Biliary tract cancers include cholangiocarcinoma and gallbladder carcinoma, which are both rare diseases with very poor prognoses. Cholangiocarcinoma is classified as either intrahepatic or extrahepatic according to the anatomical site of the tumor. Extrahepatic carcinoma, which is the more common form, can be further classified as perihilar (Klatskin tumor; occurs at the bifurcation of the hepatic duct) and distal extrahepatic carcinoma. Risk factors for cholangiocarcinoma include primary sclerosing cholangitis and chronic biliary tract inflammation. The greatest risk factor for gallbladder carcinoma is cholelithiasis. Patients are often initially asymptomatic or only present with nonspecific symptoms (e.g., abdominal pain, fever, weight loss) until late stages of disease, meaning that most tumors are already advanced at the time of diagnosis. Extrahepatic cholangiocarcinoma may manifest with signs of cholestasis (e.g., jaundice, dark urine, pruritus) and a painless, enlarged gallbladder (Courvoisier sign). If liver transaminases and tumor markers are raised and/or ultrasound imaging suggests bile duct or gallbladder carcinoma, MRCP or MDCT are recommended for diagnosis. Although surgical resection of early-stage tumors is curative, approximately 90% of patients have more advanced, unresectable tumors at the time of diagnosis.
- Cholangiocarcinomas: originate in the bile ducts and are classified based on their anatomical site of origin 
- Gallbladder carcinomas: originate within the mucosal lining of the gallbladder 
- Incidence: ∼ 1/100,000 per year in the US
- Prevalence: < 1% of all cancers
- Peak incidence: 60–70 years of age
- Sex: ♂ > ♀
- Incidence: ∼ 2/100,000 per year in the US but significantly higher in India, Chile, and Eastern Europe
- Sex: ♀ > ♂
Epidemiological data refers to the US, unless otherwise specified.
Risk factors for cholangiocarcinoma 
- Primary sclerosing cholangitis
- Liver fluke infection (e.g., Clonorchis sinensis, Opisthorchis viverrini)
- Choledocholithiasis (both with and without hepatic duct involvement)
- Chronic viral hepatitis (e.g., hepatitis B, hepatitis C)
- Liver cirrhosis
- Environmental toxin exposure (e.g., asbestos, Thorotrast contrast agent)
- Congenital biliary tract abnormalities (e.g., choledochal cysts, congenital hepatic fibrosis)
- Risk factors for gallbladder carcinoma 
Clinical features depend on the location and stage of the tumor.
- Extrahepatic cholangiocarcinoma
- Intrahepatic cholangiocarcinoma
- Asymptomatic in early stages
- Most commonly diagnosed incidentally (e.g., during routine histological examination after simple cholecystectomy)
- Symptoms of biliary colic or chronic cholecystitis
- Advanced disease
Subtypes and variants
Ampullary cancer 
- Definition: a rare type of gastrointestinal cancer that forms in the ampulla of Vater, usually causing symptoms of cholestasis
- Epidemiology: rare (< 1% of all gastrointestinal malignancies) 
- Etiology: usually occurs sporadically 
- Clinical features
- Diagnostics: Endoscopic retrograde cholangiopancreatography is used to confirm the diagnosis.
- Pathology: Adenocarcinoma of the ampulla of Vater (AAV) is the most common type of ampullary cancer. 
- Treatment: curative pancreaticoduodenectomy
- 3-year survival rate ∼ 60%
- Pancreatobiliary-type AAV is associated with a poorer prognosis than intestinal-type AVC.
The diagnostic approach varies depending on the location of the tumor and whether PSC is present. If the patient's presentation, laboratory findings (especially tumor markers), and/or transabdominal ultrasound suggest biliary cancer, then MRCP or MDCT is generally recommended for diagnosis. A biopsy is generally unnecessary. 
- Liver function tests: possible ↑ INR, ↑ ALT, and ↑ AST (with chronic biliary obstruction and eventual hepatic dysfunction)
- Parameters of cholestasis (e.g., ALP, GGT, total bilirubin) may initially be normal.
- Tumor markers (to determine the baseline; should not be used to confirm the diagnosis)
- Transabdominal ultrasound should be the initial imaging modality for suspected biliary tract carcinoma
- Recommended for definitive diagnosis
- Findings: bile duct dilatation and/or mass lesion
- Abdominal MDCT is commonly used as an alternative to MRCP
- Endoscopic ultrasound (especially for distal extrahepatic lesions and staging)
- Chest CT for staging
- PET scan: indicated if other diagnostic procedures are inconclusive and for staging
Cholangiocarcinoma: ERCP with ductal brushings or biopsy is recommended but not always necessary for diagnosis.
- May be indicated if MRCP or MDCT are inconclusive
- Allows for confirmation of tumor type via tissue sampling
- Sometimes preferred by surgeons to assess tumor resectability; allows for immediate placement of a stent if the tumor is inoperable
- Rarely, percutaneous transhepatic cholangiography (PTC) is used for proximal lesions.
- Gallbladder cancer: biopsy is usually unnecessary; typically proceeds directly to surgical exploration/resection if clinical suspicion is high
Exploratory laparoscopy is often performed for definitive diagnosis and/or staging prior to resection.
Biliary cyst 
- Definition: : a rare, premalignant condition characterized by extrahepatic and/or intrahepatic cystic dilation of the biliary tree
- Etiology: The exact cause is still unknown but pancreaticobiliary maljunction is thought to play a role in the majority of cases.
- Pathophysiology: pancreaticobiliary maljunction → formation of a long common channel → reflux and activation of pancreatic secretions in the common bile duct → inflammation and elevation of intraductal pressure → cystic degeneration 
Clinical features: symptoms typically develop before the age of 10
- The classic triad of abdominal pain, palpable abdominal mass, and jaundice is present in < 30% of affected individuals.
- Clinical presentation varies with age:
- The first manifestation can be that of one of the complications listed below.
- Laboratory studies
- CT of the abdomen: higher sensitivity than ultrasound; better for visualization of the intrahepatic ducts, the distal common bile duct, and the pancreatic head
- Cholangiography: essential for diagnosis confirmation, identification of associated ductal pathology (e.g., choledocholithiasis, cholangiocarcinoma), and mapping of the biliary tree for surgical planning
- Treatment: complete excision of the choledocus, cholecystectomy, and Roux-en-Y hepaticojejunostomy is required for the majority of cysts
- Secondary biliary cirrhosis
- Cyst rupture and bile peritonitis
- Malignancy: The entire biliary tree, not just those parts that appear dilated, are at risk of malignant transformation.
Other differential diagnoses
- Gallbladder carcinoma
The differential diagnoses listed here are not exhaustive.
- < 10% of cases are resectable.
- Resection is the only curative therapy.
- Procedure: radical resection plus lymphadenectomy
|Intrahepatic cholangiocarcinoma|| |
- Unresectable carcinoma or metastatic disease accounts for > 90% of cases.
- Treatment is palliative
- Transarterial chemoembolization (TACE): local application of chemotherapy and occlusive substance → induces fibrosis and shrinkage of intrahepatic cholangiocarcinoma
- Biliary obstruction
- Biliary cirrhosis
- Liver failure
- Pancreatic duct obstruction
- Malignant ascites
We list the most important complications. The selection is not exhaustive.