Choledochal Cyst 

Choledochal Cyst – 12 Interesting Facts

1. Choledochal cysts are congenital dilations or aneurysms of the intrahepatic or extrahepatic biliary tract ¹
2. Disease is classified into 5 types based on location and degree of biliary tract dilatation; types I and IV are most common
3. Presenting manifestations are age dependent; disease often presents with cholestatic jaundice, abdominal pain, and/or right upper quadrant mass
4. Older patients often present with manifestation related to complications of disease
5. Suspect diagnosis based on clinical presentation with laboratory evidence of cholestasis; confirm diagnosis with imaging
6. Multitiered imaging evaluation is often required beginning with ultrasonography, then cross-sectional imaging (eg, CT, magnetic resonance cholangiopancreatography); cholangiography is the gold standard to define anatomy of biliary system
7. Complete surgical excision of cyst with bilioenteric reconstruction is the goal for common types; early excision can prevent complications and progression of liver fibrosis ²
8. Complications may include increased risk of malignancy (eg, cholangiocarcinoma), cholelithiasis, cholangitis, pancreatitis, and biliary cirrhosis ¹
9. Entire biliary tract is at increased risk for malignancy; complete excision greatly diminishes but does not completely eliminate risk
10. Risk reduction for malignancy with surgical resection is variable and depends on age at time of resection and type of choledochal cyst; types I and IV are at highest risk for malignant transformation ³
11. Long-term surveillance for malignancy is required even after complete resection ³
12. Prognosis for most cases is excellent with expedient management and choledochal cyst resection ³

Pitfalls

• Competing diagnoses can lead to confusion in young children presenting with cholestasis ¹
  • Algorithmic approach to evaluation of neonatal cholestasis can be helpful in consultation with pediatric radiologist for proper selection of imaging ¹
  • Consultation of pediatric surgeon for potential liver biopsy should occur as early as possible when diagnosis remains elusive
• Common presenting manifestations in older patients are actually complications of underlying disease; maintain a high degree of suspicion for possible underlying choledochal cyst in patients presenting with possible complications of disease, such as recurrent cholelithiasis and recurrent pancreatitis

Urgent Action

• Conjugated hyperbilirubinemia in a neonate or infant often indicates a serious hepatobiliary abnormality and requires expedient imaging beginning with right upper quadrant (liver and biliary system) ultrasonography for further evaluation to discern cause¹⁴
• Treat suspected acute cholangitis associated with a choledochal cyst immediately
  • Begin broad-spectrum parenteral antibiotics to cover gram-negative and anaerobic bacteria
  • Be observant for onset of septic shock
• Consult surgeon for suspected choledochal cyst rupture in the presence of abdominal peritoneal signs (ie, distended abdomen with rebound tenderness)

Terminology

Clinical Clarification

• Choledochal cyst is a congenital dilation or aneurysm of the intrahepatic or extrahepatic biliary tract ¹
• Presenting manifestations are age dependent; disease often presents with cholestatic jaundice, abdominal pain, and/or right upper quadrant mass

Classification

• Based on location of biliary dilatation
  • Type I ³
    • Cystic or fusiform dilatation of extrahepatic bile ducts ²
    • Accounts for over 80% of cases ³
    • Subtypes are classified by extent of lesion and its relationship to gallbladder
      • Type Ia (cystic)
        • Marked cystic dilatation occurs in all or most of common bile duct ⁵
        • Gallbladder originates from the choledochal cyst ³
      • Type Ib (focal)
        • Smaller area of cystic dilatation isolated to the distal common bile duct ^3 6
        • Uninvolved portion of the extrahepatic biliary tree is otherwise normal ³
      • Type Ic (fusiform)
        • Smooth, fusiform (cylindrical), diffuse dilatation of both common bile duct and common hepatic duct ³
  • Type II (true diverticula) ³
    • Saccular (spherical) diverticula of the common bile duct ²
    • Accounts for about 2% of cases ³
  • Type III (choledochocele) ³
    • Cystic dilatation located entirely in duodenal wall at pancreaticobiliary junction ^2 3
    • Anomalous pancreaticobiliary junction is uncommon ³
    • Accounts for about 1% to 4% of cases ³
  • Type IV ³
    • Multiple cysts ⁷
    • Accounts for about 15% of cases ³
    • Subtypes based on degree of intra- and extrahepatic duct involvement
      • Type IVa
        • Both intra- and extrahepatic ducts are involved
        • Diffuse fusiform extrahepatic duct involvement with at least 1 intrahepatic cyst ²⁷
          • Bilobar involvement is most common, followed by isolated left lobar involvement ³
        • Primary ductal stricture at hepatic hilum is common ³
      • Type IVb
        • Only extrahepatic ducts are involved
        • Multiple extrahepatic cysts with no intrahepatic duct involvement ²
  • Type V (Caroli disease) ³
    • Rare disease marked by fibrosing and scarring of intrahepatic bile ducts ⁷
    • 1 or more saccular and fusiform cysts confined to intrahepatic biliary tract ^3 7
    • Distribution may involve entire liver or be limited to a solitary lobe of the liver
    • Concomitant polycystic kidney disease may be present ⁸
    • Caroli syndrome
      • Cystic intrahepatic biliary tree disease associated with congenital fibrosis ⁹

Diagnosis

Clinical Presentation

• Classification of choledochal cysts. – Type I cysts are fusiform dilatations of the common bile duct. Type II cysts are true diverticula of the common bile duct, and type III choledochal cysts (choledochoceles) are intraduodenal dilatations of the common channel. Type IVa choledochal cysts consist of multiple intrahepatic and extrahepatic biliary dilatations, whereas type IVb choledochal cysts have extrahepatic biliary dilatation with a normal intrahepatic biliary tree. Type V choledochal cysts, or Caroli disease, consist of cystic dilatation of the intrahepatic biliary tree. RHD, right hepatic duct; LHD, left hepatic duct; CHD, common hepatic duct; DUO, duodenum.From Soares KC et al: Choledochal cysts: presentation, clinical differentiation, and management. J Am Coll Surg. 219(6):1167-80, 2014, Figure 3.

History

• Classic triad of symptoms/signs includes right upper quadrant abdominal pain, jaundice, and abdominal fullness (ie, right upper quadrant mass)
  • Overall, uncommon for all 3 to be present
  • More common overall in children, especially infants ¹⁰
• Pattern of presentation varies among different age groups
  • Infants
    • Most present with jaundice from cholestasis ¹
  • Children
    • More likely to present with abdominal fullness (ie, right upper quadrant mass) and jaundice
  • Adults
    • More likely to present with nonspecific symptoms leading to delay in diagnosis ¹¹
    • Right upper quadrant pain alone is most common presentation ²
    • More likely to have had previous biliary procedure (eg, surgery, stenting) ³
• Other nonspecific symptoms may include:
  • Nausea and vomiting ¹²
  • Weight loss and failure to thrive ¹³
  • Dark urine and acholic stools ¹
• Initial presentation may reflect presence of complications
  • More common in adults and older children with long-standing cysts
    • Pancreatitis
      • Up to 30% of patients present with initial diagnosis of pancreatitis ²
      • Most cases are secondary to obstructing stone or anomalous pancreaticobiliary junction
      • Particularly common presentation for type III (choledochocele) ³
    • Choledocholithiasis
      • 45% to 75% of adult patients present with symptomatic gallstones ³
    • Acute cholecystitis or cholangitis
      • Common presentation occurring mainly in adults ¹²
    • Biliary cirrhosis
      • Presenting feature in up to 10% of children and 15% of adults ²
      • Particularly common presentation for type IV and V disease
    • Malignancy
      • Any part of the biliary tree or gallbladder may be affected
    • Duodenal obstruction
      • Large type III cysts may obstruct the bowel lumen
• Initial detection may occur via incidental discovery
  • In utero diagnosis based on prenatal ultrasonography findings is common ³
  • Incidental radiographic finding on study obtained for other indication (eg, ultrasonography or CT to evaluate for renal pathology) ⁶
  • Cystic disease noted at time of cholecystectomy for gallstones or recurrent cholecystitis
• Previous history of cholecystectomy
  • Particularly common presentation for type III (choledochocele) ³
  • Present in up to 40% of adults ²
    • Cholecystectomy is performed for recurrent pain attributable to gallbladder disease
    • Continued symptoms result in further evaluation that finds choledochal cyst

Physical examination

• Variable findings may include:
  • Jaundice and scleral icterus
  • Right upper quadrant mass
  • Hepatomegaly

Causes and Risk Factors

Causes

• Largely unknown and likely multifactorial
  • Anomalous pancreaticobiliary junction may to contribute to cyst formation, particularity types I and IV ⁶
  • Abnormal early union of pancreatic duct and common bile duct occurring outside of the duodenal wall is noted in the majority of patients (up to 90%) ⁷
  • Results in a long common bile-pancreatic duct channel, before entering sphincter of Oddi ⁵
  • Allows reflux of pancreatic fluid into biliary tract, raising intraductal pressure and exposing mucosa to pancreatic digestive enzymes
• Type V specific cause
  • May be due to abnormal embryonic ductal plate development ¹²

Risk factors and/or associations

Age

• 80% of cases are diagnosed in infants and children younger than 10 years ³
• Caroli disease often presents when patients are in their early 20s ²
• Caroli syndrome presents in infancy or is diagnosed prenatally ²

Sex

• Female to male ratio is 4 to 1 ³

Genetics

• Type V (Caroli disease) (OMIM #600643) ¹⁴
  • Most cases are sporadic; occasional familial clustering occurs ⁸
  • Most familial cases occur through autosomal recessive mode of inheritance; autosomal dominant inheritance is less common ⁸
  • Some cases are associated with mutations in PKHD1 (fibrocystin/polyductin) or WDR19 (WD repeat domain 19) ¹⁴

Ethnicity/race

• Highest incidence is among East Asian people ¹
  • 1:1000 in Japan ^7 10
• Incidence is much lower in Western countries (1:100,000-1:150,000) ³

Other risk factors/associations

• Associated congenital anomalies
  • Congenital cardiac anomalies
    • Most manifest in infancy ³
    • Occur in up to 33% of patients presenting in childhood ³
  • Double common bile duct ³
  • Sclerosing cholangitis ³
  • Congenital hepatic fibrosis ³
  • Pancreatic cyst ³
  • Annular pancreas ³

Diagnostic Procedures

• Algorithmic approach to evaluation of neonatal cholestasis.From Lane E et al: Neonatal cholestasis. Pediatr Clin North Am. 64(3):621-39, 2017, Figure 1.

Primary diagnostic tools

• Suspect diagnosis based on history and physical examination findings ¹
• Obtain fractionated bilirubin level and liver function tests
  • Supporting laboratory evidence for disease includes: ¹
    • Findings of cholestasis
      • Elevated conjugated hyperbilirubinemia and γ-glutamyltransferase level with less dramatically elevated serum aminotransferase levels ¹
    • Findings associated with complications may be present
      • Laboratory evidence of pancreatitis or cholangitis secondary to obstruction from stone or compromised function of pancreaticobiliary junction ³
• Imaging confirms diagnosis
  • Abdominal ultrasonography is first line imaging modality of choice ¹
    • Often confirms diagnosis in children ²
    • Second study is often required in adults because findings of ductal dilation of the biliary tree can be multifactorial (eg, stone impaction, malignancy) ²
  • 3-dimensional CT is often second test ordered to narrow differential diagnosis in adults ²¹¹
    • Evaluates for cause of nonspecific biliary duct dilatation, such as malignancy and other liver or pancreaticobiliary disease ²
  • Secondary imaging may be necessary to delineate complicated biliary anatomy and may include:
    • Magnetic resonance cholangiopancreatography ¹
      • Noninvasive imaging technique of choice to define precise hepatobiliary anatomy in adults and children ^3 15
    • Endoscopic retrograde cholangiopancreatography ²
    • Percutaneous transhepatic cholangiography ²
    • HIDA scan ¹

• Algorithmic approach to evaluation of neonatal cholestasis can be helpful in consultation with pediatric radiologist for proper selection of imaging ¹

Laboratory

• Fractionated bilirubin level
  • Unconjugated hyperbilirubinemia reflects biliary obstruction
• Liver function tests
  • Marginally elevated serum aminotransferase levels are common
  • Significant elevation may indicate:
    • Liver involvement with primary disease (types IVa or V)
    • Liver affected by complications (eg, portal hypertension, hepatic fibrosis)
  • Serum γ-glutamyltransferase
    • Elevated level may be present and reflects biliary obstruction ¹
• Alkaline phosphatase
  • Elevated level may be present and reflects biliary obstruction ¹⁶

Imaging

• Right upper quadrant ultrasonography
  • Evaluates intrahepatic and extrahepatic biliary anatomy
    • Right upper quadrant cyst physically separated from gallbladder suggests diagnosis ³
    • Visualization of communication between cyst and biliary tract supports diagnosis ³
  • Overall diagnostic sensitivity and specificity of right upper quadrant ultrasonography are greater than 90% (similar to CT) ³
    • In children, ultrasonography is a definitive diagnostic study
      • Accurate, reliable, and definitive diagnostic modality; children may not require a follow-up secondary study ³
    • In adults, a secondary study is often required to evaluate suggestive findings of ductal dilation of the biliary tree
  • Endoscopic ultrasonography
    • Effective modality to:
      • Assess for presence of anomalous pancreaticobiliary junction and elongated common channel ³
      • Diagnose type III (choledochocele) disease ³
      • Differentiate simple biliary duct dilatation from choledochal cyst ¹⁷
  • Intraductal ultrasonography
    • Effective modality to evaluate for malignancy when other imaging finds thickening and/or irregularity of choledochal cyst wall ³
  • Associated findings may include:
    • Normal or distended gallbladder (typical) ³
    • Common bile duct and/or intrahepatic bile duct dilatation ¹⁸
      • Duct diameter wider than 2 mm in infants, greater than 4 mm in children, or greater than 7 mm after adolescence (abnormal) ¹⁸
      • Intrahepatic duct dilation (not uncommon) ³
        • Significant intrahepatic biliary dilatation requires further imaging to differentiate type I from type IVa cystic disease ³
  • Limitations include:
    • Cannot accurately identify presence of anomalous pancreaticobiliary junction ³
    • Fails to determine cause of dilated common bile duct in up to one-third of patients, particularly adults ³
    • Lacks precision to establish definitive cyst communication with bile duct ¹²
• 3-dimensional CT
  • Overall diagnostic sensitivity and specificity are greater than 90% (similar to ultrasonography) ³
  • Use to delineate extent of cystic disease and assess for malignancy ¹¹
• Magnetic resonance cholangiopancreatography
  • Preferred initial secondary diagnostic imaging modality to confirm and classify choledochal cysts ³¹⁵
    • Advantages include absence of radiation exposure, absence of need for IV or enteral contrast material, and noninvasive nature of test ³
    • 70% to 100% sensitive and 90% to 100% specific means to diagnose and classify type of choledochal cyst ³
    • Reliably identifies anomalous pancreaticobiliary junction, concomitant choledocholithiasis, and concurrent cholangiocarcinoma ³
    • Identifies commonly associated biliary ductal and vascular anomalies, which aids in surgical planning ³
  • Limitations include:
    • May not readily identify small choledochoceles or minor ductal abnormalities ³
    • Lacks option to perform therapeutic intervention (compared with cholangiography techniques) ³
  • Characteristic findings specific to patients with type V disease include:
    • Central dot sign: enhancement of the portal vein surrounded by dilated intrahepatic bile ducts ³
    • Pathognomonic finding is contrast material filling in well-defined intrahepatic cystic dilatations ³
    • Up to 90% of unilobar cystic disease occurs in the left lobe of the liver ¹²
• Cholangiography
  • Most sensitive technique to define anatomy of biliary system ³
  • Limitations include need for general anesthesia in children, potential complications (eg, cholangitis, pancreatitis, perforation), and technical difficulty ³
  • Endoscopic retrograde cholangiopancreatography
    • Gold standard study to define distal biliary system ³
      • Best tool to diagnose type III cysts because pancreaticobiliary junction is well defined ³
    • Potential limitation is the occasional inability to define very proximal biliary anatomy ²
    • Interventional technique that may be therapeutic
      • May facilitate biliary drainage, stone removal, stent placement, and stricture dilatation ^3 6
      • Endoscopic sphincterotomy of choledochocele can be performed at time of study ³
  • Percutaneous transhepatic cholangiography
    • Gold standard to define intrahepatic biliary system and provides excellent imaging of the entire biliary duct system ^2 3
    • A potential limitation is the occasional inability to adequately delineate distal and intraduodenal portions of biliary system ³
    • May be preferred imaging modality in adults, particularly with type IV and V cysts ²
    • Interventional technique that may be therapeutic
      • May facilitate biliary drainage and placement of long-term transhepatic stents for postoperative drainage ²
• HIDA scan
  • Technetium Tc 99m–labeled iminodiacetic acid tracer is administered via IV and taken up early by hepatocytes, then excreted in biliary system ⁵
  • Indications include:
    • Need to investigate and establish a communication between cyst and biliary tree ⁵
    • Perforated extrahepatic bile duct ⁵
  • Sensitivity for choledochal cyst detection is 67% to 100% ¹⁹

Differential Diagnosis

Most common

• Biliary atresia
  • Biliary atresia is a fibroinflammatory process that leads to complete or partial obliteration of the extrahepatic biliary system and is the most common cause of infantile obstructive cholangiopathy ⁴
    • Note that cystic biliary atresia is a subtype of biliary atresia that can be particularly difficult to distinguish from choledochal cyst disease ²⁰
  • Similarly to choledochal cyst, biliary atresia presents in neonates or infants with obstructive jaundice and hepatomegaly; both may also be suspected based on prenatal ultrasonography findings ³
  • Differences in manifestations include:
    • Timing of typical presentation: most patients with biliary atresia present by age 2 to 3 weeks ⁶
    • Severity of illness: about one-third of patients with cystic biliary atresia develop liver failure or require liver transplant ³
    • Ultrasonography findings:
      • Cystic biliary atresia cysts are smaller than choledochal cysts and are associated with less dilatation of intrahepatic bile ducts compared with choledochal cyst disease ³
      • Atretic or elongated gallbladder is common, as opposed to normal or distended gallbladder seen with choledochal cyst disease ³
      • Triangular cord sign and presence of biliary sludge suggest cystic biliary atresia ³
  • Differentiation between conditions and definitive diagnosis is sometimes indeterminate until time of surgical intervention ³⁶
    • Intraoperative cholangiography, direct visualization of atretic extrahepatic biliary system, and immunohistochemical findings on liver biopsy confirm diagnosis ¹
• Alagille syndrome ²¹
  • Autosomal dominant disorder caused by pathologic variants of JAG1 (jagged canonical notch ligand 1) and NOTCH2 (notch receptor 2); characterized by paucity of intralobular bile ducts on liver biopsy ⁶
  • Most present in the first 3 months of life with cholestasis; jaundice may wax and wane; associated pruritus is often severe ¹
  • Dysmorphic facial features are almost universal (eg, inverted triangular facial appearance with prominent forehead, deep-set eyes, hypertelorism, pointed chin, and saddle or straight nose with a bulbous tip)
  • Other associated variable congenital anomalies may include: ²¹
    • Cardiac disease: peripheral pulmonary artery stenosis is most common
    • Skeletal anomalies: butterfly vertebrae are most common
    • Ophthalmologic abnormalities: posterior embryotoxon is most common
    • Renal anomalies: structural (eg, cysts, ureteropelvic obstruction) and functional (eg, renal tubular acidosis)
    • Vascular anomalies of central nervous system, aorta, and renal vasculature
  • Confirm diagnosis by clinical diagnostic criteria; confirmation by liver biopsy may be necessary in some patients ^1 6
• Sclerosing cholangitis
  • Chronic disorder characterized by inflammation and progressive obliterative fibrosis of the intrahepatic and/or extrahepatic bile ducts ²²
  • May present with manifestations similar to choledochal cyst, such as cholestasis and hepatomegaly in any age group; neonatal disease presents within 2 weeks of life ²³
  • Other presenting manifestations may include pruritus, fatigue, abdominal pain, weight loss, and disease complications (eg, cholangitis) ²⁴
  • Primary sclerosing cholangitis is frequently associated with hypergammaglobulinemia and serum autoantibodies (ie, perinuclear antineutrophil cytoplasmic antibodies) ²⁴
  • Differentiation and definitive diagnosis often require a combination of radiographic findings (eg, magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography) and liver biopsy results ²³
• Choledocholithiasis²⁵
  • Gallstones in the common bile duct present with biliary colic and obstructive jaundice in both adults and children, thus mimicking choledochal cyst
    • Gallstones may be a manifestation of choledochal cyst disease secondary to biliary stasis; recurrent choledocholithiasis may later be identified as a manifestation of choledochal cyst disease
  • May present with complications of stone disease such as cholangitis or gallstone pancreatitis ²⁵
  • Hemolytic disease, sepsis, prematurity, and prolonged exposure to total parenteral nutrition increase risk for the development of gallstones in children ¹
  • Ultrasonography is the imaging method of choice to diagnose choledocholithiasis ²⁵
  • Exclusion of underlying choledochal cyst disease requires a high index of suspicion and may require additional radiographic studies (eg, magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography)
• Cystic lesions in the pancreas
  • May present similarly to choledochal cyst with abdominal pain, jaundice, and a cystic lesion on ultrasonography
  • Pancreatic pseudocysts account for the majority of cystic lesions and often occur after disruption of the pancreatic duct after acute pancreatitis or abdominal trauma; most resolve spontaneously ²⁶
  • Laboratory abnormalities typical for pancreatic disease (eg, elevated amylase and lipase) are often present
  • Suspect diagnosis based on initial imaging with ultrasonography or cross-sectional imaging (eg, MRI, CT) by delineating an encapsulated fluid collection within a well-defined inflammatory wall outside the pancreas ²⁷
  • Magnetic resonance cholangiopancreatography and endoscopic ultrasonography may be required to further differentiate when the diagnosis remains unclear ²⁶
  • Endoscopic ultrasonography with fine-needle aspiration is diagnostic modality of choice to differentiate pancreatic pseudocyst from other cystic lesions involving the pancreas ²⁶
• Infections in neonates and infants
  • Various congenital infections, perinatal infections, and sepsis can lead to cholestasis in infants and neonates¹
  • TORCH infections (ie, toxoplasmosis, rubella, cytomegalovirus, herpes, syphilis) and viral infections (eg, hepatitis B, parvovirus B19, adenovirus, echoviruses) can result in neonatal cholestasis and hepatitis ^1 4
  • Differentiate from choledochal cyst by overall clinical presentation, ultrasonography to investigate cause of coexisting conjugated hyperbilirubinemia, and clinical course (ie, resolution after antimicrobial therapy)
  • Confirmation of infectious cause for cholestasis requires positive bacterial culture results and/or improvement with antimicrobials, or positive results from evaluation for other causes of congenital and perinatal infections
• Biliary duct dilation after cholecystectomy
  • Mild biliary duct dilation after cholecystectomy is a common incidental radiologic finding in adults, especially in those older than 70 years ²⁸
  • Nonpathologic dilatation of the bile duct (which can reach an upper limit of 10 mm after cholecystectomy ²⁹) can appear similar to choledochal cyst on some imaging studies
  • Definitively differentiate biliary duct dilatation from choledochal cyst with endoscopic ultrasonography ¹⁷

Treatment

• A, Roux-en-Y hepaticojejunostomy after resection of extrahepatic cyst. B, Temporary percutaneous transhepatic stents may be placed across the hepaticojejunostomy.From Chan AOO et al: Choledochal cysts. In: Baron TH et al, eds: ERCP. Elsevier; 2008:387-92, Figure 36.7.

Goals

• Surgical treatment to resolve biliary obstruction, restore normal biliary drainage, and eliminate long-term risk for malignancy ¹

Disposition

Admission criteria

• Most patients with possible choledochal cyst diagnosis will require admission for further diagnostic studies and expedient management

Recommendations for specialist referral

• Consult hepatobiliary surgical specialist for diagnostic and treatment recommendations ³
• Consult surgeon for suspected choledochal cyst rupture in the presence of abdominal peritoneal signs (ie, distended abdomen with rebound tenderness)

Treatment Options

Treat preexisting conditions in standard fashion before surgical intervention ¹

• Treat suspected acute cholangitis associated with a choledochal cyst immediately
  • Begin broad-spectrum parenteral antibiotics to cover gram-negative and anaerobic bacteria
  • Be observant for onset of septic shock
• Treat preexisting pancreatitis

Definitive treatment is surgical resection ¹

• Current recommended surgical approach depends on type of choledochal cyst
  • Type I
    • Complete cyst excision, extrahepatic bile duct resection, cholecystectomy, and bilioenteric reconstruction (eg, Roux-en-Y hepaticojejunostomy) ³
  • Type II
    • Diverticulectomy and closure of common bile duct at diverticular neck ³
  • Type III
    • Small choledochocele
      • Endoscopic complete cyst excision with sphincterotomy ³
    • Large choledochocele associated with complications (eg, pancreatitis, gastric outlet obstruction)
      • Transduodenal complete cyst excision with hepatopancreatic ampulla sphincteroplasty ^2 3
  • Type IV
    • Individualized treatment is required
      • Treat any extrahepatic involvement with complete cyst excision, extrahepatic bile duct resection, cholecystectomy, and bilioenteric reconstruction (eg, Roux-en-Y hepaticojejunostomy) ⁷
      • Treat any intrahepatic involvement with either: ⁷
        • Resection of involved portion of liver when possible, or
        • Temporizing measures (eg, stents) and supportive care pending liver transplant
  • Type V
    • Individualized treatment is required
      • Resection of involved portion of liver or liver transplantation if inadequate liver reserve is expected ³
      • Temporizing measures and supportive care pending liver transplant ⁷
        • Stents for strictures and/or external biliary drainage techniques ²
        • Management of recurrent and ongoing complications (eg, biliary stones, cholangitis, liver abscess, cirrhosis) ²
• Surgical approach and technique largely depend on type of cyst and surgeon experience
  • Some extrahepatic cysts are amenable to laparoscopic approach ²
  • Type III cysts are often amenable to endoscopic management ³
  • Robotic surgery may be an option for some procedures ⁷
• Timing of surgery
  • Early excision is recommended for all discovered lesions at any age ³
    • This recommendation includes asymptomatic individuals with incidental discovery of choledochal cyst ¹⁰
  • Severely ill patients may require staged procedure ³
    • Initial external drainage followed by complete cyst excision and hepaticoenterostomy

Nondrug and supportive care

Procedures

Complete excision of cyst with Roux-en-Y hepaticojejunostomy

General explanation

• Intraoperative cholangiography is often performed if patient does not have previous magnetic resonance cholangiopancreatography or cholangiography imaging to define exact biliary anatomy
• Excision of cyst, removal of extrahepatic bile duct down to the level of the communication with the pancreatic duct, and cholecystectomy are performed ³
• Restoration of biliary drainage is established with Roux-en-Y hepaticojejunostomy (ie, bilioenteric anastomosis) after removal of extrahepatic biliary tract ^30 31
• Extent of liver involvement dictates treatment of intrahepatic lesions in patients with type IVa disease ³
• Pancreaticoduodenectomy may be additionally required for patients with:
  • History of chronic severe pancreatitis ³
  • Atrophic pancreatic head due to anomalous pancreaticobiliary junction ³

Indication

• Extrahepatic involvement of type I and IV choledochal cysts
• Patients who have undergone previous internal drainage procedures for choledochal cyst ¹³

Complications

• Intraoperative complications
  • Injury to surrounding structures (eg, pancreatic duct, vasculature) ¹²
• Early postoperative complications
  • Pancreatitis ²
  • Anastomotic leakage ²
  • Cholangitis and/or subhepatic abscess ¹¹
  • Wound infection ²
• Late postoperative complications
  • Formation of intrahepatic strictures and stones ²
  • Anastomotic stricture ²
  • Infectious (eg, intrahepatic abscess, cholangitis) ²
  • Bowel obstruction ²
  • Pancreatic duct obstruction or fistula ¹²
  • Recurrent pancreatitis ²
  • Cirrhosis ²
  • Malignancy ²

Interpretation of results

• Prognosis is often excellent after procedure, especially in younger age groups
  • Complications are rare in pediatric population, especially when procedure is performed in patients younger than 5 years ²
  • Increased risk for postoperative complications occurs with:
    • Increasing age at time of procedure ²
      • Up to 40% of adult patients develop late postoperative complications ³
    • Increasing size of cyst ²
    • Type IVa disease (ie, concomitant intrahepatic involvement of biliary tree) ²
    • Greater degree of cyst inflammation at time of removal ²
• Common histopathology finds:
  • Fibrosis of the cyst wall lined with columnar epithelium with variable lymphocytic infiltration ³
  • Few to no mucus-producing glands ³
  • With increased patient age, the following abnormalities are noted:
    • Increasing evidence of acute and chronic mucosal inflammation ³
    • Worsening degrees of hyperplasia and dysplasia ³
    • Increasing rate of metaplasia and biliary intraepithelial neoplasia ³
  • Distinct differences in histopathology for various choledochal cyst types include:
    • Type I and sometimes type IV: lacks biliary mucosa ³
    • Type II: closely resembles gallbladder duplication ³
    • Type III: lined with duodenal mucosa ³
    • Type V: associated with extensive hepatic fibrosis ³
  • Associated changes in the liver are common and include:
    • Variable degrees of portal fibrosis, central venous distention, parenchymal inflammation, and bile duct proliferation ³

Orthotopic liver transplant

General explanation

• Liver allograft sources include cadaveric and living related donors
• Model for End-Stage Liver Disease score is used to determine how urgently a patient needs a liver transplant within the next 3 months
• Patient undergoes multidisciplinary preselection evaluation, including cardiovascular and pulmonary testing, screening for malignancies, and identification of infections, vaccination needs, and psychosocial or psychiatric issues

Indication

• Type IVa or V disease with:
  • Failure of bilioenteric drainage procedure with or without partial hepatectomy ²
  • Bilobar or diffuse liver involvement after failed temporizing measures (eg, stents) ²
  • Presence of severe complications (eg, recurrent cholangitis, severe portal hypertension, malignancy) ³

Contraindications

• Absolute
  • Severe cardiopulmonary disease
  • Active alcohol or other drug use
  • AIDS that is not well controlled
  • Severe pulmonary hypertension
  • Active bacterial or fungal infection (other than infection confined to the liver in certain circumstances)
• Relative
  • Morbid obesity or severe cachexia
  • History of recent extrahepatic malignancy (depending on risk of recurrence)
  • Lack of psychosocial support
  • Severe, uncontrolled psychiatric illness

Interpretation of results

• Outcomes after liver transplant are comparable to those in other patient populations requiring liver transplant ²

Special populations

• Elderly patients
  • If no malignancy is detected on radiography, risk-benefit ratio of surgery performed simply to prevent malignant cell population or malignant transformation is less favorable in elderly patients
  • Value of bile duct resection in patients older than 70 years with a nonmalignant appearing, incidentally discovered choledochal cyst is questionable at best
  • If surgery is not an option, cysts can be followed up by annual cross-sectional imaging with CT or magnetic resonance cholangiopancreatography

Monitoring

• Malignancy surveillance
  • No rigorously agreed-upon routine monitoring schedule is available ³²
  • Individualized surveillance may be based on risk factors (eg, age at presentation) and type of choledochal cyst
    • Frequent surveillance is particularly important for:
      • High-risk cystic disease (ie, type I or type IV) ¹²
      • Disease associated with an anomalous pancreaticobiliary junction ¹²
      • Patients with persistent intrahepatic biliary dilatation ³
      • Presence of any residual cystic component ¹²
  • Methods of surveillance include:
    • Biochemical evaluation (ie, liver function tests) and imaging (eg, abdominal ultrasonography or cross-sectional imaging) ³
      • 1 suggested screening regimen includes both of the following:
        • Aspartate transaminase and alkaline phosphatase levels every 4 months for 2 years, then every 6 months for 5 years ¹¹
        • Ultrasonography every 5 years ¹¹

Complications

• Common presenting manifestations in older patients are actually complications of underlying disease; maintain a high degree of suspicion for possible underlying choledochal cyst in patients presenting with possible complications of disease, such as recurrent cholelithiasis and recurrent pancreatitis
• Malignancy
  • Overall incidence of malignancy ranges from 10% to 30% ³
    • Relative risk is up to 121-fold greater than that of general population ⁶
  • Most occur in the cyst but entire biliary system is at risk ¹¹
  • Risk remains high in any residual cystic tissue after resection
  • Risk is diminished, but not eliminated, after full resection ^2 33
  • Risk associations
    • Risk based on choledochal cyst type
      • Types I and IV are at highest risk for cancer (approximately 10%-30%) ³
        • Types V and II are at lower risk for malignant transformation ³
        • Type III has minimal risk (2.5%) of malignant transformation ³
    • Risk increases with increasing age ²
      • Invasive biliary neoplasm is rare in pediatric populations at time of initial surgery (less than 1%) ³
      • Risk for malignancy increases up to 14% in patients diagnosed after 20 years of age ⁶
      • Invasive biliary neoplasm is discovered in up to 50% of patients older than 50 years at time of initial surgery ³
    • Risk is increased with:
      • Previous cholangitis ³
      • Previous internal drainage procedure ³
      • Presence of anomalous pancreaticobiliary junction ¹²
  • Common types of associated malignancies
    • Cholangiocarcinoma¹
      • Most common associated malignancy ²
      • Incidence can rise to up to 75% in untreated older age groups ²
    • Gall bladder carcinoma³
      • Accounts for 10% to 25% of associated malignancy ³
    • Squamous cell carcinoma ¹
    • Anaplastic carcinoma ¹²
• Infectious
  • Cholangitis
  • Liver abscess
    • May occur in individuals with intrahepatic biliary tract involvement ²
• Cholelithiasis
• Pancreatitis
• Biliary stricture ¹¹
• Liver fibrosis
  • Progressive liver damage and biliary cirrhosis
    • More common with type IV and V disease ²
    • More prevalent patients with delayed diagnosis and subsequent treatment ²
  • Liver failure
    • Primarily occurs in later stages of Caroli disease ²
    • Results from recurrent or prolonged biliary stasis, portal hypertension, chronic infections, and inflammation ²
• Cyst rupture with resultant peritonitis
  • Rare overall ³
  • More likely to occur in neonates and infants ³

Prognosis

• Prognosis for most cases is excellent with expedient management and choledochal cyst resection ³
  • Overall event-free survival is 89% after resection and survival rate is over 90% ³
• Liver damage
  • Portal fibrosis and central venous distention often persist after appropriate surgical management ³
  • Remaining liver changes noted at pathology typically self-resolve after appropriate surgical management ³
• Biliary malignancy
  • Associated with an extremely poor prognosis ³
  • Median survival is 6 to 21 months; 2-year survival is less than 5% ¹²

References

1.Lane E et al: Neonatal cholestasis. Pediatr Clin North Am. 64(3):621-39, 2017

View In Article|Cross Reference

2.Edil BH et al: The current management of choledochal cysts. Adv Surg. 43:221-32, 2009

View In Article|Cross Reference

3.Soares KC et al: Choledochal cysts: presentation, clinical differentiation, and management. J Am Coll Surg. 219(6):1167-80, 2014

View In Article|Cross Reference

4.Fawaz R et al: Guideline for the evaluation of cholestatic jaundice in infants: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 64(1):154-68, 2017

View In Article|Cross Reference

5.Wax BN et al: Radiology-pathology conference: choledochal cyst. Clin Imaging. 31(4):269-72, 2007

View In Article|Cross Reference

6.Liu QY et al: Endoscopic approach to the patient with congenital anomalies of the biliary tract. Gastrointest Endosc Clin N Am. 23(2):505-18, 2013

View In Article|Cross Reference

7.Martin RF: Biliary cysts: a review and simplified classification scheme. Surg Clin North Am. 94(2):219-32, 2014

View In Article|Cross Reference

8.Yonem O et al: Clinical characteristics of Caroli’s disease. World J Gastroenterol. 13(13):1930-3, 2007

View In Article|Cross Reference

9.Yonem O et al: Clinical characteristics of Caroli’s syndrome. World J Gastroenterol. 13(13):1934-7, 2007

View In Article|Cross Reference

10.Singham J et al: Choledochal cysts: analysis of disease pattern and optimal treatment in adult and paediatric patients. HPB (Oxford). 9(5):383-7, 2007

View In Article|Cross Reference

11.Wiseman K et al: Epidemiology, presentation, diagnosis, and outcomes of choledochal cysts in adults in an urban environment. Am J Surg. 189(5):527-31, 2005

View In Article|Cross Reference

12.Mesleh M et al: Bile duct cysts. Surg Clin North Am. 88(6):1369-84, 2008

View In Article|Cross Reference

13.de Vries JS et al: Choledochal cysts: age of presentation, symptoms, and late complications related to Todani’s classification. J Pediatr Surg. 37(11):1568-73, 2002

View In Article|Cross Reference

14.Caroli Disease, Isolated. Online Mendelian Inheritance in Man. OMIM website. Johns Hopkins University. Updated June 27, 2019. Accessed March 26, 2021. https://www.omim.org/entry/600643

View In Article|Cross Reference

15.Lewis VA et al: Imaging of choledochal cysts. Abdom Imaging. 40(6):1567-80, 2015

View In Article|Cross Reference

16.Badebarin D et al: Different clinical presentations of choledochal cyst among infants and older children: a 10-year retrospective study. Medicine (Baltimore). 96(17):e6679, 2017

View In Article|Cross Reference

17.Benjaminov F et al: Effects of age and cholecystectomy on common bile duct diameter as measured by endoscopic ultrasonography. Surg Endosc. 27(1):303-7, 2013

View In Article|Cross Reference

18.Lee HC: Ultrasonography of choledochal cysts in children. J Med Ultrasound. 15(3):191-6, 2007

View In Article|Cross Reference

19.Silva-Baez H et al: Treatment of choledochal cyst in a pediatric population. A single institution experience of 15-years. Case series. Ann Med Surg (Lond). 5:81-5, 2016

View In Article|Cross Reference

20.Caponcelli E et al: Cystic biliary atresia: an etiologic and prognostic subgroup. J Pediatr Surg. 43(9):1619-24, 2008

View In Article|Cross Reference

21.Spinner NB et al: Alagille syndrome. In: Pagon RA et al, eds: GeneReviews [internet]. University of Washington; 1993-2013

View In Article|Cross Reference

22.Mieli-Vergani G et al: Sclerosing cholangitis in children and adolescents. Clin Liver Dis. 20(1):99-111, 2016

View In Article|Cross Reference

23.Girard M et al: Specificities of sclerosing cholangitis in childhood. Clin Res Hepatol Gastroenterol. 36(6):530-5, 2012

View In Article|Cross Reference

24.Zein CO: Primary sclerosing cholangitis. Clin Liver Dis. 17(2):211-27, 2013

View In Article|Cross Reference

25.Littich A et al: Acute cholecystitis, choledocholithiasis, and acute cholangitis. Hosp Med Clin. 4(3):342-57, 2015

View In Article|Cross Reference

26.Habashi S et al: Pancreatic pseudocyst. World J Gastroenterol. 15(1):38-47, 2009

View In Article|Cross Reference

27.Cooperman AM: An overview of pancreatic pseudocysts: the emperor’s new clothes revisited. Surg Clin North Am. 81(2):391-7, 2001

View In Article|Cross Reference

28.Atkinson CJ et al: Mild asymptomatic intrahepatic biliary dilation after cholecystectomy, a common incidental variant. Abdom Radiol (NY). 42(5):1408-14, 2017

View In Article|Cross Reference

29.Senturk S et al: Diameters of the common bile duct in adults and postcholecystectomy patients: a study with 64-slice CT. Eur J Radiol. 81(1):39-42, 2012

View In Article|Cross Reference

30.Kayaalp C et al: Laparoscopic choledochal cyst excision and Roux-en-Y hepaticojejunostomy. Ulus Cerrahi Derg. 32(2):152-4, 2016

View In Article|Cross Reference

31.Chan AOO et al: Choledochal cysts. In: Baron TH et al, eds: ERCP. Elsevier; 2008:387–92

View In Article|Cross Reference

32.Patel T: Cholangiocarcinoma–controversies and challenges. Nat Rev Gastroenterol Hepatol. 8(4):189-200, 2011

View In Article|Cross Reference

33.Ten Hove A et al: Meta-analysis of risk of developing malignancy in congenital choledochal malformation. Br J Surg. 105(5):482-90, 2018

View In Article|Cross Reference