Portal annular pancreas (PAP) is an asymptomatic congenital pancreas anomaly, in which portal and/or mesenteric veins are encased by pancreas tissue. The aim of the study was to determine the role of PAP in pancreatic surgery as well as its management and potential complication, specifically, postoperative pancreatic fistula (POPF). On the basis of a case report, the MEDLINE and ISI Web of Science databases were systematically reviewed up to September 2012. All articles describing a case of PAP were considered. In summary, 21 studies with 59 cases were included. The overall prevalence of PAP was 2.4% and the patients' mean (SD) age was 55.9 (16.2) years. The POPF rate in patients with PAP (12 pancreaticoduodenectomies and 3 distal pancreatectomies) was 46.7% (in accordance with the definition of the International Study Group of Pancreatic Surgery). Portal annular pancreas is a quite unattended pancreatic variant with high prevalence and therefore still remains a clinical challenge to avoid postoperative complications. To decrease the risk for POPF, attentive preoperative diagnostics should also focus on PAP. In pancreaticoduodenectomy, a shift of the resection plane to the pancreas tail should be considered; in extensive pancreatectomy, coverage of the pancreatic remnant by the falciform ligament could be a treatment option.

Background.: Ischemia and reperfusion injury (IRI) determines primary allograft function after liver transplantation (LT). Primary graft dysfunction (PGD) is associated with increased morbidity and impaired graft survival and can eventually progress to graft failure requiring retransplantation. Hypoxia-inducible transcription factor–prolyl hydroxylase containing enzymes (PHD1, PHD2, and PHD3) are molecular oxygen sensors, which control the adaptive hypoxia response through the hypoxia-inducible factor (HIF). In this study, we have investigated pharmacological activation of the HIF pathway through inhibition of PHDs as a strategy to reduce PGD after LT. Methods.: Primary rat hepatocytes were isolated and the impact of the pan-PHD small-molecule inhibitor ethyl-3,4-dihydroxybenzoate (EDHB) on HIF-1 and its downstream target gene expression assessed. Subsequently, various rodent models of segmental warm liver ischemia and reperfusion and orthotopic LT were applied to study the impact of EDHB on normothermic or combined cold and warm liver IRI. Liver enzyme levels and histology were analyzed to quantify hepatic IRI. Results.: In vitro, EDHB induced HIF-1 signaling and significantly upregulated its downstream target heme-oxygenase 1 in primary rat hepatocytes. In vivo, after establishment of the optimal EDHB pretreatment conditions in a murine IRI model, EDHB pretreatment significantly mitigated hepatic IRI after warm segmental liver ischemia and reperfusion and allograft injury after orthotopic LT in rats. Mechanistically, EDHB stabilized HIF-1 in the liver and subsequently increased hepatoprotective heme-oxygenase 1 levels, which correlated with reduced hepatic IRI in these models. Conclusions.: This proof-of-concept study establishes a strong therapeutic rationale for targeting PHDs with small-molecule inhibitors to mitigate PGD after LT.

Colitis-associated colorectal cancer (CAC) is a severe complication of inflammatory bowel disease (IBD). HIF-prolyl hydroxylases (PHD1, PHD2, and PHD3) control cellular adaptation to hypoxia and are considered promising therapeutic targets in IBD. However, their relevance in the pathogenesis of CAC remains elusive. We induced CAC in Phd1 ^–/– , Phd2 ^+/– , Phd3 ^–/– , and WT mice with azoxymethane (AOM) and dextran sodium sulfate (DSS). Phd1 ^–/– mice were protected against chronic colitis and displayed diminished CAC growth compared with WT mice. In Phd3 ^–/– mice, colitis activity and CAC growth remained unaltered. In Phd2 ^+/– mice, colitis activity was unaffected, but CAC growth was aggravated. Mechanistically, Phd2 deficiency (i) increased the number of tumor-associated macrophages in AOM/DSS-induced tumors, (ii) promoted the expression of EGFR ligand epiregulin in macrophages, and (iii) augmented the signal transducer and activator of transcription 3 and extracellular signal–regulated kinase 1/2 signaling, which at least in part contributed to aggravated tumor cell proliferation in colitis-associated tumors. Consistently, Phd2 deficiency in hematopoietic ( Vav:Cre-Phd2 ^fl/fl ) but not in intestinal epithelial cells ( Villin:Cre-Phd2 ^fl/fl ) increased CAC growth. In conclusion, the 3 different PHD isoenzymes have distinct and nonredundant effects, promoting (PHD1), diminishing (PHD2), or neutral (PHD3), on CAC growth.

Background: Recent evidence suggests that gut microbiome plays a role in the development of pancreatic ductal adenocarcinoma (PDAC) and influences treatment response. However, the association of tumor location and preoperative biliary stenting (PBS) with gut microbial composition and diversity remains poorly understood. Methods: Preoperative stool specimens were prospectively collected from patients with PDAC undergoing surgery between March 2020 and July 2021 at the Department of Surgery, Heidelberg University Hospital, Germany. Whole-genome shotgun metagenomic sequencing was performed. Microbial diversity was assessed using the Shannon index and Bray–Curtis dissimilarity with principal coordinates analysis. Results: A total of 63 preoperative stool samples were analyzed from 40 patients with pancreatic head (63.5%) and 23 with body/tail tumors (36.5%). Baseline characteristics were comparable between groups. Microbial community composition differed significantly between tumor locations (Bray–Curtis, p = 0.005), with enrichment of Ruminococcus bromii in body/tail tumors. Among patients with pancreatic head tumors, PBS was associated with reduced alpha diversity (Shannon index, p = 0.04) and depletion of taxa including Eubacteriales and Clostridiales taxa, and members of the genera Raoultella and Prevotella. PBS was associated with a higher rate of major complications > 3a according to the Clavien–Dindo classification (28.6% vs. 3.8%; p = 0.04). Conclusions: PBS was associated with reduced microbial diversity and distinct taxonomic alterations of the gut microbiome. These findings suggest that biliary stenting is associated with microbiome alterations that may be relevant for perioperative risk stratification and warrant further investigation.