Effect of duodenal-jejunal bypass on diabetes in the early postoperative period

<jats:title>Abstract</jats:title><jats:p>Metabolic surgery is an effective treatment for patients with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the effect of duodenal-jejunal bypass (DJB) in a rat model of T2DM during the early postoperative period. A rat model of non-obese T2DM was allocated to two groups: a sham group and a DJB group. On postoperative day 1 (1POD), oral glucose tolerance testing (OGTT) was performed and the changes of glucose transporter expressions in the small intestine was evaluated. [18F]-fluorodeoxyglucose ([18]-FDG) uptake was measured in sham- and DJB-operated rats using positron emission tomography-computed tomography (PET-CT). DJB improved the glucose tolerance of the rats on 1POD. The expression of sodium-glucose cotransporter 1 (SGLT1) and glucose transporter 1 (GLUT1) was high, and that of GLUT2 was low in the alimentary limb (AL) of rats in the DJB group. PET-CT showed that [18F]-FDG uptake was high in the proximal jejunum of DJB-operated rats. These results may show that DJB improve glucose tolerance in very early postoperative period as the result of glucose accumulation in the AL because of changes in glucose transporter expression.</jats:p>


Effect of duodenal-jejunal bypass on diabetes in the early postoperative period.

Metabolic surgery is an effective treatment for patients with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the effect of duodenal-jejunal bypass (DJB) in a rat model of T2DM during the early postoperative period. A rat model of non-obese T2DM was allocated to two groups: a sham group and a DJB group. On postoperative day 1 (1POD), oral glucose tolerance testing (OGTT) was performed and the changes of glucose transporter expressions in the small intestine was evaluated. [18F]-fluorodeoxyglucose ([18]-FDG) uptake was measured in sham- and DJB-operated rats using positron emission tomography-computed tomography (PET-CT). DJB improved the glucose tolerance of the rats on 1POD. The expression of sodium-glucose cotransporter 1 (SGLT1) and glucose transporter 1 (GLUT1) was high, and that of GLUT2 was low in the alimentary limb (AL) of rats in the DJB group. PET-CT showed that [18F]-FDG uptake was high in the proximal jejunum of DJB-operated rats. These results may show that DJB improve glucose tolerance in very early postoperative period as the result of glucose accumulation in the AL because of changes in glucose transporter expression.


Muscle strength is a stronger prognostic factor than muscle mass in patients with gastrointestinal and hepatobiliary-pancreatic cancers.

Sarcopenia has been reported as a prognostic risk factor in patients with gastrointestinal (GI) and hepatobiliary pancreatic (HBP) cancers. This study aimed to investigate whether the loss of muscle mass or strength is a stronger prognostic factor, and explore the cutoff values of skeletal muscle mass index (SMI) and handgrip strength (HGS) based on the survival outcome in patients with GI and HBP cancers. A total of 480 elderly patients with primary GI and HBP cancers who underwent their first resection surgery were analyzed retrospectively. Patients were divided into four groups: Appropriate SMI and HGS, low SMI alone, low HGS alone, and low SMI and HGS. Low SMI was derived from a bioelectrical impedance analysis, and low HGS was defined according to the Asian Working Group for Sarcopenia 2019 criteria. The multivariate analysis showed that low SMI was a significant risk factor for mortality in men only, but low HGS was significant in both sexes. From the multivariate analysis of the four groups, low HGS alone and low SMI and HGS showed a significantly higher hazard ratio than appropriate SMI and HGS in both sexes. An SMI of 7.21 kg/m and HGS of 28 kg were obtained as cutoff values based on the 3-y survival outcomes in men. Low muscle strength was a stronger prognostic factor than low muscle mass. Therefore, measuring muscle strength in all patients is essential.


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.


Development and Validation of Cutoff Value for Reduced Muscle Mass for GLIM Criteria in Patients with Gastrointestinal and HepatobiliaryPancreatic Cancers

The Global Leadership Initiative on Malnutrition (GLIM) criteria recommends using race- and sex-adjusted cutoff values for reduced muscle mass (RMM), but the only cutoff values available for Asians are the skeletal muscle mass index (SMI) established by the Asian Working Group for Sarcopenia (AWGS). This retrospective study aimed to develop and validate cutoff values for the fat-free mass index (FFMI) and arm circumference (AC) of Asians, and to investigate the association between GLIM malnutrition and prognosis. A total of 660 patients with primary gastrointestinal (GI) and hepatobiliary-pancreatic (HBP) cancers who underwent their first resection surgery were recruited and randomly divided into development and validation groups. The FFMI and AC cutoff values were calculated by receiver operating characteristic curve analysis for the AWGS SMI as the gold standard. The cutoff values for each RMM were used to diagnose malnutrition on the basis of GLIM criteria, and the survival rates were compared. The optimal FFMI cutoff values for RMM were 17 kg/m for men and 15 kg/m for women, and for AC were 27 cm for men and 25 cm for women. In the validation group, the accuracy of the FFMI and AC cutoff values to discriminate RMM were 85.2% and 68.8%, respectively. Using any of the three measures of RMM, overall survival rates were significantly lower in the GLIM malnutrition group. In conclusion, the cutoff values for the FFMI and AC in this study could discriminate RMM, and GLIM malnutrition using these cutoff values was associated with decreased survival.


Two Cases of Robot-Assisted Total Pelvic Exenteration and Intracorporeal Ileal Conduit for Locally Advanced Rectal Cancer

局所進行直腸癌に対してロボット支援骨盤内臓全摘除術および体腔内回腸導管造設術を施行した2例

We describe two cases of locally advanced rectal cancer (LARC) treated with robot-assisted total pelvic exenteration (Ra-TPE) and intracorporeal ileal conduit (ICIC). The first case was in a 71-year-old man with LARC (RbP, T4bN2bM0, cStage IIIc). He was started on bevacizumab+S-1/oxaliplatin therapy in July 2019. In April 2020, he developed Fournier's gangrene due to subcutaneous penetration of rectal cancer. Emergency drainage and colostomy were performed simultaneously, and a percutaneous vesical fistula was created. In May 2020, Ra-TPE and ICIC were performed. Histopathological analysis revealed moderately differentiated tubular adenocarcinoma (ypT3N0, RM0). At postoperative 9 months, thoracoscopic right upper lobectomy was performed for a right metastatic lung tumor. At present, ie, at postoperative 12 months, the patient has been free of recurrence and metastasis, with a carcinoembryonic antigen (CEA) level of 1.4 ng/ml and carcinoma antigen (CA) 19-9 level of 11 U/ml. The second case was in a 61-year-old man with fistula-associated anal cancer (PRb, T4N3M1b, cStage IVb). In April 2019, he was started on FOLFOXIRI+cetuximab therapy. In August 2020, Ra-TPE, ICIC, and transperineal total mesenteric excision were performed. Histopathological analysis revealed adenocarcinoma (ypT4N0, RM0). At postoperative 11 months, thoracoscopic left lower lobectomy was performed for a left metastatic lung tumor. At present, ie, at postoperative 12 months, the patient remains free of recurrence and metastasis, with a CEA level of 7.3 ng/ml and CA19-9 level of 12 U/ml. Ra-TPE, which allows transperineal removal of a specimen, can be performed as a minimally invasive surgery in combination with ICIC.


Malnutrition by European Society for Clinical Nutrition and Metabolism criteria predicts prognosis in patients with gastrointestinal and hepatobiliary-pancreatic cancer

The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed the ESPEN diagnostic criteria (EDC) for malnutrition in 2015. There is no report on the association between the EDC and prognosis in patients with gastrointestinal (GI) and hepatobiliary-pancreatic (HBP) cancer. This study aimed to (1) determine the prevalence of EDC malnutrition, (2) investigate the validity of the EDC as a nutritional and prognostic indicator, and (3) examine which components of the EDC are most related to long-term prognosis in patients with GI and HBP cancers. A total of 634 patients with primary GI and HBP cancers who underwent their first resection surgery between July 2014 and March 2018 were retrospectively recruited. According to the EDC, patients were divided into malnourished and non-malnourished groups. Clinical parameters and survival between these two groups were compared. The prognostic effects of the EDC and the EDC components were analyzed using Cox proportional hazard models. The prevalence of EDC malnutrition was 22%. Anthropometric data and biochemical data were associated with EDC malnutrition. The 5-year survival rate was lower in the malnourished group (72%) than in the non-malnourished group (73%; P = 0.007). The multivariate analysis demonstrated that the malnourished group was an independent risk factor for mortality (hazard ratio = 1.70 in the malnourished group; 95% confidence interval 1.08-2.63; P = 0.024). Among EDC components, body mass index (BMI) of <18.5 kg/m was an independent poor prognostic factor. EDC malnutrition is associated with poor postoperative long-term prognosis. Among the EDC components, BMI of <18.5 kg/m is most associated with prognosis in patients with preoperative GI and HBP cancers.


Impact of phase angle on postoperative prognosis in patients with gastrointestinal and hepatobiliary-pancreatic cancer


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.


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.


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.

Journal of Gastroenterology and Hepatology


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.


手術手技 合併症から学ぶ腹腔鏡下胃全摘出術R-Y再建の工夫

手術手技 合併症から学ぶ腹腔鏡下胃全摘出術R-Y再建の工夫


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.


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


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.


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.


Metabolic surgeryのインパクト 肥満・糖尿病の治療が変わる

Metabolic surgeryのインパクト 肥満・糖尿病の治療が変わる


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.


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.


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.


Transoral Anvil Delivery System With Tension-Free Method for Esophagojejunostomy After Laparoscopic Total Gastrectomy Prevents The Postoperative Stenosis.


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.


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.


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


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.


クリニカルカンファレンスから(第23回) 徳島大学病院の症例 高度肥満による続発性無月経に対し腹腔鏡下スリーブ状胃切除術を施行し妊娠・出産に至った一例


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.


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.


【大腸外科医のための骨盤解剖学】直腸癌手術に必要な画像シミュレーション

【大腸外科医のための骨盤解剖学】直腸癌手術に必要な画像シミュレーション


【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.


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.


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


Lymphocyte to C-reactive protein ratio predicts long-term outcomes for patients with lower rectal cancer.

The lymphocyte to C-reactive protein (CRP) ratio (LCR) is an indicator of systemic inflammation and host-tumor cell interactions. The aim of this study was to investigate the prognostic significance of LCR in lower rectal cancer patients who received preoperative chemo-radiotherapy (CRT). Forty-eight patients with lower rectal cancer who underwent CRT followed by curative surgery were enrolled in this study. Routine blood examinations were performed before and after CRT were used to calculate pre-CRT LCR and post-CRT LCR. The median LCR was used to stratify patients into low and high LCR groups for analysis. The correlation between pre- and post-CRT LCR and clinical outcomes was retrospectively investigated. The pre-CRT LCR was significantly higher than the post-CRT LCR (11,765 and 6780, respectively, P < 0.05). The 5-year overall survival rate was significantly higher for patients with high post-CRT LCR compared with low post-CRT LCR (90.6% and 65.5%, respectively, P < 0.05). In univariate analysis, post-CRT LCR, post-CRT neutrophil to lymphocyte ratio, and fStage were significant prognostic factors for overall survival. In multivariate analysis, post-CRT LCR, but not other clinicopathological factors or prognostic indexes, was a significant prognostic factor for overall survival (P < 0.05). Post-CRT LCR could be a prognostic biomarker for patients with lower rectal cancer.


Intestinal hypoperfusion in patients with Crohn's disease revealed by intraoperative indocyanine green fluorescence imaging.

Anastomotic leakage has been reported as an independent risk factor for surgical recurrence at the anastomotic site in patients with Crohn's disease. An inadequate blood supply may contribute to this leakage. Real-time indocyanine green angiography has been useful for confirming vascular perfusion of the intestines. The aim of this study was to evaluate the use of intraoperative indocyanine green angiography to detect vascular perfusion of the intestines during ileocaecal resection in patients with Crohn's disease and colon cancer. We retrospectively evaluated the medical records of 26 consecutive patients with colon cancer arising in the caecum or ascending colon and 3 consecutive patients with Crohn's disease without a history of disease-related surgery. The patients in the 2 cohorts had undergone ileocaecal resection at Tokushima University Hospital between January 2018 and January 2021. After ileocaecal resection, blood flow was evaluated in ileal (oral) and colon (anal) stapled stumps by indocyanine green fluorescence angiography. The fluorescence time was defined as the time from indocyanine green injection and flush of the injection route to the point when the stump showed the strongest fluorescent signal in the monitor. The fluorescence time for the ileal and colon stumps in patients with Crohn's disease was 43.3 8.8 s each and was significantly longer than the fluorescence time in the patients with colon cancer (29.4 6.5 s and 29.6 6.8 s, respectively) (P < 0.05). Intraoperative indocyanine green fluorescence imaging is safe and reproducible for assessing intestinal perfusion prior to anastomosis in patients with colon cancer and Crohn's disease.


The influence and countermeasure of obesity in laparoscopic colorectal resection.

The aim of this study was to investigate the influence of obesity and the usefulness of a preoperative weight loss program (PWLP) for obese patients undergoing laparoscopic colorectal resection (LCR). Study 1: 392 patients who underwent LCR for colorectal cancer were divided into two groups: those with a body mass index (BMI) ·25 kg/m (n = 113) and those with a BMI <25 kg/m (n = 279). The influence of BMI on LCR was investigated. Study 2: Patients with a BMI ·28 kg/m who were scheduled to undergo LCR (n = 7, mean body weight 87.0 kg, mean BMI 33.9 kg/m) undertook a PWLP including caloric restriction and exercise for 29.6 (15-70) days. The effects of this program were evaluated. Study 1: The BMI ·25 kg/m group had a prolongation of operation time and hospital stay than the BMI <25 kg/m group. Study 2: The patients achieved a mean weight loss of 6.9% (-6.0 kg). The mean visceral fat area was significantly decreased by 18.0%, whereas the skeletal muscle mass was unaffected. The PWLP group had a significantly lower prevalence of postoperative complications compared with the BMI ·25 kg/m group. Obesity affected the surgical outcomes in LCR. A PWLP may be useful for obese patients undergoing LCR.


Effect of TU-100 on Peyer's patches in a bacterial translocation rat model.

Daikenchuto (TU-100), a Japanese herbal medicine, is widely used for various gastrointestinal diseases. We have previously reported that TU-100 suppresses CPT-11-induced bacterial translocation (BT) by maintaining the diversity of the microbiome. In this study we show that TU-100 modulates the immune response during BT by inducing PD-1 expression in Peyer's patches. Eighteen male Wistar rats were divided into four groups: a control group; a control + TU-100 group, given TU-100 1000 mg/kg orally for 5 d; a BT group, given CPT-11 250 mg/kg intra-peritoneal for 2 d; and a TU-100 group, given TU-100 1000 mg/kg orally for 5 d with CPT-11 250 mg/kg intra-peritoneal on days 4 and 5. The size of Peyer's patch was significantly bigger in the BT group compared to the control group (9.0 104 m vs 29.4 104 m, < .05), but improved in the TU-100 group (15.4 104 m, < .005). TU-100 significantly induced PD-1 expression in Peyer's patch compared to the control group and the BT group (control vs BT vs TU-100 = 4.3 4.9 vs 5.1 10.3 vs 17.9 17.8). The CD4 cells were increased in the BT group ( < .05) compared to the control group but decreased in the TU-100 group. The Foxp3 cells were increased in the BT group compared to the control group ( < .05), and further increased in the TU-100 group compared to the BT group. CPT-11 significantly increased TLR4, NF- , TNF- mRNA expressions in the BT group. TU-100 cotreatment significantly reversed these mRNA expressions. TU-100 may have a protective effect against BT through PD-1 expression in Peyer's patch.


Robotic-assisted total gastrectomy in a patient with gastric cancer associated with situs inversus totalis: With video.

Situs inversus totalis (SIT) refers to an inverted position of the major visceral organ as a "mirror image" of the regular location. We present a video of a robotic-assisted total gastrectomy in a 84-year-old man with SIT. The patient was diagnosed with advanced gastric cancer in the U region. The port placement was done as mirror images of our usual settings. Lymph node dissection was performed with a completely reverse approach to the usual procedure. After total gastrectomy, an intracorporal esophagojejunostomy was performed by circular method. All procedures were performed safely with no intraoperative complications and the patient was discharged uneventfully. Pathological diagnosis confirmed moderately differentiated adenocarcinoma and the depth of invasion was to the subserosa; there were five metastatic lymph nodes. In patients who have gastric cancer with SIT, a robotic-assisted total gastrectomy can be performed safely without surgical complication. Robots are useful for performing a total gastrectomy in SIT.


Pre-operative Weight Loss Program for Obese Patients Undergoing Laparoscopic Gastrectomy.

Background : The aim of this study was to investigate the influence of obesity and the usefulness of a pre-operative weight loss program (PWLP) for obese patients undergoing laparoscopic gastrectomy (LG) for gastric cancer (GC). Materials and Methods : Study1 : 219 patients who underwent laparoscopic distal gastrectomy (LDG) for GC were divided into 2 groups : body mass index (BMI) 28 and BMI < 28kg /2. The influence of BMI in LG surgery was investigated. Study2 : The BMI 28 kg /2 patients with a planned LG (n = 8) undertook a PWLP including calorie restriction and exercise. The effects of this program were evaluated. Results : Study1 : The BMI 28kg /2 group showed significantly longer operation times, more blood loss and a higher frequency of post-operative complications than that of the BMI < 28kg /2 group. Study 2 : The patients achieved a weight loss of 4.2%. The visceral fat area (VFA) was significantly decreased by 10.6%, whereas skeletal muscle mass was unaffected. The PWLP group showed shorter operation times, less blood loss and a lower frequency of post-operative complications compared with that of the BMI 28kg /2 group. Conclusion : Obesity is an important risk factor and a pre-operative weight loss program is useful for obese patients undergoing a LG. J. Med. Invest. 68 : 165-169, February, 2021.

The Journal of Medical Investigation : JMI


A multicenter phase II trial of preoperative chemoradiotherapy with S-1 plus oxaliplatin and bevacizumab for locally advanced rectal cancer.

We clarified the safety and efficacy of preoperative chemoradiotherapy for locally advanced rectal cancer using a multidrug regimen (S-1 +xaliplatin +evacizumab). This multicenter phase II trial involved 47 patients with locally advanced rectal cancer. All patients received S-1 orally (80 mg/m/day on days 1-5, 8-12, 15-19, and 22-26) and infusions of oxaliplatin (50 mg/m on days 1, 8, 15, and 22) and bevacizumab (5 mg/kg on days 1 and 15). The total radiation dose was 40 Gy delivered in daily fractions of 2 Gy via the four-field technique. The primary endpoint was the pathological complete response rate. The secondary endpoints were safety (incidence of adverse events) and clinical response, relapse-free survival, overall survival, local recurrence, R0 resection, downstaging, and treatment completion rates. All 47 patients received chemoradiotherapy, and 44 patients underwent curative resection. Two patients refused surgery and selected a watch-and-wait strategy. The pathological complete response rate was 18.2% in patients who underwent curative resection. The clinical response rate was 91.3% in 46 patients. Concerning hematotoxicity, there was one grade 4 adverse event (2.1%) and seven grade 3 events (14.9%). Diarrhea was the most frequent non-hematotoxic event, and the grade 3 event rate was 25.5%. Although preoperative chemoradiotherapy for patients with locally advanced rectal cancer using the S-1 +xaliplatin +evacizumab regimen did not achieve the expected pathological complete response rate, this regimen led to an improved clinical response rate.

International Journal of Clinical Oncology


Clinical analysis of postoperative venous thromboembolism in Japanese patients after colorectal cancer surgery.

Venous thromboembolism (VTE) is a major complication after abdominal surgery; however, the best strategy for preventing VTE after surgery is not yet established. We performed this study to investigate the incidence of perioperative VTE and evaluate the efficacy of a VTE preventive strategy for patients undergoing surgery for colorectal cancer (CRC). The subjects of this retrospective analysis were 228 patients who underwent curative surgical resection for CRC between 2012 and 2016. The patients were treated with thromboprophylaxis including enoxaparin. We assessed the perioperative VTE occurrence rate and investigated the risk factors for postoperative VTE. Among the 228 patients, 77 had a preoperative D-dimer level of > 1.0 g/mL and 12 had deep vein thrombosis (DVT) diagnosed by ultrasonography preoperatively. Of the remaining 216 patients, short-term VTE (< 30 days) developed in two patients (0.9%) and long-term VTE (30 days-3 years) developed in seven (3.2%). The mortality rate of patients with VTE was 0%. The univariate analysis indicated that pulmonary disease was the risk factor for short-term VTE, whereas obesity, hyperlipidemia, and a preoperative history of pulmonary embolism were the risk factors for long-term VTE (p < 0.05). The findings of this analysis show that our preventive protocol including enoxaparin is an effective strategy for preventing postoperative VTE.


SDF-1 expression after preoperative chemoradiotherapy is associated with prognosis in patients with advanced lower rectal cancer.

Stromal cell-derived factor-1 (SDF-1) expression is associated with cancer progression, as a biomarker of prognosis. We clarified the significance of SDF-1 expression on chemoradiotherapy (CRT) resistance and prognosis in advanced lower rectal cancer patients. We evaluated 98 patients with advanced lower rectal cancer who underwent preoperative CRT. All patients received 40 Gy of radiation therapy, with concurrent chemotherapy containing fluorinated pyrimidines, followed by surgical resection. SDF-1 expression in surgical specimens was examined by immunohistochemistry. We divided the patients into SDF-1-positive- (n = 52) and SDF-1-negative groups (n = 46) and compared the clinicopathological factors and survival rates. The SDF-1-positive group was more resistant to CRT than the SDF-1-negative group (non-responder rate, 63.5% vs. 47.8%, respectively ; p = 0.12). Overall survival (OS) in the SDF-1 positive group was significantly poorer vs. the SDF-1-negative group (5-year OS, 73.4% vs. 88.0%, respectively ; p = 0.02), and disease-free survival (DFS) was worse (5-year DFS, 61.0% vs. 74.1%, respectively ; p = 0.07). Multivariate analysis confirmed that SDF-1 expression was a significant independent prognostic predictor of OS (p = 0.04). SDF-1 expression after preoperative CRT is significantly associated with a poor prognosis in advanced lower rectal cancer patients and is a promising biomarker. J. Med. Invest. 68 : 309-314, August, 2021.


Usefulness of a multidisciplinary surgical site infection team in colorectal surgery.

Background : Surgical site infection (SSI) is an adverse event that places a major burden on patients and staff. In this study, we examined the occurrence of SSI and the characteristics of patients referred to the SSI team after colorectal surgery. Methods : In total, 955 patients underwent colorectal surgery at our hospital from 2014 to 2019. Of these 955 patients, 516 received therapeutic support by the SSI team from 2017 to 2019. All patients were evaluated using an SSI surveillance sheet, and we checked for reports of SSI once a month. Each attending physician performed SSI prophylaxis (use of new instruments before wound irrigation and closure). Results : SSI occurred in 80 (8.4%) patients. The incidence of SSI and the incidence of surface SSI were higher in the patients who did not receive intervention by the SSI team than in the patients who did. Organ /pace SSI occurred in 18 patients. Among patients with surface SSI, Enterococcus was the most commonly detected bacteria. Among the 18 patients with organ /pace SSI, 5 developed anastomotic leakage and 4 developed intra-abdominal abscesses. Conclusions : An SSI team for prevention and treatment of infection may contribute to reduction of SSI. J. Med. Invest. 68 : 256-259, August, 2021.