Background and study aims The anatomical meaning of the terms “proximal” and “distal” in relation to the pancreaticobiliary anatomy can be confusing. We aimed to investigate practice patterns of use of the terms “proximal” and “distal” for pancreaticobiliary anatomy amongst various medical specialties. Materials and methods An online survey link to a normal pancreaticobiliary diagram was emailed to a multispecialty physician pool. Respondents were asked to label various parts of the common bile duct (CBD) and pancreatic duct (PD) using the terms “proximal,” “distal,” “not sure,” or “other.” Variability in use of these terms between specialties was assessed. Results We received 370 completed surveys from 182 gastroenterologists (49.2 %), 97 surgeons (26.2 %), 68 radiologists (18.4 %), and 23 other physicians (6.2 %). There was overall consensus in describing the upper/sub-hepatic CBD as “proximal CBD” (73.8 %, P = 0.1499) and the lower/pre-ampullary portion as “distal CBD” (84.6 %, P = 0.1821). However, there was marked variability when describing the PD. The PD in the head of the pancreas was labeled as “proximal PD” by 42.4 % and “distal PD” also by 42.4 % (P < 0.0001); and in the tail as “proximal PD” by 41.4 % and “distal PD” by 43.2 % (P < 0.0001). Only 13.8 % of respondents used descriptive terminology (“PD in the head” or “PD in the tail”) for the PD. Radiologists most often used descriptive terminology for both the CBD and PD. Surgeons most consistently called “proximal PD” in the head, and “distal PD” in the tail of the pancreas. Conclusions Although use of the terms “proximal” and “distal” is still very common to describe pancreaticobiliary anatomy, there is a discordance about its meaning, particularly for the PD. Use of descriptive terminology may be a more accurate alternative to prior ambiguous terminologies such as “proximal” or “distal” and can serve to improve communication and decrease the possibility of medical errors.

Pancreatic cystic lesions can be benign, premalignant or malignant. The recent increase in detection and tremendous clinical variability of pancreatic cysts has presented a significant therapeutic challenge to physicians. Mucinous cystic neoplasms are of particular interest given their known malignant potential. This review article provides a brief but comprehensive review of premalignant pancreatic cystic lesions with advanced endoscopic ultrasound (EUS) management approaches. A comprehensive literature search was performed using PubMed, Cochrane, OVID and EMBASE databases. Preneoplastic pancreatic cystic lesions include mucinous cystadenoma and intraductal papillary mucinous neoplasm. The 2012 International Sendai Guidelines guide physicians in their management of pancreatic cystic lesions. Some of the advanced EUS management techniques include ethanol ablation, chemotherapeutic (paclitaxel) ablation, radiofrequency ablation and cryotherapy. In future, EUS-guided injections of drug-eluting beads and neodymium:yttrium aluminum agent laser ablation is predicted to be an integral part of EUS-guided management techniques. In summary, International Sendai Consensus Guidelines should be used to make a decision regarding management of pancreatic cystic lesions. Advanced EUS techniques are proving extremely beneficial in management, especially in those patients who are at high surgical risk.

BACKGROUND/AIMS:Surgery is the mainstay of treatment for cholecystitis. However, gallbladder stenting (GBS) has shown promise in debilitated or high-risk patients. Endoscopic transpapillary GBS and endoscopic ultrasound-guided GBS (EUS-GBS) have been proposed as safe and effective modalities for gallbladder drainage.METHODS:Data from patients with cholecystitis were prospectively collected from August 2004 to May 2013 from two United States academic university hospitals and analyzed retrospectively. The following treatment algorithm was adopted. Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and cystic duct stenting was initially attempted. If deemed feasible by the endoscopist, EUS-GBS was then pursued.RESULTS:During the study period, 139 patients underwent endoscopic gallbladder drainage. Among these, drainage was performed in 94 and 45 cases for benign and malignant indications, respectively. Successful endoscopic gallbladder drainage was defined as decompression of the gallbladder without incidence of cholecystitis, and was achieved with ERCP and cystic duct stenting in 117 of 128 cases (91%). Successful endoscopic gallbladder drainage was also achieved with EUS-guided gallbladder drainage using transmural stent placement in 11 of 11 cases (100%). Complications occurred in 11 cases (8%).CONCLUSIONS:Endoscopic gallbladder drainage techniques are safe and efficacious methods for gallbladder decompression in non-surgical patients with comorbidities.

The use of the terms "proximal" and "distal" in an anatomical context is well established in the medical literature. However, when used as part of endoscopic, surgical or radiologic reporting for describing pancreatic anatomy, the terms "proximal" and "distal" can create confusion and potential for serious implications, if misinterpreted.

Background and AimCurrent diagnostic modalities for indeterminate biliary strictures offer low accuracy. Probe‐based confocal laser endomicroscopy (pCLE) permits microscopic assessment of mucosal structures by obtaining real‐time high‐resolution images of the mucosal layers of the gastrointestinal tract. Previously, an interobserver study demonstrated poor to fair agreement even among experienced confocal endomicroscopy operators. Our objective was to assess interobserver agreement and diagnostic accuracy upon completion of a pCLE training session.MethodsForty de‐identified pCLE video clips of indeterminate biliary strictures were sent to five endoscopists at four tertiary care centers for scoring. Observers subsequently attended a teaching session by an expert pCLE user that included 20 training clips and rescored the same pCLE video clips, which were randomized and renumbered.ResultsPre‐training interobserver agreement for all observers was ‘fair’ (Κ: 0.31, P‐value: <0.0001) and diagnostic accuracy was 72% (55–80%). Post‐training interobserver agreement for all observers was ‘substantial’ (Κ: 0.74, P‐value: <0.0001) and diagnostic accuracy was 89% (80–95%). Using a paired t‐test, we observed an increase of 17% (95% CI 7.6–26.4) in post‐training diagnostic accuracy (t = 5.01, df = 4, P‐value 0.007).ConclusionsInterobserver agreement and diagnostic accuracy improved after observers underwent training by an expert pCLE user with a specific sequence set. Users should participate in such training programs to maximize diagnostic accuracy of pCLE evaluation.

INTRODUCTION:The most cost-effective diagnostic algorithm for gastroesophageal reflux disease (GERD) remains controversial. We hypothesized that prompt referral for esophageal pH monitoring is more cost-effective than prolonged empiric courses of proton-pump inhibitors (PPIs).DISCUSSION:A cost model was created based on a cohort of 100 patients with possible GERD who underwent pH monitoring. The additional costs incurred from pH monitoring were compared to the potential savings from avoiding unnecessary PPI usage in patients with a negative pH study. The costs of PPI therapy reach equivalence with pH monitoring after 6.4 to 23.7 weeks, depending on the PPI regimen. A total of 21,411 weeks of PPIs were prescribed beyond the recommended 8-week trial, of which 32 % were for patients who had a negative 24-h pH monitoring study. If the sensitivity of pH monitoring was 96 %, early referral for pH monitoring would have saved between $1,197 and $6,303 per patient over 10 years. This strategy remains cost-effective as long as the sensitivity of pH monitoring is above 35 %. Prompt referral for pH monitoring after a brief empiric PPI trial is a more cost-effective strategy than prolonged empiric PPI trials for patients with both esophageal and extraesophageal GERD symptoms.

BACKGROUND AND STUDY AIMS:Migration is the most common complication of the fully covered metallic self-expanding esophageal stent (FCSEMS). Recent studies have demonstrated migration rates between 30% and 60%. The aim of this study was to determine the effect of fixation of the FCSEMS by endoscopic suturing on migration rate.PATIENT AND METHODS:Patients who underwent stent placement for esophageal strictures and leaks over the last year were captured and reviewed retrospectively. Group A, cases, were patients who underwent suture placement and group B, controls, were patients who had stents without sutures. Basic demographics, indications, and adverse events (AEs) were collected. Kaplan-Meier analysis and Cox regression modeling were conducted to determine estimates and predictors of stent migration in patients with and without suture placement.RESULTS:Thirty-seven patients (18 males, 48.65%), mean age 57.2 years (±16.3 y), were treated with esophageal FCSEMS. A total of 17 patients received sutures (group A) and 20 patients received stents without sutures (group B). Stent migration was noted in a total of 13 of the 37 patients (35%) [2 (11%) in group A and 11 (55%) in group B]. Using Kaplan-Meier analysis and log-rank analysis, fixation of the stent with suturing reduced the risk of migration (P=0.04). There were no AEs directly related to suture placement.CONCLUSIONS:Anchoring of the upper flare of the FCSEMS with endoscopic sutures is technically feasible and significantly reduces stent migration rate when compared with no suturing, and is a safe procedure with very low AEs rates.

BACKGROUND:Confocal endomicroscopy provides real-time evaluation of various sites and has been used to provide detailed endomicroscopic imaging of the biliary tree. We aimed to evaluate the feasibility and utility of probe-based confocal laser endomicroscopy of the pancreatic duct as compared to cytologic and histologic results in patients with indeterminate pancreatic duct strictures. METHODS:Retrospective data on patients with indeterminate pancreatic strictures undergoing endoscopic retrograde cholangiopancreatography (ERCP) and confocal endomicroscopy were collected from two tertiary care centres. Real-time confocal endomicroscopy images were obtained during ERCP and immediate interpretation according to the Miami Classification was performed. RESULTS:18 patients underwent confocal endomicroscopy for evaluation of pancreatic strictures from July 2011 to December 2012. Mean pancreatic duct size was 4.2mm (range 2.2-8mm). Eight cases were interpreted as benign, 4 as malignant, 4 suggestive of intraductal papillary mucinous neoplasms, and 2 appeared normal. Cytology/histopathology for 15/16 cases showed similar results to confocal endomicroscopy interpretation. Kappa coefficient of agreement between cyto/histopathology and confocal endomicroscopy was 0.8 (p=0.0001). Pancreatic confocal endomicroscopy changed management in four patients, changing the type of surgery from total pancreatectomy to whipple. CONCLUSIONS:Confocal endomicroscopy is effective in assisting with diagnosis of indeterminate pancreatic duct strictures as well as mapping of abnormal pancreatic ducts prior to surgery.

Background: ERCP is effective for treating a bile leak (BL) after cholecystectomy (CCY), but few data exist on its effectiveness after hepatobiliary surgery (HBS).Objective: To determine the effectiveness of ERCP for treating BLs after HBS compared with BLs after cholecystectomy and to identify factors associated with treatment success.Design: Retrospective cohort.Setting: Academic tertiary-care referral center.Patients: Patients referred from 2001 to 2009 for ERCP treatment of BL after cholecystectomy or HBS.Interventions: ERCP.Main Outcome Measurements: Resolution of BL after a single ERCP.Results: A total of 223 patients were identified and 46 were excluded. Fifty underwent ERCP for treatment of BL after HBS and 127 after CCY. A single ERCP was successful at resolving BL in 89% of patients. Failure occurred in 7 HBS patients (14%) and 12 CCY patients (9%) (P = .379). After multiple ERCPs, success improved to 95% of the CCY group and 86% of the HBS group (P = .033). HBS patients underwent 30% more ERCPs (P = .049). ERCP was 3.3 times more likely to be successful in patients with cystic duct or duct of Luschka BLs (P = .028). Patients undergoing biliary stent placement were significantly more likely to have successful outcomes (odds ratio 71.0, P < .001). Surgical history or biliary sphincterotomy did not affect outcome. Odds of treatment failure were 3.5 times higher for each additional ERCP performed (P < .001).Limitations: Single-center, retrospective study.Conclusions: ERCP is effective for treating postoperative BLs. Location of a BL and placement of a biliary stent are the best predictors of endoscopic treatment success. (Gastrointest Endosc 2013;77:601-8.)

Introduction: Type VI collagen (COL6) forms a microfibrillar network associated with type I collagen fibrils and constitutes a major component of the prominent desmoplastic reaction in pancreatic ductal adenocarcinoma (PDA).We have demonstrated recently that a subunit of COL6, COL6A3, is expressed in high levels in PDA tissue.We also showed that COL6A3 gene undergoes tumor-specific alternative splicing to produce 3 isoforms E3, E4 and E6 that are tumor tissue-specific.The aim of this study is to investigate the diagnostic value and clinical significance of circulating COL6A3 isoforms mRNA in PDA.Methods: Serum samples were obtained from patients that underwent pancreatic resection at a single institution between 2006 and 2009.COL6A3 levels in the sera from patients with pathologically confirmed PDA (n=40), intraductal papillary mucinous neoplasms (IPMN) (n=20), and chronic pancreatitis (n=10) were analyzed by real time PCR using isoform-specific primers for E3, E4 and E6 .In addition, sera from age-matched healthy volunteers were analyzed (n=30).The prediction levels for malignancy were determined by the area under the receiver operating characteristic curve (AUC).In vitro, wound healing, cell proliferation and softagar colony formation assays evaluated the functional impact of each isoform in PDA cells (MIAPACA-2 and ASP-C-1) transfected with isoform-specific siRNA.A panel of inflammationand invasion/angiogenesis-related genes was also evaluated.Results: Circulating E6 mRNA levels were significantly (p=0.006)elevated in PDA patients when compared to all benign lesions.E3 and E4 were expressed at extremely low levels in all patients.Compared to IPMN alone, E6 levels were significantly higher in PDA (p=0.0036).There were no significant differences between E6 levels in IPMN and Normal sera (p= 0.59).Using a logistic regression model, we found that for each increasing unit of log E6 COL6A3, patients are 9.5 times more likely to harbor a cancer rather than a benign lesion, 95% CI (2.4, 38.1), p=0.002.The area under the ROC curve, AUC, was 0.72.Knocking down E3 or E4 or E6 with isoform-specific siRNA resulted in reduced PDA cell migration and invasion and concomitant reduction of the expression of several inflammation and angiogenesis-related genes, such as MMP-9, OPN, MCP-1 and VEGF.Interestingly, knocking down any of the 3 isoforms resulted in increased expression of TNF-alpha.Conclusions: Our data show for the first time the potential clinical significance of circulating E6 COL6A3 levels in the diagnosis of pancreatic malignancy.Our in vitro data suggests a role for COL6A3 isoforms in PDA progression and metastatic potential.

BACKGROUND:Endoscopic necrosectomy for necrotizing pancreatitis has been increasingly used as an alternative to surgical or percutaneous interventions. The use of fully covered esophageal self-expandable metallic stents may provide a safer and more efficient route for internal drainage. The aim of this study was to evaluate the safety and efficacy of endoscopic treatment of pancreatic necrosis with these stents.METHODS:A retrospective study at 2 US academic hospitals included patients with infected pancreatic necrosis from July 2009 to November 2012. These patients underwent transgastric placement of fully covered esophageal metallic stents draining the necrosis. After necrosectomy, patients underwent regular sessions of endoscopic irrigation and debridement of cystic contents. The efficacy endpoint was successful resolution of infected pancreatic necrosis without the need for surgical or percutaneous interventions.RESULTS:Seventeen patients were included with the mean age of 41±12 years. A mean of 5.3±3.4 sessions were required for complete drainage and the follow-up period was 237.6±165 days. Etiology included gallstone pancreatitis (6), alcohol abuse (6), s/p distal pancreatectomy (2), postendoscopic retrograde cholangiopancreatography pancreatitis (1), medication-induced pancreatitis (1), and hyperlipidemia (1). Mean size of the necrosis was 14.8 cm (SD 5.6 cm), ranging from 8 to 19 cm. Two patients failed endoscopic intervention and required surgery. The only complication was a perforation during tract dilation, which was managed conservatively. Fifteen patients (88%) achieved complete resolution.CONCLUSIONS:Endoscopic necrosectomy with covered esophageal metal stents is a safe and successful treatment option for infected pancreatic necrosis.

Surgery is the mainstay of treatment for cholecystitis; however, gallbladder stenting has shown promise in debilitated or high risk patients. Endoscopic transpapillary gallbladder stenting (ETGS) and endoscopic ultrasound guided gallbladder stenting (EUS-GBS) have been proposed as safe and effective modalities for gallbladder drainage.

Endoscopic necrosectomy for necrotizing pancreatitis has been increasingly employed at expert centers as an alternative to surgical or percutaneous interventions. The use of larger diameter fully covered esophageal self-expandable metallic stents (CSEMS) may potentially provide a safer and more efficient route for internal drainage. The objective of our study was to evaluate the safety and efficacy of endoscopic treatment of pancreatic necrosis with fully covered esophageal metallic stents.

Transesophageal NOTES is a promising new surgical platform that offers hope for a less-invasive means of accessing the mediastinum and thoracic cavity. Its evolution could result in decreased operative times and reduced short- and long-term postoperative pain. Continued technological advances will make transesophageal NOTES a viable approach in humans, and preliminary studies suggest this technique will be of great potential to the field of thoracic surgery.

Traditionally, the management of necrotizing pancreatitis has been surgical debridement. Endoscopic Necrosectomy has been offered as an alternative. Incorporating the use of fully covered esophageal self-expandable metallic stents (CSEMS) might provide a safer and more efficient platform for internal drainage through a larger diameter stent while offering enteral feeding. We are reporting our experience in the treatment of infected pancreatic necrosis employing esophageal CSEMS.

tests in selected cases. A rational approach would be to perform conventional cytological analysis on all bile duct brushings during which time excess material in the brush could be suspended in fluid rather than discarded. Only cases that were cytologically indeterminate, or clinically suspicious but cytologically benign, would then be processed to produce slides for FISH analysis and ThinPrep to improve diagnostic yield.

Current diagnostic modalities for diagnosing indeterminate biliary lesions or strictures have low rate of accuracy. Probe-based confocal endomicroscopy (pCLE) permits in vivo microscopic assessment of mucosal structures by obtaining high resolution images of the mucosal layers of the gastrointestinal tract in real time. Previously, an interobserver study demonstrated poor to fair agreement, even within experienced confocal endomicroscopy operators. The objective of this pilot study was to assess the interobserver agreement and improvement of accuracy after holding a teaching session accompanied by a 20 training sequences for the observers.