[BRCA2 Mutation Profile in a Proband with Hereditary Breast and Ovarian Cancer-Two Germline Pathogenic Variants Aligned in the Cis Position].

We report the first Japanese case of hereditary breast and ovarian cancer(HBOC)carrying 2 germline pathogenic variants (GPVs)in the BRCA2 gene. Genetic testing of the BRCA1 and BRCA2 genes was performed in a young woman with HBOC and 2 GPVs were identified in the BRCA2 gene. Since simultaneous GPVs in both parental alleles(ie, trans)in the BRCA2 gene is diagnostic of Fanconi anemia, which is characterized by bone marrow dysfunction and susceptibility to malignancy, we genetically tested her relatives. The same variants were revealed, and both variants were located in the cis position. For patients with multiple GPVs in the BRCA2 gene, we should consider genetic testing of the relatives to confirm whether the variants are located in the cis or trans position under appropriate genetic counseling.

Important risk factors for gallstones after laparoscopic gastrectomy: a retrospective study.

BACKGROUND: The frequency of gallstones is higher in patients who have undergone gastrectomy than in the general population. While there have been some studies of gallstone formation after open gastrectomy, there are few reports of gallstones after laparoscopic gastrectomy (LG). Therefore, this study aimed to evaluate the incidence of gallstones after LG. METHODS: We retrospectively reviewed the records of 184 patients who underwent LG between January 2011 and May 2016 at Saiseikai Utsunomiya Hospital. After gastrectomy, abdominal ultrasonography was generally performed every 6 months for 5 years. Patients who underwent cholecystectomy before LG, underwent simultaneous cholecystectomy, and did not undergo abdominal ultrasonography, with an observation period of < 24 months, were excluded from the study. Finally, 90 patients were analyzed. Laparoscopic cholecystectomy was performed whenever biliary complications occurred. Patient characteristics were compared using the two-tailed Fisher's exact test or Chi-square test. In addition, the risk factors for postoperative gallstones were analyzed using logistic regression analysis. RESULTS: Among the 90 patients included in this study, 60 were men (78%), and the mean age was 65.5 years. Laparoscopic total gastrectomy was performed for 15 patients and laparoscopic distal gastrectomy for 75 patients. D2 lymph node dissection was performed for 8 patients (9%), whereas 68 patients underwent LG with Roux-en-Y reconstruction (76%). Gallstones were detected after LG in 27 of the 90 (30%) patients. Multivariate analysis identified Roux-en-Y reconstruction and male sex as significant risk factors of gallstones after gastrectomy. The incidence of gallstones was significantly higher (53%) in male patients who underwent Roux-en-Y reconstruction. Symptomatic gallstones after laparoscopic cholecystectomy were found in 6 cases (6/27, 22%), and all patients underwent laparoscopic cholecystectomy. CONCLUSION: Roux-en-Y reconstruction and male sex were identified as significant risk factors for gallstones after LG.

A prospective feasibility study of one-year administration of adjuvant S-1 therapy for resected biliary tract cancer in a multi-institutional trial (Tokyo Study Group for Biliary Cancer: TOSBIC01).

BACKGROUND: Although surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. This study examined the safety and efficacy of 1 year adjuvant S-1 therapy for BTC in a multi-institutional trial. METHODS: The inclusion criteria were as follows: histologically proven BTC, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, R0 or R1 surgery performed, cancer classified as Stage IB to III. Within 10 weeks post-surgery, a 42-day cycle of treatment with S-1 (80 mg/m2/day orally twice daily on days 1-28 of each cycle) was initiated and continued up to 1 year post surgery. The primary endpoint was adjuvant therapy completion rate. The secondary endpoints were toxicities, disease-free survival (DFS), and overall survival (OS). RESULTS: Forty-six patients met the inclusion criteria of whom 19 had extrahepatic cholangiocarcinoma, 10 had gallbladder carcinoma, 9 had ampullary carcinoma, and 8 had intrahepatic cholangiocarcinoma. Overall, 25 patients completed adjuvant chemotherapy, with a 54.3% completion rate while the completion rate without recurrence during the 1 year administration was 62.5%. Seven patients (15%) experienced adverse events (grade 3/4). The median number of courses administered was 7.5. Thirteen patients needed dose reduction or temporary therapy withdrawal. OS and DFS rates at 1/2 years were 91.2/80.0% and 84.3/77.2%, respectively. Among patients who were administered more than 3 courses of S-1, only one patient discontinued because of adverse events. CONCLUSIONS: One-year administration of adjuvant S-1 therapy for resected BTC was feasible and may be a promising treatment for those with resected BTC. Now, a randomized trial to determine the optimal duration of S-1 is ongoing. TRIAL REGISTRATION: UMIN-CTR, UMIN000009029. Registered 5 October 2012-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009347.

[A Case of Duodenal Perforation during Bevacizumab Combination Chemotherapy in a Patient with Multiple Lung Metastasis after a Sigmoidectomy].

A 73-year-old man underwent laparoscopic sigmoidectomy for sigmoid colon cancer. Two years after the operation, multiple lung metastasis was diagnosed and chemotherapy with bevacizumab, irinotecan, and TS-1®was started in the patient. However, epigastric pain developed 73 days after the initial course of chemotherapy. Abdominal CT revealed duodenal perforation and generalized peritonitis. Emergency operation with omental patch closure was immediately performed. The patient was discharged 15 days after the emergency operation without any complication. This is an extremely rare case of bevacizu- mab-related duodenal perforation.

Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2-positive gastric cancer: a phase II trial and biomarker study (WJOG7212G).

BACKGROUND: Five-weekly S-1 plus cisplatin (SP) therapy is the standard care for advanced gastric or esophagogastric junction cancer (GC/EGJC) in East Asia. However, its efficacy and safety when combined with trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced GC/EGJC remains unclear. METHODS: Patients received 5-weekly SP therapy (S-1 at 40-60 mg twice daily for 21 days plus cisplatin at 60 mg/m2 on day 8, every 5 weeks) plus trastuzumab therapy (first dose of 8 mg/kg, then 6 mg/kg every 3 weeks). The primary end point was the response rate, and the secondary end points included progression-free survival, overall survival, safety, and serum biomarker levels. RESULTS: Forty-four patients were enrolled. The response rate, progression-free survival, and overall survival were 61% (95% confidence interval 46-76%), 5.9 months, and 16.5 months respectively. The commonest grade 3 or grade 4 adverse events were neutropenia (30%) and anorexia (25%). A significantly higher response rate (92% vs 43%; P = 0.008) and longer progression-free survival (median 14.5 months vs 4.2 months; P = 0.028) were observed in patients with high (n = 14) compared with low (n = 17) pretreatment serum neuregulin 1 levels. CONCLUSIONS: Five-weekly SP therapy combined with trastuzumab therapy showed a good antitumor response and acceptable toxicity in HER2-positive advanced GC/EGJC. Serum neuregulin 1 might be associated with the efficacy of this treatment regimen.

[A Case of Fournier's Gangrene Caused by Small Intestinal Perforation during Bevacizumab Combination Chemotherapy].

A 51-year-old man underwent abdominoperineal resection for advanced rectal cancer at a hospital. He attended our outpatient clinic 58 months later with pain in the external genitalia, and was diagnosed with local pelvic recurrence and metastasis to the para-aortic lymph node and both adrenal glands. He received a total of 30 Gy of radiation for analgesia; subsequently, chemotherapy(mFOLFOX6 plus bevacizumab)was initiated. However, extreme left buttock and left femoral pain developed after the 6 courses of chemotherapy. Abdominal CT revealed Fournier's gangrene caused by small intestinal perforation. Emergency drainage under spinal anesthesia was immediately performed. Two additional drainage procedures were required thereafter and an ileostomy was constructed. The patient was discharged 100 days after the initial drainage. This is an extremely rare example of a bevacizumab-related small intestinal perforation that developed into Fournier's gan- grene.

Extensive bowel necrosis related to bevacizumab in metastatic rectal cancer patient: a case report and review of literature.

Recently, bevacizumab has become a key drug for treatment of metastatic colorectal cancer. Molecularly targeted agents such as bevacizumab can cause life-threatening adverse effects, though they are generally considered less toxic than cytotoxic drugs. Here, we review the case of a 76-year-old male rectal cancer patient with liver metastasis who suffered extensive bowel necrosis after administration of 5-fluorouracil-based chemotherapy with bevacizumab, and required a subtotal colectomy and end-ileostomy. Microscopic findings revealed extensive mucosal necrosis in the resected colon specimen and necrosis at the muscularis propria of the descending colon. Pathological findings suggested that the mucosal damage induced by chemotherapy may be exacerbated by treatment with bevacizumab, resulting in extensive necrosis.

Clinical outcomes after surgical decompression of median arcuate ligament syndrome-An observational study.

BACKGROUND AND OBJECTIVES: Median arcuate ligament syndrome is caused by compression and stenosis of the celiac artery. Incision of the median arcuate ligament improves persistent abdominal symptoms. The study aimed at evaluating the outcomes in patients who underwent median arcuate ligament syndrome decompression using a self-report questionnaire. METHODS: This single-center retrospective study included patients with median arcuate ligament syndrome who underwent decompression surgery between April 2021 and February 2023. The medical records were retrospectively reviewed. RESULTS: Ten patients were included in the study. Laparotomy and laparoscopic surgeries were performed in seven and three patients, respectively. The median operation time was 147 minutes. The median hospitalization period after the operation was seven days. The degrees of celiac artery stenosis before and after surgery were compared and the per cent diameter stenosis did not significantly improve; five of 10 patients (50%) had > 50% stenosis in the celiac artery after the operation. Compared to the baseline, the scores of upper gastrointestinal symptoms significantly improved during the six months' period (p < 0.001). Additionally, we evaluated the influence of post-operative per cent diameter stenosis and divided the patients into two groups (≥ 50% vs, < 50%). The scores of upper gastrointestinal (GI) symptoms in both groups improved significantly from baseline. However, the symptomatic improvement at six months in the post-operative per cent diameter stenosis < 50% group was significantly greater than that in the ≥ 50% group (p = 0.016). The scores of lower gastrointestinal symptoms did not change significantly during the six-month period. CONCLUSION: Decompression surgery for median arcuate ligament syndrome could improve upper gastrointestinal symptoms regardless of the post-operative per cent diameter stenosis.

Pancreatic metastases from renal cell carcinoma: a case report and literature review of the clinical and radiological characteristics.

Metastatic pancreatic cancer is rare, accounting for approximately 2% of all pancreatic malignancies, and most cases arise from renal cell carcinoma. We report the case of a 63-year-old woman, who presented with a pancreatic tumor detected during her annual health examination. She had undergone left nephrectomy 13 years previously for renal cell carcinoma. Computed tomography (CT) revealed two tumors in the head and body of the pancreas, a hypervascular tumor and a hypovascular tumor with an enhanced rim, respectively. She underwent pylorus-preserving pancreaticoduodenectomy, and metastatic pancreatic tumors arising from the kidney with clustered clear cell carcinoma immunohistochemically positive for CD10 were diagnosed. This report presents the different enhancement features of different lesions on CT scans. Because the enhancement features of lesions have been reported to vary according to the size of the metastatic tumor, a knowledge of the history of renal cell carcinoma is crucial for diagnosis.

Laparoscopic Heller myotomy and Dor fundoplication following an unsuccessful peroral endoscopic myotomy.

BACKGROUND: Achalasia is an esophageal motility disorder that presents as dysphagia and severely affects quality of life. An esophageal myotomy has been the golden standard for treatment. Peroral endoscopic myotomy (POEM) as a first-line therapy has an acceptable outcome. However, after the clinical failure of POEM, appropriate second-line therapy is rather controversial. Here, we present the first published case in English of a patient who was successfully treated using laparoscopic Heller myotomy (LHM) with Dor fundoplication following an unsuccessful POEM. CASE PRESENTATION: A 64-year-old man with type 1 achalasia who had been previously treated with POEM visited our hospital for further treatment. After undergoing LHM with Dor fundoplication, his Eckardt score improved from 3 to 0 points. On a timed barium esophagogram (TBE), the barium height improved from 119 mm/119 mm (1 min/5 min) to 50 mm/45 mm. No significant complications have occurred postoperatively for 1 year. CONCLUSION: Treating refractory achalasia is challenging, and treatment options are controversial. LHM with Dor fundoplication after POEM could be a safe and efficient option for the treatment of refractory achalasia.

The Sasaki-W anastomosis for recurrent Crohn's disease stenosis after the Kono-S anastomosis.

BACKGROUND: Postoperative recurrence is frequently encountered in the management of patients with Crohn's disease and is most often found at the anastomotic site. A novel technique, the Sasaki-W anastomosis, is an antimesenteric cutback end-to-end isoperistaltic anastomosis. We report a patient with Crohn's disease who underwent partial intestinal resection for postoperative anastomotic stenosis, reconstructed with the Sasaki-W anastomosis, after initial intestinal resection reconstructed with a Kono-S anastomosis. CASE PRESENTATION: A 30-year-old male was diagnosed with Crohn's disease and treated with mesalamine and adalimumab, and he underwent ileocecal resection using the Kono-S anastomosis at the time of diagnosis. He was treated with infliximab without any symptoms or recurrence for 7 years. He was admitted presenting with upper abdominal pain. Physical examination showed mild tenderness and distension in the upper abdomen. Laboratory data showed no remarkable findings. Computed tomography scan showed wall thickening in the ileum with proximal dilation and fluid retention. Non-operative management with antibiotics and fasting did not improve the symptoms within 7 days. Ten days after admission, ileocecal resection reconstructed with the Sasaki-W anastomosis was performed. At operation, there was a 15-cm intestinal stenosis at the site of the previous Kono-S anastomosis. The transverse colon and ileum were reconstructed with the Sasaki-W anastomosis. The postoperative course was uneventful, and the patient was discharged 17 days postoperatively. The patient had no obstructive symptoms and no findings consistent with bowel obstruction were observed on computed tomography scan one year postoperatively. CONCLUSIONS: The Sasaki-W anastomosis is a viable option for intestinal reconstruction in patients with postoperative recurrence after a Kono-S anastomosis.

Optimal tentative abdominal closure for open abdomen: a multicenter retrospective observational study (OPTITAC study).

BACKGROUND: Primary fascia closure is often difficult following an open abdomen (OA). While negative-pressure wound therapy (NPWT) is recommended to enhance successful primary fascia closure, the optimal methods and degree of negative pressure remain unclear. This study aimed to elucidate optimal methods of NPWT as a tentative abdominal closure for OA to achieve primary abdominal fascia closure. MATERIALS AND METHODS: A multicenter, retrospective, cohort study of adults who survived OA greater than 48 h was conducted in 12 institutions between 2010 and 2022. The achievement of primary fascia closure and incidence of enteroatmospheric fistula were examined based on methods (homemade, superficial NPWT kit, or open-abdomen kit) or degrees of negative pressure (<50, 50-100, or >100 mmHg). A generalized estimating equation was used to adjust for age, BMI, comorbidities, etiology for laparotomy requiring OA, vital signs, transfusion, severity of critical illness, and institutional characteristics. RESULTS: Of the 279 included patients, 252 achieved primary fascia closure. A higher degree of negative pressure (>100 mmHg) was associated with fewer primary fascia closures than less than 50 mmHg [OR, 0.18 (95% CI: 0.50-0.69), P =0.012] and with more frequent enteroatmospheric fistula [OR, 13.83 (95% CI: 2.30-82.93)]. The methods of NPWT were not associated with successful primary fascia closure. However, the use of the open-abdomen kit was related to a lower incidence of enteroatmospheric fistula [OR, 0.02 (95% CI: 0.00-0.50)]. CONCLUSION: High negative pressure (>100 mmHg) should be avoided in NPWT during tentative abdominal closure for OA.

Transrenal Ureter Embolization for Refractory Urine Leaks from Iatrogenic Ureteric Injury Following Colorectal Surgery.

We present the cases of two patients who underwent ureteral occlusion using coils and/or Amplatzer Vascular Plug with N-butyl cyanoacrylate glue after extensive advanced rectal surgery. Both patients had complex urine leaks unresponsive to urinary diversion. In view of the progress of the disease and the history of polysurgery, reconstructive surgery or anterograde ureteral stent insertion was not chosen. All patients had immediate resolution of urinary leakage after ureteral embolization, resulting in symptom relief throughout the follow-up period. There were no procedure-related complications or side effects.

Normalization of Flow in the Common Hepatic Artery after Decompression of Median Arcuate Ligament Syndrome with Diminution of a Pancreatoduodenal Arcade Aneurysm.

Median arcuate ligament syndrome (MALS) is caused by constriction of the celiac artery (CA) by the median arcuate ligament of the diaphragm. Ligament release improves perfusion of the CA, resulting in resolution of abdominal symptoms. A 51-year-old female had postprandial abdominal pain for 10 years and underwent computed tomography (CT) scan showing severe stenosis of the CA with pancreatoduodenal arcade aneurysm formation. MALS was diagnosed, and open median arcuate ligament incision was performed to decompress the CA. Intraoperative ultrasonography showed bidirectional turbulent flow in the common hepatic artery (CHA). The median arcuate ligament was uneventfully incised, and compression of the CA released. The perfusion in the CHA was changed to an antegrade direction, and the flow increased. Seven days after the laparotomy, the patient was discharged uneventfully. Follow-up CT scan 20 days after operation showed a diminished pancreatoduodenal arcade aneurysm and inferior pancreatoduodenal artery. Epigastric pain and postprandial distress symptoms were improved. In conclusion, perfusion of the CHA became normalized after median arcuate ligament release. Surgical intervention for MALS not only improved blood flow in the tributaries but also diminished the pancreatoduodenal arcade aneurysm.

Perioperative clinical parameters associated with short-term mortality after colorectal perforation.

PURPOSE: Although early prediction of mortality is useful for the management of patients with colorectal perforations, no significant perioperative predictive factors have been identified. The purpose of this study was to identify useful prognostic factors for patients with colorectal perforation. METHODS: This single-center retrospective study included consecutive patients undergoing emergency surgery for colorectal perforation from January 2012 to December 2019. The primary outcome was combined 30 day and in-hospital mortality. Patient- and disease-related factors obtained perioperatively were evaluated for mortality prediction. A scoring system was developed to enhance clinical utility. RESULTS: Overall, 146 patients were included and 20 (14%) died after surgery. Multivariate logistic regression identified five predictive factors: age, hemodialysis, uncommon perforation etiology, plasma albumin level, and decreased platelet count. The area under the receiver operating curve for the scoring system using these parameters was 0.894 (95% CI 0.835-0.952). Patients at high-risk of mortality were classified by the proposed score with a sensitivity of 90.0% and negative predictive value of 98.0%. CONCLUSION: This study identified five perioperative factors significantly associated with mortality of patients with colorectal perforation. Although these parameters predict mortality of patients with colorectal perforation using a score with high discrimination, further study is required to confirm these findings.

Pharmacological treatment to reduce pulmonary morbidity after esophagectomy.

Esophagectomy for esophageal cancer is one of the most invasive procedures in gastrointestinal surgery. An invasive surgical procedure causes postoperative lung injury through the surgical procedure and one-lung ventilation during anesthesia. Lung injury developed by inflammatory response to surgical insults and oxidative stress is associated with pulmonary morbidity after esophagectomy. Postoperative pulmonary complications negatively affect the long-term outcomes; therefore, an effort to reduce lung injury improves overall survival after esophagectomy. Although significant evidence has not been established, various pharmacological treatments for reducing lung injury, such as administration of a corticosteroid, neutrophil elastase inhibitor, and vitamins are considered to have efficacy for pulmonary morbidity. In this review we survey the following topics: mediators during the perioperative periods of esophagectomy and the efficacy of pharmacological therapies for patients with esophagectomy on pulmonary complications.

Nonsurgical rescue after basket-stone impaction by endoscopic cutting of a metallic lithotripter and laser lithotripsy.

Video 1Endoscopic rescue strategy for basket-stone impaction.

Delayed mesh infection after inguinal hernia repair: a case report.

Delayed deep mesh infection is a rare complication and the precise mechanism of its development is unknown. We report a case of delayed deep mesh infection after inguinal hernia repair. A 65-year-old man was admitted for treatment of colon cancer. He had a history of bilateral hernioplasty repaired with mesh-plugs 6 years previously. Fluorine-18 fluorodeoxyglucose positron emission tomographic scan showed positive findings in the right inguinal region similar to cancer. He had no complaints or findings to suspect mesh infection. Postoperative computed tomography scan over time revealed a fluid collection with inflammation. Eleven years after hernia repair, the patient presented with inflammation in the right inguinal region and emergency operation was performed. An abscess cavity was found and the mesh-plug covered with granulation tissue was removed. The patient remains free of recurrence of inguinal hernia or inflammatory changes after 3 years of follow-up.

Antithrombotic drugs have a minimal effect on intraoperative blood loss during emergency surgery for generalized peritonitis: a nationwide retrospective cohort study in Japan.

BACKGROUND: The effect of antithrombotic drugs on intraoperative operative blood loss volume in patients undergoing emergency surgery for generalized peritonitis is not well defined. The purpose of this study was to investigate the effect of antithrombotic drugs on intraoperative blood loss in patients with generalized peritonitis using a nationwide surgical registry in Japan. METHOD: This retrospective cohort study used a nationwide surgical registry data from 2011 to 2017 in Japan. Propensity score matching for the use of antithrombotic drugs was used for the adjustment of age, gender, comorbidities, frailty, preoperative state, types of surgery, surgical approach, laboratory data, and others. The main outcome was intraoperative blood loss: comparison of intraoperative blood loss, ratio of intraoperative blood loss after adjusted for confounding factors, and variable importance of all covariates. RESULTS: A total of 70,105 of the eligible 75,666 patients were included in this study, and 2947 patients were taking antithrombotic drugs. Propensity score matching yielded 2864 well-balanced pairs. The blood loss volume was slightly higher in the antithrombotic drug group (100 [10-349] vs 70 [10-299] ml). After adjustment for confounding factors, the use of antithrombotic drugs was related to a 1.30-fold increase in intraoperative blood loss compared to non-use of antithrombotic drugs (95% CI, 1.16-1.45). The variable importance revealed that the effect of the use of antithrombotic drugs was minimal compared with surgical approach or type of surgery. CONCLUSION: This study shows that while taking antithrombotic drugs is associated with a slight increase in intraoperative blood loss in patients undergoing emergency surgery for generalized peritonitis, the effect is likely of minimal clinical significance.