Endoscopic retrograde cholangiopancreatography (ERCP) for biliary disease in children

INTRODUCTION — Endoscopic retrograde cholangiopancreatography (ERCP) has an important role in the care of children with a variety of biliary tract disorders, which can be divided broadly as congenital or acquired (table 1). This topic review will summarize indications for ERCP in children with biliary diseases, focusing on some of the more common disorders. Most of these disorders are discussed in further detail in their corresponding topic reviews. The technical aspects of performing ERCP in children, including complications, and for the use of ERCP for pancreatic disorders are presented separately. (See "Endoscopic retrograde cholangiopancreatography (ERCP) in children: Technique, success, and adverse events" and "Endoscopic retrograde cholangiopancreatography (ERCP) for pancreatic disease in children".)

INDICATIONS — ERCP is an important diagnostic and therapeutic tool for biliary disease in infants and children, as it is in adults. With the advent of new diagnostic imaging techniques such as magnetic resonance cholangiopancreatography (MRCP), ERCP has become a predominantly therapeutic procedure. The usefulness and safety of ERCP in the pediatric age group depends in large part on the experience of the endoscopist. If the necessary experience and equipment are available at an institution, the following are appropriate biliary indications for ERCP:

Diagnostic indications

●Neonatal cholestasis (for biliary cysts and, at some institutions, as part of the evaluation for suspected biliary atresia)

●Investigation of inconclusive abnormal findings on other examinations (eg, MRCP, computed tomography [CT] scan, or endoscopic ultrasound)

Therapeutic indications

●Biliary obstruction (eg, due to known or suspected choledocholithiasis, primary sclerosing cholangitis (PSC), bile plug syndrome, parasitic infestation, or biliary strictures)

●Postoperative complications after biliary surgery (eg, bile leaks)

●Biliary obstruction or leaks after liver transplant

The following techniques can be used during therapeutic ERCP:

●Biliary and/or pancreatic sphincterotomy

●Sphincteroplasty (balloon dilation)

●Stone extraction

●Stricture dilation

●Stent placement and/or removal

●Tissue acquisition (cytology brush and biopsy)

●Cholangioscopy

●Pancreatoscopy

●Ampullectomy

Considerations relevant to specific disorders for which ERCP may be indicated, including alternate approaches to the evaluation if ERCP is not available, are discussed below.

CONGENITAL DISORDERS

Neonatal cholestasis — Neonatal cholestasis is defined as conjugated hyperbilirubinemia that occurs in the newborn period. It results from diminished bile flow and/or excretion. Although it can be caused by a large number of disorders, relatively few diagnoses account for the majority of defined cases. Biliary atresia, which typically occurs in term infants, accounts for approximately 30 percent of cases [1,2]. Biliary atresia is characterized by inflammation of the bile ducts leading to progressive obliteration of the extrahepatic biliary tract. As diagnostic techniques improve, specific entities that result in a pathologic picture of neonatal hepatitis have been identified. As an example, alpha-1 antitrypsin deficiency was previously included in the broad category of neonatal hepatitis but is now recognized as a distinct condition. (See "Causes of cholestasis in neonates and young infants" and "Biliary atresia".)

Evaluation of an infant with neonatal cholestasis should be undertaken in a staged approach. Extrahepatic biliary atresia must be promptly diagnosed or excluded. Infants should be evaluated as rapidly as possible because the success of the surgical intervention (Kasai hepatoportoenterostomy) diminishes progressively with older age at surgery. (See "Approach to evaluation of cholestasis in neonates and young infants".)

Biliary atresia — The diagnosis of biliary atresia is made with a series of imaging and laboratory tests and liver biopsy to exclude other causes of cholestasis. The definitive diagnosis is made by performing a cholangiogram. This is typically performed intraoperatively (see "Biliary atresia", section on 'Cholangiogram'). However, imaging the biliary system via ERCP is an alternative approach at centers where the necessary expertise and equipment are available. ERCP should be considered when anatomical information from less-invasive imaging modalities is insufficient and experienced ERCP practitioners are available to perform the procedure without delay. Multiple reports have demonstrated that ERCP can distinguish biliary atresia from other causes of neonatal cholestasis in most patients and thus assists in avoiding unnecessary surgery [3-12]. In one report of 140 infants with suspected biliary atresia, ERCP was successfully performed in 87 percent [10]. If the ERCP findings were compatible with biliary atresia, subsequent intraoperative cholangiogram confirmed biliary atresia in approximately 80 percent. In another series, ERCP was 86 percent sensitive and 94 percent specific for detecting biliary atresia and 100 percent sensitive and 90 percent specific for detecting choledochal cysts [11].

Biliary atresia was classified by Kasai into three main types depending on the level of biliary obstruction [13]. In Kasai type I, the common bile duct is obliterated. In Kasai type IIa, the common hepatic duct is obliterated; in type IIb, there is atresia of the common bile duct, common hepatic duct, and cystic duct. In Kasai type III, the entire extrahepatic biliary tree is obstructed. Kasai types I, IIb, and III are indistinguishable based on ERCP findings because the obstructed common bile duct prevents visualization of the remainder of the biliary tree.

A separate classification is used to describe ERCP findings (figure 1) [14]:

●ERCP type 1 – Nonvisualization of the biliary tree (image 1)

●ERCP type 2 – Visualization of the distal common duct and gallbladder (image 2)

●ERCP type 3 – Visualization of the gallbladder and the complete common duct, with both hepatic ducts, or visualization of biliary lakes at the porta hepatis (image 3)

Successful evaluation of the biliary tree by ERCP depends upon the experience of the endoscopist. In particular, the endoscopist must have confidence that nonvisualization of the common bile duct was not related to technical problems, such as positioning of the catheter. When a skilled endoscopist is available, ERCP may be considered as a first-line test in distinguishing between intra- and extrahepatic biliary obstruction.

Alagille syndrome — Alagille syndrome is an autosomal dominant multisystem disorder with variable phenotypic penetrance. The biliary manifestation is characterized by the paucity of interlobular bile ducts and the following associated features (see "Causes of cholestasis in neonates and young infants", section on 'Alagille syndrome' and "Alagille syndrome"):

●Chronic cholestasis (87 to 100 percent)

●Cardiac anomalies, most commonly peripheral pulmonic stenosis (63 to 98 percent)

●Butterfly vertebrae (24 to 87 percent)

●Posterior embryotoxon (prominent Schwalbe line) of the eye (56 to 95 percent)

●Dysmorphic facies, consisting of broad nasal bridge, triangular facies, and deep-set eyes (78 to 95 percent)

●Renal involvement (19 to 74 percent), most commonly renal dysplasia

ERCP generally is not performed as part of the evaluation for Alagille syndrome, although the diagnosis may be suggested in children undergoing ERCP for evaluation of neonatal cholestasis. In children with Alagille syndrome, the ERCP typically shows normal extrahepatic ducts (although hypoplasia is also reported). In contrast, the intrahepatic ducts are diffusely narrowed and demonstrate reduced arborization [7,15].

Caroli disease and congenital hepatic fibrosis — Caroli disease is a congenital disorder characterized by multifocal, segmental dilatation of large intrahepatic bile ducts. The condition usually is associated with renal cystic disease of varying severity. (See "Caroli disease".)

Caroli initially described two variants, which have led to some confusion in terminology.

●Caroli disease is the less common form and is characterized by bile ductular ectasia without other apparent hepatic abnormalities

●The more common variant is Caroli syndrome, in which bile duct dilatation is associated with congenital hepatic fibrosis

The diagnosis is established by imaging studies that demonstrate bile duct ectasia and irregular cystic dilation of the large proximal intrahepatic bile ducts with a normal common bile duct. These findings can be seen readily with ultrasonography, magnetic resonance cholangiography, or ERCP. Because ERCP is the most invasive of these tests, it is generally not required for diagnosis but can be utilized if the diagnosis is unclear or in doubt.

Biliary cysts — Biliary cysts are cystic dilatations, which may occur singly or in multiples throughout the bile ducts. They originally were termed choledochal cysts (involving the extrahepatic bile duct), but the clinical classification was revised in 1977 to include intrahepatic cysts. (See "Biliary cysts".)

Several theories of biliary cyst formation have been proposed, and it seems likely that no one mechanism accounts for all biliary cysts. Cysts may be congenital or acquired and have been associated with a variety of anatomic abnormalities. Familial occurrence of cysts has been described. The increased incidence in some Asian countries suggests a genetic or environmental predisposition.

The diagnosis of biliary cysts can be made by abdominal ultrasound, CT, or magnetic resonance cholangiopancreatography (MRCP). ERCP can be used as a supplementary test to confirm the diagnosis and categorize the type of cyst to facilitate surgical planning. The classification scheme defines five types of biliary cyst, of which type I is the most common (figure 2). The cysts may be fusiform (spindle-like, ie, wider in the middle and tapering towards the ends) or cystic (spherical). A type III cyst is a cystic dilation of the distal common bile duct, which may protrude into the duodenum and is also known as a choledochocele. An overall approach is discussed separately (see "Biliary cysts"); a few technical points that are particularly relevant in children are discussed below.

Anomalous pancreaticobiliary junction — An anomalous pancreaticobiliary junction (APBJ; also known as anomalous junction of the pancreatic and biliary ducts [AJPBD] or anomalous pancreaticobiliary union [APBU]) can be demonstrated in virtually all patients with type 1 biliary cysts (figure 2) (see "Biliary cysts"). It is characterized by a junction of the bile duct and pancreatic duct outside the duodenal wall with a long common duct channel (figure 3). In children, the maximum length of the common channel in healthy neonates and infants younger than one year is 3 mm. It increases with age to a maximum of 5 mm in children and adolescents between 13 and 15 years of age [16]. In adults, a common channel longer than 8 mm is considered abnormal [17].

Three types of anomalous ductal union have been described. All three types are characterized by a long common channel, and this is dilated in the first two types (Kimura classification) (figure 4) [17]:

●Type B-P – Common bile duct joining the main pancreatic duct (image 4)

●Type P-B – Pancreatic duct joining the common bile duct; this type is more likely to be associated with recurrent pancreatitis than the B-P type [16]

●Long Y type – A long common channel, without common bile duct dilatation (image 5)

Other classification systems have classified pancreatobiliary maljunction based on functional anatomy (stenotic, nonstenotic, dilated channel, complex) [18].

Sphincterotomy — Routine endoscopic sphincterotomy is not indicated for most cysts. Possible exceptions include the following types of cysts:

●Fusiform bile duct dilation with a widely dilated common channel [19]. In contrast to cystic dilation, fusiform dilation is more commonly associated with low-grade, short strictures located at or distal to the pancreaticobiliary junction [20].

●Distal bile duct stricture, which typically occurs at the point of connection with the pancreatic duct. Up to 8 percent of such patients develop cystolithiasis (which may be multiple) involving intrahepatic and extrahepatic ducts [21].

●Choledochocele (type III cyst, in which the cyst is located within the duodenal wall) (picture 1). (See "Biliary cysts", section on 'Type III cysts'.)

Malignancy risk — Types I, II, and IV biliary cysts are associated with an increased risk of malignancy. As a result, their surgical excision is often recommended. (See "Biliary cysts", section on 'Type I and IV cysts'.)

ACQUIRED DISORDERS — Acquired disorders in which ERCP can be helpful are summarized below (table 1).

Choledocholithiasis

●Infants and children – Gallstones occasionally are seen in neonates, infants, and young children [22-24]. In this age group, gallstones are usually associated with hemolysis, chronic liver disease (eg, intestinal failure-associated liver disease), biliary tract malformations such as choledochal cyst (image 6), or infection. In a review of 382 infants and children with gallstones, approximately one-half had recognized risk factors [25]. The most common risk factors identified were sickle cell disease, parenteral nutrition, and cardiac surgery. The highest frequency of gallstones was in infants, 80 percent of whom were asymptomatic. In this very young age group, the most common risk factors were parenteral nutrition (with or without short bowel syndrome), diuretic use, cephalosporins, and cardiac surgery. In infants, gallstones are often asymptomatic, do not require intervention, and often resolve spontaneously. Other rare causes (eg, erythropoietic protoporphyria) may be worth considering if the initial evaluation is unrevealing. (See "Overview of the clinical manifestations of sickle cell disease" and "Chronic complications of short bowel syndrome in children" and "Overview of hemolytic anemias in children".)

Symptoms such as jaundice or laboratory findings suggesting biliary obstruction require further evaluation for biliary duct stones (choledocholithiasis). Ultrasonography does not always identify small stones in the biliary system. Thus, magnetic resonance cholangiopancreatography (MRCP); endoscopic ultrasound, when available; or ERCP usually is required to evaluate symptomatic children in whom there is high clinical suspicion of choledocholithiasis [26-28].

For symptomatic individuals with choledocholithiasis, including young infants, we recommend ERCP with biliary sphincterotomy to extract biliary stones, if appropriate expertise is available [22,29-35]. Those who have small common bile duct stones on an imaging study but are asymptomatic should usually be managed conservatively since the stones (or sludge) are likely to pass spontaneously [36,37].

●Adolescents – The incidence of gallstones rises sharply during puberty. It is more common among females (approximately 60 to 70 percent of cases) and is associated with obesity [38-40]. For this age group, diagnosis and management of choledocholithiasis is similar to that in adults. (See "Choledocholithiasis: Clinical manifestations, diagnosis, and management" and "Endoscopic management of bile duct stones".)

Primary sclerosing cholangitis — Primary sclerosing cholangitis (PSC) in children typically is associated with an underlying disorder, including inflammatory bowel disease (IBD; particularly ulcerative colitis), autoimmune hepatitis [41-44], Langerhans cell histiocytosis (formerly known as histiocytosis X) [41,45], immune deficiency states [41,46], and, less frequently, reticular cell sarcoma [47] and sickle cell anemia [48,49].

IBD is a common predisposing factor for PSC. In most series, at least 80 percent of adults or children diagnosed with PSC have underlying IBD (usually ulcerative colitis) [50-52]. Conversely, 2 to 10 percent of children with IBD develop sclerosing cholangitis [50]. (See "Primary sclerosing cholangitis: Epidemiology and pathogenesis", section on 'PSC and inflammatory bowel disease' and "Clinical manifestations and complications of inflammatory bowel disease in children and adolescents", section on 'Sclerosing cholangitis'.)

The diagnosis of PSC can be established by magnetic resonance cholangiopancreatography (MRCP) or ERCP [53-55]. The cholangiogram demonstrates pruning of the peripheral biliary tree and areas of stenosis and ectasia [7,56]. (See "Primary sclerosing cholangitis in adults: Clinical manifestations and diagnosis", section on 'Diagnosis'.)

An advantage of ERCP over MRCP is that it permits therapeutic interventions and tissue acquisition among children with obstructive symptoms. Patients with dominant ductal strictures (stenosis with a diameter of ≤1.5 mm in the common bile duct) are candidates for endoscopic treatment with sphincterotomy and balloon or tapered-catheter dilation to relieve the obstruction [55,57-59]. During the ERCP, tissue can also be obtained (cytology brushing and biopsies). Most of the data on the risks and benefits of therapeutic endoscopic intervention are from adult patients; indications and individual considerations are discussed in a separate topic review. (See "Primary sclerosing cholangitis in adults: Management", section on 'Endoscopic therapy'.)

Bile plug syndrome — Bile plug syndrome refers to obstruction of the extrahepatic bile ducts by bile sludge in patients with normal biliary tract and is generally correctable. The diagnosis is suspected by ultrasonography or magnetic resonance cholangiopancreatography (MRCP) and confirmed and treated by ERCP. Irrigation during the ERCP may relieve the obstruction [7]. Any condition leading to alteration in bile composition may cause this syndrome. It can develop in patients with cytomegalovirus infections, cystic fibrosis, hepatocellular damage, prolonged erythroblastic jaundice, or total parenteral nutrition.

Hepatobiliary trauma — ERCP can be safely performed in patients with liver trauma and may permit endoscopic therapy, or may be helpful in identifying the need for surgery [60]. Hemodynamically stable patients with a biliary leak can be treated with transpapillary stents and with sphincterotomy as indicated [61,62]. Surgery is generally reserved for the rare patient in whom stenting is unsuccessful.

Bile duct complications after liver transplantation — Bile duct complications are common after liver transplantation. These include bile duct strictures, leaks, and stones and may occur either early (within the first week) or late after transplantation [63,64]. (See "Liver transplantation in adults: Endoscopic management of biliary adverse events".)

Patients are evaluated with magnetic resonance cholangiopancreatography (MRCP) before embarking on more invasive procedures. In patients requiring further evaluation, ERCP offers an alternative to percutaneous or transhepatic cholangiography. ERCP is the procedure of choice in those who have a coagulopathy and is preferred over percutaneous cholangiography in patients with a duct-to-duct anastomosis. ERCP also permits therapeutic interventions, such as stenting for bile leaks and dilation and stenting of postoperative strictures [65,66]. (See "Liver transplantation in adults: Endoscopic management of biliary adverse events".)

Ascariasis — Ascaris infestation can produce acute biliary obstruction with cholangitis and is a common problem in endemic areas [67,68]. During ERCP, the worm can be identified (image 7) and removed with a stone extraction balloon or a basket [7,68]. Patients are also treated with anthelminthic therapy to eradicate the remaining worms. (See "Ascariasis".)

Malignant strictures — Malignant strictures of extrahepatic ducts are rare in children. However, they have been described in case reports in which successful relief of obstruction was achieved with stenting [69,70]. The most common malignant tumor of the biliary tree in children is rhabdomyosarcoma, a tumor of the wall of the extrahepatic bile ducts that forms primitive skeletal muscle [71]. Other tumors include cholangiocarcinoma (often associated with primary sclerosing cholangitis and IBD) [72-74] and carcinoid tumors of the bile duct [75]. Obstructive jaundice due to external compression of the extrahepatic bile duct has been reported in non-Hodgkin lymphoma, acute promyelocytic leukemia, histiocytosis X, and neuroblastoma.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Endoscopic retrograde cholangiopancreatography (ERCP)".)

SUMMARY

●Overview of indications – Endoscopic retrograde cholangiopancreatography (ERCP) has an important role in the evaluation and treatment of a variety of biliary tract disorders in children if the special expertise and equipment that is needed to perform ERCP in this age group are available.

ERCP is particularly helpful in the evaluation of neonatal cholestasis (to exclude or support a diagnosis of biliary atresia) and a variety of other causes of biliary obstruction, including choledocholithiasis (table 1). Therapeutic maneuvers that can be accomplished during ERCP include sphincterotomy, sphincteroplasty (balloon dilation), extraction of stones from the biliary tree, stricture dilation, and stent placement. (See 'Indications' above.)

●Congenital disorders

•Cholestasis in neonates and young infants

-Biliary atresia – Infants with suspected biliary atresia are evaluated with a series of imaging and laboratory tests and liver biopsy to exclude other causes of cholestasis. A cholangiogram is the final step in the diagnostic process. This is done by intraoperative cholangiogram at many centers, but ERCP is a reasonable alternative at centers in which special expertise and equipment are available. Nonvisualization of the common bile duct is highly suggestive of biliary atresia, provided that this was not caused by technical problems, such as positioning of the catheter. (See 'Biliary atresia' above.)

-Other causes – ERCP is generally not needed for the diagnosis of other causes of neonatal cholestasis, including Alagille syndrome and Caroli disease. (See 'Alagille syndrome' above and 'Caroli disease and congenital hepatic fibrosis' above.)

•Biliary cysts – Biliary cysts are cystic dilatations, which may occur singly or in multiples throughout the bile ducts. The diagnosis can be made by abdominal or endoscopic ultrasound, CT, or magnetic resonance cholangiopancreatography (MRCP). ERCP confirms the diagnosis and categorizes the type of cyst (figure 2) to facilitate surgical planning. Most individuals with biliary cysts also have an anomalous pancreaticobiliary junction (APBJ). (See 'Biliary cysts' above and 'Anomalous pancreaticobiliary junction' above.)

●Acquired disorders

•Choledocholithiasis – Among infants and children with choledocholithiasis, approximately one-half of affected patients have underlying risk factors, which include hemolytic disease (eg, sickle cell disease), chronic liver disease (eg, intestinal failure-associated liver disease), cardiac surgery, or biliary tract malformations. Infants and children who are asymptomatic but have small common bile duct stones can be managed conservatively. For symptomatic individuals of any age with bile duct stones, we recommend ERCP with biliary sphincterotomy to extract the stones, if expertise in ERCP in this age group and appropriate instruments are available (Grade 2C). (See 'Choledocholithiasis' above.)

Management of adolescents with choledocholithiasis is similar to that in adults. (See "Choledocholithiasis: Clinical manifestations, diagnosis, and management" and "Endoscopic management of bile duct stones".)

•Sclerosing cholangitis – Primary sclerosing cholangitis (PSC) in children typically is associated with an underlying disorder, including histiocytosis X, immune deficiency states, reticular cell sarcoma, or sickle cell anemia. At least 80 percent of children with PSC have underlying inflammatory bowel disease (IBD). The diagnosis of PSC can be established by liver biopsy, ERCP, or MRCP. Individuals with symptomatic dominant ductal strictures are candidates for therapeutic ERCP to dilate the strictures and relieve the obstruction. (See 'Primary sclerosing cholangitis' above.)

•Post-liver transplantation – Bile duct complications are common after liver transplantation. These include bile duct strictures, leaks, and stones and may occur either early (within the first week) or late after transplantation. Most patients are initially evaluated with MRCP. ERCP can be used for therapeutic intervention for most of patients with these complications. (See 'Bile duct complications after liver transplantation' above and "Liver transplantation in adults: Endoscopic management of biliary adverse events".)

•Ascariasis – ERCP is indicated for relief of biliary obstruction by ascariasis and other parasites and is used in combination with anthelminthic therapy to eradicate the remaining worms. (See 'Ascariasis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Moises Guelrud, MD, who contributed to earlier versions of this topic review.