Background and study aims: Postsurgical benign bilioenteric anastomotic strictures are a major adverse event of biliary surgery and endoscopic treatment, including endoscopic retrograde cholangiopancreatography (ERCP), is challenging in this setting. We present an innovative approach to treating this complication. Patients and methods: Patients underwent endoscopic ultrasound (EUS)-hepaticogastrostomy (HG) to treat nonmalignant biliary obstructions. A first endoscopy was performed to create the hepaticogastrostomy and to drain the biliary tree. The second step had a therapeutic purpose: antegrade dilation of the anastomosis. Results: Four men and three women with benign bilioenteric anastomotic strictures were included. Patients presented with jaundice or recurrent cholangitis. A fully covered HG stent was successfully deployed during the first endoscopy. During the second step, repeat antegrade dilation was performed through the HG in four cases (1 – 4 dilations) followed by double pigtail stenting in three cases. In three other patients, the stenosis was not crossable and a double pigtail stent was placed to maintain biliary drainage. All patients had symptom relief at the end of follow-up (45 weeks, range 33 – 64). Conclusions: Dilation of anastomotic stenosis through a hepaticogastrostomy is feasible and may provide permanent biliary drainage or recurrent access to the biliary tree in patients with altered anatomy. Double pigtail stents might prevent migration.

Both clinical and experimental evidence have firmly established that chronic pancreatitis, in particular in the context of Kras oncogenic mutations, predisposes to pancreatic ductal adenocarcinoma (PDAC). However, the repertoire of molecular mediators of pancreatitis involved in Kras-mediated initiation of pancreatic carcinogenesis remains to be fully defined. In this study we demonstrate a novel role for vacuole membrane protein 1 (VMP1), a pancreatitis-associated protein critical for inducible autophagy, in the regulation of Kras-induced PDAC initiation. Using a newly developed genetically engineered model, we demonstrate that VMP1 increases the ability of Kras to give rise to preneoplastic lesions, pancreatic intraepithelial neoplasias (PanINs). This promoting effect of VMP1 on PanIN formation is due, at least in part, by an increase in cell proliferation combined with a decrease in apoptosis. Using chloroquine, an inhibitor of autophagy, we show that this drug antagonizes the effect of VMP1 on PanIN formation. Thus, we conclude that VMP1-mediated autophagy cooperate with Kras to promote PDAC initiation. These findings are of significant medical relevance, molecules targeting autophagy are currently being tested along chemotherapeutic agents to treat PDAC and other tumors in human trials.