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Background: Despite the fact that primary percutaneous catheter drainage has become standard practice, some patients with pancreatic fistula after pancreatoduodenectomy ultimately undergo a relaparotomy. The aim of this study was to compare completion pancreatectomy with a pancreas-preserving procedure in patients undergoing relaparotomy for pancreatic fistula after pancreatoduodenectomy. Methods: This retrospective cohort study of nine institutions included patients who underwent relaparotomy for pancreatic fistula after pancreatoduodenectomy from 2005-2018. Furthermore, a systematic review and meta-analysis were performed according to the PRISMA guidelines. Results: From 4877 patients undergoing pancreatoduodenectomy, 786 (16 per cent) developed a pancreatic fistula grade B/C and 162 (3 per cent) underwent a relaparotomy for pancreatic fistula. Of these patients, 36 (22 per cent) underwent a completion pancreatectomy and 126 (78 per cent) a pancreas-preserving procedure. Mortality was higher after completion pancreatectomy (20 (56 per cent) versus 40 patients (32 per cent); P=0.009), which remained after adjusting for sex, age, BMI, ASA score, previous reintervention, and organ failure in the 24 h before relaparotomy (adjusted odds ratio 2.55, 95 per cent c.i. 1.07 to 6.08). The proportion of additional reinterventions was not different between groups (23 (64 per cent) versus 84 patients (67 per cent); P=0.756). The meta-analysis including 33 studies evaluating 745 patients, confirmed the association between completion pancreatectomy and mortality (Mantel-Haenszel random-effects model: odds ratio 1.99, 95 per cent c.i. 1.03 to 3.84). Conclusion: Based on the current data, a pancreas-preserving procedure seems preferable to completion pancreatectomy in patients in whom a relaparotomy is deemed necessary for pancreatic fistula after pancreatoduodenectomy. [ABSTRACT FROM AUTHOR]

Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae (POPF). The present study proposes a model based on Amylase Value in the Drain (AVD) measured in the first three postoperative days to predict a POPF. Amylase cut-offs were selected from a previous published systematic review and the accuracy were validated in a multicentre database from 12 centres in 2 countries. The present study defined POPF the 2016 ISGPS criteria (3 times the upper limit of normal serum amylase). A learning machine method was used to correlate AVD with the diagnosis of POPF. Overall, 454 (27%) of 1638 patients developed POPF. Machine learning excluded a clinically relevant postoperative pancreatic fistulae with an AUC of 0.962 (95% CI 0.940–0.984) in the first five postoperative days. An AVD at a cut-off of 270 U/L in 2 days in the first three postoperative days excluded a POPF with an AUC of 0.869 (CI 0.81–0.90, p < 0.0001). A single AVD in the first three postoperative days may not exclude POPF after pancreatoduodenectomy. The levels should be monitored until day 3 and have two negative values before removing the drain. In the group with a positive level, the drain should be kept in and AVD monitored until postoperative day five. [ABSTRACT FROM AUTHOR]

Background: Centralization of pancreatic surgery in the Netherlands has been ongoing since 2011. The aim of this study was to assess how centralization has affected the likelihood of resection and survival of patients with non-metastatic pancreatic head and periampullary cancer, diagnosed in hospitals with and without pancreatic surgery services. Methods: An observational cohort study was performed on nationwide data from the Netherlands Cancer Registry (2009-2017), including patients diagnosed with non-metastatic pancreatic head or periampullary cancer. The period of diagnosis was divided into three time intervals: 2009-2011, 2012-2014 and 2015-2017. Hospital of diagnosis was classified as a pancreatic or non-pancreatic surgery centre. Analyses were performed using multivariable logistic and Cox regression models. Results: In total, 10 079 patients were included, of whom 3114 (30.9 per cent) were diagnosed in pancreatic surgery centres. Between 2009-2011 and 2015-2017, the number of patients undergoing resection increased from 1267 of 3169 (40.0 per cent) to 1705 of 3566 (47.8 per cent) (P for trend < 0.001). In multivariable analysis, in 2015-2017, unlike the previous periods, patients diagnosed in pancreatic and non-pancreatic surgery centres had a similar likelihood of resection (odds ratio 1.08, 95 per cent c.i. 0.90 to 1.28; P = 0.422). In this period, however, overall survival was higher in patients diagnosed in pancreatic surgery than in those diagnosed in non-pancreatic surgery centres (hazard ratio 0.92, 95 per cent c.i. 0.85 to 0.99; P = 0.047). Conclusion: Aftercentralization of pancreatic surgery, the resection rate forpatients with pancreatic head and periampullary cancer diagnosed in non-pancreatic surgery centres increased and became similar to that in pancreatic surgery centres. Overall survival remained higherin patients diagnosed in pancreatic surgery centres. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients.Methods: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up.Discussion: The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer.Trial Registration: Primary registry and trial identifying number: EudraCT: 2017-002036-17 . Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register - NL7094 , NL61961.078.17, MEC-2018-004. [ABSTRACT FROM AUTHOR]