B. Joseph Elmunzer

A Randomized Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis

BACKGROUND Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). METHODS In this multicenter, randomized, placebo-controlled, double-blind clinical trial, we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP. Patients were determined to be at high risk on the basis of validated patient- and procedure-related risk factors. The primary outcome was post-ERCP pancreatitis, which was defined as new upper abdominal pain, an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least 2 nights. RESULTS A total of 602 patients were enrolled and completed follow-up. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in the indomethacin group and in 52 of 307 patients (16.9%) in the placebo group (P=0.005). Moderate-to-severe pancreatitis developed in 13 patients (4.4%) in the indomethacin group and in 27 patients (8.8%) in the placebo group (P=0.03). CONCLUSIONS Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00820612.).

Prophylaxis of post-ERCP pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - updated June 2014.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the prophylaxis of post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis. Main recommendations 1 ESGE recommends routine rectal administration of 100 mg of diclofenac or indomethacin immediately before or after ERCP in all patients without contraindication. In addition to this, in the case of high risk for post-ERCP pancreatitis (PEP), the placement of a 5-Fr prophylactic pancreatic stent should be strongly considered. Sublingually administered glyceryl trinitrate or 250 µg somatostatin given in bolus injection might be considered as an option in high risk cases if nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated and if prophylactic pancreatic stenting is not possible or successful. 2 ESGE recommends keeping the number of cannulation attempts as low as possible. 3 ESGE suggests restricting the use of a pancreatic guidewire as a backup technique for biliary cannulation to cases with repeated inadvertent cannulation of the pancreatic duct; if this method is used, deep biliary cannulation should be attempted using a guidewire rather than the contrast-assisted method and a prophylactic pancreatic stent should be placed. 4 ESGE suggests that needle-knife fistulotomy should be the preferred precut technique in patients with a bile duct dilated down to the papilla. Conventional precut and transpancreatic sphincterotomy present similar success and complication rates; if conventional precut is selected and pancreatic cannulation is easily obtained, ESGE suggests attempting to place a small-diameter (3-Fr or 5-Fr) pancreatic stent to guide the cut and leaving the pancreatic stent in place at the end of ERCP for a minimum of 12 - 24 hours. 4 ESGE does not recommend endoscopic papillary balloon dilation as an alternative to sphincterotomy in routine ERCP, but it may be advantageous in selected patients; if this technique is used, the duration of dilation should be longer than 1 minute.

Primary Sclerosing Cholangitis: Meta-Analysis of Diagnostic Performance of MR Cholangiopancreatography

PURPOSE To determine the diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) for detection of primary sclerosing cholangitis (PSC) in patients with biochemical cholestasis. MATERIALS AND METHODS Two reviewers searched MEDLINE, EMBASE, and other electronic databases to identify prospective studies in which MRCP was evaluated and compared with endoscopic retrograde cholangiopancreatography (ERCP), clinical examination, and/or histologic analysis for diagnosis of PSC in cholestasis and control cases. Main study inclusion criteria were (a) use of ERCP or percutaneous transhepatic cholangiography (PTC) as part of the reference standard for the diagnosis of PSC, (b) inclusion of patients with hepatobiliary disease other than PSC (ie, nonhealthy control subjects), (c) blinding of MRCP image readers to reference-standard results, (d) prospective study with ERCP or MRCP performed after subject recruitment into the study, and (e) inclusion of raw data (for true-positive, false-positive, true-negative, and false-negative results) that could be found or calculated from the original study data. Major exclusion criteria were duplicate article (on a primary study) that contained all or some of the original study data and inclusion of fewer than 10 patients with PSC. Methodologic quality was assessed by using the Quality Assessment of Diagnostic Accuracy Studies tool. Bivariate random-effects meta-analytic methods were used to estimate summary, sensitivity, specificity, and receiver operating characteristic (ROC) curves. RESULTS Six manuscripts with 456 subjects (with 623 independent readings)--185 with PSC--met the study inclusion criteria. The summary area under the ROC curve was 0.91. High heterogeneity (inconsistency index, 78%) was found but became moderate (inconsistency index, 36%) with the exclusion of one study in which the diagnostic threshold was set for high sensitivity. There was no evidence of publication bias (P = .27, bias coefficient analysis). Sensitivity and specificity of MRCP for PSC detection across all studies were 0.86 and 0.94, respectively. Positive and negative likelihood ratios with MRCP were 15.3 and 0.15, respectively. In patients with high pretest probabilities, MRCP enabled confirmation of PSC; in patients with low pretest probabilities, MRCP enabled exclusion of PSC. Worst-case-scenario (pretest probability, 50%) posttest probabilities were 94% and 13% for positive and negative MRCP results, respectively. CONCLUSION MRCP has high sensitivity and very high specificity for diagnosis of PSC. In many cases of suspected PSC, MRCP is sufficient for diagnosis, and, thus, the risks associated with ERCP can be avoided.

Effect of Flexible Sigmoidoscopy-Based Screening on Incidence and Mortality of Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

A systematic review and meta-analysis of randomized trials conducted by B. Joseph Elmunzer and colleagues reports that that flexible sigmoidoscopy-based screening reduces the incidence of colorectal cancer in average-risk patients, as compared to usual care or no screening.

Systematic review of the predictors of recurrent hemorrhage after endoscopic hemostatic therapy for bleeding peptic ulcers

BACKGROUND:An increased knowledge regarding the predictors of rebleeding after endoscopic therapy for bleeding ulcers should improve clinical management and outcomes. The aim of this systematic review was to identify the strongest and most consistent predictors of rebleeding to assist in the development of tools to stratify and appropriately manage patients after endoscopic therapy.METHODS:Bibliographic database searches for prospective studies assessing rebleeding after endoscopic therapy for bleeding ulcers were performed. Relevant studies were identified, and data were abstracted in a duplicate and independent fashion. The primary outcomes sought were significant independent predictors of rebleeding by multivariable analyses in ≥2 studies.RESULTS:Ten articles met the prespecified inclusion criteria. The pooled rate of rebleeding after endoscopic therapy was 16.4%. The independent pre-endoscopic predictors of rebleeding were hemodynamic instability (significant in 5 of 5 studies; summary odds ratio [OR] 2.75, 95% confidence interval [CI] 1.99–3.51) and comorbid illness (significant in 2 of 7 studies; insufficient data to calculate summary OR or report OR range). The independent endoscopic predictors of rebleeding were active bleeding at endoscopy (significant in 5 of 8 studies; summary OR 1.93, 95% CI 1.30–2.55), large ulcer size (significant in 4 of 5 studies; summary OR 2.01, 95% CI 1.21–2.80), posterior duodenal ulcer (significant in 2 of 3 studies; insufficient data to calculate summary OR or report OR range), and lesser gastric curvature ulcer (significant in 2 of 2 studies; insufficient data to calculate summary OR or report OR range).CONCLUSIONS:The independent predictors of recurrent hemorrhage after endoscopic therapy, particularly those that are the strongest and most consistent in the literature, may be used to select patients who are most likely to benefit from aggressive post-hemostasis care, including intensive care unit (ICU) observation and second-look endoscopy. Prospective studies designed to formally assess the relative utilities of these factors in predicting rebleeding and dictating management are needed.

Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials

BACKGROUND Data regarding the incidence and severity of post-ERCP pancreatitis (PEP) are primarily from nonrandomized studies. OBJECTIVE To determine the incidence, severity, and mortality of PEP from a systematic review of the placebo or no-stent arms of randomized, controlled trials (RCTs). DESIGN MEDLINE, EMBASE, and Cochrane databases were searched to identify RCTs evaluating the efficacy of drugs and/or pancreatic stents to prevent PEP. SETTING Systematic review of patients enrolled in RCTs evaluating agents for PEP prophylaxis. PATIENTS Patients in the placebo or no-stent arms of the RCTs INTERVENTION ERCP. MAIN OUTCOME MEASUREMENTS Incidence, severity, and mortality of PEP. RESULTS There were 108 RCTs with 13,296 patients in the placebo or no-stent arms. Overall, the PEP incidence was 9.7% and the mortality rate was 0.7%. Severity of PEP was reported for 8857 patients: 5.7%, 2.6%, and 0.5% of cases were mild, moderate, and severe, respectively. The incidence of PEP in 2345 high-risk patients was 14.7% and the severity of PEP was mild, moderate, and severe in 8.6%, 3.9%, and 0.8%, respectively, with a 0.2% mortality rate. The incidence of PEP was 13% in North American RCTs compared with 8.4% in European and 9.9% in Asian RCTs. ERCPs conducted before and after 2000 had a PEP incidence of 7.7% and 10%, respectively. LIMITATIONS Difference in PEP risk among patients in the included RCTs. CONCLUSION The incidence of PEP and severe PEP is similar in high-risk patients and the overall cohort. Discrepancies in the incidence of PEP across geographic regions require further study.

Does rectal indomethacin eliminate the need for prophylactic pancreatic stent placement in patients undergoing high-risk ercp post hoc efficacy and cost-benefit analyses using prospective clinical trial data

OBJECTIVES:A recent large-scale randomized controlled trial (RCT) demonstrated that rectal indomethacin administration is effective in addition to pancreatic stent placement (PSP) for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. We performed a post hoc analysis of this RCT to explore whether rectal indomethacin can replace PSP in the prevention of PEP and to estimate the potential cost savings of such an approach.METHODS:We retrospectively classified RCT subjects into four prevention groups: (1) no prophylaxis, (2) PSP alone, (3) rectal indomethacin alone, and (4) the combination of PSP and indomethacin. Multivariable logistic regression was used to adjust for imbalances in the prevalence of risk factors for PEP between the groups. Based on these adjusted PEP rates, we conducted an economic analysis comparing the costs associated with PEP prevention strategies employing rectal indomethacin alone, PSP alone, or the combination of both.RESULTS:After adjusting for risk using two different logistic regression models, rectal indomethacin alone appeared to be more effective for preventing PEP than no prophylaxis, PSP alone, and the combination of indomethacin and PSP. Economic analysis revealed that indomethacin alone was a cost-saving strategy in 96% of Monte Carlo trials. A prevention strategy employing rectal indomethacin alone could save approximately

Machine learning algorithms outperform conventional regression models in predicting development of hepatocellular carcinoma

150 million annually in the United States compared with a strategy of PSP alone, and

Factors associated with esophageal stricture formation after endoscopic mucosal resection for neoplastic Barrett's esophagus

85 million compared with a strategy of indomethacin and PSP.CONCLUSIONS:This hypothesis-generating study suggests that prophylactic rectal indomethacin could replace PSP in patients undergoing high-risk ERCP, potentially improving clinical outcomes and reducing healthcare costs. A RCT comparing rectal indomethacin alone vs. indomethacin plus PSP is needed.

Effect of Covered Metallic Stents Compared With Plastic Stents on Benign Biliary Stricture Resolution: A Randomized Clinical Trial

OBJECTIVES:Predictive models for hepatocellular carcinoma (HCC) have been limited by modest accuracy and lack of validation. Machine-learning algorithms offer a novel methodology, which may improve HCC risk prognostication among patients with cirrhosis. Our studys aim was to develop and compare predictive models for HCC development among cirrhotic patients, using conventional regression analysis and machine-learning algorithms.METHODS:We enrolled 442 patients with Child A or B cirrhosis at the University of Michigan between January 2004 and September 2006 (UM cohort) and prospectively followed them until HCC development, liver transplantation, death, or study termination. Regression analysis and machine-learning algorithms were used to construct predictive models for HCC development, which were tested on an independent validation cohort from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. Both models were also compared with the previously published HALT-C model. Discrimination was assessed using receiver operating characteristic curve analysis, and diagnostic accuracy was assessed with net reclassification improvement and integrated discrimination improvement statistics.RESULTS:After a median follow-up of 3.5 years, 41 patients developed HCC. The UM regression model had a c-statistic of 0.61 (95% confidence interval (CI) 0.56–0.67), whereas the machine-learning algorithm had a c-statistic of 0.64 (95% CI 0.60–0.69) in the validation cohort. The HALT-C model had a c-statistic of 0.60 (95% CI 0.50–0.70) in the validation cohort and was outperformed by the machine-learning algorithm. The machine-learning algorithm had significantly better diagnostic accuracy as assessed by net reclassification improvement (P<0.001) and integrated discrimination improvement (P=0.04).CONCLUSIONS:Machine-learning algorithms improve the accuracy of risk stratifying patients with cirrhosis and can be used to accurately identify patients at high-risk for developing HCC.