Vincent Moutardier

Endoscopic biliary stenting is the most common method of treating obstructive jaundice. We present a new technique of biliary drainage using endoscopic ultrasound (EUS) and EUS-guided puncture of the common bile duct (CBD). A 56-year-old man with obstructive jaundice was referred for EUS and endoscopic retrograde cholangiopancreatography (ERCP) because a computed tomography (CT) scan had shown a pancreatic mass in the head of the pancreas and a dilated CBD. The patient was enrolled in a preoperative chemoradiotherapy protocol and biliary stenting was required. Deep cannulation was not obtained even after a precut and the procedure was stopped. Using a therapeutic EUS scope (FG 38X Pentax), the CBD was punctured with a 5-F needle-knife under EUS guidance and a cholangiogram was obtained. A 0.35-inch guide wire was introduced into the CBD. The EUS scope was removed and a duodenoscope was introduced, allowing the placement through the duodenum of a 10-F plastic stent. The CBD was drained properly. No complication occurred.

Tissue architecture contributes to pancreatic ductal adenocarcinoma (PDAC) phenotypes. Cancer cells within PDAC form gland-like structures embedded in a collagen-rich meshwork where nutrients and oxygen are scarce. Altered metabolism is needed for tumour cells to survive in this environment, but the metabolic modifications that allow PDAC cells to endure these conditions are incompletely understood. Here we demonstrate that collagen serves as a proline reservoir for PDAC cells to use as a nutrient source when other fuels are limited. We show PDAC cells are able to take up collagen fragments, which can promote PDAC cell survival under nutrient limited conditions, and that collagen-derived proline contributes to PDAC cell metabolism. Finally, we show that proline oxidase (PRODH1) is required for PDAC cell proliferation in vitro and in vivo. Collectively, our results indicate that PDAC extracellular matrix represents a nutrient reservoir for tumour cells highlighting the metabolic flexibility of this cancer.

STUDY AIMS: The purpose of this study is to evaluate a new drainage technique for pancreatic pseudocysts or pancreatic abscesses entirely guided by endoscopic ultrasound (EUS) and using an interventional echo endoscope with a linear curved array transducer. PATIENTS AND METHODS: Between July 1996 and September 1999, EUS-guided drainage of a pancreatic pseudocyst or pancreatic abscess was carried out in 35 patients (26 men, 9 women; mean age 56.7, range 29-69). The mean size of the 35 pancreatic cysts was 7.8 cm (4-12 cm). Pancreatic pseudocysts were located in the head of the pancreas in two cases, in the body in six cases and in the tail in seven cases. On the other hand, the pancreatic abscesses were located in the tail of the pancreas in 17 cases and in the gastric wall in three cases. The EUS instrument used was the FG 38X endoscope manufactured by Pentax-Hitachi. RESULTS: No major complication occurred except in one case of a pneumoperitoneum, which was managed medically. Placement of the 7-F nasocystic drain was successful in 18/20 cases of pancreatic abscess. Surgery was performed in the two other patients. Concerning the pancreatic pseudocysts, placement of an 8.5-French stent was successful in 10 patients and of a nasopancreatic drain in five patients. In one case, only a puncture-aspiration was performed. One recurrence among the 15 pancreatic pseudocysts and two relapses of the 18 pancreatic abscesses have been observed, over a mean follow-up of 27 months (6-48 months). EUS-guided drainage was successful in 31/35 patients (88.5%); only four patients with pancreatic abscesses underwent surgery. No bleeding occurred during the time of this study. CONCLUSION: Internal drainage of pancreatic pseudocysts and abscesses exclusively performed with an echo endoscope is a safe and efficient method which should be evaluated further in larger studies.

Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival. Moreover, we describe the state of promoters, enhancers, super-enhancers, euchromatic, and heterochromatic regions for each subtype. Further analyses indicate that the distinct epigenomic landscapes are regulated by different membrane-to-nucleus pathways. Inactivation of a basal-specific super-enhancer associated pathway reveals the existence of plasticity between subtypes. Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets.