The risk of cholangitis immediately after ERCP is very low—0.7% in a large series from a single referral center where drainage of obstructed ducts is practiced aggressively.⁶ The incidence of cholangitis increases 10-fold if diagnostic ERCP is undertaken without performing biliary drainage when an obstruction is found.⁷ This increased incidence is due to contaminating sterile bile with enteric bacteria, which in the presence of obstruction results in cholangitis. Any obstructed segment of the biliary tract opacified during cholangiography should be drained. Improper disinfection of duodenoscopes or use of contaminated water also increases the risk of post-ERCP cholangitis and bacteremia, especially with Pseudomonas aeruginosa.^8,⁹

Long-Term Postsphincterotomy Cholangitis

Surgical or endoscopic sphincterotomy is a risk factor for bacterial contamination of the biliary tract,¹⁰ likely by facilitating transpapillary migration of enteric bacteria. Escherichia coli is the most common organism identified. Analysis of patients after cholecystectomy who underwent sphincterotomy revealed a predisposition for developing brown stones or sludge within the common bile duct (CBD) in association with bacteriobilia.¹¹ However, these data may be biased by predilection in choledocholithiasis prompting sphincterotomy in the first place.

Cholangitis

Bacterial cholangitis results from bile duct obstruction or previous biliary instrumentation. Enterobacteriaceae are the most common causative organisms, and blood cultures are positive in 50% of patients.¹² Isolation of enterococci or multiple organisms from bile is more common in patients with a biliary endoprosthesis¹³ or bilioenteric anastomosis. Charcot’s triad of right upper quadrant pain, fever, and jaundice is present in 70% of patients with acute bacterial cholangitis. The addition of hypotension and confusion constitutes Reynolds’ pentad, which is present in less than 5% of patients with cholangitis but is significantly associated with mortality.¹⁴ Right upper quadrant pain and fever may be absent in elderly patients, diabetic patients, or patients treated with systemic corticosteroids.

Anatomy

Postoperative Cholangitis

Patients who have undergone bile duct reconstruction with creation of a hepatojejunostomy are at risk of postoperative cholangitis. This condition is especially prevalent in patients with biliary atresia.¹⁵ Bacterial colonization of the hepatojejunostomy and stoma obstruction by food debris may be pathogenic factors.

Sump Syndrome

Sump syndrome occurs after creation of a choledochoduodenostomy to manage retained CBD stones in a dilated bile duct. The distal bile duct between the papilla and the anastomosis becomes a stagnant reservoir or sump into which sludge, calculi, and food can collect. The clinical presentation may include recurrent pain, cholangitis, hepatic abscess, or pancreatitis. Management with endoscopic sphincterotomy with extraction of debris from the bile duct is successful in most patients.¹⁶ In case series, recurrence of symptoms has been noted in 0 to 19% and results from stenosis of the sphincter of Oddi.^17,¹⁸ A repeat sphincterotomy should be considered.¹⁸

Preparation

Prophylactic antibiotics are not recommended routinely in patients with biliary obstruction undergoing ERCP for prevention of endocarditis or post-ERCP cholangitis.^19,²⁰ However, in patients with cholangitis, broad-spectrum antibiotics providing coverage of gram-negative bacilli and Enterococcus species are indicated until biliary drainage is successfully completed.

Procedure

ERCP is performed in the usual manner.

A scout film should be examined for pneumobilia, which may be present if a sphincterotomy had been performed previously, if gas-forming bacteria are present in the biliary tract, or if there is a biliary parasitic infestation with Ascaris.

After biliary cannulation has been accomplished, aspiration of bile and pus decompresses the biliary tract and reduces the risk of bacteremia from the pressure of contrast agent injection.

A specimen of aspirated bile can be placed in a sterile tube and submitted to microbiology for Gram stain and culture.

Cholangiography usually shows the site and cause of biliary obstruction.

Intraluminal Obstruction

An adequate biliary sphincterotomy is required for removal of choledocholithiasis or other intraluminal debris.

Use of a balloon or basket for stone extraction is appropriate. Only the distalmost stone is removed on each sweep to prevent impaction.

Mechanical lithotripsy or DACP-assisted EHL is performed for stones larger than the distal bile duct. The stone fragments are removed as described previously.

Biliary Stricture

A guidewire is passed across the stricture.

The length of stent required is measured during withdrawal of the sphincterotome at the level of the biopsy channel.

The stricture is sampled by brushing or biopsy, either fluoroscopically guided or under direct vision during choledochoscopy.

Balloon or catheter dilation may be necessary to accommodate stent placement.

A stent is placed across the stricture to relieve obstruction (Fig. 45.1). Although a larger diameter stent is usually preferred, both stent size and type depend on the underlying etiology of the biliary stricture. For most benign strictures, the authors prefer a straight stent with internal and external flaps to prevent stent migration. For malignant strictures in palliative patients, a covered or uncovered self-expandable metal stent is another appropriate choice.

Patients with strictures involving the biliary hilum should undergo stent placement into both the right and the left hepatic ducts when technically possible; this is accomplished by placing two guidewires, one into each ductal system, and sequential stent placement.

Drainage of bile and contrast agent through the stent should be noted endoscopically and fluoroscopically to ascertain successful decompression.

Fig. 45.1 A and B, Patient with cholangitis resulting from a benign postoperative bile duct stricture shown by endoscopic retrograde cholangiopancreatography (ERCP) (A) and after placement of three 10-Fr plastic stents (B).

Stent Occlusion

An occluded plastic stent can be removed with a polypectomy snare through the biopsy channel of the duodenoscope.

An occluded metal stent should be trawled with a biliary extraction basket or balloon to remove any debris.

If metal stent occlusion is due to tumor ingrowth or overgrowth, deployment of another stent within the occluded stent may be performed.

Complications

Complications of cholangitis include hepatic abscess, distant metastatic abscess, bacteremia, systemic inflammatory response syndrome, and multiple organ dysfunction. There is a 10% risk of death.

Outcomes

Treatment of acute cholangitis includes resuscitation, antimicrobials, and biliary tract drainage (Fig. 45.2). Management of respiratory and circulatory insufficiency in a monitored setting and administration of broad-spectrum antibiotics should precede, but not delay, definitive biliary tract decompression in a severely ill or deteriorating patient.

Fig. 45.2 Algorithm for management of cholangitis. ERCP, endoscopic retrograde cholangiopancreatography.

Calculous Cholangitis

Biliary drainage can be accomplished endoscopically, percutaneously, or surgically. Endoscopic treatment, either sphincterotomy with stone extraction ^21,²² or biliary stent or nasobiliary drain insertion, is superior to surgical treatment in patients with severe cholangitis. Endoscopic sphincterotomy with stone extraction resulted in increased survival compared with surgery in a retrospective cohort of patients with acute calculous cholangitis²¹; this was despite a higher number of concomitant medical problems and increased age in the patients managed endoscopically. Lai and colleagues²³ randomly assigned 82 patients with calculous cholangitis requiring emergent therapy to surgery or ERCP with nasobiliary catheter placement. The mortality in the surgical arm was significantly higher than in the endoscopic arm—32% and 10%. In addition, there were an increased number of nonfatal complications in the group undergoing surgery.

Sphincterotomy and stone extraction is usually attempted during the initial ERCP. However, in critically ill patients with acute cholangitis secondary to choledocholithiasis, it may be prudent to achieve biliary drainage endoscopically, by insertion of a stent or nasobiliary catheter, and defer stone extraction to a later time. Therapeutic response, procedure-related complications, and length of procedure are similar for biliary stents and nasobiliary catheters, but inadvertent catheter removal and patient discomfort are greater in patients who receive a nasobiliary catheter.²⁴ Approximately 10% of patients have cholangitis owing to stones that cannot be removed by standard means, including mechanical lithotripsy. These stones include large stones, stones located proximal to a stricture, or stones greater than the diameter of the distal bile duct. Options are endoscopic EHL, extracorporeal shock wave lithotripsy, endoscopic laser lithotripsy, and permanent biliary stent placement.²⁵^–²⁷ Increasingly, the use of adjunctive biliary balloon sphincteroplasty is being used to remove CBD stones safely and effectively. An occlusion cholangiogram at completion of ERCP may ensure clearance but carries a significant risk of bacteremia in this situation.

If all stones or stone fragments cannot be removed during the initial endoscopic session, a stent should be left in place to provide bile drainage and prevent further cholangitis (Fig. 45.3). Long-term stent therapy is no longer advisable because of the high incidence of cholangitis and related deaths.^28,²⁹ Similar techniques can be employed in the cystic duct to treat Mirizzi’s syndrome.^26,^30,³¹ In a patient with cholangitis and gallstones but no evidence of choledocholithiasis on cholangiography, empiric endoscopic sphincterotomy does not appear to decrease the risk of subsequent episodes of cholangitis and results in a higher ERCP complication rate.³²

Fig. 45.3 A, Magnetic resonance cholangiopancreatography (MRCP) shows two large bile duct stones in a patient with cholangitis. B, Endoscopic retrograde cholangiopancreatography (ERCP) in the same patient with basket extraction of one of the stones. C, ERCP shows dilated bile duct packed with stones. D, Basket extraction. E, Mechanical lithotripsy.

Cholangitis Secondary to a Biliary Stricture

Biliary tract obstruction secondary to a malignant stricture rarely causes cholangitis, unless the bile has been contaminated with bacteria during a previous biliary intervention. Patients with strictures involving the biliary hilum should undergo stent placement into the right and the left hepatic ducts when technically possible because bilateral decompression would improve patient survival.³³ This is especially important if the biliary tract proximal to the stricture has filled with contrast material.

Cholangitis Secondary to Stent Occlusion

Plastic biliary stents develop a bacterial biofilm on their surface,³⁴ which leads to stent occlusion and risk of cholangitis. Uncovered self-expandable metal stents, by virtue of their larger diameter and composition, do not develop encrustation at the same rate and have a longer patency.³⁴ If metal stent obstruction does occur, it is usually the result of tumor ingrowth between the metal struts or tumor overgrowth at either end. Metal stents covered with a synthetic coating to prevent tumor ingrowth seem to have a similar or increased duration of patency (Fig. 45.4).³⁵

Fig. 45.4 Patient with cholangitis secondary to an occluded biliary metal stent (the patient also has three internal stents in the duodenum). A, Endoscopic retrograde cholangiopancreatography (ERCP.) B, Insertion of a 10-Fr plastic stent inside the metal stent. C, Final position of stent.

Recurrent Pyogenic Cholangitis

Recurrent pyogenic cholangitis, also known as Oriental cholangiohepatitis, is a clinical syndrome comprising repetitive episodes of bacterial cholangitis resulting from intrahepatic biliary obstruction with calcium bilirubinate stones or strictures or both. The bile ducts in the left lateral segment of the liver are often the only ducts affected or the most severely affected. This segment may be anatomically predisposed to stasis because of duct angulations slowing bile drainage. Chronic obstruction eventually causes permanent dilation of the proximal biliary tract, often filled with intrahepatic stones. Bile stasis and bacterial contamination may result in the development of multiple hepatic abscesses. Enterobacteriaceae bacteria are the most frequent organisms cultured from bile. P. aeruginosa may be seen in patients who have previously undergone endoscopic or surgical biliary intervention. Anaerobes are less common. Growth of multiple organisms, although unusual in other causes of cholangitis, often occurs in recurrent pyogenic cholangitis.³⁶ Isolation of biliary parasites in patients with recurrent pyogenic cholangitis is common,^37,³⁸ but it is unclear whether the parasite is an etiologic agent or an incidental finding.

Indications

ERCP is indicated to provide drainage to obstructed bile ducts when cholangitis is not responding adequately to supportive measures. Otherwise, ERCP in recurrent pyogenic cholangitis should be timed between episodes of acute cholangitis. The goal of endoscopic management is to treat biliary obstruction by stricture dilation and stone removal with the intent of decreasing the frequency of cholangitis.

Preparation

Prophylactic antibiotics have been recommended to decrease the risk of cholangitis during ERCP in patients with recurrent pyogenic cholangitis.³⁹ Magnetic resonance (MR) cholangiography before ERCP should be considered. The major advantage of MR cholangiography is complete visualization of the biliary tract including segments obstructed by calculi or strictures⁴⁰ that may not be apparent by ERCP. Detailed knowledge of intrahepatic segment anatomy is necessary to correlate MR imaging to the opacified ducts at ERCP and guide endoscopic management.

Procedure

Cholangiography during ERCP also accurately documents duct dilation, intraductal stones, and gallstones (Fig. 45.5). The intrahepatic ducts appear straightened and acutely angulated at branches, likely secondary to periductal fibrosis. There is often distinct tapering of the intrahepatic ducts proximally, described as the “arrowhead” sign, and decreased duct branching. Complete occlusion of an intrahepatic duct by a stone may be represented by segmental absence of contrast material and is better assessed by MR cholangiography.

ERCP is performed in the usual manner.

Obtaining a complete cholangiogram may be difficult because of intrahepatic duct obstruction by impacted stones or strictures or both. Occlusion cholangiography using a biliary balloon can be useful in this situation but carries a risk of cholangitis by contaminating obstructed ducts with contrast material and of bacteremia by increasing the intraluminal pressure. A complete cholangiogram should not be aggressively pursued if drainage of obstructed ducts is not intended.

An adequate endoscopic sphincterotomy is essential for definitive endoscopic management of recurrent pyogenic cholangitis.

Standard stone extraction techniques are attempted, but it is often necessary to place a guidewire into the desired hepatic or intrahepatic ducts.

Removal of multiple stones is accomplished distal to proximal to reduce the risk of stone impaction. Given the propensity of pigment stones to fragment, extraction balloons or baskets may be used.

When extracting from smaller caliber intrahepatic ducts, it is necessary to have a variety of balloon diameters available or a multistep balloon that inflates in a stepwise fashion through a range of sizes. Baskets are more flexible and may reach deeply into difficult intrahepatic ducts, and when the size of a stone exceeds the caliber of the distal duct, basket lithotripsy can be used to fragment the stone before extraction.

Fig. 45.5 Patient with recurrent pyogenic cholangitis. A, Computed tomography (CT) scan shows dilated air-filled left intrahepatic ductal system with stones and two stents. B, Endoscopic retrograde cholangiography (ERC) shows multiple lucent stones in the same system.

If the aforementioned methods are unsuccessful, choledochoscopy should be considered.

The choledochoscope can assist in correct guidewire placement proximal to intrahepatic stones with subsequent exchange of the choledochoscope for an extraction device.

Choledochoscopy also provides further therapeutic options for stones resistant to removal by conventional methods such as EHL. The stone debris is removed by balloon or basket extraction.

Strictures occur in the extrahepatic and intrahepatic ducts, often with proximal calculi. At or immediately distal to the hepatic duct confluence is a common site for strictures. It is essential to treat strictures before attempting proximal stone removal to prevent stone impaction at the stricture.

Either wire-guided balloon or catheter dilation is an acceptable method. The ideal posttherapy duct size should be equal to or larger than the proximal stones but is guided by the size of the duct distal to the stricture.

If the wire cannot be directed across an intrahepatic duct stricture, aligning the choledochoscope with the duct of interest and passing a guidewire through the accessory channel of the choledochoscope often provides access.

The choledochoscope can be exchanged for a biliary dilation balloon or catheter. Multiple endoscopic sessions may be required for adequate stricture dilation, and a stent should be inserted between procedures.

If a dominant stricture is evident on cholangiography, further evaluation to exclude cholangiocarcinoma should be undertaken; this includes biliary cytology brushing and biopsy under fluoroscopy or direct brushing or biopsy through the accessory channel of the choledochoscope. Another endoscopic finding that is suspicious for cholangiocarcinoma in recurrent pyogenic cholangitis is mucin within the bile duct.⁴¹

Parasitic biliary infestation may occur in recurrent pyogenic cholangitis. Endoscopic treatment of parasitic cholangitis is described subsequently.

Postprocedure Care

If complete drainage is not achieved, the patient is at risk of post-ERCP cholangitis, and prophylactic broad-spectrum antibiotics should be administered. Endoscopic therapy in recurrent pyogenic cholangitis is a temporizing measure and does not cure the underlying disease, and repeat interventions are required as stones and strictures recur.

Complications

The clinical course may be complicated by recurrent sepsis, hepatic abscess rupture with peritonitis,³⁷ portal pyelothrombophlebitis, and, rarely, hepatic failure.⁴² Patients may present with acute pancreatitis, presumably secondary to obstruction of the pancreatic duct by a stone or parasite, but this is uncommon. In the long-term, patients are at risk of cirrhosis, atrophy of hepatic segments supplied by thrombosed portal branches, clinical manifestations of portal hypertension, and cholangiocarcinoma.^41,⁴²

Outcomes

ERCP has been successfully used in the treatment of recurrent pyogenic cholangitis for 25 years.⁴³ ERCP was traditionally used to provide a detailed “map” of the biliary tract, noting the location of stones and strictures, to guide definitive therapy. However, with the development of MR cholangiography, diagnostic ERCP should be reserved for situations in which MR imaging expertise is unavailable.⁴⁰ Endoscopic sphincterotomy with stricture dilation and stone extraction is uncomplicated for extrahepatic disease. The soft pigment stones readily deform and fragment, enabling delivery into the duodenum.

In contrast, management of hepatolithiasis is often technically challenging. Accessing intrahepatic branches obstructed by calculi or strictures to perform dilation or stone removal is frequently difficult. Obstructed intrahepatic ducts requiring treatment may not be apparent to the endoscopist. Intrahepatic ducts that have “vanished” proximal to a high-grade stricture or obstructing calculi are not always appreciated at cholangiography. Duodenoscope-assisted choledochoscopy is very useful in this situation, not only to identify the presence of the obstructed intrahepatic branch but also to provide further therapy, such as EHL. These techniques of endoscopic therapy can also be applied percutaneously or through a surgically created biliary-enteric conduit as described subsequently. In the management of hepatolithiasis, multiple treatment sessions are usually necessary, conducted endoscopically or percutaneously, to perform sequential stricture dilation and to attempt complete stone removal. Percutaneous access to the biliary tree can be accomplished by formation of a transhepatic tract under ultrasound guidance. As the tract matures, biliary dilation catheters and stone extraction devices are passed into the biliary tree to provide therapy. Choledochoscopy and EHL are also possible by this route.

Complete clearance of hepatolithiasis is attained in 96% of patients after an average of six treatments.⁴⁴ However, one-third of patients have recurrent disease by 5 years. Cheung⁴⁵ reported 190 patients with residual hepatolithiasis after surgical choledocholithotomy and choledochoscopic lithotripsy who were treated via a T-tube tract. Treatment consisted of sequential biliary stricture dilation with stent placement between dilation sessions. After the strictures were adequately treated, choledochoscopy and EHL were performed to fragment intrahepatic calculi with basket retrieval of stone debris. Complete clearance was achieved in 88% of patients; 15% of these patients developed evidence of recurrent disease during a mean follow-up period of 4 years. Complications were mild and included hemobilia and fever. Biliary enteric bypass procedures for repeated access to the intrahepatic ducts involve creation of a Roux-en-Y hepatojejunostomy or choledochojejunostomy with one jejunal limb brought to the skin as a cutaneous stoma^46,⁴⁷ or a jejunoduodenostomy.⁴⁸ Treatment of strictures and stones is possible using a duodenoscope, gastroscope, or choledochoscope (Fig. 45.6). When treatment is complete, the stoma can be buried subcutaneously, but it may be reaccessed by a simple surgical procedure in the event of disease recurrence.

Fig. 45.6 Patient with recurrent pyogenic cholangitis, previously treated surgically with the creation of a cutaneous-jejunal-hepatic duct conduit. A, Gastroscope passed through the conduit shows a large left intrahepatic duct stone. B, After electrohydraulic lithotripsy and extraction of fragments.

Avoidance of hepatic resection and resolution of hepatic abscesses can be achieved; however, repeat therapy or hepatic resection are most likely to be required as stones and strictures recur.⁴⁷ Segmental hepatic resection is often used to treat localized disease, primarily involving the left lateral or right posterior segments. Initial stone clearance is 96% with a disease recurrence of 6% at 5 years.⁴⁴ The complications are greater compared with hepatic-preserving procedures and include hepatic insufficiency, postoperative hemorrhage, and bile leak. Liver transplantation is rarely performed in patients with recurrent pyogenic cholangitis.^49,⁵⁰ Appropriate indications are advanced biliary cirrhosis or diffuse hepatic disease unresponsive to the aforementioned measures. The potential for disease recurrence in the transplanted liver is unknown. There is no evidence to support the use of long-term antibiotics or ursodeoxycholic acid in the management of recurrent pyogenic cholangitis.

Parasitic Cholangitis

Ascaris lumbricoides is a nematode or roundworm that matures within the small intestine and causes cholangitis by entering the bile duct across the major papilla. The trematodes Opisthorchis sinensis, Opisthorchis viverrini, Opisthorchis felineus, and Fasciola hepatica mature to adulthood within the human bile duct and are collectively known as liver flukes. A. lumbricoides and the liver flukes cause inflammation of the bile duct and secondary bacterial cholangitis by allowing ascending bacterial contamination of bile, obstructing the bile duct and stimulating choledocholithiasis. Hepatic infection by Echinococcus species frequently involves the biliary tract by hydatid cyst compression or rupture and direct extension of alveolar echinococcosis.

Ascaris Cholangitis

A. lumbricoides exists worldwide but is most prevalent in Asia, Africa, and South America as a result of crowded living conditions and poor sanitation. Ova are passed in the human feces and are ingested on contaminated fruit or vegetables. Previous endoscopic or surgical sphincterotomy,^51,⁵² bilioenteric bypass surgery,⁵¹ and cholecystectomy⁵² increase the likelihood of biliary involvement. A. lumbricoides causes inflammation of the bile duct and secondary bacterial cholangitis by allowing ascending bacterial contamination of bile, obstructing the bile duct and stimulating pigment stone formation. Migration into the gallbladder to cause acalculous or calculous cholecystitis seems to be facilitated by a low insertion of the cystic duct at the level of the ampulla and by pregnancy.⁵³

Indications

ERCP is indicated in Ascaris cholangitis to remove worms from the biliary tract when anthelmintic therapy is unsuccessful or after medical therapy when the dying worm releases numerous eggs, and these, combined with the worm’s own remnants, obstruct the biliary or pancreatic duct and act as a nidus for pigment stone formation (Fig. 45.7). The sequelae of Ascaris cholangitis, such as bile duct strictures and choledocholithiasis, may result in biliary obstruction necessitating endoscopic therapy.

Fig. 45.7 A, Endoscopic retrograde cholangiopancreatography (ERCP) shows Ascaris lumbricoides within the proximal bile duct. B, Living Ascaris crossing the papilla. C, Ascaris crossing the papilla with the motile tip of the worm approaching the papilla. D, Extracted adult Ascaris.

(C, Courtesy of Dr. Angelo Ferrari, São Paulo, Brazil; D, courtesy of Dr. Alok Gupta, Kanpur, India.)

Outcomes

ERCP is indicated for diagnosis and management of Ascaris cholangitis. ERCP enables sampling of bile to determine the presence of ova, which may be more sensitive than stool microscopy,⁵⁴ and to show the mature parasite within the biliary system (Fig. 45.8). Endoscopic extraction of biliary A. lumbricoides is successful and safe in 99% of patients.⁵² Although endoscopic sphincterotomy increases the risk of reinfection, it is necessary for worm extraction in 95% of cases.⁵⁵ Surgical removal of A. lumbricoides from the biliary tract was a common practice before the advent of therapeutic endoscopy. Present surgical indications include cholecystitis owing to worms or calculi and failure of endoscopic bile duct clearance.

Fig. 45.8 A, Fasciola hepatica being extracted at endoscopic retrograde cholangiopancreatography (ERCP). B, Adult worm after extraction.

(A, Courtesy of Dr. Claudio Navarette, Santiago, Chile; B, courtesy of Dr. Alok Gupta, Kanpur, India.)

Liver Fluke Cholangitis

Opisthorchis trematodes occur in Asia and Eastern Europe, whereas Fasciola flukes are prevalent worldwide. Human infection occurs from eating uncooked or undercooked freshwater fish or plants such as watercress, alfalfa, and parsley. Opisthorchis enter the biliary tree through the major papilla, whereas Fasciola penetrate the intestinal wall into the peritoneal cavity and enter the biliary tree transhepatically. Adult liver flukes most commonly reside in the intrahepatic branches but may be observed in the distal biliary tract. Infection of the gallbladder and pancreatic duct has also been reported.

Indications

ERCP is indicated for diagnosis of liver fluke cholangitis and endoscopic management including worm extraction and treatment of secondary bile duct strictures and choledocholithiasis.

Procedure

The goals and techniques of endoscopic treatment of liver fluke cholangitis are similar to Ascaris cholangitis. Because liver flukes frequently inhabit the proximal biliary tree, their clearance can be challenging.

ERCP is performed in the usual manner.

Cholangiography may show saccular dilation of the intrahepatic ducts, often diffusely, with blunted terminal ends.⁵⁶

Filling defects represent the fluke, choledocholithiasis, or mucosal hyperplasia or dysplasia. The fluke has a filamentous curvilinear or elliptical shape and may be quickly obscured by contrast material.^54,⁵⁶ The flukes are primarily in the secondary and tertiary branches of the intrahepatic ducts but may appear throughout the biliary tract and in the pancreatic duct.

Contrast agent injection may wash adult flukes distally. They appear at duodenoscopy as brownish, flat, leaf-shaped organisms 1 to 2 cm long and usually less than 1 cm wide.¹²

The flukes should be grasped with forceps and removed from the bile duct.⁵⁷

Endoscopic sphincterotomy is usually required for liver fluke extraction.

Extraction of flukes should be undertaken with a biliary extraction basket or balloon. Wire guidance may be necessary to access the affected intrahepatic duct.

Irregularities in the biliary wall should be sampled to evaluate for cholangiocarcinoma.

Placement of a nasobiliary tube to perform biliary infusion of povidone-iodine has been described in the management of F. hepatica cholangitis.

Complications

Long-standing liver fluke cholangitis can lead to chronic liver disease with portal hypertension and, with Opisthorchis infection, cholangiocarcinoma.

Outcomes

Anthelmintic therapy is indicated in all infected individuals. Given the potentially severe complications and ongoing parasite transmission, even asymptomatic individuals should receive eradication treatment. ERCP enables sampling of bile to show the presence of ova, which may be more sensitive than stool microscopy,⁵⁴ and demonstration of the mature parasite within the biliary system. Placement of a nasobiliary tube to perform biliary infusion of povidone-iodine has been described in the management of F. hepatica cholangitis.⁵⁸ Nine patients who had failed oral anthelmintic therapy became negative for stool ova after biliary administration of povidone-iodine. Surgical intervention is indicated for biliary or pancreatic obstruction after unsuccessful endoscopic therapy and for cholecystitis.

Echinococcal Cholangitis

Echinococcus granulosus accounts for up to 95% of all human echinococcal infections and is present throughout the world, particularly in regions where dogs are used to raise livestock. E. granulosus, Echinococcus vogeli, and Echinococcus oligarthrus form a unilocular cyst, the hydatid cyst, within the liver. The cyst is composed of three layers. The outermost layer is granulation and fibrous tissue produced by the host and may calcify over time. The middle layer is a laminated membrane. The innermost layer is the germinal layer of the parasite, which forms the daughter cysts and protoscolices. Biliary disease results from compression by the cyst or rupture of the cyst into the biliary tree. Echinococcus multilocularis cysts are not contained by an outer fibrous membrane and extend through the liver and into adjacent structures, such as the biliary tree, in a malignant fashion. Infection of the biliary tree occurs by invading into the bifurcation of the right and left hepatic ducts.

Procedure

The goals of ERCP are to document suspected Echinococcus cholangitis and treat biliary obstruction.

ERCP is performed in the usual manner.

Duodenoscopy may show glistening, white membranes within the duodenum.

The laminated membranes can be removed with biopsy forceps if protruding from the papilla.

On cholangiography, three patterns of filling defects have been reported (Fig. 45.9). The membranes appear filiform, the daughter cysts round, and hydatid sand as debris.⁵⁹

Endoscopic sphincterotomy should be performed if filling defects are shown.

The membranes, daughter cysts, and protoscolices should be removed with a biliary extraction balloon or basket.⁶⁰

Saline irrigation through the sphincterotome facilitates removal of the protoscolices.

Placement of a nasobiliary tube allows instillation of hypertonic saline solution after ERCP. If technically possible, the nasobiliary tube should be advanced into the cyst cavity.

Biliary strictures resulting from hydatid cyst compression or alveolar echinococcosis invasion can be managed with stent insertion.

Endoscopic therapy may be required after surgical treatment or PAIR (puncture, aspiration of cyst contents, injection of scolicidal agent, reaspiration) to manage bile leaks, communication between the biliary tract and the surgical site with hydatid remnants causing biliary obstruction, or biliary strictures from scolicidal agents.⁶⁰

Fig. 45.9 A, Echinococcus (hydatidosis) infection shown in right lobe of the liver on computed tomography (CT) scan. B–D, Sequence of cyst wall extraction at endoscopic retrograde cholangiopancreatography (ERCP) after sphincterotomy.

(A, Courtesy of Dr. Nageshwar Reddy, Hyderabad, India; B-D, Courtesy of Dr. Claudio Navarette, Santiago, Chile.)

Complications

E. multilocularis may invade into the portal venous system resulting in portal hypertension.⁶¹

Outcomes

Endoscopic management of biliary obstruction secondary to E. granulosus infection through extraction of hydatid debris or biliary endoprosthesis placement is successful at alleviating patient symptoms.⁶⁰ Case reports have documented resolution of a hydatid cyst communicating with the biliary tree after endoscopic extraction of cyst material followed by instillation of hypertonic saline solution via a nasobiliary tube placed in the cyst cavity and administration of albendazole orally.⁶² In E. granulosus infection, approximately 30% of patients experience cure with medical therapy alone.^63,⁶⁴ Successful therapy is more likely with small, simple cysts and treatment duration greater than 3 months.^63,^65,⁶⁶ Complete surgical excision by cystectomy, pericystectomy, or partial hepatic resection is usually curative in E. granulosus infection. Albendazole administered before surgery results in a higher number of nonviable cysts^66,⁶⁷ and may decrease the risk of local recurrence or intraperitoneal seeding should spillage of cyst contents occur. Surgical mortality is 1% to 2%.⁶⁸ Complications include infection, bile leak, and leakage of cyst contents with hypersensitivity reaction and dissemination of disease.

Percutaneous evacuation with ultrasound-guided PAIR is widely used to treat unilocular E. granulosus cysts. Scolicidal agents employed for PAIR include 95% ethanol and hypertonic saline. Khuroo and associates ⁶⁹ randomly assigned 50 patients to undergo cystectomy or PAIR and receive albendazole. At a mean follow-up of 17 months, the cyst diameter was similar in the two groups, but the surgical arm had significantly more complications and a longer length of hospital stay. After PAIR, initial treatment failures occurred in less than 1%, and probability of relapse ranged from 1% to 4.5%. Complications of PAIR include hypersensitivity reaction, infection, intraabdominal seeding, and fistula formation to adjacent organs. In a review of 765 abdominal hydatid cysts treated with PAIR, anaphylaxis occurred in four instances with one death, and minor complications occurred in 14%.⁷⁰

ERCP should be performed before protoscolicide administration to ensure there is no communication between the cyst and biliary tree because contact with protoscolicidal agents produces sclerosing cholangitis and pancreatitis. Treatment with albendazole at least 4 hours before PAIR and up to 4 weeks following has been recommended.⁷⁰ The endoscopic management of E. multilocularis cholangitis consists of stent placement to relieve biliary obstruction. Sezgin and colleagues⁶¹ have published the largest case series of hepatic E. multilocularis complicated by biliary strictures. Seven of nine patients underwent successful stent placement. The stent provided adequate biliary drainage but was ineffective in treating biliary fistula disease present in two patients.

Radical surgery with complete excision of larvae tissue is the only curative therapy for E. multilocularis infection. Treatment with albendazole for an additional 2 years postoperatively decreases the risk of local recurrence.^64,⁷¹ Patients deemed inoperable at diagnosis likely benefit from long-term albendazole therapy,⁷¹ and a combination of palliative resection, aimed at lessening the mass of larvae tissue, and benzimidazole therapy is advocated.⁷² Liver transplantation is a treatment option for unresectable alveolar echinococcosis. A retrospective study of European transplant centers reported 45 patients who underwent liver transplantation with an overall 5-year survival of 71% and disease-free 5-year survival of 58%.⁷³ Given the high probability of graft recurrence, long-term benzimidazole therapy should be considered in posttransplant patients.

Acquired Immunodeficiency Syndrome Cholangiopathy

AIDS cholangiopathy is a syndrome of right upper quadrant pain, elevated alkaline phosphatase, and typical cholangiography findings associated with human immunodeficiency virus (HIV) infection. Opportunistic infection of the biliary tract is likely a causative factor. Cryptosporidium, most commonly Cryptosporidium parvum, is isolated from the bile or stool in two-thirds of individuals with AIDS cholangiopathy,⁷⁴ but other organisms have also been associated, including Microsporida, cytomegalovirus, Isospora, Cyclospora, and Mycobacterium avium intracellulare.^75,⁷⁶ Acalculous cholecystitis secondary to opportunistic infection of the gallbladder may occur alone or concomitant to cholangiopathy and is associated with similar underlying pathogens. Cholangiopathy is the AIDS-defining illness in a few patients, but most patients have had AIDS for at least 1 year.⁷⁷

Indications

ERCP is the “gold standard” in diagnosing AIDS cholangiopathy (Fig. 45.10). The differential diagnosis of AIDS cholangiopathy and the management approach are shown in Box 45.3 and Fig. 45.11, respectively.

Fig. 45.10 A, Acquired immunodeficiency syndrome (AIDS) cholangiopathy shown by endoscopic retrograde cholangiopancreatography (ERCP) with narrowed distal bile duct and irregular bile duct walls. B, Relatively normal bile duct epithelium on biopsy and standard hematoxylin and eosin staining. C, Microsporidia shown on the surface as black with silver staining.

(Courtesy of Dr. Richard Tilson, Boston, MA.)

Fig. 45.11 Algorithm for management of suspected acquired immunodeficiency syndrome (AIDS) cholangiopathy. CBD, common bile duct; CMV, cytomegalovirus; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound; HAART, highly active antiretroviral therapy; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV human immunodeficiency; UCDA, ursodeoxycholic acid.

Precautions

Protease inhibitors and benzodiazepines are both metabolized through the P-450 enzyme complex. Protease inhibitors decrease benzodiazepine metabolism, increasing their serum levels and potentiating their effects, including respiratory depression.⁷⁸ Because midazolam and diazepam are commonly used for sedation during endoscopic procedures, endoscopists should be cognizant of this drug interaction while administering benzodiazepines in patients receiving protease inhibitors.

Procedure

Cholangiography findings have been described as sclerosing cholangitis with segmental stricture formation to create a beaded appearance similar to primary sclerosing cholangitis. The patterns of biliary tract strictures are listed in Table 45.1. Papillary stenosis with intrahepatic strictures is the most common pattern observed.^75,^77,⁷⁹ Other reported cholangiography abnormalities include adherent polypoid filling defects; biopsy specimens of these defects show granulation tissue.⁸⁰ Pancreatography is abnormal in one-half of patients with AIDS cholangiopathy, revealing pancreatic duct strictures in the head of the pancreas.^75,⁸¹

ERCP is performed in the usual manner.

The duodenum should be inspected for mucosal abnormalities such as erosions or ulcerations that may indicate enteric infection. Biopsy specimens of lesions or random mucosal biopsy specimens should be obtained and sent for microbiologic and cytologic analysis.

Bile should be sampled after cannulation and submitted for analysis.

Evidence of papillary stenosis should be noted during cannulation and by observing bile drainage after cholangiography.

If papillary stenosis is present, an endoscopic sphincterotomy should be performed in a patient with abdominal pain, jaundice, or fever. Sphincterotomy is not beneficial in the absence of papillary stenosis.

Dominant strictures should be sampled for cytology with a cytology brush or biopsy forceps to exclude cholangiocarcinoma or another malignant process.

In a symptomatic patient, balloon or catheter dilation of the stricture may be performed, but long-term stent placement should be avoided to limit migration of enteric pathogens into the biliary tract.

When ERCP is completed, biopsy specimens of the major papilla may be obtained and sent for microbiologic and pathologic analysis.

Table 45.1 Cholangiography Findings in Acquired Immunodeficiency Syndrome Cholangiopathy

Finding	Frequency (%)
Papillary stenosis and intrahepatic duct strictures	33
Papillary stenosis alone	21
Papillary stenosis and intrahepatic and extrahepatic duct strictures	20
Intrahepatic duct strictures alone	12
Intrahepatic and extrahepatic duct strictures	8
Extrahepatic duct strictures alone	5
Papillary stenosis and extrahepatic duct strictures	1

Data from Benhamou Y, Caumes E, Gerosa Y, et al: AIDS-related cholangiopathy: Critical analysis of a prospective series of 26 patients. Dig Dis Sci 38:1113–1118, 1993; Bouche H, Housset C, Dumont JL, et al: AIDS-related cholangitis: Diagnostic features and course in 15 patients. J Hepatol 17:34–39, 1993; Cello JP: AIDS-related biliary tract disease. Gastrointest Endosc Clin N Am 8:963, 1998; Ducreux M, Buffet C, Lamy P, et al: Diagnosis and prognosis of AIDS-related cholangitis. AIDS 9:875–880, 1995; Farman J, Brunetti J, Baer JW, et al: AIDS-related cholangiopancreatographic changes. Abdom Imaging 19:417–422, 1994.

Complications

Cholangitis with secondary fibrosis leads to bile duct stricture formation and papillary stenosis. Secondary biliary cirrhosis has not been described as a complication of AIDS cholangiopathy, perhaps because of the shortened life span of this patient population, but these patients may be at risk of cholangiocarcinoma.⁸²

Outcomes

Aspiration of bile for culture and multiple biopsy specimens of the duodenum and papilla reveal an underlying pathogen in up to 92% of cases.⁸¹ One study reported that isolation of Cryptosporidium or cytomegalovirus was more common when intrahepatic duct irregularities were present on cholangiography.⁸³ The medical management of AIDS cholangiopathy is divided into antimicrobial agents directed against the causative organism, highly active antiretroviral therapy (HAART) directed against the underlying HIV infection, and ursodeoxycholic acid.

Case series assessing the effect of treatment of cytomegalovirus, C. parvum, and Microsporida on patient symptoms, liver enzymes, and cholangiography findings have not been encouraging.^74,^83,⁸⁴ The use of HAART to restore the immune system has been effective in suppressing enteritis and possibly cholangiopathy associated with C. parvum and Microsporida, although eradication probably does not occur.⁸⁵ Castiella and associates⁸⁶ treated four patients with AIDS cholangiopathy with ursodeoxycholic acid (10 mg/kg body weight). At a mean follow-up of 4.5 months, improvement in symptoms and alkaline phosphatase levels was observed in all patients.

Endoscopic therapy has been the most extensively studied treatment in AIDS cholangiopathy. Endoscopic sphincterotomy in patients with papillary stenosis results in improvement of abdominal pain in 32% to 100% of patients.^81,^83,⁸⁷ Cello and Chan⁸⁸ reported improvement in pain scores at a mean of 9.4 months after sphincterotomy; this did not correspond to an improvement in liver enzymes or cholangiography abnormalities, both of which appeared to worsen. Patient survival after a diagnosis of AIDS cholangiopathy is not affected by the pattern of cholangiogram abnormalities or the presence of an endoscopic sphincterotomy but appears to be most strongly associated with the administration of HAART.⁸⁹

Cholecystitis

Acute cholecystitis is an inflammatory injury to the gallbladder mucosa from bile stasis, ischemia, or infection. Bile stasis usually results from cystic duct obstruction by a gallstone or from decreased gallbladder motility. Less common causes of cystic duct obstruction are worms, hemobilia, and tumor. Decreased gallbladder motility and ischemia are implicated in the development of acalculous cholecystitis in critically ill patients. Infection of the gallbladder complicates cholecysitis in approximately 50% of cases but is not usually the causative factor, with the exception of parasitic and AIDS cholecystitis.

Indications

ERCP is indicated for gallbladder drainage in patients who are medically unfit for surgery and in whom percutaneous drainage is contraindicated or unsuccessful.

Preparation

Antibiotic coverage is directed against Enterobacteriaceae and Enterococcus species until directed therapy can be instituted against specific organisms identified in blood or bile cultures.

Procedure

ERCP is performed in the usual manner.

The cystic duct insertion is identified and entered. A guidewire may facilitate selective cystic duct cannulation.

Endoscopic cholecystography identifies calculi within the cystic duct and gallbladder.

Wire-guided balloon extraction of stones or placement of a biliary endoprosthesis through the cystic duct and into the gallbladder can be undertaken. Occasionally, an obstructing stone is dislodged into the gallbladder as instruments are advanced into the cystic duct.⁹⁰

Irrigation of the gallbladder with 1% N-acetyl cysteine through a nasobiliary catheter has been described in acalculous cholecystitis.⁹¹ The use of N-acetyl cysteine appeared to thin the gallbladder contents and enable gallbladder drainage and collapse around the catheter.

Complications

Complications of cholecystitis usually occur with secondary bacterial infection and include empyema, gallbladder wall necrosis resulting in a gangrenous gallbladder, perforation, and emphysematous cholecystitis. Gallbladder perforation may result in abscess formation, peritonitis, or fistula formation. Migration of a large gallstone through a cholecystoenteric fistula may lead to bowel obstruction, usually at the level of the ileocecal valve, referred to as gallstone ileus. Emphysematous cholecystitis refers to gas within the gallbladder wall owing to infection with gas-producing bacteria.

Outcomes

Cholecystectomy is the definitive therapy. Although patients may recover from an episode of acute cholecystitis, the risk of recurrent symptoms is 70% within the next 2 years.⁹² Patients without serious concomitant medical problems should undergo cholecystectomy during the same hospital admission, usually 24 to 48 hours after admission. In particular, diabetics, given their increased risk of gallbladder necrosis and perforation, should be considered for cholecystectomy after their first attack of cholecystitis. Patients who are medically unfit for surgery and do not improve with supportive therapy require gallbladder drainage; this is generally achieved by percutaneous cholecystostomy tube placement, although successful endoscopic drainage of the gallbladder has been described. Placement of a biliary endoprosthesis into the gallbladder during ERCP can alleviate symptoms resulting from recurrent biliary colic, calculous cholecystitis, acalculous cholecystitis, and gallbladder perforation (Fig. 45-12).⁹¹^–⁹³ Endoscopic gallbladder drainage can be performed in the presence of coagulopathy and ascites when percutaneous cholecystostomy tube placement is contraindicated.