Endoscopic Retrograde Cholangiopancreatography (ERCP)
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Endoscopic retrograde cholangiopancreatography (ERCP) is a technique that uses a combination of luminal endoscopy and fluoroscopic imaging to diagnose and treat conditions associated with the pancreatobiliary system. The endoscopic portion of the examination uses a side-viewing duodenoscope that is passed through the esophagus and stomach and into the second portion of the duodenum (see the video and image below).
With the scope in this position, the major duodenal papilla is identified and inspected for abnormalities. This structure is a protrusion of the hepatopancreatic ampulla (also known as the ampulla of Vater) into the duodenal lumen. The ampulla is the convergence point of the ventral pancreatic duct and common bile duct (CBD) and thus acts as a conduit for drainage of bile and pancreatic secretions into the duodenum.
The minor duodenal papilla is also located in the second portion of the duodenum and serves as the access point for the dorsal pancreatic duct. Evaluation of the dorsal pancreatic duct with ERCP is rarely performed; indications are discussed below.
After the papilla has been examined with the side-viewing endoscope, selective cannulation of either the CBD or the ventral pancreatic duct is performed. Once the chosen duct is cannulated, either a cholangiogram (CBD) or a pancreatogram (pancreatic duct) is obtained fluoroscopically after injection of radiopaque contrast material into the duct. ERCP is now primarily a therapeutic procedure; thus, abnormalities that are visualized fluoroscopically can typically be addressed by means of specialized accessories passed through the working channel of the endoscope.
Because ERCP is an advanced technique, it is associated with a higher frequency of serious complications than other endoscopic procedures are. Accordingly, specialized training and equipment are required, and the procedure should be reserved for appropriate indications.
A review by Freeman et al, using data from 2004, estimated that about 500,000 procedures were performed annually in the United States. [1] However, because of a decrease in diagnostic ERCP with the advent of endoscopic ultrasonography (EUS) and magnetic resonance cholangiopancreatography (MRCP), this number is likely decreasing.
Since its first description in the late 1960s as a diagnostic technique, [2] ERCP has evolved into an almost exclusively therapeutic procedure. The main reason for this evolution is that diagnostic modalities have been developed that are less invasive than ERCP but possess similar sensitivity and specificity for disease processes of the hepatobiliary system. [3]
Imaging techniques currently used in the diagnosis of hepatobiliary processes include computed tomography (CT), ultrasonography (US), EUS, and MRCP. The use of these modalities, in conjunction with pertinent clinical information (eg, the clinical history, physical examination findings, and laboratory data), can help select those patients for whom ERCP is most appropriate.
Because ERCP has a higher rate of severe complications than most other endoscopic procedures do, having an appropriate indication for its use is extremely important. In fact, most ERCP-related legal claims center on the aptness of the indication for the procedure. [4] In 2005, the American Society for Gastrointestinal Endoscopy (ASGE) published guidelines regarding the role of ERCP in biliary tract and pancreatic diseases. [5] The guidelines were updated in 2015 to include the following recommendations for benign biliary tract disease [6] :
Indications for benign pancreatic disease in the 2015 ASGE guidelines include the following [7] :
ERCP may also be indicated for treatment of symptomatic pancreatic pseudocysts (see the image below) or benign pancreatic fluid collections. [8]
Indications for diagnosis of pancreatic malignancies include the following [9] :
Indications for ampullary disease include the following:
Absolute contraindications for ERCP include the following:
Structural abnormalities of the esophagus, stomach, or small intestine may be relative contraindications for ERCP. Examples are acquired conditions such as esophageal stricture, paraesophageal herniation, esophageal diverticulum, gastric volvulus, gastric outlet obstruction, and small-bowel obstruction. An altered surgical anatomy, such as is seen after partial gastrectomy with Billroth II or Roux-en-Y jejunostomy, may also be a relative contraindication for ERCP.
Several factors play a role in choosing the best approach for ERCP access in patients with altered surgical anatomy in cases where ERCP is indeed indicated. These factors include long versus short Roux limb, native papilla versus bilioenteric anastomosis, prior sphincterotomy, anticipated accessory use (eg, sphincter of Oddi manometry), surgical risk, likelihood of repeat procedures, and possibility of internal hernias.
The different approaches in patients with Roux-en-Y anatomy include duodenoscope through the anatomic route, colonoscope or enteroscope through the anatomic route, single/double balloon enteroscopes, spiral/rotational enteroscope, ERCP through gastrostomy or jejunostomy, laparoscopically assisted ERCP, or biliary access obtained by interventional radiology. [12, 13]
EUS-guided biliary access has been described in cases of difficult primary cannulation of a native papilla or in the appropriate setting with altered surgical anatomy. [14] (See the image below.)
The presence of acute pancreatitis is typically considered a relative contraindication as well, unless the etiology of the pancreatitis is gallstone-related and the therapeutic goal is to improve the clinical course by means of stone extraction. [15, 16] In addition, ERCP with sphincterotomy or ampullectomy is relatively contraindicated in coagulopathic patients (international normalized ratio [INR] >1.5 or platelet count <50,000/µL).
Before ERCP, all of the patient’s previous abdominal imaging findings (from CT, magnetic resonance imaging [MRI], ultrasonography, and cholangiography or pancreatography) should be reviewed; this can facilitate location of the pathology during ERCP, as well as help pinpoint any changes that occurred since the previous imaging was performed.
A scout radiograph should be obtained while the patient is on the fluoroscopy table and before insertion of the duodenoscope; this image can act as a baseline for comparison with subsequent fluoroscopic images taken after contrast injection.
The patient’s surgical history should be reviewed before the procedure to determine whether there is anything in the surgical anatomy that may be a contraindication for ERCP.
To minimize the patient’s exposure to radiation, fluoroscopic images should be obtained only as necessary during the procedure; some fluoroscopy machines can be adjusted to minimize the frequency of image acquisition.
Deep sedation is desirable during ERCP because a stable endoscopic position in the duodenum is important for proper cannulation, therapeutic intervention, and avoidance of complications.
If the pancreatic duct is cannulated several times or if contrast is injected into the pancreatic duct, placement of a temporary pancreatic duct stent or rectally administered NSAIDs (indomethacin or diclofenac) should be considered in order to decrease the risk of PEP. [17] These two prevention modalities have proved effective for PEP prophylaxis. Numerous other pharmacologic agents have been studied, including gabexate, somatostatin, octreotide, steroids, heparin, allopurinol, and nitroglycerin, but with disappointing results. [18]
Multiple randomized controlled trials and meta-analyses have shown rectally administered NSAIDs to be effective in reducing the incidence of PEP, the occurrence of moderate to severe pancreatitis, and the length of hospital stay in high-risk patients who develop PEP. [19, 20, 18, 21, 17] Indirect comparative effectiveness studies have suggested that rectal NSAIDs alone may be superior to pancreatic duct stenting in preventing PEP as a simple, easily administered, safe, inexpensive, and effective treatment modality, [21] but further studies are needed to help confirm these results through direct comparison with prospective randomized controlled data.
Whether rectal NSAIDs should be given to all patients or employed selectively in high-risk patients is a topic of debate among experts. Widespread adoption of this simple strategy may minimize the incidence of PEP and modulate its severity, resulting in major clinical and economic benefit. [18, 17] NSAIDs have been shown to inhibit prostaglandin synthesis, phospholipase A2 activity, and neutrophil/endothelial cell attachment, which are all believed to play a key role in the pathogenesis of the initial inflammatory cascade of acute pancreatitis. [19, 22, 23, 18]
Single-dose administration is not associated with enhanced risk of bleeding or renal insufficiency. Rectal administration seems to work better than other routes, including oral, intramuscular, intravenous, or intraduodenal. [18]
The optimal timing of administering rectal NSAIDs has not been clearly defined. Two meta-analyses found no difference in efficacy, whether the medication is given before or immediately after the procedure. [18, 17]
A pilot study suggested that aggressive intravenous hydration with lactated Ringer solution (LR) may reduce the development of PEP and is not associated with volume overload. [24]
In a subsequent prospective randomized, double-blinded, placebo-controlled trial, 192 patients at high risk for PEP received standard normal saline solution (NS) plus placebo (n=48), NS plus indomethacin (n=48), LR plus placebo (n=48), or LR plus indomethacin (n=48). [25] The primary outcome was PEP; the secondary outcomes were severe acute pancreatitis, localized adverse events, death, length of stay, and readmission. The investigators found that the combination of LR and indomethacin led to reductions in PEP incidence and readmission rate as compared with the combination of NS and placebo.
The first step in preventing post-ERCP complications is to identify those patients who are most likely to experience adverse events. Factors that place patients at higher risk for PEP, the most common serious complication associated with this procedure, may be broadly grouped as follows:
It is important to distinguish between asymptomatic postprocedural pancreatic enzyme elevations of serum amylase and lipase, which can be seen in more than half of all patients undergoing ERCP in the first 24 hours after the procedure, and true clinical pancreatitis induced by the ERCP, which presents with pancreatic-type pain or cross-sectional imaging confirming inflammation. [23]
Proposed underlying mechanisms that can induce PEP include the following [19, 23] :
Patient-related factors include the following [19, 22, 23, 26] :
The term SOD is used to define motility abnormalities caused by stenosis or dyskinesia of the sphincter of Oddi. [19] A history of chronic calcific pancreatitis seems to confer a protective effect on the risk of developing PEP. [23]
Procedure-specific risk factors for PEP include the following [19, 21, 22, 23, 27] :
Data support the use of prophylactic pancreatic duct stents or the administration of rectal NSAIDs in patients at increased risk for pancreatitis, because it has been shown to reduce the incidence of PEP in this high-risk cohort of patients. [28, 19, 22, 23, 20, 18, 21]
Operator-dependent factors include the following:
The significance of low case volume in this setting was challenged by a multicenter prospective study showing that the risk of PEP was not associated with the case volume of either the single endoscopist or the center. [27]
Those at higher risk for post-ERCP hemorrhage include patients with either a pathologic or an iatrogenic coagulopathy. Anticoagulant or antithrombotic therapy should be discontinued before elective ERCP (generally 5-7 days beforehand), and the prothrombin time (PT) and partial thromboplastin time (PTT) should be evaluated on the day of the procedure. If the PT and PTT are significantly abnormal, the procedure should be rescheduled if it is not an emergency. If there is an urgent need for ERCP, reversal of the coagulopathy with fresh frozen plasma may be required.
Routine use of prophylactic antibiotics in elective ERCP is controversial. The infectious risks of ERCP (ie, bacteremia and cholangitis) are most likely to occur in patients who present with biliary obstruction. Current guidelines recommend prophylactic antibiotic therapy in all patients presenting with biliary obstruction and cholangitis or with biliary obstruction that is unlikely to be drained at the time of ERCP, such as in the case of complex hilar strictures and patients with primary sclerosing cholangitis. Antibiotic therapy is also recommended after any unsuccessful ERCP biliary drainage procedure. [29]
A Cochrane analysis of nine randomized clinical trials found that the rates of bacteremia and cholangitis were lower in patients who received prophylactic antibiotics before elective ERCP than in those who did not, though subgroup analysis demonstrated that the effect of antibiotics was less evident in patients who underwent uncomplicated ERCP with successful biliary drainage. [30]
In March 2015, the American Gastroenterological Association suggested the following recommendations for reducing endoscope-associated infections in ERCP [31] :
Most mucosal perforations occurring during ERCP are periampullary and are associated with sphincterotomy. Periampullary perforations are usually retroperitoneal and can often be managed with supportive care rather than immediate surgical intervention. This complication can be prevented in many cases by following proper landmarks while performing sphincterotomy and by taking care to not cut beyond the intraduodenal portion of the CBD.
Perforations occurring away from the ampulla are typically due to traumatic endoscope passage, often related to limited visualization of the lumen.
As a general rule, the duodenoscope should never be forced against significant resistance during insertion. The forceps elevator should be in the closed position during passage of the endoscope down the lumen because it may lacerate the adjacent tissue if left in the open position.
Because of inherent bias and patient underreporting, an accurate estimate of the procedural complication rate is difficult to obtain. However, comparisons with complication data pertaining to other endoscopic procedures makes it clear that ERCP is associated with approximately fourfold higher rates of severe complications. [32]
In a study of post-ERCP complications that pooled prospective patient survey data from almost 17,000 patients undergoing the procedure, ERCP-related morbidity secondary to pancreatitis, bleeding, perforations, and infections was 6.85%, of which 5.17% was graded as mild-to-moderate and 1.67% as severe; ERCP-specific mortality was 0.33%. [33] Pancreatitis was the most common complication (3.47% of patients), followed by infection (1.44%), bleeding (1.34%), and perforations (0.6%).
The incidence of PEP ranges from 1% to 10% in average-risk patients but can exceed 25-30% in certain high-risk patient populations. This wide range is due to the heterogenous interplay of multiple patient-, procedure-, and operator-related factors. [22] Acute PEP is not a uniform disorder and varies in intensity. Most cases are mild and resolve with proper treatment without any permanent sequelae. [23]
The relatively high risk associated with ERCP underscores the importance of having this procedure performed by experienced practitioners. It also helps explain the trend toward therapeutic as opposed to diagnostic ERCP. Although the absolute complication risk is greater with therapeutic ERCP than with diagnostic ERCP, the potential benefits are also greater, and the risk-to-benefit ratio favors therapeutic ERCP. [34, 35, 36, 26]
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Ahmad Malas, MD Fellow, Department of Gastroenterology, Providence Hospital and Medical Centers
Ahmad Malas, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.
Roberto M Gamarra, MD Consulting Gastroenterologist, Digestive Health Associates, PLC
Roberto M Gamarra, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Crohn’s and Colitis Foundation of America
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Kurt E Roberts, MD Assistant Professor, Section of Surgical Gastroenterology, Department of Surgery, Director, Surgical Endoscopy, Associate Director, Surgical Skills and Simulation Center and Surgical Clerkship, Yale University School of Medicine
Kurt E Roberts, MD is a member of the following medical societies: American College of Surgeons, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Laparoendoscopic Surgeons
Disclosure: Nothing to disclose.
Medscape Drugs & Diseases thanks Dawn Sears, MD, Associate Professor of Internal Medicine, Division of Gastroenterology and Hepatology, Scott and White Memorial Hospital, and Dan C Cohen, MD, Fellow in Gastroenterology, Scott and White Hospital, Texas A&M Health Science Center College of Medicine, for assistance with the video contribution to this article.
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