Joseph Romagnuolo

A lexicon for endoscopic adverse events: report of an ASGE workshop

Patients and practitioners expect that their endoscopy procedures will go smoothly and according to plan. There are several reasons why they may be disappointed. The procedure may fail technically (eg, incomplete colonoscopy, failed biliary cannulation). It may seem to be successful technically but turn out to be clinically unhelpful (eg, a diagnosis missed, an unsuccessful treatment), or there may be an early relapse (eg, stent dysfunction). In addition, some patients and relatives may be disappointed by a lack of courtesy and poor communication, even when everything otherwise works well. The most feared negative outcome is when something ‘‘goes wrong’’ and the patient experiences a ‘‘complication.’’ This term has unfortunate medicolegal connotations and is perhaps better avoided. Describing these deviations from the plan as ‘‘unplanned events’’ fits nicely

Risk factors for complications after ERCP: a multivariate analysis of 11,497 procedures over 12 years

BACKGROUND Complications of ERCP are an important concern. We sought to determine predictors of post-ERCP complications at our institution. METHODS GI TRAC is a comprehensive data set of patients who underwent ERCP at our institution from 1994 through 2006. Logistic regression models were used to evaluate 4 categories of complications: (1) overall complications, (2) pancreatitis, (3) bleeding, and (4) severe or fatal complications. Independent predictors of complications were determined with multivariable logistic regression. RESULTS A total of 11,497 ERCP procedures were analyzed. There were 462 complications (4.0%), 42 of which were severe (0.36%) and 7 were fatal (0.06%). Specific complications of pancreatitis (2.6%) and bleeding (0.3%) were identified. Overall complications were statistically more likely among individuals with suspected sphincter of Oddi dysfunction (SOD) (odds ratio [OR] 1.91) and after a biliary sphincterotomy (OR 1.32). Subjects with a history of acute or chronic pancreatitis (OR 0.78) or who received a temporary small-caliber pancreatic stent (OR 0.69) had fewer complications. Post-ERCP pancreatitis was more likely to occur after a pancreatogram via the major papilla (OR 1.70) or minor papilla (OR 1.54) and among subjects with suspected SOD with stent placement (OR 1.45) or without stent placement (OR 1.84). Individuals undergoing biliary-stent exchange had less-frequent pancreatitis (OR 0.38). Biliary sphincterotomy was associated with bleeding (OR 4.71). Severe or fatal complications were associated with severe (OR 2.38) and incapacitating (OR 7.65) systemic disease, obesity (OR 5.18), known or suspected bile-duct stones (OR 4.08), pancreatic manometry (OR 3.57), and complex (grade 3) procedures (OR 2.86). CONCLUSIONS This study characterizes a large series of ERCP procedures from a single institution and outlines the incidence and predictors of complications.

Magnetic Resonance Cholangiopancreatography: A Meta-Analysis of Test Performance in Suspected Biliary Disease

Context Noninvasive imaging of the biliary tree with magnetic resonance cholangiopancreatography (MRCP) may detect certain abnormalities better than others. Contribution This meta-analysis summarized 67 studies that compared MRCP with other gold standard tests for diagnosing biliary obstruction (for example, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, and intraoperative or intravenous cholangiography). Magnetic resonance cholangiopancreatography compared well with most other tests, but it seemed slightly less sensitive for diagnosing stones (92%) and for differentiating benign from malignant obstruction (85%) than it was for identifying the presence (99%) and level (96%) of biliary obstruction. Cautions Study quality varied, and some sensitivity estimates had wide confidence intervals. The Editors Biliary diseases and conditions associated with biliary obstruction are a major cause of morbidity and mortality in North America. The accurate diagnosis of the presence and cause of biliary obstruction is key to the cost-effective work-up of patients with suspected biliary disease. Since its introduction in 1968, endoscopic retrograde cholangiopancreatography (ERCP) has become the gold standard in this setting. However, 1.3% to 9% of patients undergoing ERCP will have clinically significant pancreatitis, and 0.2% to 0.5% of patients will die of procedural complications (1-5). In a larger series, diagnostic ERCP was associated with a mortality rate of 0.2% and a moderate to severe pancreatitis rate of 0.7% (1). In 1992, the development of magnetic resonance cholangiopancreatography (MRCP), which used heavy T2-weighting and rapid image acquisition (thus avoiding breathing artifact), allowed the accurate noninvasive imaging of the biliary and pancreatic trees. The weighting involved in selected MRCP sequences is unique because it allows relatively stagnant fluids, such as bile and pancreatic juice, to have a high-signal intensity. Without use of a contrast agent, these fluids appear bright compared with the dark, low-signal intensity of adjacent solid hepatic and pancreatic tissue and fast-flowing fluids (such as circulating blood). Concurrently performed enhanced T1-weighted magnetic resonance imaging (MRI) of the liver and pancreatic parenchyma can complement MRCP by adding important staging information when a malignant disorder is suspected. Although MRCP offered the potential of avoiding ERCP and its attendant risks, evidence for this is lacking because some patients undergoing MRCP will also require ERCP for invasive diagnostic tests (for example, bile sampling or cytologic testing) or for therapy (sphincterotomy, stone removal, or stenting) (6). The possible morbid implication of false-positive and false-negative results also needs to be considered. The identification of clinical scenarios for which MRCP may have limitations is therefore important for the development of adapted clinical guidelines and work-up algorithms in this area. Over the past decade, a plethora of reports have dealt with the accuracy of MRCP in biliary imaging. Most have shown excellent performance in comparison to ERCP or composite gold standards that have included computed tomography (CT), percutaneous transhepatic cholangiography, intraoperative cholangiography, intravenous cholangiography, endoscopic ultrasonography, and surgery, with or without subsequent clinical follow-up (772). However, individually, the studies are too small to allow precise comment on the performance of MRCP in selected diagnostic subgroups, such as patients with suspected stone disease or biliary cancer. In addition, because of variation in study quality, patient samples, MRI technology, and gold standards used, simple pooling of performance characteristics would be inappropriate and potentially misleading. Therefore, we undertook a meta-analysis to better characterize MRCP performance, stratified by clinically important diagnostic scenarios. Methods Search Strategy We searched MEDLINE (from January 1987 to March 2003) and bibliographies using magnetic resonance imaging and biliary tract diseases as Medical Subject Headings terms. The search was a priori restricted to English- and French-language articles. Because of the nature of the articles and subject matter of interest, we believed that MEDLINE would contain all relevant articles and that the use of other databases would be unlikely to reveal additional published studies. We manually screened and assessed abstracts to identify comparative studies with a single or composite gold standard. Most abstracts described articles that were reviews, comparisons of MRI techniques, or case series without comparison with any gold standard (Figure 1). Figure 1. Flowchart of study and abstract exclusions. Inclusion Criteria We included the following types of articles: 1) comparative studies with a defined single or composite gold standard and 2) articles that contained sufficient detail to reconstruct 2 2 tables expressing MRCP results by disease status. Acceptable gold standards included ERCP, intraoperative cholangiography, percutaneous transhepatic cholangiography, intravenous cholangiography, endoscopic ultrasonography, and surgical exploration. We also allowed composite gold standards, including CT and clinical follow-up until clinical and biological abnormalities had resolved or until a diagnosis had been made. If the study type was unclear from the abstract or if no abstract was available but the title suggested a comparative study, the full manuscript was manually reviewed. For bibliographic screening, we also examined relevant reviews. Two international experts were also contacted in an attempt to identify any additional relevant unpublished reports; however, no such reports were found. Exclusion Criteria We excluded case series of patients with a particular diagnosis who were undergoing MRCP and studies in which only patients with positive results on MRCP had other imaging techniques or ERCP to confirm the diagnosis. If a comparative study preselected only patients with a positive test result by using a gold standard to see how MRCP could visualize the abnormalities, we judged the study to be inadequate (even if a group of healthy control persons had been added for comparison). In addition to an artificially set prevalence of disease in such studies and somewhat artificial corresponding predictive values, hand selection of clearly positive and clearly healthy cases may lead to bias. This spectrum bias can occur when a diagnostic test seems to have better performance because more easily diagnosed extremes have been chosen (73, 74). If more than 1 study was included from the same author, we carefully assessed the absence of overlap by using the recruitment periods noted in the manuscript or by contacting the author if the report did not provide these data. Quality Assessment Two authors independently assessed the quality of acceptable manuscripts, and a third author independently settled discrepancies. Studies were graded by using 4 criteria for quality, defined a priori, as described by Irwig and colleagues [75, 76]: 1) blinding, 2) consecutive recruitment of patients, 3) single [versus composite] gold standards, and 4) the nonselective use of the gold standard (that is, the gold standard was performed in all patients). The latter criterion was used to avoid verification bias, which occurs when only abnormal results on the index test lead to the performance of the gold standard to verify the diagnosis (77, 78). To compare the result of MRCP versus that of the gold standard, we then reconstructed 2 2 tables from each study to determine the presence, level, and cause of biliary obstruction, as well as to distinguish benign from malignant obstruction and to detect common bile duct stones. In a particular study, if 22 tables could be reconstructed for more than 1 radiologist, we used the overall results reported in this study, as determined by consensus or a third-party arbitrator, depending on the protocol of the study. Data Stratification and Definition of Imaging End Points We extracted data from the studies and categorized the imaging end points into 4 groupings to diagnose 1) the presence of obstruction; 2) the level of obstruction (here, a diseased patient in terms of the 2 2 table was considered to have hilar or intrahepatic disease, except for the study by Zidi and colleagues [35], which exclusively studied hilar tumors and considered intrahepatic extension to be diseased]; and the presence of either 3) biliary lithiasis or 4) malignancy. Only studies that had more than 5 patients with common bile duct stones were considered in the stone detection subcategory. Potential Confounders We considered 4 other variables, apart from study quality, to be of potential importance for explaining heterogeneity and interstudy variability: 1) imaging end point of the study [presence of obstruction, level of obstruction, presence of common bile duct stones, or presence of malignancy]; 2) clinical context [suspicion of stone, suspicion of malignancy, suspicion of either stone or malignancy, or suspicion of a wide variety of pancreaticobiliary diseases]; 3) MRCP technology era [dichotomized at December 1996, 5 years after its introduction in 1991]; 4) frequency of direct visualization (79-81) of the common bile duct by a conventional gold standard [dichotomized at greater or less than 90% of patients having had ERCP, intraoperative cholangiography, or percutaneous transhepatic cholangiography]; and 4) prevalence of disease. For the MRCP technology era variable, we divided patients into the post-1996 category if most patients seemed to have been recruited after 1 January 1997. Meta-Analytic Statistical Methods and Modeling We assessed the sensitivity and specificity of MRCP by noting the number of true-positive, false-positive, true-negative, and false-negative results. The overall observed sensit

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.).

Multisociety guideline on reprocessing flexible gastrointestinal endoscopes: 2011.

● The beneficial role of GI endoscopy for the prevention, diagnosis, and treatment of many digestive diseases and cancer is well established. Like many sophisticated medical devices, the endoscope is a complex, reusable instrument that requires reprocessing before being used on subsequent patients. The most commonly used methods for reprocessing endoscopes result in high-level disinfection. To date, all published occurrences of pathogen transmission related to GI endoscopy have been associated with failure to follow established cleaning and disinfection/ sterilization guidelines or use of defective equipment. Despite the strong published data regarding the safety of endoscope reprocessing, concern over the potential for pathogen transmission during endoscopy has raised questions about the best methods for disinfection or sterilization of these devices between patient uses. To this end, in 2003, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Healthcare Epidemiology of America collaborated with multiple physician and nursing organizations, infection prevention and control organizations, federal and state agencies, and industry leaders to develop evidence-based guidelines for reprocessing GI endoscopes.1,2 Since that ime, high-level disinfectants, automated reprocessing mahines, endoscopes and endoscopic accessories have all volved.3-6 However, the efficacy of decontamination and high-level disinfection is unchanged and the principles guiding both remain valid.7 Additional outbreaks of infection related to suboptimal infection prevention practices during endoscopy or lapses in endoscope reprocessing have been well publicized. A cluster of hepatitis C cases was attributed to grossly inappropriate intravenous medication and sedation practices.8 In numerous other instances, risk of infection transission has been linked to less willful, but incorrect, eprocessing as a result of unfamiliarity with endoscope hannels, accessories, and the specific steps required for eprocessing of attachments.9 Recent on-site ambulatory urgery center surveys confirm widespread gaps in infecion prevention practices.10 Given the ongoing occurrences of endoscopy-associated infections attributed to

Grading the complexity of endoscopic procedures: results of an ASGE working party

BACKGROUND Working parties of the American Society for Gastrointestinal Endoscopy (ASGE) Quality Committee recently published a proposed new lexicon for adverse events and a separate extensive review of risk factors. The complexity of procedures also affects outcomes. OBJECTIVE To establish a system for grading the complexity of endoscopic procedures. DESIGN Voting on levels 1 (easiest) to 4 (most difficult) on a list of possible procedures and contexts. SETTING Community and academic gastroenterologists in the United States, Canada, and Britain. MAIN OUTCOME MEASUREMENTS Median scores of votes cast. RESULTS Consensus list of levels 1 through 4 contexts and procedures. LIMITATIONS Eminence rather than evidence based. CONCLUSIONS A consensus list was developed for comments and testing to complement the proposed lexicons for adverse events and risk factors.

Predictors of Endoscopic Findings After Roux-en-Y Gastric Bypass

OBJECTIVES:To evaluate predictors of endoscopic findings in symptomatic patients after Roux-en-Y gastric bypass (RYGBP) for obesity.METHODS:A retrospective chart review of 1,001 RYGBP procedures was performed. Two hundred twenty-six (23%) patients were identified as having endoscopy to evaluate upper gastrointestinal symptoms following surgery. Polychotomous logistic regression analysis was used to assess predictors of normal endoscopy, marginal ulcers, stomal stenosis, and staple-line dehiscence.RESULTS:The most common endoscopic findings were 99 (44%) normal postsurgical anatomy, 81 (36%) marginal ulcer, 29 (13%) stomal stenosis, and 8 (4%) staple-line dehiscence. Factors that significantly increase the risk of marginal ulcers following surgery include smoking (AOR = 30.6, 95% CI 6.4–146) and NSAID use (AOR = 11.5, 95% CI 4.8–28). PPI therapy following surgery was protective against marginal ulcers (AOR = 0.33, 95% CI 0.11–0.97). Median time for diagnosis of marginal ulcers following surgery was 2 months, and 77 of 81 (95%) presented within 12 months.CONCLUSIONS:Following RYGBP surgery for obesity, smoking and NSAID use significantly increase the risk of marginal ulceration, and PPI therapy is protective. Because a significant majority of marginal ulcers present within 12 months of surgery, it may be reasonable to consider prophylactic PPI therapy during this time period, especially for high risk patients.

Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial.

IMPORTANCE Abdominal pain after cholecystectomy is common and may be attributed to sphincter of Oddi dysfunction. Management often involves endoscopic retrograde cholangiopancreatography (ERCP) with manometry and sphincterotomy. OBJECTIVE To determine whether endoscopic sphincterotomy reduces pain and whether sphincter manometric pressure is predictive of pain relief. DESIGN, SETTING, AND PATIENTS Multicenter, sham-controlled, randomized trial involving 214 patients with pain after cholecystectomy without significant abnormalities on imaging or laboratory studies, and no prior sphincter treatment or pancreatitis randomly assigned (August 6, 2008-March 23, 2012) to undergo sphincterotomy or sham therapy at 7 referral medical centers. One-year follow-up was blinded. The final follow-up visit was March 21, 2013. INTERVENTIONS After ERCP, patients were randomized 2:1 to sphincterotomy (n = 141) or sham (n = 73) irrespective of manometry findings. Those randomized to sphincterotomy with elevated pancreatic sphincter pressures were randomized again (1:1) to biliary or to both biliary and pancreatic sphincterotomies. Seventy-two were entered into an observational study with conventional ERCP managemeny. MAIN OUTCOMES AND MEASURES Success of treatment was defined as less than 6 days of disability due to pain in the prior 90 days both at months 9 and 12 after randomization, with no narcotic use and no further sphincter intervention. RESULTS Twenty-seven patients (37%; 95% CI, 25.9%-48.1%) in the sham treatment group vs 32 (23%; 95% CI, 15.8%-29.6%) in the sphincterotomy group experienced successful treatment (adjusted risk difference, -15.6%; 95% CI, -28.0% to -3.3%; P = .01). Of the patients with pancreatic sphincter hypertension, 14 (30%; 95% CI, 16.7%-42.9%) who underwent dual sphincterotomy and 10 (20%; 95% CI, 8.7%-30.5%) who underwent biliary sphincterotomy alone experienced successful treatment. Thirty-seven treated patients (26%; 95% CI,19%-34%) and 25 patients (34%; 95% CI, 23%-45%) in the sham group underwent repeat ERCP interventions (P = .22). Manometry results were not associated with the outcome. No clinical subgroups appeared to benefit from sphincterotomy more than others. Pancreatitis occurred in 15 patients (11%) after primary sphincterotomies and in 11 patients (15%) in the sham group. Of the nonrandomized patients in the observational study group, 5 (24%; 95% CI, 6%-42%) who underwent biliary sphincterotomy, 12 (31%; 95% CI, 16%-45%) who underwent dual sphincterotomy, and 2 (17%; 95% CI, 0%-38%) who did not undergo sphincterotomy had successful treatment. CONCLUSIONS AND RELEVANCE In patients with abdominal pain after cholecystectomy undergoing ERCP with manometry, sphincterotomy vs sham did not reduce disability due to pain. These findings do not support ERCP and sphincterotomy for these patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00688662.

Cost-effectiveness of computerized tomographic colonography versus colonoscopy for colorectal cancer screening

Background: Computerized tomographic (CT) colonography is a potential alternative to colonoscopy for colorectal cancer screening. Its main advantage, a better safety profile, may be offset by its limitations: lower sensitivity, need for colonoscopy in cases where results are positive, and expense. Methods: We performed an economic evaluation, using decision analysis, to compare CT colonography with colonoscopy for colorectal cancer screening in patients over 50 years of age. Three-year outcomes included number of colonoscopies, perforations and adenomas removed; deaths from perforation and from colorectal cancer from missed adenomas; and direct health care costs. The expected prevalence of adenomas, test performance characteristics of CT colonography and colonoscopy, and probability of colonoscopy complications and cancer from missed adenomas were derived from the literature. Costs were determined in detail locally. Results: Using the base-case assumptions, a strategy of CT colonography for colorectal cancer screening would cost

Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

2.27 million extra per 100 000 patients screened; 3.78 perforation-related deaths would be avoided, but 4.11 extra deaths would occur from missed adenomas. Because screening with CT colonography would cost more and result in more deaths overall compared with colonoscopy, the latter remained the dominant strategy. Our results were sensitive to CT colonographys test performance characteristics, the malignant risk of missed adenomas, the risk of perforation and related death, the procedural costs and differences in screening adherence. Interpretation: At present, CT colonography cannot be recommended as a primary means of population-based colorectal cancer screening in Canada.