Impact of CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) expression in gastric cancer.

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.


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


Impact of sidedness of colorectal cancer on tumor immunity.

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.


Usefulness of an ICG fluorescence catheter system in TaTME for avoiding intraoperative urethral injury.

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.

The Journal of Medical Investigation : JMI


Trans-abdominal Pre-peritoneal (TAPP) Inguinal Hernia Repair with Liquid-injection and Gauze Dissection.

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.


Desmoid-type fibromatosis difficult to distinguish from GIST : A case report.

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.


Usefulness of virtual three-dimensional image analysis in inguinal hernia as an educational tool.

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.


【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


The usefulness of intraoperative X-ray fluoroscopy in avoiding urethral injury during transanal total mesorectal excision.

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.


The Role of Neutrophil-to-lymphocyte Ratio on the Effect of CRT for Patients With 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.


Duodenal-Jejunal Bypass Maintains Gut Permeability by Suppressing 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.


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


A case of gastric heterotopic pancreas with gastroduodenal invagination.

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.


Usefulness of blood flow evaluation by indocyanine green fluorescence system in laparoscopic anterior resection.

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.

The Journal of Medical Investigation : JMI


Utility of virtual three-dimensional image analysis for laparoscopic gastrectomy conducted by trainee surgeons.

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.


The Effect of Laparoscopic Sleeve Gastrectomy on Obesity and Obesity-related Disease : the Results of 10 Initial Cases.

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.


Blue light-emitting diodes induce autophagy in colon cancer cells by Opsin 3.

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.


High STAT4 Expression Indicates Better Disease-free Survival in Patients with Gastric Cancer.

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.


Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection.

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.


Limited lymph node dissection in elderly patients with gastric cancer.

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.


Cyclopamine decreased the expression of Sonic Hedgehog and its downstream genes in colon cancer stem cells.

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.


CD133 expression is correlated with poor prognosis in colorectal cancer.

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.


Effect of light irradiation by light emitting diode on colon cancer cells.

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.


Protein kinase Cι is a new prognostic factor in 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.


Expression of Stathmin1 in 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.


Hybrid technique for laparoscopic incisional ventral hernia repair combining laparoscopic primary closure and mesh repair.

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.


Duodenal-Jejunal Bypass Improves Insulin Resistance by Enhanced Glucagon-Like Peptide-1 Secretion Through Increase of Bile Acids.

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.


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


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


The role of activation-induced cytidine deaminase expression in 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.


Characteristics of internal hernia after gastrectomy with Roux-en-Y reconstruction for gastric cancer.

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.