Resection margin is not a valid prognostic marker in publications before 2010 due to heterogeneity of cohorts and lack of standardized histopathological examination. Within standardized pathology protocols, R-status' prognostic validity may be primarily confined to pancreatic head cancers.

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There are fundamental differences in the biliary microbiome of patients with periampullary cancer who undergo PBD and those who do not. PBD induces a shift of the biliary microbiome towards a more aggressive and resistant spectrum, which requires a differentiated perioperative antibiotic treatment strategy.

Dysfunctional regulation of signalling pathways downstream of the insulin receptor plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. In this study we report both in vitro and in vivo experimental evidence for a role of Cullin-RING E3 ubiquitin ligase 7 (CRL7) in the regulation of insulin signalling and glucose homeostasis. We show that Cul7−/− mouse embryonic fibroblasts displayed enhanced AKT and Erk MAP kinase phosphorylation upon insulin stimulation. Depletion of CUL7 by RNA interference in C2C12 myotubes led to increased activation of insulin signalling pathways and cellular glucose uptake, as well as a reduced capacity of these cells to execute insulin-induced degradation of insulin receptor substrate 1 (IRS1). In vivo, heterozygosity of either Cul7 or Fbxw8, both key components of CRL7, resulted in elevated PI3 kinase / AKT activation in skeletal muscle tissue upon insulin stimulation when compared to wild-type controls. Finally, Cul7+/− or Fbxw8+/− mice exhibited enhanced insulin sensitivity and plasma glucose clearance. Collectively, our findings point to a yet unrecognized role of CRL7 in insulin-mediated control of glucose homeostasis by restraining PI3 kinase / AKT activities in skeletal muscle cells.

BackgroundPancreatic fistula/PF is the most frequent and feared complication after distal pancreatectomy/DP. However, the safest technique of pancreatic stump closure remains an ongoing debate. Here, we aimed to compare the safety of different pancreatic stump closure techniques for preventing PF during DP.MethodsWe performed a PRISMA-based meta-analysis of all relevant studies that compared at least two techniques of stump closure during DP with regard to PF rates/PFR. We further performed a retrospective analysis of our institutional PFR in correlation with stump closure techniques.Results8301 studies were initially identified. From these, ten randomized controlled trials/RCTs, eleven prospective and 59 retrospective studies were eligible. Stapler closure (26%vs.31%, OR:0.73, p = 0.02), combination of stapler and suture (30%vs.33%, OR:0.70, p = 0.05), or stump anastomosis (14%vs.28%, OR:0.51, p = 0.02) were associated with lower PFR than suture closure alone. Spleen preservation/splenectomy, or laparoscopic/open DP, TachoSil®, fibrin-like glue-application, or bioabsorbable-stapler-reinforcements (Seamguard®) did not influence PFR after DP. In contrast, autologous patches (falciform ligament/seromuscular patches) resulted in lower PFR than no patch application (21.9%vs.25,8%, OR:0.60, p = 0.006). In our institution, the major three techniques of stump closure resulted in comparable PFR (suture:27%, stapler:29%, or combination:24%). However, selective suturing/clipping of the main pancreatic duct during pancreatic stump closure prevented severe PF (p = 0.02).ConclusionAfter DP, stapler closure, pancreatic anastomosis, or falciform/seromuscular patches lead to lower PFR than suture closure alone. However, the differences are rather small, and further RCTs are needed to test these effects. Selective closure of the main pancreatic duct during stump closure may prevent severe PF.

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BackgroundNeoadjuvant therapy may increase the rate of radical tumour resection in patients with pancreatic cancer. Its impact on tumour recurrence has not been investigated fully. This study aimed to assess the impact of neoadjuvant therapy on patterns of recurrence.MethodsA systematic review was performed of articles identified through the PubMed, Scopus, Embase, Ovid and Google Scholar databases that analysed the relationship between neoadjuvant therapy and recurrence published to January 2016. The main endpoint was overall tumour recurrence. Other endpoints included local recurrence, any kind of distant, hepatic, pulmonary or peritoneal metastasis.ResultsA total of 4257 citations were reviewed. Twelve observational studies comprising 1365 patients were analysed. Neoadjuvant therapy significantly reduced the risk of overall (risk ratio (RR) 0·82, 95 per cent c.i. 0·74 to 0·90; P < 0·001) and local (RR 0·42, 0·32 to 0·55; P < 0·001) recurrence. Neoadjuvant therapy did not reduce the risk of any kind of distant (RR 1·02, 0·91 to 1·14; P = 0·78), hepatic (RR 0·86, 0·68 to 1·10; P = 0·23), pulmonary (RR 0·99, 0·37 to 2·66; P = 0·98) or peritoneal (RR 0·88, 0·57 to 1·38; P = 0·58) metastasis.ConclusionNeoadjuvant therapy reduced the risk of local recurrence but not that of distant metastasis.