Characteristic submucosal alteration in biliary carcinogenesis of pancreaticobiliary maljunction with a focus on inflammasome activation.

Activated fibroblasts and M2 macrophages in the GB lamina propria may be associated with biliary carcinogenesis of PBM, possibly through inflammasome activation.

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.

Journal of Hepato-Biliary-Pancreatic Sciences


Four cases of gastric adenocarcinoma and proximal polyposis of the stomach treated by robotic total gastrectomy

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 carcinoma with lymphoid stroma derived from hamartomatous inverted polyp with osteoclast-like giant cells: a case report.

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.


Robot-assisted total gastrectomy for gastric cancer in a patient with amyotrophic lateral sclerosis receiving long-term tracheostomy invasive ventilation

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.


A new pathological classification of intrahepatic cholangiocarcinoma according to protein expression 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.


Bevacizumab-associated intestinal perforation and perioperative complications in patients receiving bevacizumab.

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.


Anastomotic recurrence after laparoscopic distal gastrectomy with delta-shaped anastomosis : report of a case.

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.

The Journal of Medical Investigation : JMI


Expression Level of MicroRNA-449a Predicts the Prognosis of Patients With Gastric Cancer.

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.


Establishment of an evaluation system for non-technical skills in surgery : Surgeon and paramedical staff assessments.

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.


The Significance of MicroRNA-449a and Its Potential Target HDAC1 in Patients With Colorectal Cancer.

miR-449a level might be a prognostic indicator for colorectal cancer and miR-449a might regulate HDAC1 expression.


Epigallocatechin-3-gallate Enhances Radiation Sensitivity in Colorectal Cancer Cells Through Nrf2 Activation 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.


The Effect of Roux-en-Y Reconstruction on Type 2 Diabetes in the Early Postoperative Period.

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.


Role of heat shock factor 1 expression in the microenvironment of intrahepatic cholangiocarcinomas.

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.

Journal of Gastroenterology and Hepatology


Programmed Cell Death Ligand 1 Expression Is an Independent Prognostic Factor in Colorectal Cancer.

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.


The Impact of Indoleamine 2,3-dioxygenase (IDO) Expression on Stage III Gastric Cancer.

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.


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.

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.

Surgical Laparoscopy, Endoscopy & Percutaneous Techniques


Ki-67 and Survivin as Predictive Factors for Rectal Cancer Treated with Preoperative Chemoradiotherapy.

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.


The Outcome of Sorafenib Therapy on Unresectable Hepatocellular Carcinoma: Experience of Conversion and Salvage Hepatectomy.

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.


Propensity score-matched study of laparoscopic and open surgery 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.


Combined liver mobilization and retraction: A novel technique to obtain the optimal surgical field during 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.


Prediction of response to preoperative chemoradiotherapy and establishment of individualized therapy in advanced 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.


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

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


The relationship of CD133, histone deacetylase 1 and thrombospondin-1 in 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.


Effective use of a vessel-sealing system for laparoscopic unroofing of 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.


Duodenal-jejunal bypass improves diabetes and liver steatosis via enhanced glucagon-like peptide-1 elicited by bile acids.

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.

Journal of Gastroenterology and Hepatology


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


New ports placement in laparoscopic central lymph nodes dissection with left colic artery 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.

The Journal of Medical Investigation : JMI


Hypomethylation of Long Interspersed Nuclear Element-1 (LINE-1) is Associated with Poor Prognosis via Activation of c-MET in Hepatocellular Carcinoma.

LINE-1 hypomethylation is significantly associated with poor prognosis in patients with HCC, possibly due to activation of c-MET expression.

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).


Beneficial effects of green tea catechin on massive hepatectomy model in rats.

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.


【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


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

産婦人科漢方研究のあゆみ

産婦人科漢方研究のあゆみ


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


High susceptibility to zymbal gland and intestinal carcinogenesis in diabetic Otsuka Long-Evans Tokushima Fatty rats.

Diabetes mellitus (DM) and obesity are believed to be risk factors for colorectal cancer in humans. In experiment 1, male nondiabetic Long-Evans Tokushima Otsuka (LETO) rats and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model animal of type 2 DM, were whole-body X-irradiated (4 Gy) at 6 and 8 weeks of age and euthanized at 78 weeks of age (n=15, respectively). The incidences of small intestine adenocarcinoma in LETO and OLETF rats were 0% and 30%, respectively. In experiment 2, male LETO and OLETF rats (n=24, respectively) were given s.c. injections of 15 mg/kg azoxymethane (AOM) once weekly for 3 weeks and euthanized at 36 weeks of age. The incidences of Zymbal gland tumors in LETO and OLETF rats were 0% and 67%, respectively (P<0.001), whereas those of small intestine adenocarcinoma were 0% and 43% (P<0.001) and those of cecum/colon adenocarcinoma were 46% and 79% (P<0.05), respectively. Fatty change of hepatocytes was common in OLETF rats (63%) but not in LETO rats. Serum triglyceride and free fatty acid levels in OLETF rats were significantly higher than in LETO rats at sacrifice, whereas serum insulin levels in OLETF rats were very diverse. These data suggest that hyperlipidemia plays a significant role in high susceptibility to lower intestinal tract carcinogenesis in OLETF rats; this strain is susceptible to AOM-induced Zymbal gland carcinogenesis.


Evaluation of the usefulness of Roux-en-Y reconstruction with jejunal pouch by radioisotope scintigraphy and 13C breath test

【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


【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


Preoperative evaluation to determine the difficulty of No. 6 lymphadenectomy in laparoscopic gastrectomy.

Laparoscopic gastrectomy (LG) requires a long learning curve because of the complicated surgical procedures. Infrapyloric (No. 6) lymph node dissection (LND) is one of the difficult procedures in LG, especially for trainees. This study investigated the impact of the prediction of the difficulty of No. 6 LND. We retrospectively reviewed the preoperative computed tomography (CT) images and individual operative video records of 57 patients who underwent LG with No. 6 LND to define and predict the No. 6 LND difficulty. To evaluate whether prediction of the difficulty of No. 6 LND could improve surgical outcomes, 48 patients who underwent laparoscopic distal gastrectomy were assessed (30 patients without prediction by a qualified surgeon and 18 patients with prediction by a trainee). The anatomical characteristic that LND required > 2 cm of dissection along the right gastroepiploic vein was defined as difficulty of No. 6 LND. Of the 57 LG patients, difficulty was identified intraoperatively in 21 patients (36.8%). Among the several evaluated anatomical parameters, the length between the right gastroepiploic vein and the right gastroepiploic artery in the maximum intensity projection in contrast-enhanced CT images was significantly correlated with the intraoperative difficulty of No. 6 LND (p < 0.0001). Surgical outcomes, namely intraoperative minor bleeding, postoperative pancreatic fistula, and drain amylase concentration were not significantly different between LG performed by a trainee with prediction compared with that by a specialist without prediction. Preoperative evaluation of the difficulty of No. 6 LND is useful for trainees, to improve surgical outcomes.


Role of stromal PD-L1 expression in colorectal liver metastasis.

The outcomes of immune checkpoint blockade for colorectal cancer (CRC) treatment are unsatisfactory. Furthermore, the efficacy of immune checkpoint blockade for liver metastasis of various cancer is poor. Here, we investigated the relationship between stromal programmed death-ligand 1 (PD-L1) expression and the prognosis of patients with colorectal cancer liver metastasis (CRLM). The present study enrolled 84 CRLM patients who underwent surgery (R0) for CRC. Immunohistochemistry was performed to analyze stromal PD-L1 expression in CRLM. Stromal PD-L1 was expressed in 52.3% of CRLM samples, which was associated with fewer not optimally resectable metastases (p = 0.04). Stromal PD-L1 also tended to associate with a lower tumor grade (p = 0.08). Stromal PD-L1-positive patients had longer overall survival (p = 0.003). Multivariate analysis identified stromal PD-L1 expression (p = 0.008) and poorer differentiation (p < 0.001) as independent prognostic indicators. Furthermore, stromal PD-L1 expression was correlated to a high number of tumor-infiltrating lymphocytes (TILs). Stromal PD-L1- and low TIL groups had shorter OS than stromal PD-L1 + and high TIL groups (46.6% vs. 81.8%, p = 0.05) Stromal PD-L1-positive patients had longer disease-free survival (DFS) (p = 0.03) and time to surgical failure (p = 0.001). Interestingly, stromal PD-L1 expression was positively related to the desmoplastic subtype (p = 0.0002) and inversely related to the replacement subtype of the histological growth pattern (p = 0.008). Stromal PD-L1 expression may be a significant prognostic marker for CRLM.


Association between high expression of intratumoral fibroblast activation protein and survival in patients with intrahepatic cholangiocarcinoma.

Cancer-associated fibroblasts (CAFs) have been reported to exhibit protumorigenic effects. Among the well-known CAF markers such as smooth muscle actin (SMA) and fibroblast activation protein (FAP), high expression of SMA in the peritumoral stroma has been reported to be a prognostic factor in various cancers. However, the effect of high FAP expression in intrahepatic cholangiocarcinoma (IHCC) has not been fully clarified. We evaluated the expression of CAF markers, focusing on FAP expression in the peripheral and intratumoral regions, to clarify the association with survival in patients with IHCC. The study cohort comprised 37 patients who underwent curative resection for IHCC. The FAP expressions were evaluated in the peripheral and intratumoral regions of the resected tissues. Clinicopathological factors and survival outcomes were investigated between patients with high versus low FAP expression. Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival and relapse-free survival. The median area percentages of FAP expression in the peripheral and intratumoral regions were 15.5% and 17.8%, respectively. High FAP expression in the intratumoral region was significantly associated with worse overall survival and disease-free survival than low FAP expression in the intratumoral region. Multivariate analysis identified high intratumoral FAP expression as a risk factor for worse overall survival (hazard ratio, 2.450; p = 0.049) and relapse-free survival (hazard ratio, 2.743; p = 0.034). High intratumoral FAP expression was associated with worse survival, suggesting that intratumoral FAP expression represents malignant progression in patients with IHCC.


Conversion surgery after successful response to chemotherapy (S-1 + oxaliplatin + nivolumab) in a patient with stage IV gastric cancer with peritoneal metastasis (P1, CY1): a case report.

We here present a case report of a patient with Stage IV gastric cancer with peritoneal metastasis (P1, CY1) who underwent conversion surgery after a successful response to chemotherapy (S-1 + oxaliplatin + nivolumab). The patient was a woman in her 60 s. Her chief complaint was epigastric pain. Upper gastrointestinal endoscopy showed Type 4 advanced carcinoma on the lesser curvature of the gastric body. Biopsy showed Group 5 (poorly differentiated adenocarcinoma) and HER2 was negative. Staging laparoscopy revealed seeding in the round ligament of the liver (P1) and adenocarcinoma cells in ascites (CY1). Ten courses of chemotherapy (S-1 + oxaliplatin + nivolumab) were administered, after which contrast-enhanced computed tomography showed that the primary tumor had shrunk and seeding was no longer detectable. Upper gastrointestinal endoscopy revealed scar-like changes. A second staging laparoscopy revealed that ascites cytology was negative and a biopsy of the round ligament of the liver showed no malignant cells (P0, CY0). Conversion surgery comprising laparoscopic total gastrectomy with D2 lymph node dissection and resection of the round ligament of the liver was performed. The postoperative course was uneventful. Histopathological examination of the resected specimen revealed no tumor cells in the gastric mesentery or the round ligament of the liver. The pathological diagnosis was gastric cancer [M, U, L, Less, Ant, Post, type4, T3(SS), N0, M0 (H0, P0, CY0), ypStage IIA]. Adjuvant chemotherapy (S-1) was commenced. The patient is still alive 7 months later with no evidence of recurrence.


Utility of robotic surgery for Siewert type II/III adenocarcinoma of esophagogastric junction: transhiatal robotic versus laparoscopic approach.

Robotic surgery (RS) has been rapidly adopted for gastric cancer and adenocarcinoma of the esophagogastric junction (AEG). However, the utility of RS for Siewert type II/III AEG remains unclear. Forty-one patients who underwent either transhiatal RS (n = 15) or laparoscopic surgery (LS) (n = 26) for Siewert type II/III AEG were enrolled in this study. The surgical outcomes of the two groups were compared. In the entire cohort, there were no significant intergroup differences in the operative time, blood loss volume, or number of retrieved lymph nodes. The length of the postoperative hospital stay was shorter in the RS group than in the LS group (14.20 ± 7.10 days vs. 18.73 ± 17.82 days, respectively; p = 0.0388). The morbidity rate (Clavien-Dindo grade ≥ 2) was similar between the groups. In the Siewert II cohort, there were no significant intergroup differences in short-term outcomes. In the entire cohort, there was no significant difference between the RS and LS groups in the 3-year overall survival rate (91.67% vs. 91.48%, N.S.) or 3-year disease-free survival rate (91.67% vs. 91.78%, N.S.), respectively. Likewise, in the Siewert type II cohort, there was no significant difference between the RS and LS groups in the 3-year overall survival rate (80.00% vs. 93.33%, N.S.) or 3-year disease-free survival rate (80.00% vs. 94.12%, N.S.), respectively. Transhiatal RS for Siewert II/III AEG was safe and contributed to similar short-term and long-term outcomes compared with LS.


The application of enhanced recovery after surgery in total gastrectomy: a propensity score-matched analysis.

This study aimed to investigate the feasibility and safety of our enhanced recovery after surgery protocol including early oral intake and omitting nasogastric tube (NGT) placement after total gastrectomy. We analyzed 182 consecutive patients who underwent total gastrectomy. The clinical pathway was changed in 2015, and patients were divided into 2 groups (conventional group and modified group). Postoperative complications, bowel movement, and postoperative hospital stays were compared in the two groups in all cases and propensity score matching (PSM). Flatus and defecation were significantly earlier in the modified group compared with those in the conventional group (flatus: 2 (1-5) days vs 3 (2-12) days, p = 0.03; defecation: 4 (1-14) days vs 6 (2-12) days p = 0.04). The postoperative hospital stay was 18 (6-90) days in the conventional group and 14 (7-74) days in the modified group (p = 0.009). Days until discharge criteria were met were earlier in the modified group compared with that in the conventional group (10 (7-69) days vs 14 (6-84) days p = 0.01). Overall and severe complications occurred in nine patients (12.6%) and three patients (4.2%) in the conventional group and twelve patients (10.8%) and four patients (3.6%) in the modified group, respectively (p = 0.70 and p = 0.83) in all cases. In PSM, there is no significant difference between the two groups concerning the postoperative complications (overall complication 6 (12.5%) vs 8 (16.7%) p = 0.56, severe complications 1 (2%) vs 2 (4.2%) p = 0.83). Modified ERAS for total gastrectomy may be feasible and safe.


Surgical Outcomes of Gastrectomy in Hemodialysis Patients with Gastric Cancer.


Transanal lateral lymph node dissection with intraoperative hologram support in low rectal cancer.

In Japan, the standard treatment for stage II/III advanced low rectal cancer is total mesorectal excision plus lateral lymph node dissection (LLND). There are also recent reports on the use of transanal LLND. However, the transanal anatomy is difficult to understand, and additional support tools are required to improve the surgical safety. The present study examined the utility of holograms with mixed reality as an intraoperative support tool for assessing the complex pelvic anatomy. Polygon (stereolithography) files of patients' pelvic organs were created and exported from the SYNAPSE VINCENT imaging system and uploaded into the Holoeyes MD virtual reality software. Three-dimensional images were automatically converted into patient-specific holograms. Each hologram was then installed into a head mount display (HoloLens2), and the surgeons and assistants wore the HoloLens2 when they performed transanal LLND. Twelve digestive surgeons with prior practice in hologram manipulation evaluated the utility of the intraoperative hologram support by means of a questionnaire. Intraoperative hologram support improved the surgical understanding of the lateral lymph node region anatomy. In the questionnaire, 75% of the surgeons answered that the hologram accurately reflected the anatomy, and 92% of the surgeons answered that the anatomy was better understood by simulating the hologram intraoperatively than preoperatively. Moreover, 92% of the surgeons agreed that intraoperative holograms were a useful support tool for improving the surgical safety. Intraoperative hologram support improved the surgical understanding of the pelvic anatomy for transanal LLND. Intraoperative holograms may represent a next-generation surgical tool for transanal LLND.


Stapler insertion angle toward the esophagus reduces the incidence of early postoperative Roux stasis syndrome after distal gastrectomy in minimally invasive surgery.

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.


The Impact of the Pre-operative Neutrophil-lymphocyte Ratio as the Predictive Marker of Post-operative Weight Loss and Improving Diabetes in Sleeve Gastrectomy.

The aim was to investigate the impact of the neutrophil-lymphocyte ratio (NLR) in sleeve gastrectomy (SG). 15 obese patients were enrolled in this study ; mean body weight (BW) 127.5kg ; mean body mass index (BMI) 46.7kg/m. 10 of these were diabetics who underwent a SG. The impact of the pre-operative NLR on the percentage of excess weight loss (%EWL) and remission of diabetes 1 year post-operative were examined. The %EWL at 1 year post-operative were 46.3%. Improvements were also evident in the diabetes at 1 year post-operative : complete remission (CR) 40%, partial remission (PR) 20% and Improve 40%. Comparing pre-operative NLR in %EWL<50% and ≧50% in 1 year post-operative, <50% was 2.64 and ≧50% was 2.03. The NLR in CR and PR was significantly lower than that in Improve. The pre-operative NLR may be a predictive marker of weight loss and improving diabetes after SG. J. Med. Invest. 70 : 140-144, February, 2023.

The Journal of Medical Investigation : JMI


Prognostic impact of frailty after gastrectomy in elderly gastric cancer patients.

Frailty plays a crucial role in cancer patients who have received surgery in this recent aging society. We aimed to investigate frailty as a prognostic factor in elderly gastric cancer (GC) patients who underwent curative gastrectomy. We analyzed 86 elderly (over 75 years old) GC patients who underwent curative gastrectomy. Patients were assigned to two groups;frailty group (n=29) and no-frailty group (n=57). Clinicopathological values were compared between the two groups. The OS rate of the frailty group was significantly poorer than that of the no-frailty group (5-yr OS rate;frailty group 52.49% vs. no-frailty group 74.87%, p<0.05). Multivariate analysis of the OS showed that frailty tended to be significant prognostic factor (p=0.09). The DFS rate of the frailty group was significantly poorer than that of the no-frailty group (5-yr DFS rate;frailty group 42.30% vs. no-frailty group 71.55%, p<0.05). Multivariate analysis of the DFS showed that frailty tended to be significant prognostic factor (p=0.14). We identified the clinical impact of frailty prognostic factor for elderly GC patients who underwent gastrectomy. J. Med. Invest. 70 : 423-429, August, 2023.

The journal of medical investigation : JMI


Impact of L-type amino acid transporter 1 on intrahepatic cholangiocarcinoma.

Amino acid transporters, such as L-type amino acid transporter 1 (LAT1), have an effect on tumor growth, metastasis, and survival of various solid tumors. However, the role of LAT1 in patients with intrahepatic cholangiocarcinoma (IHCC) remains unknown. Forty-six patients who had undergone initial hepatic resection for IHCC at Tokushima University Hospital were enrolled in this study. Immunohistochemical analysis of LAT1 and phosphorylated Akt (p-AKT) was performed using resected specimens. Clinicopathological factors, including prognosis, were analyzed between LAT1-high and LAT1-low groups. The LAT1-high group showed a higher proportion of periductal infiltrating type and higher carcinoembryonic antigen/carbohydrate antigen 19-9 levels compared with the LAT1-low group. Multivariate analysis revealed that LAT1-high expression was an independent prognostic factor for disease-free survival. Furthermore, the proportion of p-AKT positivity was higher in the LAT1-high group than in the LAT1-low group. LAT1 expression was associated with poor prognosis of IHCC and higher p-Akt expression. J. Med. Invest. 70 : 160-165, February, 2023.


Role of IDO expression in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy.

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.


Visualization of the pelvic nerves using magnetic resonance imaging for 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.


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

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)

The Japanese Journal of Gastroenterological Surgery


Impact of L-type amino acid transporter 3 on the prognosis of hepatocellular carcinoma.

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.


Lymph node response to neoadjuvant chemotherapy as an independent prognostic factor in gastric cancer.

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.


Computed tomography texture analysis for the prediction of lateral pelvic lymph node 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.


Impact of osteopenia and neutropenia in patients with colorectal cancer treated with FOLFOXIRI: a retrospective cohort study.

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.

International Journal of Clinical Oncology


Intraoperative holographic image-guided surgery in a transanal approach for rectal cancer.

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.

Langenbeck's Archives of Surgery / Deutsche Gesellschaft für Chirurgie


Preoperative nutrition and exercise intervention in frailty patients with gastric cancer undergoing gastrectomy.

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.


Polymethoxylated flavone sudachitin is a safe anticancer adjuvant that targets glycolysis in cancer-associated fibroblasts.

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.


Pincer Approach to Gastrosplenic Ligament in Robotic Total Gastrectomy for Gastric Cancer.


Vascular variations encountered during laparoscopic surgery for transverse colon, splenic flexure, and descending colon cancer: a retrospective cohort study.

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.


Four cases of gastric adenocarcinoma and proximal polyposis of the stomach treated by robotic total gastrectomy.

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.


Blue light irradiation inhibits the growth of colon cancer and activation of cancer-associated fibroblasts.

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.


Risk factors for postoperative ileus after diverting loop 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.


【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

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)

The Japanese Journal of Surgical Metabolism and Nutrition


The correlation of immunoscore and frailty in colorectal cancer.

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.

International Journal of Clinical Oncology


Epigallocatechin 3allate hinders metabolic coupling to suppress colorectal cancer malignancy through targeting aerobic glycolysis in cancerssociated fibroblasts.

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.


Usefulness of a stepwise training program for laparoscopic gastrectomy.

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.


Strategy for laparoscopic repair of inguinal hernia after robot-assisted radical prostatectomy.

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.


A "diversity and inclusion" lecture for promoting self-awareness among medical students.

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.


Propensity Score-Matched Analysis of the Short- and Long-Term Outcomes of Robotic Versus Laparoscopic Gastrectomy for Gastric Cancer.

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.


ASO Author Reflections: The Role of Robotic Gastrectomy for Gastric Cancer.


Short-term outcomes of laparoscopic / robotic gastrectomy compared with open gastrectomy for advanced gastric cancer following chemotherapy.

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.

The Journal of Medical Investigation : JMI


High Ligation of the Inferior Mesenteric Artery Induces Hypoperfusion of the Sigmoid Colon Stump During Anterior 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.


The role of the immunoescape in colorectal cancer liver metastasis.

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.


Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma 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.


Usefulness of Diagnostic Staging Laparoscopy for Advanced Gastric Cancer.

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.


The BAFF/NF B axis is crucial to interactions between sorafenib-resistant HCC cells and cancer-associated fibroblasts.

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.


A Transabdominal Robotic Purse-String Suture Technique for Transanal Total Mesorectal Excision.

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.

Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A