408 Editorial Mayo Clin Proc, May 2002, Vol 77 its ability to remove stones at the same time, ERCP is often the first modality chosen in a patient wit

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1 Mayo Clin Proc, May 2002, Vol 77 Editorial 407 Editorial Past, Present, and Future of Endoscopic Retrograde Cholangiopancreatography: Perspectives on the National Institutes of Health Consensus Conference In this issue of Mayo Clinic Proceedings, Calvo et al 1 examine the diagnostic efficacy of noninvasive magnetic resonance cholangiopancreatography (MRCP) in patients with possible choledocholithiasis. Specifically, the authors evaluated whether stratifying patients to low, intermediate, or high probability of risk for choledocholithiasis would influence the value of biliary tree imaging by MRCP compared with the more traditional and more widely used invasive endoscopic retrograde cholangiopancreatography (ERCP). The importance of this timely topic is underscored by the recent assembling of a National Institutes of Health (NIH) consensus conference to discuss ERCP and related imaging techniques. The NIH conference was convened in Bethesda, Md, January 14 through 16, Specialists in gastroenterology, radiology, surgery, and outcomes research presented data to an independent nonfederal panel of practicing clinicians, biomedical scientists, clinical study methodologists, and a public representative. The goal of the conference was to review, by using an evidence-based approach, diagnostic and therapeutic ERCP alone and as it relates to other diagnostic and therapeutic procedures. The following questions were specifically addressed during the consensus conference: (1) What is the role of ERCP in gallstone disease? (2) What is the role of ERCP in pancreatic and biliary malignancy? (3) What is the role of ERCP in pancreatitis? (4) What is the role of ERCP in abdominal pain of possible pancreatic or biliary origin? (5) What are the factors determining adverse events or success of ERCP? (6) What future ERCP research directions are needed? This editorial summarizes the outcome of the NIH consensus conference on ERCP and provides perspective as it relates to the clinical practice of ERCP. Overview of ERCP Endoscopic retrograde cholangiopancreatography is both an endoscopic and a radiological procedure performed primarily by gastroenterologists. 2 Endoscopic retrograde cholangiopancreatography is usually performed with use of conscious sedation: an endoscope is passed to the ampulla (the opening of the bile and pancreatic ducts) located in the second portion of the duodenum. For diagnostic studies, Address reprint requests and correspondence to Todd H. Baron, MD, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN ( baron.todd@mayo.edu). Mayo Clin Proc. 2002;77: catheters are passed through the channel of the endoscope into the duct of interest, and contrast medium is injected under fluoroscopic guidance to outline the ductal structures or to measure sphincter pressure. Therapeutic maneuvers may be performed by incising the sphincter muscle at the opening of the bile duct or pancreatic duct (biliary and pancreatic duct sphincterotomy, respectively). Subsequently, other accessories may be passed through the endoscope channel into the duct of interest to remove stones, insert stents, or ablate tissue. ERCP Past Approximately 30 years ago, ERCP was developed as a diagnostic modality, primarily to facilitate radiographic images of the pancreas. 3,4 At that time, computed tomography (CT) was in its infancy. As the technology of both endoscopes and endoscopic accessories has improved, the procedure has evolved from a primarily diagnostic modality to a more therapeutic modality. This change has occurred as other less invasive pancreaticobiliary imaging modalities, such as abdominal ultrasonography, CT, magnetic resonance imaging, MRCP, and endoscopic ultrasonography (EUS), have emerged and evolved. ERCP Present Specified disease processes and clinical issues as well as the role of ERCP are discussed subsequently. The consensus of the NIH panel on each of these issues is also presented. See also page 422. Gallstones. Gallstone disease (cholelithiasis) is common. Gallstones within the common bile duct, or choledocholithiasis, may be diagnosed and treated with use of ERCP. Choledocholithiasis may be encountered in the patient before and after cholecystectomy. Common bile duct stones may also be encountered intraoperatively at the time of cholecystectomy. In the patient with an intact gallbladder, common bile duct stones may be removed preoperatively with ERCP and sphincterotomy or operatively at the time of cholecystectomy with bile duct exploration. Postoperatively, ERCP is the preferred method for removing bile duct stones. Standard transabdominal ultrasonography and abdominal CT scanning have modest sensitivities and specificities for diagnosing choledocholithiasis. Because of its high sensitivity for detecting choledocholithiasis and 2002 Mayo Foundation for Medical Education and Research

2 408 Editorial Mayo Clin Proc, May 2002, Vol 77 its ability to remove stones at the same time, ERCP is often the first modality chosen in a patient with suspected choledocholithiasis. However, ERCP is invasive and has associated risks, including pancreatitis and perforation. 5 Recently, MRCP 6,7 and EUS 8,9 emerged as noninvasive imaging modalities with a high accuracy for diagnosing choledocholithiasis. Recommendations from the NIH consensus conference panel are that noninvasive imaging studies of the bile duct should be performed when there is a low index of clinical suspicion for choledocholithiasis. Endoscopic retrograde cholangiopancreatography should be reserved for patients in whom choledocholithiasis (eg, clinical cholangitis) is highly suspected 10 or used when other imaging modalities suggest choledocholithiasis. When possible, choledocholithiasis detected at the time of intraoperative cholangiography during laparoscopic cholecystectomy should be managed by laparoscopic bile duct exploration. The report by Calvo et al offers additional support for selective use of noninvasive imaging modalities to supplant ERCP. These authors used clinical criteria to predict the presence of choledocholithiasis and stratified patients into 1 of 3 groups: high, intermediate, and low probability. All patients subsequently underwent both ERCP and MRCP. None of the patients stratified to low probability for having common bile duct stones had evidence of choledocholithiasis on ERCP. Choledocholithiasis was detected on ERCP in approximately two thirds of patients with high probability and one third of patients with low probability of having choledocholithiasis. Findings on MRCP correlated well with findings on ERCP. The authors concluded that patients with low or intermediate risk of choledocholithiasis can avoid diagnostic ERCP by undergoing MRCP, as has been suggested in other studies. 6,7 Although the radiologists who interpreted the MRCP findings in the study by Calvo et al were not blinded to clinical and routine transabdominal ultrasound findings, their report nevertheless supports the growing body of literature advocating the use of MRCP as a noninvasive test to avoid a potentially dangerous and unhelpful diagnostic ERCP. Malignancies. Ampullary Carcinoma. Ampullary malignancies may be diagnosed readily with ERCP since they may be visible endoscopically and are amenable to biopsy with high accuracy. The NIH conference panel concluded that ERCP is the best modality for diagnosing ampullary carcinoma. Pancreaticobiliary Malignancies. The consensus conference did not distinguish between primary pancreatic and primary biliary malignancies. Clinically, this may be important, and therefore these are addressed separately. Although ERCP has been used to diagnose pancreatic carcinoma, 11 more recent noninvasive imaging modalities have limited its use in this regard. The radiographic diagnosis of pancreatic carcinoma by ERCP is sensitive but nonspecific. A definitive tissue diagnosis of malignancy may be made at the time of ERCP by using brush cytology, fineneedle aspiration, and biopsy but with a relatively low yield 12 unless several techniques are used at the same time. 13 Abdominal CT, magnetic resonance imaging, MRCP, and EUS have good accuracy in the radiographic diagnosis and staging of pancreatic cancer Also, EUS facilitates tissue sampling and staging for potential operative resection. 17 Therefore, almost no role exists for using ERCP as a purely diagnostic modality for pancreatic carcinoma. Most patients with pancreatic carcinoma present with obstructive jaundice. During ERCP, stents may be placed in the common bile duct to relieve biliary obstruction. 18 Because evidence is insufficient that preoperative decompression of the biliary tree improves the outcome of patients with pancreatic cancer, 19 those with surgically resectable disease based on other imaging studies are best managed by attempted operative resection without ERCP. In patients with unresectable disease, ERCP with stent placement is best reserved for palliation of obstructive jaundice. Randomized studies 20 comparing surgical palliation of obstructive jaundice with ERCP-placed plastic stents show a better short-term outcome with ERCP with a lower morbidity and mortality but with more frequent reintervention for recurrent biliary obstruction. In randomized prospective trials, 21 expandable metal biliary stents remain patent significantly longer than plastic stents, reducing the need for reintervention for recurrent jaundice due to stent occlusion. No randomized trials have compared expandable metal biliary stent placement and surgery for palliation of obstructive jaundice in patients with pancreatic carcinoma. It is acknowledged that in clinical practice some patients may undergo ERCP preoperatively to relieve intractable pruritus while awaiting operative intervention. In summary, the NIH panel recommended that ERCP be avoided as a diagnostic or preoperative modality in patients with potentially resectable pancreatic carcinoma and be used as a nonoperative palliative modality for relief of malignant biliary obstruction. Cholangiocarcinoma is a relatively uncommon neoplasm. 22 Many of the issues discussed for patients with pancreatic carcinoma apply to those with cholangiocarcinoma. One major difference is that cholangiocarcinomas frequently involve the bifurcation of the right and left hepatic ducts and the more proximal biliary tree. Thus, ERCP before consideration of operative resection may be hazardous because forceful injection of radiographic contrast material into multiple biliary strictures is needed to assess the biliary anatomy for potential operative

3 Mayo Clin Proc, May 2002, Vol 77 Editorial 409 resection. These biliary segments may not be technically drainable endoscopically, and the undrained radiographic contrast promotes cholangitis because ERCP is not a sterile procedure and bacteria are introduced during the procedure. 23 Although not separately addressed by the consensus panel, it is recommended that such patients not undergo routine ERCP to determine operative resectability but rather should undergo EUS, CT, or MRCP. 24 In nonoperative patients, ERCP and stent placement can be used to palliate obstructive jaundice by selective contrast injection to minimize the risk of cholangitis. 25 Treatment of Pancreatitis. Acute Biliary Pancreatitis. Gallstones that pass into the common bile duct and ampulla account for biliary pancreatitis, the most common cause of acute pancreatitis. The offending stone has often passed out of the bile duct by the time the patient clinically presents with pancreatitis. The role of ERCP in such patients is to remove residual bile duct stone(s) and promote clinical improvement of pancreatitis. Data from randomized prospective trials of patients with acute biliary pancreatitis undergoing early ERCP and sphincterotomy (if bile duct stones are present) vs conservative care show a reduction in morbidity and mortality in those with clinically severe pancreatitis who undergo early ERCP. Therefore, the NIH panel suggested that early ERCP be used in the setting of acute pancreatitis only in patients with clinically severe gallstone pancreatitis and suspected ongoing biliary obstruction. Acute Recurrent Pancreatitis. Patients with idiopathic or unexplained acute recurrent pancreatitis after routine clinical, laboratory, and imaging evaluation may undergo ERCP in anticipation of endoscopically diagnosable and treatable conditions, such as pancreas divisum and dysfunction of the sphincter of Oddi. The latter is diagnosed by manometric catheters passed through the pancreatic and biliary sphincters. Data from several studies 29,30 are weak but suggest that patients with pancreas divisum have a reduction in episodes of acute recurrent pancreatitis, need for hospitalization, and pain after endoscopic sphincterotomy of the minor pancreatic papilla. The data suggesting benefit from severing of the pancreatic and biliary sphincter of Oddi at the major papilla for sphincter of Oddi dysfunction induced hypertension are inconclusive. Therefore, the NIH panel cautiously recommended ERCP and sphincterotomy of the minor papilla in patients with idiopathic acute recurrent pancreatitis and pancreas divisum but realizes that further studies are needed to validate this approach. Endoscopic retrograde cholangiopancreatography with sphincter of Oddi manometry (SOM) can be considered for patients with unexplained acute recurrent pancreatitis, but ERCP without concomitant SOM has no role, with the possible exception of when pancreas divisum is being considered. Severe Necrotizing Pancreatitis. Many patients with severe acute pancreatitis, regardless of etiology, have disruptions of the main pancreatic duct. Preliminary data show that endoscopic placement of a stent within the main pancreatic duct may result in clinical improvement in a subset of patients whose clinical course of pancreatitis is not improving. 31 At present, the NIH consensus panel believes there is insufficient evidence to support this approach before validation in prospective randomized trials. Chronic Pancreatitis. Patients with documented chronic pancreatitis may have intractable abdominal pain due to a poorly draining pancreatic duct from underlying benign pancreatic duct strictures and/or pancreatic duct stones. Traditional management of these patients has been surgical. With use of ERCP, endoscopic relief of obstruction is technically feasible by balloon dilation of dominant strictures, placement of stents, and removal of pancreatic duct stones, with or without assistance of extracorporeal shock wave lithotripsy The NIH consensus panel thought that, although data suggest efficacy with endoscopic treatment of chronic pancreatitis, studies are needed to compare endoscopic treatment of chronic pancreatitis to traditional surgical and nonsurgical therapies. Pancreatic Fluid Collections. Although endoscopic drainage of various pancreatic fluid collections (pseudocysts, abscesses, pancreatic necrosis), especially pancreatic pseudocysts, is technically feasible with reported outcomes similar to surgery, there are no comparative studies of endoscopic drainage and surgery or percutaneous therapy. The NIH consensus panel recommended randomized prospective trials be performed that compare endoscopic, surgical, and percutaneous therapy for pseudocyst drainage. Abdominal Pain of Possible Pancreatic or Biliary Origin. Patients who present with unexplained abdominal pain and normal findings on diagnostic, noninvasive studies and (frequently) prior cholecystectomy remain difficult to manage. In some such patients, diagnostic ERCP with SOM can diagnose and treat possible underlying dysfunction of the sphincter of Oddi. Patients may be classified clinically by objective criteria before ERCP is performed. 42 A subset of patients who present with some documented objective evidence of either abnormal liver enzymes during an attack or an abnormally dilated bile duct on noninvasive imaging studies appear to benefit from SOM, followed by endoscopic biliary sphincterotomy if abnormally high sphincter pressures are identified. 43 Patients with abdominal pain alone with no objective clinical or radiographic findings of biliary disease do not appear to benefit from this approach and may have visceral hyperalgesia. 44 The NIH panel recommended selective use of SOM in patients with some objective findings of delayed biliary drainage.

4 410 Editorial Mayo Clin Proc, May 2002, Vol 77 Patients with multiple objective findings of poor biliary drainage benefit from endoscopic biliary sphincterotomy without need for manometry. 45 The panel emphasized that patients with unexplained abdominal pain but no objective findings should not undergo a diagnostic ERCP alone (without manometry) because there is little likelihood these patients will benefit, and severe complications are likely to occur. Adverse Events or Success. Several serious complications may occur as a result of diagnostic or therapeutic ERCP. These complications include pancreatitis, bleeding, infection, perforation, and problems with sedation 5 and may result in death. The literature suggests that risk factors for complications after ERCP are patient related, procedure related, and operator related. 46 The main patient-related risk factors for an adverse outcome after ERCP are underlying coagulopathy and suspected dysfunction of the sphincter of Oddi. The highest complication rates are in patients who will least likely benefit from the procedure. 47,48 Procedure-related complications include difficult bile duct cannulation, injection of radiographic contrast material into the pancreatic duct, and precut biliary sphincterotomy. 46,47 Low ERCP caseloads have been found to be an endoscopist-related risk factor for higher post-ercp complications and lower success rates. 46,47 Finally, at smaller medical centers in which fewer than 200 ERCPs per year are performed, post-ercp complications are a risk. 49 The NIH panel strongly recommended that only physicians with adequate training and experience should perform ERCP (training guidelines described subsequently). Further studies are needed to determine factors responsible for ERCP-induced pancreatitis and whether medical therapy administered to high-risk patients will reduce the risk of post-ercp complications. Miscellaneous. A diagnostic ERCP issue not specifically addressed by the panel is using ERCP for diagnosing primary sclerosing cholangitis. Although ERCP remains the gold standard for this diagnosis, MRCP may be a useful alternative. 50 Additionally, although ERCP may also be useful for diagnosing intraductal papillary mucinous tumors of the pancreas by the endoscopic finding of mucin exiting the pancreatic duct, 51 its role compared with MRCP 52 and EUS 53 has not been defined. Finally, therapeutic applications of ERCP in which its efficacy has been proved but were not discussed by the panel include endoscopic treatment of bile duct leaks after cholecystectomy, 54 benign biliary strictures, 55 and postorthotopic liver transplantation bile duct diseases. 56 ERCP Future The consensus panel made some clear-cut recommendations. The most important was the need for improvement in the quality of clinical trials involving ERCP in the management of pancreaticobiliary disorders. The panel was unified and strong in its belief that this need could be met by initiating a cooperative group mechanism with the development of an infrastructure for multicenter participation in the design of high-quality clinical trials. This would require NIH funding. A blueprint for this action is in the Oncology Cooperative Studies, which the NIH supports. The panel recognized that ERCP has evolved to a predominantly therapeutic procedure. The article by Calvo et al shows the efficacy of MRCP for improving the diagnosis of choledocholithiasis, and the advances in other technologies that are less invasive than ERCP allow them to be used initially for diagnostic purposes and for ERCP to be used for therapeutic purposes. An important distinction between ERCP and other modalities is that it has both diagnostic and therapeutic potential. Endoscopic retrograde cholangiopancreatography should be performed by endoscopists with appropriate training and expertise. This issue is extremely important because patient safety and outcome are affected. Another important issue concerns training physicians to perform ERCP and what methods should be used. Data regarding training for ERCP are limited, but studies 57 show that gastroenterology fellows achieved overall competence after completing 180 to 200 ERCPs. Controversy exists over whether a certain number of cases performed is a good index for determining who should perform ERCP (and other procedures), but it is a factor. The American Society for Gastrointestinal Endoscopy 58 previously recommended the minimum number of ERCPs that should be performed before competency can be assessed (not granted) is 100 cases, of which at least 25 were therapeutic (including 20 sphincterotomies and 5 stent placements). The American Society for Gastrointestinal Endoscopy recently revised its recommendations and now suggests that the minimum number of procedures before ERCP competency can be assessed is 200, of which 50 are therapeutic (M. B. Kimmey, MD, oral communication, April 2002). These issues are similar to those regarding the training of surgeons to perform laparoscopic bile duct exploration and stone extraction. The NIH panel discussed the use of simulators 59,60 and other training guides and thought that their application would be important. The panel recommended future research in the following areas: (1) role of therapeutic ERCP in the management of chronic pancreatitis compared with traditional surgical management, (2) role of ERCP and pancreatic duct stent placement in patients with acute necrotizing pancreatitis, (3) causes of unexplained acute recurrent pancreatitis and the role of endoscopic therapy, and (4) clinical importance, natural history, and management of microlithiasis or bil-

5 Mayo Clin Proc, May 2002, Vol 77 Editorial 411 iary sludge. The time is ripe for high-quality studies to show clearly the role of ERCP as a therapeutic alternative to medical, surgical, and percutaneous modalities. Todd H. Baron, MD Mayo Clinic Rochester, Minn David E. Fleischer, MD Mayo Clinic Scottsdale, Ariz 1. Calvo MM, Bujanda L, Calderón A, et al. Role of magnetic resonance cholangiopancreatography in patients with suspected choledocholithiasis. Mayo Clin Proc. 2002;77: American Society for Gastrointestinal Endoscopy. ASGE guidelines for clinical application: the role of ERCP in diseases of the biliary tract and pancreas. Gastrointest Endosc. 1999;50: McCune WS, Shorb PE, Moscovitz H. Endoscopic cannulation of the ampulla of vater: a preliminary report. Ann Surg. 1968;167: Cotton PB, Blumgart LH, Davies GT, et al. Cannulation of papilla of vater via fiber-duodenoscope: assessment of retrograde cholangiopancreatography in 60 patients. Lancet. 1972;1: Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. 1991;37: Boraschi P, Neri E, Braccini G, et al. Choledocholithiasis: diagnostic accuracy of MR cholangiopancreatography: three-year experience. Magn Reson Imaging. 1999;17: Stiris MG, Tennoe B, Aadland E, Lunde OC. MR cholangiopancreaticography and endoscopic retrograde cholangiopancreaticography in patients with suspected common bile duct stones: a prospective blinded study. Acta Radiol. 2000;41: Sugiyama M, Atomi Y. Endoscopic ultrasonography for diagnosing choledocholithiasis: a prospective comparative study with ultrasonography and computed tomography. Gastrointest Endosc. 1997;45: Canto MI, Chak A, Stellato T, Sivak MV Jr. Endoscopic ultrasonography versus cholangiography for the diagnosis of choledocholithiasis. Gastrointest Endosc. 1998;47: Onken JE, Brazer SR, Eisen GM, et al. Predicting the presence of choledocholithiasis in patients with symptomatic cholelithiasis. Am J Gastroenterol. 1996;91: Gilinsky NH, Bornman PC, Girdwood AH, Marks IN. Diagnostic yield of endoscopic retrograde cholangiopancreatography in carcinoma of the pancreas. Br J Surg. 1986;73: Schoefl R, Haefner M, Wrba F, et al. Forceps biopsy and brush cytology during endoscopic retrograde cholangiopancreatography for the diagnosis of biliary stenoses. Scand J Gastroenterol. 1997;32: Jailwala J, Fogel EL, Sherman S, et al. Triple-tissue sampling at ERCP in malignant biliary obstruction. Gastrointest Endosc. 2000;51(4, pt 1): Adamek HE, Albert J, Breer H, Weitz M, Schilling D, Riemann JF. Pancreatic cancer detection with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography: a prospective controlled study. Lancet. 2000;356: Georgopoulos SK, Schwartz LH, Jarnagin WR, et al. Comparison of magnetic resonance and endoscopic retrograde cholangiopancreatography in malignant pancreaticobiliary obstruction. Arch Surg. 1999;134: Ariyama J, Suyama M, Satoh K, Sai J. Imaging of small pancreatic ductal adenocarcinoma. Pancreas. 1998;16: Chang KJ, Nguyen P, Erickson RA, Durbin TE, Katz KD. The clinical utility of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of pancreatic carcinoma. Gastrointest Endosc. 1997;45: Cvetkovski B, Gerdes H, Kurtz RC. Outpatient therapeutic ERCP with endobiliary stent placement for malignant common bile duct obstruction. Gastrointest Endosc. 1999;50: Heslin MJ, Brooks AD, Hochwald SN, Harrison LE, Blumgart LH, Brennan MF. A preoperative biliary stent is associated with increased complications after pancreatoduodenectomy. Arch Surg. 1998;133: Smith AC, Dowsett JF, Russell RC, Hatfield AR, Cotton PB. Randomised trial of endoscopic stenting versus surgical bypass in malignant low bileduct obstruction. Lancet. 1994;344: Davids PH, Groen AK, Rauws EA, Tytgat GN, Huibregtse K. Randomised trial of self-expanding metal stents versus polyethylene stents for distal malignant biliary obstruction. Lancet. 1992;340: de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM. Biliary tract cancers. N Engl J Med. 1999;341: Motte S, Deviere J, Dumonceau JM, Serruys E, Thys JP, Cremer M. Risk factors for septicemia following endoscopic biliary stenting. Gastroenterology. 1991;101: Yeh TS, Jan YY, Tseng JH, et al. Malignant perihilar biliary obstruction: magnetic resonance cholangiopancreatographic findings. Am J Gastroenterol. 2000;95: Hintze RE, Abou-Rebyeh H, Adler A, Veltzke-Schlieker W, Felix R, Wiedenmann B. Magnetic resonance cholangiopancreatography-guided unilateral endoscopic stent placement for Klatskin tumors. Gastrointest Endosc. 2001;53: Neoptolemos JP, Carr-Locke DL, London NJ, Bailey IA, James D, Fossard DP. Controlled trial of urgent endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy versus conservative treatment for acute pancreatitis due to gallstones. Lancet. 1988;2: Fan S-T, Lai ECS, Mok FPT, Lo C-M, Zheng S-S, Wong J. Early treatment of acute biliary pancreatitis by endoscopic papillotomy. N Engl J Med. 1993;328: Fölsch UR, Nitsche R, Lüdtke R, Hilgers RA, Creutzfeldt W, German Study Group on Acute Biliary Pancreatitis. Early ERCP and papillotomy compared with conservative treatment for acute biliary pancreatitis. N Engl J Med. 1997;336: Lehman GA, Sherman S, Nisi R, Hawes RH. Pancreas divisum: results of minor papilla sphincterotomy. Gastrointest Endosc. 1993;39: Lans JI, Geenen JE, Johanson JF, Hogan WJ. Endoscopic therapy in patients with pancreas divisum and acute pancreatitis: a prospective, randomized, controlled clinical trial. Gastrointest Endosc. 1992;38: Lau ST, Simchuk EJ, Kozarek RA, Traverso LW. A pancreatic ductal leak should be sought to direct treatment in patients with acute pancreatitis. Am J Surg. 2001;181: Kozarek RA, Traverso LW. Endotherapy for chronic pancreatitis. Int J Pancreatol. 1996;19: Matthews K, Correa RJ, Gibbons RP, Weissman RM, Kozarek RA. Extracorporeal shock wave lithotripsy for obstructing pancreatic duct calculi. J Urol. 1997;158: Smits ME, Rauws EA, Tytgat GN, Huibregtse K. Endoscopic treatment of pancreatic stones in patients with chronic pancreatitis. Gastrointest Endosc. 1996;43: Smits ME, Badiga SM, Rauws EA, Tytgat GN, Huibregtse K. Long-term results of pancreatic stents in chronic pancreatitis. Gastrointest Endosc. 1995;42: Dumonceau JM, Deviere J, Le Moine O, et al. Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: long-term results. Gastrointest Endosc. 1996;43:

6 412 Editorial Mayo Clin Proc, May 2002, Vol Libera ED, Siqueira ES, Morais M, et al. Pancreatic pseudocysts transpapillary and transmural drainage. HPB Surg. 2000;11: Howell DA, Elton E, Parsons WG. Endoscopic management of pseudocysts of the pancreas. Gastrointest Endosc Clin N Am. 1998; 8: Catalano MF, Geenen JE, Schmalz MJ, Johnson GK, Dean RS, Hogan WJ. Treatment of pancreatic pseudocysts with ductal communication by transpapillary pancreatic duct endoprosthesis. Gastrointest Endosc. 1995;42: Barthet M, Sahel J, Bodiou-Bertei C, Bernard JP. Endoscopic transpapillary drainage of pancreatic pseudocysts. Gastrointest Endosc. 1995;42: Smits ME, Rauws EA, Tytgat GN, Huibregtse K. The efficacy of endoscopic treatment of pancreatic pseudocysts. Gastrointest Endosc. 1995;42: Hogan WJ, Geenen JE. Biliary dyskinesia. Endoscopy. 1988; 20(suppl 1): Geenen JE, Hogan WJ, Dodds WJ, Toouli J, Venu RP. The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with sphincter-of-oddi dysfunction. N Engl J Med. 1989;320: Desautels SG, Slivka A, Hutson WR, et al. Postcholecystectomy pain syndrome: pathophysiology of abdominal pain in sphincter of Oddi type III. Gastroenterology. 1999;116: Rolny P, Geenen JE, Hogan WJ. Post-cholecystectomy patients with objective signs of partial bile outflow obstruction: clinical characteristics, sphincter of Oddi manometry findings, and results of therapy. Gastrointest Endosc. 1993;39: Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996;335: Freeman ML, DiSario JA, Nelson DB, et al. Risk factors for post- ERCP pancreatitis: a prospective, multicenter study. Gastrointest Endosc. 2001;54: Cotton PB. ERCP is most dangerous for people who need it least [editorial]. Gastrointest Endosc. 2001;54: Loperfido S, Angelini G, Benedetti G, et al. Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc. 1998;48: Angulo P, Pearce DH, Johnson CD, et al. Magnetic resonance cholangiography in patients with biliary disease: its role in primary sclerosing cholangitis. J Hepatol. 2000;33: Nickl NJ, Lawson JM, Cotton PB. Mucinous pancreatic tumors: ERCP findings. Gastrointest Endosc. 1991;37: Albert J, Schilling D, Breer H, Jungius KP, Riemann JF, Adamek HE. Mucinous cystadenomas and intraductal papillary mucinous tumors of the pancreas in magnetic resonance cholangiopancreatography. Endoscopy. 2000;32: Kubo H, Chijiiwa Y, Akahoshi K, et al. Intraductal papillarymucinous tumors of the pancreas: differential diagnosis between benign and malignant tumors by endoscopic ultrasonography. Am J Gastroenterol. 2001;96: Ryan ME, Geenen JE, Lehman GA, et al. Endoscopic intervention for biliary leaks after laparoscopic cholecystectomy: a multicenter review. Gastrointest Endosc. 1998;47: Costamagna G, Pandolfi M, Mutignani M, Spada C, Perri V. Longterm results of endoscopic management of postoperative bile duct strictures with increasing numbers of stents. Gastrointest Endosc. 2001;54: Pfau PR, Kochman ML, Lewis JD, et al. Endoscopic management of postoperative biliary complications in orthotopic liver transplantation. Gastrointest Endosc. 2000;52: Jowell PS, Baillie J, Branch MS, Affronti J, Browning CL, Bute BP. Quantitative assessment of procedural competence: a prospective study of training in endoscopic retrograde cholangiopancreatography. Ann Intern Med. 1996;125: American Society for Gastrointestinal Endoscopy. Guidelines for credentialing and granting privileges for gastrointestinal endoscopy. Gastrointest Endosc. 1998;48: Neumann M, Mayer G, Ell C, et al. The Erlangen Endo- Trainer: life-like simulation for diagnostic and interventional endoscopic retrograde cholangiography. Endoscopy. 2000;32: Peifer JW, Curtis WD, Sinclair MJ. Applied virtual reality for simulation of endoscopic retrograde cholangio-pancreatography (ERCP). Stud Health Technol Inform. 1996;29:36-42.