Biliary cancer

Last updated: July 21, 2023

Summarytoggle arrow icon

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.

Definitiontoggle arrow icon

Epidemiologytoggle arrow icon

Cholangiocarcinoma [2]

Gallbladder carcinoma [4]

  • 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.

Etiologytoggle arrow icon

Chronic gallbladder inflammation increases the risk of gallbladder carcinoma.

Clinical featurestoggle arrow icon

Clinical features depend on the location and stage of the tumor.

Cholangiocarcinoma [2]

Gallbladder carcinoma [4]

Subtypes and variantstoggle arrow icon

Ampullary cancer [5]

Diagnosticstoggle arrow icon

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. [2][9]

Laboratory tests


Biopsy [4]

Surgical exploration

Exploratory laparoscopy is often performed for definitive diagnosis and/or staging prior to resection.

Gallbladder carcinoma is usually diagnosed incidentally after elective cholecystectomy.

Pathologytoggle arrow icon

Differential diagnosestoggle arrow icon

Biliary cyst [12][13]

Individuals with biliary cysts have an increased risk of cholangiocarcinoma; therefore, all patients should undergo surgery, even if asymptomatic. [16]

Other differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

The prognosis for cholangiocarcinoma and gallbladder cancer is generally poor, especially for gallbladder cancer and intrahepatic cholangiocarcinoma. Treatment is determined by tumor resectability.

Resectable disease

Surgical approach Contraindications
Intrahepatic cholangiocarcinoma
  • Hepatic resection: usually partial resection (in rare cases, liver transplant)
Extrahepatic cholangiocarcinoma
Gallbladder carcinoma

Unresectable disease

Complicationstoggle arrow icon

We list the most important complications. The selection is not exhaustive.

Prognosistoggle arrow icon

Referencestoggle arrow icon

  1. Razumilava N, Gores GJ. Classification, Diagnosis, and Management of Cholangiocarcinoma. Clin Gastroenterol Hepatol. 2012; 11 (1): p.13-e4.doi: 10.1016/j.cgh.2012.09.009 . | Open in Read by QxMD
  2. Nestor F. Esnaola, Joshua E. Meyer, Andreas Karachristos, Jennifer L. Maranki, E. Ramsay Camp, Crystal S. Denlinger. Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma. Cancer. 2016; 122 (9): p.1349-1369.doi: 10.1002/cncr.29692 . | Open in Read by QxMD
  3. Goljan EF. Rapid Review Pathology. Elsevier Saunders ; 2013
  4. Valle JW, Borbath I, Khan SA, Huguet F, Gruenberger T, Arnold D. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Annals of Oncology. 2016; 27 (suppl_5): p.v28-v37.doi: 10.1093/annonc/mdw324 . | Open in Read by QxMD
  5. Van Beers BE. Diagnosis of cholangiocarcinoma. HPB (Oxford). 2008; 10 (2): p.87-93.doi: 10.1080/13651820801992716 . | Open in Read by QxMD
  6. Wang C, Jing H, Sha D, et al. HBV-associated intrahepatic cholangiocarcinoma with high serum alpha-fetoprotein: a case report with review of literature. BMC Infect Dis. 2016; 16 (1).doi: 10.1186/s12879-016-1643-7 . | Open in Read by QxMD
  7. Wang B, Chen L, Chang H-T. Potential diagnostic and prognostic biomarkers for cholangiocarcinoma in serum and bile. Biomarkers in Medicine. 2016; 10 (6): p.613-619.doi: 10.2217/bmm-2015-0062 . | Open in Read by QxMD
  8. Dhanasekaran R, Hemming AW, Zendejas I, et al. Treatment outcomes and prognostic factors of intrahepatic cholangiocarcinoma.. Oncol Rep. 2013; 29 (4): p.1259-67.doi: 10.3892/or.2013.2290 . | Open in Read by QxMD
  9. Jang JY, Kim SW, Park DJ, et al. Actual long-term outcome of extrahepatic bile duct cancer after surgical resection.. Ann Surg. 2005; 241 (1): p.77-84.doi: 10.1097/01.sla.0000150166.94732.88 . | Open in Read by QxMD
  10. Goetze TO. Gallbladder carcinoma: Prognostic factors and therapeutic options.. World journal of gastroenterology. 2015; 21 (43): p.12211-7.doi: 10.3748/wjg.v21.i43.12211 . | Open in Read by QxMD
  11. Townsend CM Jr, Beauchamp RD, Evers BM, Mattox KL. Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice. Elsevier ; 2016
  12. Hoilat GJ, John S. Choledochal Cyst. StatPearls. 2021.
  13. Singham J, Yoshida EM, Scudamore CH. Choledochal cysts: part 2 of 3: Diagnosis.. Can J Surg. 2009; 52 (6): p.506-11.
  14. Brunicardi FC, Andersen DK, Billiar TR, et al.. SCHWARTZ'S PRINCIPLES OF SURGERY 2-volume set 11th edition. McGraw Hill Professional ; 2019
  15. Jabłońska B. Biliary cysts: Etiology, diagnosis and management. World Journal of Gastroenterology. 2012; 18 (35): p.4801.doi: 10.3748/wjg.v18.i35.4801 . | Open in Read by QxMD
  16. Xia T, Wu X, Mou Y, et al. Clinicopathological Prognostic Factors and Chemotherapeutic Outcome for Two Histopathological Types of Ampulla of Vater Adenocarcinoma. Frontiers in Oncology. 2021; 11.doi: 10.3389/fonc.2021.616108 . | Open in Read by QxMD
  17. Albores-Saavedra J, Schwartz AM, Batich K, Henson DE. Cancers of the ampulla of vater: Demographics, morphology, and survival based on 5,625 cases from the SEER program. J Surg Oncol. 2009; 100 (7): p.598-605.doi: 10.1002/jso.21374 . | Open in Read by QxMD
  18. JAGELMAN D. UPPER GASTROINTESTINAL CANCER IN FAMILIAL ADENOMATOUS POLYPOSIS. The Lancet. 1988; 331 (8595): p.1149-1151.doi: 10.1016/s0140-6736(88)91962-9 . | Open in Read by QxMD
  19. Ahn DH, Bekaii-Saab T. Ampullary Cancer: An Overview. American Society of Clinical Oncology Educational Book. 2014: p.112-115.doi: 10.14694/edbook_am.2014.34.112 . | Open in Read by QxMD
  20. What are the risk factors for bile duct cancer?. Updated: January 11, 2014. Accessed: December 22, 2016.
  21. Cholangiocarcinoma and gallbladder cancer. Updated: August 7, 2017. Accessed: February 26, 2019.

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