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Purposes The aim of this study was to clarify the impact of a board certification system and the implementation of clinical practice guidelines for pancreatic cancer (PC) on the mortality of pancreaticoduodenectomy in Japan. Methods By a web questionnaire survey via the National Clinical Database (NCD) for departments participating in the NCD, quality indicators (QIs) related to the treatment for PC, namely the board certification systems of various societies and the adherence to clinical practice guidelines for PC, were investigated between October 2014 and January 2015. A multivariable logistic regression analysis was performed to evaluate the relationship between the QIs and mortality of pancreaticoduodenectomy. Results Of 1415 departments that registered at least 1 pancreaticoduodenectomy between 2013 and 2014 in NCD, 631 departments (44.6%), which performed pancreaticoduodenectomy for a total of 11,684 cases, answered the questionnaire. The mortality of pancreaticoduodenectomy was positively affected by the board certification systems of the Japanese Society of Gastroenterological Surgery, Japanese Society of Hepato-Biliary-Pancreatic Surgery, Japanese Society of Gastroenterology, and Japanese Society of Medical Oncology as well as by institutions that used magnetic resonance imaging of ≥ 3 T for the diagnosis of PC in principle. Conclusions The measurement of the appropriate QIs is suggested to help improve the mortality in pancreaticoduodenectomy. Masamichi Mizuma and Hiroyuki Yamamoto equally contributed

Minimally invasive surgery (MIS) is the optimal treatment for congenital biliary dilatation (CBD), but few studies on adults have been reported. We compared the postoperative outcomes of MIS with those of open surgery (OS) in adult patients with CBD.The subjects of this retrospective study were 36 adult patients who underwent surgery for CBD. We compared the postoperative outcomes of 20 patients who underwent laparoscopic (n = 15) or robotic (n = 5) surgery with those of 16 patients who underwent OS.MIS was associated with a significantly higher rate of type I (p 0.001), significantly less blood loss (p 0.001), a significantly lower rate of internal stents (p = 0.048), significantly longer operation times (p = 0.009), and a significantly shorter postoperative hospital stay (p = 0.007) than OS. The postoperative outcomes of MIS for type I CBD were similar to those of the whole cohort. There were no significant differences in late complications between the groups. The robotic procedure had a significantly shorter operative time than laparoscopic surgery for hepaticojejunostomy (HJ; p = 0.029).MIS achieved favorable short-term outcomes without compromising mid-term outcomes compared to OS and is appropriate for adult patients with CBD. Robotic HJ may be more ideal than its laparoscopic counterpart.

To investigate the impact of early postoperative drainage fluid culture positivity on the development of clinically relevant postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). We assessed the positive prevalence, distribution, and drug sensitivity of microorganisms in drainage fluid collected on postoperative day (POD) 1 after PD from 465 patients. Culture results were positive in pancreaticojejunostomy (PJ) drainage fluid from 26.0% of patients. Similar distributions of microorganisms were observed in the bile juice and PJ/hepaticojejunostomy (HJ) drainage fluid from these patients. PJ drain culture positivity was associated with an elevated drainage amylase level and with preoperative biliary drainage. No associations were seen between HJ drainage culture positivity and the drainage amylase and bilirubin levels. PJ drainage culture positivity was found to be an independent predictor of grade B/C POPF. According to the antibiogram, the bacteria identified were likely to be resistant to prophylactic antibiotics. PJ drainage culture positivity on POD 1 in combination with an elevated drainage amylase level is an early predictor of grade B/C POPF. PJ drainage culture positivity may be attributable to bile juice contamination caused by intraoperative spillage and early postoperative leakage from the PJ anastomotic sites.

We introduced a superior approach and a unique technique to retract the stomach, called the “stomach roll-up technique”, to standardize laparoscopic distal pancreatectomy and increase educational effectiveness. The aim of this study was to evaluate the clinical outcomes of these procedures. Forty-five patients who underwent laparoscopic distal pancreatectomy by surgeons-in-training between January 2015 and December 2018 were included. Twenty laparoscopic distal pancreatectomies were performed using the inferior approach, and 25 procedures were performed using the superior approach. The stomach roll-up technique was used in all cases. The perioperative outcomes were retrospectively analyzed. Compared with the inferior approach, the superior approach was associated with a significantly shorter operation time (p

The aims of this study were to compare the perioperative outcomes after hepatectomy with prior bilioenteric anastomosis to those without prior anastomosis, and to elucidate the mechanisms and preventative measures of its characteristic complications. The demographic data and perioperative outcomes of 525 hepatectomies performed between January 2007 and December 2018, including 40 hepatectomies with prior bilioenteric anastomosis, were retrospectively analyzed. A propensity score matching analysis demonstrated that hepatectomies with prior bilioenteric anastomosis were associated with a higher frequency of major complications (p = 0.015), surgical site infection (p = 0.005), organ/space surgical site infection (p = 0.003), and bile leakage (p = 0.007) compared to those without. A multivariate analysis also elucidated that prior bilioenteric anastomosis was one of the independent risk factors of organ/space surgical site infection. In the patients with prior bilioenteric anastomosis, bile leakage was associated with organ/space surgical site infection at a significantly higher rate than those without prior bilioenteric anastomosis (p

Staging laparoscopy is considered useful for determining treatment plans for advanced pancreatic cancer. However, the indications for staging laparoscopy are not clear. This study aimed to evaluate the safety of staging laparoscopy and its usefulness for detecting distant metastases in patients with pancreatic cancer. A total of 146 patients with pancreatic cancer who underwent staging laparoscopy between 2013 and 2019 were analyzed. Staging laparoscopy was performed in all pancreatic cancer patients in whom surgery was considered possible. In this cohort, 42 patients (29%) were diagnosed with malignant cells on peritoneal lavage cytology, 9 (6%) had peritoneal dissemination, and 11 (8%) had liver metastases. A total of 48 (33%) had radiologically negative metastases. On a multivariate analysis, body and tail cancer [odds ratio (OR) 5.00, 95% confidence interval (CI) 2.15–11.6, p

Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic endogenous pluripotent-like cells residing in the bone marrow that exert a tissue reparative effect by replacing damaged/apoptotic cells through spontaneous differentiation into tissue-constituent cells. Post-hepatectomy liver failure (PHLF) is a potentially fatal complication. The main purpose of this study was to evaluate the safety and efficiency of allogeneic Muse cell administration via the portal vein in a swine model of PHLF. Swine Muse cells, collected from swine bone marrow-mesenchymal stem cells (MSCs) as SSEA-3(+) cells, were examined for their characteristics. Then, 1 × 107 allogeneic-Muse cells and allogeneic-MSCs and vehicle were injected via the portal vein in a 70% hepatectomy swine model. Swine Muse cells exhibited characteristics comparable to previously reported human Muse cells. Compared to the MSC and vehicle groups, the Muse group showed specific homing of the administered cells into the liver, resulting in improvements in the control of hyperbilirubinemia (P = 0.04), prothrombin international normalized ratio (P = 0.05), and suppression of focal necrosis (P = 0.04). Integrated Muse cells differentiated spontaneously into hepatocyte marker-positive cells. Allogeneic Muse cell administration may provide a reparative effect and functional recovery in a 70% hepatectomy swine model and thus may contribute to the treatment of PHLF.

The Frey procedure is an effective surgery for chronic pancreatitis (CP) patients who have pancreatic head lesions with dilation of the main pancreatic duct. However, pancreatic tail lesions can cause relapsing pancreatitis after the procedure. Therefore, additional distal pancreatectomy (DP) might complement the therapeutic effect of the Frey procedure in controlling inflammation of the pancreatic tail. The Frey procedure with DP (Frey + DP) is indicated for inflammatory lesions in the pancreatic head and tail. In this study, we assessed the usefulness of Frey + DP using the retrospective clinical data of our cases. The clinical outcomes were compared between CP patients who underwent the Frey procedure (N = 44) and Frey + DP (N = 13) from January 2005 to April 2016. Frey + DP showed similarly good therapeutic effects to the Frey procedure with regard to the postoperative stay, morbidity, mortality, pain relief and nutrition, although the Frey + DP had a longer operative time, more bleeding and higher incidence of diabetes mellitus than the Frey procedure because of the additional DP. One patient in the Frey group received additional DP because of recurrent pain due to the tail lesion. Frey + DP can be a promising treatment for CP patients with pancreatic head and tail lesions.

To clarify the usefulness of cancer-related inflammation, hypermetabolism, and subsequent host malnutrition biomarkers for predicting the histological grades of intraductal papillary mucinous neoplasms of the pancreas (IPMNs). The systemic immune-inflammation index (SII), prognostic nutritional index (PNI), and maximum standardized uptake value (SUVmax) on fluorodeoxyglucose-positron emission tomography were compared across 171 resected IPMN cases of different histological grades. The diagnostic performance of each marker and of their combinations for predicting IPMN with high-grade dysplasia (HGD)/associated invasive carcinoma (INV) was also tested. Of the 171 IPMNs, the IPMN cases with HGD showed significantly higher values of SII (median 406 vs. 340; P = 0.041) and SUVmax (median 2.5 vs. 2.0; P = 0.001) than those with low-grade dysplasia (LGD). On a multivariate analysis, the SII and SUVmax were both independent markers for predicting HGD/INV. A combination analysis including the tumor- and host-derived markers in combination with imaging findings showed an improved diagnostic performance (area under the curve 0.824; sensitivity 75.9%; specificity 80.0%). The combination of multiple markers of host-derived inflammation and tumor-derived focal hypermetabolism can serve as a predictor for the presence of HGD/INV.

The aim of surgical intervention for chronic pancreatitis (CP) is to relieve symptoms and improve quality of life. However, the precise effect of surgery on the nutritional status of CP patients, which is often impaired by exocrine and endocrine pancreatic dysfunction, has not been elucidated. We conducted this study to evaluate whether Frey’s procedure improves the nutritional status of CP patients. The nutritional status of 35 patients who underwent Frey’s procedure for CP at our institute between April 2005 and December 2014, was assessed by the controlling nutritional status (CONUT) scoring before and 1 year after the surgery, and compared with that of seven CP patients who underwent pancreatoduodenectomy. The occurrence of postoperative hepatic steatosis was also monitored. The nutritional status improved after Frey’s procedure, but not after pancreatoduodenectomy. The median postoperative CONUT score after Frey’s procedure was significantly lower than the preoperative score (1.0 ± 0.5 vs. 4.0 ± 2.5; p

To evaluate the long-term outcomes of total pancreatectomy in a modern cohort of pancreatic cancer patients and to establish whether any factors identified prior to pancreatic resection were related to poor survival. We analyzed, retrospectively, patients who underwent total pancreatectomy for pancreatic cancer between 2007 and 2016. The short- and long-term outcomes were investigated and Cox regression analysis was used to evaluate the prognostic factors identified before resection. The subjects were 49 patients with a mean age of 65 years, who underwent total pancreatectomy in our hospital during the study period. Peritoneal washing cytology was performed in 48 patients, with positive results in 4 (8.3%). There was no 30-day mortality. The median overall survival was 22.5 months, with a 5-year survival rate of 28.5%. Univariate analyses of the pre-resection variables revealed that overall survival was associated with tumor location, resectability classification, maximum standardized uptake value of positron emission tomography, the preoperative carbohydrate antigen 19–9 level, and peritoneal washing cytology status. Multivariate analysis revealed that positive peritoneal washing cytology status and the maximum standardized uptake value were independent predictors of poor survival. Total pancreatectomy for pancreatic cancer is appropriate for selected patients, but peritoneal washing cytology and positron emission tomography should be performed preoperatively.

The aim of this study was to compare the clinical outcomes between laparoscopic partial liver resection and open partial hepatectomy for tumors in the posterosuperior segments. The clinical outcomes of patients who underwent either laparoscopic (n = 20) or open (n = 44) resection in segments 7/8 of the liver were initially evaluated. Because of disparities in the background characteristics, a case-matched study (1:1) was conducted. In addition, a comparative study of the patients who met the institutional criteria for laparoscopic partial hepatectomy was performed. In the case-matched study, the laparoscopic technique required a longer operation time (p = 0.001), but was associated with less intraoperative blood loss (p = 0.021), a lower incidence of major complications (p = 0.014), higher levels of serum albumin on postoperative days 3 and 7 (p = 0.031 and p = 0.035), and earlier discharge (p = 0.001) than open resection. The results of the latter study were similar to those of the case-matched analysis. Laparoscopic partial hepatectomy was a feasible procedure for treating tumors in the posterosuperior segments without compromising oncological safety and yielded better short-term outcomes than open techniques. In addition, this study provides concrete selection criteria for laparoscopic partial hepatectomy for difficult lesions.

To evaluate the risk factors for peritoneal recurrence (PR) of pancreatic adenocarcinoma and to discuss the appropriate management strategies. We reviewed the medical records of 236 patients who underwent pancreatectomy for pancreatic adenocarcinoma. We then compared the clinicopathological characteristics of patients with vs. those without PR. The independent risk factors for PR were defined using the Cox proportional hazards regression model. The median survival of patients with PR was 13.3 months after surgical treatment. The PR group had a significantly higher incidence of portal vein resection, longer operative time (≥648 min), greater blood loss (≥2179 mL), blood transfusion, tumor size, portal vein invasion, artery invasion, pancreatic nerve plexus invasion, and histological grade. Multivariate analysis revealed that excessive blood loss (≥2179 mL; P = 0.010), artery invasion (P = 0.025), pancreatic nerve plexus invasion (P = 0.001), and histological grade 3 (P = 0.011) were independent risk factors for PR. Excessive blood loss was also strongly related to tumor size (P = 0.018). Local invasion and tumor size-related factors suggested the possibility of intraoperative dissemination at the time of tumor resection. Preoperative treatment and an operative procedure to prevent tumor exposure may help prevent PR.

Thromboprophylaxis is recommended for preventing postoperative venous thromboembolism (VTE) after abdominal surgery; however, its use after major hepatobiliary–pancreatic surgery is typically avoided as it increases the risk of bleeding. We conducted this study to evaluate the safety of thromboprophylaxis after major hepatobiliary–pancreatic surgery. We analyzed the rates of postoperative bleeding, VTE, morbidity, and prolonged hospital stay in 349 patients who underwent major hepatobiliary–pancreatic surgery, such as pancreaticoduodenectomy, hemihepatectomy or greater, and hepatopancreaticoduodenectomy. Chemical thromboprophylaxis was associated with significantly increased rates and risks of overall bleeding events vs. no chemical thromboprophylaxis (26.6 vs. 8.5 %, respectively). The rate of minor hemorrhage was significantly higher in patients who received chemical thromboprophylaxis (21.7 vs. 3.5 %); however, there were no differences in the rate of major hemorrhage requiring blood transfusion or hemostatic intervention between the groups (4.8 vs. 4.9 %). The postoperative VTE rate was also significantly decreased by chemical thromboprophylaxis (2.9 vs. 7.7 %). However, chemical thromboprophylaxis did not affect the rate of SSI, severe morbidity, or duration of the postoperative hospital stay. We consider that chemical thromboprophylaxis is beneficial and can be safely used even after major hepatobiliary–pancreatic surgery.

To evaluate the anti-tumor effects of a novel adenovirus expressing mutant p27(kip1) (Adp27-mt), which consists of a mutation of Thr-187/Pro-188 to Met-187/Ile-188.Using the human breast cancer cell lines, MDA-MB-231, ZR-75-1, and MCF-7, we tested Adp27-mt for cell cycle assay, growth inhibition assay, and TdT-mediated dUTP-biotin nick end labeling in a human breast cancer-grafted severe combined immunodeficiency (SCID) mouse model.The mutant p27(kip1) induced stronger apoptosis in the breast cancer cell lines than adenovirus expressing wild-type p27(kip1) (Adp27-wt). Adp27-mt inhibits cell growth significantly; being about 5- and 3.5-fold stronger for IC50 than Adp27-wt in the breast cancer cell lines, MDA-MD-231 and ZR-75-1, respectively. In the human breast cancer-grafted SCID mouse model, Adp27-mt induced tumor regression and antitumor effects significantly better than Adp27-wt. Furthermore, Adp27-mt mainly caused G2/M arrest in the cell cycle progression, whereas Adp27-wt mediated a G1/S arrest 48 h after infection.The mutant p27(kip1) protein induced apoptosis, and inhibited cell growth more efficiently with stronger anti-tumor effects than wild-type p27(kip1). Thus, the recombinant adenovirus expressing mutant p27(kip1) could be useful in gene therapy against breast cancer.