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Cholangiocarcinoma, susceptibility to

MedGen UID:
816486
Concept ID:
C3810156
Finding
Synonym: CHLC, SUSCEPTIBILITY TO
 
Monarch Initiative: MONDO:0014281
OMIM®: 615619

Definition

Carcinomas of the biliary tract are aggressive malignancies, with 5-year survival of less than 10%. These carcinomas arise throughout the biliary tree and are anatomically classified as either intrahepatic or extrahepatic cholangiocarcinomas. Gallbladder carcinomas also arise from the biliary tree but have distinct natural histories compared to cholangiocarcinomas, suggesting different underlying tumor biology. Cholangiocarcinoma incidence varies widely between geographic regions, reflecting the impact of different underlying etiologies. In endemic areas, liver fluke infections by O. viverrini and Clonorchis sinensis, both group I carcinogens, represent the major risk factor for cholangiocarcinomas. In nonendemic regions, other risk factors, including choledochal cysts (603003), hepatolithiasis, and primary sclerosing cholangitis (613806), are likely contributors (summary by Chan-on et al., 2013). Overall, the majority of patients lack such identifiable risk factors (summary by Jiao et al., 2013). [from OMIM]

Additional description

From MedlinePlus Genetics
Cholangiocarcinoma is a group of cancers that begin in the bile ducts. Bile ducts are branched tubes that connect the liver and gallbladder to the small intestine. They carry bile, which is a fluid that helps the body digest fats that are in food. Bile is made in the liver and stored in the gallbladder before being released in the small intestine after a person eats.

Cholangiocarcinoma is classified by its location in relation to the liver. Intrahepatic cholangiocarcinoma begins in the small bile ducts within the liver. This is the least common form of the disease, accounting for less than 10 percent of all cases. Perihilar cholangiocarcinoma (also known as a Klatskin tumor) begins in an area called the hilum, where the right and left major bile ducts join and leave the liver. It is the most common form of the disease, accounting for more than half of all cases. The remaining cases are classified as distal cholangiocarcinomas, which begin in bile ducts outside the liver. The perihilar and distal forms of the disease, which both occur outside the liver, are sometimes grouped together and called extrahepatic cholangiocarcinoma.

The three types of cholangiocarcinoma do not usually cause any symptoms in their early stages, and this cancer is usually not diagnosed until it has already spread beyond the bile ducts to other tissues. Symptoms often result when bile ducts become blocked by the tumor. The most common symptom is jaundice, in which the skin and whites of the eyes turn yellow. Other symptoms can include extreme tiredness (fatigue), itching, dark-colored urine, loss of appetite, unintentional weight loss, abdominal pain, and light-colored and greasy stools. These symptoms are described as "nonspecific" because they can be features of many different diseases.

Most people who develop cholangiocarcinoma are older than 65. Because this cancer is often not discovered until it has already spread, it can be challenging to treat effectively. Affected individuals can survive for several months to several years after diagnosis, depending on the location of the cancer and how advanced it is.  https://medlineplus.gov/genetics/condition/cholangiocarcinoma

Clinical features

From HPO
Cholangiocarcinoma
MedGen UID:
60210
Concept ID:
C0206698
Neoplastic Process
Cholangiocarcinoma is a primary cancer originating in the biliary epithelium i.e., the cholangiocytes, of the extrahepatic and intrahepatic biliary ducts. It is extremely invasive, develops rapidly, often metastasizes, and has a very poor prognosis. They are slow growing tumors which spread longitudinally along the bile ducts with neural, perineural and subepithelial extension.

Professional guidelines

PubMed

Javle M, King G, Spencer K, Borad MJ
Oncologist 2023 Nov 2;28(11):928-943. doi: 10.1093/oncolo/oyad149. PMID: 37390492Free PMC Article
Mahipal A, Tella SH, Kommalapati A, Yu J, Kim R
Crit Rev Oncol Hematol 2020 Nov;155:103091. Epub 2020 Sep 1 doi: 10.1016/j.critrevonc.2020.103091. PMID: 32961472
Rahnemai-Azar AA, Weisbrod AB, Dillhoff M, Schmidt C, Pawlik TM
Expert Rev Gastroenterol Hepatol 2017 May;11(5):439-449. Epub 2017 Mar 29 doi: 10.1080/17474124.2017.1309290. PMID: 28317403

Curated

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Biliary Tract Cancers, 2024

Recent clinical studies

Etiology

Kendall T, Verheij J, Gaudio E, Evert M, Guido M, Goeppert B, Carpino G
Liver Int 2019 May;39 Suppl 1:7-18. doi: 10.1111/liv.14093. PMID: 30882996
Labib PL, Goodchild G, Pereira SP
BMC Cancer 2019 Feb 28;19(1):185. doi: 10.1186/s12885-019-5391-0. PMID: 30819129Free PMC Article
Karlsen TH, Folseraas T, Thorburn D, Vesterhus M
J Hepatol 2017 Dec;67(6):1298-1323. Epub 2017 Aug 10 doi: 10.1016/j.jhep.2017.07.022. PMID: 28802875
Li L, Wang H
Cancer Lett 2016 Sep 1;379(2):191-7. Epub 2015 Jul 23 doi: 10.1016/j.canlet.2015.07.018. PMID: 26213370
Wu YM, Su F, Kalyana-Sundaram S, Khazanov N, Ateeq B, Cao X, Lonigro RJ, Vats P, Wang R, Lin SF, Cheng AJ, Kunju LP, Siddiqui J, Tomlins SA, Wyngaard P, Sadis S, Roychowdhury S, Hussain MH, Feng FY, Zalupski MM, Talpaz M, Pienta KJ, Rhodes DR, Robinson DR, Chinnaiyan AM
Cancer Discov 2013 Jun;3(6):636-47. Epub 2013 Apr 4 doi: 10.1158/2159-8290.CD-13-0050. PMID: 23558953Free PMC Article

Diagnosis

Du J, Lan T, Liao H, Feng X, Chen X, Liao W, Hou G, Xu L, Feng Q, Xie K, Liao M, Chen X, Huang J, Yuan K, Zeng Y
Mol Cancer 2022 Jan 17;21(1):18. doi: 10.1186/s12943-021-01482-9. PMID: 35039066Free PMC Article
Kendall T, Verheij J, Gaudio E, Evert M, Guido M, Goeppert B, Carpino G
Liver Int 2019 May;39 Suppl 1:7-18. doi: 10.1111/liv.14093. PMID: 30882996
Labib PL, Goodchild G, Pereira SP
BMC Cancer 2019 Feb 28;19(1):185. doi: 10.1186/s12885-019-5391-0. PMID: 30819129Free PMC Article
Wardell CP, Fujita M, Yamada T, Simbolo M, Fassan M, Karlic R, Polak P, Kim J, Hatanaka Y, Maejima K, Lawlor RT, Nakanishi Y, Mitsuhashi T, Fujimoto A, Furuta M, Ruzzenente A, Conci S, Oosawa A, Sasaki-Oku A, Nakano K, Tanaka H, Yamamoto Y, Michiaki K, Kawakami Y, Aikata H, Ueno M, Hayami S, Gotoh K, Ariizumi SI, Yamamoto M, Yamaue H, Chayama K, Miyano S, Getz G, Scarpa A, Hirano S, Nakamura T, Nakagawa H
J Hepatol 2018 May;68(5):959-969. Epub 2018 Jan 31 doi: 10.1016/j.jhep.2018.01.009. PMID: 29360550
Karlsen TH, Folseraas T, Thorburn D, Vesterhus M
J Hepatol 2017 Dec;67(6):1298-1323. Epub 2017 Aug 10 doi: 10.1016/j.jhep.2017.07.022. PMID: 28802875

Therapy

Javle M, King G, Spencer K, Borad MJ
Oncologist 2023 Nov 2;28(11):928-943. doi: 10.1093/oncolo/oyad149. PMID: 37390492Free PMC Article
Al-Rajabi R, Sun W
Curr Opin Gastroenterol 2021 Mar 1;37(2):105-111. doi: 10.1097/MOG.0000000000000715. PMID: 33507028
Dhillon S
Drugs 2018 Sep;78(14):1509-1516. doi: 10.1007/s40265-018-0978-3. PMID: 30209701Free PMC Article
Li L, Wang H
Cancer Lett 2016 Sep 1;379(2):191-7. Epub 2015 Jul 23 doi: 10.1016/j.canlet.2015.07.018. PMID: 26213370
Karlsen TH, Schrumpf E, Boberg KM
Best Pract Res Clin Gastroenterol 2010 Oct;24(5):655-66. doi: 10.1016/j.bpg.2010.07.005. PMID: 20955968

Prognosis

Liu Y, Baba Y, Ishimoto T, Gu X, Zhang J, Nomoto D, Okadome K, Baba H, Qiu P
Int J Biol Sci 2022;18(10):4101-4117. Epub 2022 Jun 21 doi: 10.7150/ijbs.69331. PMID: 35844804Free PMC Article
Du J, Lan T, Liao H, Feng X, Chen X, Liao W, Hou G, Xu L, Feng Q, Xie K, Liao M, Chen X, Huang J, Yuan K, Zeng Y
Mol Cancer 2022 Jan 17;21(1):18. doi: 10.1186/s12943-021-01482-9. PMID: 35039066Free PMC Article
Wardell CP, Fujita M, Yamada T, Simbolo M, Fassan M, Karlic R, Polak P, Kim J, Hatanaka Y, Maejima K, Lawlor RT, Nakanishi Y, Mitsuhashi T, Fujimoto A, Furuta M, Ruzzenente A, Conci S, Oosawa A, Sasaki-Oku A, Nakano K, Tanaka H, Yamamoto Y, Michiaki K, Kawakami Y, Aikata H, Ueno M, Hayami S, Gotoh K, Ariizumi SI, Yamamoto M, Yamaue H, Chayama K, Miyano S, Getz G, Scarpa A, Hirano S, Nakamura T, Nakagawa H
J Hepatol 2018 May;68(5):959-969. Epub 2018 Jan 31 doi: 10.1016/j.jhep.2018.01.009. PMID: 29360550
Li L, Wang H
Cancer Lett 2016 Sep 1;379(2):191-7. Epub 2015 Jul 23 doi: 10.1016/j.canlet.2015.07.018. PMID: 26213370
Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M, Hama N, Hosoda F, Urushidate T, Ohashi S, Hiraoka N, Ojima H, Shimada K, Okusaka T, Kosuge T, Miyagawa S, Shibata T
Nat Genet 2015 Sep;47(9):1003-10. Epub 2015 Aug 10 doi: 10.1038/ng.3375. PMID: 26258846

Clinical prediction guides

Javle M, King G, Spencer K, Borad MJ
Oncologist 2023 Nov 2;28(11):928-943. doi: 10.1093/oncolo/oyad149. PMID: 37390492Free PMC Article
Liu Y, Baba Y, Ishimoto T, Gu X, Zhang J, Nomoto D, Okadome K, Baba H, Qiu P
Int J Biol Sci 2022;18(10):4101-4117. Epub 2022 Jun 21 doi: 10.7150/ijbs.69331. PMID: 35844804Free PMC Article
Du J, Lan T, Liao H, Feng X, Chen X, Liao W, Hou G, Xu L, Feng Q, Xie K, Liao M, Chen X, Huang J, Yuan K, Zeng Y
Mol Cancer 2022 Jan 17;21(1):18. doi: 10.1186/s12943-021-01482-9. PMID: 35039066Free PMC Article
Labib PL, Goodchild G, Pereira SP
BMC Cancer 2019 Feb 28;19(1):185. doi: 10.1186/s12885-019-5391-0. PMID: 30819129Free PMC Article
Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M, Hama N, Hosoda F, Urushidate T, Ohashi S, Hiraoka N, Ojima H, Shimada K, Okusaka T, Kosuge T, Miyagawa S, Shibata T
Nat Genet 2015 Sep;47(9):1003-10. Epub 2015 Aug 10 doi: 10.1038/ng.3375. PMID: 26258846

Recent systematic reviews

Sicklick JK, Fanta PT, Shimabukuro K, Kurzrock R
Cancer Metastasis Rev 2016 Jun;35(2):263-75. doi: 10.1007/s10555-016-9602-8. PMID: 26857926Free PMC Article
Sharma RR, London MJ, Magenta LL, Posner MC, Roggin KK
J Gastrointest Surg 2009 Oct;13(10):1874-87. Epub 2009 Jun 10 doi: 10.1007/s11605-009-0935-2. PMID: 19513795

Supplemental Content

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    Genetic Testing Registry

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    Practice guidelines

    • PubMed
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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NCCN, 2024
      NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Biliary Tract Cancers, 2024

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