Cholangiocarcinoma
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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.
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] :
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]
International
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.
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 2018 is estimated to be 30,610 for men and 11,610 for women, with deaths estimated at 20,540 and 9,660, respectively. The estimated number of new cases of gallbladder and other biliary cancers (extrahepatic cholangiocarcinoma) are 5,450 for men and 6,740 for women, with estimated deaths of 1,530 and 2,260, respectively. [12]
Blechacz B. Cholangiocarcinoma: Current Knowledge and New Developments. Gut Liver. 2017 Jan 15. 11 (1):13-26. [Medline]. [Full Text].
Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014 Jun 21. 383 (9935):2168-79. [Medline]. [Full Text].
Blechacz B, Gores GJ. Tumors of the Bile Ducts, Gallbladder, and Ampulla. In: Fledman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 10th ed. Philadelphia, PA: Elsevier Saunders; 2015. 1171-83.
Patel T, Borad MJ. Cancer of the Biliary Tree. DeVita VT Jr, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th. Philadelphia, Pa: Wolters Kluwer Health; 2015. 715-33.
Banales JM, Cardinale V, Carpino G, Marzioni M, Andersen JB, et al. Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016 May. 13 (5):261-80. [Medline].
Klatskin G. Adenocarcinoma of the hepatic duct at its bifurcation within the porta hepatis. An unusual tumor with distinctive clinical and pathological features. Am J Med. 1965 Feb. 38:241-56. [Medline].
Clary B, Jarnigan W, Pitt H, et al. Hilar cholangiocarcinoma. J Gastrointest Surg. 2004 Mar-Apr. 8(3):298-302. [Medline].
Doherty B, Nambudiri VE, Palmer WC. Update on the Diagnosis and Treatment of Cholangiocarcinoma. Curr Gastroenterol Rep. 2017 Jan. 19 (1):2. [Medline].
Singal AK, Vauthey JN, Grady JJ, Stroehlein JR. Intra-hepatic cholangiocarcinoma–frequency and demographic patterns: thirty-year data from the M.D. Anderson Cancer Center. J Cancer Res Clin Oncol. 2011 Jul. 137(7):1071-8. [Medline].
Mimaki S, Totsuka Y, Suzuki Y, Nakai C, Goto M, Kojima M, et al. Hypermutation and unique mutational signatures of occupational cholangiocarcinoma in printing workers exposed to haloalkanes. Carcinogenesis. 2016 Aug. 37 (8):817-26. [Medline].
Kim TS, Pak JH, Kim JB, Bahk YY. Clonorchis sinensis, an Oriental Liver Fluke, as a Human Biological Agent (Carcinogen) of Cholangiocarcinoma: A Brief Review. BMB Rep. 2016 Jul 7. [Medline].
Cancer Facts & Figures 2018. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf. Accessed: August 29, 2018.
McGee EE, Castro FA, Engels EA, Freedman ND, Pfeiffer RM, Nogueira L, et al. Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults. Int J Cancer. 2018 Aug 28. [Medline].
Koshiol J, Ferreccio C, Devesa SS, Roa JC, Fraumeni JF Jr. Biliary Tract Cancer. Thun MJ, Linet MS, Cerhan JR, Haiman CA, Schottenfeld D, eds. Cancer. Epidemiology and Prevention. 4th Edition. New York, NY: Oxford University Press; 2018. 661-671.
Chalasani N, Baluyut A, Ismail A, et al. Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study. Hepatology. 2000 Jan. 31(1):7-11. [Medline].
Travis LB, Hauptmann M, Gaul LK, Storm HH, Goldman MB, Nyberg U, et al. Site-specific cancer incidence and mortality after cerebral angiography with radioactive thorotrast. Radiat Res. 2003 Dec. 160(6):691-706. [Medline].
Li JS, Han TJ, Jing N, Li L, Zhang XH, Ma FZ, et al. Obesity and the risk of cholangiocarcinoma: a meta-analysis. Tumour Biol. 2014 Apr 13. [Medline].
Ramage JK, Donaghy A, Farrant JM, Iorns R, Williams R. Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Gastroenterology. 1995 Mar. 108 (3):865-9. [Medline]. [Full Text].
Bergquist JR, Ivanics T, Storlie CB, Groeschl RT, Tee MC, Habermann EB, et al. Implications of CA19-9 elevation for survival, staging, and treatment sequencing in intrahepatic cholangiocarcinoma: A national cohort analysis. J Surg Oncol. 2016 Jul 20. [Medline].
Keiding S, Hansen SB, Rasmussen HH, et al. Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography. Hepatology. 1998 Sep. 28(3):700-6. [Medline].
Petrowsky H, Wildbrett P, Husarik DB. Impact of Integrated PET and CT on staging and management of glabladder cancer and cholangiocarcinoma. J Hepatol. 2006. Epub Apr 19:
Fritscher-Ravens A, Broering DC, Knoefel WT, et al. EUS-guided fine-needle aspiration of suspected hilar cholangiocarcinoma in potentially operable patients with negative brush cytology. Am J Gastroenterol. 2004 Jan. 99(1):45-51. [Medline].
American Joint Committee on Cancer. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, et al, eds. AJCC Cancer Staging Manual. 8th Edition. New York: Springer; 2017.
Simmons DT, Baron TH, Peterson BT. A Novel Endoscopic Approach to Brachytherapy in the Management of Hilar Cholangiocarcinoma. Am J Gastroenterol. 2006. Epub ahead of print:
Butros SR, Shenoy-Bhangle A, Mueller PR, Arellano RS. Radiofrequency ablation of intrahepatic cholangiocarcinoma: feasability, local tumor control, and long-term outcome. Clin Imaging. 2014 Feb 7. [Medline].
Kida M, Miyazawa S, Iwai T, et al. Endoscopic management of malignant biliary obstruction by means of covered metallic stents: primary stent placement vs. re-intervention. Endoscopy. 2011 Dec. 43(12):1039-44. [Medline].
Ortner MA, Liebetruth J, Schreiber S, et al. Photodynamic therapy of nonresectable cholangiocarcinoma. Gastroenterology. 1998 Mar. 114(3):536-42. [Medline].
Ortner ME, Caca K, Berr F, et al. Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. Gastroenterology. 2003 Nov. 125(5):1355-63. [Medline].
Jackson MW, Amini A, Jones BL, Rusthoven CG, Schefter TE, Goodman KA. Treatment Selection and Survival Outcomes With and Without Radiation for Unresectable, Localized Intrahepatic Cholangiocarcinoma. Cancer J. 2016 Jul-Aug. 22 (4):237-42. [Medline].
Mosconi C, Gramenzi A, Ascanio S, Cappelli A, Renzulli M, Pettinato C, et al. Yttrium-90 radioembolization for unresectable/recurrent intrahepatic cholangiocarcinoma: a survival, efficacy and safety study. Br J Cancer. 2016 Jul 26. 115 (3):297-302. [Medline].
Thongprasert S, Napapan S, Charoentum C, Moonprakan S. Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. Ann Oncol. 2005 Feb. 16(2):279-81. [Medline].
Thongprasert S. The role of chemotherapy in cholangiocarcinoma. Ann Oncol. 2005. 16 Suppl 2:ii93-6. [Medline].
[Guideline] NCCN Clinical Practice Guidelines in Oncology. Hepatobiliary Cancers. National Comprehensive Cancer Network. Available at https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. Version 3.2018 — August 29, 2018; Accessed: August 29, 2018.
Heimbach JK, Haddock MG, Alberts SR, et al. Transplantation for hilar cholangiocarcinoma. Liver Transpl. 2004 Oct. 10(10 Suppl 2):S65-8. [Medline].
Shen WF, Zhong W, Liu Q, Sui CJ, Huang YQ, Yang JM. Adjuvant Transcatheter Arterial Chemoembolization for Intrahepatic Cholangiocarcinoma after Curative Surgery: Retrospective Control Study. World J Surg. 2011 Jun 23. [Medline].
Seshadri RA, Majhi U. Endobiliary metastasis from rectal cancer mimicking intrahepatic cholangiocarcinoma: a case report and review of literature. J Gastrointest Cancer. 2009. 40 (3-4):123-7. [Medline].
Anderson MA, Appalaneni V, Ben-Menachem T, Decker GA, Early DS, Evans JA, et al. The role of endoscopy in the evaluation and treatment of patients with biliary neoplasia. Gastrointest Endosc. 2013 Feb. 77 (2):167-74. [Medline].
[Guideline] Valle JW, Borbath I, Khan SA, Huguet F, Gruenberger T, Arnold D, et al. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016 Sep. 27 (suppl 5):v28-v37. [Medline]. [Full Text].
Polistina FA, Guglielmi R, Baiocchi C, et al. Chemoradiation treatment with gemcitabine plus stereotactic body radiotherapy for unresectable, non-metastatic, locally advanced hilar cholangiocarcinoma. Results of a five year experience. Radiother Oncol. 2011 May. 99(2):120-3. [Medline].
Atanasov G, Schierle K, Hau HM, Dietel C, Krenzien F, Brandl A, et al. Prognostic Significance of Tumor Necrosis in Hilar Cholangiocarcinoma. Ann Surg Oncol. 2016 Aug 1. [Medline].
Ghafoori AP, Nelson JW, Willett CG, et al. Radiotherapy in the treatment of patients with unresectable extrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys. 2011 Nov 1. 81(3):654-9. [Medline].
McMillan DC. The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer. Cancer Treat Rev. 2013 Aug. 39 (5):534-40. [Medline].
Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014 Jun. 106 (6):dju124. [Medline]. [Full Text].
Okuno M, Ebata T, Yokoyama Y, Igami T, Sugawara G, Mizuno T, et al. Appraisal of inflammation-based prognostic scores in patients with unresectable perihilar cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 2016 Jul 30. [Medline].
Gunderson LL, Willett CG. Pancreas and hepatobiliary tract. Perez CA, Brady LW, et al. Principles and Practice of Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven; 1998: 1467-1488.
Lillemoe K, Kennedy A, Picus J. Clinical management of carcinoma of the biliary tree. Kelsen DP, Daly JM, Kern SE, et al. Gastrointestinal Oncology: Principles and Practices. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001.
Uchida M, Ishibashi M, Tomita N, et al. Hilar and suprapancreatic cholangiocarcinoma: value of 3D angiography and multiphase fusion images using MDCT. AJR Am J Roentgenol. 2005 May. 184(5):1572-7. [Medline].
T – Primary tumor
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ (intraductal tumor)
T1
Solitary tumor without vascular invasion, ≤5 cm or > 5 cm
T1a
Solitary tumor ≤5 cm without vascular invasion
T1b
Solitary tumor > 5 cm without vascular invasion
T2
Solitary tumor with intrahepatic vascular invasion, or multiple tumors with or without vascular invasion
T3
Tumor perforating the visceral peritoneum
T4
Tumor involving local extrahepatic structures by direct invasion
N – Regional lymph nodes
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Regional lymph node metastasis present
M – Distant metastasis
M0
No distant metastasis
M1
Distant metastasis present
T – Primary tumor
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ – high-grade dysplasia
T1
Tumor confined to the bile duct, with extension up to the muscle layer or fibrous tissue
T2
Tumor invades beyond the wall of the bile duct to surrounding adipose tissue, or tumor invades adjacent hepatic parenchyma
T2a
Tumor invades beyond the wall of the bile duct to surrounding adipose tissue
T2b
Tumor invades adjacent hepatic parenchyma
T3
Tumor invades unilateral branches of the portal vein or hepatic artery
T4
Tumor invades main portal vein or its branches bilaterally, or the common hepatic artery; or unilateral second-order biliary radicals bilaterally with contralateral portal vein or hepatic artery involvement
N – Regional lymph nodes
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
One to three positive lymph nodes typically involving the hilar, cystic duct, common bile duct, hepatic artery, posterior pancreatoduodenal, and portal vein lymph nodes
N2
Four or more positive lymph nodes from the sites described for N1
M – Distant metastasis
M0
No distant metastasis
M1
Distant metastasis
T – Primary tumor
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ – high-grade dysplasia
T1
Tumor invades the bile duct wall with a depth less than 5 m
T2
Tumor invades the bile duct wall with a depth of 5–12 m
T3
Tumor invades the bile duct wall with a depth greater than 12 mm
T4
Tumor involves the celiac axis, superior mesenteric artery, and/or common hepatic artery
N – Regional lymph nodes
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Metastasis in 1-3 regional lymph nodes
N2
Metastasis in ≥4 regional lymph nodes
M – Distant metastasis
M0
No distant metastasis
M1
Distant metastasis
Intrahepatic bile duct tumor
Stage
T
N
M
0
Tis
N0
M0
IA
T1a
N0
M0
IB
T1b
N0
M0
II
T2
N0
M0
IIIA
T3
N0
M0
IIIB
T4
N0
M0
Any T
N1
M0
IV
Any T
Any N
M1
Perihilar bile duct tumor
Stage
T
N
M
0
Tis
N0
M0
I
T1
N0
M0
II
T2a-b
N0
M0
IIIA
T3
N0
M0
IIIB
T4
N0
M0
IIIC
Any T
N1
M0
IVA
T4
N2
M0
IVB
Any T
Any N
M1
Distal bile duct tumor
Stage
T
N
M
0
Tis
N0
M0
I
T1
N0
M0
IIA
T1
N1
M0
T2
N0
M0
IIB
T2
N1
M0
T3
N0
M0
T3
N1
M0
IIIA
T1-3
N2
M0
IIIB
T4
N0-2
M0
IV
Any T
Any N
M1
Peter E Darwin, MD Professor of Medicine, Director of GI Endoscopy, Department of Medicine, Division of Gastroenterology, University of Maryland School of Medicine
Peter E Darwin, MD is a member of the following medical societies: American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.
Andrew Scott Kennedy, MD Physician-in-Chief, Radiation Oncology
Andrew Scott Kennedy, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Society for Radiation Oncology, Radiological Society of North America, Americas Hepato-Pancreato-Biliary Association, American Society of Clinical Oncology
Disclosure: Nothing to disclose.
Jennifer Lynn Bonheur, MD Attending Physician, Division of Gastroenterology, Lenox Hill Hospital
Jennifer Lynn Bonheur, MD is a member of the following medical societies: American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, New York Society for Gastrointestinal Endoscopy, New York Academy of Sciences, Sigma Xi
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Benjamin Movsas, MD
Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, American Society for Radiation Oncology
Disclosure: Nothing to disclose.
N Joseph Espat, MD, MS, FACS Harold J Wanebo Professor of Surgery, Assistant Dean of Clinical Affairs, Boston University School of Medicine; Chairman, Department of Surgery, Director, Adele R Decof Cancer Center, Roger Williams Medical Center
N Joseph Espat, MD, MS, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Parenteral and Enteral Nutrition, American Society of Clinical Oncology, Americas Hepato-Pancreato-Biliary Association, Association for Academic Surgery, Central Surgical Association, Chicago Medical Society, International Hepato-Pancreato-Biliary Association, Pancreas Club, Sigma Xi, Society for Leukocyte Biology, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Surgical Oncology, Society of University Surgeons, Southeastern Surgical Congress, Southern Medical Association, Surgical Infection Society
Disclosure: Nothing to disclose.
Elwyn C Cabebe, MD Physician Partner, Valley Medical Oncology Consultants; Medical Director of Oncology, Clinical Liason Physician, Cancer Care Committee, Good Samaritan Hospital
Elwyn C Cabebe, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology, Philippine Medical Society of Northern California, Santa Clara County Medical Association, Monterey County Medical Society, Association of Northern California Oncologists
Disclosure: Nothing to disclose.
Cholangiocarcinoma
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