Jeffrey J. Easler

Impact of Retroflexion Vs. Second Forward View Examination of the Right Colon on Adenoma Detection: A Comparison Study

OBJECTIVES:Although screening colonoscopy is effective in preventing distal colon cancers, effectiveness in preventing right-sided colon cancers is less clear. Previous studies have reported that retroflexion in the right colon improves adenoma detection. We aimed to determine whether a second withdrawal from the right colon in retroflexion vs. forward view alone leads to the detection of additional adenomas.METHODS:Patients undergoing screening or surveillance colonoscopy were invited to participate in a parallel, randomized, controlled trial at two centers. After cecal intubation, the colonoscope was withdrawn to the hepatic flexure, all visualized polyps removed, and endoscopist confidence recorded on a 5-point Likert scale. Patients were randomized to a second exam of the proximal colon in forward (FV) or retroflexion view (RV), and adenoma detection rates (ADRs) compared. Logistic regression analysis was used to evaluate predictors of identifying adenomas on the second withdrawal from the proximal colon.RESULTS:A total of 850 patients (mean age 59.1±8.3 years, 59% female) were randomly assigned to FV (N=400) or RV (N=450). Retroflexion was successful in 93.5%. The ADR (46% FV and 47% RV) and numbers of adenomas per patient (0.9±1.4 FV and 1.1±2.1 RV) were similar (P=0.75 for both). At least one additional adenoma was detected on second withdrawal in similar proportions (10.5% FV and 7.5% RV, P=0.13). Predictors of identifying adenomas on the second withdrawal included older age (odds ratio (OR)=1.04, 95% confidence interval (CI)=1.01–1.08), adenomas seen on initial withdrawal (OR=2.8, 95% CI=1.7–4.7), and low endoscopist confidence in quality of first examination of the right colon (OR=4.8, 95% CI=1.9–12.1). There were no adverse events.CONCLUSIONS:Retroflexion in the right colon can be safely achieved in the majority of patients undergoing colonoscopy for colorectal cancer screening. Reexamination of the right colon in either retroflexed or forward view yielded similar, incremental ADRs. A second exam of the right colon should be strongly considered in patients who have adenomas discovered in the right colon, particularly when endoscopist confidence in the quality of initial examination is low.

Elevated Serum Triglycerides are Independently Associated With Persistent Organ Failure in Acute Pancreatitis

Objectives:Hypertriglyceridemia (HTG) represents a major health problem with prevalence exceeding 30% in the U.S. The present study aims to assess the effect of elevated serum triglyceride (TG) levels on the severity of acute pancreatitis (AP).Methods:Prospectively enrolled AP patients were categorized into normal, mild, moderate, and severe/very severe categories based on their TG levels and compared in respect to demographics, comorbidities, and clinical outcomes. Multivariate analysis determined whether elevated TG levels were independently associated with persistent organ failure.Results:Two hundred and one out of 400 AP patients had serum TGs measured within 72 h of presentation, of which 115 had normal TG levels and 86 HTG (20 mild, 41 moderate, and 25 severe/very severe). Patients with HTG were of younger age (44 vs. 52 years), predominantly male (65% vs. 45%), obese (57% vs. 34%), diabetic (38% vs. 17%), and developed more frequently persistent organ failure (40% vs. 17%) compared with those with normal TGs (P<0.02). The rate of persistent organ failure increased proportionally with HTG severity grades (17% when normal TGs, 30% in mild, 39% in moderate, and 48% in severe/very severe HTG, Ptrend<0.001). On multivariate analysis controlling for age, gender, body mass index, diabetes, and alcohol etiology, moderate HTG (odds ratio (OR), 2.6; P=0.04) and severe/very severe HTG (OR, 4.9; P=0.009) were independently associated with persistent organ failure.Conclusions:Elevated serum TGs in AP patients are independently and proportionally correlated with persistent organ failure regardless of etiology. TG-mediated lipotoxicity may be an attractive target to design novel interventions for severe AP.

Portosplenomesenteric Venous Thrombosis in Patients With Acute Pancreatitis Is Associated With Pancreatic Necrosis and Usually Has a Benign Course

BACKGROUND & AIMS Although there are some data on prevalence of portosplenomesenteric venous thrombosis (PSMVT) in patients with acute pancreatitis (AP), the progression of PSMVT in patients who have and have not received anticoagulants has not been studied systematically. We evaluated the prevalence and natural history of PSMVT in a well-defined cohort of individuals with AP. METHODS In a retrospective study, we analyzed data from the University of Pittsburgh Medical Center on 162 patients with a sentinel attack of AP from 2003-2010. Data were collected on patient demographics, clinical presentation, etiology, clinical course, and outcomes. One hundred twenty-two patients underwent contrast-enhanced computed tomography; the scans were reviewed to identify thromboses and/or narrowing of splanchnic veins (splenic, superior mesenteric, and portal). RESULTS PSMVT was detected in 22 patients overall (14%; 18% among patients who underwent contrast-enhanced computed tomography). Median time to detection of PSMVT was 17 days (interquartile range, 11-40 days). PSMVT formed most frequently in the splenic vein (19 of 22, 86%), followed by portal (8 of 22, 36%) and superior mesenteric (6/22, 27%) veins. Development of PSMVT was associated with presence (21 of 22, 95%), location, and extent of pancreatic necrosis. Fifty-three percent of patients (21 of 40) with necrosis developed PSMVT. Anticoagulants were administered infrequently (6 of 22, 27%) and always for indications unrelated to PSMVT. Most patients with PSMVT developed collateral veins (19 of 22, 86%), and 27% (6 of 22) were found to have varices during endoscopic evaluation, but clot resolution was infrequent (2 of 22, 9%). No patient developed complications directly related to PSMVT. CONCLUSIONS PSMVT develops in about half of patients with necrotizing AP and is rare in the absence of necrosis. Despite infrequent administration of anticoagulants, complications directly related to PSMVT are rare.

Hydrogen Peroxide-Assisted Endoscopic Necrosectomy for Walled-Off Pancreatic Necrosis: A Dual Center Pilot Experience

Pancreatic necrosis (PNec) is a serious local complication occurring in 10–15 % of patients with acute pancreatitis (AP). Necrotizing pancreatitis can organize into necrotic collections, termed walled-off necrosis (WON) [1, 2]. Symptomatic WON has traditionally been treated operatively [3]. In several recent trials, successful resolution of WON was achieved using endoscopic therapy, termed direct endoscopic necrosectomy (DEN) [4, 5]. A challenge to DEN is removal of all necrotic material from within the collection [6, 7]. Hydrogen peroxide (H2O2) is acknowledged as an effective means to achieve mechanical debridement of wounds [8–11]. In this case series, we describe a dual center experience with the use of H2O2 to facilitate removal of necrotic debris in patients undergoing DEN as the preliminary measure for management of WON.

Variation in learning curves and competence for ERCP among advanced endoscopy trainees by using cumulative sum analysis

BACKGROUND AND AIMS There are limited data on learning curves and competence in ERCP. By using a standardized data collection tool, we aimed to prospectively define learning curves and measure competence among advanced endoscopy trainees (AETs) by using cumulative sum (CUSUM) analysis. METHODS AETs were evaluated by attending endoscopists starting with the 26th hands-on ERCP examination and then every ERCP examination during the 12-month training period. A standardized ERCP competency assessment tool (using a 4-point scoring system) was used to grade the examination. CUSUM analysis was applied to produce learning curves for individual technical and cognitive components of ERCP performance (success defined as a score of 1, acceptable and unacceptable failures [p1] of 10% and 20%, respectively). Sensitivity analyses varying p1 and by using a less-stringent definition of success were performed. RESULTS Five AETs were included with a total of 1049 graded ERCPs (mean ± SD, 209.8 ± 91.6/AET). The majority of cases were performed for a biliary indication (80%). The overall and native papilla allowed cannulation times were 3.1 ± 3.6 and 5.7 ± 4, respectively. Overall learning curves demonstrated substantial variability for individual technical and cognitive endpoints. Although nearly all AETs achieved competence in overall cannulation, none achieved competence for cannulation in cases with a native papilla. Sensitivity analyses increased the proportion of AETs who achieved competence. CONCLUSION This study demonstrates that there is substantial variability in ERCP learning curves among AETs. A specific case volume does not ensure competence, especially for native papilla cannulation.

Advanced Techniques for Endoscopic Biliary Imaging: Cholangioscopy, Endoscopic Ultrasonography, Confocal, and Beyond

Cholangioscopy, endosonography, and confocal microscopy represent important technologies that expand biliary imaging beyond a level previously realized by noninvasive modalities (ultrasonography, computed tomography, and magnetic resonance cholangiopancreatography) and endoscopic retrograde cholangiopancreatography. Endoscopic ultrasonography has shown efficacy for the evaluation of indeterminate biliary strictures; however, this modality seems most reliable for distal bile duct abnormalities and in the setting of a moderate to high pretest probability for malignancy. Further refinement of these technologies, validation of their respective diagnostic criteria, and study within the context of comparative, randomized trials are needed and will contribute greatly to expedient patient care.

Invasive, mixed-type intraductal papillary mucinous neoplasm: superior prognosis compared to invasive main-duct intraductal papillary mucinous neoplasm.

PURPOSE It is unclear whether the duct involvement subtypes of intraductal papillary mucinous neoplasm (IPMN), ie, main (MD), mixed (MT), and branch (BD), confer any survival advantage when invasive IPMN occurs. We hypothesized that invasive MT-IPMN was associated with a better prognosis than invasive MD-IPMN. METHODS A retrospective review of a prospectively maintained database was performed of patients who underwent resection for IPMN at a single academic institution from 1992 to 2014. Characterization of IPMN subtype was assessed on final operative pathology. Statistics included univariate analysis, Kaplan-Meier survival curves, and Cox regression for independent predictors of increased survival. RESULTS Of 390 patients eligible for study, 74 had invasive IPMN (IPMC). Of these, 71 patients had complete data and were included in the analysis (17 MD-IPMC, 39 MT-IPMC, and 15 BD-IPMC). Median follow-up was 20 months (range, 2-174). MT-IPMC was associated with significantly greater overall survival (OS) (47 months) compared with MD-IPMC (12 months) (P = .049), but not with BD-IPMC (44 months) (P = .67). Multivariate Cox regression yielded a family history of pancreatic cancer, absence of jaundice, N0 status, negative margins, absence of lymphovascular invasion, and MT subtype as independent predictors of greater OS (P = .035, .015, .013, .036, .045, .043, respectively). No characteristic of IPMN (including MD diameter, solid component/mural nodule) was predictive of OS. CONCLUSION MT-IPMC appeared to be associated with a greater OS compared with pure MD-IPMC. This begs the question of a different underlying biology of MT-IPMN and argues against classification of all main duct involved IPMN into a single category.

An update on minimally invasive therapies for pancreatic necrosis

Pancreatic necrosis is a local complication of severe acute pancreatitis associated with multiple organ dysfunction, infection and increased mortality. While surgery is the mainstay for invasive management, studies have demonstrated that delaying necrosectomy translates to improved patient outcomes. Minimally invasive therapies have been described both for early and late management of necrotic pancreatic collections and fall into three broad categories: endoscopic, radiology assisted percutaneous drainage and laparoscopic or retroperitoneal surgical techniques. Such interventions may serve as temporizing measures delaying necrosectomy, but more importantly, as best demonstrated in recent randomized controlled trials, can serve as alternative approaches resulting in improved patient outcomes. Access to these techniques is based on their availability at expert centers. Minimally invasive therapies have increased in popularity, with a general consensus among experts being that reduced complications and mortality rates are realized by approaches other than open necrosectomy. However, additional well-designed, randomized trials are needed.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis

Background We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. Methods The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Results Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. Conclusion APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

Endotherapy is effective for pancreatic ductal disruption: A dual center experience.

BACKGROUND AND STUDY AIMS Pancreatic duct (PD) disruptions occur as a result of different etiologies and can be managed medically, endoscopically, or surgically. The aim of this study was to provide an evaluation on the efficacy of endotherapy for treatment of PD disruption in a large cohort of patients and identify factors that predict successful treatment outcome. PATIENTS AND METHODS We retrospectively evaluated consecutive patients who underwent endoscopic retrograde pancreatography (ERP) for transpapillary pancreatic stent placement for PD disruption from 2008 to 2013 at two tertiary referral institutions. PD disruption was defined as extravasation of contrast from the pancreatic duct as seen on ERP. Therapeutic success was defined by resolution of PD leak on ERP, clinical, and/or imaging evaluation. RESULTS We evaluated 107 patients (58% male, mean age 53 years) with PD disruption. Etiologies of PD disruption were acute pancreatitis (36%), post-operative (31%), chronic pancreatitis (29%), and trauma (4%). PD disruption was successfully bridged by a stent in 45 (44%) patients. Two patients developed post-sphincterotomy bleeding, two had stent migration, and two patients died as a result of post-ERP related complications. Placement of a PD stent was successful in 103/107 (96%) patients. Therapeutic success was achieved in 80/107 (75%) patients. Non-acute pancreatitis etiologies and absence of complete duct disruption were independent predictors of therapeutic success. CONCLUSIONS Endoscopic therapy using a transpapillary stent for PD disruption is safe and effective. Absence of complete duct disruption and non-AP etiologies determine a favorable endoscopic outcome.