James L. Watkins

Risk factors for post-ERCP pancreatitis: a prospective multicenter study.

OBJECTIVES:Pancreatitis is the most common and serious complication of diagnostic and therapeutic ERCP. The aim of this study is to examine the potential patient- and procedure-related risk factors for post-ERCP pancreatitis in a prospective multicenter study.METHODS:A 160-variable database was prospectively collected by a defined protocol on patients undergoing diagnostic or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group and participating in a randomized controlled study evaluating whether prophylactic corticosteroids will reduce the incidence of post-ERCP pancreatitis. Data were collected prior to the procedure, at the time of procedure, and 24–72 h after discharge. Post-ERCP pancreatitis was diagnosed and its severity graded according to consensus criteria.RESULTS:Of the 1,115 patients enrolled, diagnostic ERCP with or without sphincter of Oddi manometry (SOM) was performed in 536 (48.1%) and therapeutic ERCP in 579 (51.9%). Suspected sphincter of Oddi dysfunction (SOD) was the indication for the ERCP in 378 patients (33.9%). Pancreatitis developed in 168 patients (15.1%) and was graded mild in 112 (10%), moderate in 45 (4%), and severe in 11(1%). There was no difference in the incidence of pancreatitis or the frequency of investigated potential pancreatitis risk factors between the corticosteroid and placebo groups. By univariate analysis, the incidence of post-ERCP pancreatitis was significantly higher in 19 of 30 investigated variables. In the multivariate risk model, significant risk factors with adjusted odds ratios (OR) were: minor papilla sphincterotomy (OR: 3.8), suspected SOD (OR: 2.6), history of post-ERCP pancreatitis (OR: 2.0), age <60 yr (OR: 1.6), ≥2 contrast injections into the pancreatic duct (OR: 1.5), and trainee involvement (OR: 1.5). Female gender, history of recurrent idiopathic pancreatitis, pancreas divisum, SOM, difficult cannulation, and major papilla sphincterotomy (either biliary or pancreatic) were not multivariate risk factors for post-ERCP pancreatitis.CONCLUSION:This study emphasizes the role of patient factors (age, SOD, prior history of post-ERCP pancreatitis) and technical factors (number of PD injections, minor papilla sphincterotomy, and operator experience) as the determining high-risk predictors for post-ERCP pancreatitis.

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.).

Tissue sampling at ERCP in suspected malignant biliary strictures (Part 2)

Part I of this review in the previous issue of Gastrointestinal Endoscopy outlined the key points of tissue sampling at ERCP and considered intraductal bile aspiration cytology, cytologic/histologic analysis of retrieved plastic biliary stents and fine needle aspiration cytology. Specimen adequacy, slide preparation, and accuracy of slide interpretation, which is often influenced by the interpretation “philosophy” of individual cytopathologists, are fundamental to the effort to optimize cancer detection by using tissue sampling techniques at ERCP. Intraductal bile aspiration is simple and inexpensive but adds little to the other methods, which have higher rates of cancer detection. Therefore, bile aspiration is recommended only when other sampling techniques cannot be used. Cytologic evaluation of material from retrieved plastic biliary stents is relatively insensitive (32%) and impractical as a firstline approach to the diagnosis of malignant biliary obstruction because diagnosis is delayed until the stent is removed. However, it can be considered in patients undergoing stent exchange when other methods of tissue sampling fail to confirm the suspected diagnosis of malignancy. Endoscopic fineneedle aspiration (FNA) cytology has a lower rate of cancer detection (33%) than initially reported and is technically difficult. It is usually used to supplement other simpler methods. Part II of this review considers the remaining tissue sampling methods for use at ERCP: brush cytology, endobiliary forceps biopsy, and the multimodal tissue sampling. Methods for improving diagnostic yield are discussed. BRUSH CYTOLOGY

Large-diameter biliary orifice balloon dilation to aid in endoscopic bile duct stone removal: a multicenter series

BACKGROUND The utility and safety of endoscopic biliary orifice balloon dilation (EBD) for bile duct stone removal (with use of large-diameter balloons) after biliary endoscopic sphincterotomy (BES) is currently not well established. OBJECTIVE Our purpose was to evaluate the efficacy and complications of BES followed by > or = 12 mm diameter EBD for bile duct stone removal. DESIGN Retrospective, multicenter series. SETTING Five ERCP referral centers in the United States. PATIENTS AND INTERVENTIONS Patients who underwent attempted removal of bile duct stones by BES followed by EBD with > or = 12 mm diameter dilating balloons were identified by searching the prospectively recorded endoscopic databases from 1999 to 2007. Clinical parameters, endoscopic data, and outcomes were collected and analyzed. RESULTS One hundred three patients, mean age 70 +/- 17 years (range 23-98 years), with 56 (54%) women, underwent 107 procedures. Eleven patients (11%) had a prior history of acute pancreatitis. Pancreatogram was performed in 15 (14%) patients. Median stone size and median balloon diameter used was 13 mm. Complete stone removal in the first session of EBD was accomplished in 102 (95%) procedures, and mechanical lithotripsy was required in 29 (27%). Six patients (5.4%) had documented procedure-related complications including one patient with severe bleeding and one with severe cystic duct perforation. No acute pancreatitis occurred. CONCLUSION EBD with a large-diameter balloon in conjunction with BES for bile duct stone removal is effective and relatively safe. This technique appears to be a reasonable alternative option when standard BES and basket or balloon sweep are inadequate to remove bile duct stones.

Endoscopic snare papillectomy for tumors of the duodenal papillae

BACKGROUND Tumors of the major and the minor duodenal papillae can be malignant or premalignant, and traditionally are treated by surgical excision. This study evaluated the safety and the outcome of endoscopic snare resection of such tumors. METHODS All patients with tumors of the major or the minor papilla treated by endoscopic snare resection over a 10-year period (1994-2003) were identified from an ERCP database. Patients with tumors that had endoscopic features of malignancy and those proven to be cancerous by biopsy were excluded. Papillectomy was performed by electrosurgical snare resection. A pancreatic stent usually was placed before or after excision. Residual tumor was eradicated by repeated procedures. Endoscopic surveillance was at the discretion of the endoscopist. RESULTS Seventy snare resections were performed in 55 patients (mean age 59 years). Histopathologic diagnoses were the following: adenoma (45 patients; 7 with focal high-grade dysplasia, 6 with intraductal extension), adenocarcinoma (5), carcinoid tumor (2), gastric heterotopia (1), and normal histology (2). Fourteen patients had familial adenomatous polyposis. Of the 39 patients with isolated extraductal adenoma per cholangiogram, two underwent surgical resection because of persistent high-grade dysplasia, and 37 were successfully treated by endoscopic papillectomy alone. During follow-up (mean 30 months), 18 of 37 patients (49%) had no recurrence, 7 had recurrent adenoma (mean time interval to recurrence 27 months), two died of unrelated illnesses, and 10 are awaiting follow-up. Of the 6 patients with intraductal adenoma per cholangiogram, two underwent surgical resection, two had intraductal photodynamic therapy, and two had endoscopic snare resection. Intraductal tumor in the 4 latter patients was eliminated, although it recurred in one of the patients who had photodynamic therapy. Of the 7 patients with adenocarcinoma or carcinoid tumor, pancreaticoduodenectomy was performed in 3 and palliative papillectomy was performed in 4 unsuitable for surgery. One patient with carcinoid tumor of the minor papilla is alive, without recurrence, at 5 years after papillectomy. There were 10 procedure-related complications (14.5%), including pancreatitis (5), bleeding (4), and mild perforation (1). There was no procedure-related death. CONCLUSIONS Most adenomas of the duodenal papillae without intraductal extension can be fully resected by snare papillectomy. However, adenoma recurs in about a third of patients. Endoscopic therapy appears to be a reasonable alternative to surgery for management of papillary tumors. Longer follow-up is needed to determine the true recurrence rate and if endoscopic re-treatments are effective.

Role of EUS for preoperative evaluation of cholangiocarcinoma: a large single-center experience.

BACKGROUND Accurate preoperative diagnosis and staging of cholangiocarcinoma (CCA) remain difficult. OBJECTIVE To evaluate the utility of EUS in the diagnosis and preoperative evaluation of CCA. DESIGN Observational study of prospectively collected data. SETTING Single tertiary referral hospital in Indianapolis, Indiana. PATIENTS Consecutive patients with CCA from January 2003 through October 2009. INTERVENTIONS EUS and EUS-guided FNA (EUS-FNA). MAIN OUTCOME MEASUREMENTS Sensitivity of EUS for the detection of a tumor and prediction of unresectability compared with CT and magnetic resonance imaging (MRI); sensitivity of EUS-FNA to provide tissue diagnosis, by using surgical pathology as a reference standard. RESULTS A total of 228 patients with biliary strictures undergoing EUS were identified. Of these, 81 (mean age 70 years, 45 men) had CCA. Fifty-one patients (63%) had distal and 30 (37%) had proximal CCA. For those with available imaging, tumor detection was superior with EUS compared with triphasic CT (76 of 81 [94%] vs 23 of 75 [30%], respectively; P < .001). MRI identified the tumor in 11 of 26 patients (42%; P = .07 vs EUS). EUS identified CCA in all 51 (100%) distal and 25 (83%) of 30 proximal tumors (P < .01). EUS-FNA (median, 5 passes; range, 1-12 passes) was performed in 74 patients (91%). The overall sensitivity of EUS-FNA for the diagnosis of CCA was 73% (95% confidence interval, 62%-82%) and was significantly higher in distal compared with proximal CCA (81% vs 59%, respectively; P = .04). Fifteen tumors were definitely unresectable. EUS correctly identified unresectability in 8 of 15 and correctly identified the 38 of 39 patients with resectable tumors (53% sensitivity and 97% specificity for unresectability). CT and/or MRI failed to detect unresectability in 6 of these 8 patients. LIMITATION Single-center study. CONCLUSION EUS and EUS-FNA are sensitive for the diagnosis of CCA and very specific in predicting unresectability. The sensitivity of EUS-FNA is significantly higher in distal than in proximal CCA.

Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography in children: a large series report.

Objectives: Our goal is to evaluate the indications, findings, therapies, safety, and technical success of endoscopic retrograde cholangiopancreatography (ERCP) in children. Methods: Our database was searched for patients 17 years of age or younger undergoing ERCP between January 1994 and March 2003. Additional information was obtained by chart review. The safety and technical success of ERCP were examined. Complications were classified by the consensus criteria. Results: A total of 245 patients (95 M, 150 F; mean age 12.3 years) underwent 329 examinations. Indications included biliary pathology (n = 93), pancreatic pathology (n = 111), and chronic abdominal pain of suspected biliary or pancreatic origin (n = 41). The ERCP findings were bile duct stone(s) (n = 29), benign biliary stricture (n = 19), primary sclerosing cholangitis (n = 7), anomalous pancreaticobiliary union (n = 8), choledochal cyst (n = 5), bile duct leak (n = 6), malignant biliary stricture (n = 2), biliary atresia (n = 1), chronic pancreatitis (n = 44), pancreas divisum (n = 26), pancreatic duct stricture with (n = 6) or without (n = 9) leak, pancreatic tumor (n = 1), periampullary adenoma (n = 2), and sphincter of Oddi dysfunction (n = 65). Endoscopic therapies were performed in 71% of the procedures and included sphincterotomy, stone extraction, stricture dilation, endoprosthesis placement, snare papillectomy, and cystoduodenostomy. Thirty-two (9.7%) post-ERCP complications occurred and included cholangitis in 1 patient and pancreatitis in 31. The pancreatitis was graded mild in 24, moderate in 5, and severe in 2. No mortality related to ERCP occurred. Conclusions: Diagnostic and therapeutic ERCP results are similar in children and adults except for a lower incidence of malignant disease in children. Technical success rates are high. However, ERCP-related pancreatitis is not uncommon, and the risk and benefits should be carefully reviewed before proceeding. Outcome data are necessary and is currently being accumulated at our institution.

Mechanical lithotripsy of pancreatic and biliary stones: Complications and available treatment options collected from expert centers

INTRODUCTION:IPD and common bile duct (CBD) stones often require mechanical lithotripsy (ML) at ERCP for successful extraction. The frequency and spectrum of complications is not well described in the literature.AIM: To describe the frequency and spectrum of complications of ML.METHODS: A comprehensive retrospective review of cases requiring ML of large or resistant PC and/or CBD stones using a 46-point data questionnaire on type(s) of complication, treatment attempted, and success of treatment. The study involved 7 tertiary referral centers with 712 ML cases (643 biliary and 69 pancreatic).RESULTS: Overall incidence of complications were: 4–4% (31/712); 23/643 biliary, 8/69 pancreatic; 21 single, 10 multiple. Biliary complications: trapped (TR)/broken (BR) basket (N = 11), wire fracture (FX) (N = 8), broken (BR) handle (N = 7), perforation/duct injury (N = 3). Pancreatic complications: TR/BR basket (N = 7), wire FX (N = 4), BR handle (N = 5), pancreatic duct leak (N = 1). Endoscopic intervention successfully treated complications in 29/31 cases (93.5%). Biliary group treatments: sphincterotomy (ES) extension (N = 7), electrohydraulic lithotripsy (EHL) (N = 11), stent (N = 3), per-oral Soehendra lithotripsy (N = 8), surgery (N = 1), extracorporeal lithotripsy (N = 5), and dislodge stones/change basket (N = 4). Pancreatic group treatments: ES extension (N = 3), EHL (N = 2), stent (N = 5), Soehendra lithotriptor (N = 4), dislodge stones/change basket (N = 2), extracorporeal lithotripsy (ECL) (N = 1), surgery (N = 1). Perforated viscus patient died at 30 days.CONCLUSION: The majority of ML in expert centers involved the bile duct. The complication rate of pancreatic ML is threefold greater than biliary lithotripsy. The most frequent complication of biliary and pancreatic ML is trapped/broken baskets. Extension of ES and EHL are the most frequently utilized treatment options.

Therapeutic EUS-assisted endoscopic retrograde pancreatography after failed pancreatic duct cannulation at ERCP

BACKGROUND Cannulation of the pancreatic duct (PD) during endoscopic retrograde pancreatography (ERP) can fail even in experienced hands. A technique for therapeutic EUS-assisted rendezvous ERP has been described in a few case reports. OBJECTIVE To investigate the efficacy and safety of therapeutic EUS-assisted ERP. DESIGN Retrospective study. SETTING Tertiary-care medical center. PATIENTS This study involved 21 patients after failed ERP. INTERVENTION EUS-guided transgastric pancreatography by using a mixture of contrast media and methylene blue was attempted. If that was successful, ERP was attempted by using methylene blue flow as an indicator of the PD orifice or by a rendezvous technique using a wire passed into the PD and the small bowel through the EUS needle. MAIN OUTCOME MEASUREMENTS Technical success rate and complications. RESULTS The PD was of a normal diameter in 7 patients and was dilated in 14 patients. EUS-guided pancreatography was successfully done in all patients with a dilated PD but only in 4 of 7 patients (57%) with normal-diameter PDs. In 6 patients, ERP was successfully performed by using methylene blue flow as an indicator of the PD orifice. The rendezvous technique was successful in 4 of 12 cases (33%), and reasons for failure were either a tight stricture (n = 5) or a suboptimal angle of EUS needle insertion (n = 3). Overall, EUS-assisted ERP was successful in 10 of 21 patients (48%). Complications included peripancreatic abscess in 1 patient and mild pancreatitis in 1 patient. LIMITATIONS Retrospective study, small sample size. CONCLUSION EUS-assisted ERP is a complex procedure that can provide access to the PD in selected cases after failed standard ERP.

Does leaving a main pancreatic duct stent in place reduce the incidence of precut biliary sphincterotomy-associated pancreatitis? A randomized, prospective study.

BACKGROUND Pancreatitis is the most common major complication of ERCP and precut endoscopic sphincterotomy (ES). Prophylactic pancreatic duct (PD) stent placement has been shown to reduce the incidence and severity of post-ERCP pancreatitis (PEP) in high-risk settings. OBJECTIVE To determine whether leaving a main PD stent in place after precut ES would reduce the incidence and severity of PEP. DESIGN Single-center, randomized, prospective study. SETTING Tertiary care ERCP referral center. PATIENTS Consecutive patients who underwent ERCP with a clear indication for biliary access and standard biliary ES whereby free cannulation of the bile duct was not possible and precut ES was undertaken. INTERVENTIONS When free bile duct cannulation for ES was not possible and selective PD cannulation was achieved, a PD stent was placed. Using the PD stent as a guide, we used a needle-knife sphincterotome to perform precut ES. The patients were then randomized to either leaving the PD stent in place for 7 to 10 days (stent group) or immediate removal after the procedure (stent removed group). The remaining patients who did not undergo selective PD cannulation and stent placement were not randomized (no stent group) and had a free-hand needle-knife ES performed. MAIN OUTCOME MEASUREMENTS Patients were prospectively followed for the development of complications. Standardized criteria were used to diagnose and grade the severity of PEP. RESULTS A total of 151 patients were enrolled. The groups were similar with regard to patient demographics and patient and procedure risk factors for PEP. The overall incidence of PEP was 13.2% (20/151). It occurred in 4.3% (2/46), 21.3% (10/47), and 13.8% (8/58) of patients in the stent, stent removed, and no stent groups, respectively. The stent group had a significantly lower frequency and severity of PEP compared with the stent removed group (4.3% vs 21.3%; P = .027 for frequency and 0% vs 12.8%; P = .026 for moderate and severe pancreatitis). LIMITATIONS Single center. Randomization scheme not optimal. CONCLUSIONS These data suggest that placing and maintaining a PD stent for needle-knife precut ES reduces the frequency and severity of postprocedure pancreatitis.