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.

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.

SUMMARYPreclinical models based on patient-derived xenografts have remarkable specificity in distinguishing transformed human tumor cells from non-transformed murine stromal cells computationally. We obtained 29 pancreatic ductal adenocarcinoma (PDAC) xenografts from either resectable or non-resectable patients (surgery and endoscopic ultrasound-guided fine-needle aspirate, respectively). Extensive multiomic profiling revealed two subtypes with distinct clinical outcomes. These subtypes uncovered specific alterations in DNA methylation and transcription as well as in signaling pathways involved in tumor-stromal cross-talk. The analysis of these pathways indicates therapeutic opportunities for targeting both compartments and their interactions. In particular, we show that inhibiting NPC1L1 with Ezetimibe, a clinically available drug, might be an efficient approach for treating pancreatic cancers. These findings uncover the complex and diverse interplay between PDAC tumors and the stroma and demonstrate the pivotal role of xenografts for drug discovery and relevance to PDAC.

Different diagnostic and prognostic groups of colorectal carcinoma (CRC) have been defined. However, accurate diagnosis and prediction of survival are sometimes difficult. Gene expression profiling might improve these classifications and bring new insights into underlying molecular mechanisms. We profiled 50 cancerous and noncancerous colon tissues using DNA microarrrays consisting of B8000 spotted human cDNA. Global hierarchical clustering was to some extent able to distinguish clinically relevant subgroups, normal versus cancer tissues and metastatic versus nonmetastatic tumours. Supervised analyses improved these segregations by identifying sets of genes that discriminated between normal and tumour tissues, tumours associated or not with lymph node invasion or genetic instability, and tumours from the right or left colon. A similar approach identified a gene set that divided patients with significantly different 5-year survival (100% in one group and 40% in the other group; P ¼ 0.005). Discriminator genes were associated with various cellular processes. An immunohistochemical study on 382 tumour and normal samples deposited onto a tissue microarray subsequently validated the upregulation of NM23 in CRC and a downregulation in poor prognosis tumours. These results suggest that microarrays may provide means to improve the classification of CRC, provide new potential targets against carcinogenesis and new diagnostic and/or prognostic markers and therapeutic targets.

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.

OLT can achieve control of hormonal symptoms and prolong survival in selected patients with liver metastasis of carcinoid tumors. It does not seem indicated for other NET.

PCT and IL-6 appear to be early markers of subsequent postoperative sepsis in patients undergoing major surgery for cancer. These findings could allow identification of postoperative septic complications.

EUS elastography is potentially capable of further defining the tissue characteristics of benign and malignant lesions but specifity has to be improved. It can be used to guide biopsy sampling for diagnosis.