Endoscopic Retrograde Cholangiopancreatography

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REVIEW Endoscopic Retrograde Cholangiopancreatography Sumit Singla, MD,* and Cyrus Piraka, MD Introduction Since its introduction in 1968, endoscopic retrograde cholangiopancreatography (ERCP) has

1 REVIEW Endoscopic Retrograde Cholangiopancreatography Sumit Singla, MD,* and Cyrus Piraka, MD Introduction Since its introduction in 1968, endoscopic retrograde cholangiopancreatography (ERCP) has revolutionized the diagnosis and management of pancreatobiliary disease. During most of the intervening years, ERCP has been invaluable as both a diagnostic and therapeutic procedure. However, advances in noninvasive radiographic and less invasive endoscopic imaging have transformed ERCP into an almost exclusively therapeutic procedure. Procedure ERCP involves the passage of a side-viewing duodenoscope transorally to the second portion of the duodenum. Various catheters, which directly exit the working channel of the duodenoscope, may be used for cannulation of the common bile duct and/or pancreatic duct. Contrast injection and real-time fluoroscopy allows the endoscopist to image ductal structures (see Figure 1). A guidewire is commonly used as a monorail to maintain position within the duct and to facilitate the passage and proper placement of catheters and stents. Various diagnostic and therapeutic procedures can be performed and are briefly outlined below. Sphincterotomy refers to an incision made with electrocautery through the sphincter of Oddi, a fibromuscular sheath encapsulating the distal common bile duct, pancreatic duct, and shared common channel. Retrieval balloons can be inflated within the duct and then withdrawn to remove stones and sludge. Wire baskets may also be used to grasp and/or crush stones within the duct to facilitate removal. Ductal or ampullary strictures can be dilated with a hydrostatic balloon or a graduated catheter passed over a guidewire. Stents composed of plastic or metal can ameliorate obstruction caused by benign and malignant biliary strictures; they also have a role in the management of postoperative biliary leaks and in reducing the risk of post-ercp pancreatitis. Strictures can be sampledwithforcepsbiopsyandbrushcytologywhencancer is suspected. Direct endoscopic visualization of the duct is also possible and is useful in diagnosing indeterminate strictures and in managing large or otherwise difficult stones. Indications ERCP is indicated for the evaluation and management of various pancreatobiliary disease states (see Table 1). In addition to the indications below, it is used to protect the bile duct and pancreatic duct during resection of ampullary polyps (ampullectomy). See Table 2 for several situations in which the performance of ERCP may not be indicated. Biliary Biliary indications for ERCP include choledocholithiasis, malignant or benign strictures, and bile leaks. Gallstone Disease The most common etiology of biliary obstruction is choledocholithiasis, 1 and sphincterotomy with stone extraction is successful in > 90% of cases 2 (see Figure 2). After sphincterotomy, stones may be removed from the duct with a balloon and/or wire basket. If the stone is too large to exit the duct, it may be crushed with a mechanical lithotripsy basket or via cholangioscopy and intraductal lithotripsy (commonly with electrohydraulic or laser lithotripsy). Alternatively, the biliary orifice may be dilated to a large enough diameter to facilitate stone removal. Transpapillary gallbladder access and stenting can be achieved with ERCP. In patients with symptomatic cholelithiasis or cholecystitis who are poor surgical candidates (i.e., advanced cirrhosis, multiple medical comorbidities), this strategy can potentially obviate the need for cholecystostomy tube placement. Abbreviations: ASGE, The American Society for Gastrointestinal Endoscopy; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound; PEP, post-ercp pancreatitis; PSC, primary sclerosing cholangitis; SOD, sphincter of Oddi dysfunction From the *Division of Gastroenterology, Henry Ford Health System, Detroit, MI; and the Section of Advanced Therapeutic Endoscopy, Division of Gastroenterology, Henry Ford Health System, Detroit, MI Potential conflict of interest: Nothing to report. View this article online at wileyonlinelibrary.com VC 2014 by the American Association for the Study of Liver Diseases doi: /cld Clinical Liver Disease, Vol 4, No 6, December 2014 An Official Learning Resource of AASLD

TABLE 2 Scenarios Where ERCP Is Not Definitely Indicated Acute pancreatitis in the absence of cholangitis or ongoing biliary obstruction. A single episode of idiopathic pancreatitis.

Suspected pancreatobiliary abdominal pain in the absence of elevated liver/pancreatic enzymes and/or a dilated duct (type III sphincter of Oddi dysfunction).

cholangiopancreatography is recommended in this context). Figure 1 Normal cholangiogram.

2 TABLE 2 Scenarios Where ERCP Is Not Definitely Indicated Acute pancreatitis in the absence of cholangitis or ongoing biliary obstruction. A single episode of idiopathic pancreatitis. Acute cholecystitis in the absence of biliary obstruction. Malignant jaundice without cholangitis prior to surgery (without planned neoadjuvant therapy). Suspected pancreatobiliary abdominal pain in the absence of elevated liver/pancreatic enzymes and/or a dilated duct (type III sphincter of Oddi dysfunction). For duct clearance prior to cholecystectomy in the absence of a documented stone or high clinical suspicion for a bile duct stone (alternative imaging such as EUS or magnetic resonance cholangiopancreatography is recommended in this context). Figure 1 Normal cholangiogram. TABLE 1 Indications for ERCP Ampullectomy for Ampullary Polyp Biliary Choledocholithiasis Bile leak Biliary stricture Malignant Pancreatic cancer Cholangiocarcinoma Ampullary adenocarcinoma Benign Primary sclerosing cholangitis Posttransplant stricture Chronic pancreatitis Sphincter of Oddi dysfunction Pancreatic Recurrent acute pancreatitis Chronic pancreatitis Pancreatic duct leak Sphincter of Oddi dysfunction Figure 2 Biliary stricture secondary to chronic pancreatitis. Benign Strictures Benign biliary strictures are generally managed with dilation and stent placement. Benign strictures may be due to compression from chronic pancreatitis, primary sclerosing cholangitis (PSC), or postoperatively (e.g., postliver transplant anastomotic stricture or cholecystectomy-related injury). Whereas success rates for the treatment of biliary strictures secondary to chronic pancreatitis were initially discouraging, 3 the use of multiple stents and more frequent endoscopic sessions has led to improved and more durable outcomes 4 (see Figure 3). Dominant strictures associated with PSC may be more optimally managed with balloon dilation as opposed to stent placement because limited data seems to suggest an increased risk of cholangitis with stent Figure 3 duct. Cholangiogram showing multiple stones in a dilated main bile 134 Clinical Liver Disease, Vol 4, No 6, December 2014 An Official Learning Resource of AASLD

TABLE 3 Risk Factors for the Development of Post-ERCP Pancreatitis Balloon dilation of biliary sphincter History of post-ercp pancreatitis Normal bilirubin Pancreatic duct injection Pancreatic

3 TABLE 3 Risk Factors for the Development of Post-ERCP Pancreatitis Balloon dilation of biliary sphincter History of post-ercp pancreatitis Normal bilirubin Pancreatic duct injection Pancreatic sphincterotomy Precut sphincterotomy Suspected sphincter of Oddi dysfunction Young age Modified from Freeman. 27 Bile Leaks ERCP with stent placement for the management of postoperative biliary leaks leads to endoscopic closure in 80% to 100% of patients. 11 Sphincterotomy is not absolutely required for the treatment of bile leaks when stenting. Figure 4 Pancreatogram demonstrating chronic pancreatitis, with a dilated and irregular main pancreatic duct, prominent side branches, and intraductal stones. placement. 5 Biliary anastomotic strictures following liver transplantation can lead to a considerable amount of morbidity. The overall success rates for therapy of anastomotic strictures with balloon dilation with or without plastic stent placement are excellent, although repeated sessions may be required due to stricture recurrence. 6 Fully covered metal stents have increasingly been used for benign strictures recalcitrant to traditional endotherapy. Malignant Strictures ERCP and biliary stenting are indicated for the relief of jaundice secondary to pancreatic cancer. The diagnostic yield of stricture brush cytology, however, is low (30%- 50%), albeit somewhat higher when combined with forceps biopsy (65%-70%). 7 Endoscopic ultrasound (EUS)-guided fine needle aspiration, where available, has largely supplanted ERCP for this indication because it has a higher sensitivity (75%-94% in multiple studies). The sensitivity of brushings/biopsies for the diagnosis of cholangiocarcinoma has also been disappointing, ranging from 18% to 60%. 8 Cholangioscopy-guided biopsies may increase diagnostic yield of sampling indeterminate strictures, with recent studies suggesting an improvement in sensitivity (76.5% versus 29.4%) and negative predictive value (69.2% versus 42.8%), respectively, as compared to traditional techniques. 9 Newer diagnostic tests, including the use of digital imaging analysis and fluorescence in situ hybridization, may also offer increased sensitivity but are not yet widely available. 10 Sphincter of Oddi Dysfunction The role of ERCP and sphincterotomy with or without manometry in patients with suspected sphincter of Oddi dysfunction (SOD) continues to evolve. The complications related to ERCP and sphincterotomy, particularly pancreatitis, are higher than for other indications. More than 90% of patients with type 1 SOD (biliary pain with elevated liver chemistries and a dilated bile duct) experience relief of pain with biliary sphincterotomy; manometry is not necessary in this setting. 12 Patients with type 2 SOD (biliary pain with either elevated liver enzymes or a dilated bile duct) also respond to sphincterotomy, albeit at a lower rate (39%-66%). 12 The decision to use sphincter of Oddi manometry to guide the decision regarding sphincterotomy in patients with suspected type 2 SOD remains controversial. 12 A recent multicenter randomized controlled trial demonstrated a lack of significant pain improvement with biliary sphincterotomy in patients with type 3 SOD. 13 Pancreatic ERCP has a limited role in the diagnostic evaluation of recurrent acute pancreatitis because noninvasive methods are generally preferred (at least initially). Most causes of recurrent acute pancreatitis (including medications, hypertriglyceridemia, hypercalcemia, biliary sludge/stone, chronic pancreatitis, pancreatic masses or cysts, ampullary lesions, and pancreas divisum) may be diagnosed with a good history, laboratory testing, cross-sectional imaging, transabdominal ultrasound, and/or endoscopic ultrasound. ERCP and sphincter of Oddi manometry is typically reserved for the subset of patients with idiopathic recurrent acute pancreatitis without a cause identified with this rigorous evaluation and testing. Pancreas divisum as a cause for recurrent acute pancreatitis remains controversial because the congenital anomaly is commonly present (approximately 7% incidence) in normal subjects, 14 and only a small proportion of those with divisum develop pancreatitis. However, in patients without 135 Clinical Liver Disease, Vol 4, No 6, December 2014 An Official Learning Resource of AASLD

4 TABLE 4 Understanding ERCP Patient Guide: What to Expect During Endoscopic Retrograde Cholangiopancreatography (ERCP) Why is this test done? How should I prepare for my procedure? What do I do during the procedure? What happens after the procedure? Are there risks involved? When should I contact my doctor? - This test allows the doctor to evaluate your bile duct and pancreatic duct by obtaining high-quality x-ray images - Blockages can be treated with a combination of sphincterotomy (incision into the bile duct opening), dilation, and stent placement - Abnormal strictures can be sampled with forceps and brush devices to rule out cancer - A stent (plastic or metal tube) can be inserted into the bile duct if a narrowing is noted, to allow for adequate bile flow - Do not eat or drink after midnight on the night before your procedure. - Tell your doctor about your complete medical history, including medications, allergies, and any indwelling cardiac devices - Some of your medications may require adjustment prior to scheduling, particularly if you take any blood thinners - You will need to arrange for a friend or family member to drive you home from the procedure, as you cannot operate heavy machinery after undergoing sedation - Vital signs will be taken and an intravenous catheter placed for medication administration. - You will receive moderate to deep sedation prior to the scope being advanced - Depending on the center at which you are undergoing your procedure, you may be placed on your back, your side, or your stomach - After sedation, the scope will be passed through your mouth, down your esophagus and into the stomach and beginning of your small intestine. - The procedure length is variable, though an ERCP typically lasts minutes. - You will be monitored while the medications wear off; you may feel drowsy during this time period - You may notice a sore throat and bloating after the procedure. This is not uncommon and will get better. - Call your doctor immediately if you experience any complications (see below). - Complications are rare but can occur. These include: - Inflammation of your pancreas known as pancreatitis. Endoscopists use a variety of maneuvers to reduce this risk. - Bleeding - Infection - Heart or lung trouble - A tear in the lining of the digestive tract, which can require emergency surgery - Call if you have any concerns, or should you experience any of the following: - Fever of F or higher - Trouble swallowing - Difficulty breathing - Blood in vomit or stool - Increasing throat, chest or abdominal pain another etiology for recurrent pancreatitis, some studies have demonstrated a trend toward better outcomes following endoscopic therapy (including minor papillotomy and possible stent placement). 15 Pancreatic duct endotherapy of symptomatic stones, strictures, or pseudocysts can ameliorate pain associated with chronic pancreatitis, although studies are mixed as to the rate and durability of pain relief. Stones and strictures are treated in a similar manner as in the bile duct, with pancreatic sphincterotomy, balloon or basket stone extraction, mechanical or pancreatoscopy-guided lithotripsy, balloon or catheter dilation, and stenting (see Figure 4). Pancreatic duct leaks leading to pancreatic ascites or pseudocyst formation are managed with transpapillary stenting. Although not required in every case, stents that cross (or bridge ) the disrupted ductal segment may lead to better outcomes. 16 Transpapillary drainage of pancreatic fluid collections can be accomplished when the collection communicates with the pancreatic duct. Complications of ERCP Pancreatitis is the most common serious complication of ERCP (see Table 3). Although an asymptomatic increase in pancreatic enzymes can occur in up to 75% of patients following ERCP, a consensus definition for post-ercp pancreatitis (PEP) has been widely adopted and takes into account such factors as new or worsened abdominal pain, the need for hospitalization or extension of current hospitalization, and significantly elevated pancreatic enzymes > 24 hours after the procedure. Using these more stringent criteria, the actual incidence of post-ercp pancreatitis ranges from 1.6% to 15.7%. 17 Recent mounting evidence has revealed several maneuvers that may reduce the risk of PEP, including placement of a prophylactic pancreatic duct stent 18 and administration of rectal indomethacin. 19 Vigorous periprocedural hydration with lactated ringer s solution has shown promise in a pilot study, although larger studies are required to confirm these data. 20 Because rectal indomethacin can adversely affect renal function, and aggressive IVF can worsen fluid overload, these strategies should be utilized with caution in cirrhotic patients. Post-ERCP hemorrhage is typically secondary to sphincterotomy and complicates up to 1.3% of cases. 21 However, the incidence of severe hemorrhage is less than 1/ Because ERCP with sphincterotomy is deemed a higher risk procedure for bleeding, antiplatelet/anticoagulant therapy 136 Clinical Liver Disease, Vol 4, No 6, December 2014 An Official Learning Resource of AASLD

5 should be adjusted as recommended by The American Society for Gastrointestinal Endoscopy (ASGE) guidelines. 23 The incidence of perforation during ERCP ranges from 0.1% to 0.6% 24 and is broadly classified as guidewireinduced periampullary perforation during sphincterotomy and luminal perforation at a distinct site. Prompt recognition and management with endoscopic therapy (if possible), antibiotics, and early collaboration with surgeons can help mitigate related morbidity. Infectious complications occur in less than 1% of patients. 25 ASGE guidelines recommend consideration of prophylactic antibiotics in the following situations: achievement of complete biliary drainage is unlikely (e.g., primary References 1. Standards of Practice Committee of American Society for Gastrointestinal Endoscopy, Adler DG, Baron TH, Davila RE, Egan J, Hirota WK. ASGE guideline: the role of ERCP in diseases of the biliary tract and the pancreas. Gastrointest Endosc 2005;62: Carr-Locke DL. Therapeutic role of ERCP in the management of suspected common bile duct stones. Gastrointest Endosc 2002;56(suppl 6):S170-S Kahl S, Zimmermann S, Genz I, Glasbrenner B, Pross M, Schulz HU, et al. Risk factors for failure of endoscopic stenting of biliary strictures in chronic pancreatitis: a prospective follow-up study. Am J Gastroenterol 2003;98: Catalano MF, Linder JD, George S, Alcocer E, Geenen JE. Treatment of symptomatic distal common bile duct stenosis secondary to chronic pancreatitis: comparison of single vs. multiple simultaneous stents. Gastrointest Endosc 2004;60: Baluyut AR, Sherman S, Lehman GA, Hoen H, Chalasani N. Impact of endoscopic therapy on the survival of patients with primary sclerosing cholangitis. Gastrointest Endosc 2001;53: Seehofer D, Eurich D, Veltzke-Schlieker W, Neuhaus P. Biliary complications after liver transplantation: old problems and new challenges. Am J Transplant 2013;13: doi: /ajt Hawes RH. Diagnostic and therapeutic uses of ERCP in pancreatic and biliary tract malignancies. Gastrointest Endosc 2002;56(suppl 6):S201-S De Bellis M, Sherman S, Fogel EL, Cramer H, Chappo J, McHenry L Jr, et al. Tissue sampling at ERCP in suspected malignant biliary strictures (Part 1). Gastrointest Endosc 2002;56: Draganov PV, Chauhan S, Wagh MS, Gupte AR, Lin T, Hou W, Forsmark CE. Diagnostic accuracy of conventional and cholangioscopy-guided sampling of indeterminate biliary lesions at the time of ERCP: a prospective, long-term follow-up study. Gastrointest Endosc 2012;75: Moreno Luna LE, Kipp B, Halling KC, Sebo TJ, Kremers WK, Roberts LR, Barr Fritcher EG, Levy MJ, Gores GJ. Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures. Gastroenterology 2006; 131: Costamagna G, Shah SK, Tringali A. Current management of postoperative complications and benign biliary strictures. Gastrointest Endosc Clin N Am 2003;13: , ix. 12. Petersen, BT. An evidence-based review of sphincter of Oddi dysfunction: part 1, presentations with objective biliary findings (types 1 and 2) and of presumptive type 3. Gastrointest Endosc 2004;59: Cotton PB, Durkalski V, Romagnuolo J, Pauls Q, Fogel E, Tarnasky P, et al. Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy. JAMA 2014; 311: doi: /jama sclerosing cholangitis, hilar mass), posttransplant strictures, anticipated transmural or transpapillary pseudocyst drainage, and immunocompromised patients. 26,27 Conclusion Over approximately 50 years, ERCP has largely evolved into a therapeutic procedure and is indicated for a variety of pancreatobiliary disease states. n CORRESPONDENCE Cyrus Piraka, Section Chief, Advanced Therapeutic Endoscopy, Division of Gastroenterology, Henry Ford Health System, Detroit, MI USA cpiraka1@hfhs.org. 14. Stimec B, Bulajic M, Korneti V, Milosavljevic T, Krstic R, Ugljesic M. Ductal morphometry of ventral pancreas in pancreas divisum. Comparison between clinical and anatomical results. Ital J Gastroenterol 1996;28: Fogel EL, Toth TG, Lehman GA, DiMagno MJ, DiMagno EP. Does endoscopic therapy favorably affect the outcome of patients who have recurrent acute pancreatitis and pancreas divisum? Pancreas 2007;34: Telford JJ, Farrell JJ, Saltzman JR, Shields SJ, Banks PA, Lichtenstein DR, Johannes RS, Kelsey PB, Carr-Locke DL. Pancreatic stent placement for duct disruption. Gastrointest Endosc. 2002;56: Cotton PB, Garrow DA, Gallagher J, Romagnuolo J. Risk factors for complications after ERCP: a multivariate analysis of 11,497 procedures over 12 years. Gastrointest Endosc 2009;70: doi: /j.gie Mazaki T, Masuda H, Takayama T. Prophylactic pancreatic stent placement and post-ercp pancreatitis: a systematic review and meta-analysis. Endoscopy 2010;42: doi: /s Elmunzer BJ, Waljee AK, Elta GH, Taylor JR, Fehmi SM, Higgins PD. A metaanalysis of rectal NSAIDs in the prevention of post-ercp pancreatitis. Gut 2008;57: doi: /gut Buxbaum J, Yan A, Yeh K, Lane C, Nguyen N, Laine L. Aggressive hydration with lactated Ringer s solution reduces pancreatitis after endoscopic retrograde cholangiopancreatography. Clin Gastroenterol Hepatol 2014;12: e1. doi: /j.cgh Andriulli A, Loperfido S, Napolitano G, Niro G, Valvano MR, Spirito F, Pilotto A, Forlano R. Incidence rates of post-ercp complications: a systematic survey of prospective studies. Am J Gastroenterol 2007;102: Freeman ML. Adverse outcomes of endoscopic retrograde cholangiopancreatography: avoidance and management. Gastrointest Endosc Clinic N Am 2003;13: , xi. 23. ASGE Standards of Practice Committee, Anderson MA, Ben-Menachem T, Gan SI, Appalaneni V, Banerjee S, et al. Management of antithrombotic agents for endoscopic procedures. Gastrointest Endosc. 2009;70: doi: /j.gie Colton JB, Curran CC. Quality indicators, including complications, of ERCP in a community setting: a prospective study. Gastrointest Endosc 2009;70: doi: /j.gie ASGE STANDARDS OF PRACTICE COMMITTEE, Banerjee S, Shen B, Baron TH, Nelson DB, Anderson MA, et al. Antibiotic prophylaxis for GI endoscopy. Gastrointest Endosc 2008;67: doi: /j.gie Cotton PB, Connor P, Rawls E, Romagnuolo J. Infection after ERCP, and antibiotic prophylaxis: a sequential quality-improvement approach over 11 years. Gastrointest Endosc 2008;67: Freeman ML. Adverse outcomes of ERCP. Gastrointest Endosc 2002;56(suppl 6):S273-S Clinical Liver Disease, Vol 4, No 6, December 2014 An Official Learning Resource of AASLD

ERCP and EUS: What s New and What Should We Do?

ERCP and EUS: What s New and What Should We Do? Rajesh N. Keswani, MD Associate Professor of Medicine Division of Gastroenterology Northwestern University Feinberg School of Medicine EUS/ERCP in 2015 THE