Patrick Mosler

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.).

Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) Guideline

With the increasing use of antiplatelet agents (APA), their management during the periendoscopic period has become a more common and more difficult problem. The increase in use is due to the availability of new drugs and the widespread use of drug-eluting coronary stents. Acute coronary syndromes can occur when APA therapy is withheld for noncardiovascular interventions. Guidelines about APA management during the periendoscopic period are traditionally based on assessments of the procedure-related risk of bleeding and the risk of thrombosis if APA are stopped. New data allow better assessment of these risks, of the necessary duration of APA discontinuation before endoscopy, of the use of alternative procedures (mostly for endoscopic retrograde cholangiopancreatography [ERCP]), and of endoscopic methods that can be used to prevent bleeding (following colonic polypectomy). This guideline makes graded, evidence-based, recommendations for the management of APA for all currently performed endoscopic procedures. A short summary and two tables are included for quick reference.

Diagnosis and Management of Acute Cholangitis

Acute cholangitis is a potentially life-threatening systemic disease resulting from a combination of infection and obstruction of the biliary tree, secondary to different underlying etiologies. Common causes of cholangitis (eg, gallstones, benign and malignant biliary strictures) are well known. However, others (eg, immunoglobulin-G subclass-4–related sclerosing cholangitis) have been described only recently, are still under evaluation, and need to gain broader attention from clinicians. The diagnosis of acute cholangitis is based on clinical presentation and laboratory data indicating systemic infection, as well as diagnostic imaging modalities revealing signs of biliary obstruction and possibly an underlying etiology. The clinical presentation varies, and initial risk stratification is important to guide further management. Early medical therapy, including fluid resuscitation and appropriate antibiotic coverage, is of major importance in all cases, followed by a biliary drainage procedure and, if possible, definitive therapy of the underlying etiology. The type and timing of biliary drainage should be based on the severity of the clinical presentation, and the availability and feasibility of drainage techniques, such as endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiography (PTC), and open surgical drainage. ERCP plays a central role in the management of biliary obstruction in patients with acute cholangitis. Endoscopic ultrasound–guided biliary drainage recently emerged as a possible alternative to PTC for second-line therapy if ERCP fails or is not possible.

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

Oral allopurinol does not prevent the frequency or the severity of post-ERCP pancreatitis.

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

Accuracy of Magnetic Resonance Cholangiopancreatography in the Diagnosis of Pancreas Divisum

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.

The risk of post-ERCP pancreatitis and the protective effect of rectal indomethacin in cases of attempted but unsuccessful prophylactic pancreatic stent placement

BACKGROUND Pancreatitis is the most common major complication of ERCP. Efforts have been made to identify pharmacologic agents capable of reducing its incidence and severity. The aim of this trial was to determine whether prophylactic allopurinol, an inhibitor of oxygen-derived free radical production, would reduce the frequency and severity of post-ERCP pancreatitis. Methods A total of 701 patients were randomized to receive either allopurinol or placebo 4 hours and 1 hour before ERCP. A database was prospectively collected by a defined protocol on patients who underwent ERCP. Standardized criteria were used to diagnose and grade the severity of postprocedure pancreatitis. RESULTS The groups were similar with regard to patient demographics and to patient and procedure risk factors for pancreatitis. The overall incidence of pancreatitis was 12.55%. It occurred in 46 of 355 patients in the allopurinol group (12.96%) and in 42 of 346 patients in the control group (12.14%; p = 0.52). The pancreatitis was graded mild in 7.89%, moderate in 4.51%, and severe in 0.56% of the allopurinol group, and mild in 6.94%, moderate in 4.62%, and severe in 0.58% of the control group. There was no significant difference between the groups in the frequency or the severity of pancreatitis. CONCLUSIONS Prophylactic oral allopurinol did not reduce the frequency or the severity of post-ERCP pancreatitis.

Effect of Endoscopic Stenting of Malignant Bile Duct Obstruction on Quality of Life

BackgroundPatients with pancreas divisum may develop pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for diagnosing pancreas divisum. Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive test reported to be highly accurate in diagnosing pancreas divisum.AimTo evaluate the diagnostic accuracy of MRCP in detecting pancreas divisum at our institution.MethodsWe reviewed patients who underwent both ERCP and MRCP. Patients who had diagnostic endoscopic pancreatograms (ERP) after MRCP comprise the study population. Secretin was given in 113/146 patients (S-MRCP). The remaining 33/146 patients had MRCP without secretin. In 7/33 patients who underwent MRCP without secretin (21.2%), the studies were non-diagnostic and, therefore, this group was not further analyzed and the study focused on the S-MRCP group only.ResultsERP identified pancreas divisum in 19/113 (16.8%) patients. S-MRCP identified 14/19 pancreas divisum and was false-positive in three cases (sensitivity 73.3%, specificity 96.8%, positive predictive value 82.4%, negative predictive value 94.8%). Of the eight patients with inaccurate S-MRCP, 5 (63%) had changes of chronic pancreatitis by ERP. This differs from the frequency of chronic pancreatitis by ERP in 24/105 (23%) patients with accurate MRCP findings. The ERCP findings of chronic pancreatitis were more frequent among incorrect S-MRCP interpretations than among correct interpretations (odds ratio [OR] 5.5 [95% confidence interval (CI) 1.3–25.3]).SummaryMRCP without secretin is non-diagnostic for pancreas divisum in a significant proportion of patients. S-MRCP had a satisfactory specificity for detecting pancreas divisum. However, the sensitivity of S-MRCP for the diagnosis of pancreas divisum was modest at 73.3%. This is low compared to previous smaller studies, which reported a sensitivity of MRCP of up to 100%.

Predicting pancreas divisum by inspection of the minor papilla: a prospective study.

BACKGROUND It is believed, based on limited observational data, that an unsuccessful attempt to place a prophylactic pancreatic stent substantially increases the risk of post-ERCP pancreatitis (PEP). OBJECTIVE To better understand the risk of PEP in patients with failed pancreatic stent placement (FPS) and the impact of rectal indomethacin on this risk. DESIGN Secondary analysis of randomized, controlled trial data. SETTING University of Michigan and Indiana University. PATIENTS A total of 577 clinical trial participants at elevated risk for PEP. INTERVENTIONS Pancreatic stent placement. MAIN OUTCOME MEASUREMENTS Within the placebo group, we compared PEP rates in patients with FPS, patients who underwent successful stent placement, and in those without a stent attempt. We also performed a regression analysis evaluating the association between FPS and PEP. To define the protective effect of indomethacin, we repeated these analyses in the indomethacin group and in the full study cohort. RESULTS The incidence of PEP among patients in the placebo group who experienced FPS was 34.7%, significantly exceeding rates in patients who underwent successful stent placement (16.4%) and in those without a stent attempt (12.1%). After we adjusted for known PEP risk factors, FPS was found to be independently associated with PEP. Among the indomethacin group and in the full cohort, FPS was not associated with a higher risk of PEP. LIMITATIONS Low event rate, FPS not prospectively captured. CONCLUSION FPS appears to confer an increased risk of PEP, which is attenuated by rectal indomethacin administration. These findings highlight the importance of adequate training and proficiency before endoscopists attempt pancreatic stent placement and the routine use of rectal indomethacin in high-risk ERCP cases.

Recurrence rate of anastomotic biliary strictures in patients who have had previous successful endoscopic therapy for anastomotic narrowing after orthotopic liver transplantation.

Background and Goals: Endoscopic stent insertion is considered the method of choice for palliation of malignant bile duct obstruction (MBDO). However, it can cause complications and requires periodic stent exchanges. Although endoscopic stenting is clearly indicated for relief of cholangitis or refractory pruritus, its role in patients with jaundice alone is less clear. Endoscopic stenting for this relative indication might be justified, if there is a significant improvement in quality of life (QOL) of such patients. The aim of our study was to determine whether endoscopic stenting for MBDO results in improved QOL. Patients and Methods: Patients undergoing endoscopic retrograde cholangiopancreatography for MBDO and participating in a randomized trial comparing patency duration of 10 and 11.5-Fr biliary plastic stents, completed the Functional Assessment of Cancer Therapy-General questionnaire at baseline, at 1 month after stent insertion, and at 180 days after stent insertion. Results: A total of 164 patients answered the QOL questionnaire at baseline, 95 patients answered the questionnaire at 30 days, and 54 patients answered the questionnaire at 180 days after stent insertion. Endoscopic biliary stenting resulted in a statistically significant improvement in overall score of QOL, and different aspects of QOL such as physical, emotional, and functional well-being. There was a statistically significant improvement in most of the symptoms specific for MBDO at 30 and 180 days after stenting. Conclusions: Endoscopic stenting significantly improves QOL in patients with MBDO, and, therefore, is an appropriate part of palliative treatment in this patient population.