A Patient with Transverse Colon Cancer Complicated by Cowden Syndrome Administered FOLFOXIRI + Bevacizumab Therapy.

Cowden syndrome is characterized by several clinical features related to tumorous lesions primarily consisting of systemic hamartomas. The mutation of a tumor suppressor gene, the PTEN gene, is etiologically involved. As gastrointestinal lesions, polyps of all digestive tracts involving the esophagus to rectum develop. In patients with Cowden syndrome, the risk of colorectal cancer may increase. However, the characteristics of colorectal cancer in these patients remain to be clarified and sufficient findings regarding chemotherapy have not been obtained. A 39-year-old man was treated with a colonic stent for colitis obstructive due to circumferential transverse colon carcinoma. After decompression, elective extended laparoscopic right hemicolectomy was performed. Preoperative systemic detailed examination revealed characteristic dermal/mucosal findings, polyposis of the upper digestive tract, and a thyroid tumor. On PTEN gene sequencing, a mutation was detected at codon 130 of exon 5, leading to a diagnosis of Cowden syndrome. Postoperative adjuvant chemotherapy was performed for 6 months, but recurrent peritoneal dissemination was observed 1 month after its completion. FOLFOXIRI + bevacizumab therapy was started. Transiently, a partial response was achieved in peritoneally disseminated nodes according to the RECIST. There was no increase in the volume of cancerous ascites. However, an increase in the volume of ascites and local relapse were noted at the completion of the tenth course. The regimen was switched to FOLFIRI + panitumumab, but peritoneal dissemination exacerbated and the patient died 18 months after surgery.

Case report: Whole genome sequence of Clostridium perfringens JUM001 causing acute emphysematous cholecystitis.

A strain of Clostridium perfringens was isolated from the bile sample of a patient with emphysematous cholecystitis who underwent a laparoscopic cholecystectomy, followed by treatment with meropenem and recovery. Metagenomic analysis of the bile sample showed that 99.73% of the bile microbiota consisted of C. perfringens, indicating that C. perfringens JUM001 was the causative pathogen of acute emphysematous cholecystitis in this patient. Complete genome sequencing showed that C. perfringens JUM001 contained a circular chromosome of 3,231,023 bp and two circular plasmids, pJUM001-1 of 49,289 bp and pJUM001-2 of 47,855 bp. JUM001 was found to possess a typing toxin gene, plc, but no other typing toxin genes, indicating that its toxinotype is type A. The plasmids pJUM001-1 and pJUM001-2 belonged to the pCP13-like and pCW3-like families of plasmids, respectively, which are characteristic conjugative and archetypical plasmids of C. perfringens. Phylogenetic analysis showed that JUM001 was closely related to C. perfringens strain JXNC-DD isolated from a dog in China. To our knowledge, this is the first report of whole-genome sequences of a clinical isolate of C. perfringens causing acute emphysematous cholecystitis.

Impact of post-operative paralytic ileus on post-operative outcomes after surgery for colorectal cancer: a single-institution, retrospective study.

PURPOSE: Post-operative paralytic ileus (POI) occurs after surgery because of gastrointestinal dysfunction caused by surgical invasion. We therefore investigated the frequency of POI after laparoscopic colorectal surgery in patients with colorectal cancer using a strictly defined POI diagnosis and identified associated risk factors. METHODS: Patients who underwent initial laparoscopic surgery for colorectal cancer between January 2014 and December 2018 were included. The primary end point was the incidence of POI. A multivariate logistic regression analysis revealed the contributing risk factors for POI. RESULTS: Of the 436 patients, 94 (21.6%) had POI. Compared with the non-POI group, the POI group had significantly higher frequencies of infectious complications (p < 0.001), pneumonia (p < 0.001), intra-abdominal abscess (p = 0.012), anastomotic leakage (p = 0.016), and post-operative bleeding (p = 0.001). In the multivariate analysis, the right colon (odds ratio [OR] 2.180, p = 0.005), pre-operative chemotherapy (OR 2.530, p = 0.047), pre-operative antithrombotic drug (OR 2.210, p = 0.032), and post-operative complications of CD grade ≥ 3 (OR 12.90, p < 0.001) were independent risk factors for POI. CONCLUSION: Post-operative management considering the risk of post-operative bowel palsy may be necessary for patients with right colon, pre-operative chemotherapy, pre-operative antithrombotic drug or severe post-operative complications.

Laparoscopic Triple Segmental Bowel Resection for Endometriosis Revealed by Rectal Obstruction during Infertility Treatment.

Intestinal endometriosis is a benign disease characterized by ectopic growth of the endometrium and causes extensive fibrosis and adhesions in response to repeated episodes of bleeding and inflammation with the menstrual cycle. We encountered a rare case of intestinal endometriosis that caused complete rectal obstruction in a 34-year-old woman undergoing infertility treatment. Colonoscopy showed rectal stenosis and obstruction but no evidence of a tumor. Bowel obstruction due to endometriosis was diagnosed based on the history and imaging findings. Transanal decompression was performed. Subsequent laparoscopic surgery revealed severe inflammation around both ovaries and a tumor-like rectal stenosis. Similar findings were obtained in the transverse colon and terminal ileum. We performed laparoscopic low anterior resection, partial transverse colon resection, ileocecal resection, bilateral cystectomy, and left salpingectomy. Infertility treatment was restarted and resulted in a successful term pregnancy. The patient remains well. Laparoscopic surgery, which has the advantage of being minimally invasive, allows for early postoperative recovery and discharge in patients with endometriosis; furthermore, the uterus and adnexa can be preserved due to the magnifying effect of the laparoscope. In this case, it was possible to resume infertility treatment. Intestinal endometriosis is a rare cause of bowel obstruction, but should be kept in mind if intestinal obstruction occurs during infertility treatment. Laparoscopic surgery may be useful for multiple endometriotic lesions and serve as a bridge to infertility treatment.

Microwell bag culture for large-scale production of homogeneous islet-like clusters.

Pluripotent stem-cell derived cells can be used for type I diabetes treatment, but we require at least 105-106 islet-like clusters per patient. Although thousands of uniform cell clusters can be produced using a conventional microwell plate, numerous obstacles need to be overcome for its clinical use. In this study, we aimed to develop a novel bag culture method for the production of uniform cell clusters on a large scale (105-106 clusters). We prepared small-scale culture bags (< 105 clusters) with microwells at the bottom and optimized the conditions for producing uniform-sized clusters in the bag using undifferentiated induced pluripotent stem cells (iPSCs). Subsequently, we verified the suitability of the bag culture method using iPSC-derived pancreatic islet cells (iPICs) and successfully demonstrate the production of 6.5 × 105 uniform iPIC clusters using a large-scale bag. In addition, we simplified the pre- and post-process of the culture-a degassing process before cell seeding and a cluster harvesting process. In conclusion, compared with conventional methods, the cluster production method using bags exhibits improved scalability, sterility, and operability for both clinical and research use.

Body composition assessment and sarcopenia in patients with biliary tract cancer: A systematic review and meta-analysis.

BACKGROUND: Sarcopenia, as assessed by body composition, can affect morbidity and survival in several gastrointestinal cancer. However, the impact of sarcopenia, referring to both quantity and quality of skeletal muscle, in biliary tract cancer (BTC) is debatable. We aimed to investigate the impact of sarcopenia on morbidity and mortality in patients with BTC. METHODS: Electronic databases and trial registries were searched through July 2021 to perform random-effects meta-analyses. Study selection, data abstraction and quality assessment were independently performed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Twenty-nine studies (4443 patients) were included; 28 used computed tomography and one used dual-energy X-ray absorptiometry to assess body composition. Eighteen studies reported the impact of pre-operative sarcopenia on postoperative outcomes; namely, sarcopenia increased postoperative complications (risk ratio = 1.23, 95% confidence interval [CI] = 1.07 to 1.41; I2 = 2%), and decreased recurrence-free survival (hazard ratio [HR] = 2.20, 95% CI = 1.75 to 2.75; I2 = 0%) in multivariable analyses. Low muscle quantity (HR = 2.26, 95% CI = 1.75 to 2.92; I2 = 66%) and quality (HR = 1.75, 95% CI = 1.33 to 2.29; I2 = 50%) decreased overall survival in multivariable analyses. The certainty of the evidence was low because of heterogeneity and imprecision. CONCLUSIONS: In sarcopenia, low muscle quantity and quality by body composition conferred an independent risk of morbidity and mortality in patients with BTC. Further studies are needed to confirm these findings and mitigate risk.

Surgical Procedures and Results of Modified Intraperitoneal Onlay Mesh Repair for Inguinal Hernia After Radical Prostatectomy.

Background: Although inguinal hernia occurs frequently after radical prostatectomy, transabdominal preperitoneal (TAPP) inguinal hernia repair occasionally poses challenges due to fibrosis of the preperitoneal cavity. In patients with severe intrapelvic fibrosis, we have adopted a modified intraperitoneal onlay mesh (IPOM) technique. The surgical factors were compared between patients who underwent modified IPOM and those who underwent TAPP for inguinal hernia repair. Materials and Methods: In total, 57 patients underwent laparoscopic surgery for inguinal hernias after radical prostatectomy between February 2013 and January 2020. TAPP was successfully completed in 44 patients, whereas 13 patients underwent modified IPOM converted from TAPP. The surgical results were retrospectively compared. Results: The median follow-up duration was 36.0 months (range, 1-84 months). Intraoperative complications, recurrence of hernia, and chronic pain were not observed in both groups. The average duration of surgery in the modified IPOM group was longer than that in the TAPP group (137 versus 107 minutes, P < .05). There was no significant difference in the incidence of the inguinal-related complications such as inguinal pain or inguinal swelling. Conclusions: Postoperative complications including recurrence of hernia after modified IPOM are comparable to those after TAPP hernia repair. Modified IPOM repair is a surgical option for repairing inguinal hernias following radical prostatectomy.

Transabdominal preperitoneal repair using barbed sutures for bilateral inguinal hernia in liver cirrhosis with ascites.

The appropriate surgical treatment for inguinal hernia in patients with liver cirrhosis and ascites remains controversial. A 79-year-old male undergoing treatment for Child-Pugh B hepatitis C-induced liver cirrhosis and hepatocellular carcinoma complicated with bilateral inguinal hernia underwent transabdominal preperitoneal (TAPP) repair. During surgery, barbed sutures were used to facilitate appropriate peritoneal closure. His postoperative course was uneventful. Information on TAPP repair for inguinal hernia in patients with liver cirrhosis and ascites is limited. The International Guidelines for Inguinal Hernia Management recommend Lichtenstein repair for patients with ascites. TAPP repair requires peritonectomy via a posterior endoscopic approach; therefore, proper peritoneal closure is important to prevent the leakage of ascitic fluid. Herein, TAPP repair was safely and successfully completed using barbed sutures to achieve proper and strong peritoneal closure. TAPP repair using barbed sutures can be an effective treatment option for patients with liver cirrhosis and ascites.

Factors Affecting Persistent Splenomegaly After Adult-to-Adult Living Donor Liver Transplantation Using a Left Lobe.

BACKGROUND: The aim of the present study was to evaluate spleen volume (SV) and the factors influencing it after adult-to-adult living donor liver transplantation (A2LDLT) using a left lobe. METHODS: Pretransplant computed tomography (CT) and post-transplant CT 2 years after A2LDLT were examined by volumetric analysis in 24 patients. We divided the recipients into the following 2 groups according to the post-transplant SV: >500 mL (Group A) and ≤500 mL (Group B). The factors affecting the change in post-transplant SV were compared between the 2 groups. RESULTS: The mean pretransplant SV decreased significantly after A2LDLT. Platelet counts after living donor liver transplantation increased significantly relative to the pretransplant values. Post-transplant SV was >500 mL in 9 patients (Group A) and ≤500 mL in 15 (Group B). Pretransplant SV, platelet count, anhepatic time, operative time, intraoperative blood loss, post-transplant portal vein pressure >20 mm Hg, and post-transplant portal vein flow >250 mL/min/100 g graft weight showed significant differences between the 2 groups. Actual graft volume (GV) and GV/standard liver volume ratio showed no intergroup differences. Multivariate analysis showed that the only significant factor related to a post-transplant SV of >500 mL was the pretransplant SV. Post-transplant platelet counts were significantly increased from the pretransplant values in both Group A and Group B. CONCLUSIONS: Pretransplant SV is the only significant factor predicting a SV of >500 mL after A2LDLT. However, even in patients with a SV of >500 mL, the platelet count increased significantly from the pretransplant value.

Significance of hypovascular lesions on dynamic computed tomography and/or gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in patients with hepatocellular carcinoma.

BACKGROUND AND AIM: The natural course and clinical implications of hypovascular lesions on dynamic computed tomography and/or gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging were investigated. METHODS: We followed the patients with hepatocellular carcinoma (HCC) who underwent hepatectomy between April 2009 and August 2012 to determine whether new classical HCCs developed from these unresected borderline lesions or emerged in different areas. RESULTS: One hundred and eleven patients with HCC were identified to have undergone examinations using both imaging methods before hepatic resection. A total of 54 hypovascular lesions were detected. Gadolinium ethoxybenzyl-enhanced magnetic resonance imaging detected 51 lesions, while dynamic computed tomography identified 21 lesions. Eleven lesions were resected at the time of the hepatectomy together with the main HCCs. Classical HCCs had developed from 52.5% of the 43 unresected lesions at 3 years after hepatic resection. Subsequently, we conducted a patient-by-patient analysis to compare the development of classical HCC from these hypovascular lesions and the emergence of de novo classical HCC in other areas. The 3-year occurrence rate was 62.2% for the former group and 55.0% for the latter group (P = 0.83). Thus, although 52.2% of these hypovascular lesions had developed into classical HCCs at 3 years after the initial hepatectomy, de novo HCCs also occurred at other sites. Furthermore, new hypovascular lesions emerged after hepatectomy in 18-29% of patients irrespective of the presence or absence of hypovascular lesions at hepatectomy. CONCLUSIONS: It remains uncertain whether these hypovascular lesions should be resected together with the main tumors at the time of hepatectomy.

Clinical significance of macroscopic no-margin hepatectomy for hepatocellular carcinoma.

BACKGROUND: Hepatectomy with a sufficient margin is often impossible for hepatocellular carcinomas that are close to the large intrahepatic vascular structures, and macroscopically complete resection along the tumor capsule is the only choice. The aim of this retrospective study was to evaluate the clinical significance of macroscopic no-margin hepatectomy (MNMH). METHODS: Among patients undergoing macroscopically curative resection for untreated hepatocellular carcinoma, outcomes were compared between patients undergoing MNMH (n = 87) and those undergoing hepatectomy with a macroscopic margin (n = 192). RESULTS: MNMH was significantly associated with a longer operation time (P < 0.001), greater intraoperative blood loss (P < 0.001), a greater need for blood transfusion (P = 0.018), a higher incidence of major postoperative complications (P = 0.031), multiple tumors (P = 0.015), tumor capsule formation (P = 0.030), and a microscopically positive surgical margin (P = 0.021). There was no significant difference between the groups in terms of recurrence-free survival (P = 0.946) and overall survival (P = 0.259). DISCUSSION: MNMH is technically demanding and results more frequently in a microscopically positive surgical margin, however, it can yield a long-term outcome comparable to hepatectomy with a macroscopic margin even in patients with otherwise unresectable hepatocellular carcinoma.

Liver transplantation for deterioration in native liver function after portoenterostomy for biliary atresia in Japan: Short- versus long-term survivors.

PURPOSE: We reviewed our post-Kasai portoenterostomy biliary atresia (BA) patients who required liver transplantation (LTx) for deterioration in native liver (NL) function to investigate mortality in relation to age at LTx. METHODS: BA patients indicated for LTx when less than 18years old (U18; n=17) and when 18 or older (18+; n=13) were compared. All achieved jaundice clearance postoperatively (TBil ≤1.2mg/dL (≈20µmol/L)). RESULTS: In U18, living-donor (LD) LTxs were performed at a median of 6.1years (range: 0.5-16.7; n=14) and cadaveric (CD) LTxs at a median of 1.3years (1.1-1.5; n=3). In 18+, LDLTxs were performed at a median of 28years (18-37; n=8), and 1 case died from graft versus host disease. CDLTxs were indicated in 5, but 4 died at a median of 30years (26-32), a mean of 1.4years (0.7-1.8) after NL deterioration commenced. One case is awaiting CDLTx. At the time of review, all U18 and 7 LDLTx cases in 18+ were clinically stable. Mortality rates were 0% in U18 and 38% in 18+ (P=.006). CONCLUSION: Our results highlight the extremely grave prognosis for long-term BA patients requiring LTx when 18 or older because of poor donor availability in Japan. LEVEL OF EVIDENCE: Level III.

Risk Factors for Intractable Ascites After Adult-to-Adult Living Donor Liver Transplantation Using Left Lobe.

BACKGROUND: Intractable ascites is one of the causes of graft loss after adult-to-adult living donor liver transplantation (LDLT) using a small graft. Identification of factors associated with increasing posttransplant ascites has important implications for prevention and treatment. METHODS: All 59 consecutive adult patients who underwent left lobe LDLT without portal inflow modulation between October 2002 and February 2016 were prospectively enrolled. Factors associated with the average daily amount of ascites for 2 weeks after LDLT were assessed. RESULTS: The median daily amount of ascites during the 2 weeks was 1052 mL (range, 52-3480 mL). Although 16 of the 59 patients developed intractable ascites, exceeding 1500 mL daily (massive ascites group), the remaining 43 patients produced less than 1500 mL of ascites daily (nonmassive ascites group). The presence of pretransplant ascites (P = 0.001), albumin (P = 0.011), albumin/globulin ratio (P = 0.026), cold ischemia time (P = 0.004), operation time (P = 0.022), and pretransplant portal vein pressure (PVP) (P = 0.047) differed significantly between the 2 groups. Neither posttransplant PVP nor portal vein flow differed between the 2 groups. The variables associated with intractable ascites that remained significant after logistic regression analysis were pretransplant PVP (P = 0.047) and cold ischemia time (P = 0.049). After appropriate fluid resuscitation for intractable ascites, 58 (98%) of the 59 recipients were discharged from hospital after removal of the indwelling drains. CONCLUSIONS: It is important to shorten the scold ischemia time to reduce massive ascites after LDLT. Pretransplant portal hypertension is more closely associated with ascites production than posttransplant hemodynamic status.

Three hundred and sixty-eight consecutive pancreaticoduodenectomies with zero mortality.

BACKGROUND: Only a limited number of reports have documented zero mortality in consecutive pancreaticoduodenectomy series. The aim of this study is to review and verify our management aiming to eliminate mortality after pancreaticoduodenectomy. METHODS: Three hundred and sixty-eight consecutive patients undergoing pancreaticoduodenectomy between 2002 and 2015 were retrospectively reviewed. During this period, in order to enhance the safety of pancreaticoduodenectomy, we have used a consistent strategy consisting of early ligation of the inferior pancreatoduodenal artery, mucosal sutureless pancreaticojejunostomy combined with external pancreatic duct stenting, conditional two-stage pancreaticojejunostomy, jejunal decompression using tube jejunostomy, application of an omental flap to cover the stump of the gastroduodenal artery, and careful postoperative drain management. RESULTS: Major postoperative complications (Clavien-Dindo grade ≥ IIIa) occurred in 20 patients (5%). Grade A/B/C pancreatic fistula was observed in 49/29/4 patients (13%/8%/1%), respectively. Reoperation and readmission was necessary in five and four patients (1% and 1%), respectively. There was no in-hospital or 90-day mortality. CONCLUSIONS: To achieve zero mortality in pancreaticoduodenectomy, it is crucial to incorporate various strategies to minimize the degree of surgical invasiveness and the damage caused by pancreatic fistula with a meticulous approach to perioperative management.

Randomized Controlled Trial for Evaluation of the Routine Use of Nasogastric Tube Decompression After Elective Liver Surgery.

BACKGROUND: The value of routine nasogastric tube (NGT) decompression after elective hepatetctomy is not yet established. Previous studies in the setting of non-liver abdominal surgery suggested that the use of NGT decreased the incidence of nausea or vomiting, while increasing the frequency of pulmonary complications. STUDY DESIGN: Out of a total of 284 consecutive patients undergoing hepatectomy, 210 patients were included in this study. The patients were randomized to a group that received NGT decompression (NGT group; n = 108), in which a NGT was left in place after surgery until the patient passed flatus or stool, or a group that did not receive NGT decompression (no-NGT group; n = 102), in which the NGT was removed at the end of surgery. RESULTS: There were no differences between the NGT group and no-NGT group in terms of the overall morbidity (34.3 vs 35.3 %; P = 0.99), incidence of pulmonary complications (18.5 vs 19.5 %; P = 0.84), frequency of postoperative vomiting (6.5 vs 7.8 %; P = 0.70), time to start of oral intake (median (range) 3 (2-6) vs 3 (2-6) days; P = 0.69), or postoperative duration of hospital stay (19 (7-74) vs 18 (9-186) days; P = 0.37). In the no-NGT group, three patients required reinsertion of the tube 0 (0-3) days after surgery. In the NGT group, severe discomfort was recorded in five patients. CONCLUSIONS: Routine NGT decompression after elective hepatectomy does not appear to have any advantages.

Liver metastases from gastric cancer represent systemic disease in comparison with those from colorectal cancer.

BACKGROUND: The aim of this retrospective study was to clarify the difference in behavior and outcome after initial hepatectomy between gastric cancer liver metastases (GCLM) and colorectal cancer liver metastases (CCLM). METHODS: Data for patients undergoing curative hepatectomy for liver-only metastases from colorectal cancer (n = 193) and gastric cancer (n = 26) performed at single institution with the same criteria regarding the status of liver metastases were reviewed. Post-hepatectomy recurrence pattern, re-resection for recurrence, and three different endpoints were evaluated. RESULTS: There was no significant difference between the GCLM and the CCLM in the incidence of recurrence (69% vs. 63%, P = 0.553) and recurrence-free survival (median, 15.2 months vs. 16.5 months, P = 0.230) following initial hepatectomy for liver metastases. However, the GCLM had a higher frequency of systemic unresectable recurrences than the CCLM. Time to surgical failure (median, 15.2 months vs. 39.7 months, P = 0.006) and overall survival (median, 20.1 months vs. 66.2 months, P < 0.001) were significantly shorter in the GCLM than in the CCLM. CONCLUSIONS: GCLM shows more systemic and aggressive oncological behavior than CCLM after curative hepatectomy even when metastases are confined only to the liver at the time of initial hepatectomy.

Hypertrophy of the Left Liver in Patients with Large Tumors in the Right Liver.

BACKGROUND: It has been speculated that, when right-sided major hepatectomy (RSMH) is planned for patients with large tumors in the right liver, it may not lead to a marked decrease in normally functional hepatic mass. METHODS: We collected data for patients who had undergone RSMH for tumors more than 8 cm in diameter (n=50) and compared them with control patients who had undergone RSMH for tumors less than 5 cm in diameter (n=21). RESULTS: The ratio of the remnant left liver volume to the nontumorous liver volume (left liver ratio) in the patients with large tumors was significantly greater than that in the control group (50.0±12.8% vs. 40.2±8.3%, p=0.002). Left liver ratio was significantly correlated with tumor volume (p<0.001). Preoperative portal vein embolization was performed in only four of the 50 patients with large tumors. None of the patients with large tumors developed postoperative liver failure. CONCLUSIONS: Left liver volume in patients with large tumors in the right liver was larger than usual, perhaps reducing the risk of postoperative liver insufficiency after RSMH.

Anemia attributed to vitamin B6 deficiency in post-pancreaticoduodenectomy patients.

Micronutrient deficiencies such as vitamin A, iron, zinc, and selenium have been known to occur as a consequence of pancreaticoduodenectomy (PD), but vitamin B6 deficiency has not been previously reported. We report two post-PD patients who developed anemias attributed to vitamin B6 deficiency. Oral supplementations of vitamin B6 significantly improved anemias in both cases. Micronutrients including vitamin B6 should be monitored in post-PD patients, and supplementations should be carried out when necessary.