Abstract
Cholangiocarcinomas are rare malignant tumors composed of cells that resemble those of the biliary tract. On the basis of their anatomic location, cholangiocarcinomas can be classified as intrahepatic, extrahepatic and hilar tumors. For reasons that are not clear, the incidence of cholangiocarcinoma is increasing globally. Established risk factors, including conditions associated with chronic biliary tract inflammation, account for a small proportion of cases. Additional risk factors such as cirrhosis, infection with hepatitis B virus and hepatitis C virus are now becoming recognized. The diagnosis of cholangiocarcinoma requires the integration of clinical information, imaging studies of the hepatic parenchyma and biliary tract, tumor markers, and histology. In terms of the treatment options for cholangiocarcinoma, surgery can be curative, although few patients are candidates for surgery. Palliative biliary decompression can provide symptomatic relief. Advances in MRI and positron-emission tomography scanning, identification of new tumor markers, improved utility of biliary cytology, and the use of photodynamic therapy for adjunct treatment are all expected to enhance the diagnosis, evaluation and management of cholangiocarcinoma.
Key Points
-
Optimal management requires accurate diagnosis and staging, and assessment of candidacy for surgical intervention or palliative therapy
-
Diagnosis and staging requires consideration of the clinical scenario, imaging studies, tumor markers and histologic evaluation
-
Treatment is determined by the local extent of disease, vascular involvement, the presence or absence of metastases, comorbidities and available expertise
-
Complete resection or transplantation remain the only potentially curative therapy
-
Palliation can improve the quality of life and might also improve survival in patients with unresectable disease
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Khan SA et al. (2002) Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document. Gut 51 (Suppl 6): S1–S9
Ishak K.G et al. 1999 Tumors of the liver and intrahepatic bile ducts. In Atlas of Tumor Pathology, 3rd Series [Fascicle 31]. Washington, DC: Armed Forces Institute of Pathology
Liver Cancer Study Group of Japan (2000) The General Rules for the Clinical and Pathological Study of Primary Liver Cancer. Tokyo: Kanehara
Yamasaki S (2003) Intrahepatic cholangiocarcinoma: macroscopic type and stage classification. J Hepatobiliary Pancreat Surg 10: 288–291
Lim JH and Park CK (2004) Pathology of cholangiocarcinoma. Abdom Imaging 29: 540–547
Weinbren K and Mutum SS (1983) Pathological aspects of cholangiocarcinoma. J Pathol 139: 217–238
Shaib Y and El-Serag HB (2004) The epidemiology of cholangiocarcinoma. Semin Liver Dis 24: 115–125
Patel T (2001) Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 33: 1353–1357
Patel T (2002) Worldwide trends in mortality from biliary tract malignancies. BMC Cancer 2: 10
Taylor-Robinson SD et al. (2001) Increase in mortality rates from intrahepatic cholangiocarcinoma in England and Wales 1968–1998. Gut 48: 816–820
Khan SA et al. (2002) Changing international trends in mortality rates for liver, biliary and pancreatic tumours. J Hepatol 37: 806–813
Lazaridis KN and Gores GJ (2005) Cholangiocarcinoma. Gastroenterology 128: 1655–1667
Farrant JM et al. (1991) Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology 100: 1710–1717
Broome U et al. (1996) Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 38: 610–615
Bergquist A et al. (1998) Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study. Hepatology 27: 311–316
Chalasani N et al. (2000) Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study. Hepatology 31: 7–11
Watanapa P and Watanapa WB (2002) Liver fluke-associated cholangiocarcinoma. Br J Surg 89: 962–970
Kubo S et al. (1995) Hepatolithiasis associated with cholangiocarcinoma. World J Surg 19: 637–641
Shaib YH et al. (2005) Risk factors of intrahepatic cholangiocarcinoma in the United States: a case-control study. Gastroenterology 128: 620–626
Kobayashi M et al. (2000) Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus-related cirrhosis. Cancer 88: 2471–2477
Chapman RW (1999) Risk factors for biliary tract carcinogenesis. Ann Oncol 10 (Suppl 4): S308–S311
Sharp GB (2002) The relationship between internally deposited alpha-particle radiation and subsite-specific liver cancer and liver cirrhosis: an analysis of published data. J Radiat Res (Tokyo) 43: 371–380
Tocchi A et al. (2001) Late development of bile duct cancer in patients who had biliary-enteric drainage for benign disease: a follow-up study of more than 1,000 patients. Ann Surg 234: 210–214
Walker NJ et al. (2005) Dose-additive carcinogenicity of a defined mixture of “dioxin-like compounds”. Environ Health Perspect 113: 43–48
Bond GG et al. (1990) Liver and biliary tract cancer among chemical workers. Am J Ind Med 18: 19–24
Boberg KM et al. (2001) The HLA-DR3,DQ2 heterozygous genotype is associated with an accelerated progression of primary sclerosing cholangitis. Scand J Gastroenterol 36: 886–890
Prawan A et al. (2005) Association between genetic polymorphisms of CYP1A2, arylamine N-acetyltransferase 1 and 2 and susceptibility to cholangiocarcinoma. Eur J Cancer Prev 14: 245–250
Bloom CM et al. (1999) Role of US in the detection, characterization, and staging of cholangiocarcinoma. Radiographics 19: 1199–1218
Zhang Y et al. (1999) Intrahepatic peripheral cholangiocarcinoma: comparison of dynamic CT and dynamic MRI. J Comput Assist Tomogr 23: 670–677
Tillich M et al. (1998) Multiphasic helical CT in diagnosis and staging of hilar cholangiocarcinoma. AJR Am J Roentgenol 171: 651–658
Cherqui D et al. (2000) Major liver resection for carcinoma in jaundiced patients without preoperative biliary drainage. Arch Surg 135: 302–308
Hochwald SN et al. (1999) Association of preoperative biliary stenting with increased postoperative infectious complications in proximal cholangiocarcinoma. Arch Surg 134: 261–266
Manfredi R et al. (2004) Magnetic resonance imaging of cholangiocarcinoma. Semin Liver Dis 24: 155–164
Vilgrain V et al. (1997) Intrahepatic cholangiocarcinoma: MRI and pathologic correlation in 14 patients. J Comput Assist Tomogr 21: 59–65
Kim YJ et al. (2003) Usefulness of 18F-FDG PET in intrahepatic cholangiocarcinoma. Eur J Nucl Med Mol Imaging 30: 1467–1472
Anderson CD et al. (2004) Fluorodeoxyglucose PET imaging in the evaluation of gallbladder carcinoma and cholangiocarcinoma. J Gastrointest Surg 8: 90–97
Fritscher-Ravens A et al. (2004) EUS-guided fine-needle aspiration of suspected hilar cholangiocarcinoma in potentially operable patients with negative brush cytology. Am J Gastroenterol 99: 45–51
Farrell RJ et al. (2002) Intraductal US is a useful adjunct to ERCP for distinguishing malignant from benign biliary strictures. Gastrointest Endosc 56: 681–687
Clayton RA et al. (2003) Incidence of benign pathology in patients undergoing hepatic resection for suspected malignancy. Surgeon 1: 32–38
Mansfield JC et al. (1997) A prospective evaluation of cytology from biliary strictures. Gut 40: 671–677
Sugiyama M et al. (1996) Endoscopic transpapillary bile duct biopsy without sphincterotomy for diagnosing biliary strictures: a prospective comparative study with bile and brush cytology. Am J Gastroenterol 91: 465–467
Kipp BR et al. (2004) A comparison of routine cytology and fluorescence in situ hybridization for the detection of malignant bile duct strictures. Am J Gastroenterol 99: 1675–1681
Nakeeb A et al. (1996) Biliary carcinoembryonic antigen levels are a marker for cholangiocarcinoma. Am J Surg 171: 147–152
Bjornsson E et al. (1999) CA 19-9 and CEA are unreliable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis. Liver 19: 501–508
Ramage JK et al. (1995) Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Gastroenterology 108: 865–869
Nichols JC et al. (1993) Diagnostic role of serum CA 19-9 for cholangiocarcinoma in patients with primary sclerosing cholangitis. Mayo Clin Proc 68: 874–879
Patel AH et al. (2000) The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis. Am J Gastroenterol 95: 204–207
Nehls O et al. (2004) Serum and bile markers for cholangiocarcinoma. Semin Liver Dis 24: 139–154
Koopmann J et al. (2004) Mac-2-binding protein is a diagnostic marker for biliary tract carcinoma. Cancer 101: 1609–1615
Lieser MJ et al. (1998) Surgical management of intrahepatic cholangiocarcinoma: a 31-year experience. J Hepatobiliary Pancreat Surg 5: 41–47
Hemming AW et al. (2003) Preoperative portal vein embolization for extended hepatectomy. Ann Surg 237: 686–691
Neuhaus P et al. (1999) Extended resections for hilar cholangiocarcinoma. Ann Surg 230: 808–818
Yoshida T et al. (2002) Prognostic factors after pancreatoduodenectomy with extended lymphadenectomy for distal bile duct cancer. Arch Surg 137: 69–73
Corvera CU et al. (2002) Role of laparoscopy in the evaluation of biliary tract cancer. Surg Oncol Clin N Am 11: 877–891
Jarnagin WR and Shoup M (2004) Surgical management of cholangiocarcinoma. Semin Liver Dis 24: 189–199
McMasters KM et al. (1997) Neoadjuvant chemoradiation for extrahepatic cholangiocarcinoma. Am J Surg 174: 605–608
Wiedmann M et al. (2003) Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma: a phase II pilot study. Cancer 97: 2783–2790
Meyer CG et al. (2000) Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation 69: 1633–1637
Iwatsuki S et al. (1998) Treatment of hilar cholangiocarcinoma (Klatskin tumors) with hepatic resection or transplantation. J Am Coll Surg 187: 358–364
Rea DJ et al. (2005) Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg 242: 451–461
Pitt HA et al. (1995) Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival. Ann Surg 221: 788–797
Nakeeb A et al. (2002) Improved survival in resected biliary malignancies. Surgery 132: 555–563
Kelley ST et al. (2004) Cholangiocarcinoma: advocate an aggressive operative approach with adjuvant chemotherapy. Am Surg 70: 743–748
Daines WP et al. (2004) Gallbladder and biliary tract carcinoma: a comprehensive update, Part 2. Oncology (Williston Park) 18: 1049–1059
Olnes MJ and Erlich R (2004) A review and update on cholangiocarcinoma. Oncology 66: 167–179
Dougherty TJ et al. (1998) Photodynamic therapy. J Natl Cancer Inst 90: 889–905
Berr F (2004) Photodynamic therapy for cholangiocarcinoma. Semin Liver Dis 24: 177–187
Ortner MA (2004) Photodynamic therapy in cholangiocarcinomas. Best Pract Res Clin Gastroenterol 18: 147–154
Ortner ME et al. (2003) Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. Gastroenterology 125: 1355–1363
Bismuth H et al. (1992) Management strategies in resection for hilar cholangiocarcinoma. Ann Surg 215: 31–38
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The author declares no competing financial interests.
Rights and permissions
About this article
Cite this article
Patel, T. Cholangiocarcinoma. Nat Rev Gastroenterol Hepatol 3, 33–42 (2006). https://doi.org/10.1038/ncpgasthep0389
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ncpgasthep0389
This article is cited by
-
Usefulness of serum microRNA as a predictive marker of recurrence and prognosis in biliary tract cancer after radical surgery
Scientific Reports (2019)
-
O-GlcNAcylation mediates metastasis of cholangiocarcinoma through FOXO3 and MAN1A1
Oncogene (2018)
-
Dicer promotes tumorigenesis by translocating to nucleus to promote SFRP1 promoter methylation in cholangiocarcinoma cells
Cell Death & Disease (2017)
-
Differentiating peripheral cholangiocarcinoma in stages T1N0M0 and T2N0M0 from hepatic hypovascular nodules using dynamic contrast-enhanced MRI
Scientific Reports (2017)