[A Case of Unresectable Pancreatic Cancer with Massive Cancerous Ascites Responsive to KM-CART].

A 79-year-old woman visited our hospital complaining of bloating. An abdominal enhanced CT scan revealed pancreatic body cancer with cancerous ascites and multiple liver metastases. We started gemcitabine(GEM)plus nab-paclitaxel chemotherapy. Chemotherapy was not continued because she was unable to take oral medication owing to increased cancerous ascites. We conducted modified KM-cell-free and concentrated ascites reinfusion therapy(KM-CART). Her symptoms improved, and she began having oral intake after KM-CART. Chemotherapy was then re-initiated. Seven months have now passed since we started chemotherapy, and we can continue chemotherapy while conducting KM-CART repeatedly. KM- CART is useful for treating unresectable pancreatic cancer with massive cancerous ascites in terms of continuing chemotherapy.

Persistence and epidemic propagation of a Pseudomonas aeruginosa sequence type 235 clone harboring an IS26 composite transposon carrying the blaIMP-1 integron in Hiroshima, Japan, 2005 to 2012.

A 9-year surveillance for multidrug-resistant (MDR) Pseudomonas aeruginosa in the Hiroshima region showed that the number of isolates harboring the metallo-ß-lactamase gene bla(IMP-1) abruptly increased after 2004, recorded the highest peak in 2006, and showed a tendency to decline afterwards, indicating a history of an epidemic. PCR mapping of the variable regions of the integrons showed that this epidemic was caused by the clonal persistence and propagation of an MDR P. aeruginosa strain harboring the bla(IMP-1) gene and an aminoglycoside 6'-N-acetyltransferase gene, aac(6')-Iae in a class I integron (In113), whose integrase gene intl1 was disrupted by an IS26 insertion. Sequence analysis of the representative strain PA058447 resistance element containing the In113-derived gene cassette array showed that the element forms an IS26 transposon embedded in the chromosome. It has a Tn21 backbone and is composed of two segments sandwiched by three IS26s. In Japan, clonal nationwide expansion of an MDR P. aeruginosa NCGM2.S1 harboring chromosomally encoded In113 with intact intl1 is reported. Multilocus sequence typing and genomic comparison strongly suggest that PA058447 and NCGM2.S1 belong to the same clonal lineage. Moreover, the structures of the resistance element in the two strains are very similar, but the sites of insertion into the chromosome are different. Based on tagging information of the IS26 present in both resistance elements, we suggest that the MDR P. aeruginosa clone causing the epidemic in Hiroshima for the past 9 years originated from a common ancestor genome of PA058447 and NCGM2.S1 through an IS26 insertion into intl1 of In113 and through IS26-mediated genomic rearrangements.

Safe suprapancreatic lymph node dissection for gastric cancer with ectopic common hepatic artery.

Suprapancreatic lymph node dissection for patients with gastric cancer in whom the common hepatic artery is located neither at the suprapancreatic margin nor in front of the portal vein is a more difficult procedure than when the common hepatic artery is in a more typical position. There is an increased risk of injury to the vessels that need to be preserved and inadequate lymph node dissection. Measures that have been reported for use in this situation are preoperative diagnosis with three-dimensional computed tomography angiography, dissection using the portal vain as a guide, and safe exposure of the portal vein with dissection to preserve the nerves at the suprapancreatic margin and in front of the portal vein. We review the literature and report our experience with a patient whose common hepatic artery was not located in the suprapancreatic margin who safely underwent suprapancreatic lymph node dissection using these methods.

Intrahepatic cholangiocarcinoma with extensive intraductal extension of high-grade biliary intraepithelial neoplasia: a case report.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is frequently associated with precursor lesions, and biliary intraepithelial neoplasia (BilIN) may play a significant role in the development of ICC. However, the exact sequence and progression of these lesions remain to be elucidated. We report a rare case of ICC that exhibited extensive longitudinal intraductal extension of high-grade BilIN in the posterior bile ducts and involved the hepatic hilum and the peripheral hepatic parenchyma. CASE PRESENTATION: A 70-year-old female presented with anorexia. Computed tomography (CT) revealed a 15 mm enhancing intrahepatic tumor extending to the right intrahepatic secondary confluence. This was associated with a 7 mm diameter cystic dilatation of the segment 6 bile duct (B6). Endoscopic retrograde cholangiopancreatography (ERCP) revealed stenosis at the bifurcation of the posterior bile duct branch. Bile cytology confirmed the diagnosis of adenocarcinoma cells. Therefore, the patient was diagnosed with an ICC involving the right glissonean pedicle and underwent a right hepatectomy and lymph node dissection. Histologic examination revealed the tumor consisted of moderately differentiated adenocarcinoma. In connection with this lesion, diffuse intraductal atypical epithelial cells, which were diagnosed as high-grade BilIN, was observed not only in the dilated B6 but in the entire posterior bile ducts, which measured approximately 120 mm in diameter. Furthermore, two distinct foci of adenocarcinomas were identified in the peripheral hepatic parenchyma. A lymph node metastasis was also present. The pathological diagnosis was ICC pT4N1M0 stage IVA. The patient underwent adjuvant chemotherapy and has shown no recurrence 5 years after surgery. Imaging modalities were unable to accurately assess the extent of the intraductal neoplastic lesions due to their low papillary or sessile intraductal tubular growth. No risk factors for BilIN development, which has the potential to predispose to cholangiocarcinoma, were identified in the present case. CONCLUSIONS: We present a case of ICC involving the right hepatic hilum, accompanied by extensive longitudinal extensions of high-grade BilIN and multifocal microscopic invasions in peripheral hepatic parenchyma. Notably, the intraductal lesions involved the entire posterior intrahepatic bile ducts. The presence of biliary neoplasia with extensive intraductal extension, in conjunction with ICC, should be considered as a variant of BilIN.

Nutritional Status Indicators Affecting the Tolerability of Postoperative Chemotherapy After Total Gastrectomy in Patients With Gastric Cancer.

Purpose: Nutritional problems after gastrectomy affect continuation of postoperative chemotherapy. There have been no studies limited to total gastrectomy, which is particularly prone to nutritional problems. In this study, we aimed to investigate the factors that predict the continuation of postoperative chemotherapy. Materials and Methods: We included 101 patients who underwent curative total gastrectomy and postoperative chemotherapy at Hiroshima Memorial Hospital. The effects of 37 factors, including perioperative inflammatory, nutritional, and tumor status, on the persistence of postoperative chemotherapy were analyzed. Results: In univariate analysis of preoperative factors, age, carbohydrate antigen 19-9, platelet-to-neutrophil ratio, Onodera's prognostic nutritional index (PNI), controlling nutritional status score, and nutritional risk screening (NRS-2002) score were significantly associated with the duration of postoperative chemotherapy. In multivariate analysis of preoperative factors, age (≥74 years) was an independent factor for a shorter duration of postoperative chemotherapy (hazard ratio [HR], 5.24; 95% confidence interval [CI], 2.19-12.96; P<0.01). In univariate analysis of factors before postoperative chemotherapy, intraoperative blood loss, perioperative weight loss rate, postoperative performance status, PNI, albumin-to-bilirubin index, and NRS-2002 score were significantly associated with the duration of postoperative chemotherapy. In multivariate analysis of factors before postoperative therapy, age (≥74 years) (HR, 5.75; 95% CI, 1.90-19.49; P<0.01) and PNI (<39) (HR, 3.29; 95% CI, 1.26-8.56; P=0.02) were independent factors for a shorter duration of postoperative chemotherapy. Conclusions: Age and PNI are useful predictors of postoperative chemotherapy intolerance after total gastrectomy and may determine the treatment strategy and timing of chemotherapy initiation.

Triple metachronous primary pancreatic and gallbladder cancer associated with pancreaticobiliary maljunction: a case report.

BACKGROUND: Metachronous pancreatic and gallbladder cancer is a rare condition and has a dismal prognosis. Herein, we present a patient with triple metachronous primary pancreatic and gallbladder cancer associated with pancreaticobiliary maljunction who achieved long-term survival after undergoing repeat curative surgery. CASE PRESENTATION: A 65-year-old female patient with advanced gallbladder cancer associated with pancreaticobiliary maljunction underwent extended cholecystectomy with extrahepatic bile duct resection. The pathological diagnosis was T3N0M0 stage III A papillary adenocarcinoma with hepatic invasion. During a monthly follow-up, a diffuse hypovascular 2.0 × 1.5-cm mass was detected in the pancreatic head 6.2 years after the initial surgery. Hence, the patient underwent pancreaticoduodenectomy. Histological examination revealed T3N0M0 stage IIA well-differentiated adenocarcinoma without lymph node metastases. Marked inflammatory reaction was observed in the non-cancerous lesions of the proximal pancreatic head parenchyma containing bile pigment within ductular lumens. After 12.5 years from the initial surgery, total pancreatectomy for a 4.0 × 3.0-cm mass in the remnant pancreas was performed. Histological examination revealed T3N1M0 stage IIB moderately differentiated adenocarcinoma with lymph node metastases. Hence, surgical curative resection was achieved. Based on the pathological findings, a definitive diagnosis of triple metachronous pancreatic and gallbladder cancer was made. The pathology suggests no precursor lesions such as pancreatic intraepithelial neoplasia (PanIN) and atypical flat lesions, but marked inflammations in the non-cancerous lesions, strengthening our hypothesis that chronic inflammation induced by the pancreaticobiliary maljunction is related to carcinogenesis of the pancreas. Despite further adjuvant chemotherapy, the patient's general condition worsened; however, she remained alive 15.2 years after the initial surgery while receiving the best supportive care. CONCLUSIONS: Repeat curative surgery for triple metachronous cancer was associated with a favorable prognosis. Both the biliary tract and the pancreas should be closely monitored during follow-up among patients with pancreaticobiliary maljunction, which can be managed with curative surgery.

A case of multiple metastatic gastric cancer with primary lesion vanished after administrating nivolumab, and the effect remains even after discontinuance of therapy.

Nivolumab is one of the immune checkpoint inhibitors available for chemotherapy-resistant gastric cancer. There have been few reports of confirmed prominent shrinkage of the primary tumor and some reports of prolonged antitumor effect after discontinuance of the drug, but it is not universal. A 67-year-old male was admitted to our hospital and diagnosed with metastatic gastric cancer that had spread to the bilateral lobe of the liver, distant lymph nodes, and peritoneum. He received five courses of S-1 plus oxaliplatin, followed by three courses of ramucirumab plus paclitaxel leading to disease progression. Then, the patient was administered nivolumab as third-line therapy. Tumor size was markedly reduced after three courses, esophagogastroduodenoscopy (EGD) revealed scar formation on the lower gastric corpus after seven courses, and biopsy specimen showed no malignancy. When a slight lower limb muscle weakness manifested, possibly an immune-related adverse event (irAE) after 15 courses, we stopped administration of nivolumab. The patient has survived for 26 months since his first visit, and elimination of the primary tumor and ascites with noted shrinkage of liver and lymph node metastases have followed for more than 10 months since discontinuance of nivolumab.

A long-term survival case of unresectable gastric cancer with multidisciplinary therapy including immunotherapy and abscopal effect.

The prognosis of unresectable gastric cancer remains poor. Multidisciplinary treatment of unresectable gastric cancer is, therefore, thought to be essential for improving patients' outcomes. Here, we report a successful case of multidisciplinary therapy for unresectable gastric cancer. The patient was a 69-year-old woman who was diagnosed with type 2 gastric cancer with remote lymph node metastases and peritoneal dissemination. Although shrinkage of the primary lesion and remote lymph nodes were observed following chemotherapy, we performed distal gastrectomy to deal with continuous bleeding from the primary lesion. Combination therapy with radiation and chemotherapy was effective for multiple metastases in both subclavian lymph nodes and metachronous multiple axillary lymph nodes. Nivolumab combined with radiation therapy also induced regression of remote lymph node metastases, peritoneal dissemination, and adrenal metastasis. Abscopal effects, i.e., shrinkage of the non-irradiated lesions, were also observed. Thus far, the patient has been able to maintain a good quality of life while receiving continued nivolumab therapy. Multidisciplinary therapy including immunotherapy and abscopal effect may improve the quality of life and contribute to long-term survival of patients with unresectable gastric cancer.

Surgical Recurrence at Anastomotic Site After Bowel Resection in Crohn's Disease: Comparison of Kono-S and End-to-end Anastomosis.

BACKGROUND: Anastomotic surgical recurrence after bowel resection in Crohn's disease patients is problematic. This study was performed to evaluate the increased risk of anastomotic surgical recurrence. METHODS: From 2006 to 2016, we performed anastomoses in 215 consecutive Crohn's disease patients. The cohort was divided into two groups: Kono-S anastomosis (n = 117) and end-to-end anastomosis (n = 98). Multivariate analysis of predictors of anastomotic surgical recurrence and Kaplan-Meier analysis for the 5-year anastomotic surgical recurrence rate were evaluated. RESULTS: The two groups showed no statistically significant differences in patient backgrounds. During a median follow-up of 54 months, 28 patients required anastomotic surgical recurrence [4 (3.4%) in the Kono-S group and 24 (24.4%) in the end-to-end group]. Six leaks (5.1%) were detected in the Kono-S group and 17 leaks (17.3%) in the end-to-end group; all were successfully treated conservatively. End-to-end anastomosis, leakage, age < 45 years, and body mass index of ≥ 18 kg/m2 at the first surgery had a higher risk of anastomotic surgical recurrence. Kono-S anastomosis significantly reduced the risk of anastomotic surgical recurrence after 1 year (odds ratio, 0.14). Anastomotic leakage influenced anastomotic surgical recurrence within 1 year (odds ratio, 4.84). The 5-year surgery-free survival rate at the anastomosis site with Kono-S anastomosis (95.0%) was significantly higher than that with end-to-end anastomosis (81.3%; P < 0.001). CONCLUSIONS: Anastomotic leakage after bowel resection in Crohn's disease patients increased anastomotic surgical recurrence within 1 year, and Kono-S anastomosis is associated with a low risk of anastomotic surgical recurrence after > 1 year.

Rapid identification of carbapenemase-type blaGES and ESBL-type blaGES using multiplex PCR.

Guiana extended-spectrum (GES) ß-lactamases are emerging in Japan. The GES family can be classified into 2 groups, one with extended-spectrum ß-lactamase (ESBL)-like activity, which hydrolyzes penicillins and cephalosporins, and the other with carbapenemase-like activity with an extended spectrum toward carbapenems. This difference is mediated by variations in a specific amino acid in the GES protein: G170 N or G170S substitutions. We developed an amplification refractory mutation system (ARMS) PCR assay that enabled rapid identification of these variant genes without sequencing.

Pharmacokinetics of piperacillin-tazobactam in plasma, peritoneal fluid and peritoneum of surgery patients, and dosing considerations based on site-specific pharmacodynamic target attainment.

Piperacillin-tazobactam (PIP-TAZ) is commonly used to treat intraabdominal infections; however, its penetration into abdominal sites is unclear. A pharmacokinetic analysis of plasma, peritoneal fluid, and peritoneum drug concentrations was conducted to simulate dosing regimens needed to attain the pharmacodynamic target in abdominal sites. PIP-TAZ (4 g-0.5 g) was intravenously administered to 10 patients before abdominal surgery for inflammatory bowel disease. Blood, peritoneal fluid, and peritoneum samples were obtained at the end of infusion (0.5 h) and up to 4 h thereafter. PIP and TAZ concentrations were measured, both noncompartmental and compartmental pharmacokinetic parameters were estimated, and a simulation was conducted to evaluate site-specific pharmacodynamic target attainment. The mean peritoneal fluid:plasma ratios in the area under the drug concentration-time curve (AUC) were 0.75 for PIP and 0.79 for TAZ, and the mean peritoneal fluid:plasma ratios in the AUC were 0.49 for PIP and 0.53 for TAZ. The mean PIP:TAZ ratio was 8.1 at both peritoneal sites. The regimens that achieved a bactericidal effect with PIP (time above minimum inhibitory concentration [MIC] >50%) at both peritoneal sites were PIP-TAZ 4.5 g twice daily for an MIC of 8 mg/L, as well as 4.5 g three times daily, and 3.375 g four times daily for an MIC of 16 mg/L. These findings clarify the peritoneal pharmacokinetics of PIP-TAZ, and help consider the dosing regimens for intraabdominal infections based on site-specific pharmacodynamic target attainment.

Hand-assisted laparoscopic restorative proctocolectomy for ulcerative colitis.

AIM: To evaluate the utility of hand-assisted laparoscopic restorative proctocolectomy (HALS-RP) compared with the conventional open procedure (OPEN-RP). METHODS: Fifty-one patients who underwent restorative total proctocolectomy with rectal mucosectomy and ileal pouch anal anastomosis between January 2008 and July 2015 were retrospectively analyzed. Twenty-three patients in the HALS-RP group and twenty-four patients in the OPEN-RP group were compared. Four patients who had purely laparoscopic surgery were excluded. Restorative total proctocolectomy was performed with mucosectomy and a hand-sewn ileal-pouch-anal anastomosis. Preoperative comorbidities, intraoperative factors such as blood loss and operative time, postoperative complications, and postoperative course were compared between two groups. RESULTS: Patients in both groups were matched with regards to patient age, gender, and American Society of Anesthesiologists score. There were no significant differences in extent of colitis, indications for surgery, preoperative comorbidities, and preoperative medications in the two groups. The median operative time for the HALS-RP group was 369 (320-420) min, slightly longer than the OPEN-RP group at 355 (318-421) min; this was not statistically significant. Blood loss was significantly less in HALS-RP [300 (230-402) mL] compared to OPEN-RP [512 (401-1162) mL, P = 0.003]. Anastomotic leakage was noted in 3 patients in the HALS-RP group and 2 patients in the OPEN-RP group (13% vs 8.3%, NS). The rates of other postoperative complications and the length of hospital stay were not different between the two groups. CONCLUSION: HALS-RP can be performed with less blood loss and smaller skin incisions. This procedure is a feasible technique for total proctocolectomy for ulcerative colitis.

Inhibition by long-term fermented miso of induction of pulmonary adenocarcinoma by diisopropanolnitrosamine in Wistar rats.

The present study was designed to investigate the effects of fermented miso in the diet on the development of lung tumors initiated by diisopropanolnitrosamine (BHP) in male Slc:Wistar rats. A total of 63 animals, 6 weeks of age, were divided into 4 groups and given BHP (2000 ppm) in their drinking water for 10 weeks. After the carcinogen treatment the rats were fed a normal control MF solid diet, or the same diet containing 10% long-term or short-term fermented miso for 12 weeks. The long-term fermented miso significantly reduced the number of lung tumors, adenocarcinomas and PCNA strongly positive tumors as compared with the short-term fermented miso. The present results thus indicate that dietary supplementation with long-term fermented miso could exert chemopreventive effects on lung carcinogenesis.