Updated: Aug 27, 2021
  • Author: Peter E Darwin, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Practice Essentials

Cholangiocarcinomas (CCCs) are malignancies of the biliary duct system that may originate in the liver and extrahepatic bile ducts, which terminate at the ampulla of Vater. [1, 2, 3, 4, 5] CCCs are encountered in three anatomic regions: intrahepatic, extrahepatic (ie, perihilar), and distal extrahepatic. See the image below.

Bismuth classification for perihilar cholangiocarc Bismuth classification for perihilar cholangiocarcinoma. Shaded areas represent tumor location.

Perihilar tumors are the most common CCCs, and intrahepatic tumors are the least common. Perihilar tumors, also called Klatskin tumors (after Klatskin's description of them in 1965 [6] ), occur at the bifurcation of right and left hepatic ducts. [7] Distal extrahepatic tumors are located from the upper border of the pancreas to the ampulla. More than 95% of these tumors are ductal adenocarcinomas; many patients present with unresectable or metastatic disease.

Complete surgical resection is the only therapy to afford a chance of cure for cholangiocarcinoma. Unfortunately, many patients present with unresectable disease. Additional treatment measures in cholangiocarcinoma may include the following [8] :

  • Stenting
  • Photodynamic therapy (PDT)
  • Radiation therapy
  • Chemotherapy
  • Targeted agents, in cases with actionable driver mutations

See Treatment and Medication.



Cholangiocarcinomas arise from the intrahepatic or extrahepatic biliary epithelium. More than 90% are adenocarcinomas, and the remainder are squamous cell tumors. The etiology of most bile duct cancers remains undetermined. Long-standing inflammation, as with primary sclerosing cholangitis (PSC) or chronic parasitic infection, has been suggested to play a role by inducing hyperplasia, cellular proliferation, and, ultimately, malignant transformation. Intrahepatic cholangiocarcinoma may be associated with chronic ulcerative colitis and chronic cholecystitis.

Cholangiocarcinomas tend to grow slowly and to infiltrate the walls of the ducts, dissecting along tissue planes. Local extension occurs into the liver, porta hepatis, and regional lymph nodes of the celiac and pancreaticoduodenal chains. Life-threatening infection (cholangitis) may occur that requires immediate antibiotic intervention and aggressive biliary drainage.




United States

Each year, approximately 2500 cases of cholangiocarcinoma occur, compared with 5000 cases of gallbladder cancer and 15,000 cases of hepatocellular cancer. The average incidence is one case per 100,000 population per year.

A study by Singal et al found that the frequency of intrahepatic cholangiocarcinoma has increased over time and is most commonly noted in women older than 60 years. [9]


Incidence in most Western countries ranges from 2 to 6 cases per 100,000 people per year. The highest annual incidences are in Japan, at 5.5 cases per 100,000 people, and in Israel, at 7.3 cases per 100,000 people.

Occupational cholangiocarcinoma has been documented in workers at printing companies in Japan who had been exposed to high concentrations of chemical compounds, including 1,2-dichloropropane (1,2-DCP) and/or dichloromethane. [10] Heavy infestation by the liver flukes Clonorchis sinensis (endemic predominantly in Asian countries, including Korea, China, Taiwan, Vietnam, and far eastern Russia) and Opisthorchis viverrini (the Southeast Asian liver fluke) has been linked to the development of cholangiocarcinoma. [11]


Despite aggressive anticancer therapy and interventional supportive care (ie, wall stents or percutaneous biliary drainage), the median survival rate is low, since most patients (90%) are not eligible for curative resection. The overall survival is approximately 6 months.

Race-, sex-, and age-related demographics

Native Americans have the highest annual incidence in North America, at 6.5 cases per 100,000 people. This rate is about 6 times higher than that in non–Native American populations. The high prevalence of cholangiocarcinoma in people of Asian descent is attributable to endemic chronic parasitic infestation.

In both males and females, cholangiocarcinoma is most common in persons in their 60s and 70s. The male-to-female ratio for cholangiocarcinoma is 1:2.5 in patients in their 60s and 70s and 1:15 in patients younger than 40 years. According to the American Cancer Society, the number of new cases of liver and intrahepatic bile duct cancer in 2021 is estimated to be 29,890 for men and 12,340 for women, with deaths estimated at 20,300 and 9,930, respectively. The estimated number of new cases of gallbladder and other biliary cancers (extrahepatic cholangiocarcinoma) are 5,730 for men and 6,250 for women, with estimated deaths of 1,770 and 2,540, respectively. [12]