Gastroenterology Hepatology

Endoscopic diagnosis and therapy of biliary diseases

General description of procedure, equipment, and endoscopic technique

Endoscopic retrograde cholangiopancreatography (ERCP) has assisted in the care of patients with pancreaticobiliary diseases for almost four decades. This technique involves passing a specially designed endoscope into the second portion of the duodenum. There, its side-viewing optics allow for identification of the major duodenal papilla. Through its working channel, a variety of catheters can be advanced into the bile duct and the pancreatic duct, and using fluoroscopic guidance and injection of iodinated contrast, visualization of the biliary tree and pancreatic duct can be obtained.

Indications and patient selection

Common bile duct stones

Gallbladder stones are extremely prevalent worldwide. Asymptomatic stones in the gallbladder should be left alone. Stones can get caught in the cystic duct and create biliary pain. This pain typically occurs between 10 and 30 minutes after eating, is located in the epigastrium or right upper quadrant, and may radiate to the back or right scapula. It is commonly associated with nausea and occasionally emesis. It is crescendo/decrescendo in severity and may last for hours. If the stone becomes lodged in the cystic duct, the gallbladder may become infected leading to fevers, chills, and bacteremia. This defines acute cholecystitis. The stone may become dislodged and fall back into the gallbladder, and symptoms then abate, or it may fall into the bile duct.

Once the stone enters the bile duct, it becomes lodged in the biliary sphincter at the pancreaticobiliary junction and results in two conditions, which carry significant morbidity and mortality. The first is ascending cholangitis, which presents with right upper quadrant pain, fever, and jaundice, the so-called Charcot’s triad. The second condition is gallstone pancreatitis presenting with epigastric pain radiating to the back, nausea, vomiting, and elevated serum pancreatic enzymes in the setting of abnormal liver injury tests, under most circumstances.

In stable patients in whom there is a suspicion for a bile duct stones, other modalities should be employed prior to ERCP. These modalities include endoscopic ultrasound and MRCP. Both of these modalities have high diagnostic accuracy for detecting bile duct stones.

In patients with a gallbladder in-situ who present with transient symptoms suggestive of choledocholithiasis and are clinically stable, performance of a laparoscopic cholecystectomy with an intra-operative cholangiogram is often a reasonable alternative, reserving ERCP for the post-operative management of common bile duct stones. As an example, mild acute gallstone pancreatitis, which responds rapidly to conservative therapy, does not mandate an emergent ERCP. If the patient’s symptoms and laboratory abnormalities resolve and cross-sectional imaging fails to demonstrate biliary dilation or an established bile duct stone, an interval laparoscopical cholecystectomy with intra-operative cholangiogram is safe and reasonable.

Patients with severe acute gallstone pancreatitis, however, have been demonstrated to benefit from early ERCP. It is largely believed that the clinical benefits seen in these patients is a direct result of clearing the bile duct from stones and attenuating cholangitis, rather than its direct effect on pancreatic injury and the associated immune response to that injury.

Once a stone is identified in the common bile duct, standard of care is to remove it even in the absence of symptoms. ERCP has evolved as the safest and most efficacious technique to treat common bile duct stones. The alternatives to ERCP include medical management with antibiotics and bowel rest, percutaneous transhepatic cholangiography (PTC) by interventional radiologists, and surgical common duct exploration. These alternatives are all less effective and associated with significantly worse outcomes compared to ERCP.

During ERCP for common bile duct stones, a catheter is introduced into the biliary tree, a guide wire is advanced with fluoroscopic guidance, and a biliary sphincterotomy is performed. The stones are removed with either a Dormier basket or an extraction balloon. Under these circumstances, they are swept into the duodenum and allowed to pass down the GI tract. In patients who are septic and/or coagulopathic, or have a stone too big to be removed with standard endoscopic techniques, a biliary stent, preferably 10 Fr in diameter, should be placed to allow biliary drainage. Complete duct clearance can be accomplished at a later date once the patient recovers.

A subset of biliary stones is refractory to initial extraction by standard techniques. This may occur because of the absolute size of the stone, the relative size of the stone compared to the duct downstream, or the location of the stone within the biliary tree.

A variety of ancillary techniques have evolved to manage difficult stones. Hydrostatic dilating balloons can be used to open the biliary sphincter or stretch the bile duct distal to an impacted stone. This technique should be performed after biliary sphincterotomy in most cases. An increasing experience with balloon dilation of an intact biliary sphincter to preserve sphincter function or to avoid bleeding risks in coagulopathic patients has been reported and has been shown to increase the risk of acute pancreatitis. This technique should be reserved for unique circumstances. However, dilation after a biliary sphincterotomy can be easily and safely performed to facilitate the extraction of large stones.

A number of ancillary devices are also used for the treatment of large bile ducts stones. These include mechanical lithotripsy, in which the stone is encaptured in a basket, which can be closed over a metal sleeve using manual traction to fragment the stone, and electrohydrolic or laser lithotripsy delivered through fibers placed in direct contact or adjacent to the bile duct stones. These latter devices are most safely performed using a choledochoscope, which is a small diameter scope that can be passed through the working channel of the duodenoscope up into the bile duct for direct visualization of the stones.

Difficult stones may also be encountered in the hepatic bifurcation and/or the intrahepatic ducts. Advanced techniques, such as lithotripsy, are usually required in these patients.

Mirizzi’s syndrome is a historical term used to define extrinsic obstruction of the common hepatic duct from a stone impacted in the neck of the gallbladder. This can be recognized or suggested by cross sectional imaging including CT and MRI. ERCP is used to confirm the diagnosis and attempt to place stents upstream from the obstruction in the common hepatic duct. Although there are case reports of successful endoscopic therapy using advanced lithotripsy techniques in this population, these patients are largely managed through surgery.

There is a growing literature on the use of ERCP to treat acute cholecystitis. This may be simply accomplished with pressure injection of the biliary tree forcing stones impacted in the cystic duct back into the gallbladder. In more difficult cases and in patients who are unfit for surgery, the cystic duct may be negotiated with a soft tipped guidewire and a stent can be placed into the gallbladder and brought out into the duodenal lumen to facilitate drainage. The alternative to this nonoperative management of acute cholecystitis is placement of a percutaneous pigtail drain into the infected gallbladder using ultrasound guidance.

Bile duct leaks

Bile duct leaks can be seen following surgery to the biliary tree or liver, or as a result of trauma – either blunt or penetrating. The hallmark of therapy for bile duct leaks is to provide a path of least resistance for the bile to flow from the biliary tree into the duodenum. Bile duct leaks most commonly occur following cholecystectomy. They can occur at the cystic duct remnant from failure of clips placed prior to dividing the cystic duct or can occur from the gallbladder fossa via peripheral branches of the right intrahepatic ducts that run close to the surface of the liver in this location (duct of Luschka). They also occur in the setting of cholecystectomy with concomitant bile duct obstruction either from ampullary stenosis, a biliary stricture, or common bile duct stones.

They typically present with pain following a laparoscopic cholecystectomy, usually 1 to 7days later. Diagnosis is suggested by the presence of ascites or a biloma in the gallbladder fossa on imaging in a patient presenting with pain post cholecystectomy. The diagnosis may be confirmed by a hepatobiliary iminodiacetic acid (HIDA) scan, which shows uptake of radiotracer in the liver and excretion outside of the intestines.

The diagnosis is confirmed at ERCP and therapy is provided using a combination of sphincterotomy and bile duct stents. Poiseuille’s equation for luminal flow suggests that resistance to flow through a tube is directly proportional to the length of the tube and inversely proportional to the 4th power of the radius of the tube. Ideally, the shortest stent with the largest diameter will provide the least resistance to flow and the fastest resolution of a bile leak. Theoretically, this could be obtained by performing a large complete sphincterotomy alone. However, in practice, the sphincter muscle fibers may extend slightly above the duodenal wall, making complete safe division during sphincterotomy impossible. In addition, the swelling and edema that is seen for several days after a biliary sphincterotomy may impair bile flow into the duodenum for that period of time.

For these reasons, a sphincterotomy alone is usually not performed for therapy of cystic duct leaks and gallbladder fossa leaks following a laparoscopic cholecystectomy. Placement of a short stent with or without the performance of a sphincterotomy is successful in the management of over 95% of these cases. The plastic biliary stents may be removed several weeks later after the patient has clinically recovered. Any sizable biloma or significant ascites should be drained percutaneously with a temporary pigtail catheter to prevent secondary infection and to alleviate symptoms.

Traumatic injury to the bile duct may result in a laceration of the liver with subsequent bile leaks. These usually occur in secondary or tertiary branches of the intrahepatic ducts. A short transpapillary stent provides a path of least resistance for bile flow and can result in successful resolution of these leaks in the majority of patients. Similarly, patients with hepatic resections who have leaks from the cut surface of the liver can be treated successfully with short plastic stents largely 10 Fr in diameter.

In patients with major hepatic traumatic injury (Grade IV laceration), the main right or left common hepatic duct may be transected. Under these circumstances, ERCP with stent placement may simply provide a conduit for intestinal bacteria to enter the peritoneum. Such patients will likely decompensate following an ERCP unless the peritoneum is adequately and completely drained with either percutaneous or surgical placed drains.

Bile leaks that occur above or at the site of a biliary stricture or injury must be treated differently; access to the biliary tree proximal to any stricture or injury is necessary to enable resolution of the leak. This may be seen in bile duct injuries following a cholecystectomy, after common duct exploration, or in patients with liver transplants who are leaking from the donor to recipient duct anastomosis, or after sustained injury to the donor ducts.

Sphincter of Oddi dysfunction

Sphincter of Oddi dysfunction is a functional disease of the biliary sphincter, which presents with attacks of right upper quadrant or epigastric pain associated with transient liver injury test abnormalities. Consensus criteria mandate that these pain attacks are transient, not daily, and interrupted by significant pain free intervals (Rome III criteria). They largely occur in patients post cholecystectomy and may be associated with bile duct dilation.

Patients who present with intermittent attacks of pain, associated liver injury test elevations that return to normal when the pain resolves and dilation of the biliary tree of more than 12 mm in diameter on imaging are thought to have type I disease. This condition does not mandate further investigation and responds almost completely to biliary sphincterotomy.

The occurrence of pain associated with transient liver injury test abnormalities, in the absence of duct dilation is considered to represent type II disease. Some experts suggest the performance of biliary manometry in this subset of patients, reserving biliary sphincterotomy for those who manifest elevated basal sphincter pressures (>40 mmHg). However, the paucity of good quality outcome data for abnormal manometry to guide biliary sphincterotomy, along with the poor reliability of this test, and the absence of a differential diagnosis in carefully selected patients, have resulted in treating the majority of these patients with empiric biliary sphincterotomy. Because of the increased risk of post-ERCP pancreatitis in this population, the placement of a prophylactic temporary pancreatic stent is becoming standard of care.

Patients with pain only in the absence of lab abnormalities or bile duct dilation are considered to have Sphincter of Oddi type III disease. This is a heterogeneous group of patients that is difficult to manage. The majority of these patients respond poorly to endoscopic sphincterotomy. It is the authors’ opinion that endoscopic management of patients with type III disease should be best studied in randomized controlled trials looking at the role of manometry and response to endotherapy. Routine ERCP with biliary sphincterotomy is not advised in these patients.

Benign biliary strictures

A variety of medical conditions or postoperative states can result in bile duct strictures. ERCP plays a major role in the management of these patients. Post-operative strictures of the bile duct can be seen following injury from laparoscopic cholecystectomy, at the duct-to-duct anastomosis following liver transplantation or as a complication of hepatic resection.

Bile duct strictures following laparoscopic cholecystectomy come in two varieties: the first is ischemic or thermal injury caused from placing clips at the cystic duct or clips to control bleeding close to the common hepatic duct. Under these circumstances, the small arterioles that supply blood to the bile duct (vasa ductorum) may become injured and ischemic injury can result in biliary strictures. In addition, direct thermal injury from cautery devices used to control hemostasis may cause similar injury. In the absence of a concomitant bile leak, these patients may present insidiously post-operatively with cholestasis or frank jaundice. The diagnosis can be confirmed by MRCP.

The treatment includes endoscopic therapy with serial biliary dilation and stenting. Alternatively, surgical therapy with transection of the common hepatic duct and creation of a hepaticojejunostomy into a Roux jejunal limb may be required. In the authors' opinion, this latter therapy should be reserved for endoscopic failures.

The second mechanism of injury includes placement of a clip directly across the biliary tree. This results in complete disruption of the biliary flow and typically requires surgical management. Although case reports exist for endoscopically gaining access to the intrahepatic ducts and popping clips off the bile duct using hydrostatic balloons, in the majority of these cases access to the proximal biliary tree above the clips is impossible endoscopically. Under these circumstances, a PTC can be placed to temporize the obstruction and allow for an interval operation at an ideal time when the inflammatory state of the porta hepatis has resolved following the acute injury.

During ERCP, once access above the stricture has been obtained, typically, balloon dilation may be performed and a stent or multiple stents placed. At the index procedure, typically, a single 10 Fr stent is used and the balloon is sized to match the distal duct diameter (smaller side below the stricture). In subsequent ERCP, the duct is stretched with larger balloons and multiple stents are placed. A long-term follow-up study reported 80% resolution in post-operative strictures with serial placement of multiple stents in the biliary tree in procedures separated by several months and spread out over the course of a year. The use of fully covered self-expanding metal stents, which can be removed endoscopically, to treat postoperative biliary strictures is being studied. However, their routine use cannot be endorsed at this time. Uncovered metal stents that cannot be removed have no role in the management of benign post-operative strictures. Finally, absolute confirmation that a stricture was not present pre-operatively should be established to ensure that a preexisting malignancy is not being missed.

Strictures at the duct-to-duct anastomosis are one of the most common biliary complications following liver transplantation (approximately 12%). These should be managed similarly to post-operative strictures with dilation and serial stenting. When they are recognized within 1 month of the transplant, they may be simply due to edema, and placement of a stent without dilation is warranted. If they are persistent at stent removal 6 to 8 weeks later, therapy with a series of serial balloon dilations and subsequent stenting with multiple plastic stents should be pursued. Again, the use of removable covered metal stents in this population is currently under study but should not be advised as routine at this time.

Patients with chronic pancreatitis can present with biliary strictures by several mechanisms. These may be chronic due to fibrosis and scaring of the pancreas affecting the distal bile duct as it passes through the head of the pancreas. Alternatively, during an acute flare of pancreatitis, edema in the head of the pancreas compresses the distal bile duct can and results in biliary stricture and jaundice. These strictures are transient, may disappear with resolution of the acute inflammatory component, do not mandate endoscopic treatment, and may respond to tincture of time. Finally, pseudocysts that complicate chronic pancreatitis can compress the bile duct and result in cholestasis or jaundice. Treatment of the pseudocyst either with conservative management or active intervention will resolve the biliary obstruction.

Chronic fibrotic strictures of the distal bile duct in the setting of chronic pancreatitis are problematic. They may be temporized with the placement of a biliary stent. Efforts to treat these with a series of hydrostatic balloon dilations of increasing diameter and placement of multiple biliary stents have not resulted in the same outcomes seen with post-operative strictures. Only the minority of chronic pancreatitis patients with fibrotic strictures manifests durable biliary drainage following endoscopic therapy. The use of removable covered metal stents is also being actively studied in this population. Surgical management of these strictures either with a biliary bypass, resection of the head of the pancreas, or a coring out of diseased pancreatic tissue in the head results in more durable biliary drainage in appropriately selected patients.

Immunoglobulin G4 (IgG4)-related disease is an increasingly recognized entity that can cause strictures in the biliary tree by two mechanisms. The first is a distal bile duct stricture in the intrapancreatic segment in patients with a pseudotumor of the pancreatic head caused by autoimmune pancreatitis. These patients are usually recognized from the results of clinical presentation and cross sectional imaging. Confirmatory tests include increased serum IgG4 levels, which can be found in about 75% of these patients. The challenge with these patients is to exclude pancreatic malignancy, which can be done with endoscopic ultrasound and fine needle aspiration or core biopsies. Furthermore, based on a high clinical index of suspicion, a short course of systemic steroids can be ordered, which will result in the disappearance of the mass and resolution of the biliary stricture.

The second mechanism of biliary strictures seen in this population is direct autoimmune cholangiopathy. Such patients present with single or multiple strictures proximal to the intrapancreatic biliary tree. Again, a high index of suspicion coupled with cross-sectional imaging, evaluation of the strictures during ERCP using brush cytology or intraductal biopsies with IGg4 staining, and serum IGg4 levels are helpful to establish the diagnosis. A short course of steroids with resolution of the biliary strictures is confirmatory.

Primary sclerosing cholangitis. An autoimunne disease, typically seen in patients with inflammatory bowel disease, in which progressive inflammatory and fribrotic strictures are seen in the intra- and extrahepatic bile duct. It can be differentiated from IgG4-related cholangiopathy by a failure to respond to steroids and in the appropriate clinical setting. Diagnosis can be obtained largely through MRCP; however, ERCP is sometimes required in patients with small duct intrahepatic disease.

Patients with dominant strictures of the extrahepatic bile duct or major intrahepatic radicals may respond to endoscopic therapy. This is undertaken with judicious use of balloon dilation and temporary stenting. The authors favor the Amsterdam protocol, using a balloon sized to the smaller size of the bile duct and stents for a period of 1 to 3 weeks. Because of an increased risk of cholangiocarcinoma in PSC patients, all dominant strictures need to be sampled for the presence of malignancy. In addition, careful selection of appropriate strictures for therapy need to be undertaken to ensure that the upstream bile duct is going to be affected in a favorable fashion by endotherapy.

Despite some controversy in the literature, we do not believe that endoscopic therapy alters the long-term course of PSC. Certainly, it can palliate acute biliary obstruction and improve symptoms of cholestasis in carefully selected patients. The liberal use of pre- and post-ERCP antibiotics is mandatory in this patient population.

Fibroinflammatory biliary strictures (FIBS). A newly recognized condition of inflammatory pseudotumors that can involve the biliary tree. This diagnosis is usually made post operatively in patients who undergo resection for presumed malignancy. It can only be diagnosed preoperatively, when there is a high index of suspicion. The natural history of these strictures is not well established, but an empiric trial of systemic steroids is reasonable in selected patients.

ICU cholangiopathy. Also is a newly recognized entity in which critically ill patients typically with sepsis and multiorgan failure present with profound cholestasis due to diffuse stricturing of the biliary tree. This diagnosis may be made by MRCP or ERCP and may partially respond to endoscopic interventions including biliary sphincterotomy, sweeping of the duct, and stent placement.

Congenital cystic disease of the biliary tree. May be responsible for pancreaticobiliary symptoms. Endoscopy has a limited role in the diagnosis and management of these patients. Choledochocysts occur in five subtypes according to the Todani classification. Normally these congenital cysts present or are recognized in childhood. MRCP usually provides a definitive diagnosis. ERCP may be required in the operative planning in order to clearly define the pancreaticobiliary union, if not apparent at MRCP. Patients generally require excision of the cyst to reduce the risk of subsequent cancer formation, which is significantly increased in this patient population, in addition to treating cholestatic complications. ERCP may also be required as a pre-operative adjunct to evaluate for the presence of preexisting malignancy or to treat concomitant stone disease.

Special mention should be made at this point to patients with type III choledochocysts or choledochoceles. The cancer risk in this patient population is considered extremely low and endoscopic management is common. The cystic dilation occurs at or about the pancreaticobiliary union. It typically can be seen as a cystic outpouching that extrudes into the duodenal lumen. It may be responsible for cholangitis, biliary pancreatitis, and/or symptomatic cholestasis. It can be treated endoscopically by performing a biliary sphincterotomy, which will unroof the choledochocyst and facilitate biliary drainage.

Malignant biliary obstruction

Therapeutic endoscopists are frequently called on to assist in the diagnosis and management of patients with malignant biliary obstruction. Intrinsic (cholangiocarcinoma) or extrinsic compression of the bile duct will result in a stricture that is frequently indistinguishable from benign causes of biliary obstruction.

Typically, one relies on cross-sectional imaging and endoscopic ultrasound to evaluate for a mass lesion in the head of the pancreas or other tumors amenable to fine needle aspiration. In cases in which EUS FNA does not provide a diagnosis, sampling of the biliary stricture to exclude or confirm a malignant diagnosis has become routine during the performance of ERCP. Most typically, a wire-guided brush is advanced across the stricture and agitated several times through the stricture to pick up cells for subsequent cytology. In addition, intraductal biopsy forceps can be advanced through the working channel of the duodenoscope into the stricture and provide specimens for histologic evaluation. Finally, the use of fine needle aspirate into the wall of the bile duct have been reported, using specially designed needles that can be advanced tangentially outside of endoscopically placed catheters. This latter technique has not been widely adapted.

All of these sampling techniques suffer from low sensitivity, with reports varying between 25% to 50%. Specificity of tissue sampling at ERCP is extremely high, approaching 100%. Therefore, positive results can be interpreted as malignant, but negative results are not helpful, as malignancy cannot be excluded. The sensitivity of these techniques increases with the number of modalities used and is the highest for intrinsic malignancy (i.e., cholangiocarcinoma).

Assessing an indeterminate stricture can be clinically challenging, based on the performance characteristics of tissue sampling obtained at ERCP. The use of a choledochoscope advanced through the working channel of a duodenoscope and into the stricture may assist in the diagnosis of malignancy and malignant scoring systems have been suggested, improving the sensitivity to values between 50% to 75%.

Probe-based confocal laser endomicroscopy is another technique that allows in-vivo microscopic evaluation of tissue. Patients are given a fluorocene intravenously and the special probe is advanced through a catheter or choledochoscope and placed in direct contact with the epithelium within the stricture. Malignant criteria have recently been identified increasing the accuracy of diagnosing malignancy to approximately 90%. However, specificity suffers and false positives are not uncommon.

Palliating a malignant biliary obstruction with biliary stents has evolved over the last several decades. Originally, plastic endoprotheses varying from 7 to 10 Fr in diameter were placed across malignant obstructions and resulted in excellent palliation of jaundice with markedly improved outcomes compared with surgical bypass. Ten-Fr stents were proven to be superior to 7-Fr stents based on improved patency. However, because bacterial biofilm forms on the surface of stents, resulting in the precipitation of biliary sludge containing cholesterol and calcium bilirubinate in a composition similar to that seen with mixed pigment bile duct stones, these stents become occluded at a median time of 3 months, necessitating stent exchanges.

Stent occlusion presents most typically with acute cholangitis. If patients are not expected to survive beyond 3 months, placement of a plastic stent is reasonable. For patients who have a longer life expectancy, it has been suggested that elective changes every 3 months result in improved patient outcome, compared to emergent stent changes performed when patients present with cholangitis. The use of ursodiaxicholic acid, rotating antibiotics, aspirin, and antibiotic impregnated stents has not been demonstrated to increase the duration of plastic stent patency. Plastic stents traditionally are made of polyethelene; the use of Teflon stents has not improved patency in a large randomized controlled trial.

To overcome the problem of premature plastic stent occlusion, self-expanding metal stents have been designed, and a number of modifications have been made over the past decade. The original stent (Wallstent) was a stainless steel stent constrained on a 9-Fr delivery catheter that expanded to a maximum diameter of 10 mm. It was shown to have a significantly longer duration of patency compared to plastic stents in a number of randomized controlled trials, usually about doubling the half-life of plastic stents.

More recent iterations of the original Wallstent have been designed with a more open weave and using a nickel titanium alloy, which is a softer more pliable metal that will conform to the bends and deformity of the bile duct occurring in patients with malignant obstruction. None of these newer designs has been demonstrated to improve patency over the original Wallstent. All uncovered metal stents may occlude, based on ingrowth of tissue through the mesh of the stent. Although originally classified as “tumor ingrowth,” autopsy studies have indicated that this is largely epithelial hyperplasia, which occurs as a foreign body reaction to these stents.

In an effort to eliminate this, covering the stents with a variety of plastic materials has been tried and a variety of covered metal stents are available, including completely covered stents, which offer the advantage of being able to be removed, and partially covered stents, which imbed in the bile duct proximally to prevent migration. In multiple randomized controlled trials, these covered metal stents have not demonstrated improved patency compared to the uncovered stents. The mechanism of failure may be related to sludge developing within the stents, similar to that seen in plastic stents, epithelial hyperplasia that occurs at the proximal margin above the stent, tumor overgrowth, or stent migration.

Malignant hilar obstruction

Technical challenges are common in patients with malignant obstruction at the liver hilum. This typically is due to the presence of cholangiocarcinoma (Klatskin tumor) but may be seen with metastatic disease or primary hepatoma. There is great controversy surrounding the optimal management of these patients. Attempts at classification of the stricture (Bismuth classification) have not been terribly helpful due to wide variations in biliary anatomy. What has become very clear is the utility and importance of getting an accurate roadmap of the extent and location of the stricture prior to performing an ERCP with palliative stenting. This is best accomplished with an MRCP.

Generally speaking, excellent palliation of obstructive jaundice can be obtained when approximately 50% of the hepatic parenchyma is drained. In complex hilar strictures, this may require draining more than one segment of liver. In lesions that obstruct the biliary tree below the bifurcation, a single stent placed in either the right or left lobe should suffice. A retrospective study from Toronto demonstrated poorer outcomes when segments were opacified with contrast at ERCP and not drained.

The advantages of performing unilateral versus bilateral drainage in patients with malignant biliary obstruction involving the liver hilum, still remain controversial. Certainly, if the obstruction is above the bifurcation and both lobes of the liver are filled with contrast at ERCP, then bilateral stenting is reasonable. However, techniques have evolved to avoid contrast injection in one lobe of the liver using guide wire assisted cannulation. Therefore, if based on a preprocedure MRCP, it is felt that unilateral drainage is reasonable, care should be taken to avoid contrast opacification on the side of the liver not planned to be drained. This is extremely important in patients with malignant obstruction at the hilum that have demonstrated atrophy of one hepatic lobe. Under these circumstances, long-standing obstruction has led to marked dilation of the duct in that lobe with resulting parenchymal atrophy. Usually, this alone does not cause jaundice and it is not until the tumor has crept down below the bifurcation and obstructed the previously normal lobe that the patient becomes jaundice. In such cases, great care should be taken to avoid injecting any contrast in the chronically obstructed duct and only decompress unilaterally the freshly obstructed liver lobe in order to optimize palliation of jaundice and minimize subsequent complications.

Equally controversial is the use of metal stents in hilar malignant obstruction. The slow-growing nature of these tumors associated with improvements in the oncologic care of patients, have led to longer-term survival in this patient population. The use of covered metal stents in the hilum is contraindicated because the plastic covering obstructs multiple side branches and results in poor outcomes, including a high rate of cholangitis. Uncovered metal stents can be used successfully; however, they cannot be removed and frequently as the tumor progresses additional ducts may become obstructed.

Because the expected survival of these patients may exceed 6 months, late complications in this group of patients are common and the use of percutaneous transhepatic drainage with subsequent deterioration in the patient’s quality of life is often required. Therefore, the ideal stent to treat malignant hilar obstruction has yet to be developed and the use of unilateral, bilateral, plastic, and/or uncovered metal stents should all be weighed and considered carefully and individually in detailed discussion with the patients and other members of the healthcare team.

Endotherapy of cholangiocarcinoma

ERCP may be used for therapeutic intent to treat malignant bile duct obstruction from cholangiocarcinoma. Photodynamic therapy is a technique in which a photoactive drug is given to patients intravenously 24 to 48 hours prior to an ERCP. The drug permeates all cell membranes but is selectively retained in malignant cells. A laser fiber is then advanced into the malignant stricture and light at a given wavelength is subsequently applied through the laser fiber for varying periods of time.

This light photo-activates the drug retained within the malignant cells and results in the intracellular generation of oxygen radicals with resultant cytotoxicity.

This technique has been employed mainly in Europe to treat malignant biliary obstruction at the hepatic hilum. Initial reports claimed significantly improved survival over historical cohorts of patients managed medically. However, tumor sloughing with resultant cholangitis is extremely common and multiple procedures are required. In addition, published studies have used old or historical data rather than appropriate comparative controls, meaning cohorts of patients in whom adequate biliary drainage was achieved; thus, the beneficial effects of PDT may not be as profound as reported. A newly developed thermal probe using radio-frequency energy to generate heat is also being applied therapeutically to patients with malignant biliary obstruction, and is under current investigation.

Contraindications

There are several relative contraindications to be considered before performing an ERCP. Currently, ERCP is used mainly as a therapeutic modality. Thus, when there is not a clear indication for ERCP, an imaging study such as MRCP, or contrast enhanced CT scan should be performed first to confirm appropriate indication rather than performing an ERCP for diagnostic purposes (i.e., to look for CBD stones).

ERCP is a complex, technically demanding endoscopic procedure that requires the patient to be deeply sedated during the procedure. In patients with compromised respiratory or cardiac status, the need of performing the procedure under general anesthesia should be discussed with the patient and the family.

Presence of coagulopathy is also a relative contraindication. In patients receiving anticoagulation in the form of Coumadin or Heparin, ERCP should be delayed until INR is less than or equal to 1.5 and PTT is within normal limits. In thrombocytopenic patients (platelet count <50,000) or patients with high INR (i.e., patients with cirrhosis) that require an urgent ERCP, blood products should be transfused first, especially when a sphincterotomy is expected to be performed. Finally, in elective cases, our practice is to request clopidrogel to be held for 7 days prior to ERCP.

Details of how the procedure is performed

The specially designed side-viewing duodenoscope is 120 mm in length and, generally for an adult population, has an outer diameter of 11 to 13 mm. It is advanced through the mouth, down the esophagus past the stomach, and into the second portion of the duodenum.

The optics is situated such that the view is through the side of the duodenoscope, allowing enface identification and manipulation of the major duodenal papilla. The working channel of the scope generally varies between 3.8 and 4.2 mm and allows passage of devices up to 12 Fr in diameter. Using the endoscopic controls, such devices can then be advanced into the bile duct under fluoroscopic guidance.

In addition to right, left, and up/down deflection, a separate control operated with the use of the thumb allows manipulation of an elevator. The elevator provides additional up/down lifting of instruments passed through the working channel. Low ionic strength iodinated contrast is typically injected through these catheters to opacify the bile duct. A number of guide wires with diameters of 0.018 to 0.035 inch can be advanced into the bile duct. Catheters can be exchanged over-the-wire using classic Seldinger technique.

High-resolution fluoroscopy is required for optimal performance of ERCP. The use of fixed C-arms is particularly helpful to position the image intensifier, allowing for optimal visualization of the biliary tree. An endoscopic assistant with experience and working knowledge of all equipment involved is required for the safe and successful performance of ERCP. Pediatric scopes with an outer diameter of 7 mm and a working channel of 2 mm are also available. These instruments may be required when ERCP is performed in young children and infants.

In the vast majority of patients, the major duodenal papilla sits in the duodenal sweep along the cranial border of the duodenum. The bile duct and pancreatic duct join to drain into the ampulla of Vater or a common channel. The length of this common channel is quite variable from patient to patient. In some patients, a long common channel may extend up to 1 cm from the ampullary orifice. In some patients, separate orifices (no common channel) may be encountered. A common anomaly is malunion of the pancreaticobiliary junction. Under these circumstances, the pancreatic duct and bile duct separate over 1 cm from the ampullary orifice. This malunion is commonly seen in patients with congenital cystic disease of the bile ducts. It may be seen in the absence of cystic disease and has been suggested to be associated with an increased risk of pancreaticobiliary malignancy.

In the decades prior to the use of proton pump inhibitors, complications of peptic ulcer disease were frequent and surgical operations for ulcer disease including an antrectomy with a Billroth II gastro-jejunostomy were common. In these patients, the duodenum sits at the end of the afferent limb, which can be entered with a standard duodenoscope and advanced all the way up into the duodenum in a retrograde fashion. Under this circumstance, the papilla is oriented in a reverse direction, so that the bile duct runs in a 6 o’clock direction instead of its usual 12 o’clock orientation. Experienced endoscopists can use standard equipment to access the bile duct and perform therapeutic maneuvers in these patients; however, the success rates may be somewhat lower.

Although surgery for peptic ulcer disease is performed less and less commonly, surgery for morbid obesity is becoming extremely common, and the most effective and most commonly performed procedure is the Roux-en-Y gastric bypass. In this operation, a small gastric pouch is created by stapling the stomach several centimeters below the GE junction and a Roux limb of the jejunum is brought up to drain the gastric pouch. The distal stomach is left intact, which is in continuity with the duodenum.

Patients lose weight by a combination of restricted oral intake due to the small gastric pouch and malabsorption due to bypass of part of the small bowel. The length of the bypassed limbs makes endoscopic access to the papilla quite challenging. When the gallbladder is left in-situ, the rapid weight loss following gastric bypass predisposes to gallbladder stone and/or sludge formation in a significant percentage of patients. Therefore, endoscopists are frequently called to manage complication of bile duct stones in this patient population.

Several clinicians espouse the use of long enteroscopes (i.e., single or double balloon enteroscopes) advanced through the bypassed jejunum and up the bile-containing limb of the jejunojejunostomy to the duodenum in a retrograde fashion. Standard duodenoscopes are typically too short to be used in such patients. Once the enteroscopes reach the papilla, a series of specially designed devices long enough to fit through the long scopes may be employed to facilitate therapeutic maneuvers. These maneuvers are technically challenging and even reports at expert centers provide definitive success in only the minority of cases.

It has become our standard practice to perform these procedures with laparoscopic assistance. The patient is taken to the operating room, the excluded stomach is mobilized, and an anterior gastrotomy is created, which allows the passage of the duodenoscope via a port into the distal stomach. This allows easy access to the papilla and the performance of ERCP in the standard fashion. Tacking the excluded stomach to the anterior abdominal wall and using a gastrostomy tube for access can address cases requiring repeat intervention.

In patients with failed endoscopic biliary access either due to anatomic variations, such as a large periampullary diverticulum, technical failure in biliary cannulation, or a complete stricture of the distal bile duct, which precludes retrograde access, a combined procedure may be used with percutaneous guidance or with endoscopic ultrasound. In the former situation, the interventional radiologist may simply pass a guidewire into the biliary tree and advance it down to the duodenum. A duodenoscope may then be advanced in a standard fashion and access to the bile duct achieved retrograde by drawing the wire through the scope and advancing a catheter over the wire in a retrograde fashion. Alternatively, the endoscopic ultrasound may be used to access the biliary tree above the point of obstruction using a transduodenal approach, usually at the duodenal bulb. Intrahepatic access has also been described using an endoscopic ultrasound and a transgastric approach.

The most distal portion of the biliary tree is termed the common bile duct. From this, the cystic duct will originate and form the conduit between the gallbladder and the extrahepatic bile duct. The location and orientation of the cystic duct varies widely and defines the length of the common bile duct. The extrahepatic bile duct above the cystic duct is called the common hepatic duct. The common hepatic duct branches into the right intrahepatic ducts and left intrahepatic ducts at the so-called bifurcation. Many anomalies exist between the origin of the cystic duct, which can be seen originating from both the right and left intrahepatic ducts. The intrahepatic biliary drainage may also be quite variable.

Interpretation of results

This topic was incorporated in details under the “Indications and patient selection” section.

Performance characteristics of the procedure (applies only to diagnostic procedures)

N/A

Outcomes (applies only to therapeutic procedures)

ERCP was originally designed to diagnose disorders of the pancreaticobiliary tree. Over the last 20 years, this technique has evolved into largely a therapeutic modality used to treat a variety of conditions.A number of imaging modalities have supplanted ERCP for diagnostic evaluation of the pancreaticobiliary tree, including high-resolution multidetector computerized tomography (CT) scanning, magnetic resonance cholangiopancreatography (MRCP), and endoscopic ultrasound (EUS). These latter modalities are less invasive than ERCP and typically performed for diagnosis prior to performing ERCP.

Alternative and/or additional procedures to consider

ERCP was originally designed to diagnose disorders of the pancreaticobiliary tree. Over the last 20 years, this technique has evolved into largely a therapeutic modality used to treat a variety of conditions. A number of imaging modalities have supplanted ERCP for diagnostic evaluation of the pancreaticobiliary tree, including high-resolution multidetector computerized tomography (CT) scanning, magnetic resonance cholangiopancreatography (MRCP), and endoscopic ultrasound (EUS). These latter modalities are less invasive than ERCP and typically performed for diagnosis prior to performing ERCP.

Complications and their management

ERCP is not only technically demanding but also imposes unique risks to patients, not found in standard endoscopic procedures. In addition to the complications involved with routine endoscopy, including sedation-related complications and perforations of the posterior oral pharynx, esophagus, and stomach, some complications unique to ERCP and its associated techniques can occur.

Complications unique to ERCP include pancreatitis, sphincterotomy bleeding, retroperitoneal perforation, and cholangitis. The incidence of complications varies widely dependent on multiple factors including high-risk patients, high-risk procedures, and high-risk physicians.

Pancreatitis. Generally considered the most common complication from ERCP, and its occurrence is widely variable depending on the above-mentioned factors. Young women, patients with a prior history of recurrent pancreatitis, the absence of chronic pancreatitis, normal bilirubin, and the presence of Sphincter of Oddi dysfunction are all considered patients at increased risk for post ERCP pancreatitis. Multiple pancreatic injections, performance of a biliary sphincterotomy for sphincter of Oddi dysfunction or in the treatment of acute recurrent pancreatitis, sphinter of Oddi manometry, pancreatic endotherapy on patients without chronic pancreatitis, precut sphincterotomy, and balloon dilation of an intact biliary sphincter are considered high risk procedures for the development of post ERCP pancreatitis. Finally, inexperienced endoscopists impose higher risks on patients. In high-risk patients, the prophylactic placement of a pancreatic stent and administration of rectal indomethacin have been shown to reduce the incidence and severity of post-ERCP pancreatitis.

Spincterotomy bleeding. Endoscopic sphincterotomy, during which a catheter fitted with a monopolar cutting wire – which can be bowed and used to deliver a current, allowing for division of the sphincter of Oddi – is typically performed during therapeutic ERCP. This can cause bleeding at the cut surface of the papilla. Bleeding risks are increased in patients with coagulopathy, including patients who are thrombocytopenic, patients who have an elevated INR, patients who are taking blood thinners and, perhaps, those with end-stage renal disease.

Retroperitoneal perforation. When the sphincterotomy cut is carried beyond the wall of the duodenum, a perforation may occur. Such perforations largely occur in the retroperitoneum and present with fever, leukocytosis, and back pain. They may be difficult to diagnose or subclinical during early presentation and suspicion of perforation should warrant CT scan of the abdomen.

Cholangitis. Infection in the biliary tree that may occur following ERCP. ERCP is not a sterile procedure as the duodenoscope is introduced through the mouth and GI flora, and catheters that are advanced through the scope access the normally sterile biliary tree. Endoscopic sphincterotomy also disrupts the natural barrier between the unsterile intestine and the sterile biliary tree. Provided there is antegrade flow of bile from the liver into the intestines, a sphincterotomy is usually well tolerated. In patients who have obstructed bile ducts that are not relieved with ERCP, cholangitis may occur. If this is anticipated both pre and post procedure, antibiotics can reduce the risk of infection. This is most notable in patients with complex stone disease, primary sclerosing cholangitis, and patients with a malignant obstruction of the liver hilum.

Risk of complications can be attenuated by careful patient selection, the judicious use of antibiotics, the correction of coagulopathy, and the prompt recognition and treatment for suspected perforation or pancreatitis.

What’s the evidence?

Itoi, T, Coelho-Prabhu, N, Baron, TH. "Endoscopic gallbladder drainage for management of acute cholecystitis". Gastrointest Endosc. vol. 71. 2010. pp. 1038-45.

(This systematic review of small retrospective studies suggests that endoscopic gallbladder drainage may have a high potential as an alternative drainage procedure in acute cholecystitis.)

Fan, ST, Lai, EC, Mok, FP. "Early treatment of acute biliary pancreatitis by endoscopic papillotomy". N Engl J Med. vol. 328. 1993. pp. 228-32.

(This landmark randomized controlled trial of urgent ERCP versus conservative management in 195 patients with acute biliary pancreatitis showed significant reduction of biliary sepsis in the ERCP arm.)

Behar, J, Corazziari, E, Guelrud, M. "Functional gallbladder and sphincter of Oddi disorders". Gastroenterology. vol. 130. 2006. pp. 1498.

(This expert committee consensus describes the presentation, diagnostic criteria, and different types of sphincter of Oddi dysfunction.)

Costamagna, G, Tringali, A, Mutignani, M. "Endotherapy of postoperative biliary strictures with multiple stents: results after more than 10 years of follow-up". Gastrointest Endosc. vol. 72. 2010. pp. 551-7.

(In this study of 40 patients who underwent multiple endoscopic stenting for postoperative biliary strictures, results remained excellent after long-term follow-up with a low stricture recurrence rate.)

Ghazale, A, Chari, ST, Smyrk, TC. "Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer". Am J Gastroenterol. vol. 102. 2007. pp. 1646.

(This study showed that elevated serum IgG4 has a sensitivity of 76%, specificity of 93%, and positive predictive value of 36% in diagnosing autoimmune pancreatitis. However, mild IgG4 elevations are seen in 10% of pancreatic cancer patients.)

Ponsioen, CY, Lam, K, van Milligen de Wit, AW. "Four years experience with short-term stenting in primary sclerosing cholangitis". Am J Gastroenterol. vol. 94. 1999. pp. 2403-9.

(In this small study of 32 patients with PSC and symptomatic dominant biliary strictures, short-term endoscopic stenting proved to be effective and safe, with the beneficial effect sustained for several years.)

Todani, T, Watamabe, Y, Toki, A, Morotomi, Y. "Classification of congenital biliary cystic disease: special reference to type Ic and IVA cysts with primary ductal stricture". J Hepatobiliary Pancreat Surg. vol. 10. 2003. pp. 340.

(This is an update of the landmark 1977 classification of congenital biliary cysts by Todani et al., with special reference to pancreaticobiliary malunion and primary ductal strictures.)

Papachristou, GI, Smyrk, TC, Baron, TH. "Endoscopic retrograde cholangiopancreatography tissue sampling: when and how?". Clin Gastroenterol Hepatol. vol. 5. 2007. pp. 783-90.

(This is a comprehensive review of the evidence of existing tissue sampling techniques during ERCP.)

Chen, YK, Parsi, MA, Binmoeller, KF. "Single-operator cholangioscopy in patients requiring evaluation of bile duct disease or therapy of biliary stones (with videos)". Gastrointest Endosc. vol. 74. 2011. pp. 805-14.

(In this landmark multicenter prospective study, single-operator cholangioscopy was safe in evaluating bile duct disease with an overall procedural success of 89%, adequate tissue sampling in 88%, 78% sensitivity in diagnosing malignancy, and complete stone clearance in 71% of cases.)

Meining, A, Chen, YK, Pleskow, D. "Direct visualization of indeterminate pancreaticobiliary strictures with probe-based confocal laser endomicroscopy: a multicenter experience". Gastrointest Endosc. vol. 74. 2011. pp. 961-8.

(In this multicenter study of 102 patients, probe-based confocal laser endomicroscopy was found for the first time to provide reliable microscopic examination with very high sensitivity and negative predictive value.)

Chang, WH, Kortan, P, Haber, GB. "Outcome in patients with bifurcation tumors who undergo unilateral versus bilateral hepatic duct drainage". Gastrointest Endosc. vol. 47. 1998. pp. 354-62.

(In this landmark retrospective study of 141 patients with biliary bifurcation tumors who underwent ERCP, best survival was seen in those with bilateral drainage and worst outcome in patients with cholangiographic opacification of both liver lobes but drainage of only one.)

Freeman, ML, Guda, NM. "Prevention of post-ERCP pancreatitis: a comprehensive review". Gastrointest Endosc. vol. 59. 2004. pp. 845-64.

(This is a comprehensive review on the evidence of patient selection and endoscopic techniques in preventing post-ERCP pancreatitis.)

Choudhary, A, Bechtold, ML, Arif, M. "Pancreatic stents for prophylaxis against post-ERCP pancreatitis: a meta-analysis and systematic review". Gastrointest Endosc. vol. 73. 2011. pp. 275-82.

(This is a meta-analysis on the evidence supporting the use of pancreatic stents for prophylaxis against post-ERCP pancreatitis.)

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