic unroofing of liver cysts.","Mami Kanamoto, Satoru Imura, Yuji Morine, Tohru Utsunomiya, Hiroki Mori, Yusuke Arakawa, Chie Takasu, Mitsuo Shimada","Mami Kanamoto, Satoru Imura, Yuji Morine, Tohru Utsunomiya, Hiroki Mori, Yusuke Arakawa, Chie Takasu, Mitsuo Shimada","null","Liver cysts that present with symptoms such as jaundice, abdominal pain, and intra-cystic infection require treatment. In laparoscopic unroofing of liver cysts, appropriate treatment is needed in cases where the cystic walls contain vessels or bile ducts. A vessel-sealing system can seal not only vessels, but also bile ducts. We experienced four cases in which laparoscopic unroofing of liver cysts was performed with a vessel-sealing system. Case 1 was a woman in her 70s who presented at our hospital with abdominal pressure. Abdominal CT showed liver cysts with a maximum diameter of 13 cm. Laparoscopic unroofing was performed with LigaSure Impact. Case 2 was a woman in her 50s with abdominal discomfort. CT showed a cyst 15 cm in diameter situated in the right lobe. We performed SILS using a LigaSure Blunt Tip to unroof the cyst. Case 3 was a man in his 80s with abdominal pain. CT showed a huge cyst 25 cm in diameter in the right lobe. We performed hybrid SILS with a LigaSure Blunt Tip to unroof the cysts. Case 4 was a woman in her 70s with upper abdominal pain. CT showed multiple cysts with a maximum diameter of 15 cm in the bilateral lobes. We performed hybrid SILS to successfully unroof her cysts. None of the cases experienced postoperative complications, such as bleeding or bile leakage, and none experienced recurrence of cysts. A laparoscopic unroofing using a vessel-sealing system can be a minimally invasive and safe treatment for liver cysts.","Liver cysts that present with symptoms such as jaundice, abdominal pain, and intra-cystic infection require treatment. In laparoscopic unroofing of liver cysts, appropriate treatment is needed in cases where the cystic walls contain vessels or bile ducts. A vessel-sealing system can seal not only vessels, but also bile ducts. We experienced four cases in which laparoscopic unroofing of liver cysts was performed with a vessel-sealing system. Case 1 was a woman in her 70s who presented at our hospital with abdominal pressure. Abdominal CT showed liver cysts with a maximum diameter of 13 cm. Laparoscopic unroofing was performed with LigaSure Impact. Case 2 was a woman in her 50s with abdominal discomfort. CT showed a cyst 15 cm in diameter situated in the right lobe. We performed SILS using a LigaSure Blunt Tip to unroof the cyst. Case 3 was a man in his 80s with abdominal pain. CT showed a huge cyst 25 cm in diameter in the right lobe. We performed hybrid SILS with a LigaSure Blunt Tip to unroof the cysts. Case 4 was a woman in her 70s with upper abdominal pain. CT showed multiple cysts with a maximum diameter of 15 cm in the bilateral lobes. We performed hybrid SILS to successfully unroof her cysts. None of the cases experienced postoperative complications, such as bleeding or bile leakage, and none experienced recurrence of cysts. A laparoscopic unroofing using a vessel-sealing system can be a minimally invasive and safe treatment for liver cysts.","null","null","2015-02","Asian Journal of Endoscopic Surgery","Asian Journal of Endoscopic Surgery","Vol.8","No.1","91","94","eng","true","null","scientific_journal","null","null","10.1111/ases.12134","1758-5910","null","null","null","null","null"
"Effect of TU-100, a traditional Japanese medicine, administered after hepatic resection in patients with liver cancer: a multi-center, phase III trial (JFMC40-1001).","Effect of TU-100, a traditional Japanese medicine, administered after hepatic resection in patients with liver cancer: a multi-center, phase III trial (JFMC40-1001).","Mitsuo Shimada, Yuji Morine, Hiroaki Nagano, Etsuro Hatano, Takashi Kaiho, Masaru Miyazaki, Toru Kono, Toshiya Kamiyama, Satoshi Morita, Junichi Sakamoto, Mitsuo Kusano, Shigetoyo Saji, Takashi Kanematsu, Masaki Kitajima","Mitsuo Shimada, Yuji Morine, Hiroaki Nagano, Etsuro Hatano, Takashi Kaiho, Masaru Miyazaki, Toru Kono, Toshiya Kamiyama, Satoshi Morita, Junichi Sakamoto, Mitsuo Kusano, Shigetoyo Saji, Takashi Kanematsu, Masaki Kitajima","null","This multi-center, phase III trial assesses the efficacy of daikenchuto (TU-100) on gastrointestinal disorders after hepatic resection (UMIN Registration No. 000003103). A total of 231 patients, who underwent hepatic resection at 26 Japanese centers, were enrolled. Patients were randomly assigned to receive either oral doses (15 g/day, three times a day) of TU-100 or placebo control from preoperative day 3 to postoperative day 10, except on the day of surgery. Primary end points were the time from extubation until the first postoperative bowel movement (FBM-T), serum C-reactive protein (CRP) and ammonia levels. Finally, 209 patients (TU-100: n = 108, placebo: n = 101) were included in the statistical analysis. The median FBM-T was 88.2 h (95 % CI 74.0-94.1) in the TU-100 group and 93.1 h (95 % CI 83.3-99.4) in the placebo group, demonstrating that TU-100 accelerated the time to first bowel movement significantly more than placebo control. Serum CRP levels did not differ significantly during the study period, although serum CRP levels in the TU-100 group tended to be lower than those in the placebo group in patients with grade B liver damage. Meanwhile, the two groups had similar serum ammonia levels. TU-100-related serious adverse events did not occur during the study. TU-100 appears to improve gastrointestinal dysmotility and reduce serum CRP levels in patients with grade B liver damage after hepatectomy. TU-100 is an effective treatment option after hepatic resection in patients with liver cancer.","This multi-center, phase III trial assesses the efficacy of daikenchuto (TU-100) on gastrointestinal disorders after hepatic resection (UMIN Registration No. 000003103). A total of 231 patients, who underwent hepatic resection at 26 Japanese centers, were enrolled. Patients were randomly assigned to receive either oral doses (15 g/day, three times a day) of TU-100 or placebo control from preoperative day 3 to postoperative day 10, except on the day of surgery. Primary end points were the time from extubation until the first postoperative bowel movement (FBM-T), serum C-reactive protein (CRP) and ammonia levels. Finally, 209 patients (TU-100: n = 108, placebo: n = 101) were included in the statistical analysis. The median FBM-T was 88.2 h (95 % CI 74.0-94.1) in the TU-100 group and 93.1 h (95 % CI 83.3-99.4) in the placebo group, demonstrating that TU-100 accelerated the time to first bowel movement significantly more than placebo control. Serum CRP levels did not differ significantly during the study period, although serum CRP levels in the TU-100 group tended to be lower than those in the placebo group in patients with grade B liver damage. Meanwhile, the two groups had similar serum ammonia levels. TU-100-related serious adverse events did not occur during the study. TU-100 appears to improve gastrointestinal dysmotility and reduce serum CRP levels in patients with grade B liver damage after hepatectomy. TU-100 is an effective treatment option after hepatic resection in patients with liver cancer.","null","null","2015-02","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.20","No.1","95","104","eng","true","null","scientific_journal","null","null","10.1007/s10147-014-0678-2","1437-7772","null","null","null","null","null"
"Duodenal-jejunal bypass improves diabetes and liver steatosis via enhanced glucagon-like peptide-1 elicited by bile acids.","Duodenal-jejunal bypass improves diabetes and liver steatosis via enhanced glucagon-like peptide-1 elicited by bile acids.","Hideya Kashihara, Mitsuo Shimada, Nobuhiro Kurita, Hirohiko Sato, Kouzou Yoshikawa, Jun Higashijima, Motoya Chikakiyo, Masaaki Nishi, Chie Takasu","Hideya Kashihara, Mitsuo Shimada, Nobuhiro Kurita, Hirohiko Sato, Kouzou Yoshikawa, Jun Higashijima, Motoya Chikakiyo, Masaaki Nishi, Chie Takasu","null","Bariatric surgery not only elicits weight loss but also rapidly resolves diabetes. However, the mechanisms remain unclear. The present study investigates how diabetes and liver steatosis are improved after duodenal-jejunal bypass (DJB) compared with a glucagon-like peptide-1 (GLP-1) analog and correlations between bile acids and GLP-1 secretion. We initially determined the effects of bile acids on GLP-1 in vitro and then assigned 12 male 16-week-old Otsuka Long-Evans Tokushima Fatty rats to groups that underwent DJB, a sham operation, or were treated with the GLP-1 receptor agonist, liraglutide (n = 4 each). Blood glucose, insulin, GLP-1, serum bile acids, liver steatosis, and the number of GLP-1 positive cells (L cells) in the small intestine and colon were investigated in the three groups at eight weeks postoperatively. Levels of GLP-1mRNA were upregulated and GLP-1 secretion increased in cells incubated with bile acids in vitro. Weight gain was suppressed more in the DJB than in the sham group in vivo. Diabetes was more improved and GLP-1 levels were significantly higher in the DJB than in the sham group. Serum bile acids were significantly increased, the number of L cells in the ileum was upregulated compared with the sham group, and liver steatosis was significantly improved in the DJB compared with the other two groups. Duodenal-jejunal bypass might improve diabetes and liver steatosis by enhancing GLP-1 secretion through increasing serum bile acids and the proliferation of L cells in the ileum, compared with liraglutide.","Bariatric surgery not only elicits weight loss but also rapidly resolves diabetes. However, the mechanisms remain unclear. The present study investigates how diabetes and liver steatosis are improved after duodenal-jejunal bypass (DJB) compared with a glucagon-like peptide-1 (GLP-1) analog and correlations between bile acids and GLP-1 secretion. We initially determined the effects of bile acids on GLP-1 in vitro and then assigned 12 male 16-week-old Otsuka Long-Evans Tokushima Fatty rats to groups that underwent DJB, a sham operation, or were treated with the GLP-1 receptor agonist, liraglutide (n = 4 each). Blood glucose, insulin, GLP-1, serum bile acids, liver steatosis, and the number of GLP-1 positive cells (L cells) in the small intestine and colon were investigated in the three groups at eight weeks postoperatively. Levels of GLP-1mRNA were upregulated and GLP-1 secretion increased in cells incubated with bile acids in vitro. Weight gain was suppressed more in the DJB than in the sham group in vivo. Diabetes was more improved and GLP-1 levels were significantly higher in the DJB than in the sham group. Serum bile acids were significantly increased, the number of L cells in the ileum was upregulated compared with the sham group, and liver steatosis was significantly improved in the DJB compared with the other two groups. Duodenal-jejunal bypass might improve diabetes and liver steatosis by enhancing GLP-1 secretion through increasing serum bile acids and the proliferation of L cells in the ileum, compared with liraglutide.","null","null","2015-02","Journal of Gastroenterology and Hepatology","Journal of Gastroenterology and Hepatology","Vol.30","No.2","308","315","eng","true","null","scientific_journal","null","null","10.1111/jgh.12690","1440-1746","null","null","null","null","null"
"Impact of newly developed, next-generation artificial endocrine pancreas","Impact of newly developed, next-generation artificial endocrine pancreas","Noriko Kambe, Shinji Kawahito, Naoji Mita, Kazumi Takaishi, Tosiko Katayama, Yoko Sakai, Tomohiro Soga, Hiroaki Kawano, Munehide Matsuhisa, Mitsuo Shimada, Tetsuya Kitagawa, Hiroshi Kitahata","Noriko Kambe, Shinji Kawahito, Naoji Mita, Kazumi Takaishi, Tosiko Katayama, Yoko Sakai, Tomohiro Soga, Hiroaki Kawano, Munehide Matsuhisa, Mitsuo Shimada, Tetsuya Kitagawa, Hiroshi Kitahata","null","Recent studies have shown that strict perioperative blood glucose management may reduce mortality and morbidity in critically ill adult patients. The purpose of this study was to assess the accuracy and efficacy of the intraoperative application of a newly developed, next-generation artificial endocrine pancreas (STG-55, Nikkiso Co., Ltd., Tokyo, Japan). Twenty patients scheduled to undergo surgery were enrolled in this study. The STG-55 is designed to be more user-friendly than its conventional counterpart (STG-22) while maintaining the latter's fundamental functions, such as a closed-loop system using algorithms for insulin and glucose infusion. After anesthetic induction, a 20G intravenous catheter was inserted into a peripheral forearm vein and connected to a continuous blood glucose monitor. The resultant 105 scores for paired blood glucose values were compared by Bland-Altman analysis. Stable blood glucose values were maintained automatically, and there were no complications related to use of the STG-55. A close correlation (r=0.96) was observed between continuous glucose measurements using the STG-55 and conventional intermittent glucose measurements. The difficulty of manipulation using this system was decreased by improved preparation procedures. The glycemic control system using the STG-55 could provide an alternative way to achieve effective and safe perioperative glycemic control.","Recent studies have shown that strict perioperative blood glucose management may reduce mortality and morbidity in critically ill adult patients. The purpose of this study was to assess the accuracy and efficacy of the intraoperative application of a newly developed, next-generation artificial endocrine pancreas (STG-55, Nikkiso Co., Ltd., Tokyo, Japan). Twenty patients scheduled to undergo surgery were enrolled in this study. The STG-55 is designed to be more user-friendly than its conventional counterpart (STG-22) while maintaining the latter's fundamental functions, such as a closed-loop system using algorithms for insulin and glucose infusion. After anesthetic induction, a 20G intravenous catheter was inserted into a peripheral forearm vein and connected to a continuous blood glucose monitor. The resultant 105 scores for paired blood glucose values were compared by Bland-Altman analysis. Stable blood glucose values were maintained automatically, and there were no complications related to use of the STG-55. A close correlation (r=0.96) was observed between continuous glucose measurements using the STG-55 and conventional intermittent glucose measurements. The difficulty of manipulation using this system was decreased by improved preparation procedures. The glycemic control system using the STG-55 could provide an alternative way to achieve effective and safe perioperative glycemic control.","null","null","2015-02","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.62","No.1-2","41","44","eng","true","null","scientific_journal","null","null","10.2152/jmi.62.41","1349-6867","null","null","null","null","null"
"再発抑制のための抗ウイルス療法","再発抑制のための抗ウイルス療法","荒川 悠佑, 島田 光生","Yusuke Arakawa, Mitsuo Shimada","null","null","null","null","null","2015-01","Pharma Medica","Pharma Medica","Vol.33","No.1","59","62","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"Dysfunction of liver regeneration in aged liver after partial hepatectomy.","Dysfunction of liver regeneration in aged liver after partial hepatectomy.","Chinbold Enkhbold, Yuji Morine, Tohru Utsunomiya, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Yu Saitou, Shinichiro Yamada, Daichi Ishikawa, Mitsuo Shimada","Chinbold Enkhbold, Yuji Morine, Tohru Utsunomiya, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Yu Saitou, Shinichiro Yamada, Daichi Ishikawa, Mitsuo Shimada","null","A remarkable feature of the liver is its regenerative capacity following partial hepatectomy. However, the regenerative capacity of many organs and tissues loses its natural ability to divide with aging. In this study, we investigated the association of aging with endoplasmic reticulum stress, the cell cycle, autophagy, and apoptosis-related genes during liver regeneration after hepatectomy. Balb/c 4-week and 40-week-old male mice were subjected to 70% hepatectomy. Animals were sacrificed at 24, 48, and 72 h after hepatectomy. Immunohistochemical stainings for proliferating cell nuclear antigen, LC3, Atg5, and caspase-3 were used to quantify protein expression. Real-time reverse transcription-polymerase chain reaction was used to detect p16, CHOP, LC3, Atg5, hepatocyte growth factor, cMet, cyclin D1, cyclin A2, and caspase-3 expression. After hepatectomy, old group showed a lower survival rate and significantly lower expression of hepatocyte growth factor, cMet, cyclin D1, cyclin A2, proliferating cell nuclear antigen labeling index, and SMP30 compared with young group. The liver weight/body weight ratio was significantly lower at 48 h and 72 h after hepatectomy and was accompanied by markedly elevated levels of the liver cell injury markers, LC3 and caspase-3. Immunohistochemical results showed that LC3, Atg5, and caspase-3 protein expression were higher in old group than in young group. These results revealed that impaired liver regeneration was due to aging, which was expressed by decreased cell cycle and increased autophagy and apoptosis. Therefore, understanding the molecular basis for aged liver regeneration might provide a new therapeutic option for old patients.","A remarkable feature of the liver is its regenerative capacity following partial hepatectomy. However, the regenerative capacity of many organs and tissues loses its natural ability to divide with aging. In this study, we investigated the association of aging with endoplasmic reticulum stress, the cell cycle, autophagy, and apoptosis-related genes during liver regeneration after hepatectomy. Balb/c 4-week and 40-week-old male mice were subjected to 70% hepatectomy. Animals were sacrificed at 24, 48, and 72 h after hepatectomy. Immunohistochemical stainings for proliferating cell nuclear antigen, LC3, Atg5, and caspase-3 were used to quantify protein expression. Real-time reverse transcription-polymerase chain reaction was used to detect p16, CHOP, LC3, Atg5, hepatocyte growth factor, cMet, cyclin D1, cyclin A2, and caspase-3 expression. After hepatectomy, old group showed a lower survival rate and significantly lower expression of hepatocyte growth factor, cMet, cyclin D1, cyclin A2, proliferating cell nuclear antigen labeling index, and SMP30 compared with young group. The liver weight/body weight ratio was significantly lower at 48 h and 72 h after hepatectomy and was accompanied by markedly elevated levels of the liver cell injury markers, LC3 and caspase-3. Immunohistochemical results showed that LC3, Atg5, and caspase-3 protein expression were higher in old group than in young group. These results revealed that impaired liver regeneration was due to aging, which was expressed by decreased cell cycle and increased autophagy and apoptosis. Therefore, understanding the molecular basis for aged liver regeneration might provide a new therapeutic option for old patients.","null","null","2015-01","Journal of Gastroenterology and Hepatology","Journal of Gastroenterology and Hepatology","Vol.30","No.7","1217","1224","eng","true","null","scientific_journal","null","null","10.1111/jgh.12930","1440-1746","null","null","null","null","null"
"Clinical role of Notch signaling pathway in intraductal papillary mucinous neoplasm of the pancreas.","Clinical role of Notch signaling pathway in intraductal papillary mucinous neoplasm of the pancreas.","Tetsuya Ikemoto, Koji Sugimoto, Mitsuo Shimada, Tohru Utsunomiya, Yuji Morine, Satoru Imura, Yusuke Arakawa, Mami Kanamoto, Shuichi Iwahashi, Yu Saitou, Shinichiro Yamada","Tetsuya Ikemoto, Koji Sugimoto, Mitsuo Shimada, Tohru Utsunomiya, Yuji Morine, Satoru Imura, Yusuke Arakawa, Mami Kanamoto, Shuichi Iwahashi, Yu Saitou, Shinichiro Yamada","null","This study was performed to elucidate the expression of the Notch signaling pathway and its correlations to clinicopathological factors of intraductal papillary mucinous neoplasms (IPMNs). It is incontrovertible that regulatory T cells (Tregs) play an important role in tumor immunity. However, the whole mechanism of control of peripheral Tregs remains unclear. It is also known that the Notch signaling pathway is involved in Treg suppressor function. Moreover, IPMNs have a high malignant potential. Peripheral blood samples and resected specimens from 18 patients with IPMN were evaluated. All patients were pathologically diagnosed with IPMN. Resected specimens were immunohistochemically evaluated (anti-Notch1, anti-Notch2, and anti-Notch2-intracellular domain antibody staining) and compared in terms of clinicopathological factors. Peripheral Treg populations were analyzed with an automated flow cytometer. Disease-free survival was significantly worse in the Notch1 high-expression group (P = 0.023). Notch2 family expressions were higher in intraductal papillary mucinous carcinoma (IPMC) than in intraductal papillary mucinous adenoma (IPMA) (Notch2, P = 0.012; Notch2-intracellular domain, P = 0.036). Jagged1 expression was significantly higher in IPMC than in IPMA (P < 0.05) and was significantly related to recurrence. The Treg population in peripheral blood was higher in patients with IPMC than in those with IPMA (P < 0.01). Notch signaling, especially Jagged1 expression, reflects IPMN aggressiveness. Our data may suggest that the Notch signaling pathway is a key pathway that determines IPMN pathological aggressiveness and reflects the peripheral Treg population.","This study was performed to elucidate the expression of the Notch signaling pathway and its correlations to clinicopathological factors of intraductal papillary mucinous neoplasms (IPMNs). It is incontrovertible that regulatory T cells (Tregs) play an important role in tumor immunity. However, the whole mechanism of control of peripheral Tregs remains unclear. It is also known that the Notch signaling pathway is involved in Treg suppressor function. Moreover, IPMNs have a high malignant potential. Peripheral blood samples and resected specimens from 18 patients with IPMN were evaluated. All patients were pathologically diagnosed with IPMN. Resected specimens were immunohistochemically evaluated (anti-Notch1, anti-Notch2, and anti-Notch2-intracellular domain antibody staining) and compared in terms of clinicopathological factors. Peripheral Treg populations were analyzed with an automated flow cytometer. Disease-free survival was significantly worse in the Notch1 high-expression group (P = 0.023). Notch2 family expressions were higher in intraductal papillary mucinous carcinoma (IPMC) than in intraductal papillary mucinous adenoma (IPMA) (Notch2, P = 0.012; Notch2-intracellular domain, P = 0.036). Jagged1 expression was significantly higher in IPMC than in IPMA (P < 0.05) and was significantly related to recurrence. The Treg population in peripheral blood was higher in patients with IPMC than in those with IPMA (P < 0.01). Notch signaling, especially Jagged1 expression, reflects IPMN aggressiveness. Our data may suggest that the Notch signaling pathway is a key pathway that determines IPMN pathological aggressiveness and reflects the peripheral Treg population.","null","null","2015-01","Journal of Gastroenterology and Hepatology","Journal of Gastroenterology and Hepatology","Vol.30","No.1","217","222","eng","true","null","scientific_journal","null","null","10.1111/jgh.12660","1440-1746","null","null","null","null","null"
"Recovery of nutritional metabolism after liver transplantation","Recovery of nutritional metabolism after liver transplantation","Kohei Sugihara, Hisami Okumura, Arisa Teramoto, Eri Urano, Takafumi Katayama, Yuji Morine, Satoru Imura, Tohru Utsunomiya, Mitsuo Shimada, Eiji Takeda","Kohei Sugihara, Hisami Okumura, Arisa Teramoto, Eri Urano, Takafumi Katayama, Yuji Morine, Satoru Imura, Tohru Utsunomiya, Mitsuo Shimada, Eiji Takeda","null","Perioperative nutritional assessment is critically important to reflect nutritional management because liver transplantation (LTx) often is undertaken in patients with poor nutritional status. The aim of this study was to evaluate nutritional status, including the non-protein respiratory quotient (npRQ), resting energy expenditure (REE), nitrogen balance, and blood biochemical parameters in patients before and after LTx. Fourteen patients undergoing LTx and 10 healthy controls were enrolled in this study. The npRQ and REE were measured using indirect calorimetry before LTx and at 2, 3, and 4 wk after the procedure. Blood biochemistry and nitrogen balance calculated by 24-h urine collection were performed concurrently with indirect calorimetric measurement; the results were compared between the two groups. Before LTx, npRQ was significantly lower and serum non-esterified fatty acid levels were significantly higher in the patients than in the controls. Furthermore, a negative nitrogen balance was observed in the patients. These, however, improved significantly at 4 wk after LTx. REE did not significantly increase compared with the preoperative values in recipients. Blood biochemistry showed gradually increasing levels of serum cholinesterase and albumin. These failed to reach to normal levels by 4 wk post-transplant. The findings revealed that improvement of nutritional metabolism after LTx may require 4 wk. Additional nutritional strategies, therefore, may be needed to minimize catabolic state during the early post-transplant period. Adequate, individualized nutritional guidance before and after LTx should be performed in these patients.","Perioperative nutritional assessment is critically important to reflect nutritional management because liver transplantation (LTx) often is undertaken in patients with poor nutritional status. The aim of this study was to evaluate nutritional status, including the non-protein respiratory quotient (npRQ), resting energy expenditure (REE), nitrogen balance, and blood biochemical parameters in patients before and after LTx. Fourteen patients undergoing LTx and 10 healthy controls were enrolled in this study. The npRQ and REE were measured using indirect calorimetry before LTx and at 2, 3, and 4 wk after the procedure. Blood biochemistry and nitrogen balance calculated by 24-h urine collection were performed concurrently with indirect calorimetric measurement; the results were compared between the two groups. Before LTx, npRQ was significantly lower and serum non-esterified fatty acid levels were significantly higher in the patients than in the controls. Furthermore, a negative nitrogen balance was observed in the patients. These, however, improved significantly at 4 wk after LTx. REE did not significantly increase compared with the preoperative values in recipients. Blood biochemistry showed gradually increasing levels of serum cholinesterase and albumin. These failed to reach to normal levels by 4 wk post-transplant. The findings revealed that improvement of nutritional metabolism after LTx may require 4 wk. Additional nutritional strategies, therefore, may be needed to minimize catabolic state during the early post-transplant period. Adequate, individualized nutritional guidance before and after LTx should be performed in these patients.","null","null","2015-01","Nutrition","Nutrition","Vol.31","No.1","105","110","eng","true","null","scientific_journal","null","null","10.1016/j.nut.2014.05.016","1873-1244","null","null","null","null","null"
"膵癌・胆道癌 ─基礎・臨床の最新研究動向─","膵癌・胆道癌 ─基礎・臨床の最新研究動向─","山田 眞一郎, 島田 光生, 森根 裕二","Shin-ichiro Yamada, Mitsuo Shimada, Yuji Morine","null","null","null","null","null","2015","日本臨牀","Nihon Rinsho. Japanese Journal of Clinical Medicine","null","null","618","621","jpn","true","null","scientific_journal","null","null","null","0047-1852","null","null","null","null","null"
"外科の立場からのキャリアアップ支援","外科の立場からのキャリアアップ支援","髙須 千絵, 金本 真美, 松本 規子, 岩田 貴, 吉川 幸造, 東島 潤, 中尾 寿宏, 西 正暁, 江藤 祥平, 島田 光生","Chie Takasu, Mami Kanamoto, 松本 規子, Takashi Iwata, Kouzou Yoshikawa, Jun Higashijima, Toshihiro Nakao, Masaaki Nishi, 江藤 祥平, Mitsuo Shimada","null","null","null","null","null","2015","日本外科系連合学会誌","Journal of Japanese College of Surgeons","Vol.40","No.2","170","173","jpn","true","null","scientific_journal","null","null","10.4030/jjcs.40.170","1882-9112","null","null","null","null","null"
"New ports placement in laparoscopic central lymph nodes dissection with left colic artery preservation for sigmoid colon and rectal cancer.","New ports placement in laparoscopic central lymph nodes dissection with left colic artery preservation for sigmoid colon and rectal cancer.","Jun Higashijima, Mitsuo Shimada, Takashi Iwata, Kouzou Yoshikawa, Toshihiro Nakao, Masaaki Nishi, Hideya Kashihara, Chie Takasu","Jun Higashijima, Mitsuo Shimada, Takashi Iwata, Kouzou Yoshikawa, Toshihiro Nakao, Masaaki Nishi, Hideya Kashihara, Chie Takasu","null","Lymph nodes (LNs) dissection around inferior mesenteric artery (IMA) with left colic artery (LCA) preservation is difficult due to the anatomical feature of IMA. The aim of this study is to evaluate the usefulness of new ports placement inserted from a suprapubic region in laparoscopic LNs dissection around IMA with LCA preservation for sigmoid colon and ractal cancer. Twenty-two patients who underwent laparoscopic colectomy for sigmoid colon and recal cancer were included. The new ports placement group (n=15, new group) was compared with the basic ports placement group (n=7, basic group). Average number of harvested LNs, total operation time, central LNs dissection time, intraoperative blood loss were compared. There was no significant difference in the average number of harvested LNs. The mean of intraoperative blood loss of new group was significantly lower than that of the basic group (40.0±39.8 ml vs 95.7±81.0 ml, p<0.05). In addition, the mean of operation time of the new group was significantly shorter than that of the basic group (250.0±55.7 min vs 353.4±80.2 min, p<0.05). The new ports placement is useful in laparoscopic LNs dissection around IMA with LCA preservation for sigmoid colon and rectal cancer.","Lymph nodes (LNs) dissection around inferior mesenteric artery (IMA) with left colic artery (LCA) preservation is difficult due to the anatomical feature of IMA. The aim of this study is to evaluate the usefulness of new ports placement inserted from a suprapubic region in laparoscopic LNs dissection around IMA with LCA preservation for sigmoid colon and ractal cancer. Twenty-two patients who underwent laparoscopic colectomy for sigmoid colon and recal cancer were included. The new ports placement group (n=15, new group) was compared with the basic ports placement group (n=7, basic group). Average number of harvested LNs, total operation time, central LNs dissection time, intraoperative blood loss were compared. There was no significant difference in the average number of harvested LNs. The mean of intraoperative blood loss of new group was significantly lower than that of the basic group (40.0±39.8 ml vs 95.7±81.0 ml, p<0.05). In addition, the mean of operation time of the new group was significantly shorter than that of the basic group (250.0±55.7 min vs 353.4±80.2 min, p<0.05). The new ports placement is useful in laparoscopic LNs dissection around IMA with LCA preservation for sigmoid colon and rectal cancer.","null","null","2015","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.62","No.3-4","223","227","eng","true","null","scientific_journal","null","null","10.2152/jmi.62.223","1349-6867","null","null","null","null","null"
"Clinical role of Foxp3+ regulatory T cell in Living donor related liver transplantation for prediction of life-threatening complications.","Clinical role of Foxp3+ regulatory T cell in Living donor related liver transplantation for prediction of life-threatening complications.","Michihito Asanoma, Hiroki Mori, Tetsuya Ikemoto, Toru Utsunomiya, Satoru Imura, Yuji Morine, Jun Hanaoka, Mami Kanamoto, Yu Saitou, Shinichiro Yamada, Mitsuo Shimada","Michihito Asanoma, Hiroki Mori, Tetsuya Ikemoto, Toru Utsunomiya, Satoru Imura, Yuji Morine, Jun Hanaoka, Mami Kanamoto, Yu Saitou, Shinichiro Yamada, Mitsuo Shimada","null","It is no doubt that regulatory T cells (Foxp3(+)CD4(+)CD25(+)T cells: Treg) play important roles in transplant immunity. We investigated the significance of Treg expression in acute stage of living donorrelated liver transplantation (LDLT) for the possibility of the sensitive marker for immunological state and homeostatic stress after liver transplantation. Peripheral blood was drawn from 5 recipients of LDLT preoperatively and on post operative 1, 4, 7, and 14 days. The peripheral blood mononuclear cells (PBMCs) were stained with CD4, CD25, Foxp3, and were analyzed with FACScan. This data was compared with clinical output of LDLT. The populations of Treg were significantly decreased in all patients on day 1 after LDLT and significantly increased in patients who had early postoperative complications compared with patients who had no complications. The population of Treg in peripheral blood may reflect the surgical stress such as life-threatening complications after LDLT.","It is no doubt that regulatory T cells (Foxp3(+)CD4(+)CD25(+)T cells: Treg) play important roles in transplant immunity. We investigated the significance of Treg expression in acute stage of living donorrelated liver transplantation (LDLT) for the possibility of the sensitive marker for immunological state and homeostatic stress after liver transplantation. Peripheral blood was drawn from 5 recipients of LDLT preoperatively and on post operative 1, 4, 7, and 14 days. The peripheral blood mononuclear cells (PBMCs) were stained with CD4, CD25, Foxp3, and were analyzed with FACScan. This data was compared with clinical output of LDLT. The populations of Treg were significantly decreased in all patients on day 1 after LDLT and significantly increased in patients who had early postoperative complications compared with patients who had no complications. The population of Treg in peripheral blood may reflect the surgical stress such as life-threatening complications after LDLT.","null","null","2015","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.62","No.1-2","37","40","eng","true","null","scientific_journal","null","null","10.2152/jmi.62.37","1349-6867","null","null","null","null","null"
"Usefulness of artificial endocrine pancreas during resection of insulinoma.","Usefulness of artificial endocrine pancreas during resection of insulinoma.","Kayo Hirose, Shinji Kawahito, Naoji Mita, Kazumi Takaishi, Tomiya Kawahara, Tomohiro Soga, Toshiko Katayama, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Mitsuo Shimada, Munehide Matsuhisa, Hiroshi Kitahata","Kayo Hirose, Shinji Kawahito, Naoji Mita, Kazumi Takaishi, Tomiya Kawahara, Tomohiro Soga, Toshiko Katayama, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Mitsuo Shimada, Munehide Matsuhisa, Hiroshi Kitahata","null","A 71-year-old woman had an episode of syncope due to hypoglycemia of 27 mg/dl. She was diagnosed with insulinoma and scheduled for laparoscopic enucleation along with the use of an artificial endocrine pancreas (STG-22, Nikkiso Co., Ltd., Tokyo, Japan). Anesthesia was maintained with sevoflurane and remifentanil. Her blood glucose level was controlled using the artificial endocrine pancreas, which enabled continuous blood glucose monitoring and computer-operated glucose and insulin infusion to maintain the blood glucose level at a steady state. The target concentration of blood glucose was set at 80-120 mg/dl during surgery. Until removal of the tumor, the blood glucose level was kept at around 80-100 mg/dl. After removal of the tumor, the blood glucose level gradually increased, but it was kept in the normal range by the artificial endocrine pancreas. The artificial endocrine pancreas was useful to monitor and maintain blood glucose levels during and after the removal of insulinoma, without any hyper- or hypoglycemia. J. Med. Invest. 61: 421-425, August, 2014.","A 71-year-old woman had an episode of syncope due to hypoglycemia of 27 mg/dl. She was diagnosed with insulinoma and scheduled for laparoscopic enucleation along with the use of an artificial endocrine pancreas (STG-22, Nikkiso Co., Ltd., Tokyo, Japan). Anesthesia was maintained with sevoflurane and remifentanil. Her blood glucose level was controlled using the artificial endocrine pancreas, which enabled continuous blood glucose monitoring and computer-operated glucose and insulin infusion to maintain the blood glucose level at a steady state. The target concentration of blood glucose was set at 80-120 mg/dl during surgery. Until removal of the tumor, the blood glucose level was kept at around 80-100 mg/dl. After removal of the tumor, the blood glucose level gradually increased, but it was kept in the normal range by the artificial endocrine pancreas. The artificial endocrine pancreas was useful to monitor and maintain blood glucose levels during and after the removal of insulinoma, without any hyper- or hypoglycemia. J. Med. Invest. 61: 421-425, August, 2014.","null","null","2014-08","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.61","No.3-4","421","425","eng","true","null","scientific_journal","null","null","10.2152/jmi.61.421","1349-6867","null","null","null","null","null"
"Hypomethylation of Long Interspersed Nuclear Element-1 (LINE-1) is Associated with Poor Prognosis via Activation of c-MET in Hepatocellular Carcinoma.","Hypomethylation of Long Interspersed Nuclear Element-1 (LINE-1) is Associated with Poor Prognosis via Activation of c-MET in Hepatocellular Carcinoma.","Chengzhan Zhu, Tohru Utsunomiya, Tetsuya Ikemoto, Shinichiro Yamada, Yuji Morine, Satoru Imura, Yusuke Arakawa, Chie Takasu, Daichi Ishikawa, Issei Imoto, Mitsuo Shimada","Chengzhan Zhu, Tohru Utsunomiya, Tetsuya Ikemoto, Shinichiro Yamada, Yuji Morine, Satoru Imura, Yusuke Arakawa, Chie Takasu, Daichi Ishikawa, Issei Imoto, Mitsuo Shimada","null","LINE-1 was significantly hypomethylated in tumor tissues compared with nontumor tissues (48.3 ± 12.2 % vs. 68.2 ± 2.0 %, respectively, p < 0.0001). LINE-1 hypomethylation was not associated with any clinicopathological factors in HCC patients, except sex (p < 0.05). However, patients with LINE-1 hypomethylation exhibited significantly poorer outcome, and multivariate analysis revealed that LINE-1 hypomethylation was an independent risk factor for overall survival (hazard ratio (HR) = 6.1, p = 0.031) and disease-free survival (HR = 2.34, p = 0.045). L1-MET expression was significantly higher in tumor tissues (p <0.01). L1-MET expression levels were inversely correlated with LINE-1 methylation levels, and positively correlated with c-MET expression (p < 0.05). Furthermore, higher c-MET protein expression was observed in the LINE-1 hypomethylated tumor tissues compared with hypermethylated tumor tissues (p = 0.032).","LINE-1 hypomethylation is significantly associated with poor prognosis in patients with HCC, possibly due to activation of c-MET expression.","null","null","2014-07-04","Annals of Surgical Oncology","Annals of Surgical Oncology","Vol.21","No.4","729","735","eng","true","null","scientific_journal","null","null","10.1245/s10434-014-3874-4","1534-4681","null","null","null","null","null"
"Recovery pattern of non-protein respiratory quotient and non-esterified fatty acid after liver resection","Recovery pattern of non-protein respiratory quotient and non-esterified fatty acid after liver resection","KKohei Sugihara, Hisami Okumura, Arisa Teramoto, Eri Urano, Takafumi Katayama, Hiroki Mori, Toru Utsunomiya, Mitsuo Shimada, Eiji Takeda","KKohei Sugihara, Hisami Okumura, Arisa Teramoto, Eri Urano, Takafumi Katayama, Hiroki Mori, Toru Utsunomiya, Mitsuo Shimada, Eiji Takeda","null","Perioperative nutritional care is important to maintain preoperative and postoperative nutritional status. However, few reports have investigated energy metabolism after hepatectomy. The aim of this study was to determine differences in energy metabolism, blood biochemistry, and nutritional status before and after liver resection in patients with hepatocellular carcinoma (HCC) and healthy living donors for liver transplantation. Eighteen hospitalized patients with HCC group and 13 living donors for liver transplantation (donor group) were enrolled in this study. The donor group was divided into two groups on the basis of age; Y-donor group (age < 40 y, n = 7), and O-donor group (age ≥ 40 y, n = 6). Energy metabolism was measured by indirect calorimetry at preoperative day and postoperative day (POD) 7 and 14, and blood biochemistry was also examined. Recovery of non-protein respiratory quotient (npRQ) and blood biochemical data such as total bilirubin, aspartate aminotransferase and alanine aminotransferase levels were observed in Y-donor group on POD 14. However, although biochemical data improved in the HCC and O-donor group, npRQ remained unchanged on POD 14. Improvement of npRQ took longer than blood biochemical data in patients with HCC and older donors. Because the recovery of npRQ is associated with donor age, careful nutritional management may be required for a longer time depending on the pathophysiological condition of each patient after hepatectomy.","Perioperative nutritional care is important to maintain preoperative and postoperative nutritional status. However, few reports have investigated energy metabolism after hepatectomy. The aim of this study was to determine differences in energy metabolism, blood biochemistry, and nutritional status before and after liver resection in patients with hepatocellular carcinoma (HCC) and healthy living donors for liver transplantation. Eighteen hospitalized patients with HCC group and 13 living donors for liver transplantation (donor group) were enrolled in this study. The donor group was divided into two groups on the basis of age; Y-donor group (age < 40 y, n = 7), and O-donor group (age ≥ 40 y, n = 6). Energy metabolism was measured by indirect calorimetry at preoperative day and postoperative day (POD) 7 and 14, and blood biochemistry was also examined. Recovery of non-protein respiratory quotient (npRQ) and blood biochemical data such as total bilirubin, aspartate aminotransferase and alanine aminotransferase levels were observed in Y-donor group on POD 14. However, although biochemical data improved in the HCC and O-donor group, npRQ remained unchanged on POD 14. Improvement of npRQ took longer than blood biochemical data in patients with HCC and older donors. Because the recovery of npRQ is associated with donor age, careful nutritional management may be required for a longer time depending on the pathophysiological condition of each patient after hepatectomy.","null","null","2014-04","Nutrition","Nutrition","Vol.30","No.4","443","448","eng","true","null","scientific_journal","null","null","10.1016/j.nut.2013.09.012","1873-1244","null","null","null","null","null"
"Abrogation of Rbpj attenuates experimental autoimmune uveoretinitis by inhibiting IL-22-producing CD4+ T cells.","Abrogation of Rbpj attenuates experimental autoimmune uveoretinitis by inhibiting IL-22-producing CD4+ T cells.","Ahmed Zaied Bhuyan, Michihito Asanoma, Akiko Iwata, Chieko Ishifune, Yoichi Maekawa, Mitsuo Shimada, Koji Yasutomo","Ahmed Zaied Bhuyan, Michihito Asanoma, Akiko Iwata, Chieko Ishifune, Yoichi Maekawa, Mitsuo Shimada, Koji Yasutomo","null","Experimental autoimmune uveoretinitis (EAU) is an organ-specific T cell-mediated disease induced by immunizing mice with interphotoreceptor retinoid binding protein (IRBP). Autoaggressive CD4(+) T cells are the major pathogenic population for EAU. We investigated the contribution of Notch signaling in T cells to EAU pathogenesis because Notch signaling regulates various aspects of CD4(+) T cell functions. Rbpj is required for Notch signaling, and Rbpj deficiency in T cells inhibited EAU disease severity. The amelioration of EAU in T cell-specific Rbpj-deficient mice correlated with low levels of IL-22 production from CD4(+) T cells, although IRBP-specific CD4(+) T cell proliferation and Th17 differentiation were unaffected. Administration of recombinant IL-22 during the late phase, but not the early phase, of EAU increased EAU clinical scores in T cell-specific Rbpj-deficient mice. Notch inhibition in mice immunized with IRBP with a -secretase inhibitor (GSI) suppressed EAU progression, even when GSI was administered as late as 13 days after IRBP immunization. Our data demonstrate that Rbpj/Notch-mediated IL-22 production in T cells has a key pathological role in the late phase of EAU, and suggest that Notch blockade might be a useful therapeutic approach for treating EAU.","Experimental autoimmune uveoretinitis (EAU) is an organ-specific T cell-mediated disease induced by immunizing mice with interphotoreceptor retinoid binding protein (IRBP). Autoaggressive CD4(+) T cells are the major pathogenic population for EAU. We investigated the contribution of Notch signaling in T cells to EAU pathogenesis because Notch signaling regulates various aspects of CD4(+) T cell functions. Rbpj is required for Notch signaling, and Rbpj deficiency in T cells inhibited EAU disease severity. The amelioration of EAU in T cell-specific Rbpj-deficient mice correlated with low levels of IL-22 production from CD4(+) T cells, although IRBP-specific CD4(+) T cell proliferation and Th17 differentiation were unaffected. Administration of recombinant IL-22 during the late phase, but not the early phase, of EAU increased EAU clinical scores in T cell-specific Rbpj-deficient mice. Notch inhibition in mice immunized with IRBP with a -secretase inhibitor (GSI) suppressed EAU progression, even when GSI was administered as late as 13 days after IRBP immunization. Our data demonstrate that Rbpj/Notch-mediated IL-22 production in T cells has a key pathological role in the late phase of EAU, and suggest that Notch blockade might be a useful therapeutic approach for treating EAU.","null","null","2014-02-28","PLoS ONE","PLoS ONE","Vol.9","No.2","e89266","e89266","eng","true","null","scientific_journal","null","null","10.1371/journal.pone.0089266","1932-6203","null","null","null","null","null"
"Comparison of measured and predicted energy expenditure in patients with liver cirrhosis","Comparison of measured and predicted energy expenditure in patients with liver cirrhosis","A Teramoto, Hisami Okumura, E Urano, T Nakamura-Kutsuzawa, K Sugihara, Takafumi Katayama, Hidenori Miyake, Satoru Imura, Toru Utsunomiya, Mitsuo Shimada, Eiji Takeda","A Teramoto, Hisami Okumura, E Urano, T Nakamura-Kutsuzawa, K Sugihara, Takafumi Katayama, Hidenori Miyake, Satoru Imura, Toru Utsunomiya, Mitsuo Shimada, Eiji Takeda","null","Obesity is a risk factor for the onset of liver cancer in patients with cirrhosis. To prevent overfeeding and obesity, estimation of energy requirement is important, but energy expenditure in patients with liver cirrhosis has not been fully elucidated. This study aimed to investigate resting energy expenditure (REE) and energy intake in patients with cirrhosis and determine adequate energy intake criteria. In this cross-sectional study, indirect calorimetry measurement was conducted in 488 Japanese inpatients with cirrhosis. We compared REE measured by indirect calorimetry (M-REE) with basal energy expenditure (BEE) predicted by the Harris-Benedict equation (H-BEE) and Dietary Reference Intakes (DRI) for Japanese (D-BEE). Mean M-REE (1256 kcal) was significantly lower than H-BEE (1279 kcal); however, it was not significantly different from D-BEE (1254 kcal). Mean M-REE expressed in relation to body weight (BW; REE/kg BW) was 21.7 kcal/kg BW. H-BEE was significantly higher than M-REE in patients in the first and second quartiles of BMI, and D-BEE was significantly different from MREE in patients in the highest and lowest quartiles of BMI. Average energy intake was 30.5 kcal/kg BW, which was 1.4 times greater than REE/kg BW. Although DRI is a useful tool for the estimation of REE in patients in the second and third quartiles of BMI, M-REE is recommended to ensure the provision of adequate nutritional care to patients with cirrhosis, including those in the highest and lowest quartiles of BMI.","Obesity is a risk factor for the onset of liver cancer in patients with cirrhosis. To prevent overfeeding and obesity, estimation of energy requirement is important, but energy expenditure in patients with liver cirrhosis has not been fully elucidated. This study aimed to investigate resting energy expenditure (REE) and energy intake in patients with cirrhosis and determine adequate energy intake criteria. In this cross-sectional study, indirect calorimetry measurement was conducted in 488 Japanese inpatients with cirrhosis. We compared REE measured by indirect calorimetry (M-REE) with basal energy expenditure (BEE) predicted by the Harris-Benedict equation (H-BEE) and Dietary Reference Intakes (DRI) for Japanese (D-BEE). Mean M-REE (1256 kcal) was significantly lower than H-BEE (1279 kcal); however, it was not significantly different from D-BEE (1254 kcal). Mean M-REE expressed in relation to body weight (BW; REE/kg BW) was 21.7 kcal/kg BW. H-BEE was significantly higher than M-REE in patients in the first and second quartiles of BMI, and D-BEE was significantly different from MREE in patients in the highest and lowest quartiles of BMI. Average energy intake was 30.5 kcal/kg BW, which was 1.4 times greater than REE/kg BW. Although DRI is a useful tool for the estimation of REE in patients in the second and third quartiles of BMI, M-REE is recommended to ensure the provision of adequate nutritional care to patients with cirrhosis, including those in the highest and lowest quartiles of BMI.","null","null","2014","Asia Pacific Journal of Clinical Nutrition","Asia Pacific Journal of Clinical Nutrition","Vol.23","No.2","197","204","eng","true","null","scientific_journal","null","null","10.6133/apjcn.2014.23.2.12","0964-7058","null","null","null","null","null"
"Blood vessel-based liver segmentation using the portal phase of an abdominal CT dataset","Blood vessel-based liver segmentation using the portal phase of an abdominal CT dataset","Ahmed Shawky Maklad, Mikio Matsuhiro, Hidenobu Suzuki, Yoshiki Kawata, Noboru Niki, Satake Mitsuo, Moriyama Noriyuki, Toru Utsunomiya, Mitsuo Shimada","Ahmed Shawky Maklad, Mikio Matsuhiro, Hidenobu Suzuki, Yoshiki Kawata, Noboru Niki, Satake Mitsuo, Moriyama Noriyuki, Toru Utsunomiya, Mitsuo Shimada","null","Blood vessel (BV) information can be used to guide body organ segmentation on computed tomography (CT) imaging. The proposed method uses abdominal BVs (ABVs) to segment the liver through the portal phase of an abdominal CT dataset. This method aims to address the wide variability in liver shape and size, separate liver from other organs of similar intensity, and segment hepatic low-intensity tumors (LITs). Thin ABVs are enhanced using three-dimensional (3D) opening. ABVs are extracted and classified into hepatic BVs (HBVs) and nonhepatic BVs (non-HBVs) with a small number of interactions, and HBVs and non-HBVs are used for constraining automatic liver segmentation. HBVs are used to individually segment the core region of the liver. To separate the liver from other organs, this core region and non-HBVs are used to construct an initial 3D boundary surface. To segment LITs, the core region is classified into non-LIT- and LIT-parts by fitting the histogram of the core region using a variational Bayesian Gaussian mixture model. Each part of the core region is extended based on its corresponding component of the mixture, and extension is completed when it reaches a variation in intensity or the constructed boundary surface, which is reconfirmed to fit robustly between the liver and neighboring organs of similar intensity. A solid-angle technique is used to refine main BVs at the entrances to the inferior vena cava and the portal vein. The proposed method was applied to 80 datasets: 30 Medical Image Computing and Computer Assisted Intervention (MICCAI) and 50 non-MICCAI; 30 datasets of non-MICCAI data include tumors. Our results for MICCAI-test data were evaluated by sliver07 (http://www.sliver07.org/) organizers with an overall score of 85.7, which ranks best on the site as of July 2013. These results (average ± standard deviation) include the five error measures of the 2007 MICCAI workshop for liver segmentation as follows. Results for volume overlap error, relative volume difference, average symmetric surface distance, root mean square symmetric surface distance, and maximum symmetric surface distance were 4.33 ± 0.73, 0.28 ± 0.87, 0.63 ± 0.16, 1.19 ± 0.28, and 14.01 ± 2.88, respectively; and when applying our method to non-MICCAI data, results were 3.21 ± 0.75, 0.06 ± 1.29, 0.45 ± 0.17, 0.98 ± 0.26, and 12.69 ± 3.89, respectively. These results demonstrate high performance of the method when applied to different CT datasets. BVs can be used to address the wide variability in liver shape and size, as BVs provide unique details for the structure of each studied liver. Constructing a boundary surface using HBVs and non-HBVs can separate liver from its neighboring organs of similar intensity. By fitting the histogram of the core region using a variational Bayesian Gaussian mixture model, LITs are segmented and measuring the volumetry of non-LIT- and LIT-parts becomes possible. Further examination of the proposed method on a large number of datasets is required for clinical applications, and development of the method for full automation may be possible and useful in the clinic.","Blood vessel (BV) information can be used to guide body organ segmentation on computed tomography (CT) imaging. The proposed method uses abdominal BVs (ABVs) to segment the liver through the portal phase of an abdominal CT dataset. This method aims to address the wide variability in liver shape and size, separate liver from other organs of similar intensity, and segment hepatic low-intensity tumors (LITs). Thin ABVs are enhanced using three-dimensional (3D) opening. ABVs are extracted and classified into hepatic BVs (HBVs) and nonhepatic BVs (non-HBVs) with a small number of interactions, and HBVs and non-HBVs are used for constraining automatic liver segmentation. HBVs are used to individually segment the core region of the liver. To separate the liver from other organs, this core region and non-HBVs are used to construct an initial 3D boundary surface. To segment LITs, the core region is classified into non-LIT- and LIT-parts by fitting the histogram of the core region using a variational Bayesian Gaussian mixture model. Each part of the core region is extended based on its corresponding component of the mixture, and extension is completed when it reaches a variation in intensity or the constructed boundary surface, which is reconfirmed to fit robustly between the liver and neighboring organs of similar intensity. A solid-angle technique is used to refine main BVs at the entrances to the inferior vena cava and the portal vein. The proposed method was applied to 80 datasets: 30 Medical Image Computing and Computer Assisted Intervention (MICCAI) and 50 non-MICCAI; 30 datasets of non-MICCAI data include tumors. Our results for MICCAI-test data were evaluated by sliver07 (http://www.sliver07.org/) organizers with an overall score of 85.7, which ranks best on the site as of July 2013. These results (average ± standard deviation) include the five error measures of the 2007 MICCAI workshop for liver segmentation as follows. Results for volume overlap error, relative volume difference, average symmetric surface distance, root mean square symmetric surface distance, and maximum symmetric surface distance were 4.33 ± 0.73, 0.28 ± 0.87, 0.63 ± 0.16, 1.19 ± 0.28, and 14.01 ± 2.88, respectively; and when applying our method to non-MICCAI data, results were 3.21 ± 0.75, 0.06 ± 1.29, 0.45 ± 0.17, 0.98 ± 0.26, and 12.69 ± 3.89, respectively. These results demonstrate high performance of the method when applied to different CT datasets. BVs can be used to address the wide variability in liver shape and size, as BVs provide unique details for the structure of each studied liver. Constructing a boundary surface using HBVs and non-HBVs can separate liver from its neighboring organs of similar intensity. By fitting the histogram of the core region using a variational Bayesian Gaussian mixture model, LITs are segmented and measuring the volumetry of non-LIT- and LIT-parts becomes possible. Further examination of the proposed method on a large number of datasets is required for clinical applications, and development of the method for full automation may be possible and useful in the clinic.","null","null","2013-11","Medical Physics","Medical Physics","Vol.40","No.11","113501(17pp.)","113501(17pp.)","eng","true","null","scientific_journal","null","null","10.1118/1.4823765","0094-2405","null","null","null","null","null"
"Beneficial effects of green tea catechin on massive hepatectomy model in rats.","Beneficial effects of green tea catechin on massive hepatectomy model in rats.","Yu Saitou, Hiroki Mori, Chie Takasu, Masato Komatsu, Jun Hanaoka, Shin-ichiro Yamada, 淺野間 理仁, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Toru Utsunomiya, Mitsuo Shimada","Yu Saitou, Hiroki Mori, Chie Takasu, Masato Komatsu, Jun Hanaoka, Shin-ichiro Yamada, 淺野間 理仁, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Toru Utsunomiya, Mitsuo Shimada","null","BACKGROUND: Green tea catechin, especially epigallocatechin gallate (EGCG), is a well-known scavenger of reactive oxygen species and it may also function as an antioxidant through modulation of transcriptional factors and enzyme activities. METHODS: Green tea extract (GTE(®)) which contained numerous EGCG was used. Wistar rats were performed 90 % hepatectomy and classified into 2 groups with (GTEHx, n = 25) or without GTE treatment (Hx, n = 25) and sacrificed at 1, 3, 7 and 14 days after operations. All rats had free access to drinking water supplemented with or without GTE from the 7th pre-operative day. Liver regeneration, hepatic inducible nitric oxide synthase (iNOS), anti-oxidative enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px)] and inflammatory markers [cyclooxygenase-2 (COX-2), nuclear factor kappa B (NFκB), tumor necrosis factor-α (TNF-α)] were investigated. RESULTS: The liver weight to body weight ratio (p < 0.01), proliferating cell nuclear antigen labeling index (p < 0.05) and phosphorylated extracellular signal-regulated kinase 1/2 (p < 0.05) at day 1 in the GTEHx group significantly increased compared to the Hx group. Hepatic iNOS levels at day 1 significantly decreased (p < 0.01) in the GTEHx group. Hepatic SOD, CAT and GSH-Px levels at day 1 significantly increased (SOD: p < 0.01, CAT and GSH-Px: p < 0.05) in the GTEHx group. In contrast, COX-2, NFκB and TNF-α levels at day 1 significantly decreased (COX-2: p < 0.01, NFκB and TNF-α: p < 0.05) in the GTEHx group. CONCLUSIONS: GTE pretreatment stimulated liver regeneration and improved liver damage after massive hepatectomy through anti-oxidative and anti-inflammatory effects. Green tea catechin might have the potential to attenuate liver dysfunction in early stage after massive hepatectomy.","BACKGROUND: Green tea catechin, especially epigallocatechin gallate (EGCG), is a well-known scavenger of reactive oxygen species and it may also function as an antioxidant through modulation of transcriptional factors and enzyme activities. METHODS: Green tea extract (GTE(®)) which contained numerous EGCG was used. Wistar rats were performed 90 % hepatectomy and classified into 2 groups with (GTEHx, n = 25) or without GTE treatment (Hx, n = 25) and sacrificed at 1, 3, 7 and 14 days after operations. All rats had free access to drinking water supplemented with or without GTE from the 7th pre-operative day. Liver regeneration, hepatic inducible nitric oxide synthase (iNOS), anti-oxidative enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px)] and inflammatory markers [cyclooxygenase-2 (COX-2), nuclear factor kappa B (NFκB), tumor necrosis factor-α (TNF-α)] were investigated. RESULTS: The liver weight to body weight ratio (p < 0.01), proliferating cell nuclear antigen labeling index (p < 0.05) and phosphorylated extracellular signal-regulated kinase 1/2 (p < 0.05) at day 1 in the GTEHx group significantly increased compared to the Hx group. Hepatic iNOS levels at day 1 significantly decreased (p < 0.01) in the GTEHx group. Hepatic SOD, CAT and GSH-Px levels at day 1 significantly increased (SOD: p < 0.01, CAT and GSH-Px: p < 0.05) in the GTEHx group. In contrast, COX-2, NFκB and TNF-α levels at day 1 significantly decreased (COX-2: p < 0.01, NFκB and TNF-α: p < 0.05) in the GTEHx group. CONCLUSIONS: GTE pretreatment stimulated liver regeneration and improved liver damage after massive hepatectomy through anti-oxidative and anti-inflammatory effects. Green tea catechin might have the potential to attenuate liver dysfunction in early stage after massive hepatectomy.","null","null","2013-03-30","Journal of Gastroenterology","Journal of Gastroenterology","null","null","null","null","eng","true","null","scientific_journal","null","null","10.1007/s00535-013-0799-9","1435-5922","null","null","null","null","null"
"Molecular features of triple negative breast cancer cells by genome-wide gene expression profiling analysis.","Molecular features of triple negative breast cancer cells by genome-wide gene expression profiling analysis.","Masato Komatsu, Tetsuro Yoshimaru, Taisuke Matsuo, Kazuma Kiyotani, Yasuo Miyoshi, Toshihito Tanahashi, Kazuhito Rokutan, Rui Yamaguchi, Ayumu Saito, Seiya Imoto, Satoru Miyano, Yusuke Nakamura, Mitsunori Sasa, Mitsuo Shimada, Toyomasa Katagiri","Masato Komatsu, Tetsuro Yoshimaru, Taisuke Matsuo, Kazuma Kiyotani, Yasuo Miyoshi, Toshihito Tanahashi, Kazuhito Rokutan, Rui Yamaguchi, Ayumu Saito, Seiya Imoto, Satoru Miyano, Yusuke Nakamura, Mitsunori Sasa, Mitsuo Shimada, Toyomasa Katagiri","null","Triple negative breast cancer (TNBC) has a poor outcome due to the lack of beneficial therapeutic targets. To clarify the molecular mechanisms involved in the carcinogenesis of TNBC and to identify target molecules for novel anticancer drugs, we analyzed the gene expression profiles of 30 TNBCs as well as 13 normal epithelial ductal cells that were purified by laser-microbeam microdissection. We identified 301 and 321 transcripts that were significantly upregulated and downregulated in TNBC, respectively. In particular, gene expression profile analyses of normal human vital organs allowed us to identify 104 cancer-specific genes, including those involved in breast carcinogenesis such as NEK2, PBK and MELK. Moreover, gene annotation enrichment analysis revealed prominent gene subsets involved in the cell cycle, especially mitosis. Therefore, we focused on cell cycle regulators, asp (abnormal spindle) homolog, microcephaly-associated (Drosophila) (ASPM) and centromere protein K (CENPK) as novel therapeutic targets for TNBC. Small-interfering RNA-mediated knockdown of their expression significantly attenuated TNBC cell viability due to G1 and G2/M cell cycle arrest. Our data will provide a better understanding of the carcinogenesis of TNBC and could contribute to the development of molecular targets as a treatment for TNBC patients.","Triple negative breast cancer (TNBC) has a poor outcome due to the lack of beneficial therapeutic targets. To clarify the molecular mechanisms involved in the carcinogenesis of TNBC and to identify target molecules for novel anticancer drugs, we analyzed the gene expression profiles of 30 TNBCs as well as 13 normal epithelial ductal cells that were purified by laser-microbeam microdissection. We identified 301 and 321 transcripts that were significantly upregulated and downregulated in TNBC, respectively. In particular, gene expression profile analyses of normal human vital organs allowed us to identify 104 cancer-specific genes, including those involved in breast carcinogenesis such as NEK2, PBK and MELK. Moreover, gene annotation enrichment analysis revealed prominent gene subsets involved in the cell cycle, especially mitosis. Therefore, we focused on cell cycle regulators, asp (abnormal spindle) homolog, microcephaly-associated (Drosophila) (ASPM) and centromere protein K (CENPK) as novel therapeutic targets for TNBC. Small-interfering RNA-mediated knockdown of their expression significantly attenuated TNBC cell viability due to G1 and G2/M cell cycle arrest. Our data will provide a better understanding of the carcinogenesis of TNBC and could contribute to the development of molecular targets as a treatment for TNBC patients.","null","null","2013-02-18","International Journal of Oncology","International Journal of Oncology","Vol.42","No.2","478","506","eng","true","null","scientific_journal","null","null","10.3892/ijo.2012.1744","1791-2423","null","null","null","null","null"
"Beneficial effects of enteral nutrition containing with hydrolyzed whey peptide on warm ischemia/reperfusion injury in the rat liver.","Beneficial effects of enteral nutrition containing with hydrolyzed whey peptide on warm ischemia/reperfusion injury in the rat liver.","Jun Hanaoka, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Koji Sugimoto, Yu Saitou, Shinichiro Yamada, Michihito Asanoma","Jun Hanaoka, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Koji Sugimoto, Yu Saitou, Shinichiro Yamada, Michihito Asanoma","null","This study examined the efficacy of enteral nutrition containing hydrolyzed whey peptide (HWP) on warm ischemia/reperfusion (I/R) injury in the rat liver. Male Wistar rats were subjected to 30 min of warm hepatic ischemia followed by immediate p.o. intake of enteral nutrition with WHP (HWP group) or 20% glucose solution (control group) (0.025 mL/g). The animals were killed at 6 or 12 h after reperfusion. The serum aspartate aminotransferase (AST) and alanine aminotransferase alt (ALT) levels were measured. The necrotic areas were assessed histologically. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and caspase-3 activation were assessed to evaluate apoptosis. The expressions of hepatic tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nuclear factor (NF)-κB in the liver tissue were assessed by real time reverse transcription polymerase chain reaction. Significant reductions in the serum AST and ALT levels were seen in the HWP group compared with the control group at both 6 and 12 h after reperfusion. The necrotic areas and numbers of TUNEL positive cells were significantly decreased in the HWP group at 6 and 12 h after reperfusion. The caspase-3/7 activities were significantly decreased in HWP group at 6 and 12 h after reperfusion. The mRNA expressions of TNF-α and IL-6 were significantly reduced in the HWP group at 12 h after reperfusion. NF-κB mRNA expression was significantly increased in the HWP group at 6 and 12 h after reperfusion. Enteral nutrition containing HWP ameliorated the hepatic warm I/R injury possibly through the suppression of pro-inflammatory cytokine expressions and the induction of NF-κB in the rat liver.","This study examined the efficacy of enteral nutrition containing hydrolyzed whey peptide (HWP) on warm ischemia/reperfusion (I/R) injury in the rat liver. Male Wistar rats were subjected to 30 min of warm hepatic ischemia followed by immediate p.o. intake of enteral nutrition with WHP (HWP group) or 20% glucose solution (control group) (0.025 mL/g). The animals were killed at 6 or 12 h after reperfusion. The serum aspartate aminotransferase (AST) and alanine aminotransferase alt (ALT) levels were measured. The necrotic areas were assessed histologically. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and caspase-3 activation were assessed to evaluate apoptosis. The expressions of hepatic tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nuclear factor (NF)-κB in the liver tissue were assessed by real time reverse transcription polymerase chain reaction. Significant reductions in the serum AST and ALT levels were seen in the HWP group compared with the control group at both 6 and 12 h after reperfusion. The necrotic areas and numbers of TUNEL positive cells were significantly decreased in the HWP group at 6 and 12 h after reperfusion. The caspase-3/7 activities were significantly decreased in HWP group at 6 and 12 h after reperfusion. The mRNA expressions of TNF-α and IL-6 were significantly reduced in the HWP group at 12 h after reperfusion. NF-κB mRNA expression was significantly increased in the HWP group at 6 and 12 h after reperfusion. Enteral nutrition containing HWP ameliorated the hepatic warm I/R injury possibly through the suppression of pro-inflammatory cytokine expressions and the induction of NF-κB in the rat liver.","null","null","2013-02","Hepatology Research","Hepatology Research","Vol.44","No.1","114","121","eng","true","null","scientific_journal","null","null","10.1111/hepr.12097","1386-6346","null","null","null","null","null"
"Usefulness of continuous blood glucose monitoring and control for patients undergoing liver transplantation.","Usefulness of continuous blood glucose monitoring and control for patients undergoing liver transplantation.","Tsuyoshi Okada, Shinji Kawahito, Naoji Mita, Munehide Matsuhisa, Hiroshi Kitahata, Mitsuo Shimada, Shuzo Oshita","Tsuyoshi Okada, Shinji Kawahito, Naoji Mita, Munehide Matsuhisa, Hiroshi Kitahata, Mitsuo Shimada, Shuzo Oshita","null","The STG-22 closed-loop system is effective for maintaining strict blood glucose control during liver transplantation with minimal variability in blood glucose concentration.","The STG-22 closed-loop system is effective for maintaining strict blood glucose control during liver transplantation with minimal variability in blood glucose concentration.","null","null","2013","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.60","No.3-4","205","212","eng","true","null","scientific_journal","null","null","10.2152/jmi.60.205","1349-6867","null","null","null","null","null"
"手術手技 前区域枝門脈灌流領域が上右肝静脈を包含する症例に対する,下右肝静脈温存,上右肝静脈とドレナージ領域を含む","手術手技 前区域枝門脈灌流領域が上右肝静脈を包含する症例に対する,下右肝静脈温存,上右肝静脈とドレナージ領域を含む","荒川 悠佑, 島田 光生, 宇都宮 徹, 池本 哲也, 金本 真美, 岩橋 衆一","Yusuke Arakawa, Mitsuo Shimada, Toru Utsunomiya, Tetsuya Ikemoto, Mami Kanamoto, Shuichi Iwahashi","null","null","null","null","null","2012-11","手術","Operation","Vol.66","No.(12)","1741","1745","jpn","true","null","scientific_journal","null","null","null","0037-4423","null","http://ci.nii.ac.jp/naid/40019481821/","null","null","null"
"肝切除支援ソフトによる術前シミュレーション,術中ナビゲーション,部分肝臓機能解析","肝切除支援ソフトによる術前シミュレーション,術中ナビゲーション,部分肝臓機能解析","居村 暁, 島田 光生, 宇都宮 徹, 森根 裕二, 池本 哲也, 森 大樹, 荒川 悠佑, 花岡 潤, 金本 真美, 岩橋 衆一, 山田 眞一郎, 淺野間 理仁","Satoru Imura, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Tetsuya Ikemoto, Hiroki Mori, Yusuke Arakawa, Jun Hanaoka, Mami Kanamoto, Shuichi Iwahashi, 山田 眞一郎, 淺野間 理仁","null","null","null","null","null","2012-10","JJSCAS","JJSCAS","Vol.14","No.(3)","148","149","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"[達人こだわりの手術テクニック] II. 肝胆膵領域 3. 肝癌に対する区域切除","[達人こだわりの手術テクニック] II. 肝胆膵領域 3. 肝癌に対する区域切除","居村 暁, 宇都宮 徹, 森根 裕二, 池本 哲也, 三宅 秀則, 島田 光生","Satoru Imura, Toru Utsunomiya, Yuji Morine, Tetsuya Ikemoto, Hidenori Miyake, Mitsuo Shimada","null","null","null","null","null","2012-09","手術","Operation","Vol.66","No.(10)","1399","1405","jpn","true","null","scientific_journal","null","null","null","0037-4423","null","http://ci.nii.ac.jp/naid/40019429416/","null","null","null"
"The novel hypoxic cytotoxin, TX-2098 has antitumor effect in pancreatic cancer; possible mechanism through inhibiting VEGF and hypoxia inducible factor-1 targeted gene expression","The novel hypoxic cytotoxin, TX-2098 has antitumor effect in pancreatic cancer; possible mechanism through inhibiting VEGF and hypoxia inducible factor-1 targeted gene expression","Kotaro Miyake, Masanori Nishioka, Satoru Imura, Erdenebulgan Batmunkh, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori, Mitsuo Shimada","Kotaro Miyake, Masanori Nishioka, Satoru Imura, Erdenebulgan Batmunkh, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori, Mitsuo Shimada","null","Tumor hypoxia has been considered to be a potential therapeutic target, because hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. In the present study, we investigated the antitumor effect of a novel hypoxic cytotoxin, 3-[2-hydroxyethyl(methyl)amino]-2-quinoxalinecarbonitrile 1,4-dioxide (TX-2098) in inhibiting the expression of hypoxia inducible factor-1α (HIF-1α), and consequently vascular endothelial cell growth factor (VEGF) expression in pancreatic cancer. The antitumor effects of TX-2098 under hypoxia were tested against various human pancreatic cancer cell lines using WST-8 assay. VEGF protein induced pancreatic cancer was determined on cell-free supernatant by ELISA. Moreover, nude mice bearing subcutaneously (s.c.) or orthotopically implanted human SUIT-2 were treated with TX-2098. Tumor volume, survival and expression of HIF-1 and associated molecules were evaluated in treatment versus control groups. In vitro, TX-2098 inhibited the proliferation of various pancreatic cancer cell lines. In s.c model, tumors from nude mice injected with pancreatic cancer cells and treated with TX-2098 showed significant reductions in volume (P<0.01 versus control). Quantitative real-time reverse transcription-PCR analysis revealed that TX-2098 significantly inhibited mRNA expression of the HIF-1 associated molecules, VEGF, glucose transporter 1 and Aldolase A (P<0.01 versus control). These treatments also prolong the survival in orthotopic models. These results suggest that the effect of TX-2098 in pancreatic cancer might be correlated with the expression of VEGF and HIF-1 targeted molecules.","Tumor hypoxia has been considered to be a potential therapeutic target, because hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. In the present study, we investigated the antitumor effect of a novel hypoxic cytotoxin, 3-[2-hydroxyethyl(methyl)amino]-2-quinoxalinecarbonitrile 1,4-dioxide (TX-2098) in inhibiting the expression of hypoxia inducible factor-1α (HIF-1α), and consequently vascular endothelial cell growth factor (VEGF) expression in pancreatic cancer. The antitumor effects of TX-2098 under hypoxia were tested against various human pancreatic cancer cell lines using WST-8 assay. VEGF protein induced pancreatic cancer was determined on cell-free supernatant by ELISA. Moreover, nude mice bearing subcutaneously (s.c.) or orthotopically implanted human SUIT-2 were treated with TX-2098. Tumor volume, survival and expression of HIF-1 and associated molecules were evaluated in treatment versus control groups. In vitro, TX-2098 inhibited the proliferation of various pancreatic cancer cell lines. In s.c model, tumors from nude mice injected with pancreatic cancer cells and treated with TX-2098 showed significant reductions in volume (P<0.01 versus control). Quantitative real-time reverse transcription-PCR analysis revealed that TX-2098 significantly inhibited mRNA expression of the HIF-1 associated molecules, VEGF, glucose transporter 1 and Aldolase A (P<0.01 versus control). These treatments also prolong the survival in orthotopic models. These results suggest that the effect of TX-2098 in pancreatic cancer might be correlated with the expression of VEGF and HIF-1 targeted molecules.","null","null","2012-08-01","Experimental Cell Research","Experimental Cell Research","Vol.318","No.13","1554","1563","eng","true","null","scientific_journal","null","null","10.1016/j.yexcr.2012.03.013","1090-2422","null","null","null","null","null"
"縦隔腫瘍と鑑別を要した左肺葉外肺分画症の1例","縦隔腫瘍と鑑別を要した左肺葉外肺分画症の1例","矢田 圭吾, 島田 光生, 石橋 広樹, 佐藤 宏彦, 森 大樹, 淺野間 理仁","矢田 圭吾, Mitsuo Shimada, Hiroki Ishibashi, Horohiko Sato, Hiroki Mori, 淺野間 理仁","null","null","null","null","null","2012-05-01","日本小児外科学会雑誌","Journal of the Japanese Society of Pediatric Surgeons","Vol.48","No.3","592","592","jpn","true","null","scientific_journal","null","null","null","0288-609X","null","http://ci.nii.ac.jp/naid/110009582200/","null","null","null"
"腹腔鏡補助下肝部分切除術を施行した肝芽腫の1例","腹腔鏡補助下肝部分切除術を施行した肝芽腫の1例","石橋 広樹, 森 大樹, 矢田 圭吾, 淺野間 理仁, 佐藤 宏彦, 島田 光生","Hiroki Ishibashi, Hiroki Mori, 矢田 圭吾, 淺野間 理仁, Horohiko Sato, Mitsuo Shimada","null","null","null","null","null","2012-05-01","日本小児外科学会雑誌","Journal of the Japanese Society of Pediatric Surgeons","Vol.48","No.3","450","450","jpn","true","null","scientific_journal","null","null","null","0288-609X","null","http://ci.nii.ac.jp/naid/110009581985/","null","null","null"
"「内視鏡外科医のための微細局所解剖アトラス」肝胆膵 肝外側区域切除-脈管処理のコツ","「内視鏡外科医のための微細局所解剖アトラス」肝胆膵 肝外側区域切除-脈管処理のコツ","森根 裕二, 島田 光生, 宇都宮 徹, 居村 暁, 池本 哲也","Yuji Morine, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Tetsuya Ikemoto","null","null","null","null","null","2012-05","手術.2012","手術.2012","Vol.66","No.(6)","753","759","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"【必読 イレウスの診断から治療まで】機械的イレウス 複雑性または絞扼性イレウス ヘルニア嵌頓","【必読 イレウスの診断から治療まで】機械的イレウス 複雑性または絞扼性イレウス ヘルニア嵌頓","佐藤 宏彦, 島田 光生, 栗田 信浩, 岩田 貴, 西岡 将規, 森本 慎也, 吉川 幸造, 宮谷 知彦, 後藤 正和, 柏原 秀也, 髙須 千絵","Horohiko Sato, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Tomohiko Miyatani, Masakazu Goto, 柏原 秀也, Chie Takasu","null","null","null","null","null","2012-05","外科","Surgery","Vol.74","No.3","273","278","jpn","true","null","scientific_journal","null","null","null","0016-593X","null","null","null","null","null"
"Treatment of rapid weight loss in a donor with hepatic steatosis in a living donor liver transplantation: a case report","Treatment of rapid weight loss in a donor with hepatic steatosis in a living donor liver transplantation: a case report","Hisami Okumura, Akihiko Kawaura, Satoru Imura, Toru Utsunomiya, Mitsuo Shimada, Eiji Takeda","Hisami Okumura, Akihiko Kawaura, Satoru Imura, Toru Utsunomiya, Mitsuo Shimada, Eiji Takeda","null","The use of steatotic livers for transplantation is often associated with increased primary non-function. To reduce the risk of liver injury, steatosis of the donor liver in living donor liver transplantation (LDLT) was treated with restricted diet and exercise. A 21-year-old male donor, 167cm in height and 87kg in body weight, initially received a 1800kcal/day diet for 9 days which was then gradually reduced using a 1600kcal/day diet for 43 days, followed by a 1500kcal/day diet for one day and was finally maintained on a 1400kcal/day diet for 52 days. Daily exercise consumed 500kcal/day. The non-protein respiratory quotient (npRQ) gradually increased while the non-esterified fatty acids (NEFA) decreased during the course of the 105-day treatment. Consequently, the initial 80% steatosis was reduced to 10% and was accompanied by 13% weight loss for 81 days. The npRQ values and NEFA concentrations in the later period of dietary and exercise treatment were higher and lower, respectively, than in the early treatment period, indicating compensation through long-term treatment. Therefore, energy metabolism and NEFA levels represent important biomarkers for short-term intensive treatment by restricted diet and exercise in donors with hepatic steatosis.","The use of steatotic livers for transplantation is often associated with increased primary non-function. To reduce the risk of liver injury, steatosis of the donor liver in living donor liver transplantation (LDLT) was treated with restricted diet and exercise. A 21-year-old male donor, 167cm in height and 87kg in body weight, initially received a 1800kcal/day diet for 9 days which was then gradually reduced using a 1600kcal/day diet for 43 days, followed by a 1500kcal/day diet for one day and was finally maintained on a 1400kcal/day diet for 52 days. Daily exercise consumed 500kcal/day. The non-protein respiratory quotient (npRQ) gradually increased while the non-esterified fatty acids (NEFA) decreased during the course of the 105-day treatment. Consequently, the initial 80% steatosis was reduced to 10% and was accompanied by 13% weight loss for 81 days. The npRQ values and NEFA concentrations in the later period of dietary and exercise treatment were higher and lower, respectively, than in the early treatment period, indicating compensation through long-term treatment. Therefore, energy metabolism and NEFA levels represent important biomarkers for short-term intensive treatment by restricted diet and exercise in donors with hepatic steatosis.","null","null","2012-05","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.59","No.115","869","871","eng","true","null","scientific_journal","null","null","10.5754/hge10237","0172-6390","null","null","null","null","null"
"小腸間膜脂肪肉腫の1例","A case of small intestinal mesenteric liposarcoma","佐藤 宏彦, 島田 光生, 小笠原 卓, 大塚 敏弘, 安藤 勤, 長堀 順二","Horohiko Sato, Mitsuo Shimada, 小笠原 卓, 大塚 敏弘, Tsutomu Ando, 長堀 順二","null","We report a case of small intestinal mesenteric liposarcoma. An 84-year-old woman wasadmitted to our hospital with a chief complaint of abdominal distension and pointing out a tumor inher abdomen. On physical examination an adult's head-sized tumor was palpated from the leftupper portion of the pelvis. Abdominal computed tomography(CT)revealed the mass24×18×13cm in size which had clear borderline and smooth surface. Multi-detector-CT scan revealed aheterogeneously enhanced mass fed by the Superior mesenteric artery. With a clinical diagnosisof liposarcoma arisen from the small intestinal mesentery, the patient was operated on. The tumorwas present in the mesentery of the small intestine and a removal of the tumor with associatedresection of the small intestine was perfomed. The histological diagnosis was well-differentiatedliposarcoma. The patient has been followed for nine months after the operation without evidenceof local recurrence.","We report a case of small intestinal mesenteric liposarcoma. An 84-year-old woman wasadmitted to our hospital with a chief complaint of abdominal distension and pointing out a tumor inher abdomen. On physical examination an adult's head-sized tumor was palpated from the leftupper portion of the pelvis. Abdominal computed tomography(CT)revealed the mass24×18×13cm in size which had clear borderline and smooth surface. Multi-detector-CT scan revealed aheterogeneously enhanced mass fed by the Superior mesenteric artery. With a clinical diagnosisof liposarcoma arisen from the small intestinal mesentery, the patient was operated on. The tumorwas present in the mesentery of the small intestine and a removal of the tumor with associatedresection of the small intestine was perfomed. The histological diagnosis was well-differentiatedliposarcoma. The patient has been followed for nine months after the operation without evidenceof local recurrence.","null","null","2012-04-25","四国医学雑誌","Shikoku Acta Medica","Vol.68","No.1-2","41","44","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","http://ci.nii.ac.jp/naid/40019338837/","null","null","null"
"血流障害,遊走脾を伴った急性胃軸捻転症の1例","血流障害,遊走脾を伴った急性胃軸捻転症の1例","石橋 広樹, 佐藤 宏彦, 森 大樹, 島田 光生","Hiroki Ishibashi, Horohiko Sato, Hiroki Mori, Mitsuo Shimada","null","null","null","null","null","2012-04-20","日本小児外科学会雑誌","Journal of the Japanese Society of Pediatric Surgeons","Vol.48","No.2","274","274","jpn","true","null","scientific_journal","null","null","null","0288-609X","null","http://ci.nii.ac.jp/naid/110009437133/","null","null","null"
"Possible utility of MRI using Gd-EOB-DTPA for estimating liver functional reserve","Possible utility of MRI using Gd-EOB-DTPA for estimating liver functional reserve","Toru Utsunomiya, Mitsuo Shimada, Jun Hanaoka, Mami Kanamoto, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Masafumi Harada","Toru Utsunomiya, Mitsuo Shimada, Jun Hanaoka, Mami Kanamoto, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Masafumi Harada","null","Preoperative estimation of the liver functional reserve is important in liver surgery. We evaluated the role of dynamic magnetic resonance (MR) imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), i.e., EOB-MRI, for determining liver functional reserve. Fifty patients who underwent EOB-MRI to examine their liver tumors were included in this study. We first performed a pixel-by-pixel comparison of registered MR images and activity images with Tc-99m galactosyl human serum albumin (GSA) on each slice, and the correlation coefficient was calculated for 8 patients. We also determined the correlation coefficient between the relative signal intensity (SI) values of EOB-MRI and preoperative liver function, such as the GSA, indocyanine green dye retention at 15 min (ICGR15), and prothrombin time. The mean of the correlation coefficients for 512 × 512 matrices between the EOB-MRI and the GSA was 0.83 ± 0.05 (ranging from 0.73 to 0.87). The correlation coefficient between the relative SI of the EOB-MRI and the receptor index (LHL15) of GSA was 0.56 (P < 0.01). Better correlation coefficients were observed between the relative SI and the liver function test, including ICGR15 (r = -0.67, P < 0.01) and prothrombin time (r = 0.59, P < 0.01). In a patient with hilar cholangiocarcinoma whose right hepatic duct was obstructed, the relative SI in the right lobe (2.4 ± 0.3) was significantly lower than that in the left lobe (3.1 ± 0.1). EOB-MRI represents a practical and reliable imaging technique that may be used to estimate regional liver functional reserve in the clinical setting.","Preoperative estimation of the liver functional reserve is important in liver surgery. We evaluated the role of dynamic magnetic resonance (MR) imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), i.e., EOB-MRI, for determining liver functional reserve. Fifty patients who underwent EOB-MRI to examine their liver tumors were included in this study. We first performed a pixel-by-pixel comparison of registered MR images and activity images with Tc-99m galactosyl human serum albumin (GSA) on each slice, and the correlation coefficient was calculated for 8 patients. We also determined the correlation coefficient between the relative signal intensity (SI) values of EOB-MRI and preoperative liver function, such as the GSA, indocyanine green dye retention at 15 min (ICGR15), and prothrombin time. The mean of the correlation coefficients for 512 × 512 matrices between the EOB-MRI and the GSA was 0.83 ± 0.05 (ranging from 0.73 to 0.87). The correlation coefficient between the relative SI of the EOB-MRI and the receptor index (LHL15) of GSA was 0.56 (P < 0.01). Better correlation coefficients were observed between the relative SI and the liver function test, including ICGR15 (r = -0.67, P < 0.01) and prothrombin time (r = 0.59, P < 0.01). In a patient with hilar cholangiocarcinoma whose right hepatic duct was obstructed, the relative SI in the right lobe (2.4 ± 0.3) was significantly lower than that in the left lobe (3.1 ± 0.1). EOB-MRI represents a practical and reliable imaging technique that may be used to estimate regional liver functional reserve in the clinical setting.","null","null","2012-04","Journal of Gastroenterology","Journal of Gastroenterology","Vol.47","No.4","470","476","eng","true","null","scientific_journal","null","null","10.1007/s00535-011-0513-8","1435-5922","null","null","null","null","null"
"癌治療に求められる漢方の意義 臨床現場にどのように活かすか""牛車腎気丸""によるFOLFOX関連末梢神経障害の軽減","癌治療に求められる漢方の意義 臨床現場にどのように活かすか""牛車腎気丸""によるFOLFOX関連末梢神経障害の軽減","西岡 将規, 島田 光生, 栗田 信浩, 佐藤 宏彦, 岩田 貴, 森本 慎也, 吉川 幸造, 宮谷 知彦, 柏原 秀也, 髙須 千絵","Masanori Nishioka, Mitsuo Shimada, Nobuhiro Kurita, Horohiko Sato, Takashi Iwata, Shinya Morimoto, Kouzou Yoshikawa, Tomohiko Miyatani, 柏原 秀也, Chie Takasu","null","null","null","null","null","2012-04","産婦人科漢方研究のあゆみ","産婦人科漢方研究のあゆみ","Vol.29","null","22","27","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"[達人が教える肝胆膵高度技能専門医手術-コツとピットフォール] 肝葉切除(右肝・左肝切除)非手割法","[達人が教える肝胆膵高度技能専門医手術-コツとピットフォール] 肝葉切除(右肝・左肝切除)非手割法","花岡 潤, 島田 光生, 宇都宮 徹, 居村 暁, 森根 裕二, 三宅 秀則","Jun Hanaoka, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Hidenori Miyake","null","null","null","null","null","2012-03","手術","Operation","Vol.66","No.(3)","287","293","jpn","true","null","scientific_journal","null","null","null","0037-4423","null","http://ci.nii.ac.jp/naid/40019221576/","null","null","null"
"II-4 抗癌剤 「肝胆膵」","II-4 抗癌剤 「肝胆膵」","池本 哲也, 島田 光生","Tetsuya Ikemoto, Mitsuo Shimada","null","null","null","null","null","2012-03","消化器外科レビュー","消化器外科レビュー","Vol.2012","null","216","221","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"Bevacizumab併用化学療法中に大腸穿孔・穿通をきたした症例の検討","Bevacizumab併用化学療法中に大腸穿孔・穿通をきたした症例の検討","髙須 千絵, 島田 光生, 吉川 幸造, 栗田 信浩, 岩田 貴, 佐藤 宏彦, 西岡 将規, 森本 慎也, 宮谷 知彦, 柏原 秀也","Chie Takasu, Mitsuo Shimada, Kouzou Yoshikawa, Nobuhiro Kurita, Takashi Iwata, Horohiko Sato, Masanori Nishioka, Shinya Morimoto, Tomohiko Miyatani, 柏原 秀也","null","null","null","null","null","2012-02","日本腹部救急医学会雑誌","日本腹部救急医学会雑誌","Vol.32","No.2","424","424","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"Notch2 regulates the development of marginal zone B cells through Fos.","Notch2 regulates the development of marginal zone B cells through Fos.","Shuichi Iwahashi, Yoichi Maekawa, Jun Nishida, Chieko Ishifune, Akiko Kitamura, Hideki Arimochi, Keiko Kataoka, Shigeru Chiba, Mitsuo Shimada, Koji Yasutomo","Shuichi Iwahashi, Yoichi Maekawa, Jun Nishida, Chieko Ishifune, Akiko Kitamura, Hideki Arimochi, Keiko Kataoka, Shigeru Chiba, Mitsuo Shimada, Koji Yasutomo","null","B cells are classified into several subsets depending on their functions, marker expression pattern and localization. Marginal zone B (MZB) cells are a distinct lineage from follicular B cells, and regulate host defenses against blood-borne pathogens. Notch2/RBP-J signaling regulates the development of MZB cells by interacting with delta-like 1 ligand, although the target genes for Notch2 signaling remain unclear. We identified Fos as an upregulated gene in LPS-stimulated B cells that received Notch2 signaling. Fos is expressed in CD21(high)CD23(low) MZB cells at a higher level compared to CD21(Int)CD23(high) follicular B cells. Deleting the Notch2 gene in CD19(+) B cells decreased Fos expression in B cells. Overexpression of Fos in Notch2-deficient B cells or bone marrow cells partially restored MZB development. Fos promoter activity was upregulated by Notch2 signaling, indicating that Notch2 directly controls Fos transcription associated with MZB development. These data identify Fos as one of the target genes for Notch2 signaling that is crucial for MZB development.","B cells are classified into several subsets depending on their functions, marker expression pattern and localization. Marginal zone B (MZB) cells are a distinct lineage from follicular B cells, and regulate host defenses against blood-borne pathogens. Notch2/RBP-J signaling regulates the development of MZB cells by interacting with delta-like 1 ligand, although the target genes for Notch2 signaling remain unclear. We identified Fos as an upregulated gene in LPS-stimulated B cells that received Notch2 signaling. Fos is expressed in CD21(high)CD23(low) MZB cells at a higher level compared to CD21(Int)CD23(high) follicular B cells. Deleting the Notch2 gene in CD19(+) B cells decreased Fos expression in B cells. Overexpression of Fos in Notch2-deficient B cells or bone marrow cells partially restored MZB development. Fos promoter activity was upregulated by Notch2 signaling, indicating that Notch2 directly controls Fos transcription associated with MZB development. These data identify Fos as one of the target genes for Notch2 signaling that is crucial for MZB development.","null","null","2012-01-24","Biochemical and Biophysical Research Communications","Biochemical and Biophysical Research Communications","Vol.418","No.4","701","707","eng","true","null","scientific_journal","null","null","10.1016/j.bbrc.2012.01.082","1090-2104","null","null","null","null","null"
"【脂肪由来幹細胞の臨床応用への展開】脂肪由来幹細胞を用いた肝および膵再生医療","Hepatic and pancreatic regenerative medicine using Adipose tissue-derived mesenchymal stem cell","森根 裕二, 島田 光生","Yuji Morine, Mitsuo Shimada","null","null","null","null","null","2012-01","医学のあゆみ","Journal of Clinical and Experimental Medicine","Vol.42","No.(4)","303","308","jpn","true","null","scientific_journal","null","null","null","0039-2359","null","http://ci.nii.ac.jp/naid/40019347144/","null","null","null"
"ALTA療法の効果判定としての経肛門超音波パワードップラー法の可能性","ALTA療法の効果判定としての経肛門超音波パワードップラー法の可能性","宮本 英典, 淺野間 理仁, 宮本 英之, 島田 光生","Hidenori Miyamoto, 淺野間 理仁, 宮本 英之, Mitsuo Shimada","null","null","null","null","null","2012-01","臨床肛門病学 2012","臨床肛門病学 2012","Vol.4","No.(1)","23","26","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"Effects of indole-3-carbinol and phenethyl isothiocyanate on bile and pancreatic juice excretion in rats.","Effects of indole-3-carbinol and phenethyl isothiocyanate on bile and pancreatic juice excretion in rats.","Hiroki Ishibashi, Tomomi Kuwahara, H Nakayama-Imaohji, Y Ohnishi, Hiroki Mori, Mitsuo Shimada","Hiroki Ishibashi, Tomomi Kuwahara, H Nakayama-Imaohji, Y Ohnishi, Hiroki Mori, Mitsuo Shimada","null","Bile and pancreatic juice contain a number of parameters for cancer chemoprevention. Indole-3-carbinol (I3C) and phenethyl isothiocyanate (PEITC), which are hydrolytic products of brassica plants, have been established to be anti-cancer agents. Here, we developed a method for the continuous and selective sampling of bile and pancreatic juice, and the effects of I3C and PEITC on bile and pancreatic excretion and γ-glutamyl transpeptidase (γ-GTP) activity in the samples were investigated. Male Fisher 344 rats (eight weeks of age) were challenged intragastrically with I3C (150 mg/kg) or PEITC (160 mg/kg) for five days. Twenty-four hours after the final administration, cannulation was undertaken into the rats' bile and pancreatic ducts, and the bile and pancreatic juice were separately collected for 48 h. In this rat model, bile was stably excreted, and the bile and pancreatic excretion of the control rats was 21.9 ± 1.4 ml/48 h and 12.8 ± 1.7 ml/48 h, respectively. Bile excretion for the first 24 h significantly increased in the I3C- or PEITC-treated rats compared with the control rats. In the case of pancreatic juice, excretion during the first 24 h significantly increased in the PEITC-treated rats. In bile, γ-GTP activity was significantly increased for the first 24 h in the I3C- and PEITC-treated rats, but no difference was observed in the pancreatic juice. Increases of bile excretion and γ-GTP activity in bile might be a factor involved in the anti-cancer effect of I3C and PEITC. Our rat model described here is a useful tool for the study of cancer chemoprevention.","Bile and pancreatic juice contain a number of parameters for cancer chemoprevention. Indole-3-carbinol (I3C) and phenethyl isothiocyanate (PEITC), which are hydrolytic products of brassica plants, have been established to be anti-cancer agents. Here, we developed a method for the continuous and selective sampling of bile and pancreatic juice, and the effects of I3C and PEITC on bile and pancreatic excretion and γ-glutamyl transpeptidase (γ-GTP) activity in the samples were investigated. Male Fisher 344 rats (eight weeks of age) were challenged intragastrically with I3C (150 mg/kg) or PEITC (160 mg/kg) for five days. Twenty-four hours after the final administration, cannulation was undertaken into the rats' bile and pancreatic ducts, and the bile and pancreatic juice were separately collected for 48 h. In this rat model, bile was stably excreted, and the bile and pancreatic excretion of the control rats was 21.9 ± 1.4 ml/48 h and 12.8 ± 1.7 ml/48 h, respectively. Bile excretion for the first 24 h significantly increased in the I3C- or PEITC-treated rats compared with the control rats. In the case of pancreatic juice, excretion during the first 24 h significantly increased in the PEITC-treated rats. In bile, γ-GTP activity was significantly increased for the first 24 h in the I3C- and PEITC-treated rats, but no difference was observed in the pancreatic juice. Increases of bile excretion and γ-GTP activity in bile might be a factor involved in the anti-cancer effect of I3C and PEITC. Our rat model described here is a useful tool for the study of cancer chemoprevention.","null","null","2012","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.59","No.3-4","246","252","eng","true","null","scientific_journal","null","null","10.2152/jmi.59.246","1349-6867","null","null","null","null","null"
"Torsion of an accessory spleen with situs inversus in a child.","Torsion of an accessory spleen with situs inversus in a child.","Hiroki Ishibashi, Takehito Oshio, Tomoko Sogami, Akira Nii, Hiroki Mori, Mitsuo Shimada","Hiroki Ishibashi, Takehito Oshio, Tomoko Sogami, Akira Nii, Hiroki Mori, Mitsuo Shimada","null","We present an unusual case of acute abdomen caused by torsion of an accessory spleen with situs inversus in a child. A three-year-old girl was admitted to our hospital with an 11-day history of right flank pain with fever. Her medical history revealed an operation of coarctation of the aorta with situs inversus at one month of age. Physical examination revealed a right flank mass and tenderness. A contrast-enhanced CT scan showed a normally enhanced small spleen in the right upper quadrant and a 7.0×6.0×3.5 cm, hypodense, marginal enhancing mass in the right midabdomen adjacent to the intestine. An emergency laparotomy was decided upon with a preoperative diagnosis as an acute abdomen. During surgery, a mass was found under the greater omentum and two accessory spleens of 1.5 cm in diameter were found surrounding the main spleen. Several loops of bowel were adherent to the mass. The loops of bowel were dissected away. A pediculated congested mass was observed as an accessory spleen emerging from the greater omentum. The mass was twisted on its vascular pedicle and strangulated. The necrotic mass was removed and the postoperative recovery was uneventful. Though torsion of an accessory spleen is extremely rare, it should be considered in the differential diagnosis of acute abdomen in childhood.","We present an unusual case of acute abdomen caused by torsion of an accessory spleen with situs inversus in a child. A three-year-old girl was admitted to our hospital with an 11-day history of right flank pain with fever. Her medical history revealed an operation of coarctation of the aorta with situs inversus at one month of age. Physical examination revealed a right flank mass and tenderness. A contrast-enhanced CT scan showed a normally enhanced small spleen in the right upper quadrant and a 7.0×6.0×3.5 cm, hypodense, marginal enhancing mass in the right midabdomen adjacent to the intestine. An emergency laparotomy was decided upon with a preoperative diagnosis as an acute abdomen. During surgery, a mass was found under the greater omentum and two accessory spleens of 1.5 cm in diameter were found surrounding the main spleen. Several loops of bowel were adherent to the mass. The loops of bowel were dissected away. A pediculated congested mass was observed as an accessory spleen emerging from the greater omentum. The mass was twisted on its vascular pedicle and strangulated. The necrotic mass was removed and the postoperative recovery was uneventful. Though torsion of an accessory spleen is extremely rare, it should be considered in the differential diagnosis of acute abdomen in childhood.","null","null","2012","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.59","No.1-2","220","223","eng","true","null","scientific_journal","null","null","10.2152/jmi.59.220","1349-6867","null","null","null","null","null"
"【胃癌術後QOL向上に役立つ手技・再建法とその機能的評価】13Cを用いた空腸吸収能検査・Radioisotope(RI)法による排出能検査からみた胃全摘術後空腸嚢付加Roux-en-Y再建の意義","Evaluation of the usefulness of Roux-en-Y reconstruction with jejunal pouch by radioisotope scintigraphy and 13C breath test","東島 潤, 島田 光生, 栗田 信浩, 岩田 貴, 西岡 将規, 森本 慎也, 吉川 幸造, 宮谷 知彦, 柏原 秀也, 三上 千絵","Jun Higashijima, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Tomohiko Miyatani, 柏原 秀也, Chie Mikami","null","null","null","null","null","2011-02","癌の臨床","Japanese Journal of Cancer Clinics","Vol.56","No.5","377","382","jpn","true","null","scientific_journal","null","null","null","0021-4949","null","http://ci.nii.ac.jp/naid/40018870156/","null","null","null"
"エネルギー代謝と血液生化学検査からみた肝切除前後の栄養評価","Nutritional Assessment of Pre- and Post- Liver Resection by Energy Metabolism and Laboratory Data","奥村 仙示, 浦野 恵利, 板東 友美, 山内 利香, 居村 暁, 宇都宮 徹, 島田 光生, 武田 英二","Hisami Okumura, 浦野 恵利, 板東 友美, 山内 利香, Satoru Imura, Toru Utsunomiya, Mitsuo Shimada, Eiji Takeda","null","null","null","null","null","2011-01-15","日本臨床栄養学会雑誌","Journal of Japanese Society of Clinical Nutrition","Vol.32","No.3","133","140","jpn","true","null","scientific_journal","null","null","null","0286-8202","null","http://ci.nii.ac.jp/naid/10029421521/","null","null","null"
"【内視鏡外科手術をめぐる最近のトピックス】 新たな領域への手術適応 保険収載後の腹腔鏡下肝切除術の展開","【内視鏡外科手術をめぐる最近のトピックス】 新たな領域への手術適応 保険収載後の腹腔鏡下肝切除術の展開","宇都宮 徹, 島田 光生, 居村 暁, 森根 裕二, 池本 哲也, 花岡 潤, 森 大樹, 金本 真美, 岩橋 衆一, 齋藤 裕, 三宅 秀則","Toru Utsunomiya, Mitsuo Shimada, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Jun Hanaoka, Hiroki Mori, Mami Kanamoto, Shuichi Iwahashi, Yu Saitou, Hidenori Miyake","null","null","null","null","null","2011-01","消化器外科","Gastroenterological Surgery","Vol.34","No.1","69","77","jpn","true","null","scientific_journal","null","null","null","0387-2645","null","null","null","null","null"
"薬物治療学の進歩-この30年-,IX. 肝移植 1)ネオーラル(ノバルティス)","薬物治療学の進歩-この30年-,IX. 肝移植 1)ネオーラル(ノバルティス)","宇都宮 徹, 島田 光生, 居村 暁, 森根 裕二, 池本 哲也","Toru Utsunomiya, Mitsuo Shimada, Satoru Imura, Yuji Morine, Tetsuya Ikemoto","null","null","null","null","null","2010-12","肝·胆·膵","KAN TAN SUI","Vol.61","No.6","1170","1176","jpn","true","null","scientific_journal","null","null","null","0389-4991","null","null","null","null","null"
"術後障害に対する漢方治療.","術後障害に対する漢方治療.","宇都宮 徹, 島田 光生, 森根 裕二, 居村 暁, 三宅 秀則, 栗田 信浩","Toru Utsunomiya, Mitsuo Shimada, Yuji Morine, Satoru Imura, Hidenori Miyake, Nobuhiro Kurita","null","null","null","null","null","2010-12","外科治療","Surgical Therapy","Vol.103","No.3","576","583","jpn","true","null","scientific_journal","null","null","null","0433-2644","null","http://ci.nii.ac.jp/naid/40017406362/","null","null","null"
"Serum evaluation of soluble interferon-alpha/beta receptor and high-sensitivity C-reactive protein for diagnosis of the patients with gastrointestinal and hepatobiliary-pancreatic cancer.","Serum evaluation of soluble interferon-alpha/beta receptor and high-sensitivity C-reactive protein for diagnosis of the patients with gastrointestinal and hepatobiliary-pancreatic cancer.","Kotaro Miyake, Satoru Imura, Masanori Nishioka, Erdenebulgan Batmunkh, Koji Sugimoto, Yasukazu Ohmoto, Mitsuo Shimada","Kotaro Miyake, Satoru Imura, Masanori Nishioka, Erdenebulgan Batmunkh, Koji Sugimoto, Yasukazu Ohmoto, Mitsuo Shimada","null","Serum soluble interferon-alpha/beta receptor (sIFN-alpha/betaR) and high-sensitivity C-reactive protein (hs-CRP) levels were evaluated in the patients with gastrointestinal and hepatobiliary-pancreatic cancer. We compared the sensitivity and specificity of serum sIFN-alpha/betaR with that of serum hs-CRP and evaluated the two diagnostic parameters in combination. Serum sIFN-alpha/betaR levels were measured in 92 patients and 25 healthy individuals by enzyme-linked immunosorbent assay. The diagnoses were 37 cases of hepatocellular carcinoma, 17 cases of pancreatic cancer, 15 cases of colon cancer, 13 cases of biliary tract cancer, and 10 cases of gastric cancer. Serum levels of sIFN-alpha/betaR and hs-CRP were significantly higher in the patients than in healthy individuals (p<0.05). The optimal cut-off values of sIFN-alpha/betaR and hs-CRP were 3600pg/ml and 0.5microg/ml, respectively. The sensitivity and specificity for these thresholds were 94.6% and 88.0%, whereas positive predictive and negative predictive values were 96.7% and 81.5%. These results suggest that a combination of serum sIFN-alpha/betaR and hs-CRP thresholds may be more reliable diagnostic parameter for gastrointestinal and hepatobiliary-pancreatic cancer.","Serum soluble interferon-alpha/beta receptor (sIFN-alpha/betaR) and high-sensitivity C-reactive protein (hs-CRP) levels were evaluated in the patients with gastrointestinal and hepatobiliary-pancreatic cancer. We compared the sensitivity and specificity of serum sIFN-alpha/betaR with that of serum hs-CRP and evaluated the two diagnostic parameters in combination. Serum sIFN-alpha/betaR levels were measured in 92 patients and 25 healthy individuals by enzyme-linked immunosorbent assay. The diagnoses were 37 cases of hepatocellular carcinoma, 17 cases of pancreatic cancer, 15 cases of colon cancer, 13 cases of biliary tract cancer, and 10 cases of gastric cancer. Serum levels of sIFN-alpha/betaR and hs-CRP were significantly higher in the patients than in healthy individuals (p<0.05). The optimal cut-off values of sIFN-alpha/betaR and hs-CRP were 3600pg/ml and 0.5microg/ml, respectively. The sensitivity and specificity for these thresholds were 94.6% and 88.0%, whereas positive predictive and negative predictive values were 96.7% and 81.5%. These results suggest that a combination of serum sIFN-alpha/betaR and hs-CRP thresholds may be more reliable diagnostic parameter for gastrointestinal and hepatobiliary-pancreatic cancer.","null","null","2010-10-30","Cytokine","Cytokine","Vol.49","No.3","251","255","eng","true","null","scientific_journal","null","null","10.1016/j.cyto.2009.09.010","1096-0023","null","null","null","null","null"
"New stepwise cooling system for short-term porcine islet preservation.","New stepwise cooling system for short-term porcine islet preservation.","Tetsuya Ikemoto, Hirofumi Noguchi, Yasutaka Fujita, Morihito Takita, Masayuki Shimoda, Koji Sugimoto, Andrew Jackson, Bashoo Naziruddin, Mitsuo Shimada, Marlon F. Levy, Shinichi Matsumoto","Tetsuya Ikemoto, Hirofumi Noguchi, Yasutaka Fujita, Morihito Takita, Masayuki Shimoda, Koji Sugimoto, Andrew Jackson, Bashoo Naziruddin, Mitsuo Shimada, Marlon F. Levy, Shinichi Matsumoto","null","Porcine islets are the most suitable for xeno-islet transplantation. However, it is necessary to establish an effective preservation method against its fragility. Recently, we developed a new cooling and preservation (Keep and Fresh [KFC]; FUJIYA Co, Tokushima, Japan) system, which can maintain viability of hepatocyte. In this study, we examined the KFC for porcine islet preservation.","Porcine islets are the most suitable for xeno-islet transplantation. However, it is necessary to establish an effective preservation method against its fragility. Recently, we developed a new cooling and preservation (Keep and Fresh [KFC]; FUJIYA Co, Tokushima, Japan) system, which can maintain viability of hepatocyte. In this study, we examined the KFC for porcine islet preservation.","null","null","2010-10","Pancreas","Pancreas","Vol.39","No.7","960","963","eng","true","null","scientific_journal","null","null","10.1097/MPA.0b013e3181dab19a","1536-4828","null","null","null","null","null"
"【特集】大腸がん鏡視下手術の標準化","【特集】大腸がん鏡視下手術の標準化","岩田 貴, 島田 光生, 栗田 信浩, 西岡 将規, 森本 慎也, 吉川 幸造, 宮谷 知彦, 柏原 秀也, 髙須 千絵","Takashi Iwata, Mitsuo Shimada, Nobuhiro Kurita, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Tomohiko Miyatani, 柏原 秀也, Chie Takasu","null","null","null","null","null","2010-09","癌の臨床","Japanese Journal of Cancer Clinics","Vol.56","No.9","641","648","jpn","true","null","scientific_journal","null","null","null","0021-4949","null","http://ci.nii.ac.jp/naid/40018950587/","null","null","null"
"問題を有するドナーからの生体肝移植 ∼胃癌術後ドナーおよび喘息罹患ドナー∼.","問題を有するドナーからの生体肝移植 ∼胃癌術後ドナーおよび喘息罹患ドナー∼.","宇都宮 徹, 島田 光生, 居村 暁, 森根 裕二, 池本 哲也, 花岡 潤, 森 大樹, 岩橋 衆一, 川田 祐子, 斎藤 裕","Toru Utsunomiya, Mitsuo Shimada, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Jun Hanaoka, Hiroki Mori, 岩橋 衆一, 川田 祐子, 斎藤 裕","null","null","null","null","null","2010-09","臨床と研究","The Japanese journal of clinical and experimental medicine","Vol.87","No.9","1282","1283","jpn","true","null","scientific_journal","null","null","null","0021-4965","null","null","null","null","null"
"急性肝不全に対する肝移植術施行のタイミングに難渋した症例","急性肝不全に対する肝移植術施行のタイミングに難渋した症例","森 大樹, 島田 光生, 宇都宮 徹, 居村 暁, 森根 裕二, 池本 哲也, 花岡 潤","Hiroki Mori, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Jun Hanaoka","null","null","null","null","null","2010-09","臨床と研究","The Japanese journal of clinical and experimental medicine","Vol.87","No.9","118","119","jpn","true","null","scientific_journal","null","null","null","0021-4965","null","null","null","null","null"
"Impact of splenectomy in patients with liver cirrhosis: Results from 18 patients in a single center experience.","Impact of splenectomy in patients with liver cirrhosis: Results from 18 patients in a single center experience.","Satoru Imura, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Shuichi Iwahashi, Yu Saito, Hisami Okumura, Eiji Takeda","Satoru Imura, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Shuichi Iwahashi, Yu Saito, Hisami Okumura, Eiji Takeda","null","Aim: With the recent advances in medical or surgical treatments in chronic hepatic disorders, the indications for splenectomy in hepatic disorders have greatly expanded. We performed splenectomy for cirrhotic patients and investigated the effects of splenectomy on hepatic functional reserve and nutrition metabolism. Methods: Eighteen patients (Child-Pugh B/C: 12/6; Child-Pugh A: excluded) who underwent splenectomy at our institute between 2005 and 2008 were enrolled. Twelve patients (67%) had hepatocellular carcinoma (HCC), eight of whom met the Milan criteria. Results: Overall survival rate was 83.3% at 1 year and 62.7% at 2 years. The survival rate of six patients with liver cirrhosis classified a Child-Pugh C was 80.0% at 1 year and 60.0% at 2 years. Three patients underwent hepatic resection and nine patients received ablation therapy against hepatocelluar carcinoma. Portal pressure decreased after splenectomy in most patients (mean decrease, 4.7 mmHg). Four weeks after the operation, the markers of hepatic functional reserve, indocyanine green retention rate at 15 min (ICGR15) and Technetium-99m-galactosyl human serum albumin value ((99m)Tc-GSA), improved from 38.5% to 35.1% and from 0.773 to 0.788 (LHL15), respectively. The non-protein respiratory quotient (npRQ) did not change in short period after the operation. Other outcomes, including liver function test in cirrhotic patients with long-term (1 year) follow-up after splenectomy (n = 7), did not improve significantly. Post-operative complications included portal thrombus (n = 2), ascites (n = 2) were observed in six patients (33%). Conclusion: Splenectomy improved hepatic functional reserve and nutritional metabolism in some cases. However, the long-term outcomes should still be evaluated.","Aim: With the recent advances in medical or surgical treatments in chronic hepatic disorders, the indications for splenectomy in hepatic disorders have greatly expanded. We performed splenectomy for cirrhotic patients and investigated the effects of splenectomy on hepatic functional reserve and nutrition metabolism. Methods: Eighteen patients (Child-Pugh B/C: 12/6; Child-Pugh A: excluded) who underwent splenectomy at our institute between 2005 and 2008 were enrolled. Twelve patients (67%) had hepatocellular carcinoma (HCC), eight of whom met the Milan criteria. Results: Overall survival rate was 83.3% at 1 year and 62.7% at 2 years. The survival rate of six patients with liver cirrhosis classified a Child-Pugh C was 80.0% at 1 year and 60.0% at 2 years. Three patients underwent hepatic resection and nine patients received ablation therapy against hepatocelluar carcinoma. Portal pressure decreased after splenectomy in most patients (mean decrease, 4.7 mmHg). Four weeks after the operation, the markers of hepatic functional reserve, indocyanine green retention rate at 15 min (ICGR15) and Technetium-99m-galactosyl human serum albumin value ((99m)Tc-GSA), improved from 38.5% to 35.1% and from 0.773 to 0.788 (LHL15), respectively. The non-protein respiratory quotient (npRQ) did not change in short period after the operation. Other outcomes, including liver function test in cirrhotic patients with long-term (1 year) follow-up after splenectomy (n = 7), did not improve significantly. Post-operative complications included portal thrombus (n = 2), ascites (n = 2) were observed in six patients (33%). Conclusion: Splenectomy improved hepatic functional reserve and nutritional metabolism in some cases. However, the long-term outcomes should still be evaluated.","null","null","2010-09","Hepatology Research","Hepatology Research","Vol.40","No.9","894","900","eng","true","null","scientific_journal","null","null","10.1111/j.1872-034X.2010.00688.x","1386-6346","null","null","null","null","null"
"ステロイド長期投与患者における周術期ステロイドカバー.","ステロイド長期投与患者における周術期ステロイドカバー.","浅野間 理仁, 森 大樹, 栗田 信浩, 宇都宮 徹, 島田 光生","浅野間 理仁, Hiroki Mori, Nobuhiro Kurita, Toru Utsunomiya, Mitsuo Shimada","null","In patients receiving chronic corticosteroid therapy, the adrenocortical function has decreased because of suppression of the hypothalamic-pituitary-adrenal axis. Under such a condition, it is easy to fall into a serious acute adrenocortical insufficiency during surgical stress. Corticosteroid supplementation is done as prevention of adrenocortical insufficiency. It is changing from corticosteroid supplementation of high dose into that of low dose that based on extrapolation from what constitutes a normal cortisol response to stress in recent years. On the other hand, some authors reported that patients receiving therapeutic doses of corticosteroids who undergo a surgical procedure do not routinely require corticosteroid supplementation so long as they continue to receive their usual daily dose of corticosteroid. Therefore, furthermore investigation should be necessary.","In patients receiving chronic corticosteroid therapy, the adrenocortical function has decreased because of suppression of the hypothalamic-pituitary-adrenal axis. Under such a condition, it is easy to fall into a serious acute adrenocortical insufficiency during surgical stress. Corticosteroid supplementation is done as prevention of adrenocortical insufficiency. It is changing from corticosteroid supplementation of high dose into that of low dose that based on extrapolation from what constitutes a normal cortisol response to stress in recent years. On the other hand, some authors reported that patients receiving therapeutic doses of corticosteroids who undergo a surgical procedure do not routinely require corticosteroid supplementation so long as they continue to receive their usual daily dose of corticosteroid. Therefore, furthermore investigation should be necessary.","null","null","2010-08-25","四国医学雑誌","Shikoku Acta Medica","Vol.66","No.3.4","85","90","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","http://repo.lib.tokushima-u.ac.jp/110320","null","null","null"
"手術機器の使い方-基本と応用- 鏡視下手術用機器 5.リトラクター","手術機器の使い方-基本と応用- 鏡視下手術用機器 5.リトラクター","岩田 貴, 池本 哲也, 栗田 信浩, 西岡 将規, 宇都宮 徹, 島田 光生","Takashi Iwata, Tetsuya Ikemoto, Nobuhiro Kurita, Masanori Nishioka, Toru Utsunomiya, Mitsuo Shimada","null","null","null","null","null","2010-05","手術","Operation","Vol.64","No.6","839","844","jpn","true","null","scientific_journal","null","null","null","0037-4423","null","http://ci.nii.ac.jp/naid/40017137808/","null","null","null"
"特集/必読 最新の肝切除—その2 2.Liver hanging maneuver","特集/必読 最新の肝切除—その2 2.Liver hanging maneuver","森根 裕二, 島田 光生, 宇都宮 徹, 居村 暁, 池本 哲也","Yuji Morine, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Tetsuya Ikemoto","null","null","null","null","null","2010-05","外科","Surgery","Vol.72","No.5","461","465","jpn","true","null","scientific_journal","null","null","null","0016-593X","null","http://ci.nii.ac.jp/naid/40017098406/","null","null","null"
"性差による肝胆膵疾患の臨床,病態,治療効果のDiscrepancy I.性差と各種肝疾患 7)肝移植と性差","性差による肝胆膵疾患の臨床,病態,治療効果のDiscrepancy I.性差と各種肝疾患 7)肝移植と性差","宇都宮 徹, 島田 光生, 居村 暁, 森根 裕二, 池本 哲也, 花岡 潤, 森 大樹, 岩橋 衆一, 斎藤 裕","Toru Utsunomiya, Mitsuo Shimada, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Jun Hanaoka, Hiroki Mori, 岩橋 衆一, 斎藤 裕","null","null","null","null","null","2010-05","肝·胆·膵","KAN TAN SUI","Vol.60","No.5","793","799","jpn","true","null","scientific_journal","null","null","null","0389-4991","null","null","null","null","null"
"Effect of long-term late-evening snack on health-related quality of life in cirrhotic patients.","Effect of long-term late-evening snack on health-related quality of life in cirrhotic patients.","Hisami Okumura, Taki Nakamura, Hidenori Miyake, Harumi Takeuchi, Takafumi Katayama, Yuji Morine, Satoru Imura, Mitsuo Shimada, Eiji Takeda","Hisami Okumura, Taki Nakamura, Hidenori Miyake, Harumi Takeuchi, Takafumi Katayama, Yuji Morine, Satoru Imura, Mitsuo Shimada, Eiji Takeda","null","Aim: In patients with liver cirrhosis, abnormal energy metabolism induces low health-related quality of life (HRQOL) scores. However, late-evening snack (LES) prevents morning starvation in cirrhotic patients. Our aim is to assess the effect of long-term LES on HRQOL in cirrhotic patients, using the 36-item Short Form (SF-36) health survey. Methods: Thirty-nine cirrhotic patients classified as Child-Pugh grade A were recruited. The patients were randomly divided into two groups: 24 were assigned to the non-LES group and 15 to the LES group. SF-36 scores, anthropometric data and serum biochemical parameters were examined in the non-LES and LES groups at 0, 6 and 12 months. Results: Neither anthropometric data nor laboratory data showed significant differences between the non-LES and the LES groups at 0, 6 and 12 months. The role-emotional (RE) HRQOL scores at 6 months and mental health (MH) scores at 6 and 12 months were significantly reduced from the baseline level in the non-LES group. In contrast, these scores remained unchanged in the LES group. General health perception (GH) scores at 12 months, RE at 6 months and MH at 6 and 12 months in the LES group were significantly higher than those of the non-LES group. Conclusion: Long-term LES administration may be helpful in maintaining higher HRQOL in patients with cirrhosis.","Aim: In patients with liver cirrhosis, abnormal energy metabolism induces low health-related quality of life (HRQOL) scores. However, late-evening snack (LES) prevents morning starvation in cirrhotic patients. Our aim is to assess the effect of long-term LES on HRQOL in cirrhotic patients, using the 36-item Short Form (SF-36) health survey. Methods: Thirty-nine cirrhotic patients classified as Child-Pugh grade A were recruited. The patients were randomly divided into two groups: 24 were assigned to the non-LES group and 15 to the LES group. SF-36 scores, anthropometric data and serum biochemical parameters were examined in the non-LES and LES groups at 0, 6 and 12 months. Results: Neither anthropometric data nor laboratory data showed significant differences between the non-LES and the LES groups at 0, 6 and 12 months. The role-emotional (RE) HRQOL scores at 6 months and mental health (MH) scores at 6 and 12 months were significantly reduced from the baseline level in the non-LES group. In contrast, these scores remained unchanged in the LES group. General health perception (GH) scores at 12 months, RE at 6 months and MH at 6 and 12 months in the LES group were significantly higher than those of the non-LES group. Conclusion: Long-term LES administration may be helpful in maintaining higher HRQOL in patients with cirrhosis.","null","null","2010-04-14","Hepatology Research","Hepatology Research","Vol.40","No.5","470","476","eng","true","null","scientific_journal","null","null","10.1111/j.1872-034X.2010.00637.x","1386-6346","null","null","null","null","null"
"CD133 expression is a potential prognostic indicator in intrahepatic cholangiocarcinoma.","CD133 expression is a potential prognostic indicator in intrahepatic cholangiocarcinoma.","Mitsuo Shimada, Koji Sugimoto, Shuichi Iwahashi, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto","Mitsuo Shimada, Koji Sugimoto, Shuichi Iwahashi, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto","null","CD133 is one of the most important cancer-initiating (stem) cell markers and was confirmed to be expressed in solid cancers such as colon cancer. However, no one has investigated the role of CD133 in intrahepatic cholangiocarcinoma (IHCC). The aim of this study was to clarify the clinical role of CD133 expression in IHCC.","CD133 is one of the most important cancer-initiating (stem) cell markers and was confirmed to be expressed in solid cancers such as colon cancer. However, no one has investigated the role of CD133 in intrahepatic cholangiocarcinoma (IHCC). The aim of this study was to clarify the clinical role of CD133 expression in IHCC.","null","null","2010-04-09","Journal of Gastroenterology","Journal of Gastroenterology","Vol.45","No.8","896","902","eng","true","null","scientific_journal","null","null","10.1007/s00535-010-0235-3","1435-5922","null","null","null","null","null"
"胆嚢動脈による偽性総肝管狭窄の1例","Pseudostenosis of the Common Hepatic Duct caused by Compression of the Cystic Artery","荒川 悠佑, 島田 光生, 内山 秀昭, 居村 暁, 森根 裕二, 金村 普史, 花岡 潤, 金本 真美, 杉本 光司, 西 正暁","荒川 悠佑, Mitsuo Shimada, Hideaki Uchiyama, Satoru Imura, Yuji Morine, 金村 普史, Jun Hanaoka, 金本 真美, 杉本 光司, 西 正暁","null","胆道狭窄は悪性疾患を疑う所見である.胆道は直接的診断が困難であり,間接的な画像診断が行われるため,偽性胆管狭窄の報告がみられる.症例は74歳の女性で,診断は胆嚢腫瘍および総肝管狭窄であった.超音波内視鏡検査では胆嚢腫瘍は最大径12mmであり,また総肝管狭窄は胆嚢癌の総肝管浸潤や胆管癌による可能性が否定できなかったため開腹胆嚢摘出術および術中胆道造影検査を施行した.術中所見では総肝管は胆嚢動脈に圧排されており,狭窄の原因と考えられた.胆嚢動脈の切離後,総胆管を切開し狭窄部を確認するも病変は認められなかった.胆道造影検査でも狭窄像は認められなかった.胆嚢内には12mm大の隆起性病変を認め,深達度mpの早期胆嚢癌であった.今回,我々は胆嚢動脈の圧排によって画像上偽性総肝管狭窄を生じた胆嚢癌の1例を経験したので文献的考察を加えて報告する.","Bile duct way stenosis mimic malignant such as cholangiocellular carcinoma lesions and gall bladder carcinoma invasion. A 74-year-old woman a gallbladder (GB) polyp combined with common hepatic duct (CHD) stenosis was found in admitted for surgery to treat. Preoperative evaluation revealed to have a polypoid tumor 12mm in diameter and relatively smooth CHD stenosis. Because the possibility of malignancy could not be excluded, she underwent open abdominal surgery. We conducted the usual cholecystectomy. The CHD was compressed by the cystic artery, so we thoroughly confirmed the absence of any suspicious CHD lesion by directly inspecting the inner side of the stricture by choledochotomy. The definitive diagnosis of the GB tumor was early GB carcinoma. Although CHD compression by the cystic artery is considered uncommon, we suggest that it should be included in the differential diagnosis of extrahepatic biliary stenosis, especially when biliary stenosis is relatively smooth.","null","null","2010-04-01","日本消化器外科学会雑誌","The Japanese Journal of Gastroenterological Surgery","Vol.43","No.4","405","410","jpn","true","null","scientific_journal","null","null","10.5833/jjgs.43.405","0386-9768","null","http://ci.nii.ac.jp/naid/110007593901/","null","null","null"
"High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer.","High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer.","Lu Elaine Wang, Zhi-Rong Qian, Masahiko Nakasono, Toshihito Tanahashi, Katsuhiko Yoshimoto, Yoshimi Bando, Eiji Kudo, Mitsuo Shimada, Toshiaki Sano","Lu Elaine Wang, Zhi-Rong Qian, Masahiko Nakasono, Toshihito Tanahashi, Katsuhiko Yoshimoto, Yoshimi Bando, Eiji Kudo, Mitsuo Shimada, Toshiaki Sano","null","BACKGROUND: The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC). METHODS: The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed. RESULTS: Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P=0.0001, P=0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15-4.07; P=0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31-4.13; P=0.0038 and HR: 3.03; 95% CI: 1.67-5.48; P=0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27-3.99; P=0.0053 and HR: 2.97; 95% CI: 1.64-5.38; P=0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99-3.55; P=0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01-3.67; P=0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17-4.33; P=0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS. CONCLUSION: Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC.","BACKGROUND: The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC). METHODS: The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed. RESULTS: Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P=0.0001, P=0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15-4.07; P=0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31-4.13; P=0.0038 and HR: 3.03; 95% CI: 1.67-5.48; P=0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27-3.99; P=0.0053 and HR: 2.97; 95% CI: 1.64-5.38; P=0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99-3.55; P=0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01-3.67; P=0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17-4.33; P=0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS. CONCLUSION: Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC.","null","null","2010-02-09","British Journal of Cancer","British Journal of Cancer","Vol.102","No.5","908","915","eng","true","null","scientific_journal","null","null","10.1038/sj.bjc.6605558","1532-1827","null","null","null","null","null"
"Bevasizumab併用化学療法中に緊急手術をした2例.","Two Cases of Emergency Operations in Patients Undergoing Bevacizumab Treatment","吉川 幸造, 島田 光生, 栗田 信浩, 西岡 将規, 森本 慎也, 東島 潤, 宮谷 知彦, 宮本 英典, 寺嶋 吉保","Kouzou Yoshikawa, Mitsuo Shimada, Nobuhiro Kurita, Masanori Nishioka, Shinya Morimoto, Jun Higashijima, Tomohiko Miyatani, Hidenori Miyamoto, Yoshiyasu Terashima","null","Bevacizumab使用中の手術は創傷治癒遅延のため投与後4∼6週間以降に施行することが推奨されているが,消化管穿孔などでは緊急手術が必要となる.今回,Bevacizumab使用中に緊急手術行った2例を報告する.症例1,50歳代男性.下行結腸癌同時性肝転移肺転移と診断され,腫瘍によるイレウスに対して人工肛門造設術を施行,その後,腫瘍の後腹膜への穿通に対して結腸左半切除術を施行.8日後に腸腰筋膿瘍に対して洗浄ドレナージ術を施行.症例2,70歳代男性.虫垂粘液嚢胞腺癌,腹膜播種と診断され治療を行っていた.消化管穿孔に対して緊急手術を施行.横行結腸に穿孔部が認められたが高度の癌性腹膜炎の状態であり洗浄ドレナージ術を施行し治療した.Bevacizumab使用時において消化管吻合が可能な場合においても吻合を行わず,人工肛門造設による2期的手術を行い,人工肛門閉鎖については,十分なBevacizumab休薬期間と原疾患の進行状況に合わせてその時期を検討する必要がある.
","Bevacizumab has become a widely used intervention in patients with advanced colon cancer. In view that a negative effect of wound healing has been reported, surgery should be performed 4-6 weeks after the last treatment. This study examined the approaches to the management of emergency operations in patients undergoing bevacizumab treatment. In this report, four operations were performed for two patients undergoing bevacizumab treatment. Surgical complications and the postoperative course were examined. Case1: The patient was a male in his 50s with descending colon cancer, multiple liver metastasis and lung metastasis. This patient was suffering from ileus due to descending colon cancer. A transverse colostomy was performed. In addition, a descending colectomy and drainage were conducted for the retroperitoneal abscess formation. Case2: The patient was a male in his 70s with mucinous cystadenocarcinoma of the appendix and carcinomatous peritonitis. This patient was suffering from abdominal pain. As a CT showed free air, an emergency operation was performed. Drainage was also performed. The extent of the surgical procedures should be limited, and construction of a stomy should be preferred to primary anastomosis.
","null","null","2010-02-01","日本大腸肛門病学会雑誌","Journal of the Japan Society of Coloproctology","Vol.63","No.2","56","60","jpn","true","null","scientific_journal","null","null","10.3862/jcoloproctology.63.56","1882-9619","null","http://ci.nii.ac.jp/naid/10026313732/","null","null","null"
"Expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) in patients with the gallbladder carcinoma.","Expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) in patients with the gallbladder carcinoma.","Erdenebulgan Batmunkh, Mitsuo Shimada, Yuji Morine, Satoru Imura, Hirofumi Kanemura, Yusuke Arakawa, Jun Hanaoka, Mami Kanamoto, Koji Sugimoto, Masaaki Nishi","Erdenebulgan Batmunkh, Mitsuo Shimada, Yuji Morine, Satoru Imura, Hirofumi Kanemura, Yusuke Arakawa, Jun Hanaoka, Mami Kanamoto, Koji Sugimoto, Masaaki Nishi","null","Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a central role in biologic processes under hypoxic conditions, especially concerning tumor angiogenesis. Vascular endothelial growth factor (VEGF) is a potent proangiogenic agent and a multifunctional angiogenic cytokine in many malignant tumors.","Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a central role in biologic processes under hypoxic conditions, especially concerning tumor angiogenesis. Vascular endothelial growth factor (VEGF) is a potent proangiogenic agent and a multifunctional angiogenic cytokine in many malignant tumors.","null","null","2010-02","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.15","No.1","59","64","eng","true","null","scientific_journal","null","null","10.1007/s10147-009-0011-7","1437-7772","null","null","null","null","null"
"Ⅰ.消化管 20. 肛門癌","Ⅰ.消化管 20. 肛門癌","宮谷 知彦, 西岡 将規, 島田 光生","Tomohiko Miyatani, Masanori Nishioka, Mitsuo Shimada","null","null","null","null","null","2010","外科","Surgery","Vol.72","No.12","1356","1359","jpn","true","null","scientific_journal","null","null","null","0016-593X","null","null","null","null","null"
"肝癌ステージングと予後推定.","肝癌ステージングと予後推定.","森本 慎也, 島田 光生, 宇都宮 徹, 居村 暁, 森根 裕二, 池本 哲也, 森 大樹, 花岡 潤","Shinya Morimoto, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka","null","null","null","null","null","2010","臨床消化器内科","臨床消化器内科","Vol.25","No.4","399","494","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"人工臓器.","人工臓器.","岩田 貴, 島田 光生","Takashi Iwata, Mitsuo Shimada","null","null","null","null","null","2010","標準外科学 第12版","標準外科学 第12版","null","null","213","225","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"S上結腸SM癌に対するS状結腸切除 D2郭清.","S上結腸SM癌に対するS状結腸切除 D2郭清.","西岡 将規, 島田 光生, 東島 潤, 宮谷 知彦","Masanori Nishioka, Mitsuo Shimada, Jun Higashijima, Tomohiko Miyatani","null","null","null","null","null","2010","腹腔鏡下大腸手術の基本手術手技","腹腔鏡下大腸手術の基本手術手技","null","null","1","35","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"Predictive factors of peritoneal metastasis in gastric cancer.","Predictive factors of peritoneal metastasis in gastric cancer.","Nobuhiro Kurita, Mitsuo Shimada, Toru Utsunomiya, Takashi Iwata, Masanori Nishioka, Kouzou Yoshikawa, Tomohiko Miyatani, Jun Higashijima, Toshihiro Nakao","Nobuhiro Kurita, Mitsuo Shimada, Toru Utsunomiya, Takashi Iwata, Masanori Nishioka, Kouzou Yoshikawa, Tomohiko Miyatani, Jun Higashijima, Toshihiro Nakao","null","Preoperative radiological diagnosis of gastric cancer with peritoneal metastasis is still incomplete. Staging laparoscopy is performed for patients who are diagnosed T3 or T4 preoperatively. The aim of this study is to establish a method for predicting peritoneal metastasis.","Preoperative radiological diagnosis of gastric cancer with peritoneal metastasis is still incomplete. Staging laparoscopy is performed for patients who are diagnosed T3 or T4 preoperatively. The aim of this study is to establish a method for predicting peritoneal metastasis.","null","null","2010","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.57","No.101","980","983","eng","true","null","scientific_journal","null","null","null","0172-6390","null","null","null","null","null"
"脂肪肝グラフトを用いた肝移植における移植後グラフト機能不全の機序解明.","脂肪肝グラフトを用いた肝移植における移植後グラフト機能不全の機序解明.","島田 光生","Mitsuo Shimada","null","null","null","null","null","2010","上原記念生命化学財団研究報告集","上原記念生命化学財団研究報告集","Vol.24","null","1","7","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"特集/消化器外科データベースの構築とその展開4. 高度技能医制度を包括するデータベース.","特集/消化器外科データベースの構築とその展開4. 高度技能医制度を包括するデータベース.","宇都宮 徹, 島田 光生, 三浦 文彦, 山本 雅一, 高田 忠敬","Toru Utsunomiya, Mitsuo Shimada, 三浦 文彦, 山本 雅一, 高田 忠敬","null","null","null","null","null","2010","Surgery Frontier","Surgery Frontier","Vol.17","No.4","32","38","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"全国集計からみた先天性胆道拡張症, 膵・胆管合流異常の胆道癌発生率とその特徴","全国集計からみた先天性胆道拡張症, 膵・胆管合流異常の胆道癌発生率とその特徴","森根 裕二, 島田 光生, 久山 寿子, 高松 英夫, 田代 征記","Yuji Morine, Mitsuo Shimada, 久山 寿子, 高松 英夫, Seiki Tashiro","null","null","null","null","null","2010","胆と膵","胆と膵","Vol.31","No.11","1293","1299","jpn","true","null","scientific_journal","null","null","null","null","null","http://ci.nii.ac.jp/naid/50007642709/","null","null","null"
"肝移植の画像診断ー生体ドナーの安全とレシピエントの予後向上をめざしてー","肝移植の画像診断ー生体ドナーの安全とレシピエントの予後向上をめざしてー","宇都宮 徹, 島田 光生, 居村 暁, 森根 裕二, 池本 哲也, 花岡 潤, 金本 真美, 岩橋 衆一, 斎藤 裕","Toru Utsunomiya, Mitsuo Shimada, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Jun Hanaoka, 金本 真美, 岩橋 衆一, 斎藤 裕","null","null","null","null","null","2010","肝胆膵画像","肝胆膵画像","Vol.2","No.1","69","78","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"メタボリックシンドロームと肝細胞癌","メタボリックシンドロームと肝細胞癌","花岡 潤, 島田 光生, 宇都宮 徹, 居村 暁, 森根 裕二, 池本 哲也, 森本 慎也, 森 大樹","Jun Hanaoka, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Shinya Morimoto, Hiroki Mori","null","null","null","null","null","2010","G.I.Research","G.I.Research","Vol.18","No.3","224","230","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"肝・胆・膵手術と漢方","肝・胆・膵手術と漢方","森 大樹, 島田 光生, 森根 裕二, 居村 暁, 吉川 幸造, 宇都宮 徹","Hiroki Mori, Mitsuo Shimada, Yuji Morine, Satoru Imura, Kouzou Yoshikawa, Toru Utsunomiya","null","null","null","null","null","2010","G.I.Research","G I Research","Vol.18","No.4","313","320","jpn","true","null","scientific_journal","null","null","null","null","null","http://ci.nii.ac.jp/naid/50007535666/","null","null","null"
"腹腔鏡下肝切除:腹腔鏡下肝切除術における最近の話題 ∼気腹とガス塞栓∼.","腹腔鏡下肝切除:腹腔鏡下肝切除術における最近の話題 ∼気腹とガス塞栓∼.","居村 暁, 花岡 潤, 森 大樹, 池本 哲也, 森根 裕二, 宇都宮 徹, 三宅 秀則, 島田 光生","Satoru Imura, Jun Hanaoka, Hiroki Mori, Tetsuya Ikemoto, Yuji Morine, Toru Utsunomiya, Hidenori Miyake, Mitsuo Shimada","null","null","null","null","null","2010","消化器外科","消化器外科","Vol.33","No.9","1439","1444","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"肝・胆道系症候群(Ⅱ)— その他の肝・胆道系疾患を含めて - 肝臓編(下)第2版 XIV 肝細胞癌以外の肝腫瘍 「原発性肝肉腫(Primary hepatic sarcoma)」","肝・胆道系症候群(Ⅱ)— その他の肝・胆道系疾患を含めて - 肝臓編(下)第2版 XIV 肝細胞癌以外の肝腫瘍 「原発性肝肉腫(Primary hepatic sarcoma)」","宇都宮 徹, 島田 光生, 居村 暁, 森根 裕二, 池本 哲也","Toru Utsunomiya, Mitsuo Shimada, Satoru Imura, Yuji Morine, Tetsuya Ikemoto","null","null","null","null","null","2010","日本臨床2010","日本臨床2010","null","null","276","280","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"乳癌が併存するレシピエント,高度脂肪肝ドナーという組み合わせに施行した生体肝移植.","乳癌が併存するレシピエント,高度脂肪肝ドナーという組み合わせに施行した生体肝移植.","池本 哲也, 島田 光生, 岩橋 衆一, 川田 祐子, 齋藤 裕, 花岡 潤, 森 大樹, 居村 暁, 森根 裕二, 宇都宮 徹","Tetsuya Ikemoto, Mitsuo Shimada, Shuichi Iwahashi, 川田 祐子, Yu Saitou, Jun Hanaoka, Hiroki Mori, Satoru Imura, Yuji Morine, Toru Utsunomiya","null","null","null","null","null","2010","臨床と研究","The Japanese journal of clinical and experimental medicine","Vol.87","No.9","1280","1281","jpn","true","null","scientific_journal","null","null","null","0021-4965","null","null","null","null","null"
"血液型不適合肝移植後interferon治療に難渋したC型肝炎の1例","血液型不適合肝移植後interferon治療に難渋したC型肝炎の1例","花岡 潤, 島田 光生, 宇都宮 徹, 居村 暁, 森根 裕二, 池本 哲也, 森 大樹","Jun Hanaoka, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Hiroki Mori","null","null","null","null","null","2010","臨床と研究","The Japanese journal of clinical and experimental medicine","Vol.87","No.9","1330","1331","jpn","true","null","scientific_journal","null","null","null","0021-4965","null","null","null","null","null"
"Downregulation of matrix metalloprotease-9 and urokinase plasminogen activator by TX-1877 results in decreased tumor growth and metastasis on xenograft model of rectal cancer","Downregulation of matrix metalloprotease-9 and urokinase plasminogen activator by TX-1877 results in decreased tumor growth and metastasis on xenograft model of rectal cancer","Kotaro Miyake, Mitsuo Shimada, Masanori Nishioka, Koji Sugimoto, Erdenebulgan Batmunkh, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori","Kotaro Miyake, Mitsuo Shimada, Masanori Nishioka, Koji Sugimoto, Erdenebulgan Batmunkh, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori","null","Purpose It is well known that hypoxic milieu is the primary cancer environment. Therefore, tumor hypoxia is considered to be a potential therapeutic target. In the present study, we investigated the antitumor and antimetastatic effect of hypoxic cell radiosensitizer, TX-1877 on xenograft model of rectal cancer. Methods Nude mice bearing subcutaneously or orthotopically implanted human colon cancer cell lines HCT-116 and HT-29 were treated with TX-1877, irradiation or TX-1877 with irradiation. Tumor volume, survival, expression of matrix metalloproteinase (MMP)-2, MMP-7, MMP-9 and urokinase-type plasminogen activator (uPA) and incidence of lymph node metastasis were evaluated in treatment versus control group. Results In subcutaneous model, tumor treated with TX-1877 and irradiation showed significant reductions in volume (P < 0.05 vs. control, TX-1877 or irradiation group). Quantitative real-time reverse transcription-PCR and immunohistochemical analysis revealed that TX-1877 significantly inhibited expression of the MMP-9 and uPA. These treatments also inhibited the para-aortic lymph node metastasis, however, did not prolong the survival in orthotopic model. Conclusions These data show that the treatment of TX-1877 with irradiation decreased growth of human rectal cancer and, furthermore, suppressed lymph node metastasis.","Purpose It is well known that hypoxic milieu is the primary cancer environment. Therefore, tumor hypoxia is considered to be a potential therapeutic target. In the present study, we investigated the antitumor and antimetastatic effect of hypoxic cell radiosensitizer, TX-1877 on xenograft model of rectal cancer. Methods Nude mice bearing subcutaneously or orthotopically implanted human colon cancer cell lines HCT-116 and HT-29 were treated with TX-1877, irradiation or TX-1877 with irradiation. Tumor volume, survival, expression of matrix metalloproteinase (MMP)-2, MMP-7, MMP-9 and urokinase-type plasminogen activator (uPA) and incidence of lymph node metastasis were evaluated in treatment versus control group. Results In subcutaneous model, tumor treated with TX-1877 and irradiation showed significant reductions in volume (P < 0.05 vs. control, TX-1877 or irradiation group). Quantitative real-time reverse transcription-PCR and immunohistochemical analysis revealed that TX-1877 significantly inhibited expression of the MMP-9 and uPA. These treatments also inhibited the para-aortic lymph node metastasis, however, did not prolong the survival in orthotopic model. Conclusions These data show that the treatment of TX-1877 with irradiation decreased growth of human rectal cancer and, furthermore, suppressed lymph node metastasis.","null","null","2009-10","Cancer Chemotherapy and Pharmacology","Cancer Chemotherapy and Pharmacology","Vol.64","No.5","885","892","eng","true","null","scientific_journal","null","null","10.1007/s00280-009-0937-5","1432-0843","null","null","null","null","null"
"Dual hepatic artery reconstruction in living donor liver transplantation using a left hepatic graft with 2 hepatic arterial stumps.","Dual hepatic artery reconstruction in living donor liver transplantation using a left hepatic graft with 2 hepatic arterial stumps.","Hideaki Uchiyama, Noboru Harada, Kensaku Sanefuji, Hiroto Kayashima, Akinobu Taketomi, Yuji Soejima, Toru Ikegami, Mitsuo Shimada, Yoshihiko Maehara","Hideaki Uchiyama, Noboru Harada, Kensaku Sanefuji, Hiroto Kayashima, Akinobu Taketomi, Yuji Soejima, Toru Ikegami, Mitsuo Shimada, Yoshihiko Maehara","null","A left hepatic graft in living donor liver transplantation (LDLT) often has 2 thin and short hepatic arterial stumps, which makes hepatic artery (HA) reconstructions much more difficult to perform. Consequently, some investigators regard using a left graft as a contraindication to LDLT, whereas others report that the reconstruction of only 1 HA is sufficient for most LDLTs. The aim of this retrospective study was to investigate whether 2 HAs on a left hepatic graft in an LDLT can be reconstructed safely and whether the outcomes of LDLTs are affected by reconstructing both HAs (dual reconstruction).","A left hepatic graft in living donor liver transplantation (LDLT) often has 2 thin and short hepatic arterial stumps, which makes hepatic artery (HA) reconstructions much more difficult to perform. Consequently, some investigators regard using a left graft as a contraindication to LDLT, whereas others report that the reconstruction of only 1 HA is sufficient for most LDLTs. The aim of this retrospective study was to investigate whether 2 HAs on a left hepatic graft in an LDLT can be reconstructed safely and whether the outcomes of LDLTs are affected by reconstructing both HAs (dual reconstruction).","null","null","2009-09-15","Surgery","Surgery","Vol.147","No.6","878","886","eng","true","null","scientific_journal","null","null","10.1016/j.surg.2009.06.028","1532-7361","null","null","null","null","null"
"② 意外に難しいスライディング・スケール法による血糖管理 --- 人工膵臓を用いた外科手術周術期血糖管理法","② 意外に難しいスライディング・スケール法による血糖管理 --- 人工膵臓を用いた外科手術周術期血糖管理法","川人 伸次, 中村 智芳, 神邊 紀子, 北畑 洋, 島田 光生, 西村 匡司, 大下 修造","Shinji Kawahito, 中村 智芳, 神邊 紀子, Hiroshi Kitahata, Mitsuo Shimada, Masaji Nishimura, Shuzo Oshita","null","null","null","null","null","2008-11-15","胆と膵","胆と膵","Vol.29","No.11","1021","1028","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"The novel hypoxic cell radiosensitizer, TX-1877 has antitumor activity through suppression of angiogenesis and inhibits liver metastasis on xenograft model of pancreatic cancer.","The novel hypoxic cell radiosensitizer, TX-1877 has antitumor activity through suppression of angiogenesis and inhibits liver metastasis on xenograft model of pancreatic cancer.","Kotaro Miyake, Mitsuo Shimada, Masanori Nishioka, Koji Sugimoto, Erdenebulgan Batmunkh, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori","Kotaro Miyake, Mitsuo Shimada, Masanori Nishioka, Koji Sugimoto, Erdenebulgan Batmunkh, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori","null","Tumor hypoxia has been considered to be a potential therapeutic target, because hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. In the present study, we investigated the antitumor effect of hypoxic cell radiosensitizer, TX-1877 in inhibiting angiogenesis and liver metastasis on pancreatic cancer xenograft model. The antitumor effects of TX-1877 were tested against various human tumor cell lines using cell proliferation assay. Nude mice bearing s.c. or orthotopically implanted human SUIT-2 were treated with TX-1877 alone, irradiation alone or TX-1877 and irradiation. Tumor volume, survival, expression of angiogenic molecules and liver metastasis were evaluated in treatment versus control groups. In vitro, TX-1877 inhibited the proliferation and potentiated the radiosensitivity of various pancreatic cancer cell lines. In an orthotopic model, tumors from nude mice injected with pancreatic cancer cells and treated with TX-1877 and irradiation showed significant reductions in volume (p<0.05 versus control, TX-1877 alone or irradiation alone). Quantitative real-time reverse transcription-PCR and immunohistochemical analysis revealed that treatment with TX-1877 alone or with TX-1877 and irradiation inhibited expression of the angiogenic molecules, vascular endothelial growth factor; basic fibroblast growth factor, interleukin-8 and matrix metalloproteinase 9 more than control or did treatment with irradiation alone. These treatments also induced apoptosis in cancer cells. These data show that treatment of TX-1877 and irradiation decreased growth of human pancreatic cancer, suppressed angiogenesis and inhibited liver metastasis, leading to prolonged survival.","Tumor hypoxia has been considered to be a potential therapeutic target, because hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. In the present study, we investigated the antitumor effect of hypoxic cell radiosensitizer, TX-1877 in inhibiting angiogenesis and liver metastasis on pancreatic cancer xenograft model. The antitumor effects of TX-1877 were tested against various human tumor cell lines using cell proliferation assay. Nude mice bearing s.c. or orthotopically implanted human SUIT-2 were treated with TX-1877 alone, irradiation alone or TX-1877 and irradiation. Tumor volume, survival, expression of angiogenic molecules and liver metastasis were evaluated in treatment versus control groups. In vitro, TX-1877 inhibited the proliferation and potentiated the radiosensitivity of various pancreatic cancer cell lines. In an orthotopic model, tumors from nude mice injected with pancreatic cancer cells and treated with TX-1877 and irradiation showed significant reductions in volume (p<0.05 versus control, TX-1877 alone or irradiation alone). Quantitative real-time reverse transcription-PCR and immunohistochemical analysis revealed that treatment with TX-1877 alone or with TX-1877 and irradiation inhibited expression of the angiogenic molecules, vascular endothelial growth factor; basic fibroblast growth factor, interleukin-8 and matrix metalloproteinase 9 more than control or did treatment with irradiation alone. These treatments also induced apoptosis in cancer cells. These data show that treatment of TX-1877 and irradiation decreased growth of human pancreatic cancer, suppressed angiogenesis and inhibited liver metastasis, leading to prolonged survival.","null","null","2008-08-30","Cancer Letters","Cancer Letters","Vol.272","No.2","325","335","eng","true","null","scientific_journal","null","null","10.1016/j.canlet.2008.07.020","1872-7980","null","null","null","null","null"
"Geranylgeranylacetone prevents acute liver damage after massive hepatectomy in rats through suppression of a CXC chemokine GRO1 and induction of heat shock proteins.","Geranylgeranylacetone prevents acute liver damage after massive hepatectomy in rats through suppression of a CXC chemokine GRO1 and induction of heat shock proteins.","Hirofumi Kanemura, Kenji Kusumoto, Hidenori Miyake, Seiki Tashiro, Kazuhito Rokutan, Mitsuo Shimada","Hirofumi Kanemura, Kenji Kusumoto, Hidenori Miyake, Seiki Tashiro, Kazuhito Rokutan, Mitsuo Shimada","null","BACKGROUND AND METHODS: Acute liver failure after massive hepatectomy remains a challenging problem. In this study, using a microarray designed to monitor the side effects of drugs, we examined changes in gene expression in the remnant liver during the 24 h after hepatectomy and the effects of a nontoxic heat shock protein (HSP) 70 inducer, geranylgeranylacetone (GGA), after 90% hepatectomy in rats. RESULTS: A single oral administration of 100 mg/kg GGA significantly suppressed the release of aminotransferases and improved survival compared with vehicle administration. The hepatectomy upregulated 74 genes and downregulated 95. Interestingly, ten cytokine genes were upregulated, while no cytokine-related gene was downregulated. Among the ten cytokine genes, a potent chemoattractant for neutrophils, GRO1, was most rapidly and markedly upregulated after 90% hepatectomy. GGA effectively suppressed the up-regulation of GRO1 messenger ribonucleic acid, and this was validated by Northern hybridization. Microarray and immunoblot analyses showed that, in addition to HSP70 and HSP27, GGA preferentially induced an endoplasmic reticulum chaperone, BIP. CONCLUSION: Considering hemodynamic and metabolic overloading as a primary cause of acute lever failure, the ER stress response enhanced by GGA may also play an important role in the prevention of overload-induced liver damage.","BACKGROUND AND METHODS: Acute liver failure after massive hepatectomy remains a challenging problem. In this study, using a microarray designed to monitor the side effects of drugs, we examined changes in gene expression in the remnant liver during the 24 h after hepatectomy and the effects of a nontoxic heat shock protein (HSP) 70 inducer, geranylgeranylacetone (GGA), after 90% hepatectomy in rats. RESULTS: A single oral administration of 100 mg/kg GGA significantly suppressed the release of aminotransferases and improved survival compared with vehicle administration. The hepatectomy upregulated 74 genes and downregulated 95. Interestingly, ten cytokine genes were upregulated, while no cytokine-related gene was downregulated. Among the ten cytokine genes, a potent chemoattractant for neutrophils, GRO1, was most rapidly and markedly upregulated after 90% hepatectomy. GGA effectively suppressed the up-regulation of GRO1 messenger ribonucleic acid, and this was validated by Northern hybridization. Microarray and immunoblot analyses showed that, in addition to HSP70 and HSP27, GGA preferentially induced an endoplasmic reticulum chaperone, BIP. CONCLUSION: Considering hemodynamic and metabolic overloading as a primary cause of acute lever failure, the ER stress response enhanced by GGA may also play an important role in the prevention of overload-induced liver damage.","null","null","2008-08-06","Journal of Gastrointestinal Surgery","Journal of Gastrointestinal Surgery","Vol.13","No.1","66","73","eng","true","null","scientific_journal","null","null","10.1007/s11605-008-0604-x","1873-4626","null","null","null","null","null"
"Dendritic cell-mediated NK cell activation is controlled by Jagged2-Notch interaction.","Dendritic cell-mediated NK cell activation is controlled by Jagged2-Notch interaction.","Mika Kijima, Takeshi Yamaguchi, Chieko Ishifune, Yoichi Maekawa, Akemi Koyanagi, HIdeo Yagita, Shigeru Chiba, Kenji Kishihara, Mitsuo Shimada, Koji Yasutomo","Mika Kijima, Takeshi Yamaguchi, Chieko Ishifune, Yoichi Maekawa, Akemi Koyanagi, HIdeo Yagita, Shigeru Chiba, Kenji Kishihara, Mitsuo Shimada, Koji Yasutomo","null","Natural killer (NK) cells regulate various immune responses by exerting cytotoxic activity or secreting cytokines. The interaction of NK cells with dendritic cells (DC) contributes to NK cell-mediated antitumor or antimicrobial responses. However, the cellular and molecular mechanisms for controlling this interaction are largely unknown. Here, we show an involvement of Jagged2-Notch interaction in augmenting NK cell cytotoxicity mediated by DC. Enforced expression of Jagged2 on A20 cells (Jag2-A20 cells) suppressed their growth in vivo, which was abrogated by depleting NK cells. Moreover, Jag2-A20 cells exerted a suppression on the growth of nonmanipulated A20 cells in SCID mice in an NK-dependent manner. Consistently, coinoculation of A20 cells with DC overexpressing Jagged2 (Jag2-DC) suppressed the growth of A20 cells in mice. Stimulation of NK cells with Jagged2 directly enhanced their cytotoxicity, IFN-gamma production, and proliferation. Ligation of Notch2 on NK cells enhanced their cytotoxic activity, and Jag2-DC or CpG-treated DC-mediated NK cell cytotoxicity was suppressed by a gamma-secretase inhibitor. These results indicate that the Jagged2-Notch axis plays a crucial role in DC-mediated NK cell cytotoxicity. Furthermore, manipulation of this interaction may provide an approach to induce potent tumor immunity or to inhibit certain autoimmune diseases caused by NK cell activation.","Natural killer (NK) cells regulate various immune responses by exerting cytotoxic activity or secreting cytokines. The interaction of NK cells with dendritic cells (DC) contributes to NK cell-mediated antitumor or antimicrobial responses. However, the cellular and molecular mechanisms for controlling this interaction are largely unknown. Here, we show an involvement of Jagged2-Notch interaction in augmenting NK cell cytotoxicity mediated by DC. Enforced expression of Jagged2 on A20 cells (Jag2-A20 cells) suppressed their growth in vivo, which was abrogated by depleting NK cells. Moreover, Jag2-A20 cells exerted a suppression on the growth of nonmanipulated A20 cells in SCID mice in an NK-dependent manner. Consistently, coinoculation of A20 cells with DC overexpressing Jagged2 (Jag2-DC) suppressed the growth of A20 cells in mice. Stimulation of NK cells with Jagged2 directly enhanced their cytotoxicity, IFN-gamma production, and proliferation. Ligation of Notch2 on NK cells enhanced their cytotoxic activity, and Jag2-DC or CpG-treated DC-mediated NK cell cytotoxicity was suppressed by a gamma-secretase inhibitor. These results indicate that the Jagged2-Notch axis plays a crucial role in DC-mediated NK cell cytotoxicity. Furthermore, manipulation of this interaction may provide an approach to induce potent tumor immunity or to inhibit certain autoimmune diseases caused by NK cell activation.","null","null","2008-05-13","Proceedings of the National Academy of Sciences of the United States of America","Proceedings of the National Academy of Sciences of the United States of America","Vol.105","No.19","7010","7015","eng","true","null","scientific_journal","null","null","10.1073/pnas.0709919105","1091-6490","null","null","null","null","null"
"The effect of transgenic expression of TGF-beta1 on transplanted islet graft survival.","The effect of transgenic expression of TGF-beta1 on transplanted islet graft survival.","S Yamasaki, N Kurita, J Hata, Maki Moritani, Mitsuo Itakura, Mitsuo Shimada","S Yamasaki, N Kurita, J Hata, Maki Moritani, Mitsuo Itakura, Mitsuo Shimada","null","Transgenic mice expressing the active form of porcine TGF-beta1 (NOD- TGF-beta1 Tg) were completely protected from autoimmune diabetes in the NOD genetic background in our previous study. Here, we attempted to determine whether transgenic expression of TGF-beta1 in transplanted islets prevents autoimmune destruction in NOD mice. We transplanted islets to the subcapsular region of the kidney using NOD-TGF-beta1 Tg and NOD mice as donor and recipient or vice versa. Cyclophosphamide was administered twice to streptozocin-induced diabetic females NOD-TGF-beta1 Tg or their female littermates after islet transplantation. All islets grafts of NOD-TGF-beta1 Tg in spontaneously diabetic NOD mice were rejected earlier than those of their littermates. Hyperglycemia was induced in all littermates, but three out of four NOD-TGF-beta1 Tg, which were STZ-induced diabetic female mice, remained normoglycemic in response to the administration of cyclophosphamide after islet transplantation. Our results lack direct evidence for the local paracrine TGF-beta1 to protect the transplanted islet grafts. We observed, however, prolonged survival of NOD islets grafts in diabetic NOD-TGF-beta1 Tg suggesting the protective role of transgenic TGF-beta1 to suppress the autoimmune process in our syngenic transplantation model. We are convinced that this data could help resolve many problems regarding islet transplantation for type 1 diabetes.","Transgenic mice expressing the active form of porcine TGF-beta1 (NOD- TGF-beta1 Tg) were completely protected from autoimmune diabetes in the NOD genetic background in our previous study. Here, we attempted to determine whether transgenic expression of TGF-beta1 in transplanted islets prevents autoimmune destruction in NOD mice. We transplanted islets to the subcapsular region of the kidney using NOD-TGF-beta1 Tg and NOD mice as donor and recipient or vice versa. Cyclophosphamide was administered twice to streptozocin-induced diabetic females NOD-TGF-beta1 Tg or their female littermates after islet transplantation. All islets grafts of NOD-TGF-beta1 Tg in spontaneously diabetic NOD mice were rejected earlier than those of their littermates. Hyperglycemia was induced in all littermates, but three out of four NOD-TGF-beta1 Tg, which were STZ-induced diabetic female mice, remained normoglycemic in response to the administration of cyclophosphamide after islet transplantation. Our results lack direct evidence for the local paracrine TGF-beta1 to protect the transplanted islet grafts. We observed, however, prolonged survival of NOD islets grafts in diabetic NOD-TGF-beta1 Tg suggesting the protective role of transgenic TGF-beta1 to suppress the autoimmune process in our syngenic transplantation model. We are convinced that this data could help resolve many problems regarding islet transplantation for type 1 diabetes.","null","null","2007-09","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.54","No.78","1617","1621","eng","true","null","scientific_journal","null","null","null","0172-6390","null","null","null","null","null"
"Relationship between mucin expression and preoperatie bile juice cytology in biliary tract carcinoma","Relationship between mucin expression and preoperatie bile juice cytology in biliary tract carcinoma","Yoshitaka Imoto, Naoki Muguruma, Tetsuo Kimura, Eriko Aoyagi, Koichi Okamoto, Seisuke Okamura, Susumu Ito, Nobuya Sano, Mitsuo Shimada","Yoshitaka Imoto, Naoki Muguruma, Tetsuo Kimura, Eriko Aoyagi, Koichi Okamoto, Seisuke Okamura, Susumu Ito, Nobuya Sano, Mitsuo Shimada","null","The present study evaluated correlations between preoperative bile juice cytology and mucin expression of surgical specimens in biliary tract carcinoma. Twenty-five patients with biliary tract carcinoma surgically treated at our hospital, whose bile juice cytology had been evaluated before operation, were allocated to this study. Biliary cytology was classified into three categories based on the Papanicolaou classification. Immunohistochemical staining of tissues was performed using MUC1 and MUC2 monoclonal antibodies. Lesions showing MUC1 expression of ++ or higher and MUC2 expression of - were classified as Group A, and the remaining lesions as Group B. According to the epithelial site, preoperative cytology was highly correlated in Group A, while it was negative in Group B (p<0.05). In the advanced site of carcinomas, preoperative cytology tended to highly be positive in Group A, while it tended to be negative in Group B (p<0.05). These results suggest that the bile juice cytology results are affected by characteristics of mucin expression in the tissue. Based on the possibility that mucin expression correlates with the prognosis of each carcinoma, a positive cytological result suggests a poor prognosis for the carcinoma, which may be informative for predicting the post-operative courses and choosing treatments.","The present study evaluated correlations between preoperative bile juice cytology and mucin expression of surgical specimens in biliary tract carcinoma. Twenty-five patients with biliary tract carcinoma surgically treated at our hospital, whose bile juice cytology had been evaluated before operation, were allocated to this study. Biliary cytology was classified into three categories based on the Papanicolaou classification. Immunohistochemical staining of tissues was performed using MUC1 and MUC2 monoclonal antibodies. Lesions showing MUC1 expression of ++ or higher and MUC2 expression of - were classified as Group A, and the remaining lesions as Group B. According to the epithelial site, preoperative cytology was highly correlated in Group A, while it was negative in Group B (p<0.05). In the advanced site of carcinomas, preoperative cytology tended to highly be positive in Group A, while it tended to be negative in Group B (p<0.05). These results suggest that the bile juice cytology results are affected by characteristics of mucin expression in the tissue. Based on the possibility that mucin expression correlates with the prognosis of each carcinoma, a positive cytological result suggests a poor prognosis for the carcinoma, which may be informative for predicting the post-operative courses and choosing treatments.","null","null","2007-02","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.54","No.1-2","41","47","eng","true","null","scientific_journal","null","null","10.2152/jmi.54.41","1343-1420","null","null","null","null","null"
"Effect of late evening snack with rice ball on energy metabolism in liver cirrhosis.","Effect of late evening snack with rice ball on energy metabolism in liver cirrhosis.","Hisami Okumura, Taki Nakamura, Harumi Takeuchi, Hidenori Miyake, Takafumi Katayama, Hidekazu Arai, Yutaka Taketani, Masahiko Fujii, Mitsuo Shimada, Eiji Takeda","Hisami Okumura, Taki Nakamura, Harumi Takeuchi, Hidenori Miyake, Takafumi Katayama, Hidekazu Arai, Yutaka Taketani, Masahiko Fujii, Mitsuo Shimada, Eiji Takeda","null","This study investigates the effects of a late evening snack (LES), of 200 kcal of rice ball, on energy metabolism in cirrhotic patients. Impaired nutritional metabolism has been associated with cirrhosis, and frequent intake of small meals may prevent early-onset starvation, and maintain nourishment in these patients. Twenty-one cirrhotic patients and 26 control subjects (Control) were recruited for this study. Patients were subsequently treated by LES (LC-LES) and by a non-LES regimen (LC-NLES). Resting energy expenditure and respiratory quotient (RQ) were assessed by indirect calorimetry at 0830, 1130 and 1430. Blood glucose and non-esterified fatty acids (NEFA) were measured just before the energy metabolism measurements. The regular diet included three major meals and LES, at 0900, 1200, 1800 and 2100, respectively. The Control and LC-NLES groups received only the major meals, whereas the LC-LES group received three meals plus 200 kcal LES for 7 days. There was no difference in the total energy intake among Control, LC-NLES and LC-LES groups. Respiratory quotient in LC-NLES was significantly lower than that of Control at 0830. Respiratory quotient value in LC-LES significantly elevated from that in LC-NLES. The RQ values did not differ among Control, LC-NLES and LC-LES at 2 h after the meal (1130 and 1430). Non-esterified fatty acids in LC-LES were lower than that in LC-NLES after overnight fasting. The ingestion of a 200 kcal rice ball LES can improve the nutritional metabolism in cirrhotic patients.","This study investigates the effects of a late evening snack (LES), of 200 kcal of rice ball, on energy metabolism in cirrhotic patients. Impaired nutritional metabolism has been associated with cirrhosis, and frequent intake of small meals may prevent early-onset starvation, and maintain nourishment in these patients. Twenty-one cirrhotic patients and 26 control subjects (Control) were recruited for this study. Patients were subsequently treated by LES (LC-LES) and by a non-LES regimen (LC-NLES). Resting energy expenditure and respiratory quotient (RQ) were assessed by indirect calorimetry at 0830, 1130 and 1430. Blood glucose and non-esterified fatty acids (NEFA) were measured just before the energy metabolism measurements. The regular diet included three major meals and LES, at 0900, 1200, 1800 and 2100, respectively. The Control and LC-NLES groups received only the major meals, whereas the LC-LES group received three meals plus 200 kcal LES for 7 days. There was no difference in the total energy intake among Control, LC-NLES and LC-LES groups. Respiratory quotient in LC-NLES was significantly lower than that of Control at 0830. Respiratory quotient value in LC-LES significantly elevated from that in LC-NLES. The RQ values did not differ among Control, LC-NLES and LC-LES at 2 h after the meal (1130 and 1430). Non-esterified fatty acids in LC-LES were lower than that in LC-NLES after overnight fasting. The ingestion of a 200 kcal rice ball LES can improve the nutritional metabolism in cirrhotic patients.","null","null","2006-09","European Journal of Clinical Nutrition","European Journal of Clinical Nutrition","Vol.60","No.9","1067","1072","eng","true","null","scientific_journal","null","null","10.1038/sj.ejcn.1602420","0954-3007","null","null","null","null","null"
"Reconstruction of the middle hepatic vein tributaries using the recipient's recanalized umbilical vein in right-lobe living-donor liver transplantation","Reconstruction of the middle hepatic vein tributaries using the recipient's recanalized umbilical vein in right-lobe living-donor liver transplantation","Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Tomoharu Yoshizumi, Keiji Kishikawa, Yoshihiko Maehara","Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Tomoharu Yoshizumi, Keiji Kishikawa, Yoshihiko Maehara","null","Right-lobe grafts without the middle hepatic vein (MHV) can cause severe congestion of the anterior segment in living-donor liver transplantation (LDLT). However, the indications and methods for reconstructing the MHV or its tributaries remain controversial. We herein describe two cases of the successful use of the recipient's recanalized umbilical vein as an interposition graft to drain the major MHV tributaries in right-lobe LDLTs. After surgery, both right-lobe grafts are currently functioning well and all of the reconstructed venous tributaries have been confirmed to be patent by doppler ultrasonography. The histopathological features of the recanalized umbilical vein showed an intact intima with thickened media. The use of the recipient's recanalized umbilical vein is a good option for reconstructing MHV tributaries in right-lobe LDLTs.","Right-lobe grafts without the middle hepatic vein (MHV) can cause severe congestion of the anterior segment in living-donor liver transplantation (LDLT). However, the indications and methods for reconstructing the MHV or its tributaries remain controversial. We herein describe two cases of the successful use of the recipient's recanalized umbilical vein as an interposition graft to drain the major MHV tributaries in right-lobe LDLTs. After surgery, both right-lobe grafts are currently functioning well and all of the reconstructed venous tributaries have been confirmed to be patent by doppler ultrasonography. The histopathological features of the recanalized umbilical vein showed an intact intima with thickened media. The use of the recipient's recanalized umbilical vein is a good option for reconstructing MHV tributaries in right-lobe LDLTs.","null","null","2006-03","Surgery","Surgery","Vol.139","No.3","442","445","eng","true","null","scientific_journal","null","null","10.1016/j.surg.2005.08.005","0039-6060","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16546511&dopt=Abstract","null","null","null"
"Prevention of lethal hepatic injury in Long-Evans Cinnamon(LEC) rats by D-galactosamine hydrochloride","Prevention of lethal hepatic injury in Long-Evans Cinnamon(LEC) rats by D-galactosamine hydrochloride","Otsuka Toshihiro, Keisuke Izumi, Itsuo Tokunaga, Takako Gotohda, Ipposhi Kaneshige, Yoshiharu Takiguchi, Kaneda Shinya, Nobuo Satake, Takamasa Ohnishi, Seiki Tashiro, Mitsuo Shimada","Otsuka Toshihiro, Keisuke Izumi, Itsuo Tokunaga, Takako Gotohda, Ipposhi Kaneshige, Yoshiharu Takiguchi, Kaneda Shinya, Nobuo Satake, Takamasa Ohnishi, Seiki Tashiro, Mitsuo Shimada","null","Repeated injections of D-galactosamine hydrochloride (GalN) increase the survival rate of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease. The aim of the present study was to investigate the mechanism of GalN for prevention of spontaneous lethal hepatic injury in LEC rats. Male LEC rats were given a single subcutaneous injection of 300 mg/kg of GalN or vehicle (0.9% NaCl) at 14 weeks, and killed at 28 weeks of age. Next, 6-week-old male LEC rats were given weekly subcutaneous injections of 300 mg/kg of GalN or vehicle for 3 or 12 weeks, and their hepatic 8-hydroxydeoxy-2'-guanosine (8-OHdG), glutathione peroxidase (GPX), and catalase activities were measured. None of GalN-treated rats died of hepatic injury (0/12), whereas the mortality rate of control rats given 0.9% NaCl was 17% (2/12). GalN administration for 12 weeks decreased the hepatic 8-OHdG, and GalN administration for either 3 or 12 weeks increased the glutathione peroxidase activity. GalN administration increased the serum level of alanine aminotransferase, and accelerated megalocytic degeneration of the hepatocytes. GalN treatment is effective in preventing lethal hepatitis in LEC rats and decrease of oxidative DNA damage by GalN plays an important role in increase of the survival rate.","Repeated injections of D-galactosamine hydrochloride (GalN) increase the survival rate of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease. The aim of the present study was to investigate the mechanism of GalN for prevention of spontaneous lethal hepatic injury in LEC rats. Male LEC rats were given a single subcutaneous injection of 300 mg/kg of GalN or vehicle (0.9% NaCl) at 14 weeks, and killed at 28 weeks of age. Next, 6-week-old male LEC rats were given weekly subcutaneous injections of 300 mg/kg of GalN or vehicle for 3 or 12 weeks, and their hepatic 8-hydroxydeoxy-2'-guanosine (8-OHdG), glutathione peroxidase (GPX), and catalase activities were measured. None of GalN-treated rats died of hepatic injury (0/12), whereas the mortality rate of control rats given 0.9% NaCl was 17% (2/12). GalN administration for 12 weeks decreased the hepatic 8-OHdG, and GalN administration for either 3 or 12 weeks increased the glutathione peroxidase activity. GalN administration increased the serum level of alanine aminotransferase, and accelerated megalocytic degeneration of the hepatocytes. GalN treatment is effective in preventing lethal hepatitis in LEC rats and decrease of oxidative DNA damage by GalN plays an important role in increase of the survival rate.","null","null","2006-01-01","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.53","No.1-2","81","86","eng","true","null","scientific_journal","null","null","10.2152/jmi.53.81","1343-1420","null","null","null","null","null"
"肝硬変患者における就寝前夜食療法継続指導の健康関連QOLに対する効果","肝硬変患者における就寝前夜食療法継続指導の健康関連QOLに対する効果","奥村 仙示, 竹内 晴美, 中村 多希, 藤井 正彦, 三宅 秀則, 島田 光生, 武田 英二","Hisami Okumura, 竹内 晴美, 中村 多希, Masahiko Fujii, Hidenori Miyake, Mitsuo Shimada, Eiji Takeda","null","null","null","null","null","2006","日本病態栄養学会誌","日本病態栄養学会誌","Vol.9","No.2","159","164","jpn","true","null","scientific_journal","null","null","null","null","null","http://ci.nii.ac.jp/naid/50006121964/","null","null","null"
"Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation","Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation","Makoto Nakamuta, Shusuke Morizono, Yuji Soejima, Tomoharu Yoshizumi, Shinji Aishima, Shin-ichiro Takasugi, Kengo Yoshimitsu, Munechika Enjoji, Kazuhiro Kotoh, Akinobu Taketomi, Hideaki Uchiyama, Mitsuo Shimada, Hajime Nawata, Yoshihiko Maehara","Makoto Nakamuta, Shusuke Morizono, Yuji Soejima, Tomoharu Yoshizumi, Shinji Aishima, Shin-ichiro Takasugi, Kengo Yoshimitsu, Munechika Enjoji, Kazuhiro Kotoh, Akinobu Taketomi, Hideaki Uchiyama, Mitsuo Shimada, Hajime Nawata, Yoshihiko Maehara","null","The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for 11 living-donor liver transplantation (LDLT) candidates with steatosis. Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2-8 weeks. The treatment significantly improved macrovesicular steatosis (30+/-4% vs. 12+/-2% [mean +/- SEM], P = 0.0028). Body weight and BMI were significantly reduced (73.7 +/- 3.2 kg vs. 66.9 +/- 2.9 kg, P = 0.0033, 26.4 +/- 0.7 kg/m vs. 24.1 +/- 0.8 kg/m, P = 0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n = 7) and donor liver without hepatic steotosis (n = 37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen.","The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for 11 living-donor liver transplantation (LDLT) candidates with steatosis. Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2-8 weeks. The treatment significantly improved macrovesicular steatosis (30+/-4% vs. 12+/-2% [mean +/- SEM], P = 0.0028). Body weight and BMI were significantly reduced (73.7 +/- 3.2 kg vs. 66.9 +/- 2.9 kg, P = 0.0033, 26.4 +/- 0.7 kg/m vs. 24.1 +/- 0.8 kg/m, P = 0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n = 7) and donor liver without hepatic steotosis (n = 37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen.","null","null","2005-09-15","Transplantation","Transplantation","Vol.80","No.5","608","612","eng","true","null","scientific_journal","null","null","10.1097/01.tp.0000166009.77444.f3","0041-1337","null","http://www.transplantjournal.com/pt/re/transplantation/abstract.00007890-200509150-00011.htm;jsessionid=EaS19vODBq6Qsmwt28ae4KlNKlSxLFjic0c11LEoVRg0Cs7Tkt6L!-1070481199!-949856145!9001!-1","null","null","null"
"Effect of intraportal infusion to improve small for size graft injury in living donor adult liver transplantation","Effect of intraportal infusion to improve small for size graft injury in living donor adult liver transplantation","Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Shinji Hashimoto, Yoshihiko Maehara, Hiroyuki Kuwano","Taketoshi Suehiro, Mitsuo Shimada, Keiji Kishikawa, Tatsuo Shimura, Yuji Soejima, Tomoharu Yoshizumi, Kohji Hashimoto, Yasushi Mochida, Shinji Hashimoto, Yoshihiko Maehara, Hiroyuki Kuwano","null","The most important problem in the living donor adult liver transplantation (LDALT) is a small for size graft. Although a right lobe graft is used in many cases in order to avoid small for size graft, for a donor, the risk has few in left lobe graft. We evaluate the effect of an intraportal infusion treatment to the small for size graft. One hundred and twelve patients who underwent LDALT were studied. The graft weight recipient standard liver volume ratio (GV/SLV) of these patients were 50% or less. We divided the patients into following two groups; infusion group (n = 53) and control group (n = 59). For the infusion group, 16 G double lumen catheter was inserted into portal vein and nafamostat mesilate (protease inhibitor which stabilize coagulofibrinolytic state; 200 mg/day), prostaglandin E(1) (vasodilator and hepatoprotective effect; 500 microg/day) and thromboxane A(2) synthetase inhibitor (vasodilator and anticoagulant effect; 160 mg/day) were administrated continuously for 7 days. Small-for-size graft syndrome was defined as bilirubin >10 mg/dl and ascites >1000 cc on postoperative day (POD) 14. Comparison examination of a background factors and postoperative bilirubin and amount of ascites was carried out. The mean GV/SLV did not have the difference at 39.1% of infusion group, and 38.3% of control group (P = 0.58). By the control group, 15 patients (25.4%) were small-for-size graft syndrome, however, there was only two (3.8%) small-for-size graft syndrome in infusion group (P = 0.04). The bilirubin levels of infusion and control group on 7 and 14 POD were 9.9 and 7.8 vs. 9.5 and 10.5 mg/dl, respectively. The amount of ascites of infusion group on 7 and 14 POD were 870 and 430 cc, respectively. On the contrary, in control group, the amount of ascites on 7 and 14 POD were 1290 and 1070 cc, respectively. Bilirubin levels and the amount of ascites on 7 and 14 POD were lower in the patients with infusion group then those with control group. There were no differences between infusion group and control group in age, sex and Child's classification. The intraportal infusion had an effect in prevention of hyperbilirubinemia and loss in quality of excessive ascites in the patients with small for size graft. This was suggested to be what is depended on the improvement of the microcirculation insufficiency considered one of the causes of small-for-size graft syndrome.","The most important problem in the living donor adult liver transplantation (LDALT) is a small for size graft. Although a right lobe graft is used in many cases in order to avoid small for size graft, for a donor, the risk has few in left lobe graft. We evaluate the effect of an intraportal infusion treatment to the small for size graft. One hundred and twelve patients who underwent LDALT were studied. The graft weight recipient standard liver volume ratio (GV/SLV) of these patients were 50% or less. We divided the patients into following two groups; infusion group (n = 53) and control group (n = 59). For the infusion group, 16 G double lumen catheter was inserted into portal vein and nafamostat mesilate (protease inhibitor which stabilize coagulofibrinolytic state; 200 mg/day), prostaglandin E(1) (vasodilator and hepatoprotective effect; 500 microg/day) and thromboxane A(2) synthetase inhibitor (vasodilator and anticoagulant effect; 160 mg/day) were administrated continuously for 7 days. Small-for-size graft syndrome was defined as bilirubin >10 mg/dl and ascites >1000 cc on postoperative day (POD) 14. Comparison examination of a background factors and postoperative bilirubin and amount of ascites was carried out. The mean GV/SLV did not have the difference at 39.1% of infusion group, and 38.3% of control group (P = 0.58). By the control group, 15 patients (25.4%) were small-for-size graft syndrome, however, there was only two (3.8%) small-for-size graft syndrome in infusion group (P = 0.04). The bilirubin levels of infusion and control group on 7 and 14 POD were 9.9 and 7.8 vs. 9.5 and 10.5 mg/dl, respectively. The amount of ascites of infusion group on 7 and 14 POD were 870 and 430 cc, respectively. On the contrary, in control group, the amount of ascites on 7 and 14 POD were 1290 and 1070 cc, respectively. Bilirubin levels and the amount of ascites on 7 and 14 POD were lower in the patients with infusion group then those with control group. There were no differences between infusion group and control group in age, sex and Child's classification. The intraportal infusion had an effect in prevention of hyperbilirubinemia and loss in quality of excessive ascites in the patients with small for size graft. This was suggested to be what is depended on the improvement of the microcirculation insufficiency considered one of the causes of small-for-size graft syndrome.","null","null","2005-08","Transplant International","Transplant International","Vol.18","No.8","923","928","eng","true","null","scientific_journal","null","null","10.1111/j.1432-2277.2005.00159.x","0934-0874","null","http://www.blackwell-synergy.com/doi/abs/10.1111/j.1432-2277.2005.00159.x","null","null","null"
"Overexpression of a novel superoxide-producing enzyme,NADPH oxidase 1,in adenoma and well differentiated adenocarcinoma of the human colon","Overexpression of a novel superoxide-producing enzyme,NADPH oxidase 1,in adenoma and well differentiated adenocarcinoma of the human colon","Mitsutoshi Fukuyama, Kazuhito Rokutan, Toshiaki Sano, Hidenori Miyake, Mitsuo Shimada, Seiki Tashiro","Mitsutoshi Fukuyama, Kazuhito Rokutan, Toshiaki Sano, Hidenori Miyake, Mitsuo Shimada, Seiki Tashiro","null","A superoxide-producing enzyme, NADPH oxidase 1 (Nox1), dominantly expressed in the colon, is implicated in the pathogenesis of colon cancer. Immunohistochemistry showed that Nox1 was constitutively expressed in surface mucous cells. Adenomas and well differentiated adenocarcinomas up-regulated Nox1 expression. Ki-67-negative, well differentiated tumor cells contained abundant Nox1, whereas Ki-67-positive, proliferating cells did not express it. This differentiation-dependent expression in normal as well as tumor tissues suggests distinct roles of Nox1 besides mitogenic function. Nuclear factor (NF)-kappaB was predominantly activated in adenoma and adenocarcinoma cells expressing abundant Nox1, suggesting that Nox1 may stimulate NF-kappaB-dependent antiapoptotic pathways in colon tumors.","A superoxide-producing enzyme, NADPH oxidase 1 (Nox1), dominantly expressed in the colon, is implicated in the pathogenesis of colon cancer. Immunohistochemistry showed that Nox1 was constitutively expressed in surface mucous cells. Adenomas and well differentiated adenocarcinomas up-regulated Nox1 expression. Ki-67-negative, well differentiated tumor cells contained abundant Nox1, whereas Ki-67-positive, proliferating cells did not express it. This differentiation-dependent expression in normal as well as tumor tissues suggests distinct roles of Nox1 besides mitogenic function. Nuclear factor (NF)-kappaB was predominantly activated in adenoma and adenocarcinoma cells expressing abundant Nox1, suggesting that Nox1 may stimulate NF-kappaB-dependent antiapoptotic pathways in colon tumors.","null","null","2005-04-18","Cancer Letters","Cancer Letters","Vol.221","No.1","97","104","eng","true","null","scientific_journal","null","null","10.1016/j.canlet.2004.08.031","0304-3835","null","null","null","null","null"
"Living donor liver transplantation for hepatocellular carcinoma: a special reference to a preoperative des-gamma-carboxy prothrombin value","Living donor liver transplantation for hepatocellular carcinoma: a special reference to a preoperative des-gamma-carboxy prothrombin value","Mitsuo Shimada, Yusuke Yonemura, Hideki Ijichi, Noboru Harada, Satoko Shiotani, Mizuki Ninomiya, Takahiro Terashi, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara","Mitsuo Shimada, Yusuke Yonemura, Hideki Ijichi, Noboru Harada, Satoko Shiotani, Mizuki Ninomiya, Takahiro Terashi, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara","null","Des-gamma-carboxy prothrombin (DCP) is a sensitive marker related to vascular invasion of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence in living donor liver transplantation (LDLT) with special reference to preoperative DCP values. Forty consecutive adult HCC patients who underwent LDLT were examined for a correlation between the DCP value and vascular invasion. Risk factors for recurrence were also investigated using clinicopathological variables including preoperative DCP levels. The incidence of positive histological vascular invasion in patients with DCP values above 300 mAU/mL was higher than that with those with DCP value below 300 mAU/mL. Other significant risk factors for recurrence were over 5 cm tumor diameter, not meeting the Milan criteria, AFP value >400 ng/mL, histological vascular invasion, poorly differentiated histology, and male gender. Among the patients who did not meet the Milan criteria, those with both no more than 5 cm of tumor diameter and no more than 300 mAU/mL DCP exhibited a good prognosis. A high DCP value, namely >300 mAU/mL correlated with histological vascular invasion and was one of the strongest prognostic variables. Therefore, special attention should be paid to HCC patients with high DCP values. No correlation between the number of tumor nodules and recurrence was found; therefore, the Milan criteria may require revision regarding the number of tumor nodules.","Des-gamma-carboxy prothrombin (DCP) is a sensitive marker related to vascular invasion of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence in living donor liver transplantation (LDLT) with special reference to preoperative DCP values. Forty consecutive adult HCC patients who underwent LDLT were examined for a correlation between the DCP value and vascular invasion. Risk factors for recurrence were also investigated using clinicopathological variables including preoperative DCP levels. The incidence of positive histological vascular invasion in patients with DCP values above 300 mAU/mL was higher than that with those with DCP value below 300 mAU/mL. Other significant risk factors for recurrence were over 5 cm tumor diameter, not meeting the Milan criteria, AFP value >400 ng/mL, histological vascular invasion, poorly differentiated histology, and male gender. Among the patients who did not meet the Milan criteria, those with both no more than 5 cm of tumor diameter and no more than 300 mAU/mL DCP exhibited a good prognosis. A high DCP value, namely >300 mAU/mL correlated with histological vascular invasion and was one of the strongest prognostic variables. Therefore, special attention should be paid to HCC patients with high DCP values. No correlation between the number of tumor nodules and recurrence was found; therefore, the Milan criteria may require revision regarding the number of tumor nodules.","null","null","2005-03","Transplantation Proceedings","Transplantation Proceedings","Vol.37","No.2","1177","1179","eng","true","null","scientific_journal","null","null","10.1016/j.transproceed.2004.12.030","0041-1345","null","http://dx.doi.org/10.1016/j.transproceed.2004.12.030","null","null","null"
"Rab13 Mediates the Continuous Endocytic Recycling of Occludin to the Cell Surface","Rab13 Mediates the Continuous Endocytic Recycling of Occludin to the Cell Surface","Shinya Morimoto, Noriyuki Nishimura, Tomoya Terai, Shinji Manabe, Yasuyo Yamamoto, Wakako Shinahara, Hidenori Miyake, Seiki Tashiro, Mitsuo Shimada, Takuya Sasaki","Shinya Morimoto, Noriyuki Nishimura, Tomoya Terai, Shinji Manabe, Yasuyo Yamamoto, Wakako Shinahara, Hidenori Miyake, Seiki Tashiro, Mitsuo Shimada, Takuya Sasaki","null","During epithelial morphogenesis, adherens junctions (AJs) and tight junctions (TJs) undergo dynamic reorganization, whereas epithelial polarity is transiently lost and reestablished. Although ARF6-mediated endocytic recycling of E-cadherin has been characterized and implicated in the rapid remodeling of AJs, the molecular basis for the dynamic rearrangement of TJs remains elusive. Occludin and claudins are integral membrane proteins comprising TJ strands and are thought to be responsible for establishing and maintaining epithelial polarity. Here we investigated the intracellular transport of occludin and claudins to and from the cell surface. Using cell surface biotinylation and immunofluorescence, we found that a pool of occludin was continuously endocytosed and recycled back to the cell surface in both fibroblastic baby hamster kidney cells and epithelial MTD-1A cells. Biochemical endocytosis and recycling assays revealed that a Rab13 dominant active mutant (Rab13 Q67L) inhibited the postendocytic recycling of occludin, but not that of transferrin receptor and polymeric immunoglobulin receptor in MTD-1A cells. Double immunolabelings showed that a fraction of endocytosed occludin was colocalized with Rab13 in MTD-1A cells. These results suggest that Rab13 specifically mediates the continuous endocytic recycling of occludin to the cell surface in both fibroblastic and epithelial cells.","During epithelial morphogenesis, adherens junctions (AJs) and tight junctions (TJs) undergo dynamic reorganization, whereas epithelial polarity is transiently lost and reestablished. Although ARF6-mediated endocytic recycling of E-cadherin has been characterized and implicated in the rapid remodeling of AJs, the molecular basis for the dynamic rearrangement of TJs remains elusive. Occludin and claudins are integral membrane proteins comprising TJ strands and are thought to be responsible for establishing and maintaining epithelial polarity. Here we investigated the intracellular transport of occludin and claudins to and from the cell surface. Using cell surface biotinylation and immunofluorescence, we found that a pool of occludin was continuously endocytosed and recycled back to the cell surface in both fibroblastic baby hamster kidney cells and epithelial MTD-1A cells. Biochemical endocytosis and recycling assays revealed that a Rab13 dominant active mutant (Rab13 Q67L) inhibited the postendocytic recycling of occludin, but not that of transferrin receptor and polymeric immunoglobulin receptor in MTD-1A cells. Double immunolabelings showed that a fraction of endocytosed occludin was colocalized with Rab13 in MTD-1A cells. These results suggest that Rab13 specifically mediates the continuous endocytic recycling of occludin to the cell surface in both fibroblastic and epithelial cells.","null","null","2005-01-21","The Journal of Biological Chemistry","The Journal of Biological Chemistry","Vol.280","No.3","2220","2228","eng","true","null","scientific_journal","null","null","10.1074/jbc.M406906200","0021-9258","null","null","null","null","null"
"九州大学病院第三内科における急性肝不全の治療 --- 生体肝移植への適応検討","Evaluation of Acute Hepatic Failure Treated at the Department of Medicine III, Kyushu University Hospital : Indications for Living-donor Liver Transplantation --- 生体肝移植への適応検討","森園 周祐, 中牟田 誠, 国府島 庸之, 宮城 譲, 吉本 剛志, 有村 英一郎, 古藤 和浩, 遠城寺 宗近, 副島 雄二, 武冨 紹信, 吉住 朋晴, 内山 秀昭, 島田 光生, 前原 喜彦, 名和田 新","森園 周祐, 中牟田 誠, 国府島 庸之, 宮城 譲, 吉本 剛志, 有村 英一郎, 古藤 和浩, 遠城寺 宗近, Yuji Soejima, 武冨 紹信, 吉住 朋晴, 内山 秀昭, Mitsuo Shimada, 前原 喜彦, 名和田 新","null","To evaluate indications for living-donor liver transplantation (LDLT), we examined 25 consecutive patients with acute hepatic failure admitted to the Department of Medicine III, Kyushu University Hospital between November 2001 and July 2004. These cases were diagnosed as fluminant hepatitis (n=13), severe-type acute hepatitis (n=11), or late-onset hepatic failure (n=1). Nine patients (36 %) improved with conservative treatment (conservative treatment group), and the other 16 patients (64 %) needed LDLT (LDLT indicated group). In the LDLT indicated group, 11 patients received LDLT, and 4 died because of lack of LDLT donors (n=3), or renal failure (n=1). The LDLT survival rate was 82 % (9/11) ; two patients died due to hepatic infarction and brain edema, respectively. It is very important to predict whether a patient with acute hepatic failure belongs to the conservative treatment group or the LDLT indicated group on admission. Therefore, we analyzed variables that could influence prognosis, including, parameters of hepatic function and platelet counts on admission, and relative hepatic volume (%), which represents the ratio of hepatic volume measured by CT relative to standard hepatic volume calculated with body surface area. Univariate logistic analysis showed that relative hepatic volume, gammaglutamyl transpeptidase (γ-GTP), alkaline phosphatase (ALP), and the ratio of direct bilirubin to total bilirubin (DB/TB) were significant predictors of survival (p < 0.05). Using these factors plus prothrombin time (PT) and total cholesterol, both of which were relatively significant predictors of survival (p < 0.2), we proposed a model for predicting the probability of survival by the stepwise method. Consequently, we proposed a model using four parameters : ALP, GGTP, PT, and relative hepatic volume (Volume) as shown below : P(%) = 1/1+exp { ?(-36 .2375+ALP x 0.0251+ γ-GTP x 0.0102+PT x 0.2558+Volume x 21.2158)} ×100 This model showed a significant correlation between prediction and consequence of survival (r2 = 0.7388, p = 0.0003). In conclusion, LDLT is an effective treatment for acute hepatic failure. The results of this study suggested that our model can adequately predict prognosis in the early phase of acute hepatic failure.","To evaluate indications for living-donor liver transplantation (LDLT), we examined 25 consecutive patients with acute hepatic failure admitted to the Department of Medicine III, Kyushu University Hospital between November 2001 and July 2004. These cases were diagnosed as fluminant hepatitis (n=13), severe-type acute hepatitis (n=11), or late-onset hepatic failure (n=1). Nine patients (36 %) improved with conservative treatment (conservative treatment group), and the other 16 patients (64 %) needed LDLT (LDLT indicated group). In the LDLT indicated group, 11 patients received LDLT, and 4 died because of lack of LDLT donors (n=3), or renal failure (n=1). The LDLT survival rate was 82 % (9/11) ; two patients died due to hepatic infarction and brain edema, respectively. It is very important to predict whether a patient with acute hepatic failure belongs to the conservative treatment group or the LDLT indicated group on admission. Therefore, we analyzed variables that could influence prognosis, including, parameters of hepatic function and platelet counts on admission, and relative hepatic volume (%), which represents the ratio of hepatic volume measured by CT relative to standard hepatic volume calculated with body surface area. Univariate logistic analysis showed that relative hepatic volume, gammaglutamyl transpeptidase (γ-GTP), alkaline phosphatase (ALP), and the ratio of direct bilirubin to total bilirubin (DB/TB) were significant predictors of survival (p < 0.05). Using these factors plus prothrombin time (PT) and total cholesterol, both of which were relatively significant predictors of survival (p < 0.2), we proposed a model for predicting the probability of survival by the stepwise method. Consequently, we proposed a model using four parameters : ALP, GGTP, PT, and relative hepatic volume (Volume) as shown below : P(%) = 1/1+exp { ?(-36 .2375+ALP x 0.0251+ γ-GTP x 0.0102+PT x 0.2558+Volume x 21.2158)} ×100 This model showed a significant correlation between prediction and consequence of survival (r2 = 0.7388, p = 0.0003). In conclusion, LDLT is an effective treatment for acute hepatic failure. The results of this study suggested that our model can adequately predict prognosis in the early phase of acute hepatic failure.","null","null","2004-12-25","福岡医学雑誌","Fukuoka Acta Medica","Vol.95","No.12","321","331","jpn","true","null","scientific_journal","null","null","10.15017/19252","0016-254X","null","http://ci.nii.ac.jp/naid/120002834532/","null","null","null"
"IL-12 gene therapy is an effective therapeutic strategy for hepatocellular carcinoma in immunosuppressed mice","IL-12 gene therapy is an effective therapeutic strategy for hepatocellular carcinoma in immunosuppressed mice","Noboru Harada, Mitsuo Shimada, Shinji Okano, Taketoshi Suehiro, Yuji Soejima, Yukihiro Tomita, Yoshihiko Maehara","Noboru Harada, Mitsuo Shimada, Shinji Okano, Taketoshi Suehiro, Yuji Soejima, Yukihiro Tomita, Yoshihiko Maehara","null","Immunosuppressive therapy for organ transplantation is essential for controlling rejection. When liver transplantation is performed as a therapy for hepatocellular carcinoma (HCC), recurrent HCC is one of the most fatal complications. In this study, we show that intratumoral murine IL-12 (mIL-12) gene therapy has the potential to be an effective treatment for malignancies under immunosuppression. C3H mice (H-2(k)), injected with FK506 (3 mg/kg) i.p., were s.c. implanted with 2.5 x 10(6) MH134 cells (H-2(k)) and we treated the established HCC with electroporation-mediated gene therapy using mIL-12 plasmid DNA. Intratumoral gene transfer of mIL-12 elevated intratumoral mIL-12, IFN-gamma, and IFN-gamma-inducible protein-10, significantly reduced the number of microvessels and inhibited the growth of HCC, compared with HCC-transferred control pCAGGS plasmid. The inhibition of tumor growth in immunosuppressed mice was comparable with that of mIL-12 gene therapy in immunocompetent mice. Intratumoral mIL-12 gene therapy enhanced lymphocytic infiltration into the tumor and elicited the MH134-specific CTL response even under FK506. The dose of FK506 was sufficient to prevent the rejection of distant allogenic skin grafts (BALB/c mice, H-2(d)) and tumors, B7-p815 (H-2(d)) used as transplants, during mIL-12 gene therapy against MH134. Ab-mediated depletion studies suggested that the inhibition of tumor growth, neovascularization, and spontaneous lung metastasis by mIL-12 was dependent almost entirely on NK cells and partially on T cells. These results suggest that intratumoral mIL-12 gene therapy is a potent effective strategy not only to treat recurrences of HCC in liver transplantation, but also to treat solid malignant tumors in immunosuppressed patients with transplanted organ.","Immunosuppressive therapy for organ transplantation is essential for controlling rejection. When liver transplantation is performed as a therapy for hepatocellular carcinoma (HCC), recurrent HCC is one of the most fatal complications. In this study, we show that intratumoral murine IL-12 (mIL-12) gene therapy has the potential to be an effective treatment for malignancies under immunosuppression. C3H mice (H-2(k)), injected with FK506 (3 mg/kg) i.p., were s.c. implanted with 2.5 x 10(6) MH134 cells (H-2(k)) and we treated the established HCC with electroporation-mediated gene therapy using mIL-12 plasmid DNA. Intratumoral gene transfer of mIL-12 elevated intratumoral mIL-12, IFN-gamma, and IFN-gamma-inducible protein-10, significantly reduced the number of microvessels and inhibited the growth of HCC, compared with HCC-transferred control pCAGGS plasmid. The inhibition of tumor growth in immunosuppressed mice was comparable with that of mIL-12 gene therapy in immunocompetent mice. Intratumoral mIL-12 gene therapy enhanced lymphocytic infiltration into the tumor and elicited the MH134-specific CTL response even under FK506. The dose of FK506 was sufficient to prevent the rejection of distant allogenic skin grafts (BALB/c mice, H-2(d)) and tumors, B7-p815 (H-2(d)) used as transplants, during mIL-12 gene therapy against MH134. Ab-mediated depletion studies suggested that the inhibition of tumor growth, neovascularization, and spontaneous lung metastasis by mIL-12 was dependent almost entirely on NK cells and partially on T cells. These results suggest that intratumoral mIL-12 gene therapy is a potent effective strategy not only to treat recurrences of HCC in liver transplantation, but also to treat solid malignant tumors in immunosuppressed patients with transplanted organ.","null","null","2004-12-01","The Journal of Immunology","The Journal of Immunology","Vol.173","No.11","6635","6644","eng","true","null","scientific_journal","null","null","null","0022-1767","null","http://www.jimmunol.org/cgi/content/abstract/173/11/6635","null","null","null"
"S100beta protein: The preoperative new clinical indicator of brain damage in patients with fulminant hepatic failure","S100beta protein: The preoperative new clinical indicator of brain damage in patients with fulminant hepatic failure","Satoko Shiotani, Mitsuo Shimada, Yuji Soejima, Tomoharu Yoshizumi, Shinji Uemoto, Tetsuya Kiuchi, Koichi Tanaka, Yoshihiko Maehara","Satoko Shiotani, Mitsuo Shimada, Yuji Soejima, Tomoharu Yoshizumi, Shinji Uemoto, Tetsuya Kiuchi, Koichi Tanaka, Yoshihiko Maehara","null","The aim of this study was to clarify the role of serum S100 beta on the accurate assessment of reversibility of brain damage after fulminant hepatic failure (FHF). Among the 13 patients with FHF enrolled in this study, 12 underwent living donor liver transplantation; one patient could not the procedure because of volvulus of the sigmoid colon. Serum S100 beta was serially measured using a chemiluminescent immunoassay. Preoperative serum S100 beta in patients with diffuse brain edema was significantly higher than that in patients with localized brain edema (P < 0.05). Patients with preoperative brain death showed serum S100 beta levels over 7.0 microg/L. Serum S100 beta levels correlated with the degree of brain edema of FHF. It has the potential to be a new clinical, noninvasive indicator of brain damage due to FHF.","The aim of this study was to clarify the role of serum S100 beta on the accurate assessment of reversibility of brain damage after fulminant hepatic failure (FHF). Among the 13 patients with FHF enrolled in this study, 12 underwent living donor liver transplantation; one patient could not the procedure because of volvulus of the sigmoid colon. Serum S100 beta was serially measured using a chemiluminescent immunoassay. Preoperative serum S100 beta in patients with diffuse brain edema was significantly higher than that in patients with localized brain edema (P < 0.05). Patients with preoperative brain death showed serum S100 beta levels over 7.0 microg/L. Serum S100 beta levels correlated with the degree of brain edema of FHF. It has the potential to be a new clinical, noninvasive indicator of brain damage due to FHF.","null","null","2004-11","Transplantation Proceedings","Transplantation Proceedings","Vol.36","No.9","2713","2716","eng","true","null","scientific_journal","null","null","10.1016/j.transproceed.2004.09.030","0041-1345","null","http://dx.doi.org/10.1016/j.transproceed.2004.09.030","null","null","null"
"Involvement of Rho-kinase in cold ischemia-reperfusion injury after liver transplantation in rats","Involvement of Rho-kinase in cold ischemia-reperfusion injury after liver transplantation in rats","Satoko Shiotani, Mitsuo Shimada, Taketoshi Suehiro, Yuji Soejima, Tomoharu Yosizumi, Hiroaki Shimokawa, Yoshihiko Maehara","Satoko Shiotani, Mitsuo Shimada, Taketoshi Suehiro, Yuji Soejima, Tomoharu Yosizumi, Hiroaki Shimokawa, Yoshihiko Maehara","null","Reperfusion of ischemic tissues is known to cause the generation of reactive oxygen species (ROS) with resultant tissue damage. However, the sources of ROS in reperfused tissues are not fully characterized. We hypothesized that the small GTPase Rho and its target effector Rho-kinase/ROK/ROCK are involved in the oxidative burst in reperfused tissue with resultant reperfusion injury. In an in vivo rat model of liver transplantation using cold ischemia for 12 hr followed by reperfusion, a specific Rho-kinase inhibitor, fasudil (30 mg/kg), was administered orally 1 hr before the transplantation. Fasudil suppressed the ischemia-reperfusion (I/R)-induced generation of ROS after reperfusion (P<0.01) and also suppressed the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta) 3 hr after reperfusion, resulting in a significant reduction of I/R-induced hepatocellular injury (P<0.05), necrosis, apoptosis (P<0.01), and neutrophil infiltration (P<0.0001) 12 hr after reperfusion. All animals receiving a graft without fasudil died within 3 days, whereas 40% of those receiving fasudil survived (P<0.001). The present study demonstrates that Rho-kinase-mediated production of ROS and inflammatory cytokines are substantially involved in the pathogenesis of hepatocellular necrosis and apoptosis induced by cold I/R in vivo and that Rho-kinase may be regarded as a novel therapeutic target for the disorder.","Reperfusion of ischemic tissues is known to cause the generation of reactive oxygen species (ROS) with resultant tissue damage. However, the sources of ROS in reperfused tissues are not fully characterized. We hypothesized that the small GTPase Rho and its target effector Rho-kinase/ROK/ROCK are involved in the oxidative burst in reperfused tissue with resultant reperfusion injury. In an in vivo rat model of liver transplantation using cold ischemia for 12 hr followed by reperfusion, a specific Rho-kinase inhibitor, fasudil (30 mg/kg), was administered orally 1 hr before the transplantation. Fasudil suppressed the ischemia-reperfusion (I/R)-induced generation of ROS after reperfusion (P<0.01) and also suppressed the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta) 3 hr after reperfusion, resulting in a significant reduction of I/R-induced hepatocellular injury (P<0.05), necrosis, apoptosis (P<0.01), and neutrophil infiltration (P<0.0001) 12 hr after reperfusion. All animals receiving a graft without fasudil died within 3 days, whereas 40% of those receiving fasudil survived (P<0.001). The present study demonstrates that Rho-kinase-mediated production of ROS and inflammatory cytokines are substantially involved in the pathogenesis of hepatocellular necrosis and apoptosis induced by cold I/R in vivo and that Rho-kinase may be regarded as a novel therapeutic target for the disorder.","null","null","2004-08-15","Transplantation","Transplantation","Vol.78","No.3","375","382","eng","true","null","scientific_journal","null","null","10.1097/01.TP.0000128618.41619.E7","0041-1337","null","null","null","null","null"
"Is graft size a major risk factor in living-donor adult liver transplantation?","Is graft size a major risk factor in living-donor adult liver transplantation?","Mitsuo Shimada, Hideki Ijichi, Yusuke Yonemura, Noboru Harada, Satoko Shiotani, Mizuki Ninomiya, Tomoharu Yoshizumi, Yuji Soejima, Taketoshi Suehiro, Yoshihiko Maehara","Mitsuo Shimada, Hideki Ijichi, Yusuke Yonemura, Noboru Harada, Satoko Shiotani, Mizuki Ninomiya, Tomoharu Yoshizumi, Yuji Soejima, Taketoshi Suehiro, Yoshihiko Maehara","null","Graft size is known to be a major risk factor in living donor adult liver transplantation (LDALT). The aim of this study is to reassess whether graft size is a critical factor in LDALT or not. A series of 75 LDALTs excluding auxiliary transplantation and ABO blood-type incompatible transplantation were analyzed. The patients were divided into two groups, according to graft volume (GV) and standard liver volume (SLV): group 1 (small-size group) (GV/SLV: <40%), and group 2 (non-small-size group) (> or =40%). Perioperative clinical data were compared between the two groups, including graft survival and postoperative complications. These parameters were also compared under the conditions of cirrhotic recipients. No difference in graft survival was found between the two groups. No difference was found in incidence of postoperative complications, such as intractable ascites and persistent hyperbilirubinemia. Even in cirrhotic patients with Child-Pugh's class C, there was no difference in graft survival between the two groups. Risk factors related to graft loss were a preoperative urgent status due to chronic liver disease, pre-operative hyperbilirubinemia of over 10 mg/dl, and ABO blood type of not identical but compatible combination between donor and recipient. Graft size is not always considered to be a major risk factor in LDALT, although the number of patients was small in this study. Therefore, a left-lobe graft, even a ""small-for-size"" graft for adult recipients, remains a feasible option in LDALT.","Graft size is known to be a major risk factor in living donor adult liver transplantation (LDALT). The aim of this study is to reassess whether graft size is a critical factor in LDALT or not. A series of 75 LDALTs excluding auxiliary transplantation and ABO blood-type incompatible transplantation were analyzed. The patients were divided into two groups, according to graft volume (GV) and standard liver volume (SLV): group 1 (small-size group) (GV/SLV: <40%), and group 2 (non-small-size group) (> or =40%). Perioperative clinical data were compared between the two groups, including graft survival and postoperative complications. These parameters were also compared under the conditions of cirrhotic recipients. No difference in graft survival was found between the two groups. No difference was found in incidence of postoperative complications, such as intractable ascites and persistent hyperbilirubinemia. Even in cirrhotic patients with Child-Pugh's class C, there was no difference in graft survival between the two groups. Risk factors related to graft loss were a preoperative urgent status due to chronic liver disease, pre-operative hyperbilirubinemia of over 10 mg/dl, and ABO blood type of not identical but compatible combination between donor and recipient. Graft size is not always considered to be a major risk factor in LDALT, although the number of patients was small in this study. Therefore, a left-lobe graft, even a ""small-for-size"" graft for adult recipients, remains a feasible option in LDALT.","null","null","2004-07","Transplant International","Transplant International","Vol.17","No.6","310","316","eng","true","null","scientific_journal","null","null","10.1111/j.1432-2277.2004.tb00448.x","0934-0874","null","http://www.springerlink.com/link.asp?id=n89hxcq71fu9kay9","null","null","null"
"A simple and accurate formula to estimate left hepatic graft volume in living-donor adult liver transplantation","A simple and accurate formula to estimate left hepatic graft volume in living-donor adult liver transplantation","Noboru Harada, Mitsuo Shimada, Tomoharu Yoshizumi, Taketoshi Suehiro, Yuji Soejima, Yoshihiko Maehara","Noboru Harada, Mitsuo Shimada, Tomoharu Yoshizumi, Taketoshi Suehiro, Yuji Soejima, Yoshihiko Maehara","null","In the field of living-donor adult liver transplantation, a small-for-size graft often occurs, particularly when using left-lobe grafts. This is because of the limited volumes associated with left-lobe grafts. The accurate preoperative evaluation of graft volumes is crucial to avoid this complication. The aim of this study is to clarify the usefulness of a new formula to estimate the left-lobe graft volume. In 61 left-lobe grafts, a new formula was created with stepwise regression analysis using the following variables: height, weight, the thoracic and abdominal distance from anterior to posterior side (A-P), and distance from left to right side (L-R) of the initial 20 donors. With another 41 donors, the difference between the actual and estimated graft volume using the formula and two- and three-dimensional computed tomography was prospectively evaluated. On the basis of the results of the stepwise regression analysis, a new formula was created as follows: graft volume (ml) = 313.4 + 7.7 x weight (kg)-12.6 x thoracic L-R (cm). The difference between the actual and estimated graft volumes using the formula was significantly better (10.8 +/- 9.5%) than that of the volumetry using two-dimensional computed tomography (16.3 +/- 10.1%) (P < 0.05). In conclusion, the new formula can estimate the actual graft volume more accurately than conventional volumetry with two-dimensional computed tomography. The formula is useful to estimate the volume of left-lobe graft in living-donor adult liver transplantation.","In the field of living-donor adult liver transplantation, a small-for-size graft often occurs, particularly when using left-lobe grafts. This is because of the limited volumes associated with left-lobe grafts. The accurate preoperative evaluation of graft volumes is crucial to avoid this complication. The aim of this study is to clarify the usefulness of a new formula to estimate the left-lobe graft volume. In 61 left-lobe grafts, a new formula was created with stepwise regression analysis using the following variables: height, weight, the thoracic and abdominal distance from anterior to posterior side (A-P), and distance from left to right side (L-R) of the initial 20 donors. With another 41 donors, the difference between the actual and estimated graft volume using the formula and two- and three-dimensional computed tomography was prospectively evaluated. On the basis of the results of the stepwise regression analysis, a new formula was created as follows: graft volume (ml) = 313.4 + 7.7 x weight (kg)-12.6 x thoracic L-R (cm). The difference between the actual and estimated graft volumes using the formula was significantly better (10.8 +/- 9.5%) than that of the volumetry using two-dimensional computed tomography (16.3 +/- 10.1%) (P < 0.05). In conclusion, the new formula can estimate the actual graft volume more accurately than conventional volumetry with two-dimensional computed tomography. The formula is useful to estimate the volume of left-lobe graft in living-donor adult liver transplantation.","null","null","2004-05-27","Transplantation","Transplantation","Vol.77","No.10","1571","1575","eng","true","null","scientific_journal","null","null","10.1097/01.TP.0000131991.10802.AA","0041-1337","null","http://www.transplantjournal.com/pt/re/transplantation/abstract.00007890-200405270-00017.htm;jsessionid=EadMPVp2BMLh8ultEElPf7h4vz66pW1wYPVL6KaX7KuG2c9VitBI!-1070481199!-949856145!9001!-1","null","null","null"
"The impact of splenectomy or splenic artery ligation on the outcome of a living donor adult liver transplantation using a left lobe graft","The impact of splenectomy or splenic artery ligation on the outcome of a living donor adult liver transplantation using a left lobe graft","Mitsuo Shimada, Hideki Ijichi, Yusuke Yonemura, Noboru Harada, Satoko Shiotani, Mizuki Ninomiya, Takahiro Terashi, Tomoharu Yoshizumi, Yuji Soejima, Taketoshi Suehiro, Yoshihiko Maehara","Mitsuo Shimada, Hideki Ijichi, Yusuke Yonemura, Noboru Harada, Satoko Shiotani, Mizuki Ninomiya, Takahiro Terashi, Tomoharu Yoshizumi, Yuji Soejima, Taketoshi Suehiro, Yoshihiko Maehara","null","The aim of this study was to clarify the impact of splenectomy or splenic artery ligation on the outcome in living donor adult liver transplantation (LDALT) using a left lobe graft. Forty-eight LDALT cases using a left lobe graft were enrolled in this study. The patients were classified into two groups: Group A (n=40), in which neither a splenectomy nor a splenic artery ligation was performed, and Group B (n=8), in which a splenectomy (n=6) or a splenic artery ligation (n=2) was performed. Indications for splenectomy were as follows: 1) demonstrating a hypersplenism and/or 2) having splenic aneurysms. None of the patients receiving a splenectomy or a splenic artery ligation experienced any septic complication in this series. The graft-recipient weight ratio in group B tended to be smaller than in group A. In group B, all patients were classified into Child's class C or B. The incidence of esophageal varices in group B was significantly higher than in group A. Moreover, the platelet count and the white blood cell count in group B were significantly lower than in group A. No statistical difference was found in postoperative functional cholestasis and intractable ascites. None of the participants in group B experienced both postoperative hyperbilirubinemia and intractable ascites, which were characterized as a small-for-size graft after LDALT. The patient survival rate in group B seems to be better than in group A. In a majority of the cases the portal pressure as well as the portal vein flow after a splenectomy decreased in comparison to that before the splenectomy. Splenectomy or splenic artery ligation is considered to be beneficial for improving the outcome in LDALT using a left lobe graft.","The aim of this study was to clarify the impact of splenectomy or splenic artery ligation on the outcome in living donor adult liver transplantation (LDALT) using a left lobe graft. Forty-eight LDALT cases using a left lobe graft were enrolled in this study. The patients were classified into two groups: Group A (n=40), in which neither a splenectomy nor a splenic artery ligation was performed, and Group B (n=8), in which a splenectomy (n=6) or a splenic artery ligation (n=2) was performed. Indications for splenectomy were as follows: 1) demonstrating a hypersplenism and/or 2) having splenic aneurysms. None of the patients receiving a splenectomy or a splenic artery ligation experienced any septic complication in this series. The graft-recipient weight ratio in group B tended to be smaller than in group A. In group B, all patients were classified into Child's class C or B. The incidence of esophageal varices in group B was significantly higher than in group A. Moreover, the platelet count and the white blood cell count in group B were significantly lower than in group A. No statistical difference was found in postoperative functional cholestasis and intractable ascites. None of the participants in group B experienced both postoperative hyperbilirubinemia and intractable ascites, which were characterized as a small-for-size graft after LDALT. The patient survival rate in group B seems to be better than in group A. In a majority of the cases the portal pressure as well as the portal vein flow after a splenectomy decreased in comparison to that before the splenectomy. Splenectomy or splenic artery ligation is considered to be beneficial for improving the outcome in LDALT using a left lobe graft.","null","null","2004-05","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.51","No.57","625","629","eng","true","null","scientific_journal","null","null","null","0172-6390","null","null","null","null","null"
"Role of expression of focal adhesion kinase in progression of hepatocellular carcinoma","Role of expression of focal adhesion kinase in progression of hepatocellular carcinoma","Shinji Itoh, Takashi Maeda, Mitsuo Shimada, Shin-ichi Aishima, Ken Shirabe, Shinji Tanaka, Yoshihiko Maehara","Shinji Itoh, Takashi Maeda, Mitsuo Shimada, Shin-ichi Aishima, Ken Shirabe, Shinji Tanaka, Yoshihiko Maehara","null","Although hepatocellular carcinoma (HCC) is the most common cancer of the human liver, the mechanisms that regulate HCC development and progression remain unclear. The aim of this study was to investigate whether focal adhesion kinase (FAK) is involved in the progression of human HCC. Western blot analysis for FAK was performed on three HCC cell lines. We reviewed 64 consecutive patients who had undergone initial liver resection for HCC without preoperative treatment. Immunohistochemistry analysis for FAK was performed on paraffin-embedded tissues. FAK expression was confirmed by Western blot analysis in several clinical samples. We investigated the correlation between FAK expression and clinical outcome. FAK proteins were detected in all HCC cell lines. Hepatocytes in the normal liver and chronic hepatitis with or without cirrhosis were negative for immunohistochemical staining for FAK expression. Cytoplasmic FAK expression was observed in 18 of 64 patients (28.1%), and this positive staining was correlated with gender (P < 0.05), a lower level of serum albumin (P < 0.05), and portal venous invasion (P < 0.01). Positive staining for FAK was associated with significantly poorer survival (P < 0.05). In multivariate analysis, FAK overexpression was an independent factor in determining the prognosis of patients. These data suggest that FAK plays an important role in promoting tumor progression, especially vascular invasion, in HCC. FAK could play an important role in HCC progression and would be a novel target for HCC therapeutics as well as a prognostic marker.","Although hepatocellular carcinoma (HCC) is the most common cancer of the human liver, the mechanisms that regulate HCC development and progression remain unclear. The aim of this study was to investigate whether focal adhesion kinase (FAK) is involved in the progression of human HCC. Western blot analysis for FAK was performed on three HCC cell lines. We reviewed 64 consecutive patients who had undergone initial liver resection for HCC without preoperative treatment. Immunohistochemistry analysis for FAK was performed on paraffin-embedded tissues. FAK expression was confirmed by Western blot analysis in several clinical samples. We investigated the correlation between FAK expression and clinical outcome. FAK proteins were detected in all HCC cell lines. Hepatocytes in the normal liver and chronic hepatitis with or without cirrhosis were negative for immunohistochemical staining for FAK expression. Cytoplasmic FAK expression was observed in 18 of 64 patients (28.1%), and this positive staining was correlated with gender (P < 0.05), a lower level of serum albumin (P < 0.05), and portal venous invasion (P < 0.01). Positive staining for FAK was associated with significantly poorer survival (P < 0.05). In multivariate analysis, FAK overexpression was an independent factor in determining the prognosis of patients. These data suggest that FAK plays an important role in promoting tumor progression, especially vascular invasion, in HCC. FAK could play an important role in HCC progression and would be a novel target for HCC therapeutics as well as a prognostic marker.","null","null","2004-04-15","Clinical Cancer Research","Clinical Cancer Research","Vol.10","No.8","2812","2817","eng","true","null","scientific_journal","null","null","10.1158/1078-0432.CCR-1046-03","1078-0432","null","http://clincancerres.aacrjournals.org/cgi/content/abstract/10/8/2812","null","null","null"
"Prognosis factors in node-negative intrahepatic cholangiocaecinoma eith special reference to angiogenesis","Prognosis factors in node-negative intrahepatic cholangiocaecinoma eith special reference to angiogenesis","Ken Shirabe, Mitsuo Shimada, Eiji Tsujita, Shin-ichi Aishima, Shin-ichiro Maehara, Shinji Tanaka, Kenji Takenaka, Yoshihiko Maehara","Ken Shirabe, Mitsuo Shimada, Eiji Tsujita, Shin-ichi Aishima, Shin-ichiro Maehara, Shinji Tanaka, Kenji Takenaka, Yoshihiko Maehara","null","The aim of this study was to clarify prognostic factors and recurrence patterns in patients with node-negative intrahepatic cholangiocarcinoma (IHCC). A retrospective study was performed to review prognostic factors and recurrence patterns (1) in 22 patients with node-negative IHCC after curative hepatic resection and (2) in 49 patients who underwent resection and lymph node dissection for IHCC. In addition to determining the clinicopathologic factors, the investigators also performed immunohistochemical examination of microvessel counts using antihuman CD-31 and antibody. The significant poor prognostic factors in node-negative IHCC were the presence of intrahepatic metastasis, portal vein invasion of cancer cells, and high microvessel counts. After multivariate analysis was conducted, the independent poor prognostic factors were the presence of intrahepatic metastases and high microvessel counts. Of 9 patients who had postoperative recurrence of their disease, intrahepatic recurrence was observed in 7 (78 %). The factors linked to poor prognosis in IHCC were tumor angiogenesis and the presence of intrahepatic metastasis. Because intrahepatic recurrence was common, regional and adjuvant chemotherapy to the liver may improve the outcome of patients with these risk factors and node-negative IHCC.","The aim of this study was to clarify prognostic factors and recurrence patterns in patients with node-negative intrahepatic cholangiocarcinoma (IHCC). A retrospective study was performed to review prognostic factors and recurrence patterns (1) in 22 patients with node-negative IHCC after curative hepatic resection and (2) in 49 patients who underwent resection and lymph node dissection for IHCC. In addition to determining the clinicopathologic factors, the investigators also performed immunohistochemical examination of microvessel counts using antihuman CD-31 and antibody. The significant poor prognostic factors in node-negative IHCC were the presence of intrahepatic metastasis, portal vein invasion of cancer cells, and high microvessel counts. After multivariate analysis was conducted, the independent poor prognostic factors were the presence of intrahepatic metastases and high microvessel counts. Of 9 patients who had postoperative recurrence of their disease, intrahepatic recurrence was observed in 7 (78 %). The factors linked to poor prognosis in IHCC were tumor angiogenesis and the presence of intrahepatic metastasis. Because intrahepatic recurrence was common, regional and adjuvant chemotherapy to the liver may improve the outcome of patients with these risk factors and node-negative IHCC.","null","null","2004-04","The American Journal of Surgery","The American Journal of Surgery","Vol.187","No.4","538","542","eng","true","null","scientific_journal","null","null","10.1016/j.amjsurg.2003.12.044","0002-9610","null","null","null","null","null"
"Graft-versus-host disease following living donor liver transplantation","Graft-versus-host disease following living donor liver transplantation","Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Shoji Hiroshige, Hisashi Gondo, Akiyoshi Takami, Shizuka Yasue, Yoshihiko Maehara","Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Shoji Hiroshige, Hisashi Gondo, Akiyoshi Takami, Shizuka Yasue, Yoshihiko Maehara","null","Graft-versus-host disease (GVHD) is the most common and well-known cause of morbidity and mortality following allogeneic bone marrow transplantation. Sporadic cases have been reported after cadaveric donor liver transplantation with usually fatal outcomes, however, the actual incidence and the characteristics of GVHD after living donor liver transplantation (LDLT) remain unknown. We herein report a person who developed fatal GVHD following LDLT and discuss the applicability of an HLA-homozygous donor to an HLA-haploidentical recipient. A 48-year-old male underwent LDLT for unresectable hepatocellular carcinoma with alcoholic liver cirrhosis. The donor was his 20-year-old son whose pretransplant HLA typing was homozygous at all loci. GVHD occurred 35 days after LDLT and was characterized by fever, diarrhea, maculopapular rash, and leukopenia, which led to the development of fatal pneumonia. We identified 4 cases of GVHD after LDLT in Japan and 1 in the United States, all associated with the use of an HLA-homozygous donor. The use of an HLA homozygous donor which results in a complete 1-way donor-recipient HLA match carries an extremely high risk of developing GVHD after LDLT. Therefore, it is possible that LDLT should be ruled out for such donors. A pretransplant work-up of the HLA type in both the donors and recipients is therefore imperative before determining the indications for LDLT.","Graft-versus-host disease (GVHD) is the most common and well-known cause of morbidity and mortality following allogeneic bone marrow transplantation. Sporadic cases have been reported after cadaveric donor liver transplantation with usually fatal outcomes, however, the actual incidence and the characteristics of GVHD after living donor liver transplantation (LDLT) remain unknown. We herein report a person who developed fatal GVHD following LDLT and discuss the applicability of an HLA-homozygous donor to an HLA-haploidentical recipient. A 48-year-old male underwent LDLT for unresectable hepatocellular carcinoma with alcoholic liver cirrhosis. The donor was his 20-year-old son whose pretransplant HLA typing was homozygous at all loci. GVHD occurred 35 days after LDLT and was characterized by fever, diarrhea, maculopapular rash, and leukopenia, which led to the development of fatal pneumonia. We identified 4 cases of GVHD after LDLT in Japan and 1 in the United States, all associated with the use of an HLA-homozygous donor. The use of an HLA homozygous donor which results in a complete 1-way donor-recipient HLA match carries an extremely high risk of developing GVHD after LDLT. Therefore, it is possible that LDLT should be ruled out for such donors. A pretransplant work-up of the HLA type in both the donors and recipients is therefore imperative before determining the indications for LDLT.","null","null","2004-03","Liver Transplantation","Liver Transplantation","Vol.10","No.3","460","464","eng","true","null","scientific_journal","null","null","10.1002/lt.20101","1527-6465","null","http://www3.interscience.wiley.com/cgi-bin/abstract/107630113/ABSTRACT","null","null","null"
"Sustained spatial disturbance of bile canalicular networks during regeneration of the steatotic rat liver","Sustained spatial disturbance of bile canalicular networks during regeneration of the steatotic rat liver","Mizuki Ninomiya, Mitsuo Shimada, Takahiro Terashi, Hideki Ijichi, Yusuke Yonemura, Noboru Harada, Yuji Soejima, Taketoshi Suehiro, Yoshihiko Maehara","Mizuki Ninomiya, Mitsuo Shimada, Takahiro Terashi, Hideki Ijichi, Yusuke Yonemura, Noboru Harada, Yuji Soejima, Taketoshi Suehiro, Yoshihiko Maehara","null","Although it is generally considered that livers with moderate steatosis can be safely used in the setting of living-donor liver transplantation, the effect of the regenerative process of such a graft on postoperative liver function is incompletely understood. We assessed the morphologic and functional alterations during the regeneration of fatty liver, with special reference to the biliary system. Wistar rats with normal or fatty livers induced by a choline-deficient diet were subjected to 70% partial hepatectomy (PH). The regenerated liver weight and serum parameters were compared. Furthermore, to assess the spatial alterations of bile canalicular networks, the distribution of AGp110, a fibronectin receptor that localizes on the apical (bile canalicular) membrane of the hepatocytes, was analyzed immunohistochemically. The serum albumin levels of the fatty-liver rats decreased significantly after 24 hours, and this continued until day 7. The increase in the total bile acid levels of the fatty-liver group was higher and more prolonged compared with that of the normal-liver group. At 24 hours after PH, discontinuity of the AGp110-positive canalicular network was evident in both groups. At 7 days after PH, the typical AGp110-positive canalicular network was almost restored in the normal-liver group. In contrast, the fatty-liver group showed sustained discontinuity of canalicular networks at the same time point. The livers with moderate steatosis are associated with prolonged cholestasis after 70% PH, and this was caused, in part, by sustained spatial disturbance of bile canalicular networks during the regenerative process.","Although it is generally considered that livers with moderate steatosis can be safely used in the setting of living-donor liver transplantation, the effect of the regenerative process of such a graft on postoperative liver function is incompletely understood. We assessed the morphologic and functional alterations during the regeneration of fatty liver, with special reference to the biliary system. Wistar rats with normal or fatty livers induced by a choline-deficient diet were subjected to 70% partial hepatectomy (PH). The regenerated liver weight and serum parameters were compared. Furthermore, to assess the spatial alterations of bile canalicular networks, the distribution of AGp110, a fibronectin receptor that localizes on the apical (bile canalicular) membrane of the hepatocytes, was analyzed immunohistochemically. The serum albumin levels of the fatty-liver rats decreased significantly after 24 hours, and this continued until day 7. The increase in the total bile acid levels of the fatty-liver group was higher and more prolonged compared with that of the normal-liver group. At 24 hours after PH, discontinuity of the AGp110-positive canalicular network was evident in both groups. At 7 days after PH, the typical AGp110-positive canalicular network was almost restored in the normal-liver group. In contrast, the fatty-liver group showed sustained discontinuity of canalicular networks at the same time point. The livers with moderate steatosis are associated with prolonged cholestasis after 70% PH, and this was caused, in part, by sustained spatial disturbance of bile canalicular networks during the regenerative process.","null","null","2004-02-15","Transplantation","Transplantation","Vol.77","No.3","373","379","eng","true","null","scientific_journal","null","null","10.1097/01.TP.0000109777.51902.09","0041-1337","null","http://www.transplantjournal.com/pt/re/transplantation/abstract.00007890-200402150-00011.htm;jsessionid=EakvDaveJRpb11oT5BnXvM59VtmFAWq1ZrjbpDkENl1JTzgFLKTA!-1070481199!-949856145!9001!-1","null","null","null"
"The hydroxyl radical scavenger MCI-186 protects the liver from exprimental cold ischaemia-reperfusion injury","The hydroxyl radical scavenger MCI-186 protects the liver from exprimental cold ischaemia-reperfusion injury","Mizuki Ninomiya, Mitsuo Shimada, Noboru Harada, Yuji Soejima, Taketoshi Suehiro, Yoshihiko Maehara","Mizuki Ninomiya, Mitsuo Shimada, Noboru Harada, Yuji Soejima, Taketoshi Suehiro, Yoshihiko Maehara","null","Oxidative stress contributes to hepatic ischaemia-reperfusion (IR) injury in a biphasic pattern. In addition to direct cytotoxic effects, oxidative stress also initiates the signal transduction processes that promote second-phase liver injury. The present study investigated the effects of the hydroxyl radical scavenger MCI-186 on the biphasic process of hepatic cold IR injury. After cold preservation for 16 h, rat livers were reperfused on an isolated liver perfusion system for 120 min with oxygenated Krebs-Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. To determine whether MCI-186 affected cytokine levels that control the second-phase injury, levels of interleukin (IL) 10 and tumour necrosis factor (TNF) alpha were measured in the perfusate. Addition of MCI-186 1 mg/l into the perfusate significantly improved portal flow (P<0.050), hepatic enzyme release into the perfusate (P=0.038), total bile production (P=0.029) and malondialdehyde concentration (P=0.038). Furthermore, treatment with MCI-186 led to a substantial increase in IL-10 release (P=0.032). TNF-alpha levels were not affected. MCI-186, an agent ready for clinical use, appears to have direct and indirect protective effects against hepatic cold IR injury.","Oxidative stress contributes to hepatic ischaemia-reperfusion (IR) injury in a biphasic pattern. In addition to direct cytotoxic effects, oxidative stress also initiates the signal transduction processes that promote second-phase liver injury. The present study investigated the effects of the hydroxyl radical scavenger MCI-186 on the biphasic process of hepatic cold IR injury. After cold preservation for 16 h, rat livers were reperfused on an isolated liver perfusion system for 120 min with oxygenated Krebs-Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. To determine whether MCI-186 affected cytokine levels that control the second-phase injury, levels of interleukin (IL) 10 and tumour necrosis factor (TNF) alpha were measured in the perfusate. Addition of MCI-186 1 mg/l into the perfusate significantly improved portal flow (P<0.050), hepatic enzyme release into the perfusate (P=0.038), total bile production (P=0.029) and malondialdehyde concentration (P=0.038). Furthermore, treatment with MCI-186 led to a substantial increase in IL-10 release (P=0.032). TNF-alpha levels were not affected. MCI-186, an agent ready for clinical use, appears to have direct and indirect protective effects against hepatic cold IR injury.","null","null","2004-02","The British Journal of Surgery","The British Journal of Surgery","Vol.91","No.2","184","190","eng","true","null","scientific_journal","null","null","10.1002/bjs.4401","0007-1323","null","http://www3.interscience.wiley.com/cgi-bin/abstract/106565848/ABSTRACT","null","null","null"
"進行肝細胞癌に対する根治的治療法としての生体肝移植","進行肝細胞癌に対する根治的治療法としての生体肝移植","副島 雄二, 武冨 紹信, 吉住 朋晴, 内山 秀昭, 祇園 智信, 島田 光生, 前原 喜彦","Yuji Soejima, 武冨 紹信, 吉住 朋晴, 内山 秀昭, 祇園 智信, Mitsuo Shimada, 前原 喜彦","null","null","null","null","null","2004","癌の臨床","Japanese Journal of Cancer Clinics","Vol.50","null","913","919","jpn","true","null","scientific_journal","null","null","null","0021-4949","null","null","null","null","null"
"急性肝不全生体肝移植症例の再検討","急性肝不全生体肝移植症例の再検討","末廣 剛敏, 島田 光生, 副島 雄二, 吉住 朋晴, 前原 喜彦","末廣 剛敏, Mitsuo Shimada, Yuji Soejima, 吉住 朋晴, 前原 喜彦","null","null","null","null","null","2004","消化器科","消化器科","Vol.38","null","122","130","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"Use of steatotic graft in living-donor liver transplantation","Use of steatotic graft in living-donor liver transplantation","Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Keiji Kishikawa, Tomoharu Yoshizumi, Koji Hashimoto, Ryosuke Minagawa, Shoji Hiroshige, Takahiro Terashi, Mizuki Ninomiya, Satoko Shiotani, Noboru Harada, Keizo Sugimachi","Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Keiji Kishikawa, Tomoharu Yoshizumi, Koji Hashimoto, Ryosuke Minagawa, Shoji Hiroshige, Takahiro Terashi, Mizuki Ninomiya, Satoko Shiotani, Noboru Harada, Keizo Sugimachi","null","The degree of fatty infiltration in hepatic grafts is known to be an important risk factor for primary graft nonfunction in cadaveric liver transplantation. However, the effect of hepatic steatosis in living-donor liver transplantation (LDLT) has not yet been well defined. In this study, we evaluated the impact that the degree of hepatic graft steatosis has on the outcome of LDLT. Sixty consecutive donors and recipients who underwent LDLT between October 1996 and August 2001 at Kyushu University Hospital were the subjects of this study. The pathologic findings of the prereperfusion biopsy of the graft were classified into the following three groups according to the degree of macrovesicular steatosis: None (n=23), 0% steatosis; Mild (n=23), 0% to 20% steatosis; and Moderate (n=6), 20% to 50% steatosis. Liver function tests including total bilirubin (at postoperative day [POD] 7), the peak alanine aminotransferase (ALT) and prothrombin time (at POD 3), and both patient and graft survival were compared among the groups. Furthermore, we also compared the donor parameters including the peak ALT and total bilirubin (at POD 3) and the operative time, blood loss, and length of hospital stay after surgery. The 1-year patient and graft survival were comparable among the groups. The peak ALT was significantly higher in the Moderate group (606+/-641 IU/L) than in the None (290+/-190 IU/L) and Mild (376+/-296 IU/L) groups. Total bilirubin (POD 7) and prothrombin time (POD 3) were comparable among the groups. The donor parameters were comparable among the groups except for the fact that the donor body weight of the Mild and Moderate groups were significantly heavier (P<0.0001) than that of the None group. In conclusion, the use of a fatty liver graft up to the moderate level can be justified in LDLT, even though ischemia-reperfusion injury tends to be severe in such grafts.","The degree of fatty infiltration in hepatic grafts is known to be an important risk factor for primary graft nonfunction in cadaveric liver transplantation. However, the effect of hepatic steatosis in living-donor liver transplantation (LDLT) has not yet been well defined. In this study, we evaluated the impact that the degree of hepatic graft steatosis has on the outcome of LDLT. Sixty consecutive donors and recipients who underwent LDLT between October 1996 and August 2001 at Kyushu University Hospital were the subjects of this study. The pathologic findings of the prereperfusion biopsy of the graft were classified into the following three groups according to the degree of macrovesicular steatosis: None (n=23), 0% steatosis; Mild (n=23), 0% to 20% steatosis; and Moderate (n=6), 20% to 50% steatosis. Liver function tests including total bilirubin (at postoperative day [POD] 7), the peak alanine aminotransferase (ALT) and prothrombin time (at POD 3), and both patient and graft survival were compared among the groups. Furthermore, we also compared the donor parameters including the peak ALT and total bilirubin (at POD 3) and the operative time, blood loss, and length of hospital stay after surgery. The 1-year patient and graft survival were comparable among the groups. The peak ALT was significantly higher in the Moderate group (606+/-641 IU/L) than in the None (290+/-190 IU/L) and Mild (376+/-296 IU/L) groups. Total bilirubin (POD 7) and prothrombin time (POD 3) were comparable among the groups. The donor parameters were comparable among the groups except for the fact that the donor body weight of the Mild and Moderate groups were significantly heavier (P<0.0001) than that of the None group. In conclusion, the use of a fatty liver graft up to the moderate level can be justified in LDLT, even though ischemia-reperfusion injury tends to be severe in such grafts.","null","null","2003-07-27","Transplantation","Transplantation","Vol.76","No.2","344","348","eng","true","null","scientific_journal","null","null","10.1097/01.TP.0000071205.52835.A4","0041-1337","null","http://www.transplantjournal.com/pt/re/transplantation/abstract.00007890-200307270-00013.htm;jsessionid=EYHAwiQ6XrKtNTTHu1DMmM03swS1AfasjO5byljCKtrF2E1Xd8gz!-1070481199!-949856145!9001!-1","null","null","null"
"Gore-Tex jump graft for portal vein thrombosis following living donor liver transplantation","Gore-Tex jump graft for portal vein thrombosis following living donor liver transplantation","Koji Hashimoto, Mitsuo Shimada, Taketoshi Suehiro, Yuji Soejima, Ryosuke Minagawa, Shoji Hiroshige, Satoko Shiotani, Mizuki Ninomiya, Noboru Harada, Kimihiro Komori, Keizo Sugimachi","Koji Hashimoto, Mitsuo Shimada, Taketoshi Suehiro, Yuji Soejima, Ryosuke Minagawa, Shoji Hiroshige, Satoko Shiotani, Mizuki Ninomiya, Noboru Harada, Kimihiro Komori, Keizo Sugimachi","null","Portal vein thrombosis is a rare surgical complication following liver transplantation, which remains a cause of graft loss and death. We describe here the treatment of portal vein thrombosis following living donor liver transplantation using an extended left lobe graft. The patient was treated with a Gore-Tex vascular jump graft extra-anatomically interposed between the recipient superior mesenteric vein and the donor umbilical vein. This technique allowed the hepatic hilum to be left untouched and supplied suitable blood flow to the hepatic allograft. Our experience suggests that this innovative technical solution can be helpful in the effort to rescue cases of hepatic allograft with vascular complications.","Portal vein thrombosis is a rare surgical complication following liver transplantation, which remains a cause of graft loss and death. We describe here the treatment of portal vein thrombosis following living donor liver transplantation using an extended left lobe graft. The patient was treated with a Gore-Tex vascular jump graft extra-anatomically interposed between the recipient superior mesenteric vein and the donor umbilical vein. This technique allowed the hepatic hilum to be left untouched and supplied suitable blood flow to the hepatic allograft. Our experience suggests that this innovative technical solution can be helpful in the effort to rescue cases of hepatic allograft with vascular complications.","null","null","2003-07","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.50","No.52","1146","1148","eng","true","null","scientific_journal","null","null","null","0172-6390","null","http://cat.inist.fr/?aModele=afficheN&cpsidt=14906318","null","null","null"
"Outcome analysis in adult-to-adult living donor liver transplantation using the left lobe","Outcome analysis in adult-to-adult living donor liver transplantation using the left lobe","Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Shoji Hiroshige, Mizuki Ninomiya, Satoko Shiotani, Noboru Harada, Ijichi Hideki, Yusuke Yonemura, Yoshihiko Maehara","Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Shoji Hiroshige, Mizuki Ninomiya, Satoko Shiotani, Noboru Harada, Ijichi Hideki, Yusuke Yonemura, Yoshihiko Maehara","null","Graft size problems remain the greatest limiting factor for expansion of living donor liver transplantation (LDLT) to the adult population. The result of adult-to-adult LDLT using the left lobe with special reference to graft size has not been fully evaluated to date. In this study, we evaluated the outcome of adult-to-adult LDLT using the left lobe and also analyze the impact of using small-for-size grafts on outcome. Thirty-six recipients who underwent adult-to-adult LDLT using the left lobe (n = 14) or left lobe plus caudate lobe (n = 22) were included in the study. Variables including preoperative and operative data, patient and graft survival, complications, and causes of graft loss were studied. Furthermore, the incidence of small-for-size syndrome and its impact on graft survival were studied. Mean graft volume (GV) was 420 +/- 85 g (range, 260 to 620 g), which resulted in 38.2% +/- 8.1% (range, 22.8% to 53.8%) of the recipient standard liver volume (SLV). Overall 1-year patient and graft survival rates were 85.7% and 82.9%, respectively. Seven grafts were lost. Small-for-size syndrome occurred in 7 of 16 patients (43.8%) with cirrhosis and only 1 of 20 patients (5.0%) without cirrhosis (P =.005). Recipients who developed small-for-size syndrome had inferior graft survival to those who did not (P =.07). In conclusion, adult-to-adult LDLTs were found to be feasible without affecting patient or graft survival. Small-for-size syndrome developed more frequently in patients with cirrhosis. Minimum GV in adult-to-adult LDLT should be 30% less than the recipient's SLV in patients without cirrhosis, whereas 45% less was required in patients with cirrhosis.","Graft size problems remain the greatest limiting factor for expansion of living donor liver transplantation (LDLT) to the adult population. The result of adult-to-adult LDLT using the left lobe with special reference to graft size has not been fully evaluated to date. In this study, we evaluated the outcome of adult-to-adult LDLT using the left lobe and also analyze the impact of using small-for-size grafts on outcome. Thirty-six recipients who underwent adult-to-adult LDLT using the left lobe (n = 14) or left lobe plus caudate lobe (n = 22) were included in the study. Variables including preoperative and operative data, patient and graft survival, complications, and causes of graft loss were studied. Furthermore, the incidence of small-for-size syndrome and its impact on graft survival were studied. Mean graft volume (GV) was 420 +/- 85 g (range, 260 to 620 g), which resulted in 38.2% +/- 8.1% (range, 22.8% to 53.8%) of the recipient standard liver volume (SLV). Overall 1-year patient and graft survival rates were 85.7% and 82.9%, respectively. Seven grafts were lost. Small-for-size syndrome occurred in 7 of 16 patients (43.8%) with cirrhosis and only 1 of 20 patients (5.0%) without cirrhosis (P =.005). Recipients who developed small-for-size syndrome had inferior graft survival to those who did not (P =.07). In conclusion, adult-to-adult LDLTs were found to be feasible without affecting patient or graft survival. Small-for-size syndrome developed more frequently in patients with cirrhosis. Minimum GV in adult-to-adult LDLT should be 30% less than the recipient's SLV in patients without cirrhosis, whereas 45% less was required in patients with cirrhosis.","null","null","2003-06","Liver Transplantation","Liver Transplantation","Vol.9","No.6","581","586","eng","true","null","scientific_journal","null","null","10.1053/jlts.2003.50114","1527-6465","null","http://www3.interscience.wiley.com/cgi-bin/abstract/106593790/ABSTRACT","null","null","null"
"Transcriptional repressor snail and progression of human hepatocellular carcinoma.","Transcriptional repressor snail and progression of human hepatocellular carcinoma.","Keishi Sugimachi, Shinji Tanaka, Toshifumi Kameyama, Ken-ichi Taguchi, Shin-ichi Aishima, Mitsuo Shimada, Keizo Sugimachi, Masazumi Tsuneyoshi","Keishi Sugimachi, Shinji Tanaka, Toshifumi Kameyama, Ken-ichi Taguchi, Shin-ichi Aishima, Mitsuo Shimada, Keizo Sugimachi, Masazumi Tsuneyoshi","null","Snail protein is a suppressive transcriptional factor of E-cadherin that mediates cell-to-cell adhesion, tumor progression, and metastases. We explored the expression and function of Snail and its family member Slug in human hepatocellular carcinoma (HCC) to identify its role in tumor progression. Transfection of Snail cDNA in Li-7, endogenous E-cadherin-positive human HCC cells, selectively induced the loss of E-cadherin protein expression. We then investigated the expression of Snail and Slug mRNA in 43 human tissue samples of HCC. Using in situ hybridization, Snail mRNA was determined to dominantly express in HCC cells, but not in bile duct cells, blood vessels or infiltrating leukocytes. The mRNA of Snail and Slug were quantified using real-time reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. Snail mRNA was overexpressed in 7 cases (16%) of HCC compared with adjacent noncancerous liver tissue. E-Cadherin protein expression determined in the same 43 cases by immunohistochemistry was significantly down-regulated in those cases with Snail mRNA overexpression (P = 0.04). The tumor and nontumor ratio of Snail mRNA independently correlated with tumor invasiveness (P = 0.04). However, Slug mRNA correlated with neither E-cadherin expression nor tumor invasiveness. The data indicate that Snail both down-regulates E-cadherin expression and promotes the invasion in human HCC.","Snail protein is a suppressive transcriptional factor of E-cadherin that mediates cell-to-cell adhesion, tumor progression, and metastases. We explored the expression and function of Snail and its family member Slug in human hepatocellular carcinoma (HCC) to identify its role in tumor progression. Transfection of Snail cDNA in Li-7, endogenous E-cadherin-positive human HCC cells, selectively induced the loss of E-cadherin protein expression. We then investigated the expression of Snail and Slug mRNA in 43 human tissue samples of HCC. Using in situ hybridization, Snail mRNA was determined to dominantly express in HCC cells, but not in bile duct cells, blood vessels or infiltrating leukocytes. The mRNA of Snail and Slug were quantified using real-time reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. Snail mRNA was overexpressed in 7 cases (16%) of HCC compared with adjacent noncancerous liver tissue. E-Cadherin protein expression determined in the same 43 cases by immunohistochemistry was significantly down-regulated in those cases with Snail mRNA overexpression (P = 0.04). The tumor and nontumor ratio of Snail mRNA independently correlated with tumor invasiveness (P = 0.04). However, Slug mRNA correlated with neither E-cadherin expression nor tumor invasiveness. The data indicate that Snail both down-regulates E-cadherin expression and promotes the invasion in human HCC.","null","null","2003-06","Clinical Cancer Research","Clinical Cancer Research","Vol.9","No.7","2657","2664","eng","true","null","scientific_journal","null","null","null","1078-0432","null","http://clincancerres.aacrjournals.org/cgi/content/abstract/9/7/2657","null","null","null"
"Accurate preoperative estimatin of liver-graft volumetry using three-dimensional computed tomography","Accurate preoperative estimatin of liver-graft volumetry using three-dimensional computed tomography","Shoji Hiroshige, Mitsuo Shimada, Noboru Harada, Satoko Shiotani, Mizuki Ninomiya, Ryousuke Minagawa, Yuji Soejima, Taketoshi Suehiro, Hiroshi Honda, Makoto Hashizume, Keizo Sugimachi","Shoji Hiroshige, Mitsuo Shimada, Noboru Harada, Satoko Shiotani, Mizuki Ninomiya, Ryousuke Minagawa, Yuji Soejima, Taketoshi Suehiro, Hiroshi Honda, Makoto Hashizume, Keizo Sugimachi","null","The aim of this study was to clarify the value of three-dimensional computed-tomography (3D-CT) volumetry for size matching in living-donor liver transplantation (LDLT). 3D-CT volumetry was applied to 25 donors who underwent hepatectomy for a living relative needing an orthotopic liver transplantation. Fifteen patients underwent extended left lobectomy, one patient an extended left lateral lobectomy, and nine patients right lobectomy. 3D-CT imaging was performed with the workstation ZIO M900 (Zio Software Inc., Tokyo, Japan). The estimated volume of the grafts in two-dimensional (2D) and 3D images were compared, and an error ratio was calculated. 3D-CT imaging revealed the anatomy of the hepatic vein bifurcation and the shape of the graft. The error ratio was 12.8+/-2.3% in 3D, compared with 19.4+/-2.5% in 2D. As such, 3D-CT volumetry appears to be more exact than conventional 2D-CT volumetry, but volumetry by 3D-CT still produces an error ratio of approximately 13%. The weight transition of the rats' livers under preservation in University of Wisconsin (UW) solution indicated that the graft volume seems to decrease during perfusion with UW solution. Mismatch of the cutting line and volume reduction by dehydration (approximately 5% reduction 1 hour after perfusion) seems to cause the error in 3D-CT volumetry. Three-dimensional CT volumetry is useful for size matching in cases of living-related orthotopic liver transplantation.","The aim of this study was to clarify the value of three-dimensional computed-tomography (3D-CT) volumetry for size matching in living-donor liver transplantation (LDLT). 3D-CT volumetry was applied to 25 donors who underwent hepatectomy for a living relative needing an orthotopic liver transplantation. Fifteen patients underwent extended left lobectomy, one patient an extended left lateral lobectomy, and nine patients right lobectomy. 3D-CT imaging was performed with the workstation ZIO M900 (Zio Software Inc., Tokyo, Japan). The estimated volume of the grafts in two-dimensional (2D) and 3D images were compared, and an error ratio was calculated. 3D-CT imaging revealed the anatomy of the hepatic vein bifurcation and the shape of the graft. The error ratio was 12.8+/-2.3% in 3D, compared with 19.4+/-2.5% in 2D. As such, 3D-CT volumetry appears to be more exact than conventional 2D-CT volumetry, but volumetry by 3D-CT still produces an error ratio of approximately 13%. The weight transition of the rats' livers under preservation in University of Wisconsin (UW) solution indicated that the graft volume seems to decrease during perfusion with UW solution. Mismatch of the cutting line and volume reduction by dehydration (approximately 5% reduction 1 hour after perfusion) seems to cause the error in 3D-CT volumetry. Three-dimensional CT volumetry is useful for size matching in cases of living-related orthotopic liver transplantation.","null","null","2003-05-15","Transplantation","Transplantation","Vol.75","No.9","1561","1564","eng","true","null","scientific_journal","null","null","10.1097/01.TP.0000053755.08825.12","0041-1337","null","http://www.transplantjournal.com/pt/re/transplantation/abstract.00007890-200305150-00026.htm;jsessionid=EZIy92S7aRZ8rg8H2kAlI5cE9RelcquY1w6bRgmEOUvasbxPmOee!-1070481199!-949856145!9001!-1","null","null","null"
"Human WISP1v, a menber of CCN family, is associated with invasive cholangiocarcinoma","Human WISP1v, a menber of CCN family, is associated with invasive cholangiocarcinoma","Shinji Tanaka, Keishi Sugimachi, Toshifumi Kameyama, Shin-ichiro Maehara, Ken Shirabe, Mitsuo Shimada, Jack R. Wands, Yoshihiko Maehara","Shinji Tanaka, Keishi Sugimachi, Toshifumi Kameyama, Shin-ichiro Maehara, Ken Shirabe, Mitsuo Shimada, Jack R. Wands, Yoshihiko Maehara","null","Family members of the connective tissue growth factor, cysteine-rich 61, nephroblastoma over-expressed gene (CCN) encode cysteine-rich secreted proteins with roles in human fibrotic disorders and tumor progression. In this study, we identified a CCN family member, WISP1v, as over-expressed in human cholangiocarcinomas. Genetic analysis of WISP1v was performed on surgically resected specimens of cholangiocarcinoma. The WISP1v biological effects were analyzed using the HuCCT1 human cholangiocarcinoma cell line. The WISP1v gene was expressed in 19 of 39 cholangiocarcinoma tissues (49%) but not in normal livers. Expression of WISP1v was significantly associated with lymphatic and perineural invasion of tumor cells (P <.05), as well as a poor clinical prognosis (P <.01). In the intraductal papillary cholangiocarcinomas, WISP1v was detected only in the cases with duct wall invasion but not in the cases without duct wall invasion (P <.05). No mutation of WISP1v gene was detected in the examined samples. In vitro analysis revealed that WISP1v stimulated the invasive phenotype of cholangiocarcinoma cells with activation of both p38 and p42/p44 mitogen-activated protein kinases (MAPKs). Furthermore, WISP1v-induced cholangiocarcinoma invasion was significantly suppressed by the p38 MAPK inhibitor SB203580 but not by the p42/p44 MAPK kinase (MEK) inhibitor PD98059. Our findings suggest that WISP1v-mediated signaling is involved in the generation of invasive cellular properties and leads to progression of cholangiocarcinoma.","Family members of the connective tissue growth factor, cysteine-rich 61, nephroblastoma over-expressed gene (CCN) encode cysteine-rich secreted proteins with roles in human fibrotic disorders and tumor progression. In this study, we identified a CCN family member, WISP1v, as over-expressed in human cholangiocarcinomas. Genetic analysis of WISP1v was performed on surgically resected specimens of cholangiocarcinoma. The WISP1v biological effects were analyzed using the HuCCT1 human cholangiocarcinoma cell line. The WISP1v gene was expressed in 19 of 39 cholangiocarcinoma tissues (49%) but not in normal livers. Expression of WISP1v was significantly associated with lymphatic and perineural invasion of tumor cells (P <.05), as well as a poor clinical prognosis (P <.01). In the intraductal papillary cholangiocarcinomas, WISP1v was detected only in the cases with duct wall invasion but not in the cases without duct wall invasion (P <.05). No mutation of WISP1v gene was detected in the examined samples. In vitro analysis revealed that WISP1v stimulated the invasive phenotype of cholangiocarcinoma cells with activation of both p38 and p42/p44 mitogen-activated protein kinases (MAPKs). Furthermore, WISP1v-induced cholangiocarcinoma invasion was significantly suppressed by the p38 MAPK inhibitor SB203580 but not by the p42/p44 MAPK kinase (MEK) inhibitor PD98059. Our findings suggest that WISP1v-mediated signaling is involved in the generation of invasive cellular properties and leads to progression of cholangiocarcinoma.","null","null","2003-05","Hepatology","Hepatology","Vol.37","No.5","1122","1129","eng","true","null","scientific_journal","null","null","10.1053/jhep.2003.50187","0270-9139","null","null","null","null","null"
"Feasibility of duct-to-duct biliary reconstruction in left-lobe adult-living-donor liver transplantation","Feasibility of duct-to-duct biliary reconstruction in left-lobe adult-living-donor liver transplantation","Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Keiji Kishikawa, Ryosuke Minagawa, Shoji Hiroshige, Mizuki Ninomiya, Satoko Shiotani, Noboru Harada, Keizo Sugimachi","Yuji Soejima, Mitsuo Shimada, Taketoshi Suehiro, Keiji Kishikawa, Ryosuke Minagawa, Shoji Hiroshige, Mizuki Ninomiya, Satoko Shiotani, Noboru Harada, Keizo Sugimachi","null","A Roux-en-Y choledochojejunostomy (CDJ) has been the sole method of choice for the reconstruction of the bile duct in living-donor liver transplantation (LDLT) using left-lobe grafts. In this study, we evaluated the feasibility of duct-to-duct (DD) biliary reconstruction in adult-to-adult LDLT using left-lobe grafts. Between October 1996 and October 2001, 46 adult-to-adult LDLTs using the left lobe were performed at our institution. The DD biliary reconstruction (hepaticocholedochostomy) over a T-tube was performed for seven of the last nine recipients (DD group, n=7), whereas the conventional Roux-en-Y CDJ was used for the remaining cases (CDJ group, n=39). The technical problems and the incidence of biliary complications were compared between the groups. Bile leakage developed in only 1 of 7 (14%) in the DD group (leakage from a T-tube exit site), whereas it occurred in 8 of 39 (20%) in the CDJ group. Up to now, no patients from the DD group developed anastomotic stricture, whereas twelve (30.7%) patients from the CDJ group did. Other complications included bleeding from the Roux-en-Y jejunojejunostomy (n=1) and anastomotic occlusion caused by an internal stent (n=1), and both complications were associated with CDJ. In conclusion, DD anastomosis is a simple and viable option for biliary reconstruction in left-lobe LDLTs. A long-term follow-up, especially regarding the incidence of biliary stricture, is thus warranted in such patients.","A Roux-en-Y choledochojejunostomy (CDJ) has been the sole method of choice for the reconstruction of the bile duct in living-donor liver transplantation (LDLT) using left-lobe grafts. In this study, we evaluated the feasibility of duct-to-duct (DD) biliary reconstruction in adult-to-adult LDLT using left-lobe grafts. Between October 1996 and October 2001, 46 adult-to-adult LDLTs using the left lobe were performed at our institution. The DD biliary reconstruction (hepaticocholedochostomy) over a T-tube was performed for seven of the last nine recipients (DD group, n=7), whereas the conventional Roux-en-Y CDJ was used for the remaining cases (CDJ group, n=39). The technical problems and the incidence of biliary complications were compared between the groups. Bile leakage developed in only 1 of 7 (14%) in the DD group (leakage from a T-tube exit site), whereas it occurred in 8 of 39 (20%) in the CDJ group. Up to now, no patients from the DD group developed anastomotic stricture, whereas twelve (30.7%) patients from the CDJ group did. Other complications included bleeding from the Roux-en-Y jejunojejunostomy (n=1) and anastomotic occlusion caused by an internal stent (n=1), and both complications were associated with CDJ. In conclusion, DD anastomosis is a simple and viable option for biliary reconstruction in left-lobe LDLTs. A long-term follow-up, especially regarding the incidence of biliary stricture, is thus warranted in such patients.","null","null","2003-02-27","Transplantation","Transplantation","Vol.75","No.4","557","559","eng","true","null","scientific_journal","null","null","10.1097/01.TP.0000048220.90971.5A","0041-1337","null","http://www.transplantjournal.com/pt/re/transplantation/abstract.00007890-200302270-00025.htm;jsessionid=EYHAwiQ6XrKtNTTHu1DMmM03swS1AfasjO5byljCKtrF2E1Xd8gz!-1070481199!-949856145!9001!-1","null","null","null"
"Effecacy of a larger version of the hybrid artificial liver support system using a polyurethane foam/spheroid packed-bed module in a warm ischemic liver failure pig model for preclinical experiments","Effecacy of a larger version of the hybrid artificial liver support system using a polyurethane foam/spheroid packed-bed module in a warm ischemic liver failure pig model for preclinical experiments","Yo-ichi Yamashita, Mitsuo Shimada, Eiji Tsujita, Ken Shirabe, Hiroyuki Ijima, Kohji Nakazawa, Ryoichi Sakiyama, Junji Fukuda, Kazumori Funatsu, Keizo Sugimachi","Yo-ichi Yamashita, Mitsuo Shimada, Eiji Tsujita, Ken Shirabe, Hiroyuki Ijima, Kohji Nakazawa, Ryoichi Sakiyama, Junji Fukuda, Kazumori Funatsu, Keizo Sugimachi","null","We have reported the usefulness of a polyurethane foam packed-bed culture system of hepatocyte spheroids as a hybrid artificial liver support system (PUF-HALSS). The aim of this study was to evaluate in detail the efficacy in serum parameters regarding the liver function of a larger version of the PUF-HALSS containing 2 x 10(10) porcine hepatocytes for clinical use in warm ischemic liver failure pigs. Warm ischemic liver failure pigs weighing 25 kg were divided into two groups: (1) a control group (n = 3), in which each pig was attached to a PUF-HALSS without hepatocytes, and (2) a HALSS group (n = 3), in which each pig was attached to a PUF-HALSS. In the HALSS group, the increase of blood ammonia was completely suppressed and blood lactate levels were significantly suppressed. The Fisher's ratio was better maintained, and the increase of total bile acid, glycochenodeoxycholic acid, and taurochenodeoxycholic acid was significantly suppressed in the HALSS group. Serum creatinine levels were significantly lower, and blood glucose levels were significantly higher in the HALSS group. Serum levels of tumor necrosis factor- a were not elevated in either group. In conclusion, the larger version of the PUF-HALSS demonstrated many advantages as a liver support system in warm ischemic liver failure pigs.","We have reported the usefulness of a polyurethane foam packed-bed culture system of hepatocyte spheroids as a hybrid artificial liver support system (PUF-HALSS). The aim of this study was to evaluate in detail the efficacy in serum parameters regarding the liver function of a larger version of the PUF-HALSS containing 2 x 10(10) porcine hepatocytes for clinical use in warm ischemic liver failure pigs. Warm ischemic liver failure pigs weighing 25 kg were divided into two groups: (1) a control group (n = 3), in which each pig was attached to a PUF-HALSS without hepatocytes, and (2) a HALSS group (n = 3), in which each pig was attached to a PUF-HALSS. In the HALSS group, the increase of blood ammonia was completely suppressed and blood lactate levels were significantly suppressed. The Fisher's ratio was better maintained, and the increase of total bile acid, glycochenodeoxycholic acid, and taurochenodeoxycholic acid was significantly suppressed in the HALSS group. Serum creatinine levels were significantly lower, and blood glucose levels were significantly higher in the HALSS group. Serum levels of tumor necrosis factor- a were not elevated in either group. In conclusion, the larger version of the PUF-HALSS demonstrated many advantages as a liver support system in warm ischemic liver failure pigs.","null","null","2003","Cell Transplantation","Cell Transplantation","Vol.12","No.2","101","107","eng","true","null","scientific_journal","null","null","null","0963-6897","null","null","null","null","null"
"Beneficial effect of MCI-186 on hepatic warm ischemia-reperfusion in the rat","Beneficial effect of MCI-186 on hepatic warm ischemia-reperfusion in the rat","Mizuki Ninomiya, Mitsuo Shimada, Noboru Harada, Satoko Shiotani, Shoji Hiroshige, Yuji Soejima, Taketoshi Suehiro, Keizo Sugimachi","Mizuki Ninomiya, Mitsuo Shimada, Noboru Harada, Satoko Shiotani, Shoji Hiroshige, Yuji Soejima, Taketoshi Suehiro, Keizo Sugimachi","null","Despite growing evidence that reactive oxygen species are responsible for deleterious effects of ischemia-reperfusion (I/R) injury of the liver, there exists, until now, no reliable antioxidant therapeutics applicable in the clinical setting. We investigated the effects of free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), using an isolated liver perfusion model to elucidate its possible therapeutic effects on hepatic warm I/R injury. Isolated livers from Wistar rats were reperfused for 120 min with an oxygenated Krebs-Henseleit bicarbonate buffer after 1 hr of warm ischemia. Addition of MCI-186 (1 mg/L) into the perfusate significantly improved portal flow, hepatic enzyme release into the perfusate, total bile production, histologic alteration, and malondialdehyde concentration but not sinusoidal endothelial cell function as assessed by the clearance of hyaluronic acid. MCI-186 seems to have protective effects against hepatic warm I/R injury by attenuating the damage of the hepatocyte, which is the major target of oxidative damage in this model.","Despite growing evidence that reactive oxygen species are responsible for deleterious effects of ischemia-reperfusion (I/R) injury of the liver, there exists, until now, no reliable antioxidant therapeutics applicable in the clinical setting. We investigated the effects of free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), using an isolated liver perfusion model to elucidate its possible therapeutic effects on hepatic warm I/R injury. Isolated livers from Wistar rats were reperfused for 120 min with an oxygenated Krebs-Henseleit bicarbonate buffer after 1 hr of warm ischemia. Addition of MCI-186 (1 mg/L) into the perfusate significantly improved portal flow, hepatic enzyme release into the perfusate, total bile production, histologic alteration, and malondialdehyde concentration but not sinusoidal endothelial cell function as assessed by the clearance of hyaluronic acid. MCI-186 seems to have protective effects against hepatic warm I/R injury by attenuating the damage of the hepatocyte, which is the major target of oxidative damage in this model.","null","null","2002-11-27","Transplantation","Transplantation","Vol.74","No.10","1470","1472","eng","true","null","scientific_journal","null","null","10.1097/00007890-200211270-00021","0041-1337","null","http://www.transplantjournal.com/pt/re/transplantation/abstract.00007890-200211270-00021.htm;jsessionid=EZIy92S7aRZ8rg8H2kAlI5cE9RelcquY1w6bRgmEOUvasbxPmOee!-1070481199!-949856145!9001!-1","null","null","null"
"In Vivo Gene Transfer into Muscle via Electro-Sonoporation","In Vivo Gene Transfer into Muscle via Electro-Sonoporation","Yo-ichi Yamashita, Mitsuo Shimada, Katsuro Tachibana, Norifumi Harimoto, Eiji Tsujita, Ken Shirabe, Jun-ichi Miyazaki, Keizo Sugimachi","Yo-ichi Yamashita, Mitsuo Shimada, Katsuro Tachibana, Norifumi Harimoto, Eiji Tsujita, Ken Shirabe, Jun-ichi Miyazaki, Keizo Sugimachi","null","Among the nonviral techniques for gene transfer in vivo, electroporation is simple, potent, inexpensive, and safe. To upregulate the expression levels of the transferred gene, we investigated the applicability of in vivo electro-sonoporation, which consists of a combination of electric pulse and ultrasound, for gene transfer using plasmid DNA encoding luciferase and mouse interleukin-12 (mIL-12). The quadriceps muscles of mice were injected with plasmid DNA, then sonoporated for 5 min, and electroporated by a pair of electrode plates at the middle of the duration of sonoporation. Three days later, mice that had undergone electro-sonoporation demonstrated twofold higher luciferase activity and low tissue damage in quadriceps muscle compared to mice having undergone electroporation alone. Serum mIL-12 levels in mice that had undergone electro-sonoporation (peaking at 25.5 ng/ml) were twofold higher after gene transfer than were those in mice having undergone electroporation alone (peaking at 14.3 ng/ml), and maintained high serum level of 13.9 ng/ml at 28 days after gene transfer. The efficacy of gene transfer via electro-sonoporation was superior when the plasmid DNA solution was 0.85% NaCl compared to albumin microbubble echo-contrast material. These results demonstrated that gene transfer into muscle via electro-sonoporation could provide a new potent nonviral technique for gene transfer in vivo.","Among the nonviral techniques for gene transfer in vivo, electroporation is simple, potent, inexpensive, and safe. To upregulate the expression levels of the transferred gene, we investigated the applicability of in vivo electro-sonoporation, which consists of a combination of electric pulse and ultrasound, for gene transfer using plasmid DNA encoding luciferase and mouse interleukin-12 (mIL-12). The quadriceps muscles of mice were injected with plasmid DNA, then sonoporated for 5 min, and electroporated by a pair of electrode plates at the middle of the duration of sonoporation. Three days later, mice that had undergone electro-sonoporation demonstrated twofold higher luciferase activity and low tissue damage in quadriceps muscle compared to mice having undergone electroporation alone. Serum mIL-12 levels in mice that had undergone electro-sonoporation (peaking at 25.5 ng/ml) were twofold higher after gene transfer than were those in mice having undergone electroporation alone (peaking at 14.3 ng/ml), and maintained high serum level of 13.9 ng/ml at 28 days after gene transfer. The efficacy of gene transfer via electro-sonoporation was superior when the plasmid DNA solution was 0.85% NaCl compared to albumin microbubble echo-contrast material. These results demonstrated that gene transfer into muscle via electro-sonoporation could provide a new potent nonviral technique for gene transfer in vivo.","null","null","2002-11-20","Human Gene Therapy","Human Gene Therapy","Vol.13","No.17","2079","2084","eng","true","null","scientific_journal","null","null","10.1089/10430340260395929","1043-0342","null","http://www.liebertonline.com/doi/abs/10.1089%2F10430340260395929","null","null","null"
"薬剤師の生体肝移植チームにおける役割 --- タクロリムス血中濃度の至適化および痙攣副作用発現の減少","薬剤師の生体肝移植チームにおける役割 --- タクロリムス血中濃度の至適化および痙攣副作用発現の減少","三嶋 一登, 牧野 和隆, 島田 光生, 末廣 剛敏, 副島 雄二, 千堂 年昭, 手嶋 大輔, 伊藤 義規, 大石 了三","三嶋 一登, 牧野 和隆, Mitsuo Shimada, 末廣 剛敏, Yuji Soejima, 千堂 年昭, 手嶋 大輔, 伊藤 義規, 大石 了三","null","This study aimed to evaluate the role of the pharmacist as a member of the liver transplant team in controlling tacrolimus concentrations and the incidence of convulsions as a side effect. Interventions of the pharmacist in the liver transplant team include the indications of dose setting, the checking of drug interactions, the monitoring of adverse effects and the instruction for patient compliance. Fifty-two patients who underwent a living-related liver transplantation were enrolled. The total number of 691 whole blood samples were collected during 2 weeks after liver transplantation and then were analyzed by microparticle enzyme immunoassay (MEIA) for tacrolimus trough concentrations. The standard deviation of tacrolimus trough level was 5.9 before pharmacist participation, while it decreased markedly to 3.7 after pharmacist participation. In addition, the variance significantly decreased. Five of 25 patients treated with tacrolimus before pharmacist participation encountered convulsions, however, none of the 27 patients showed any signs of convulsion after pharmacist participation. There was no significant difference in the rejection before (32%) or after (26%) pharmacist participation. We conclude that pharmacotherapy in the liver transplant team improved after pharmacist participation.","This study aimed to evaluate the role of the pharmacist as a member of the liver transplant team in controlling tacrolimus concentrations and the incidence of convulsions as a side effect. Interventions of the pharmacist in the liver transplant team include the indications of dose setting, the checking of drug interactions, the monitoring of adverse effects and the instruction for patient compliance. Fifty-two patients who underwent a living-related liver transplantation were enrolled. The total number of 691 whole blood samples were collected during 2 weeks after liver transplantation and then were analyzed by microparticle enzyme immunoassay (MEIA) for tacrolimus trough concentrations. The standard deviation of tacrolimus trough level was 5.9 before pharmacist participation, while it decreased markedly to 3.7 after pharmacist participation. In addition, the variance significantly decreased. Five of 25 patients treated with tacrolimus before pharmacist participation encountered convulsions, however, none of the 27 patients showed any signs of convulsion after pharmacist participation. There was no significant difference in the rejection before (32%) or after (26%) pharmacist participation. We conclude that pharmacotherapy in the liver transplant team improved after pharmacist participation.","null","null","2002-08-10","医療薬学","Japanese Journal of Pharmaceutical Health Care and Sciences","Vol.28","No.4","393","400","jpn","true","null","scientific_journal","null","null","10.5649/jjphcs.28.393","1346-342X","null","http://ci.nii.ac.jp/naid/110001166624/","null","null","null"
"Early experiences of endoscopic procedures in general surgery assisted by a computer enhanced surgical system","Early experiences of endoscopic procedures in general surgery assisted by a computer enhanced surgical system","Makoto Hashizume, Mitsuo Shimada, Morimasa Tomikawa, Yasuharu Ikeda, I Takahashi, R Abe, F Koga, N Gotoh, Kozo Konishi, Shin-ichiro Maehara, Keizo Sugimachi","Makoto Hashizume, Mitsuo Shimada, Morimasa Tomikawa, Yasuharu Ikeda, I Takahashi, R Abe, F Koga, N Gotoh, Kozo Konishi, Shin-ichiro Maehara, Keizo Sugimachi","null","We performed a variety of complete total endoscopic general surgical procedures, including colon resection, distal gastrectomy, and splenectomy, successfully with the assistance of the da Vinci computer-enhanced surgical system. The robotic system allowed us to manipulate the endoscopic instruments as effectively as during open surgery. It enhanced visualization of both the operative field and precision of the necessary techniques, as well as being less stressful for the endoscopic operating team. This technological innovation can therefore help surgeons overcome many of the difficulties associated with the endoscopic approach and thus has the potential to enable more precise, safer, and more minimally invasive surgery in the future.","We performed a variety of complete total endoscopic general surgical procedures, including colon resection, distal gastrectomy, and splenectomy, successfully with the assistance of the da Vinci computer-enhanced surgical system. The robotic system allowed us to manipulate the endoscopic instruments as effectively as during open surgery. It enhanced visualization of both the operative field and precision of the necessary techniques, as well as being less stressful for the endoscopic operating team. This technological innovation can therefore help surgeons overcome many of the difficulties associated with the endoscopic approach and thus has the potential to enable more precise, safer, and more minimally invasive surgery in the future.","null","null","2002-08","Surgical Endoscopy","Surgical Endoscopy","Vol.16","No.8","1187","1191","eng","true","null","scientific_journal","null","null","10.1007/s004640080154","1432-2218","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11984681&dopt=Citation","null","null","null"
"Hepatic artery reconstruction and biliary stricture formation after living donor adult liver transplantation using the left lobe","Hepatic artery reconstruction and biliary stricture formation after living donor adult liver transplantation using the left lobe","Taketoshi Suehiro, Mizuki Ninomiya, Satoko Shiotani, Syoji Hiroshige, Noboru Harada, Minagawa Ryosuke, Yuji Soejima, Mitsuo Shimada, Keizo Sugimachi","Taketoshi Suehiro, Mizuki Ninomiya, Satoko Shiotani, Syoji Hiroshige, Noboru Harada, Minagawa Ryosuke, Yuji Soejima, Mitsuo Shimada, Keizo Sugimachi","null","Biliary complications, including bile leak, biliary stricture, and cholangitis, are seen in 15% to 29% of all cases after living related liver transplantation. We investigate risk factors and discuss the management of biliary complications after living related liver transplantation in adults using left-lobe grafts. We studied 37 adult patients who underwent living related liver transplantation using left-lobe grafts. Perioperative variables were evaluated as risk factors for biliary strictures. The overall incidence of biliary complications was 43.2% (16 of 37 patients). Anastomotic strictures occurred in 8 patients, whereas bile leaks and cholangitis occurred in 9 and 8 patients, respectively. Anastomotic stricture was strongly related to a partial artery reconstruction (P <.02) and cholangitis (P <.01). Anastomotic biliary stricture was not associated with bile leak, acute cellular rejection, or infection. Our results suggest that an important risk factor for biliary anastomotic biliary strictures is a partial artery reconstruction. To minimize the risk for biliary anastomotic strictures, we will reconstruct both the middle and left hepatic artery.","Biliary complications, including bile leak, biliary stricture, and cholangitis, are seen in 15% to 29% of all cases after living related liver transplantation. We investigate risk factors and discuss the management of biliary complications after living related liver transplantation in adults using left-lobe grafts. We studied 37 adult patients who underwent living related liver transplantation using left-lobe grafts. Perioperative variables were evaluated as risk factors for biliary strictures. The overall incidence of biliary complications was 43.2% (16 of 37 patients). Anastomotic strictures occurred in 8 patients, whereas bile leaks and cholangitis occurred in 9 and 8 patients, respectively. Anastomotic stricture was strongly related to a partial artery reconstruction (P <.02) and cholangitis (P <.01). Anastomotic biliary stricture was not associated with bile leak, acute cellular rejection, or infection. Our results suggest that an important risk factor for biliary anastomotic biliary strictures is a partial artery reconstruction. To minimize the risk for biliary anastomotic strictures, we will reconstruct both the middle and left hepatic artery.","null","null","2002-05","Liver Transplantation","Liver Transplantation","Vol.8","No.5","495","499","eng","true","null","scientific_journal","null","null","10.1053/jlts.2002.32986","1527-6465","null","http://www3.interscience.wiley.com/cgi-bin/abstract/106593543/ABSTRACT","null","null","null"
"Tie2 vascular endothelial receptor expression and function in hepatocellular carcinoma","Tie2 vascular endothelial receptor expression and function in hepatocellular carcinoma","Shinji Tanaka, Keishi Sugimachi, Yo-ichi Yamashita, Takefumi Ohga, Ken Shirabe, Mitsuo Shimada, Jack R Wands, Keizo Sugimachi","Shinji Tanaka, Keishi Sugimachi, Yo-ichi Yamashita, Takefumi Ohga, Ken Shirabe, Mitsuo Shimada, Jack R Wands, Keizo Sugimachi","null","Hepatocellular carcinoma (HCC) is generally characterized as a hypervascular tumor of rapid growth. We have previously reported that angiopoietin (Ang), a ligand for Tie2 vascular endothelial-specific receptor tyrosine kinase, may play a role in the progression of human HCC (J Clin Invest 1999;103:341-345) and matrix proteinase expression (Cancer Res 2001;61:2145-2153). However, the role of Tie2 receptor in hepatic oncogenesis is unknown. The Tie2 receptor protein was overexpressed in the neovascular endothelium of 31 of 39 (80%) human HCC tumors by immunohistochemical analysis with significant correlation to cell dedifferentiation and tumor size (P <.05). In vitro expression of a dominant-negative construct, containing a soluble Tie2 ectodomain (sTie2), led to Ang protein interaction, inhibition of endogenous Tie2 phosphorylation in vascular endothelial cells and matrix metalloproteinase 9 (MMP-9) suppression. In conclusion, tumorigenicity with neovascularization was suppressed by in vivo gene transfer and sTie2 expression in a murine HCC model, suggesting a possible role for Tie2 expression in the induction of HCC neovascularization and disease progression. Inhibition of the Ang/Tie2 signal transduction cascade is a promising approach for tumor treatment.","Hepatocellular carcinoma (HCC) is generally characterized as a hypervascular tumor of rapid growth. We have previously reported that angiopoietin (Ang), a ligand for Tie2 vascular endothelial-specific receptor tyrosine kinase, may play a role in the progression of human HCC (J Clin Invest 1999;103:341-345) and matrix proteinase expression (Cancer Res 2001;61:2145-2153). However, the role of Tie2 receptor in hepatic oncogenesis is unknown. The Tie2 receptor protein was overexpressed in the neovascular endothelium of 31 of 39 (80%) human HCC tumors by immunohistochemical analysis with significant correlation to cell dedifferentiation and tumor size (P <.05). In vitro expression of a dominant-negative construct, containing a soluble Tie2 ectodomain (sTie2), led to Ang protein interaction, inhibition of endogenous Tie2 phosphorylation in vascular endothelial cells and matrix metalloproteinase 9 (MMP-9) suppression. In conclusion, tumorigenicity with neovascularization was suppressed by in vivo gene transfer and sTie2 expression in a murine HCC model, suggesting a possible role for Tie2 expression in the induction of HCC neovascularization and disease progression. Inhibition of the Ang/Tie2 signal transduction cascade is a promising approach for tumor treatment.","null","null","2002-05","Hepatology","Hepatology","Vol.35","No.4","861","867","eng","true","null","scientific_journal","null","null","10.1053/jhep.2002.32535","0270-9139","null","http://cat.inist.fr/?aModele=afficheN&cpsidt=13738937","null","null","null"
"G protein gamma 7 expression as a new clinicopathological maeker in patients with intrahepatic cholangiocarcinoma","G protein gamma 7 expression as a new clinicopathological maeker in patients with intrahepatic cholangiocarcinoma","Tohru Utsunomiya, Hiroshi Inoue, Ken-ichi Taguchi, Mitsuo Shimada, Keizo Sugimachi, Masaki Mori","Tohru Utsunomiya, Hiroshi Inoue, Ken-ichi Taguchi, Mitsuo Shimada, Keizo Sugimachi, Masaki Mori","null","The signal alterations mediated by small G proteins such as Ras, Rho, and Rac have been reported in several cancers. The human G protein gamma 7 (G-gamma 7) gene, which is down-regulated in various digestive organ cancers, was recently identified and cloned. Thus, the G-gamma 7-coupled heterotrimeric G proteins may also contribute to carcinogenesis in human cancers. University hospital and medical institute of bioregulation. The clinicopathological significance of G-gamma 7 expression in 18 patients with intrahepatic cholangiocarcinoma (IHCC) was examined. The tumor-nontumor ratio of G-gamma 7 expression was determined using reverse transcription polymerase chain reaction analysis. To visualize the localization of G-gamma 7, an immunohistochemical study was performed. Clinicopathological significance of G-gamma 7 expression in human IHCC. Expression of G-gamma 7 messenger RNA was lower in tumor tissue than in the corresponding nontumor tissue in 17 (94%) of 18 patients with IHCC. The mean tumor-nontumor ratio was 0.54. Eleven patients with tumor-nontumor ratios less than 0.5 showed significantly poorer differentiated IHCC than 7 with tumor-nontumor ratios of 0.5 and greater (P<.01). Decreased expression of G-gamma 7 protein in the carcinoma tissue, especially in the poorly differentiated IHCC tissue, was confirmed using immunohistochemical staining. Reduced expression of G-gamma 7 is associated with the histological grade of IHCC and may therefore prove to be a useful marker for predicting the biological aggressiveness of human IHCC.","The signal alterations mediated by small G proteins such as Ras, Rho, and Rac have been reported in several cancers. The human G protein gamma 7 (G-gamma 7) gene, which is down-regulated in various digestive organ cancers, was recently identified and cloned. Thus, the G-gamma 7-coupled heterotrimeric G proteins may also contribute to carcinogenesis in human cancers. University hospital and medical institute of bioregulation. The clinicopathological significance of G-gamma 7 expression in 18 patients with intrahepatic cholangiocarcinoma (IHCC) was examined. The tumor-nontumor ratio of G-gamma 7 expression was determined using reverse transcription polymerase chain reaction analysis. To visualize the localization of G-gamma 7, an immunohistochemical study was performed. Clinicopathological significance of G-gamma 7 expression in human IHCC. Expression of G-gamma 7 messenger RNA was lower in tumor tissue than in the corresponding nontumor tissue in 17 (94%) of 18 patients with IHCC. The mean tumor-nontumor ratio was 0.54. Eleven patients with tumor-nontumor ratios less than 0.5 showed significantly poorer differentiated IHCC than 7 with tumor-nontumor ratios of 0.5 and greater (P<.01). Decreased expression of G-gamma 7 protein in the carcinoma tissue, especially in the poorly differentiated IHCC tissue, was confirmed using immunohistochemical staining. Reduced expression of G-gamma 7 is associated with the histological grade of IHCC and may therefore prove to be a useful marker for predicting the biological aggressiveness of human IHCC.","null","null","2002-02","Archives of Surgery","Archives of Surgery","Vol.137","No.2","181","185","eng","true","null","scientific_journal","null","null","10.1001/archsurg.137.2.181","0004-0010","null","null","null","null","null"
"Electroporation-mediated tumor necrosis factor related apotosis-inducing ligand (TRAIL)/Apo2L gene therapy for hepatocellular carcinoma","Electroporation-mediated tumor necrosis factor related apotosis-inducing ligand (TRAIL)/Apo2L gene therapy for hepatocellular carcinoma","Yo-ichi Yamashita, Mitsuo Shimada, Shinji Tanaka, Masahiro Okamoto, Jun-ichi Miyazaki, Keizo Sugimachi","Yo-ichi Yamashita, Mitsuo Shimada, Shinji Tanaka, Masahiro Okamoto, Jun-ichi Miyazaki, Keizo Sugimachi","null","Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2 ligand (Apo2L) has been identified as important in promoting programmed cell death in breast and colon cancer xenografts. More importantly, normal liver tissue appears not to be susceptible to the cytotoxic effects of TRAIL/Apo2L, although activation of the related Fas ligand receptor system is known to promote massive liver apoptosis terminating in fulminant hepatitis. In the present study, we investigated the therapeutic potential of TRAIL/Apo2L gene therapy in hepatocellular carcinoma (HCC) and evaluated its side effects in an immune-competent mouse model. Intratumoral administration of the TRAIL/Apo2L vector by electroporation elevated serum TRAIL/Apo2L through at least day 28 after gene therapy and significantly inhibited the growth not only of the HCC directly administered TRAIL/Apo2L vector, but also of distant subcutaneous HCC. In addition, intratumoral administration of the TRAIL/Apo2L vector inhibited spontaneous lung metastasis. Serum alanine aminotransferase was mildly elevated by TRAIL/Apo2L gene therapy, but without showing such histological signs as TUNEL staining. These results demonstrate that TRAIL/Apo2L gene therapy for HCC by electroporation in vivo is efficient without significant side effects, and is thus promising for use in future clinical trials.","Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2 ligand (Apo2L) has been identified as important in promoting programmed cell death in breast and colon cancer xenografts. More importantly, normal liver tissue appears not to be susceptible to the cytotoxic effects of TRAIL/Apo2L, although activation of the related Fas ligand receptor system is known to promote massive liver apoptosis terminating in fulminant hepatitis. In the present study, we investigated the therapeutic potential of TRAIL/Apo2L gene therapy in hepatocellular carcinoma (HCC) and evaluated its side effects in an immune-competent mouse model. Intratumoral administration of the TRAIL/Apo2L vector by electroporation elevated serum TRAIL/Apo2L through at least day 28 after gene therapy and significantly inhibited the growth not only of the HCC directly administered TRAIL/Apo2L vector, but also of distant subcutaneous HCC. In addition, intratumoral administration of the TRAIL/Apo2L vector inhibited spontaneous lung metastasis. Serum alanine aminotransferase was mildly elevated by TRAIL/Apo2L gene therapy, but without showing such histological signs as TUNEL staining. These results demonstrate that TRAIL/Apo2L gene therapy for HCC by electroporation in vivo is efficient without significant side effects, and is thus promising for use in future clinical trials.","null","null","2002-01-20","Human Gene Therapy","Human Gene Therapy","Vol.13","No.2","275","286","eng","true","null","scientific_journal","null","null","10.1089/10430340252769798","1043-0342","null","http://www.liebertonline.com/doi/abs/10.1089/10430340252769798?cookieSet=1&journalCode=hum","null","null","null"
"Living-donor liver transplantation for fulminant hepatic failure in adult patients with a left-lobe graft","Living-donor liver transplantation for fulminant hepatic failure in adult patients with a left-lobe graft","Takashi Nishizaki, Shoji Hiroshige, Toru Ikegami, Hideaki Uchiyama, Koji Hashimoto, Yuji Soejima, Mitsuo Shimada","Takashi Nishizaki, Shoji Hiroshige, Toru Ikegami, Hideaki Uchiyama, Koji Hashimoto, Yuji Soejima, Mitsuo Shimada","null","Living donors are practically the only source of organs in countries where the availability of cadaveric donors is severely restricted, such as Japan. A left-lobe graft, in which one third of the liver is donated, is therefore used for adult-to-adult living-donor liver transplantation (LDLT) in patients with fulminant hepatic failure (FHF). Fifteen adult patients with FHF, ranging from 22 to 59 years of age, were treated with LDLT with a left-lobe graft. Preoperative encephalopathy was grade II in 2 patients, grade III in 4 patients, and grade IV in 9 patients. The graft volume (GV) ranged from 260 to 570 mL, thus corresponding to 23% to 54% of the recipients' standard liver volume (SLV). The patients were divided into 2 groups according to their GV/SLV: a medium-size graft group (GV/SLV > or =30%; group M, n = 11) and a small-size graft group (GV/SLV <30%; group S, n = 4). The effects of GV/SLV on graft function and survival were compared. Postoperative neurologic complications were also evaluated. The donors are all doing well. Twelve (80%) of the 15 recipients are still alive, with a follow-up period of from 3 to 43 months. No statistically significant differences were observed in the postoperative serum levels of bilirubin and alanine aminotransferase, prothrombin time, or frequency of postoperative complications between the 2 groups. The graft and patient survival rates were 75% (3/4) and 75% (3/4) in group S and 73% (8/11) and 82% (9/11) in group M, respectively. All patients who survived the perioperative period recovered without any neurologic sequelae. The high success rate and low donor risk of LDLT may therefore justify its use for adult patients with FHF using a left-lobe graft.","Living donors are practically the only source of organs in countries where the availability of cadaveric donors is severely restricted, such as Japan. A left-lobe graft, in which one third of the liver is donated, is therefore used for adult-to-adult living-donor liver transplantation (LDLT) in patients with fulminant hepatic failure (FHF). Fifteen adult patients with FHF, ranging from 22 to 59 years of age, were treated with LDLT with a left-lobe graft. Preoperative encephalopathy was grade II in 2 patients, grade III in 4 patients, and grade IV in 9 patients. The graft volume (GV) ranged from 260 to 570 mL, thus corresponding to 23% to 54% of the recipients' standard liver volume (SLV). The patients were divided into 2 groups according to their GV/SLV: a medium-size graft group (GV/SLV > or =30%; group M, n = 11) and a small-size graft group (GV/SLV <30%; group S, n = 4). The effects of GV/SLV on graft function and survival were compared. Postoperative neurologic complications were also evaluated. The donors are all doing well. Twelve (80%) of the 15 recipients are still alive, with a follow-up period of from 3 to 43 months. No statistically significant differences were observed in the postoperative serum levels of bilirubin and alanine aminotransferase, prothrombin time, or frequency of postoperative complications between the 2 groups. The graft and patient survival rates were 75% (3/4) and 75% (3/4) in group S and 73% (8/11) and 82% (9/11) in group M, respectively. All patients who survived the perioperative period recovered without any neurologic sequelae. The high success rate and low donor risk of LDLT may therefore justify its use for adult patients with FHF using a left-lobe graft.","null","null","2002-01","Surgery","Surgery","Vol.131","No.Supplement 1","S182","S189","eng","true","null","scientific_journal","null","null","10.1067/msy.2002.119574","0039-6060","null","http://dx.doi.org/10.1067/msy.2002.119574","null","null","null"
"Auxiliary partial orthotopic liver transplantation from living donors","Auxiliary partial orthotopic liver transplantation from living donors","Toru Ikegami, Satoko Shiotani, Mizuki Ninomiya, Ryosuke Minagawa, Takashi Nishizaki, Mitsuo Shimada, Keizo Sugimachi","Toru Ikegami, Satoko Shiotani, Mizuki Ninomiya, Ryosuke Minagawa, Takashi Nishizaki, Mitsuo Shimada, Keizo Sugimachi","null","Auxiliary liver transplantation was originally started in Western countries in the form of heterotopic auxiliary liver transplantation for end-stage liver disease. It thereafter developed into the form of auxiliary partial orthotopic liver transplantation for acute liver failure. In Japan, where living-donor liver transplantation is the main mode of liver transplantation, auxiliary partial orthotopic liver transplantation was initially used for patients with metabolic liver diseases and has since developed into an effective solution for small-for-size living donor grafts. Although there has been a reported case of successful auxiliary partial orthotopic liver transplantation from a living donor for the treatment of acute liver failure, wide application of this technique is made difficult at present by such unsolved problems as functional competition, small graft size, severe clinical status, and toxic liver syndrome. Auxiliary partial orthotopic liver transplantation from a living donor is an established procedure for small-for-size living-donor grafts and metabolic liver diseases, and the future establishment of its successful application to cases of acute liver failure is anticipated.","Auxiliary liver transplantation was originally started in Western countries in the form of heterotopic auxiliary liver transplantation for end-stage liver disease. It thereafter developed into the form of auxiliary partial orthotopic liver transplantation for acute liver failure. In Japan, where living-donor liver transplantation is the main mode of liver transplantation, auxiliary partial orthotopic liver transplantation was initially used for patients with metabolic liver diseases and has since developed into an effective solution for small-for-size living donor grafts. Although there has been a reported case of successful auxiliary partial orthotopic liver transplantation from a living donor for the treatment of acute liver failure, wide application of this technique is made difficult at present by such unsolved problems as functional competition, small graft size, severe clinical status, and toxic liver syndrome. Auxiliary partial orthotopic liver transplantation from a living donor is an established procedure for small-for-size living-donor grafts and metabolic liver diseases, and the future establishment of its successful application to cases of acute liver failure is anticipated.","null","null","2002-01","Surgery","Surgery","Vol.131","No.Supplement 1","S205","210","eng","true","null","scientific_journal","null","null","10.1067/msy.2002.119578","0039-6060","null","null","null","null","null"
"Hepatic artery reconstruction in living donor liver transplantation: review of its techniques and complications","Hepatic artery reconstruction in living donor liver transplantation: review of its techniques and complications","Hideaki Uchiyama, Koji Hashimoto, Shoji Hiroshige, Noboru Harada, Yuji Soejima, Takashi Nishizaki, Mitsuo Shimada, Taketoshi Suehiro","Hideaki Uchiyama, Koji Hashimoto, Shoji Hiroshige, Noboru Harada, Yuji Soejima, Takashi Nishizaki, Mitsuo Shimada, Taketoshi Suehiro","null","Hepatic arterial reconstruction is one of the most difficult procedures in living-donor liver transplantation (LDLT) because the artery used is generally small in diameter and has a short stalk. If hepatic artery thrombosis (HAT) occurs, the recipient clinical course will be unstable. The introduction of microvascular hepatic arterial reconstruction has significantly decreased the incidence of HAT. Fifty-two cases of LDLT were performed from October 1995 to May 2001 in our institution. Hepatic arterial reconstruction was performed under microscopic guidance. HATs were recognized in 2 cases (3.8%), both of which needed reoperation. Surgeons who perform hepatic arterial reconstruction in LDLT should be highly trained in microvascular techniques to decrease the incidence of HAT. This commentary reviews the surgical techniques of hepatic arterial reconstruction and possible complications that may arise in a reconstructed hepatic artery.","Hepatic arterial reconstruction is one of the most difficult procedures in living-donor liver transplantation (LDLT) because the artery used is generally small in diameter and has a short stalk. If hepatic artery thrombosis (HAT) occurs, the recipient clinical course will be unstable. The introduction of microvascular hepatic arterial reconstruction has significantly decreased the incidence of HAT. Fifty-two cases of LDLT were performed from October 1995 to May 2001 in our institution. Hepatic arterial reconstruction was performed under microscopic guidance. HATs were recognized in 2 cases (3.8%), both of which needed reoperation. Surgeons who perform hepatic arterial reconstruction in LDLT should be highly trained in microvascular techniques to decrease the incidence of HAT. This commentary reviews the surgical techniques of hepatic arterial reconstruction and possible complications that may arise in a reconstructed hepatic artery.","null","null","2002-01","Surgery","Surgery","Vol.131","No.1 Supplement 1","S200","S204","eng","true","null","scientific_journal","null","null","10.1067/msy.2002.119577","0039-6060","null","http://dx.doi.org/10.1067/msy.2002.119577","null","null","null"
"Perioperative management and complications of donor in living donor liver transplantation","Perioperative management and complications of donor in living donor liver transplantation","Yuji Soejima, Mitsuo Shimada, Noburu Harada, Taketoshi Suehiro, Ryosuke Minagawa, Shoji Hiroshige, Mizuki Ninomiya, Satoko Shiotani, Takashi Nishizaki","Yuji Soejima, Mitsuo Shimada, Noburu Harada, Taketoshi Suehiro, Ryosuke Minagawa, Shoji Hiroshige, Mizuki Ninomiya, Satoko Shiotani, Takashi Nishizaki","null","null","null","null","null","2002-01","Surgery","Surgery","Vol.131","No.Supplement 1","S195","199","eng","true","null","scientific_journal","null","null","10.1067/msy.2002.119576","0039-6060","null","http://dx.doi.org/10.1067/msy.2002.119576","null","null","null"
"Intrahepatic cholangiocarcinoma: its mode o spreading and therapeutic modalities","Intrahepatic cholangiocarcinoma: its mode o spreading and therapeutic modalities","Ken Shirabe, Mitsuo Shimada, Norifumi Harimoto, Keishi Sugimachi, Yo-ichi Yamashita, Eiji Tsujita, Shin-ichi Aishima","Ken Shirabe, Mitsuo Shimada, Norifumi Harimoto, Keishi Sugimachi, Yo-ichi Yamashita, Eiji Tsujita, Shin-ichi Aishima","null","Intrahepatic cholangiocarcinoma (IHCC) is a primary adenocarcinoma of the liver, arising from the intrahepatic bile ducts. The prognosis is generally poor because locoregional extension is usually advanced at the time of diagnosis. Even after a resection, the outcome for patients with advanced IHCC is extremely poor, and the presence of lymph node metastasis has been reported in most previous studies to be the worst prognostic factor after a resection. There are no clear guidelines on lymph node dissection with IHCC. In this article, we review the mode of invasion and the therapeutic modalities: hepatic resection, lymph node dissection, liver transplantation, radiation, and chemotherapy for IHCC.","Intrahepatic cholangiocarcinoma (IHCC) is a primary adenocarcinoma of the liver, arising from the intrahepatic bile ducts. The prognosis is generally poor because locoregional extension is usually advanced at the time of diagnosis. Even after a resection, the outcome for patients with advanced IHCC is extremely poor, and the presence of lymph node metastasis has been reported in most previous studies to be the worst prognostic factor after a resection. There are no clear guidelines on lymph node dissection with IHCC. In this article, we review the mode of invasion and the therapeutic modalities: hepatic resection, lymph node dissection, liver transplantation, radiation, and chemotherapy for IHCC.","null","null","2002-01","Surgery","Surgery","Vol.131","No.Supplement 1","S159","164","eng","true","null","scientific_journal","null","null","10.1067/msy.2002.119498","0039-6060","null","null","null","null","null"
"生体肝移植後の遷延性門脈圧亢進症","生体肝移植後の遷延性門脈圧亢進症","副島 雄二, 末廣 剛敏, 島田 光生","Yuji Soejima, 末廣 剛敏, Mitsuo Shimada","null","null","null","null","null","2002","今日の移植","今日の移植","Vol.15","null","362","365","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"生体肝右葉移植における3D-CT肝静脈画像構成の有用性","生体肝右葉移植における3D-CT肝静脈画像構成の有用性","広重 彰二, 島田 光生, 原田 昇, 塩谷 聡子, 二宮 瑞樹, 皆川 亮介, 副島 雄二, 末廣 剛敏, 本田 浩, 橋爪 誠, 前原 喜彦","広重 彰二, Mitsuo Shimada, 原田 昇, 塩谷 聡子, 二宮 瑞樹, 皆川 亮介, Yuji Soejima, 末廣 剛敏, 本田 浩, 橋爪 誠, 前原 喜彦","null","null","null","null","null","2001-12-30","日本コンピュータ外科学会誌","Journal of Japan Society of Computer Aided Surgery","Vol.3","No.3","155","156","jpn","true","null","scientific_journal","null","null","null","1344-9486","null","http://ci.nii.ac.jp/naid/10025680801/","null","null","null"
"Beneficial effects of 3-dimensional visualization on hepatic vein reconstruction in living donor liver transplantation using rught lobe graft","Beneficial effects of 3-dimensional visualization on hepatic vein reconstruction in living donor liver transplantation using rught lobe graft","Shoji Hiroshige, Takashi Nishizaki, Yuji Soejima, Koji Hashimoto, Ryuji Ohta, Ryousuke Minagawa, Mitsuo Shimada, Hiroshi Honda, Makoto Hashizume, Keizo Sugimachi","Shoji Hiroshige, Takashi Nishizaki, Yuji Soejima, Koji Hashimoto, Ryuji Ohta, Ryousuke Minagawa, Mitsuo Shimada, Hiroshi Honda, Makoto Hashizume, Keizo Sugimachi","null","Recently, virtual operation planning and navigation systems have been introduced in the field of neurosurgery and orthopedic surgery. We report here the beneficial effects of 3-dimensional (3D) visualization on hepatic venous reconstruction in living donor liver transplantation (LDLT) using right lobe graft. 3D-image reconstruction of the liver was rendered with 3-mm slices of helical computed tomography (CT) data using zioM900 (Zio Software Inc., Tokyo, Japan). To understand the anatomy of the donor's vessels and design an operation plan, a picture of the vessels in and around the liver was reconstructed. The 3D image demonstrated two short hepatic veins next to the inferior right hepatic vein (IRHV) as well as a large IRHV. The 3D image showed a more precise diameter of the right hepatic vein (RHV) and the IRHV and a more accurate distance between the two hepatic veins than did images measured by 2-dimensional CT. This preoperative information allowed the donor surgeon to dissect the inferior vena cava (IVC) and hepatic veins with reduced blood loss because of reduced risk of injury to the blood vessels. The 3D image revealed that both the RHV and the IRHV branched off at the same angle from the cylindrical IVC. Preoperative planning based on this information secured smooth anastomosis. 3D visualization is useful for hepatic venous reconstruction of the recipient as well as for donor surgery in LDLT using right lobe graft.","Recently, virtual operation planning and navigation systems have been introduced in the field of neurosurgery and orthopedic surgery. We report here the beneficial effects of 3-dimensional (3D) visualization on hepatic venous reconstruction in living donor liver transplantation (LDLT) using right lobe graft. 3D-image reconstruction of the liver was rendered with 3-mm slices of helical computed tomography (CT) data using zioM900 (Zio Software Inc., Tokyo, Japan). To understand the anatomy of the donor's vessels and design an operation plan, a picture of the vessels in and around the liver was reconstructed. The 3D image demonstrated two short hepatic veins next to the inferior right hepatic vein (IRHV) as well as a large IRHV. The 3D image showed a more precise diameter of the right hepatic vein (RHV) and the IRHV and a more accurate distance between the two hepatic veins than did images measured by 2-dimensional CT. This preoperative information allowed the donor surgeon to dissect the inferior vena cava (IVC) and hepatic veins with reduced blood loss because of reduced risk of injury to the blood vessels. The 3D image revealed that both the RHV and the IRHV branched off at the same angle from the cylindrical IVC. Preoperative planning based on this information secured smooth anastomosis. 3D visualization is useful for hepatic venous reconstruction of the recipient as well as for donor surgery in LDLT using right lobe graft.","null","null","2001-12-27","Transplantation","Transplantation","Vol.72","No.12","1993","1996","eng","true","null","scientific_journal","null","null","10.1097/00007890-200112270-00022","0041-1337","null","http://www.transplantjournal.com/pt/re/transplantation/abstract.00007890-200112270-00022.htm;jsessionid=EYFwiNrbIVCLh08EX1ff1muYH52lu6SYqIYQfOm2v19WAl5XlTAo!-1070481199!-949856145!9001!-1","null","null","null"
"The impact of donor age on living donor liver transplantation","The impact of donor age on living donor liver transplantation","Toru Ikegami, Takashi Nishizaki, Katsuhiko Yanaga, Mitsuo Shimada, Keishi Kishikawa, Kenichi Nomoto, Hideaki Uchiyama, Keizo Sugimachi","Toru Ikegami, Takashi Nishizaki, Katsuhiko Yanaga, Mitsuo Shimada, Keishi Kishikawa, Kenichi Nomoto, Hideaki Uchiyama, Keizo Sugimachi","null","The impact of the age of the donor on the outcome of living related liver transplantation is yet to be clarified. During October 14, 1996 and December 20, 1999, 34 living related liver transplantations were performed. Of these, 26 cases were performed using the extended left lobe graft, which were classified into three groups; younger donor group (group Y, donor age < 30, n = 7), middle-aged donor group (group M, 30 < or = donor age <50, n=13), and older donor group (group O, donor age < 50, n = 6). Early allograft function and regeneration were compared between these groups. There was no difference in standard liver volume, and predicted or harvested graft size between the three groups. Although serum transaminase and total bilirubin levels within postoperative day 7 were not different between the groups, the prothrombin time on postoperative day 3 was significantly longer in group O than in group Y. One week after transplantation, group Y had significantly greater graft/standard liver volume ratio than group O, and greater graft volume than group M and O. One month after transplantation, however, there was no significant difference in such graft size parameters between the groups. Graft and patient survival were comparable between the three groups. Although function and regeneration of the allografts from older donors in living donor liver transplantation is worse than those of their younger counterparts, the outcome is not affected by the age of the liver.","The impact of the age of the donor on the outcome of living related liver transplantation is yet to be clarified. During October 14, 1996 and December 20, 1999, 34 living related liver transplantations were performed. Of these, 26 cases were performed using the extended left lobe graft, which were classified into three groups; younger donor group (group Y, donor age < 30, n = 7), middle-aged donor group (group M, 30 < or = donor age <50, n=13), and older donor group (group O, donor age < 50, n = 6). Early allograft function and regeneration were compared between these groups. There was no difference in standard liver volume, and predicted or harvested graft size between the three groups. Although serum transaminase and total bilirubin levels within postoperative day 7 were not different between the groups, the prothrombin time on postoperative day 3 was significantly longer in group O than in group Y. One week after transplantation, group Y had significantly greater graft/standard liver volume ratio than group O, and greater graft volume than group M and O. One month after transplantation, however, there was no significant difference in such graft size parameters between the groups. Graft and patient survival were comparable between the three groups. Although function and regeneration of the allografts from older donors in living donor liver transplantation is worse than those of their younger counterparts, the outcome is not affected by the age of the liver.","null","null","2001-12-27","Transplantation","Transplantation","Vol.70","No.12","1703","1707","eng","true","null","scientific_journal","null","null","10.1097/00007890-200012270-00007","0041-1337","null","null","null","null","null"
"Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection","Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection","Eiji Hiroshita, Ken-ichi Taguchi, Akihiko Inokuchi, Takeshi Uchiumi, Naoko Kinukawa, Mitsuo Shimada, Masazumi Tsuneyoshi, Keizo Sugimachi, Michihiko Kuwano","Eiji Hiroshita, Ken-ichi Taguchi, Akihiko Inokuchi, Takeshi Uchiumi, Naoko Kinukawa, Mitsuo Shimada, Masazumi Tsuneyoshi, Keizo Sugimachi, Michihiko Kuwano","null","To understand hepatic injury during the process of hepatitis viral infection, determination of liver-specific functions at molecular levels is critical. Because the transport of endogenous/exogenous toxic substances is an intrinsically important hepatic function, we examined whether expression of the ATP-binding cassette (ABC) transporter gene was affected in patients with hepatitis viral infection. To determine which ABC transporter was expressed differently in patients with hepatic viral infection, we assayed the expression of MDR1, MDR3, MRP1, MRP2, and MRP3 in non-cancerous regions in the liver of 42 patients with hepatic tumors using both quantitative RT-PCR and immunological staining analysis, and compared the hepatic expression levels between patients with hepatitis viral infection and non-infected controls. Of the five ABC transporter genes studied, the mRNAs of MRP2 and MRP3 were highly expressed in the human liver. There was a significant reduction in MRP2 expression to 29% in the virus-infected liver. Treatment of hepatic cells with inflammatory cytokines resulted in decreased mRNA levels of MRP2 and decreased MRP2 promoter activity. The down-regulation of MRP2 might induce a failure in the transport of various genotoxic substances in the liver with hepatitis virus infection.","To understand hepatic injury during the process of hepatitis viral infection, determination of liver-specific functions at molecular levels is critical. Because the transport of endogenous/exogenous toxic substances is an intrinsically important hepatic function, we examined whether expression of the ATP-binding cassette (ABC) transporter gene was affected in patients with hepatitis viral infection. To determine which ABC transporter was expressed differently in patients with hepatic viral infection, we assayed the expression of MDR1, MDR3, MRP1, MRP2, and MRP3 in non-cancerous regions in the liver of 42 patients with hepatic tumors using both quantitative RT-PCR and immunological staining analysis, and compared the hepatic expression levels between patients with hepatitis viral infection and non-infected controls. Of the five ABC transporter genes studied, the mRNAs of MRP2 and MRP3 were highly expressed in the human liver. There was a significant reduction in MRP2 expression to 29% in the virus-infected liver. Treatment of hepatic cells with inflammatory cytokines resulted in decreased mRNA levels of MRP2 and decreased MRP2 promoter activity. The down-regulation of MRP2 might induce a failure in the transport of various genotoxic substances in the liver with hepatitis virus infection.","null","null","2001-12","Journal of Hepatology","Journal of Hepatology","Vol.35","No.6","765","773","eng","true","null","scientific_journal","null","null","10.1016/S0168-8278(01)00216-1","0168-8278","null","null","null","null","null"
"Value of lymph node dissection during resection of intrahepatic cholangiocarcinoma","Value of lymph node dissection during resection of intrahepatic cholangiocarcinoma","Mitsuo Shimada, Yo-ichi Yamashita, Shinichi Aishima, Ken Shirabe, Kenji Takenaka, Keizo Sugimachi","Mitsuo Shimada, Yo-ichi Yamashita, Shinichi Aishima, Ken Shirabe, Kenji Takenaka, Keizo Sugimachi","null","Hepatectomy with extensive lymph node dissection is the standard operation for intrahepatic cholangiocarcinoma (IHCC). However, lymph node dissection may not always be effective at reducing tumour recurrence. Forty-nine patients with IHCC who underwent hepatectomy were investigated to determine patterns of tumour recurrence and to estimate the value of lymph node dissection during resection. At hepatectomy most metastatic lymph nodes were identified at least to the level of group 2 lymph nodes. Among 23 patients who developed recurrence, 17 had liver metastases and the other six had recurrence at other sites, mainly in the peritoneum. Poorly differentiated histology was related to the development of liver metastases. No patient with the intraductal growth type of IHCC had tumour recurrence. Lymph node dissection did not appear to improve patient survival. Histological findings of lymph node metastases and intrahepatic metastases were independent indicators of poor prognosis. Lymph node metastases were seldom limited to the regional lymph nodes; most tumour recurrence occurred in the liver. Lymph node dissection did not appear to improve patient survival. Lymph node dissection alone is not likely to improve the prognosis without further control of liver metastases.","Hepatectomy with extensive lymph node dissection is the standard operation for intrahepatic cholangiocarcinoma (IHCC). However, lymph node dissection may not always be effective at reducing tumour recurrence. Forty-nine patients with IHCC who underwent hepatectomy were investigated to determine patterns of tumour recurrence and to estimate the value of lymph node dissection during resection. At hepatectomy most metastatic lymph nodes were identified at least to the level of group 2 lymph nodes. Among 23 patients who developed recurrence, 17 had liver metastases and the other six had recurrence at other sites, mainly in the peritoneum. Poorly differentiated histology was related to the development of liver metastases. No patient with the intraductal growth type of IHCC had tumour recurrence. Lymph node dissection did not appear to improve patient survival. Histological findings of lymph node metastases and intrahepatic metastases were independent indicators of poor prognosis. Lymph node metastases were seldom limited to the regional lymph nodes; most tumour recurrence occurred in the liver. Lymph node dissection did not appear to improve patient survival. Lymph node dissection alone is not likely to improve the prognosis without further control of liver metastases.","null","null","2001-11","The British Journal of Surgery","The British Journal of Surgery","Vol.88","No.11","1463","1466","eng","true","null","scientific_journal","null","null","10.1046/j.0007-1323.2001.01879.x","0007-1323","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11683741","null","null","null"
"A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhosu gastric carcinoma","A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhosu gastric carcinoma","Shinji Tanaka, Keishi Sugimachi, Hiroshi Saeki, Junko Kinoshita, Takefumi Oga, Mitsuo Shimada, Yoshihiko Maehara, Keizo Sugimachi","Shinji Tanaka, Keishi Sugimachi, Hiroshi Saeki, Junko Kinoshita, Takefumi Oga, Mitsuo Shimada, Yoshihiko Maehara, Keizo Sugimachi","null","Scirrhous carcinoma of the stomach is characterized by rapid growth with a vast fibrous stroma, high invasiveness, and substantially a poor prognosis. Little is known of the molecular pathogenesis of this disease. Members of the emerging family of the CCN gene (for connective tissue growth factor, cysteine-rich 61, nephroblastoma overexpressed) encode cysteine-rich secreted proteins with roles in human fibrotic disorders and cancer progression. Using targeted differential displays, we identified a novel variant of the CCN family member WISP1 (Wnt-induced secreted protein 1), named WISP1v, as overexpressed in scirrhous gastric carcinomas. Predicted protein of the WISP1v completely lacks a module of Von Willebrand type C that is thought to participate in protein complex formation. Ectopic expression revealed WISP1v to be a secreted oncoprotein inducing a striking cellular transformation and rapid piling-up growth. It is noteworthy that WISP1v transfectants enhanced the invasive phenotype of co-cultured gastric carcinoma cells, while wild-type WISP1 had no such potential. These findings suggest that CCN protein WISP1v is involved in the aggressive progression of scirrhous gastric carcinoma.","Scirrhous carcinoma of the stomach is characterized by rapid growth with a vast fibrous stroma, high invasiveness, and substantially a poor prognosis. Little is known of the molecular pathogenesis of this disease. Members of the emerging family of the CCN gene (for connective tissue growth factor, cysteine-rich 61, nephroblastoma overexpressed) encode cysteine-rich secreted proteins with roles in human fibrotic disorders and cancer progression. Using targeted differential displays, we identified a novel variant of the CCN family member WISP1 (Wnt-induced secreted protein 1), named WISP1v, as overexpressed in scirrhous gastric carcinomas. Predicted protein of the WISP1v completely lacks a module of Von Willebrand type C that is thought to participate in protein complex formation. Ectopic expression revealed WISP1v to be a secreted oncoprotein inducing a striking cellular transformation and rapid piling-up growth. It is noteworthy that WISP1v transfectants enhanced the invasive phenotype of co-cultured gastric carcinoma cells, while wild-type WISP1 had no such potential. These findings suggest that CCN protein WISP1v is involved in the aggressive progression of scirrhous gastric carcinoma.","null","null","2001-09-06","Oncogene","Oncogene","Vol.20","No.39","5525","5532","eng","true","null","scientific_journal","null","null","10.1038/sj.onc.1204723","0950-9232","null","null","null","null","null"
"The role of macroscopic classification in nodular-type hepatocellular carcinoma","The role of macroscopic classification in nodular-type hepatocellular carcinoma","Mitsuo Shimada, Tatsuya Rikimaru, Takayuki Hamatsu, Yo-ichi Yamashita, Takahiro Terashi, Ken-ichi Taguchi, Shinji Tanaka, Ken Shirabe, Keizo Sugimachi","Mitsuo Shimada, Tatsuya Rikimaru, Takayuki Hamatsu, Yo-ichi Yamashita, Takahiro Terashi, Ken-ichi Taguchi, Shinji Tanaka, Ken Shirabe, Keizo Sugimachi","null","Little has been reported on the role of macroscopic classification of hepatocellular carcinoma (HCC). We hypothesized that macroscopic classification of HCC might have a strong correlation with long-term prognosis after hepatectomy. Four hundred and four patients with a macroscopically nodular type of HCC who underwent a hepatectomy were studied. The patients were divided into three groups: single nodular (SN) group (n = 312); single nodular with extranodular growth (SNEG) group (n = 52); and confluent multinodular (CMN) group (n = 40). Clinicopathological variables were compared among the three groups. The patient survival rate was also compared among the three groups. Finally, a multivariate analysis was performed to clarify the independent significant variables of the long-term prognosis. To confirm the consistency of the results in small-size HCC, the same analyses were made using patients whose tumor size was equal to or less than 3 cm in diameter. The alpha-fetoprotein value, tumor size, and rate of absolute noncurative operation in the SNEG group were higher than in other groups. The positive rate of both portal vein invasion of cancer cells and intrahepatic metastasis in the SN group was lower than those in other groups. The rate of poorly differentiated histology in the SN group was lower than in the other groups. Patient survival in the SNEG group was worst among the three groups. However, patient survival showed no significant difference between the SN and CMN groups. The multivariate analysis showed that the presence of intrahepatic metastasis, the macroscopic classification of SNEG type, and absolute noncurative operation were independent poor prognostic indicators. The results for patients with small HCCs measuring equal to or less than 3 cm in diameter were quite similar to the results for the other patients. Among the three subtypes of macroscopically nodular type of HCCs, the SNEG type showed higher rates of portal vein invasion of cancer cells, intrahepatic metastasis, and poorly differentiated histology. The patient survival rate in the SNEG type was worst, and the SNEG type was an independent poor prognostic indicator. The macroscopic classification of HCC, especially the SNEG type, helps predict the long-term outcome after hepatectomy.","Little has been reported on the role of macroscopic classification of hepatocellular carcinoma (HCC). We hypothesized that macroscopic classification of HCC might have a strong correlation with long-term prognosis after hepatectomy. Four hundred and four patients with a macroscopically nodular type of HCC who underwent a hepatectomy were studied. The patients were divided into three groups: single nodular (SN) group (n = 312); single nodular with extranodular growth (SNEG) group (n = 52); and confluent multinodular (CMN) group (n = 40). Clinicopathological variables were compared among the three groups. The patient survival rate was also compared among the three groups. Finally, a multivariate analysis was performed to clarify the independent significant variables of the long-term prognosis. To confirm the consistency of the results in small-size HCC, the same analyses were made using patients whose tumor size was equal to or less than 3 cm in diameter. The alpha-fetoprotein value, tumor size, and rate of absolute noncurative operation in the SNEG group were higher than in other groups. The positive rate of both portal vein invasion of cancer cells and intrahepatic metastasis in the SN group was lower than those in other groups. The rate of poorly differentiated histology in the SN group was lower than in the other groups. Patient survival in the SNEG group was worst among the three groups. However, patient survival showed no significant difference between the SN and CMN groups. The multivariate analysis showed that the presence of intrahepatic metastasis, the macroscopic classification of SNEG type, and absolute noncurative operation were independent poor prognostic indicators. The results for patients with small HCCs measuring equal to or less than 3 cm in diameter were quite similar to the results for the other patients. Among the three subtypes of macroscopically nodular type of HCCs, the SNEG type showed higher rates of portal vein invasion of cancer cells, intrahepatic metastasis, and poorly differentiated histology. The patient survival rate in the SNEG type was worst, and the SNEG type was an independent poor prognostic indicator. The macroscopic classification of HCC, especially the SNEG type, helps predict the long-term outcome after hepatectomy.","null","null","2001-08","The American Journal of Surgery","The American Journal of Surgery","Vol.182","No.2","177","182","eng","true","null","scientific_journal","null","null","10.1016/S0002-9610(01)00682-1","0002-9610","null","null","null","null","null"
"The role of overeexpression and gene amplification of cyclin D1 in intrahepatic cholangiocarcinoma","The role of overeexpression and gene amplification of cyclin D1 in intrahepatic cholangiocarcinoma","Keishi Sugimachi, Shin-ichi Aishima, Ken-ichi Taguchi, Shinji Tanaka, Mitsuo Shimada, Kiyoshi Kajiyama, Keizo Sugimachi, Masazumi Tsuneyoshi","Keishi Sugimachi, Shin-ichi Aishima, Ken-ichi Taguchi, Shinji Tanaka, Mitsuo Shimada, Kiyoshi Kajiyama, Keizo Sugimachi, Masazumi Tsuneyoshi","null","Intrahepatic cholangiocarcinoma (ICC) is a primary liver malignant tumor with an extremely poor prognosis, but less attention has been directed to factors related to molecular carcinogenesis, including cell cycle proteins. We examined the expression and gene amplification of cyclin D1, the cell cycle regulating protein. Our objective was to evaluate correlations with clinicopathological factors in ICC. Cyclin D1 overexpression and cellular proliferative activity (Ki-67 labeling index) were investigated immunohistochemically, and 20 cases were further investigated for cyclin D1 gene amplification, using differential PCR. We examined the correlation between the expression and gene amplification of cyclin D1 and clinicopathological factors, including overall survival in patients with ICC. Immunohistochemical analysis revealed an overexpression of cyclin D1 protein in 28 of 66 subjects with ICCs (42%). The cyclin D1 overexpression was associated with poor histological differentiation (P = 0.04), high cellular proliferative activity (P < 0.01), and a poor prognosis (P = 0.02) by univariate analysis, although it is not an independent prognostic factor by multivariate analysis. Cyclin D1 gene amplification was confirmed in five of the 20 patients. Of those five cases of ICC, all had poor histological differentiation, and four of the five ICCs (80%) showed evidence of cyclin D1 immunoreactivity. Overexpression and gene amplification of cyclin D1 are frequent and contribute to dedifferentiation and cellular proliferative activity of ICCs, and overexpression also indicates a poor prognosis for patients with ICC.","Intrahepatic cholangiocarcinoma (ICC) is a primary liver malignant tumor with an extremely poor prognosis, but less attention has been directed to factors related to molecular carcinogenesis, including cell cycle proteins. We examined the expression and gene amplification of cyclin D1, the cell cycle regulating protein. Our objective was to evaluate correlations with clinicopathological factors in ICC. Cyclin D1 overexpression and cellular proliferative activity (Ki-67 labeling index) were investigated immunohistochemically, and 20 cases were further investigated for cyclin D1 gene amplification, using differential PCR. We examined the correlation between the expression and gene amplification of cyclin D1 and clinicopathological factors, including overall survival in patients with ICC. Immunohistochemical analysis revealed an overexpression of cyclin D1 protein in 28 of 66 subjects with ICCs (42%). The cyclin D1 overexpression was associated with poor histological differentiation (P = 0.04), high cellular proliferative activity (P < 0.01), and a poor prognosis (P = 0.02) by univariate analysis, although it is not an independent prognostic factor by multivariate analysis. Cyclin D1 gene amplification was confirmed in five of the 20 patients. Of those five cases of ICC, all had poor histological differentiation, and four of the five ICCs (80%) showed evidence of cyclin D1 immunoreactivity. Overexpression and gene amplification of cyclin D1 are frequent and contribute to dedifferentiation and cellular proliferative activity of ICCs, and overexpression also indicates a poor prognosis for patients with ICC.","null","null","2001-07","Journal of Hepatology","Journal of Hepatology","Vol.35","No.1","74","79","eng","true","null","scientific_journal","null","null","10.1016/S0168-8278(01)00079-4","0168-8278","null","null","null","null","null"
"Laparoscopic hepatectomy for hepatocellular carcinoma","Laparoscopic hepatectomy for hepatocellular carcinoma","Mitsuo Shimada, Makoto Hashizume, Shin-ichiro Maehara, Eiji Tsujita, Tatsuya Rikimaru, Yo-ichi Yamashita, Shinji Tanaka, Eisuke Adachi, Keizo Sugimachi","Mitsuo Shimada, Makoto Hashizume, Shin-ichiro Maehara, Eiji Tsujita, Tatsuya Rikimaru, Yo-ichi Yamashita, Shinji Tanaka, Eisuke Adachi, Keizo Sugimachi","null","null","null","null","null","2001-05","Surgical Endoscopy","Surgical Endoscopy","Vol.15","No.6","541","544","eng","true","null","scientific_journal","null","null","10.1007/s004640080099","1432-2218","null","http://cat.inist.fr/?aModele=afficheN&cpsidt=1054176","null","null","null"
"The role of p27kip1 protein ezpression on the biological behavior of intrahepatic cholangiocarcinoma","The role of p27kip1 protein ezpression on the biological behavior of intrahepatic cholangiocarcinoma","Ken-Ichi Taguchi, Shin-Ichi Aishima, Yoshiki Asayama, Kiyoshi Kajiyama, Naoko Kinukawa, Mitsuo Shimada, Keizo Sugimachi, Masazumi Tsuneyoshi","Ken-Ichi Taguchi, Shin-Ichi Aishima, Yoshiki Asayama, Kiyoshi Kajiyama, Naoko Kinukawa, Mitsuo Shimada, Keizo Sugimachi, Masazumi Tsuneyoshi","null","Recent studies have reported that a decreased p27kip1 protein (p27) expression is associated with aggressive tumor behavior in several human malignancies. In this study, we examined the role of p27 expression in intrahepatic cholangiocarcinoma (ICC) and the noncancerous intrahepatic bile duct epithelium and assessed its association with clinicopathologic features, especially the influence of decreased p27 expression by the tumor on its prognosis as determined by immunohistochemistry. Almost all noncancerous bile duct epithelia show positive nuclear staining and reveal a faintly positive reaction in the cytoplasm. In 62 surgically resected ICCs, a variable degree of positive p27 nuclear staining is recognized. A subset (13 of 62 cases; 21.0%) of the carcinomas displayed cytoplasmic staining. We classified 62 cases into 2 groups, a low expression group (< 50% of p27 nuclear positive cells) and a high expression group (> or = 50% of p27 nuclear positive cells), and tested for the association between positive expression and clinicopathologic features. We found that a low expression of nuclear p27 was correlated with positive vascular invasion (P < .05). The survival curve of the group with low p27 nuclear expression was significantly lower than that of the group with high p27 nuclear expression (P < .005). According to the multivariate analyses, low p27 expression can be considered an independent prognostic factor whose occurrence indicates a worse prognosis. We conclude that a decreased p27 expression adds an independent parameter that can be used when determining the prognosis of patients with ICC.","Recent studies have reported that a decreased p27kip1 protein (p27) expression is associated with aggressive tumor behavior in several human malignancies. In this study, we examined the role of p27 expression in intrahepatic cholangiocarcinoma (ICC) and the noncancerous intrahepatic bile duct epithelium and assessed its association with clinicopathologic features, especially the influence of decreased p27 expression by the tumor on its prognosis as determined by immunohistochemistry. Almost all noncancerous bile duct epithelia show positive nuclear staining and reveal a faintly positive reaction in the cytoplasm. In 62 surgically resected ICCs, a variable degree of positive p27 nuclear staining is recognized. A subset (13 of 62 cases; 21.0%) of the carcinomas displayed cytoplasmic staining. We classified 62 cases into 2 groups, a low expression group (< 50% of p27 nuclear positive cells) and a high expression group (> or = 50% of p27 nuclear positive cells), and tested for the association between positive expression and clinicopathologic features. We found that a low expression of nuclear p27 was correlated with positive vascular invasion (P < .05). The survival curve of the group with low p27 nuclear expression was significantly lower than that of the group with high p27 nuclear expression (P < .005). According to the multivariate analyses, low p27 expression can be considered an independent prognostic factor whose occurrence indicates a worse prognosis. We conclude that a decreased p27 expression adds an independent parameter that can be used when determining the prognosis of patients with ICC.","null","null","2001-05","Hepatology","Hepatology","Vol.33","No.5","1118","1123","eng","true","null","scientific_journal","null","null","10.1053/jhep.2001.24028","0270-9139","null","null","null","null","null"
"Preclinical and therapeutic utility of HVJ liposomes as a gene transfer vecotr for hepatocellular carcinoma using herpes simplex virus thymidine kinase","Preclinical and therapeutic utility of HVJ liposomes as a gene transfer vecotr for hepatocellular carcinoma using herpes simplex virus thymidine kinase","Hirofumi Hasegawa, Mitsuo Shimada, Yoshikazu Yonemitsu, Tohru Utsunomiya, Tomonobu Gion, Yasufumi Kaneda, Keizo Sugimachi","Hirofumi Hasegawa, Mitsuo Shimada, Yoshikazu Yonemitsu, Tohru Utsunomiya, Tomonobu Gion, Yasufumi Kaneda, Keizo Sugimachi","null","Although gene therapy has been suggested to be a novel strategy to treat hepatocellular carcinoma (HCC), no study showing the clinical feasibility of vectors to treat HCC has been reported. In this preclinical study, we show evidence indicating that hemagglutinating virus of Japan (HVJ) liposomes are a feasible vector to treat HCC in a clinical setting using ganciclovir (GCV) and herpes simplex virus thymidine kinase (HSV-tk), which is driven by the cytomegalovirus immediate early enhancer/promoter (plasmid pcDNA3/HSV-tk). In in vitro experiments, almost complete tumor cell regression was achieved with the optimal GCV concentration (100 microg/mL) and more than 1/3 regression was seen even with a 20% transduction ratio using HuH7 HCC cells stably transformed by HSV-tk. HVJ liposomes showed a 19.7% (mean) transduction rate of the lacZ gene in a relatively large mass of more than 300 mm3 in vivo, which is a clinically detectable size, implanted into SCID mice. Moreover, a single HSV-tk injection of HVJ liposomes followed by GCV treatment inhibited tumor growth at least within a week, and repeat administration was more effective. Furthermore, subcutaneous injection of an HVJ liposomes vehicle induced no apparent inflammatory response in C3H/HeN mice, whereas lacZ gene transfection resulted in inflammatory pathology, suggesting a lower immunogenicity of the HVJ envelope protein than those of bacteria-derived plasmid DNA or the beta-galactosidase gene product. From these findings, we conclude that HVJ liposomes are a clinically safe and effective gene transfer vector to treat HCC.","Although gene therapy has been suggested to be a novel strategy to treat hepatocellular carcinoma (HCC), no study showing the clinical feasibility of vectors to treat HCC has been reported. In this preclinical study, we show evidence indicating that hemagglutinating virus of Japan (HVJ) liposomes are a feasible vector to treat HCC in a clinical setting using ganciclovir (GCV) and herpes simplex virus thymidine kinase (HSV-tk), which is driven by the cytomegalovirus immediate early enhancer/promoter (plasmid pcDNA3/HSV-tk). In in vitro experiments, almost complete tumor cell regression was achieved with the optimal GCV concentration (100 microg/mL) and more than 1/3 regression was seen even with a 20% transduction ratio using HuH7 HCC cells stably transformed by HSV-tk. HVJ liposomes showed a 19.7% (mean) transduction rate of the lacZ gene in a relatively large mass of more than 300 mm3 in vivo, which is a clinically detectable size, implanted into SCID mice. Moreover, a single HSV-tk injection of HVJ liposomes followed by GCV treatment inhibited tumor growth at least within a week, and repeat administration was more effective. Furthermore, subcutaneous injection of an HVJ liposomes vehicle induced no apparent inflammatory response in C3H/HeN mice, whereas lacZ gene transfection resulted in inflammatory pathology, suggesting a lower immunogenicity of the HVJ envelope protein than those of bacteria-derived plasmid DNA or the beta-galactosidase gene product. From these findings, we conclude that HVJ liposomes are a clinically safe and effective gene transfer vector to treat HCC.","null","null","2001-04","Cancer Gene Therapy","Cancer Gene Therapy","Vol.8","No.4","252","258","eng","true","null","scientific_journal","null","null","10.1038/sj.cgt.7700307","0929-1903","null","http://www.nature.com/cgt/journal/v8/n4/abs/7700307a.html","null","null","null"
"Cytokine characteristics of jaundice in mouse liver","Cytokine characteristics of jaundice in mouse liver","Yuh Fujiwara, Mitsuo Shimada, Yo-ichi Yamashita, Eisuke Adachi, Ken Shirabe, Kenji Takenaka, Keizo Sugimachi","Yuh Fujiwara, Mitsuo Shimada, Yo-ichi Yamashita, Eisuke Adachi, Ken Shirabe, Kenji Takenaka, Keizo Sugimachi","null","The aim of this study is to clarify the perioperative cytokine changes and their mechanism in jaundiced liver. Obstructive jaundice was induced using a common bile duct ligation (CBDL) and a two-thirds hepatectomy (HEP) was performed in six- to seven-week-old male C3H/HeN mice. When hepatectomy was added to CBDL, it was carried out 2 to 5 days after CBDL. The serum interleukin 6 (IL-6) levels and heat shock protein (HSP)-70 expression were evaluated. One mg per mouse of methylprednisolone (MPL) was intraperitonealy administered in some mice of CBDL+HEP group. The post-hepatectomy IL-6 values at 2 and 3 days after CBDL were significantly lower than those in the HEP group, while those at 5 days after CBDL were significantly higher than those in HEP group. The serum IL-6 value of the steroid group was significantly lower than that of non-steroid group in HEP group. However, no steroid effects were recognized on post-hepatectomy IL-6 values at 3 days after CBDL, steroid inhibited post-hepatectomy IL-6 production at 5 days after CBDL. No expression of HSP70 protein was observed in the control group, but HSP70 protein was expressed in both the hepatocytes and Kupffer cells 3 days after CBDL, then at 5 days after CBDL, no HSP70 protein was expressed in the Kupffer cells. In the early period of obstructive jaundice, the IL-6 level after hepatectomy did not increase in comparison to HEP group, and steroid had no effect on IL-6 level. According to the progression of obstructive jaundice, the IL-6 level after hepatectomy increased to a higher level than before, and the effect of MPL was restored. HSP70 is thus suggested to have an important role in cytokine production.","The aim of this study is to clarify the perioperative cytokine changes and their mechanism in jaundiced liver. Obstructive jaundice was induced using a common bile duct ligation (CBDL) and a two-thirds hepatectomy (HEP) was performed in six- to seven-week-old male C3H/HeN mice. When hepatectomy was added to CBDL, it was carried out 2 to 5 days after CBDL. The serum interleukin 6 (IL-6) levels and heat shock protein (HSP)-70 expression were evaluated. One mg per mouse of methylprednisolone (MPL) was intraperitonealy administered in some mice of CBDL+HEP group. The post-hepatectomy IL-6 values at 2 and 3 days after CBDL were significantly lower than those in the HEP group, while those at 5 days after CBDL were significantly higher than those in HEP group. The serum IL-6 value of the steroid group was significantly lower than that of non-steroid group in HEP group. However, no steroid effects were recognized on post-hepatectomy IL-6 values at 3 days after CBDL, steroid inhibited post-hepatectomy IL-6 production at 5 days after CBDL. No expression of HSP70 protein was observed in the control group, but HSP70 protein was expressed in both the hepatocytes and Kupffer cells 3 days after CBDL, then at 5 days after CBDL, no HSP70 protein was expressed in the Kupffer cells. In the early period of obstructive jaundice, the IL-6 level after hepatectomy did not increase in comparison to HEP group, and steroid had no effect on IL-6 level. According to the progression of obstructive jaundice, the IL-6 level after hepatectomy increased to a higher level than before, and the effect of MPL was restored. HSP70 is thus suggested to have an important role in cytokine production.","null","null","2001-02-07","Cytokine","Cytokine","Vol.13","No.3","188","191","eng","true","null","scientific_journal","null","null","10.1006/cyto.2000.0781","1043-4666","null","http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WDF-458PB8Y-5Y&_coverDate=02%2F28%2F2001&_alid=501633726&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=6765&_sort=d&view=c&_acct=C000008258&_version=1&_urlVersion=0&_userid=106892&md5=bc19e4d6c2e941dfbe80d647308246cb","null","null","null"
"Electroporation-mediated interleukin-12 gene therapy for hepatocellular carcinoma in the mice model","Electroporation-mediated interleukin-12 gene therapy for hepatocellular carcinoma in the mice model","Yo-ichi Yamashita, Mitsuo Shimada, Hirofumi Hasegawa, Ryosuke Minagawa, Tatsuya Rikimaru, Takayuki Hamatsu, Shinji Tanaka, Ken Shirabe, Jun-ichi Miyazaki, Keizo Sugimachi","Yo-ichi Yamashita, Mitsuo Shimada, Hirofumi Hasegawa, Ryosuke Minagawa, Tatsuya Rikimaru, Takayuki Hamatsu, Shinji Tanaka, Ken Shirabe, Jun-ichi Miyazaki, Keizo Sugimachi","null","Applications of nonviral vectors for gene transfer into tumors in vivo have been limited by the relatively low expression levels of the transferred gene. The aim of this study is to evaluate the efficacy of electroporation-mediated interleukin-12 (IL-12) gene therapy for hepatocellular carcinoma (HCC). First, we investigated the optimal conditions of electric pulses (voltage, pulsing duration, numbers of shocks) of in vivo electroporation for gene transfer into HCC established by s.c. implantation of MH134 cells to C3H mice. This process made use of plasmid DNA that express the luciferase gene. We concluded that the optimal conditions for the electric pulses are as follows: voltage at 150 V; pulsing duration at 50 ms; nonpulsing duration at 950 ms; and the number of shocks at 10. Second, we tried to treat s.c. HCC by electroporation using plasmid DNA that expresses the murine interleukin-12 (mlL-12) gene. Intratumoral administration of the mIL-12 vector elevated serum IL-12 and IFN-gamma and significantly inhibited the growth not only of HCC into which the mIL-12 vector had been directly transferred, but also of the distant HCC. In addition, intratumoral administration of the mIL-12 vector inhibited spontaneous lung metastasis and delayed establishment of HCC injected 3 days after mIL-12 gene therapy. The IL-12 gene therapy induced more lymphocyte infiltration by NK cells, CD3+ cells, and Mac-1 positive cells into the tumor and reduced the number of microvessels. Therefore, more terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive tumor cells were found. These results demonstrate that gene therapy for HCC by electroporation in vivo using IL-12 is very efficient and is thus promising for further clinical trial.","Applications of nonviral vectors for gene transfer into tumors in vivo have been limited by the relatively low expression levels of the transferred gene. The aim of this study is to evaluate the efficacy of electroporation-mediated interleukin-12 (IL-12) gene therapy for hepatocellular carcinoma (HCC). First, we investigated the optimal conditions of electric pulses (voltage, pulsing duration, numbers of shocks) of in vivo electroporation for gene transfer into HCC established by s.c. implantation of MH134 cells to C3H mice. This process made use of plasmid DNA that express the luciferase gene. We concluded that the optimal conditions for the electric pulses are as follows: voltage at 150 V; pulsing duration at 50 ms; nonpulsing duration at 950 ms; and the number of shocks at 10. Second, we tried to treat s.c. HCC by electroporation using plasmid DNA that expresses the murine interleukin-12 (mlL-12) gene. Intratumoral administration of the mIL-12 vector elevated serum IL-12 and IFN-gamma and significantly inhibited the growth not only of HCC into which the mIL-12 vector had been directly transferred, but also of the distant HCC. In addition, intratumoral administration of the mIL-12 vector inhibited spontaneous lung metastasis and delayed establishment of HCC injected 3 days after mIL-12 gene therapy. The IL-12 gene therapy induced more lymphocyte infiltration by NK cells, CD3+ cells, and Mac-1 positive cells into the tumor and reduced the number of microvessels. Therefore, more terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive tumor cells were found. These results demonstrate that gene therapy for HCC by electroporation in vivo using IL-12 is very efficient and is thus promising for further clinical trial.","null","null","2001-02-01","Cancer Research","Cancer Research","Vol.61","No.3","1005","1012","eng","true","null","scientific_journal","null","null","null","0008-5472","null","null","null","null","null"
"The efficacy of nafamostat mesilate on the performance of a hybrid-artificial liver using a polyurethane foam/ porcine hepatocyte spheroid culture system in human plasma","The efficacy of nafamostat mesilate on the performance of a hybrid-artificial liver using a polyurethane foam/ porcine hepatocyte spheroid culture system in human plasma","Yo-ichi Yamashita, Mitsuo Shimada, Eiji Tsujita, Tatsuya Rikimaru, Hiroyuki Ijima, Kohji Nakazawa, Ryo-ichi Sakiyama, Junji Fukuda, Kazumori Funatsu, Keizo Sugimachi","Yo-ichi Yamashita, Mitsuo Shimada, Eiji Tsujita, Tatsuya Rikimaru, Hiroyuki Ijima, Kohji Nakazawa, Ryo-ichi Sakiyama, Junji Fukuda, Kazumori Funatsu, Keizo Sugimachi","null","Nafamostat mesilate (FUT) is a protease inhibitor of complement activation. The present study investigates whether FUT protects porcine hepatocytes from being injured by human plasma in a multi-capillary polyurethane foam packed-bed culture system (MC-PUF) such as the hybrid-artificial liver (PUF-HAL). Human plasmas with 1 mM of added ammonia were perfused using a small-scale PUF-HAL with porcine hepatocytes. FUT was continuously infused (10 microg/ml, 50 microg/ml). The ammonia detoxification was maintained in human plasma for 24 hours and for 48 hours with FUT which suppressed the rapid increase of asparaginic acid aminotransferase (AST) and alanine aminotransferase (ALT). After 60 hours of perfusion, hepatocyte spheroids completely collapsed in the human plasma, but a small amount of hepatocyte spheroid was maintained by FUT. The effect of FUT was slightly greater at 50 microg/ml than at 10 microg/ml. Our results suggest that FUT has protective effects against porcine hepatocytes in human plasma, and our PUF-HAL using porcine hepatocytes can function in human plasma for about 48 hours with FUT.","Nafamostat mesilate (FUT) is a protease inhibitor of complement activation. The present study investigates whether FUT protects porcine hepatocytes from being injured by human plasma in a multi-capillary polyurethane foam packed-bed culture system (MC-PUF) such as the hybrid-artificial liver (PUF-HAL). Human plasmas with 1 mM of added ammonia were perfused using a small-scale PUF-HAL with porcine hepatocytes. FUT was continuously infused (10 microg/ml, 50 microg/ml). The ammonia detoxification was maintained in human plasma for 24 hours and for 48 hours with FUT which suppressed the rapid increase of asparaginic acid aminotransferase (AST) and alanine aminotransferase (ALT). After 60 hours of perfusion, hepatocyte spheroids completely collapsed in the human plasma, but a small amount of hepatocyte spheroid was maintained by FUT. The effect of FUT was slightly greater at 50 microg/ml than at 10 microg/ml. Our results suggest that FUT has protective effects against porcine hepatocytes in human plasma, and our PUF-HAL using porcine hepatocytes can function in human plasma for about 48 hours with FUT.","null","null","2001-01","The International Journal of Artificial Organs","The International Journal of Artificial Organs","Vol.24","No.1","34","40","eng","true","null","scientific_journal","null","null","null","0391-3988","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11266040&dopt=Citation","null","null","null"
"Changes in the caudate lobe that is trabsplanted with extended left lobe liver grft from living donor","Changes in the caudate lobe that is trabsplanted with extended left lobe liver grft from living donor","Toru Ikegami, Takashi Nishizaki, Katsuhiko Yanaga, Mitsuo Shimada, Saburo Kakizoe, Kenichi Nomoto, Shoji Hiroshige, Hideaki Uchiyama, Keizo Sugimachi","Toru Ikegami, Takashi Nishizaki, Katsuhiko Yanaga, Mitsuo Shimada, Saburo Kakizoe, Kenichi Nomoto, Shoji Hiroshige, Hideaki Uchiyama, Keizo Sugimachi","null","Caudate lobe transplantation with an extended left lobe graft is an innovative and promising method for increasing the graft volume in living donor liver transplantation. However, little is known about the fate of the caudate lobe after transplantation. Eight extended left lobe grafts with the caudate lobe were included in this study. No attempt was made to reconstruct the short hepatic veins. On the basis of the computed tomography scans that were obtained before the operation and 1 month after the transplantation, the increase in the graft volume by the addition of the caudate lobe and the changes in the transplanted caudate lobe were evaluated. The addition of the caudate lobe increased the graft volume by 25 +/- 2 g, corresponding to a 2% increase in graft volume/standard liver volume ratio. One month after the transplantation, the caudate lobe volume increased in all patients but 1. The regeneration rate of the caudate lobe and other segments (segments II-IV) 1 month after transplantation was 62% +/- 24% (24 +/- 4 mL- 37 +/- 4 mL) and 152% +/- 35% (374 +/- 45 mL-930 +/- 65 mL), respectively (P <.01). This technique affords a modest increase in liver volume with living donor left liver procurement.","Caudate lobe transplantation with an extended left lobe graft is an innovative and promising method for increasing the graft volume in living donor liver transplantation. However, little is known about the fate of the caudate lobe after transplantation. Eight extended left lobe grafts with the caudate lobe were included in this study. No attempt was made to reconstruct the short hepatic veins. On the basis of the computed tomography scans that were obtained before the operation and 1 month after the transplantation, the increase in the graft volume by the addition of the caudate lobe and the changes in the transplanted caudate lobe were evaluated. The addition of the caudate lobe increased the graft volume by 25 +/- 2 g, corresponding to a 2% increase in graft volume/standard liver volume ratio. One month after the transplantation, the caudate lobe volume increased in all patients but 1. The regeneration rate of the caudate lobe and other segments (segments II-IV) 1 month after transplantation was 62% +/- 24% (24 +/- 4 mL- 37 +/- 4 mL) and 152% +/- 35% (374 +/- 45 mL-930 +/- 65 mL), respectively (P <.01). This technique affords a modest increase in liver volume with living donor left liver procurement.","null","null","2001-01","Surgery","Surgery","Vol.129","No.1","86","90","eng","true","null","scientific_journal","null","null","10.1067/msy.2001.109499","0039-6060","null","null","null","null","null"
"Bile leakage after hepatic resection","Bile leakage after hepatic resection","Yo-ichi Yamashita, Takayuki Hamatsu, Tatsuya Rikimaru, Shinji Tanaka, Ken Shirabe, Mitsuo Shimada, Keizo Sugimachi","Yo-ichi Yamashita, Takayuki Hamatsu, Tatsuya Rikimaru, Shinji Tanaka, Ken Shirabe, Mitsuo Shimada, Keizo Sugimachi","null","To identify the perioperative risk factors for postoperative bile leakage after hepatic resection, to evaluate the intraoperative bile leakage test as a preventive measure, and to propose a treatment strategy for postoperative bile leakage according to the outcome of these patients. Bile leakage remains a common cause of major complications after hepatic resection. Between January 1985 and June 1999, 781 hepatic resections without bilioenteric anastomosis were performed at the authors' institution. Perioperative risk factors related to postoperative bile leakage were identified using univariate and multivariate analysis. The characteristics of patients with intractable bile leakage and the effect of intraoperative bile leakage test were also examined. Management was evaluated in relation to the outcomes and the clinical characteristics of the patients with bile leakage. Bile leakage developed in 31 (4.0%) of 781 hepatic resections. This complication carried high risks for surgical death (two patients [6.5%] died). The stepwise logistic regression analysis identified high-risk surgical procedure, in which the cut surface exposed the major Glisson's sheath and included the hepatic hilum (i.e., anterior segmentectomy, central bisegmentectomy, or total caudate lobectomy), as the independent predictor of the development of postoperative bile leakage. None of the 102 cases in which an intraoperative bile leakage test was performed were subsequently complicated by postoperative bile leakage, and the preventive effect of the test was statistically significant. Patients with fisterographically demonstrable leakage from the hepatic hilum and with postoperative uncontrollable ascites had poor outcomes. Patients with bile leakage from the hepatic hilum and postoperative uncontrollable ascites tend to have a poor prognosis. Therefore, especially when a high-risk surgical procedure is performed in patients with liver cirrhosis, more careful surgical procedures and use of an intraoperative bile leakage test are recommended.","To identify the perioperative risk factors for postoperative bile leakage after hepatic resection, to evaluate the intraoperative bile leakage test as a preventive measure, and to propose a treatment strategy for postoperative bile leakage according to the outcome of these patients. Bile leakage remains a common cause of major complications after hepatic resection. Between January 1985 and June 1999, 781 hepatic resections without bilioenteric anastomosis were performed at the authors' institution. Perioperative risk factors related to postoperative bile leakage were identified using univariate and multivariate analysis. The characteristics of patients with intractable bile leakage and the effect of intraoperative bile leakage test were also examined. Management was evaluated in relation to the outcomes and the clinical characteristics of the patients with bile leakage. Bile leakage developed in 31 (4.0%) of 781 hepatic resections. This complication carried high risks for surgical death (two patients [6.5%] died). The stepwise logistic regression analysis identified high-risk surgical procedure, in which the cut surface exposed the major Glisson's sheath and included the hepatic hilum (i.e., anterior segmentectomy, central bisegmentectomy, or total caudate lobectomy), as the independent predictor of the development of postoperative bile leakage. None of the 102 cases in which an intraoperative bile leakage test was performed were subsequently complicated by postoperative bile leakage, and the preventive effect of the test was statistically significant. Patients with fisterographically demonstrable leakage from the hepatic hilum and with postoperative uncontrollable ascites had poor outcomes. Patients with bile leakage from the hepatic hilum and postoperative uncontrollable ascites tend to have a poor prognosis. Therefore, especially when a high-risk surgical procedure is performed in patients with liver cirrhosis, more careful surgical procedures and use of an intraoperative bile leakage test are recommended.","null","null","2001-01","Annals of Surgery","Annals of Surgery","Vol.233","No.1","45","50","eng","true","null","scientific_journal","null","null","10.1097/00000658-200101000-00008","0003-4932","null","http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1421165","null","null","null"
"Polyurethane foam/spheroid culture system using human hepatoblastoma cell line (Hep G2) as a possible new hybrid artificil liver","Polyurethane foam/spheroid culture system using human hepatoblastoma cell line (Hep G2) as a possible new hybrid artificil liver","Yo-ichi Yamashita, Mitsuo Shimada, Eiji Tsujita, Shinji Tanaka, Hiroyuki Ijima, Kohji Nakazawa, Ryoichi Sakiyama, Junji Fukuda, T Ueda, Kazumori Funatsu, Keizo Sugimachi","Yo-ichi Yamashita, Mitsuo Shimada, Eiji Tsujita, Shinji Tanaka, Hiroyuki Ijima, Kohji Nakazawa, Ryoichi Sakiyama, Junji Fukuda, T Ueda, Kazumori Funatsu, Keizo Sugimachi","null","The risk of xenozoonosis infections poses the greatest obstacle against the clinical application of hybrid artificial liver support system (HALSS). Primary human hepatocytes are an ideal source for HALSS, but the shortage of human livers available for hepatocyte isolation limits this modality. To resolve this issue, we used human hepatocytes with replication capacity (fetal hepatocytes, Hep G2, and Huh 7) in a polyurethane foam (PUF)/spheroid culture system in vitro, and analyzed liver functions such as ammonia removal and albumin synthesis capacity; results were compared to those of porcine hepatocytes. Human fetal hepatocytes, Hep G2, and Huh 7 formed spheroids spontaneously within 24 h in a PUF/spheroid culture system; ammonia removal activity (micromol/10(6) nuclei/h) was upregulated, as was albumin synthesis activity (microg/10(6) nuclei/day). In particular, Hep G2 spheroids demonstrated high ammonia removal and albumin synthesis activities: 85% of the ammonia removal activity and 171.7% of the albumin synthesis activity of porcine hepatocytes in the monolayer culture. These results indicate the possibility of the development of a multicapillary PUF (MC-PUF) packed-bed culture system of hepatocyte spheroids as a HALSS using Hep G2.","The risk of xenozoonosis infections poses the greatest obstacle against the clinical application of hybrid artificial liver support system (HALSS). Primary human hepatocytes are an ideal source for HALSS, but the shortage of human livers available for hepatocyte isolation limits this modality. To resolve this issue, we used human hepatocytes with replication capacity (fetal hepatocytes, Hep G2, and Huh 7) in a polyurethane foam (PUF)/spheroid culture system in vitro, and analyzed liver functions such as ammonia removal and albumin synthesis capacity; results were compared to those of porcine hepatocytes. Human fetal hepatocytes, Hep G2, and Huh 7 formed spheroids spontaneously within 24 h in a PUF/spheroid culture system; ammonia removal activity (micromol/10(6) nuclei/h) was upregulated, as was albumin synthesis activity (microg/10(6) nuclei/day). In particular, Hep G2 spheroids demonstrated high ammonia removal and albumin synthesis activities: 85% of the ammonia removal activity and 171.7% of the albumin synthesis activity of porcine hepatocytes in the monolayer culture. These results indicate the possibility of the development of a multicapillary PUF (MC-PUF) packed-bed culture system of hepatocyte spheroids as a HALSS using Hep G2.","null","null","2001","Cell Transplantation","Cell Transplantation","Vol.10","No.8","717","722","eng","true","null","scientific_journal","null","null","null","0963-6897","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11814114&dopt=Abstract","null","null","null"
"The Importance of Hepatic Resection for Hepatocellular Carcinoma Originating from Nonfibrotic Liver","The Importance of Hepatic Resection for Hepatocellular Carcinoma Originating from Nonfibrotic Liver","Mitsuo Shimada, Tatsuya Rikimaru, Keishi Sugimachi, Takayuki Hamatsu, Yo-ichi Yamashita, Shin-ichi Aishima, Ken-ichi Taguchi, Shinji Tanaka, Ken Shirabe, Keizo Sugimachi","Mitsuo Shimada, Tatsuya Rikimaru, Keishi Sugimachi, Takayuki Hamatsu, Yo-ichi Yamashita, Shin-ichi Aishima, Ken-ichi Taguchi, Shinji Tanaka, Ken Shirabe, Keizo Sugimachi","null","Our study aimed to clarify the characteristics of hepatocellular carcinoma (HCC) in patients with a nonfibrotic liver and the role of surgical resection for HCC in nonfibrotic liver compared with patients with HCC in fibrotic or cirrhotic livers. A total of 516 patients who underwent hepatectomy between April 1985 and June 1999 were classified into two groups: a nonfibrotic liver group (n=65) and a fibrotic liver group (n=451), which included fibrotic or cirrhotic livers. Clinicopathologic variables were then compared between the groups, including disease-free survival rate and patient survival rate. Only 8 of 65 patients (12.3%) with a nonfibrotic liver showed a histologically completely normal liver. The numbers of men and patients with alcohol abuse in the nonfibrotic liver group were higher than in the fibrotic liver group. The numbers of patients with positive hepatitis B antigen and positive hepatitis C antibody in the nonfibrotic liver group were lower than in the fibrotic liver group. Results of liver function tests in the nonfibrotic liver group were better than those in the fibrotic liver group. The rates of both portal vein and hepatic vein invasion of cancer cells in the nonfibrotic liver group were higher than in the fibrotic liver group. The tumor size in the nonfibrotic liver group was larger than in the fibrotic liver group. The patient survival and disease-free survival rates in the nonfibrotic liver group were better than in the fibrotic liver group. Hepatic resection can be beneficial for patients with HCC originating from a nonfibrotic liver when compared with fibrotic or cirrhotic patients with HCC.","Our study aimed to clarify the characteristics of hepatocellular carcinoma (HCC) in patients with a nonfibrotic liver and the role of surgical resection for HCC in nonfibrotic liver compared with patients with HCC in fibrotic or cirrhotic livers. A total of 516 patients who underwent hepatectomy between April 1985 and June 1999 were classified into two groups: a nonfibrotic liver group (n=65) and a fibrotic liver group (n=451), which included fibrotic or cirrhotic livers. Clinicopathologic variables were then compared between the groups, including disease-free survival rate and patient survival rate. Only 8 of 65 patients (12.3%) with a nonfibrotic liver showed a histologically completely normal liver. The numbers of men and patients with alcohol abuse in the nonfibrotic liver group were higher than in the fibrotic liver group. The numbers of patients with positive hepatitis B antigen and positive hepatitis C antibody in the nonfibrotic liver group were lower than in the fibrotic liver group. Results of liver function tests in the nonfibrotic liver group were better than those in the fibrotic liver group. The rates of both portal vein and hepatic vein invasion of cancer cells in the nonfibrotic liver group were higher than in the fibrotic liver group. The tumor size in the nonfibrotic liver group was larger than in the fibrotic liver group. The patient survival and disease-free survival rates in the nonfibrotic liver group were better than in the fibrotic liver group. Hepatic resection can be beneficial for patients with HCC originating from a nonfibrotic liver when compared with fibrotic or cirrhotic patients with HCC.","null","null","2000-11","Journal of the American College of Surgeons","Journal of the American College of Surgeons","Vol.191","No.5","531","537","eng","true","null","scientific_journal","null","null","10.1016/S1072-7515(00)00705-5","1072-7515","null","http://cat.inist.fr/?aModele=afficheN&cpsidt=809341","null","null","null"
"Domino liver transplantation from a living related donor","Domino liver transplantation from a living related donor","Takashi Nishizaki, Keishi Kishikawa, Tomoharu Yoshizumi, Hideaki Uchiyama, Shinji Okano, Toru Ikegami, Koji Hashimoto, Kenichi Nomoto, Mitsuo Shimada, Katsuhiko Yanaga, Kenji Takenaka, Keizo Sugimachi, Yukio Ando, Masayuki Ando","Takashi Nishizaki, Keishi Kishikawa, Tomoharu Yoshizumi, Hideaki Uchiyama, Shinji Okano, Toru Ikegami, Koji Hashimoto, Kenichi Nomoto, Mitsuo Shimada, Katsuhiko Yanaga, Kenji Takenaka, Keizo Sugimachi, Yukio Ando, Masayuki Ando","null","Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery lie in the small size of the graft volume and the short length of the vascular cuffs in the graft. The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient. At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A). The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence. A domino OLT from the living related donor can therefore be done safely when careful attention is paid to the graft volume and the length of the vascular cuffs for anastomosis.","Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery lie in the small size of the graft volume and the short length of the vascular cuffs in the graft. The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient. At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A). The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence. A domino OLT from the living related donor can therefore be done safely when careful attention is paid to the graft volume and the length of the vascular cuffs for anastomosis.","null","null","2000-10-27","Transplantation","Transplantation","Vol.70","No.8","1236","1239","eng","true","null","scientific_journal","null","null","10.1097/00007890-200010270-00019","0041-1337","null","http://www.transplantjournal.com/pt/re/transplantation/abstract.00007890-200010270-00019.htm;jsessionid=FBxPLkXVs13cZBN2x44LgcGvMPTdv0kMp2wxQ4GQlt9f7Sgw072r!1699395943!-949856145!8091!-1","null","null","null"
"The role of des-g-caboxy prothrombin levels in hepatocellular carcinoma and liver tissues","The role of des-g-caboxy prothrombin levels in hepatocellular carcinoma and liver tissues","Mitsuo Shimada, Yo-ichi Yamashita, Takayuki Hamatsu, Hirofumi Hasegawa, Tohru Utsunomiya, Shin-ichi Aishima, Keizo Sugimachi","Mitsuo Shimada, Yo-ichi Yamashita, Takayuki Hamatsu, Hirofumi Hasegawa, Tohru Utsunomiya, Shin-ichi Aishima, Keizo Sugimachi","null","null","null","null","null","2000-10-16","Cancer Letters","Cancer Letters","Vol.159","No.1","87","94","eng","true","null","scientific_journal","null","null","null","0304-3835","null","null","null","null","null"
"Expression and antitumor efects of TAIL in Human Cholangiocarcinoma","Expression and antitumor efects of TAIL in Human Cholangiocarcinoma","Shinji Tanaka, Keishi Sugimachi, Ken Shirabe, Mitsuo Shimada, Jack R. Wands, Keizo Sugimachi","Shinji Tanaka, Keishi Sugimachi, Ken Shirabe, Mitsuo Shimada, Jack R. Wands, Keizo Sugimachi","null","null","null","null","null","2000-09","Hepatology","Hepatology","Vol.32","No.3","523","527","eng","true","null","scientific_journal","null","null","null","0270-9139","null","null","null","null","null"
"Clinicopathologic features and postoperative prognosis of multicentric small hepatocellular carcinoma","Clinicopathologic features and postoperative prognosis of multicentric small hepatocellular carcinoma","Tohru Utsunomiya, Mitsuo Shimada, Ken-ichi Taguchi, Hirofumi Hasegawa, Yo-ichi Yamashita, Takayuki Hamatsu, Shinichi Aishima, Keizo Sugimachi","Tohru Utsunomiya, Mitsuo Shimada, Ken-ichi Taguchi, Hirofumi Hasegawa, Yo-ichi Yamashita, Takayuki Hamatsu, Shinichi Aishima, Keizo Sugimachi","null","null","null","null","null","2000-03","Journal of American College of Surgeons","Journal of American College of Surgeons","Vol.190","No.3","331","335","eng","true","null","scientific_journal","null","null","null","null","null","http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T91-3YMW3GG-9&_coverDate=03%2F31%2F2000&_alid=501684831&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=5101&_sort=d&view=c&_acct=C000008258&_version=1&_urlVersion=0&_userid=106892&md5=6dc110e338a9b5dd5af3c1a6794f001f","null","null","null"
"The Significance of Thymidine Phosphorylase Activity in Hepatocellular Carsinoma and Chronic disease Livers: A Special Reference to Liver Fibrosis and Multicentric Tumor Occurrence","The Significance of Thymidine Phosphorylase Activity in Hepatocellular Carsinoma and Chronic disease Livers: A Special Reference to Liver Fibrosis and Multicentric Tumor Occurrence","Mitsuo Shimada, Hirofumi Hasegawa, Katsuya Rikimaru, Tomonobu Gion, Takayuki Hamatsu, Yo-ichi Yamashita, Ken Shirabe, Ken Sugimachi","Mitsuo Shimada, Hirofumi Hasegawa, Katsuya Rikimaru, Tomonobu Gion, Takayuki Hamatsu, Yo-ichi Yamashita, Ken Shirabe, Ken Sugimachi","null","null","null","null","null","2000-02-01","Cancer Letters","Cancer Letters","Vol.148","No.2","165","172","eng","true","null","scientific_journal","null","null","null","0304-3835","null","null","null","null","null"
"Expression of matrix metalloproteinase-9(MMP-9) in surgically resected intrahepatic cholangiocarcinoma(IHCC)","Expression of matrix metalloproteinase-9(MMP-9) in surgically resected intrahepatic cholangiocarcinoma(IHCC)","Ken Shirabe, Mitsuo Shimada, Kiyoshi Kajiyama, Hirofumi Hasegawa, Tomonobu Gion, Yasuharu Ikeda, Kenji Takenaka, Keizo Sugimachi","Ken Shirabe, Mitsuo Shimada, Kiyoshi Kajiyama, Hirofumi Hasegawa, Tomonobu Gion, Yasuharu Ikeda, Kenji Takenaka, Keizo Sugimachi","null","Matrix metalloproteinase-9 (MMP-9) has recently been reported to be related to cancer cell invasion. This study was performed to clarify the expression of MMP-9 in surgically resected intrahepatic cholangiocarcinoma (IHCC). In 37 patients with IHCC who underwent a surgical resection, the expression of MMP-9 and the clinicopathologic characteristics of MMP-9-positive IHCC were investigated. The expression of MMP-9 was immunohistochemically detected in 16 (43%) of 37 IHCC. The patients were divided into MMP-9 (-) IHCC (n = 21), MMP-9 (+) IHCC (n = 12), and MMP-9 (++) IHCC (n = 4). The survival rate after surgical resection in patients with MMP-9 (-), (+), and (++) IHCC, was 66%, 39%, and 0% at one year, 50%, 32% and 0% at 3 years, respectively (P = .001). The incidence rate of lymph node metastasis was 6 (28%) of 21 in MMP-9 (-) patients, 7 (58%) of 12 in MMP-9 (+) patients and 4 (100%) of 4 in MMP-9 (++) patients. The incidence rate of lymph node metastasis increased in proportion to an increase in the expression of MMP-9 in IHCC (P = .02). Recurrence in the lymph node was more common in patients with MMP-9 (+) and (++) cancers than in those with MMP-9 (-) cancers. The expression of MMP-9 in IHCC was a prognostic factor related to lymph node metastasis.","Matrix metalloproteinase-9 (MMP-9) has recently been reported to be related to cancer cell invasion. This study was performed to clarify the expression of MMP-9 in surgically resected intrahepatic cholangiocarcinoma (IHCC). In 37 patients with IHCC who underwent a surgical resection, the expression of MMP-9 and the clinicopathologic characteristics of MMP-9-positive IHCC were investigated. The expression of MMP-9 was immunohistochemically detected in 16 (43%) of 37 IHCC. The patients were divided into MMP-9 (-) IHCC (n = 21), MMP-9 (+) IHCC (n = 12), and MMP-9 (++) IHCC (n = 4). The survival rate after surgical resection in patients with MMP-9 (-), (+), and (++) IHCC, was 66%, 39%, and 0% at one year, 50%, 32% and 0% at 3 years, respectively (P = .001). The incidence rate of lymph node metastasis was 6 (28%) of 21 in MMP-9 (-) patients, 7 (58%) of 12 in MMP-9 (+) patients and 4 (100%) of 4 in MMP-9 (++) patients. The incidence rate of lymph node metastasis increased in proportion to an increase in the expression of MMP-9 in IHCC (P = .02). Recurrence in the lymph node was more common in patients with MMP-9 (+) and (++) cancers than in those with MMP-9 (-) cancers. The expression of MMP-9 in IHCC was a prognostic factor related to lymph node metastasis.","null","null","1999-11","Surgery","Surgery","Vol.126","No.5","842","846","eng","true","null","scientific_journal","null","null","null","0039-6060","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10568183&dopt=Citation","null","null","null"
"Modulation of immunologic reaction between cultured porcine hepatocytes and human sera","Modulation of immunologic reaction between cultured porcine hepatocytes and human sera","Hirofumi Hasegawa, Mitsuo Shimada, Tomonobu Gion, Hiroyuki Ijima, Kohji Nakazawa, Keizo Sugimachi","Hirofumi Hasegawa, Mitsuo Shimada, Tomonobu Gion, Hiroyuki Ijima, Kohji Nakazawa, Keizo Sugimachi","null","null","null","null","null","1999-09","ASAIO Journal","ASAIO Journal","Vol.45","No.5","392","396","eng","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"Evaluation of a hybrid artificial liver using a polyurethane foam paced-bed culture system in dogs","Evaluation of a hybrid artificial liver using a polyurethane foam paced-bed culture system in dogs","Tomonobu Gion, Mitsuo Shimada, Ken Shirabe, Kohji Nakazawa, Hiroyuki Ijima, Kazumori Funatsu, Keizo Sugimachi","Tomonobu Gion, Mitsuo Shimada, Ken Shirabe, Kohji Nakazawa, Hiroyuki Ijima, Kazumori Funatsu, Keizo Sugimachi","null","null","null","null","null","1999-04","Journal of Surgical Research","Journal of Surgical Research","Vol.82","No.2","131","136","eng","true","null","scientific_journal","null","null","null","null","null","http://www.ingentaconnect.com/content/els/00224804/1999/00000082/00000002/art95540","null","null","null"
"Rare occurrence of colorectal cancer metastasis in livers infected with hepatitis B or C virus","Rare occurrence of colorectal cancer metastasis in livers infected with hepatitis B or C virus","Tohru Utsunomiya, Hideki Saitsu, Motonori Saku, Kohji Yoshida, Takashi Matsumata, Mitsuo Shimada, Keizo Sugimachi","Tohru Utsunomiya, Hideki Saitsu, Motonori Saku, Kohji Yoshida, Takashi Matsumata, Mitsuo Shimada, Keizo Sugimachi","null","The rarity of the occurrence of metastatic malignancy in injured liver has been noted by many observers. However, since the clinicopathological features of primary carcinoma and the etiology of liver disease of these patients vary greatly, this phenomenon may not be universal. We evaluated the relationship between either hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the incidence of colorectal liver metastasis in 438 patients undergoing surgical treatment for advanced colorectal carcinoma. The liver function of the patients in the infection group (n = 37) was significantly worse than that of those in the noninfection group (n = 401). The incidences of tumor recurrence in the lung or peritoneum were comparable between the two groups. However, the percentage of patients with liver metastases in the infection group (3 of 37, 8.1%) was significantly lower (P <0.05) than that of those in the noninfection group (85 of 401, 21.2%). The patients in the infection group tended to survive longer than the patients in the noninfection group. We herein report an initial finding that colorectal carcinoma rarely metastasizes to livers infected with HBV or HCV.","The rarity of the occurrence of metastatic malignancy in injured liver has been noted by many observers. However, since the clinicopathological features of primary carcinoma and the etiology of liver disease of these patients vary greatly, this phenomenon may not be universal. We evaluated the relationship between either hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the incidence of colorectal liver metastasis in 438 patients undergoing surgical treatment for advanced colorectal carcinoma. The liver function of the patients in the infection group (n = 37) was significantly worse than that of those in the noninfection group (n = 401). The incidences of tumor recurrence in the lung or peritoneum were comparable between the two groups. However, the percentage of patients with liver metastases in the infection group (3 of 37, 8.1%) was significantly lower (P <0.05) than that of those in the noninfection group (85 of 401, 21.2%). The patients in the infection group tended to survive longer than the patients in the noninfection group. We herein report an initial finding that colorectal carcinoma rarely metastasizes to livers infected with HBV or HCV.","null","null","1999-04","The American Journal of Surgery","The American Journal of Surgery","Vol.177","No.4","279","281","eng","true","null","scientific_journal","null","null","10.1016/S0002-9610(99)00045-8","0002-9610","null","null","null","null","null"
"Postoperative liver failure after major hepatic resection for hepatocellular carcinoma in the modern era with special reference to remant liver volume","Postoperative liver failure after major hepatic resection for hepatocellular carcinoma in the modern era with special reference to remant liver volume","Ken Shirabe, Mitsuo Shimada, Tomonobu Gion, Hirofumi Hasegawa, Kenji Takenaka, Tohru Utsunomiya, Keizo Sugimachi","Ken Shirabe, Mitsuo Shimada, Tomonobu Gion, Hirofumi Hasegawa, Kenji Takenaka, Tohru Utsunomiya, Keizo Sugimachi","null","null","null","null","null","1999-03","Journal of American College of Surgeons","Journal of American College of Surgeons","Vol.188","No.3","304","309","eng","true","null","scientific_journal","null","null","null","null","null","http://www.ingentaconnect.com/content/els/10727515/1999/00000188/00000003/art00301","null","null","null"
"Preoperative change in albumin messenger RNA levels in patients with hepatocellular carcinoma","Preoperative change in albumin messenger RNA levels in patients with hepatocellular carcinoma","Tomonobu Gion, Akinobu Taketomi, Mitsuo Shimada, Ken Shirabe, Hirofumi Hasegawa, Kenji Takenaka, Keizo Sugimachi","Tomonobu Gion, Akinobu Taketomi, Mitsuo Shimada, Ken Shirabe, Hirofumi Hasegawa, Kenji Takenaka, Keizo Sugimachi","null","null","null","null","null","1998-12","Hepatology","Hepatology","Vol.28","No.6","1663","1668","eng","true","null","scientific_journal","null","null","null","0270-9139","null","null","null","null","null"
"Enhanced Expression of Thrombospondin-1 and Hypovascularity in Human Cholangiocarcinoma","Enhanced Expression of Thrombospondin-1 and Hypovascularity in Human Cholangiocarcinoma","Naoyuki Kawahara, Mayumi Ono, Ken-ichi Taguchi, Masahiro Okamoto, Mitsuo Shimada, Kenji Takenaka, Kenshi Hayashi, Dean F. Moshe, Keizo Sugimachi, Masazumi Tsuneyoshi, Michihiko Kuwano","Naoyuki Kawahara, Mayumi Ono, Ken-ichi Taguchi, Masahiro Okamoto, Mitsuo Shimada, Kenji Takenaka, Kenshi Hayashi, Dean F. Moshe, Keizo Sugimachi, Masazumi Tsuneyoshi, Michihiko Kuwano","null","null","null","null","null","1998-12","Hepatology","Hepatology","Vol.28","No.6","1512","1517","eng","true","null","scientific_journal","null","null","null","0270-9139","null","null","null","null","null"
"Nm23-H1 expression in intrahepatic or extrahepatic metastases of hepatocellular carcinoma","Nm23-H1 expression in intrahepatic or extrahepatic metastases of hepatocellular carcinoma","Mitsuo Shimada, Kenichi Taguchi, Hirofumi Hasegawa, Tomonobu Gion, Ken Shirabe, Masazumi Tuneyoshi, Keizo Sugimachi","Mitsuo Shimada, Kenichi Taguchi, Hirofumi Hasegawa, Tomonobu Gion, Ken Shirabe, Masazumi Tuneyoshi, Keizo Sugimachi","null","Decreased expression of nm23, a putative metastasis suppressor gene, has been reported to be related to either intrahepatic metastasis or a poor prognosis in hepatocellular carcinoma (HCC). The aim of this study was to elucidate the true role of nm23-H1 expression in both intrahepatic and distant metastases of HCC. Thirteen patients with single-nodule HCC, seven patients with HCC having satellite nodules and seven patients with HCCs having extrahepatic metastases were included in this study. The expression of nm23-H1 protein was immunohistochemically examined in both primary and metastatic nodules. Ten of 13 single-nodule HCCs were found to overexpress nm23-H1 protein. All main tumors, having satellite nodules, were found to overexpress nm23-H protein, except for two HCCs, which only partially expressed nm23-H1 protein. Regarding the nm23-H1 expression in intrahepatic metastases, most nodules overexpressed the protein. The expression of nm23-H1 was found to be low in only one intrahepatic metastasis specimen, while its primary tumor was also found to show a low expression of nm23-H1 protein. Microscopic portal vein invasion was found in three of the five patients studied, and all cancer cells in portal invasion overexpressed nm23-H1 protein. Nm23-H1 protein was expressed in all distant metastatic tumors and the staining intensity of most metastatic nodules was similar to that of the primary tumors. Our study demonstrated that nm23-H1 expression did not always decrease but instead tended to increase at both intrahepatic and extrahepatic metastatic sites. Based on these findings, nm23-H1 expression is not considered to be a reliable indicator of either intrahepatic or distant metastasis in HCC.","Decreased expression of nm23, a putative metastasis suppressor gene, has been reported to be related to either intrahepatic metastasis or a poor prognosis in hepatocellular carcinoma (HCC). The aim of this study was to elucidate the true role of nm23-H1 expression in both intrahepatic and distant metastases of HCC. Thirteen patients with single-nodule HCC, seven patients with HCC having satellite nodules and seven patients with HCCs having extrahepatic metastases were included in this study. The expression of nm23-H1 protein was immunohistochemically examined in both primary and metastatic nodules. Ten of 13 single-nodule HCCs were found to overexpress nm23-H1 protein. All main tumors, having satellite nodules, were found to overexpress nm23-H protein, except for two HCCs, which only partially expressed nm23-H1 protein. Regarding the nm23-H1 expression in intrahepatic metastases, most nodules overexpressed the protein. The expression of nm23-H1 was found to be low in only one intrahepatic metastasis specimen, while its primary tumor was also found to show a low expression of nm23-H1 protein. Microscopic portal vein invasion was found in three of the five patients studied, and all cancer cells in portal invasion overexpressed nm23-H1 protein. Nm23-H1 protein was expressed in all distant metastatic tumors and the staining intensity of most metastatic nodules was similar to that of the primary tumors. Our study demonstrated that nm23-H1 expression did not always decrease but instead tended to increase at both intrahepatic and extrahepatic metastatic sites. Based on these findings, nm23-H1 expression is not considered to be a reliable indicator of either intrahepatic or distant metastasis in HCC.","null","null","1998-10","Liver","Liver","Vol.18","No.5","337","342","eng","true","null","scientific_journal","null","null","null","0106-9543","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9831363&dopt=Abstract","null","null","null"
"Prognosis of hepatocellular carcinoma with diabetes mellitus after hepatic resection","Prognosis of hepatocellular carcinoma with diabetes mellitus after hepatic resection","Yasuharu Ikeda, Mitsuo Shimada, Hirofumi Hasegawa, Tomonobu Gion, Kiyoshi Kajiyama, Ken Shirabe, Katsuhiko Yanaga, Kenji Takenaka, Keizo Sugimachi","Yasuharu Ikeda, Mitsuo Shimada, Hirofumi Hasegawa, Tomonobu Gion, Kiyoshi Kajiyama, Ken Shirabe, Katsuhiko Yanaga, Kenji Takenaka, Keizo Sugimachi","null","null","null","null","null","1998-06","Hepatology","Hepatology","Vol.27","No.6","1567","1571","eng","true","null","scientific_journal","null","null","null","0270-9139","null","null","null","null","null"
"Treatment Strategy for Patients With Cystic Lesions Mimicking a Liver Tumor --- A Recent 10-Year Surgical Experience in Japan","Treatment Strategy for Patients With Cystic Lesions Mimicking a Liver Tumor --- A Recent 10-Year Surgical Experience in Japan","Mitsuo Shimada, Kenji Takenaka, Tomonobu Gion, Yuh Fujiwara, Kenichi Taguchi, Kiyoshi Kajiyama, Ken Shirabe, Keizo Sugimachi","Mitsuo Shimada, Kenji Takenaka, Tomonobu Gion, Yuh Fujiwara, Kenichi Taguchi, Kiyoshi Kajiyama, Ken Shirabe, Keizo Sugimachi","null","null","null","null","null","1998-06","Archives of Surgery","Archives of Surgery","Vol.133","No.6","643","646","eng","true","null","scientific_journal","null","null","null","null","null","http://archsurg.ama-assn.org/cgi/content/abstract/133/6/643","null","null","null"
"Risk factors linked to postoperative morbidity in patients with hepatocellular carcinoma","Risk factors linked to postoperative morbidity in patients with hepatocellular carcinoma","Mitsuo Shimada, Kenji Takenaka, Yuh Fujiwara, Tomonobu Gion, Ken Shirabe, Katsuhiko Yanaga, Keizo Sugimachi","Mitsuo Shimada, Kenji Takenaka, Yuh Fujiwara, Tomonobu Gion, Ken Shirabe, Katsuhiko Yanaga, Keizo Sugimachi","null","The aim of this study was to clarify the risk factors for morbidity as well as to establish an optimum surgical strategy for hepatocellular carcinoma (HCC). The risk factors linked to postoperative complications were analysed in 388 patients over a 10-year period, according to the kind of operative procedure. Stepwise regression analysis revealed that the most important factors related to postoperative morbidity were: age, creatinine level and the histological grade of fibrosis for the bisegmentectomy; the presence of diabetes mellitus, blood urea nitrogen level, the indocyanine green dye retention rate at 15 min and blood loss for the segmentectomy; the presence of diabetes mellitus and blood loss for subsegmentectomy; the presence of diabetes mellitus, the aspartate aminotransferase level, and the total operating time for resection less than subsegmentectomy. The most important risk factors were not always related to liver function tests, but instead to other coexisting conditions such as diabetes mellitus and operation stress including operating time and blood loss. Therefore, any future treatment strategy of hepatic resection for HCC should make every effort both to evaluate coexisting conditions carefully and to reduce operative stress as far as possible.","The aim of this study was to clarify the risk factors for morbidity as well as to establish an optimum surgical strategy for hepatocellular carcinoma (HCC). The risk factors linked to postoperative complications were analysed in 388 patients over a 10-year period, according to the kind of operative procedure. Stepwise regression analysis revealed that the most important factors related to postoperative morbidity were: age, creatinine level and the histological grade of fibrosis for the bisegmentectomy; the presence of diabetes mellitus, blood urea nitrogen level, the indocyanine green dye retention rate at 15 min and blood loss for the segmentectomy; the presence of diabetes mellitus and blood loss for subsegmentectomy; the presence of diabetes mellitus, the aspartate aminotransferase level, and the total operating time for resection less than subsegmentectomy. The most important risk factors were not always related to liver function tests, but instead to other coexisting conditions such as diabetes mellitus and operation stress including operating time and blood loss. Therefore, any future treatment strategy of hepatic resection for HCC should make every effort both to evaluate coexisting conditions carefully and to reduce operative stress as far as possible.","null","null","1998-02","The British Journal of Surgery","The British Journal of Surgery","Vol.85","No.2","195","198","eng","true","null","scientific_journal","null","null","10.1046/j.1365-2168.1998.00567.x","0007-1323","null","http://www3.interscience.wiley.com/cgi-bin/abstract/102526003/ABSTRACT?CRETRY=1&SRETRY=0","null","null","null"
"Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma","Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma","Mitsuo Shimada, kenji Takenaka, Kenichi Taguchi, Yuh Fujiwara, Tomonobu Gion, Kiyoshi Kajiyama, Takashi Maeda, Ken Shirabe, Katsuhiko Yanaga, Keizo Sugimachi","Mitsuo Shimada, kenji Takenaka, Kenichi Taguchi, Yuh Fujiwara, Tomonobu Gion, Kiyoshi Kajiyama, Takashi Maeda, Ken Shirabe, Katsuhiko Yanaga, Keizo Sugimachi","null","null","null","null","null","1998-01","Annals of Surgery","Annals of Surgery","Vol.227","No.1","80","85","eng","true","null","scientific_journal","null","null","null","null","null","http://www.annalsofsurgery.com/pt/re/annos/abstract.00000658-199801000-00012.htm;jsessionid=FCnGx3PSp4DT0TQJS1L3Tf71d3btwQsqT2YmDqWm3gD35nlM9GTY!1853810205!-949856144!8091!-1","null","null","null"
"Natural killer cell activity in patients with hepatocellular carcinoma","Natural killer cell activity in patients with hepatocellular carcinoma","Akinobu Taketomi, Mitsuo Shimada, Ken Shirabe, Kiyoshi Kajiyama, Tomonobu Gion, Keizo Sugimachi","Akinobu Taketomi, Mitsuo Shimada, Ken Shirabe, Kiyoshi Kajiyama, Tomonobu Gion, Keizo Sugimachi","null","null","null","null","null","1998","Cancer","Cancer","Vol.83","No.1","58","63","eng","true","null","scientific_journal","null","null","null","0008-543X","null","null","null","null","null"
"Clinipothological features of patients with hepatocellular carcinoma surving more than 10 year after hepatectomy","Clinipothological features of patients with hepatocellular carcinoma surving more than 10 year after hepatectomy","Ken Shirabe, Mitsuo Shimada, Kiyoshi Kajiyama, Tomonobu Gion, Yasuharu Ikeda, Hirofumi Hasegawa, Kenichi Taguchi, Kenji Takenaka, Keizo Sugimachi","Ken Shirabe, Mitsuo Shimada, Kiyoshi Kajiyama, Tomonobu Gion, Yasuharu Ikeda, Hirofumi Hasegawa, Kenichi Taguchi, Kenji Takenaka, Keizo Sugimachi","null","null","null","null","null","1998","Cancer","Cancer","Vol.83","No.11","2312","2316","eng","true","null","scientific_journal","null","null","null","0008-543X","null","null","null","null","null"
"Analysis of prognostic risk factors in hepatic resection for metastatic colorectal carcinoma with special reference to the surgical margin","Analysis of prognostic risk factors in hepatic resection for metastatic colorectal carcinoma with special reference to the surgical margin","Ken Shirabe, Kenji Takenaka, Tomonobu Gion, Yuh Fujiwara, Mitsuo Shimada, Katsuhiko Yanaga, Takashi Maeda, Kiyoshi Kajiyama, Keizo Sugimachi","Ken Shirabe, Kenji Takenaka, Tomonobu Gion, Yuh Fujiwara, Mitsuo Shimada, Katsuhiko Yanaga, Takashi Maeda, Kiyoshi Kajiyama, Keizo Sugimachi","null","Liver resection for metastatic colorectal cancer has been established. Nevertheless, it is still controversial whether the surgical margin from the tumour edge to the cut surface of the liver is a significant prognostic factor in hepatic resection for colorectal metastatic liver cancer. To clarify the prognostic risk factors in hepatic resection for colorectal metastasis, univariate and multivariate analyses were performed. Between April 1985 and April 1995, 31 patients underwent curative hepatic resection for metastatic colorectal cancer. The clinical and pathological factors were examined retrospectively. Overall 1-, 3- and 5-year survival rates of the patients were 92, 42 and 39 per cent respectively. Pathological study of 16 resected specimens with a solitary liver tumour revealed hepatic vein invasion by cancer cells in two of 16 cases, portal vein invasion in three, microsatellite lesions in two and biliary tract invasion in six cases. In resected specimens with a solitary tumour measuring less than 4 cm in diameter, one of these factors was observed in only two of nine cases, whereas in specimens with a solitary tumour measuring more than 4 cm in diameter, these factors were observed in six of seven patients (P < 0.05). The distance from the tumour edge to the intrahepatic invasion was less than 10 mm. With univariate analysis, tumour size of 4 cm or more in diameter, an interval of 6 months or less between colorectal and hepatic resection, four or more gross tumours, bilobar involvement and a resection margin from the tumour of less than 10 mm were found to be significant factors indicating a poor prognosis. Cox's proportional hazards model identified a tumour of 4 cm or more in diameter and a resection margin from the tumour of less than 10 mm as poor prognostic factors (P < 0.05). In treating metastatic colorectal cancer to the liver, the surgical margin should be more than 10 mm because occult intrahepatic invasion was always found to be located within 10 mm from the edge of the tumour.","Liver resection for metastatic colorectal cancer has been established. Nevertheless, it is still controversial whether the surgical margin from the tumour edge to the cut surface of the liver is a significant prognostic factor in hepatic resection for colorectal metastatic liver cancer. To clarify the prognostic risk factors in hepatic resection for colorectal metastasis, univariate and multivariate analyses were performed. Between April 1985 and April 1995, 31 patients underwent curative hepatic resection for metastatic colorectal cancer. The clinical and pathological factors were examined retrospectively. Overall 1-, 3- and 5-year survival rates of the patients were 92, 42 and 39 per cent respectively. Pathological study of 16 resected specimens with a solitary liver tumour revealed hepatic vein invasion by cancer cells in two of 16 cases, portal vein invasion in three, microsatellite lesions in two and biliary tract invasion in six cases. In resected specimens with a solitary tumour measuring less than 4 cm in diameter, one of these factors was observed in only two of nine cases, whereas in specimens with a solitary tumour measuring more than 4 cm in diameter, these factors were observed in six of seven patients (P < 0.05). The distance from the tumour edge to the intrahepatic invasion was less than 10 mm. With univariate analysis, tumour size of 4 cm or more in diameter, an interval of 6 months or less between colorectal and hepatic resection, four or more gross tumours, bilobar involvement and a resection margin from the tumour of less than 10 mm were found to be significant factors indicating a poor prognosis. Cox's proportional hazards model identified a tumour of 4 cm or more in diameter and a resection margin from the tumour of less than 10 mm as poor prognostic factors (P < 0.05). In treating metastatic colorectal cancer to the liver, the surgical margin should be more than 10 mm because occult intrahepatic invasion was always found to be located within 10 mm from the edge of the tumour.","null","null","1997-08","The British Journal of Surgery","The British Journal of Surgery","Vol.84","No.8","1077","1080","eng","true","null","scientific_journal","null","null","null","0007-1323","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9278644&dopt=Abstract","null","null","null"
"Indications for palliative reduction surgery in advanced hepatocellular carcinoma. The use of a remnant tumor index","Indications for palliative reduction surgery in advanced hepatocellular carcinoma. The use of a remnant tumor index","Kazuharu Yamamoto, Kenji Takenaka, Naoyuki Kawahara, Mitsuo Shimada, Ken Shirabe, Hidetoshi Itasaka, Takashi Nishizaki, Katsuhiko Yanaga, Keizo Sugimachi","Kazuharu Yamamoto, Kenji Takenaka, Naoyuki Kawahara, Mitsuo Shimada, Ken Shirabe, Hidetoshi Itasaka, Takashi Nishizaki, Katsuhiko Yanaga, Keizo Sugimachi","null","To clarify the indications for and the significance of palliative reduction surgery in the multidisciplinary treatment of advanced hepatocellular carcinoma (HCC) and to propose the use of a remnant tumor index (RTI) as a simplified criterion for palliative reduction surgery in cases of advanced HCC. A comparison of survival based on the RTI. A large university hospital in Japan. Twenty-five patients with advanced HCC who underwent palliative reduction surgery were divided into 3 groups as follows: group 1 (n = 9), the remnant tumor after operation existed only in the liver and the RTI was less than 5.0; group 2 (n = 11), the remnant tumor after operation existed only in the liver and the RTI was greater than 5.0; and group 3 (n = 5), extrahepatic metastatic tumor existed after operation. Pathological findings and survival rate after surgery. There was no significant difference in the degree of macroscopic intrahepatic metastases among the 3 groups; however, both the portal vein invasion and the histological grade tended to be more severe in groups 2 and 3. The respective 1-year and 3-year survival rates for group 1 were 67% and 33%, and those for group 2 were 21% and 0%. There were no survivors in group 3 at 1 year after surgery. Significant differences were found in the survival rates between groups 1 and 2 (P < .05), and between groups 1 and 3 (P < .05). Palliative reduction surgery for advanced HCC is only considered effective for patients with both an RTI of less than 5.0 and no extrahepatic metastasis.","To clarify the indications for and the significance of palliative reduction surgery in the multidisciplinary treatment of advanced hepatocellular carcinoma (HCC) and to propose the use of a remnant tumor index (RTI) as a simplified criterion for palliative reduction surgery in cases of advanced HCC. A comparison of survival based on the RTI. A large university hospital in Japan. Twenty-five patients with advanced HCC who underwent palliative reduction surgery were divided into 3 groups as follows: group 1 (n = 9), the remnant tumor after operation existed only in the liver and the RTI was less than 5.0; group 2 (n = 11), the remnant tumor after operation existed only in the liver and the RTI was greater than 5.0; and group 3 (n = 5), extrahepatic metastatic tumor existed after operation. Pathological findings and survival rate after surgery. There was no significant difference in the degree of macroscopic intrahepatic metastases among the 3 groups; however, both the portal vein invasion and the histological grade tended to be more severe in groups 2 and 3. The respective 1-year and 3-year survival rates for group 1 were 67% and 33%, and those for group 2 were 21% and 0%. There were no survivors in group 3 at 1 year after surgery. Significant differences were found in the survival rates between groups 1 and 2 (P < .05), and between groups 1 and 3 (P < .05). Palliative reduction surgery for advanced HCC is only considered effective for patients with both an RTI of less than 5.0 and no extrahepatic metastasis.","null","null","1997-02","Archives of Surgery","Archives of Surgery","Vol.132","No.2","120","123","eng","true","null","scientific_journal","null","null","null","0004-0010","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9041912&dopt=Citation","null","null","null"
"Characteristics of hepatocellular carcinoma associated with extrahepatic primary malignancies in southern Japan","Characteristics of hepatocellular carcinoma associated with extrahepatic primary malignancies in southern Japan","Mitsuo Shimada, Kenji Takenaka, Yuh Fujiwata, Tomonobu Gion, Ken Shirabe, Takashi Nishizaki, Katsuhiko Yanaga, Keizo Sugimachi","Mitsuo Shimada, Kenji Takenaka, Yuh Fujiwata, Tomonobu Gion, Ken Shirabe, Takashi Nishizaki, Katsuhiko Yanaga, Keizo Sugimachi","null","This study was conducted to clarify the characteristics of patients with extrahepatic primary cancers (EHPC) associated with hepatocellular carcinoma (HCC), as well as to investigate the influence of EHPC on both patient survival and disease-free survival after hepatic resection. Forty-one of 463 patients who underwent hepatic resection were included. The clinicopathological factors, including survival, were compared between patients with and without EHPC. We also compared the same factors among the prehepatectomy, synchronous, and posthepatectomy groups. Different types of extrahepatic cancers were also investigated in detail. Gastric and colorectal cancers were the most common EHPC. No definite relationship was observed between HCC and other specific cancers such as B-cell lymphoproliferative disorders. There also were no differences in either the liver function tests, alpha-fetoprotein, or prognostic pathological indicators such as portal vein invasion and intrahepatic metastases. In addition, we found no difference in patient survival between the patients with and without EHPC. However, disease-free survival rates in patients with EHPC were significantly higher than in those without EHPC. Patients in the prehepatectomy group were older than those in the synchronous and posthepatectomy groups, and no positive hepatitis B surface antigen was found in the prehepatectomy group. Patient survival was significantly higher in the posthepatectomy group than in the prehepatectomy group; however, no significant difference in disease-free survival was found among the three groups. Only one patient died of EHPC. No specific clinicopathological factors were observed in patients with HCC associated with EHPC. Furthermore, EHPC had no adverse effect on either patient survival or disease-free survival after hepatic resection. The predominant cancer was gastric cancer, whereas the most frequent cause of death was HCC itself. Therefore, a strict follow-up of HCC--as well as screening for the most common cancers, such as gastric cancers in southern Japan--should be required for patients with HCC associated with EHPC.","This study was conducted to clarify the characteristics of patients with extrahepatic primary cancers (EHPC) associated with hepatocellular carcinoma (HCC), as well as to investigate the influence of EHPC on both patient survival and disease-free survival after hepatic resection. Forty-one of 463 patients who underwent hepatic resection were included. The clinicopathological factors, including survival, were compared between patients with and without EHPC. We also compared the same factors among the prehepatectomy, synchronous, and posthepatectomy groups. Different types of extrahepatic cancers were also investigated in detail. Gastric and colorectal cancers were the most common EHPC. No definite relationship was observed between HCC and other specific cancers such as B-cell lymphoproliferative disorders. There also were no differences in either the liver function tests, alpha-fetoprotein, or prognostic pathological indicators such as portal vein invasion and intrahepatic metastases. In addition, we found no difference in patient survival between the patients with and without EHPC. However, disease-free survival rates in patients with EHPC were significantly higher than in those without EHPC. Patients in the prehepatectomy group were older than those in the synchronous and posthepatectomy groups, and no positive hepatitis B surface antigen was found in the prehepatectomy group. Patient survival was significantly higher in the posthepatectomy group than in the prehepatectomy group; however, no significant difference in disease-free survival was found among the three groups. Only one patient died of EHPC. No specific clinicopathological factors were observed in patients with HCC associated with EHPC. Furthermore, EHPC had no adverse effect on either patient survival or disease-free survival after hepatic resection. The predominant cancer was gastric cancer, whereas the most frequent cause of death was HCC itself. Therefore, a strict follow-up of HCC--as well as screening for the most common cancers, such as gastric cancers in southern Japan--should be required for patients with HCC associated with EHPC.","null","null","1996-04","The American Journal of Gastroenterology","The American Journal of Gastroenterology","Vol.91","No.4","754","758","eng","true","null","scientific_journal","null","null","null","0002-9270","null","null","null","null","null"
"Postoperative hepatitis status as a significant risk factor for recurrence in cirrhotic patients with small hepatocellular carcinoma","Postoperative hepatitis status as a significant risk factor for recurrence in cirrhotic patients with small hepatocellular carcinoma","Ken Shirabe, Kenji Takehara, Akinobu Taketomi, Naoyuki Kawahara, Kazuharu Yamamoto, Mitsuo Shimada, Keizo Sugimachi","Ken Shirabe, Kenji Takehara, Akinobu Taketomi, Naoyuki Kawahara, Kazuharu Yamamoto, Mitsuo Shimada, Keizo Sugimachi","null","null","null","null","null","1996","Cancer","Cancer","Vol.77","No.6","1050","1055","eng","true","null","scientific_journal","null","null","null","0008-543X","null","null","null","null","null"
"Surgical treatment strategy for patients with Stage IV hepatocellular carcinoma","Surgical treatment strategy for patients with Stage IV hepatocellular carcinoma","Mitsuo Shimada, Kenji Takenaka, Naoyuki Kawahara, Kiyoshi Kajiyama, Kazuharu Yamamoto, Ken Shirabe, Takashi Nishizaki, Katsuhiko Yanaga, Keizo Sugimachi","Mitsuo Shimada, Kenji Takenaka, Naoyuki Kawahara, Kiyoshi Kajiyama, Kazuharu Yamamoto, Ken Shirabe, Takashi Nishizaki, Katsuhiko Yanaga, Keizo Sugimachi","null","null","null","null","null","1996","Surgery","Surgery","Vol.119","No.5","517","522","eng","true","null","scientific_journal","null","null","null","0039-6060","null","null","null","null","null"
"The effect of a perioperative steroid pulse on surgical stress in hepatic resection","The effect of a perioperative steroid pulse on surgical stress in hepatic resection","Mitsuo Shimada, A Saitoh, T Kano, Kenji Takenaka, Keizo Sugimachi","Mitsuo Shimada, A Saitoh, T Kano, Kenji Takenaka, Keizo Sugimachi","null","null","null","null","null","1996","Int Surg","Int Surg","Vol.81","No.1","49","51","eng","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"Prognosis of recurrent hepatocellular carcinoma: a 10-year surgical experience in Japan","Prognosis of recurrent hepatocellular carcinoma: a 10-year surgical experience in Japan","Mitsuo Shimada, Kenji Takenaka, Tomonobu Gion, Yuh Fujiwara, Kiyoshi Kajiyama, Takashi Maeda, Ken Shirabe, Takashi Nishizaki, Katsuhiko Yanaga, Keizo Sugimachi","Mitsuo Shimada, Kenji Takenaka, Tomonobu Gion, Yuh Fujiwara, Kiyoshi Kajiyama, Takashi Maeda, Ken Shirabe, Takashi Nishizaki, Katsuhiko Yanaga, Keizo Sugimachi","null","null","null","null","null","1996","Gastroenterology","Gastroenterology","Vol.111","No.9","720","726","eng","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"Ammonia clearance as a rapid index of viability in liver transplantation","Ammonia clearance as a rapid index of viability in liver transplantation","Kengo Fukuzawa, Katsuhiko Yanaga, Kenji Takenaka, Mitsuo Shimada, Hidetoshi Itasaka, Keizo Sugimachi","Kengo Fukuzawa, Katsuhiko Yanaga, Kenji Takenaka, Mitsuo Shimada, Hidetoshi Itasaka, Keizo Sugimachi","null","null","null","null","null","1995-12","The American Journal of Gastroenterology","The American Journal of Gastroenterology","Vol.90","No.12","2264","2264","eng","true","null","scientific_journal","null","null","null","0002-9270","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8540539&dopt=Abstract","null","null","null"
"Thrombomodulin inhibits intrahepatic spread in human hepatocellular carcinoma","Thrombomodulin inhibits intrahepatic spread in human hepatocellular carcinoma","Taketoshi Suehiro, Mitsuo Shimada, Takashi Matsumata, Akinobu Taketomi, Kazuharu Yamamoto, Keizo Sugimachi","Taketoshi Suehiro, Mitsuo Shimada, Takashi Matsumata, Akinobu Taketomi, Kazuharu Yamamoto, Keizo Sugimachi","null","Thrombomodulin (TM) converts thrombin from procoagulant into anticoagulant protein to activate protein C. Thrombin also plays an important role in the metastatic process of cancer cells. We performed an immunohistochemical and clinicopathological study of TM in 141 cases with resected hepatocellular carcinoma (HCC) measuring less than 6 cm in diameter. Twenty-five specimens (17.73%) stained positive for TM. TM was found in the cytoplasm and surface of cancer cells. The clinicopathological findings according to the positive of TM are examined in HCC. The preoperative plasma TM level of the patients with tissue that stained positive for TM was significantly higher than that of the patients with negative results; for the postoperative TM level, there were no differences between them. In addition, the frequencies of intrahepatic metastasis, tumor thrombus in the portal vein, and capsular infiltration were significantly lower in patients whose tissue stained positive for TM than in patients whose tissue stained negative for TM. The recurrence freedom rate was significantly higher in patients whose tissue stained positive for TM than patients whose tissue stained negative for TM. Thus, TM-producing HCC shows a slow intrahepatic spread. Therefore, these findings suggest that TM may inhibit the adhesion of tumor cells to the portal vein because of anticoagulant activity and thus prevent the spread of intrahepatic metastasis.","Thrombomodulin (TM) converts thrombin from procoagulant into anticoagulant protein to activate protein C. Thrombin also plays an important role in the metastatic process of cancer cells. We performed an immunohistochemical and clinicopathological study of TM in 141 cases with resected hepatocellular carcinoma (HCC) measuring less than 6 cm in diameter. Twenty-five specimens (17.73%) stained positive for TM. TM was found in the cytoplasm and surface of cancer cells. The clinicopathological findings according to the positive of TM are examined in HCC. The preoperative plasma TM level of the patients with tissue that stained positive for TM was significantly higher than that of the patients with negative results; for the postoperative TM level, there were no differences between them. In addition, the frequencies of intrahepatic metastasis, tumor thrombus in the portal vein, and capsular infiltration were significantly lower in patients whose tissue stained positive for TM than in patients whose tissue stained negative for TM. The recurrence freedom rate was significantly higher in patients whose tissue stained positive for TM than patients whose tissue stained negative for TM. Thus, TM-producing HCC shows a slow intrahepatic spread. Therefore, these findings suggest that TM may inhibit the adhesion of tumor cells to the portal vein because of anticoagulant activity and thus prevent the spread of intrahepatic metastasis.","null","null","1995-05","Hepatology","Hepatology","Vol.21","No.5","1285","1290","eng","true","null","scientific_journal","null","null","10.1002/hep.1840210511","0270-9139","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7537712&dopt=Abstract","null","null","null"
"A new approach for liver surgery: transdiaphragmatic hepatectomy for cirrhotic patients with hepatocellular carcinoma","A new approach for liver surgery: transdiaphragmatic hepatectomy for cirrhotic patients with hepatocellular carcinoma","Mitsuo Shimada, Takashi Matsumata, Akinobu Taketomi, Ken Shirabe, Hidetoshi Itasaka, Keizo Sugimachi","Mitsuo Shimada, Takashi Matsumata, Akinobu Taketomi, Ken Shirabe, Hidetoshi Itasaka, Keizo Sugimachi","null","null","null","null","null","1995-02","Arch Surg","Arch Surg","Vol.130","No.2","157","160","eng","true","null","scientific_journal","null","null","null","null","null","null","null","null","null"
"Patial hepatic grafting: porvine stdy on criticl volume reduction","Patial hepatic grafting: porvine stdy on criticl volume reduction","Katsuhiko Yanaga, Keishi Kishikawa, Taketoshi Suehiro, Takashi Nishizaki, Mitsuo Shimada, Hidetoshi Itasaka, Kenichi Nomoto, Saburo Kakizoe, Keizo Sugimachi","Katsuhiko Yanaga, Keishi Kishikawa, Taketoshi Suehiro, Takashi Nishizaki, Mitsuo Shimada, Hidetoshi Itasaka, Kenichi Nomoto, Saburo Kakizoe, Keizo Sugimachi","null","null","null","null","null","1995","Surgery","Surgery","Vol.118","No.3","486","492","eng","true","null","scientific_journal","null","null","null","0039-6060","null","null","null","null","null"
"Liver resection for hepatocellular carcinoma in the elderly","Liver resection for hepatocellular carcinoma in the elderly","Kenji Takenaka, Mitsuo Shimada, Hidefumi Higashi, Eisuke Adachi, Takashi Nishizaki, Katsuhiko Yanaga, Takashi Matsumata, Keizo Sugimachi","Kenji Takenaka, Mitsuo Shimada, Hidefumi Higashi, Eisuke Adachi, Takashi Nishizaki, Katsuhiko Yanaga, Takashi Matsumata, Keizo Sugimachi","null","To estimate the effectiveness of hepatic resection on hepatocellular carcinoma (HCC) in the elderly. Comparison with younger patients. A municipal hospital and a large university hospital in Japan. The study included 39 patients (age > or = 70 years [the elderly group]) and 229 patients (age < 70 years [the younger group]) who underwent hepatic resection from April 1985 to March 1993. The preoperative clinical features (Child's classification, association of cirrhosis and liver functions) were comparable between two groups. The positive rate for hepatitis C virus antibody was higher in the elderly group (88% vs 59%; P = .016). Morbidity and survival following operation and the pathological features of HCC. The incidence of postoperative hepatic failure was higher in the elderly group (10% vs 2%; P = .018). However, the incidence of operative death in the elderly group (5% vs 1%) as well as the incidence of other postoperative complications and rates of long-term survival (75.9% vs 51.6% at 5 years) and disease-free survival (30.4% vs 31.0% at 5 years) were similar to those in the younger group. The pathological features of HCC were identical between the two groups. The outcome of surgical treatment of HCC in the elderly group was satisfactory when compared with that in the younger group.","To estimate the effectiveness of hepatic resection on hepatocellular carcinoma (HCC) in the elderly. Comparison with younger patients. A municipal hospital and a large university hospital in Japan. The study included 39 patients (age > or = 70 years [the elderly group]) and 229 patients (age < 70 years [the younger group]) who underwent hepatic resection from April 1985 to March 1993. The preoperative clinical features (Child's classification, association of cirrhosis and liver functions) were comparable between two groups. The positive rate for hepatitis C virus antibody was higher in the elderly group (88% vs 59%; P = .016). Morbidity and survival following operation and the pathological features of HCC. The incidence of postoperative hepatic failure was higher in the elderly group (10% vs 2%; P = .018). However, the incidence of operative death in the elderly group (5% vs 1%) as well as the incidence of other postoperative complications and rates of long-term survival (75.9% vs 51.6% at 5 years) and disease-free survival (30.4% vs 31.0% at 5 years) were similar to those in the younger group. The pathological features of HCC were identical between the two groups. The outcome of surgical treatment of HCC in the elderly group was satisfactory when compared with that in the younger group.","null","null","1994-08","Archives of Surgery","Archives of Surgery","Vol.129","No.8","846","850","eng","true","null","scientific_journal","null","null","null","0004-0010","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8048856&dopt=Citation","null","null","null"
"The significance of tissue-type plasminogen activator for pretransplant assessment of liver graft viability: analysis of effluent from the graft in rats","The significance of tissue-type plasminogen activator for pretransplant assessment of liver graft viability: analysis of effluent from the graft in rats","Mitsuo Shimada, Hidetoshi Itasaka, Taketoshi Suehiro, Shigeki Wakiyama, Yuji Soejima, Katsuhiko Yanaga, Keizo Sugimachi","Mitsuo Shimada, Hidetoshi Itasaka, Taketoshi Suehiro, Shigeki Wakiyama, Yuji Soejima, Katsuhiko Yanaga, Keizo Sugimachi","null","We studied the significance of tissue-type plasminogen activator (tPA) on the pretransplant assessment of liver graft viability in rats. The liver grafts were excised from the rats and then divided into two groups. Group 1 consisted of grafts preserved for 4 h in chilled, lactated Ringer's solution (4 degrees C) and group 2 consisted of grafts preserved for 6 h in the same solution. After preservation, the liver grafts were flushed out through the portal vein using 5 ml of chilled, lactated Ringer's solution (4 degrees C). The entire effluent from the hepatic veins was then collected and analyzed for tPA, ammonia, lactate, pyruvate, glutamic oxaloacetic transaminase, and lactate dehydrogenase. The tPA concentration of effluent in group 2 was significantly higher than that in group 1 (0.80 +/- 0.23 ng/ml vs 0.42 +/- 0.08 ng/ml, P < 0.05). The lactate, pyruvate, and ammonia levels in group 2 were also higher than those in group 1 (134 +/- 13 mg/dl vs 120 +/- 2 mg/dl, 0.34 +/- 0.40 mg/dl vs 0.09 +/- 0.01 mg/dl, and 183 +/- 79 micrograms/dl vs 102 +/- 40 micrograms/dl, respectively). However, the discriminative power of tPA was stronger than that of the other parameters. Histological findings revealed a higher number of trypan blue-stained sinusoidal lining cells that were detached and swollen in group 2. We conclude that the amount of tPA in the effluent flushed from the graft can serve as a sensitive and reliable indicator of cold-preserved liver grafts in rats.","We studied the significance of tissue-type plasminogen activator (tPA) on the pretransplant assessment of liver graft viability in rats. The liver grafts were excised from the rats and then divided into two groups. Group 1 consisted of grafts preserved for 4 h in chilled, lactated Ringer's solution (4 degrees C) and group 2 consisted of grafts preserved for 6 h in the same solution. After preservation, the liver grafts were flushed out through the portal vein using 5 ml of chilled, lactated Ringer's solution (4 degrees C). The entire effluent from the hepatic veins was then collected and analyzed for tPA, ammonia, lactate, pyruvate, glutamic oxaloacetic transaminase, and lactate dehydrogenase. The tPA concentration of effluent in group 2 was significantly higher than that in group 1 (0.80 +/- 0.23 ng/ml vs 0.42 +/- 0.08 ng/ml, P < 0.05). The lactate, pyruvate, and ammonia levels in group 2 were also higher than those in group 1 (134 +/- 13 mg/dl vs 120 +/- 2 mg/dl, 0.34 +/- 0.40 mg/dl vs 0.09 +/- 0.01 mg/dl, and 183 +/- 79 micrograms/dl vs 102 +/- 40 micrograms/dl, respectively). However, the discriminative power of tPA was stronger than that of the other parameters. Histological findings revealed a higher number of trypan blue-stained sinusoidal lining cells that were detached and swollen in group 2. We conclude that the amount of tPA in the effluent flushed from the graft can serve as a sensitive and reliable indicator of cold-preserved liver grafts in rats.","null","null","1994-07","Transplant International","Transplant International","Vol.7","No.4","233","236","eng","true","null","scientific_journal","null","null","null","0934-0874","null","http://www.springerlink.com/content/m154443702463231/","null","null","null"
"Repeat hepatectomy for recurrent hepatocellular carcinoma","Repeat hepatectomy for recurrent hepatocellular carcinoma","Mitsuo Shimada, Takashi Matsumata, Akinobu Taketomi, Hidetoshi Itasaka, Kazuharu Yamamoto, Keizo Sugimachi","Mitsuo Shimada, Takashi Matsumata, Akinobu Taketomi, Hidetoshi Itasaka, Kazuharu Yamamoto, Keizo Sugimachi","null","The significance of repeat hepatectomy for recurrent hepatocellular carcinoma remains controversial. Therefore the aim of this study was to reevaluate both the survival and the surgical risks of repeat hepatectomy. The significance of repeat hepatectomy including the survival and the surgical risks for recurrent hepatocellular carcinoma were investigated with 21 patients who underwent a curative repeat hepatectomy during the period between May 1975 and July 1993. For a comparison of survival, 253 patients who underwent a curative primary hepatectomy during the period between April 1985 and July 1993 were used. Moreover, the preoperative liver function tests were also compared between the first and second hepatectomies. Regarding the preoperative liver function tests, the indocyanine green dye excretion rate at 15 minutes in the second hepatectomy (18.7% +/- 8.7%) was significantly higher than that in the first hepatectomy (14.7% +/- 5.9%). With regard to the surgical risks, there was no difference in the clinical parameters for blood loss, operation time, and the incidence of postoperative complications between the first and second hepatectomies. The postoperative hospital stay for the second hepatectomies was relatively shorter than that for the first hepatectomies. In addition, the patient's survival and disease-free survival after a curative repeat hepatectomy were almost identical to that after a curative primary hepatectomy. A curative repeat hepatectomy is thus considered to be the most effective therapeutic modality for recurrent hepatocellular carcinoma.","The significance of repeat hepatectomy for recurrent hepatocellular carcinoma remains controversial. Therefore the aim of this study was to reevaluate both the survival and the surgical risks of repeat hepatectomy. The significance of repeat hepatectomy including the survival and the surgical risks for recurrent hepatocellular carcinoma were investigated with 21 patients who underwent a curative repeat hepatectomy during the period between May 1975 and July 1993. For a comparison of survival, 253 patients who underwent a curative primary hepatectomy during the period between April 1985 and July 1993 were used. Moreover, the preoperative liver function tests were also compared between the first and second hepatectomies. Regarding the preoperative liver function tests, the indocyanine green dye excretion rate at 15 minutes in the second hepatectomy (18.7% +/- 8.7%) was significantly higher than that in the first hepatectomy (14.7% +/- 5.9%). With regard to the surgical risks, there was no difference in the clinical parameters for blood loss, operation time, and the incidence of postoperative complications between the first and second hepatectomies. The postoperative hospital stay for the second hepatectomies was relatively shorter than that for the first hepatectomies. In addition, the patient's survival and disease-free survival after a curative repeat hepatectomy were almost identical to that after a curative primary hepatectomy. A curative repeat hepatectomy is thus considered to be the most effective therapeutic modality for recurrent hepatocellular carcinoma.","null","null","1994-06","Surgery","Surgery","Vol.115","No.6","703","706","eng","true","null","scientific_journal","null","null","null","0039-6060","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8197562&dopt=Abstract","null","null","null"
"Effect of nafamostat mesilate on coagulation and fibrinolysis in hepatic resection","Effect of nafamostat mesilate on coagulation and fibrinolysis in hepatic resection","Mitsuo Shimada, Takashi Matsumata, Ken Shirabe, Tatsuro Kamakura, Akinobu Taketomi, Keizo Sugimachi","Mitsuo Shimada, Takashi Matsumata, Ken Shirabe, Tatsuro Kamakura, Akinobu Taketomi, Keizo Sugimachi","null","The effect of nafamostat mesilate on coagulation and fibrinolysis was investigated in a study of 22 patients with hepatocellular carcinoma who underwent a hepatic resection. The patients were divided into two groups: group 1, control (n = 11) and group 2, those with the intraoperative and postoperative use of nafamostat mesilate (0.2 to 0.4 milligram per kilogram per hour, n = 11). Nafamostat mesilate tended to suppress the coagulation expressed by thrombin-antithrombin III complex and fibrinopeptide A both during and immediately after operation. Moreover, nafamostat mesilate significantly suppressed the fibrinolysis expressed by euglobulin lysis activity both during and after operation. With regard to the initial stage of the fibrinolytic system, such as tissue-type plasminogen activator and plasminogen activator inhibitor-1, there was no difference between the groups. Therefore, the suppression of the euglobulin lysis activity may be caused by the inhibition of plasmin activity. There was no difference between the groups regarding operative blood loss. However, the rate of blood transfusion in group 2 was lower than that in group 1, and no fresh frozen plasma was required for the patients who lost over 2,000 milliliters of blood. Nafamostat mesilate can suppress euglobulin lysis activity both intraoperatively and postoperatively, and thus decrease the amount of blood transfusion needed. Therefore, at present, nafamostat mesilate seems to be one of the most useful agents for stabilizing the coagulant and fibrinolytic systems in hepatic resection.","The effect of nafamostat mesilate on coagulation and fibrinolysis was investigated in a study of 22 patients with hepatocellular carcinoma who underwent a hepatic resection. The patients were divided into two groups: group 1, control (n = 11) and group 2, those with the intraoperative and postoperative use of nafamostat mesilate (0.2 to 0.4 milligram per kilogram per hour, n = 11). Nafamostat mesilate tended to suppress the coagulation expressed by thrombin-antithrombin III complex and fibrinopeptide A both during and immediately after operation. Moreover, nafamostat mesilate significantly suppressed the fibrinolysis expressed by euglobulin lysis activity both during and after operation. With regard to the initial stage of the fibrinolytic system, such as tissue-type plasminogen activator and plasminogen activator inhibitor-1, there was no difference between the groups. Therefore, the suppression of the euglobulin lysis activity may be caused by the inhibition of plasmin activity. There was no difference between the groups regarding operative blood loss. However, the rate of blood transfusion in group 2 was lower than that in group 1, and no fresh frozen plasma was required for the patients who lost over 2,000 milliliters of blood. Nafamostat mesilate can suppress euglobulin lysis activity both intraoperatively and postoperatively, and thus decrease the amount of blood transfusion needed. Therefore, at present, nafamostat mesilate seems to be one of the most useful agents for stabilizing the coagulant and fibrinolytic systems in hepatic resection.","null","null","1994-05","Journal of the American College of Surgeons","Journal of the American College of Surgeons","Vol.178","No.5","498","502","eng","true","null","scientific_journal","null","null","null","1072-7515","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8167888&dopt=Abstract","null","null","null"
"Modulation of congulation and fibrinolysis in hepatic resection; a randomized prospective control study using antithrombin concentrates","Modulation of congulation and fibrinolysis in hepatic resection; a randomized prospective control study using antithrombin concentrates","Mitsuo Shimada, Takashi Matsumata, Tatsuro Kamakura, Hiroshi Hayashi, Keiko Urata, Keizo Sugimachi","Mitsuo Shimada, Takashi Matsumata, Tatsuro Kamakura, Hiroshi Hayashi, Keiko Urata, Keizo Sugimachi","null","A randomized prospective control trial for determining the efficacy of antithrombin III concentrates in hepatic resection was performed using 24 patients with hepatocellular carcinoma. Thirteen patients were given antithrombin III concentrates (1,500 IU) immediately before operation, during hepatectomy and immediately after operation. Coagulant and fibrinolytic profiles were determined by molecular markers such as thrombin-antithrombin III complex and plasmin-alpha 2plasmin inhibitor complex. During hepatic resection, both hypercoagulability and mainly primary hyperfibrinolysis occurred. Regarding the effectiveness of antithrombin III concentrates, in the antithrombin III treatment group, only a significant lower incidence of positive soluble fibrin monomer complex at postoperative days 1 and 5 was found among all the parameters studied. Therefore, no definite evidence of clinical usefulness of the perioperative administration of antithrombin III concentrates in hepatic resection was proved.","A randomized prospective control trial for determining the efficacy of antithrombin III concentrates in hepatic resection was performed using 24 patients with hepatocellular carcinoma. Thirteen patients were given antithrombin III concentrates (1,500 IU) immediately before operation, during hepatectomy and immediately after operation. Coagulant and fibrinolytic profiles were determined by molecular markers such as thrombin-antithrombin III complex and plasmin-alpha 2plasmin inhibitor complex. During hepatic resection, both hypercoagulability and mainly primary hyperfibrinolysis occurred. Regarding the effectiveness of antithrombin III concentrates, in the antithrombin III treatment group, only a significant lower incidence of positive soluble fibrin monomer complex at postoperative days 1 and 5 was found among all the parameters studied. Therefore, no definite evidence of clinical usefulness of the perioperative administration of antithrombin III concentrates in hepatic resection was proved.","null","null","1994-04","Thrombosis Research","Thrombosis Research","Vol.74","No.2","105","114","eng","true","null","scientific_journal","null","null","null","0049-3848","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8029811&dopt=Abstract","null","null","null"
"Estimation of risk of major complications after hepatic resection: a study of multivariate analysis of 209 cases","Estimation of risk of major complications after hepatic resection: a study of multivariate analysis of 209 cases","Mitsuo Shimada, Takashi Matsumata, Kouhei Akazawa, Tatsuro Kamakura, Hidetoshi Itasaka, Keizo Sugimachi, Yoshiaki Nose","Mitsuo Shimada, Takashi Matsumata, Kouhei Akazawa, Tatsuro Kamakura, Hidetoshi Itasaka, Keizo Sugimachi, Yoshiaki Nose","null","To identify the risk factors predicting major postoperative complications from among preoperative and intraoperative variables, an extensive retrospective analysis of 209 patients who underwent hepatic resections was performed using multivariate logistic regression. The major complications were defined as liver failure, intractable ascites and pleural effusion, intraperitoneal infection, intra-abdominal hemorrhage requiring reoperation, major bile leakage, and gastrointestinal tract bleeding. First, detailed pre- and intraoperative data including medical history, laboratory data, portion and extent of hepatectomy, operative time, and amount of blood loss were univariately analyzed. Next, any significant variables were multivariately analyzed using the logistic regression method. Diabetes, increased intraoperative blood loss, resection of segment 8, and an increased serum blood urea nitrogen level were independent and significant variables predicting major postoperative complications. A higher level of serum cholesterol and a procedure involving a portion of left lateral segment were found to decrease the risk. Both more careful operative procedures and intensive management of DM and renal dysfunction in the perioperative period could result in a better quality of life after hepatic resection.","To identify the risk factors predicting major postoperative complications from among preoperative and intraoperative variables, an extensive retrospective analysis of 209 patients who underwent hepatic resections was performed using multivariate logistic regression. The major complications were defined as liver failure, intractable ascites and pleural effusion, intraperitoneal infection, intra-abdominal hemorrhage requiring reoperation, major bile leakage, and gastrointestinal tract bleeding. First, detailed pre- and intraoperative data including medical history, laboratory data, portion and extent of hepatectomy, operative time, and amount of blood loss were univariately analyzed. Next, any significant variables were multivariately analyzed using the logistic regression method. Diabetes, increased intraoperative blood loss, resection of segment 8, and an increased serum blood urea nitrogen level were independent and significant variables predicting major postoperative complications. A higher level of serum cholesterol and a procedure involving a portion of left lateral segment were found to decrease the risk. Both more careful operative procedures and intensive management of DM and renal dysfunction in the perioperative period could result in a better quality of life after hepatic resection.","null","null","1994-04","The American Journal of Surgery","The American Journal of Surgery","Vol.167","No.4","399","403","eng","true","null","scientific_journal","null","null","10.1016/0002-9610(94)90124-4","0002-9610","null","null","null","null","null"
"Characteristics of hepatocellular carcinoma originating in the caudate lobe","Characteristics of hepatocellular carcinoma originating in the caudate lobe","Mitsuo Shimada, Takashi Matsumata, Takashi Maeda, Katsuhiko Yanaga, Akinobu Taketomi, Keizo Sugimachi","Mitsuo Shimada, Takashi Matsumata, Takashi Maeda, Katsuhiko Yanaga, Akinobu Taketomi, Keizo Sugimachi","null","Nine patients with hepatocellular carcinoma originating in the caudate lobe who underwent hepatic resection were studied. The caudate lobe was divided into three parts, according to the criteria of Kumon, including the Spiegel lobe, the paracaval portion and the caudate process. The tumors were located in the Spiegel lobe in four, the paracaval portion in four and the caudate process in one. Surgical procedures consisted of right hepatic lobectomy in one, central bisegmentectomy in one and caudate lobectomy in seven. The mean surgical time was 379 +/- 129 min; the mean estimated blood loss was 2,994 +/- 2,303 ml. The above-mentioned surgical risks were more clearly recognized in the paracaval portion than in the Spiegel lobe. In addition, most patients experienced significant post-operative complications. Six of eight patients with 6 mo or longer follow-up had recurrences, and two of six patients died. The characteristics of hepatocellular carcinoma in the caudate lobe were as follows: (a) a higher surgical risk, and more definite risk in the paracaval portion; and (b) a higher rate of early recurrence. A left lobectomy for the Spiegel lobe, a right or left trisegmentectomy for the paracaval portion and a right lobectomy for the caudate process would be ideal from the point of view of the portal supply of the caudate lobe. However, in cirrhotic patients either a caudate lobectomy or partial resection might be preferable because longer survival can be expected.","Nine patients with hepatocellular carcinoma originating in the caudate lobe who underwent hepatic resection were studied. The caudate lobe was divided into three parts, according to the criteria of Kumon, including the Spiegel lobe, the paracaval portion and the caudate process. The tumors were located in the Spiegel lobe in four, the paracaval portion in four and the caudate process in one. Surgical procedures consisted of right hepatic lobectomy in one, central bisegmentectomy in one and caudate lobectomy in seven. The mean surgical time was 379 +/- 129 min; the mean estimated blood loss was 2,994 +/- 2,303 ml. The above-mentioned surgical risks were more clearly recognized in the paracaval portion than in the Spiegel lobe. In addition, most patients experienced significant post-operative complications. Six of eight patients with 6 mo or longer follow-up had recurrences, and two of six patients died. The characteristics of hepatocellular carcinoma in the caudate lobe were as follows: (a) a higher surgical risk, and more definite risk in the paracaval portion; and (b) a higher rate of early recurrence. A left lobectomy for the Spiegel lobe, a right or left trisegmentectomy for the paracaval portion and a right lobectomy for the caudate process would be ideal from the point of view of the portal supply of the caudate lobe. However, in cirrhotic patients either a caudate lobectomy or partial resection might be preferable because longer survival can be expected.","null","null","1994-04","Hepatology","Hepatology","Vol.19","No.4","911","915","eng","true","null","scientific_journal","null","null","10.1002/hep.1840190417","0270-9139","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8138265&dopt=Abstract","null","null","null"
"The role of prostaglandins in hepatic resection","The role of prostaglandins in hepatic resection","Mitsuo Shimada, Takashi Matsumata, Akinobu Taketomi, Ken Shirabe, Kazuharu Yamamoto, Keizo Sugimachi","Mitsuo Shimada, Takashi Matsumata, Akinobu Taketomi, Ken Shirabe, Kazuharu Yamamoto, Keizo Sugimachi","null","The role of prostaglandins (PGs) and the efficacy of PGE1 were investigated in hepatic resection. Patients who underwent hepatic resection were randomly assigned to two groups consisting of a control (n = 5) and a PGE1 treatment group (n = 6). Then the amount of 6-keto PF1 alpha, thromboxane B2 and (TXB2) and PGE2 were serially measured both before and after hepatic resection. Regarding changes in the PGs, a remarkable increase in TXB2 during hepatectomy was demonstrated in both groups. In the control group, both 6-keto PF1 alpha and PGE2 showed only a slight increase both during and after the operation. Regarding the efficacy of PGE1 on liver damage, no significant difference in postoperative liver function was found, however the lipoperoxide level at postoperative day 3 in the PGE1 treatment group (1.9 +/- 0.4 nmol/ml) was significantly lower than that in the control (2.6 +/- 0.5 nmol/ml: P < 0.05). Judging from the remarkable increase of TXB2, a stable metabolite of TXA2 during hepatectomy, it may be suggested that TXA2 plays an important role in the development of liver damage during hepatic resection.","The role of prostaglandins (PGs) and the efficacy of PGE1 were investigated in hepatic resection. Patients who underwent hepatic resection were randomly assigned to two groups consisting of a control (n = 5) and a PGE1 treatment group (n = 6). Then the amount of 6-keto PF1 alpha, thromboxane B2 and (TXB2) and PGE2 were serially measured both before and after hepatic resection. Regarding changes in the PGs, a remarkable increase in TXB2 during hepatectomy was demonstrated in both groups. In the control group, both 6-keto PF1 alpha and PGE2 showed only a slight increase both during and after the operation. Regarding the efficacy of PGE1 on liver damage, no significant difference in postoperative liver function was found, however the lipoperoxide level at postoperative day 3 in the PGE1 treatment group (1.9 +/- 0.4 nmol/ml) was significantly lower than that in the control (2.6 +/- 0.5 nmol/ml: P < 0.05). Judging from the remarkable increase of TXB2, a stable metabolite of TXA2 during hepatectomy, it may be suggested that TXA2 plays an important role in the development of liver damage during hepatic resection.","null","null","1994-02","Prostaglandins, Leukotrienes, and Essential Fatty Acids","Prostaglandins, Leukotrienes, and Essential Fatty Acids","Vol.50","No.2","65","68","eng","true","null","scientific_journal","null","null","null","0952-3278","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8171069&dopt=Abstract","null","null","null"
"Hapatic regeneration following right lobectomy: estimation of regenerative capacity","Hapatic regeneration following right lobectomy: estimation of regenerative capacity","Mitsuo Shimada, Takashi Matsunaga, Takashi Maeda, Hidetoshi Itasaka, Taketoshi Suehiro, Keizo Sugimachi","Mitsuo Shimada, Takashi Matsunaga, Takashi Maeda, Hidetoshi Itasaka, Taketoshi Suehiro, Keizo Sugimachi","null","null","null","null","null","1994-01","Surgery Today","Surgery Today","Vol.24","No.1","44","48","eng","true","null","scientific_journal","null","null","null","0941-1291","null","http://www.springerlink.com/link.asp?id=g11u142264g24858","null","null","null"
"A thromboxane A2 synthetase inhibitor, OKY-046, reduces liver damage in hepatectomy","A thromboxane A2 synthetase inhibitor, OKY-046, reduces liver damage in hepatectomy","Mitsuo Shimada, Takashi Matsumata, Ken Shirabe, Keizo Sugimachi","Mitsuo Shimada, Takashi Matsumata, Ken Shirabe, Keizo Sugimachi","null","null","null","null","null","1993-11","Surgery","Surgery","Vol.114","No.5","993","995","eng","true","null","scientific_journal","null","null","null","0039-6060","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8236027&dopt=Abstract","null","null","null"
"Prediction of hepatic graft viability before reperfusion: an analysis of effluent from porcine allografts","Prediction of hepatic graft viability before reperfusion: an analysis of effluent from porcine allografts","Mitsuo Shimada, Katsuhiko Yanaga, Keiji Kishikawa, Saburo Kakizoe, Hidetoshi Itasaka, Tetsuo Ikeda, Taketoshi Suehiro, Keizo Sugimachi","Mitsuo Shimada, Katsuhiko Yanaga, Keiji Kishikawa, Saburo Kakizoe, Hidetoshi Itasaka, Tetsuo Ikeda, Taketoshi Suehiro, Keizo Sugimachi","null","Rapid and reliable assessment of hepatic graft viability is important for successful orthotopic liver transplantation (OLTx). OLTx was performed in 11 pairs of pigs via a venovenous bypass. Six of these grafts were transplanted immediately (group A), while the other five were preserved in University of Wisconsin (UW) solution for 24 h and then transplanted (group B). All grafts were flushed with 300 ml of chilled (4 degrees C) Ringer's lactate solution before reperfusion of the graft, when 20 ml of effluent from the graft was collected and the concentrations of ammonia, lactic acid, GOT, and LDH were measured. Four of the six pigs in group A survived longer than 3 days, while the other two pigs died of causes other than graft dysfunction. All five pigs in group B died either of hemoperitoneum or hemodynamic instability due to liver failure. The histology of postperfusion biopsies in group A showed minimal pathological changes, while the grafts in group B revealed moderate to severe ischemic injuries. Ammonia and lactic acid in the effluent of group B were significantly higher than those of group A (1511 +/- 216 vs 417 +/- 333 micrograms/dl and 114.1 +/- 12.2 vs 91.4 +/- 12.2 mg/dl, respectively; P < 0.05 in both cases). Before reperfusion, the rate of total adenine nucleotides in all of the substances in the graft, which were measured using high performance liquid chromatography (HPLC), inversely correlated with the ammonia levels in the effluent. We conclude that an analysis of the effluent, (i.e. the levels of ammonia and lactic acid), flushed from a hepatic graft before reperfusion could serve as a predictor of hepatic graft viability.","Rapid and reliable assessment of hepatic graft viability is important for successful orthotopic liver transplantation (OLTx). OLTx was performed in 11 pairs of pigs via a venovenous bypass. Six of these grafts were transplanted immediately (group A), while the other five were preserved in University of Wisconsin (UW) solution for 24 h and then transplanted (group B). All grafts were flushed with 300 ml of chilled (4 degrees C) Ringer's lactate solution before reperfusion of the graft, when 20 ml of effluent from the graft was collected and the concentrations of ammonia, lactic acid, GOT, and LDH were measured. Four of the six pigs in group A survived longer than 3 days, while the other two pigs died of causes other than graft dysfunction. All five pigs in group B died either of hemoperitoneum or hemodynamic instability due to liver failure. The histology of postperfusion biopsies in group A showed minimal pathological changes, while the grafts in group B revealed moderate to severe ischemic injuries. Ammonia and lactic acid in the effluent of group B were significantly higher than those of group A (1511 +/- 216 vs 417 +/- 333 micrograms/dl and 114.1 +/- 12.2 vs 91.4 +/- 12.2 mg/dl, respectively; P < 0.05 in both cases). Before reperfusion, the rate of total adenine nucleotides in all of the substances in the graft, which were measured using high performance liquid chromatography (HPLC), inversely correlated with the ammonia levels in the effluent. We conclude that an analysis of the effluent, (i.e. the levels of ammonia and lactic acid), flushed from a hepatic graft before reperfusion could serve as a predictor of hepatic graft viability.","null","null","1993-01","Transplant International","Transplant International","Vol.6","No.1","4","7","eng","true","null","scientific_journal","null","null","null","0934-0874","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8452631&dopt=Abstract","null","null","null"
"Ischemic injury in liver transplantation : difference in injury sites between warm and cold ischemia in rats","Ischemic injury in liver transplantation : difference in injury sites between warm and cold ischemia in rats","Tetsuo Ikeda, Katsuhiko Yanaga, Keiji Kishikawa, Saburo Kakizoe, Mitsuo Shimada, Keizo Sugimachi","Tetsuo Ikeda, Katsuhiko Yanaga, Keiji Kishikawa, Saburo Kakizoe, Mitsuo Shimada, Keizo Sugimachi","null","Using liver allografts with warm or cold ischemia, we evaluated functional and morphological alterations in hepatocytes, sinusoidal endothelial cells and Kupffer cells in a rat transplantation model. All recipients of allografts with either 4 hr of cold or 30 min of warm ischemia lived more than 22 days and were judged viable. On the other hand, all recipients of grafts with 6 hr of cold or 60 min of warm ischemia died within 2 days and were therefore judged to be nonviable. With these viable and nonviable allograft models, hepatocyte function was evaluated by the bile output and serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase and serum lactate dehydrogenase levels; endothelial cell function was judged by the serum hyaluronic acid level, and Kupffer cell function was measured by an intravenous colloidal carbon clearance test. Hepatocyte injury was the prominent feature in warm ischemic grafts, especially in the nonviable ones. On the other hand, serum hyaluronic acid values were significantly higher in the nonviable cold ischemic group, compared with the viable counterpart, suggesting that the functional depression of endothelial cells was predominant in cold, nonviable livers. Histological examinations coincided with the above findings. The phagocytic activity of Kupffer cells was depressed by warm or cold ischemia, whereas the number of Kupffer cells was reduced in the warm ischemia group. We conclude that in liver allografts the main site of injury in warm ischemia is the hepatocytes and suggest that cold ischemia is associated with endothelial cell damage.","Using liver allografts with warm or cold ischemia, we evaluated functional and morphological alterations in hepatocytes, sinusoidal endothelial cells and Kupffer cells in a rat transplantation model. All recipients of allografts with either 4 hr of cold or 30 min of warm ischemia lived more than 22 days and were judged viable. On the other hand, all recipients of grafts with 6 hr of cold or 60 min of warm ischemia died within 2 days and were therefore judged to be nonviable. With these viable and nonviable allograft models, hepatocyte function was evaluated by the bile output and serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase and serum lactate dehydrogenase levels; endothelial cell function was judged by the serum hyaluronic acid level, and Kupffer cell function was measured by an intravenous colloidal carbon clearance test. Hepatocyte injury was the prominent feature in warm ischemic grafts, especially in the nonviable ones. On the other hand, serum hyaluronic acid values were significantly higher in the nonviable cold ischemic group, compared with the viable counterpart, suggesting that the functional depression of endothelial cells was predominant in cold, nonviable livers. Histological examinations coincided with the above findings. The phagocytic activity of Kupffer cells was depressed by warm or cold ischemia, whereas the number of Kupffer cells was reduced in the warm ischemia group. We conclude that in liver allografts the main site of injury in warm ischemia is the hepatocytes and suggest that cold ischemia is associated with endothelial cell damage.","null","null","1992-08","Hepatology","Hepatology","Vol.16","No.2","454","461","eng","true","null","scientific_journal","null","null","10.1002/hep.1840160226","0270-9139","null","http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1639355&dopt=Abstract","null","null","null"
"Significance of lecithin:cholesterol acyltransferase activity as a prognostic indicator of early allograft function in clinical liver transplantation","Significance of lecithin:cholesterol acyltransferase activity as a prognostic indicator of early allograft function in clinical liver transplantation","Mitsuo Shimada, Katsuhiko Yanaga, Leonard Makowka, Saburo Kakizoe, DH Thiel Van, Thomas E Starzl","Mitsuo Shimada, Katsuhiko Yanaga, Leonard Makowka, Saburo Kakizoe, DH Thiel Van, Thomas E Starzl","null","Rapid and accurate assessment of allograft function in the early postoperative period is critical for successful liver transplantation. This study evaluated the efficacy of lecithin:cholesterol acyltransferase (LCAT) activity as an indicator of early allograft function in human orthotopic liver transplantation (OLTx). During a three-month period between September and November 1987, 9 of 11 adult OLTx recipients whose graft exhibited poor function were studied. Poor graft function was defined as primary nonfunction, need for retransplantation within a week after OLTx, or elevation of the prothrombin time over 20 sec early after OLTx. Plasma LCAT activities (measured pretransplant and at 0, 6, 12, 18, and 24 hr, as well as 3 days, after OLTx) and pretransplant clinical variables were compared with those of 15 control patients whose graft exhibited good function. A significant correlation was found between mean LCAT activities during the first 24-hr after OLTx and early allograft function (P less than 0.05, chi 2 = 5.23). When pretransplant histological findings of the 6 grafts with poor function and the 15 controls together were correlated with the mean LCAT activity within 24 hr following OLTx, a significant association was demonstrated (P less than 0.05). This study suggests that plasma LCAT activity is an effective and practical method for assessing early allograft function following OLTx.","Rapid and accurate assessment of allograft function in the early postoperative period is critical for successful liver transplantation. This study evaluated the efficacy of lecithin:cholesterol acyltransferase (LCAT) activity as an indicator of early allograft function in human orthotopic liver transplantation (OLTx). During a three-month period between September and November 1987, 9 of 11 adult OLTx recipients whose graft exhibited poor function were studied. Poor graft function was defined as primary nonfunction, need for retransplantation within a week after OLTx, or elevation of the prothrombin time over 20 sec early after OLTx. Plasma LCAT activities (measured pretransplant and at 0, 6, 12, 18, and 24 hr, as well as 3 days, after OLTx) and pretransplant clinical variables were compared with those of 15 control patients whose graft exhibited good function. A significant correlation was found between mean LCAT activities during the first 24-hr after OLTx and early allograft function (P less than 0.05, chi 2 = 5.23). When pretransplant histological findings of the 6 grafts with poor function and the 15 controls together were correlated with the mean LCAT activity within 24 hr following OLTx, a significant association was demonstrated (P less than 0.05). This study suggests that plasma LCAT activity is an effective and practical method for assessing early allograft function following OLTx.","null","null","1989-10","Transplantation","Transplantation","Vol.48","No.4","600","603","eng","true","null","scientific_journal","null","null","null","0041-1337","null","http://www.ncbi.nlm.nih.gov/pubmed/2799912","null","null","null"
"Stapler insertion angle toward the esophagus reduces the incidence of early postoperative Roux stasis syndrome after distal gastrectomy in minimally invasive surgery.","Stapler insertion angle toward the esophagus reduces the incidence of early postoperative Roux stasis syndrome after distal gastrectomy in minimally invasive surgery.","Kouzou Yoshikawa, Mitsuo Shimada, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Yuuma Wada, Toshiaki Yoshimoto","Kouzou Yoshikawa, Mitsuo Shimada, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Yuuma Wada, Toshiaki Yoshimoto","null","Roux stasis syndrome (RSS) after Roux-en-Y (RY) reconstruction significantly prolongs the hospital stay and decreases the quality of life. The purpose of the present study was to evaluate the incidence of RSS in patients who underwent distal gastrectomy for gastric cancer and to identify the factors related to the development of RSS after mechanical RY reconstruction in minimally invasive surgery (MIS). This study included 134 patients who underwent distal gastrectomy in MIS with mechanical RY anastomosis. RSS was defined as the presence of symptoms such as nausea, vomiting, or abdominal fullness, and the confirmation of delayed gastric emptying on imaging or gastrointestinal fiber testing. Clinical data were checked, including body mass index, operative procedure, age, sex, operative time, blood loss volume, extent of lymph node dissection, final stage, stapler insertion angle, method of entry hole closure. The relationship between the incidence of RSS and these factors was analyzed. RSS occurred in 24 of 134 patients (17.9%). RSS occurred significantly more frequently in patients with D2 lymphadenectomy than in patients with D1 + lymphadenectomy (p = 0.04). All patients underwent side-to-side anastomosis via the antecolic route. The incidence of RSS was significantly greater in patients with a stapler insertion angle toward the greater curvature (n = 20, 22.5%) versus the esophagus (n = 4, 8.9%) (p = 0.04). The multivariate logistic regression model revealed that the stapler insertion angle to the greater curvature is identified as independent risk factor for RSS (OR 3.23, 95%Cl 1.01-10.3, p = 0.04). Stapler insertion angle toward the esophagus may reduce the incidence of early postoperative RSS rather than toward the greater curvature.","Roux stasis syndrome (RSS) after Roux-en-Y (RY) reconstruction significantly prolongs the hospital stay and decreases the quality of life. The purpose of the present study was to evaluate the incidence of RSS in patients who underwent distal gastrectomy for gastric cancer and to identify the factors related to the development of RSS after mechanical RY reconstruction in minimally invasive surgery (MIS). This study included 134 patients who underwent distal gastrectomy in MIS with mechanical RY anastomosis. RSS was defined as the presence of symptoms such as nausea, vomiting, or abdominal fullness, and the confirmation of delayed gastric emptying on imaging or gastrointestinal fiber testing. Clinical data were checked, including body mass index, operative procedure, age, sex, operative time, blood loss volume, extent of lymph node dissection, final stage, stapler insertion angle, method of entry hole closure. The relationship between the incidence of RSS and these factors was analyzed. RSS occurred in 24 of 134 patients (17.9%). RSS occurred significantly more frequently in patients with D2 lymphadenectomy than in patients with D1 + lymphadenectomy (p = 0.04). All patients underwent side-to-side anastomosis via the antecolic route. The incidence of RSS was significantly greater in patients with a stapler insertion angle toward the greater curvature (n = 20, 22.5%) versus the esophagus (n = 4, 8.9%) (p = 0.04). The multivariate logistic regression model revealed that the stapler insertion angle to the greater curvature is identified as independent risk factor for RSS (OR 3.23, 95%Cl 1.01-10.3, p = 0.04). Stapler insertion angle toward the esophagus may reduce the incidence of early postoperative RSS rather than toward the greater curvature.","null","null","2023-03-11","BMC Surgery","BMC Surgery","Vol.23","No.1","54","54","eng","null","null","research_institution","null","null","10.1186/s12893-023-01954-3","1471-2482","null","null","null","null","null"
"Curcumin-Mediated Resistance to Lenvatinib via EGFR Signaling Pathway in Hepatocellular Carcinoma.","Curcumin-Mediated Resistance to Lenvatinib via EGFR Signaling Pathway in Hepatocellular Carcinoma.","Katsuki Miyazaki, Yuji Morine, Caiming Xu, Chiharu Nakasu, Yuuma Wada, Hiroki Teraoku, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Mitsuo Shimada, Ajay Goel","Katsuki Miyazaki, Yuji Morine, Caiming Xu, Chiharu Nakasu, Yuuma Wada, Hiroki Teraoku, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Mitsuo Shimada, Ajay Goel","null","Lenvatinib is a multi-kinase inhibitor approved as a first-line treatment for patients with unresectable advanced hepatocellular carcinoma (HCC). However, its response rate is unsatisfactory, primarily due to the acquisition of resistance, which limits its clinical significance for treating patients with HCC. Recent evidence suggests that epidermal growth factor receptor (EGFR) activation can trigger Lenvatinib-resistance; and is considered an important therapeutic target in HCC. Curcumin, one of the most studied naturally occurring botanicals with robust anti-cancer activity, is also reported to be a potent tyrosine kinase inhibitor. In this study, we hypothesized that the anti-EGFR potential of Curcumin might help overcome Lenvatinib resistance in HCC. We established two Lenvatinib-resistant cells and discovered that a combination of Curcumin and Lenvatinib exhibited a synergistic anti-tumor efficacy in the resistant HCC cell lines. In line with previous reports, Lenvatinib-resistant cell lines revealed significant activation of the EGFR, and genomewide transcriptomic profiling analysis identified that the PI3K-AKT pathway was associated with Lenvatinib resistance. The combination treatment with Curcumin and Lenvatinib dramatically suppressed gene and protein expression of the EGFR-PI3K-AKT pathway, suggesting Curcumin overcomes Lenvatinib resistance via inhibition of EGFR. We further validated these findings in tumor spheroids derived from resistant cell lines. In conclusion, we, for the first time, report that Curcumin reverses Lenvatinib resistance in HCC, and that their combination has clinical application potential for adjunctive treatment in HCC.","Lenvatinib is a multi-kinase inhibitor approved as a first-line treatment for patients with unresectable advanced hepatocellular carcinoma (HCC). However, its response rate is unsatisfactory, primarily due to the acquisition of resistance, which limits its clinical significance for treating patients with HCC. Recent evidence suggests that epidermal growth factor receptor (EGFR) activation can trigger Lenvatinib-resistance; and is considered an important therapeutic target in HCC. Curcumin, one of the most studied naturally occurring botanicals with robust anti-cancer activity, is also reported to be a potent tyrosine kinase inhibitor. In this study, we hypothesized that the anti-EGFR potential of Curcumin might help overcome Lenvatinib resistance in HCC. We established two Lenvatinib-resistant cells and discovered that a combination of Curcumin and Lenvatinib exhibited a synergistic anti-tumor efficacy in the resistant HCC cell lines. In line with previous reports, Lenvatinib-resistant cell lines revealed significant activation of the EGFR, and genomewide transcriptomic profiling analysis identified that the PI3K-AKT pathway was associated with Lenvatinib resistance. The combination treatment with Curcumin and Lenvatinib dramatically suppressed gene and protein expression of the EGFR-PI3K-AKT pathway, suggesting Curcumin overcomes Lenvatinib resistance via inhibition of EGFR. We further validated these findings in tumor spheroids derived from resistant cell lines. In conclusion, we, for the first time, report that Curcumin reverses Lenvatinib resistance in HCC, and that their combination has clinical application potential for adjunctive treatment in HCC.","null","null","2023-02-14","Cells","Cells","Vol.12","No.4","null","null","eng","null","null","research_institution","null","null","10.3390/cells12040612","2073-4409","null","null","null","null","null"
"Multiplication of tumor maximum diameter and number as a new surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage hepatocellular carcinoma.","Multiplication of tumor maximum diameter and number as a new surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage hepatocellular carcinoma.","Yuji Morine, Yu Saitou, Shin-ichiro Yamada, Hiroki Teraoku, Yuhei Waki, Takayuki Noma, Tetsuya Ikemoto, Mitsuo Shimada","Yuji Morine, Yu Saitou, Shin-ichiro Yamada, Hiroki Teraoku, Yuhei Waki, Takayuki Noma, Tetsuya Ikemoto, Mitsuo Shimada","null","Recent advances in treatment modalities have been made, limiting the indication of hepatic resection in the treatment strategy for hepatocellular carcinoma (HCC) patients. This retrospective study investigated the significance of multiplication of tumor maximum diameter and number (MDN) as a surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage HCC. A total of 49 patients with Barcelona Clinic Liver Cancer intermediate-stage HCC who underwent curative hepatic resection between 2000 and 2020 were enrolled in this study. Prognostic factors of overall survival and disease-free survival, including the product of MDN, were analyzed. Patients with MDN >12 experienced significantly worse prognosis compared with those with MDN ≤12 (p = 0.0395), and 5-year overall survival rates after hepatic resection were 60.0% and 23.4%, respectively. Furthermore, the disease-free survival rate of patients with MDN >12 was significantly worse compared with those with MDN ≤12 (p = 0.0049), and all patients with MDN >12 experienced recurrence within 3 years after hepatic resection. In the multivariate analysis, MDN >12 was identified as the only independent prognostic factor of both overall survival and disease-free survival. In addition, patients with MDN >12 suffered from uncontrollable recurrence by locoregional treatment, such as more than four intrahepatic and extrahepatic recurrences, after hepatic resection. MDN index might be a new surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage HCC, and influence clinical decision-making for individual treatment strategies.","Recent advances in treatment modalities have been made, limiting the indication of hepatic resection in the treatment strategy for hepatocellular carcinoma (HCC) patients. This retrospective study investigated the significance of multiplication of tumor maximum diameter and number (MDN) as a surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage HCC. A total of 49 patients with Barcelona Clinic Liver Cancer intermediate-stage HCC who underwent curative hepatic resection between 2000 and 2020 were enrolled in this study. Prognostic factors of overall survival and disease-free survival, including the product of MDN, were analyzed. Patients with MDN >12 experienced significantly worse prognosis compared with those with MDN ≤12 (p = 0.0395), and 5-year overall survival rates after hepatic resection were 60.0% and 23.4%, respectively. Furthermore, the disease-free survival rate of patients with MDN >12 was significantly worse compared with those with MDN ≤12 (p = 0.0049), and all patients with MDN >12 experienced recurrence within 3 years after hepatic resection. In the multivariate analysis, MDN >12 was identified as the only independent prognostic factor of both overall survival and disease-free survival. In addition, patients with MDN >12 suffered from uncontrollable recurrence by locoregional treatment, such as more than four intrahepatic and extrahepatic recurrences, after hepatic resection. MDN index might be a new surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage HCC, and influence clinical decision-making for individual treatment strategies.","null","null","2023-02-08","Hepatology Research","Hepatology Research","null","null","null","null","eng","null","null","research_institution","null","null","10.1111/hepr.13887","1386-6346","null","null","null","null","null"
"Impact of apparent diffusion coefficient on prognosis of early hepatocellular carcinoma: a case control study.","Impact of apparent diffusion coefficient on prognosis of early hepatocellular carcinoma: a case control study.","Shin-ichiro Yamada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Hiroki Teraoku, Yuhei Waki, Chiharu Nakasu, Mitsuo Shimada","Shin-ichiro Yamada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Hiroki Teraoku, Yuhei Waki, Chiharu Nakasu, Mitsuo Shimada","null","We investigated the usefulness of apparent diffusion coefficients (ADC) from diffusion-weighted images (DWI) obtained using magnetic resonance imaging (MRI) for prognosis of early hepatocellular carcinoma (HCC): Barcelona Clinic Liver Cancer (BCLC) stage 0 and A. We enrolled 102 patients who had undergone surgical resection for early HCC: BCLC stage 0 and A, and calculated their minimum ADC using DWI-MRI. We divided patients into ADC (n = 72) and ADC (n = 30) groups, and compared clinicopathological factors between the two groups. The ADC group showed higher protein induced by vitamin K absence-II (PIVKA-II) levels (p = 0.02) compared with the ADC group. In overall survival, the ADC group showed significantly worse prognosis than the ADC group (p < 0.01). Univariate analysis identified multiple tumors, infiltrative growth, high PIVKA-II, and low ADC value as prognostic factors. Multivariate analysis identified infiltrative growth and low ADC value as an independent prognostic factor. ADC values can be used to estimate the prognosis of early HCC.","We investigated the usefulness of apparent diffusion coefficients (ADC) from diffusion-weighted images (DWI) obtained using magnetic resonance imaging (MRI) for prognosis of early hepatocellular carcinoma (HCC): Barcelona Clinic Liver Cancer (BCLC) stage 0 and A. We enrolled 102 patients who had undergone surgical resection for early HCC: BCLC stage 0 and A, and calculated their minimum ADC using DWI-MRI. We divided patients into ADC (n = 72) and ADC (n = 30) groups, and compared clinicopathological factors between the two groups. The ADC group showed higher protein induced by vitamin K absence-II (PIVKA-II) levels (p = 0.02) compared with the ADC group. In overall survival, the ADC group showed significantly worse prognosis than the ADC group (p < 0.01). Univariate analysis identified multiple tumors, infiltrative growth, high PIVKA-II, and low ADC value as prognostic factors. Multivariate analysis identified infiltrative growth and low ADC value as an independent prognostic factor. ADC values can be used to estimate the prognosis of early HCC.","null","null","2023-01-11","BMC Surgery","BMC Surgery","Vol.23","No.1","6","6","eng","null","null","research_institution","null","null","10.1186/s12893-022-01892-6","1471-2482","null","null","null","null","null"
"An exosome-based liquid biopsy signature for pre-operative identification of lymph node metastasis in patients with pathological high-risk T1 colorectal cancer.","An exosome-based liquid biopsy signature for pre-operative identification of lymph node metastasis in patients with pathological high-risk T1 colorectal cancer.","Katsuki Miyazaki, Yuuma Wada, Keisuke Okuno, Tatsuro Murano, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Hiroaki Ikematsu, Yusuke Kinugasa, Mitsuo Shimada, Ajay Goel","Katsuki Miyazaki, Yuuma Wada, Keisuke Okuno, Tatsuro Murano, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Hiroaki Ikematsu, Yusuke Kinugasa, Mitsuo Shimada, Ajay Goel","null","According to current guidelines, more than 70% of patients with invasive submucosal colorectal cancer (T1 CRC) undergo a radical operation with lymph node dissection, even though only ~ 10% have lymph node metastasis (LNM). Hence, there is imperative to develop biomarkers that can help robustly identify LNM-positive patients to prevent such overtreatments. Given the emerging interest in exosomal cargo as a source for biomarker development in cancer, we examined the potential of exosomal miRNAs as LNM prediction biomarkers in T1 CRC. We analyzed 200 patients with high-risk T1 CRC from two independent cohorts, including a training (n = 58) and a validation cohort (n = 142). Cell-free and exosomal RNAs from pre-operative serum were extracted, followed by quantitative reverse-transcription polymerase chain reactions for a panel of miRNAs. A panel of four miRNAs (miR-181b, miR-193b, miR-195, and miR-411) exhibited robust ability for detecting LNM in the exosomal vs. cell-free component. We subsequently established a cell-free and exosomal combination signature, successfully validated in two independent clinical cohorts (AUC, 0.84; 95% CI 0.70-0.98). Finally, we developed a risk-stratification model by including key pathological features, which reduced the false positive rates for LNM by 76% without missing any true LNM-positive patients. Our novel exosomal miRNA-based liquid biopsy signature robustly identifies T1 CRC patients at risk of LNM in a preoperative setting. This could be clinically transformative in reducing the significant overtreatment burden of this malignancy.","According to current guidelines, more than 70% of patients with invasive submucosal colorectal cancer (T1 CRC) undergo a radical operation with lymph node dissection, even though only ~ 10% have lymph node metastasis (LNM). Hence, there is imperative to develop biomarkers that can help robustly identify LNM-positive patients to prevent such overtreatments. Given the emerging interest in exosomal cargo as a source for biomarker development in cancer, we examined the potential of exosomal miRNAs as LNM prediction biomarkers in T1 CRC. We analyzed 200 patients with high-risk T1 CRC from two independent cohorts, including a training (n = 58) and a validation cohort (n = 142). Cell-free and exosomal RNAs from pre-operative serum were extracted, followed by quantitative reverse-transcription polymerase chain reactions for a panel of miRNAs. A panel of four miRNAs (miR-181b, miR-193b, miR-195, and miR-411) exhibited robust ability for detecting LNM in the exosomal vs. cell-free component. We subsequently established a cell-free and exosomal combination signature, successfully validated in two independent clinical cohorts (AUC, 0.84; 95% CI 0.70-0.98). Finally, we developed a risk-stratification model by including key pathological features, which reduced the false positive rates for LNM by 76% without missing any true LNM-positive patients. Our novel exosomal miRNA-based liquid biopsy signature robustly identifies T1 CRC patients at risk of LNM in a preoperative setting. This could be clinically transformative in reducing the significant overtreatment burden of this malignancy.","null","null","2023-01-06","Molecular Cancer","Molecular Cancer","Vol.22","No.1","2","2","eng","null","null","research_institution","null","null","10.1186/s12943-022-01685-8","1476-4598","null","null","null","null","null"
"Fontan associated liver disease(FALD)関連肝癌に対しての腹腔鏡肝切除の1例 Fontan循環における肝離断対策","Fontan associated liver disease(FALD)関連肝癌に対しての腹腔鏡肝切除の1例 Fontan循環における肝離断対策","齋藤 裕, 森根 裕二, 山田 眞一郎, 寺奥 大貴, 池本 哲也, 島田 光生","Yu Saitou, Yuji Morine, Shin-ichiro Yamada, Hiroki Teraoku, Tetsuya Ikemoto, Mitsuo Shimada","null","30代男性,3歳時に単心房・単心室症を背景にFontan手術を受けた.Fontan associated liver disease(FALD)として肝臓内科にフォローを開始されて以来3年後にFALD関連肝癌を疑われ,腹腔鏡肝切除を施行した.肝離断中は,Central venous pressure(CVP)圧を下げるため,positive end expiratory pressureをオフし,最小限の輸液量,利尿剤併用しながらの麻酔管理を行うも,Fontan循環の影響でCVPコントロールは不良で,静脈性出血が継続したままの肝離断となった.本症例は,術後合併症なく経過したものの,FALD関連肝癌症例は,Fontan循環による高CVP下での肝離断を余儀なくされるため,そのジレンマを解決する必要があり,その対策に関して考察を加え報告する.(著者抄録)","30代男性,3歳時に単心房・単心室症を背景にFontan手術を受けた.Fontan associated liver disease(FALD)として肝臓内科にフォローを開始されて以来3年後にFALD関連肝癌を疑われ,腹腔鏡肝切除を施行した.肝離断中は,Central venous pressure(CVP)圧を下げるため,positive end expiratory pressureをオフし,最小限の輸液量,利尿剤併用しながらの麻酔管理を行うも,Fontan循環の影響でCVPコントロールは不良で,静脈性出血が継続したままの肝離断となった.本症例は,術後合併症なく経過したものの,FALD関連肝癌症例は,Fontan循環による高CVP下での肝離断を余儀なくされるため,そのジレンマを解決する必要があり,その対策に関して考察を加え報告する.(著者抄録)","null","null","2023-01","肝臓","Acta Hepatologica Japonica","Vol.64","No.1","18","25","jpn","null","null","research_institution","null","null","10.2957/kanzo.64.18","1881-3593","null","https://search.jamas.or.jp/link/ui/2023098481","null","null","null"
"Role of IDO expression in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy.","Role of IDO expression in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy.","Chie Takasu, Masaaki Nishi, Kouzou Yoshikawa, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Yuuma Wada, Toshiaki Yoshimoto, Shohei Okikawa, Shoko Yamashita, Mitsuo Shimada","Chie Takasu, Masaaki Nishi, Kouzou Yoshikawa, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Yuuma Wada, Toshiaki Yoshimoto, Shohei Okikawa, Shoko Yamashita, Mitsuo Shimada","null","The role of the immune system in locally advanced rectal cancer (LARC) following preoperative chemoradiotherapy (CRT) has been widely investigated in recent years. This study examined the prognostic significance of indoleamine-pyrrole 2,3-dioxygenase (IDO) expression in patients with LARC who received preoperative CRT. Ninety patients with LARC who underwent preoperative CRT and curative resection were enrolled. IDO and programmed death-ligand 1 (PD-L1) expression was evaluated by immunohistochemistry. Clinicopathological factors did not significantly differ between patients with positive or negative IDO expression, excluding the correlation of positive IDO expression with better tumor differentiation (p = 0.02). IDO expression was not associated with pathological response (p = 0.44), but it was associated with PD-L1 expression. The 5-year overall survival (OS) rate was significantly worse in the IDO-positive group than in the IDO-negative group (64.8% vs. 85.4%, p = 0.02). Univariate analysis identified IDO and PD-L1 expression (p = 0.02), surgical procedure (p = 0.01), final pathological stage (p = 0.003), lymph node metastasis (p < 0.001), and lymphatic invasion (p = 0.002) as significant prognostic factors for OS. Multivariate analysis revealed that IDO expression (HR: 7.10, p = 0.0006), surgical procedure (HR: 5.03, p = 0.01), lymph node metastasis (HR: 2.37, p = 0.04) and lymphatic invasion (HR: 4.97, p = 0.01) were independent prognostic indicators. Disease-free survival was not correlated with IDO or PD-L1 expression. IDO expression in patients with LARC who received preoperative CRT could be a potential prognostic indicator. IDO expression could be a useful marker for specifying individual treatment strategies in LARC.","The role of the immune system in locally advanced rectal cancer (LARC) following preoperative chemoradiotherapy (CRT) has been widely investigated in recent years. This study examined the prognostic significance of indoleamine-pyrrole 2,3-dioxygenase (IDO) expression in patients with LARC who received preoperative CRT. Ninety patients with LARC who underwent preoperative CRT and curative resection were enrolled. IDO and programmed death-ligand 1 (PD-L1) expression was evaluated by immunohistochemistry. Clinicopathological factors did not significantly differ between patients with positive or negative IDO expression, excluding the correlation of positive IDO expression with better tumor differentiation (p = 0.02). IDO expression was not associated with pathological response (p = 0.44), but it was associated with PD-L1 expression. The 5-year overall survival (OS) rate was significantly worse in the IDO-positive group than in the IDO-negative group (64.8% vs. 85.4%, p = 0.02). Univariate analysis identified IDO and PD-L1 expression (p = 0.02), surgical procedure (p = 0.01), final pathological stage (p = 0.003), lymph node metastasis (p < 0.001), and lymphatic invasion (p = 0.002) as significant prognostic factors for OS. Multivariate analysis revealed that IDO expression (HR: 7.10, p = 0.0006), surgical procedure (HR: 5.03, p = 0.01), lymph node metastasis (HR: 2.37, p = 0.04) and lymphatic invasion (HR: 4.97, p = 0.01) were independent prognostic indicators. Disease-free survival was not correlated with IDO or PD-L1 expression. IDO expression in patients with LARC who received preoperative CRT could be a potential prognostic indicator. IDO expression could be a useful marker for specifying individual treatment strategies in LARC.","null","null","2022-12-05","BMC Cancer","BMC Cancer","Vol.22","No.1","1263","1263","eng","null","null","research_institution","null","null","10.1186/s12885-022-10357-1","1471-2407","null","null","null","null","null"
"【胆膵疾患と最新テクノロジーの融合】胆膵疾患における最新の術前術中手術支援システム","【胆膵疾患と最新テクノロジーの融合】胆膵疾患における最新の術前術中手術支援システム","齋藤 裕, 森根 裕二, 山田 眞一郎, 寺奥 大貴, 池本 哲也, 島田 光生","Yu Saitou, Yuji Morine, Shin-ichiro Yamada, Hiroki Teraoku, Tetsuya Ikemoto, Mitsuo Shimada","null","胆膵手術における術前シミュレーションは,腫瘍進展範囲あるいは主要脈管解剖をいかに正確にイメージできるかが,ポイントとなる.空間認識力という意味で,extended realityは有用である.また,術中ナビゲーションに関しては,ICG蛍光法がゴールドスタンダードとなるが,人工知能を駆使した最新の知見,ならびに自験例も踏まえて,本稿で紹介する.(著者抄録)","胆膵手術における術前シミュレーションは,腫瘍進展範囲あるいは主要脈管解剖をいかに正確にイメージできるかが,ポイントとなる.空間認識力という意味で,extended realityは有用である.また,術中ナビゲーションに関しては,ICG蛍光法がゴールドスタンダードとなるが,人工知能を駆使した最新の知見,ならびに自験例も踏まえて,本稿で紹介する.(著者抄録)","null","null","2022-12","胆と膵","Journal of Biliary Tract & Pancreas","Vol.43","No.12","1631","1636","jpn","null","null","research_institution","null","null","null","0388-9408","null","https://search.jamas.or.jp/link/ui/2023075035","null","null","null"
"Visualization of the pelvic nerves using magnetic resonance imaging for rectal cancer surgery.","Visualization of the pelvic nerves using magnetic resonance imaging for rectal cancer surgery.","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto","null","This study evaluated the visualization of the pelvic nerves using magnetic resonance imaging (MRI) combined with computed tomography (CT) to synthesize three-dimensional (3D) reconstruction images of the pelvic organs. The CT and MRI scans were performed for patients with rectal cancer who underwent surgery. The out-of-phase image of LAVA-Flex was used to identify the pelvic nerves. The images of the pelvic nerves were extracted from the MRI scans, and those of the arteries and rectum and pelvis were extracted from the CT scans. Each extracted organ image was used to synthesize 3D reconstruction images. The MRI scan allowed adequate visualization of the pelvic splanchnic nerves, inferior hypogastric plexus, and obturator nerves. The comparison of 3D reconstruction images and intraoperative findings showed matched images. We visualized the pelvic nerves using MRI and synthesized 3D reconstruction images of the pelvic organs. Preoperative confirmation of the location of the pelvic organs is important to prevent unanticipated injury during rectal cancer surgery.","This study evaluated the visualization of the pelvic nerves using magnetic resonance imaging (MRI) combined with computed tomography (CT) to synthesize three-dimensional (3D) reconstruction images of the pelvic organs. The CT and MRI scans were performed for patients with rectal cancer who underwent surgery. The out-of-phase image of LAVA-Flex was used to identify the pelvic nerves. The images of the pelvic nerves were extracted from the MRI scans, and those of the arteries and rectum and pelvis were extracted from the CT scans. Each extracted organ image was used to synthesize 3D reconstruction images. The MRI scan allowed adequate visualization of the pelvic splanchnic nerves, inferior hypogastric plexus, and obturator nerves. The comparison of 3D reconstruction images and intraoperative findings showed matched images. We visualized the pelvic nerves using MRI and synthesized 3D reconstruction images of the pelvic organs. Preoperative confirmation of the location of the pelvic organs is important to prevent unanticipated injury during rectal cancer surgery.","null","null","2022-11-23","Surgical Endoscopy","Surgical Endoscopy","null","null","null","null","eng","null","null","research_institution","null","null","10.1007/s00464-022-09771-0","1432-2218","null","null","null","null","null"
"Essential amino acids as diagnostic biomarkers of hepatocellular carcinoma based on metabolic analysis.","Essential amino acids as diagnostic biomarkers of hepatocellular carcinoma based on metabolic analysis.","Yuji Morine, Tohru Utsunomiya, Hisami Yamanaka-Okumura, Yu Saitou, Shin-ichiro Yamada, Tetsuya Ikemoto, Satoru Imura, Shohei Kinoshita, Akiyoshi Hirayama, Yasuhito Tanaka, Mitsuo Shimada","Yuji Morine, Tohru Utsunomiya, Hisami Yamanaka-Okumura, Yu Saitou, Shin-ichiro Yamada, Tetsuya Ikemoto, Satoru Imura, Shohei Kinoshita, Akiyoshi Hirayama, Yasuhito Tanaka, Mitsuo Shimada","null","Metabolomics, defined as the comprehensive identification of all small metabolites in a biological sample, has the power to shed light on phenotypic changes associated with various diseases, including cancer. To discover potential metabolomic biomarkers of hepatocellular carcinoma (HCC), we investigated the metabolomes of tumor and non-tumor tissue in 20 patients with primary HCC using capillary electrophoresis-time-of-flight mass spectrometry. We also analyzed blood samples taken immediately before and 14 days after hepatectomy to identify associated changes in the serum metabolome. Marked changes were detected in the different quantity of 61 metabolites that could discriminate between HCC tumor and paired non-tumor tissue and additionally between HCC primary tumors and colorectal liver metastases. Among the 30 metabolites significantly upregulated in HCC tumors compared with non-tumor tissues, 10 were amino acids, and 7 were essential amino acids (leucine, valine, tryptophan, isoleucine, methionine, lysine, and phenylalanine). Similarly, the serum metabolomes of HCC patients before hepatectomy revealed a significant increase in 16 metabolites, including leucine, valine, and tryptophan. Our results reveal striking differences in the metabolomes of HCC tumor tissue compared with non-tumor tissue, and identify the essential amino acids leucine, valine, and tryptophan as potential metabolic biomarkers for HCC.","Metabolomics, defined as the comprehensive identification of all small metabolites in a biological sample, has the power to shed light on phenotypic changes associated with various diseases, including cancer. To discover potential metabolomic biomarkers of hepatocellular carcinoma (HCC), we investigated the metabolomes of tumor and non-tumor tissue in 20 patients with primary HCC using capillary electrophoresis-time-of-flight mass spectrometry. We also analyzed blood samples taken immediately before and 14 days after hepatectomy to identify associated changes in the serum metabolome. Marked changes were detected in the different quantity of 61 metabolites that could discriminate between HCC tumor and paired non-tumor tissue and additionally between HCC primary tumors and colorectal liver metastases. Among the 30 metabolites significantly upregulated in HCC tumors compared with non-tumor tissues, 10 were amino acids, and 7 were essential amino acids (leucine, valine, tryptophan, isoleucine, methionine, lysine, and phenylalanine). Similarly, the serum metabolomes of HCC patients before hepatectomy revealed a significant increase in 16 metabolites, including leucine, valine, and tryptophan. Our results reveal striking differences in the metabolomes of HCC tumor tissue compared with non-tumor tissue, and identify the essential amino acids leucine, valine, and tryptophan as potential metabolic biomarkers for HCC.","null","null","2022-11-22","Oncotarget","Oncotarget","Vol.13","null","1286","1298","eng","null","null","research_institution","null","null","10.18632/oncotarget.28306","1949-2553","null","null","null","null","null"
"オンライン時代は女性医師キャリア形成の追い風となる","オンライン時代は女性医師キャリア形成の追い風となる","髙須 千絵, 調 憲, 吉川 幸造, 徳永 卓哉, 中尾 寿宏, 西 正暁, 柏原 秀也, 和田 佑馬, 良元 俊昭, 島田 光生","Chie Takasu, 調 憲, Kouzou Yoshikawa, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Hideya Kashihara, Yuuma Wada, Toshiaki Yoshimoto, Mitsuo Shimada","null","新型コロナウイルス感染症の拡大が,これまで停滞していた医師の働き方改革の推進へとつながっている.その中でも,学会のオンライン化は医師の働き方に大きな変化をもたらした.学会のリモート参加は,自宅に居ながら参加でき,地方からも参加しやすく,移動時間と費用の大きな削減となる.オンデマンド配信は,時間・場所にかかわらず学ぶ機会を得られる非常に有効なツールとなる.また,学会の委員活動など,習慣的に行われていた対面での会議が,現在はほぼ遠隔で行われている.これまで時間的制約により,積極的に学会活動に手を挙げることができなかった女性医師の同分野での活躍推進が期待される.特に子育て中の女性医師にとって,オンライン化はワーク・ライフ・バランスを維持しながらキャリアを形成していく有効なツールとなりうる.この変化を逃さず女性活躍推進へとつなげるための,オンライン学会(ハイブリット形式)の継続を強く要望したい.(著者抄録)","新型コロナウイルス感染症の拡大が,これまで停滞していた医師の働き方改革の推進へとつながっている.その中でも,学会のオンライン化は医師の働き方に大きな変化をもたらした.学会のリモート参加は,自宅に居ながら参加でき,地方からも参加しやすく,移動時間と費用の大きな削減となる.オンデマンド配信は,時間・場所にかかわらず学ぶ機会を得られる非常に有効なツールとなる.また,学会の委員活動など,習慣的に行われていた対面での会議が,現在はほぼ遠隔で行われている.これまで時間的制約により,積極的に学会活動に手を挙げることができなかった女性医師の同分野での活躍推進が期待される.特に子育て中の女性医師にとって,オンライン化はワーク・ライフ・バランスを維持しながらキャリアを形成していく有効なツールとなりうる.この変化を逃さず女性活躍推進へとつなげるための,オンライン学会(ハイブリット形式)の継続を強く要望したい.(著者抄録)","null","null","2022-11-01","日本消化器外科学会雑誌","The Japanese Journal of Gastroenterological Surgery","Vol.55","No.11","729","732","jpn","null","null","research_institution","null","null","10.5833/jjgs.2022.sr005","0386-9768","null","https://search.jamas.or.jp/link/ui/2023095045","null","null","null"
"【膵・胆管合流異常-先天性胆道拡張症の最新トピックス-】膵・胆管合流異常 先天性胆道拡張症の分類と臨床的意義","【膵・胆管合流異常-先天性胆道拡張症の最新トピックス-】膵・胆管合流異常 先天性胆道拡張症の分類と臨床的意義","森根 裕二, 島田 光生","Yuji Morine, Mitsuo Shimada","null","本邦で先天性胆道拡張症は,膵・胆管合流異常を合併するものと定義されていることから,戸谷分類のI型(Ibは除く)とIV-A型が対象となり,このため拡張胆管形態の分類に加えて,膵管胆管合流形態の分類も診断する必要がある.膵管胆管合流形態については,これまで合流形態のみの分類にとどまっていたが,臨床症状をより反映する分類が日本膵・胆管合流異常研究会診断基準検討委員会によって2015年に提案され,分類に応じて術中対処法も異なってくる.また拡張胆管に関しては,戸谷分類が広く引用されており,戸谷分類に応じて術中対処法だけでなく術後合併症も異なる.しかしながら,これまでの分類は一定の臨床的意義を示すものの,発生や病態,臨床症状,治療法すべてに対応する分類は依然確立されておらず,今後の検討課題と思われる.(著者抄録)","本邦で先天性胆道拡張症は,膵・胆管合流異常を合併するものと定義されていることから,戸谷分類のI型(Ibは除く)とIV-A型が対象となり,このため拡張胆管形態の分類に加えて,膵管胆管合流形態の分類も診断する必要がある.膵管胆管合流形態については,これまで合流形態のみの分類にとどまっていたが,臨床症状をより反映する分類が日本膵・胆管合流異常研究会診断基準検討委員会によって2015年に提案され,分類に応じて術中対処法も異なってくる.また拡張胆管に関しては,戸谷分類が広く引用されており,戸谷分類に応じて術中対処法だけでなく術後合併症も異なる.しかしながら,これまでの分類は一定の臨床的意義を示すものの,発生や病態,臨床症状,治療法すべてに対応する分類は依然確立されておらず,今後の検討課題と思われる.(著者抄録)","null","null","2022-11","胆と膵","Journal of Biliary Tract & Pancreas","Vol.43","No.11","1507","1513","jpn","null","null","research_institution","null","null","null","0388-9408","null","https://search.jamas.or.jp/link/ui/2023031099","null","null","null"
"Pleomorphic type undifferentiated gastric sarcoma, report of a case.","Pleomorphic type undifferentiated gastric sarcoma, report of a case.","Yosuke Iwakawa, Masaaki Nishi, Yuuma Wada, Kouzou Yoshikawa, Chie Takasu, Mitsuo Shimada, Yasuyo Saijo, Minoru Matsumoto, Takeshi Oya, Hisanori Uehara","Yosuke Iwakawa, Masaaki Nishi, Yuuma Wada, Kouzou Yoshikawa, Chie Takasu, Mitsuo Shimada, Yasuyo Saijo, Minoru Matsumoto, Takeshi Oya, Hisanori Uehara","null","Reports on pleomorphic type of undifferentiated sarcoma (PUS) originating from the gastrointestinal tract, especially the stomach, are extremely rare. We herein report a case of pleomorphic type undifferentiated gastric sarcoma. The patient was a 67-year-old woman. The chief complaint was upper abdominal pain. Upper gastrointestinal endoscopy, ultrasonography, and contrast-enhanced computed tomography showed two submucosal tumors at the greater curvature of the fundus and the lesser curvature of the gastric angle. Endoscopic ultrasound-guided fine-needle aspiration revealed a c-kit-negative spindle cell tumor at the greater curvature of the fundus. Total gastrectomy, splenectomy, and partial resection of the diaphragm and liver were performed. One lesion had invaded the lateral segment of the liver, left diaphragm and spleen. The postoperative course was uneventful. Histopathological and immunohistochemical examinations of the resected specimen revealed PUS. Peritoneal dissemination was detected at 8 months after surgery. However, no effective therapeutic agents were adopted for chemotherapy. The patient had poor performance status due to disease progression and underwent best supportive care. The patient died 10 months after surgery. This case highlights the imaging, histological diagnosis, and treatment strategy for PUS originating from the stomach. Surgeons should be aware of PUS as a differential diagnosis in cases with submucosal tumor of the stomach.","Reports on pleomorphic type of undifferentiated sarcoma (PUS) originating from the gastrointestinal tract, especially the stomach, are extremely rare. We herein report a case of pleomorphic type undifferentiated gastric sarcoma. The patient was a 67-year-old woman. The chief complaint was upper abdominal pain. Upper gastrointestinal endoscopy, ultrasonography, and contrast-enhanced computed tomography showed two submucosal tumors at the greater curvature of the fundus and the lesser curvature of the gastric angle. Endoscopic ultrasound-guided fine-needle aspiration revealed a c-kit-negative spindle cell tumor at the greater curvature of the fundus. Total gastrectomy, splenectomy, and partial resection of the diaphragm and liver were performed. One lesion had invaded the lateral segment of the liver, left diaphragm and spleen. The postoperative course was uneventful. Histopathological and immunohistochemical examinations of the resected specimen revealed PUS. Peritoneal dissemination was detected at 8 months after surgery. However, no effective therapeutic agents were adopted for chemotherapy. The patient had poor performance status due to disease progression and underwent best supportive care. The patient died 10 months after surgery. This case highlights the imaging, histological diagnosis, and treatment strategy for PUS originating from the stomach. Surgeons should be aware of PUS as a differential diagnosis in cases with submucosal tumor of the stomach.","null","null","2022-10-26","Clinical Journal of Gastroenterology","Clinical Journal of Gastroenterology","Vol.16","No.1","20","25","eng","null","null","research_institution","null","null","10.1007/s12328-022-01729-y","1865-7265","null","null","null","null","null"
"【術前画像の読み解きガイド-的確な術式選択と解剖把握のために】胆道 先天性胆道拡張症に対する胆管切除+胆道再建 解剖把握と術中所見","【術前画像の読み解きガイド-的確な術式選択と解剖把握のために】胆道 先天性胆道拡張症に対する胆管切除+胆道再建 解剖把握と術中所見","森根 裕二, 島田 光生","Yuji Morine, Mitsuo Shimada","null","<文献概要>先天性胆道拡張症は,戸谷分類で5型に分類され,戸谷I型(Ibは除く)とIV-A型では,膵・胆管合流異常を合併する.膵液の胆道内への逆流(膵液胆道逆流現象)の防止および胆道癌発生予防の目的のため,(肝外)胆管切除+胆道再建術が標準術式として確立されているが,拡張胆管の切除が不十分であったり,肝門部胆管形成が不適切であれば,難治性胆管炎や肝内結石,遺残胆管癌などの術後合併症が危惧される.本稿では,先天性胆道拡張症における(肝外)胆管切除+胆道再建の術中・術後合併症を回避するための基本手技とともに,理解すべき術前・術中画像による解剖把握のポイントについて概説する.","<文献概要>先天性胆道拡張症は,戸谷分類で5型に分類され,戸谷I型(Ibは除く)とIV-A型では,膵・胆管合流異常を合併する.膵液の胆道内への逆流(膵液胆道逆流現象)の防止および胆道癌発生予防の目的のため,(肝外)胆管切除+胆道再建術が標準術式として確立されているが,拡張胆管の切除が不十分であったり,肝門部胆管形成が不適切であれば,難治性胆管炎や肝内結石,遺残胆管癌などの術後合併症が危惧される.本稿では,先天性胆道拡張症における(肝外)胆管切除+胆道再建の術中・術後合併症を回避するための基本手技とともに,理解すべき術前・術中画像による解剖把握のポイントについて概説する.","null","null","2022-10","臨床外科","Journal of Clinical Surgery","Vol.77","No.11","274","281","jpn","null","null","research_institution","null","null","10.11477/mf.1407213920","0386-9857","null","https://search.jamas.or.jp/link/ui/2023039815","null","null","null"
"Impact of L-type amino acid transporter 3 on the prognosis of hepatocellular carcinoma.","Impact of L-type amino acid transporter 3 on the prognosis of hepatocellular carcinoma.","Baasansvren Selenge, Shin-ichiro Yamada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Chie Takasu, Hiroki Teraoku, Mitsuo Shimada","Baasansvren Selenge, Shin-ichiro Yamada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Chie Takasu, Hiroki Teraoku, Mitsuo Shimada","null","The aim of the present study was to investigate the impact of L-type amino acid transporter 3 (LAT3) expression on the prognosis of hepatocellular carcinoma (HCC). A total of 135 patients who had undergone initial hepatic resection for HCC at Tokushima University Hospital (Tokushima, Japan) were enrolled in the present study. Immunohistochemical analysis of LAT3 and phosphorylated AKT (p-AKT) was performed using resected specimens. Clinicopathological factors, including prognosis, were compared between the LAT3-high and -low expression groups. The results demonstrated that the LAT3-high group showed significantly higher protein induced by vitamin K absence-II levels (P=0.01) compared with the LAT3-low group. The LAT3-high group showed significantly worse prognosis compared with the LAT3-low group regarding cancer-specific survival and disease-free survival (P<0.05). Multivariate analysis revealed that high LAT3 expression and multiple tumors were independent prognostic factors for cancer-specific survival. Furthermore, the rate of p-AKT-positive cases was higher in the LAT3-high group than in the LAT3-low group. Overall, these findings suggested that LAT3 expression was associated with poor prognosis of HCC and high p-AKT expression.","The aim of the present study was to investigate the impact of L-type amino acid transporter 3 (LAT3) expression on the prognosis of hepatocellular carcinoma (HCC). A total of 135 patients who had undergone initial hepatic resection for HCC at Tokushima University Hospital (Tokushima, Japan) were enrolled in the present study. Immunohistochemical analysis of LAT3 and phosphorylated AKT (p-AKT) was performed using resected specimens. Clinicopathological factors, including prognosis, were compared between the LAT3-high and -low expression groups. The results demonstrated that the LAT3-high group showed significantly higher protein induced by vitamin K absence-II levels (P=0.01) compared with the LAT3-low group. The LAT3-high group showed significantly worse prognosis compared with the LAT3-low group regarding cancer-specific survival and disease-free survival (P<0.05). Multivariate analysis revealed that high LAT3 expression and multiple tumors were independent prognostic factors for cancer-specific survival. Furthermore, the rate of p-AKT-positive cases was higher in the LAT3-high group than in the LAT3-low group. Overall, these findings suggested that LAT3 expression was associated with poor prognosis of HCC and high p-AKT expression.","null","null","2022-09-30","Oncology Letters","Oncology Letters","Vol.24","No.5","418","418","eng","null","null","research_institution","null","null","10.3892/ol.2022.13538","1792-1082","null","null","null","null","null"
"Lymph node response to neoadjuvant chemotherapy as an independent prognostic factor in gastric cancer.","Lymph node response to neoadjuvant chemotherapy as an independent prognostic factor in gastric cancer.","Yuuma Wada, Masaaki Nishi, Kouzou Yoshikawa, Chie Takasu, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Toshiaki Yoshimoto, Mitsuo Shimada","Yuuma Wada, Masaaki Nishi, Kouzou Yoshikawa, Chie Takasu, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Toshiaki Yoshimoto, Mitsuo Shimada","null","Previous studies have revealed the usefulness of neoadjuvant chemotherapy (NAC) followed by surgery for clinical stage III gastric cancer (GC). The tumor volume at the primary tumor site (PT) is sometimes difficult to measure because of the luminal structure; therefore, evaluation of the lymph node (LN) response to NAC may help to more accurately predict survival outcomes. The present study therefore evaluated the LN response to NAC for prediction of survival outcomes in patients with GC. The study involved 160 patients with clinical stage III GC who underwent NAC (n=14) and upfront surgery (n=146). PT and LN responses to NAC were evaluated, various clinicopathological factors were evaluated and Cox proportional hazard regression analyses were performed to determine survival outcomes. Overall survival (OS) and disease-free survival (DFS) were not significantly different between patients who underwent NAC and those who underwent upfront surgery (OS, P=0.71; DFS, P=0.50). However, although there were no significant differences in PT responses, patients classified as LN non-responders to NAC had a significantly worse prognosis compared with patients classified as LN responders in terms of DFS (PT, P=0.93; LN, P<0.01) and OS (PT, P=0.84; LN, P<0.01). Moreover, a higher neutrophil-lymphocyte ratio tended to be associated with poor DFS [univariate: hazard ratio (HR)=4.23, P=0.06; multivariate: HR=6.45, P=0.04]. Finally, an LN response to NAC was significantly better for prediction of recurrence (univariate, HR=7.79, 95% confidence interval=1.16-63.51, P=0.02; multivariate, HR=7.44, P=0.01). Overall, the current study revealed the clinical importance of the LN response to NAC for predicting survival outcomes in patients with GC. These findings highlight the potential clinical impact of optimizing treatment strategies to improve the selection and management of patients.","Previous studies have revealed the usefulness of neoadjuvant chemotherapy (NAC) followed by surgery for clinical stage III gastric cancer (GC). The tumor volume at the primary tumor site (PT) is sometimes difficult to measure because of the luminal structure; therefore, evaluation of the lymph node (LN) response to NAC may help to more accurately predict survival outcomes. The present study therefore evaluated the LN response to NAC for prediction of survival outcomes in patients with GC. The study involved 160 patients with clinical stage III GC who underwent NAC (n=14) and upfront surgery (n=146). PT and LN responses to NAC were evaluated, various clinicopathological factors were evaluated and Cox proportional hazard regression analyses were performed to determine survival outcomes. Overall survival (OS) and disease-free survival (DFS) were not significantly different between patients who underwent NAC and those who underwent upfront surgery (OS, P=0.71; DFS, P=0.50). However, although there were no significant differences in PT responses, patients classified as LN non-responders to NAC had a significantly worse prognosis compared with patients classified as LN responders in terms of DFS (PT, P=0.93; LN, P<0.01) and OS (PT, P=0.84; LN, P<0.01). Moreover, a higher neutrophil-lymphocyte ratio tended to be associated with poor DFS [univariate: hazard ratio (HR)=4.23, P=0.06; multivariate: HR=6.45, P=0.04]. Finally, an LN response to NAC was significantly better for prediction of recurrence (univariate, HR=7.79, 95% confidence interval=1.16-63.51, P=0.02; multivariate, HR=7.44, P=0.01). Overall, the current study revealed the clinical importance of the LN response to NAC for predicting survival outcomes in patients with GC. These findings highlight the potential clinical impact of optimizing treatment strategies to improve the selection and management of patients.","null","null","2022-09-28","Oncology Letters","Oncology Letters","Vol.24","No.5","415","415","eng","null","null","research_institution","null","null","10.3892/ol.2022.13535","1792-1082","null","null","null","null","null"
"Computed tomography texture analysis for the prediction of lateral pelvic lymph node metastasis of rectal cancer.","Computed tomography texture analysis for the prediction of lateral pelvic lymph node metastasis of rectal cancer.","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto","null","This study aimed to investigate the usefulness of computed tomography (CT) texture analysis in the diagnosis of lateral pelvic lymph node (LPLN) metastasis of rectal cancer. This was a retrospective cohort study of 45 patients with rectal cancer who underwent surgery with LPLN dissection at Tokushima University Hospital from January 2017 to December 2021. The texture analysis of the LPLNs was performed on preoperative CT images, and 18 parameters were calculated. The correlation between each parameter and pathological LPLN metastasis was evaluated. The texture parameters were compared between pathologically metastasis-positive LPLNs and metastasis-negative LPLNs. A total of 40 LPLNs were extracted from 25 patients by preoperative CT scans. No LPLNs could be identified in the remaining 19 patients. Eight of the 25 patients had pathologically positive LPLN metastasis. Extracted LPLNs were analyzed by the texture analysis. Pathologically metastasis-positive LPLNs had significantly lower mean Hounsfield unit, gray-level co-occurrence matrix (GLCM) energy, and GLCM Entropy_log2 values, and a significantly larger volume than pathologically metastasis-negative LPLNs. Multivariate analysis revealed that the independent predictive factors for LPLN metastasis were volume (a conventional parameter) (odds ratio 7.81, 95% confidence interval 1.42-43.1, p value 0.018) and GLCM Entropy_log2 (a texture parameter) (odds ratio 12.7, 95% confidence interval 1.28-126.0, p value 0.030). The combination of both parameters improved the diagnostic specificity while maintaining the sensitivity compared with each parameter alone. Combining the CT texture analysis with conventional diagnostic imaging may increase the accuracy of the diagnosis of LPLN metastasis of rectal cancer.","This study aimed to investigate the usefulness of computed tomography (CT) texture analysis in the diagnosis of lateral pelvic lymph node (LPLN) metastasis of rectal cancer. This was a retrospective cohort study of 45 patients with rectal cancer who underwent surgery with LPLN dissection at Tokushima University Hospital from January 2017 to December 2021. The texture analysis of the LPLNs was performed on preoperative CT images, and 18 parameters were calculated. The correlation between each parameter and pathological LPLN metastasis was evaluated. The texture parameters were compared between pathologically metastasis-positive LPLNs and metastasis-negative LPLNs. A total of 40 LPLNs were extracted from 25 patients by preoperative CT scans. No LPLNs could be identified in the remaining 19 patients. Eight of the 25 patients had pathologically positive LPLN metastasis. Extracted LPLNs were analyzed by the texture analysis. Pathologically metastasis-positive LPLNs had significantly lower mean Hounsfield unit, gray-level co-occurrence matrix (GLCM) energy, and GLCM Entropy_log2 values, and a significantly larger volume than pathologically metastasis-negative LPLNs. Multivariate analysis revealed that the independent predictive factors for LPLN metastasis were volume (a conventional parameter) (odds ratio 7.81, 95% confidence interval 1.42-43.1, p value 0.018) and GLCM Entropy_log2 (a texture parameter) (odds ratio 12.7, 95% confidence interval 1.28-126.0, p value 0.030). The combination of both parameters improved the diagnostic specificity while maintaining the sensitivity compared with each parameter alone. Combining the CT texture analysis with conventional diagnostic imaging may increase the accuracy of the diagnosis of LPLN metastasis of rectal cancer.","null","null","2022-09-03","World Journal of Surgical Oncology","World Journal of Surgical Oncology","Vol.20","No.1","281","281","eng","null","null","research_institution","null","null","10.1186/s12957-022-02750-8","1477-7819","null","null","null","null","null"
"腹腔鏡下切除を行った限局性盲腸壊死の1例","腹腔鏡下切除を行った限局性盲腸壊死の1例","淺野間 理仁, 吉川 幸造, 田上 誉史, 正宗 克浩, 吉田 禎宏, 島田 光生","淺野間 理仁, Kouzou Yoshikawa, 田上 誉史, 正宗 克浩, 吉田 禎宏, Mitsuo Shimada","null","症例は82歳,男性.来院前日から腹痛が出現し,血便も認めたため当院紹介となった.腹部は平坦・硬で腹部全体に圧痛を認め,反跳痛,筋性防御も伴っていた.腹部単純CTで回盲部から上行結腸に著明な壁肥厚,周囲の炎症所見,腸管外ガスを認め,また血液生化学所見では白血球数とCRPの上昇を認めた.結腸穿孔と診断し同日腹腔鏡下に緊急手術を行い,術中所見で盲腸に虚血壊死所見を認めたため腹腔鏡下回盲部切除術を行った.術後経過は問題なく術後11日目に退院となった.稀な疾患である限局性盲腸壊死に対し腹腔鏡下に切除を行った1例を経験したので,若干の文献的考察を加えて報告する.(著者抄録)","症例は82歳,男性.来院前日から腹痛が出現し,血便も認めたため当院紹介となった.腹部は平坦・硬で腹部全体に圧痛を認め,反跳痛,筋性防御も伴っていた.腹部単純CTで回盲部から上行結腸に著明な壁肥厚,周囲の炎症所見,腸管外ガスを認め,また血液生化学所見では白血球数とCRPの上昇を認めた.結腸穿孔と診断し同日腹腔鏡下に緊急手術を行い,術中所見で盲腸に虚血壊死所見を認めたため腹腔鏡下回盲部切除術を行った.術後経過は問題なく術後11日目に退院となった.稀な疾患である限局性盲腸壊死に対し腹腔鏡下に切除を行った1例を経験したので,若干の文献的考察を加えて報告する.(著者抄録)","null","null","2022-09","日本臨床外科学会雑誌","Journal of Japan Surgical Association","Vol.83","No.9","1615","1619","jpn","null","null","research_institution","null","null","10.3919/jjsa.83.1615","1345-2843","null","https://search.jamas.or.jp/link/ui/2023000867","null","null","null"
"Impact of osteopenia and neutropenia in patients with colorectal cancer treated with FOLFOXIRI: a retrospective cohort study.","Impact of osteopenia and neutropenia in patients with colorectal cancer treated with FOLFOXIRI: a retrospective cohort study.","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto, Syoko Yamashita","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto, Syoko Yamashita","null","This study was performed to assess the impact of osteopenia on chemotherapy-induced neutropenia and the prognosis for patients treated with FOLFOXIRI for colorectal cancer. In total, 77 patients who underwent FOLFOXIRI for un-resectable metastatic and advanced colorectal cancer were retrospectively evaluated. Osteopenia was evaluated by the bone mineral density, which was measured using the average pixel density of the trabecular bone in the 11th thoracic vertebra by computed tomography before the introduction of chemotherapy. The relationship between osteopenia and neutropenia was evaluated. Progression-free survival and overall survival of patients with osteopenia and patients with neutropenia were evaluated. Grade ≥ 3 neutropenia was significantly more common in patients with than without osteopenia (p = 0.002). The multivariate analysis showed that osteopenia was a significant independent predictive factor for grade ≥ 3 neutropenia (p = 0.016). There was no significant difference in progression-free survival or overall survival between patients with and without osteopenia. Patients with grade ≥ 3 neutropenia tended to have a higher progression-free survival rate than others (p = 0.059). The overall survival rate was significantly higher in patients with grade ≥ 3 neutropenia than in others (p = 0.011). Osteopenia might be a predictor of chemotherapy-induced neutropenia, and neutropenia might be a prognostic factor for progression-free survival and overall survival in patients with colorectal cancer treated with FOLFOXIRI.","This study was performed to assess the impact of osteopenia on chemotherapy-induced neutropenia and the prognosis for patients treated with FOLFOXIRI for colorectal cancer. In total, 77 patients who underwent FOLFOXIRI for un-resectable metastatic and advanced colorectal cancer were retrospectively evaluated. Osteopenia was evaluated by the bone mineral density, which was measured using the average pixel density of the trabecular bone in the 11th thoracic vertebra by computed tomography before the introduction of chemotherapy. The relationship between osteopenia and neutropenia was evaluated. Progression-free survival and overall survival of patients with osteopenia and patients with neutropenia were evaluated. Grade ≥ 3 neutropenia was significantly more common in patients with than without osteopenia (p = 0.002). The multivariate analysis showed that osteopenia was a significant independent predictive factor for grade ≥ 3 neutropenia (p = 0.016). There was no significant difference in progression-free survival or overall survival between patients with and without osteopenia. Patients with grade ≥ 3 neutropenia tended to have a higher progression-free survival rate than others (p = 0.059). The overall survival rate was significantly higher in patients with grade ≥ 3 neutropenia than in others (p = 0.011). Osteopenia might be a predictor of chemotherapy-induced neutropenia, and neutropenia might be a prognostic factor for progression-free survival and overall survival in patients with colorectal cancer treated with FOLFOXIRI.","null","null","2022-07-30","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.27","No.9","1439","1449","eng","null","null","research_institution","null","null","10.1007/s10147-022-02199-5","1437-7772","null","null","null","null","null"
"Intraoperative holographic image-guided surgery in a transanal approach for rectal cancer.","Intraoperative holographic image-guided surgery in a transanal approach for rectal cancer.","Takuya Tokunaga, Maki Sugimoto, Yu Saitou, Hideya Kashihara, Kouzou Yoshikawa, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto, Shoko Yamashita, Yosuke Iwakawa, Noriko Yokota, Mitsuo Shimada","Takuya Tokunaga, Maki Sugimoto, Yu Saitou, Hideya Kashihara, Kouzou Yoshikawa, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto, Shoko Yamashita, Yosuke Iwakawa, Noriko Yokota, Mitsuo Shimada","null","Urethral injury is one of the most important complications in transanal total mesorectal excision (TaTME) in male patients with rectal cancer. The purpose of this study was to investigate holographic image-guided surgery in TaTME. Polygon (stereolithography) files were created and exported from SYNAPSE VINCENT, and then uploaded into the Holoeyes MD system (Holoeyes Inc., Tokyo, Japan). After uploading the data, the three-dimensional image was automatically converted into a case-specific hologram. The hologram was then installed into the head mount display, HoloLens (Microsoft Corporation, Redmond, WA). The surgeons and assistants wore the HoloLens when they performed TaTME. In a Wi-Fi-enabled operating room, each surgeon, wearing a HoloLens, shared the same hologram and succeeded in adjusting the hologram by making simple hand gestures from their respective angles. The hologram contributed to better comprehension of the positional relationships between the urethra and the surrounding pelvic organs during surgery. All surgeons were able to properly determine the dissection line. This first experience suggests that intraoperative holograms contributed to reducing the risk of urethral injury and understanding transanal anatomy. Intraoperative holograms have the potential to become a new next-generation surgical support tool for use in spatial awareness and the sharing of information between surgeons.","Urethral injury is one of the most important complications in transanal total mesorectal excision (TaTME) in male patients with rectal cancer. The purpose of this study was to investigate holographic image-guided surgery in TaTME. Polygon (stereolithography) files were created and exported from SYNAPSE VINCENT, and then uploaded into the Holoeyes MD system (Holoeyes Inc., Tokyo, Japan). After uploading the data, the three-dimensional image was automatically converted into a case-specific hologram. The hologram was then installed into the head mount display, HoloLens (Microsoft Corporation, Redmond, WA). The surgeons and assistants wore the HoloLens when they performed TaTME. In a Wi-Fi-enabled operating room, each surgeon, wearing a HoloLens, shared the same hologram and succeeded in adjusting the hologram by making simple hand gestures from their respective angles. The hologram contributed to better comprehension of the positional relationships between the urethra and the surrounding pelvic organs during surgery. All surgeons were able to properly determine the dissection line. This first experience suggests that intraoperative holograms contributed to reducing the risk of urethral injury and understanding transanal anatomy. Intraoperative holograms have the potential to become a new next-generation surgical support tool for use in spatial awareness and the sharing of information between surgeons.","null","null","2022-07-15","Langenbeck's Archives of Surgery / Deutsche Gesellschaft für Chirurgie","Langenbeck's Archives of Surgery / Deutsche Gesellschaft für Chirurgie","Vol.407","No.6","2579","2584","eng","null","null","research_institution","null","null","10.1007/s00423-022-02607-4","1435-2451","null","null","null","null","null"
"Preoperative nutrition and exercise intervention in frailty patients with gastric cancer undergoing gastrectomy.","Preoperative nutrition and exercise intervention in frailty patients with gastric cancer undergoing gastrectomy.","Yuuma Wada, Masaaki Nishi, Kozo Yoshikawa, Chie Takasu, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Toshiaki Yoshimoto, Mitsuo Shimada","Yuuma Wada, Masaaki Nishi, Kozo Yoshikawa, Chie Takasu, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Toshiaki Yoshimoto, Mitsuo Shimada","null","The frailty was associated with the worse surgical outcomes and poor prognosis in several cancers. Therefore, we aimed to identify the usefulness of nutrition and exercise intervention (NEI) in frailty patients with GC. We analyzed 58 frailty patients with GC who underwent radical surgery. Among these, 15 patients were performed NEI by nutritional and rehabilitation support team. We compared the surgical outcomes between NEI and non-NEI groups with frailty patients and evaluated the nutrition and rehabilitation markers in pre- and post-NEI groups. The postoperative complication of NEI groups was 6.7% and less than that of non-NEI groups (p = 0.08). The mean postoperative hospital stay of NEI groups was 13.0 ± 1.0 days for NEI groups and significantly shorter than that of non-NEI groups (p = 0.03). The NLR was 4.3 ± 0.6 for pre-NEI and significantly improved by NEI between pre- and post-NEI (p = 0.03). We identified the clinical importance of NEI for improving the surgical outcomes in frailty patients with GC. Our findings highlight the potential clinical impact of optimizing treatment strategies to select and manage the frailty patients.","The frailty was associated with the worse surgical outcomes and poor prognosis in several cancers. Therefore, we aimed to identify the usefulness of nutrition and exercise intervention (NEI) in frailty patients with GC. We analyzed 58 frailty patients with GC who underwent radical surgery. Among these, 15 patients were performed NEI by nutritional and rehabilitation support team. We compared the surgical outcomes between NEI and non-NEI groups with frailty patients and evaluated the nutrition and rehabilitation markers in pre- and post-NEI groups. The postoperative complication of NEI groups was 6.7% and less than that of non-NEI groups (p = 0.08). The mean postoperative hospital stay of NEI groups was 13.0 ± 1.0 days for NEI groups and significantly shorter than that of non-NEI groups (p = 0.03). The NLR was 4.3 ± 0.6 for pre-NEI and significantly improved by NEI between pre- and post-NEI (p = 0.03). We identified the clinical importance of NEI for improving the surgical outcomes in frailty patients with GC. Our findings highlight the potential clinical impact of optimizing treatment strategies to select and manage the frailty patients.","null","null","2022-06-30","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.27","No.9","1421","1427","eng","null","null","research_institution","null","null","10.1007/s10147-022-02202-z","1437-7772","null","null","null","null","null"
"The TTYH3/MK5 Positive Feedback Loop regulates Tumor Progression via GSK3-β/β-catenin signaling in HCC.","The TTYH3/MK5 Positive Feedback Loop regulates Tumor Progression via GSK3-β/β-catenin signaling in HCC.","Yixiu Wang, Yuwei Xie, Bingzi Dong, Weijie Xue, Shuhai Chen, Mitsuo Shimada, Hao Zou, Yujie Feng, Kai Ma, Qian Dong, Jingyu Cao, Chengzhan Zhu","Yixiu Wang, Yuwei Xie, Bingzi Dong, Weijie Xue, Shuhai Chen, Mitsuo Shimada, Hao Zou, Yujie Feng, Kai Ma, Qian Dong, Jingyu Cao, Chengzhan Zhu","null","Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and identification of novel targets is necessary for its diagnosis and treatment. This study aimed to investigate the biological function and clinical significance of tweety homolog 3 (TTYH3) in HCC. TTYH3 overexpression promoted cell proliferation, migration, and invasion and inhibited HCCM3 and Hep3B cell apoptosis. TTYH3 promoted tumor formation and metastasis . TTYH3 upregulated calcium influx and intracellular chloride concentration, thereby promoting cellular migration and regulating epithelial-mesenchymal transition-related protein expression. The interaction between TTYH3 and MK5 was identified through co-immunoprecipitation assays and protein docking. TTYH3 promoted the expression of MK5, which then activated the GSK3β/β-catenin signaling pathway. knockdown attenuated the activation of GSK3β/β-catenin signaling by TTYH3. TTYH3 expression was regulated in a positive feedback manner. In clinical HCC samples, TTYH3 was upregulated in the HCC tissues compared to nontumor tissues. Furthermore, high TTYH3 expression was significantly correlated with poor patient survival. The CpG islands were hypomethylated in the promoter region of in HCC tissues. In conclusion, we identified TTYH3 regulates tumor development and progression via MK5/GSK3-β/β-catenin signaling in HCC and promotes itself expression in a positive feedback loop.","Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and identification of novel targets is necessary for its diagnosis and treatment. This study aimed to investigate the biological function and clinical significance of tweety homolog 3 (TTYH3) in HCC. TTYH3 overexpression promoted cell proliferation, migration, and invasion and inhibited HCCM3 and Hep3B cell apoptosis. TTYH3 promoted tumor formation and metastasis . TTYH3 upregulated calcium influx and intracellular chloride concentration, thereby promoting cellular migration and regulating epithelial-mesenchymal transition-related protein expression. The interaction between TTYH3 and MK5 was identified through co-immunoprecipitation assays and protein docking. TTYH3 promoted the expression of MK5, which then activated the GSK3β/β-catenin signaling pathway. knockdown attenuated the activation of GSK3β/β-catenin signaling by TTYH3. TTYH3 expression was regulated in a positive feedback manner. In clinical HCC samples, TTYH3 was upregulated in the HCC tissues compared to nontumor tissues. Furthermore, high TTYH3 expression was significantly correlated with poor patient survival. The CpG islands were hypomethylated in the promoter region of in HCC tissues. In conclusion, we identified TTYH3 regulates tumor development and progression via MK5/GSK3-β/β-catenin signaling in HCC and promotes itself expression in a positive feedback loop.","null","null","2022-06-21","International Journal of Biological Sciences","International Journal of Biological Sciences","Vol.18","No.10","4053","4070","eng","null","null","research_institution","null","null","10.7150/ijbs.73009","1449-2288","null","null","null","null","null"
"クリニカルカンファレンスから(第23回) 徳島大学病院の症例 高度肥満による続発性無月経に対し腹腔鏡下スリーブ状胃切除術を施行し妊娠・出産に至った一例","クリニカルカンファレンスから(第23回) 徳島大学病院の症例 高度肥満による続発性無月経に対し腹腔鏡下スリーブ状胃切除術を施行し妊娠・出産に至った一例","柏原 秀也, 吉川 幸造, 島田 光生, 松久 宗英, 吉田 守美子","Hideya Kashihara, Kouzou Yoshikawa, Mitsuo Shimada, Munehide Matsuhisa, Sumiko Yoshida","null","null","null","null","null","2022-06","肥満症治療学展望","肥満症治療学展望","Vol.9","No.3","34","35","jpn","null","null","research_institution","null","null","null","null","null","https://search.jamas.or.jp/link/ui/2022249364","null","null","null"
"A Hepatectomy Based on a Hybrid Concept of Portal Perfusion of Anterior Segment and Venous Drainage Area of Superior Right Hepatic Vein.","A Hepatectomy Based on a Hybrid Concept of Portal Perfusion of Anterior Segment and Venous Drainage Area of Superior Right Hepatic Vein.","Yu Saitou, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Shin-ichiro Yamada, Mitsuo Shimada","Yu Saitou, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Shin-ichiro Yamada, Mitsuo Shimada","null","Right hepatic vein sometimes could not be a reliable landmark between the anterior and posterior segment. The aim of this study was to clarify the portal perfusion area of the anterior segment and to propose a less invasive hepatectomy based on both the portal perfusion and the hepatic venous drainage. Three-dimensional computerized tomography images of 66 patients were constructed. A case, in which the perfusion area of the anterior segment crossed over superior right hepatic vein (SRHV), was called as SRHV-inclusion. It was defined as inclusion of more than 1 cm of the proximal site of SRHV surrounded by the portal perfusion area of the anterior segment. SRHV-inclusion was observed in 26%. The cases with large inferior right hepatic vein (IRHV) had more frequent SRHV-inclusion (47%). The elderly patient with hepatic disorder, who had hepatocellular carcinoma near the root of the SRHV, underwent a less invasive hepatectomy (anterior segment + SRHV drainage area) resulting in the preservation of the IRHV. The perfusion area of the anterior segment crossed over SRHV in one fourth of patients in the study. Our proposed less invasive hepatectomy based on a hybrid concept might be an alternative operative procedure other than right hepatectomy.","Right hepatic vein sometimes could not be a reliable landmark between the anterior and posterior segment. The aim of this study was to clarify the portal perfusion area of the anterior segment and to propose a less invasive hepatectomy based on both the portal perfusion and the hepatic venous drainage. Three-dimensional computerized tomography images of 66 patients were constructed. A case, in which the perfusion area of the anterior segment crossed over superior right hepatic vein (SRHV), was called as SRHV-inclusion. It was defined as inclusion of more than 1 cm of the proximal site of SRHV surrounded by the portal perfusion area of the anterior segment. SRHV-inclusion was observed in 26%. The cases with large inferior right hepatic vein (IRHV) had more frequent SRHV-inclusion (47%). The elderly patient with hepatic disorder, who had hepatocellular carcinoma near the root of the SRHV, underwent a less invasive hepatectomy (anterior segment + SRHV drainage area) resulting in the preservation of the IRHV. The perfusion area of the anterior segment crossed over SRHV in one fourth of patients in the study. Our proposed less invasive hepatectomy based on a hybrid concept might be an alternative operative procedure other than right hepatectomy.","null","null","2022-06","The American Surgeon","The American Surgeon","null","null","3134820984872","3134820984872","eng","null","null","research_institution","null","null","10.1177/0003134820984872","1555-9823","null","null","null","null","null"
"Polymethoxylated flavone sudachitin is a safe anticancer adjuvant that targets glycolysis in cancer-associated fibroblasts.","Polymethoxylated flavone sudachitin is a safe anticancer adjuvant that targets glycolysis in cancer-associated fibroblasts.","Shuhai Chen, Masaaki Nishi, Yuji Morine, Kouzou Yoshikawa, Takuya Tokunaga, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto, Akiko Nakamoto, Tohru Sakai, Mitsuo Shimada","Shuhai Chen, Masaaki Nishi, Yuji Morine, Kouzou Yoshikawa, Takuya Tokunaga, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto, Akiko Nakamoto, Tohru Sakai, Mitsuo Shimada","null","Sudachitin is a polymethoxylated flavone found in the peel of , a unique specialty citrus fruit in Tokushima Prefecture, Japan. Previous reports have demonstrated that sudachitin has anti-inflammatory and metabolic regulatory activities. However, to the best of our knowledge, no studies have explored whether sudachitin can act as an antitumor therapeutic agent by regulating metabolic functions in the tumor microenvironment. In the present study, cell proliferation and cytotoxicity assays were used to determine whether sudachitin inhibited the growth of liver cancer and pancreatic carcinoma, cholangiocarcinoma and colorectal cancer cells and to compare its toxicity against normal fibroblasts and induced cancer-associated fibroblasts (CAFs). Using lactate assays and reverse transcription-quantitative PCR, the effects of sudachitin on glycolysis in CAFs were investigated. The effects of CAFs on malignant tumor cells were evaluated using cell proliferation, wound healing and invasion assays. As result, sudachitin inhibited various types of tumor cells with different half-maximal inhibitory concentrations. Treatment with 50 µM sudachitin for 48 h suppressed tumor and CAFs proliferation but was not cytotoxic against normal fibroblasts. This dose also inhibited glycolysis in CAFs and, thus, diminished their pro-tumorigenic activities. Overall, the present study revealed that sudachitin has promise as a safe and widely available natural antitumor adjuvant.","Sudachitin is a polymethoxylated flavone found in the peel of , a unique specialty citrus fruit in Tokushima Prefecture, Japan. Previous reports have demonstrated that sudachitin has anti-inflammatory and metabolic regulatory activities. However, to the best of our knowledge, no studies have explored whether sudachitin can act as an antitumor therapeutic agent by regulating metabolic functions in the tumor microenvironment. In the present study, cell proliferation and cytotoxicity assays were used to determine whether sudachitin inhibited the growth of liver cancer and pancreatic carcinoma, cholangiocarcinoma and colorectal cancer cells and to compare its toxicity against normal fibroblasts and induced cancer-associated fibroblasts (CAFs). Using lactate assays and reverse transcription-quantitative PCR, the effects of sudachitin on glycolysis in CAFs were investigated. The effects of CAFs on malignant tumor cells were evaluated using cell proliferation, wound healing and invasion assays. As result, sudachitin inhibited various types of tumor cells with different half-maximal inhibitory concentrations. Treatment with 50 µM sudachitin for 48 h suppressed tumor and CAFs proliferation but was not cytotoxic against normal fibroblasts. This dose also inhibited glycolysis in CAFs and, thus, diminished their pro-tumorigenic activities. Overall, the present study revealed that sudachitin has promise as a safe and widely available natural antitumor adjuvant.","null","null","2022-05","Oncology Letters","Oncology Letters","Vol.24","No.1","236","236","eng","null","null","research_institution","null","null","10.3892/ol.2022.13356","1792-1082","null","null","null","null","null"
"Intraoperative support with three-dimensional holographic cholangiography in hepatobiliary surgery.","Intraoperative support with three-dimensional holographic cholangiography in hepatobiliary surgery.","Yu Saitou, Maki Sugimoto, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Shin-ichiro Yamada, Mitsuo Shimada","Yu Saitou, Maki Sugimoto, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Shin-ichiro Yamada, Mitsuo Shimada","null","This study was performed to investigate the potential of intraoperative three-dimensional (3D) holographic cholangiography, which provides a computer graphics model of the biliary tract, with mixed reality techniques. Two patients with intraductal papillary neoplasm of the bile duct were enrolled in the study. Intraoperative 3D cholangiography was performed in a hybrid operating room. Three-dimensional polygon data using the acquired cholangiography data were installed into a head mount display (HoloLens; Microsoft Corporation, Redmond, WA, USA). Upon completion of intraoperative 3D cholangiography, a hologram was immediately and successfully made in the operating room using the acquired cholangiography data, and several surgeons wearing the HoloLens succeeded in sharing the same hologram. Compared with usual two-dimensional cholangiography, this 3D holographic cholangiography technique contributed to more accurate reappearance of the bile ducts, especially the B1 origination site, and moving the hologram from the respective operators' angles by means of easy gesture-handling without any monitors. Intraoperative 3D holographic cholangiography might be a new next-generation operation-support tool in terms of immediacy, accurate anatomical reappearance, and ease of handling.","This study was performed to investigate the potential of intraoperative three-dimensional (3D) holographic cholangiography, which provides a computer graphics model of the biliary tract, with mixed reality techniques. Two patients with intraductal papillary neoplasm of the bile duct were enrolled in the study. Intraoperative 3D cholangiography was performed in a hybrid operating room. Three-dimensional polygon data using the acquired cholangiography data were installed into a head mount display (HoloLens; Microsoft Corporation, Redmond, WA, USA). Upon completion of intraoperative 3D cholangiography, a hologram was immediately and successfully made in the operating room using the acquired cholangiography data, and several surgeons wearing the HoloLens succeeded in sharing the same hologram. Compared with usual two-dimensional cholangiography, this 3D holographic cholangiography technique contributed to more accurate reappearance of the bile ducts, especially the B1 origination site, and moving the hologram from the respective operators' angles by means of easy gesture-handling without any monitors. Intraoperative 3D holographic cholangiography might be a new next-generation operation-support tool in terms of immediacy, accurate anatomical reappearance, and ease of handling.","null","null","2022-05-23","Langenbeck's Archives of Surgery / Deutsche Gesellschaft für Chirurgie","Langenbeck's Archives of Surgery / Deutsche Gesellschaft für Chirurgie","Vol.407","No.3","1285","1289","eng","null","null","research_institution","null","null","10.1007/s00423-021-02336-0","1435-2451","null","null","null","null","null"
"Pincer Approach to Gastrosplenic Ligament in Robotic Total Gastrectomy for Gastric Cancer.","Pincer Approach to Gastrosplenic Ligament in Robotic Total Gastrectomy for Gastric Cancer.","Masaaki Nishi, Yuuma Wada, Kouzou Yoshikawa, Chie Takasu, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Toshiaki Yoshimoto, Chiharu Nakasu, Mitsuo Shimada","Masaaki Nishi, Yuuma Wada, Kouzou Yoshikawa, Chie Takasu, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Toshiaki Yoshimoto, Chiharu Nakasu, Mitsuo Shimada","null","null","null","null","null","2022-05-16","Journal of Gastrointestinal Surgery","Journal of Gastrointestinal Surgery","Vol.26","No.7","1552","1555","eng","null","null","research_institution","null","null","10.1007/s11605-022-05356-3","1873-4626","null","null","null","null","null"
"Vascular variations encountered during laparoscopic surgery for transverse colon, splenic flexure, and descending colon cancer: a retrospective cohort study.","Vascular variations encountered during laparoscopic surgery for transverse colon, splenic flexure, and descending colon cancer: a retrospective cohort study.","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto, Syoko Yamashita, Yosuke Iwakawa","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto, Syoko Yamashita, Yosuke Iwakawa","null","Laparoscopic surgery for cancer located in the transverse colon or splenic flexure is difficult because of vascular variability in this region and adjacent vital organs such as the pancreas, spleen, and duodenum. This retrospective cohort study involved 51 patients who underwent laparoscopic surgery for colon cancer at Tokushima University Hospital from July 2015 to December 2020. Variations of the middle colic artery (MCA), left colic artery (LCA), middle colic vein (MCV), and first jejunal vein (FJV) and short-term outcomes of laparoscopic surgery in patients with each vascular variation were evaluated. Variations of the MCA, LCA, MCV, and FJV were classified into four, three, five, and three patterns, respectively. The short-term outcomes of laparoscopic surgery for transverse colon cancer in patients with MCA variations and those with FJV variations were evaluated, and no significant difference was found in the operation time, blood loss, postoperative complication rate, time from surgery to start of dietary intake, or time from surgery to discharge among the different variations. Additionally, no significant differences were found in the short-term outcomes of laparoscopic surgery for descending colon cancer in patients with LCA variations. Preoperative assessment of vascular variations may contribute to the stability of short-term outcomes of laparoscopic surgery for transverse colon, splenic flexure, and descending colon cancer.","Laparoscopic surgery for cancer located in the transverse colon or splenic flexure is difficult because of vascular variability in this region and adjacent vital organs such as the pancreas, spleen, and duodenum. This retrospective cohort study involved 51 patients who underwent laparoscopic surgery for colon cancer at Tokushima University Hospital from July 2015 to December 2020. Variations of the middle colic artery (MCA), left colic artery (LCA), middle colic vein (MCV), and first jejunal vein (FJV) and short-term outcomes of laparoscopic surgery in patients with each vascular variation were evaluated. Variations of the MCA, LCA, MCV, and FJV were classified into four, three, five, and three patterns, respectively. The short-term outcomes of laparoscopic surgery for transverse colon cancer in patients with MCA variations and those with FJV variations were evaluated, and no significant difference was found in the operation time, blood loss, postoperative complication rate, time from surgery to start of dietary intake, or time from surgery to discharge among the different variations. Additionally, no significant differences were found in the short-term outcomes of laparoscopic surgery for descending colon cancer in patients with LCA variations. Preoperative assessment of vascular variations may contribute to the stability of short-term outcomes of laparoscopic surgery for transverse colon, splenic flexure, and descending colon cancer.","null","null","2022-05-10","BMC Surgery","BMC Surgery","Vol.22","No.1","170","170","eng","null","null","research_institution","null","null","10.1186/s12893-022-01603-1","1471-2482","null","null","null","null","null"
"【1型糖尿病-診療と研究の最前線】治療研究 膵β細胞再生医療の可能性 脂肪由来幹細胞の有用性","【1型糖尿病-診療と研究の最前線】治療研究 膵β細胞再生医療の可能性 脂肪由来幹細胞の有用性","池本 哲也, 島田 光生","Tetsuya Ikemoto, Mitsuo Shimada","null","1型糖尿病治療としての再生医療はいまだ研究段階の域をでていないが,本領域は急速に発展しており,さまざまなコンセプトのもとで臨床応用も目前に迫っている.本稿では,再生医療における幹細胞の役割,分類(分化能力,その起源)を明らかにし,現在,最も臨床応用が近いと考えられる体性幹細胞(なかでも脂肪由来幹細胞)における筆者らの研究成果と,医師主導治験確立に向けた取り組みを示すとともに,すでに行われている1型糖尿病に対する幹細胞を用いた臨床研究など(幹細胞を直接投与するもの,幹細胞からβ細胞様細胞へ分化誘導させるもの)をレビューし,将来,再生医療がどのように1型糖尿病治療にコミットメントしていくかの展望を示す.(著者抄録)","1型糖尿病治療としての再生医療はいまだ研究段階の域をでていないが,本領域は急速に発展しており,さまざまなコンセプトのもとで臨床応用も目前に迫っている.本稿では,再生医療における幹細胞の役割,分類(分化能力,その起源)を明らかにし,現在,最も臨床応用が近いと考えられる体性幹細胞(なかでも脂肪由来幹細胞)における筆者らの研究成果と,医師主導治験確立に向けた取り組みを示すとともに,すでに行われている1型糖尿病に対する幹細胞を用いた臨床研究など(幹細胞を直接投与するもの,幹細胞からβ細胞様細胞へ分化誘導させるもの)をレビューし,将来,再生医療がどのように1型糖尿病治療にコミットメントしていくかの展望を示す.(著者抄録)","null","null","2022-05","医学のあゆみ","Journal of Clinical and Experimental Medicine","Vol.281","No.6","729","734","jpn","null","null","research_institution","null","null","null","0039-2359","null","https://search.jamas.or.jp/link/ui/2022156437","null","null","null"
"Four cases of gastric adenocarcinoma and proximal polyposis of the stomach treated by robotic total gastrectomy.","Four cases of gastric adenocarcinoma and proximal polyposis of the stomach treated by robotic total gastrectomy.","Yosuke Iwakawa, Kouzou Yoshikawa, Koichi Okamoto, Tetsuji Takayama, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Yuuma Wada, Toshiaki Yoshimoto, Shoko Yamashita, Mitsuo Shimada","Yosuke Iwakawa, Kouzou Yoshikawa, Koichi Okamoto, Tetsuji Takayama, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Yuuma Wada, Toshiaki Yoshimoto, Shoko Yamashita, Mitsuo Shimada","null","Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare disease and characterized by a unique point mutation in the promoter 1B region of the adenomatous polyposis coli (APC) gene. There are two aims in surgery for GAPPS; the first is prophylactic gastrectomy, and the second is excising concurrent cancer. We performed robotic total gastrectomy (RTG) for four cases of GAPPS. Case 1 was a woman in her 40 s whose sister had died from gastric cancer. Mutational analysis revealed mutation of APC exon 1B. We performed prophylactic gastrectomy. Case 2 was a woman in her 30 s who had a mutation of APC exon 1B, and preoperative biopsy revealed suspected adenocarcinoma. Case 3 was a woman in her 40 s who was diagnosed with gastric cancer with multiple polyps in the stomach and a mutation of APC exon 1B. Case 4 was a woman in her 20 s in whom biopsy revealed low-grade dysplasia of a raised lesion. She had a mutation in APC exon 1B. We performed RTG with D1 + lymphadenectomy in all patients, and there were no intraoperative complications. Patients with GAPPS are mainly followed regularly with repeat biopsy, and tumors are detected in an early stage. As the safety of robotic surgery for the early gastric cancer is reported, RTG is an option for these patients. This is the first report of RTG for GAPPS patients.","Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare disease and characterized by a unique point mutation in the promoter 1B region of the adenomatous polyposis coli (APC) gene. There are two aims in surgery for GAPPS; the first is prophylactic gastrectomy, and the second is excising concurrent cancer. We performed robotic total gastrectomy (RTG) for four cases of GAPPS. Case 1 was a woman in her 40 s whose sister had died from gastric cancer. Mutational analysis revealed mutation of APC exon 1B. We performed prophylactic gastrectomy. Case 2 was a woman in her 30 s who had a mutation of APC exon 1B, and preoperative biopsy revealed suspected adenocarcinoma. Case 3 was a woman in her 40 s who was diagnosed with gastric cancer with multiple polyps in the stomach and a mutation of APC exon 1B. Case 4 was a woman in her 20 s in whom biopsy revealed low-grade dysplasia of a raised lesion. She had a mutation in APC exon 1B. We performed RTG with D1 + lymphadenectomy in all patients, and there were no intraoperative complications. Patients with GAPPS are mainly followed regularly with repeat biopsy, and tumors are detected in an early stage. As the safety of robotic surgery for the early gastric cancer is reported, RTG is an option for these patients. This is the first report of RTG for GAPPS patients.","null","null","2022-04-18","Surgical Case Reports","Surgical Case Reports","Vol.8","No.1","70","70","eng","null","null","research_institution","null","null","10.1186/s40792-022-01425-6","2198-7793","null","null","null","null","null"
"Blue light irradiation inhibits the growth of colon cancer and activation of cancer-associated fibroblasts.","Blue light irradiation inhibits the growth of colon cancer and activation of cancer-associated fibroblasts.","Toshiaki Yoshimoto, Mitsuo Shimada, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Yuuma Wada, Shohei Okikawa, Kouzou Yoshikawa","Toshiaki Yoshimoto, Mitsuo Shimada, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Yuuma Wada, Shohei Okikawa, Kouzou Yoshikawa","null","Irradiation with a specific wavelength of light using light-emitting diodes (LEDs) has various effects on cells and organisms. Recently, the antitumor effects of visible blue light on tumor cells were reported; however, the mechanism and effects on the tumor microenvironment remain unclear. Human colon cancer cells (HCT-116) were injected into the rectal wall of nude mice. Tumors were irradiated with a 465-nm LED light at 30 mW/cm for 30 min. Tumor volumes and the expression levels of opsin 3 (Opn3), autophagy-related factors, cancer-associated fibroblast (CAF) markers, and programmed cell death 1-ligand (PD-L1) were measured. Additionally, human intestinal fibroblasts were cultured in HCT116-conditioned medium (CM) to prepare CAFs. CAFs were divided into an LED group and a control group, and the effect of the LED light on CAF activation in colon cancer cells was examined. Irradiation with blue LED light suppressed tumor growth; Opn3 expression was localized to the cell membrane in the LED group. Irradiated tumors exhibited increased autophagy-related gene expression. Furthermore, in the LED group, TGF-β and α-SMA expression levels in the fibroblasts were decreased. Regarding CAFs, α-SMA and IL-6 expression levels were decreased in the LED group. HCT-116 cells cultured in CAF-CM with LED irradiation showed no enhanced migration or invasion. In the HCT-116 cells cultured in CM of CAFs irradiated with LED, the relative increase in PD-L1 expression was lower than that noted in the CAF-CM without LED irradiation. Blue LED light may have a direct antitumor effect on colon cancer and also an inhibitory effect on CAFs.","Irradiation with a specific wavelength of light using light-emitting diodes (LEDs) has various effects on cells and organisms. Recently, the antitumor effects of visible blue light on tumor cells were reported; however, the mechanism and effects on the tumor microenvironment remain unclear. Human colon cancer cells (HCT-116) were injected into the rectal wall of nude mice. Tumors were irradiated with a 465-nm LED light at 30 mW/cm for 30 min. Tumor volumes and the expression levels of opsin 3 (Opn3), autophagy-related factors, cancer-associated fibroblast (CAF) markers, and programmed cell death 1-ligand (PD-L1) were measured. Additionally, human intestinal fibroblasts were cultured in HCT116-conditioned medium (CM) to prepare CAFs. CAFs were divided into an LED group and a control group, and the effect of the LED light on CAF activation in colon cancer cells was examined. Irradiation with blue LED light suppressed tumor growth; Opn3 expression was localized to the cell membrane in the LED group. Irradiated tumors exhibited increased autophagy-related gene expression. Furthermore, in the LED group, TGF-β and α-SMA expression levels in the fibroblasts were decreased. Regarding CAFs, α-SMA and IL-6 expression levels were decreased in the LED group. HCT-116 cells cultured in CAF-CM with LED irradiation showed no enhanced migration or invasion. In the HCT-116 cells cultured in CM of CAFs irradiated with LED, the relative increase in PD-L1 expression was lower than that noted in the CAF-CM without LED irradiation. Blue LED light may have a direct antitumor effect on colon cancer and also an inhibitory effect on CAFs.","null","null","2022-04-13","Oncology Reports","Oncology Reports","Vol.47","No.5","null","null","eng","null","null","research_institution","null","null","10.3892/or.2022.8315","1791-2431","null","null","null","null","null"
"Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice.","Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice.","Kazunori Tokuda, Tetsuya Ikemoto, Shoko Yamashita, Katsuki Miyazaki, Shohei Okikawa, Shin-ichiro Yamada, Yu Saitou, Yuji Morine, Mitsuo Shimada","Kazunori Tokuda, Tetsuya Ikemoto, Shoko Yamashita, Katsuki Miyazaki, Shohei Okikawa, Shin-ichiro Yamada, Yu Saitou, Yuji Morine, Mitsuo Shimada","null","Insulin-producing cells (IPCs) generated by our established protocol have reached the non-clinical 'proof of concept' stage. Our strategy for their clinical application is the autotransplantation of IPCs into patients with type 1 diabetes mellitus (T1DM). In this context, the autoimmunity that characterized T1DM is important, rather than allorejection. We aimed to determine how these IPCs respond to T1DM autoimmunity. IPCs were generated from the subcutaneous fat tissue of non-obese diabetic (NOD) mice using our protocol. IPCs derived from NOD mice were transplanted under the kidney capsules of NOD mice at the onset of diabetes and the subsequent changes in blood glucose concentration were characterized. Blood glucose decreased within 30 days of transplantation, but increased again after 40-60 days in three of four recipient NOD mice. In tissue samples, the numbers of CD4 and CD8 T cells were significantly higher 60 days after transplantation than 30 days after transplantation. In conclusion, IPCs significantly ameliorate the diabetes of mice in the short term, but are damaged by autoimmunity in the longer term, as evidenced by local T cells accumulation. This study provides new insights into potential stem cell therapies for T1DM.","Insulin-producing cells (IPCs) generated by our established protocol have reached the non-clinical 'proof of concept' stage. Our strategy for their clinical application is the autotransplantation of IPCs into patients with type 1 diabetes mellitus (T1DM). In this context, the autoimmunity that characterized T1DM is important, rather than allorejection. We aimed to determine how these IPCs respond to T1DM autoimmunity. IPCs were generated from the subcutaneous fat tissue of non-obese diabetic (NOD) mice using our protocol. IPCs derived from NOD mice were transplanted under the kidney capsules of NOD mice at the onset of diabetes and the subsequent changes in blood glucose concentration were characterized. Blood glucose decreased within 30 days of transplantation, but increased again after 40-60 days in three of four recipient NOD mice. In tissue samples, the numbers of CD4 and CD8 T cells were significantly higher 60 days after transplantation than 30 days after transplantation. In conclusion, IPCs significantly ameliorate the diabetes of mice in the short term, but are damaged by autoimmunity in the longer term, as evidenced by local T cells accumulation. This study provides new insights into potential stem cell therapies for T1DM.","null","null","2022-04-07","Scientific Reports","Scientific Reports","Vol.12","No.1","5852","5852","eng","null","null","research_institution","null","null","10.1038/s41598-022-09838-x","2045-2322","null","null","null","null","null"
"Risk factors for postoperative ileus after diverting loop ileostomy closure.","Risk factors for postoperative ileus after diverting loop ileostomy closure.","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto, Syoko Yamashita, Yosuke Iwakawa","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto, Syoko Yamashita, Yosuke Iwakawa","null","Postoperative ileus is one of the most common complications after diverting loop ileostomy closure. Some reports have investigated the risk factors for postoperative complications or ileus after ileostomy closure; however, these studies did not evaluate the index surgery sufficiently. In this study, we evaluated the risk factors, including the details of the index surgery, for ileus after diverting ileostomy closure. This was a retrospective study of patients who underwent ileostomy closure following index surgery for rectal cancer. Patients who developed postoperative ileus [POI (+)] and patients who did not [POI (-)] after ileostomy closure were compared. Sixty-eight patients were evaluated and were divided into two groups: POI (+) (n = 11) and POI (-) (n = 57), and the groups were compared. There were no significant differences in the details of the index surgery, operative procedure, transanal total mesorectal excision, lateral lymph node dissection, operating time, or blood loss. The incidence of Clavien-Dindo grade ≥ III complications and adjuvant chemotherapy after index surgery were significantly higher in the POI (+) group. The incidence of Clavien-Dindo grade ≥ III complications and adjuvant chemotherapy after index surgery may increase the risk of postoperative ileus after ileostomy closure.","Postoperative ileus is one of the most common complications after diverting loop ileostomy closure. Some reports have investigated the risk factors for postoperative complications or ileus after ileostomy closure; however, these studies did not evaluate the index surgery sufficiently. In this study, we evaluated the risk factors, including the details of the index surgery, for ileus after diverting ileostomy closure. This was a retrospective study of patients who underwent ileostomy closure following index surgery for rectal cancer. Patients who developed postoperative ileus [POI (+)] and patients who did not [POI (-)] after ileostomy closure were compared. Sixty-eight patients were evaluated and were divided into two groups: POI (+) (n = 11) and POI (-) (n = 57), and the groups were compared. There were no significant differences in the details of the index surgery, operative procedure, transanal total mesorectal excision, lateral lymph node dissection, operating time, or blood loss. The incidence of Clavien-Dindo grade ≥ III complications and adjuvant chemotherapy after index surgery were significantly higher in the POI (+) group. The incidence of Clavien-Dindo grade ≥ III complications and adjuvant chemotherapy after index surgery may increase the risk of postoperative ileus after ileostomy closure.","null","null","2022-04-07","BMC Surgery","BMC Surgery","Vol.22","No.1","131","131","eng","null","null","research_institution","null","null","10.1186/s12893-022-01583-2","1471-2482","null","null","null","null","null"
"【大腸外科医のための骨盤解剖学】直腸癌手術に必要な画像シミュレーション","【大腸外科医のための骨盤解剖学】直腸癌手術に必要な画像シミュレーション","徳永 卓哉, 柏原 秀也, 島田 光生","Takuya Tokunaga, Hideya Kashihara, Mitsuo Shimada","null","null","null","null","null","2022-04","手術","Operation","Vol.76","No.5","709","714","jpn","null","null","research_institution","null","null","10.18888/op.0000002751","0037-4423","null","https://search.jamas.or.jp/link/ui/2022220861","null","null","null"
"【外科代謝栄養と東洋医学:漢方による周術期管理へのサポート】大建中湯による周術期管理のサポート","【外科代謝栄養と東洋医学:漢方による周術期管理へのサポート】大建中湯による周術期管理のサポート","西 正暁, 島田 光生, 森根 裕二, 吉川 幸造, 徳永 卓哉, 中尾 寿宏, 柏原 秀也, 髙須 千絵, 良元 俊昭, 和田 佑馬","Masaaki Nishi, Mitsuo Shimada, Yuji Morine, Kouzou Yoshikawa, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Chie Takasu, Toshiaki Yoshimoto, Yuuma Wada","null","近年では漢方の分子生物学的な作用機序の解明が進み,臨床においても質の高いランダム化比較試験により漢方の有用性が明らかになってきた.現在では大建中湯を含む多くの漢方製剤が広く臨床の現場で用いられている.大建中湯は乾姜,人参,山椒の3つの生薬に膠飴を加えた漢方で,外科領域においては癒着性イレウスや麻痺性イレウス,過敏性腸症候群,クローン病などを適応とし,消化管運動促進作用,腸管血流増加作用,抗炎症作用などが報告されている.近年では,食道・胃・大腸・肝臓・膵臓・肝移植外科それぞれの領域でランダム化試験が実施され,大建中湯の周術期管理における有効性が証明されている.また分子生物学的なメカニズムについても解明がすすみ,現在,大建中湯は消化管外科・肝胆膵外科の分野を問わず消化器外科全般における周術期管理のkey drugとして位置付けられている.本稿では消化器外科領域における大建中湯による周術期管理のサポートについて概説する.(著者抄録)","近年では漢方の分子生物学的な作用機序の解明が進み,臨床においても質の高いランダム化比較試験により漢方の有用性が明らかになってきた.現在では大建中湯を含む多くの漢方製剤が広く臨床の現場で用いられている.大建中湯は乾姜,人参,山椒の3つの生薬に膠飴を加えた漢方で,外科領域においては癒着性イレウスや麻痺性イレウス,過敏性腸症候群,クローン病などを適応とし,消化管運動促進作用,腸管血流増加作用,抗炎症作用などが報告されている.近年では,食道・胃・大腸・肝臓・膵臓・肝移植外科それぞれの領域でランダム化試験が実施され,大建中湯の周術期管理における有効性が証明されている.また分子生物学的なメカニズムについても解明がすすみ,現在,大建中湯は消化管外科・肝胆膵外科の分野を問わず消化器外科全般における周術期管理のkey drugとして位置付けられている.本稿では消化器外科領域における大建中湯による周術期管理のサポートについて概説する.(著者抄録)","null","null","2022-04","外科と代謝·栄養","The Japanese Journal of Surgical Metabolism and Nutrition","Vol.56","No.2","59","61","jpn","null","null","research_institution","null","null","10.11638/jssmn.56.2_59","0389-5564","null","https://search.jamas.or.jp/link/ui/2022182366","null","null","null"
"The correlation of immunoscore and frailty in colorectal cancer.","The correlation of immunoscore and frailty in colorectal cancer.","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto, Shoko Yamashita, Yosuke Iwakawa","Toshihiro Nakao, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Yuuma Wada, Toshiaki Yoshimoto, Shoko Yamashita, Yosuke Iwakawa","null","The Immunoscore is a useful prognostic and predictive factor for colorectal cancer. Frailty predicts overall and recurrence-free survival following resection of colorectal cancer, and the immunosuppressive state of frailty might affect tumor progression. This study investigated the relationship between the Immunoscore and frailty in colorectal cancer. This retrospective study included patients who underwent radical surgery for stage II and III colorectal cancer (n = 108). Patients were divided into frail (n = 11) and non-frail (n = 97) groups, and low (IS0-2) (n = 70) and high (IS3-4) Immunoscore groups (n = 38), for comparison. American Society of Anesthesiologists physical status was higher, tumor diameter was larger, number of well-differentiated tumors was higher, albumin was lower, 5-year overall survival (OS) was lower (frail group: 50.0%, non-frail group: 90.5%, p < 0.001) and 5-year disease-free survival (DFS) was lower (frail group: 36.4%, non-frail group: 75.2%, p = 0.024) in the frail than in the non-frail group. Left colon cancer was more, 5-year OS was lower (IS0-2 group: 82.0%, IS3-4 group: 96.7%, p = 0.040) and 5-year DFS was lower (IS0-2 group: 66.3%, IS3-4 group: 83.3%, p = 0.043) in the IS0-2 than in the IS3-4 group. The Immunoscore was lower in the frail than in the non-frail group. Immunoscore and frailty are prognostic and predictive factors in colorectal cancer, and they are correlated with each other. The immunosuppressive state from frailty might affect this correlation.","The Immunoscore is a useful prognostic and predictive factor for colorectal cancer. Frailty predicts overall and recurrence-free survival following resection of colorectal cancer, and the immunosuppressive state of frailty might affect tumor progression. This study investigated the relationship between the Immunoscore and frailty in colorectal cancer. This retrospective study included patients who underwent radical surgery for stage II and III colorectal cancer (n = 108). Patients were divided into frail (n = 11) and non-frail (n = 97) groups, and low (IS0-2) (n = 70) and high (IS3-4) Immunoscore groups (n = 38), for comparison. American Society of Anesthesiologists physical status was higher, tumor diameter was larger, number of well-differentiated tumors was higher, albumin was lower, 5-year overall survival (OS) was lower (frail group: 50.0%, non-frail group: 90.5%, p < 0.001) and 5-year disease-free survival (DFS) was lower (frail group: 36.4%, non-frail group: 75.2%, p = 0.024) in the frail than in the non-frail group. Left colon cancer was more, 5-year OS was lower (IS0-2 group: 82.0%, IS3-4 group: 96.7%, p = 0.040) and 5-year DFS was lower (IS0-2 group: 66.3%, IS3-4 group: 83.3%, p = 0.043) in the IS0-2 than in the IS3-4 group. The Immunoscore was lower in the frail than in the non-frail group. Immunoscore and frailty are prognostic and predictive factors in colorectal cancer, and they are correlated with each other. The immunosuppressive state from frailty might affect this correlation.","null","null","2022-03-30","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.27","No.3","528","537","eng","null","null","research_institution","null","null","10.1007/s10147-021-02096-3","1437-7772","null","null","null","null","null"
"Inhibition of the VEGF signaling pathway attenuates tumor-associated macrophage activity in liver cancer.","Inhibition of the VEGF signaling pathway attenuates tumor-associated macrophage activity in liver cancer.","Shohei Okikawa, Yuji Morine, Yu Saitou, Shin-ichiro Yamada, Kazunori Tokuda, Hiroki Teraoku, Katsuki Miyazaki, Shoko Yamashita, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada","Shohei Okikawa, Yuji Morine, Yu Saitou, Shin-ichiro Yamada, Kazunori Tokuda, Hiroki Teraoku, Katsuki Miyazaki, Shoko Yamashita, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada","null","Tumor-associated macrophage (TAMs) are paramount for tumor progression and immune tolerance in the tumor microenvironment of various types of cancer, including liver cancer. The aim of the present study was to investigate the effect of vascular endothelial growth factor (VEGF) inhibition on TAM polarization and function during their interactions with macrophages and liver cancer cells. TAMs were induced by culturing M0 macrophages with cancer cell-conditioned medium. TAMs cultured with cancer cell-conditioned medium and vascular endothelial growth factor (VEGF) inhibitor were defined as modified TAMs, and the expression levels of TAM-associated markers and VEGF receptor 2 were evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of TAMs and modified TAMs on cancer cell proliferation and migration were investigated using conditioned medium. Programmed death-ligand 1 (PD-L1) mRNA expression in modified TAMs and cancer cells cultured in modified TAM-conditioned medium (TAM-CM) for 48 h was examined using RT-qPCR. In order to investigate signaling pathways in macrophages, western blot analysis was performed. CD163 and CD206 and M2 macrophage marker expression was upregulated in TAMs and modified TAMs. Modified TAM-CM exhibited a decreased ability to promote cancer cell proliferation and migration in comparison with the use of TAM-CM. The VEGF concentration was significantly higher in the TAMs than in M0 macrophages; however, the modified TAMs displayed a significantly lower VEGF secretion than TAMs. PD-L1 expression was decreased in modified TAMs as compared with TAMs. Western blot analysis revealed that the Akt/mTOR signaling pathway was significantly suppressed in the modified TAMs compared with TAMs. It was observed that TAMs cultured in a VEGF-depleted environment displayed lower secretion levels of cytokines involved in tumor progression and a decreased immune tolerance-inducing ability. On the whole, the results of the present study suggested that VEGF inhibition in TAMs may be a potential therapeutic target for liver cancer.","Tumor-associated macrophage (TAMs) are paramount for tumor progression and immune tolerance in the tumor microenvironment of various types of cancer, including liver cancer. The aim of the present study was to investigate the effect of vascular endothelial growth factor (VEGF) inhibition on TAM polarization and function during their interactions with macrophages and liver cancer cells. TAMs were induced by culturing M0 macrophages with cancer cell-conditioned medium. TAMs cultured with cancer cell-conditioned medium and vascular endothelial growth factor (VEGF) inhibitor were defined as modified TAMs, and the expression levels of TAM-associated markers and VEGF receptor 2 were evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of TAMs and modified TAMs on cancer cell proliferation and migration were investigated using conditioned medium. Programmed death-ligand 1 (PD-L1) mRNA expression in modified TAMs and cancer cells cultured in modified TAM-conditioned medium (TAM-CM) for 48 h was examined using RT-qPCR. In order to investigate signaling pathways in macrophages, western blot analysis was performed. CD163 and CD206 and M2 macrophage marker expression was upregulated in TAMs and modified TAMs. Modified TAM-CM exhibited a decreased ability to promote cancer cell proliferation and migration in comparison with the use of TAM-CM. The VEGF concentration was significantly higher in the TAMs than in M0 macrophages; however, the modified TAMs displayed a significantly lower VEGF secretion than TAMs. PD-L1 expression was decreased in modified TAMs as compared with TAMs. Western blot analysis revealed that the Akt/mTOR signaling pathway was significantly suppressed in the modified TAMs compared with TAMs. It was observed that TAMs cultured in a VEGF-depleted environment displayed lower secretion levels of cytokines involved in tumor progression and a decreased immune tolerance-inducing ability. On the whole, the results of the present study suggested that VEGF inhibition in TAMs may be a potential therapeutic target for liver cancer.","null","null","2022-02-16","Oncology Reports","Oncology Reports","Vol.47","No.4","null","null","eng","null","null","research_institution","null","null","10.3892/or.2022.8282","1791-2431","null","null","null","null","null"
"Risk of carcinogenesis in the biliary epithelium of children with congenital biliary dilatation through epigenetic and genetic regulation.","Risk of carcinogenesis in the biliary epithelium of children with congenital biliary dilatation through epigenetic and genetic regulation.","Hiroki Mori, Kazunori Masahata, Satoshi Umeda, Yuji Morine, Hiroki Ishibashi, Noriaki Usui, Mitsuo Shimada","Hiroki Mori, Kazunori Masahata, Satoshi Umeda, Yuji Morine, Hiroki Ishibashi, Noriaki Usui, Mitsuo Shimada","null","Congenital biliary dilatation (CBD), defined as pancreaticobiliary maljunction (PBM) with biliary dilatation, is a high risk factor for biliary tract cancer (BTC). KRAS and p53 mutations reportedly affect this process, but the mechanisms are unclear, as is the likelihood of BTC later in life in children with CBD. We investigated potential carcinogenetic pathways in children with CBD compared with adults. The subjects of this study were nine children with CBD and 13 adults with PBM (10 dilated, 3 non-dilated) without BTC who underwent extrahepatic bile duct resections, as well as four control patients who underwent pancreaticoduodenectomy for non-biliary cancer. We evaluated expressions of Ki-67, KRAS, p53, histone deacetylase (HDAC) and activation-induced cytidine deaminase (AID) in the biliary tract epithelium immunohistochemically. The Ki-67 labeling index (LI) and expressions of KRAS, p53, HDAC, and AID in the gallbladder epithelium were significantly higher or tended to be higher in both the children with CBD and the adults with PBM than in the controls. BTC may develop later in children with CBD and in adults with PBM, via HDAC and AID expression and through epigenetic and genetic regulation.","Congenital biliary dilatation (CBD), defined as pancreaticobiliary maljunction (PBM) with biliary dilatation, is a high risk factor for biliary tract cancer (BTC). KRAS and p53 mutations reportedly affect this process, but the mechanisms are unclear, as is the likelihood of BTC later in life in children with CBD. We investigated potential carcinogenetic pathways in children with CBD compared with adults. The subjects of this study were nine children with CBD and 13 adults with PBM (10 dilated, 3 non-dilated) without BTC who underwent extrahepatic bile duct resections, as well as four control patients who underwent pancreaticoduodenectomy for non-biliary cancer. We evaluated expressions of Ki-67, KRAS, p53, histone deacetylase (HDAC) and activation-induced cytidine deaminase (AID) in the biliary tract epithelium immunohistochemically. The Ki-67 labeling index (LI) and expressions of KRAS, p53, HDAC, and AID in the gallbladder epithelium were significantly higher or tended to be higher in both the children with CBD and the adults with PBM than in the controls. BTC may develop later in children with CBD and in adults with PBM, via HDAC and AID expression and through epigenetic and genetic regulation.","null","null","2022-02-16","Surgery Today","Surgery Today","Vol.52","No.2","215","223","eng","null","null","research_institution","null","null","10.1007/s00595-021-02325-2","1436-2813","null","null","null","null","null"
"Droplet digital PCR assay provides intrahepatic HBV cccDNA quantification tool for clinical application.","Droplet digital PCR assay provides intrahepatic HBV cccDNA quantification tool for clinical application.","Sanae Hayashi, Masanori Isogawa, Keigo Kawashima, Kyoko Ito, Natthaya Chuaypen, Yuji Morine, Mitsuo Shimada, Nobuyo Higashi-Kuwata, Takehisa Watanabe, Pisit Tangkijvanich, Hiroaki Mitsuya, Yasuhito Tanaka","Sanae Hayashi, Masanori Isogawa, Keigo Kawashima, Kyoko Ito, Natthaya Chuaypen, Yuji Morine, Mitsuo Shimada, Nobuyo Higashi-Kuwata, Takehisa Watanabe, Pisit Tangkijvanich, Hiroaki Mitsuya, Yasuhito Tanaka","null","The persistence of covalently closed circular DNA (cccDNA) poses a major obstacle to curing chronic hepatitis B (CHB). Here, we used droplet digital PCR (ddPCR) for cccDNA quantitation. The cccDNA-specific ddPCR showed high accuracy with the dynamic range of cccDNA detection from 10 to 10 copies/assay. The ddPCR had higher sensitivity, specificity and precisely than qPCR. The results of ddPCR correlated closely with serum HB core-related antigen and HB surface antigen (HBsAg) in 24 HBV-infected human-liver-chimeric mice (PXB-mice). We demonstrated that in 2 PXB-mice after entecavir treatment, the total cccDNA content did not change during liver repopulation, although the cccDNA content per hepatocyte was reduced after the treatment. In the 6 patients with HBV-related hepatocellular carcinoma, ddPCR detected cccDNA in both tumor and non-tumor tissues. In 13 HBeAg-negative CHB patients with pegylated interferon alpha-2a, cccDNA contents from paired biopsies were more significantly reduced in virological response (VR) than in non-VR at week 48 (p = 0.0051). Interestingly, cccDNA levels were the lowest in VR with HBsAg clearance but remained detectable after the treatment. Collectively, ddPCR revealed that cccDNA content is stable during hepatocyte proliferation and persists at quantifiable levels, even after serum HBsAg clearance.","The persistence of covalently closed circular DNA (cccDNA) poses a major obstacle to curing chronic hepatitis B (CHB). Here, we used droplet digital PCR (ddPCR) for cccDNA quantitation. The cccDNA-specific ddPCR showed high accuracy with the dynamic range of cccDNA detection from 10 to 10 copies/assay. The ddPCR had higher sensitivity, specificity and precisely than qPCR. The results of ddPCR correlated closely with serum HB core-related antigen and HB surface antigen (HBsAg) in 24 HBV-infected human-liver-chimeric mice (PXB-mice). We demonstrated that in 2 PXB-mice after entecavir treatment, the total cccDNA content did not change during liver repopulation, although the cccDNA content per hepatocyte was reduced after the treatment. In the 6 patients with HBV-related hepatocellular carcinoma, ddPCR detected cccDNA in both tumor and non-tumor tissues. In 13 HBeAg-negative CHB patients with pegylated interferon alpha-2a, cccDNA contents from paired biopsies were more significantly reduced in virological response (VR) than in non-VR at week 48 (p = 0.0051). Interestingly, cccDNA levels were the lowest in VR with HBsAg clearance but remained detectable after the treatment. Collectively, ddPCR revealed that cccDNA content is stable during hepatocyte proliferation and persists at quantifiable levels, even after serum HBsAg clearance.","null","null","2022-02-08","Scientific Reports","Scientific Reports","Vol.12","No.1","2133","2133","eng","null","null","research_institution","null","null","10.1038/s41598-022-05882-9","2045-2322","null","null","null","null","null"
"A case of Gross E esophageal atresia discovered following a unique clinical course.","A case of Gross E esophageal atresia discovered following a unique clinical course.","Noriko Yokota, Hiroki Ishibashi, Kenichi Suga, Hiroki Mori, Akiko Kitamura, Ryuji Nakagawa, Mitsuo Shimada","Noriko Yokota, Hiroki Ishibashi, Kenichi Suga, Hiroki Mori, Akiko Kitamura, Ryuji Nakagawa, Mitsuo Shimada","null","The patient was a 15 months-old boy who had been diagnosed CHARGE syndrome, which is a multiple congenital anomaly syndrome caused by mutations in the CHD7 gene. Mechanical ventilation management was initiated 2 hours after birth for dysphagia and respiratory failure, and tracheotomy was performed 3 months after birth for dysphagia and failed extubation. He was repeatedly hospitalized due to pneuomoniae. Approximately 1 year after birth, the boy had two consecutive episodes of sudden ventilatory insufficiency while replacing the tracheotomy cannula. A bronchoscopic examination under general anesthesia revealed a tracheoesophageal fistula directly below the tracheostomy. The patient was diagnosed with Gross E esophageal atresia, and we speculated that the cannula migrated to the esophagus via the fistula during tracheostomy cannula replacement. Gross E esophageal atresia is a rare disease. Its diagnosis is often delayed, and it is discovered by recurrent pneumonia in many cases. A tracheoesophageal fistula may also be found in children with deformities of the respiratory system. Furthermore, tracheoesophageal fistulae are often found in the neck. Therefore, when sudden ventilatory insufficiency occurs in a child with a tracheostomy after replacing the tracheostomy cannula, caution must be exercised since the cannula may have migrated to the esophagus via a fistula. J. Med. Invest. 69 : 141-144, February, 2022.","The patient was a 15 months-old boy who had been diagnosed CHARGE syndrome, which is a multiple congenital anomaly syndrome caused by mutations in the CHD7 gene. Mechanical ventilation management was initiated 2 hours after birth for dysphagia and respiratory failure, and tracheotomy was performed 3 months after birth for dysphagia and failed extubation. He was repeatedly hospitalized due to pneuomoniae. Approximately 1 year after birth, the boy had two consecutive episodes of sudden ventilatory insufficiency while replacing the tracheotomy cannula. A bronchoscopic examination under general anesthesia revealed a tracheoesophageal fistula directly below the tracheostomy. The patient was diagnosed with Gross E esophageal atresia, and we speculated that the cannula migrated to the esophagus via the fistula during tracheostomy cannula replacement. Gross E esophageal atresia is a rare disease. Its diagnosis is often delayed, and it is discovered by recurrent pneumonia in many cases. A tracheoesophageal fistula may also be found in children with deformities of the respiratory system. Furthermore, tracheoesophageal fistulae are often found in the neck. Therefore, when sudden ventilatory insufficiency occurs in a child with a tracheostomy after replacing the tracheostomy cannula, caution must be exercised since the cannula may have migrated to the esophagus via a fistula. J. Med. Invest. 69 : 141-144, February, 2022.","null","null","2022-02","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.69","No.1.2","141","144","eng","null","null","research_institution","null","null","10.2152/jmi.69.141","1349-6867","null","null","null","null","null"
"A blood-based noninvasive miRNA signature for predicting survival outcomes in patients with intrahepatic cholangiocarcinoma.","A blood-based noninvasive miRNA signature for predicting survival outcomes in patients with intrahepatic cholangiocarcinoma.","Yuuma Wada, Mitsuo Shimada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Hideo Baba, Masaki Mori, Ajay Goel","Yuuma Wada, Mitsuo Shimada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Hideo Baba, Masaki Mori, Ajay Goel","null","The prognosis in patients with intrahepatic cholangiocarcinoma (ICC) is generally poor. To improve treatment selection, we sought to identify microRNA (miRNA) signature associated with survival outcomes in ICC. We first analysed the miRNA expression profiles of primary ICC from two public datasets to identify a miRNA panel to detect patients for short-term survival. We then analysed 309 specimens, including 241 FFPE samples from two clinical cohorts (training: n = 177; validation: n = 64) and matched plasma samples (n = 68), and developed a risk-stratification model incorporating the panel and CA 19-9 levels to predict survival outcomes in ICC. We identified a 7-miRNA panel that robustly classified patients with poor outcomes in the discovery cohorts (AUC = 0.80 and 0.88, respectively). We subsequently trained this miRNA panel in a clinical cohort (AUC = 0.83) and evaluated its performance in an independent validation cohort (AUC = 0.82) and plasma samples from the additional validation cohort (AUC = 0.78). Patients in both clinical cohorts who were classified as high-risk had significantly worse prognosis (p < 0.01). The risk-stratification model demonstrated superior performance compared to models (AUC = 0.85). We established a novel miRNA signature that could robustly predict survival outcomes in resected tissues and liquid biopsies to improve the clinical management of patients with ICC.","The prognosis in patients with intrahepatic cholangiocarcinoma (ICC) is generally poor. To improve treatment selection, we sought to identify microRNA (miRNA) signature associated with survival outcomes in ICC. We first analysed the miRNA expression profiles of primary ICC from two public datasets to identify a miRNA panel to detect patients for short-term survival. We then analysed 309 specimens, including 241 FFPE samples from two clinical cohorts (training: n = 177; validation: n = 64) and matched plasma samples (n = 68), and developed a risk-stratification model incorporating the panel and CA 19-9 levels to predict survival outcomes in ICC. We identified a 7-miRNA panel that robustly classified patients with poor outcomes in the discovery cohorts (AUC = 0.80 and 0.88, respectively). We subsequently trained this miRNA panel in a clinical cohort (AUC = 0.83) and evaluated its performance in an independent validation cohort (AUC = 0.82) and plasma samples from the additional validation cohort (AUC = 0.78). Patients in both clinical cohorts who were classified as high-risk had significantly worse prognosis (p < 0.01). The risk-stratification model demonstrated superior performance compared to models (AUC = 0.85). We established a novel miRNA signature that could robustly predict survival outcomes in resected tissues and liquid biopsies to improve the clinical management of patients with ICC.","null","null","2022-01-25","British Journal of Cancer","British Journal of Cancer","Vol.126","No.8","1196","1204","eng","null","null","research_institution","null","null","10.1038/s41416-022-01710-z","1532-1827","null","null","null","null","null"
"Epigallocatechin 3allate hinders metabolic coupling to suppress colorectal cancer malignancy through targeting aerobic glycolysis in cancerssociated fibroblasts.","Epigallocatechin 3allate hinders metabolic coupling to suppress colorectal cancer malignancy through targeting aerobic glycolysis in cancerssociated fibroblasts.","Shuhai Chen, Masaaki Nishi, Yuji Morine, Mitsuo Shimada, Takuya Tokunaga, Hideya Kashihara, Chie Takasu, Shinichiro Yamada, Yuma Wada","Shuhai Chen, Masaaki Nishi, Yuji Morine, Mitsuo Shimada, Takuya Tokunaga, Hideya Kashihara, Chie Takasu, Shinichiro Yamada, Yuma Wada","null","In recent times, researchers working on tumor metabolism have paid increasing attention to the tumor microenvironment. Emerging evidence has confirmed that epigenetic modifications of cancerssociated fibroblasts (CAFs) alters the characteristics of glucose metabolism to achieve a symbiotic relationship with the cancer cells. Epigallocatechin 3allate (EGCG) exerts antiumor effects via a variety of mechanisms, although the underlying mechanism that accounts for the effects of EGCG on glucose metabolic alterations of CAFs have yet to be elucidated. In the present study, through coulture with colorectal cancer (CRC) cells, human intestinal fibroblasts were transformed into CAFs, and exhibited enhanced aerobic glycolysis. Induced CAFs were able to enhance the proliferation, migration and invasion of CRC cells . EGCG treatment led to direct inhibition of the proliferation and migration of CRC cells; furthermore, EGCG treatment of CAFs suppressed their tumorromoting capabilities by inhibiting their glycolytic activity. Blocking the lactic acid efflux of CAFs with a monocarboxylate transporter 4 (MCT4) inhibitor or through silencing MCT4 could also suppress their tumorromoting capabilities, indicating that lactate fulfills an important role in the metabolic coupling that occurs between CAFs and cancer cells. Taken together, the results of the present study showed that EGCG targeting of the metabolism of tumor stromal cells provided a safe and effective strategy of antiancer therapy.","In recent times, researchers working on tumor metabolism have paid increasing attention to the tumor microenvironment. Emerging evidence has confirmed that epigenetic modifications of cancerssociated fibroblasts (CAFs) alters the characteristics of glucose metabolism to achieve a symbiotic relationship with the cancer cells. Epigallocatechin 3allate (EGCG) exerts antiumor effects via a variety of mechanisms, although the underlying mechanism that accounts for the effects of EGCG on glucose metabolic alterations of CAFs have yet to be elucidated. In the present study, through coulture with colorectal cancer (CRC) cells, human intestinal fibroblasts were transformed into CAFs, and exhibited enhanced aerobic glycolysis. Induced CAFs were able to enhance the proliferation, migration and invasion of CRC cells . EGCG treatment led to direct inhibition of the proliferation and migration of CRC cells; furthermore, EGCG treatment of CAFs suppressed their tumorromoting capabilities by inhibiting their glycolytic activity. Blocking the lactic acid efflux of CAFs with a monocarboxylate transporter 4 (MCT4) inhibitor or through silencing MCT4 could also suppress their tumorromoting capabilities, indicating that lactate fulfills an important role in the metabolic coupling that occurs between CAFs and cancer cells. Taken together, the results of the present study showed that EGCG targeting of the metabolism of tumor stromal cells provided a safe and effective strategy of antiancer therapy.","null","null","2022-01-14","International Journal of Oncology","International Journal of Oncology","Vol.60","No.2","null","null","eng","null","null","research_institution","null","null","10.3892/ijo.2022.5309","1791-2423","null","null","null","null","null"
"A transcriptomic signature that predicts cancer recurrence after hepatectomy in patients with colorectal liver metastases.","A transcriptomic signature that predicts cancer recurrence after hepatectomy in patients with colorectal liver metastases.","Yuuma Wada, Mitsuo Shimada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Hideo Baba, Masaki Mori, Ajay Goel","Yuuma Wada, Mitsuo Shimada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Hideo Baba, Masaki Mori, Ajay Goel","null","Cancer recurrence is an important predictor of survival outcomes in patients with colorectal cancer-associated liver metastasis (CRLM), who undergo radical hepatectomy. Therefore, identification of patients with the greatest risk of recurrence is critical for developing a precision oncology strategy that might include frequent surveillance (in low-risk patients) or a more aggressive treatment approach (in high-risk patients). We performed genome-wide expression profiling, to identify and develop a transcriptomic signature for predicting recurrence in patients with CRLM. We analysed a total of 383 patients with CRLM, including 63 patients from a publicly available data set (the NCBI's Gene Expression Omnibus with accession number GSE81423). and 320 patients from whom surgical specimens were collected for independent training (n = 169) and validation (n = 151) of identified biomarkers. Using Cox's proportional hazard regression analysis, we evaluated the clinical significance of the identified gene signature by comparing its performance with several key clinical factors. We identified a six-gene panel that robustly categorised patients with recurrence in the discovery (area under the curve (AUC) = 0.90). We showed that the panel was a significant predictor of recurrence in the clinical training (AUC = 0.83) and validation cohorts (AUC = 0.81). By combining our panel with key clinical factors, we established a risk-stratification model that emerged as an independent predictor of recurrence (AUC = 0.85; univariate: hazard ratio (HR) = 4.34, 95% confidence interval (CI) = 2.71-6.93, P < 0.001; multivariate: HR = 3.40, 95% CI = 1.76-6.56, P < 0.001). The stratification model revealed recurrence prediction in 89% of high-risk group and non-recurrence in 62% of low-risk group. We established a novel transcriptomic signature that robustly predicts recurrence, which has significant implications for the management of patients with CRLM.","Cancer recurrence is an important predictor of survival outcomes in patients with colorectal cancer-associated liver metastasis (CRLM), who undergo radical hepatectomy. Therefore, identification of patients with the greatest risk of recurrence is critical for developing a precision oncology strategy that might include frequent surveillance (in low-risk patients) or a more aggressive treatment approach (in high-risk patients). We performed genome-wide expression profiling, to identify and develop a transcriptomic signature for predicting recurrence in patients with CRLM. We analysed a total of 383 patients with CRLM, including 63 patients from a publicly available data set (the NCBI's Gene Expression Omnibus with accession number GSE81423). and 320 patients from whom surgical specimens were collected for independent training (n = 169) and validation (n = 151) of identified biomarkers. Using Cox's proportional hazard regression analysis, we evaluated the clinical significance of the identified gene signature by comparing its performance with several key clinical factors. We identified a six-gene panel that robustly categorised patients with recurrence in the discovery (area under the curve (AUC) = 0.90). We showed that the panel was a significant predictor of recurrence in the clinical training (AUC = 0.83) and validation cohorts (AUC = 0.81). By combining our panel with key clinical factors, we established a risk-stratification model that emerged as an independent predictor of recurrence (AUC = 0.85; univariate: hazard ratio (HR) = 4.34, 95% confidence interval (CI) = 2.71-6.93, P < 0.001; multivariate: HR = 3.40, 95% CI = 1.76-6.56, P < 0.001). The stratification model revealed recurrence prediction in 89% of high-risk group and non-recurrence in 62% of low-risk group. We established a novel transcriptomic signature that robustly predicts recurrence, which has significant implications for the management of patients with CRLM.","null","null","2022-01-14","European Journal of Cancer","European Journal of Cancer","Vol.163","null","66","76","eng","null","null","research_institution","null","null","10.1016/j.ejca.2021.12.013","1879-0852","null","null","null","null","null"
"Identification of microRNA-96-5p as a postoperative, prognostic microRNA predictor in nonviral hepatocellular carcinoma.","Identification of microRNA-96-5p as a postoperative, prognostic microRNA predictor in nonviral hepatocellular carcinoma.","Takeshi Matsui, Susumu Hamada-Tsutsumi, Yutaka Naito, Masanori Nojima, Etsuko Iio, Akihiro Tamori, Shoji Kubo, Tatsuya Ide, Yasuteru Kondo, Yuichiro Eguchi, Atsumasa Komori, Yuji Morine, Mitsuo Shimada, Tohru Utsunomiya, Ken Shirabe, Koichi Kimura, Yoichi Hiasa, Natthaya Chuaypen, Pisit Tangkijvanich, Aya Naiki-Ito, Satoru Takahashi, Takahiro Ochiya, Yasuhito Tanaka","Takeshi Matsui, Susumu Hamada-Tsutsumi, Yutaka Naito, Masanori Nojima, Etsuko Iio, Akihiro Tamori, Shoji Kubo, Tatsuya Ide, Yasuteru Kondo, Yuichiro Eguchi, Atsumasa Komori, Yuji Morine, Mitsuo Shimada, Tohru Utsunomiya, Ken Shirabe, Koichi Kimura, Yoichi Hiasa, Natthaya Chuaypen, Pisit Tangkijvanich, Aya Naiki-Ito, Satoru Takahashi, Takahiro Ochiya, Yasuhito Tanaka","null","The microRNA (miR) clusters miR-183/96/182 and miR-217/216a/216b are significantly upregulated in nonviral hepatocellular carcinoma (NBNC-HCC). Here, we investigate the impact of each member of these clusters on the clinical outcome of NBNC-HCC and analyze the antitumor effects of miR-96-5p. The association between recurrence-free survival of 111 NBNC-HCC patients and the levels of miR-183-5p, miR-96-5p, miR-182-5p, miR-217-5p, miR-216a-5p, and miR-216b-5p in tumor and adjacent tissues was investigated. The impact of miR-96-5p on apoptosis and invasion of a hepatoma cell line, HepG2, was investigated by cell counting, Transwell assay, and flow cytometry, respectively. MicroRNA-183-5p, miR-96-5p, miR-182-5p, miR-217-5p, and miR-216b-5p were significantly upregulated in tumor tissues compared to the adjacent tissues (p = 0.0005, p = 0.0030, p = 0.0002, p = 0.0011, and p = 0.0288, respectively). By multivariate Cox regression analysis, high tumor/adjacent ratios of miR-182-5p (p = 0.007) and miR-217-5p (p = 0.008) were associated with poor recurrence-free survival. In contrast, a low tumor/adjacent ratio of miR-96-5p (p < 0.001) was associated with poor recurrence-free survival. It suggested that further upregulation of miR-96-5p in tumors might have an inhibitory effect on recurrence. Transfection of miR-96-5p mimic significantly induced apoptosis of HepG2 cells, in association with downregulation of Nucleophosmin 1 (NPM1) and a decrease of phosphorylated AKT protein. Interestingly, simultaneous knockdown of the NPM1 and AKT genes induced apoptosis. MicroRNA-96-5p also suppressed proliferation and invasion, which inhibited epithelial-to-mesenchymal transition of HCC cells. MicroRNA-96-5p as a tumor suppressor would be valuable to stratify NBNC-HCC patients at high risk of recurrence.","The microRNA (miR) clusters miR-183/96/182 and miR-217/216a/216b are significantly upregulated in nonviral hepatocellular carcinoma (NBNC-HCC). Here, we investigate the impact of each member of these clusters on the clinical outcome of NBNC-HCC and analyze the antitumor effects of miR-96-5p. The association between recurrence-free survival of 111 NBNC-HCC patients and the levels of miR-183-5p, miR-96-5p, miR-182-5p, miR-217-5p, miR-216a-5p, and miR-216b-5p in tumor and adjacent tissues was investigated. The impact of miR-96-5p on apoptosis and invasion of a hepatoma cell line, HepG2, was investigated by cell counting, Transwell assay, and flow cytometry, respectively. MicroRNA-183-5p, miR-96-5p, miR-182-5p, miR-217-5p, and miR-216b-5p were significantly upregulated in tumor tissues compared to the adjacent tissues (p = 0.0005, p = 0.0030, p = 0.0002, p = 0.0011, and p = 0.0288, respectively). By multivariate Cox regression analysis, high tumor/adjacent ratios of miR-182-5p (p = 0.007) and miR-217-5p (p = 0.008) were associated with poor recurrence-free survival. In contrast, a low tumor/adjacent ratio of miR-96-5p (p < 0.001) was associated with poor recurrence-free survival. It suggested that further upregulation of miR-96-5p in tumors might have an inhibitory effect on recurrence. Transfection of miR-96-5p mimic significantly induced apoptosis of HepG2 cells, in association with downregulation of Nucleophosmin 1 (NPM1) and a decrease of phosphorylated AKT protein. Interestingly, simultaneous knockdown of the NPM1 and AKT genes induced apoptosis. MicroRNA-96-5p also suppressed proliferation and invasion, which inhibited epithelial-to-mesenchymal transition of HCC cells. MicroRNA-96-5p as a tumor suppressor would be valuable to stratify NBNC-HCC patients at high risk of recurrence.","null","null","2022-01-14","Hepatology Research","Hepatology Research","Vol.52","No.1","93","104","eng","null","null","research_institution","null","null","10.1111/hepr.13674","1386-6346","null","null","null","null","null"
"Usefulness of a stepwise training program for laparoscopic gastrectomy.","Usefulness of a stepwise training program for laparoscopic gastrectomy.","Masaaki Nishi, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Hideya Kashihara, Chie Takasu, Toshiaki Yoshimoto, Shoko Iwahashi","Masaaki Nishi, Mitsuo Shimada, Kouzou Yoshikawa, Takuya Tokunaga, Hideya Kashihara, Chie Takasu, Toshiaki Yoshimoto, Shoko Iwahashi","null","Laparoscopic gastrectomy (LG) is a complicated procedure with a long learning curve. This study was performed to investigate the usefulness of our stepwise training program for LG for improving the quality of the surgery. The stepwise training method comprised the following four steps: (1) basic training using a dry box and checking by mentors; (2) advanced training, including the use of animals and cadavers; (3) clinical experience, including standardization and preoperative three-dimensional simulation; and (4) self-assessment and feedback. In total, 153 patients who underwent curative gastrectomy for gastric cancer were included in this study. The operative time gradually decreased for both laparoscopic distal gastrectomy (LDG) (2013, 395inutes; 2017, 278inutes; P < .001; = -0.68) and laparoscopic total gastrectomy (LTG) (2013, 476inutes; 2017, 319inutes; P < .001; = -0.56). The blood loss volume gradually decreased for both LDG (2013, 43.0 mL; 2017, 18.6 mL; P < .005; = -0.30) and LTG (2013, 143.8 mL; 2017, 13.5 mL; P < .005; = -0.41). Our stepwise training program contributes to reduce operation time and blood loss in LG.","Laparoscopic gastrectomy (LG) is a complicated procedure with a long learning curve. This study was performed to investigate the usefulness of our stepwise training program for LG for improving the quality of the surgery. The stepwise training method comprised the following four steps: (1) basic training using a dry box and checking by mentors; (2) advanced training, including the use of animals and cadavers; (3) clinical experience, including standardization and preoperative three-dimensional simulation; and (4) self-assessment and feedback. In total, 153 patients who underwent curative gastrectomy for gastric cancer were included in this study. The operative time gradually decreased for both laparoscopic distal gastrectomy (LDG) (2013, 395inutes; 2017, 278inutes; P < .001; = -0.68) and laparoscopic total gastrectomy (LTG) (2013, 476inutes; 2017, 319inutes; P < .001; = -0.56). The blood loss volume gradually decreased for both LDG (2013, 43.0 mL; 2017, 18.6 mL; P < .005; = -0.30) and LTG (2013, 143.8 mL; 2017, 13.5 mL; P < .005; = -0.41). Our stepwise training program contributes to reduce operation time and blood loss in LG.","null","null","2022-01-12","Asian Journal of Endoscopic Surgery","Asian Journal of Endoscopic Surgery","Vol.15","No.1","121","127","eng","null","null","research_institution","null","null","10.1111/ases.12979","1758-5910","null","null","null","null","null"
"Strategy for laparoscopic repair of inguinal hernia after robot-assisted radical prostatectomy.","Strategy for laparoscopic repair of inguinal hernia after robot-assisted radical prostatectomy.","Shohei Eto, Kouzou Yoshikawa, Toshiaki Yoshimoto, Chie Takasu, Hideya Kashihara, Masaaki Nishi, Takuya Tokunaga, Toshihiro Nakao, Jun Higashijima, Takashi Iwata, Mitsuo Shimada","Shohei Eto, Kouzou Yoshikawa, Toshiaki Yoshimoto, Chie Takasu, Hideya Kashihara, Masaaki Nishi, Takuya Tokunaga, Toshihiro Nakao, Jun Higashijima, Takashi Iwata, Mitsuo Shimada","null","Robot-assisted radical prostatectomy (RARP) is nowadays being performed worldwide, and inguinal hernia (IH) continues to be a common complication of radical prostatectomy. Laparoscopic repair of IH is often difficult via internal dissection because of adhesion of the preperitoneal cavity. This study aimed to categorize the intraoperative condition of, and devise a strategy for, IH after RARP. Of 577 patients who underwent RARP, 18 developed IH. These 18 patients then underwent laparoscopic IH repair using the transabdominal preperitoneal approach (TAPP) or modified intraperitoneal onlay mesh repair (mIPOM). Internal dissection was categorized into two groups according to the appearance of Cooper's ligament (exposed or not exposed). After RARP, four patients had exposure of Cooper's ligament while 14 patients showed no exposure. Both patients in the exposed group underwent TAPP and all patients in the not-exposed group underwent mIPOM. There was no significant difference between normal TAPP and RARP regarding operative factors, and IH recurrence was not observed. Laparoscopic repair of IH after RARP is rendered safe and efficient by using our categorization based on the exposure of Cooper's ligament and extension of preperitoneal space.","Robot-assisted radical prostatectomy (RARP) is nowadays being performed worldwide, and inguinal hernia (IH) continues to be a common complication of radical prostatectomy. Laparoscopic repair of IH is often difficult via internal dissection because of adhesion of the preperitoneal cavity. This study aimed to categorize the intraoperative condition of, and devise a strategy for, IH after RARP. Of 577 patients who underwent RARP, 18 developed IH. These 18 patients then underwent laparoscopic IH repair using the transabdominal preperitoneal approach (TAPP) or modified intraperitoneal onlay mesh repair (mIPOM). Internal dissection was categorized into two groups according to the appearance of Cooper's ligament (exposed or not exposed). After RARP, four patients had exposure of Cooper's ligament while 14 patients showed no exposure. Both patients in the exposed group underwent TAPP and all patients in the not-exposed group underwent mIPOM. There was no significant difference between normal TAPP and RARP regarding operative factors, and IH recurrence was not observed. Laparoscopic repair of IH after RARP is rendered safe and efficient by using our categorization based on the exposure of Cooper's ligament and extension of preperitoneal space.","null","null","2022-01-12","Asian Journal of Endoscopic Surgery","Asian Journal of Endoscopic Surgery","Vol.15","No.1","155","161","eng","null","null","research_institution","null","null","10.1111/ases.12985","1758-5910","null","null","null","null","null"
"A ""diversity and inclusion"" lecture for promoting self-awareness among medical students.","A ""diversity and inclusion"" lecture for promoting self-awareness among medical students.","Chie Takasu, Emiko Kono, Yuji Morine, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Toshiaki Yoshimoto, Shoko Yamashita, Mitsuo Shimada","Chie Takasu, Emiko Kono, Yuji Morine, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Toshiaki Yoshimoto, Shoko Yamashita, Mitsuo Shimada","null","The concept of 'diversity and inclusion' is being adopted worldwide, but it is not yet understood well in Japan. We conducted this study to evaluate the impact of a lecture aimed at increasing awareness of academic careers and the benefits of having diversity and inclusion. Two female surgeons delivered a 120-min lecture on ""diversity and inclusion"" to third-year medical students at Tokushima University. To assess the impact of the lecture, a questionnaire was distributed, for participants to complete anonymously before and after the lecture. Eighty-two students participated in the study (39 men, 38 women, and 5 unknown). Based on the questionnaire responses, 57.1% of the students had already perceived inequality in conduct because of gender. A comparison of pre- and post-lecture responses revealed a significant increase in confidence to succeed in their medical career (56.5% vs. 77.5%, p < 0.01). Learners were more likely to believe that gender would not become a barrier to career development (42.4% vs. 66.7%, p < 0.01). Moreover, 90.4% of the students felt positively about a career in surgery following the lecture. The lecture promoted awareness about diversity, self-awareness, and career development and motivated students to consider specializing in surgery later in their career.","The concept of 'diversity and inclusion' is being adopted worldwide, but it is not yet understood well in Japan. We conducted this study to evaluate the impact of a lecture aimed at increasing awareness of academic careers and the benefits of having diversity and inclusion. Two female surgeons delivered a 120-min lecture on ""diversity and inclusion"" to third-year medical students at Tokushima University. To assess the impact of the lecture, a questionnaire was distributed, for participants to complete anonymously before and after the lecture. Eighty-two students participated in the study (39 men, 38 women, and 5 unknown). Based on the questionnaire responses, 57.1% of the students had already perceived inequality in conduct because of gender. A comparison of pre- and post-lecture responses revealed a significant increase in confidence to succeed in their medical career (56.5% vs. 77.5%, p < 0.01). Learners were more likely to believe that gender would not become a barrier to career development (42.4% vs. 66.7%, p < 0.01). Moreover, 90.4% of the students felt positively about a career in surgery following the lecture. The lecture promoted awareness about diversity, self-awareness, and career development and motivated students to consider specializing in surgery later in their career.","null","null","2022-01-10","Surgery Today","Surgery Today","Vol.52","No.6","964","970","eng","null","null","research_institution","null","null","10.1007/s00595-021-02424-0","1436-2813","null","null","null","null","null"
"Propensity Score-Matched Analysis of the Short- and Long-Term Outcomes of Robotic Versus Laparoscopic Gastrectomy for Gastric Cancer.","Propensity Score-Matched Analysis of the Short- and Long-Term Outcomes of Robotic Versus Laparoscopic Gastrectomy for Gastric Cancer.","Masaaki Nishi, Mitsuo Shimada, Kouzou Yoshikawa, Chie Takasu, Yuuma Wada, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Toshiaki Yoshimoto, Shoko Yamashita","Masaaki Nishi, Mitsuo Shimada, Kouzou Yoshikawa, Chie Takasu, Yuuma Wada, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Toshiaki Yoshimoto, Shoko Yamashita","null","Robotic gastrectomy (RG) has been rapidly adopted for gastric cancer (GC) treatment. However, the benefits of RG over laparoscopic gastrectomy (LG) for GC remain unclear. A total of 451 patients who underwent either RG (n = 83) or LG (n = 368) for GC were enrolled in this study. A 1:1 matched, propensity score-matched analysis was performed using the following factors: age, sex, body mass index, pT, pN, pStage, tumor location, vessel invasion, tumor markers, surgical procedure, reconstruction method, extent of lymphadenectomy, and Endoscopic Surgical Skill Qualification System qualified surgeon as an operator. The surgical outcomes of the two groups were compared. A well-balanced cohort of 158 patients was analyzed (n = 79 in the RG group, n = 79 in the LG group). Regarding the short-term outcomes, the respective blood loss volume, drain amylase content, and number of retrieved lymph nodes in the RG and LG groups were 38.62 ± 73.06 ml and 67.53 ± 108.20 ml (p < 0.05), 450 ± 371 IU/l and 1590 ± 6392 IU/l (p < 0.01), and 35.02 ± 15.51 and 25.28 ± 11.70 (p < 0.01). The morbidity rate was similar between the RG and LG groups (not significant [NS]). Regarding the long-term survival outcomes, there were no intergroup differences in 3-year overall survival (91.72% in the RG group vs. 83.39% in the LG group: NS) and 3-year, disease-free survival (93.31% in the vs. 90.44%: NS). RG was safe and contributed to better short-term outcomes and similar long-term survival outcomes compared with LG.","Robotic gastrectomy (RG) has been rapidly adopted for gastric cancer (GC) treatment. However, the benefits of RG over laparoscopic gastrectomy (LG) for GC remain unclear. A total of 451 patients who underwent either RG (n = 83) or LG (n = 368) for GC were enrolled in this study. A 1:1 matched, propensity score-matched analysis was performed using the following factors: age, sex, body mass index, pT, pN, pStage, tumor location, vessel invasion, tumor markers, surgical procedure, reconstruction method, extent of lymphadenectomy, and Endoscopic Surgical Skill Qualification System qualified surgeon as an operator. The surgical outcomes of the two groups were compared. A well-balanced cohort of 158 patients was analyzed (n = 79 in the RG group, n = 79 in the LG group). Regarding the short-term outcomes, the respective blood loss volume, drain amylase content, and number of retrieved lymph nodes in the RG and LG groups were 38.62 ± 73.06 ml and 67.53 ± 108.20 ml (p < 0.05), 450 ± 371 IU/l and 1590 ± 6392 IU/l (p < 0.01), and 35.02 ± 15.51 and 25.28 ± 11.70 (p < 0.01). The morbidity rate was similar between the RG and LG groups (not significant [NS]). Regarding the long-term survival outcomes, there were no intergroup differences in 3-year overall survival (91.72% in the RG group vs. 83.39% in the LG group: NS) and 3-year, disease-free survival (93.31% in the vs. 90.44%: NS). RG was safe and contributed to better short-term outcomes and similar long-term survival outcomes compared with LG.","null","null","2022-01-10","Annals of Surgical Oncology","Annals of Surgical Oncology","Vol.29","No.6","3887","3895","eng","null","null","research_institution","null","null","10.1245/s10434-021-11203-7","1534-4681","null","null","null","null","null"
"ASO Author Reflections: The Role of Robotic Gastrectomy for Gastric Cancer.","ASO Author Reflections: The Role of Robotic Gastrectomy for Gastric Cancer.","Masaaki Nishi, Mitsuo Shimada, Kouzou Yoshikawa, Chie Takasu, Yuuma Wada","Masaaki Nishi, Mitsuo Shimada, Kouzou Yoshikawa, Chie Takasu, Yuuma Wada","null","null","null","null","null","2022-01-05","Annals of Surgical Oncology","Annals of Surgical Oncology","Vol.29","No.6","3896","3897","eng","null","null","research_institution","null","null","10.1245/s10434-021-11226-0","1534-4681","null","null","null","null","null"
"リーダーを担う女性外科医の育成 わが国の女性外科医がリーダーシップを発揮するためのヒント アメリカ外科学会での女性外科医のリーダーシップ教育の例","リーダーを担う女性外科医の育成 わが国の女性外科医がリーダーシップを発揮するためのヒント アメリカ外科学会での女性外科医のリーダーシップ教育の例","川瀬 和美, 長谷川 潔, 江口 晋, 北川 雄光, 島田 光生, 高折 恭一, 吉田 和彦, 矢永 勝彦, 國土 典宏","川瀬 和美, 長谷川 潔, 江口 晋, 北川 雄光, Mitsuo Shimada, 高折 恭一, 吉田 和彦, 矢永 勝彦, 國土 典宏","null","null","null","null","null","2022-01","日本外科学会雑誌","Journal of Japan Surgical Society","Vol.123","No.1","133","135","jpn","null","null","research_institution","null","null","null","0301-4894","null","https://search.jamas.or.jp/link/ui/2022105346","null","null","null"
"【改訂:肝癌診療ガイドライン】肝癌診療ガイドライン 手術","【改訂:肝癌診療ガイドライン】肝癌診療ガイドライン 手術","久保 正二, 島田 光生, 永野 浩昭, 波多野 悦朗, 海堀 昌樹, 玄田 拓哉, 田中 肖吾, 居村 暁, 松井 康輔, 徳光 幸生, 中村 育夫, 新川 寛二, 木下 正彦, 長谷川 潔","久保 正二, Mitsuo Shimada, 永野 浩昭, 波多野 悦朗, 海堀 昌樹, 玄田 拓哉, 田中 肖吾, 居村 暁, 松井 康輔, 徳光 幸生, 中村 育夫, 新川 寛二, 木下 正彦, 長谷川 潔","null","null","null","null","null","2022-01","消化器・肝臓内科","消化器・肝臓内科","Vol.11","No.1","91","98","jpn","null","null","research_institution","null","null","null","null","null","https://search.jamas.or.jp/link/ui/2022107490","null","null","null"
"Newly Generated 3D Schwann-Like Cell Spheroids From Human Adipose-Derived Stem Cells Using a Modified Protocol.","Newly Generated 3D Schwann-Like Cell Spheroids From Human Adipose-Derived Stem Cells Using a Modified Protocol.","Shuhai Chen, Tetsuya Ikemoto, Takuya Tokunaga, Shohei Okikawa, Katsuki Miyazaki, Shin-ichiro Yamada, Yu Saitou, Yuji Morine, Mitsuo Shimada","Shuhai Chen, Tetsuya Ikemoto, Takuya Tokunaga, Shohei Okikawa, Katsuki Miyazaki, Shin-ichiro Yamada, Yu Saitou, Yuji Morine, Mitsuo Shimada","null","Peripheral nerve injury (PNI) is a relatively frequent type of trauma that results in the suffering of many patients worldwide every year. Schwann cells (SCs) are expected to be applied in cell therapy because of their ability to promote peripheral nerve regeneration. However, the lack of clinically renewable sources of SCs hinders the application of SC-based therapies. Adipose-derived stem cells (ADSCs) have generated great interest in recent years because of their multipotency and ease of harvest, and they have already been verified to differentiate into Schwann-like cells (SLCs) in vitro. However, the efficiency of differentiation and the functions of SLCs remain unsatisfactory. We newly generated three-dimensional (3D) SLC spheroids from ADSCs using a modified protocol with human recombinant peptide (RCP) petaloid -piece. Morphological analysis, gene expression analysis by qRT-PCR, ELISA measurement of the secretion capabilities of neurotrophic factors, and neurite formation assay were performed to evaluate the functions of these 3D SLCs in vitro. Motor function recovery was measured in a sciatic nerve injury mouse model to analyze the nerve regeneration-promoting effect of 3D SLCs in vivo. The differentiation efficiency and the secretion of neurotrophic factors were enhanced in 3D SLCs compared with conventional SLCs. 3D SLCs could more effectively promote neurite growth and longer neurite extension in a neuron-like SH-SY5Y model. Additionally, 3D SLCs had a better therapeutic effect on nerve regeneration after transplantation into the sciatic nerve injury mouse model. These findings demonstrated that the potential of ADSC-derived SLCs to promote nerve regeneration could be significantly increased using our modified differentiation protocol and by assembling cells into a 3D sphere conformation. Therefore, these cells have great potential and can be used in the clinical treatment of PNI.","Peripheral nerve injury (PNI) is a relatively frequent type of trauma that results in the suffering of many patients worldwide every year. Schwann cells (SCs) are expected to be applied in cell therapy because of their ability to promote peripheral nerve regeneration. However, the lack of clinically renewable sources of SCs hinders the application of SC-based therapies. Adipose-derived stem cells (ADSCs) have generated great interest in recent years because of their multipotency and ease of harvest, and they have already been verified to differentiate into Schwann-like cells (SLCs) in vitro. However, the efficiency of differentiation and the functions of SLCs remain unsatisfactory. We newly generated three-dimensional (3D) SLC spheroids from ADSCs using a modified protocol with human recombinant peptide (RCP) petaloid -piece. Morphological analysis, gene expression analysis by qRT-PCR, ELISA measurement of the secretion capabilities of neurotrophic factors, and neurite formation assay were performed to evaluate the functions of these 3D SLCs in vitro. Motor function recovery was measured in a sciatic nerve injury mouse model to analyze the nerve regeneration-promoting effect of 3D SLCs in vivo. The differentiation efficiency and the secretion of neurotrophic factors were enhanced in 3D SLCs compared with conventional SLCs. 3D SLCs could more effectively promote neurite growth and longer neurite extension in a neuron-like SH-SY5Y model. Additionally, 3D SLCs had a better therapeutic effect on nerve regeneration after transplantation into the sciatic nerve injury mouse model. These findings demonstrated that the potential of ADSC-derived SLCs to promote nerve regeneration could be significantly increased using our modified differentiation protocol and by assembling cells into a 3D sphere conformation. Therefore, these cells have great potential and can be used in the clinical treatment of PNI.","null","null","2022-01","Cell Transplantation","Cell Transplantation","Vol.31","null","9636897221093312","9636897221093312","eng","null","null","research_institution","null","null","10.1177/09636897221093312","1555-3892","null","null","null","null","null"
"Short-term outcomes of laparoscopic / robotic gastrectomy compared with open gastrectomy for advanced gastric cancer following chemotherapy.","Short-term outcomes of laparoscopic / robotic gastrectomy compared with open gastrectomy for advanced gastric cancer following chemotherapy.","Kouzou Yoshikawa, Mitsuo Shimada, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Yuuma Wada, Toshiaki Yoshimoto, Shoko Yamashita","Kouzou Yoshikawa, Mitsuo Shimada, Takuya Tokunaga, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Yuuma Wada, Toshiaki Yoshimoto, Shoko Yamashita","null","Purpose : This study aimed to investigate the short-term outcomes of laparoscopic gastrectomy / robotic gastrectomy after chemotherapy in patients with advanced gastric cancer and compare these outcomes with those of open gastrectomy. Methods : Fifty patients who underwent radical gastrectomy for advanced gastric cancer after chemotherapy between 2007 and 2021 were retrospectively analyzed. The patients were divided into two groups : the laparoscopic gastrectomy / robotic gastrectomy (n = 11) and open gastrectomy (n = 39) groups. The short-term outcomes of these procedures were subsequently examined. Results : The laparoscopic gastrectomy / robotic gastrectomy group had significantly shorter hospital stays and lower intraoperative blood loss than the open gastrectomy group. The overall complication rates were 12.8% (5 of 39 patients) and 0% (0 of 11 patients) in the open gastrectomy and laparoscopic gastrectomy / robotic gastrectomy groups, respectively (P = 0.1). Conclusions : Laparoscopic gastrectomy / robotic gastrectomy may be a surgical option after chemotherapy for patients with advanced gastric cancer. J. Med. Invest. 69 : 261-265, August, 2022.","Purpose : This study aimed to investigate the short-term outcomes of laparoscopic gastrectomy / robotic gastrectomy after chemotherapy in patients with advanced gastric cancer and compare these outcomes with those of open gastrectomy. Methods : Fifty patients who underwent radical gastrectomy for advanced gastric cancer after chemotherapy between 2007 and 2021 were retrospectively analyzed. The patients were divided into two groups : the laparoscopic gastrectomy / robotic gastrectomy (n = 11) and open gastrectomy (n = 39) groups. The short-term outcomes of these procedures were subsequently examined. Results : The laparoscopic gastrectomy / robotic gastrectomy group had significantly shorter hospital stays and lower intraoperative blood loss than the open gastrectomy group. The overall complication rates were 12.8% (5 of 39 patients) and 0% (0 of 11 patients) in the open gastrectomy and laparoscopic gastrectomy / robotic gastrectomy groups, respectively (P = 0.1). Conclusions : Laparoscopic gastrectomy / robotic gastrectomy may be a surgical option after chemotherapy for patients with advanced gastric cancer. J. Med. Invest. 69 : 261-265, August, 2022.","null","null","2022","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.69","No.3.4","261","265","eng","null","null","research_institution","null","null","10.2152/jmi.69.261","1349-6867","null","null","null","null","null"
"High Ligation of the Inferior Mesenteric Artery Induces Hypoperfusion of the Sigmoid Colon Stump During Anterior Resection.","High Ligation of the Inferior Mesenteric Artery Induces Hypoperfusion of the Sigmoid Colon Stump During Anterior Resection.","Jun Higashijima, Toru Kono, Mitsuo Shimada, Ayumu Sugitani, Hideya Kashihara, Chie Takasu, Masaaki Nishi, Takuya Tokunaga, Kouzou Yoshikawa","Jun Higashijima, Toru Kono, Mitsuo Shimada, Ayumu Sugitani, Hideya Kashihara, Chie Takasu, Masaaki Nishi, Takuya Tokunaga, Kouzou Yoshikawa","null","Anastomotic leakage (AL) after colorectal surgery is associated with insufficient vascular perfusion of the anastomotic ends. This study aimed to evaluate the effect of high vs. low ligation of the ileocolic artery and inferior mesenteric artery, respectively, on the vascular perfusion of the bowel stumps during ileocecal resection (ICR) and anterior rectal resection (AR). We retrospectively evaluated patients who underwent ICR or AR between 2016 and 2020. Real-time indocyanine green fluorescence angiography was performed to measure the fluorescence time (FT) as a marker of the blood flow in the proximal and distal stumps before anastomosis. Thirty-four patients with lower right-sided colon cancer underwent laparoscopic ICR. Forty-one patients with rectosigmoid colon or rectal cancer underwent robotic high AR (HAR) ( = 8), robotic low AR (LAR) ( = 6), laparoscopic HAR ( = 8), or laparoscopic LAR ( = 19). The FT was similar in the ileal and ascending colon stumps ( = 1.000) and did not differ significantly between high vs. low ligation of the ileocolic artery ( = 0.934). The FT was similar in the sigmoid colon and rectal stumps ( = 0.642), but high inferior mesenteric artery ligation significantly prolonged FT in the sigmoid colon during AR compared with low ligation ( = 0.004), indicating that the high ligation approach caused significant hypoperfusion compared with low ligation. The AL rate was similar after low vs. high ligation. Low vascular perfusion of the bowel stumps may not be an absolute risk factor for AL. High inferior mesenteric artery ligation could induce sigmoid colon stump hypoperfusion during anterior rectal resection.","Anastomotic leakage (AL) after colorectal surgery is associated with insufficient vascular perfusion of the anastomotic ends. This study aimed to evaluate the effect of high vs. low ligation of the ileocolic artery and inferior mesenteric artery, respectively, on the vascular perfusion of the bowel stumps during ileocecal resection (ICR) and anterior rectal resection (AR). We retrospectively evaluated patients who underwent ICR or AR between 2016 and 2020. Real-time indocyanine green fluorescence angiography was performed to measure the fluorescence time (FT) as a marker of the blood flow in the proximal and distal stumps before anastomosis. Thirty-four patients with lower right-sided colon cancer underwent laparoscopic ICR. Forty-one patients with rectosigmoid colon or rectal cancer underwent robotic high AR (HAR) ( = 8), robotic low AR (LAR) ( = 6), laparoscopic HAR ( = 8), or laparoscopic LAR ( = 19). The FT was similar in the ileal and ascending colon stumps ( = 1.000) and did not differ significantly between high vs. low ligation of the ileocolic artery ( = 0.934). The FT was similar in the sigmoid colon and rectal stumps ( = 0.642), but high inferior mesenteric artery ligation significantly prolonged FT in the sigmoid colon during AR compared with low ligation ( = 0.004), indicating that the high ligation approach caused significant hypoperfusion compared with low ligation. The AL rate was similar after low vs. high ligation. Low vascular perfusion of the bowel stumps may not be an absolute risk factor for AL. High inferior mesenteric artery ligation could induce sigmoid colon stump hypoperfusion during anterior rectal resection.","null","null","2021-12-13","Frontiers in Surgery","Frontiers in Surgery","Vol.8","null","756873","756873","eng","null","null","research_institution","null","null","10.3389/fsurg.2021.756873","2296-875X","null","null","null","null","null"
"Circulating miRNA Signature Predicts Response to Preoperative Chemoradiotherapy in Locally Advanced Rectal Cancer.","Circulating miRNA Signature Predicts Response to Preoperative Chemoradiotherapy in Locally Advanced Rectal Cancer.","Yuuma Wada, Mitsuo Shimada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Zhongxu Zhu, Xin Wang, Ane Etxart, Yangsoon Park, Luis Bujanda, In Ja Park, Ajay Goel","Yuuma Wada, Mitsuo Shimada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Zhongxu Zhu, Xin Wang, Ane Etxart, Yangsoon Park, Luis Bujanda, In Ja Park, Ajay Goel","null","Patients with locally advanced rectal cancer (LARC) are recommended to receive preoperative chemoradiotherapy (PCRT) followed by surgery. Response to PCRT varies widely: 60%-70% of patients with LARC do not derive therapeutic benefit from PCRT, whereas 15%-20% of patients achieve pathologic complete response (pCR). We sought to develop a liquid biopsy assay for identifying response to PCRT in patients with LARC. We analyzed two genome-wide microRNA (miRNA) expression profiling data sets from tumor tissue samples for discovery (GSE68204) and validation (GSE29298). We prioritized biomarkers in pretreatment plasma specimens from clinical training (n = 41; 15 responders and 26 nonresponders) and validation (n = 65; 29 responders and 36 nonresponders) cohorts of patients with LARC. We developed an integrated miRNA panel and established a risk assessment model, which was combined with the miRNA panel and carcinoembryonic antigen levels. Our comprehensive discovery effort identified an 8-miRNA panel that robustly predicted response to PCRT, with an excellent accuracy in the discovery (area under the curve [AUC] = 0.95) and validation (AUC = 0.92) cohorts. We successfully established a circulating miRNA panel with remarkable diagnostic accuracy in the clinical training (AUC = 0.82) and validation (AUC = 0.81) cohorts. Moreover, the predictive accuracy of the panel was significantly superior to conventional clinical factors in both cohorts ( < .01) and the risk assessment model was superior (AUC = 0.83). Finally, we applied our model to detect patients with pathologic complete response and showed that it was dramatically superior to currently used pathologic features (AUC = 0.92). Our novel risk assessment signature for predicting response to PCRT has a potential for clinical translation as a liquid biopsy assay in patients with LARC.","Patients with locally advanced rectal cancer (LARC) are recommended to receive preoperative chemoradiotherapy (PCRT) followed by surgery. Response to PCRT varies widely: 60%-70% of patients with LARC do not derive therapeutic benefit from PCRT, whereas 15%-20% of patients achieve pathologic complete response (pCR). We sought to develop a liquid biopsy assay for identifying response to PCRT in patients with LARC. We analyzed two genome-wide microRNA (miRNA) expression profiling data sets from tumor tissue samples for discovery (GSE68204) and validation (GSE29298). We prioritized biomarkers in pretreatment plasma specimens from clinical training (n = 41; 15 responders and 26 nonresponders) and validation (n = 65; 29 responders and 36 nonresponders) cohorts of patients with LARC. We developed an integrated miRNA panel and established a risk assessment model, which was combined with the miRNA panel and carcinoembryonic antigen levels. Our comprehensive discovery effort identified an 8-miRNA panel that robustly predicted response to PCRT, with an excellent accuracy in the discovery (area under the curve [AUC] = 0.95) and validation (AUC = 0.92) cohorts. We successfully established a circulating miRNA panel with remarkable diagnostic accuracy in the clinical training (AUC = 0.82) and validation (AUC = 0.81) cohorts. Moreover, the predictive accuracy of the panel was significantly superior to conventional clinical factors in both cohorts ( < .01) and the risk assessment model was superior (AUC = 0.83). Finally, we applied our model to detect patients with pathologic complete response and showed that it was dramatically superior to currently used pathologic features (AUC = 0.92). Our novel risk assessment signature for predicting response to PCRT has a potential for clinical translation as a liquid biopsy assay in patients with LARC.","null","null","2021-12-02","JCO Precision Oncology","JCO Precision Oncology","Vol.5","null","null","null","eng","null","null","research_institution","null","null","10.1200/PO.21.00015","2473-4284","null","null","null","null","null"
"The role of the immunoescape in colorectal cancer liver metastasis.","The role of the immunoescape in colorectal cancer liver metastasis.","Chie Takasu, Shoko Yamashita, Yuji Morine, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Toshiaki Yoshimoto, Mitsuo Shimada","Chie Takasu, Shoko Yamashita, Yuji Morine, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Toshiaki Yoshimoto, Mitsuo Shimada","null","The expression of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) indicate the efficacy of anti-PD-1/PD-L1 therapy in colorectal cancer (CRC), but are less useful for monitoring the efficacy of therapy of CRC liver metastasis (CRLM). This study investigated the effects of immune molecules on the prognosis of CRLM. We enrolled 71 patients with CRLM who underwent curative resection for CRC. We used immunohistochemistry to analyze the expression of PD-1, PD-L1, indoleamine-pyrrole 2,3-dioxygenase (IDO), and CD163 (a marker of tumor-associated macrophages [TAMs]) in metastatic tumors. The immune molecules PD-1, PD-L1, IDO, and TAMs were expressed in 32.3%, 47.8%, 45.0%, and 47.9% of metastatic CRC samples, respectively. The 5-year overall survival rates associated with immune molecule-positive groups were significantly better than in the negative groups (PD-1: 87.7% vs 53.2%, p = 0.023; PD-L1: 82.4% vs 42.3%, p = 0.007; IDO: 80.7% vs 43.5%, p = 0.007; TAMs: 82.6% vs 48.0%, p = 0.005). Multivariate analysis revealed PD-1 expression (p = 0.032, hazard ratio: 0.19), IDO expression (p = 0.049, hazard ratio: 0.37), and tumor differentiation (p<0.001, hazard ratio: 0.02) as independent prognostic indicators. PD-1 and TAMs in metastases were associated with less aggressive features such as smaller tumors. Furthermore, TAMs positively and significantly correlated with PD-1 expression (p = 0.011), PD-L1 expression (p = 0.024), and tended to correlate with IDO expression (p = 0.078). PD-1, PD-L1, IDO, and TAMs in CRLM were associated with less aggressive features and better prognosis of patients with CRC, indicating adaptive antitumor immunity vs immune tolerance. These molecules may therefore serve as prognostic markers for CRLM.","The expression of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) indicate the efficacy of anti-PD-1/PD-L1 therapy in colorectal cancer (CRC), but are less useful for monitoring the efficacy of therapy of CRC liver metastasis (CRLM). This study investigated the effects of immune molecules on the prognosis of CRLM. We enrolled 71 patients with CRLM who underwent curative resection for CRC. We used immunohistochemistry to analyze the expression of PD-1, PD-L1, indoleamine-pyrrole 2,3-dioxygenase (IDO), and CD163 (a marker of tumor-associated macrophages [TAMs]) in metastatic tumors. The immune molecules PD-1, PD-L1, IDO, and TAMs were expressed in 32.3%, 47.8%, 45.0%, and 47.9% of metastatic CRC samples, respectively. The 5-year overall survival rates associated with immune molecule-positive groups were significantly better than in the negative groups (PD-1: 87.7% vs 53.2%, p = 0.023; PD-L1: 82.4% vs 42.3%, p = 0.007; IDO: 80.7% vs 43.5%, p = 0.007; TAMs: 82.6% vs 48.0%, p = 0.005). Multivariate analysis revealed PD-1 expression (p = 0.032, hazard ratio: 0.19), IDO expression (p = 0.049, hazard ratio: 0.37), and tumor differentiation (p<0.001, hazard ratio: 0.02) as independent prognostic indicators. PD-1 and TAMs in metastases were associated with less aggressive features such as smaller tumors. Furthermore, TAMs positively and significantly correlated with PD-1 expression (p = 0.011), PD-L1 expression (p = 0.024), and tended to correlate with IDO expression (p = 0.078). PD-1, PD-L1, IDO, and TAMs in CRLM were associated with less aggressive features and better prognosis of patients with CRC, indicating adaptive antitumor immunity vs immune tolerance. These molecules may therefore serve as prognostic markers for CRLM.","null","null","2021-11-19","PLoS ONE","PLoS ONE","Vol.16","No.11","e0259940","e0259940","eng","null","null","research_institution","null","null","10.1371/journal.pone.0259940","1932-6203","null","null","null","null","null"
"Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.","Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.","Luping Gao, Yuji Morine, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Kazunori Tokuda, Chie Takasu, Katsuki Miyazaki, Mitsuo Shimada","Luping Gao, Yuji Morine, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Kazunori Tokuda, Chie Takasu, Katsuki Miyazaki, Mitsuo Shimada","null","As a multiple tyrosine kinase inhibitor, sorafenib is widely used to treat hepatocellular carcinoma (HCC), but patients frequently face resistance problems. Because the mechanism controlling sorafenib-resistance is not well understood, this study focused on the connection between tumor characteristics and the Nrf2 signaling pathway in a sorafenib-resistant HCC cell line. A sorafenib-resistant HCC cell line (Huh7) was developed by increasing the dose of sorafenib in the culture medium until the target concentration was reached. Cell morphology, migration/invasion rates, and expression of stemness-related and ATP-binding cassette (ABC) transporter genes were compared between sorafenib-resistant Huh7 cells and parental Huh7 cells. Next, a small interfering RNA was used to knock down Nrf2 expression in sorafenib-resistant Huh7 cells, after which cell viability, stemness, migration, and ABC transporter gene expression were examined again. Proliferation, migration, and invasion rates of sorafenib-resistant Huh7 cells were significantly increased relative to the parental cells with or without sorafenib added to the medium. The expression levels of stemness markers and ABC transporter genes were up-regulated in sorafenib-resistant cells. After Nrf2 was knocked down in sorafenib-resistant cells, cell migration and invasion rates were reduced, and expression levels of stemness markers and ABC transporter genes were reduced. Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant HCC cells.","As a multiple tyrosine kinase inhibitor, sorafenib is widely used to treat hepatocellular carcinoma (HCC), but patients frequently face resistance problems. Because the mechanism controlling sorafenib-resistance is not well understood, this study focused on the connection between tumor characteristics and the Nrf2 signaling pathway in a sorafenib-resistant HCC cell line. A sorafenib-resistant HCC cell line (Huh7) was developed by increasing the dose of sorafenib in the culture medium until the target concentration was reached. Cell morphology, migration/invasion rates, and expression of stemness-related and ATP-binding cassette (ABC) transporter genes were compared between sorafenib-resistant Huh7 cells and parental Huh7 cells. Next, a small interfering RNA was used to knock down Nrf2 expression in sorafenib-resistant Huh7 cells, after which cell viability, stemness, migration, and ABC transporter gene expression were examined again. Proliferation, migration, and invasion rates of sorafenib-resistant Huh7 cells were significantly increased relative to the parental cells with or without sorafenib added to the medium. The expression levels of stemness markers and ABC transporter genes were up-regulated in sorafenib-resistant cells. After Nrf2 was knocked down in sorafenib-resistant cells, cell migration and invasion rates were reduced, and expression levels of stemness markers and ABC transporter genes were reduced. Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant HCC cells.","null","null","2021-09-02","PLoS ONE","PLoS ONE","Vol.16","No.9","e0256755","e0256755","eng","null","null","research_institution","null","null","10.1371/journal.pone.0256755","1932-6203","null","null","null","null","null"
"【肝内胆管癌診療の最前線∼ガイドラインReview∼】肝内胆管癌の外科治療:リンパ節郭清 しない立場から","【肝内胆管癌診療の最前線∼ガイドラインReview∼】肝内胆管癌の外科治療:リンパ節郭清 しない立場から","山田 眞一郎, 森根 裕二, 島田 光生","Shin-ichiro Yamada, Yuji Morine, Mitsuo Shimada","null","肝内胆管癌に対する治療は根治的外科切除が基本であるが,リンパ節郭清の意義については一定の見解が得られていない.われわれは末梢型肝内胆管癌において,リンパ節転移陰性例では予防的郭清を行わず,陽性例でもサンプリングにとどめている.その理由として,肝のリンパ流にはさまざまな経路があり遠隔・全身のリンパ流とつながっているため,領域リンパ節郭清は単にサンプリングの意義しかないことがあげられる.実際にリンパ節転移陽性例は,リンパ節郭清を行っても予後は極めて不良であり,肝内胆管癌の予後向上のためには手術のみならず化学療法を含めた集学的治療が必要であると考えられる.(著者抄録)","肝内胆管癌に対する治療は根治的外科切除が基本であるが,リンパ節郭清の意義については一定の見解が得られていない.われわれは末梢型肝内胆管癌において,リンパ節転移陰性例では予防的郭清を行わず,陽性例でもサンプリングにとどめている.その理由として,肝のリンパ流にはさまざまな経路があり遠隔・全身のリンパ流とつながっているため,領域リンパ節郭清は単にサンプリングの意義しかないことがあげられる.実際にリンパ節転移陽性例は,リンパ節郭清を行っても予後は極めて不良であり,肝内胆管癌の予後向上のためには手術のみならず化学療法を含めた集学的治療が必要であると考えられる.(著者抄録)","null","null","2021-09","胆と膵","Journal of Biliary Tract & Pancreas","Vol.42","No.9","835","842","jpn","null","null","research_institution","null","null","null","0388-9408","null","http://search.jamas.or.jp/link/ui/2022004256","null","null","null"
"Frailty Can Predict Prognosis After Hepatectomy in Patients With Colorectal Liver Metastasis.","Frailty Can Predict Prognosis After Hepatectomy in Patients With Colorectal Liver Metastasis.","Kazunori Tokuda, Yuji Morine, Katsuki Miyazaki, Shin-ichiro Yamada, Yu Saitou, Masaaki Nishi, Tetsuya Ikemoto, Mitsuo Shimada","Kazunori Tokuda, Yuji Morine, Katsuki Miyazaki, Shin-ichiro Yamada, Yu Saitou, Masaaki Nishi, Tetsuya Ikemoto, Mitsuo Shimada","null","The aim of this study was to investigate frailty as a prognostic factor in patients with colorectal liver metastasis undergoing hepatectomy. Eighty-seven patients who underwent hepatectomy at our institution were enrolled. Frailty was defined as a score of ·4 on a clinical frailty scale. Patients were divided into frailty (n=29) and non-frailty (n=58) groups. Overall and cancer-specific survival rates were significantly worse in the frailty group compared with the non-frailty group, and multivariate analysis revealed frailty as an independent prognostic factor. Disease-free survival tended to be worse in the frailty group. Fifty-eight patients relapsed after the first hepatectomy. Twenty-one of 58 recurrent patients were allocated to the frailty group. After recurrence, chemotherapy was significantly more frequently performed in the non-frailty group compared with the frailty group. Frailty can predict the prognosis of patients with colorectal liver metastasis undergoing hepatectomy.","The aim of this study was to investigate frailty as a prognostic factor in patients with colorectal liver metastasis undergoing hepatectomy. Eighty-seven patients who underwent hepatectomy at our institution were enrolled. Frailty was defined as a score of ·4 on a clinical frailty scale. Patients were divided into frailty (n=29) and non-frailty (n=58) groups. Overall and cancer-specific survival rates were significantly worse in the frailty group compared with the non-frailty group, and multivariate analysis revealed frailty as an independent prognostic factor. Disease-free survival tended to be worse in the frailty group. Fifty-eight patients relapsed after the first hepatectomy. Twenty-one of 58 recurrent patients were allocated to the frailty group. After recurrence, chemotherapy was significantly more frequently performed in the non-frailty group compared with the frailty group. Frailty can predict the prognosis of patients with colorectal liver metastasis undergoing hepatectomy.","null","null","2021-09","Anticancer Research","Anticancer Research","Vol.41","No.9","4637","4644","eng","null","null","research_institution","null","null","10.21873/anticanres.15277","1791-7530","null","null","null","null","null"
"Usefulness of Diagnostic Staging Laparoscopy for Advanced Gastric Cancer.","Usefulness of Diagnostic Staging Laparoscopy for Advanced Gastric Cancer.","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Shohei Eto, Toshiaki Yoshimoto","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Shohei Eto, Toshiaki Yoshimoto","null","For advanced gastric cancer (AGC), peritoneal metastasis is the most common determinant of unresectability, but accurate preoperative diagnosis for peritoneal metastasis is challenging. Staging laparoscopy (SL) can detect unsuspected peritoneal metastasis. This study retrospectively evaluated the utility of SL and its indication in patients with AGC. In this study, we enrolled 114 patients with pathologically diagnosed gastric adenocarcinoma who underwent SL. Of the 114 patients, 43 (37.7%) had peritoneal metastasis (P1 or CY1). Higher age, larger tumor size, type 4 GC, deeper tumor depth, elevated CA125, and ascites findings in preoperative CT were found to be significant predictors of peritoneal metastasis. In multivariate analysis, peritoneal metastasis was associated with type 4 GC (odds ratio [OR]: 6.11; 95% confidence interval [CI]: 1.87-19.8; P < .01) and ascites in CT (OR: 4.25; 95% CI: 1.48-12.1; P < .01). Staging laparoscopy is an effective tool to detect peritoneal metastasis from AGC. It can increase the curative resection rate and decrease unnecessary laparotomies.","For advanced gastric cancer (AGC), peritoneal metastasis is the most common determinant of unresectability, but accurate preoperative diagnosis for peritoneal metastasis is challenging. Staging laparoscopy (SL) can detect unsuspected peritoneal metastasis. This study retrospectively evaluated the utility of SL and its indication in patients with AGC. In this study, we enrolled 114 patients with pathologically diagnosed gastric adenocarcinoma who underwent SL. Of the 114 patients, 43 (37.7%) had peritoneal metastasis (P1 or CY1). Higher age, larger tumor size, type 4 GC, deeper tumor depth, elevated CA125, and ascites findings in preoperative CT were found to be significant predictors of peritoneal metastasis. In multivariate analysis, peritoneal metastasis was associated with type 4 GC (odds ratio [OR]: 6.11; 95% confidence interval [CI]: 1.87-19.8; P < .01) and ascites in CT (OR: 4.25; 95% CI: 1.48-12.1; P < .01). Staging laparoscopy is an effective tool to detect peritoneal metastasis from AGC. It can increase the curative resection rate and decrease unnecessary laparotomies.","null","null","2021-08-12","The American Surgeon","The American Surgeon","null","null","31348211038554","31348211038554","eng","null","null","research_institution","null","null","10.1177/00031348211038554","1555-9823","null","null","null","null","null"
"The BAFF/NF B axis is crucial to interactions between sorafenib-resistant HCC cells and cancer-associated fibroblasts.","The BAFF/NF B axis is crucial to interactions between sorafenib-resistant HCC cells and cancer-associated fibroblasts.","Luping Gao, Yuji Morine, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Kazunori Tokuda, Katsuki Miyazaki, Shouhei Okikawa, Chie Takasu, Mitsuo Shimada","Luping Gao, Yuji Morine, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Kazunori Tokuda, Katsuki Miyazaki, Shouhei Okikawa, Chie Takasu, Mitsuo Shimada","null","The tumor microenvironment affects malignancy in hepatocellular carcinoma (HCC) cells, and cancer-associated fibroblasts (CAFs) play an important role in the microenvironment. As recent studies indicated a difference between CAFs isolated from chemoresistant and non-resistant cancer tissues, therefore we investigated the intracellular mechanism in resistant HCC co-cultured CAFs and interactions between these CAFs with cancer cells. We established a sorafenib-resistant (SR) Huh7 (human HCC) cell line, and characterized it with cytokine assays, then developed CAFs by co-culturing human hepatic stellate cells with resistant or parental Huh7 cells. The 2 types of CAFs were co-cultured with parental Huh7 cells, thereafter the cell viability of these Huh7 cells was checked under sorafenib treatment. The SR Huh7 (Huh7 ) cells expressed increased B-cell activating factor (BAFF), which promoted high expression of CAF-specific markers in Huh7 -co-cultured CAFs, showed activated BAFF, BAFF-R, and downstream of the NF B-Nrf2 pathway, and aggravated invasion, migration, and drug resistance in co-cultured Huh7 cells. When we knocked down BAFF expression in Huh7 cells, the previously increased malignancy and BAFF/NF B axis in Huh7 -co-cultured CAFs reversed, and enhanced chemoresistance in co-cultured Huh7 cells returned as well. In conclusion, the BAFF/NF B pathway was activated in CAFs co-cultured with cell-culture medium from resistant Huh7, which promoted chemoresistance, and increased the malignancy in co-cultured non-resistant Huh7 cells. This suggests that the BAFF/NF B axis in CAFs might be a potential therapeutic target in chemoresistance of HCC.","The tumor microenvironment affects malignancy in hepatocellular carcinoma (HCC) cells, and cancer-associated fibroblasts (CAFs) play an important role in the microenvironment. As recent studies indicated a difference between CAFs isolated from chemoresistant and non-resistant cancer tissues, therefore we investigated the intracellular mechanism in resistant HCC co-cultured CAFs and interactions between these CAFs with cancer cells. We established a sorafenib-resistant (SR) Huh7 (human HCC) cell line, and characterized it with cytokine assays, then developed CAFs by co-culturing human hepatic stellate cells with resistant or parental Huh7 cells. The 2 types of CAFs were co-cultured with parental Huh7 cells, thereafter the cell viability of these Huh7 cells was checked under sorafenib treatment. The SR Huh7 (Huh7 ) cells expressed increased B-cell activating factor (BAFF), which promoted high expression of CAF-specific markers in Huh7 -co-cultured CAFs, showed activated BAFF, BAFF-R, and downstream of the NF B-Nrf2 pathway, and aggravated invasion, migration, and drug resistance in co-cultured Huh7 cells. When we knocked down BAFF expression in Huh7 cells, the previously increased malignancy and BAFF/NF B axis in Huh7 -co-cultured CAFs reversed, and enhanced chemoresistance in co-cultured Huh7 cells returned as well. In conclusion, the BAFF/NF B pathway was activated in CAFs co-cultured with cell-culture medium from resistant Huh7, which promoted chemoresistance, and increased the malignancy in co-cultured non-resistant Huh7 cells. This suggests that the BAFF/NF B axis in CAFs might be a potential therapeutic target in chemoresistance of HCC.","null","null","2021-07-16","Cancer Science","Cancer Science","Vol.112","No.9","3545","3554","eng","null","null","research_institution","null","null","10.1111/cas.15041","1349-7006","null","null","null","null","null"
"A Transabdominal Robotic Purse-String Suture Technique for Transanal Total Mesorectal Excision.","A Transabdominal Robotic Purse-String Suture Technique for Transanal Total Mesorectal Excision.","Takuya Tokunaga, Hideya Kashihara, Jun Higashijima, Kouzou Yoshikawa, Masaaki Nishi, Chie Takasu, Shohei Eto, Toshiaki Yoshimoto, Mitsuo Shimada","Takuya Tokunaga, Hideya Kashihara, Jun Higashijima, Kouzou Yoshikawa, Masaaki Nishi, Chie Takasu, Shohei Eto, Toshiaki Yoshimoto, Mitsuo Shimada","null","Transanal total mesorectal excision (TaTME) is a novel technique that overcomes the problem of access to the deep pelvis during radical surgery for mid-rectal and lower rectal cancer. Although TaTME has several important steps, the creation of the distal purse-string suture following TaTME plays an important role in ensuring the integrity of the colorectal anastomosis. However, this procedure represents a major technical challenge for the surgeon. Robot-assisted surgery may make this suturing procedure easier than laparoscopic surgery because it permits intuitive wrist movements and a three-dimensional view. The aim of the present study was to investigate the usefulness of transabdominal robotic purse-string suture during anastomosis in TaTME. Twenty-seven patients, who underwent anastomosis using a single stapling technique (SST) during the TaTME of mid-rectal or lower rectal cancer, were enrolled in the study. The patients were allocated to two groups: 11 patients underwent transabdominal robotic purse-string suturing (the Robot group) and 16 patients underwent transanal purse-string suturing (the Transanal group). The characteristics and short-term surgical outcomes of the participants were compared between the two groups. The Robot group tended to have a shorter purse-string suturing time (541 206 seconds versus 729 310 seconds; = .07). Regarding the shape of the ""donut"" after SST anastomosis, in the Transanal group, 5 of the 16 participants had incomplete donuts with muscular defects and required additional suturing, whereas in the Robot group, all the participants had complete donuts ( = .04). Transabdominal robotic purse-string suturing may facilitate the suturing procedure and contribute to reliable anastomosis.","Transanal total mesorectal excision (TaTME) is a novel technique that overcomes the problem of access to the deep pelvis during radical surgery for mid-rectal and lower rectal cancer. Although TaTME has several important steps, the creation of the distal purse-string suture following TaTME plays an important role in ensuring the integrity of the colorectal anastomosis. However, this procedure represents a major technical challenge for the surgeon. Robot-assisted surgery may make this suturing procedure easier than laparoscopic surgery because it permits intuitive wrist movements and a three-dimensional view. The aim of the present study was to investigate the usefulness of transabdominal robotic purse-string suture during anastomosis in TaTME. Twenty-seven patients, who underwent anastomosis using a single stapling technique (SST) during the TaTME of mid-rectal or lower rectal cancer, were enrolled in the study. The patients were allocated to two groups: 11 patients underwent transabdominal robotic purse-string suturing (the Robot group) and 16 patients underwent transanal purse-string suturing (the Transanal group). The characteristics and short-term surgical outcomes of the participants were compared between the two groups. The Robot group tended to have a shorter purse-string suturing time (541 206 seconds versus 729 310 seconds; = .07). Regarding the shape of the ""donut"" after SST anastomosis, in the Transanal group, 5 of the 16 participants had incomplete donuts with muscular defects and required additional suturing, whereas in the Robot group, all the participants had complete donuts ( = .04). Transabdominal robotic purse-string suturing may facilitate the suturing procedure and contribute to reliable anastomosis.","null","null","2021-07-09","Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A","Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A","Vol.31","No.8","937","941","eng","null","null","research_institution","null","null","10.1089/lap.2021.0286","1557-9034","null","null","null","null","null"
"Lymphocyte to C-reactive protein ratio predicts long-term outcomes for patients with lower rectal cancer.","Lymphocyte to C-reactive protein ratio predicts long-term outcomes for patients with lower rectal cancer.","Masaaki Nishi, Mitsuo Shimada, Takuya Tokunaga, Jun Higashijima, Kouzou Yoshikawa, Hideya Kashihara, Chie Takasu, Daichi Ishikawa, Yuuma Wada, Shohei Eto, Toshiaki Yoshimoto","Masaaki Nishi, Mitsuo Shimada, Takuya Tokunaga, Jun Higashijima, Kouzou Yoshikawa, Hideya Kashihara, Chie Takasu, Daichi Ishikawa, Yuuma Wada, Shohei Eto, Toshiaki Yoshimoto","null","The lymphocyte to C-reactive protein (CRP) ratio (LCR) is an indicator of systemic inflammation and host-tumor cell interactions. The aim of this study was to investigate the prognostic significance of LCR in lower rectal cancer patients who received preoperative chemo-radiotherapy (CRT). Forty-eight patients with lower rectal cancer who underwent CRT followed by curative surgery were enrolled in this study. Routine blood examinations were performed before and after CRT were used to calculate pre-CRT LCR and post-CRT LCR. The median LCR was used to stratify patients into low and high LCR groups for analysis. The correlation between pre- and post-CRT LCR and clinical outcomes was retrospectively investigated. The pre-CRT LCR was significantly higher than the post-CRT LCR (11,765 and 6780, respectively, P < 0.05). The 5-year overall survival rate was significantly higher for patients with high post-CRT LCR compared with low post-CRT LCR (90.6% and 65.5%, respectively, P < 0.05). In univariate analysis, post-CRT LCR, post-CRT neutrophil to lymphocyte ratio, and fStage were significant prognostic factors for overall survival. In multivariate analysis, post-CRT LCR, but not other clinicopathological factors or prognostic indexes, was a significant prognostic factor for overall survival (P < 0.05). Post-CRT LCR could be a prognostic biomarker for patients with lower rectal cancer.","The lymphocyte to C-reactive protein (CRP) ratio (LCR) is an indicator of systemic inflammation and host-tumor cell interactions. The aim of this study was to investigate the prognostic significance of LCR in lower rectal cancer patients who received preoperative chemo-radiotherapy (CRT). Forty-eight patients with lower rectal cancer who underwent CRT followed by curative surgery were enrolled in this study. Routine blood examinations were performed before and after CRT were used to calculate pre-CRT LCR and post-CRT LCR. The median LCR was used to stratify patients into low and high LCR groups for analysis. The correlation between pre- and post-CRT LCR and clinical outcomes was retrospectively investigated. The pre-CRT LCR was significantly higher than the post-CRT LCR (11,765 and 6780, respectively, P < 0.05). The 5-year overall survival rate was significantly higher for patients with high post-CRT LCR compared with low post-CRT LCR (90.6% and 65.5%, respectively, P < 0.05). In univariate analysis, post-CRT LCR, post-CRT neutrophil to lymphocyte ratio, and fStage were significant prognostic factors for overall survival. In multivariate analysis, post-CRT LCR, but not other clinicopathological factors or prognostic indexes, was a significant prognostic factor for overall survival (P < 0.05). Post-CRT LCR could be a prognostic biomarker for patients with lower rectal cancer.","null","null","2021-07-06","World Journal of Surgical Oncology","World Journal of Surgical Oncology","Vol.19","No.1","201","201","eng","null","null","research_institution","null","null","10.1186/s12957-021-02319-x","1477-7819","null","null","null","null","null"
"Cancerssociated fibroblastnduced M2olarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor 1 pathway.","Cancerssociated fibroblastnduced M2olarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor 1 pathway.","Shuhai Chen, Yuji Morine, Kazunori Tokuda, Shin-ichiro Yamada, Yu Saitou, Masaaki Nishi, Tetsuya Ikemoto, Mitsuo Shimada","Shuhai Chen, Yuji Morine, Kazunori Tokuda, Shin-ichiro Yamada, Yu Saitou, Masaaki Nishi, Tetsuya Ikemoto, Mitsuo Shimada","null","Targeting the tumor stroma is an important strategy in cancer treatment. Cancerssociated fibroblasts (CAFs) and tumorssociated macrophages (TAMs) are two main components in the tumor microenvironment (TME) in hepatocellular carcinoma (HCC), which can promote tumor progression. Plasminogen activator inhibitor 1 (PAI 1) upregulation in HCC is predictive of unfavorable tumor behavior and prognosis. However, the crosstalk between cancer cells, TAMs and CAFs, and the functions of PAI 1 in HCC remain to be fully investigated. In the present study, macrophage polarization and key paracrine factors were assessed during their interactions with CAFs and cancer cells. Cell proliferation, wound healing and Transwell and Matrigel assays were used to investigate the malignant behavior of HCC cells . It was found that cancer cells and CAFs induced the M2 polarization of TAMs by upregulating the mRNA expression levels of CD163 and CD206, and downregulating IL 6 mRNA expression and secretion in the macrophages. Both TAMs derived from cancer cells and CAFs promoted HCC cell proliferation and invasion. Furthermore, PAI 1 expression was upregulated in TAMs after being stimulated with CAFonditioned medium and promoted the malignant behavior of the HCC cells by mediating epithelialesenchymal transition. CAFs were the main producer of C motif chemokine ligand 12 (CXCL12) in the TME and CXCL12 contributed to the induction of PAI 1 secretion in TAMs. In conclusion, the results of the present study suggested that CAFs promoted the M2 polarization of macrophages and induced PAI 1 secretion via CXCL12. Furthermore, it was found that PAI 1 produced by the TAMs enhanced the malignant behavior of the HCC cells. Therefore, these factors may be targets for inhibiting the crosstalk between tumor cells, CAFs and TAMs.","Targeting the tumor stroma is an important strategy in cancer treatment. Cancerssociated fibroblasts (CAFs) and tumorssociated macrophages (TAMs) are two main components in the tumor microenvironment (TME) in hepatocellular carcinoma (HCC), which can promote tumor progression. Plasminogen activator inhibitor 1 (PAI 1) upregulation in HCC is predictive of unfavorable tumor behavior and prognosis. However, the crosstalk between cancer cells, TAMs and CAFs, and the functions of PAI 1 in HCC remain to be fully investigated. In the present study, macrophage polarization and key paracrine factors were assessed during their interactions with CAFs and cancer cells. Cell proliferation, wound healing and Transwell and Matrigel assays were used to investigate the malignant behavior of HCC cells . It was found that cancer cells and CAFs induced the M2 polarization of TAMs by upregulating the mRNA expression levels of CD163 and CD206, and downregulating IL 6 mRNA expression and secretion in the macrophages. Both TAMs derived from cancer cells and CAFs promoted HCC cell proliferation and invasion. Furthermore, PAI 1 expression was upregulated in TAMs after being stimulated with CAFonditioned medium and promoted the malignant behavior of the HCC cells by mediating epithelialesenchymal transition. CAFs were the main producer of C motif chemokine ligand 12 (CXCL12) in the TME and CXCL12 contributed to the induction of PAI 1 secretion in TAMs. In conclusion, the results of the present study suggested that CAFs promoted the M2 polarization of macrophages and induced PAI 1 secretion via CXCL12. Furthermore, it was found that PAI 1 produced by the TAMs enhanced the malignant behavior of the HCC cells. Therefore, these factors may be targets for inhibiting the crosstalk between tumor cells, CAFs and TAMs.","null","null","2021-07-01","International Journal of Oncology","International Journal of Oncology","Vol.59","No.2","59","59","eng","null","null","research_institution","null","null","10.3892/ijo.2021.5239","1791-2423","null","null","null","null","null"
"Utility of cone unit liver resection for small hepatocellular carcinoma: a propensity score matched analysis.","Utility of cone unit liver resection for small hepatocellular carcinoma: a propensity score matched analysis.","Satoru Imura, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Yuji Morine, Mitsuo Shimada","Satoru Imura, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Yuji Morine, Mitsuo Shimada","null","Anatomical resection (AR) is performed widely for hepatocellular carcinoma (HCC). However, it is controversial whether typical AR, which removes the whole feeding territory of the tumor-bearing portal branch bordered by the landmark veins, is necessary. The aim of this study was to investigate the utility of small AR, so-called cone unit resection, for small HCC. Between 2007 and 2019, 372 hepatectomies were performed for HCC. Among them, 91 initial resections for small (<5 cm) solitary HCC were performed by typical AR (n = 44) or cone unit AR (n = 47). Propensity score matching was performed and clinicopathological features including prognosis were compared. At baseline, platelet count was higher, and liver function (serum albumin level) and indocyanine green retention at 15 min were better in the typical AR than cone unit AR group. There was no significant difference between the typical AR and cone unit AR group for tumor characteristics, short- and long-term outcomes. Even after propensity score matching (n = 29), the short- and long-term outcomes were also equivalent in between the two groups. There was no difference in prognosis of typical and cone unit AR. Therefore, cone unit AR is a feasible procedure for small HCC.","Anatomical resection (AR) is performed widely for hepatocellular carcinoma (HCC). However, it is controversial whether typical AR, which removes the whole feeding territory of the tumor-bearing portal branch bordered by the landmark veins, is necessary. The aim of this study was to investigate the utility of small AR, so-called cone unit resection, for small HCC. Between 2007 and 2019, 372 hepatectomies were performed for HCC. Among them, 91 initial resections for small (<5 cm) solitary HCC were performed by typical AR (n = 44) or cone unit AR (n = 47). Propensity score matching was performed and clinicopathological features including prognosis were compared. At baseline, platelet count was higher, and liver function (serum albumin level) and indocyanine green retention at 15 min were better in the typical AR than cone unit AR group. There was no significant difference between the typical AR and cone unit AR group for tumor characteristics, short- and long-term outcomes. Even after propensity score matching (n = 29), the short- and long-term outcomes were also equivalent in between the two groups. There was no difference in prognosis of typical and cone unit AR. Therefore, cone unit AR is a feasible procedure for small HCC.","null","null","2021-05-26","HPB","HPB","Vol.23","No.5","739","745","eng","null","null","research_institution","null","null","10.1016/j.hpb.2020.09.010","1477-2574","null","null","null","null","null"
"Intestinal hypoperfusion in patients with Crohn's disease revealed by intraoperative indocyanine green fluorescence imaging.","Intestinal hypoperfusion in patients with Crohn's disease revealed by intraoperative indocyanine green fluorescence imaging.","Jun Higashijima, Toru Kono, Mitsuo Shimada, Hideya Kashihara, Chie Takasu, Masaaki Nishi, Takuya Tokunaga, Ayumu Sugitani, Kouzou Yoshikawa","Jun Higashijima, Toru Kono, Mitsuo Shimada, Hideya Kashihara, Chie Takasu, Masaaki Nishi, Takuya Tokunaga, Ayumu Sugitani, Kouzou Yoshikawa","null","Anastomotic leakage has been reported as an independent risk factor for surgical recurrence at the anastomotic site in patients with Crohn's disease. An inadequate blood supply may contribute to this leakage. Real-time indocyanine green angiography has been useful for confirming vascular perfusion of the intestines. The aim of this study was to evaluate the use of intraoperative indocyanine green angiography to detect vascular perfusion of the intestines during ileocaecal resection in patients with Crohn's disease and colon cancer. We retrospectively evaluated the medical records of 26 consecutive patients with colon cancer arising in the caecum or ascending colon and 3 consecutive patients with Crohn's disease without a history of disease-related surgery. The patients in the 2 cohorts had undergone ileocaecal resection at Tokushima University Hospital between January 2018 and January 2021. After ileocaecal resection, blood flow was evaluated in ileal (oral) and colon (anal) stapled stumps by indocyanine green fluorescence angiography. The fluorescence time was defined as the time from indocyanine green injection and flush of the injection route to the point when the stump showed the strongest fluorescent signal in the monitor. The fluorescence time for the ileal and colon stumps in patients with Crohn's disease was 43.3 8.8 s each and was significantly longer than the fluorescence time in the patients with colon cancer (29.4 6.5 s and 29.6 6.8 s, respectively) (P < 0.05). Intraoperative indocyanine green fluorescence imaging is safe and reproducible for assessing intestinal perfusion prior to anastomosis in patients with colon cancer and Crohn's disease.","Anastomotic leakage has been reported as an independent risk factor for surgical recurrence at the anastomotic site in patients with Crohn's disease. An inadequate blood supply may contribute to this leakage. Real-time indocyanine green angiography has been useful for confirming vascular perfusion of the intestines. The aim of this study was to evaluate the use of intraoperative indocyanine green angiography to detect vascular perfusion of the intestines during ileocaecal resection in patients with Crohn's disease and colon cancer. We retrospectively evaluated the medical records of 26 consecutive patients with colon cancer arising in the caecum or ascending colon and 3 consecutive patients with Crohn's disease without a history of disease-related surgery. The patients in the 2 cohorts had undergone ileocaecal resection at Tokushima University Hospital between January 2018 and January 2021. After ileocaecal resection, blood flow was evaluated in ileal (oral) and colon (anal) stapled stumps by indocyanine green fluorescence angiography. The fluorescence time was defined as the time from indocyanine green injection and flush of the injection route to the point when the stump showed the strongest fluorescent signal in the monitor. The fluorescence time for the ileal and colon stumps in patients with Crohn's disease was 43.3 8.8 s each and was significantly longer than the fluorescence time in the patients with colon cancer (29.4 6.5 s and 29.6 6.8 s, respectively) (P < 0.05). Intraoperative indocyanine green fluorescence imaging is safe and reproducible for assessing intestinal perfusion prior to anastomosis in patients with colon cancer and Crohn's disease.","null","null","2021-05-24","Annals of Medicine and Surgery","Annals of Medicine and Surgery","Vol.66","null","102402","102402","eng","null","null","research_institution","null","null","10.1016/j.amsu.2021.102402","2049-0801","null","null","null","null","null"
"Preoperative lymphocyte/C-reactive protein ratio and its correlation with CD8 tumor-infiltrating lymphocytes as a predictor of prognosis after resection of intrahepatic cholangiocarcinoma.","Preoperative lymphocyte/C-reactive protein ratio and its correlation with CD8 tumor-infiltrating lymphocytes as a predictor of prognosis after resection of intrahepatic cholangiocarcinoma.","Katsuki Miyazaki, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Shin-ichiro Yamada, Kazunori Tokuda, Shohei Okikawa, Shoko Yamashita, Takeshi Oya, Koichi Tsuneyama, Mitsuo Shimada","Katsuki Miyazaki, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Shin-ichiro Yamada, Kazunori Tokuda, Shohei Okikawa, Shoko Yamashita, Takeshi Oya, Koichi Tsuneyama, Mitsuo Shimada","null","To clarify whether the preoperative lymphocyte/C-reactive protein (CRP) ratio (LCR) is a prognostic factor for patients with intrahepatic cholangiocarcinoma (IHCC), and investigate its mechanism via tumor-infiltrating lymphocytes. The subjects of this retrospective study were 42 patients who had undergone hepatectomy for IHCC. We divided the patients into low LCR and high LCR groups (cutoff value: 8780) and analyzed their overall survival (OS) and disease-free survival (DFS) with respect to LCR and other clinicopathological factors. We also investigated the levels of stromal tumor-infiltrating lymphocytes (TILs) and CD8 TILs in surgical specimens, and the relationship between LCR and TILs. A low LCR was identified in 21 patients and was significantly correlated with older age, a high CRP-albumin ratio, and advanced disease stage, and was a prognostic factor for OS and DFS. Multivariate analysis revealed that a low LCR was an independent prognostic factor for worse OS (HR 10.40, P = 0.0077). Although the LCR and levels of stromal TILs were not significantly related, LCR and levels of CD8 TILs were significantly related (P = 0.0297). The preoperative LCR may predict the postsurgical prognosis of patients with IHCC and reflect the CD8 TILs.","To clarify whether the preoperative lymphocyte/C-reactive protein (CRP) ratio (LCR) is a prognostic factor for patients with intrahepatic cholangiocarcinoma (IHCC), and investigate its mechanism via tumor-infiltrating lymphocytes. The subjects of this retrospective study were 42 patients who had undergone hepatectomy for IHCC. We divided the patients into low LCR and high LCR groups (cutoff value: 8780) and analyzed their overall survival (OS) and disease-free survival (DFS) with respect to LCR and other clinicopathological factors. We also investigated the levels of stromal tumor-infiltrating lymphocytes (TILs) and CD8 TILs in surgical specimens, and the relationship between LCR and TILs. A low LCR was identified in 21 patients and was significantly correlated with older age, a high CRP-albumin ratio, and advanced disease stage, and was a prognostic factor for OS and DFS. Multivariate analysis revealed that a low LCR was an independent prognostic factor for worse OS (HR 10.40, P = 0.0077). Although the LCR and levels of stromal TILs were not significantly related, LCR and levels of CD8 TILs were significantly related (P = 0.0297). The preoperative LCR may predict the postsurgical prognosis of patients with IHCC and reflect the CD8 TILs.","null","null","2021-05-19","Surgery Today","Surgery Today","Vol.51","No.12","1985","1995","eng","null","null","research_institution","null","null","10.1007/s00595-021-02295-5","1436-2813","null","null","null","null","null"
"The influence and countermeasure of obesity in laparoscopic colorectal resection.","The influence and countermeasure of obesity in laparoscopic colorectal resection.","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Toshiaki Yoshimoto","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Toshiaki Yoshimoto","null","The aim of this study was to investigate the influence of obesity and the usefulness of a preoperative weight loss program (PWLP) for obese patients undergoing laparoscopic colorectal resection (LCR). Study 1: 392 patients who underwent LCR for colorectal cancer were divided into two groups: those with a body mass index (BMI) ·25 kg/m (n = 113) and those with a BMI <25 kg/m (n = 279). The influence of BMI on LCR was investigated. Study 2: Patients with a BMI ·28 kg/m who were scheduled to undergo LCR (n = 7, mean body weight 87.0 kg, mean BMI 33.9 kg/m) undertook a PWLP including caloric restriction and exercise for 29.6 (15-70) days. The effects of this program were evaluated. Study 1: The BMI ·25 kg/m group had a prolongation of operation time and hospital stay than the BMI <25 kg/m group. Study 2: The patients achieved a mean weight loss of 6.9% (-6.0 kg). The mean visceral fat area was significantly decreased by 18.0%, whereas the skeletal muscle mass was unaffected. The PWLP group had a significantly lower prevalence of postoperative complications compared with the BMI ·25 kg/m group. Obesity affected the surgical outcomes in LCR. A PWLP may be useful for obese patients undergoing LCR.","The aim of this study was to investigate the influence of obesity and the usefulness of a preoperative weight loss program (PWLP) for obese patients undergoing laparoscopic colorectal resection (LCR). Study 1: 392 patients who underwent LCR for colorectal cancer were divided into two groups: those with a body mass index (BMI) ·25 kg/m (n = 113) and those with a BMI <25 kg/m (n = 279). The influence of BMI on LCR was investigated. Study 2: Patients with a BMI ·28 kg/m who were scheduled to undergo LCR (n = 7, mean body weight 87.0 kg, mean BMI 33.9 kg/m) undertook a PWLP including caloric restriction and exercise for 29.6 (15-70) days. The effects of this program were evaluated. Study 1: The BMI ·25 kg/m group had a prolongation of operation time and hospital stay than the BMI <25 kg/m group. Study 2: The patients achieved a mean weight loss of 6.9% (-6.0 kg). The mean visceral fat area was significantly decreased by 18.0%, whereas the skeletal muscle mass was unaffected. The PWLP group had a significantly lower prevalence of postoperative complications compared with the BMI ·25 kg/m group. Obesity affected the surgical outcomes in LCR. A PWLP may be useful for obese patients undergoing LCR.","null","null","2021-05-13","Annals of Gastroenterological Surgery","Annals of Gastroenterological Surgery","Vol.5","No.5","677","682","eng","null","null","research_institution","null","null","10.1002/ags3.12455","2475-0328","null","null","null","null","null"
"Effect of TU-100 on Peyer's patches in a bacterial translocation rat model.","Effect of TU-100 on Peyer's patches in a bacterial translocation rat model.","Chie Takasu, Katsuki Miyazaki, Kouzou Yoshikawa, Masaaki Nishi, Takuya Tokunaga, Hideya Kashihara, Toshiaki Yoshimoto, Hirohisa Ogawa, Yuji Morine, Mitsuo Shimada","Chie Takasu, Katsuki Miyazaki, Kouzou Yoshikawa, Masaaki Nishi, Takuya Tokunaga, Hideya Kashihara, Toshiaki Yoshimoto, Hirohisa Ogawa, Yuji Morine, Mitsuo Shimada","null","Daikenchuto (TU-100), a Japanese herbal medicine, is widely used for various gastrointestinal diseases. We have previously reported that TU-100 suppresses CPT-11-induced bacterial translocation (BT) by maintaining the diversity of the microbiome. In this study we show that TU-100 modulates the immune response during BT by inducing PD-1 expression in Peyer's patches. Eighteen male Wistar rats were divided into four groups: a control group; a control + TU-100 group, given TU-100 1000 mg/kg orally for 5 d; a BT group, given CPT-11 250 mg/kg intra-peritoneal for 2 d; and a TU-100 group, given TU-100 1000 mg/kg orally for 5 d with CPT-11 250 mg/kg intra-peritoneal on days 4 and 5. The size of Peyer's patch was significantly bigger in the BT group compared to the control group (9.0 104 m vs 29.4 104 m, < .05), but improved in the TU-100 group (15.4 104 m, < .005). TU-100 significantly induced PD-1 expression in Peyer's patch compared to the control group and the BT group (control vs BT vs TU-100 = 4.3 4.9 vs 5.1 10.3 vs 17.9 17.8). The CD4 cells were increased in the BT group ( < .05) compared to the control group but decreased in the TU-100 group. The Foxp3 cells were increased in the BT group compared to the control group ( < .05), and further increased in the TU-100 group compared to the BT group. CPT-11 significantly increased TLR4, NF- , TNF- mRNA expressions in the BT group. TU-100 cotreatment significantly reversed these mRNA expressions. TU-100 may have a protective effect against BT through PD-1 expression in Peyer's patch.","Daikenchuto (TU-100), a Japanese herbal medicine, is widely used for various gastrointestinal diseases. We have previously reported that TU-100 suppresses CPT-11-induced bacterial translocation (BT) by maintaining the diversity of the microbiome. In this study we show that TU-100 modulates the immune response during BT by inducing PD-1 expression in Peyer's patches. Eighteen male Wistar rats were divided into four groups: a control group; a control + TU-100 group, given TU-100 1000 mg/kg orally for 5 d; a BT group, given CPT-11 250 mg/kg intra-peritoneal for 2 d; and a TU-100 group, given TU-100 1000 mg/kg orally for 5 d with CPT-11 250 mg/kg intra-peritoneal on days 4 and 5. The size of Peyer's patch was significantly bigger in the BT group compared to the control group (9.0 104 m vs 29.4 104 m, < .05), but improved in the TU-100 group (15.4 104 m, < .005). TU-100 significantly induced PD-1 expression in Peyer's patch compared to the control group and the BT group (control vs BT vs TU-100 = 4.3 4.9 vs 5.1 10.3 vs 17.9 17.8). The CD4 cells were increased in the BT group ( < .05) compared to the control group but decreased in the TU-100 group. The Foxp3 cells were increased in the BT group compared to the control group ( < .05), and further increased in the TU-100 group compared to the BT group. CPT-11 significantly increased TLR4, NF- , TNF- mRNA expressions in the BT group. TU-100 cotreatment significantly reversed these mRNA expressions. TU-100 may have a protective effect against BT through PD-1 expression in Peyer's patch.","null","null","2021-04-05","Annals of Gastroenterological Surgery","Annals of Gastroenterological Surgery","Vol.5","No.5","683","691","eng","null","null","research_institution","null","null","10.1002/ags3.12460","2475-0328","null","null","null","null","null"
"A Liquid Biopsy Assay for Noninvasive Identification of Lymph Node Metastases in T1 Colorectal Cancer.","A Liquid Biopsy Assay for Noninvasive Identification of Lymph Node Metastases in T1 Colorectal Cancer.","Yuuma Wada, Mitsuo Shimada, Tatsuro Murano, Hiroyuki Takamaru, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Francesc Balaguer, Luis Bujanda, Maria Pellise, Ken Kato, Yutaka Saito, Hiroaki Ikematsu, Ajay Goel","Yuuma Wada, Mitsuo Shimada, Tatsuro Murano, Hiroyuki Takamaru, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Francesc Balaguer, Luis Bujanda, Maria Pellise, Ken Kato, Yutaka Saito, Hiroaki Ikematsu, Ajay Goel","null","We recently reported use of tissue-based transcriptomic biomarkers (microRNA [miRNA] or messenger RNA [mRNA]) for identification of lymph node metastasis (LNM) in patients with invasive submucosal colorectal cancers (T1 CRC). In this study, we translated our tissue-based biomarkers into a blood-based liquid biopsy assay for noninvasive detection of LNM in patients with high-risk T1 CRC. We analyzed 330 specimens from patients with high-risk T1 CRC, which included 188 serum samples from 2 clinical cohorts-a training cohort (N = 46) and a validation cohort (N = 142)-and matched formalin-fixed paraffin-embedded samples (N = 142). We performed quantitative reverse-transcription polymerase chain reaction, followed by logistic regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model combined with clinical risk factors. We used comprehensive expression profiling of a training cohort of LNM-positive and LMN-negative serum specimens to identify an optimized transcriptomic panel of 4 miRNAs (miR-181b, miR-193b, miR-195, and miR-411) and 5 mRNAs (AMT, forkhead box A1 [FOXA1], polymeric immunoglobulin receptor [PIGR], matrix metalloproteinase 1 [MMP1], and matrix metalloproteinase 9 [MMP9]), which robustly identified patients with LNM (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.72-0.94). We validated panel performance in an independent validation cohort (AUC, 0.82; 95% CI, 0.74-0.88). Our risk-stratification model was more accurate than the panel and an independent predictor for identification of LNM (AUC, 0.90; univariate: odds ratio [OR], 37.17; 95% CI, 4.48-308.35; P < .001; multivariate: OR, 17.28; 95% CI, 1.82-164.07; P = .013). The model limited potential overtreatment to only 18% of all patients, which is dramatically superior to pathologic features that are currently used (92%). A novel risk-stratification model for noninvasive identification of T1 CRC has the potential to avoid unnecessary operations for patients classified as high-risk by conventional risk-classification criteria.","We recently reported use of tissue-based transcriptomic biomarkers (microRNA [miRNA] or messenger RNA [mRNA]) for identification of lymph node metastasis (LNM) in patients with invasive submucosal colorectal cancers (T1 CRC). In this study, we translated our tissue-based biomarkers into a blood-based liquid biopsy assay for noninvasive detection of LNM in patients with high-risk T1 CRC. We analyzed 330 specimens from patients with high-risk T1 CRC, which included 188 serum samples from 2 clinical cohorts-a training cohort (N = 46) and a validation cohort (N = 142)-and matched formalin-fixed paraffin-embedded samples (N = 142). We performed quantitative reverse-transcription polymerase chain reaction, followed by logistic regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model combined with clinical risk factors. We used comprehensive expression profiling of a training cohort of LNM-positive and LMN-negative serum specimens to identify an optimized transcriptomic panel of 4 miRNAs (miR-181b, miR-193b, miR-195, and miR-411) and 5 mRNAs (AMT, forkhead box A1 [FOXA1], polymeric immunoglobulin receptor [PIGR], matrix metalloproteinase 1 [MMP1], and matrix metalloproteinase 9 [MMP9]), which robustly identified patients with LNM (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.72-0.94). We validated panel performance in an independent validation cohort (AUC, 0.82; 95% CI, 0.74-0.88). Our risk-stratification model was more accurate than the panel and an independent predictor for identification of LNM (AUC, 0.90; univariate: odds ratio [OR], 37.17; 95% CI, 4.48-308.35; P < .001; multivariate: OR, 17.28; 95% CI, 1.82-164.07; P = .013). The model limited potential overtreatment to only 18% of all patients, which is dramatically superior to pathologic features that are currently used (92%). A novel risk-stratification model for noninvasive identification of T1 CRC has the potential to avoid unnecessary operations for patients classified as high-risk by conventional risk-classification criteria.","null","null","2021-04-02","Gastroenterology","Gastroenterology","Vol.161","No.1","151","162.e1","eng","null","null","research_institution","null","null","10.1053/j.gastro.2021.03.062","1528-0012","null","null","null","null","null"
"Robotic-assisted total gastrectomy in a patient with gastric cancer associated with situs inversus totalis: With video.","Robotic-assisted total gastrectomy in a patient with gastric cancer associated with situs inversus totalis: With video.","Toshiaki Yoshimoto, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Chiharu Nakasu, Mitsuo Shimada","Toshiaki Yoshimoto, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Chiharu Nakasu, Mitsuo Shimada","null","Situs inversus totalis (SIT) refers to an inverted position of the major visceral organ as a ""mirror image"" of the regular location. We present a video of a robotic-assisted total gastrectomy in a 84-year-old man with SIT. The patient was diagnosed with advanced gastric cancer in the U region. The port placement was done as mirror images of our usual settings. Lymph node dissection was performed with a completely reverse approach to the usual procedure. After total gastrectomy, an intracorporal esophagojejunostomy was performed by circular method. All procedures were performed safely with no intraoperative complications and the patient was discharged uneventfully. Pathological diagnosis confirmed moderately differentiated adenocarcinoma and the depth of invasion was to the subserosa; there were five metastatic lymph nodes. In patients who have gastric cancer with SIT, a robotic-assisted total gastrectomy can be performed safely without surgical complication. Robots are useful for performing a total gastrectomy in SIT.","Situs inversus totalis (SIT) refers to an inverted position of the major visceral organ as a ""mirror image"" of the regular location. We present a video of a robotic-assisted total gastrectomy in a 84-year-old man with SIT. The patient was diagnosed with advanced gastric cancer in the U region. The port placement was done as mirror images of our usual settings. Lymph node dissection was performed with a completely reverse approach to the usual procedure. After total gastrectomy, an intracorporal esophagojejunostomy was performed by circular method. All procedures were performed safely with no intraoperative complications and the patient was discharged uneventfully. Pathological diagnosis confirmed moderately differentiated adenocarcinoma and the depth of invasion was to the subserosa; there were five metastatic lymph nodes. In patients who have gastric cancer with SIT, a robotic-assisted total gastrectomy can be performed safely without surgical complication. Robots are useful for performing a total gastrectomy in SIT.","null","null","2021-04-01","Asian Journal of Endoscopic Surgery","Asian Journal of Endoscopic Surgery","Vol.14","No.2","297","300","eng","null","null","research_institution","null","null","10.1111/ases.12860","1758-5910","null","null","null","null","null"
"Significance of frailty in prognosis after surgery in patients with pancreatic ductal adenocarcinoma.","Significance of frailty in prognosis after surgery in patients with pancreatic ductal adenocarcinoma.","Shin-ichiro Yamada, Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Katsuki Miyazaki, Takuya Tokunaga, Masaaki Nishi","Shin-ichiro Yamada, Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Katsuki Miyazaki, Takuya Tokunaga, Masaaki Nishi","null","Frailty is an important consideration for older patients undergoing surgery. We aimed to investigate whether frailty could be a prognostic factor in patients with pancreatic ductal adenocarcinoma who underwent pancreatic resection. One hundred and twenty patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma were enrolled. Frailty was defined as a clinical frailty scale score ·4. Patients were divided into frailty (n = 29) and non-frailty (n=91) groups, and clinicopathological factors were compared between the two groups. The frailty group showed an older age, lower serum albumin concentration, lower prognostic nutritional index, larger tumor diameter, and higher rate of lymph node metastasis than the non-frailty group (p < 0.05). Neutrophil-lymphocyte ratio and modified Glasgow prognostic score tended to be higher in the frailty group. Cancer-specific and disease-free survival rates were significantly poor in the frailty group (p < 0.05). With a multivariate analysis, frailty was an independent prognostic factor of cancer-specific survival. Frailty can predict the prognosis of patients with pancreatic ductal adenocarcinoma who undergo pancreatic resection.","Frailty is an important consideration for older patients undergoing surgery. We aimed to investigate whether frailty could be a prognostic factor in patients with pancreatic ductal adenocarcinoma who underwent pancreatic resection. One hundred and twenty patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma were enrolled. Frailty was defined as a clinical frailty scale score ·4. Patients were divided into frailty (n = 29) and non-frailty (n=91) groups, and clinicopathological factors were compared between the two groups. The frailty group showed an older age, lower serum albumin concentration, lower prognostic nutritional index, larger tumor diameter, and higher rate of lymph node metastasis than the non-frailty group (p < 0.05). Neutrophil-lymphocyte ratio and modified Glasgow prognostic score tended to be higher in the frailty group. Cancer-specific and disease-free survival rates were significantly poor in the frailty group (p < 0.05). With a multivariate analysis, frailty was an independent prognostic factor of cancer-specific survival. Frailty can predict the prognosis of patients with pancreatic ductal adenocarcinoma who undergo pancreatic resection.","null","null","2021-03-29","World Journal of Surgical Oncology","World Journal of Surgical Oncology","Vol.19","No.1","94","94","eng","null","null","research_institution","null","null","10.1186/s12957-021-02205-6","1477-7819","null","null","null","null","null"
"A Transcriptomic Signature for Risk-Stratification and Recurrence Prediction in Intrahepatic Cholangiocarcinoma.","A Transcriptomic Signature for Risk-Stratification and Recurrence Prediction in Intrahepatic Cholangiocarcinoma.","Yuuma Wada, Mitsuo Shimada, Kensuke Yamamura, Takeo Toshima, Jasjit K. Banwait, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Hideo Baba, Masaki Morishima, Ajay Goel","Yuuma Wada, Mitsuo Shimada, Kensuke Yamamura, Takeo Toshima, Jasjit K. Banwait, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Hideo Baba, Masaki Morishima, Ajay Goel","null","Tumor recurrence is frequent even in intrahepatic cholangiocarcinoma (ICC), and improved strategies are needed to identify patients at highest risk for such recurrence. We performed genome-wide expression profile analyses to discover and validate a gene signature associated with recurrence in patients with ICC. For biomarker discovery, we analyzed genome-wide transcriptomic profiling in ICC tumors from two public data sets: The Cancer Genome Atlas (n = 27) and GSE107943 (n = 28). We identified an eight-gene panel (BIRC5 [baculoviral IAP repeat containing 5], CDC20 [cell division cycle 20], CDH2 [cadherin 2], CENPW [centromere protein W], JPH1 [junctophilin 1], MAD2L1 [mitotic arrest deficient 2 like 1], NEIL3 [Nei like DNA glycosylase 3], and POC1A [POC1 centriolar protein A]) that robustly identified patients with recurrence in the discovery (AUC = 0.92) and in silico validation cohorts (AUC = 0.91). We next analyzed 241 specimens from patients with ICC (training cohort, n = 64; validation cohort, n = 177), followed by Cox proportional hazard regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model for recurrence in ICC. We subsequently trained this transcriptomic panel in a clinical cohort (AUC = 0.89; 95% confidence interval [CI] = 0.79-0.95), followed by evaluating its performance in an independent validation cohort (AUC = 0.86; 95% CI = 0.80-0.90). By combining our transcriptomic panel with various clinicopathologic features, we established a risk-stratification model that was significantly superior for the identification of recurrence (AUC = 0.89; univariate HR = 6.08, 95% CI = 3.55-10.41, P < 0.01; and multivariate HR = 3.49, 95% CI = 1.81-6.71, P < 0.01). The risk-stratification model identified potential recurrence in 85% of high-risk patients and nonrecurrence in 76% of low-risk patients, which is dramatically superior to currently used pathological features. We report a transcriptomic signature for risk-stratification and recurrence prediction that is superior to currently used clinicopathological features in patients with ICC.","Tumor recurrence is frequent even in intrahepatic cholangiocarcinoma (ICC), and improved strategies are needed to identify patients at highest risk for such recurrence. We performed genome-wide expression profile analyses to discover and validate a gene signature associated with recurrence in patients with ICC. For biomarker discovery, we analyzed genome-wide transcriptomic profiling in ICC tumors from two public data sets: The Cancer Genome Atlas (n = 27) and GSE107943 (n = 28). We identified an eight-gene panel (BIRC5 [baculoviral IAP repeat containing 5], CDC20 [cell division cycle 20], CDH2 [cadherin 2], CENPW [centromere protein W], JPH1 [junctophilin 1], MAD2L1 [mitotic arrest deficient 2 like 1], NEIL3 [Nei like DNA glycosylase 3], and POC1A [POC1 centriolar protein A]) that robustly identified patients with recurrence in the discovery (AUC = 0.92) and in silico validation cohorts (AUC = 0.91). We next analyzed 241 specimens from patients with ICC (training cohort, n = 64; validation cohort, n = 177), followed by Cox proportional hazard regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model for recurrence in ICC. We subsequently trained this transcriptomic panel in a clinical cohort (AUC = 0.89; 95% confidence interval [CI] = 0.79-0.95), followed by evaluating its performance in an independent validation cohort (AUC = 0.86; 95% CI = 0.80-0.90). By combining our transcriptomic panel with various clinicopathologic features, we established a risk-stratification model that was significantly superior for the identification of recurrence (AUC = 0.89; univariate HR = 6.08, 95% CI = 3.55-10.41, P < 0.01; and multivariate HR = 3.49, 95% CI = 1.81-6.71, P < 0.01). The risk-stratification model identified potential recurrence in 85% of high-risk patients and nonrecurrence in 76% of low-risk patients, which is dramatically superior to currently used pathological features. We report a transcriptomic signature for risk-stratification and recurrence prediction that is superior to currently used clinicopathological features in patients with ICC.","null","null","2021-03-16","Hepatology","Hepatology","Vol.74","No.3","1371","1383","eng","null","null","research_institution","null","null","10.1002/hep.31803","1527-3350","null","null","null","null","null"
"【肝胆膵外科における再切除と再手術-最新の治療戦略】肝細胞癌切除後再発に対する再肝切除 適応と治療成績","【肝胆膵外科における再切除と再手術-最新の治療戦略】肝細胞癌切除後再発に対する再肝切除 適応と治療成績","齋藤 裕, 居村 暁, 森根 裕二, 池本 哲也, 山田 眞一郎, 島田 光生","Yu Saitou, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Shin-ichiro Yamada, Mitsuo Shimada","null","null","null","null","null","2021-03","手術","Operation","Vol.75","No.3","249","256","jpn","null","null","research_institution","null","null","10.18888/op.0000002091","0037-4423","null","http://search.jamas.or.jp/link/ui/2021176594","null","null","null"
"Current status of hepatocyte-like cell therapy from stem cells.","Current status of hepatocyte-like cell therapy from stem cells.","Yu Saitou, Tetsuya Ikemoto, Yuji Morine, Mitsuo Shimada","Yu Saitou, Tetsuya Ikemoto, Yuji Morine, Mitsuo Shimada","null","Organ liver transplantation and hepatocyte transplantation are not performed to their full potential because of donor shortage, which could be resolved by identifying new donor sources for the development of hepatocyte-like cells (HLCs). HLCs have been differentiated from some stem cell sources as alternative primary hepatocytes throughout the world; however, the currently available techniques cannot differentiate HLCs to the level of normal adult primary hepatocytes. The outstanding questions are as follows: which stem cells are the best cell sources? which protocol is the best way to differentiate them into HLCs? what is the definition of differentiated HLCs? how can we enforce the function of HLCs? what is the difference between HLCs and primary hepatocytes? what are the problems with HLC transplantation? This review summarizes the current status of HLCs, focusing on stem cell sources, the differentiation protocol for HLCs, the general characterization of HLCs, the generation of more functional HLCs, comparison with primary hepatocytes, and HLCs in cell-transplantation-based liver regeneration.","Organ liver transplantation and hepatocyte transplantation are not performed to their full potential because of donor shortage, which could be resolved by identifying new donor sources for the development of hepatocyte-like cells (HLCs). HLCs have been differentiated from some stem cell sources as alternative primary hepatocytes throughout the world; however, the currently available techniques cannot differentiate HLCs to the level of normal adult primary hepatocytes. The outstanding questions are as follows: which stem cells are the best cell sources? which protocol is the best way to differentiate them into HLCs? what is the definition of differentiated HLCs? how can we enforce the function of HLCs? what is the difference between HLCs and primary hepatocytes? what are the problems with HLC transplantation? This review summarizes the current status of HLCs, focusing on stem cell sources, the differentiation protocol for HLCs, the general characterization of HLCs, the generation of more functional HLCs, comparison with primary hepatocytes, and HLCs in cell-transplantation-based liver regeneration.","null","null","2021-03","Surgery Today","Surgery Today","Vol.51","No.3","340","349","eng","null","null","research_institution","null","null","10.1007/s00595-020-02092-6","1436-2813","null","null","null","null","null"
"Preoperative prognostic nutritional index predicts short- and long-term outcomes after liver resection in patients with hepatocellular carcinoma.","Preoperative prognostic nutritional index predicts short- and long-term outcomes after liver resection in patients with hepatocellular carcinoma.","Yu Saitou, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Shin-ichiro Yamada, Mitsuo Shimada","Yu Saitou, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Shin-ichiro Yamada, Mitsuo Shimada","null","The prognostic nutritional index (PNI) is one of the immune parameters calculated on the basis of the serum albumin and the total lymphocyte count. The aim of the present study was to investigate the prognostic significance of the PNI for short- and long-term outcomes after liver resection for patients with hepatocellular carcinoma (HCC). Data from 162 surgically treated patients with HCC (without any previous treatment) were retrospectively analyzed. The cutoff value of preoperative PNI was 45.0, which was calculated by a receiver operating characteristic curve for predicting the recurrence of HCC after liver resection. Patients were divided into low (n=86) and high (n=76) PNI groups. In short-term outcomes, patients in the low PNI group were more likely to experience postoperative complications compared with those in the high PNI group. The 5-year disease-free survival (DFS) rate in the low PNI group was significantly lower compared with that in the high PNI group (20.5% vs. 48.7%). In the multivariate analysis, a low PNI was an independent prognostic factor for DFS (HR, 1.65; 95% CI, 1.00-2.71). In conclusion, the preoperative PNI may be a prognostic factor for evaluating short- and long-term outcomes after liver resection in patients with HCC.","The prognostic nutritional index (PNI) is one of the immune parameters calculated on the basis of the serum albumin and the total lymphocyte count. The aim of the present study was to investigate the prognostic significance of the PNI for short- and long-term outcomes after liver resection for patients with hepatocellular carcinoma (HCC). Data from 162 surgically treated patients with HCC (without any previous treatment) were retrospectively analyzed. The cutoff value of preoperative PNI was 45.0, which was calculated by a receiver operating characteristic curve for predicting the recurrence of HCC after liver resection. Patients were divided into low (n=86) and high (n=76) PNI groups. In short-term outcomes, patients in the low PNI group were more likely to experience postoperative complications compared with those in the high PNI group. The 5-year disease-free survival (DFS) rate in the low PNI group was significantly lower compared with that in the high PNI group (20.5% vs. 48.7%). In the multivariate analysis, a low PNI was an independent prognostic factor for DFS (HR, 1.65; 95% CI, 1.00-2.71). In conclusion, the preoperative PNI may be a prognostic factor for evaluating short- and long-term outcomes after liver resection in patients with HCC.","null","null","2021-02-21","Oncology Letters","Oncology Letters","Vol.21","No.2","153","153","eng","null","null","research_institution","null","null","10.3892/ol.2020.12414","1792-1074","null","null","null","null","null"
"The interaction between cancer associated fibroblasts and tumor associated macrophages via the osteopontin pathway in the tumor microenvironment of hepatocellular carcinoma.","The interaction between cancer associated fibroblasts and tumor associated macrophages via the osteopontin pathway in the tumor microenvironment of hepatocellular carcinoma.","Kazunori Tokuda, Yuji Morine, Katsuki Miyazaki, Shin-ichiro Yamada, Yu Saitou, Masaaki Nishi, Takuya Tokunaga, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada","Kazunori Tokuda, Yuji Morine, Katsuki Miyazaki, Shin-ichiro Yamada, Yu Saitou, Masaaki Nishi, Takuya Tokunaga, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada","null","Cancer-tumor associated macrophage (TAM)-cancer associated fibroblast (CAF) interactions are an important factor in the tumor microenvironment of hepatocellular carcinoma. Hepatic stellate cells (HSCs) were cultured with cancer cell-conditioned medium (Ca.-CM), TAM-CM and CAF-CM, and the expression of CAF markers were evaluated by RT-PCR. Whether HSCs cultured with Ca.-CM, TAM-CM and CAF-CM contributed to the enhanced malignancy of cancer cells was examined using proliferation, invasion and migration assays. Furthermore, the differences between these three types of CM were evaluated using cytokine arrays. HSCs cultured with Ca.-CM, TAM-CM and CAF-CM showed significantly increased mRNA expression of SMA, FAP and IL-6. All HSCs cultured with each CM exhibited significantly increased proliferation, invasion and migration of cancer cells. The osteopontin concentration was significantly higher in HSCs cultured with TAM-CM than the other CAF-CMs. Osteopontin inhibition significantly reduced osteopontin secretion from HSCs cultured with TAM-CM and suppressed the proliferation and invasion of cancer cells enhanced by HSCs cultured with TAM-CM. We observed enhanced osteopontin secretion from TAMs, and this increased osteopontin further promoted osteopontin secretion from HSCs cultured with TAM-CM, leading to increased malignancy. For the first time, we demonstrated the importance of cancer-TAM-CAF interactions via osteopontin in hepatocellular carcinoma.","Cancer-tumor associated macrophage (TAM)-cancer associated fibroblast (CAF) interactions are an important factor in the tumor microenvironment of hepatocellular carcinoma. Hepatic stellate cells (HSCs) were cultured with cancer cell-conditioned medium (Ca.-CM), TAM-CM and CAF-CM, and the expression of CAF markers were evaluated by RT-PCR. Whether HSCs cultured with Ca.-CM, TAM-CM and CAF-CM contributed to the enhanced malignancy of cancer cells was examined using proliferation, invasion and migration assays. Furthermore, the differences between these three types of CM were evaluated using cytokine arrays. HSCs cultured with Ca.-CM, TAM-CM and CAF-CM showed significantly increased mRNA expression of SMA, FAP and IL-6. All HSCs cultured with each CM exhibited significantly increased proliferation, invasion and migration of cancer cells. The osteopontin concentration was significantly higher in HSCs cultured with TAM-CM than the other CAF-CMs. Osteopontin inhibition significantly reduced osteopontin secretion from HSCs cultured with TAM-CM and suppressed the proliferation and invasion of cancer cells enhanced by HSCs cultured with TAM-CM. We observed enhanced osteopontin secretion from TAMs, and this increased osteopontin further promoted osteopontin secretion from HSCs cultured with TAM-CM, leading to increased malignancy. For the first time, we demonstrated the importance of cancer-TAM-CAF interactions via osteopontin in hepatocellular carcinoma.","null","null","2021-02-16","Oncotarget","Oncotarget","Vol.12","No.4","333","343","eng","null","null","research_institution","null","null","10.18632/oncotarget.27881","1949-2553","null","null","null","null","null"
"How pregnancy and childbirth affect the working conditions and careers of women surgeons in Japan: findings of a nationwide survey conducted by the Japan Surgical Society.","How pregnancy and childbirth affect the working conditions and careers of women surgeons in Japan: findings of a nationwide survey conducted by the Japan Surgical Society.","Kazumi Kawase, Kyoko Nomura, Sachiyo Nomura, Sadako Akashi-Tanaka, Tomoko Ogawa, Ikuko Shibasaki, Mitsuo Shimada, Tomoaki Taguchi, Emiko Takeshita, Yasuko Tomizawa, Kazuhiro Hanazaki, Tomoko Hanashi, Hideko Yamauchi, Hiroko Yamashita, Seigo Nakamura","Kazumi Kawase, Kyoko Nomura, Sachiyo Nomura, Sadako Akashi-Tanaka, Tomoko Ogawa, Ikuko Shibasaki, Mitsuo Shimada, Tomoaki Taguchi, Emiko Takeshita, Yasuko Tomizawa, Kazuhiro Hanazaki, Tomoko Hanashi, Hideko Yamauchi, Hiroko Yamashita, Seigo Nakamura","null","To identify the conflicts between a career as a surgeon and pregnancy and childbirth for women in Japan. The Japan Surgical Society conducted a nationwide survey on pregnancy and childbirth among its members who are women. The questionnaire included items regarding demography, working styles, and pregnancy and childbirth, including adverse events and harassment. The response rate was 29.9% (1068 responses, median age, 37 years). Among the responders, 61% were married and 47% had children (average number of children, 1.7). Half of the respondents reported having experienced sexual harassment and 62% reported having received unwelcome comments about pregnancy. About 20% had undergone fertility treatment. In total, 51% had pregnancies, with miscarriages in 33% of these. The top answer for the best timing for pregnancy and childbirth was after becoming board-certified. Nearly one-third of first-time mothers experienced adverse events during pregnancy and delivery, and 28% quit or changed their job because of their pregnancy and the birth of their first child. Japanese women who choose a career as a surgeon face obstacles during pregnancy and childbirth. It is vital to share the findings of this study and understand the issues associated with pregnancy and childbirth regardless of gender. Interventions are essential to ensure that every pregnant surgeon has a safe working environment to allow unobstructed development of her career.","To identify the conflicts between a career as a surgeon and pregnancy and childbirth for women in Japan. The Japan Surgical Society conducted a nationwide survey on pregnancy and childbirth among its members who are women. The questionnaire included items regarding demography, working styles, and pregnancy and childbirth, including adverse events and harassment. The response rate was 29.9% (1068 responses, median age, 37 years). Among the responders, 61% were married and 47% had children (average number of children, 1.7). Half of the respondents reported having experienced sexual harassment and 62% reported having received unwelcome comments about pregnancy. About 20% had undergone fertility treatment. In total, 51% had pregnancies, with miscarriages in 33% of these. The top answer for the best timing for pregnancy and childbirth was after becoming board-certified. Nearly one-third of first-time mothers experienced adverse events during pregnancy and delivery, and 28% quit or changed their job because of their pregnancy and the birth of their first child. Japanese women who choose a career as a surgeon face obstacles during pregnancy and childbirth. It is vital to share the findings of this study and understand the issues associated with pregnancy and childbirth regardless of gender. Interventions are essential to ensure that every pregnant surgeon has a safe working environment to allow unobstructed development of her career.","null","null","2021-02","Surgery Today","Surgery Today","Vol.51","No.2","309","321","eng","null","null","research_institution","null","null","10.1007/s00595-020-02129-w","1436-2813","null","null","null","null","null"
"Pre-operative Weight Loss Program for Obese Patients Undergoing Laparoscopic Gastrectomy.","Pre-operative Weight Loss Program for Obese Patients Undergoing Laparoscopic Gastrectomy.","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Toshiaki Yoshimoto","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Toshiaki Yoshimoto","null","Background : The aim of this study was to investigate the influence of obesity and the usefulness of a pre-operative weight loss program (PWLP) for obese patients undergoing laparoscopic gastrectomy (LG) for gastric cancer (GC). Materials and Methods : Study1 : 219 patients who underwent laparoscopic distal gastrectomy (LDG) for GC were divided into 2 groups : body mass index (BMI) 28 and BMI < 28kg /2. The influence of BMI in LG surgery was investigated. Study2 : The BMI 28 kg /2 patients with a planned LG (n = 8) undertook a PWLP including calorie restriction and exercise. The effects of this program were evaluated. Results : Study1 : The BMI 28kg /2 group showed significantly longer operation times, more blood loss and a higher frequency of post-operative complications than that of the BMI < 28kg /2 group. Study 2 : The patients achieved a weight loss of 4.2%. The visceral fat area (VFA) was significantly decreased by 10.6%, whereas skeletal muscle mass was unaffected. The PWLP group showed shorter operation times, less blood loss and a lower frequency of post-operative complications compared with that of the BMI 28kg /2 group. Conclusion : Obesity is an important risk factor and a pre-operative weight loss program is useful for obese patients undergoing a LG. J. Med. Invest. 68 : 165-169, February, 2021.","Background : The aim of this study was to investigate the influence of obesity and the usefulness of a pre-operative weight loss program (PWLP) for obese patients undergoing laparoscopic gastrectomy (LG) for gastric cancer (GC). Materials and Methods : Study1 : 219 patients who underwent laparoscopic distal gastrectomy (LDG) for GC were divided into 2 groups : body mass index (BMI) 28 and BMI < 28kg /2. The influence of BMI in LG surgery was investigated. Study2 : The BMI 28 kg /2 patients with a planned LG (n = 8) undertook a PWLP including calorie restriction and exercise. The effects of this program were evaluated. Results : Study1 : The BMI 28kg /2 group showed significantly longer operation times, more blood loss and a higher frequency of post-operative complications than that of the BMI < 28kg /2 group. Study 2 : The patients achieved a weight loss of 4.2%. The visceral fat area (VFA) was significantly decreased by 10.6%, whereas skeletal muscle mass was unaffected. The PWLP group showed shorter operation times, less blood loss and a lower frequency of post-operative complications compared with that of the BMI 28kg /2 group. Conclusion : Obesity is an important risk factor and a pre-operative weight loss program is useful for obese patients undergoing a LG. J. Med. Invest. 68 : 165-169, February, 2021.","null","null","2021-02","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.68","No.1.2","165","169","eng","null","null","research_institution","null","null","10.2152/jmi.68.165","1349-6867","null","null","null","null","null"
"A multicenter phase II trial of preoperative chemoradiotherapy with S-1 plus oxaliplatin and bevacizumab for locally advanced rectal cancer.","A multicenter phase II trial of preoperative chemoradiotherapy with S-1 plus oxaliplatin and bevacizumab for locally advanced rectal cancer.","Jun Higashijima, Takuya Tokunaga, Toshiaki Yoshimoto, Shohei Eto, Hideya Kashihara, Chie Takasu, Masaaki Nishi, Kouzou Yoshikawa, Hiroshi Okitsu, Masashi Ishikawa, Hidenori Miyake, Toshiyuki Yagi, Toru Kono, Mitsuo Shimada","Jun Higashijima, Takuya Tokunaga, Toshiaki Yoshimoto, Shohei Eto, Hideya Kashihara, Chie Takasu, Masaaki Nishi, Kouzou Yoshikawa, Hiroshi Okitsu, Masashi Ishikawa, Hidenori Miyake, Toshiyuki Yagi, Toru Kono, Mitsuo Shimada","null","We clarified the safety and efficacy of preoperative chemoradiotherapy for locally advanced rectal cancer using a multidrug regimen (S-1 +xaliplatin +evacizumab). This multicenter phase II trial involved 47 patients with locally advanced rectal cancer. All patients received S-1 orally (80 mg/m/day on days 1-5, 8-12, 15-19, and 22-26) and infusions of oxaliplatin (50 mg/m on days 1, 8, 15, and 22) and bevacizumab (5 mg/kg on days 1 and 15). The total radiation dose was 40 Gy delivered in daily fractions of 2 Gy via the four-field technique. The primary endpoint was the pathological complete response rate. The secondary endpoints were safety (incidence of adverse events) and clinical response, relapse-free survival, overall survival, local recurrence, R0 resection, downstaging, and treatment completion rates. All 47 patients received chemoradiotherapy, and 44 patients underwent curative resection. Two patients refused surgery and selected a watch-and-wait strategy. The pathological complete response rate was 18.2% in patients who underwent curative resection. The clinical response rate was 91.3% in 46 patients. Concerning hematotoxicity, there was one grade 4 adverse event (2.1%) and seven grade 3 events (14.9%). Diarrhea was the most frequent non-hematotoxic event, and the grade 3 event rate was 25.5%. Although preoperative chemoradiotherapy for patients with locally advanced rectal cancer using the S-1 +xaliplatin +evacizumab regimen did not achieve the expected pathological complete response rate, this regimen led to an improved clinical response rate.","We clarified the safety and efficacy of preoperative chemoradiotherapy for locally advanced rectal cancer using a multidrug regimen (S-1 +xaliplatin +evacizumab). This multicenter phase II trial involved 47 patients with locally advanced rectal cancer. All patients received S-1 orally (80 mg/m/day on days 1-5, 8-12, 15-19, and 22-26) and infusions of oxaliplatin (50 mg/m on days 1, 8, 15, and 22) and bevacizumab (5 mg/kg on days 1 and 15). The total radiation dose was 40 Gy delivered in daily fractions of 2 Gy via the four-field technique. The primary endpoint was the pathological complete response rate. The secondary endpoints were safety (incidence of adverse events) and clinical response, relapse-free survival, overall survival, local recurrence, R0 resection, downstaging, and treatment completion rates. All 47 patients received chemoradiotherapy, and 44 patients underwent curative resection. Two patients refused surgery and selected a watch-and-wait strategy. The pathological complete response rate was 18.2% in patients who underwent curative resection. The clinical response rate was 91.3% in 46 patients. Concerning hematotoxicity, there was one grade 4 adverse event (2.1%) and seven grade 3 events (14.9%). Diarrhea was the most frequent non-hematotoxic event, and the grade 3 event rate was 25.5%. Although preoperative chemoradiotherapy for patients with locally advanced rectal cancer using the S-1 +xaliplatin +evacizumab regimen did not achieve the expected pathological complete response rate, this regimen led to an improved clinical response rate.","null","null","2021-01-23","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.26","No.5","875","882","eng","null","null","research_institution","null","null","10.1007/s10147-021-01868-1","1437-7772","null","null","null","null","null"
"Clinical analysis of postoperative venous thromboembolism in Japanese patients after colorectal cancer surgery.","Clinical analysis of postoperative venous thromboembolism in Japanese patients after colorectal cancer surgery.","Shoko Yamashita, Masaaki Nishi, Tetsuya Ikemoto, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Shohei Eto, Toshiaki Yoshimoto, Mitsuo Shimada","Shoko Yamashita, Masaaki Nishi, Tetsuya Ikemoto, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Shohei Eto, Toshiaki Yoshimoto, Mitsuo Shimada","null","Venous thromboembolism (VTE) is a major complication after abdominal surgery; however, the best strategy for preventing VTE after surgery is not yet established. We performed this study to investigate the incidence of perioperative VTE and evaluate the efficacy of a VTE preventive strategy for patients undergoing surgery for colorectal cancer (CRC). The subjects of this retrospective analysis were 228 patients who underwent curative surgical resection for CRC between 2012 and 2016. The patients were treated with thromboprophylaxis including enoxaparin. We assessed the perioperative VTE occurrence rate and investigated the risk factors for postoperative VTE. Among the 228 patients, 77 had a preoperative D-dimer level of > 1.0 g/mL and 12 had deep vein thrombosis (DVT) diagnosed by ultrasonography preoperatively. Of the remaining 216 patients, short-term VTE (< 30 days) developed in two patients (0.9%) and long-term VTE (30 days-3 years) developed in seven (3.2%). The mortality rate of patients with VTE was 0%. The univariate analysis indicated that pulmonary disease was the risk factor for short-term VTE, whereas obesity, hyperlipidemia, and a preoperative history of pulmonary embolism were the risk factors for long-term VTE (p < 0.05). The findings of this analysis show that our preventive protocol including enoxaparin is an effective strategy for preventing postoperative VTE.","Venous thromboembolism (VTE) is a major complication after abdominal surgery; however, the best strategy for preventing VTE after surgery is not yet established. We performed this study to investigate the incidence of perioperative VTE and evaluate the efficacy of a VTE preventive strategy for patients undergoing surgery for colorectal cancer (CRC). The subjects of this retrospective analysis were 228 patients who underwent curative surgical resection for CRC between 2012 and 2016. The patients were treated with thromboprophylaxis including enoxaparin. We assessed the perioperative VTE occurrence rate and investigated the risk factors for postoperative VTE. Among the 228 patients, 77 had a preoperative D-dimer level of > 1.0 g/mL and 12 had deep vein thrombosis (DVT) diagnosed by ultrasonography preoperatively. Of the remaining 216 patients, short-term VTE (< 30 days) developed in two patients (0.9%) and long-term VTE (30 days-3 years) developed in seven (3.2%). The mortality rate of patients with VTE was 0%. The univariate analysis indicated that pulmonary disease was the risk factor for short-term VTE, whereas obesity, hyperlipidemia, and a preoperative history of pulmonary embolism were the risk factors for long-term VTE (p < 0.05). The findings of this analysis show that our preventive protocol including enoxaparin is an effective strategy for preventing postoperative VTE.","null","null","2021-01-02","Surgery Today","Surgery Today","Vol.51","No.6","1022","1027","eng","null","null","research_institution","null","null","10.1007/s00595-020-02201-5","1436-2813","null","null","null","null","null"
"Significance of Frailty in Prognosis After Hepatectomy for Elderly Patients with Hepatocellular Carcinoma.","Significance of Frailty in Prognosis After Hepatectomy for Elderly Patients with Hepatocellular Carcinoma.","Shin-ichiro Yamada, Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Yu Saitou, Masato Yoshikawa, Katsuki Miyazaki","Shin-ichiro Yamada, Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Yu Saitou, Masato Yoshikawa, Katsuki Miyazaki","null","The concept of frailty becomes important for patients who undergo surgery in this recent aging society. The aim of this study is to investigate the frailty as a prognostic factor in elderly patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. A total of 92 patients over 75 years old who underwent hepatectomy were enrolled in this study. Frailty was defined as clinical frailty scale (CFS) 4. Patients were divided into two groups, i.e., frailty group (n = 21) and no-frailty group (n = 71), and clinicopathological features were compared between them. The frailty group showed significant higher PIVKA-II level and larger tumor diameter (p < 0.05). CRP level and modified Glasgow prognostic score were significantly higher in the frailty group (p < 0.05). The frailty group showed higher rate of postoperative complications of Clavien-Dindo III (p = 0.06) and longer postoperative stay (p = 0.08). Cancer-specific, overall, and disease-free survival rates were significantly worse in the frailty group (p < 0.05). Frailty was detected as an independent prognostic factor on multivariate analysis of cancer-specific survival. Frailty can estimate the prognosis of HCC patients who underwent hepatectomy.","The concept of frailty becomes important for patients who undergo surgery in this recent aging society. The aim of this study is to investigate the frailty as a prognostic factor in elderly patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. A total of 92 patients over 75 years old who underwent hepatectomy were enrolled in this study. Frailty was defined as clinical frailty scale (CFS) 4. Patients were divided into two groups, i.e., frailty group (n = 21) and no-frailty group (n = 71), and clinicopathological features were compared between them. The frailty group showed significant higher PIVKA-II level and larger tumor diameter (p < 0.05). CRP level and modified Glasgow prognostic score were significantly higher in the frailty group (p < 0.05). The frailty group showed higher rate of postoperative complications of Clavien-Dindo III (p = 0.06) and longer postoperative stay (p = 0.08). Cancer-specific, overall, and disease-free survival rates were significantly worse in the frailty group (p < 0.05). Frailty was detected as an independent prognostic factor on multivariate analysis of cancer-specific survival. Frailty can estimate the prognosis of HCC patients who underwent hepatectomy.","null","null","2021-01","Annals of Surgical Oncology","Annals of Surgical Oncology","Vol.28","No.1","439","446","eng","null","null","research_institution","null","null","10.1245/s10434-020-08742-w","1534-4681","null","null","null","null","null"
"Bile Metabolites and Risk of Carcinogenesis in Patients With Pancreaticobiliary Maljunction: A Pilot Study.","Bile Metabolites and Risk of Carcinogenesis in Patients With Pancreaticobiliary Maljunction: A Pilot Study.","Hiroki Mori, Yuji Morine, Kazuaki Mawatari, Ayumi Chiba, Shin-ichiro Yamada, Yu Saitou, Hiroki Ishibashi, Akira Takahashi, Mitsuo Shimada","Hiroki Mori, Yuji Morine, Kazuaki Mawatari, Ayumi Chiba, Shin-ichiro Yamada, Yu Saitou, Hiroki Ishibashi, Akira Takahashi, Mitsuo Shimada","null","Pancreaticobiliary maljunction (PBM), a disease with reflux of pancreatic and bile juice in the pancreaticobiliary tract, is a high-risk factor for biliary tract cancer. The aim of this study was to investigate the mechanism of carcinogenesis in PBM using a metabolomics analysis of bile sampled during surgery. Three patients with PBM without biliary tract cancer, four patients with extrahepatic bile duct cancer (EHBC), and three controls with benign disease were enrolled. Metabolomics analysis of bile samples was performed using capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry to discriminate the amino acid and lipidomic profiles. The principal component analysis in the capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry revealed similar metabolites in patients with PBM and those with EHBC; furthermore, there was a clear difference between patients with PBM or EHBC compared to controls. The amino acid profiles revealed the following 20 potential carcinogenic candidates for PBM: isoleucine, phenylalanine, tyrosine, leucine, tryptophan, arginine, lysine, valine, asparagine, methionine, aspartic acid, serine, threonine, histidine, glutamine, alanine, proline, glutamic acid, and pyruvic acid. The lipidomic profiles revealed the following 11 carcinogenic candidates: lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidyl glycerol, lysophosphatidyl glycerol, triacylglycerol, diacylglycerol, ceramide, sphyngomyeline, fatty acid, hyperforin, and vitamin D. Among these characteristic metabolites, the branched-chain amino acids, methionine and lysophosphatidylcholine are known to be related to carcinogenesis. The bile metabolites were extremely similar in patients with PBM and those with EHBC. Furthermore, amino acid and lipid metabolism was markedly different in patients with PBM or EHBC compared to healthy controls.","Pancreaticobiliary maljunction (PBM), a disease with reflux of pancreatic and bile juice in the pancreaticobiliary tract, is a high-risk factor for biliary tract cancer. The aim of this study was to investigate the mechanism of carcinogenesis in PBM using a metabolomics analysis of bile sampled during surgery. Three patients with PBM without biliary tract cancer, four patients with extrahepatic bile duct cancer (EHBC), and three controls with benign disease were enrolled. Metabolomics analysis of bile samples was performed using capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry to discriminate the amino acid and lipidomic profiles. The principal component analysis in the capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry revealed similar metabolites in patients with PBM and those with EHBC; furthermore, there was a clear difference between patients with PBM or EHBC compared to controls. The amino acid profiles revealed the following 20 potential carcinogenic candidates for PBM: isoleucine, phenylalanine, tyrosine, leucine, tryptophan, arginine, lysine, valine, asparagine, methionine, aspartic acid, serine, threonine, histidine, glutamine, alanine, proline, glutamic acid, and pyruvic acid. The lipidomic profiles revealed the following 11 carcinogenic candidates: lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidyl glycerol, lysophosphatidyl glycerol, triacylglycerol, diacylglycerol, ceramide, sphyngomyeline, fatty acid, hyperforin, and vitamin D. Among these characteristic metabolites, the branched-chain amino acids, methionine and lysophosphatidylcholine are known to be related to carcinogenesis. The bile metabolites were extremely similar in patients with PBM and those with EHBC. Furthermore, amino acid and lipid metabolism was markedly different in patients with PBM or EHBC compared to healthy controls.","null","null","2021-01","Anticancer Research","Anticancer Research","Vol.41","No.1","327","334","eng","null","null","research_institution","null","null","10.21873/anticanres.14779","1791-7530","null","null","null","null","null"
"SDF-1 expression after preoperative chemoradiotherapy is associated with prognosis in patients with advanced lower rectal cancer.","SDF-1 expression after preoperative chemoradiotherapy is associated with prognosis in patients with advanced lower rectal cancer.","Shohei Okikawa, Jun Higashijima, Masaaki Nishi, Toshiaki Yoshimoto, Shohei Eto, Chie Takasu, Hideya Kashihara, Takuya Tokunaga, Kouzou Yoshikawa, Mitsuo Shimada","Shohei Okikawa, Jun Higashijima, Masaaki Nishi, Toshiaki Yoshimoto, Shohei Eto, Chie Takasu, Hideya Kashihara, Takuya Tokunaga, Kouzou Yoshikawa, Mitsuo Shimada","null","Stromal cell-derived factor-1 (SDF-1) expression is associated with cancer progression, as a biomarker of prognosis. We clarified the significance of SDF-1 expression on chemoradiotherapy (CRT) resistance and prognosis in advanced lower rectal cancer patients. We evaluated 98 patients with advanced lower rectal cancer who underwent preoperative CRT. All patients received 40 Gy of radiation therapy, with concurrent chemotherapy containing fluorinated pyrimidines, followed by surgical resection. SDF-1 expression in surgical specimens was examined by immunohistochemistry. We divided the patients into SDF-1-positive- (n = 52) and SDF-1-negative groups (n = 46) and compared the clinicopathological factors and survival rates. The SDF-1-positive group was more resistant to CRT than the SDF-1-negative group (non-responder rate, 63.5% vs. 47.8%, respectively ; p = 0.12). Overall survival (OS) in the SDF-1 positive group was significantly poorer vs. the SDF-1-negative group (5-year OS, 73.4% vs. 88.0%, respectively ; p = 0.02), and disease-free survival (DFS) was worse (5-year DFS, 61.0% vs. 74.1%, respectively ; p = 0.07). Multivariate analysis confirmed that SDF-1 expression was a significant independent prognostic predictor of OS (p = 0.04). SDF-1 expression after preoperative CRT is significantly associated with a poor prognosis in advanced lower rectal cancer patients and is a promising biomarker. J. Med. Invest. 68 : 309-314, August, 2021.","Stromal cell-derived factor-1 (SDF-1) expression is associated with cancer progression, as a biomarker of prognosis. We clarified the significance of SDF-1 expression on chemoradiotherapy (CRT) resistance and prognosis in advanced lower rectal cancer patients. We evaluated 98 patients with advanced lower rectal cancer who underwent preoperative CRT. All patients received 40 Gy of radiation therapy, with concurrent chemotherapy containing fluorinated pyrimidines, followed by surgical resection. SDF-1 expression in surgical specimens was examined by immunohistochemistry. We divided the patients into SDF-1-positive- (n = 52) and SDF-1-negative groups (n = 46) and compared the clinicopathological factors and survival rates. The SDF-1-positive group was more resistant to CRT than the SDF-1-negative group (non-responder rate, 63.5% vs. 47.8%, respectively ; p = 0.12). Overall survival (OS) in the SDF-1 positive group was significantly poorer vs. the SDF-1-negative group (5-year OS, 73.4% vs. 88.0%, respectively ; p = 0.02), and disease-free survival (DFS) was worse (5-year DFS, 61.0% vs. 74.1%, respectively ; p = 0.07). Multivariate analysis confirmed that SDF-1 expression was a significant independent prognostic predictor of OS (p = 0.04). SDF-1 expression after preoperative CRT is significantly associated with a poor prognosis in advanced lower rectal cancer patients and is a promising biomarker. J. Med. Invest. 68 : 309-314, August, 2021.","null","null","2021","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.68","No.3.4","309","314","eng","null","null","research_institution","null","null","10.2152/jmi.68.309","1349-6867","null","null","null","null","null"
"Usefulness of a multidisciplinary surgical site infection team in colorectal surgery.","Usefulness of a multidisciplinary surgical site infection team in colorectal surgery.","Shohei Eto, Kouzou Yoshikawa, Yukako Takehara, Toshiaki Yoshimoto, Chie Takasu, Hideya Kashihara, Masaaki Nishi, Takuya Tokunaga, Toshihiro Nakao, Jun Higashijima, Takashi Iwata, Mitsuo Shimada","Shohei Eto, Kouzou Yoshikawa, Yukako Takehara, Toshiaki Yoshimoto, Chie Takasu, Hideya Kashihara, Masaaki Nishi, Takuya Tokunaga, Toshihiro Nakao, Jun Higashijima, Takashi Iwata, Mitsuo Shimada","null","Background : Surgical site infection (SSI) is an adverse event that places a major burden on patients and staff. In this study, we examined the occurrence of SSI and the characteristics of patients referred to the SSI team after colorectal surgery. Methods : In total, 955 patients underwent colorectal surgery at our hospital from 2014 to 2019. Of these 955 patients, 516 received therapeutic support by the SSI team from 2017 to 2019. All patients were evaluated using an SSI surveillance sheet, and we checked for reports of SSI once a month. Each attending physician performed SSI prophylaxis (use of new instruments before wound irrigation and closure). Results : SSI occurred in 80 (8.4%) patients. The incidence of SSI and the incidence of surface SSI were higher in the patients who did not receive intervention by the SSI team than in the patients who did. Organ /pace SSI occurred in 18 patients. Among patients with surface SSI, Enterococcus was the most commonly detected bacteria. Among the 18 patients with organ /pace SSI, 5 developed anastomotic leakage and 4 developed intra-abdominal abscesses. Conclusions : An SSI team for prevention and treatment of infection may contribute to reduction of SSI. J. Med. Invest. 68 : 256-259, August, 2021.","Background : Surgical site infection (SSI) is an adverse event that places a major burden on patients and staff. In this study, we examined the occurrence of SSI and the characteristics of patients referred to the SSI team after colorectal surgery. Methods : In total, 955 patients underwent colorectal surgery at our hospital from 2014 to 2019. Of these 955 patients, 516 received therapeutic support by the SSI team from 2017 to 2019. All patients were evaluated using an SSI surveillance sheet, and we checked for reports of SSI once a month. Each attending physician performed SSI prophylaxis (use of new instruments before wound irrigation and closure). Results : SSI occurred in 80 (8.4%) patients. The incidence of SSI and the incidence of surface SSI were higher in the patients who did not receive intervention by the SSI team than in the patients who did. Organ /pace SSI occurred in 18 patients. Among patients with surface SSI, Enterococcus was the most commonly detected bacteria. Among the 18 patients with organ /pace SSI, 5 developed anastomotic leakage and 4 developed intra-abdominal abscesses. Conclusions : An SSI team for prevention and treatment of infection may contribute to reduction of SSI. J. Med. Invest. 68 : 256-259, August, 2021.","null","null","2021","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.68","No.3.4","256","259","eng","null","null","research_institution","null","null","10.2152/jmi.68.256","1349-6867","null","null","null","null","null"
"Impact of CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) expression in gastric cancer.","Impact of CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) expression in gastric cancer.","Masaaki Nishi, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Hideya Kashihara, Chie Takasu, Shohei Eto, Toshiaki Yoshimoto","Masaaki Nishi, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Hideya Kashihara, Chie Takasu, Shohei Eto, Toshiaki Yoshimoto","null","Background : CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is the master regulator of programmed cell death-ligand 1 (PD-L1). We aimed to clarify the significance of CMTM6 expression in gastric cancer (GC). Methods : A total of 105 patients who had undergone curative surgical resection for stage II /II GC at Tokushima University Hospital were included in this study. The expression of CMTM6 was examined by immunohistochemistry. Additionally, the relationship of each expression level to several prognostic factors was examined using univariate and multivariate analyses. Results : CMTM6 was not positively correlated with any of the factors examined. The overall survival (OS) rates were significantly poorer in the CMTM6 high-expression group than in the CMTM low-expression group (5-year OS : 57.2% vs. 79.2%, respectively ; p < 0.05). Disease-free survival (DFS) was significantly poorer in the CMTM high-expression group than in the CMTM6 low-expression group (5-year DFS : 52.8% vs. 72.4%, respectively ; p < 0.05). Multivariate analysis confirmed CMTM6 expression as an independent prognostic factor in DFS (p < 0.05). CMTM6 expression tended to be correlated with PD-L1 expression (p = 0.07). Conclusions : CMTM6 is associated with a poor prognosis and immunotolerance through PD-L1 in GC. J. Med. Invest. 68 : 362-367, August, 2021.","Background : CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is the master regulator of programmed cell death-ligand 1 (PD-L1). We aimed to clarify the significance of CMTM6 expression in gastric cancer (GC). Methods : A total of 105 patients who had undergone curative surgical resection for stage II /II GC at Tokushima University Hospital were included in this study. The expression of CMTM6 was examined by immunohistochemistry. Additionally, the relationship of each expression level to several prognostic factors was examined using univariate and multivariate analyses. Results : CMTM6 was not positively correlated with any of the factors examined. The overall survival (OS) rates were significantly poorer in the CMTM6 high-expression group than in the CMTM low-expression group (5-year OS : 57.2% vs. 79.2%, respectively ; p < 0.05). Disease-free survival (DFS) was significantly poorer in the CMTM high-expression group than in the CMTM6 low-expression group (5-year DFS : 52.8% vs. 72.4%, respectively ; p < 0.05). Multivariate analysis confirmed CMTM6 expression as an independent prognostic factor in DFS (p < 0.05). CMTM6 expression tended to be correlated with PD-L1 expression (p = 0.07). Conclusions : CMTM6 is associated with a poor prognosis and immunotolerance through PD-L1 in GC. J. Med. Invest. 68 : 362-367, August, 2021.","null","null","2021","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.68","No.3.4","362","367","eng","null","null","research_institution","null","null","10.2152/jmi.68.362","1349-6867","null","null","null","null","null"
"Regeneration of caudate lobe after living donor liver transplantation : Comparison with a surrogate model of left lobe graft.","Regeneration of caudate lobe after living donor liver transplantation : Comparison with a surrogate model of left lobe graft.","Yu Saitou, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Shin-ichiro Yamada, Mitsuo Shimada","Yu Saitou, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Shin-ichiro Yamada, Mitsuo Shimada","null","Background : The aim of this study is to clarify the regeneration of the CL (caudate lobe) without any reconstructions of short hepatic veins (SHVr) after LDLT (living donor liver transplantation) and compare the regeneration of the CL after right hepatectomy (Rt. Hx), as the surrogate model of extended left lobe graft (Ex LLG) with complete SHVr. Methods : Eleven Ex LLGs with CL were included in this study. SHVr was not performed in all cases. The volumetry was performed before, one month and six months after LDLT. Seven patients who underwent Rt. Hx were also included in this study as the surrogate model. Results : In Ex LLGs with CL, the regeneration rate of the large CL (> 30 ml) was worse than that of small CL (< 30 ml). In the surrogate model, the regeneration rate of the CL was not worse than other segments. However, the regeneration rate of the large CL was also worse than that of small CL even in the presence of complete SHVr. Conclusions : The regeneration of the large CL was worse than that of the small CL regardless of the presence or absence of SHVr, indicating that SHVr in Ex LLG with CL might not be necessary. J. Med. Invest. 68 : 330-333, August, 2021.","Background : The aim of this study is to clarify the regeneration of the CL (caudate lobe) without any reconstructions of short hepatic veins (SHVr) after LDLT (living donor liver transplantation) and compare the regeneration of the CL after right hepatectomy (Rt. Hx), as the surrogate model of extended left lobe graft (Ex LLG) with complete SHVr. Methods : Eleven Ex LLGs with CL were included in this study. SHVr was not performed in all cases. The volumetry was performed before, one month and six months after LDLT. Seven patients who underwent Rt. Hx were also included in this study as the surrogate model. Results : In Ex LLGs with CL, the regeneration rate of the large CL (> 30 ml) was worse than that of small CL (< 30 ml). In the surrogate model, the regeneration rate of the CL was not worse than other segments. However, the regeneration rate of the large CL was also worse than that of small CL even in the presence of complete SHVr. Conclusions : The regeneration of the large CL was worse than that of the small CL regardless of the presence or absence of SHVr, indicating that SHVr in Ex LLG with CL might not be necessary. J. Med. Invest. 68 : 330-333, August, 2021.","null","null","2021","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.68","No.3.4","330","333","eng","null","null","research_institution","null","null","10.2152/jmi.68.330","1349-6867","null","null","null","null","null"
"Value of the CRP-albumin ratio in patients with resectable pancreatic cancer.","Value of the CRP-albumin ratio in patients with resectable pancreatic cancer.","Yusuke Arakawa, Katsuki Miyazaki, Masato Yoshikawa, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Mitsuo Shimada","Yusuke Arakawa, Katsuki Miyazaki, Masato Yoshikawa, Shin-ichiro Yamada, Yu Saitou, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Mitsuo Shimada","null","Background : The C-reactive protein (CRP)-albumin ratio (CAR) was reported as a prognostic factor of resectable hepatocellular carcinoma. The aim of this study was to analyse the significance of CAR in resectable pancreatic cancer. Patients and Methods : 163 patients with curative resection for pancreatic cancer were enrolled in this retrospective study. Cases of non-curative resection were excluded. The CAR was calculated with the preoperative plasma CRP and albumin values, with a cut-off value of 0.06, as calculated in a previous report. Results : Patients in the low CAR group had significantly better overall survival (OS) and disease-free survival (DFS) compared with the high CAR group (P < 0.05). On multivariate analysis, for high CAR, CA19-9 > 300 U /l and receipt of adjuvant chemotherapy were independent risk factors for OS and DFS. High CAR was significantly associated with advanced T stage. Conclusion : The CAR might be a prognostic factor for patients with resectable pancreatic cancer. J. Med. Invest. 68 : 244-248, August, 2021.","Background : The C-reactive protein (CRP)-albumin ratio (CAR) was reported as a prognostic factor of resectable hepatocellular carcinoma. The aim of this study was to analyse the significance of CAR in resectable pancreatic cancer. Patients and Methods : 163 patients with curative resection for pancreatic cancer were enrolled in this retrospective study. Cases of non-curative resection were excluded. The CAR was calculated with the preoperative plasma CRP and albumin values, with a cut-off value of 0.06, as calculated in a previous report. Results : Patients in the low CAR group had significantly better overall survival (OS) and disease-free survival (DFS) compared with the high CAR group (P < 0.05). On multivariate analysis, for high CAR, CA19-9 > 300 U /l and receipt of adjuvant chemotherapy were independent risk factors for OS and DFS. High CAR was significantly associated with advanced T stage. Conclusion : The CAR might be a prognostic factor for patients with resectable pancreatic cancer. J. Med. Invest. 68 : 244-248, August, 2021.","null","null","2021","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.68","No.3.4","244","255","eng","null","null","research_institution","null","null","10.2152/jmi.68.244","1349-6867","null","null","null","null","null"
"Effective in vitro differentiation of adipose-derived stem cells into Schwann-like cells with folic acid supplementation.","Effective in vitro differentiation of adipose-derived stem cells into Schwann-like cells with folic acid supplementation.","Shuhai Chen, Tetsuya Ikemoto, Takuya Tokunaga, Shohei Okikawa, Katsuki Miyazaki, Kazunori Tokuda, Shin-ichiro Yamada, Yu Saitou, Satoru Imura, Yuji Morine, Mitsuo Shimada","Shuhai Chen, Tetsuya Ikemoto, Takuya Tokunaga, Shohei Okikawa, Katsuki Miyazaki, Kazunori Tokuda, Shin-ichiro Yamada, Yu Saitou, Satoru Imura, Yuji Morine, Mitsuo Shimada","null","Peripheral nerve injury (PNI) after pelvic surgery is a common issue with a significant impact on patients. Autologous nerve grafting is the gold standard treatment for PNI, but this technique cannot be applied to fine nerve fibers in the pelvis. Schwann-like cell (SLC) differentiation is a novel therapeutic strategy for this clinical condition. However, the efficiency of SLC differentiation remains unsatisfactory. We modified an SLC differentiation protocol using adipose-derived stem cells (ADSCs) and folic acid. Morphology, gene expression and secretion of neurotrophic factors were examined to assess the differentiation quality and phenotypic characteristics. Our new modified protocol effectively induced a Schwann cell (SC) phenotype in ADSCs as assessed by morphology and expression of SC markers [S100 calcium-binding protein B (S100B), P < 0.01 ; p75 neurotrophic receptor (p75NTR), P < 0.05]. SLCs produced by the new protocol displayed a repair phenotype with decreased expression of ERBB2 and early growth response protein 2 (EGR2) /ROX20 (P < 0.01). Furthermore, our new protocol enhanced both mRNA expression and secretion of nerve growth factors by SLCs (P < 0.01). This protocol enhanced the SC characteristics and functions of ADSC-derived SLCs. This promising protocol requires further research and may contribute to SC-based nerve regeneration. J. Med. Invest. 68 : 347-353, August, 2021.","Peripheral nerve injury (PNI) after pelvic surgery is a common issue with a significant impact on patients. Autologous nerve grafting is the gold standard treatment for PNI, but this technique cannot be applied to fine nerve fibers in the pelvis. Schwann-like cell (SLC) differentiation is a novel therapeutic strategy for this clinical condition. However, the efficiency of SLC differentiation remains unsatisfactory. We modified an SLC differentiation protocol using adipose-derived stem cells (ADSCs) and folic acid. Morphology, gene expression and secretion of neurotrophic factors were examined to assess the differentiation quality and phenotypic characteristics. Our new modified protocol effectively induced a Schwann cell (SC) phenotype in ADSCs as assessed by morphology and expression of SC markers [S100 calcium-binding protein B (S100B), P < 0.01 ; p75 neurotrophic receptor (p75NTR), P < 0.05]. SLCs produced by the new protocol displayed a repair phenotype with decreased expression of ERBB2 and early growth response protein 2 (EGR2) /ROX20 (P < 0.01). Furthermore, our new protocol enhanced both mRNA expression and secretion of nerve growth factors by SLCs (P < 0.01). This protocol enhanced the SC characteristics and functions of ADSC-derived SLCs. This promising protocol requires further research and may contribute to SC-based nerve regeneration. J. Med. Invest. 68 : 347-353, August, 2021.","null","null","2021","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.68","No.3.4","347","353","eng","null","null","research_institution","null","null","10.2152/jmi.68.347","1349-6867","null","null","null","null","null"
"Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma.","Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma.","Yuji Morine, Toru Utsunomiya, Yu Saitou, Shin-ichiro Yamada, Satoru Imura, Tetsuya Ikemoto, Akihiro Kitagawa, Yuta Kobayashi, Seiichiro Takao, Keisuke Kosai, Koshi Mimori, Yasuhito Tanaka, Mitsuo Shimada","Yuji Morine, Toru Utsunomiya, Yu Saitou, Shin-ichiro Yamada, Satoru Imura, Tetsuya Ikemoto, Akihiro Kitagawa, Yuta Kobayashi, Seiichiro Takao, Keisuke Kosai, Koshi Mimori, Yasuhito Tanaka, Mitsuo Shimada","null","Genome-wide analysis is widely applied to detect molecular alterations during oncogenesis and tumor progression. We analyzed DNA methylation profiles of hepatocellular carcinoma (HCC), and investigated the clinical role of most heypermethylated of tumor, encodes T-box 15 (TBX15), which was originally involved in mesodermal differentiation. We conducted a genome-wide analysis of DNA methylation of tumor and non-tumor tissue of 15 patients with HCC, and revealed was the most hypermethylated gene of tumor (Beta-value in tumor tissue = 0.52 compared with non-tumor tissue). Another validation set, which comprised 58 HCC with radical resection, was analyzed to investigate the relationships between tumor phenotype and mRNA expression. mRNA levels in tumor tissues were significantly lower compared with those of nontumor tissues ( < 0.0001). When we assigned a cutoff value = 0.5-fold, the overall survival 5-year survival rates of the low-expression group ( = 17) were significantly shorter compared with those of the high-expression group ( = 41) (43.3% vs. 86.2%, = 0.001). Multivariate analysis identified low expression as an independent prognostic factor for overall and disease-free survival. Therefore, genome-wide DNA methylation profiling indicates that hypermethylation and reduced expression of in tumor tissue represents a potential biomarker for predicting poor survival of patients with HCC.","Genome-wide analysis is widely applied to detect molecular alterations during oncogenesis and tumor progression. We analyzed DNA methylation profiles of hepatocellular carcinoma (HCC), and investigated the clinical role of most heypermethylated of tumor, encodes T-box 15 (TBX15), which was originally involved in mesodermal differentiation. We conducted a genome-wide analysis of DNA methylation of tumor and non-tumor tissue of 15 patients with HCC, and revealed was the most hypermethylated gene of tumor (Beta-value in tumor tissue = 0.52 compared with non-tumor tissue). Another validation set, which comprised 58 HCC with radical resection, was analyzed to investigate the relationships between tumor phenotype and mRNA expression. mRNA levels in tumor tissues were significantly lower compared with those of nontumor tissues ( < 0.0001). When we assigned a cutoff value = 0.5-fold, the overall survival 5-year survival rates of the low-expression group ( = 17) were significantly shorter compared with those of the high-expression group ( = 41) (43.3% vs. 86.2%, = 0.001). Multivariate analysis identified low expression as an independent prognostic factor for overall and disease-free survival. Therefore, genome-wide DNA methylation profiling indicates that hypermethylation and reduced expression of in tumor tissue represents a potential biomarker for predicting poor survival of patients with HCC.","null","null","2020-12-29","Oncotarget","Oncotarget","Vol.11","No.52","4803","4812","eng","null","null","research_institution","null","null","10.18632/oncotarget.27852","1949-2553","null","null","null","null","null"
"Transoral Anvil Delivery System With Tension-Free Method for Esophagojejunostomy After Laparoscopic Total Gastrectomy Prevents The Postoperative Stenosis.","Transoral Anvil Delivery System With Tension-Free Method for Esophagojejunostomy After Laparoscopic Total Gastrectomy Prevents The Postoperative Stenosis.","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Shohei Eto, Toshiaki Yoshimoto","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Shohei Eto, Toshiaki Yoshimoto","null","null","null","null","null","2020-12-13","The American Surgeon","The American Surgeon","null","null","3134820973393","3134820973393","eng","null","null","research_institution","null","null","10.1177/0003134820973393","1555-9823","null","null","null","null","null"
"The inhibitory effect of TU-100 on hepatic stellate cell activation in the tumor microenvironment.","The inhibitory effect of TU-100 on hepatic stellate cell activation in the tumor microenvironment.","Yuuma Wada, Kazunori Tokuda, Yuji Morine, Shohei Okikawa, Shoko Yamashita, Tetsuya Ikemoto, Satoru Imura, Yu Saitou, Shin-ichiro Yamada, Mitsuo Shimada","Yuuma Wada, Kazunori Tokuda, Yuji Morine, Shohei Okikawa, Shoko Yamashita, Tetsuya Ikemoto, Satoru Imura, Yu Saitou, Shin-ichiro Yamada, Mitsuo Shimada","null","The tumor microenvironment is involved in acquiring tumor malignancies of colorectal liver metastasis (CRLM). We have reported that TU-100 (Daikenchuto) suppresses hepatic stellate cell (HSC) activation in obstructive jaundice. In this study, we report new findings as the direct and indirect inhibitory effects of TU-100 on cancer cell growth through the suppression of HSC activation. The HSCs (LX2) were cultured in colon cancer cells (HCT116 and HT29)-conditioned medium (CM) with or without TU-100 treatment (90, 270, 900 g/ml). Activated HSCs (aHSCs) were detected by -SMA and IL-6 mRNA expressions and cytokine arrays of HSC's culture supernatants. Cancer cell growth was analyzed for proliferation and migration ability, compared with TU-100 treatment. To investigate the direct anti-tumor effect of TU-100, cancer cells were cultured in the presence of aHSC-CM and TU-100 (90, 270, 900) or aHSC-CM alone, and assessed autophagosomes, conversion to LC3-II protein, and Beclin-1 mRNA expression. Colon cancer-CM significantly increased -SMA and IL-6 mRNA expressions of aHSC. -SMA and IL-6 mRNA expressions of aHSC, and IL-6 secretions from aHSCs were significantly decreased with TU-100 (270, 900) treatment, compared to colon cancer-CM alone. Compared with normal culture medium, aHSC-CM led to a significantly increased cell number and modified HSC-CM (TU-100; 270, 900) significantly suppressed cancer cell growth and migration. TU-100 (900) treatment induced autophagy and significantly promoted the autophagic cell death. TU-100 inhibited colon cancer cell malignant potential by both suppressing HSC activation and inducing directly autophagy of cancer cells.","The tumor microenvironment is involved in acquiring tumor malignancies of colorectal liver metastasis (CRLM). We have reported that TU-100 (Daikenchuto) suppresses hepatic stellate cell (HSC) activation in obstructive jaundice. In this study, we report new findings as the direct and indirect inhibitory effects of TU-100 on cancer cell growth through the suppression of HSC activation. The HSCs (LX2) were cultured in colon cancer cells (HCT116 and HT29)-conditioned medium (CM) with or without TU-100 treatment (90, 270, 900 g/ml). Activated HSCs (aHSCs) were detected by -SMA and IL-6 mRNA expressions and cytokine arrays of HSC's culture supernatants. Cancer cell growth was analyzed for proliferation and migration ability, compared with TU-100 treatment. To investigate the direct anti-tumor effect of TU-100, cancer cells were cultured in the presence of aHSC-CM and TU-100 (90, 270, 900) or aHSC-CM alone, and assessed autophagosomes, conversion to LC3-II protein, and Beclin-1 mRNA expression. Colon cancer-CM significantly increased -SMA and IL-6 mRNA expressions of aHSC. -SMA and IL-6 mRNA expressions of aHSC, and IL-6 secretions from aHSCs were significantly decreased with TU-100 (270, 900) treatment, compared to colon cancer-CM alone. Compared with normal culture medium, aHSC-CM led to a significantly increased cell number and modified HSC-CM (TU-100; 270, 900) significantly suppressed cancer cell growth and migration. TU-100 (900) treatment induced autophagy and significantly promoted the autophagic cell death. TU-100 inhibited colon cancer cell malignant potential by both suppressing HSC activation and inducing directly autophagy of cancer cells.","null","null","2020-12-08","Oncotarget","Oncotarget","Vol.11","No.49","4593","4604","eng","null","null","research_institution","null","null","10.18632/oncotarget.27835","1949-2553","null","null","null","null","null"
"Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis.","Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis.","Hitoshi Ozawa, Akiyoshi Hirayama, Futaba Shoji, Midori Maruyama, Kumi Suzuki, Hisami Yamanaka-Okumura, Hiroshi Tatano, Yuji Morine, Tomoyoshi Soga, Mitsuo Shimada, Masaru Tomita","Hitoshi Ozawa, Akiyoshi Hirayama, Futaba Shoji, Midori Maruyama, Kumi Suzuki, Hisami Yamanaka-Okumura, Hiroshi Tatano, Yuji Morine, Tomoyoshi Soga, Mitsuo Shimada, Masaru Tomita","null","As the physical properties and functionality of dipeptides differ from those of amino acids, they have attracted attention in metabolomics; however, their functions in vivo have not been clarified in detail. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and its major cause is chronic hepatitis. This study was conducted to explore tumor-specific dipeptide characteristics by performing comprehensive dipeptide analysis in the tumor and surrounding nontumor tissue of patients with HCC. Dipeptides were analyzed by liquid chromatography tandem mass spectrometry and capillary electrophoresis tandem mass spectrometry. Principal component analysis using 236 detected dipeptides showed differences in the dipeptide profiles between nontumor and tumor tissues; however, no clear difference was observed in etiological comparison. In addition, the N- and C-terminal amino acid compositions of the detected dipeptides significantly differed, suggesting the substrate specificity of enzyme proteins, such as peptidase. Furthermore, hepatitis-derived HCC may show a characteristic dipeptide profile even before tumor formation. These results provide insight into HCC pathogenesis and may help identify novel biomarkers for diagnosis.","As the physical properties and functionality of dipeptides differ from those of amino acids, they have attracted attention in metabolomics; however, their functions in vivo have not been clarified in detail. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and its major cause is chronic hepatitis. This study was conducted to explore tumor-specific dipeptide characteristics by performing comprehensive dipeptide analysis in the tumor and surrounding nontumor tissue of patients with HCC. Dipeptides were analyzed by liquid chromatography tandem mass spectrometry and capillary electrophoresis tandem mass spectrometry. Principal component analysis using 236 detected dipeptides showed differences in the dipeptide profiles between nontumor and tumor tissues; however, no clear difference was observed in etiological comparison. In addition, the N- and C-terminal amino acid compositions of the detected dipeptides significantly differed, suggesting the substrate specificity of enzyme proteins, such as peptidase. Furthermore, hepatitis-derived HCC may show a characteristic dipeptide profile even before tumor formation. These results provide insight into HCC pathogenesis and may help identify novel biomarkers for diagnosis.","null","null","2020-11-01","Metabolites","Metabolites","Vol.10","No.11","null","null","eng","null","null","research_institution","null","null","10.3390/metabo10110442","2218-1989","null","null","null","null","null"
"夢を実現し,輝く女性外科医たち-求められるサポート体制と働き方改革- 地方外科から発信するダイバーシティ・インクルージョンを目指した取り組み","夢を実現し,輝く女性外科医たち-求められるサポート体制と働き方改革- 地方外科から発信するダイバーシティ・インクルージョンを目指した取り組み","髙須 千絵, 島田 光生, 吉川 幸造, 宮谷 知彦, 西 正暁, 徳永 卓哉, 柏原 秀也, 武原 悠花子","Chie Takasu, Mitsuo Shimada, Kouzou Yoshikawa, Tomohiko Miyatani, Masaaki Nishi, Takuya Tokunaga, Hideya Kashihara, Yukako Takehara","null","null","null","null","null","2020-11","日本外科学会雑誌","Journal of Japan Surgical Society","Vol.121","No.6","692","693","jpn","null","null","research_institution","null","null","null","0301-4894","null","http://search.jamas.or.jp/link/ui/2021096489","null","null","null"
"【臨床に役立つ胆と膵の解剖学】膵・胆管合流異常の解剖と病型分類","【臨床に役立つ胆と膵の解剖学】膵・胆管合流異常の解剖と病型分類","山田 眞一郎, 森根 裕二, 石橋 広樹, 島田 光生","Shin-ichiro Yamada, Yuji Morine, Hiroki Ishibashi, Mitsuo Shimada","null","膵・胆管合流異常(pancreaticobiliary maljunction:PBM)は,解剖学的に膵管と胆管が十二指腸壁外で合流する先天性の形成異常であり,膵液と胆汁の相互逆流により高率な胆道発癌や膵炎をはじめとしたさまざまな病態を引き起こす.PBMの発生には,腹側膵原基と背側膵原基が癒合する以前の,下部胆管と腹側膵の異常が影響し,背側膵の関与はないと考えられている.PBMの分類においては胆管拡張の有無がとくに重要であり,拡張があるもの(先天性胆道拡張症)とないもの(胆道非拡張型)に分けられ,さらに胆管と膵管の合流形式などによってこれまでいくつかの分類が報告されている.また,共通管が6mm以上で合流部に括約筋作用が及ぶ例は膵胆管高位合流と定義され,PBMとは異なる病態として扱われる.今後の課題として,胆管拡張の定義や型分類の統一,高位合流との鑑別があげられる.(著者抄録)","膵・胆管合流異常(pancreaticobiliary maljunction:PBM)は,解剖学的に膵管と胆管が十二指腸壁外で合流する先天性の形成異常であり,膵液と胆汁の相互逆流により高率な胆道発癌や膵炎をはじめとしたさまざまな病態を引き起こす.PBMの発生には,腹側膵原基と背側膵原基が癒合する以前の,下部胆管と腹側膵の異常が影響し,背側膵の関与はないと考えられている.PBMの分類においては胆管拡張の有無がとくに重要であり,拡張があるもの(先天性胆道拡張症)とないもの(胆道非拡張型)に分けられ,さらに胆管と膵管の合流形式などによってこれまでいくつかの分類が報告されている.また,共通管が6mm以上で合流部に括約筋作用が及ぶ例は膵胆管高位合流と定義され,PBMとは異なる病態として扱われる.今後の課題として,胆管拡張の定義や型分類の統一,高位合流との鑑別があげられる.(著者抄録)","null","null","2020-11","胆と膵","Journal of Biliary Tract & Pancreas","Vol.41","No.11","1085","1092","jpn","null","null","research_institution","null","null","null","0388-9408","null","http://search.jamas.or.jp/link/ui/2021054913","null","null","null"
"Impact of sidedness of colorectal cancer on tumor immunity.","Impact of sidedness of colorectal cancer on tumor immunity.","Chie Takasu, Masaaki Nishi, Kouzou Yoshikawa, Takuya Tokunaga, Hideya Kashihara, Toshiaki Yoshimoto, Mitsuo Shimada","Chie Takasu, Masaaki Nishi, Kouzou Yoshikawa, Takuya Tokunaga, Hideya Kashihara, Toshiaki Yoshimoto, Mitsuo Shimada","null","Clinical and molecular characteristics differ between right-sided and left-sided colorectal cancer (CRC). This study aimed to clarify the correlation between CRC sidedness and tumor immunity. A total of 102 patients who underwent curative colectomy for stage II/III CRC were included in this study. The expression of programmed cell death (PD)-1, PD1-ligand 1 (PD-L1), forkhead box P3 (Foxp3), transforming growth factor (TGF)-β, and indoleamine-pyrrole 2,3-dioxygenase (IDO) were examined using immunohistochemistry and the relationships between sidedness and several prognostic factors were examined. Clinicopathological factors were not significantly different between right- and left-sided CRC. The tumor immunity-related molecule PD-L1 was more highly expressed in right-sided than in left-sided CRC (62.9% vs. 30.6%, p<0.01). No significant difference was found in overall survival (OS) and disease-free survival (DFS) by sidedness. PD-1 and Foxp3 expression were significant prognostic factors for OS. Lymph node metastasis (N), lymphatic invasion (ly), and PD-L1 expression were significant prognostic factors for DFS. In right-sided CRC, IDO-positive patients had a poor OS (p<0.05), and IDO was the only independent prognostic indicator for OS. N and venous invasion were identified as independent prognostic indicators for DFS. In left-sided CRC, univariate analysis identified PD-1, PD-L1, and Foxp3 expression as significant predictors of poor OS. Multivariate analysis confirmed PD-L1 expression as an independent prognostic indicator. N, ly, and PD-L1 expression levels were identified as significant predictors of poor DFS. The prognostic factors were IDO in right-sided CRC and PD-L1 and Foxp3 in left-sided CRC. These findings indicated that tumor immunity might play different roles depending upon sidedness. Tumor location may be an important factor to consider when assessing immune response and therapeutic decisions in CRC patients.","Clinical and molecular characteristics differ between right-sided and left-sided colorectal cancer (CRC). This study aimed to clarify the correlation between CRC sidedness and tumor immunity. A total of 102 patients who underwent curative colectomy for stage II/III CRC were included in this study. The expression of programmed cell death (PD)-1, PD1-ligand 1 (PD-L1), forkhead box P3 (Foxp3), transforming growth factor (TGF)-β, and indoleamine-pyrrole 2,3-dioxygenase (IDO) were examined using immunohistochemistry and the relationships between sidedness and several prognostic factors were examined. Clinicopathological factors were not significantly different between right- and left-sided CRC. The tumor immunity-related molecule PD-L1 was more highly expressed in right-sided than in left-sided CRC (62.9% vs. 30.6%, p<0.01). No significant difference was found in overall survival (OS) and disease-free survival (DFS) by sidedness. PD-1 and Foxp3 expression were significant prognostic factors for OS. Lymph node metastasis (N), lymphatic invasion (ly), and PD-L1 expression were significant prognostic factors for DFS. In right-sided CRC, IDO-positive patients had a poor OS (p<0.05), and IDO was the only independent prognostic indicator for OS. N and venous invasion were identified as independent prognostic indicators for DFS. In left-sided CRC, univariate analysis identified PD-1, PD-L1, and Foxp3 expression as significant predictors of poor OS. Multivariate analysis confirmed PD-L1 expression as an independent prognostic indicator. N, ly, and PD-L1 expression levels were identified as significant predictors of poor DFS. The prognostic factors were IDO in right-sided CRC and PD-L1 and Foxp3 in left-sided CRC. These findings indicated that tumor immunity might play different roles depending upon sidedness. Tumor location may be an important factor to consider when assessing immune response and therapeutic decisions in CRC patients.","null","null","2020-10-12","PLoS ONE","PLoS ONE","Vol.15","No.10","e0240408","e0240408","eng","null","null","research_institution","null","null","10.1371/journal.pone.0240408","1932-6203","null","null","null","null","null"
"同時性・異時性に多発した小児脂肪芽腫の1例","同時性・異時性に多発した小児脂肪芽腫の1例","横田 典子, 石橋 広樹, 森 大樹, 島田 光生, 遠藤 秀子, 坂東 良美","Noriko Yokota, Hiroki Ishibashi, Hiroki Mori, Mitsuo Shimada, 遠藤 秀子, Yoshimi Bando","null","症例は3歳,男児.両側鼠径部外側と右背部の紡錘状の皮下腫瘤を認めたため,当科紹介受診となった.外来で経過観察を行っていたが,その後,左腋窩部及び右季肋部にも同様の皮下腫瘤が出現した.非典型的に多発し,悪性の可能性も否定できなかったため,背部皮下腫瘤を摘出し,脂肪芽腫と診断した.残りの4ヶ所を追加で切除したところ,最初の病変と同様に,脂肪芽細胞や小型の脂肪細胞を認め,同時・異時性に多発した脂肪芽腫と診断した.術後,約1年半が経過しているが,新たな腫瘤の発生や再発は認めていない.脂肪芽腫では,発見後の早期摘出が一般的であるが,稀に本症例のような多発例が存在することも念頭におき,早期摘出後も慎重な経過観察が必要であると思われた.(著者抄録)","症例は3歳,男児.両側鼠径部外側と右背部の紡錘状の皮下腫瘤を認めたため,当科紹介受診となった.外来で経過観察を行っていたが,その後,左腋窩部及び右季肋部にも同様の皮下腫瘤が出現した.非典型的に多発し,悪性の可能性も否定できなかったため,背部皮下腫瘤を摘出し,脂肪芽腫と診断した.残りの4ヶ所を追加で切除したところ,最初の病変と同様に,脂肪芽細胞や小型の脂肪細胞を認め,同時・異時性に多発した脂肪芽腫と診断した.術後,約1年半が経過しているが,新たな腫瘤の発生や再発は認めていない.脂肪芽腫では,発見後の早期摘出が一般的であるが,稀に本症例のような多発例が存在することも念頭におき,早期摘出後も慎重な経過観察が必要であると思われた.(著者抄録)","null","null","2020-10","日本小児外科学会雑誌","Journal of the Japanese Society of Pediatric Surgeons","Vol.56","No.6","988","991","jpn","null","null","research_institution","null","null","10.11164/jjsps.56.6_988","0288-609X","null","http://search.jamas.or.jp/link/ui/2021006247","null","null","null"
"【そこが知りたいシリーズ:手術で必要な局所解剖(腹壁・後腹膜・泌尿器・腫瘍編)】大腿ヘルニア","【そこが知りたいシリーズ:手術で必要な局所解剖(腹壁・後腹膜・泌尿器・腫瘍編)】大腿ヘルニア","石橋 広樹, 横田 典子, 森 大樹, 島田 光生","Hiroki Ishibashi, Noriko Yokota, Hiroki Mori, Mitsuo Shimada","null","null","null","null","null","2020-10","小児外科","Japanese Journal of Pediatric Surgery","Vol.52","No.10","1049","1053","jpn","null","null","research_institution","null","null","null","0385-6313","null","http://search.jamas.or.jp/link/ui/2021019652","null","null","null"
"Adipose Tissue From Type 1 Diabetes Mellitus Patients Can Be Used to Generate Insulin-Producing Cells.","Adipose Tissue From Type 1 Diabetes Mellitus Patients Can Be Used to Generate Insulin-Producing Cells.","Tetsuya Ikemoto, Kazunori Tokuda, Yuuma Wada, Luping Gao, Katsuki Miyazaki, Shin-ichiro Yamada, Yu Saitou, Satoru Imura, Yuji Morine, Mitsuo Shimada","Tetsuya Ikemoto, Kazunori Tokuda, Yuuma Wada, Luping Gao, Katsuki Miyazaki, Shin-ichiro Yamada, Yu Saitou, Satoru Imura, Yuji Morine, Mitsuo Shimada","null","We aimed to determine whether responsive insulin-producing cells (IPCs) could be generated from adipose-derived stem cells (ADSCs) isolated from patients with type 1 diabetes mellitus (T1DM). We isolated ADSCs from adipose tissue of 4 patients (one patient with T1DM and 3 nondiabetic patients), who underwent surgery and differentiated them into IPCs with using a 2-step xeno-antigen free, 3-dimensional culture method. Characteristics of isolated ADSCs, in vitro cell quality, programmed cell death ligand-1 (PDL-1) expression, and transplantation into streptozotocin induced diabetic nude mice were investigated. Adipose-derived stem cells from T1DM patients and commercially obtained ADSCs showed the same surface markers; CD31CD34CD45CD90CD105CD146. Moreover, the generated IPCs at day 21 demonstrated appropriate autonomous insulin secretion (stimulation index, 3.5; standard deviation, 0.8). Nonfasting blood glucose concentrations of IPC-transplanted mice were normal at 30 days. The normalized rate of IPC-transplanted mice was significantly higher than that of the sham-operated group (P < 0.05). Insulin-producing cells generated from T1DM adipose tissue expressed high levels of PDL-1. Insulin-producing cells obtained from adipose tissue of T1DM patients are capable of secreting insulin long-term and achieve normoglycemia after transplantation. Expression of PDL-1 suggests the potential for immune circumvention.","We aimed to determine whether responsive insulin-producing cells (IPCs) could be generated from adipose-derived stem cells (ADSCs) isolated from patients with type 1 diabetes mellitus (T1DM). We isolated ADSCs from adipose tissue of 4 patients (one patient with T1DM and 3 nondiabetic patients), who underwent surgery and differentiated them into IPCs with using a 2-step xeno-antigen free, 3-dimensional culture method. Characteristics of isolated ADSCs, in vitro cell quality, programmed cell death ligand-1 (PDL-1) expression, and transplantation into streptozotocin induced diabetic nude mice were investigated. Adipose-derived stem cells from T1DM patients and commercially obtained ADSCs showed the same surface markers; CD31CD34CD45CD90CD105CD146. Moreover, the generated IPCs at day 21 demonstrated appropriate autonomous insulin secretion (stimulation index, 3.5; standard deviation, 0.8). Nonfasting blood glucose concentrations of IPC-transplanted mice were normal at 30 days. The normalized rate of IPC-transplanted mice was significantly higher than that of the sham-operated group (P < 0.05). Insulin-producing cells generated from T1DM adipose tissue expressed high levels of PDL-1. Insulin-producing cells obtained from adipose tissue of T1DM patients are capable of secreting insulin long-term and achieve normoglycemia after transplantation. Expression of PDL-1 suggests the potential for immune circumvention.","null","null","2020-10","Pancreas","Pancreas","Vol.49","No.9","1225","1231","eng","null","null","research_institution","null","null","10.1097/MPA.0000000000001663","1536-4828","null","null","null","null","null"
"HIF-1 expression in liver metastasis but not primary colorectal cancer is associated with prognosis of patients with colorectal liver metastasis.","HIF-1 expression in liver metastasis but not primary colorectal cancer is associated with prognosis of patients with colorectal liver metastasis.","Yuuma Wada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Chie Takasu, Shin-ichiro Yamada, Mitsuo Shimada","Yuuma Wada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Chie Takasu, Shin-ichiro Yamada, Mitsuo Shimada","null","The role of hypoxia-inducible factor-1 (HIF-1 ) in primary colorectal cancer (CRC) and colorectal liver metastasis (CRLM) has remained unclear. The aim of this study was to investigate HIF-1 expression and its association with prognosis in patients with CRLM with a focus on hepatic stellate cells (HSCs). Colon cancer cells were cultured in HSC-conditioned medium (CM), and HIF-1 expression and cell migration were analyzed. Seventy-five patients with CRLM who underwent an initial curative hepatectomy were enrolled. We examined HIF-1 expressions and patient prognosis between primary CRCs and the matched liver metastatic specimens. Activated HSCs induced HIF-1 mRNA and protein expression in colon cancer cells (p < 0.01) and promoted cell migration (p < 0.01). The positive rates of HIF-1 expression in primary CRCs and liver metastases were 68.0 and 72.0%, respectively. There were no differences in overall (OS) and disease-free survival (DFS) of HIF-1 expression in primary CRC. However, HIF-1 expression in liver metastasis correlated to poor prognosis in both OS and DFS. Furthermore, patients with HIF-1 positive expression in liver metastasis had poor prognosis. HIF-1 expression in liver metastasis determines poor prognosis of CRLM patients. HSCs might play a key role in aggressive phenotypes of tumor cells.","The role of hypoxia-inducible factor-1 (HIF-1 ) in primary colorectal cancer (CRC) and colorectal liver metastasis (CRLM) has remained unclear. The aim of this study was to investigate HIF-1 expression and its association with prognosis in patients with CRLM with a focus on hepatic stellate cells (HSCs). Colon cancer cells were cultured in HSC-conditioned medium (CM), and HIF-1 expression and cell migration were analyzed. Seventy-five patients with CRLM who underwent an initial curative hepatectomy were enrolled. We examined HIF-1 expressions and patient prognosis between primary CRCs and the matched liver metastatic specimens. Activated HSCs induced HIF-1 mRNA and protein expression in colon cancer cells (p < 0.01) and promoted cell migration (p < 0.01). The positive rates of HIF-1 expression in primary CRCs and liver metastases were 68.0 and 72.0%, respectively. There were no differences in overall (OS) and disease-free survival (DFS) of HIF-1 expression in primary CRC. However, HIF-1 expression in liver metastasis correlated to poor prognosis in both OS and DFS. Furthermore, patients with HIF-1 positive expression in liver metastasis had poor prognosis. HIF-1 expression in liver metastasis determines poor prognosis of CRLM patients. HSCs might play a key role in aggressive phenotypes of tumor cells.","null","null","2020-09-07","World Journal of Surgical Oncology","World Journal of Surgical Oncology","Vol.18","No.1","241","241","eng","null","null","research_institution","null","null","10.1186/s12957-020-02012-5","1477-7819","null","null","null","null","null"
"Effectiveness of repeat surgery for recurrence after primary hepatectomy in patients with intrahepatic cholangiocarcinoma.","Effectiveness of repeat surgery for recurrence after primary hepatectomy in patients with intrahepatic cholangiocarcinoma.","Kazunori Tokuda, Yuji Morine, Yu Saitou, Shin-ichiro Yamada, Katsuki Miyazaki, Shoko Yamashita, Shohei Okikawa, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada","Kazunori Tokuda, Yuji Morine, Yu Saitou, Shin-ichiro Yamada, Katsuki Miyazaki, Shoko Yamashita, Shohei Okikawa, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada","null","Intrahepatic cholangiocarcinoma (IHCC) has a poor prognosis, and surgery remains the only effective treatment. However, tumor recurrence after primary hepatectomy is common. We examined the significance of repeat surgery for IHCC. We collected data for all patients with IHCC between 1992 and 2018 (n = 67) in our database. Fifty-three (79.1%) of all 67 patients experienced recurrence after primary hepatectomy and we analyzed data for those 53 recurrent patients. We divided recurrent patients into a repeat surgery group (n = 9), chemotherapy group (n = 19), and best supportive care group (n = 25). We analyzed differences in patients' clinicopathological factors, including prognosis, between the three groups. The IHCC recurrence rate after hepatectomy in our institution was 79.1%. Of the 53 patients with recurrence, nine underwent repeat surgery (17.0%). The characteristics of the patients undergoing repeat surgery was lower stage at primary hepatectomy. Recurrence sites in the repeat surgery group were liver (n = 6), lung (n = 2), and adrenal gland (n = 1), as a single nodule. The period between primary hepatectomy and recurrence was comparatively longer in the repeat surgery group, at 1.8 years. The prognosis in patients undergoing repeat surgery was significantly better compared with the other groups. Not undergoing repeat surgery (hazard ratio: 5.506; p = 0.0077) and positive lymph node metastasis (hazard ratio: 2.207; p = 0.0242) were independent poor prognostic factors. Repeat surgery should be considered in patients with IHCC with a single recurrence site and negative lymph node metastasis at primary surgery and at least more than 6 months of disease-free period after primary surgery.","Intrahepatic cholangiocarcinoma (IHCC) has a poor prognosis, and surgery remains the only effective treatment. However, tumor recurrence after primary hepatectomy is common. We examined the significance of repeat surgery for IHCC. We collected data for all patients with IHCC between 1992 and 2018 (n = 67) in our database. Fifty-three (79.1%) of all 67 patients experienced recurrence after primary hepatectomy and we analyzed data for those 53 recurrent patients. We divided recurrent patients into a repeat surgery group (n = 9), chemotherapy group (n = 19), and best supportive care group (n = 25). We analyzed differences in patients' clinicopathological factors, including prognosis, between the three groups. The IHCC recurrence rate after hepatectomy in our institution was 79.1%. Of the 53 patients with recurrence, nine underwent repeat surgery (17.0%). The characteristics of the patients undergoing repeat surgery was lower stage at primary hepatectomy. Recurrence sites in the repeat surgery group were liver (n = 6), lung (n = 2), and adrenal gland (n = 1), as a single nodule. The period between primary hepatectomy and recurrence was comparatively longer in the repeat surgery group, at 1.8 years. The prognosis in patients undergoing repeat surgery was significantly better compared with the other groups. Not undergoing repeat surgery (hazard ratio: 5.506; p = 0.0077) and positive lymph node metastasis (hazard ratio: 2.207; p = 0.0242) were independent poor prognostic factors. Repeat surgery should be considered in patients with IHCC with a single recurrence site and negative lymph node metastasis at primary surgery and at least more than 6 months of disease-free period after primary surgery.","null","null","2020-08","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.25","No.12","2083","2089","eng","null","null","research_institution","null","null","10.1007/s10147-020-01775-x","1437-7772","null","null","null","null","null"
"Predictability of postoperative recurrence on hepatocellular carcinoma through data mining method.","Predictability of postoperative recurrence on hepatocellular carcinoma through data mining method.","Shuichi Iwahashi, AHMAD AMMAR GHAIBEH, Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Jun Hirose","Shuichi Iwahashi, AHMAD AMMAR GHAIBEH, Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Jun Hirose","null","Hepatocellular carcinoma (HCC) is a highly lethal tumor and the majority of postoperative patients experience recurrence. In the present study, we focus on the predictability of postoperative recurrence on HCC through the data mining method. In total, 323 patients with HCC who underwent hepatic resection were included in the present study, 156 of whom suffered from cancer recurrence. Clinicopathological data including prognosis were analyzed using the data mining method for the predictability of postoperative recurrence on HCC. The resulting alternating decision tree (ADT) was described using data mining method. This tree was validated using a 10-fold cross validation process. The average and standard deviation of the accuracy, sensitivity, and specificity were 69.0 8.2, 59.7 14.5 and 77.7 10.2%, respectively. The identified postoperative recurrence factors were age, viral hepatitis, stage, GOT and T-cholesterol. Data mining method could identify the factors associated at different levels of significance with postoperative recurrence of HCC. These factors could help to predict the postoperative recurrence of HCC.","Hepatocellular carcinoma (HCC) is a highly lethal tumor and the majority of postoperative patients experience recurrence. In the present study, we focus on the predictability of postoperative recurrence on HCC through the data mining method. In total, 323 patients with HCC who underwent hepatic resection were included in the present study, 156 of whom suffered from cancer recurrence. Clinicopathological data including prognosis were analyzed using the data mining method for the predictability of postoperative recurrence on HCC. The resulting alternating decision tree (ADT) was described using data mining method. This tree was validated using a 10-fold cross validation process. The average and standard deviation of the accuracy, sensitivity, and specificity were 69.0 8.2, 59.7 14.5 and 77.7 10.2%, respectively. The identified postoperative recurrence factors were age, viral hepatitis, stage, GOT and T-cholesterol. Data mining method could identify the factors associated at different levels of significance with postoperative recurrence of HCC. These factors could help to predict the postoperative recurrence of HCC.","null","null","2020-08-14","Molecular and Clinical Oncology","Molecular and Clinical Oncology","Vol.13","No.5","46","46","eng","null","null","research_institution","null","null","10.3892/mco.2020.2116","2049-9450","null","null","null","null","null"
"Usefulness of an ICG fluorescence catheter system in TaTME for avoiding intraoperative urethral injury.","Usefulness of an ICG fluorescence catheter system in TaTME for avoiding intraoperative urethral injury.","Shogo Oota, Masaaki Nishi, Takuya Tokunaga, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Hideya Kashihara, Chie Takasu, Daichi Ishikawa, Mitsuo Shimada","Shogo Oota, Masaaki Nishi, Takuya Tokunaga, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Hideya Kashihara, Chie Takasu, Daichi Ishikawa, Mitsuo Shimada","null","Sometimes intraoperative urethral injury occurs in Transanal total mesorectal excision (TaTME). The aim of this study is to investigate the usefulness of indocyanine green (ICG) fluorescent catheter system for avoiding intraoperative urethral injury in TaTME in experimental model. A urethral catheter was filled with the mixture of albumin and ICG and raw hams were applied in layers as the surrogate model of rectourethral muscle. The detectability of ICG fluorescence in this catheter was investigated by using laparoscope-type fluorescence camera system. Fluorescence was detected when ICG was mixed with albumin or peripheral blood. ICG fluorescence could be detected within 4 mm depth of layered raw hams as the surrogate model. Quantitative analysis of the picture detected that ICG fluorescence plateaued in lower concentration than that of serum. ICG fluorescent catheter system may be useful for avoiding intraoperative urethral injury in TaTME. J. Med. Invest. 67 : 285-288, August, 2020.","Sometimes intraoperative urethral injury occurs in Transanal total mesorectal excision (TaTME). The aim of this study is to investigate the usefulness of indocyanine green (ICG) fluorescent catheter system for avoiding intraoperative urethral injury in TaTME in experimental model. A urethral catheter was filled with the mixture of albumin and ICG and raw hams were applied in layers as the surrogate model of rectourethral muscle. The detectability of ICG fluorescence in this catheter was investigated by using laparoscope-type fluorescence camera system. Fluorescence was detected when ICG was mixed with albumin or peripheral blood. ICG fluorescence could be detected within 4 mm depth of layered raw hams as the surrogate model. Quantitative analysis of the picture detected that ICG fluorescence plateaued in lower concentration than that of serum. ICG fluorescent catheter system may be useful for avoiding intraoperative urethral injury in TaTME. J. Med. Invest. 67 : 285-288, August, 2020.","null","null","2020-08","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.67","No.3.4","285","288","eng","null","null","research_institution","null","null","10.2152/jmi.67.285","1349-6867","null","null","null","null","null"
"Trans-abdominal Pre-peritoneal (TAPP) Inguinal Hernia Repair with Liquid-injection and Gauze Dissection.","Trans-abdominal Pre-peritoneal (TAPP) Inguinal Hernia Repair with Liquid-injection and Gauze Dissection.","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Toshiaki Yoshimoto","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Toshiaki Yoshimoto","null","Purpose : This report describes a novel technique for trans-abdominal pre-peritoneal (TAPP) inguinal hernia repair using liquid injection and gauze dissection. Methods : Twenty-five cases underwent TAPP inguinal hernia repair with liquid-injection and gauze dissection. Before the initial peritoneal incision, liquid injection was performed percutaneously into the pre-peritoneal space at the outside of the internal inguinal ring and the inside of the seminal duct. Especially, at the inside of the seminal duct, the liquid was injected into the space between the superficial and deep lobe of pre-peritoneal fascia. Gauze was effectively used to dissect this liquid-injected space. Results : In comparison with the cases of inguinal hernia repair without liquid-injection and gauze dissection, the cases who underwent TAPP inguinal hernia repair with liquid-injection and gauze dissection experienced shorter operation times and no complications or recurrence. Conclusions : TAPP inguinal hernia repair with liquid-injection and gauze dissection appears to be a safe and feasible procedure. J. Med. Invest. 67 : 271-273, August, 2020.","Purpose : This report describes a novel technique for trans-abdominal pre-peritoneal (TAPP) inguinal hernia repair using liquid injection and gauze dissection. Methods : Twenty-five cases underwent TAPP inguinal hernia repair with liquid-injection and gauze dissection. Before the initial peritoneal incision, liquid injection was performed percutaneously into the pre-peritoneal space at the outside of the internal inguinal ring and the inside of the seminal duct. Especially, at the inside of the seminal duct, the liquid was injected into the space between the superficial and deep lobe of pre-peritoneal fascia. Gauze was effectively used to dissect this liquid-injected space. Results : In comparison with the cases of inguinal hernia repair without liquid-injection and gauze dissection, the cases who underwent TAPP inguinal hernia repair with liquid-injection and gauze dissection experienced shorter operation times and no complications or recurrence. Conclusions : TAPP inguinal hernia repair with liquid-injection and gauze dissection appears to be a safe and feasible procedure. J. Med. Invest. 67 : 271-273, August, 2020.","null","null","2020-08","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.67","No.3.4","271","273","eng","null","null","research_institution","null","null","10.2152/jmi.67.271","1349-6867","null","null","null","null","null"
"Desmoid-type fibromatosis difficult to distinguish from GIST : A case report.","Desmoid-type fibromatosis difficult to distinguish from GIST : A case report.","Yukako Takehara, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Toshiaki Yoshimoto, Mitsuo Shimada","Yukako Takehara, Kouzou Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Toshiaki Yoshimoto, Mitsuo Shimada","null","Background : Desmoid-type fibromatosis is a very rare disease that has no characteristic image findings, so it is often difficult to differentiate from gastrointestinal stromal tumor (GIST). A case of desmoid-type fibromatosis that was difficult to differentiate from GIST is reported. The decisive factor in the diagnosis was positive nuclear immunostaining for β-catenin nucleus. Case presentation : A man is his 30s had no significant past medical history, including no abdominal surgery. A medical check-up found a large tumor in the right lateral abdomen. After some examinations, a preoperative diagnosis of GIST was made, and open ileocecal resection was performed. However, the final diagnosis based on the pathological findings was desmoid-type fibromatosis. Conclusions : We should consider desmoid-type fibromatosis when we find a large abdominal mass, but it may be difficult to diagnose based only on imaging findings. Immunohistochemical examination of the specimen may make the diagnosis. J. Med. Invest. 67 : 375-377, August, 2020.","Background : Desmoid-type fibromatosis is a very rare disease that has no characteristic image findings, so it is often difficult to differentiate from gastrointestinal stromal tumor (GIST). A case of desmoid-type fibromatosis that was difficult to differentiate from GIST is reported. The decisive factor in the diagnosis was positive nuclear immunostaining for β-catenin nucleus. Case presentation : A man is his 30s had no significant past medical history, including no abdominal surgery. A medical check-up found a large tumor in the right lateral abdomen. After some examinations, a preoperative diagnosis of GIST was made, and open ileocecal resection was performed. However, the final diagnosis based on the pathological findings was desmoid-type fibromatosis. Conclusions : We should consider desmoid-type fibromatosis when we find a large abdominal mass, but it may be difficult to diagnose based only on imaging findings. Immunohistochemical examination of the specimen may make the diagnosis. J. Med. Invest. 67 : 375-377, August, 2020.","null","null","2020-08","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.67","No.3.4","375","377","eng","null","null","research_institution","null","null","10.2152/jmi.67.375","1349-6867","null","null","null","null","null"
"Impact of using a perioperative artificial endocrine pancreas in pancreatic resection.","Impact of using a perioperative artificial endocrine pancreas in pancreatic resection.","Toshiaki Yoshimoto, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Yu Saitou, Shin-ichiro Yamada, Katsuki Miyazaki, Yukako Takehara, Mitsuo Shimada","Toshiaki Yoshimoto, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Yu Saitou, Shin-ichiro Yamada, Katsuki Miyazaki, Yukako Takehara, Mitsuo Shimada","null","Pancreatectomy causes both hyperglycemia, secondary to surgical stress, and pancreatic diabetes, which leads to difficult-to-control postoperative blood glucose levels. We investigated whether using an artificial pancreas perioperatively to provide appropriate blood glucose control could reduce postoperative complications following pancreatectomy. We retrospectively enrolled 52 patients who underwent pancreatectomy at Tokushima University Hospital from 2015 to 2019. The most recent 26/52 patients received perioperative blood glucose control using an artificial pancreas. Postoperative blood glucose control with manual insulin injections based on a sliding scale was performed in the earlier 26 patients (controls). We compared surgical outcomes between the artificial pancreas group and the control group. There was no significant difference in patients' white blood cell or neutrophil counts, prognostic nutritional index, neutrophil-lymphocyte ratio, and C-reactive protein-to-albumin ratio on postoperative day 1; however, lymphocyte counts were higher in the artificial pancreas group. The number of serious complications of Clavien-Dindo grade >IIIa was significantly lower in the artificial pancreas group ( < .05). Using an artificial pancreas for perioperative blood glucose control in patients undergoing pancreatectomy decreased the number of serious complications through proper management of blood glucose levels without hypoglycemia, and may influence peripheral lymphocytes.","Pancreatectomy causes both hyperglycemia, secondary to surgical stress, and pancreatic diabetes, which leads to difficult-to-control postoperative blood glucose levels. We investigated whether using an artificial pancreas perioperatively to provide appropriate blood glucose control could reduce postoperative complications following pancreatectomy. We retrospectively enrolled 52 patients who underwent pancreatectomy at Tokushima University Hospital from 2015 to 2019. The most recent 26/52 patients received perioperative blood glucose control using an artificial pancreas. Postoperative blood glucose control with manual insulin injections based on a sliding scale was performed in the earlier 26 patients (controls). We compared surgical outcomes between the artificial pancreas group and the control group. There was no significant difference in patients' white blood cell or neutrophil counts, prognostic nutritional index, neutrophil-lymphocyte ratio, and C-reactive protein-to-albumin ratio on postoperative day 1; however, lymphocyte counts were higher in the artificial pancreas group. The number of serious complications of Clavien-Dindo grade >IIIa was significantly lower in the artificial pancreas group ( < .05). Using an artificial pancreas for perioperative blood glucose control in patients undergoing pancreatectomy decreased the number of serious complications through proper management of blood glucose levels without hypoglycemia, and may influence peripheral lymphocytes.","null","null","2020-07-18","Annals of Gastroenterological Surgery","Annals of Gastroenterological Surgery","Vol.4","No.5","591","596","eng","null","null","research_institution","null","null","10.1002/ags3.12374","2475-0328","null","null","null","null","null"
"Role of Central Hypo-enhancement in the Hepatic Arterial Phase of Dynamic Computed Tomography in Patients with Mass-Forming Intrahepatic Cholangiocarcinoma.","Role of Central Hypo-enhancement in the Hepatic Arterial Phase of Dynamic Computed Tomography in Patients with Mass-Forming Intrahepatic Cholangiocarcinoma.","Hiroki Teraoku, Yuji Morine, Naoto Uyama, Tetsuya Ikemoto, Shuichi Iwahashi, Yu Saitou, Chie Takasu, Satoru Imura, Masafumi Harada, Mitsuo Shimada","Hiroki Teraoku, Yuji Morine, Naoto Uyama, Tetsuya Ikemoto, Shuichi Iwahashi, Yu Saitou, Chie Takasu, Satoru Imura, Masafumi Harada, Mitsuo Shimada","null","The enhancement pattern in the hepatic arterial phase (HAP) of dynamic computed tomography (CT) is reportedly a prognostic marker in patients with intrahepatic cholangiocarcinoma (IHCC). This study was performed to clarify the significance of central hypo-enhancement in the HAP in patients with mass-forming IHCC. Forty patients who had undergone initial surgical resection for mass-forming IHCC were enrolled. The dynamic CT was scanned 40 s after contrast agent injection as the HAP. A radiologist classified the patients into three groups based on the vascular pattern: the hyper-enhancement group (Hyper group), rim-enhancement group (Rim group), and hypo-enhancement group (Hypo group). The surgical specimens were immunohistochemically stained for hypoxia-inducible factor 1 (HIF-1). The correlation with clinicopathological findings and HIF-1 expression was investigated. The Hyper, Rim, and Hypo groups comprised 8, 7, and 25 patients, respectively. There were no significant correlations between the groups and clinicopathological factors. Overall survival (OS) was significantly worse in the Hypo than in the Hyper group (p = 0.03). OS was also significantly worse in the Rim +ypo group (i.e., hypo-enhancement in the central tumor) than in the Hyper group (p = 0.04). Furthermore, inclusion in the Rim +ypo group was a prognostic factor for OS (hazard ratio 6.68). High HIF-1 expression in the central part of the tumor was correlated with central hypo-enhancement (Hyper group: 25% and Rim +ypo group: 72%). Central hypo-enhancement was a prognostic factor in patients with IHCC. The high malignant potential of tumors with central hypo-enhancement might be associated with HIF-1 upregulation.","The enhancement pattern in the hepatic arterial phase (HAP) of dynamic computed tomography (CT) is reportedly a prognostic marker in patients with intrahepatic cholangiocarcinoma (IHCC). This study was performed to clarify the significance of central hypo-enhancement in the HAP in patients with mass-forming IHCC. Forty patients who had undergone initial surgical resection for mass-forming IHCC were enrolled. The dynamic CT was scanned 40 s after contrast agent injection as the HAP. A radiologist classified the patients into three groups based on the vascular pattern: the hyper-enhancement group (Hyper group), rim-enhancement group (Rim group), and hypo-enhancement group (Hypo group). The surgical specimens were immunohistochemically stained for hypoxia-inducible factor 1 (HIF-1). The correlation with clinicopathological findings and HIF-1 expression was investigated. The Hyper, Rim, and Hypo groups comprised 8, 7, and 25 patients, respectively. There were no significant correlations between the groups and clinicopathological factors. Overall survival (OS) was significantly worse in the Hypo than in the Hyper group (p = 0.03). OS was also significantly worse in the Rim +ypo group (i.e., hypo-enhancement in the central tumor) than in the Hyper group (p = 0.04). Furthermore, inclusion in the Rim +ypo group was a prognostic factor for OS (hazard ratio 6.68). High HIF-1 expression in the central part of the tumor was correlated with central hypo-enhancement (Hyper group: 25% and Rim +ypo group: 72%). Central hypo-enhancement was a prognostic factor in patients with IHCC. The high malignant potential of tumors with central hypo-enhancement might be associated with HIF-1 upregulation.","null","null","2020-07","World Journal of Surgery","World Journal of Surgery","Vol.44","No.7","2350","2358","eng","null","null","research_institution","null","null","10.1007/s00268-020-05456-8","1432-2323","null","null","null","null","null"
"Pancreatoduodenectomy co-morbid with celiac axis compression syndrome: a report of three cases.","Pancreatoduodenectomy co-morbid with celiac axis compression syndrome: a report of three cases.","Katsuki Miyazaki, Yuji Morine, Yu Saitou, Shin-ichiro Yamada, Kazunori Tokuda, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada","Katsuki Miyazaki, Yuji Morine, Yu Saitou, Shin-ichiro Yamada, Kazunori Tokuda, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada","null","Celiac axis compression syndrome (CACS) is a relatively rare disease. Because of the nature of the blood flow in the celiac region when a pancreatoduodenectomy (PD) is performed for CACS, the celiac region can become ischemic. The aim of this study is to report on the importance of pre-operative diagnosis of CACS in terms of the outcomes for patients post-operatively. In this study, three 3 cases of PD co-morbid with CACS are reported: one intra-operative diagnosis case and two pre-operative diagnosis cases. The one case, not diagnosed with CACS prior to the operation, had a hard post-operative course because of complication caused by ischemia of the celiac region compared with the two cases diagnosed prior to the operation, who had a good post-operative course because of pre-operative or intra-operative intervention. Post-operative complications due to CACS are preventable by pre-operative diagnosis and appropriate interventions.","Celiac axis compression syndrome (CACS) is a relatively rare disease. Because of the nature of the blood flow in the celiac region when a pancreatoduodenectomy (PD) is performed for CACS, the celiac region can become ischemic. The aim of this study is to report on the importance of pre-operative diagnosis of CACS in terms of the outcomes for patients post-operatively. In this study, three 3 cases of PD co-morbid with CACS are reported: one intra-operative diagnosis case and two pre-operative diagnosis cases. The one case, not diagnosed with CACS prior to the operation, had a hard post-operative course because of complication caused by ischemia of the celiac region compared with the two cases diagnosed prior to the operation, who had a good post-operative course because of pre-operative or intra-operative intervention. Post-operative complications due to CACS are preventable by pre-operative diagnosis and appropriate interventions.","null","null","2020-05-24","Surgical Case Reports","Surgical Case Reports","Vol.6","No.1","113","113","eng","null","null","research_institution","null","null","10.1186/s40792-020-00878-x","2198-7793","null","null","null","null","null"
"Usefulness of virtual three-dimensional image analysis in inguinal hernia as an educational tool.","Usefulness of virtual three-dimensional image analysis in inguinal hernia as an educational tool.","Yuuma Wada, Masaaki Nishi, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Daichi Ishikawa, Toshiaki Yoshimoto, Mitsuo Shimada","Yuuma Wada, Masaaki Nishi, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Daichi Ishikawa, Toshiaki Yoshimoto, Mitsuo Shimada","null","The pre-operative three-dimensional (3D) imaging technique has resulted in a better surgical outcome for patients and has been used as an education and diagnostic tool. However, there are no reports concerning the usefulness of the 3D imaging technique in laparoscopic transabdominal pre-peritoneal repair (TAPP) so the aim of this study was to investigate the usefulness of the 3D imaging technique in laparoscopic TAPP as an educational tool for medical students. Six (6) patients who underwent laparoscopic TAPP for inguinal hernia were enrolled in this study. 3D reconstruction was performed from pre-operative computed tomography (CT) and the usefulness of pre-operative 3D simulation compared with intra-operative laparoscopic imaging was validated. Moreover, thirty (30) medical students at the university completed a multiple-choice questionnaire (MCQ) to determine the level of their satisfaction and understanding of anatomy resulting from the study. The local anatomy of the patients was identified as the same during the operation as the pre-operative 3D simulation. The results of the MCQ showed that most of the medical students were extremely (23%) or very (67%) satisfied with the effect of pre-operative 3D simulation on the quality of the surgery. Moreover, most students could understand the surgery anatomy by the 3D simulation extremely well (40%) or very well (47%) and agreed on the usefulness of this procedure for learning anatomy. Pre-operative 3D simulation increases the understanding of detailed anatomy and virtual three-dimensional image analysis in laparoscopic TAPP is useful as an educational tool for medical students.","The pre-operative three-dimensional (3D) imaging technique has resulted in a better surgical outcome for patients and has been used as an education and diagnostic tool. However, there are no reports concerning the usefulness of the 3D imaging technique in laparoscopic transabdominal pre-peritoneal repair (TAPP) so the aim of this study was to investigate the usefulness of the 3D imaging technique in laparoscopic TAPP as an educational tool for medical students. Six (6) patients who underwent laparoscopic TAPP for inguinal hernia were enrolled in this study. 3D reconstruction was performed from pre-operative computed tomography (CT) and the usefulness of pre-operative 3D simulation compared with intra-operative laparoscopic imaging was validated. Moreover, thirty (30) medical students at the university completed a multiple-choice questionnaire (MCQ) to determine the level of their satisfaction and understanding of anatomy resulting from the study. The local anatomy of the patients was identified as the same during the operation as the pre-operative 3D simulation. The results of the MCQ showed that most of the medical students were extremely (23%) or very (67%) satisfied with the effect of pre-operative 3D simulation on the quality of the surgery. Moreover, most students could understand the surgery anatomy by the 3D simulation extremely well (40%) or very well (47%) and agreed on the usefulness of this procedure for learning anatomy. Pre-operative 3D simulation increases the understanding of detailed anatomy and virtual three-dimensional image analysis in laparoscopic TAPP is useful as an educational tool for medical students.","null","null","2020-05","Surgical Endoscopy","Surgical Endoscopy","Vol.34","No.2","1923","1928","eng","null","null","research_institution","null","null","10.1007/s00464-019-06964-y","1432-2218","null","null","null","null","null"
"【最先端医療を支える病理学】肝胆膵外科の最先端 手術画像支援と病理診断のコラボ","【最先端医療を支える病理学】肝胆膵外科の最先端 手術画像支援と病理診断のコラボ","齋藤 裕, 島田 光生","Yu Saitou, Mitsuo Shimada","null","We introduced the pre and intra-operative3D hologram support system, which was a computer graphics model, with extended reality(XR)techniques. It contributed to a more extensive view of 3D anatomy from various angles and the sharing of the same hologram from several respective operators' angles. The colabolation between such an operative supporrt and pathological diagnosis enables more safe and higher quality operations.","We introduced the pre and intra-operative3D hologram support system, which was a computer graphics model, with extended reality(XR)techniques. It contributed to a more extensive view of 3D anatomy from various angles and the sharing of the same hologram from several respective operators' angles. The colabolation between such an operative supporrt and pathological diagnosis enables more safe and higher quality operations.","null","null","2020-04-25","四国医学雑誌","Shikoku Acta Medica","Vol.76","No.1-2","9","12","jpn","null","null","research_institution","null","null","null","0037-3699","null","http://search.jamas.or.jp/link/ui/2020295673","null","null","null"
"Prognostic prediction of apparent diffusion coefficient obtained by diffusion-weighted MRI in mass-forming intrahepatic cholangiocarcinoma.","Prognostic prediction of apparent diffusion coefficient obtained by diffusion-weighted MRI in mass-forming intrahepatic cholangiocarcinoma.","Shin-ichiro Yamada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Yu Saitou, Masato Yoshikawa, Katsuki Miyazaki, Mitsuo Shimada","Shin-ichiro Yamada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Yu Saitou, Masato Yoshikawa, Katsuki Miyazaki, Mitsuo Shimada","null","We evaluated apparent diffusion coefficient (ADC) of diffusion-weighted image MRI as a prognostic factor for mass-forming intrahepatic cholangiocarcinoma (IHCC). We enrolled 26 patients who had undergone hepatic resections for mass-forming-type IHCC in this study, and calculated their mean ADC, using diffusion-weighted image MRI (b: 0, 20, 800 seconds/mm ; 1.5 T MRI). Patients were divided into the ADC and the ADC groups at the median ADC value (n = 13 for both). We also immunohistochemically evaluated hypoxia-inducible factor (HIF)-1 in tumor tissue. Median age in the ADC was older (P = .03), and showed significant higher rate of scirrhous tumor (P = .02). The 5-year overall survival rate in the ADC group was significantly worse than in the ADC group (P = .04). In multivariate analysis, hilar tumor, portal vein invasion and low ADC were independent prognostic factors (P < .05). The ADC group also had a higher rate of high HIF-1 expression than the ADC group (P < .05). Representative case of ADC group showed rich stroma and high HIF-1 expression. The ADC values in MRIs can predict IHCC prognosis, and correlated with stromal density and HIF-1 expression.","We evaluated apparent diffusion coefficient (ADC) of diffusion-weighted image MRI as a prognostic factor for mass-forming intrahepatic cholangiocarcinoma (IHCC). We enrolled 26 patients who had undergone hepatic resections for mass-forming-type IHCC in this study, and calculated their mean ADC, using diffusion-weighted image MRI (b: 0, 20, 800 seconds/mm ; 1.5 T MRI). Patients were divided into the ADC and the ADC groups at the median ADC value (n = 13 for both). We also immunohistochemically evaluated hypoxia-inducible factor (HIF)-1 in tumor tissue. Median age in the ADC was older (P = .03), and showed significant higher rate of scirrhous tumor (P = .02). The 5-year overall survival rate in the ADC group was significantly worse than in the ADC group (P = .04). In multivariate analysis, hilar tumor, portal vein invasion and low ADC were independent prognostic factors (P < .05). The ADC group also had a higher rate of high HIF-1 expression than the ADC group (P < .05). Representative case of ADC group showed rich stroma and high HIF-1 expression. The ADC values in MRIs can predict IHCC prognosis, and correlated with stromal density and HIF-1 expression.","null","null","2020-04-06","Journal of Hepato-Biliary-Pancreatic Sciences","Journal of Hepato-Biliary-Pancreatic Sciences","Vol.27","No.7","388","395","eng","null","null","research_institution","null","null","10.1002/jhbp.732","1868-6982","null","null","null","null","null"
"【最先端医療を支える病理学】消化管最新外科手術における病理の役割","【最先端医療を支える病理学】消化管最新外科手術における病理の役割","柏原 秀也, 島田 光生, 吉川 幸造, 宮谷 知彦, 徳永 卓哉, 西 正暁, 髙須 千絵, 良元 俊昭, 武原 悠花子","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Toshiaki Yoshimoto, Yukako Takehara","null","null","null","null","null","2020-04","四国医学雑誌","Shikoku Acta Medica","Vol.76","No.1-2","3","8","jpn","null","null","research_institution","null","null","null","0037-3699","null","http://search.jamas.or.jp/link/ui/2020295672","null","null","null"
"The usefulness of intraoperative X-ray fluoroscopy in avoiding urethral injury during transanal total mesorectal excision.","The usefulness of intraoperative X-ray fluoroscopy in avoiding urethral injury during transanal total mesorectal excision.","Takuya Tokunaga, Jun Higashijima, Kouzou Yoshikawa, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Mitsuo Shimada","Takuya Tokunaga, Jun Higashijima, Kouzou Yoshikawa, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Mitsuo Shimada","null","Urethral injury is one of the most important complications that can occur during transanal total mesorectal excision in male patients with rectal cancer. This report shows the usefulness of intraoperative X-ray fluoroscopy to avoid urethral injury associated with transanal total mesorectal excision. Real-time navigation using fluoroscopy was performed to check the distance between the urethra and the dissection line at the level of the exposed rectourethral muscle, the middle level of the divided rectourethral muscle, and the level at which the prostate was identified. The dissection was completed transanally up to the level of peritoneal reflection on the anterior side without urethral injury. Pathological examination confirmed that the circumferential resection margin was tumor free. This novel technique using intraoperative X-ray fluoroscopy is an easy-to-use approach that helps prevent urethral injury in male patient who undergo transanal total mesorectal excision for rectal cancer.","Urethral injury is one of the most important complications that can occur during transanal total mesorectal excision in male patients with rectal cancer. This report shows the usefulness of intraoperative X-ray fluoroscopy to avoid urethral injury associated with transanal total mesorectal excision. Real-time navigation using fluoroscopy was performed to check the distance between the urethra and the dissection line at the level of the exposed rectourethral muscle, the middle level of the divided rectourethral muscle, and the level at which the prostate was identified. The dissection was completed transanally up to the level of peritoneal reflection on the anterior side without urethral injury. Pathological examination confirmed that the circumferential resection margin was tumor free. This novel technique using intraoperative X-ray fluoroscopy is an easy-to-use approach that helps prevent urethral injury in male patient who undergo transanal total mesorectal excision for rectal cancer.","null","null","2020-04","Asian Journal of Endoscopic Surgery","Asian Journal of Endoscopic Surgery","Vol.13","No.2","242","245","eng","null","null","research_institution","null","null","10.1111/ases.12717","1758-5910","null","null","null","null","null"
"各分野のガイドラインを紐解く 肝癌診療ガイドライン","各分野のガイドラインを紐解く 肝癌診療ガイドライン","居村 暁, 島田 光生","Satoru Imura, Mitsuo Shimada","null","null","null","null","null","2020-03","日本外科学会雑誌","Journal of Japan Surgical Society","Vol.121","No.2","277","278","jpn","null","null","research_institution","null","null","null","0301-4894","null","http://search.jamas.or.jp/link/ui/2020199313","null","null","null"
"The Role of Neutrophil-to-lymphocyte Ratio on the Effect of CRT for Patients With Rectal Cancer.","The Role of Neutrophil-to-lymphocyte Ratio on the Effect of CRT for Patients With Rectal Cancer.","Daichi Ishikawa, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Takuya Tokunaga, Jun Higashijima, Kouzou Yoshikawa, Mitsuo Shimada","Daichi Ishikawa, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Takuya Tokunaga, Jun Higashijima, Kouzou Yoshikawa, Mitsuo Shimada","null","Neutrophil-to-lymphocyte ratio (NLR) is an indicator of systemic inflammation and could be a predictive factor in malignant tumors. The aim of this study was to investigate the impact of NLR in patients with lower rectal cancer who received preoperative chemo-radiotherapy (CRT). Forty-eight patients with lower rectal cancer who underwent preoperative CRT and curative resection were enrolled. Blood samples were obtained before and after CRT. The relationship of NLR with clinical outcome was investigated. Post-CRT NLR was higher compared to pre-CRT NLR. The patients with higher post-CRT NLR tended to have worse pathological response to CRT compared to those with low post-CRT NLR. The patients with high post-CRT NLR showed poorer 5-year overall survival and 3-year disease free survival while there was no correlation according to pre-CRT NLR. The univariate analysis showed that post-CRT stage and post-CRT NLR were associated with a poorer 5-year overall survival. NLR after preoperative CRT could be a potential prognostic indicator for patients with lower rectal cancer.","Neutrophil-to-lymphocyte ratio (NLR) is an indicator of systemic inflammation and could be a predictive factor in malignant tumors. The aim of this study was to investigate the impact of NLR in patients with lower rectal cancer who received preoperative chemo-radiotherapy (CRT). Forty-eight patients with lower rectal cancer who underwent preoperative CRT and curative resection were enrolled. Blood samples were obtained before and after CRT. The relationship of NLR with clinical outcome was investigated. Post-CRT NLR was higher compared to pre-CRT NLR. The patients with higher post-CRT NLR tended to have worse pathological response to CRT compared to those with low post-CRT NLR. The patients with high post-CRT NLR showed poorer 5-year overall survival and 3-year disease free survival while there was no correlation according to pre-CRT NLR. The univariate analysis showed that post-CRT stage and post-CRT NLR were associated with a poorer 5-year overall survival. NLR after preoperative CRT could be a potential prognostic indicator for patients with lower rectal cancer.","null","null","2020-03","In Vivo","In Vivo","Vol.34","No.2","863","868","eng","null","null","research_institution","null","null","10.21873/invivo.11850","1791-7549","null","null","null","null","null"
"【そこが知りたいシリーズ:手術で必要な局所解剖(腹部編)】PSARP(中間位直腸肛門奇形)","【そこが知りたいシリーズ:手術で必要な局所解剖(腹部編)】PSARP(中間位直腸肛門奇形)","石橋 広樹, 横田 典子, 森 大樹, 島田 光生","Hiroki Ishibashi, Noriko Yokota, Hiroki Mori, Mitsuo Shimada","null","null","null","null","null","2020-02","小児外科","Japanese Journal of Pediatric Surgery","Vol.52","No.2","158","162","jpn","null","null","research_institution","null","null","null","0385-6313","null","http://search.jamas.or.jp/link/ui/2021019652","null","null","null"
"Intraoperative 3D Hologram Support With Mixed Reality Techniques in Liver Surgery.","Intraoperative 3D Hologram Support With Mixed Reality Techniques in Liver Surgery.","Yu Saitou, Maki Sugimoto, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Shuichi Iwahashi, Shin-ichiro Yamada, Mitsuo Shimada","Yu Saitou, Maki Sugimoto, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Shuichi Iwahashi, Shin-ichiro Yamada, Mitsuo Shimada","null","The aim of this study was to investigate the potential of an intraoperative 3D hologram, which was a computer graphics model liver, with mixed reality techniques in liver surgery. The merits for the application of a hologram for surgical support are: 1) no sterilized display monitor; 2) better spatial awareness; and 3) 3D images shared by all the surgeons. 3D polygon data using preoperative computed tomography data was installed into head mount displays, HoloLens (Microsoft Corporation, Redmond, WA). In a Wi-Fi-enabled operative room, several surgeons wearing HoloLens succeeded in sharing the same hologram and moving that hologram from respective operators' angles by means of easy gesture-handling without any monitors. The intraoperative hologram contributed to better imagination of tumor locations, and for determining the parenchymal dissection line in the hepatectomy for the patients with more than 20 multiple colo-rectal liver metastases. In another case, the hologram enabled a safe Gliisonean pedicle approach for hepato-cellular carcinoma with a hilar anatomical anomaly. Surgeons could easily compare the real patient's anatomy and that of the hologram just before the hepatic hilar procedure. This initial experience suggested that an intraoperative hologram with mixed reality techniques contributed to ""last-minute simulation,"" not for ""navigation."" The intraoperative hologram might be a new next-generation operation-supportive tool in terms of spatial awareness, sharing, and simplicity.","The aim of this study was to investigate the potential of an intraoperative 3D hologram, which was a computer graphics model liver, with mixed reality techniques in liver surgery. The merits for the application of a hologram for surgical support are: 1) no sterilized display monitor; 2) better spatial awareness; and 3) 3D images shared by all the surgeons. 3D polygon data using preoperative computed tomography data was installed into head mount displays, HoloLens (Microsoft Corporation, Redmond, WA). In a Wi-Fi-enabled operative room, several surgeons wearing HoloLens succeeded in sharing the same hologram and moving that hologram from respective operators' angles by means of easy gesture-handling without any monitors. The intraoperative hologram contributed to better imagination of tumor locations, and for determining the parenchymal dissection line in the hepatectomy for the patients with more than 20 multiple colo-rectal liver metastases. In another case, the hologram enabled a safe Gliisonean pedicle approach for hepato-cellular carcinoma with a hilar anatomical anomaly. Surgeons could easily compare the real patient's anatomy and that of the hologram just before the hepatic hilar procedure. This initial experience suggested that an intraoperative hologram with mixed reality techniques contributed to ""last-minute simulation,"" not for ""navigation."" The intraoperative hologram might be a new next-generation operation-supportive tool in terms of spatial awareness, sharing, and simplicity.","null","null","2020-01","Annals of Surgery","Annals of Surgery","Vol.271","No.1","e4","e7","eng","null","null","research_institution","null","null","10.1097/SLA.0000000000003552","1528-1140","null","null","null","null","null"
"The Fragility of Cryopreserved Insulin-producing Cells Differentiated from Adipose-tissue-derived Stem Cells.","The Fragility of Cryopreserved Insulin-producing Cells Differentiated from Adipose-tissue-derived Stem Cells.","Kazunori Tokuda, Tetsuya Ikemoto, Yu Saitou, Katsuki Miyazaki, Shoko Yamashita, Shin-ichiro Yamada, Satoru Imura, Yuji Morine, Mitsuo Shimada","Kazunori Tokuda, Tetsuya Ikemoto, Yu Saitou, Katsuki Miyazaki, Shoko Yamashita, Shin-ichiro Yamada, Satoru Imura, Yuji Morine, Mitsuo Shimada","null","The aim of our study is to determine whether insulin-producing cells (IPCs) differentiated from adipose-tissue-derived stem cells (ADSCs) can be cryopreserved. Human ADSCs were differentiated into IPCs using our two-step protocol encompassing a three-dimensional culture and xenoantigen-free method. Thereafter, IPCs were frozen using three different methods. First, IPCs were immediately frozen at -80 C (-80 C group). Second, IPCs were initially placed into a Bicell freezing container before freezing at -80 C (BICELL group). Third, a vitrification method for oocytes and embryos was used (CRYOTOP group). Cell counting kit-8 (CCK-8) assay showed that cell viability was decreased in all groups after cryopreservation ( < 0.01). Corroboratively, the amount of adenosine triphosphate was markedly decreased after cryopreservation in all groups ( < 0.01). Immunofluorescence staining showed a reduced positive staining area for insulin in all cryopreservation groups. Furthermore, 4',6-diamidino-2-phenylindole and merged immunofluorescence images showed that cryopreserved cells appeared to be randomly reduced in the -80 C group and CRYOTOP group, while only the central region was visibly reduced in the BICELL group. Using immunohistochemical staining, IPCs after cryopreservation were shown to be positive for cleaved caspase-3 antibody in all groups. Finally, insulin secretion following glucose stimulation was significantly reduced in IPCs from all groups after cryopreservation ( < 0.01). In conclusion, IPCs may be too fragile for cryopreservation with accomplished methods and further investigations for a suitable preservation method are required.","The aim of our study is to determine whether insulin-producing cells (IPCs) differentiated from adipose-tissue-derived stem cells (ADSCs) can be cryopreserved. Human ADSCs were differentiated into IPCs using our two-step protocol encompassing a three-dimensional culture and xenoantigen-free method. Thereafter, IPCs were frozen using three different methods. First, IPCs were immediately frozen at -80 C (-80 C group). Second, IPCs were initially placed into a Bicell freezing container before freezing at -80 C (BICELL group). Third, a vitrification method for oocytes and embryos was used (CRYOTOP group). Cell counting kit-8 (CCK-8) assay showed that cell viability was decreased in all groups after cryopreservation ( < 0.01). Corroboratively, the amount of adenosine triphosphate was markedly decreased after cryopreservation in all groups ( < 0.01). Immunofluorescence staining showed a reduced positive staining area for insulin in all cryopreservation groups. Furthermore, 4',6-diamidino-2-phenylindole and merged immunofluorescence images showed that cryopreserved cells appeared to be randomly reduced in the -80 C group and CRYOTOP group, while only the central region was visibly reduced in the BICELL group. Using immunohistochemical staining, IPCs after cryopreservation were shown to be positive for cleaved caspase-3 antibody in all groups. Finally, insulin secretion following glucose stimulation was significantly reduced in IPCs from all groups after cryopreservation ( < 0.01). In conclusion, IPCs may be too fragile for cryopreservation with accomplished methods and further investigations for a suitable preservation method are required.","null","null","2020","Cell Transplantation","Cell Transplantation","Vol.29","null","963689720954798","963689720954798","eng","null","null","research_institution","null","null","10.1177/0963689720954798","1555-3892","null","null","null","null","null"
"Carbohydrate Antigen 19-9 Is a Prognostic Factor Which Correlates With HDAC1 and HIF-1 for Intrahepatic Cholangiocarcinoma.","Carbohydrate Antigen 19-9 Is a Prognostic Factor Which Correlates With HDAC1 and HIF-1 for Intrahepatic Cholangiocarcinoma.","Shogo Oota, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Shuichi Iwahashi, Yu Saitou, Shin-ichiro Yamada, Yuuma Wada, Shoko Iwahashi, Yoshimi Bando, Mitsuo Shimada","Shogo Oota, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Shuichi Iwahashi, Yu Saitou, Shin-ichiro Yamada, Yuuma Wada, Shoko Iwahashi, Yoshimi Bando, Mitsuo Shimada","null","Carbohydrate antigen 19-9 (CA19-9) is a poor prognostic marker in intrahepatic cholangiocarcinoma (IHCC). Previous studies have shown a link between hypoxia and CA19-9 in cancer, and we have previously demonstrated a correlation between HDAC1 and HIF-1 in IHCC. Here, we evaluated the expression and correlation of CA19-9 with HIF-1 and HDAC in IHCC. This study included 62 patients with IHCC who underwent primary hepatectomy at our department. Clinicopathological characteristics were examined. Immunohistochemical expression of HIF-1 and HDAC1 in specimens was quantitatively evaluated. Patients with high preoperative serum CA19-9 levels showed clinicopathological characteristics associated with tumour progression. High CA19-9 levels were associated with worse overall and recurrence-free survival. Univariate and multivariate analysis detected high CA19-9 levels as an independent poor prognostic factor for IHCC. Serum CA19-9 was significantly correlated with both HIF-1 and HDAC1 expression. High serum CA19-9 level is a poor prognostic factor for overall survival in IHCC and correlates with HIF-1 and HDAC1 expression.","Carbohydrate antigen 19-9 (CA19-9) is a poor prognostic marker in intrahepatic cholangiocarcinoma (IHCC). Previous studies have shown a link between hypoxia and CA19-9 in cancer, and we have previously demonstrated a correlation between HDAC1 and HIF-1 in IHCC. Here, we evaluated the expression and correlation of CA19-9 with HIF-1 and HDAC in IHCC. This study included 62 patients with IHCC who underwent primary hepatectomy at our department. Clinicopathological characteristics were examined. Immunohistochemical expression of HIF-1 and HDAC1 in specimens was quantitatively evaluated. Patients with high preoperative serum CA19-9 levels showed clinicopathological characteristics associated with tumour progression. High CA19-9 levels were associated with worse overall and recurrence-free survival. Univariate and multivariate analysis detected high CA19-9 levels as an independent poor prognostic factor for IHCC. Serum CA19-9 was significantly correlated with both HIF-1 and HDAC1 expression. High serum CA19-9 level is a poor prognostic factor for overall survival in IHCC and correlates with HIF-1 and HDAC1 expression.","null","null","2019-11","Anticancer Research","Anticancer Research","Vol.39","No.11","6025","6033","eng","null","null","research_institution","null","null","10.21873/anticanres.13808","1791-7530","null","null","null","null","null"
"The Differences in the Characteristics of Insulin-producing Cells Using Human Adipose-tissue Derived Mesenchymal Stem Cells from Subcutaneous and Visceral Tissues.","The Differences in the Characteristics of Insulin-producing Cells Using Human Adipose-tissue Derived Mesenchymal Stem Cells from Subcutaneous and Visceral Tissues.","Yuuma Wada, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Yu Saitou, Shin-ichiro Yamada, Mitsuo Shimada","Yuuma Wada, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Yu Saitou, Shin-ichiro Yamada, Mitsuo Shimada","null","The aim of this study was to investigate the characteristics of insulin producing cells (IPCs) differentiated from adipose-tissue derived stem cells (ADSCs) isolated from human subcutaneous and visceral adipose tissues and identify ADSCs suitable for differentiation into efficient and functional IPCs. Subcutaneous and visceral adipose tissues collected from four (4) patients who underwent digestive surgeries at The Tokushima University (000035546) were included in this study. The insulin secretion of the generated IPCs was investigated using surface markers by: fluorescence activated cell sorting (FACS) analysis; cytokine release; proliferation ability of ADSCs; in vitro (glucose-stimulated insulin secretion: (GSIS) test/in vivo (transplantation into streptozotocin-induced diabetic nude mice). The less fat-related inflammatory cytokines secretions were observed (P < 0.05), and the proliferation ability was higher in the subcutaneous ADSCs (P < 0.05). Insulin expression and GISI were higher in the subcutaneous IPCs (P < 0.01 and P < 0.05, respectively). The hyperglycaemic state of all mice that received IPCs from subcutaneous fat tissue converted into normo-glycaemia in thirty (30) days post-transplantation (4/4,100%). Transplanted IPCs were stained using anti-insulin and anti-human leukocyte antigen antibodies. The IPCs generated from the ADSCs freshly isolated from the human fat tissue had sufficient insulin secreting ability in vitro and in vivo.","The aim of this study was to investigate the characteristics of insulin producing cells (IPCs) differentiated from adipose-tissue derived stem cells (ADSCs) isolated from human subcutaneous and visceral adipose tissues and identify ADSCs suitable for differentiation into efficient and functional IPCs. Subcutaneous and visceral adipose tissues collected from four (4) patients who underwent digestive surgeries at The Tokushima University (000035546) were included in this study. The insulin secretion of the generated IPCs was investigated using surface markers by: fluorescence activated cell sorting (FACS) analysis; cytokine release; proliferation ability of ADSCs; in vitro (glucose-stimulated insulin secretion: (GSIS) test/in vivo (transplantation into streptozotocin-induced diabetic nude mice). The less fat-related inflammatory cytokines secretions were observed (P < 0.05), and the proliferation ability was higher in the subcutaneous ADSCs (P < 0.05). Insulin expression and GISI were higher in the subcutaneous IPCs (P < 0.01 and P < 0.05, respectively). The hyperglycaemic state of all mice that received IPCs from subcutaneous fat tissue converted into normo-glycaemia in thirty (30) days post-transplantation (4/4,100%). Transplanted IPCs were stained using anti-insulin and anti-human leukocyte antigen antibodies. The IPCs generated from the ADSCs freshly isolated from the human fat tissue had sufficient insulin secreting ability in vitro and in vivo.","null","null","2019-09-13","Scientific Reports","Scientific Reports","Vol.9","No.1","13204","13204","eng","null","null","research_institution","null","null","10.1038/s41598-019-49701-0","2045-2322","null","null","null","null","null"
"Impact of Bevacizumab on Liver Damage After Massive Hepatectomy in Rats.","Impact of Bevacizumab on Liver Damage After Massive Hepatectomy in Rats.","Hiroki Mori, Yu Saitou, Shuichi Iwahashi, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Mitsuo Shimada","Hiroki Mori, Yu Saitou, Shuichi Iwahashi, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Mitsuo Shimada","null","The aim of this study was to evaluate the impact of pretreatment with bevacizumab on liver damage in a rat model of massive hepatectomy (Hx) model, as a surrogate model of massive Hx for liver metastasis from colorectal cancer. Male Wister rats (n=24) were separated into the following two groups: 90% Hx and 90% Hx plus bevacizumab group. Bevacizumab (5 mg/kg) was injected intraperitoneally 7 days before Hx. Samples of blood and remnant liver tissue were obtained 24 hours after hepatectomy and the following parameters were evaluated: Biochemical analysis; liver regeneration rate; survival rate; and real-time polymerase chain reaction for interleukin-1 beta (Il1b), tumor necrosis factor alpha (Tnfa), matrix metalloproteinase (Mmp) 2 and Mmp9 mRNA. In addition, samples of whole liver tissue were obtained immediately before Hx and real-time polymerase chain reaction was performed for X-box binding protein 1 (Xbp1), activating transcription factor 6 (Atf6), C/EBP homologous protein (Chop), glucose-regulated protein 78 (Grp78) and heat-shock protein 70 (Hsp70), as markers of endoplasmic reticulum stress response. The levels of transaminases 24 hours after Hx were significantly reduced in the group pretreated with bevacizumab compared to that not pretreated (p<0.05). The liver regeneration rate at 24 hours after Hx was significantly increased in the group pretreated with bevacizumab compared with the group which underwent Hx alone (p<0.05). The survival rate for the group pretreated with bevacizumab tended to be higher than that of the Hx-only group, 72 hours after Hx (p=0.09). The expressions of Il1b, Mmp2 and Mmp9 mRNA 24 hours after Hx in the group pretreated with bevacizumab tended to be lower than that of rats which underwent Hx alone (p=0.11, 0.09 and 0.15, respectively). The expression of Xbp1, Chop, Grp78 and Hsp70 mRNA immediately before Hx in the group pretreated with bevacizumab were significantly higher than the 90% Hx group (p<0.05). Bevacizumab pretreatment had protective effects on liver injury after massive hepatectomy in rats, apparently via the induction of the endoplasmic reticulum stress response, i.e. the so-called unfolded protein response.","The aim of this study was to evaluate the impact of pretreatment with bevacizumab on liver damage in a rat model of massive hepatectomy (Hx) model, as a surrogate model of massive Hx for liver metastasis from colorectal cancer. Male Wister rats (n=24) were separated into the following two groups: 90% Hx and 90% Hx plus bevacizumab group. Bevacizumab (5 mg/kg) was injected intraperitoneally 7 days before Hx. Samples of blood and remnant liver tissue were obtained 24 hours after hepatectomy and the following parameters were evaluated: Biochemical analysis; liver regeneration rate; survival rate; and real-time polymerase chain reaction for interleukin-1 beta (Il1b), tumor necrosis factor alpha (Tnfa), matrix metalloproteinase (Mmp) 2 and Mmp9 mRNA. In addition, samples of whole liver tissue were obtained immediately before Hx and real-time polymerase chain reaction was performed for X-box binding protein 1 (Xbp1), activating transcription factor 6 (Atf6), C/EBP homologous protein (Chop), glucose-regulated protein 78 (Grp78) and heat-shock protein 70 (Hsp70), as markers of endoplasmic reticulum stress response. The levels of transaminases 24 hours after Hx were significantly reduced in the group pretreated with bevacizumab compared to that not pretreated (p<0.05). The liver regeneration rate at 24 hours after Hx was significantly increased in the group pretreated with bevacizumab compared with the group which underwent Hx alone (p<0.05). The survival rate for the group pretreated with bevacizumab tended to be higher than that of the Hx-only group, 72 hours after Hx (p=0.09). The expressions of Il1b, Mmp2 and Mmp9 mRNA 24 hours after Hx in the group pretreated with bevacizumab tended to be lower than that of rats which underwent Hx alone (p=0.11, 0.09 and 0.15, respectively). The expression of Xbp1, Chop, Grp78 and Hsp70 mRNA immediately before Hx in the group pretreated with bevacizumab were significantly higher than the 90% Hx group (p<0.05). Bevacizumab pretreatment had protective effects on liver injury after massive hepatectomy in rats, apparently via the induction of the endoplasmic reticulum stress response, i.e. the so-called unfolded protein response.","null","null","2019-09","In Vivo","In Vivo","Vol.33","No.5","1469","1476","eng","null","null","research_institution","null","null","10.21873/invivo.11626","1791-7549","null","null","null","null","null"
"Clinical Impact of FOLFOXIRI Aiming for Conversion Surgery in Unresectable Multiple Colorectal Liver Metastasis.","Clinical Impact of FOLFOXIRI Aiming for Conversion Surgery in Unresectable Multiple Colorectal Liver Metastasis.","Yuji Morine, Tetsuya Ikemoto, Shuichi Iwahashi, Yu Saitou, Shin-ichiro Yamada, Chie Takasu, Jun Higashijima, Satoru Imura, Mitsuo Shimada","Yuji Morine, Tetsuya Ikemoto, Shuichi Iwahashi, Yu Saitou, Shin-ichiro Yamada, Chie Takasu, Jun Higashijima, Satoru Imura, Mitsuo Shimada","null","We evaluated the clinical impact of FOLFOXIRI regimen aiming for conversion surgery in patients with unresectable multiple colorectal liver metastasis (CRLM). A total of 42 patients with unresectable multiple CRLM who received chemotherapy with molecular agents were included in the analysis. The clinical results of FOLFOXIRI with other regimens were compared. The total conversion rate of 42 unresectable CRLM was 48.1%, and conversion cases had a better prognosis. Clinicopathological characteristics of conversion cases were more frequent in FOLFOXIRI induction, liver limited disease and maximum diameter number (MDN) over 70. FOLFOXIRI achieved a higher conversion rate compared to other regimens (72.2% vs. 37.5%, p=0.0334), and significantly reduced the medication period until conversion surgery (median 5.8 courses) with a higher tumour necrotic rate. Consequently, the overall survival of conversion cases with FOLFOXIRI was better than that with other regimens (p=0.0055). FOLFOXIRI plus molecular agents might provide a higher probability of conversion surgery with a prognostic benefit.","We evaluated the clinical impact of FOLFOXIRI regimen aiming for conversion surgery in patients with unresectable multiple colorectal liver metastasis (CRLM). A total of 42 patients with unresectable multiple CRLM who received chemotherapy with molecular agents were included in the analysis. The clinical results of FOLFOXIRI with other regimens were compared. The total conversion rate of 42 unresectable CRLM was 48.1%, and conversion cases had a better prognosis. Clinicopathological characteristics of conversion cases were more frequent in FOLFOXIRI induction, liver limited disease and maximum diameter number (MDN) over 70. FOLFOXIRI achieved a higher conversion rate compared to other regimens (72.2% vs. 37.5%, p=0.0334), and significantly reduced the medication period until conversion surgery (median 5.8 courses) with a higher tumour necrotic rate. Consequently, the overall survival of conversion cases with FOLFOXIRI was better than that with other regimens (p=0.0055). FOLFOXIRI plus molecular agents might provide a higher probability of conversion surgery with a prognostic benefit.","null","null","2019-09","Anticancer Research","Anticancer Research","Vol.39","No.9","5089","5096","eng","null","null","research_institution","null","null","10.21873/anticanres.13703","1791-7530","null","null","null","null","null"
"Duodenal-Jejunal Bypass Maintains Gut Permeability by Suppressing Gut Inflammation.","Duodenal-Jejunal Bypass Maintains Gut Permeability by Suppressing Gut Inflammation.","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu","null","The aim of this study was to investigate gut inflammation and permeability in rats after duodenal-jejunal bypass (DJB) and in rats injected with a glucagon-like peptide-1 (GLP-1) receptor analog. Twelve male 16-week-old obese diabetic rats were divided into three groups: the DJB group, the sham group, and the group injected daily with a GLP-1 receptor agonist (liraglutide). Gut inflammation and the expression of tight junction protein (claudin-1) were analyzed in the three groups at 8 weeks after surgery. The DJB group showed significantly lower levels of gut inflammatory cytokines than the liraglutide group. Claudin-1 showed stronger intensity on immunofluorescent staining in the DJB group than that in the liraglutide group. In summary, DJB surgery might maintain gut permeability via suppression of gut inflammation.","The aim of this study was to investigate gut inflammation and permeability in rats after duodenal-jejunal bypass (DJB) and in rats injected with a glucagon-like peptide-1 (GLP-1) receptor analog. Twelve male 16-week-old obese diabetic rats were divided into three groups: the DJB group, the sham group, and the group injected daily with a GLP-1 receptor agonist (liraglutide). Gut inflammation and the expression of tight junction protein (claudin-1) were analyzed in the three groups at 8 weeks after surgery. The DJB group showed significantly lower levels of gut inflammatory cytokines than the liraglutide group. Claudin-1 showed stronger intensity on immunofluorescent staining in the DJB group than that in the liraglutide group. In summary, DJB surgery might maintain gut permeability via suppression of gut inflammation.","null","null","2019-09","Obesity Surgery","Obesity Surgery","Vol.29","No.9","2745","2749","eng","null","null","research_institution","null","null","10.1007/s11695-019-03922-4","1708-0428","null","null","null","null","null"
"骨髄異形成症候群・発作性夜間血色素尿症合併胃癌に対する腹腔鏡手術の1例","骨髄異形成症候群・発作性夜間血色素尿症合併胃癌に対する腹腔鏡手術の1例","岩橋 祥子, 柏原 秀也, 髙須 千絵, 西 正暁, 徳永 卓哉, 宮谷 知彦, 東島 潤, 吉川 幸造, 島田 光生","Shoko Iwahashi, Hideya Kashihara, Chie Takasu, Masaaki Nishi, Takuya Tokunaga, Tomohiko Miyatani, Jun Higashijima, Kouzou Yoshikawa, Mitsuo Shimada","null","null","null","null","null","2019-08","日本外科系連合学会誌","Journal of Japanese College of Surgeons","Vol.44","No.4","706","712","jpn","null","null","research_institution","null","null","10.4030/jjcs.44.706","1882-9112","null","http://search.jamas.or.jp/link/ui/2019353742","null","null","null"
"Two cases of non-mucinous cystadenomas of the pancreas with pancreatobiliary phenotype and ovarian-like stroma.","Two cases of non-mucinous cystadenomas of the pancreas with pancreatobiliary phenotype and ovarian-like stroma.","Shoko Iwahashi, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Shuichi Iwahashi, Yu Saitou, Shin-ichiro Yamada, Toshiaki Yoshimoto, Koichi Tsuneyama, Mitsuo Shimada","Shoko Iwahashi, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Shuichi Iwahashi, Yu Saitou, Shin-ichiro Yamada, Toshiaki Yoshimoto, Koichi Tsuneyama, Mitsuo Shimada","null","Diagnosis of cystic tumor of the pancreas is based on the World Health Organization criteria that classify pancreatic cystadenomas into four types: intra-ductal papillary mucinous neoplasms, mucinous cystic neoplasms (MCNs), serous cystic neoplasms, and solid pseudo-papillary neoplasms depending on their secretion and presence of ovarian-like stroma. Recently, Albores-Saavedra identified non-mucinous cystadenomas of the pancreas with pancreato-biliary phenotype and ovarian-like stroma. This precipitated examination of the proportions of these rare tumors in patients treated at Tokushima University Hospital. Case 1 was a 40-year-old woman with a cystic tumor in the tail of the pancreas. Computed tomography (CT) revealed a diffuse and non-enhanced cystic tumor in the tail of the pancreas. This tumor was diagnosed as a simple cyst at this point. However, 2ears later, the tumor had increased in size by 3m. Thus, laparoscopic distal pancreatectomy was performed. The content of the cyst was serous. The epithelial cells were lined with a single layer of cuboidal cells and the tumor had ovarian-like stroma pathologically. The final pathological diagnosis was non-mucinous cystadenoma of the pancreas with ovarian-like stroma. In Case 2, a cystic tumor in the pancreas was found by medical examination in a woman in her sixties who presented without symptoms. CT showed a 1.5-cm cystic tumor in the tail and body of the pancreas and a septum in the cyst. Nine years later, the tumor had grown to 2.4m in diameter and had a clear septum in the cyst. This tumor was diagnosed preoperatively as MCN. Thus, laparoscopic distal pancreatectomy was performed. The cyst contained serous fluid. Microscopic examination showed no ovarian-like stroma and the epithelial cells were lined by a single layer of cuboidal cells. The final pathological diagnosis was non-mucinous cystadenoma of the pancreas with ovarian-like stroma. Accurate preoperative diagnosis of this type of pancreatic cystic tumor may be difficult, although it occurs more often than expected. Non-mucinous cystadenomas of the pancreas with ovarian-like stroma need to be considered as a differential diagnosis.","Diagnosis of cystic tumor of the pancreas is based on the World Health Organization criteria that classify pancreatic cystadenomas into four types: intra-ductal papillary mucinous neoplasms, mucinous cystic neoplasms (MCNs), serous cystic neoplasms, and solid pseudo-papillary neoplasms depending on their secretion and presence of ovarian-like stroma. Recently, Albores-Saavedra identified non-mucinous cystadenomas of the pancreas with pancreato-biliary phenotype and ovarian-like stroma. This precipitated examination of the proportions of these rare tumors in patients treated at Tokushima University Hospital. Case 1 was a 40-year-old woman with a cystic tumor in the tail of the pancreas. Computed tomography (CT) revealed a diffuse and non-enhanced cystic tumor in the tail of the pancreas. This tumor was diagnosed as a simple cyst at this point. However, 2ears later, the tumor had increased in size by 3m. Thus, laparoscopic distal pancreatectomy was performed. The content of the cyst was serous. The epithelial cells were lined with a single layer of cuboidal cells and the tumor had ovarian-like stroma pathologically. The final pathological diagnosis was non-mucinous cystadenoma of the pancreas with ovarian-like stroma. In Case 2, a cystic tumor in the pancreas was found by medical examination in a woman in her sixties who presented without symptoms. CT showed a 1.5-cm cystic tumor in the tail and body of the pancreas and a septum in the cyst. Nine years later, the tumor had grown to 2.4m in diameter and had a clear septum in the cyst. This tumor was diagnosed preoperatively as MCN. Thus, laparoscopic distal pancreatectomy was performed. The cyst contained serous fluid. Microscopic examination showed no ovarian-like stroma and the epithelial cells were lined by a single layer of cuboidal cells. The final pathological diagnosis was non-mucinous cystadenoma of the pancreas with ovarian-like stroma. Accurate preoperative diagnosis of this type of pancreatic cystic tumor may be difficult, although it occurs more often than expected. Non-mucinous cystadenomas of the pancreas with ovarian-like stroma need to be considered as a differential diagnosis.","null","null","2019-07-23","Surgical Case Reports","Surgical Case Reports","Vol.5","No.1","117","117","eng","null","null","research_institution","null","null","10.1186/s40792-019-0673-y","2198-7793","null","null","null","null","null"
"A case of gastric heterotopic pancreas with gastroduodenal invagination.","A case of gastric heterotopic pancreas with gastroduodenal invagination.","Shoko Iwahashi, Masaaki Nishi, Toshiaki Yoshimoto, Hideya Kashihara, Chie Takasu, Takuya Tokunaga, Tomohiko Miyatani, Jun Higashijima, Kouzou Yoshikawa, Yuuma Wada, Yoshimi Bando, Mitsuo Shimada","Shoko Iwahashi, Masaaki Nishi, Toshiaki Yoshimoto, Hideya Kashihara, Chie Takasu, Takuya Tokunaga, Tomohiko Miyatani, Jun Higashijima, Kouzou Yoshikawa, Yuuma Wada, Yoshimi Bando, Mitsuo Shimada","null","Heterotopic pancreas (HP) is a rare disease commonly found incidentally on imaging studies, at endoscopy or at autopsy and can be associated with abdominal pain, vomiting, heart burn, gastric outlet obstruction, and even dysphagia in very rare cases. Heinrich's classified HP into three groups, types1-3, with Heinrich's type 3 HP the rarest and difficult to diagnose properly because it has only pancreatic ducts but has no islet and acini. The aim of this study is to report a case of gastric outlet obstruction caused by type 3 HP with gastroduodenal invagination with reference to the literature and diagnosed finally by immuno-histochemical analysis. The case presented is a 40-year-old male presenting with vomiting and abdominal pain. Computed tomography (CT) revealed a cystic mass in the upper abdomen and he was referred to the Tokushima University. Gastric fiber showed that the pedunculated mass originated from the stomach. An open distal gastrectomy was performed. Pathologically, there was small glands proliferation in the sub-mucosal (SM) layer which was membrane and cytoplasm (MUC)1 positive and muscle proliferation. This finding revealed the tumor as HP. Postoperative course was uneventful and the patient was discharged 12 days after surgery. The patient has remained well 12 months after surgery. HP should be considered in the differential diagnosis of SM tumors with gastroduodenal invagination even if this is a rare symptom.","Heterotopic pancreas (HP) is a rare disease commonly found incidentally on imaging studies, at endoscopy or at autopsy and can be associated with abdominal pain, vomiting, heart burn, gastric outlet obstruction, and even dysphagia in very rare cases. Heinrich's classified HP into three groups, types1-3, with Heinrich's type 3 HP the rarest and difficult to diagnose properly because it has only pancreatic ducts but has no islet and acini. The aim of this study is to report a case of gastric outlet obstruction caused by type 3 HP with gastroduodenal invagination with reference to the literature and diagnosed finally by immuno-histochemical analysis. The case presented is a 40-year-old male presenting with vomiting and abdominal pain. Computed tomography (CT) revealed a cystic mass in the upper abdomen and he was referred to the Tokushima University. Gastric fiber showed that the pedunculated mass originated from the stomach. An open distal gastrectomy was performed. Pathologically, there was small glands proliferation in the sub-mucosal (SM) layer which was membrane and cytoplasm (MUC)1 positive and muscle proliferation. This finding revealed the tumor as HP. Postoperative course was uneventful and the patient was discharged 12 days after surgery. The patient has remained well 12 months after surgery. HP should be considered in the differential diagnosis of SM tumors with gastroduodenal invagination even if this is a rare symptom.","null","null","2019-07-10","Surgical Case Reports","Surgical Case Reports","Vol.5","No.1","110","110","eng","null","null","research_institution","null","null","10.1186/s40792-019-0669-7","2198-7793","null","null","null","null","null"
"Daikenchuto accelerates the recovery from prolonged postoperative ileus after open abdominal surgery: a subgroup analysis of three randomized controlled trials.","Daikenchuto accelerates the recovery from prolonged postoperative ileus after open abdominal surgery: a subgroup analysis of three randomized controlled trials.","Tooru Kouno, Mitsuo Shimada, Masaaki Nishi, Yuji Morine, Kouzou Yoshikawa, Hidetoshi Katsuno, Koutarou Maeda, Keisuke Koeda, Satoshi Morita, Masahiko Watanabe, Mitsuo Kusano, Junichi Sakamoto, Shigetoyo Saji, Hiroki Sokuoka, Yasuto Sato, Yoshihiko Maehara, Takashi Kanematsu, Masaki Kitajima","Tooru Kouno, Mitsuo Shimada, Masaaki Nishi, Yuji Morine, Kouzou Yoshikawa, Hidetoshi Katsuno, Koutarou Maeda, Keisuke Koeda, Satoshi Morita, Masahiko Watanabe, Mitsuo Kusano, Junichi Sakamoto, Shigetoyo Saji, Hiroki Sokuoka, Yasuto Sato, Yoshihiko Maehara, Takashi Kanematsu, Masaki Kitajima","null","Prolonged postoperative ileus (POI) is a common complication after open abdominal surgery (OAS). Daikenchuto (DKT), a traditional Japanese medicine that peripherally stimulates the neurogenic pathway, is used to treat prolonged POI in Japan. To analyze whether DKT accelerates the recovery from prolonged POI after OAS, we conducted a secondary analysis of three multicenter randomized controlled trials (RCTs). A secondary analysis of the three RCTs supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer (project numbers 39-0902, 40-1001, 42-1002) assessing the effect of DKT on prolonged POI in patients who had undergone OAS for colon, liver, or gastric cancer was performed. The subgroup included 410 patients with no bowel movement (BM) before the first diet, a DKT group (n = 214), and a placebo group (n = 196). Patients received either 5 g DKT or a placebo orally, three times a day. The primary endpoint was defined as the time from the end of surgery to the first bowel movement (FBM). A sensitivity analysis was also performed on the age, body mass index and dosage as subgroup analyses. The primary endpoint was significantly accelerated in the DKT group compared with the placebo group (p = 0.004; hazard ratio 1.337). The median time to the FBM was 113.8 h in the placebo group and 99.1 h in the DKT treatment group. The subgroup analysis showed that DKT significantly accelerated the recovery from prolonged POI following OAS. UMIN000026292.","Prolonged postoperative ileus (POI) is a common complication after open abdominal surgery (OAS). Daikenchuto (DKT), a traditional Japanese medicine that peripherally stimulates the neurogenic pathway, is used to treat prolonged POI in Japan. To analyze whether DKT accelerates the recovery from prolonged POI after OAS, we conducted a secondary analysis of three multicenter randomized controlled trials (RCTs). A secondary analysis of the three RCTs supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer (project numbers 39-0902, 40-1001, 42-1002) assessing the effect of DKT on prolonged POI in patients who had undergone OAS for colon, liver, or gastric cancer was performed. The subgroup included 410 patients with no bowel movement (BM) before the first diet, a DKT group (n = 214), and a placebo group (n = 196). Patients received either 5 g DKT or a placebo orally, three times a day. The primary endpoint was defined as the time from the end of surgery to the first bowel movement (FBM). A sensitivity analysis was also performed on the age, body mass index and dosage as subgroup analyses. The primary endpoint was significantly accelerated in the DKT group compared with the placebo group (p = 0.004; hazard ratio 1.337). The median time to the FBM was 113.8 h in the placebo group and 99.1 h in the DKT treatment group. The subgroup analysis showed that DKT significantly accelerated the recovery from prolonged POI following OAS. UMIN000026292.","null","null","2019-02-25","Surgery Today","Surgery Today","Vol.49","No.8","704","711","eng","null","null","research_institution","null","null","10.1007/s00595-019-01787-9","1436-2813","null","null","null","null","null"
"The protective effect of epigallocatechin 3-gallate on mouse pancreatic islets via the Nrf2 pathway.","The protective effect of epigallocatechin 3-gallate on mouse pancreatic islets via the Nrf2 pathway.","Yuuma Wada, Atsushi Takata, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Shuichi Iwahashi, Yu Saitou, Mitsuo Shimada","Yuuma Wada, Atsushi Takata, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Shuichi Iwahashi, Yu Saitou, Mitsuo Shimada","null","Epigallocatechin 3-gallate (EGCG), a green tea polyphenol, has been shown to have anti-oxidant and anti-inflammatory effects in vitro and in vivo. The aim of this study was to investigate the effects and mechanism of EGCG on isolated pancreatic islets as pre-conditioning for pancreatic islet transplantation. The pancreatic islets were divided into two groups: an islet culture medium group (control) and an islet culture medium with EGCG (100 M) group. We investigated the islet viability, Nrf2 expression, reactive oxygen species (ROS) production, and heme oxygenase-1 (HO-1) mRNA. Five hundred islet equivalents after 12 h of culture for the EGCG 100 M and control group were transplanted under the kidney capsule of streptozotocin-induced diabetic ICR mice. The cell viability and insulin secretion ability in the EGCG group were preserved, and the nuclear translocation of Nrf2 was increased in the EGCG group (p < 0.01). While the HO-1 mRNA levels were also higher in the EGCG group than in the control group (p < 0.05), the ROS production was lower (p < 0.01). An in vivo functional assessment showed that the blood glucose level had decreased in the EGCG group after transplantation (p < 0.01). EGCG protects the viability and function of islets by suppressing ROS production via the Nrf2 pathway.","Epigallocatechin 3-gallate (EGCG), a green tea polyphenol, has been shown to have anti-oxidant and anti-inflammatory effects in vitro and in vivo. The aim of this study was to investigate the effects and mechanism of EGCG on isolated pancreatic islets as pre-conditioning for pancreatic islet transplantation. The pancreatic islets were divided into two groups: an islet culture medium group (control) and an islet culture medium with EGCG (100 M) group. We investigated the islet viability, Nrf2 expression, reactive oxygen species (ROS) production, and heme oxygenase-1 (HO-1) mRNA. Five hundred islet equivalents after 12 h of culture for the EGCG 100 M and control group were transplanted under the kidney capsule of streptozotocin-induced diabetic ICR mice. The cell viability and insulin secretion ability in the EGCG group were preserved, and the nuclear translocation of Nrf2 was increased in the EGCG group (p < 0.01). While the HO-1 mRNA levels were also higher in the EGCG group than in the control group (p < 0.05), the ROS production was lower (p < 0.01). An in vivo functional assessment showed that the blood glucose level had decreased in the EGCG group after transplantation (p < 0.01). EGCG protects the viability and function of islets by suppressing ROS production via the Nrf2 pathway.","null","null","2019-02-07","Surgery Today","Surgery Today","Vol.49","No.6","536","545","eng","null","null","research_institution","null","null","10.1007/s00595-019-1761-0","1436-2813","null","null","null","null","null"
"A new formula to calculate the resection limit in hepatectomy based on Gd-EOB-DTPA-enhanced magnetic resonance imaging.","A new formula to calculate the resection limit in hepatectomy based on Gd-EOB-DTPA-enhanced magnetic resonance imaging.","Shin-ichiro Yamada, Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Chie Takasu, Masato Yoshikawa, Hiroki Teraoku, Toshiaki Yoshimoto","Shin-ichiro Yamada, Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Chie Takasu, Masato Yoshikawa, Hiroki Teraoku, Toshiaki Yoshimoto","null","Dynamic magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (EOB-MRI) can be used not only to detect liver tumors but also to estimate liver function. The aim of this study was to establish a new EOB-MRI-based formula to determine the resection limit in patients undergoing hepatectomy. Twenty-eight patients with a normal liver (NL group) and five with an unresectable cirrhotic liver (UL group) who underwent EOB-MRI were included. Standardized liver function (SLF) was calculated based on the signal intensity (SI), the volume of each subsegment (S1-S8), and body surface area. A formula defining the resection limit was devised based on the difference in the SLF values of patients in the NL and UL groups. The formula was validated in 50 patients who underwent EOB-MRI and hepatectomy. The average SLF value in the NL and UL groups was 2038 and 962 FV/m2, respectively. The difference (1076 FV/m2) was consistent with a 70% in resection volume. Thus, the resection limit for hepatectomy was calculated as a proportion of 70%: 70 (SLF-962)/1076 (%). The one patient who underwent hepatectomy over the resection limit died due to liver failure. In other 49 patients, in whom the resection volume was less than the resection limit, procedures were safely performed. Our formula for resection limit based on EOB-MRI can improve the safety of hepatectomy.","Dynamic magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (EOB-MRI) can be used not only to detect liver tumors but also to estimate liver function. The aim of this study was to establish a new EOB-MRI-based formula to determine the resection limit in patients undergoing hepatectomy. Twenty-eight patients with a normal liver (NL group) and five with an unresectable cirrhotic liver (UL group) who underwent EOB-MRI were included. Standardized liver function (SLF) was calculated based on the signal intensity (SI), the volume of each subsegment (S1-S8), and body surface area. A formula defining the resection limit was devised based on the difference in the SLF values of patients in the NL and UL groups. The formula was validated in 50 patients who underwent EOB-MRI and hepatectomy. The average SLF value in the NL and UL groups was 2038 and 962 FV/m2, respectively. The difference (1076 FV/m2) was consistent with a 70% in resection volume. Thus, the resection limit for hepatectomy was calculated as a proportion of 70%: 70 (SLF-962)/1076 (%). The one patient who underwent hepatectomy over the resection limit died due to liver failure. In other 49 patients, in whom the resection volume was less than the resection limit, procedures were safely performed. Our formula for resection limit based on EOB-MRI can improve the safety of hepatectomy.","null","null","2019-01-25","PLoS ONE","PLoS ONE","Vol.14","No.1","e0210579","e0210579","eng","null","null","research_institution","null","null","10.1371/journal.pone.0210579","1932-6203","null","null","null","null","null"
"Usefulness of blood flow evaluation by indocyanine green fluorescence system in laparoscopic anterior resection.","Usefulness of blood flow evaluation by indocyanine green fluorescence system in laparoscopic anterior resection.","Jun Higashijima, Mitsuo Shimada, Kouzou Yoshikawa, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu","Jun Higashijima, Mitsuo Shimada, Kouzou Yoshikawa, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Chie Takasu","null","One of the major cause of anastomotic leakage (AL) in anterior resection of the rectum is insufficient blood flow of the remnant colon. The indocyanine green fluorescence system (ICG-FS) can visualize the blood flow of organs intra-operatively. The aim of this study is to investigate the usefulness of ICG-FS for evaluating the blood flow of the remnant colon in laparoscopic anterior resection. Rectal cancer patients (n=24) who underwent laparoscopic anterior resection were included in this study. After resection of the rectum, 7.5mg of ICG was administered intravenously, and the blood flow of the oral stump was evaluated by the ICG-FS. The relationship between the fluorescence time (FT) of the oral stump and AL was investigated retrospectively. Two of twenty-four patients (8.3%) suffered AL. The FT of these two cases were over 60 seconds. In the case with the FT was over 80 seconds, we performed additional resection of the late fluorescence portion of the remnant colon and could avoid AL. In patients whose FT was under 60 seconds, no patients suffered AL. ICG-FS may be useful for evaluating the blood flow of the remnant colon to avoid AL in laparoscopic anterior resection. J. Med. Invest. 66 : 65-69, February, 2019.","One of the major cause of anastomotic leakage (AL) in anterior resection of the rectum is insufficient blood flow of the remnant colon. The indocyanine green fluorescence system (ICG-FS) can visualize the blood flow of organs intra-operatively. The aim of this study is to investigate the usefulness of ICG-FS for evaluating the blood flow of the remnant colon in laparoscopic anterior resection. Rectal cancer patients (n=24) who underwent laparoscopic anterior resection were included in this study. After resection of the rectum, 7.5mg of ICG was administered intravenously, and the blood flow of the oral stump was evaluated by the ICG-FS. The relationship between the fluorescence time (FT) of the oral stump and AL was investigated retrospectively. Two of twenty-four patients (8.3%) suffered AL. The FT of these two cases were over 60 seconds. In the case with the FT was over 80 seconds, we performed additional resection of the late fluorescence portion of the remnant colon and could avoid AL. In patients whose FT was under 60 seconds, no patients suffered AL. ICG-FS may be useful for evaluating the blood flow of the remnant colon to avoid AL in laparoscopic anterior resection. J. Med. Invest. 66 : 65-69, February, 2019.","null","null","2019","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.66","No.1.2","65","69","eng","null","null","research_institution","null","null","10.2152/jmi.66.65","1349-6867","null","null","null","null","null"
"Utility of virtual three-dimensional image analysis for laparoscopic gastrectomy conducted by trainee surgeons.","Utility of virtual three-dimensional image analysis for laparoscopic gastrectomy conducted by trainee surgeons.","Masaaki Nishi, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Daichi Ishikawa, Mitsuo Shimada","Masaaki Nishi, Kouzou Yoshikawa, Jun Higashijima, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Daichi Ishikawa, Mitsuo Shimada","null","Purpose The aim of this study was to investigate the utility the three-dimensional (3D) imaging for laparoscopic gastrectomy performed by trainee surgeons. Methods 3D-reconstruction was performed using multi-detector computed tomography (MDCT) and SYNAPSE VINCENT software. Trainee surgeons made 3D-imaging and checked the anatomical structure. Thirty-three patients who underwent laparoscopic gastrectomy (LG) for gastric cancer were examined. Trainees performed 19 LG, while specialists performed 14 LG. The vascular pattern and the surgical outcomes were evaluated. Result 3D imaging depicted the correct positional relationship between the gastric vasculatures and the organs. Regarding vascular pattern detected by 3D imaging, the origins of the infrapyloric artery were the right gastroepiploic artery in 12 cases (36%), the gastroduodenal artery in eight cases (24%), the bifurcation of the right gastroepiploic artery and gastroduodenal artery in seven cases (21%), and not detected in one case (3%). The types of confluence of the infrapyloric vein were the right gastroepiploic vein in 16 cases (48%), the anterior superior pancreatoduodenal vein in 10 cases (30%), and not detected in seven cases (21%). Surgical outcomes were not different between trainee group using intraoperative 3D image with the specialist in instruction group without the intraoperative 3D image. Conclusions Preoperative 3D imaging might contribute to successful and safe LG by trainee surgeons. J. Med. Invest. 66 : 280-284, August, 2019.","Purpose The aim of this study was to investigate the utility the three-dimensional (3D) imaging for laparoscopic gastrectomy performed by trainee surgeons. Methods 3D-reconstruction was performed using multi-detector computed tomography (MDCT) and SYNAPSE VINCENT software. Trainee surgeons made 3D-imaging and checked the anatomical structure. Thirty-three patients who underwent laparoscopic gastrectomy (LG) for gastric cancer were examined. Trainees performed 19 LG, while specialists performed 14 LG. The vascular pattern and the surgical outcomes were evaluated. Result 3D imaging depicted the correct positional relationship between the gastric vasculatures and the organs. Regarding vascular pattern detected by 3D imaging, the origins of the infrapyloric artery were the right gastroepiploic artery in 12 cases (36%), the gastroduodenal artery in eight cases (24%), the bifurcation of the right gastroepiploic artery and gastroduodenal artery in seven cases (21%), and not detected in one case (3%). The types of confluence of the infrapyloric vein were the right gastroepiploic vein in 16 cases (48%), the anterior superior pancreatoduodenal vein in 10 cases (30%), and not detected in seven cases (21%). Surgical outcomes were not different between trainee group using intraoperative 3D image with the specialist in instruction group without the intraoperative 3D image. Conclusions Preoperative 3D imaging might contribute to successful and safe LG by trainee surgeons. J. Med. Invest. 66 : 280-284, August, 2019.","null","null","2019","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.66","No.3.4","280","284","eng","null","null","research_institution","null","null","10.2152/jmi.66.280","1349-6867","null","null","null","null","null"
"The Effect of Laparoscopic Sleeve Gastrectomy on Obesity and Obesity-related Disease : the Results of 10 Initial Cases.","The Effect of Laparoscopic Sleeve Gastrectomy on Obesity and Obesity-related Disease : the Results of 10 Initial Cases.","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Yasuhiro Hamada","Hideya Kashihara, Mitsuo Shimada, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Masaaki Nishi, Chie Takasu, Yasuhiro Hamada","null","Introduction : The number of patients who undergo laparoscopic sleeve gastrectomy (LSG) has been increasing. Department of Surgery, Tokushima University performed the first LSG in 2013. The aim of this study was to report the results of the initial ten cases who underwent a LSG. Patients and methods : Ten obese patients : five males and five females ; age range from thirty-three years to fifty-six years (mean age 42.2 years) ; mean body mass index (BMI) 50.3 ; five with diabetes ; nine with hypertension (HT) ; four with hyperlipidemia (HL) ; eight with sleep apnea syndrome (SAS) who underwent LSG were enrolled in this study. The data was analyzed retrospectively and included short- and long-term outcomes. Results : There were no post-operative complications in this study. The %EWL at three and six months and one year post-operative were 44.2%, 50.2% and 48.6% respectively. In three months post-operative the non-alcoholic fatty liver (NAFLD) and non-alcoholic steatohepatitis (NASH) had improved transaminase (AST/ALT), liver to spleen ratio in plain CT value. Improvements were also evident in the obesity-related diseases : diabetes 80% (4/5) ; HT 67% (6/9) ; HL 75% (3/4) ; and SAS 88% (7/8). Conclusion : LSG is a promising option for the treatment of morbid obesity and obesity-related diseases. J. Med. Invest. 66 : 289-292, August, 2019.","Introduction : The number of patients who undergo laparoscopic sleeve gastrectomy (LSG) has been increasing. Department of Surgery, Tokushima University performed the first LSG in 2013. The aim of this study was to report the results of the initial ten cases who underwent a LSG. Patients and methods : Ten obese patients : five males and five females ; age range from thirty-three years to fifty-six years (mean age 42.2 years) ; mean body mass index (BMI) 50.3 ; five with diabetes ; nine with hypertension (HT) ; four with hyperlipidemia (HL) ; eight with sleep apnea syndrome (SAS) who underwent LSG were enrolled in this study. The data was analyzed retrospectively and included short- and long-term outcomes. Results : There were no post-operative complications in this study. The %EWL at three and six months and one year post-operative were 44.2%, 50.2% and 48.6% respectively. In three months post-operative the non-alcoholic fatty liver (NAFLD) and non-alcoholic steatohepatitis (NASH) had improved transaminase (AST/ALT), liver to spleen ratio in plain CT value. Improvements were also evident in the obesity-related diseases : diabetes 80% (4/5) ; HT 67% (6/9) ; HL 75% (3/4) ; and SAS 88% (7/8). Conclusion : LSG is a promising option for the treatment of morbid obesity and obesity-related diseases. J. Med. Invest. 66 : 289-292, August, 2019.","null","null","2019","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.66","No.3.4","289","292","eng","null","null","research_institution","null","null","10.2152/jmi.66.289","1349-6867","null","null","null","null","null"
"Changes of liver metabolites following hepatectomy with ischemia reperfusion towards liver regeneration.","Changes of liver metabolites following hepatectomy with ischemia reperfusion towards liver regeneration.","Yu Saitou, Yuji Morine, Shuichi Iwahashi, Tetsuya Ikemoto, Satoru Imura, Hisami Yamanaka-Okumura, Akiyoshi Hirayama, Tomoyoshi Soga, Masaru Tomita, Mitsuo Shimada","Yu Saitou, Yuji Morine, Shuichi Iwahashi, Tetsuya Ikemoto, Satoru Imura, Hisami Yamanaka-Okumura, Akiyoshi Hirayama, Tomoyoshi Soga, Masaru Tomita, Mitsuo Shimada","null","Metabolome analysis is one of the omics which investigates the final product of a central dogma. Changes of liver metabolites during liver regeneration following hepatectomy (Hx) continue to remain unclear. The aim of the present study was to investigate the changes of liver metabolites following Hx with ischemia reperfusion (I/R) towards liver regeneration. Twenty-three patients who underwent Hx were enrolled in this study. Non-tumor tissues were sampled immediately before and after Hx and a comparison was made between the liver samples taken before and after Hx using capillary electrophoresis (CE)-time-of-flight mass spectrometry (TOFMS) as metabolome analysis. The metabolic pathway showed that there was a significant increase in ""lactate"" following Hx. There was a significant decrease in metabolites only in the first half of the tricarboxylic acid cycle (TCA) cycle, and adenosine triphosphate (ATP) by anaerobiotic glycolysis did not occur in time for energy consumption of the Hx. Principal component analysis revealed remarkably different component profiles between the samples taken before and after Hx. One hundred and three metabolites were selected as critical metabolites for separating components. Valine and tryptophan increased significantly after Hx and they were regulated by resected liver volume, ischemic time and liver function. The liver metabolites changed remarkably between before and after Hx. Especially, liver valine and tryptophan were increased.","Metabolome analysis is one of the omics which investigates the final product of a central dogma. Changes of liver metabolites during liver regeneration following hepatectomy (Hx) continue to remain unclear. The aim of the present study was to investigate the changes of liver metabolites following Hx with ischemia reperfusion (I/R) towards liver regeneration. Twenty-three patients who underwent Hx were enrolled in this study. Non-tumor tissues were sampled immediately before and after Hx and a comparison was made between the liver samples taken before and after Hx using capillary electrophoresis (CE)-time-of-flight mass spectrometry (TOFMS) as metabolome analysis. The metabolic pathway showed that there was a significant increase in ""lactate"" following Hx. There was a significant decrease in metabolites only in the first half of the tricarboxylic acid cycle (TCA) cycle, and adenosine triphosphate (ATP) by anaerobiotic glycolysis did not occur in time for energy consumption of the Hx. Principal component analysis revealed remarkably different component profiles between the samples taken before and after Hx. One hundred and three metabolites were selected as critical metabolites for separating components. Valine and tryptophan increased significantly after Hx and they were regulated by resected liver volume, ischemic time and liver function. The liver metabolites changed remarkably between before and after Hx. Especially, liver valine and tryptophan were increased.","null","null","2018-01-30","Annals of Gastroenterological Surgery","Annals of Gastroenterological Surgery","Vol.2","No.3","204","211","eng","null","null","research_institution","null","null","10.1002/ags3.12058","2475-0328","null","null","null","null","null"
"Blue light-emitting diodes induce autophagy in colon cancer cells by Opsin 3.","Blue light-emitting diodes induce autophagy in colon cancer cells by Opsin 3.","Toshiaki Yoshimoto, Yuji Morine, Chie Takasu, Rui Feng, Tetsuya Ikemoto, Kouzou Yoshikawa, Shuichi Iwahashi, Yu Saitou, Hideya Kashihara, Masatake Akutagawa, Takahiro Emoto, Yosuke Kinouchi, Mitsuo Shimada","Toshiaki Yoshimoto, Yuji Morine, Chie Takasu, Rui Feng, Tetsuya Ikemoto, Kouzou Yoshikawa, Shuichi Iwahashi, Yu Saitou, Hideya Kashihara, Masatake Akutagawa, Takahiro Emoto, Yosuke Kinouchi, Mitsuo Shimada","null","Light emitting-diodes (LED) have various effects on living organisms and recent studies have shown the efficacy of visible light irradiation from LED for anticancer therapies. However, the mechanism of LED's effects on cancer cells remains unclear. The aim of the present study was to investigate the effects of LED on colon cancer cell lines and the role of photoreceptor Opsin 3 (Opn3) on LED irradiation in vitro. Human colon cancer cells (HT-29 or HCT-116) were seeded onto laboratory dishes and irradiated with 465-nm LED at 30 mW/cm for 30 minutes. Cell Counting Kit-8 was used to measure cell viability, and apoptosis and caspase 3/8 expression were evaluated by AnnexinV/PI and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Autophagy and expression of LC-3 and beclin-1 were also evaluated by autophagy assays, RT-PCR and Western blotting. We further tested Opn3 knockdown by Opn3 siRNA and the G G-protein inhibitor NF023 in these assays. Viability of HT-29 and HCT-116 cells was lower in 465-nm LED-irradiated cultures than in control cultures. LC-3 and beclin-1 expressions were significantly higher in LED-irradiated cultures, and autophagosomes were detected in irradiated cells. The reductive effect of cancer cell viability following blue LED irradiation was reversed by Opn3 knockdown or NF023 treatment. Furthermore, increased LC-3 and beclin-1 expression that resulted from blue LED irradiation was suppressed by Opn3 knockdown or NF023 treatment. Blue LED irradiation suppressed the growth of colon cancer cells and Opn3 may play an important role as a photoreceptor.","Light emitting-diodes (LED) have various effects on living organisms and recent studies have shown the efficacy of visible light irradiation from LED for anticancer therapies. However, the mechanism of LED's effects on cancer cells remains unclear. The aim of the present study was to investigate the effects of LED on colon cancer cell lines and the role of photoreceptor Opsin 3 (Opn3) on LED irradiation in vitro. Human colon cancer cells (HT-29 or HCT-116) were seeded onto laboratory dishes and irradiated with 465-nm LED at 30 mW/cm for 30 minutes. Cell Counting Kit-8 was used to measure cell viability, and apoptosis and caspase 3/8 expression were evaluated by AnnexinV/PI and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Autophagy and expression of LC-3 and beclin-1 were also evaluated by autophagy assays, RT-PCR and Western blotting. We further tested Opn3 knockdown by Opn3 siRNA and the G G-protein inhibitor NF023 in these assays. Viability of HT-29 and HCT-116 cells was lower in 465-nm LED-irradiated cultures than in control cultures. LC-3 and beclin-1 expressions were significantly higher in LED-irradiated cultures, and autophagosomes were detected in irradiated cells. The reductive effect of cancer cell viability following blue LED irradiation was reversed by Opn3 knockdown or NF023 treatment. Furthermore, increased LC-3 and beclin-1 expression that resulted from blue LED irradiation was suppressed by Opn3 knockdown or NF023 treatment. Blue LED irradiation suppressed the growth of colon cancer cells and Opn3 may play an important role as a photoreceptor.","null","null","2018-01-11","Annals of Gastroenterological Surgery","Annals of Gastroenterological Surgery","Vol.2","No.2","154","161","eng","null","null","research_institution","null","null","10.1002/ags3.12055","2475-0328","null","null","null","null","null"
"High STAT4 Expression Indicates Better Disease-free Survival in Patients with Gastric Cancer.","High STAT4 Expression Indicates Better Disease-free Survival in Patients with Gastric Cancer.","Masaaki Nishi, Bat-Erdene Batsaikhan, Kozo Yoshikawa, Jun Higashijima, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Daichi Ishikawa, Mitsuo Shimada","Masaaki Nishi, Bat-Erdene Batsaikhan, Kozo Yoshikawa, Jun Higashijima, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Daichi Ishikawa, Mitsuo Shimada","null","The aim of this study was to investigate the significance of signal transducer and activator of transcription 4 (STAT4) expression and the correlation between STAT4 and interferon gamma (IFN- ) in patients with gastric cancer. Sixty-two patients who underwent gastrectomy for gastric cancer were enrolled in the study. STAT4 and IFNG mRNA expression was evaluated by quantitative real-time polymerase chain reaction (PCR). Immunohistochemistry was performed to examine CD8 T-cells, and STAT4 and IFN- expression. STAT4 mRNA expression was significantly correlated with IFNG mRNA expression (p<0.05). Regarding disease-free survival, there was a significant difference between the groups with high and low STAT4 expression (5-year disease-free survival: 77.8% and 56.4%, p<0.05). Univariate analysis revealed that tumor differentiation and STAT4 expression were significant factors for tumor recurrence. High expression of STAT4 in gastric cancer predicted a better clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after gastrectomy.","The aim of this study was to investigate the significance of signal transducer and activator of transcription 4 (STAT4) expression and the correlation between STAT4 and interferon gamma (IFN- ) in patients with gastric cancer. Sixty-two patients who underwent gastrectomy for gastric cancer were enrolled in the study. STAT4 and IFNG mRNA expression was evaluated by quantitative real-time polymerase chain reaction (PCR). Immunohistochemistry was performed to examine CD8 T-cells, and STAT4 and IFN- expression. STAT4 mRNA expression was significantly correlated with IFNG mRNA expression (p<0.05). Regarding disease-free survival, there was a significant difference between the groups with high and low STAT4 expression (5-year disease-free survival: 77.8% and 56.4%, p<0.05). Univariate analysis revealed that tumor differentiation and STAT4 expression were significant factors for tumor recurrence. High expression of STAT4 in gastric cancer predicted a better clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after gastrectomy.","null","null","2017-12","Anticancer Research","Anticancer Research","Vol.37","No.12","6723","6729","eng","null","null","research_institution","null","null","10.21873/anticanres.12131","1791-7530","null","null","null","null","null"
"Maximum Diameter and Number of Tumors as a New Prognostic Indicator of Colorectal Liver Metastases.","Maximum Diameter and Number of Tumors as a New Prognostic Indicator of Colorectal Liver Metastases.","Toshiaki Yoshimoto, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Shuichi Iwahashi, Yu Saitou, Shin-ichiro Yamada, Daichi Ishikawa, Hiroki Teraoku, Masato Yoshikawa, Jun Higashijima, Chie Takasu, Mitsuo Shimada","Toshiaki Yoshimoto, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Shuichi Iwahashi, Yu Saitou, Shin-ichiro Yamada, Daichi Ishikawa, Hiroki Teraoku, Masato Yoshikawa, Jun Higashijima, Chie Takasu, Mitsuo Shimada","null","Surgical resection is currently considered the only potentially curative option as a treatment strategy of colorectal liver metastases (CRLM). However, the criteria for selection of resectable CRLM are not clear. The aim of this study was to confirm a new prognostic indicator of CRLM after hepatic resection. One hundred thirty nine patients who underwent initial surgical resection from 1994 to 2015 were investigated retrospectively. Prognostic factors of overall survival including the product of maximum diameter and number of metastases (MDN) were analyzed. Primary tumor differentiation, vessel invasion, lymph node (LN) metastasis, non-optimally resectable metastases, H score, grade of liver metastases, resection with non-curative intent and MDN were found to be prognostic factors of overall survival (OS). In multivariate analyses of clinicopathological features associated with OS, MDN and non-curative intent were independent prognostic factors. Patients with MDN ·30 had shown significantly poorer prognosis than patients with MDN <30 in OS and relapse-free survival (RFS). MDN ·30 is an independent prognostic factor of survival in patients with CRLM and optimal surgical criterion of hepatectomy for CRLM.","Surgical resection is currently considered the only potentially curative option as a treatment strategy of colorectal liver metastases (CRLM). However, the criteria for selection of resectable CRLM are not clear. The aim of this study was to confirm a new prognostic indicator of CRLM after hepatic resection. One hundred thirty nine patients who underwent initial surgical resection from 1994 to 2015 were investigated retrospectively. Prognostic factors of overall survival including the product of maximum diameter and number of metastases (MDN) were analyzed. Primary tumor differentiation, vessel invasion, lymph node (LN) metastasis, non-optimally resectable metastases, H score, grade of liver metastases, resection with non-curative intent and MDN were found to be prognostic factors of overall survival (OS). In multivariate analyses of clinicopathological features associated with OS, MDN and non-curative intent were independent prognostic factors. Patients with MDN ·30 had shown significantly poorer prognosis than patients with MDN <30 in OS and relapse-free survival (RFS). MDN ·30 is an independent prognostic factor of survival in patients with CRLM and optimal surgical criterion of hepatectomy for CRLM.","null","null","2017-06","In Vivo","In Vivo","Vol.31","No.3","419","423","eng","null","null","research_institution","null","null","10.21873/invivo.11076","1791-7549","null","null","null","null","null"
"Elevated Preoperative Serum CEA Level Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma Through the Epithelial-Mesenchymal Transition.","Elevated Preoperative Serum CEA Level Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma Through the Epithelial-Mesenchymal Transition.","Masato Yoshikawa, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Jun Higashijima, Shuichi Iwahashi, Yu Saitou, Chie Takasu, Shin-ichiro Yamada, Daichi Ishikawa, Hiroki Teraoku, Atsushi Takata, Toshiaki Yoshimoto, Mitsuo Shimada","Masato Yoshikawa, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Jun Higashijima, Shuichi Iwahashi, Yu Saitou, Chie Takasu, Shin-ichiro Yamada, Daichi Ishikawa, Hiroki Teraoku, Atsushi Takata, Toshiaki Yoshimoto, Mitsuo Shimada","null","Serum carcinoembryonic antigen (CEA) is used as an indicator of tumor progression in a variety of carcinomas. A subset of patients with hepatocellular carcinoma (HCC) exhibit increased serum CEA level, but the significance of this is unclear. In this study, we investigated the prognosis of patients with HCC with increased serum CEA, and explored the correlations with expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and epithelial-mesenchymal transition (EMT) and tumor angiogenesis. One hundred and twenty-three patients with HCC who underwent radical resection were divided into two groups according to a cut-off value of 5.0 ng/ml for serum CEA: high (n=24) and normal (n=99) groups. We compared the clinicopathological factors with serum CEA levels and its correlations with CEACAM1 expression, EMT-related factors and microvessel density (MVD) of tumor tissues by immunohistochemistry. In the high CEA group, the disease-free survival (DFS) rate was significantly worse than in the normal CEA group. Multivariate analysis revealed that a high CEA level was an independent factor predictive of recurrence. Furthermore, increased serum CEA levels were positively correlated with CEACAM1 expression. Moreover, CEACAM1 expression was positively correlated with expression of EMT-related factors and MVD of tumor tissues. Increased serum CEA level reflected CEACAM1 expression and was an independent factor predictive of recurrence in HCC through EMT and tumor angiogenesis.","Serum carcinoembryonic antigen (CEA) is used as an indicator of tumor progression in a variety of carcinomas. A subset of patients with hepatocellular carcinoma (HCC) exhibit increased serum CEA level, but the significance of this is unclear. In this study, we investigated the prognosis of patients with HCC with increased serum CEA, and explored the correlations with expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and epithelial-mesenchymal transition (EMT) and tumor angiogenesis. One hundred and twenty-three patients with HCC who underwent radical resection were divided into two groups according to a cut-off value of 5.0 ng/ml for serum CEA: high (n=24) and normal (n=99) groups. We compared the clinicopathological factors with serum CEA levels and its correlations with CEACAM1 expression, EMT-related factors and microvessel density (MVD) of tumor tissues by immunohistochemistry. In the high CEA group, the disease-free survival (DFS) rate was significantly worse than in the normal CEA group. Multivariate analysis revealed that a high CEA level was an independent factor predictive of recurrence. Furthermore, increased serum CEA levels were positively correlated with CEACAM1 expression. Moreover, CEACAM1 expression was positively correlated with expression of EMT-related factors and MVD of tumor tissues. Increased serum CEA level reflected CEACAM1 expression and was an independent factor predictive of recurrence in HCC through EMT and tumor angiogenesis.","null","null","2017-03","Anticancer Research","Anticancer Research","Vol.37","No.3","1169","1175","eng","null","null","research_institution","null","null","10.21873/anticanres.11430","1791-7530","null","null","null","null","null"
"Impact of intra-abdominal absorbable sutures on surgical site infection in gastrointestinal and hepato-biliary-pancreatic surgery: results of a multicenter, randomized, prospective, phase II clinical trial.","Impact of intra-abdominal absorbable sutures on surgical site infection in gastrointestinal and hepato-biliary-pancreatic surgery: results of a multicenter, randomized, prospective, phase II clinical trial.","Yoshihiko Maehara, Ken Shirabe, Shunji Kohnoe, Yasunori Emi, Eiji Oki, Yoshihiro Kakeji, Hideo Baba, Masataka Ikeda, Michiya Kobayashi, Tadatoshi Takayama, Shoji Natsugoe, Masashi Haraguchi, Kazuhiro Yoshida, Masanori Terashima, Mitsuru Sasako, Hiroki Yamaue, Norihiro Kokudo, Katsuhiko Uesaka, Shinji Uemoto, Tomoo Kosuge, Yoshiki Sawa, Mitsuo Shimada, Yuichiro Doki, Masakazu Yamamoto, Akinobu Taketomi, Masahiro Takeuchi, Kouhei Akazawa, Takeharu Yamanaka, Mototsugu Shimokawa","Yoshihiko Maehara, Ken Shirabe, Shunji Kohnoe, Yasunori Emi, Eiji Oki, Yoshihiro Kakeji, Hideo Baba, Masataka Ikeda, Michiya Kobayashi, Tadatoshi Takayama, Shoji Natsugoe, Masashi Haraguchi, Kazuhiro Yoshida, Masanori Terashima, Mitsuru Sasako, Hiroki Yamaue, Norihiro Kokudo, Katsuhiko Uesaka, Shinji Uemoto, Tomoo Kosuge, Yoshiki Sawa, Mitsuo Shimada, Yuichiro Doki, Masakazu Yamamoto, Akinobu Taketomi, Masahiro Takeuchi, Kouhei Akazawa, Takeharu Yamanaka, Mototsugu Shimokawa","null","The use of absorbable sutures in wound closure has been shown to reduce the incidence of surgical site infection (SSI); however, there is no evidence that the intra-abdominal use of absorbable rather than silk sutures reduces the incidence of SSI after gastrointestinal surgery. We report the findings of a phase II trial, designed to evaluate the impact of the intra-abdominal use of absorbable sutures on the incidence of SSI. At 19 Japanese hospitals, 1147 patients undergoing elective gastrectomy, colorectal surgery, hepatectomy, or pancreaticoduodenectomy (PD) were randomly assigned to absorbable or silk intra-abdominal suture groups. The primary efficacy endpoint was the incidence of SSI. The secondary efficacy endpoints were the locations of SSI, time to resolution of SSI, length of hospital stay, and the incidence of bile leakage in hepatectomy and pancreatic fistula. The incidence of SSI was 11.3%, 15.5%, 11.3%, and 36.9% after gastrectomy, colorectal surgery, hepatectomy, and PD, respectively. The incidence of SSI was higher in the absorbable suture group than in the silk suture group for all the surgical procedures, but the difference was not significant. The intra-abdominal use of absorbable sutures did not have enough of an effect on the reduction of SSI in this phase II trial to justify the planning of a large-scale phase III trial.","The use of absorbable sutures in wound closure has been shown to reduce the incidence of surgical site infection (SSI); however, there is no evidence that the intra-abdominal use of absorbable rather than silk sutures reduces the incidence of SSI after gastrointestinal surgery. We report the findings of a phase II trial, designed to evaluate the impact of the intra-abdominal use of absorbable sutures on the incidence of SSI. At 19 Japanese hospitals, 1147 patients undergoing elective gastrectomy, colorectal surgery, hepatectomy, or pancreaticoduodenectomy (PD) were randomly assigned to absorbable or silk intra-abdominal suture groups. The primary efficacy endpoint was the incidence of SSI. The secondary efficacy endpoints were the locations of SSI, time to resolution of SSI, length of hospital stay, and the incidence of bile leakage in hepatectomy and pancreatic fistula. The incidence of SSI was 11.3%, 15.5%, 11.3%, and 36.9% after gastrectomy, colorectal surgery, hepatectomy, and PD, respectively. The incidence of SSI was higher in the absorbable suture group than in the silk suture group for all the surgical procedures, but the difference was not significant. The intra-abdominal use of absorbable sutures did not have enough of an effect on the reduction of SSI in this phase II trial to justify the planning of a large-scale phase III trial.","null","null","2017-02-23","Surgery Today","Surgery Today","Vol.47","No.9","1060","1071","eng","null","null","research_institution","null","null","10.1007/s00595-017-1480-3","1436-2813","null","null","null","null","null"
"Loss of Secreted Frizzled-Related Protein-1 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma.","Loss of Secreted Frizzled-Related Protein-1 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma.","M Davaadorj, Yu Saitou, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Chie Takasu, Shin-ichiro Yamada, Hiroki Teraoku, Masato Yoshikawa, Mitsuo Shimada","M Davaadorj, Yu Saitou, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Chie Takasu, Shin-ichiro Yamada, Hiroki Teraoku, Masato Yoshikawa, Mitsuo Shimada","null","Secreted Frizzled-Related Protein-1 (SFRP1) is a well-known negative regulator of the wingless type (Wnt)- -catenin pathway and its inactivation plays an important role in the development and progression of many cancers. In this study, we aimed to determine the clinical significance of SFRP1 expression in intrahepatic cholangiocarcinoma (IHCC) and to define the relationship to Wnt- -catenin pathway. Fifty IHCC patients who had liver resection were enrolled in this study. SFRP1 protein expression was examined by immunohistochemistry in tumor tissues. The patients were divided into two groups: SFRP1 positive (n = 30) and negative (n = 20). Clinicopathological characteristics were analyzed. SFRP1 significantly correlated with curability (Cur A, B vs. C, p = 0.029); and recurrent pattern (intrahepatic vs. extrahepatic, p = 0.010). The negative SFRP1 group had significantly poorer prognosis, and 5-year survival rates were 8.1% of the negative SFRP1 group and 44.6% of the positive SFRP1 group, respectively. Moreover, the disease-free survival rate in the negative SFRP1 group was significantly poorer (p < 0.001). Multivariate analysis revealed that loss of SFRP1served as an independent prognostic factor in IHCC for both overall (HR, 2.923; 95% CI, 1.30-6.56; p = 0.009) and disease-free (HR, 2.631; 95% CI, 1.31-5.27; p = 0.006) survival. In addition, SFRP1 expression negatively correlated to -catenin expression (p = 0.005). Those results suggested that the loss of SFRP1 could be a poor prognostic factor for IHCC, through the Wnt- -catenin pathway.","Secreted Frizzled-Related Protein-1 (SFRP1) is a well-known negative regulator of the wingless type (Wnt)- -catenin pathway and its inactivation plays an important role in the development and progression of many cancers. In this study, we aimed to determine the clinical significance of SFRP1 expression in intrahepatic cholangiocarcinoma (IHCC) and to define the relationship to Wnt- -catenin pathway. Fifty IHCC patients who had liver resection were enrolled in this study. SFRP1 protein expression was examined by immunohistochemistry in tumor tissues. The patients were divided into two groups: SFRP1 positive (n = 30) and negative (n = 20). Clinicopathological characteristics were analyzed. SFRP1 significantly correlated with curability (Cur A, B vs. C, p = 0.029); and recurrent pattern (intrahepatic vs. extrahepatic, p = 0.010). The negative SFRP1 group had significantly poorer prognosis, and 5-year survival rates were 8.1% of the negative SFRP1 group and 44.6% of the positive SFRP1 group, respectively. Moreover, the disease-free survival rate in the negative SFRP1 group was significantly poorer (p < 0.001). Multivariate analysis revealed that loss of SFRP1served as an independent prognostic factor in IHCC for both overall (HR, 2.923; 95% CI, 1.30-6.56; p = 0.009) and disease-free (HR, 2.631; 95% CI, 1.31-5.27; p = 0.006) survival. In addition, SFRP1 expression negatively correlated to -catenin expression (p = 0.005). Those results suggested that the loss of SFRP1 could be a poor prognostic factor for IHCC, through the Wnt- -catenin pathway.","null","null","2017-02","EJSO - European Journal of Surgical Oncology","EJSO - European Journal of Surgical Oncology","Vol.43","No.2","344","350","eng","null","null","research_institution","null","null","10.1016/j.ejso.2016.11.017","1532-2157","null","null","null","null","null"
"【100字de看護・説明を深める!きわめる!消化器外科の病棟で行う治療・処置】","【100字de看護・説明を深める!きわめる!消化器外科の病棟で行う治療・処置】","髙須 千絵, 島田 光生","Chie Takasu, Mitsuo Shimada","null","null","null","null","null","2016-10","消化器外科Nursing","Gastroenterological Surgery Nursing","Vol.21","No.10","909","924","jpn","null","null","research_institution","null","null","null","1341-7819","null","http://search.jamas.or.jp/link/ui/2017017062","null","null","null"
"Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection.","Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection.","Shohei Eto, Kouzou Yoshikawa, Masaaki Nishi, Jun Higashijima, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Chie Takasu, Takashi Iwata, Mitsuo Shimada","Shohei Eto, Kouzou Yoshikawa, Masaaki Nishi, Jun Higashijima, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Chie Takasu, Takashi Iwata, Mitsuo Shimada","null","Programmed cell death protein 1 (PD-1) and its ligand PD-L1 downregulate T cell activation and are related to immune tolerance. The aim of this study was to clarify the significance of PD-1 and PD-L1 expression and to analyze the relationships among PD-1, PD-L1, and Foxp3 expression in gastric cancer. A total of 105 patients who underwent curative gastrectomy for stage II/III gastric cancer were included in this study. PD-1, PD-L1, and Foxp3 expression were examined by immunohistochemistry and related to prognostic factors by univariate and multivariate analyses. PD-1 expression was correlated with both PD-L1 and Foxp3 expression. Disease-free survival (DFS) was significantly poorer in PD-1-positive patients than in PD-1-negative patients (3-year DFS, 36.1 % vs. 64.7 %, respectively; p < 0.05). Overall survival also tended to be poorer in PD-L1-positive patients than in PD-L1-negative patients. Univariate analysis identified sex, T factor, lymphatic invasion, and PD-1 positivity as significant predictors of poor DFS. Multivariate analysis confirmed male sex, lymphatic invasion, and positive PD-1 expression as independent prognostic indicators. PD-1 expression is associated with a poor prognosis and is correlated with PD-L1 and Foxp3 expression in patients with gastric cancer.","Programmed cell death protein 1 (PD-1) and its ligand PD-L1 downregulate T cell activation and are related to immune tolerance. The aim of this study was to clarify the significance of PD-1 and PD-L1 expression and to analyze the relationships among PD-1, PD-L1, and Foxp3 expression in gastric cancer. A total of 105 patients who underwent curative gastrectomy for stage II/III gastric cancer were included in this study. PD-1, PD-L1, and Foxp3 expression were examined by immunohistochemistry and related to prognostic factors by univariate and multivariate analyses. PD-1 expression was correlated with both PD-L1 and Foxp3 expression. Disease-free survival (DFS) was significantly poorer in PD-1-positive patients than in PD-1-negative patients (3-year DFS, 36.1 % vs. 64.7 %, respectively; p < 0.05). Overall survival also tended to be poorer in PD-L1-positive patients than in PD-L1-negative patients. Univariate analysis identified sex, T factor, lymphatic invasion, and PD-1 positivity as significant predictors of poor DFS. Multivariate analysis confirmed male sex, lymphatic invasion, and positive PD-1 expression as independent prognostic indicators. PD-1 expression is associated with a poor prognosis and is correlated with PD-L1 and Foxp3 expression in patients with gastric cancer.","null","null","2016-07-26","Gastric Cancer","Gastric Cancer","Vol.19","No.2","466","471","eng","null","null","research_institution","null","null","10.1007/s10120-015-0519-7","1436-3305","null","null","null","null","null"
"Limited lymph node dissection in elderly patients with gastric cancer.","Limited lymph node dissection in elderly patients with gastric cancer.","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Toshihiro Nakao, Masaaki Nishi, Hideya Kashihara, Chie Takasu","Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Toshihiro Nakao, Masaaki Nishi, Hideya Kashihara, Chie Takasu","null","The number of elderly patients with gastric cancer is continuing to increase along with the life expectancy of the general population. The purpose of this study was to investigate both the impact of age on postoperative outcome and the effect of limited lymph node dissection for elderly patients. Patients were classified into the following three groups: Group A, ·80 years old (n=44); Group B, 70-80 years old (n=139); Group C, <70 years old (n=219). Postoperative complication and survival rates were compared between the three groups Results: Limited lymph node dissection was performed significantly more frequently in Group A. In terms of surgery-related complications, no significant difference was seen between groups. In terms of general related complications, the complication rate increased with age, from 4% in Group C to 13% in Group B and 14% in Group A (p<0.05 each). Although limited lymph node dissection was frequently performed in Group A, cancer-specific survival showed no significant difference in R0 patients. Limited lymph node dissection for gastric cancer did not affect the cancer-specific survival in elderly patients.","The number of elderly patients with gastric cancer is continuing to increase along with the life expectancy of the general population. The purpose of this study was to investigate both the impact of age on postoperative outcome and the effect of limited lymph node dissection for elderly patients. Patients were classified into the following three groups: Group A, ·80 years old (n=44); Group B, 70-80 years old (n=139); Group C, <70 years old (n=219). Postoperative complication and survival rates were compared between the three groups Results: Limited lymph node dissection was performed significantly more frequently in Group A. In terms of surgery-related complications, no significant difference was seen between groups. In terms of general related complications, the complication rate increased with age, from 4% in Group C to 13% in Group B and 14% in Group A (p<0.05 each). Although limited lymph node dissection was frequently performed in Group A, cancer-specific survival showed no significant difference in R0 patients. Limited lymph node dissection for gastric cancer did not affect the cancer-specific survival in elderly patients.","null","null","2016","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.63","No.1-2","91","95","eng","null","null","research_institution","null","null","10.2152/jmi.63.91","1349-6867","null","null","null","null","null"
"Effect of Twist and Bmi1 on intraductal papillary mucinous neoplasm of the pancreas.","Effect of Twist and Bmi1 on intraductal papillary mucinous neoplasm of the pancreas.","Daichi Ishikawa, Mitsuo Shimada, Tohru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Mami Kanamoto, Shuichi Iwahashi, Yu Saitou, Shinichiro Yamada, Hidenori Miyake","Daichi Ishikawa, Mitsuo Shimada, Tohru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Mami Kanamoto, Shuichi Iwahashi, Yu Saitou, Shinichiro Yamada, Hidenori Miyake","null","Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity among pancreatic neoplasms that ranges from low-grade dysplasia to invasive carcinoma. Epithelial-mesenchymal transition (EMT) contributes to tumor progression in various cancers. Moreover, Notch signaling is one of the important upstream effectors of EMT promotion. Currently, it is unclear whether EMT causes pathological progression of IPMN. We evaluated the expression of EMT-promoting transcription factors Twist and B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) in IPMN. Patients who underwent resections at our institute and its affiliated hospital were enrolled in this study (n = 35). Protein expression of EMT markers Twist, Bmi1, Jagged1, and E-cadherin in resected specimens was investigated by immunohistochemistry. Expression of these proteins was compared with the clinicopathological factors and patient survival. Positive expression of Twist and Bmi1 was observed in 40.0% and 42.9% of IPMNs, respectively. Twist and Bmi1 expression was significantly higher in IPMNs with high-grade dysplasia (P < 0.05) and invasive carcinoma (P < 0.05) than that in IPMNs with low-grade dysplasia. High expression of Twist was correlated with Jagged1 expression and inversely correlated with expression of E-cadherin (P = 0.06 and P < 0.05, respectively). In survival analyses, the recurrence rate was significantly higher in the group that showed simultaneous high expression of Twist and Bmi1 (P < 0.05). Expression of Twist and Bmi1 is associated with aggressiveness and poor prognoses of IPMN through EMT promotion that might be induced by Notch signaling.","Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity among pancreatic neoplasms that ranges from low-grade dysplasia to invasive carcinoma. Epithelial-mesenchymal transition (EMT) contributes to tumor progression in various cancers. Moreover, Notch signaling is one of the important upstream effectors of EMT promotion. Currently, it is unclear whether EMT causes pathological progression of IPMN. We evaluated the expression of EMT-promoting transcription factors Twist and B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) in IPMN. Patients who underwent resections at our institute and its affiliated hospital were enrolled in this study (n = 35). Protein expression of EMT markers Twist, Bmi1, Jagged1, and E-cadherin in resected specimens was investigated by immunohistochemistry. Expression of these proteins was compared with the clinicopathological factors and patient survival. Positive expression of Twist and Bmi1 was observed in 40.0% and 42.9% of IPMNs, respectively. Twist and Bmi1 expression was significantly higher in IPMNs with high-grade dysplasia (P < 0.05) and invasive carcinoma (P < 0.05) than that in IPMNs with low-grade dysplasia. High expression of Twist was correlated with Jagged1 expression and inversely correlated with expression of E-cadherin (P = 0.06 and P < 0.05, respectively). In survival analyses, the recurrence rate was significantly higher in the group that showed simultaneous high expression of Twist and Bmi1 (P < 0.05). Expression of Twist and Bmi1 is associated with aggressiveness and poor prognoses of IPMN through EMT promotion that might be induced by Notch signaling.","null","null","2014-12","Journal of Gastroenterology and Hepatology","Journal of Gastroenterology and Hepatology","Vol.29","No.12","2032","2037","eng","null","null","research_institution","null","null","10.1111/jgh.12652","1440-1746","null","null","null","null","null"
"Cyclopamine decreased the expression of Sonic Hedgehog and its downstream genes in colon cancer stem cells.","Cyclopamine decreased the expression of Sonic Hedgehog and its downstream genes in colon cancer stem cells.","Bat-Erdene Batsaikhan, Kozo Yoshikawa, Nobuhiro Kurita, Takashi Iwata, Chie Takasu, Hideya Kashihara, Mitsuo Shimada","Bat-Erdene Batsaikhan, Kozo Yoshikawa, Nobuhiro Kurita, Takashi Iwata, Chie Takasu, Hideya Kashihara, Mitsuo Shimada","null","Backround: Most solid cancers including colon cancer are believed to be initiated from and maintained by cancer stem cells (CSCs), that are responsible for treatment resistance, resulting in tumor relapse. The aim of this study was to clarify the possible role of the Sonic Hedgehog (Shh) signaling pathway in the regulation of cancer stem cells. The HCT-116 cell line was cultured with fetal bovine serum in RPMI-1640 medium and its sphere was grown in serum-free non-adherent culture. Gene expressions were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) from cells treated with and without cyclopamine. HCT-116 sphere-derived cells grown in serum-free, non-adherent culture, showed significantly increased expression of stem cell markers, Shh downstream genes and epithelial-mesenchymal transition (EMT) markers compared to parental cells grown in conventional culture. The expression of stemness markers, Shh downstream genes and EMT markers were higher in cancer spheres than the parental cell line and down-regulated by cyclopamine treatment in a dose-dependent manner. Overall, these findings show that cyclopamine treatment could down-regulate the expression of stemness markers, shh downstream genes and EMT markers on HCT-116 spheres.","Backround: Most solid cancers including colon cancer are believed to be initiated from and maintained by cancer stem cells (CSCs), that are responsible for treatment resistance, resulting in tumor relapse. The aim of this study was to clarify the possible role of the Sonic Hedgehog (Shh) signaling pathway in the regulation of cancer stem cells. The HCT-116 cell line was cultured with fetal bovine serum in RPMI-1640 medium and its sphere was grown in serum-free non-adherent culture. Gene expressions were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) from cells treated with and without cyclopamine. HCT-116 sphere-derived cells grown in serum-free, non-adherent culture, showed significantly increased expression of stem cell markers, Shh downstream genes and epithelial-mesenchymal transition (EMT) markers compared to parental cells grown in conventional culture. The expression of stemness markers, Shh downstream genes and EMT markers were higher in cancer spheres than the parental cell line and down-regulated by cyclopamine treatment in a dose-dependent manner. Overall, these findings show that cyclopamine treatment could down-regulate the expression of stemness markers, shh downstream genes and EMT markers on HCT-116 spheres.","null","null","2014-11","Anticancer Research","Anticancer Research","Vol.34","No.11","6339","6344","eng","null","null","research_institution","null","null","null","1791-7530","null","null","null","null","null"
"CD133 expression is correlated with poor prognosis in colorectal cancer.","CD133 expression is correlated with poor prognosis in colorectal cancer.","Hideya Kashihara, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Hirohiko Sato, Yoshikawa Kozo, Jun Higashijima, Motoya Chikakiyo, Masaaki Nishi, Noriko Matsumoto","Hideya Kashihara, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Hirohiko Sato, Yoshikawa Kozo, Jun Higashijima, Motoya Chikakiyo, Masaaki Nishi, Noriko Matsumoto","null","Cancer stem cells (CSC) was reported to play an important role in various kinds of cancer. CD133 is one of the cancer stem cell markers in solid cancers. However, the correlation between CD133 expression and the clinicopathological factors in colorectal cancer (CRC) remains unclear. Forty patients with CRC who underwent operations were enrolled. Expression of CD133 was investigated by immunohistochemistry (IHC). The staining was observed in the cytoplasm of cancer cells and the patients who have the staining were defined as CD133-positive cases. The patients were divided into two groups: the CD133-positive group (n = 22) and negative group (n = 18). Clinicopathological factors were compared between the two groups. The prognostic factors were investigated by multivariate analysis. In the CD133-positive group, the incidence of lymph node and liver metastasis, lymphatic and venous invasion, as well as the progression of stage of cancer were higher than that in the CD133-negative group. The 5-year survival rate and the disease-free survival rate in the CD133-positive group were lower than that in the CD133-negative group. The multivariate analysis revealed that CD133 expression tended to be an independent prognostic factor. CD133 expression is correlated with poor prognosis in CRC.","Cancer stem cells (CSC) was reported to play an important role in various kinds of cancer. CD133 is one of the cancer stem cell markers in solid cancers. However, the correlation between CD133 expression and the clinicopathological factors in colorectal cancer (CRC) remains unclear. Forty patients with CRC who underwent operations were enrolled. Expression of CD133 was investigated by immunohistochemistry (IHC). The staining was observed in the cytoplasm of cancer cells and the patients who have the staining were defined as CD133-positive cases. The patients were divided into two groups: the CD133-positive group (n = 22) and negative group (n = 18). Clinicopathological factors were compared between the two groups. The prognostic factors were investigated by multivariate analysis. In the CD133-positive group, the incidence of lymph node and liver metastasis, lymphatic and venous invasion, as well as the progression of stage of cancer were higher than that in the CD133-negative group. The 5-year survival rate and the disease-free survival rate in the CD133-positive group were lower than that in the CD133-negative group. The multivariate analysis revealed that CD133 expression tended to be an independent prognostic factor. CD133 expression is correlated with poor prognosis in CRC.","null","null","2014-09","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.61","No.134","1563","1567","eng","null","null","research_institution","null","null","10.5754/hge13657","0172-6390","null","null","null","null","null"
"Effect of light irradiation by light emitting diode on colon cancer cells.","Effect of light irradiation by light emitting diode on colon cancer cells.","Noriko Matsumoto, Kouzou Yoshikawa, Mitsuo Shimada, Nobuhiro Kurita, Horohiko Sato, Takashi Iwata, Jun Higashijima, Motoya Chikakiyo, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Shohei Eto, Akira Takahashi, Masatake Akutagawa, Takahiro Emoto","Noriko Matsumoto, Kouzou Yoshikawa, Mitsuo Shimada, Nobuhiro Kurita, Horohiko Sato, Takashi Iwata, Jun Higashijima, Motoya Chikakiyo, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Shohei Eto, Akira Takahashi, Masatake Akutagawa, Takahiro Emoto","null","Recent studies have demonstrated the efficacy of irradiation from light emitting diodes (LED) for wound healing, anti-inflammation and anticancer therapies. However, little is known about the effects of visible light in colon cancer cells. The purpose of this study was to evaluate the biological response (including gene expression changes) of human colon cancer cells to different wavelengths of LED irradiation. Human colon cancer cells (HT29 or HCT116) were seeded onto laboratory dishes that were then put on LED irradiation equipment with a 465 nm-, 525 nm-, or 635 nm-LED. Irradiation at 15 or 30 mW was performed 10 min/day, each day for 5 days. The cell counting kit8 was then used to measure cell viability. Apoptosis and expression of several mRNAs (caspase, MAPK and autophagy pathway) in HT29 cultures irradiated with 465 nm LED were evaluated via AnnexinV/PI and RT-PCR, respectively. Viability of HT29 and HCT116 cells was lower in 465 nm-LED irradiated cultures than in control cultures, but viability of HT29 cells did not differ between control cultures and 525 nm-LED or 635 nm-LED irradiated cultures. Moreover, the expression of FAS, caspase-3, capase-8, and JUK were significantly higher in 465 nm-LED irradiated cultures than in control cultures, and expression of ERK1/2 and LC3 was lower in blue-irradiated cells. LED irradiation at 465 nm inhibited the proliferation of HT29 cells and of HCT116 cells. Notably, LED irradiation at 465 nm promoted apoptosis inHT29 cultures via the extrinsic apoptosis pathway and the MAPK pathway.","Recent studies have demonstrated the efficacy of irradiation from light emitting diodes (LED) for wound healing, anti-inflammation and anticancer therapies. However, little is known about the effects of visible light in colon cancer cells. The purpose of this study was to evaluate the biological response (including gene expression changes) of human colon cancer cells to different wavelengths of LED irradiation. Human colon cancer cells (HT29 or HCT116) were seeded onto laboratory dishes that were then put on LED irradiation equipment with a 465 nm-, 525 nm-, or 635 nm-LED. Irradiation at 15 or 30 mW was performed 10 min/day, each day for 5 days. The cell counting kit8 was then used to measure cell viability. Apoptosis and expression of several mRNAs (caspase, MAPK and autophagy pathway) in HT29 cultures irradiated with 465 nm LED were evaluated via AnnexinV/PI and RT-PCR, respectively. Viability of HT29 and HCT116 cells was lower in 465 nm-LED irradiated cultures than in control cultures, but viability of HT29 cells did not differ between control cultures and 525 nm-LED or 635 nm-LED irradiated cultures. Moreover, the expression of FAS, caspase-3, capase-8, and JUK were significantly higher in 465 nm-LED irradiated cultures than in control cultures, and expression of ERK1/2 and LC3 was lower in blue-irradiated cells. LED irradiation at 465 nm inhibited the proliferation of HT29 cells and of HCT116 cells. Notably, LED irradiation at 465 nm promoted apoptosis inHT29 cultures via the extrinsic apoptosis pathway and the MAPK pathway.","null","null","2014-09","Anticancer Research","Anticancer Research","Vol.34","No.9","4709","4716","eng","null","null","research_institution","null","null","null","1791-7530","null","null","null","null","null"
"Branched chain amino acid suppressed insulin-initiated proliferation of human cancer cells through induction of autophagy.","Branched chain amino acid suppressed insulin-initiated proliferation of human cancer cells through induction of autophagy.","Gizachew Yismaw Wubetu, Tohru Utsunomiya, Daichi Ishikawa, Tetsuya Ikemoto, Shinichiro Yamada, Yuji Morine, Shuichi Iwahashi, Yu Saitou, Yusuke Arakawa, Satoru Imura, Hideki Arimochi, Mitsuo Shimada","Gizachew Yismaw Wubetu, Tohru Utsunomiya, Daichi Ishikawa, Tetsuya Ikemoto, Shinichiro Yamada, Yuji Morine, Shuichi Iwahashi, Yu Saitou, Yusuke Arakawa, Satoru Imura, Hideki Arimochi, Mitsuo Shimada","null","Branched chain amino acid (BCAA) dietary supplementation inhibits activation of the insulin-like growth factor (IGF)/IGF-I receptor (IGF-IR) axis in diabetic animal models. However, the in vitro effect of BCAA on human cancer cell lines under hyper-insulinemic conditions remains unclear. Colon (HCT-116) and hepatic (HepG2) tumor cells were treated with varying concentrations of BCAA with or without fluorouracil (5-FU). The effect of BCAA on insulin-initiated proliferation was determined. Gene and protein expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. BCAA supplementation had no significant effect on cell proliferation and did not show significant synergistic or antagonistic effects with 5-FU. However, BCAA significantly decreased insulin-initiated proliferation of human colon and hepatic cancer cell lines in vitro. BCAA supplementation caused a marked decrease in activated IGF-IR expression and significantly enhanced both mRNA and protein expression of LC3-II and BECN1 (BECLIN-1). BCAA could be a useful chemopreventive modality for cancer in hyperinsulinemic conditions.","Branched chain amino acid (BCAA) dietary supplementation inhibits activation of the insulin-like growth factor (IGF)/IGF-I receptor (IGF-IR) axis in diabetic animal models. However, the in vitro effect of BCAA on human cancer cell lines under hyper-insulinemic conditions remains unclear. Colon (HCT-116) and hepatic (HepG2) tumor cells were treated with varying concentrations of BCAA with or without fluorouracil (5-FU). The effect of BCAA on insulin-initiated proliferation was determined. Gene and protein expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. BCAA supplementation had no significant effect on cell proliferation and did not show significant synergistic or antagonistic effects with 5-FU. However, BCAA significantly decreased insulin-initiated proliferation of human colon and hepatic cancer cell lines in vitro. BCAA supplementation caused a marked decrease in activated IGF-IR expression and significantly enhanced both mRNA and protein expression of LC3-II and BECN1 (BECLIN-1). BCAA could be a useful chemopreventive modality for cancer in hyperinsulinemic conditions.","null","null","2014-09","Anticancer Research","Anticancer Research","Vol.34","No.9","4789","4796","eng","null","null","research_institution","null","null","null","1791-7530","null","null","null","null","null"
"Protein kinase Cι is a new prognostic factor in gastric cancer.","Protein kinase Cι is a new prognostic factor in gastric cancer.","Hideya Kashihara, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Hirohiko Sato, Kozo Yoshikawa, Tomohiko Miyatani, Chie Takasu, Noriko Matsumoto","Hideya Kashihara, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Hirohiko Sato, Kozo Yoshikawa, Tomohiko Miyatani, Chie Takasu, Noriko Matsumoto","null","Protein kinase Cι (PKCι) is an important oncogenic K-ras effector, and its expression is correlated with tumor angiogenesis. The role of PKCι in gastric cancer remains unclear. The aim of this study was to clarify the role of PKCι in gastric cancer. Twenty-eight patients with gastric cancer who underwent gastrectomy were enrolled in this study. The expression of PKCι mRNA was determined, as were the clinicopathological factors. The patients were divided into PKCι high and low expression groups. The 5-year survival rate, ERK mRNA level and VEGF mRNA level were compared between the two groups. The prognostic factors were investigated by a multivariate analysis. High expression of PKCι was observed to be associated with a lack of differentiation, tumor invasion ≥muscularis propria≤, stage III and IV disease and peritoneal dissemination. The 5-year survival rate in the PKCι high group was lower than that in the PKCι low group. The multivariate analysis revealed that a high expression level of PKCι was an independent prognostic factor. The expression levels of ERK and VEGF in the PKCι high group were higher than those in the PKCι low group. Our results indicate that PKCι is correlated with tumor progression and angiogenesis. PKCι may be a new prognostic factor for gastric cancer.","Protein kinase Cι (PKCι) is an important oncogenic K-ras effector, and its expression is correlated with tumor angiogenesis. The role of PKCι in gastric cancer remains unclear. The aim of this study was to clarify the role of PKCι in gastric cancer. Twenty-eight patients with gastric cancer who underwent gastrectomy were enrolled in this study. The expression of PKCι mRNA was determined, as were the clinicopathological factors. The patients were divided into PKCι high and low expression groups. The 5-year survival rate, ERK mRNA level and VEGF mRNA level were compared between the two groups. The prognostic factors were investigated by a multivariate analysis. High expression of PKCι was observed to be associated with a lack of differentiation, tumor invasion ≥muscularis propria≤, stage III and IV disease and peritoneal dissemination. The 5-year survival rate in the PKCι high group was lower than that in the PKCι low group. The multivariate analysis revealed that a high expression level of PKCι was an independent prognostic factor. The expression levels of ERK and VEGF in the PKCι high group were higher than those in the PKCι low group. Our results indicate that PKCι is correlated with tumor progression and angiogenesis. PKCι may be a new prognostic factor for gastric cancer.","null","null","2014-08-10","Surgery Today","Surgery Today","Vol.45","No.6","759","764","eng","null","null","research_institution","null","null","10.1007/s00595-014-1010-5","1436-2813","null","null","null","null","null"
"Laparoscopic resection of hepatoblastoma: report of a case.","Laparoscopic resection of hepatoblastoma: report of a case.","Keigo Yada, Hiroki Ishibashi, Hiroki Mori, Mitsuo Shimada","Keigo Yada, Hiroki Ishibashi, Hiroki Mori, Mitsuo Shimada","null","Despite the increasing number of recent reports on laparoscopic resection of malignant liver tumors in adults, there have been few reports involving children. In this paper we discuss the laparoscopic resection of a hepatoblastoma in a 1-year-old boy. The CT scan revealed an exophytic hepatic tumor on S5 measuring 6 × 5 × 4 cm after preoperative chemotherapy. The operation time was 225 min with an estimated blood loss of about 38 mL; intraoperative transfusion was not required. Radiofrequency-assisted precoagulation was performed. The patient had an uncomplicated recovery and started postoperative chemotherapy on postoperative day 12. Our literature search revealed only five reported cases of laparoscopic resection of hepatoblastoma in which there was no postoperative complication or recurrence. Laparoscopic resection of a hepatoblastoma in a selected subgroup of patients can be safe and feasible.","Despite the increasing number of recent reports on laparoscopic resection of malignant liver tumors in adults, there have been few reports involving children. In this paper we discuss the laparoscopic resection of a hepatoblastoma in a 1-year-old boy. The CT scan revealed an exophytic hepatic tumor on S5 measuring 6 × 5 × 4 cm after preoperative chemotherapy. The operation time was 225 min with an estimated blood loss of about 38 mL; intraoperative transfusion was not required. Radiofrequency-assisted precoagulation was performed. The patient had an uncomplicated recovery and started postoperative chemotherapy on postoperative day 12. Our literature search revealed only five reported cases of laparoscopic resection of hepatoblastoma in which there was no postoperative complication or recurrence. Laparoscopic resection of a hepatoblastoma in a selected subgroup of patients can be safe and feasible.","null","null","2014-08","Asian Journal of Endoscopic Surgery","Asian Journal of Endoscopic Surgery","Vol.7","No.3","267","270","eng","null","null","research_institution","null","null","10.1111/ases.12106","1758-5910","null","null","null","null","null"
"Expression of Stathmin1 in gastric adenocarcinoma.","Expression of Stathmin1 in gastric adenocarcinoma.","Bat-Erdene Batsaikhan, Kozo Yoshikawa, Nobuhiro Kurita, Takashi Iwata, Chie Takasu, Hideya Kashihara, Mitsuo Shimada","Bat-Erdene Batsaikhan, Kozo Yoshikawa, Nobuhiro Kurita, Takashi Iwata, Chie Takasu, Hideya Kashihara, Mitsuo Shimada","null","Over expression of Stathmin1 (STMN1), activation-induced cytidine deaminase (AID) and protein kinase C iota (PKCi) proteins participate in the regulation of carcinogenesis. In the present study, we investigated the expression of STMN1 in patients with gastric adenocarcinoma and also determined the correlation of STMN1 with AID and PKCi proteins. This study was conducted in the Tokushima University Hospital between September 2009 and September 2010 on a total of 59 patients with gastric adenocarcinoma. Stathmin1, AID and PKCi protein expressions were evaluated by immuno-histochemistry in gastric adenocarcinoma. A strong expression of STMN1 was significantly associated with gender- and poorly differentiated gastric adenocarcinoma (p<0.05). A high mRNA level of STMN1 was found in the tumor tissue of gastric adenocarcinoma compared to non-tumor tissue (p<0.05). In addition, STMN1 expression was significantly correlated with AID and PKCi protein expressions in gastric adenocarcinoma (p<0.05). High mRNA level of the Stathmin1 gene was significantly expressed in gastric tumor tissue than non-tumor and strong expression of STMN1 protein is correlated with poorly-differentiated gastric adenocarcinoma.","Over expression of Stathmin1 (STMN1), activation-induced cytidine deaminase (AID) and protein kinase C iota (PKCi) proteins participate in the regulation of carcinogenesis. In the present study, we investigated the expression of STMN1 in patients with gastric adenocarcinoma and also determined the correlation of STMN1 with AID and PKCi proteins. This study was conducted in the Tokushima University Hospital between September 2009 and September 2010 on a total of 59 patients with gastric adenocarcinoma. Stathmin1, AID and PKCi protein expressions were evaluated by immuno-histochemistry in gastric adenocarcinoma. A strong expression of STMN1 was significantly associated with gender- and poorly differentiated gastric adenocarcinoma (p<0.05). A high mRNA level of STMN1 was found in the tumor tissue of gastric adenocarcinoma compared to non-tumor tissue (p<0.05). In addition, STMN1 expression was significantly correlated with AID and PKCi protein expressions in gastric adenocarcinoma (p<0.05). High mRNA level of the Stathmin1 gene was significantly expressed in gastric tumor tissue than non-tumor and strong expression of STMN1 protein is correlated with poorly-differentiated gastric adenocarcinoma.","null","null","2014-08","Anticancer Research","Anticancer Research","Vol.34","No.8","4217","4221","eng","null","null","research_institution","null","null","null","1791-7530","null","null","null","null","null"
"Hybrid technique for laparoscopic incisional ventral hernia repair combining laparoscopic primary closure and mesh repair.","Hybrid technique for laparoscopic incisional ventral hernia repair combining laparoscopic primary closure and mesh repair.","Kozo Yoshikawa, Mitsuo Shimada, Nobuhiro Kurita, Hirohiko Sato, Takashi Iwata, Jun Higashijima, Motoya Chikakiyo, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Noriko Matsumoto, Syohei Eto","Kozo Yoshikawa, Mitsuo Shimada, Nobuhiro Kurita, Hirohiko Sato, Takashi Iwata, Jun Higashijima, Motoya Chikakiyo, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Noriko Matsumoto, Syohei Eto","null","Incisional ventral hernia is one of the most common surgical complications after laparotomy. Laparoscopic repair of incisional ventral hernia has been conducted recently, and the advantages of this procedure have been reported. However, in large orifice cases, the recurrence rate is increased. To improve recurrence rates in large cases, a hybrid method combining laparoscopic primary closure and mesh repair can be applied. Monofilament thread was inserted into the abdominal cavity for hernia closure and pulled from the other side of the orifice. The same procedure was performed from the upper side to the lower side without closure, and all thread was placed in line. Both sides of the thread were then introduced to the midline of the incision through a subcutaneous route. This procedure was conducted with an introducer. All threads were tied, and then a mesh was placed. Hybrid techniques already combine mini-laparotomy for hernia closure and subsequent laparoscopic intraoperative onlay mesh for reinforcement, but such techniques require laparotomy. In our technique, closure of the linea alba does not require laparotomy. All procedures were performed laparoscopically. This procedure is very easy and safe, and does not require the abdominal cavity to be opened. Thus, hybrid methods are effective for treating cases of incisional hernia involving a large orifice.","Incisional ventral hernia is one of the most common surgical complications after laparotomy. Laparoscopic repair of incisional ventral hernia has been conducted recently, and the advantages of this procedure have been reported. However, in large orifice cases, the recurrence rate is increased. To improve recurrence rates in large cases, a hybrid method combining laparoscopic primary closure and mesh repair can be applied. Monofilament thread was inserted into the abdominal cavity for hernia closure and pulled from the other side of the orifice. The same procedure was performed from the upper side to the lower side without closure, and all thread was placed in line. Both sides of the thread were then introduced to the midline of the incision through a subcutaneous route. This procedure was conducted with an introducer. All threads were tied, and then a mesh was placed. Hybrid techniques already combine mini-laparotomy for hernia closure and subsequent laparoscopic intraoperative onlay mesh for reinforcement, but such techniques require laparotomy. In our technique, closure of the linea alba does not require laparotomy. All procedures were performed laparoscopically. This procedure is very easy and safe, and does not require the abdominal cavity to be opened. Thus, hybrid methods are effective for treating cases of incisional hernia involving a large orifice.","null","null","2014-08","Asian Journal of Endoscopic Surgery","Asian Journal of Endoscopic Surgery","Vol.7","No.3","282","285","eng","null","null","research_institution","null","null","10.1111/ases.12113","1758-5910","null","null","null","null","null"
"High STAT4 expression is a better prognostic indicator in patients with hepatocellular carcinoma after hepatectomy.","High STAT4 expression is a better prognostic indicator in patients with hepatocellular carcinoma after hepatectomy.","Gizachew Yismaw Wubetu, Tohru Utsunomiya, Daichi Ishikawa, Shinichiro Yamada, Tetsuya Ikemoto, Yuji Morine, Shuichi Iwahashi, Yu Saitou, Yusuke Arakawa, Satoru Imura, Mami Kanamoto, Chengzhan Zhu, Yoshimi Bando, Mitsuo Shimada","Gizachew Yismaw Wubetu, Tohru Utsunomiya, Daichi Ishikawa, Shinichiro Yamada, Tetsuya Ikemoto, Yuji Morine, Shuichi Iwahashi, Yu Saitou, Yusuke Arakawa, Satoru Imura, Mami Kanamoto, Chengzhan Zhu, Yoshimi Bando, Mitsuo Shimada","null","Signal transducer and activator of transcription 4 (STAT4) mediates the intracellular effects of interleukin-12, leading to the production of interferon gamma (IFN-γ) and natural killer cells cytotoxicity. However, the clinical significance of STAT4 expression in patients with hepatocellular carcinoma (HCC) remains virtually unknown. A total of 66 HCC patients who underwent hepatectomy were enrolled in this study. Quantitative real-time polymerase chain reaction was performed to determine STAT4 and IFNG mRNA expression levels. Tissue microarray-based immunohistochemistry was performed to examine CD8(+) T cells, STAT4, and INF-γ proteins. STAT4 was differentially expressed in tumor and nontumor tissues (P = 0.001) and positively correlated with IFNG expression (R (2) = 0.506, P < 0.05) and CD8(+) T cell infiltration (R (2) = 0.53, P < 0.001). Significant correlations were observed between STAT4 expression and tumor TNM stage (P = 0.043), hepatic venous invasion (P = 0.003), des-gamma-carboxy prothrombin (P = 0.011), tumor size (P = 0.036), and tumor differentiation (P = 0.034). Patients with high STAT4 expression had significantly better recurrence-free survival (P = 0.009). Low STAT4 expression (P = 0.030) and presence of portal venous invasion or hepatic venous invasion (P = 0.006) were independent risk factors for HCC recurrence. Downregulation of STAT4 in HCC indicated aggressive tumor behavior and predicted a worse clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after hepatectomy.","Signal transducer and activator of transcription 4 (STAT4) mediates the intracellular effects of interleukin-12, leading to the production of interferon gamma (IFN-γ) and natural killer cells cytotoxicity. However, the clinical significance of STAT4 expression in patients with hepatocellular carcinoma (HCC) remains virtually unknown. A total of 66 HCC patients who underwent hepatectomy were enrolled in this study. Quantitative real-time polymerase chain reaction was performed to determine STAT4 and IFNG mRNA expression levels. Tissue microarray-based immunohistochemistry was performed to examine CD8(+) T cells, STAT4, and INF-γ proteins. STAT4 was differentially expressed in tumor and nontumor tissues (P = 0.001) and positively correlated with IFNG expression (R (2) = 0.506, P < 0.05) and CD8(+) T cell infiltration (R (2) = 0.53, P < 0.001). Significant correlations were observed between STAT4 expression and tumor TNM stage (P = 0.043), hepatic venous invasion (P = 0.003), des-gamma-carboxy prothrombin (P = 0.011), tumor size (P = 0.036), and tumor differentiation (P = 0.034). Patients with high STAT4 expression had significantly better recurrence-free survival (P = 0.009). Low STAT4 expression (P = 0.030) and presence of portal venous invasion or hepatic venous invasion (P = 0.006) were independent risk factors for HCC recurrence. Downregulation of STAT4 in HCC indicated aggressive tumor behavior and predicted a worse clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after hepatectomy.","null","null","2014-06-26","Annals of Surgical Oncology","Annals of Surgical Oncology","Vol.21 Suppl 4","null","S721","8","eng","null","null","research_institution","null","null","10.1245/s10434-014-3861-9","1534-4681","null","null","null","null","null"
"Role of CD151 expression in gallbladder carcinoma.","Role of CD151 expression in gallbladder carcinoma.","Noriko Matsumoto, Yuji Morine, Tohru Utsunomiya, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Shuichi Iwahashi, Yu Saitou, Shiniciro Yamada, Daichi Ishikawa, Chie Takasu, Hidenori Miyake, Mitsuo Shimada","Noriko Matsumoto, Yuji Morine, Tohru Utsunomiya, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Shuichi Iwahashi, Yu Saitou, Shiniciro Yamada, Daichi Ishikawa, Chie Takasu, Hidenori Miyake, Mitsuo Shimada","null","CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. CD151 is involved in several pathologic activities associated with tumor progression, including metastasis and angiogenesis. The aim of this study was to clarify the clinical use of CD151 expression in gallbladder cancer (GBC). Forty-five patients with GBC who had undergone operative treatment were enrolled in this study. Expressions of CD151 in the resected GBC specimens were evaluated with anti-CD151 antibody. The patients were divided into positive and negative groups according to CD151 expression: CD151-positive group (n = 26) and CD151-negative group (n = 19). Clinicopathologic factors, including Ki-67 and matrix metallopeptidase 9, also were compared between the two groups. CD151-positive expression was 58% and correlated with poorer prognosis; 5-year survival of CD151-positive and CD151-negative groups was 29% and 78%, respectively (P = .006). CD151 expression also correlated with lymphatic invasion and curability. Multivariate analysis revealed that CD151-positive expression was an independent prognostic factor (hazard ratio 2.97, P = .02). In addition, CD151 expression correlated with matrix metallopeptidase 9 expression (P < .05) but not with Ki67 expression. Those findings suggested that CD151-positive expression might be a potential prognostic indicator and one of the target molecules for the regulation of tumor metastasis for patients with GBC.","CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. CD151 is involved in several pathologic activities associated with tumor progression, including metastasis and angiogenesis. The aim of this study was to clarify the clinical use of CD151 expression in gallbladder cancer (GBC). Forty-five patients with GBC who had undergone operative treatment were enrolled in this study. Expressions of CD151 in the resected GBC specimens were evaluated with anti-CD151 antibody. The patients were divided into positive and negative groups according to CD151 expression: CD151-positive group (n = 26) and CD151-negative group (n = 19). Clinicopathologic factors, including Ki-67 and matrix metallopeptidase 9, also were compared between the two groups. CD151-positive expression was 58% and correlated with poorer prognosis; 5-year survival of CD151-positive and CD151-negative groups was 29% and 78%, respectively (P = .006). CD151 expression also correlated with lymphatic invasion and curability. Multivariate analysis revealed that CD151-positive expression was an independent prognostic factor (hazard ratio 2.97, P = .02). In addition, CD151 expression correlated with matrix metallopeptidase 9 expression (P < .05) but not with Ki67 expression. Those findings suggested that CD151-positive expression might be a potential prognostic indicator and one of the target molecules for the regulation of tumor metastasis for patients with GBC.","null","null","2014-06-02","Surgery","Surgery","Vol.156","No.5","1212","1217","eng","null","null","research_institution","null","null","10.1016/j.surg.2014.04.053","1532-7361","null","null","null","null","null"
"Duodenal-Jejunal Bypass Improves Insulin Resistance by Enhanced Glucagon-Like Peptide-1 Secretion Through Increase of Bile Acids.","Duodenal-Jejunal Bypass Improves Insulin Resistance by Enhanced Glucagon-Like Peptide-1 Secretion Through Increase of Bile Acids.","Hideya Kashihara, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Hirohiko Sato, Kozo Yoshikawa, Tomohiko Miyatani, Chie Takasu, Noriko Matsumoto, Hiroki Ishibashi","Hideya Kashihara, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Hirohiko Sato, Kozo Yoshikawa, Tomohiko Miyatani, Chie Takasu, Noriko Matsumoto, Hiroki Ishibashi","null","The aim of this study is to investigate the mechanisms of improvement in insulin resistance after duodenal-jejunal bypass (DIB), especially regarding the correlation between bile acids and glucagon-like peptide-1 (GLP-1). SD rats were divided into two groups: DIB or Sham group. Blood glucose, insulin, GLP-1, bile acids, and the number of L cells in the small intestine were investigated three weeks after the operations. Next, to assess the effect of the bile acids on GLP-1 secretion in ileum, bile diversion model (=inhibition of rapid bile exposure to the ileum; BD group) were performed and postoperative glycemic parameters were measured. DJB improved insulin resistance and increased GLP-1 compared with sham. Higher bile acids in DJB were found than that in sham. The number of L cells in the common limb of DJB was increased compared with that in the distal segment of sham. In BD group, insulin resistance had not improved. GLP-1, bile acids, and the number of L cells revealed no significant changes compared with sham. DJB has a potential to improve insulin resistance, which may be related to enhanced GLP-1 secretion through the increase of bile acids in the common limb of the small intestine.","The aim of this study is to investigate the mechanisms of improvement in insulin resistance after duodenal-jejunal bypass (DIB), especially regarding the correlation between bile acids and glucagon-like peptide-1 (GLP-1). SD rats were divided into two groups: DIB or Sham group. Blood glucose, insulin, GLP-1, bile acids, and the number of L cells in the small intestine were investigated three weeks after the operations. Next, to assess the effect of the bile acids on GLP-1 secretion in ileum, bile diversion model (=inhibition of rapid bile exposure to the ileum; BD group) were performed and postoperative glycemic parameters were measured. DJB improved insulin resistance and increased GLP-1 compared with sham. Higher bile acids in DJB were found than that in sham. The number of L cells in the common limb of DJB was increased compared with that in the distal segment of sham. In BD group, insulin resistance had not improved. GLP-1, bile acids, and the number of L cells revealed no significant changes compared with sham. DJB has a potential to improve insulin resistance, which may be related to enhanced GLP-1 secretion through the increase of bile acids in the common limb of the small intestine.","null","null","2014-06","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.61","No.132","1049","1054","eng","null","null","research_institution","null","null","10.5754/hge13029","0172-6390","null","null","null","null","null"
"The Role Of Surgical Treatment In The Multidisciplinary Therapy For Hepatoblastoma.","The Role Of Surgical Treatment In The Multidisciplinary Therapy For Hepatoblastoma.","Keigo Yada, Hiroki Ishibashi, Hiroki Mori, Hirohiko Sato, Mitsuo Shimada","Keigo Yada, Hiroki Ishibashi, Hiroki Mori, Hirohiko Sato, Mitsuo Shimada","null","The aim of this study was to evaluate the clinico-patholigical features and effects of multi-disciplinary therapy for pediatric patients with hepatoblastoma (HB). Ten cases who underwent hepatectomy from 1996 to 2013 were studied. Our therapeutic protocol included neoadjuvant chemotherapy (NAC) + hepatectomy + adjuvant chemotherapy (AC). The regimens were CDDP+THP-ADR (n = 2), CITA (n = 1), PLADO (n = 5), and CDDP(n = 1). One case with 18-trisomy underwent only hepatectomy. Medical records were reviewed to evaluate characteristics, the effects of chemotherapy and prognosis. The median age at operation was 1.2 years (male: 7 and female: 3). PRETEXT classification was assigned to groups I (n = 2), II (n = 4), and III (n = 4). 15 years overall survival and disease-free survival rates were 100% and 80%, respectively. Two cases, who had post-operative lung metastasis, underwent chemotherapy with or without complete resection of lung tumors. No further recurrence was observed in these two cases. One case with 18 trisomy underwent right hepatectomy for PRETEXT II HB and is still doing well 67 months after hepatectomy. It was found that multidisciplinary therapy based on surgery, including complete resections of recurrent lesions, offers long-term survival, even for cases which develop recurrent metastatic tumors or cases complicated with 18 trisomy.","The aim of this study was to evaluate the clinico-patholigical features and effects of multi-disciplinary therapy for pediatric patients with hepatoblastoma (HB). Ten cases who underwent hepatectomy from 1996 to 2013 were studied. Our therapeutic protocol included neoadjuvant chemotherapy (NAC) + hepatectomy + adjuvant chemotherapy (AC). The regimens were CDDP+THP-ADR (n = 2), CITA (n = 1), PLADO (n = 5), and CDDP(n = 1). One case with 18-trisomy underwent only hepatectomy. Medical records were reviewed to evaluate characteristics, the effects of chemotherapy and prognosis. The median age at operation was 1.2 years (male: 7 and female: 3). PRETEXT classification was assigned to groups I (n = 2), II (n = 4), and III (n = 4). 15 years overall survival and disease-free survival rates were 100% and 80%, respectively. Two cases, who had post-operative lung metastasis, underwent chemotherapy with or without complete resection of lung tumors. No further recurrence was observed in these two cases. One case with 18 trisomy underwent right hepatectomy for PRETEXT II HB and is still doing well 67 months after hepatectomy. It was found that multidisciplinary therapy based on surgery, including complete resections of recurrent lesions, offers long-term survival, even for cases which develop recurrent metastatic tumors or cases complicated with 18 trisomy.","null","null","2014-05","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.61","No.131","553","556","eng","null","null","research_institution","null","null","10.5754/hge14068","0172-6390","null","null","null","null","null"
"P1胃癌に対しS-1+PTXi.p.を行い5年生存が得られた1例","P1胃癌に対しS-1+PTXi.p.を行い5年生存が得られた1例","松本 規子, 島田 光生, 栗田 信浩, 佐藤 宏彦, 岩田 貴, 吉川 幸造, 東島 潤, 近清 素也, 西 正暁, 柏原 秀也","松本 規子, Mitsuo Shimada, Nobuhiro Kurita, Horohiko Sato, Takashi Iwata, Kouzou Yoshikawa, Jun Higashijima, Motoya Chikakiyo, Masaaki Nishi, Hideya Kashihara","null","null","null","null","null","2014-04","日本外科系連合学会誌","Journal of Japanese College of Surgeons","Vol.39","No.2","199-203","199-203","jpn","null","null","research_institution","null","null","null","0385-7883","null","null","null","null","null"
"腹腔鏡下切除を施行した骨形成性直腸癌同時肝転移の1例","腹腔鏡下切除を施行した骨形成性直腸癌同時肝転移の1例","柏原 秀也, 島田 光生, 栗田 信浩, 佐藤 宏彦, 吉川 幸造, 東島 潤","Hideya Kashihara, Mitsuo Shimada, Nobuhiro Kurita, Horohiko Sato, Kouzou Yoshikawa, Jun Higashijima","null","null","null","null","null","2014-04","日本臨床外科学会雑誌","Journal of Japan Surgical Association","Vol.75","No.7","185","190","jpn","null","null","research_institution","null","null","10.3919/jjsa.75.1949","1882-5133","null","null","null","null","null"
"Loss of FBXW7 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma.","Loss of FBXW7 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma.","Chinbold Enkhbold, Tohru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Mami Kanamoto, Shuichi Iwahashi, Yu Saitou, Daichi Ishikawa, Mitsuo Shimada","Chinbold Enkhbold, Tohru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Mami Kanamoto, Shuichi Iwahashi, Yu Saitou, Daichi Ishikawa, Mitsuo Shimada","null","FBXW7 acts as a tumor suppressor gene by targeting several oncogenic regulators of proliferation, growth and apoptosis for proteasomal degradation. However, the significance of this protein is not yet well understood in intrahepatic cholangiocarcinoma (IHCC). In this study, we aimed to investigate the correlation between FBXW7 expression and clinicopathological variables in IHCC patients. Thirty-one patients with IHCC who underwent hepatic resection were enrolled. FBXW7 expression in tumor tissue was determined by immunohistochemistry and patients were divided into two groups, the FBXW7 high expression group (n = 11) and the FBXW7 low expression group (n = 20). We then compared clinicopathological variables including prognosis between the high and low expression groups in tumor tissue. FBXW7 expression was significantly correlated with staging (P = 0.006), and tended to correlate with lymph node metastasis. The FBXW7 low expression group had significantly poorer prognosis compared with the FBXW7 high expression group (P = 0.020); 3-year survival rates were 29.4% and 72.7%, respectively. Furthermore, the disease-free survival rate in the FBXW7 low expression group was significantly worse than in the FBXW7 high expression group (P = 0.022). On multivariate analysis, intrahepatic metastasis (P = 0.006) was a significant independent prognostic factor for disease-free survival, and FBXW7 low expression tended to be an independent prognostic factor for both overall (P = 0.067) and disease-free survival (P = 0.083). Our results confirmed that low expression of FBXW7 in IHCC correlates with tumor progression and poor prognosis in IHCC.","FBXW7 acts as a tumor suppressor gene by targeting several oncogenic regulators of proliferation, growth and apoptosis for proteasomal degradation. However, the significance of this protein is not yet well understood in intrahepatic cholangiocarcinoma (IHCC). In this study, we aimed to investigate the correlation between FBXW7 expression and clinicopathological variables in IHCC patients. Thirty-one patients with IHCC who underwent hepatic resection were enrolled. FBXW7 expression in tumor tissue was determined by immunohistochemistry and patients were divided into two groups, the FBXW7 high expression group (n = 11) and the FBXW7 low expression group (n = 20). We then compared clinicopathological variables including prognosis between the high and low expression groups in tumor tissue. FBXW7 expression was significantly correlated with staging (P = 0.006), and tended to correlate with lymph node metastasis. The FBXW7 low expression group had significantly poorer prognosis compared with the FBXW7 high expression group (P = 0.020); 3-year survival rates were 29.4% and 72.7%, respectively. Furthermore, the disease-free survival rate in the FBXW7 low expression group was significantly worse than in the FBXW7 high expression group (P = 0.022). On multivariate analysis, intrahepatic metastasis (P = 0.006) was a significant independent prognostic factor for disease-free survival, and FBXW7 low expression tended to be an independent prognostic factor for both overall (P = 0.067) and disease-free survival (P = 0.083). Our results confirmed that low expression of FBXW7 in IHCC correlates with tumor progression and poor prognosis in IHCC.","null","null","2014-03-18","Hepatology Research","Hepatology Research","Vol.44","No.14","E346","52","eng","null","null","research_institution","null","null","10.1111/hepr.12314","1386-6346","null","null","null","null","null"
"肝切除後のVTE予防策は?","肝切除後のVTE予防策は?","栗田 信浩, 島田 光生","Nobuhiro Kurita, Mitsuo Shimada","null","null","null","null","null","2014-03","エキスパートによる消化器外科静脈血栓塞栓症診療指針","エキスパートによる消化器外科静脈血栓塞栓症診療指針","null","null","103-105","103-105","jpn","null","null","research_institution","null","null","null","null","null","null","null","null","null"
"Expressions of hypoxia-inducible factor-1 and epithelial cell adhesion molecule are linked with aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation therapy.","Expressions of hypoxia-inducible factor-1 and epithelial cell adhesion molecule are linked with aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation therapy.","Shinichiro Yamada, Tohru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusue Arakawa, Mami Kanamoto, Shuichi Iwahashi, Yu Saitou, Chie Takasu, Daichi Ishikawa, Mitsuo Shimada","Shinichiro Yamada, Tohru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusue Arakawa, Mami Kanamoto, Shuichi Iwahashi, Yu Saitou, Chie Takasu, Daichi Ishikawa, Mitsuo Shimada","null","Radiofrequency ablation (RFA) is a widely used therapy for hepatocellular carcinoma (HCC). Several reports have demonstrated the aggressive local recurrence of HCC after RFA, suggesting that induction of further malignant transformation of HCC has occurred. Eighty-eight (88) patients with HCC who underwent hepatic resection were included in this study. Hepatectomy was indicated for local recurrence of HCC after RFA (n = 10, RFA group) and for HCC without prior RFA (n = 78, non-RFA group). Clinicopathological data and the patient's prognosis after hepatectomy were compared between the two groups. Expression levels of hypoxia-inducible factor-1 (HIF-1), epithelial cell adhesion molecule (EpCAM), CD44, and vascular endothelial growth factor messenger RNA (mRNA) in the tumor tissues were also examined. The RFA group showed higher frequency of portal vein invasion and less tumor differentiation compared with the non-RFA group (p < 0.05). Overall and disease-free survival rates in the RFA group were significantly worse than those in the non-RFA group (p < 0.05). HIF-1 and EpCAM mRNA expression levels in the RFA group were significantly higher than those in the non-RFA group (p < 0.05). These results suggest that local HCC recurrence after RFA shows an aggressive tumor phenotype and poor prognosis through the enhanced expressions of HIF-1 and EpCAM in the residual HCC tumors after insufficient or sub-lethal treatment by RFA.","Radiofrequency ablation (RFA) is a widely used therapy for hepatocellular carcinoma (HCC). Several reports have demonstrated the aggressive local recurrence of HCC after RFA, suggesting that induction of further malignant transformation of HCC has occurred. Eighty-eight (88) patients with HCC who underwent hepatic resection were included in this study. Hepatectomy was indicated for local recurrence of HCC after RFA (n = 10, RFA group) and for HCC without prior RFA (n = 78, non-RFA group). Clinicopathological data and the patient's prognosis after hepatectomy were compared between the two groups. Expression levels of hypoxia-inducible factor-1 (HIF-1), epithelial cell adhesion molecule (EpCAM), CD44, and vascular endothelial growth factor messenger RNA (mRNA) in the tumor tissues were also examined. The RFA group showed higher frequency of portal vein invasion and less tumor differentiation compared with the non-RFA group (p < 0.05). Overall and disease-free survival rates in the RFA group were significantly worse than those in the non-RFA group (p < 0.05). HIF-1 and EpCAM mRNA expression levels in the RFA group were significantly higher than those in the non-RFA group (p < 0.05). These results suggest that local HCC recurrence after RFA shows an aggressive tumor phenotype and poor prognosis through the enhanced expressions of HIF-1 and EpCAM in the residual HCC tumors after insufficient or sub-lethal treatment by RFA.","null","null","2014-02-25","Annals of Surgical Oncology","Annals of Surgical Oncology","Vol.21 Suppl 3","null","S436","42","eng","null","null","research_institution","null","null","10.1245/s10434-014-3575-z","1534-4681","null","null","null","null","null"
"A hydrolyzed whey peptide-based diet ameliorates hepatic ischemia-reperfusion injury in the rat nonalcoholic fatty liver.","A hydrolyzed whey peptide-based diet ameliorates hepatic ischemia-reperfusion injury in the rat nonalcoholic fatty liver.","Akira Nii, Tohru Utsunomiya, Mitsuo Shimada, Toru Ikegami, Hiroki Ishibashi, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Hajime Sasaki, Akihiro Kawashima","Akira Nii, Tohru Utsunomiya, Mitsuo Shimada, Toru Ikegami, Hiroki Ishibashi, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Hajime Sasaki, Akihiro Kawashima","null","The number of patients with nonalcoholic fatty liver disease (NAFLD) is increasing. Hepatic steatosis is a major risk factor for hepatic failure after ischemia-reperfusion (I/R) injury. Hydrolyzed whey peptide (HWP) is a functional liquid-type nutritional diet containing whey peptide, which has previously been shown to exert anti-inflammatory effects. In the present study, we examined the effects of HWP on the hepatic I/R injury in a rat NAFLD model. Rats fed a methionine/choline-deficient diet for 4 weeks were divided into two groups after 30 min of whole liver ischemia. In Group-M, HWP was given immediately after reperfusion and every 6 h thereafter. In Group-C, the vehicle was given in the same manner. The liver function tests and microscopic findings of the liver after reperfusion were compared between the two groups. The serum transaminase levels in Group-M were significantly lower than those in Group-C after reperfusion. The gene expression levels of IL-6 and inducible nitric oxide synthase (iNOS) were significantly lower in Group-M compared to Group-C. The TNF-α and uncoupling protein-2 (UCP-2) expression levels were also markedly lower in Group-M. The hepatic necrotic areas in Group-M were significantly smaller than those in Group-C. The administration of a HWP diet ameliorated the hepatic I/R injury in rats with NAFLD.","The number of patients with nonalcoholic fatty liver disease (NAFLD) is increasing. Hepatic steatosis is a major risk factor for hepatic failure after ischemia-reperfusion (I/R) injury. Hydrolyzed whey peptide (HWP) is a functional liquid-type nutritional diet containing whey peptide, which has previously been shown to exert anti-inflammatory effects. In the present study, we examined the effects of HWP on the hepatic I/R injury in a rat NAFLD model. Rats fed a methionine/choline-deficient diet for 4 weeks were divided into two groups after 30 min of whole liver ischemia. In Group-M, HWP was given immediately after reperfusion and every 6 h thereafter. In Group-C, the vehicle was given in the same manner. The liver function tests and microscopic findings of the liver after reperfusion were compared between the two groups. The serum transaminase levels in Group-M were significantly lower than those in Group-C after reperfusion. The gene expression levels of IL-6 and inducible nitric oxide synthase (iNOS) were significantly lower in Group-M compared to Group-C. The TNF-α and uncoupling protein-2 (UCP-2) expression levels were also markedly lower in Group-M. The hepatic necrotic areas in Group-M were significantly smaller than those in Group-C. The administration of a HWP diet ameliorated the hepatic I/R injury in rats with NAFLD.","null","null","2014-02-04","Surgery Today","Surgery Today","Vol.44","No.12","2354","2360","eng","null","null","research_institution","null","null","10.1007/s00595-014-0853-0","1436-2813","null","null","null","null","null"
"The role of activation-induced cytidine deaminase expression in gastric adenocarcinoma.","The role of activation-induced cytidine deaminase expression in gastric adenocarcinoma.","Bat-Erdene Batsaikhan, Nobuhiro Kurita, Takashi Iwata, Hirohiko Sato, Kozo Yoshikawa, Chie Takasu, Hideya Kashihara, Noriko Matsumoto, Hiroki Ishibashi, Mitsuo Shimada","Bat-Erdene Batsaikhan, Nobuhiro Kurita, Takashi Iwata, Hirohiko Sato, Kozo Yoshikawa, Chie Takasu, Hideya Kashihara, Noriko Matsumoto, Hiroki Ishibashi, Mitsuo Shimada","null","Gastric adenocarcinoma is one of the most common malignant tumors and the leading cause of malignancy-related death worldwide. Studies have reported overexpression of activation-induced cytidine deaminase (AID) and protein kinase c iota (PKCi) proteins showing involvement in the regulation of carcinogenesis. In the present study, we investigated the expression of AID and PKCi in patients with gastric adenocarcinoma and determined the correlation between these proteins. This study was conducted between September 2009 and September 2010 on a total of 59 patients with gastric adenocarcinoma at the Tokushima University Hospital. AID, PKCi and mutated p53 protein expressions were evaluated by immunohistochemistry in gastric adenocarcinoma. High AID and PKCi expression was significantly (p<0.05) associated with poorly-differentiated gastric adenocarcinoma. In addition, PKCi expression was significantly correlated with clinicopathological findings such as a lymph node metastasis, and venous and lymphatic invasion (p<0.05). Furthermore, AID expression was significantly correlated with PKCi and mutated p53 protein expression in gastric adenocarcinoma (p<0.05). High AID and PKCi expressions were significantly correlated with poorly-differentiated gastric adenocarcinoma.","Gastric adenocarcinoma is one of the most common malignant tumors and the leading cause of malignancy-related death worldwide. Studies have reported overexpression of activation-induced cytidine deaminase (AID) and protein kinase c iota (PKCi) proteins showing involvement in the regulation of carcinogenesis. In the present study, we investigated the expression of AID and PKCi in patients with gastric adenocarcinoma and determined the correlation between these proteins. This study was conducted between September 2009 and September 2010 on a total of 59 patients with gastric adenocarcinoma at the Tokushima University Hospital. AID, PKCi and mutated p53 protein expressions were evaluated by immunohistochemistry in gastric adenocarcinoma. High AID and PKCi expression was significantly (p<0.05) associated with poorly-differentiated gastric adenocarcinoma. In addition, PKCi expression was significantly correlated with clinicopathological findings such as a lymph node metastasis, and venous and lymphatic invasion (p<0.05). Furthermore, AID expression was significantly correlated with PKCi and mutated p53 protein expression in gastric adenocarcinoma (p<0.05). High AID and PKCi expressions were significantly correlated with poorly-differentiated gastric adenocarcinoma.","null","null","2014-02","Anticancer Research","Anticancer Research","Vol.34","No.2","995","1000","eng","null","null","research_institution","null","null","null","1791-7530","null","null","null","null","null"
"Characteristics of internal hernia after gastrectomy with Roux-en-Y reconstruction for gastric cancer.","Characteristics of internal hernia after gastrectomy with Roux-en-Y reconstruction for gastric cancer.","Kozo Yoshikawa, Mitsuo Shimada, Nobuhiro Kurita, Hirohiko Sato, Takashi Iwata, Jun Higashijima, Motoya Chikakiyo, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Noriko Matsumoto, Syohei Eto","Kozo Yoshikawa, Mitsuo Shimada, Nobuhiro Kurita, Hirohiko Sato, Takashi Iwata, Jun Higashijima, Motoya Chikakiyo, Masaaki Nishi, Hideya Kashihara, Chie Takasu, Noriko Matsumoto, Syohei Eto","null","Although the internal hernias have been a huge topic in the field of bariatric surgery, there were a few reports in gastric cancer. The purpose of this study was to analyze the incidence, clinical features, and prevention of internal hernia after gastrectomy for gastric cancer. Twelve patients who underwent surgical treatment for internal hernia in our hospital after gastrectomy were analyzed. Features, including incidence, symptoms, and signs, were investigated in detail. The operative procedures for preceding gastrectomies were open distal gastrectomy in three patients, open total gastrectomy in three patients, laparoscopic-assisted distal gastrectomy in two patients, and laparoscopic total gastrectomy in four patients. The most frequent sites of internal hernias were jejunojejunostomy mesenteric defects (five patients) and Petersen's defect (five patients), mesenterium of transverse colon (one patient), and esophagus hiatus (one patient). There was no significant difference between open and laparoscopic preceding gastrectomies. After closure of the mesenteric defect was introduced, no further internal hernias occurred. On CT examination, the whirl sign was present in ten patients on 3D images. The present data suggest the importance of early recognition and treatment of internal hernia, as well as its prevention by closure of mesenteric defects.","Although the internal hernias have been a huge topic in the field of bariatric surgery, there were a few reports in gastric cancer. The purpose of this study was to analyze the incidence, clinical features, and prevention of internal hernia after gastrectomy for gastric cancer. Twelve patients who underwent surgical treatment for internal hernia in our hospital after gastrectomy were analyzed. Features, including incidence, symptoms, and signs, were investigated in detail. The operative procedures for preceding gastrectomies were open distal gastrectomy in three patients, open total gastrectomy in three patients, laparoscopic-assisted distal gastrectomy in two patients, and laparoscopic total gastrectomy in four patients. The most frequent sites of internal hernias were jejunojejunostomy mesenteric defects (five patients) and Petersen's defect (five patients), mesenterium of transverse colon (one patient), and esophagus hiatus (one patient). There was no significant difference between open and laparoscopic preceding gastrectomies. After closure of the mesenteric defect was introduced, no further internal hernias occurred. On CT examination, the whirl sign was present in ten patients on 3D images. The present data suggest the importance of early recognition and treatment of internal hernia, as well as its prevention by closure of mesenteric defects.","null","null","2014-01-08","Surgical Endoscopy","Surgical Endoscopy","Vol.28","No.6","1774","1778","eng","null","null","research_institution","null","null","10.1007/s00464-013-3384-7","1432-2218","null","null","null","null","null"
"Indigo carmine dye-assisted lymphatic-sparing laparoscopic Palomo varicocelectomy in children.","Indigo carmine dye-assisted lymphatic-sparing laparoscopic Palomo varicocelectomy in children.","Hiroki Ishibashi, Hiroki Mori, Keigo Yada, Mitsuo Shimada, Tomoko Sogami, Akira Nii","Hiroki Ishibashi, Hiroki Mori, Keigo Yada, Mitsuo Shimada, Tomoko Sogami, Akira Nii","null","The ideal method for varicocelectomy in children remains controversial. We present our experience with dye-assisted lymphatic-sparing laparoscopic varicocelectomy (LSLV) in children, which overcomes the limitations of previously described techniques. Five consecutive LSLVs were performed over a period of three years on children with a mean age of twelve years. The varicocele grade was three in one case and grade 2 in four cases, respectively. A left subdartos injection of 2 ml of Indigo carmine dye was done using a 25-gauge needle at ten minutes before an operation. A scrotal injection of lymphatic dye was utilized to spare at least one lymphatic and the remaining spermatic vessels were divided. Lymphatic-sparing was accomplished in all cases. No peri-operative complication was noted. We spared one lymphatic channel in one patient (20%) and two channels in four patients (80%). There were no cases of hydrocele or residual varicocele. Dye-assisted LSLV is easily accomplished with an excellent surgical outcome and sparing one or two lymphatics appears to be sufficient to avoid secondary hydrocele.","The ideal method for varicocelectomy in children remains controversial. We present our experience with dye-assisted lymphatic-sparing laparoscopic varicocelectomy (LSLV) in children, which overcomes the limitations of previously described techniques. Five consecutive LSLVs were performed over a period of three years on children with a mean age of twelve years. The varicocele grade was three in one case and grade 2 in four cases, respectively. A left subdartos injection of 2 ml of Indigo carmine dye was done using a 25-gauge needle at ten minutes before an operation. A scrotal injection of lymphatic dye was utilized to spare at least one lymphatic and the remaining spermatic vessels were divided. Lymphatic-sparing was accomplished in all cases. No peri-operative complication was noted. We spared one lymphatic channel in one patient (20%) and two channels in four patients (80%). There were no cases of hydrocele or residual varicocele. Dye-assisted LSLV is easily accomplished with an excellent surgical outcome and sparing one or two lymphatics appears to be sufficient to avoid secondary hydrocele.","null","null","2014","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.61","No.1-2","151","155","eng","null","null","research_institution","null","null","10.2152/jmi.61.151","1349-6867","null","null","null","null","null"
"Iliopsoas abscess in an infant.","Iliopsoas abscess in an infant.","Hiroki Ishibashi, Takehito Oshio, Tomoko Sogami, Akira Nii, Hiroki Mori, Keigo Yada, Mitsuo Shimada","Hiroki Ishibashi, Takehito Oshio, Tomoko Sogami, Akira Nii, Hiroki Mori, Keigo Yada, Mitsuo Shimada","null","Iliopsoas abscess (IPA) is uncommon in childhood and very rare in the neonate and infant. We present a case of IPA after an umbilical granuloma in an infant. A baby girl with a birth weight of 2,970 g was born at thirty-seven weeks and two days gestation by Caesarean Section. On the fourteenth day after birth, her umbilicus was wet and developed the granulomatous formation. At two months of age, she presented with right leg and groin swelling with mild bluish discoloration and without fever. She had poor movement of her right leg and showed apparent discomfort. Her umbilicus was dry and there was no granulomatous material. Ultrasonography and computed tomography demonstrated an iliopsoas abscess in the right position. Therefore, an extraperitoneal surgical drainage was performed, aspirating yellowish pus. Culture of the purulent material revealed Staphylococcus aureus. Systemic antibiotic therapy was continued for ten days. After three days of drainage, full-range motion of the right leg was gained, and then after eleven days, CT findings comfirmed the disappearance of the iliopsoas abscess. IPA is extremely rare and it is difficult to diagnose. However, it should be included in the differential diagnosis of an infant with poor leg movement and swelling of the groin to the femur.","Iliopsoas abscess (IPA) is uncommon in childhood and very rare in the neonate and infant. We present a case of IPA after an umbilical granuloma in an infant. A baby girl with a birth weight of 2,970 g was born at thirty-seven weeks and two days gestation by Caesarean Section. On the fourteenth day after birth, her umbilicus was wet and developed the granulomatous formation. At two months of age, she presented with right leg and groin swelling with mild bluish discoloration and without fever. She had poor movement of her right leg and showed apparent discomfort. Her umbilicus was dry and there was no granulomatous material. Ultrasonography and computed tomography demonstrated an iliopsoas abscess in the right position. Therefore, an extraperitoneal surgical drainage was performed, aspirating yellowish pus. Culture of the purulent material revealed Staphylococcus aureus. Systemic antibiotic therapy was continued for ten days. After three days of drainage, full-range motion of the right leg was gained, and then after eleven days, CT findings comfirmed the disappearance of the iliopsoas abscess. IPA is extremely rare and it is difficult to diagnose. However, it should be included in the differential diagnosis of an infant with poor leg movement and swelling of the groin to the femur.","null","null","2014","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.61","No.1-2","213","216","eng","null","null","research_institution","null","null","10.2152/jmi.61.213","1349-6867","null","null","null","null","null"
"3.肝疾患 ウイルス性肝炎","3.肝疾患 ウイルス性肝炎","荒川 悠佑, 島田 光生, 石川 大地, 齋藤 裕, 岩橋 衆一, 池本 哲也, 居村 暁, 森根 裕二, 宇都宮 徹","Yusuke Arakawa, Mitsuo Shimada, 石川 大地, Yu Saitou, Shuichi Iwahashi, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Toru Utsunomiya","null","null","null","null","null","2014","日本臨床外科学会誌","日本臨床外科学会誌","Vol.69","No.11","null","null","jpn","null","null","research_institution","null","null","null","null","null","null","null","null","null"
"肝移植","肝移植","岩橋 衆一, 居村 暁, 宇都宮 徹, 森根 裕二, 池本 哲也, 森 大樹, 荒川 悠佑, 金本 真美, 齋藤 裕, 髙須 千絵, 島田 光生","Shuichi Iwahashi, Satoru Imura, Toru Utsunomiya, Yuji Morine, Tetsuya Ikemoto, Hiroki Mori, Yusuke Arakawa, Mami Kanamoto, Yu Saitou, Chie Takasu, Mitsuo Shimada","null","null","null","null","null","2014","日本臨床外科学会誌","日本臨床外科学会誌","Vol.69","No.4","null","null","jpn","null","null","research_institution","null","null","null","null","null","null","null","null","null"
"Insulin resistance as early sign of hepatic dysfunction in liver cirrhosis","Insulin resistance as early sign of hepatic dysfunction in liver cirrhosis","K Taguchi, Hisami Okumura, A Mizuno, T Nakamura, Mitsuo Shimada, Toshio Doi, E Takeda","K Taguchi, Hisami Okumura, A Mizuno, T Nakamura, Mitsuo Shimada, Toshio Doi, E Takeda","null","Glucose intolerance characterized by postprandial hyperglycemia and hyperinsulinemia is commonly seen in patients with liver cirrhosis (LC). The aim of this study is to clarify the relation between glucose intolerance and disorder of liver function in patients with LC. The 75 g oral glucose tolerance test (75 g OGTT) and the hyperinsulinemic euglycemic clamp combined with 0.2 g/kg oral glucose load (HECGL) were conducted in 61 patients with LC. Based on the results of 75 g OGTT, the 61 patients with LC were divided into groups, 21 (34.4%) patients with normal glucose tolerance (LC-NGT), 12 (19.7%) patients with impaired glucose tolerance (LC-IGT) and 28 (45.9%) patients with diabetes mellitus (LC-DM). Fasting plasma glucose (FPG) level was normal in 50 (82.0%) patients with LC. All patients with LC showed insulin resistance in both peripheral (skeletal and adipose) and hepatic tissues evaluated by HECGL, although significant correlation between the degree of glucose intolerance and the severity of hepatic dysfunction was not observed. Insulin resistance in both liver and peripheral tissues is the early sign in the patients with LC. This fact indicates that nutritional care from early stages of LC would be necessary in the patients.","Glucose intolerance characterized by postprandial hyperglycemia and hyperinsulinemia is commonly seen in patients with liver cirrhosis (LC). The aim of this study is to clarify the relation between glucose intolerance and disorder of liver function in patients with LC. The 75 g oral glucose tolerance test (75 g OGTT) and the hyperinsulinemic euglycemic clamp combined with 0.2 g/kg oral glucose load (HECGL) were conducted in 61 patients with LC. Based on the results of 75 g OGTT, the 61 patients with LC were divided into groups, 21 (34.4%) patients with normal glucose tolerance (LC-NGT), 12 (19.7%) patients with impaired glucose tolerance (LC-IGT) and 28 (45.9%) patients with diabetes mellitus (LC-DM). Fasting plasma glucose (FPG) level was normal in 50 (82.0%) patients with LC. All patients with LC showed insulin resistance in both peripheral (skeletal and adipose) and hepatic tissues evaluated by HECGL, although significant correlation between the degree of glucose intolerance and the severity of hepatic dysfunction was not observed. Insulin resistance in both liver and peripheral tissues is the early sign in the patients with LC. This fact indicates that nutritional care from early stages of LC would be necessary in the patients.","null","null","2014","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.61","No.1.2","180","189","eng","null","null","research_institution","null","null","10.2152/jmi.61.180","1349-6867","null","null","null","null","null"
"CXC receptor 4 and stromal cell-derived factor 1 in primary tumors and liver metastases of colorectal cancer.","CXC receptor 4 and stromal cell-derived factor 1 in primary tumors and liver metastases of colorectal cancer.","Shinichiro Yamada, Mitsuo Shimada, Tohru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Yusuke Arakawa, Mami Kanamoto, Shuichi Iwahashi, Yu Saitou","Shinichiro Yamada, Mitsuo Shimada, Tohru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Yusuke Arakawa, Mami Kanamoto, Shuichi Iwahashi, Yu Saitou","null","It has been determined that the chemokine receptor CXC receptor 4 (CXCR4) and its ligand, stromal cell-derived factor 1 (SDF-1), regulate several key processes in a wide variety of cancers. In this study, we investigate the possible role of SDF-1 (noncancerous liver tissue) and CXCR4 in liver metastases of colorectal cancer (CRC). Reverse transcription-polymerase chain reaction was performed to examine the expression of SDF-1 in noncancerous liver tissues of 16 CRC patients with liver metastasis and in normal liver tissues of six patients with benign liver disease. We also examined the expression of CXCR4 in cancerous tissues from primary and metastatic tumors. Using reverse transcription-polymerase chain reaction, CXCR4 expression in metastatic tumors tended to be higher than that in primary tumors (P = 0.16). High CXCR4 expression in a primary tumor was found to be related to an increased lymphatic invasion (P = 0.01), an advanced depth of tumor invasion (P = 0.07), and a decrease in the overall survival rate. The SDF-1 expression observed in noncancerous liver tissues of CRC with liver metastasis was significantly higher than that observed in normal liver tissues of benign liver disease (P < 0.05). In CRC with liver metastasis, CXCR4 expression demonstrated associations with local progression, liver metastasis, and poor overall survival.","It has been determined that the chemokine receptor CXC receptor 4 (CXCR4) and its ligand, stromal cell-derived factor 1 (SDF-1), regulate several key processes in a wide variety of cancers. In this study, we investigate the possible role of SDF-1 (noncancerous liver tissue) and CXCR4 in liver metastases of colorectal cancer (CRC). Reverse transcription-polymerase chain reaction was performed to examine the expression of SDF-1 in noncancerous liver tissues of 16 CRC patients with liver metastasis and in normal liver tissues of six patients with benign liver disease. We also examined the expression of CXCR4 in cancerous tissues from primary and metastatic tumors. Using reverse transcription-polymerase chain reaction, CXCR4 expression in metastatic tumors tended to be higher than that in primary tumors (P = 0.16). High CXCR4 expression in a primary tumor was found to be related to an increased lymphatic invasion (P = 0.01), an advanced depth of tumor invasion (P = 0.07), and a decrease in the overall survival rate. The SDF-1 expression observed in noncancerous liver tissues of CRC with liver metastasis was significantly higher than that observed in normal liver tissues of benign liver disease (P < 0.05). In CRC with liver metastasis, CXCR4 expression demonstrated associations with local progression, liver metastasis, and poor overall survival.","null","null","2013-10-21","The Journal of Surgical Research","The Journal of Surgical Research","Vol.187","No.1","107","112","eng","null","null","research_institution","null","null","10.1016/j.jss.2013.10.030","1095-8673","null","null","null","null","null"
"Benefits of simultaneous laparoscopic resection of primary colorectal cancer and liver metastases.","Benefits of simultaneous laparoscopic resection of primary colorectal cancer and liver metastases.","Chie Takasu, Mitsuo Shimada, Hirohiko Sato, Tomohiko Miyatani, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Mami Kanamoto, Nobuhiro Kurita, Shohei Eto, Tohru Utsunomiya","Chie Takasu, Mitsuo Shimada, Hirohiko Sato, Tomohiko Miyatani, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Mami Kanamoto, Nobuhiro Kurita, Shohei Eto, Tohru Utsunomiya","null","Recently, consensus on the optimal strategy for resectable synchronous colorectal liver metastases (LM) seems to have shifted toward simultaneous resection. However, there are still relatively few reports about simultaneous laparoscopic resection. The aim of this study is to evaluate the outcomes of patients who underwent simultaneous laparoscopic resection. We evaluated 14 patients who underwent simultaneous resection of primary colorectal cancer and LM in our hospital from 2004 to 2012. Patients were selected by matched pair analysis based on the number of LM (≤4) and tumor size (≤5 cm). We divided them into two groups: the simultaneous laparoscopic resection of primary colorectal cancer and LM (Lap-S) group (n = 7) and the simultaneous open resection of primary colorectal cancer and LM (Open-S) group (n = 7). Clinical and oncologic outcomes were compared between the groups. The Lap-S patients were significantly older than the Open-S patients. The mean operative times of Lap-S and Open-S were 472 min and 466 min, respectively. The mean blood loss was significantly smaller in the Lap-S group (153 mL) than in the Open-S group (496 mL). There was no surgical mortality in either group. The incidence of postoperative complications in the Lap-S and Open-S groups was 12.3% and 33.0%, respectively. The mean postoperative hospital stay was significantly shorter in the Lap-S group (16 days) than in the Open-S group (36 days). There was no significant difference in long-term survival between the two groups. Lap-S patients had equivalent long-term outcomes to Open-S patients. Therefore, given its technical feasibility and safety, Lap-S may be one of the most promising options in selected patients.","Recently, consensus on the optimal strategy for resectable synchronous colorectal liver metastases (LM) seems to have shifted toward simultaneous resection. However, there are still relatively few reports about simultaneous laparoscopic resection. The aim of this study is to evaluate the outcomes of patients who underwent simultaneous laparoscopic resection. We evaluated 14 patients who underwent simultaneous resection of primary colorectal cancer and LM in our hospital from 2004 to 2012. Patients were selected by matched pair analysis based on the number of LM (≤4) and tumor size (≤5 cm). We divided them into two groups: the simultaneous laparoscopic resection of primary colorectal cancer and LM (Lap-S) group (n = 7) and the simultaneous open resection of primary colorectal cancer and LM (Open-S) group (n = 7). Clinical and oncologic outcomes were compared between the groups. The Lap-S patients were significantly older than the Open-S patients. The mean operative times of Lap-S and Open-S were 472 min and 466 min, respectively. The mean blood loss was significantly smaller in the Lap-S group (153 mL) than in the Open-S group (496 mL). There was no surgical mortality in either group. The incidence of postoperative complications in the Lap-S and Open-S groups was 12.3% and 33.0%, respectively. The mean postoperative hospital stay was significantly shorter in the Lap-S group (16 days) than in the Open-S group (36 days). There was no significant difference in long-term survival between the two groups. Lap-S patients had equivalent long-term outcomes to Open-S patients. Therefore, given its technical feasibility and safety, Lap-S may be one of the most promising options in selected patients.","null","null","2013-10-15","Asian Journal of Endoscopic Surgery","Asian Journal of Endoscopic Surgery","Vol.7","No.1","31","37","eng","null","null","research_institution","null","null","10.1111/ases.12066","1758-5910","null","null","null","null","null"
"The role of Aurora B expression in non-tumor liver tissues of patients with hepatocellular carcinoma.","The role of Aurora B expression in non-tumor liver tissues of patients with hepatocellular carcinoma.","Lkhagva-Ochir Tovuu, Tohru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Yusuke Arakawa, Hiroki Mori, Jun Hanaoka, Mami Kanamoto, Koji Sugimoto, Yu Saitou, Shinichiro Yamada, Michihito Asanoma, Mitsuo Shimada","Lkhagva-Ochir Tovuu, Tohru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Yusuke Arakawa, Hiroki Mori, Jun Hanaoka, Mami Kanamoto, Koji Sugimoto, Yu Saitou, Shinichiro Yamada, Michihito Asanoma, Mitsuo Shimada","null","Aurora B is a serine-threonine kinase and chromosomal passenger protein involved in the control of chromosome assembly and segregation during mitosis. Aberrant expression of Aurora B has been reported in some tumors, including lung and hepatocellular carcinoma (HCC). We investigated the role of Aurora B expression in both HCC and matched adjacent non-tumor tissue. Sixty-three patients with HCC who underwent hepatic resection were enrolled in this study. Aurora B expression in tumor and non-tumor tissue was examined by use of quantitative reverse transcription-polymerase chain reaction. The patients were divided into high and low gene expression groups by median value, and clinicopathological data were compared between the two groups. Aurora B expression was significantly higher in tumor tissue than in non-cancerous tissue (P < 0.001). Disease-free survival was not significantly different between groups with high and low expression in the tumor tissues. For non-tumor tissues, disease-free survival of the low-expression group was significantly better than that of the high-expression group (P < 0.05). The gene expression level of Aurora B correlated with results from liver function tests, for example prothrombin time. Aurora B expression in non-cancerous tissues may be a prognostic factor for HCC.","Aurora B is a serine-threonine kinase and chromosomal passenger protein involved in the control of chromosome assembly and segregation during mitosis. Aberrant expression of Aurora B has been reported in some tumors, including lung and hepatocellular carcinoma (HCC). We investigated the role of Aurora B expression in both HCC and matched adjacent non-tumor tissue. Sixty-three patients with HCC who underwent hepatic resection were enrolled in this study. Aurora B expression in tumor and non-tumor tissue was examined by use of quantitative reverse transcription-polymerase chain reaction. The patients were divided into high and low gene expression groups by median value, and clinicopathological data were compared between the two groups. Aurora B expression was significantly higher in tumor tissue than in non-cancerous tissue (P < 0.001). Disease-free survival was not significantly different between groups with high and low expression in the tumor tissues. For non-tumor tissues, disease-free survival of the low-expression group was significantly better than that of the high-expression group (P < 0.05). The gene expression level of Aurora B correlated with results from liver function tests, for example prothrombin time. Aurora B expression in non-cancerous tissues may be a prognostic factor for HCC.","null","null","2013-07-27","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.19","No.4","622","628","eng","null","null","research_institution","null","null","10.1007/s10147-013-0593-y","1437-7772","null","null","null","null","null"
"肝硬変患者に対するテーラーメイド栄養管理の血液生化学指標についての検討","肝硬変患者に対するテーラーメイド栄養管理の血液生化学指標についての検討","奥村 仙示, 山内 利香, 浦野 恵理, 寺本 有沙, 居村 暁, 宇都宮 徹, 島田 光生, 武田 英二","Hisami Okumura, 山内 利香, 浦野 恵理, 寺本 有沙, Satoru Imura, Toru Utsunomiya, Mitsuo Shimada, Eiji Takeda","null","null","null","null","null","2011","栄養アセスメント","栄養アセスメント","Vol.28","No.1","18","20","jpn","null","null","research_institution","null","null","null","null","null","null","null","null","null"
"Fatty liver caused by portal vein thrombosis after living donor liver transplantation: a case report","Fatty liver caused by portal vein thrombosis after living donor liver transplantation: a case report","Keiko Ogita, Tomoaki Taguchi, Yuji Soejima, Satoshi Ieiri, Shunsaku Katsura, Narito Takada, Toshiharu Matsuura, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Sachiyo Suita","Keiko Ogita, Tomoaki Taguchi, Yuji Soejima, Satoshi Ieiri, Shunsaku Katsura, Narito Takada, Toshiharu Matsuura, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara, Sachiyo Suita","null","Portal vein thrombosis (PVT) is a rare complication that occurs after liver transplantation: however, it cannot be ignored as a cause of graft loss and death. We herein report a pediatric case of PVT that caused a fatty change in the graft after living donor liver transplantation. The portal vein was successfully reconstructed using the left great saphenous vein of the same donor. Moreover, the fatty liver recovered after the operation. Our case suggests that the finding of fatty liver is an important marker of PVT and immediate portal reconstruction is performed.","Portal vein thrombosis (PVT) is a rare complication that occurs after liver transplantation: however, it cannot be ignored as a cause of graft loss and death. We herein report a pediatric case of PVT that caused a fatty change in the graft after living donor liver transplantation. The portal vein was successfully reconstructed using the left great saphenous vein of the same donor. Moreover, the fatty liver recovered after the operation. Our case suggests that the finding of fatty liver is an important marker of PVT and immediate portal reconstruction is performed.","null","null","2005-08","Journal of Pediatric Surgery","Journal of Pediatric Surgery","Vol.40","No.8","E7","E9","eng","null","null","research_institution","null","null","10.1016/j.jpedsurg.2005.05.029","1531-5037","null","http://dx.doi.org/10.1016/j.jpedsurg.2005.05.029","null","null","null"
"Unusual endoscopic findings of CMV esophagitis after liver transplantation","Unusual endoscopic findings of CMV esophagitis after liver transplantation","Noboru Harada, Mitsuo Shimada, Taketoshi Suehiro, Yuji Soejima, Mizuki Ninomiya, Satoko Shiotani, Keizo Sugimachi","Noboru Harada, Mitsuo Shimada, Taketoshi Suehiro, Yuji Soejima, Mizuki Ninomiya, Satoko Shiotani, Keizo Sugimachi","null","Cytomegalovirus infections are associated with a high mortality rate after liver transplantation, but they are treated successfully by administration of the combination of ganciclovir plus intravenous immunoglobulin. We herein describe cytomegalovirus esophagitis in a patient having gastrointestinal symptoms such as dysphagia, retrosternal pain and epigastralgia after liver transplantation was detected by performing the surveillance of endoscopy. At first, the findings of endoscopy that were segmental erosive areas but no ulcerative areas on the esophageal lumen were unusual in this case of cytomegalovirus infections, but cytomegalovirus esophagitis was confirmed by cytomegalovirus immunohistochemical stain using biopsies. The patient was treated by ganciclovir at an oral dosage of 5mg/kg twice a day for 2 weeks. Our experience suggests that cytomegalovirus esophagitis should be taken into consideration when a patient has gastrointestinal symptoms such as dysphagia, retrosternal pain and epigastralgia and has endoscopic findings such as segmental erosions on the esophageal lumen despite having no cytomegalovirus-specific endoscopic findings such as ulcerative lesions.","Cytomegalovirus infections are associated with a high mortality rate after liver transplantation, but they are treated successfully by administration of the combination of ganciclovir plus intravenous immunoglobulin. We herein describe cytomegalovirus esophagitis in a patient having gastrointestinal symptoms such as dysphagia, retrosternal pain and epigastralgia after liver transplantation was detected by performing the surveillance of endoscopy. At first, the findings of endoscopy that were segmental erosive areas but no ulcerative areas on the esophageal lumen were unusual in this case of cytomegalovirus infections, but cytomegalovirus esophagitis was confirmed by cytomegalovirus immunohistochemical stain using biopsies. The patient was treated by ganciclovir at an oral dosage of 5mg/kg twice a day for 2 weeks. Our experience suggests that cytomegalovirus esophagitis should be taken into consideration when a patient has gastrointestinal symptoms such as dysphagia, retrosternal pain and epigastralgia and has endoscopic findings such as segmental erosions on the esophageal lumen despite having no cytomegalovirus-specific endoscopic findings such as ulcerative lesions.","null","null","2005-07","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.52","No.64","1236","1239","eng","null","null","research_institution","null","null","null","0172-6390","null","null","null","null","null"
"Effect of liver transplantation on multiple bone fractures in an infant with end-stage biliary atresia: a case report","Effect of liver transplantation on multiple bone fractures in an infant with end-stage biliary atresia: a case report","Shunsaku Katsura, Keiko Ogita, Tomoaki Taguchi, Sachiyo Suita, Tomoharu Yoshizumi, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara","Shunsaku Katsura, Keiko Ogita, Tomoaki Taguchi, Sachiyo Suita, Tomoharu Yoshizumi, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara","null","Osteodystrophy is frequently found in children with chronic cholestatic liver disease. We herein report an end-stage case of biliary atresia that was associated with multiple bone fractures and severe growth retardation. The patient, an 8-month-old female, underwent a living-related liver transplantation and thereafter showed a dramatic improvement in growth and decrease in bone fractures. A correction of the liver function is therefore considered to be a key factor in treating osteodystrophy that is related to chronic cholestatic liver disease. It is also essential to perform liver transplantation at the most appropriate time to enhance and support the growth of these patients.","Osteodystrophy is frequently found in children with chronic cholestatic liver disease. We herein report an end-stage case of biliary atresia that was associated with multiple bone fractures and severe growth retardation. The patient, an 8-month-old female, underwent a living-related liver transplantation and thereafter showed a dramatic improvement in growth and decrease in bone fractures. A correction of the liver function is therefore considered to be a key factor in treating osteodystrophy that is related to chronic cholestatic liver disease. It is also essential to perform liver transplantation at the most appropriate time to enhance and support the growth of these patients.","null","null","2005-01","Pediatric Surgery International","Pediatric Surgery International","Vol.21","No.1","47","49","eng","null","null","research_institution","null","null","10.1007/s00383-004-1262-z","0179-0358","null","http://www.springerlink.com/link.asp?id=3ul82f3uapj3h093","null","null","null"
"Renal tubular acidosis secondary to FK506 in living donor liver transplantation: a case report","Renal tubular acidosis secondary to FK506 in living donor liver transplantation: a case report","Keiko Ogita, Narito Takada, Tomoaki Taguchi, Sachiyo Suita, Yuji Soejima, Taketoshi Suehiro, Mitsuo Shimada, Yoshihiko Maehara","Keiko Ogita, Narito Takada, Tomoaki Taguchi, Sachiyo Suita, Yuji Soejima, Taketoshi Suehiro, Mitsuo Shimada, Yoshihiko Maehara","null","FK506 is an immunosuppressant that is thought to be less nephrotoxic than cyclosporine A. However, complications due to renal tubular acidosis (RTA) have recently been reported. We report a case of RTA secondary to FK506 administration in liver transplantation. A 6-month-old girl was treated with FK506 after undergoing living donor liver transplantation for fulminant hepatitis. On postoperative day 17, she demonstrated hyperkalaemia and metabolic acidosis; she was diagnosed to have hyperkalaemic distal RTA with aldosterone deficiency (type IV). Intravenous sodium bicarbonate and furosemide, and intrarectal calcium polystyrenesulfonate were administered to correct the acidosis and promote potassium secretion. Thereafter, the FK506 concentration in whole blood gradually decreased, and the hyperkalaemia and metabolic acidosis following RTA improved. RTA is one type of nephrotoxicity induced by FK506, and it is reversible in mild cases when appropriately treated. The mechanism of RTA induced by FK506 has not yet been clearly elucidated. Surgeons and physicians should therefore be aware of the potential for RTA to occur with FK506 after any organ transplantation. The treatment for acidosis and hyperkalaemia should be started as soon as RTA is diagnosed, and the dosage of FK506 should also be reduced if possible.","FK506 is an immunosuppressant that is thought to be less nephrotoxic than cyclosporine A. However, complications due to renal tubular acidosis (RTA) have recently been reported. We report a case of RTA secondary to FK506 administration in liver transplantation. A 6-month-old girl was treated with FK506 after undergoing living donor liver transplantation for fulminant hepatitis. On postoperative day 17, she demonstrated hyperkalaemia and metabolic acidosis; she was diagnosed to have hyperkalaemic distal RTA with aldosterone deficiency (type IV). Intravenous sodium bicarbonate and furosemide, and intrarectal calcium polystyrenesulfonate were administered to correct the acidosis and promote potassium secretion. Thereafter, the FK506 concentration in whole blood gradually decreased, and the hyperkalaemia and metabolic acidosis following RTA improved. RTA is one type of nephrotoxicity induced by FK506, and it is reversible in mild cases when appropriately treated. The mechanism of RTA induced by FK506 has not yet been clearly elucidated. Surgeons and physicians should therefore be aware of the potential for RTA to occur with FK506 after any organ transplantation. The treatment for acidosis and hyperkalaemia should be started as soon as RTA is diagnosed, and the dosage of FK506 should also be reduced if possible.","null","null","2003-10","Asian Journal of Surgery","Asian Journal of Surgery","Vol.26","No.4","218","220","eng","null","null","research_institution","null","null","10.1016/S1015-9584(09)60307-9","1015-9584","null","http://asia.elsevierhealth.com/ajs/abstract.asp?art_id=324&art_journals=3","null","null","null"
"術前急性腎不全合併症例に対する生体肝移植の一例","術前急性腎不全合併症例に対する生体肝移植の一例","伊地知 秀樹, 島田 光生, 末廣 剛敏, 副島 雄二, 前原 喜彦, 中牟田 誠, 名和田 新","伊地知 秀樹, Mitsuo Shimada, 末廣 剛敏, Yuji Soejima, 前原 喜彦, 中牟田 誠, 名和田 新","null","null","null","null","null","2002","福岡医学雑誌","Fukuoka Acta Medica","Vol.93","null","266","271","jpn","null","null","research_institution","null","null","null","0016-254X","null","null","null","null","null"
"肝移植後液性拒絶反応が疑われた1症例","肝移植後液性拒絶反応が疑われた1症例","寺師 貴啓, 田口 健一, 恒吉 正澄, 島田 光生, 末廣 剛敏, 副島 雄二, 杉町 圭蔵, 柿添 三郎","寺師 貴啓, 田口 健一, 恒吉 正澄, Mitsuo Shimada, 末廣 剛敏, Yuji Soejima, 杉町 圭蔵, 柿添 三郎","null","null","null","null","null","2001","今日の移植","今日の移植","Vol.14","null","667","668","jpn","null","null","research_institution","null","null","null","null","null","null","null","null","null"
"Repeat hepatectomy is the most useful treatment for recurrent hepatocellular carcinoma","Repeat hepatectomy is the most useful treatment for recurrent hepatocellular carcinoma","Keizo Sugimachi, Shinichiro Maehara, Shinji Tanaka, Mitsuo Shimada, Keishi Sugimachi","Keizo Sugimachi, Shinichiro Maehara, Shinji Tanaka, Mitsuo Shimada, Keishi Sugimachi","null","Hepatic resection has been regarded as a curative treatment for primary hepatocellular carcinoma (HCC), but a high incidence of postoperative recurrence is general. Thus it is important to predict the patterns of recurrence and select the appropriate treatment for recurrence for a better long-term prognosis of patients with HCC. Clinicopathological studies on 80 patients with intrahepatic recurrence after curative hepatectomy suggested that nodular-type recurrence with up to three nodules is mainly due to metachronous multicentric hepatocarcinogenesis rather than intrahepatic metastases. We reviewed 300 patients with recurrent HCC, and repeat hepatectomy was done in 78 cases (26.0%). The 3- and 5-year survival rates after repeat hepatectomy were 82.8% and 47.5%, respectively, showing better prognosis than those for other treatments. Repeat hepatectomy is the preferred treatment offering a hope of long-term survival for patients with recurrent HCC as long as liver function is sufficient; thus early detection of recurrence should be ensured.","Hepatic resection has been regarded as a curative treatment for primary hepatocellular carcinoma (HCC), but a high incidence of postoperative recurrence is general. Thus it is important to predict the patterns of recurrence and select the appropriate treatment for recurrence for a better long-term prognosis of patients with HCC. Clinicopathological studies on 80 patients with intrahepatic recurrence after curative hepatectomy suggested that nodular-type recurrence with up to three nodules is mainly due to metachronous multicentric hepatocarcinogenesis rather than intrahepatic metastases. We reviewed 300 patients with recurrent HCC, and repeat hepatectomy was done in 78 cases (26.0%). The 3- and 5-year survival rates after repeat hepatectomy were 82.8% and 47.5%, respectively, showing better prognosis than those for other treatments. Repeat hepatectomy is the preferred treatment offering a hope of long-term survival for patients with recurrent HCC as long as liver function is sufficient; thus early detection of recurrence should be ensured.","null","null","2001-10","Journal of Hepato-Biliary-Pancreatic Surgery","Journal of Hepato-Biliary-Pancreatic Surgery","Vol.8","No.5","410","416","eng","null","null","null","null","null","10.1007/s005340100002","0944-1166","null","http://www.springerlink.com/content/dwcetjp7uu7wlc28/","null","null","null"
"Three-dimensional power Doppler transanal ultrasonography, to monitor haemorrhoidal blood flow after Doppler-guided ALTA sclerosing therapy.","Three-dimensional power Doppler transanal ultrasonography, to monitor haemorrhoidal blood flow after Doppler-guided ALTA sclerosing therapy.","Hidenori Miyamoto, 浅野間 理仁, 宮本 英之, Chie Takasu, Mitsuo Shimada","Hidenori Miyamoto, 浅野間 理仁, 宮本 英之, Chie Takasu, Mitsuo Shimada","null","The study aimed to use power Doppler imaging (PDI) transanal ultrasonography to produce three-dimensional power Doppler angiography images of haemorrhoidal tissue and to monitor the effects of Doppler-guided aluminium potassium sulfate and tannic acid (DGALTA) sclerotherapy. Ninety-six haemorrhoids in 43 patients were examined using PDI transanal ultrasonography, and DGALTA sclerotherapy was performed from April 2011 to April 2012. DGALTA sclerotherapy was conducted using a four-step injection process with pulse wave Doppler ultrasound under perianal local anaesthesia. A three-dimensional power Doppler angiography image of the blood flow in haemorrhoidal tissue was produced using PDI transanal ultrasonography. The cross-sectional area of blood flow in the haemorrhoidal tissue (PDI area) significantly decreased after DGALTA sclerotherapy. The PDI areas in the preoperative state and 1 and 3 months after treatment were 0.35±0.27, 0.03±0.05 and 0.04±0.05 cm(2) (P<0.0001). A three-dimensional power Doppler angiography image of the haemorrhoidal tissue was technically possible and showed blood flow in the haemorrhoidal tissue to be significantly decreased after DGALTA sclerotherapy.","The study aimed to use power Doppler imaging (PDI) transanal ultrasonography to produce three-dimensional power Doppler angiography images of haemorrhoidal tissue and to monitor the effects of Doppler-guided aluminium potassium sulfate and tannic acid (DGALTA) sclerotherapy. Ninety-six haemorrhoids in 43 patients were examined using PDI transanal ultrasonography, and DGALTA sclerotherapy was performed from April 2011 to April 2012. DGALTA sclerotherapy was conducted using a four-step injection process with pulse wave Doppler ultrasound under perianal local anaesthesia. A three-dimensional power Doppler angiography image of the blood flow in haemorrhoidal tissue was produced using PDI transanal ultrasonography. The cross-sectional area of blood flow in the haemorrhoidal tissue (PDI area) significantly decreased after DGALTA sclerotherapy. The PDI areas in the preoperative state and 1 and 3 months after treatment were 0.35±0.27, 0.03±0.05 and 0.04±0.05 cm(2) (P<0.0001). A three-dimensional power Doppler angiography image of the haemorrhoidal tissue was technically possible and showed blood flow in the haemorrhoidal tissue to be significantly decreased after DGALTA sclerotherapy.","null","null","2013-02","Colorectal Disease","Colorectal Disease","Vol.15","No.2","84","88","eng","null","null","null","null","null","10.1111/codi.12024","1463-1318","null","null","null","null","null"
"CD11b(+) cells in donor-specific transfusion prolonged allogenic skin graft survival through indoleamine 2,3-dioxygenase.","CD11b(+) cells in donor-specific transfusion prolonged allogenic skin graft survival through indoleamine 2,3-dioxygenase.","Tetsuya Ikemoto, M Takita, MF Levy, Mitsuo Shimada, B Naziruddin","Tetsuya Ikemoto, M Takita, MF Levy, Mitsuo Shimada, B Naziruddin","null","The aim of this study is to show the effect of donor-specific transfusion (DST) in inducing immunological tolerance mediated by regulatory T cells (Treg) and indoleamine 2,3-dioxygenase (IDO). Skin grafts from H2(d) Balb/c were transplanted into H2(k) C3H/He 7days after the infusion of donor splenocytes, isolated each immune cell populations. Graft survival prolonged in recipients who received splenocytes, MHC class II(+) CD90(-) cells and CD3(-)CD19(-) cells (p<0.001, p<0.05 and p<0.01, respectively). CD11b(+) cell infusion resulted in prolongation of graft survival when compared to CD11c(+) cell infusion (p<0.01). Foxp3(+)CD4(+)CD25(+) T cells were increased after the transplant in recipients infused with CD11b(+) cells (p<0.05). The mixed lymphocyte reaction showed donor-specificity (p<0.001). High IDO expression was observed in CD11b(+) cell infusion group. Graft survival with DST using IDO antagonist (1MT) were not prolonged. In conclusion, DST allows induction of donor-specific tolerance which involves Foxp3(+)CD4(+)CD25(+) T cells and IDO expression.","The aim of this study is to show the effect of donor-specific transfusion (DST) in inducing immunological tolerance mediated by regulatory T cells (Treg) and indoleamine 2,3-dioxygenase (IDO). Skin grafts from H2(d) Balb/c were transplanted into H2(k) C3H/He 7days after the infusion of donor splenocytes, isolated each immune cell populations. Graft survival prolonged in recipients who received splenocytes, MHC class II(+) CD90(-) cells and CD3(-)CD19(-) cells (p<0.001, p<0.05 and p<0.01, respectively). CD11b(+) cell infusion resulted in prolongation of graft survival when compared to CD11c(+) cell infusion (p<0.01). Foxp3(+)CD4(+)CD25(+) T cells were increased after the transplant in recipients infused with CD11b(+) cells (p<0.05). The mixed lymphocyte reaction showed donor-specificity (p<0.001). High IDO expression was observed in CD11b(+) cell infusion group. Graft survival with DST using IDO antagonist (1MT) were not prolonged. In conclusion, DST allows induction of donor-specific tolerance which involves Foxp3(+)CD4(+)CD25(+) T cells and IDO expression.","null","null","2013-05","Cellular Immunology","Cellular Immunology","Vol.283","No.1-2","81","90","eng","null","null","null","null","null","10.1016/j.cellimm.2013.06.004","1090-2163","null","null","null","null","null"
"Effects of splenectomy on hepatic gene expression profiles after massive hepatectomy in rats.","Effects of splenectomy on hepatic gene expression profiles after massive hepatectomy in rats.","Yusuke Arakawa, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Chie Takasu","Yusuke Arakawa, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Chie Takasu","null","Possible spleno-hepatic relationships affected by hepatectomy still remained unclear. We have previously reported that splenectomy may ameliorate liver injuries and promote appropriate liver regeneration after massive hepatectomy. Therefore, we investigated the effects of splenectomy on the DNA expression profile in the liver after massive hepatectomy in rats. Rats were divided into the following two groups: 90% hepatectomy (Hx group) and 90% hepatectomy with splenectomy (Hx + Sp group). Rats were sacrificed 3 and 6 h after surgery, and mRNA from liver tissue was isolated and hybridized to Affymetrix GeneChip Rat Genome 230 2.0 Array (Affymetrix, Santa Clara, CA, USA) and a pathway analysis was done with Ingenuity Pathway Analysis (Ingenuity Systems, Mountain View, CA, USA). We determined the Hx + Sp/Hx ratio to assess the influence of splenectomy, and cut-off values were set at more than 2.0-fold or less than 1/2 (0.5)-fold. Immediate early response gene including early growth response-1 and FBJ murine osteosarcoma-related pathways were markedly downregulated by splenectomy. In contrast, heme oxygenase-1 gene-related pathway was upregulated by splenectomy. Splenectomy provided the protective effects for liver failure and promoted liver regeneration, possibly owing to the downregulation of immediate early response genes and upregulation of the heat shock protein, heme oxygenase-1.","Possible spleno-hepatic relationships affected by hepatectomy still remained unclear. We have previously reported that splenectomy may ameliorate liver injuries and promote appropriate liver regeneration after massive hepatectomy. Therefore, we investigated the effects of splenectomy on the DNA expression profile in the liver after massive hepatectomy in rats. Rats were divided into the following two groups: 90% hepatectomy (Hx group) and 90% hepatectomy with splenectomy (Hx + Sp group). Rats were sacrificed 3 and 6 h after surgery, and mRNA from liver tissue was isolated and hybridized to Affymetrix GeneChip Rat Genome 230 2.0 Array (Affymetrix, Santa Clara, CA, USA) and a pathway analysis was done with Ingenuity Pathway Analysis (Ingenuity Systems, Mountain View, CA, USA). We determined the Hx + Sp/Hx ratio to assess the influence of splenectomy, and cut-off values were set at more than 2.0-fold or less than 1/2 (0.5)-fold. Immediate early response gene including early growth response-1 and FBJ murine osteosarcoma-related pathways were markedly downregulated by splenectomy. In contrast, heme oxygenase-1 gene-related pathway was upregulated by splenectomy. Splenectomy provided the protective effects for liver failure and promoted liver regeneration, possibly owing to the downregulation of immediate early response genes and upregulation of the heat shock protein, heme oxygenase-1.","null","null","2013-10","Journal of Gastroenterology and Hepatology","Journal of Gastroenterology and Hepatology","Vol.28","No.10","1669-1677","1669-1677","eng","null","null","null","null","null","10.1111/jgh.12316","1440-1746","null","null","null","null","null"
"One-stop shop for 3-dimensional anatomy of hepatic vasculature and bile duct with special reference to biliary image reconstruction.","One-stop shop for 3-dimensional anatomy of hepatic vasculature and bile duct with special reference to biliary image reconstruction.","C Enkhbold, Mitsuo Shimada, Toru Utsunomiya, Hiroki Ishibashi, S Yamada, Mami Kanamoto, Yusuke Arakawa, Tetsuya Ikemoto, Yuji Morine, Satoru Imura","C Enkhbold, Mitsuo Shimada, Toru Utsunomiya, Hiroki Ishibashi, S Yamada, Mami Kanamoto, Yusuke Arakawa, Tetsuya Ikemoto, Yuji Morine, Satoru Imura","null","Three-dimensional CT has become an essential tool for successful hepatic surgery. Up to now, efforts have been made to simultaneously visualize hepatic vasculature and bile ducts. Herein, we introduce a new one-stop shop approach to hepatic 3D-anatomy, using a standard enhanced MDCT alone. A 3D-reconstruction of hepatic vasculature was made using data from contrast enhanced MDCT and SYNAPSE VINCENT software. We identified bile ducts from axial 2D image, and then reconstructed the 3D image. Both hepatic vasculature and bile duct images were integrated into a single image and it was compared with the 3D image, utilized with MRCP or DIC-CT. The first branches of both the right and left hepatic ducts were hand-traced and visualized for all 100 cases. The second branches of these ducts were visualized in 69 cases, and only the right second branch was recognized in 52 cases. Anomalous variations of bile ducts, such as posterior branch joining into common hepatic duct, were recognized in 12 cases. These biliary tract variations were all confirmed by MRCP or DIC-CT. Our new one-stop shop approach using the 3D imaging technique might contribute to successful hepatectomy as well as reduce medical costs and radiation exposure by omission of MRCP and DIC-CT.","Three-dimensional CT has become an essential tool for successful hepatic surgery. Up to now, efforts have been made to simultaneously visualize hepatic vasculature and bile ducts. Herein, we introduce a new one-stop shop approach to hepatic 3D-anatomy, using a standard enhanced MDCT alone. A 3D-reconstruction of hepatic vasculature was made using data from contrast enhanced MDCT and SYNAPSE VINCENT software. We identified bile ducts from axial 2D image, and then reconstructed the 3D image. Both hepatic vasculature and bile duct images were integrated into a single image and it was compared with the 3D image, utilized with MRCP or DIC-CT. The first branches of both the right and left hepatic ducts were hand-traced and visualized for all 100 cases. The second branches of these ducts were visualized in 69 cases, and only the right second branch was recognized in 52 cases. Anomalous variations of bile ducts, such as posterior branch joining into common hepatic duct, were recognized in 12 cases. These biliary tract variations were all confirmed by MRCP or DIC-CT. Our new one-stop shop approach using the 3D imaging technique might contribute to successful hepatectomy as well as reduce medical costs and radiation exposure by omission of MRCP and DIC-CT.","null","null","2013-11","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.60","No.128","1861","1864","eng","null","null","null","null","null","10.5754/hge13536","0172-6390","null","null","null","null","null"
"Clinical features of pancreaticobiliary maljunction: update analysis of 2nd Japan-nationwide survey.","Clinical features of pancreaticobiliary maljunction: update analysis of 2nd Japan-nationwide survey.","Yuji Morine, Mitsuo Shimada, H Takamatsu, T Araida, I Endo, M Kubota, A Toki, T Noda, T Matsumura, S Miyakawa, Hiroki Ishibashi, T Kamisawa, H Shimada","Yuji Morine, Mitsuo Shimada, H Takamatsu, T Araida, I Endo, M Kubota, A Toki, T Noda, T Matsumura, S Miyakawa, Hiroki Ishibashi, T Kamisawa, H Shimada","null","Pancreaticobiliary maljunction (PBM) is a congenital anomaly, which can be defined as a union of the pancreatic and biliary ducts located outside off the duodenal wall. We herein investigate clinical features of PBM including as the 2nd report of a Japanese nationwide survey. During a period of 18 years (from 1990 to 2007), 2,561 patients with PBM were registered at 141 medical institutions in Japan. Among them, eligible patients (n = 2,529) were divided into two groups: adult (n = 1,511) and pediatric patients (n = 1,018). Comparisons of clinical features including associated biliary cancers were performed according to the biliary dilatation (BD), age factor, and time era. Only one case in pediatric patients with BD combined with a bile duct cancer (0.1 %). In adult patients, the bile duct cancer and the gallbladder cancer was seen in 6.9 and 13.4 % patients with BD and in 3.1 and 37.4 % patients without BD, respectively. In adult patients with BD, the occurrence rates of biliary cancers were increased in latter period (00'-07') compared with former period (90'-99'). The ratio of biliary cancer localization was changed between former and latter period, and the bile duct cancer was increased in latter period (from 5.5 to 9.3 %). The largest series of PBM were evaluated to clarify the clinical features including the associated biliary cancer in this Japan-nationwide survey. This report could be widely used in the future as a reference data for diagnosis and treatment of PBM.","Pancreaticobiliary maljunction (PBM) is a congenital anomaly, which can be defined as a union of the pancreatic and biliary ducts located outside off the duodenal wall. We herein investigate clinical features of PBM including as the 2nd report of a Japanese nationwide survey. During a period of 18 years (from 1990 to 2007), 2,561 patients with PBM were registered at 141 medical institutions in Japan. Among them, eligible patients (n = 2,529) were divided into two groups: adult (n = 1,511) and pediatric patients (n = 1,018). Comparisons of clinical features including associated biliary cancers were performed according to the biliary dilatation (BD), age factor, and time era. Only one case in pediatric patients with BD combined with a bile duct cancer (0.1 %). In adult patients, the bile duct cancer and the gallbladder cancer was seen in 6.9 and 13.4 % patients with BD and in 3.1 and 37.4 % patients without BD, respectively. In adult patients with BD, the occurrence rates of biliary cancers were increased in latter period (00'-07') compared with former period (90'-99'). The ratio of biliary cancer localization was changed between former and latter period, and the bile duct cancer was increased in latter period (from 5.5 to 9.3 %). The largest series of PBM were evaluated to clarify the clinical features including the associated biliary cancer in this Japan-nationwide survey. This report could be widely used in the future as a reference data for diagnosis and treatment of PBM.","null","null","2013-06-01","Journal of Hepato-Biliary-Pancreatic Sciences","Journal of Hepato-Biliary-Pancreatic Sciences","Vol.20","No.5","472-480","472-480","eng","null","null","null","null","null","10.1007/s00534-013-0606-2","1868-6974","null","http://ci.nii.ac.jp/naid/10031183502/","null","null","null"
"High expressions of cancer stem cell markers in cholangiolocellular carcinoma.","High expressions of cancer stem cell markers in cholangiolocellular carcinoma.","Shuichi Iwahashi, Toru Utsunomiya, Mitsuo Shimada, Yu Saitou, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Yoshimi Bando","Shuichi Iwahashi, Toru Utsunomiya, Mitsuo Shimada, Yu Saitou, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Yoshimi Bando","null","Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor. It is thought to originate from the ductules and/or canals of Hering, where hepatic stem cells (HpSC) are located, but there are few reports on cancer stem cell markers in CLC. Thus, we evaluated the significance of cancer stem cell markers, including CD133, CD44, and EpCAM, in CLC. The subjects of this study were three patients with CLC and one patient with an intermediate type of combined hepatocellular cholangiocarcinoma (CHC). The cancer cell markers, CK7, CK19, and EMA, were evaluated immunohistochemically. Histological examination of the CLC revealed morphologically cholangiolar features and immunohistochemical examination revealed positivity for CD133, CD44, and EpCAM. On the other hand, in the intermediate type of CHC, only CD44 was positive, whereas CD133 and EpCAM were negative. CLC may have stronger features derived from HpSCs than an intermediate type of CHC.","Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor. It is thought to originate from the ductules and/or canals of Hering, where hepatic stem cells (HpSC) are located, but there are few reports on cancer stem cell markers in CLC. Thus, we evaluated the significance of cancer stem cell markers, including CD133, CD44, and EpCAM, in CLC. The subjects of this study were three patients with CLC and one patient with an intermediate type of combined hepatocellular cholangiocarcinoma (CHC). The cancer cell markers, CK7, CK19, and EMA, were evaluated immunohistochemically. Histological examination of the CLC revealed morphologically cholangiolar features and immunohistochemical examination revealed positivity for CD133, CD44, and EpCAM. On the other hand, in the intermediate type of CHC, only CD44 was positive, whereas CD133 and EpCAM were negative. CLC may have stronger features derived from HpSCs than an intermediate type of CHC.","null","null","2013-06","Surgery Today","Surgery Today","Vol.43","No.6","654","660","eng","null","null","null","null","null","10.1007/s00595-012-0437-9","1436-2813","null","null","null","null","null"
"The protective effect of adipose-derived stem cells against liver injury by trophic molecules.","The protective effect of adipose-derived stem cells against liver injury by trophic molecules.","Yu Saitou, Mitsuo Shimada, Toru Utsunomiya, Tetsuya Ikemoto, 山田 眞一郎, Yuji Morine, Satoru Imura, Hiroki Mori, 杉本 光司, Shuichi Iwahashi, 浅野間 理仁","Yu Saitou, Mitsuo Shimada, Toru Utsunomiya, Tetsuya Ikemoto, 山田 眞一郎, Yuji Morine, Satoru Imura, Hiroki Mori, 杉本 光司, Shuichi Iwahashi, 浅野間 理仁","null","In this study we investigated whether adipose-derived stem cells (ADSCs) had any beneficial protective effects on liver injury and regeneration in vivo. Moreover, we examined whether ADSCs protect hepatocytes via trophic molecules. We transplanted ADSCs into mice after 70% hepatectomy and ischemia-reperfusion, and observed liver injury and regeneration after reperfusion. We co-cultured hepatocytes with ADSCs using a Transwell system for 7 d and evaluated the viabilities of hepatocytes and the cytokine levels in the culture medium. Bevacizumab was used to confirm the effect of vascular endothelial growth factor (VEGF) on hepatocytes. ADSCs improved serum liver function at 6 h after reperfusion in a nonlethal model and stimulated liver regeneration at 24 h after reperfusion in a lethal model. VEGF levels in the culture medium were increased by co-culture ADSCs with hepatocytes. ADSCs improved the viabilities of hepatocytes. The inhibited production of VEGF by bevacizumab did not affect the viability of hepatocytes. ADSCs were able to ameliorate liver injury and stimulate liver regeneration in subsequent hepatectomy and ischemia-reperfusion-injured model mice. Furthermore, hepatocytes were protected by the trophic molecules of the ADSCs. However, such protective effects might be provided by mechanisms other than VEGF signaling.","In this study we investigated whether adipose-derived stem cells (ADSCs) had any beneficial protective effects on liver injury and regeneration in vivo. Moreover, we examined whether ADSCs protect hepatocytes via trophic molecules. We transplanted ADSCs into mice after 70% hepatectomy and ischemia-reperfusion, and observed liver injury and regeneration after reperfusion. We co-cultured hepatocytes with ADSCs using a Transwell system for 7 d and evaluated the viabilities of hepatocytes and the cytokine levels in the culture medium. Bevacizumab was used to confirm the effect of vascular endothelial growth factor (VEGF) on hepatocytes. ADSCs improved serum liver function at 6 h after reperfusion in a nonlethal model and stimulated liver regeneration at 24 h after reperfusion in a lethal model. VEGF levels in the culture medium were increased by co-culture ADSCs with hepatocytes. ADSCs improved the viabilities of hepatocytes. The inhibited production of VEGF by bevacizumab did not affect the viability of hepatocytes. ADSCs were able to ameliorate liver injury and stimulate liver regeneration in subsequent hepatectomy and ischemia-reperfusion-injured model mice. Furthermore, hepatocytes were protected by the trophic molecules of the ADSCs. However, such protective effects might be provided by mechanisms other than VEGF signaling.","null","null","2013-03","The Journal of Surgical Research","The Journal of Surgical Research","Vol.180","No.1","162-168","162-168","eng","null","null","null","null","null","10.1016/j.jss.2012.10.009","1095-8673","null","null","null","null","null"
"Regulatory T cells in the blood: a new marker of surgical stress.","Regulatory T cells in the blood: a new marker of surgical stress.","Yu Saitou, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Shuichi Iwahashi, 山田 眞一郎, 浅野間 理仁","Yu Saitou, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Shuichi Iwahashi, 山田 眞一郎, 浅野間 理仁","null","null","null","null","null","2013-01","Surgery Today","Surgery Today","Vol.43","No.6","608-612","608-612","eng","null","null","null","null","null","10.1007/s00595-013-0517-5","0941-1291","null","http://ci.nii.ac.jp/naid/10031176080/","null","null","null"
"Hand-assisted laparoscopic splenectomy for a huge splenic vascular lesion with aneurysms in a patient with impending Kasabach-Merritt syndrome-like phenomenon.","Hand-assisted laparoscopic splenectomy for a huge splenic vascular lesion with aneurysms in a patient with impending Kasabach-Merritt syndrome-like phenomenon.","杉本 光司, Toru Utsunomiya, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Chie Takasu, Mitsuo Shimada","杉本 光司, Toru Utsunomiya, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Chie Takasu, Mitsuo Shimada","null","Splenic vascular lesions are relatively rare and are usually found incidentally. However, the vascular lesions associated with Kasabach-Merritt syndrome, such as hemangioma, can be life-threatening. We herein describe the case of a young adult female patient with a huge splenic vascular lesion, aneurysms of the splenic artery, and increased plasma levels of fibrin/fibrinogen degradation products and D-dimers. Hand-assisted laparoscopic splenectomy was performed, after which the coagulopathy was drastically improved. Minimally invasive surgical intervention such as hand-assisted laparoscopic splenectomy should be considered as the first treatment choice in such a case.","Splenic vascular lesions are relatively rare and are usually found incidentally. However, the vascular lesions associated with Kasabach-Merritt syndrome, such as hemangioma, can be life-threatening. We herein describe the case of a young adult female patient with a huge splenic vascular lesion, aneurysms of the splenic artery, and increased plasma levels of fibrin/fibrinogen degradation products and D-dimers. Hand-assisted laparoscopic splenectomy was performed, after which the coagulopathy was drastically improved. Minimally invasive surgical intervention such as hand-assisted laparoscopic splenectomy should be considered as the first treatment choice in such a case.","null","null","2013","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.60","No.3-4","276-279","276-279","eng","null","null","null","null","null","10.2152/jmi.60.276","1349-6867","null","null","null","null","null"
"Oxaliplatin-related sinusoidal obstruction syndrome mimicking metastatic liver tumors.","Oxaliplatin-related sinusoidal obstruction syndrome mimicking metastatic liver tumors.","Yusuke Arakawa, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Jun Hanaoka, 杉本 光司, Yoshimi Bando","Yusuke Arakawa, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Jun Hanaoka, 杉本 光司, Yoshimi Bando","null","A 40-year-old woman who had undergone a curative low anterior resection for advanced rectal cancer was admitted to our hospital. She had been administrated oxaliplatin-based chemotherapy as postoperative adjuvant chemotherapy. The contrast-enhanced computed tomography revealed three hypovascular tumors, 3.0, 1.5 and 1.0 cm in diameter, located in the right hepatic lobe. The hepatocyte phase of the gadoxetic acid-enhanced magnetic resonance imaging demonstrated these lesions as hypointense tumors relative to the surrounding hepatic parenchyma. All these findings of the preoperative imaging modalities were compatible to metastatic liver tumors from the rectal cancer, and right hepatic lobectomy was successfully performed. Histopathologically, the tumors revealed sinusoidal dilation and severe congestion outlined by atrophic hepatocyte trabeculae, which was known as peliosis hepatis. The perisinusoidal space of Disse was extensively dilated and contained many erythrocytes. Taking these findings into account, the hepatic tumors were considered to be the space-occupying lesions resulting from the sinusoidal obstruction syndrome. We herein report the first case of focal sinusoidal obstruction syndrome mimicking metastatic liver tumors.","A 40-year-old woman who had undergone a curative low anterior resection for advanced rectal cancer was admitted to our hospital. She had been administrated oxaliplatin-based chemotherapy as postoperative adjuvant chemotherapy. The contrast-enhanced computed tomography revealed three hypovascular tumors, 3.0, 1.5 and 1.0 cm in diameter, located in the right hepatic lobe. The hepatocyte phase of the gadoxetic acid-enhanced magnetic resonance imaging demonstrated these lesions as hypointense tumors relative to the surrounding hepatic parenchyma. All these findings of the preoperative imaging modalities were compatible to metastatic liver tumors from the rectal cancer, and right hepatic lobectomy was successfully performed. Histopathologically, the tumors revealed sinusoidal dilation and severe congestion outlined by atrophic hepatocyte trabeculae, which was known as peliosis hepatis. The perisinusoidal space of Disse was extensively dilated and contained many erythrocytes. Taking these findings into account, the hepatic tumors were considered to be the space-occupying lesions resulting from the sinusoidal obstruction syndrome. We herein report the first case of focal sinusoidal obstruction syndrome mimicking metastatic liver tumors.","null","null","2013-06","Hepatology Research","Hepatology Research","Vol.43","No.6","685","689","eng","null","null","null","null","null","10.1111/j.1872-034X.2012.01114.x","1386-6346","null","null","null","null","null"
"Hybrid-artificial liver support system","Hybrid-artificial liver support system","Yo-ichi Yamashita, Mitsuo Shimada, Hiroyuki Ijima, Kohji Nakazawa, Kazumori Funatsu, Keizo Sugimachi","Yo-ichi Yamashita, Mitsuo Shimada, Hiroyuki Ijima, Kohji Nakazawa, Kazumori Funatsu, Keizo Sugimachi","null","We originally developed a multi-capillary polyurethane foam packed-bed module as a hybrid-artificial liver support system (HALSS) and have applied for the permission of the clinical application to our institutional ethical committee. We summarized here the history, recent obstacles in clinical applications, and future prospects of HALSS, including our own.","We originally developed a multi-capillary polyurethane foam packed-bed module as a hybrid-artificial liver support system (HALSS) and have applied for the permission of the clinical application to our institutional ethical committee. We summarized here the history, recent obstacles in clinical applications, and future prospects of HALSS, including our own.","null","null","2002-01","Surgery","Surgery","Vol.131","No.Supplement 1","S334","S340","eng","null","null","null","null","null","10.1067/msy.2002.120118","0039-6060","null","http://dx.doi.org/10.1067/msy.2002.120118","null","null","null"
"抗癌剤【肝胆膵】","抗癌剤【肝胆膵】","居村 暁, 島田 光生","Satoru Imura, Mitsuo Shimada","null","null","null","null","null","2013-01","消化器外科レビュー.","消化器外科レビュー.","Vol.2013-14","null","215-220","215-220","jpn","null","null","null","null","null","null","null","null","null","null","null","null"
"Angiogenic switch as a molecular target of malignant tumors","Angiogenic switch as a molecular target of malignant tumors","Shinji Tanaka, Keishi Sugimachi, Yo-ichi Yamashita, Ken Shirabe, Mitsuo Shimada, Jack R Wands, Keizo Sugimachi","Shinji Tanaka, Keishi Sugimachi, Yo-ichi Yamashita, Ken Shirabe, Mitsuo Shimada, Jack R Wands, Keizo Sugimachi","null","In vivo progression to malignancy is characterized by the switch to an angiogenic phenotype. The angiogenic switch is a critical control point for tumor expansion. The ability of a tumor to become neovascularized permits rapid expansion of tumor growth and increases the likelihood of metastases. The genetic alterations that accompany the switch to the angiogenic phenotype are unknown. Discoveries of such genes lead to comprehension of molecular mechanisms of the tumor progression, as well as development of novel therapeutic tools. We have isolated a novel ""angiogenic switch molecule,"" angiopoietin-2, upregulated specifically in hypervascular hepatocellular carcinoma (HCC). Angiopoietin family proteins have been originally identified as ligands of the vascular endothelial receptor of tyrosine kinase Tie2. Ectopic expression of angiopoietin-2 promotes the rapid development of human HCCs and produces hemorrhage within tumors in nude mice. These results suggest a role for angiopoietin-2 in the neovascularization of HCC. In vitro expression of a dominant-negative construct, containing a soluble Tie2 ectodomain (sTie2), led to Angiopoietin protein interaction, inhibition of endogenous Tie2 phosphorylation in vascular endothelial cells. Tumorigenicity with angiogenesis was suppressed by in vivo gene transfer and sTie2 expression in a murine HCC model, suggesting a possible role for angiopoietin/Tie2 signaling in the induction of HCC neovascularization and disease progression. More important, inhibition of the angiopoietin/Tie2 signal transduction cascade is a promising approach for HCC treatment.","In vivo progression to malignancy is characterized by the switch to an angiogenic phenotype. The angiogenic switch is a critical control point for tumor expansion. The ability of a tumor to become neovascularized permits rapid expansion of tumor growth and increases the likelihood of metastases. The genetic alterations that accompany the switch to the angiogenic phenotype are unknown. Discoveries of such genes lead to comprehension of molecular mechanisms of the tumor progression, as well as development of novel therapeutic tools. We have isolated a novel ""angiogenic switch molecule,"" angiopoietin-2, upregulated specifically in hypervascular hepatocellular carcinoma (HCC). Angiopoietin family proteins have been originally identified as ligands of the vascular endothelial receptor of tyrosine kinase Tie2. Ectopic expression of angiopoietin-2 promotes the rapid development of human HCCs and produces hemorrhage within tumors in nude mice. These results suggest a role for angiopoietin-2 in the neovascularization of HCC. In vitro expression of a dominant-negative construct, containing a soluble Tie2 ectodomain (sTie2), led to Angiopoietin protein interaction, inhibition of endogenous Tie2 phosphorylation in vascular endothelial cells. Tumorigenicity with angiogenesis was suppressed by in vivo gene transfer and sTie2 expression in a murine HCC model, suggesting a possible role for angiopoietin/Tie2 signaling in the induction of HCC neovascularization and disease progression. More important, inhibition of the angiopoietin/Tie2 signal transduction cascade is a promising approach for HCC treatment.","null","null","2003-03","Journal of Gastroenterology","Journal of Gastroenterology","Vol.38","No.Suppl 15","93","97","eng","null","null","null","null","null","null","0944-1174","null","null","null","null","null"
"[Novel molecularly targeted peptides interfering the specific signal transduction of cancer metastasis]","[Novel molecularly targeted peptides interfering the specific signal transduction of cancer metastasis]","Shinji Tanaka, Mitsuo Shimada, Ken Shirabe, Yoshihiko Maehara","Shinji Tanaka, Mitsuo Shimada, Ken Shirabe, Yoshihiko Maehara","null","null","null","null","null","2004-07","Nihon Rinsho. Japanese Journal of Clinical Medicine","Nihon Rinsho. Japanese Journal of Clinical Medicine","Vol.62","No.7","1251","1256","eng","null","null","null","null","null","null","0047-1852","null","null","null","null","null"
"The effect of polysaccharide k with S-1 based chemotherapy in advanced gastric cancer.","The effect of polysaccharide k with S-1 based chemotherapy in advanced gastric cancer.","Kouzou Yoshikawa, Mitsuo Shimada, Nobuhiro Kurita, Hirohiko Sato, Takashi Iwata, Masanori Nishioka, Shinya Morimoto, Tomohiko Miyatani, Masato Komatsu, Kashihara hideya, Chie Takasu","Kouzou Yoshikawa, Mitsuo Shimada, Nobuhiro Kurita, Hirohiko Sato, Takashi Iwata, Masanori Nishioka, Shinya Morimoto, Tomohiko Miyatani, Masato Komatsu, Kashihara hideya, Chie Takasu","null","Polysaccharide K (PSK) is widely used in Japan as a biological response modifier for cancer patients. We investigated the effects of PSK with S-1 based chemotherapy for advanced gastric cancer patients in immune response. Nine advanced gastric cancer patients who underwent chemotherapy at the University of Tokushima were included in this study. In all patients, 3g PSK was received orally and S-1 based chemotherapy for 2 weeks alternately for 8 weeks. Serial changes in immunological parameters (Foxp3, Natural killer (NK), CD4/CD8) were monitored. The levels of Foxp3 at 8 weeks was significantly decreased compared with 2 weeks (4.26% vs. 3.11%). In NK activity at 8 weeks was significantly increased compared with 2 weeks (27% vs. 47%). These results of this study suggested that chemotherapy with PSK improved the immune response in advanced gastric cancer patients. Especially Foxp3 was concerned in this mechanism.","Polysaccharide K (PSK) is widely used in Japan as a biological response modifier for cancer patients. We investigated the effects of PSK with S-1 based chemotherapy for advanced gastric cancer patients in immune response. Nine advanced gastric cancer patients who underwent chemotherapy at the University of Tokushima were included in this study. In all patients, 3g PSK was received orally and S-1 based chemotherapy for 2 weeks alternately for 8 weeks. Serial changes in immunological parameters (Foxp3, Natural killer (NK), CD4/CD8) were monitored. The levels of Foxp3 at 8 weeks was significantly decreased compared with 2 weeks (4.26% vs. 3.11%). In NK activity at 8 weeks was significantly increased compared with 2 weeks (27% vs. 47%). These results of this study suggested that chemotherapy with PSK improved the immune response in advanced gastric cancer patients. Especially Foxp3 was concerned in this mechanism.","null","null","2013-09","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.60","No.126","1387","1390","eng","null","null","null","null","null","10.5754/hge11355","0172-6390","null","null","null","null","null"
"Effect of Kampo medicine ""Dai-kenchu-to"" on microbiome in the intestine of the rats with fast stress.","Effect of Kampo medicine ""Dai-kenchu-to"" on microbiome in the intestine of the rats with fast stress.","Kouzou Yoshikawa, Mitsuo Shimada, Tomomi Kuwahara, Hideki Hirakawa, Nobuhiro Kurita, Horohiko Sato, Toru Utsunomiya, Takashi Iwata, Tomohiko Miyatani, Jun Higashijima, Hideya Kashihara, Chie Takasu, Noriko Matsumoto, Haruyuki Nakayama-Imaohji","Kouzou Yoshikawa, Mitsuo Shimada, Tomomi Kuwahara, Hideki Hirakawa, Nobuhiro Kurita, Horohiko Sato, Toru Utsunomiya, Takashi Iwata, Tomohiko Miyatani, Jun Higashijima, Hideya Kashihara, Chie Takasu, Noriko Matsumoto, Haruyuki Nakayama-Imaohji","null","Diversity of gut microbiome has been recently reported to be lost in inflammatory bowel disease. We have previously reported that the Dai-kenchu-to (DKT) prevented the bacterial translocation through suppression of cytokine and apoptosis in rat's fast stress model. The aim of this study was to evaluate the effect of DKT on maintenance of microbial diversity in rat's intestine with inflammation. Wister rats were received the fast stress for 5 days. In DKT group, rats were administered with DKT (300 mg/kg/day) during the fast stress (DKT-group). The gut microbiomes were analyzed at before- and after- fast stress, and the effect of DKT for on microbial diversities of the gut were evaluated by the PCR-clone library method targeting the 16 S ribosomal RNA gene. In Control-group, Erysipelotrichaceae increased to 86% in after fast stress, OTU of before-fast stress was 111 and after fast stress was only 9 (changing rate: 58%). The diversity of microbiome was severely decreased. On the other hand, in DKT-group, diversity of microbiome was kept after fast stress (Lachnospiraceae: Ruminococcaceae: Coriobacteriales 54%, 22%, 5%), Operational taxonomic units of before fast stress was 52 and after fast stress was 55 (changing rate: 6%). Family Lachnospiraceae which includes butyrate-producing Clostridia (Clostridium IV and XIVa). DKT prevented the reduction of diversity of microbiome in rat's fast stress model. Our data suggested the new anti-inflammatory mechanism of DKT through gut microbiome.","Diversity of gut microbiome has been recently reported to be lost in inflammatory bowel disease. We have previously reported that the Dai-kenchu-to (DKT) prevented the bacterial translocation through suppression of cytokine and apoptosis in rat's fast stress model. The aim of this study was to evaluate the effect of DKT on maintenance of microbial diversity in rat's intestine with inflammation. Wister rats were received the fast stress for 5 days. In DKT group, rats were administered with DKT (300 mg/kg/day) during the fast stress (DKT-group). The gut microbiomes were analyzed at before- and after- fast stress, and the effect of DKT for on microbial diversities of the gut were evaluated by the PCR-clone library method targeting the 16 S ribosomal RNA gene. In Control-group, Erysipelotrichaceae increased to 86% in after fast stress, OTU of before-fast stress was 111 and after fast stress was only 9 (changing rate: 58%). The diversity of microbiome was severely decreased. On the other hand, in DKT-group, diversity of microbiome was kept after fast stress (Lachnospiraceae: Ruminococcaceae: Coriobacteriales 54%, 22%, 5%), Operational taxonomic units of before fast stress was 52 and after fast stress was 55 (changing rate: 6%). Family Lachnospiraceae which includes butyrate-producing Clostridia (Clostridium IV and XIVa). DKT prevented the reduction of diversity of microbiome in rat's fast stress model. Our data suggested the new anti-inflammatory mechanism of DKT through gut microbiome.","null","null","2013","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.60","No.3-4","221","227","eng","null","null","null","null","null","10.2152/jmi.60.221","1349-6867","null","null","null","null","null"
"Impact of C-reactive protein on prognosis of patients with colorectal carcinoma.","Impact of C-reactive protein on prognosis of patients with colorectal carcinoma.","Chie Takasu, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Tomohiko Miyatani, Hideya Kashihara, Toru Utsunomiya","Chie Takasu, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Tomohiko Miyatani, Hideya Kashihara, Toru Utsunomiya","null","The aim of this study was to investigate the impact of preoperative serum C-reactive protein (CRP) level as a prognostic indicator in patients with colorectal carcinoma (CRC). We investigated the correlation between preoperative CRP level and clinicopathological factors including prognosis of 167 patients who underwent resection for CRC retrospectively. Clinicopathological variables were compared between patients with serum CRP levels >1mg/dL (29 patients; high-CRP group) and patients with serum CRP levels <1mg/dL (138 patients; low-CRP group). In high-CRP group, 9 patients were stage I+II and 20 patients ware stage III+IV. In low-CRP group, 93 patients were stage I+II and 45 patients were stage III+IV. There were significant differences in the clinical stage, tumor diameter, curativity, final stage between the two groups (p<0.01). The overall survival and recurrence-free survival rates in high-CRP group were lower compared with the rates in low-CRP group (p<0.05 and p=0.14). In addition, the overall survival rate in stage I+II patients with high-CRP was significantly lower than that in patients with low-CRP (p<0.05). Using multivariate analysis, the preoperative elevation of serum CRP level was an independent prognostic factor in patients with CRC (p<0.05). We found that the preoperative elevation of serum CRP to be an independent prognostic indicator of CRC.","The aim of this study was to investigate the impact of preoperative serum C-reactive protein (CRP) level as a prognostic indicator in patients with colorectal carcinoma (CRC). We investigated the correlation between preoperative CRP level and clinicopathological factors including prognosis of 167 patients who underwent resection for CRC retrospectively. Clinicopathological variables were compared between patients with serum CRP levels >1mg/dL (29 patients; high-CRP group) and patients with serum CRP levels <1mg/dL (138 patients; low-CRP group). In high-CRP group, 9 patients were stage I+II and 20 patients ware stage III+IV. In low-CRP group, 93 patients were stage I+II and 45 patients were stage III+IV. There were significant differences in the clinical stage, tumor diameter, curativity, final stage between the two groups (p<0.01). The overall survival and recurrence-free survival rates in high-CRP group were lower compared with the rates in low-CRP group (p<0.05 and p=0.14). In addition, the overall survival rate in stage I+II patients with high-CRP was significantly lower than that in patients with low-CRP (p<0.05). Using multivariate analysis, the preoperative elevation of serum CRP level was an independent prognostic factor in patients with CRC (p<0.05). We found that the preoperative elevation of serum CRP to be an independent prognostic indicator of CRC.","null","null","2013-05","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.60","No.123","507","511","eng","null","null","null","null","null","10.5754/hge11425","0172-6390","null","null","null","null","null"
"Survivin expression can predict the effect of chemoradiotherapy for advanced lower rectal cancer.","Survivin expression can predict the effect of chemoradiotherapy for advanced lower rectal cancer.","Chie Takasu, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Horohiko Sato, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Tomohiko Miyatani, H Kashihara, Toru Utsunomiya, H Uehara","Chie Takasu, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Horohiko Sato, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Tomohiko Miyatani, H Kashihara, Toru Utsunomiya, H Uehara","null","BACKGROUND: Chemoradiotherapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients show poor response to adjuvant CRT. We thus investigated the usefulness of survivin expression as a predictive marker of the CRT response and its characteristics. METHODS: Forty-three patients with lower rectal cancer who underwent CRT were investigated. All patients received preoperative CRT consisting of TS-1 concurrent with 40 Gy of pelvic irradiation followed by curative resection. The relationship between clinical response, or pathological response, and the expression of survivin of pre-CRT biopsy specimens was evaluated by immunohistochemistry and compared with post-CRT expression. RESULTS: Positive expression of survivin was observed in 26 of 43 patients (60 %) in pre-CRT specimens. Survivin was positively expressed in 77 % of stable disease cases, and 43 % of partial response (p < 0.05). Regarding the correlation between pathological response and survivin expression, positive expression of survivin was recognized in 75 % (18 of 24) of Grade 0 + 1 cases, 50 % (7 of 14) of Grade 2 cases, and 20 % (1 of 5) of Grade 3 cases. A reverse correlation was recognized between pathological responses and survivin expression (p < 0.05). There were differences in the tumor differentiation between the survivin-positive group and the negative group (p < 0.05). The expression concordance rate was 66 % between pre- and post-CRT tissues. In post-CRT tissues, nuclear survivin expression disappeared completely and cytoplasmic expression increased, especially in responder cases. CONCLUSION: Survivin expression in biopsy could be an important predictive factor of preoperative CRT response.","BACKGROUND: Chemoradiotherapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients show poor response to adjuvant CRT. We thus investigated the usefulness of survivin expression as a predictive marker of the CRT response and its characteristics. METHODS: Forty-three patients with lower rectal cancer who underwent CRT were investigated. All patients received preoperative CRT consisting of TS-1 concurrent with 40 Gy of pelvic irradiation followed by curative resection. The relationship between clinical response, or pathological response, and the expression of survivin of pre-CRT biopsy specimens was evaluated by immunohistochemistry and compared with post-CRT expression. RESULTS: Positive expression of survivin was observed in 26 of 43 patients (60 %) in pre-CRT specimens. Survivin was positively expressed in 77 % of stable disease cases, and 43 % of partial response (p < 0.05). Regarding the correlation between pathological response and survivin expression, positive expression of survivin was recognized in 75 % (18 of 24) of Grade 0 + 1 cases, 50 % (7 of 14) of Grade 2 cases, and 20 % (1 of 5) of Grade 3 cases. A reverse correlation was recognized between pathological responses and survivin expression (p < 0.05). There were differences in the tumor differentiation between the survivin-positive group and the negative group (p < 0.05). The expression concordance rate was 66 % between pre- and post-CRT tissues. In post-CRT tissues, nuclear survivin expression disappeared completely and cytoplasmic expression increased, especially in responder cases. CONCLUSION: Survivin expression in biopsy could be an important predictive factor of preoperative CRT response.","null","null","2012-08","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.18","No.5","869","876","eng","null","null","null","null","null","10.1007/s10147-012-0470-0","1437-7772","null","null","null","null","null"
"A Modified liver-hanging maneuver focusing on the ligamentum venosum in left hepatic lobectomy","A Modified liver-hanging maneuver focusing on the ligamentum venosum in left hepatic lobectomy","Satoru Imura, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Shuichi Iwahashi, 齋藤 裕, Hidenori Miyake","Satoru Imura, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Shuichi Iwahashi, 齋藤 裕, Hidenori Miyake","null","The liver-hanging maneuver (LHM) is a useful technique in major hepatectomy. We made modifications to this technique with special reference to the ligamentum venosum for performing a left hepatectomy (LH). The aim of this study was to clarify the usefulness of our new technique. Between August 2007 and May 2009, five patients underwent LH using our modified LHM and 12 patients underwent LH using a conventional procedure. The two groups were compared in terms of the patient characteristics, preoperative hepatic functions, surgical records, and outcomes. The characteristics and preoperative hepatic function tests were similar between the modified LHM and non-LHM groups. Intraoperative blood loss was significantly reduced in the modified LHM group compared with the non-LHM group (193 ± 133 vs. 375 ± 167 ml, P < 0.05). The lengths of the operations and time required to perform a parenchymal transection did not differ significantly between the two groups (duration of operations 273 ± 37 vs. 337 ± 70 min; transection times 29 ± 10 vs. 28 ± 13 min). The postoperative complications and hospital stays did not differ significantly between the two groups. Our modified LHM can reduce the intraoperative blood loss during LH, and our results have shown the usefulness of this modified technique for LH.","The liver-hanging maneuver (LHM) is a useful technique in major hepatectomy. We made modifications to this technique with special reference to the ligamentum venosum for performing a left hepatectomy (LH). The aim of this study was to clarify the usefulness of our new technique. Between August 2007 and May 2009, five patients underwent LH using our modified LHM and 12 patients underwent LH using a conventional procedure. The two groups were compared in terms of the patient characteristics, preoperative hepatic functions, surgical records, and outcomes. The characteristics and preoperative hepatic function tests were similar between the modified LHM and non-LHM groups. Intraoperative blood loss was significantly reduced in the modified LHM group compared with the non-LHM group (193 ± 133 vs. 375 ± 167 ml, P < 0.05). The lengths of the operations and time required to perform a parenchymal transection did not differ significantly between the two groups (duration of operations 273 ± 37 vs. 337 ± 70 min; transection times 29 ± 10 vs. 28 ± 13 min). The postoperative complications and hospital stays did not differ significantly between the two groups. Our modified LHM can reduce the intraoperative blood loss during LH, and our results have shown the usefulness of this modified technique for LH.","null","null","2012-08","Surgery Today","Surgery Today","Vol.42","No.8","720","723","eng","null","null","null","null","null","10.1007/s00595-011-0051-2","1436-2813","null","null","null","null","null"
"Outcome of hepatectomy in super-elderly patients with hepatocellular carcinoma.","Outcome of hepatectomy in super-elderly patients with hepatocellular carcinoma.","山田 眞一郎, Mitsuo Shimada, Hidenori Miyake, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Shuichi Iwahashi, 齋藤 裕","山田 眞一郎, Mitsuo Shimada, Hidenori Miyake, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Shuichi Iwahashi, 齋藤 裕","null","Aim: The aim of this study was to investigate the characteristics of super-elderly hepatocellular carcinoma (HCC) patients aged 80 years or more who underwent hepatectomy and to clarify whether elderly patients with HCC benefit from hepatectomy. Methods: Between March 1992 and December 2008, 278 patients who underwent curative hepatectomy for HCC were investigated. Super-elderly patients were defined as those aged 80 years or more. Clinicopathological data and outcomes after hepatectomy were compared between super-elderly and non-super-elderly groups. Results: Preoperative parameters, such as biochemical examinations, and liver function tests in the non-super-elderly group were comparable with those of the super-elderly group (n = 11). Exceptionally, albumin level in the super-elderly group was lower than that in the non-super-elderly group (P = 0.03). Surgical data and the prevalence of postoperative complications did not differ significantly between the two groups. No mortality was observed in the super-elderly and non-super-elderly group. Conclusions: Hepatectomy for HCC was a feasible option even in super elderly patients aged 80 years or older with accurate selection.","Aim: The aim of this study was to investigate the characteristics of super-elderly hepatocellular carcinoma (HCC) patients aged 80 years or more who underwent hepatectomy and to clarify whether elderly patients with HCC benefit from hepatectomy. Methods: Between March 1992 and December 2008, 278 patients who underwent curative hepatectomy for HCC were investigated. Super-elderly patients were defined as those aged 80 years or more. Clinicopathological data and outcomes after hepatectomy were compared between super-elderly and non-super-elderly groups. Results: Preoperative parameters, such as biochemical examinations, and liver function tests in the non-super-elderly group were comparable with those of the super-elderly group (n = 11). Exceptionally, albumin level in the super-elderly group was lower than that in the non-super-elderly group (P = 0.03). Surgical data and the prevalence of postoperative complications did not differ significantly between the two groups. No mortality was observed in the super-elderly and non-super-elderly group. Conclusions: Hepatectomy for HCC was a feasible option even in super elderly patients aged 80 years or older with accurate selection.","null","null","2012-05","Hepatology Research","Hepatology Research","Vol.42","No.5","454","458","eng","null","null","null","null","null","10.1111/j.1872-034X.2011.00952.x","1386-6346","null","null","null","null","null"
"Role of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expressions in gallbladder carcinoma","Role of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expressions in gallbladder carcinoma","Shuichi Iwahashi, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka","Shuichi Iwahashi, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka","null","Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are important enzymes in the metabolism of 5-fluorouracil, which have been examined as possible predictive markers. We conducted this study to clarify the role of TS and DPD expressions in gallbladder carcinoma (GBC). The subjects were 28 patients who underwent surgical resection of GBC. We examined intratumoral TS and DPD mRNA expressions, using the Danenberg tumor profile method. The expression levels were classified into two groups, based on median values. Clinicopathological variables, including prognosis, were then compared between the high and low expression groups. There was a significant difference in the incidence of lymph node metastasis between the high and low TS expression groups. The incidence of advanced clinical stage was higher in the low TS expression group than in the high TS expression group. However, no clear correlation was observed between the DPD mRNA expression and any clinicopathological variable. There was no significant difference in the postoperative survival rates between the groups, in accordance with the expression of TS or DPD genes. Low TS mRNA was correlated with a high incidence of lymph node metastasis and advanced clinical stage. Therefore, TS gene expression may help identify patients at increased risk of the progression of GBC.","Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are important enzymes in the metabolism of 5-fluorouracil, which have been examined as possible predictive markers. We conducted this study to clarify the role of TS and DPD expressions in gallbladder carcinoma (GBC). The subjects were 28 patients who underwent surgical resection of GBC. We examined intratumoral TS and DPD mRNA expressions, using the Danenberg tumor profile method. The expression levels were classified into two groups, based on median values. Clinicopathological variables, including prognosis, were then compared between the high and low expression groups. There was a significant difference in the incidence of lymph node metastasis between the high and low TS expression groups. The incidence of advanced clinical stage was higher in the low TS expression group than in the high TS expression group. However, no clear correlation was observed between the DPD mRNA expression and any clinicopathological variable. There was no significant difference in the postoperative survival rates between the groups, in accordance with the expression of TS or DPD genes. Low TS mRNA was correlated with a high incidence of lymph node metastasis and advanced clinical stage. Therefore, TS gene expression may help identify patients at increased risk of the progression of GBC.","null","null","2012-06","Surgery Today","Surgery Today","Vol.42","No.6","565","569","eng","null","null","null","null","null","10.1007/s00595-012-0118-8","1436-2813","null","null","null","null","null"
"Impact of a new refrigerator on the preservation of hepatic grafts.","Impact of a new refrigerator on the preservation of hepatic grafts.","Mami Kanamoto, Mitsuo Shimada, Toru Utsunomiya, 齋藤 裕, Shuichi Iwahashi, Jun Hanaoka, Hiroki Mori, Tetsuya Ikemoto, Yuji Morine","Mami Kanamoto, Mitsuo Shimada, Toru Utsunomiya, 齋藤 裕, Shuichi Iwahashi, Jun Hanaoka, Hiroki Mori, Tetsuya Ikemoto, Yuji Morine","null","Aim: Current medical transplantation methods focus on solutions for major problems such as the shortage of donors. To overcome these issues, expanding organ preservation time has become a major concern. A new refrigerating chamber has been recently developed, which can cool the inside of a material to the required temperature by frequently sensing the temperature of both inside and surface of the materials. The purpose of this study is to evaluate the usefulness of a new refrigerating system in hepatic preservation. Methods: The liver grafts were harvested from rats and divided into two groups. Group A consisted of grafts preserved in chilled University of Wisconsin solution (UW) solution (on ice) for 24, 72 and 168 h. Group B consisted of grafts preserved in the UW solution in a new refrigerator at 4°C. Results: In group B, aspartate aminotransferase released into effluent after cold storage for 72 h showed a marked decrease compared to group A (P < 0.05). The levels of ammonia and lactate decreased significantly in group B (P < 0.05). In group B, the levels of adenosine triphosphate were significantly preserved after cold storage for 24 h and 72 h compared to group A (P < 0.05). Immunohistochemistry showed positive cells for heme oxygenase-1 were significantly increased in group B after cold storage. Conclusion: This new refrigerator can improve preservation injury of hepatic grafts and may provide an innovative technique for liver transplantation.","Aim: Current medical transplantation methods focus on solutions for major problems such as the shortage of donors. To overcome these issues, expanding organ preservation time has become a major concern. A new refrigerating chamber has been recently developed, which can cool the inside of a material to the required temperature by frequently sensing the temperature of both inside and surface of the materials. The purpose of this study is to evaluate the usefulness of a new refrigerating system in hepatic preservation. Methods: The liver grafts were harvested from rats and divided into two groups. Group A consisted of grafts preserved in chilled University of Wisconsin solution (UW) solution (on ice) for 24, 72 and 168 h. Group B consisted of grafts preserved in the UW solution in a new refrigerator at 4°C. Results: In group B, aspartate aminotransferase released into effluent after cold storage for 72 h showed a marked decrease compared to group A (P < 0.05). The levels of ammonia and lactate decreased significantly in group B (P < 0.05). In group B, the levels of adenosine triphosphate were significantly preserved after cold storage for 24 h and 72 h compared to group A (P < 0.05). Immunohistochemistry showed positive cells for heme oxygenase-1 were significantly increased in group B after cold storage. Conclusion: This new refrigerator can improve preservation injury of hepatic grafts and may provide an innovative technique for liver transplantation.","null","null","2012-08","Hepatology Research","Hepatology Research","Vol.42","No.8","798","805","eng","null","null","null","null","null","10.1111/j.1872-034X.2012.00987.x","1386-6346","null","null","null","null","null"
"Irinotecan injures tight junction and causes bacterial translocation in rat.","Irinotecan injures tight junction and causes bacterial translocation in rat.","Toshihiro Nakao, Nobuhiro Kurita, Masato Komatsu, Kouzou Yoshikawa, Takashi Iwata, Toru Utsunomiya, Mitsuo Shimada","Toshihiro Nakao, Nobuhiro Kurita, Masato Komatsu, Kouzou Yoshikawa, Takashi Iwata, Toru Utsunomiya, Mitsuo Shimada","null","Tight junctions are an essential component of intestinal epithelial barriers. Claudin-1, occludin, and ZO-1 are the components of tight junction. The purpose of this study was to investigate whether irinotecan induces bacterial translocation in rats, and thus elucidate the relationship between tight junction and bacterial translocation. Ten rats were divided into two groups: Five were treated with irinotecan and five were not treated with irinotecan, the control group. Irinotecan treated rats were administrated irinotecan 250 mg/kg intraperitoneally on days designated 0 and 1, were then killed at 48 h after treatment, and tissues were collected for analysis. Controls were treated with a saline solution. In eighty percent of irinotecan treated rats, bacteria were detected in the mesenteric lymph node or spleen. Large intestinal resistance of the rats was decreased. On the contrary, small intestinal resistance increased. Claudin-1 protein expression of both the small and large intestine decreased (P < 0.05), occludin protein expression of the small intestine decreased (P < 0.05), and occludin protein expression of the large intestine had decreasing tendency (P = 0.07) in irinotecan treated rats. In irinotecan treated rats, claudin-1 mRNA of the small intestine decreased (P < 0.05), claudin-1 mRNA of large intestine had a tendency to decrease (P = 0.05), occludin mRNA of both small and large intestine decreased (P < 0.05). Irinotecan injures claudin-1 and occludin. It causes disorders in the intestinal epithelial barrier and induces bacterial translocation.","Tight junctions are an essential component of intestinal epithelial barriers. Claudin-1, occludin, and ZO-1 are the components of tight junction. The purpose of this study was to investigate whether irinotecan induces bacterial translocation in rats, and thus elucidate the relationship between tight junction and bacterial translocation. Ten rats were divided into two groups: Five were treated with irinotecan and five were not treated with irinotecan, the control group. Irinotecan treated rats were administrated irinotecan 250 mg/kg intraperitoneally on days designated 0 and 1, were then killed at 48 h after treatment, and tissues were collected for analysis. Controls were treated with a saline solution. In eighty percent of irinotecan treated rats, bacteria were detected in the mesenteric lymph node or spleen. Large intestinal resistance of the rats was decreased. On the contrary, small intestinal resistance increased. Claudin-1 protein expression of both the small and large intestine decreased (P < 0.05), occludin protein expression of the small intestine decreased (P < 0.05), and occludin protein expression of the large intestine had decreasing tendency (P = 0.07) in irinotecan treated rats. In irinotecan treated rats, claudin-1 mRNA of the small intestine decreased (P < 0.05), claudin-1 mRNA of large intestine had a tendency to decrease (P = 0.05), occludin mRNA of both small and large intestine decreased (P < 0.05). Irinotecan injures claudin-1 and occludin. It causes disorders in the intestinal epithelial barrier and induces bacterial translocation.","null","null","2012-04","The Journal of Surgical Research","The Journal of Surgical Research","Vol.173","No.2","341","347","eng","null","null","null","null","null","10.1016/j.jss.2010.10.003","1095-8673","null","null","null","null","null"
"Platelet-derived endothelial cell growth factor/thymidine phosphorylase inhibitor augments radiotherapeutic efficacy in experimental colorectal cancer.","Platelet-derived endothelial cell growth factor/thymidine phosphorylase inhibitor augments radiotherapeutic efficacy in experimental colorectal cancer.","Tomohiko Miyatani, Nobuhiro Kurita, Toru Utsunomiya, Takashi Iwata, Masanori Nishioka, Kouzou Yoshikawa, Jun Higashijima, H Kashihara, Chie Takasu, M Fukushima, Mitsuo Shimada","Tomohiko Miyatani, Nobuhiro Kurita, Toru Utsunomiya, Takashi Iwata, Masanori Nishioka, Kouzou Yoshikawa, Jun Higashijima, H Kashihara, Chie Takasu, M Fukushima, Mitsuo Shimada","null","A lot of radiosensitizers have been developed. However, there are few to be available in the clinical setting. Thymidine phosphorylase inhibitor (TPI) regulates the phosphorolysis of thymidine to thymine and 2-deoxy-d-ribose-1-phosphate which is essential for tumor angiogenesis. The aim of this study is to evaluate whether TPI augments the radiotherapy for colorectal cancer in vitro and in vivo studies. The cytotoxicity of TPI with irradiation on HT29 and HCT116 cells was examined using MTT- and colony formation assay. At 10days post-inoculation, HT29 bearing orthotopic model mice (n=28) were divided into four groups and orally treated with TPI- (50mg/kg/day for 2weeks), radiation (RT, 2Gy×4: Total 8Gy), their combination or the vehicle. The mechanisms underlying the efficacy were assessed genomically and immunohistochemically. Compared to each single treatment, the combination of TPI and RT synergistically inhibited the cell viability in a time- and dose-dependent manner. In the HT-29 bearing mice, the combination of TPI and RT reduced the tumor growth compared with RT alone. Notably, the mRNA levels of VEGF, TGF-β and, Rad51 and the protein expressions of VEGF and CD34 were significantly lower in the combination than the others. Furthermore, the combination markedly increased the TUNEL-positive cells, suggesting that TPI augments the cancer cell death through inhibition of angiogenesis and DNA repair system in the radiotherapy. Our study first demonstrated that the combination of TPI and irradiation was effective in colon cancer. TPI would provide a promising therapeutic strategy as a radiosensitizer.","A lot of radiosensitizers have been developed. However, there are few to be available in the clinical setting. Thymidine phosphorylase inhibitor (TPI) regulates the phosphorolysis of thymidine to thymine and 2-deoxy-d-ribose-1-phosphate which is essential for tumor angiogenesis. The aim of this study is to evaluate whether TPI augments the radiotherapy for colorectal cancer in vitro and in vivo studies. The cytotoxicity of TPI with irradiation on HT29 and HCT116 cells was examined using MTT- and colony formation assay. At 10days post-inoculation, HT29 bearing orthotopic model mice (n=28) were divided into four groups and orally treated with TPI- (50mg/kg/day for 2weeks), radiation (RT, 2Gy×4: Total 8Gy), their combination or the vehicle. The mechanisms underlying the efficacy were assessed genomically and immunohistochemically. Compared to each single treatment, the combination of TPI and RT synergistically inhibited the cell viability in a time- and dose-dependent manner. In the HT-29 bearing mice, the combination of TPI and RT reduced the tumor growth compared with RT alone. Notably, the mRNA levels of VEGF, TGF-β and, Rad51 and the protein expressions of VEGF and CD34 were significantly lower in the combination than the others. Furthermore, the combination markedly increased the TUNEL-positive cells, suggesting that TPI augments the cancer cell death through inhibition of angiogenesis and DNA repair system in the radiotherapy. Our study first demonstrated that the combination of TPI and irradiation was effective in colon cancer. TPI would provide a promising therapeutic strategy as a radiosensitizer.","null","null","2012-05","Cancer Letters","Cancer Letters","Vol.318","No.2","199","205","eng","null","null","null","null","null","10.1016/j.canlet.2011.12.010","1872-7980","null","null","null","null","null"
"Effects of a whey peptide-based enteral formula diet on liver dysfunction following living donor liver transplantation.","Effects of a whey peptide-based enteral formula diet on liver dysfunction following living donor liver transplantation.","Yusuke Arakawa, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Jun Hanaoka","Yusuke Arakawa, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Jun Hanaoka","null","BACKGROUND AND AIMS: Whey protein, a protein complex derived from milk is well known as a functional food with a number of health benefits. MEIN(®) (Meiji Dairies Co., Tokyo Japan) is a functional liquid-type nutritional diet containing whey-hydrolyzed peptide. In this study, we examined the effects of MEIN(®) on postoperative liver dysfunction in patients who underwent living donor-related liver transplantation (LDLT). METHODS: Sixteen adult patients transplanted between 2005 and 2011 at our institute were evaluated retrospectively. In MEIN group (n = 8), administration of MEIN(®) was started around 14 days after liver transplantation when serum liver enzymes were re-elevated, while MEIN(®) was not administered in the control group (n = 8) who did not have postoperative liver dysfunction. RESULTS: In the preoperative clinical characteristics, the model for end-stage liver disease score in the MEIN group was significantly lower than that in the control group. The graft-to-recipient body weight ratio in the MEIN group was lower than that in the control group. Elevation of enzymes in the liver function tests such as alanine aminotransferase and total bilirubin, and C-reactive protein in the MEIN group had significantly improved, and became almost normal values which were the same as those in the control group. CONCLUSION: These findings suggest that administration of whey-hydrolyzed peptide attenuates the post-transplant liver dysfunction and may avoid an unnecessary liver biopsy.","BACKGROUND AND AIMS: Whey protein, a protein complex derived from milk is well known as a functional food with a number of health benefits. MEIN(®) (Meiji Dairies Co., Tokyo Japan) is a functional liquid-type nutritional diet containing whey-hydrolyzed peptide. In this study, we examined the effects of MEIN(®) on postoperative liver dysfunction in patients who underwent living donor-related liver transplantation (LDLT). METHODS: Sixteen adult patients transplanted between 2005 and 2011 at our institute were evaluated retrospectively. In MEIN group (n = 8), administration of MEIN(®) was started around 14 days after liver transplantation when serum liver enzymes were re-elevated, while MEIN(®) was not administered in the control group (n = 8) who did not have postoperative liver dysfunction. RESULTS: In the preoperative clinical characteristics, the model for end-stage liver disease score in the MEIN group was significantly lower than that in the control group. The graft-to-recipient body weight ratio in the MEIN group was lower than that in the control group. Elevation of enzymes in the liver function tests such as alanine aminotransferase and total bilirubin, and C-reactive protein in the MEIN group had significantly improved, and became almost normal values which were the same as those in the control group. CONCLUSION: These findings suggest that administration of whey-hydrolyzed peptide attenuates the post-transplant liver dysfunction and may avoid an unnecessary liver biopsy.","null","null","2012-12-26","Surgery Today","Surgery Today","null","null","null","null","eng","null","null","null","null","null","10.1007/s00595-012-0466-4","1436-2813","null","null","null","null","null"
"Surgical results of pancreatoduodenectomy in elderly patients.","Surgical results of pancreatoduodenectomy in elderly patients.","山田 眞一郎, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Mami Kanamoto, Jun Hanaoka, Shuichi Iwahashi, 齋藤 裕","山田 眞一郎, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Mami Kanamoto, Jun Hanaoka, Shuichi Iwahashi, 齋藤 裕","null","To assess the safety and feasibility of pancreatoduodenectomy (PD) in elderly patients, we investigated the clinical characteristics of patients aged ≥75 years, who underwent this procedure at our hospital. Between November 2005 and December 2010, 84 patients underwent PD at Tokushima University Hospital. We analyzed the clinicopathological data and outcomes after PD in patients aged ≥75 years compared with those in patients <75 years. The preoperative characteristics of the elderly group (n = 28) were similar to those of the younger group (n = 56). The hemoglobin and albumin levels were significantly lower in the elderly patients (P < 0.05), who also had a higher rate of preoperative pulmonary dysfunction (P < 0.05). The operation time and intraoperative blood loss did not differ significantly between the groups, but the incidence of pneumonia was higher in the elderly group (P < 0.05). The overall survival rate did not differ significantly between the groups. Advanced age alone does not have an adverse effect on surgical outcomes, including postoperative complications and long-term prognosis. Therefore, PD may be justified for selected elderly patients.","To assess the safety and feasibility of pancreatoduodenectomy (PD) in elderly patients, we investigated the clinical characteristics of patients aged ≥75 years, who underwent this procedure at our hospital. Between November 2005 and December 2010, 84 patients underwent PD at Tokushima University Hospital. We analyzed the clinicopathological data and outcomes after PD in patients aged ≥75 years compared with those in patients <75 years. The preoperative characteristics of the elderly group (n = 28) were similar to those of the younger group (n = 56). The hemoglobin and albumin levels were significantly lower in the elderly patients (P < 0.05), who also had a higher rate of preoperative pulmonary dysfunction (P < 0.05). The operation time and intraoperative blood loss did not differ significantly between the groups, but the incidence of pneumonia was higher in the elderly group (P < 0.05). The overall survival rate did not differ significantly between the groups. Advanced age alone does not have an adverse effect on surgical outcomes, including postoperative complications and long-term prognosis. Therefore, PD may be justified for selected elderly patients.","null","null","2012-09","Surgery Today","Surgery Today","Vol.42","No.9","857","862","eng","null","null","null","null","null","10.1007/s00595-012-0169-x","1436-2813","null","null","null","null","null"
"Prediction of recurrence of hepatocellular carcinoma after curative hepatectomy using preoperative Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein.","Prediction of recurrence of hepatocellular carcinoma after curative hepatectomy using preoperative Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein.","齋藤 裕, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, 山田 眞一郎, 淺野間 理仁","齋藤 裕, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, 山田 眞一郎, 淺野間 理仁","null","Aim: Lens culinaris agglutinin A-reactive fraction of α-fetoprotein (AFP-L3) status has been reported to be an independent prognostic factor in patients with hepatocellular carcinoma (HCC). In this study, we evaluated the clinical usefulness of measuring preoperative AFP-L3 to predict the recurrence and prognosis of HCC after curative hepatectomy. Methods: One hundred and forty-two HCC patients who underwent curative hepatectomy were examined for the correlation between preoperative tumor marker, including AFP, des-γ-carboxy prothrombin (DCP) and AFP-L3, and clinicopathological variables. The prognostic factors of disease-free survival rates and overall survival rates were also determined using clinicopathological variables including these three tumor markers. Results: There were similar tendencies in the relationship between these three markers and malignant behaviors including lower grade tumor differentiation or vascular invasion. In multivariate analysis, increased AFP-L3 value (P = 0.019) was found to be an independent prognostic factor of disease-free survival after curative hepatectomy. In addition, elevated DCP (P = 0.013) and AFP-L3 values (P = 0.012) were found to be independent prognostic factors. Furthermore, the preoperative AFP-L3 value in the patients with early recurrence (within 1 year after hepatectomy) was significantly higher than that in those without early recurrence (26.9 ± 19.5 % vs 14.2 ± 19.8 %, P = 0.047). Conclusion: Preoperative AFP-L3 value was strongly correlated to disease-free and overall survival rate and the timing of recurrence, so it appears that it would be useful to predict the recurrence and prognosis of HCC after curative hepatectomy.","Aim: Lens culinaris agglutinin A-reactive fraction of α-fetoprotein (AFP-L3) status has been reported to be an independent prognostic factor in patients with hepatocellular carcinoma (HCC). In this study, we evaluated the clinical usefulness of measuring preoperative AFP-L3 to predict the recurrence and prognosis of HCC after curative hepatectomy. Methods: One hundred and forty-two HCC patients who underwent curative hepatectomy were examined for the correlation between preoperative tumor marker, including AFP, des-γ-carboxy prothrombin (DCP) and AFP-L3, and clinicopathological variables. The prognostic factors of disease-free survival rates and overall survival rates were also determined using clinicopathological variables including these three tumor markers. Results: There were similar tendencies in the relationship between these three markers and malignant behaviors including lower grade tumor differentiation or vascular invasion. In multivariate analysis, increased AFP-L3 value (P = 0.019) was found to be an independent prognostic factor of disease-free survival after curative hepatectomy. In addition, elevated DCP (P = 0.013) and AFP-L3 values (P = 0.012) were found to be independent prognostic factors. Furthermore, the preoperative AFP-L3 value in the patients with early recurrence (within 1 year after hepatectomy) was significantly higher than that in those without early recurrence (26.9 ± 19.5 % vs 14.2 ± 19.8 %, P = 0.047). Conclusion: Preoperative AFP-L3 value was strongly correlated to disease-free and overall survival rate and the timing of recurrence, so it appears that it would be useful to predict the recurrence and prognosis of HCC after curative hepatectomy.","null","null","2012-09","Hepatology Research","Hepatology Research","Vol.42","No.9","887","894","eng","null","null","null","null","null","10.1111/j.1872-034X.2012.01004.x","1386-6346","null","null","null","null","null"
"The Impact of Pegylated-Interferon alpha-2b on Partial and Massive Hepatectomy Model in Rats.","The Impact of Pegylated-Interferon alpha-2b on Partial and Massive Hepatectomy Model in Rats.","Hiroki Mori, Mitsuo Shimada, Toru Ikegami, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Jun Hanaoka, Shuichi Iwahashi, 齋藤 裕, 淺野間 理仁, 山田 眞一郎, Hidenori Miyake","Hiroki Mori, Mitsuo Shimada, Toru Ikegami, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Jun Hanaoka, Shuichi Iwahashi, 齋藤 裕, 淺野間 理仁, 山田 眞一郎, Hidenori Miyake","null","The impact of pegylated-interferon (PEG-IFN) α-2b on liver regeneration has not yet been elucidated. Rats were divided into the following four groups: 70% hepatectomy (Hx); 70% Hx+PEG-IFN; 90% Hx and 90% Hx+PEG-IFN group (n=6 each). Rats were pretreated with subcutaneous of PEGIFN α-2b (1.5 μg/kg) administration 24 hours before Hx. Samples were taken 24, 48 and 72 hours after Hx and the following parameters were investigated: blood analysis (AST, WBC, PLT); liver weight to body weight ratio (Lw/Bw ratio); survival and PCNA labeling index (LI). In the 90% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group in blood analysis; AST after postoperative 24 hours (2511 vs. 2466 IU/L), WBC (1200 vs. 1290) and PLT (107 vs. 111 x 104/mm³), in Lw/Bw ratio at postoperative 0, 24, 48, 72 hours, respectively (0.38, 0.60, 1.14, 1.69 vs. 0.37, 0.64, 1.12, 1.63), in postoperative survival (40% vs. 45%), and in PCNA LI at postoperative 0, 24, 48, 72 hours, respectively (10.4%, 16.8%, 14.6%, 12.8% vs. 10.0%, 17.1%, 15.6%, 13.7%). In the 70% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group for all parameters. Our data demonstrated that PEG-IFN α-2b did not affect liver regeneration and the early use of PEG-IFN α-2b would cause no problems after liver transplantation using partial grafts including living donor liver transplantation.","The impact of pegylated-interferon (PEG-IFN) α-2b on liver regeneration has not yet been elucidated. Rats were divided into the following four groups: 70% hepatectomy (Hx); 70% Hx+PEG-IFN; 90% Hx and 90% Hx+PEG-IFN group (n=6 each). Rats were pretreated with subcutaneous of PEGIFN α-2b (1.5 μg/kg) administration 24 hours before Hx. Samples were taken 24, 48 and 72 hours after Hx and the following parameters were investigated: blood analysis (AST, WBC, PLT); liver weight to body weight ratio (Lw/Bw ratio); survival and PCNA labeling index (LI). In the 90% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group in blood analysis; AST after postoperative 24 hours (2511 vs. 2466 IU/L), WBC (1200 vs. 1290) and PLT (107 vs. 111 x 104/mm³), in Lw/Bw ratio at postoperative 0, 24, 48, 72 hours, respectively (0.38, 0.60, 1.14, 1.69 vs. 0.37, 0.64, 1.12, 1.63), in postoperative survival (40% vs. 45%), and in PCNA LI at postoperative 0, 24, 48, 72 hours, respectively (10.4%, 16.8%, 14.6%, 12.8% vs. 10.0%, 17.1%, 15.6%, 13.7%). In the 70% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group for all parameters. Our data demonstrated that PEG-IFN α-2b did not affect liver regeneration and the early use of PEG-IFN α-2b would cause no problems after liver transplantation using partial grafts including living donor liver transplantation.","null","null","2012-10","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.59","No.119","2300","2304","eng","null","null","null","null","null","10.5754/hge10401","0172-6390","null","null","null","null","null"
"Significance of sonic hedgehog signaling after massive hepatectomy in a rat.","Significance of sonic hedgehog signaling after massive hepatectomy in a rat.","Jun Hanaoka, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori","Jun Hanaoka, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori","null","To clarify the functional involvement of hedgehog signaling, especially sonic hedgehog (Shh) and glioma-associated oncogene (Gli)-1 which are known to play an important role in embryonic development and cancer, in the regeneration of a hepatectomized rat liver. Six-week-old male Wistar rats were subjected to 70 or 90 % hepatectomy (Hx). Animals were killed at 24, 48 and 72 h after Hx. The liver/body weight ratio was measured as an index of regeneration. Formalin-fixed liver samples were embedded in paraffin, stained for immunohistochemistry with proliferating cell nuclear antigen (PCNA) antibody, and the labeling index was calculated. Immunohistochemistry was also performed with Shh and Gli-1 antibodies. The liver/body weight ratio gradually increased in both the 70 and 90 % Hx, groups. The hepatocytes were strongly stained for PCNA at 24 h after Hx. Non-parenchymal cells were gradually stained by PCNA from 24 to 72 h after Hx. Shh and Gli-1 expression in hepatocytes was higher after 24 h than at other times and then gradually decreased. Shh and Gli-1 expression in non-parenchymal cells increased gradually, and was found mainly in liver zone I at 72 h after 70 and 90 % Hx. The expression of both markers suggested that Shh signaling contributes to tissue reconstruction after Hx.","To clarify the functional involvement of hedgehog signaling, especially sonic hedgehog (Shh) and glioma-associated oncogene (Gli)-1 which are known to play an important role in embryonic development and cancer, in the regeneration of a hepatectomized rat liver. Six-week-old male Wistar rats were subjected to 70 or 90 % hepatectomy (Hx). Animals were killed at 24, 48 and 72 h after Hx. The liver/body weight ratio was measured as an index of regeneration. Formalin-fixed liver samples were embedded in paraffin, stained for immunohistochemistry with proliferating cell nuclear antigen (PCNA) antibody, and the labeling index was calculated. Immunohistochemistry was also performed with Shh and Gli-1 antibodies. The liver/body weight ratio gradually increased in both the 70 and 90 % Hx, groups. The hepatocytes were strongly stained for PCNA at 24 h after Hx. Non-parenchymal cells were gradually stained by PCNA from 24 to 72 h after Hx. Shh and Gli-1 expression in hepatocytes was higher after 24 h than at other times and then gradually decreased. Shh and Gli-1 expression in non-parenchymal cells increased gradually, and was found mainly in liver zone I at 72 h after 70 and 90 % Hx. The expression of both markers suggested that Shh signaling contributes to tissue reconstruction after Hx.","null","null","2013-06-12","Surgery Today","Surgery Today","Vol.43","No.3","300","307","eng","null","null","null","null","null","10.1007/s00595-012-0248-z","1436-2813","null","null","null","null","null"
"Evaluation of relation of RAD51 and the effect of chemo-radiation therapy for advanced rectal cancer.","Evaluation of relation of RAD51 and the effect of chemo-radiation therapy for advanced rectal cancer.","Takashi Iwata, Mitsuo Shimada, Nobuhiro Kurita, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Jun Higashijima, Takayuki Nakao, Masato Komatsu","Takashi Iwata, Mitsuo Shimada, Nobuhiro Kurita, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Jun Higashijima, Takayuki Nakao, Masato Komatsu","null","Chemo-radiation therapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients shows poor response to adjuvant CRT. We thus investigated the usefulness of RAD51 expressions as a predictive maker of the CRT response. Forty two patients who suffered from lower rectal cancer were investigated. All patients received preoperative CRT consisting of TS-1, concurrent with 40Gy of pelvic irradiation before having curative radical resection. The relationship between pathological responses of the tumors after therapy and expression of RAD51 was evaluated by immunostaining of resected specimen. Positive expression of RAD51 was observed in 24 of 42 patients (57.1%). RAD51 positively expressed in 68.2% (15 of 22 cases) of SD and 42.2% (9 of 20 cases) of PR and CR. There is a tendency of reverse correlation between clinical response and expression of RAD51. Regarding the correlation between pathological response and RAD51 expression, positive expression of RAD51 was recognized in 75.0% (15 of 20 cases) of Grade 1, 47.1% (8 of 17 cases) of Grade 2 and 20.0% (1 of 5 cases) of Grade 3. A significant reverse correlation was recognized between RAD51 expression and pathological responses. RAD51 expression could be one of the most important predictive factors of preoperative CRT for advanced lower rectal cancer.","Chemo-radiation therapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients shows poor response to adjuvant CRT. We thus investigated the usefulness of RAD51 expressions as a predictive maker of the CRT response. Forty two patients who suffered from lower rectal cancer were investigated. All patients received preoperative CRT consisting of TS-1, concurrent with 40Gy of pelvic irradiation before having curative radical resection. The relationship between pathological responses of the tumors after therapy and expression of RAD51 was evaluated by immunostaining of resected specimen. Positive expression of RAD51 was observed in 24 of 42 patients (57.1%). RAD51 positively expressed in 68.2% (15 of 22 cases) of SD and 42.2% (9 of 20 cases) of PR and CR. There is a tendency of reverse correlation between clinical response and expression of RAD51. Regarding the correlation between pathological response and RAD51 expression, positive expression of RAD51 was recognized in 75.0% (15 of 20 cases) of Grade 1, 47.1% (8 of 17 cases) of Grade 2 and 20.0% (1 of 5 cases) of Grade 3. A significant reverse correlation was recognized between RAD51 expression and pathological responses. RAD51 expression could be one of the most important predictive factors of preoperative CRT for advanced lower rectal cancer.","null","null","2012-06","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.59","No.116","990","993","eng","null","null","null","null","null","10.5754/hge10068","0172-6390","null","null","null","null","null"
"Changes of immunological parameters with administration of Japanese Kampo medicine (Juzen-Taihoto/TJ-48) in patients with advanced pancreatic cancer.","Changes of immunological parameters with administration of Japanese Kampo medicine (Juzen-Taihoto/TJ-48) in patients with advanced pancreatic cancer.","Tetsuya Ikemoto, Mitsuo Shimada, Shuichi Iwahashi, Yu Saitou, Mami Kanamoto, Hiroki Mori, Yuji Morine, Satoru Imura, Toru Utsunomiya","Tetsuya Ikemoto, Mitsuo Shimada, Shuichi Iwahashi, Yu Saitou, Mami Kanamoto, Hiroki Mori, Yuji Morine, Satoru Imura, Toru Utsunomiya","null","The prognosis of pancreatic cancer is extremely poor regardless of various combination therapies. Immunoaugumentation against tumor cells was recently A focus. We reported that the population of Foxp3(+)CD25(+)CD4(+) regulatory T cells (Foxp3(+)Treg) was the new parameter for the estimation of host immunity and had correlation with tumor aggressiveness. Here we show the immunoaugumentation effects of Japanese Kampo medicine, Juzen-Taihoto/TJ-48, empirically considered as an immunoaugumentation drug, with investigation of Treg and other immunological parameters. Peripheral Foxp3(+) Treg populations, CD4/CD8 ratio, and CD57(+) cells (NK cells) populations in advanced pancreatic cancer patients (n = 30, stage VI A and B according to TNM classification) were estimated after TJ-48 administration for 14 days before the anti-cancer therapy. Treg populations were significantly increased compared to healthy donors (Mann-Whitney U test, P < 0.001). Administration of Juzen-Taihoto/TJ-48 significantly decreased Treg populations (Mann-Whitney U test, P < 0.001) and increased the CD4/CD8 ratio (Mann-Whitney U test, P < 0.01), even though CD57(+) cell populations did not change significantly. Juzen-Taihoto/TJ-48 increased regulatory activities in T cells through decreasing Foxp3(+) Treg populations in advanced pancreatic cancer patients. This effect can lead to immunoaugumentation for various combination therapies.","The prognosis of pancreatic cancer is extremely poor regardless of various combination therapies. Immunoaugumentation against tumor cells was recently A focus. We reported that the population of Foxp3(+)CD25(+)CD4(+) regulatory T cells (Foxp3(+)Treg) was the new parameter for the estimation of host immunity and had correlation with tumor aggressiveness. Here we show the immunoaugumentation effects of Japanese Kampo medicine, Juzen-Taihoto/TJ-48, empirically considered as an immunoaugumentation drug, with investigation of Treg and other immunological parameters. Peripheral Foxp3(+) Treg populations, CD4/CD8 ratio, and CD57(+) cells (NK cells) populations in advanced pancreatic cancer patients (n = 30, stage VI A and B according to TNM classification) were estimated after TJ-48 administration for 14 days before the anti-cancer therapy. Treg populations were significantly increased compared to healthy donors (Mann-Whitney U test, P < 0.001). Administration of Juzen-Taihoto/TJ-48 significantly decreased Treg populations (Mann-Whitney U test, P < 0.001) and increased the CD4/CD8 ratio (Mann-Whitney U test, P < 0.01), even though CD57(+) cell populations did not change significantly. Juzen-Taihoto/TJ-48 increased regulatory activities in T cells through decreasing Foxp3(+) Treg populations in advanced pancreatic cancer patients. This effect can lead to immunoaugumentation for various combination therapies.","null","null","2013-03","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.19","No.1","81","86","eng","null","null","null","null","null","10.1007/s10147-013-0529-6","1437-7772","null","null","null","null","null"
"Thymidylate synthase (TS) protein expression as a prognostic factor in advanced colorectal cancer: a comparison with TS mRNA expression.","Thymidylate synthase (TS) protein expression as a prognostic factor in advanced colorectal cancer: a comparison with TS mRNA expression.","T Nakagawa, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Masanori Nishioka, H Miyamoto","T Nakagawa, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Masanori Nishioka, H Miyamoto","null","The role of intratumoral thymidylate synthase (TS) mRNA or protein expression is still controversial and little has been reported regarding relation of them in colorectal cancer. Forty-six patients with advanced colorectal cancer who underwent surgical resection were included. TS mRNA expression was determined by the Danenberg tumor profile method based on laser-captured micro-dissection of the tumor cells. TS protein expression was evaluated using immunohistochemical staining. TS mRNA expression tended to relate TS protein expression. Statistical significance was not found in overall survival between the TS mRNA high group and low group regardless of performing adjuvant chemotherapy. The overall survival in the TS protein negative group was significantly higher than that in positive group in all and the patients without adjuvant chemotherapy. Multivariate analysis showed TS protein expression was as an independent prognostic factor. TS protein expression tends to be related TS mRNA expression and is an independent prognostic factor in advanced colorectal cancer.","The role of intratumoral thymidylate synthase (TS) mRNA or protein expression is still controversial and little has been reported regarding relation of them in colorectal cancer. Forty-six patients with advanced colorectal cancer who underwent surgical resection were included. TS mRNA expression was determined by the Danenberg tumor profile method based on laser-captured micro-dissection of the tumor cells. TS protein expression was evaluated using immunohistochemical staining. TS mRNA expression tended to relate TS protein expression. Statistical significance was not found in overall survival between the TS mRNA high group and low group regardless of performing adjuvant chemotherapy. The overall survival in the TS protein negative group was significantly higher than that in positive group in all and the patients without adjuvant chemotherapy. Multivariate analysis showed TS protein expression was as an independent prognostic factor. TS protein expression tends to be related TS mRNA expression and is an independent prognostic factor in advanced colorectal cancer.","null","null","2012-06","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.59","No.116","1059","1062","eng","null","null","null","null","null","10.5754/hge09243","0172-6390","null","null","null","null","null"
"Successful case with hemophagocytic syndrome after living donor liver transplantation.","Successful case with hemophagocytic syndrome after living donor liver transplantation.","Satoru Imura, Mitsuo Shimada, 齋藤 裕, Shuichi Iwahashi, Jun Hanaoka, Hiroki Mori, Tetsuya Ikemoto, Yuji Morine, Toru Utsunomiya","Satoru Imura, Mitsuo Shimada, 齋藤 裕, Shuichi Iwahashi, Jun Hanaoka, Hiroki Mori, Tetsuya Ikemoto, Yuji Morine, Toru Utsunomiya","null","Hemophagocytic syndrome (HPS) is a rare but serious complication that is associated with hypercytokinemia caused by activated T lymphocytes and macrophages in immunologically compromised patients. Living donor liver transplantation (LDLT) between adults has been performed to compensate for the shortage of available organs. There have been some reports of HPS after LDLT but its prognosis is disappointingly poor. Herein, we report a case of HPS in a 53-year-old woman who underwent LDLT using a left lobe graft. HPS was diagnosed on postoperative day 6 and successfully treated with a steroid pulse. HPS is a fatal complication in immunologically compromised patients but its early diagnosis and appropriate treatment can lead to an improved outcome.","Hemophagocytic syndrome (HPS) is a rare but serious complication that is associated with hypercytokinemia caused by activated T lymphocytes and macrophages in immunologically compromised patients. Living donor liver transplantation (LDLT) between adults has been performed to compensate for the shortage of available organs. There have been some reports of HPS after LDLT but its prognosis is disappointingly poor. Herein, we report a case of HPS in a 53-year-old woman who underwent LDLT using a left lobe graft. HPS was diagnosed on postoperative day 6 and successfully treated with a steroid pulse. HPS is a fatal complication in immunologically compromised patients but its early diagnosis and appropriate treatment can lead to an improved outcome.","null","null","2012-05","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.59","No.115","863","865","eng","null","null","null","null","null","10.5754/hge10081","0172-6390","null","null","null","null","null"
"Huge focal nodular hyperplasia difficult to distinguish from well-differentiated hepatocellular carcinoma","Huge focal nodular hyperplasia difficult to distinguish from well-differentiated hepatocellular carcinoma","Jun Hanaoka, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Hiroki Mori","Jun Hanaoka, Mitsuo Shimada, Toru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Hiroki Mori","null","We present a 43-year-old man with huge focal nodular hyperplasia (FNH) that was difficult to distinguish from well-differentiated hepatocellular carcinoma (HCC). He previously had abnormal portal vein circulation due to hypoplasia of the intrahepatic portal vein, which was treated with a superior mesenteric vein-inferior vena cava shunt. Laboratory findings included predominantly indirect hyperbilirubinemia with concomitant elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and ammonia. Serum α-fetoprotein and des-γ-carboxy prothrombin were slightly elevated. Multidetector-row computed tomography detected the primary tumor in the left liver lobe, which partially showed a central stellate scar. Gd ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging showed some low-intensity areas in the tumor in the hepatocyte phase. 99mTc-galactosyl human serum albumin scintigraphy showed normal intake of agent in the tumor. We could not rule out well-differentiated HCC. Extended left hepatectomy was performed. Final histopathological findings showed that most of the tumor was FNH against a background of portal vein hypoplasia with moderate atypia and hemorrhage. And immunohistochemical analysis revealed high expression of organic anion transporter (OATP) 1B3 and low expression of multidrug resistance-associated protein (MRP) 2 in a part of the tumor. The patient has remained alive with no hepatic lesion for 1 year after surgery. We describe a case of huge FNH that was difficult to distinguish from well-differentiated HCC even by current fully preoperative imaging technology and demonstrate the effectiveness of curative surgical resection.","We present a 43-year-old man with huge focal nodular hyperplasia (FNH) that was difficult to distinguish from well-differentiated hepatocellular carcinoma (HCC). He previously had abnormal portal vein circulation due to hypoplasia of the intrahepatic portal vein, which was treated with a superior mesenteric vein-inferior vena cava shunt. Laboratory findings included predominantly indirect hyperbilirubinemia with concomitant elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and ammonia. Serum α-fetoprotein and des-γ-carboxy prothrombin were slightly elevated. Multidetector-row computed tomography detected the primary tumor in the left liver lobe, which partially showed a central stellate scar. Gd ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging showed some low-intensity areas in the tumor in the hepatocyte phase. 99mTc-galactosyl human serum albumin scintigraphy showed normal intake of agent in the tumor. We could not rule out well-differentiated HCC. Extended left hepatectomy was performed. Final histopathological findings showed that most of the tumor was FNH against a background of portal vein hypoplasia with moderate atypia and hemorrhage. And immunohistochemical analysis revealed high expression of organic anion transporter (OATP) 1B3 and low expression of multidrug resistance-associated protein (MRP) 2 in a part of the tumor. The patient has remained alive with no hepatic lesion for 1 year after surgery. We describe a case of huge FNH that was difficult to distinguish from well-differentiated HCC even by current fully preoperative imaging technology and demonstrate the effectiveness of curative surgical resection.","null","null","2012-07","Hepatology Research","Hepatology Research","Vol.42","No.7","727","731","eng","null","null","null","null","null","10.1111/j.1872-034X.2012.00974.x","1386-6346","null","null","null","null","null"
"Hepatic screlosed hemangioma which was misdiagnosed as metastasis of gastric cancer: report of a case","Hepatic screlosed hemangioma which was misdiagnosed as metastasis of gastric cancer: report of a case","山田 眞一郎, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Shuichi Iwahashi, 齋藤 裕, 淺野間 理仁","山田 眞一郎, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Shuichi Iwahashi, 齋藤 裕, 淺野間 理仁","null","A screlosed hemangioma of the liver is rare among hepatic tumors. A 75 years old male was referred to our hospital for gastric cancer and a hepatic tumor. The histological finding of gastric cancer was revealed to be well differentiated adenocarcinoma. The liver tumor was 1.1×1.0 cm in size and located in segment 8 of the liver. Computed tomography (CT) showed it to be a tumor with ring enhancement. Magnetic resonance imaging (MRI) showed the tumor to have a low signal on T1-weighted and slightly high signal on T2-weighted images. Level of hemoglobin was 7.8 g/dl. It was thought to be persistent bleeding from gastric cancer. With diagnosis of liver metastasis from gastric cancer, chemotherapy is recommended. However, to control the bleeding from gastric cancer, we performed distal gastrectomy and wedge resection of liver (S8). The histological examination of the liver tumor revealed to be a hepatic sclerosed hemangioma with hyalinized tissue and collagen fibers. We report herein a case of the rare tumor which was misdiagnosed as a liver metastasis of gastric cancer.","A screlosed hemangioma of the liver is rare among hepatic tumors. A 75 years old male was referred to our hospital for gastric cancer and a hepatic tumor. The histological finding of gastric cancer was revealed to be well differentiated adenocarcinoma. The liver tumor was 1.1×1.0 cm in size and located in segment 8 of the liver. Computed tomography (CT) showed it to be a tumor with ring enhancement. Magnetic resonance imaging (MRI) showed the tumor to have a low signal on T1-weighted and slightly high signal on T2-weighted images. Level of hemoglobin was 7.8 g/dl. It was thought to be persistent bleeding from gastric cancer. With diagnosis of liver metastasis from gastric cancer, chemotherapy is recommended. However, to control the bleeding from gastric cancer, we performed distal gastrectomy and wedge resection of liver (S8). The histological examination of the liver tumor revealed to be a hepatic sclerosed hemangioma with hyalinized tissue and collagen fibers. We report herein a case of the rare tumor which was misdiagnosed as a liver metastasis of gastric cancer.","null","null","2012","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.59","No.3-4","270","274","eng","null","null","null","null","null","10.2152/jmi.59.270","1349-6867","null","null","null","null","null"
"Comparison of long-term prognosis of laparoscopy-assisted gastrectomy and conventional open gastrectomy with special reference to D2 lymph node dissection.","Comparison of long-term prognosis of laparoscopy-assisted gastrectomy and conventional open gastrectomy with special reference to D2 lymph node dissection.","Horohiko Sato, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Tomohiko Miyatani, Masakazu Goto, H Kashihara, Chie Takasu","Horohiko Sato, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Tomohiko Miyatani, Masakazu Goto, H Kashihara, Chie Takasu","null","Laparoscopy-assisted gastrectomy (LAG) is becoming widely used for early gastric cancer. However, how the curability and long-term prognosis of LAG and open gastrectomy (OG) for early and advanced gastric cancer compare remains unclear. This study assessed short- and long-term outcomes after LAG with lymph node dissection in early and advanced gastric cancer. A total of 332 patients who underwent LAG or OG for early and advanced gastric cancer from January 2001 through December 2010 were reviewed retrospectively. The mean operating time, estimated mean blood loss, number of dissected lymph nodes, and survival rates were compared between LAG and OG for early and advanced gastric cancer. Overall, 47.6% (158/332) of patients underwent LAG; D1, D1+ lymph node dissection was carried out in 77.2%, with D2 dissection in 22.8%. Only one patient required conversion to OG. Comparing LAG and OG with D1, D1+ lymph node dissection for early gastric cancer (EGC), mean operating time was significantly longer, estimated mean blood loss was significantly smaller, and the average number of retrieved lymph nodes was significantly greater with LAG. The rate of specific postoperative morbidity was 17.2% for LAG patients and 25.0% for OG patients, with no postoperative mortality. Survival and recurrence rates were not significantly different. Comparing LAG and OG with D2 lymph node dissection for advanced gastric cancer (AGC), mean operating time was significantly longer and estimated mean blood loss was significantly smaller with LAG, while the average number of retrieved lymph nodes, specific postoperative morbidity and mortality, and survival and recurrence rates were not significantly different. LAG with D1, D1+ lymph node dissection for EGC is safe and equivalent to open gastrectomy in curability. Moreover, LAG with D2 lymph node dissection for AGC is comparable to OG with D2 lymph node dissection with regard to short- and long-term results.","Laparoscopy-assisted gastrectomy (LAG) is becoming widely used for early gastric cancer. However, how the curability and long-term prognosis of LAG and open gastrectomy (OG) for early and advanced gastric cancer compare remains unclear. This study assessed short- and long-term outcomes after LAG with lymph node dissection in early and advanced gastric cancer. A total of 332 patients who underwent LAG or OG for early and advanced gastric cancer from January 2001 through December 2010 were reviewed retrospectively. The mean operating time, estimated mean blood loss, number of dissected lymph nodes, and survival rates were compared between LAG and OG for early and advanced gastric cancer. Overall, 47.6% (158/332) of patients underwent LAG; D1, D1+ lymph node dissection was carried out in 77.2%, with D2 dissection in 22.8%. Only one patient required conversion to OG. Comparing LAG and OG with D1, D1+ lymph node dissection for early gastric cancer (EGC), mean operating time was significantly longer, estimated mean blood loss was significantly smaller, and the average number of retrieved lymph nodes was significantly greater with LAG. The rate of specific postoperative morbidity was 17.2% for LAG patients and 25.0% for OG patients, with no postoperative mortality. Survival and recurrence rates were not significantly different. Comparing LAG and OG with D2 lymph node dissection for advanced gastric cancer (AGC), mean operating time was significantly longer and estimated mean blood loss was significantly smaller with LAG, while the average number of retrieved lymph nodes, specific postoperative morbidity and mortality, and survival and recurrence rates were not significantly different. LAG with D1, D1+ lymph node dissection for EGC is safe and equivalent to open gastrectomy in curability. Moreover, LAG with D2 lymph node dissection for AGC is comparable to OG with D2 lymph node dissection with regard to short- and long-term results.","null","null","2012-08","Surgical Endoscopy","Surgical Endoscopy","Vol.26","No.8","2240","2246","eng","null","null","null","null","null","10.1007/s00464-012-2167-x","1432-2218","null","null","null","null","null"
"Clinicopathological analysis of distal margin for rectal cancer after preoperative chemoradiation therapy.","Clinicopathological analysis of distal margin for rectal cancer after preoperative chemoradiation therapy.","Masanori Nishioka, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Shinya Morimoto, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani","Masanori Nishioka, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Shinya Morimoto, Kouzou Yoshikawa, Jun Higashijima, Tomohiko Miyatani","null","Preoperative chemoradiation therapy (CRT) for advanced rectal cancer allows anal sphincter preservation in some patients who would require an abdominoperineal resection. But adequate distal margin in patients with locally advanced rectal cancer requiring preoperative CRT is unclear. The objective was to evaluate necessary distal margin from reduced tumor by preoperative CRT for anal sphincter preservation. This study included 11 consecutive patients who performed low anterior resection and abdominoperineal resection for rectal cancer after preoperative CRT. Distal margin length from reduced tumor by preoperative CRT to residual viable cancer, tumor grade, lymph-node-metastasis stage and pathological changes of tumors were examined. Length from anal side edge of reduced tumor by preoperative CRT to pathological residual tumor ranged from +6 mm to -9 mm. Tumor stages were as follows: T0-2, N0, M0=3, T3, N0, M0=5, T4, N0, M0=1 and T3, N0, M+1=2. Median follow-up was 19 months. Recurrence occurred in one patient and was distant and not local. Pathological examinations showed that no patient had lymph-node-metastasis and residual tumors by preoperative CRT. This study suggests that for patients with locally advanced rectal cancer undergoing resection and preoperative CRT, distal margins ≥1 cm from reduced tumor by preoperative CRT seem to compromise pathological outcome.","Preoperative chemoradiation therapy (CRT) for advanced rectal cancer allows anal sphincter preservation in some patients who would require an abdominoperineal resection. But adequate distal margin in patients with locally advanced rectal cancer requiring preoperative CRT is unclear. The objective was to evaluate necessary distal margin from reduced tumor by preoperative CRT for anal sphincter preservation. This study included 11 consecutive patients who performed low anterior resection and abdominoperineal resection for rectal cancer after preoperative CRT. Distal margin length from reduced tumor by preoperative CRT to residual viable cancer, tumor grade, lymph-node-metastasis stage and pathological changes of tumors were examined. Length from anal side edge of reduced tumor by preoperative CRT to pathological residual tumor ranged from +6 mm to -9 mm. Tumor stages were as follows: T0-2, N0, M0=3, T3, N0, M0=5, T4, N0, M0=1 and T3, N0, M+1=2. Median follow-up was 19 months. Recurrence occurred in one patient and was distant and not local. Pathological examinations showed that no patient had lymph-node-metastasis and residual tumors by preoperative CRT. This study suggests that for patients with locally advanced rectal cancer undergoing resection and preoperative CRT, distal margins ≥1 cm from reduced tumor by preoperative CRT seem to compromise pathological outcome.","null","null","2012-10","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.59","No.119","2142","2146","eng","null","null","null","null","null","10.5754/hge11840","0172-6390","null","null","null","null","null"
"Preoperative radiotherapy combined with S-1 for advanced lower rectal cancer: phase I trial.","Preoperative radiotherapy combined with S-1 for advanced lower rectal cancer: phase I trial.","Shinya Morimoto, Mitsuo Shimada, Nobuhiro Kurita, Horohiko Sato, Takashi Iwata, Masanori Nishioka, Kouzou Yoshikawa, Tomohiko Miyatani, H Kashihara, Chie Takasu, Hitoshi Ikushima","Shinya Morimoto, Mitsuo Shimada, Nobuhiro Kurita, Horohiko Sato, Takashi Iwata, Masanori Nishioka, Kouzou Yoshikawa, Tomohiko Miyatani, H Kashihara, Chie Takasu, Hitoshi Ikushima","null","S-1 based chemoradiation is the recommended treatment for rectal cancer; however, the optimal scheduling and dosing are not yet established. A Phase I study was conducted to determine the maximum tolerated dose (MTD) of S-1 with radiotherapy (RT). Endpoints were the toxicity profile of this regimen and to determine the recommended dose (RD). Conformal RT was given using 4 fields at daily fractions of 2Gy on 5 days per week to a total dose of 40Gy. Concurrently S-1 was given twice daily throughout RT. Eligible patients had a newly diagnosed clinical stage T3-4 N0-2 M0 rectal adenocarcinoma located within 12cm of the anal verge suitable for curative resection. Surgery was performed 6 weeks from completion of preoperative chemoradiotherapy. The dose escalating from S-1 80mg/m2/day (Level 1) to 100mg/m2/day (Level 2). Nine patients were valid for safety. In all patients, S-1 was administered. There was no dose-limiting toxicity (DLT) in patients treated at dose Level 1. Six patients were enrolled in the dose-escalation phase. At dose Level 2, two patients developed DLT and this was considered the MTD. Objective response according to RECIST were observed in 5 of 9 patients who had measurable disease (56%). The RD of S-1 with concurrent RT was determined to be 80mg/m2/day. Preoperative RT combined with S-1 was feasible and well tolerated.","S-1 based chemoradiation is the recommended treatment for rectal cancer; however, the optimal scheduling and dosing are not yet established. A Phase I study was conducted to determine the maximum tolerated dose (MTD) of S-1 with radiotherapy (RT). Endpoints were the toxicity profile of this regimen and to determine the recommended dose (RD). Conformal RT was given using 4 fields at daily fractions of 2Gy on 5 days per week to a total dose of 40Gy. Concurrently S-1 was given twice daily throughout RT. Eligible patients had a newly diagnosed clinical stage T3-4 N0-2 M0 rectal adenocarcinoma located within 12cm of the anal verge suitable for curative resection. Surgery was performed 6 weeks from completion of preoperative chemoradiotherapy. The dose escalating from S-1 80mg/m2/day (Level 1) to 100mg/m2/day (Level 2). Nine patients were valid for safety. In all patients, S-1 was administered. There was no dose-limiting toxicity (DLT) in patients treated at dose Level 1. Six patients were enrolled in the dose-escalation phase. At dose Level 2, two patients developed DLT and this was considered the MTD. Objective response according to RECIST were observed in 5 of 9 patients who had measurable disease (56%). The RD of S-1 with concurrent RT was determined to be 80mg/m2/day. Preoperative RT combined with S-1 was feasible and well tolerated.","null","null","2012-07","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.59","No.117","1428","1432","eng","null","null","null","null","null","10.5754/hge11699","0172-6390","null","null","null","null","null"
"The effects of the Kampo medicine (Japanese herbal medicine) ``Daikenchuto'' on the surgical inflammatory response following laparoscopic colorectal resection.","The effects of the Kampo medicine (Japanese herbal medicine) ``Daikenchuto'' on the surgical inflammatory response following laparoscopic colorectal resection.","Kouzou Yoshikawa, Mitsuo Shimada, Masanori Nishioka, Nobuhiro Kurita, Takashi Iwata, Shinya Morimoto, Tomohiko Miyatani, Masato Komatsu, H Kashihara, Chie Takasu","Kouzou Yoshikawa, Mitsuo Shimada, Masanori Nishioka, Nobuhiro Kurita, Takashi Iwata, Shinya Morimoto, Tomohiko Miyatani, Masato Komatsu, H Kashihara, Chie Takasu","null","The inflammatory response after surgery is associated with various postoperative complications. The aim of the present prospective study was to evaluate the effects of Daikenchuto (DKT) (a Japanese herbal medicine) on the inflammatory response in patients following laparoscopic colorectal resection. Thirty patients who underwent laparoscopic colectomy for colorectal carcinoma were divided into two groups: a DKT intake group (D group, n = 15) and a control group (C group, n = 15). The D group took 7.5 g/day of DKT from the day after surgery until the 7th postoperative day. The body temperature, heart rate, WBC count, lymphocyte count, C-reactive protein (CRP) level, β-D: -glucan level and Candida index were compared between the two groups. The patients' mean age in the D group was significantly younger than that in the C group. D3 lymph node dissection was performed more often in the D group. The time until first flatus was significantly shorter in the D group (1.8 ± 0.5 days) than in the C group (2.7 ± 0.5 days). The CRP level was significantly lower in the D group (4.6 ± 0.6 mg/dl) than in the C group (8.3 ± 1.1 mg/dl) on the 3rd postoperative day. Postoperative DKT administration significantly suppressed the CRP level and shortened the time until first flatus. DKT administration also significantly suppressed postoperative inflammation following surgery for colorectal cancer.","The inflammatory response after surgery is associated with various postoperative complications. The aim of the present prospective study was to evaluate the effects of Daikenchuto (DKT) (a Japanese herbal medicine) on the inflammatory response in patients following laparoscopic colorectal resection. Thirty patients who underwent laparoscopic colectomy for colorectal carcinoma were divided into two groups: a DKT intake group (D group, n = 15) and a control group (C group, n = 15). The D group took 7.5 g/day of DKT from the day after surgery until the 7th postoperative day. The body temperature, heart rate, WBC count, lymphocyte count, C-reactive protein (CRP) level, β-D: -glucan level and Candida index were compared between the two groups. The patients' mean age in the D group was significantly younger than that in the C group. D3 lymph node dissection was performed more often in the D group. The time until first flatus was significantly shorter in the D group (1.8 ± 0.5 days) than in the C group (2.7 ± 0.5 days). The CRP level was significantly lower in the D group (4.6 ± 0.6 mg/dl) than in the C group (8.3 ± 1.1 mg/dl) on the 3rd postoperative day. Postoperative DKT administration significantly suppressed the CRP level and shortened the time until first flatus. DKT administration also significantly suppressed postoperative inflammation following surgery for colorectal cancer.","null","null","2012-07","Surgery Today","Surgery Today","Vol.42","No.7","646","651","eng","null","null","null","null","null","10.1007/s00595-011-0094-4","1436-2813","null","null","null","null","null"
"Hilar cholangiocarcinoma accompanied by pancreaticobiliary maljunction without bile duct dilatation 20 years after cholecystectomy: report of a case","Hilar cholangiocarcinoma accompanied by pancreaticobiliary maljunction without bile duct dilatation 20 years after cholecystectomy: report of a case","Shinichiro Yamada, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Mami Kanamoto, Jun Hanaoka, Shuichi Iwahashi, Yu Saitou, Hiroki Ishibashi","Shinichiro Yamada, Mitsuo Shimada, Toru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Mami Kanamoto, Jun Hanaoka, Shuichi Iwahashi, Yu Saitou, Hiroki Ishibashi","null","Pancreaticobiliary maljunction (PBM) is associated with the occurrence of biliary cancer due to pancreatobiliary reflux. From the perspective of carcinogenesis, the treatment for PBM is controversial. We herein report a case of hilar cholangiocarcinoma 20 years after the occurrence of gallbladder cancer. A 75-year-old man was referred to our hospital regarding an obstructive jaundice and bile duct tumor. A cholecystectomy was performed for cholelithiasis on this patient 20 years ago, and cancer in situ was detected. Computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) revealed a tumor of the portal hepatic region and PBM without dilatation of the bile duct. Adenocarcinoma was detected from bile cytology, and we diagnosed hilar cholangiocarcinoma. Despite the biliary decompression, jaundice was prolonged and the patient passed away. Our case suggests that not only cholecystectomy but also biliary diversion is needed for PBM regardless of the existence of bile duct dilatation.","Pancreaticobiliary maljunction (PBM) is associated with the occurrence of biliary cancer due to pancreatobiliary reflux. From the perspective of carcinogenesis, the treatment for PBM is controversial. We herein report a case of hilar cholangiocarcinoma 20 years after the occurrence of gallbladder cancer. A 75-year-old man was referred to our hospital regarding an obstructive jaundice and bile duct tumor. A cholecystectomy was performed for cholelithiasis on this patient 20 years ago, and cancer in situ was detected. Computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) revealed a tumor of the portal hepatic region and PBM without dilatation of the bile duct. Adenocarcinoma was detected from bile cytology, and we diagnosed hilar cholangiocarcinoma. Despite the biliary decompression, jaundice was prolonged and the patient passed away. Our case suggests that not only cholecystectomy but also biliary diversion is needed for PBM regardless of the existence of bile duct dilatation.","null","null","2013","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.60","No.1-2","169","173","eng","null","null","null","null","null","10.2152/jmi.60.169","1349-6867","null","null","null","null","null"
"The safety and usefulness of the single incision, transabdominal pre-peritoneal (TAPP) laparoscopic technique for inguinal hernia.","The safety and usefulness of the single incision, transabdominal pre-peritoneal (TAPP) laparoscopic technique for inguinal hernia.","Horohiko Sato, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Tomohiko Miyatani, Masakazu Goto, H Kashihara, Chie Takasu","Horohiko Sato, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Masanori Nishioka, Shinya Morimoto, Kouzou Yoshikawa, Tomohiko Miyatani, Masakazu Goto, H Kashihara, Chie Takasu","null","The safety and usefulness of the SILS-TAPP (transabdominal pre-peritoneal) procedure remain unclear. The aim of this study was to clarify the safety and usefulness of the SILS-TAPP procedure compared with standard laparoscopic TAPP and TEPP (totally extra-peritoneal pre-peritoneal) procedures. 85 patients underwent laparoscopic inguinal hernia repairs (TEPP, 30 patients; TAPP, 20 patients; SILS-TAPP, 35 patients) from 2007 to 2011. The operative outcomes of the three groups were compared. There was no difference in the patients' characteristics among the three groups. The TEPP Group had a longer operation time. One patient in the SILS-TAPP group had an intraoperative complication. One patient in the TAPP group had a postoperative complication, and one patient had ileus and one had an umbilical hernia in the SILS-TAPP group. The postoperative hospital stay was not significantly different among the three groups. There were no recurrences in the TEPP group, 1 case of recurrence (5.0%) in the TAPP group, and 1 case (2.9%) in the SILS-TAPP group. The present findings show that the SILS-TAPP repair is safe and feasible for the repair of adult inguinal hernia.","The safety and usefulness of the SILS-TAPP (transabdominal pre-peritoneal) procedure remain unclear. The aim of this study was to clarify the safety and usefulness of the SILS-TAPP procedure compared with standard laparoscopic TAPP and TEPP (totally extra-peritoneal pre-peritoneal) procedures. 85 patients underwent laparoscopic inguinal hernia repairs (TEPP, 30 patients; TAPP, 20 patients; SILS-TAPP, 35 patients) from 2007 to 2011. The operative outcomes of the three groups were compared. There was no difference in the patients' characteristics among the three groups. The TEPP Group had a longer operation time. One patient in the SILS-TAPP group had an intraoperative complication. One patient in the TAPP group had a postoperative complication, and one patient had ileus and one had an umbilical hernia in the SILS-TAPP group. The postoperative hospital stay was not significantly different among the three groups. There were no recurrences in the TEPP group, 1 case of recurrence (5.0%) in the TAPP group, and 1 case (2.9%) in the SILS-TAPP group. The present findings show that the SILS-TAPP repair is safe and feasible for the repair of adult inguinal hernia.","null","null","2012","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.59","No.3-4","235","240","eng","null","null","null","null","null","10.2152/jmi.59.235","1349-6867","null","null","null","null","null"
"Specific molecular signatures of non-tumor liver tissue may predict a risk of hepatocarcinogenesis.","Specific molecular signatures of non-tumor liver tissue may predict a risk of hepatocarcinogenesis.","Tohru Utsunomiya, Mitsuo Shimada, Yuji Morine, Atsushi Tajima, Issei Imoto","Tohru Utsunomiya, Mitsuo Shimada, Yuji Morine, Atsushi Tajima, Issei Imoto","null","Hepatocellular carcinoma (HCC) is one of the most common human cancers and a major cause of cancer-related death worldwide. The bleak outcomes of HCC patients even after curative treatment have been, at least partially, attributed to its multicentric origin. Therefore, it is necessary to examine not only tumor tissue but also non-tumor liver tissue to investigate the molecular mechanisms operating during hepatocarcinogenesis based on the concept of ""field cancerization"". Several studies previously investigated the association of molecular alterations in non-tumor liver tissue with clinical features and prognosis in HCC patients on a genome-wide scale. In particular, specific alterations of DNA methylation profiles have been confirmed in non-tumor liver tissue. This review focuses on the possible clinical value of array-based comprehensive analyses of molecular alterations, especially aberrant DNA methylation, in non-tumor liver tissue to clarify the risk of hepatocarcinogenesis. Carcinogenetic risk estimation based on specific methylation signatures may be advantageous for close follow-up of patients who are at high risk of HCC development. Furthermore, epigenetic therapies for patients with chronic liver diseases may be helpful to reduce the risk of HCC development because epigenetic alterations are potentially reversible, and thus provide promising molecular targets for therapeutic intervention.","Hepatocellular carcinoma (HCC) is one of the most common human cancers and a major cause of cancer-related death worldwide. The bleak outcomes of HCC patients even after curative treatment have been, at least partially, attributed to its multicentric origin. Therefore, it is necessary to examine not only tumor tissue but also non-tumor liver tissue to investigate the molecular mechanisms operating during hepatocarcinogenesis based on the concept of ""field cancerization"". Several studies previously investigated the association of molecular alterations in non-tumor liver tissue with clinical features and prognosis in HCC patients on a genome-wide scale. In particular, specific alterations of DNA methylation profiles have been confirmed in non-tumor liver tissue. This review focuses on the possible clinical value of array-based comprehensive analyses of molecular alterations, especially aberrant DNA methylation, in non-tumor liver tissue to clarify the risk of hepatocarcinogenesis. Carcinogenetic risk estimation based on specific methylation signatures may be advantageous for close follow-up of patients who are at high risk of HCC development. Furthermore, epigenetic therapies for patients with chronic liver diseases may be helpful to reduce the risk of HCC development because epigenetic alterations are potentially reversible, and thus provide promising molecular targets for therapeutic intervention.","null","null","2014-07","Cancer Science","Cancer Science","Vol.105","No.7","749","754","eng","null","true","null","null","null","10.1111/cas.12431","1349-7006","null","null","null","null","null"
"日本医学会分科会における女性医師支援2015年 第3回アンケート調査","日本医学会分科会における女性医師支援2015年 第3回アンケート調査","野村 幸世, 冨澤 康子, 大津 洋, 小川 朋子, 柴崎 郁子, 島田 光生, 竹下 恵美子, 花崎 和弘, 葉梨 智子, 山下 啓子, 明石 定子, 山内 英子, 岩瀬 弘敬, 田口 智章, 前田 耕太郎, 中村 清吾","野村 幸世, 冨澤 康子, 大津 洋, 小川 朋子, 柴崎 郁子, Mitsuo Shimada, 竹下 恵美子, 花崎 和弘, 葉梨 智子, 山下 啓子, 明石 定子, 山内 英子, 岩瀬 弘敬, 田口 智章, 前田 耕太郎, 中村 清吾","null","null","null","null","null","2017-11","日本外科学会雑誌","Journal of Japan Surgical Society","Vol.118","No.6","668","672","jpn","null","null","null","null","null","null","0301-4894","null","null","null","null","null"
"Epithelial-mesenchymal transition-related genes are linked to aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation.","Epithelial-mesenchymal transition-related genes are linked to aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation.","Shuichi Iwahashi, Mitsuo Shimada, Tohru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Chie Takasu, Yu Saitou, Shinichiro Yamada","Shuichi Iwahashi, Mitsuo Shimada, Tohru Utsunomiya, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Chie Takasu, Yu Saitou, Shinichiro Yamada","null","We reported that poor prognoses of hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA) are owing to up-regulation of expression of hypoxia-inducible factor-1 and epithelial cell adhesion molecule. We investigated aggressive progression in residual liver tumors (RLTs) after RFA to focus on expression of epithelial-mesenchymal transition (EMT)-related genes and miRNAs. Ten patients with recurrent HCC post-RFA who underwent hepatectomy (RFA group) and 78 patients with HCC without prior RFA (non-RFA group) were enrolled. We examined expression of transforming growth factor (TGF)-β, Twist, vimentin, and Snail-1 mRNAs in tumor tissues, and expression of miR-34a and miR-200c. Expression of TGF-β, Twist and Snail-1 in the RFA group was significantly higher than that in the non-RFA group (P < 0.05); vimentin expression in the RFA group was higher than that in the non-RFA group (P = 0.07). Expression of miR-200c and miR-34a in the RFA group was significantly lower than that in the non-RFA group (miR-200c: P = 0.04; miR-34a: P < 0.01). Increased expression of EMT markers through down-regulation of miRNA expression in RLTs after RFA may be related to poor prognoses of HCC patients with aggressive local recurrence after RFA.","We reported that poor prognoses of hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA) are owing to up-regulation of expression of hypoxia-inducible factor-1 and epithelial cell adhesion molecule. We investigated aggressive progression in residual liver tumors (RLTs) after RFA to focus on expression of epithelial-mesenchymal transition (EMT)-related genes and miRNAs. Ten patients with recurrent HCC post-RFA who underwent hepatectomy (RFA group) and 78 patients with HCC without prior RFA (non-RFA group) were enrolled. We examined expression of transforming growth factor (TGF)-β, Twist, vimentin, and Snail-1 mRNAs in tumor tissues, and expression of miR-34a and miR-200c. Expression of TGF-β, Twist and Snail-1 in the RFA group was significantly higher than that in the non-RFA group (P < 0.05); vimentin expression in the RFA group was higher than that in the non-RFA group (P = 0.07). Expression of miR-200c and miR-34a in the RFA group was significantly lower than that in the non-RFA group (miR-200c: P = 0.04; miR-34a: P < 0.01). Increased expression of EMT markers through down-regulation of miRNA expression in RLTs after RFA may be related to poor prognoses of HCC patients with aggressive local recurrence after RFA.","null","null","2016-03-03","Cancer Letters","Cancer Letters","Vol.375","No.1","47","50","eng","null","null","null","null","null","10.1016/j.canlet.2016.02.041","1872-7980","null","null","null","null","null"
"The beneficial effects of Kampo medicine Dai-Ken-Chu-To after hepatic resection: a prospective randomized control study.","The beneficial effects of Kampo medicine Dai-Ken-Chu-To after hepatic resection: a prospective randomized control study.","Masaaki Nishi, Mitsuo Shimada, Hideaki Uchiyama, Toru Ikegami, Yusuke Arakawa, Jun Hanaoka, 金村 普史, Yuji Morine, Satoru Imura, Hidenori Miyake","Masaaki Nishi, Mitsuo Shimada, Hideaki Uchiyama, Toru Ikegami, Yusuke Arakawa, Jun Hanaoka, 金村 普史, Yuji Morine, Satoru Imura, Hidenori Miyake","null","After hepatic resection, delayed flatus and impaired bowel movement often cause problematic postoperative ileus. Kampo medicine, Dai-kenchu-to (DKT), is reported to have a various beneficial effects on bowel systems. The aim of this study was to prospectively evaluate effects of DKT after hepatic resection. Thirty-two patients who underwent hepatic resection between July 2007 and August 2008 in Tokushima University Hospital were prospectively divided into DKT group (n=16) and control group (n=16). In DKT group, 2.5 g of DKT was administered orally three times a day from postoperative day (POD) 1. Blood was examined on POD 1, 3, 5 and 7. Postoperative first flatus, bowel movement and full recovery of oral intake, hospital stays and complications were checked. In DKT group, levels of c-reactive protein and beta-(1-3)-D-glucan on POD 3 were significantly decreased (p<0.05). Moreover, postoperative periods for the first flatus, bowel movement and the full recovery of oral intake were significantly shortened in DKT group (p<0.05). DKT suppressed inflammatory reaction, stimulated bowel movement and improved oral intake after hepatic resection, which may decrease serious morbidity after hepatic resection.","After hepatic resection, delayed flatus and impaired bowel movement often cause problematic postoperative ileus. Kampo medicine, Dai-kenchu-to (DKT), is reported to have a various beneficial effects on bowel systems. The aim of this study was to prospectively evaluate effects of DKT after hepatic resection. Thirty-two patients who underwent hepatic resection between July 2007 and August 2008 in Tokushima University Hospital were prospectively divided into DKT group (n=16) and control group (n=16). In DKT group, 2.5 g of DKT was administered orally three times a day from postoperative day (POD) 1. Blood was examined on POD 1, 3, 5 and 7. Postoperative first flatus, bowel movement and full recovery of oral intake, hospital stays and complications were checked. In DKT group, levels of c-reactive protein and beta-(1-3)-D-glucan on POD 3 were significantly decreased (p<0.05). Moreover, postoperative periods for the first flatus, bowel movement and the full recovery of oral intake were significantly shortened in DKT group (p<0.05). DKT suppressed inflammatory reaction, stimulated bowel movement and improved oral intake after hepatic resection, which may decrease serious morbidity after hepatic resection.","null","null","2012-10","Hepato-Gastroenterology","Hepato-Gastroenterology","Vol.59","No.119","2290","2294","eng","null","null","null","null","null","10.5754/hge10115","0172-6390","null","null","null","null","null"
"Pathophysiology of recurrent hepatocellular carcinoma after radiofrequency ablation.","Pathophysiology of recurrent hepatocellular carcinoma after radiofrequency ablation.","Tetsuya Ikemoto, Mitsuo Shimada, Shinichiro Yamada","Tetsuya Ikemoto, Mitsuo Shimada, Shinichiro Yamada","null","Radiofrequency ablation (RFA) is effective for the local control of hepatocellular carcinoma (HCC), particularly when a patient's liver functional reserve does not allow radical resection. There is controversy regarding the superiority of surgical resection compared with RFA for such patients, particularly those with three or fewer tumors with diameters 3 cm. Moreover, HCC often recurs after RFA, and the tumor cells show distinct phenotypic changes. Incomplete ablation accounts for tumor recurrence, and recent studies provide new insights into the biological mechanisms responsible for the pathological changes of HCC after RFA. This review focuses on the roles of epithelial-mesenchymal transition and cancer stemness that are driven by a mechanism that involves microRNA-mediated upregulation of hypoxia-inducible factor-1. The studies reviewed here provide compelling evidence that complete ablation of HCC is required to prevent recurrence and indicate that further research is urgently required to develop a new systematic strategy to prevent tumor recurrence by targeting hypoxia-inducible factor-1.","Radiofrequency ablation (RFA) is effective for the local control of hepatocellular carcinoma (HCC), particularly when a patient's liver functional reserve does not allow radical resection. There is controversy regarding the superiority of surgical resection compared with RFA for such patients, particularly those with three or fewer tumors with diameters 3 cm. Moreover, HCC often recurs after RFA, and the tumor cells show distinct phenotypic changes. Incomplete ablation accounts for tumor recurrence, and recent studies provide new insights into the biological mechanisms responsible for the pathological changes of HCC after RFA. This review focuses on the roles of epithelial-mesenchymal transition and cancer stemness that are driven by a mechanism that involves microRNA-mediated upregulation of hypoxia-inducible factor-1. The studies reviewed here provide compelling evidence that complete ablation of HCC is required to prevent recurrence and indicate that further research is urgently required to develop a new systematic strategy to prevent tumor recurrence by targeting hypoxia-inducible factor-1.","null","null","2017-06-01","Hepatology Research","Hepatology Research","Vol.47","No.1","23","30","eng","null","null","null","null","null","10.1111/hepr.12705","1386-6346","null","null","null","null","null"
"Liver regeneration after splenectomy in patients with liver cirrhosis.","Liver regeneration after splenectomy in patients with liver cirrhosis.","Shinichiro Yamada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Shuichi Iwahashi, Yu Saitou, Masato Yoshikawa, Hiroki Teraoku, Mitsuo Shimada","Shinichiro Yamada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Shuichi Iwahashi, Yu Saitou, Masato Yoshikawa, Hiroki Teraoku, Mitsuo Shimada","null","Splenectomy is a well-known procedure to improve thrombocytopenia and liver function in patients with liver cirrhosis (LC). However, the effect of splenectomy on liver regeneration remains unclear. The aim of this study is to investigate the effect of splenectomy on liver regeneration. Twenty patients with LC who underwent splenectomy were included in this study. Liver and splenic volumes were measured by a 3-D simulation imaging system. Liver volume (LV) and clinicopathological data were compared before and 6 months after splenectomy. Thereafter, patients were divided into two groups: the elevated LV group and the reduced LV group. Patient characteristics were compared between the two groups. Postoperative LV was increased in 14 patients compared with the preoperative state. Thrombocytopenia, leukopenia, total bilirubin and prothrombin time were improved after splenectomy. In the elevated LV group, four patients exhibited improved Child-Pugh grades after splenectomy, whereas no patients demonstrated improvement in the reduced LV group. The elevated LV group exhibited high albumin level, good indocyanine green retention rate at 15 min and large splenic volume compared with the same measurements in the decreased group. Patients with larger spleen volumes and higher albumin values before splenectomy showed increased rates of LV after splenectomy. Splenectomy for patients with LC improved pancytopenia and liver function. Especially, in patients with large spleen and high albumin levels, considerable increases in LV and improved liver function were observed.","Splenectomy is a well-known procedure to improve thrombocytopenia and liver function in patients with liver cirrhosis (LC). However, the effect of splenectomy on liver regeneration remains unclear. The aim of this study is to investigate the effect of splenectomy on liver regeneration. Twenty patients with LC who underwent splenectomy were included in this study. Liver and splenic volumes were measured by a 3-D simulation imaging system. Liver volume (LV) and clinicopathological data were compared before and 6 months after splenectomy. Thereafter, patients were divided into two groups: the elevated LV group and the reduced LV group. Patient characteristics were compared between the two groups. Postoperative LV was increased in 14 patients compared with the preoperative state. Thrombocytopenia, leukopenia, total bilirubin and prothrombin time were improved after splenectomy. In the elevated LV group, four patients exhibited improved Child-Pugh grades after splenectomy, whereas no patients demonstrated improvement in the reduced LV group. The elevated LV group exhibited high albumin level, good indocyanine green retention rate at 15 min and large splenic volume compared with the same measurements in the decreased group. Patients with larger spleen volumes and higher albumin values before splenectomy showed increased rates of LV after splenectomy. Splenectomy for patients with LC improved pancytopenia and liver function. Especially, in patients with large spleen and high albumin levels, considerable increases in LV and improved liver function were observed.","null","null","2016-10-02","Hepatology Research","Hepatology Research","Vol.46","No.5","443","449","eng","null","null","null","null","null","10.1111/hepr.12573","1386-6346","null","null","null","null","null"
"Complication of portal vein thrombosis after right hemihepatectomy in a patient lacking the portal vein bifurcation.","Complication of portal vein thrombosis after right hemihepatectomy in a patient lacking the portal vein bifurcation.","Hiroki Teraoku, Yusuke Arakawa, Masato Yoshikawa, Shinichiro Yamada, Yu Saitou, Shuichi Iwahashi, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Mitsuo Shimada","Hiroki Teraoku, Yusuke Arakawa, Masato Yoshikawa, Shinichiro Yamada, Yu Saitou, Shuichi Iwahashi, Tetsuya Ikemoto, Yuji Morine, Satoru Imura, Mitsuo Shimada","null","Absence of portal vein bifurcation is a rare anomaly. We report a patient with this anomaly who underwent right hemihepatectomy for treatment of hepatocellular carcinoma. Although the procedure was carefully performed with a preoperative three-dimensional simulation and intraoperative cholangiography, postoperative portal vein thrombosis occurred. J. Med. Invest. 63: 315-318, August, 2016.","Absence of portal vein bifurcation is a rare anomaly. We report a patient with this anomaly who underwent right hemihepatectomy for treatment of hepatocellular carcinoma. Although the procedure was carefully performed with a preoperative three-dimensional simulation and intraoperative cholangiography, postoperative portal vein thrombosis occurred. J. Med. Invest. 63: 315-318, August, 2016.","null","null","2016","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.63","No.3-4","315","318","eng","null","null","null","null","null","10.2152/jmi.63.315","1349-6867","null","null","null","null","null"
"Role of CD44 expression in non-tumor tissue on intrahepatic recurrence of hepatocellular carcinoma.","Role of CD44 expression in non-tumor tissue on intrahepatic recurrence of hepatocellular carcinoma.","LO Tovuu, Satoru Imura, Toru Utsunomiya, Yuji Morine, Tetsuya Ikemoto, Yusuke Arakawa, Hiroki Mori, Jun Hanaoka, Mami Kanamoto, 杉本 光司, Shuichi Iwahashi, Yu Saitou, 山田 眞一郎, 淺野間 理仁, Hidenori Miyake, Mitsuo Shimada","LO Tovuu, Satoru Imura, Toru Utsunomiya, Yuji Morine, Tetsuya Ikemoto, Yusuke Arakawa, Hiroki Mori, Jun Hanaoka, Mami Kanamoto, 杉本 光司, Shuichi Iwahashi, Yu Saitou, 山田 眞一郎, 淺野間 理仁, Hidenori Miyake, Mitsuo Shimada","null","CD44 is well known to be one of the cancer stem cell markers and is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion, and cell migration. We investigated the role of CD44 expression in both tumor and non-tumor tissues on recurrence of hepatocellular carcinoma (HCC). Forty-eight patients with HCC who underwent hepatic resection at our institution were enrolled in this study. CD44 expressions in both tumor and non-tumor tissues were examined using real time reverse transcription-polymerase chain reaction. The patients were divided into two groups: high and low gene-expression group, based on the CD44 expression level. We compared the clinicopathological factors between the high expression and low expression groups in both tumor and non-tumor tissues. In the tumor tissues, the gene-expression levels of CD44 did not correlate with any clinicopathological parameters. The disease-free survival rate showed no significant difference between the two groups. In non-tumor tissues, although there was no significant relationship between the CD44 expression levels and clinicopathological factors, disease-free survival rate in the CD44 low expression group was significantly better than that in the CD44 high expression group (P < 0.05). In multivariate analysis, the risk factors in tumor recurrence were presence of microscopic portal invasion and high expression level of CD44. The CD44 expressions in the non-tumor tissues may predict HCC recurrence.","CD44 is well known to be one of the cancer stem cell markers and is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion, and cell migration. We investigated the role of CD44 expression in both tumor and non-tumor tissues on recurrence of hepatocellular carcinoma (HCC). Forty-eight patients with HCC who underwent hepatic resection at our institution were enrolled in this study. CD44 expressions in both tumor and non-tumor tissues were examined using real time reverse transcription-polymerase chain reaction. The patients were divided into two groups: high and low gene-expression group, based on the CD44 expression level. We compared the clinicopathological factors between the high expression and low expression groups in both tumor and non-tumor tissues. In the tumor tissues, the gene-expression levels of CD44 did not correlate with any clinicopathological parameters. The disease-free survival rate showed no significant difference between the two groups. In non-tumor tissues, although there was no significant relationship between the CD44 expression levels and clinicopathological factors, disease-free survival rate in the CD44 low expression group was significantly better than that in the CD44 high expression group (P < 0.05). In multivariate analysis, the risk factors in tumor recurrence were presence of microscopic portal invasion and high expression level of CD44. The CD44 expressions in the non-tumor tissues may predict HCC recurrence.","null","null","2012-06-16","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.18","No.4","651","656","eng","null","null","null","null","null","10.1007/s10147-012-0432-6","1437-7772","null","null","null","null","null"
"Indoleamine 2,3-dioxygenase affects the aggressiveness of intraductal papillary mucinous neoplasms through Foxp3+CD4+CD25+ T cells in peripheral blood.","Indoleamine 2,3-dioxygenase affects the aggressiveness of intraductal papillary mucinous neoplasms through Foxp3+CD4+CD25+ T cells in peripheral blood.","Tetsuya Ikemoto, Mitsuo Shimada, Masato Komatsu, Shinichiro Yamada, Yu Saito, Hiroki Mori, Yuji Morine, Satoru Imura, Yoshimi Bando, Toru Utsunomiya","Tetsuya Ikemoto, Mitsuo Shimada, Masato Komatsu, Shinichiro Yamada, Yu Saito, Hiroki Mori, Yuji Morine, Satoru Imura, Yoshimi Bando, Toru Utsunomiya","null","Intraductal papillary mucinous neoplasms (IPMNs) have a high malignant potential. We previously reported that peripheral Foxp3(+)CD4(+)CD25(+) T-cell (Foxp3(+) Treg) populations significantly increase with IPMN pathological aggressiveness. Dendritic cell-mediated induction of active Tregs from naive CD4(+) T cells requires indoleamine 2,3-dioxygenase (IDO). Here, we evaluated whether an IDO-Foxp3(+) Treg interaction plays a role in IPMN pathological aggressiveness. We evaluated peripheral blood samples and resected specimens from 12 patients with IPMN. We analyzed Foxp3(+)CD4(+)CD25(+) T cells in peripheral blood by fluorescence-activated cell sorting, evaluated the resected specimens by anti-IDO antibody staining, and compared them with the patients' clinicopathological factors. The pathological aggressiveness of IPMN was significantly associated with the number of peripheral Foxp3(+) Tregs (P < 0.05) and IDO-positive cells per high-power field (HPF) (P < 0.01). There was a significant correlation between the numbers of peripheral Foxp3(+) Tregs and IDO-positive cells/HPF (r = 0.625, P < 0.01). Patients with 7 or more IDO-positive cells/HPF had a significantly higher recurrence rate than those with less than 7 IDO-positive cells/HPF (P < 0.01, log-rank test). Peripheral Foxp3(+) Tregs accurately reflect the aggressiveness of IPMNs. An increase in Foxp3(+) Tregs can be induced by local IDO-positive cells in IPMN.","Intraductal papillary mucinous neoplasms (IPMNs) have a high malignant potential. We previously reported that peripheral Foxp3(+)CD4(+)CD25(+) T-cell (Foxp3(+) Treg) populations significantly increase with IPMN pathological aggressiveness. Dendritic cell-mediated induction of active Tregs from naive CD4(+) T cells requires indoleamine 2,3-dioxygenase (IDO). Here, we evaluated whether an IDO-Foxp3(+) Treg interaction plays a role in IPMN pathological aggressiveness. We evaluated peripheral blood samples and resected specimens from 12 patients with IPMN. We analyzed Foxp3(+)CD4(+)CD25(+) T cells in peripheral blood by fluorescence-activated cell sorting, evaluated the resected specimens by anti-IDO antibody staining, and compared them with the patients' clinicopathological factors. The pathological aggressiveness of IPMN was significantly associated with the number of peripheral Foxp3(+) Tregs (P < 0.05) and IDO-positive cells per high-power field (HPF) (P < 0.01). There was a significant correlation between the numbers of peripheral Foxp3(+) Tregs and IDO-positive cells/HPF (r = 0.625, P < 0.01). Patients with 7 or more IDO-positive cells/HPF had a significantly higher recurrence rate than those with less than 7 IDO-positive cells/HPF (P < 0.01, log-rank test). Peripheral Foxp3(+) Tregs accurately reflect the aggressiveness of IPMNs. An increase in Foxp3(+) Tregs can be induced by local IDO-positive cells in IPMN.","null","null","2013-01","Pancreas","Pancreas","Vol.42","No.1","130","134","eng","null","null","null","null","null","10.1097/MPA.0b013e3182575e4a","1536-4828","null","null","null","null","null"
"Modified hanging method for liver resection.","Modified hanging method for liver resection.","Toru Utsunomiya, Mitsuo Shimada","Toru Utsunomiya, Mitsuo Shimada","null","The liver hanging maneuver (LHM) is a useful technique to transect the liver parenchyma while lifting it with a tape passed between the anterior surface of the inferior vena cava (IVC) and the liver parenchyma. The original method was employed mostly for right hepatectomy with an ""anterior approach"" for huge liver tumors. The tape serves as a guide to the transection plane and facilitates the control of bleeding in the deeper parenchyma of the liver while protecting the anterior surface of the IVC. On the other hand, several recent studies have shown the feasibility and usefulness of modified LHM techniques. These methods can be applied to left hepatectomy with or without caudate lobectomy (segmentectomy 1), even for patients undergoing orthotopic liver transplantation. This report explains the methods and pitfalls of the original and modified LHM. In addition, important anatomical and technical aspects of the mobilization of hepatic lobes are also included.","The liver hanging maneuver (LHM) is a useful technique to transect the liver parenchyma while lifting it with a tape passed between the anterior surface of the inferior vena cava (IVC) and the liver parenchyma. The original method was employed mostly for right hepatectomy with an ""anterior approach"" for huge liver tumors. The tape serves as a guide to the transection plane and facilitates the control of bleeding in the deeper parenchyma of the liver while protecting the anterior surface of the IVC. On the other hand, several recent studies have shown the feasibility and usefulness of modified LHM techniques. These methods can be applied to left hepatectomy with or without caudate lobectomy (segmentectomy 1), even for patients undergoing orthotopic liver transplantation. This report explains the methods and pitfalls of the original and modified LHM. In addition, important anatomical and technical aspects of the mobilization of hepatic lobes are also included.","null","null","2012-01","Journal of Hepato-Biliary-Pancreatic Sciences","Journal of Hepato-Biliary-Pancreatic Sciences","Vol.19","No.1","19","24","eng","null","null","null","null","null","10.1007/s00534-011-0442-1","1868-6982","null","null","null","null","null"