Skip to main content

Advertisement

SpringerLink
Log in

Diagnosis and treatment of cholangiocarcinoma

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Epidemiologic studies have demonstrated increasing mortality rates from intrahepatic cholangiocarcinoma during the past decades. Primary sclerosing cholangitis is the most important predisposing condition to the development of cholangiocarcinoma. Improvements in noninvasive diagnostic techniques have led to decreased use of invasive procedures. Magnetic resonance imaging (MRI) has the potential to depict parenchymal, ductal, and vascular tumor involvement. However, diagnosis can be difficult, and often ultrasonography, MRI, CT, and invasive cholangiography are complementary investigations. Genetic aberrations in brush cytology specimens should be explored further in prospective studies. Endoscopic ultrasonography, intraductal ultrasonography, and positron emission tomography are interesting techniques that are under evaluation. Radical surgery with negative histologic margins is the only curative option in cholangiocarcinoma. With more aggressive surgical approaches, including partial hepatectomy, 3-year survival rates of 35% to 50% can be achieved. Liver transplantation for unresectable cholangiocarcinoma was shown to be feasible in pilot studies of highly selected patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. de Groen PC, Gores GJ, LaRusso NF, et al.: Biliary tract cancers. N Engl J Med 1999, 341:1368–1378.

    Article  Google Scholar 

  2. Ahrendt SA, Nakeeb A, Pitt HA: Cholangiocarcinoma. Clin Liver Dis 2001, 5:191–218.

    Article  PubMed  CAS  Google Scholar 

  3. Patel T: Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 2001, 33:1353–1357.

    Article  PubMed  CAS  Google Scholar 

  4. Taylor-Robinson SD, Toledano MB, Arora S, et al.: Increase in mortality rates from intrahepatic cholangiocarcinoma in England and Wales 1968–1998. Gut 2001, 48:816–820.

    Article  PubMed  CAS  Google Scholar 

  5. Boberg KM, Bergquist A, Mitchell S, et al.: Cholangiocarcinoma in primary sclerosing cholangitis: risk factors and clinical presentation. Scand J Gastroenterol 2002, 37:1205–1211.

    Article  PubMed  CAS  Google Scholar 

  6. Khan SA, Davidson BR, Goldin R, et al.: Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document. Gut 2002, 51(Suppl VI):vi1-vi9. This consensus report on diagnosis and treatment of cholangiocarcinoma promoted by the British Association for the Study of the Liver offers an excellent updated review and thorough and balanced assessment of published studies. The report is recommended as an overview of current recommendations and for practical advice.

    Article  PubMed  Google Scholar 

  7. Kuszyk BS, Soyer P, Bluemke DA, Fishman EK: Intrahepatic cholangiocarcinoma: the role of imaging in detection and staging. Crit Rev Diagn Imaging 1997, 38:59–88.

    PubMed  CAS  Google Scholar 

  8. Cha JH, Han JK, Kim TK, et al.: Preoperative evaluation of Klatskin tumor: accuracy of spiral CT in determining vascular invasion as a sign of unresectability. Abdom Imaging 2000, 25:500–507.

    Article  PubMed  CAS  Google Scholar 

  9. Yeh T-S, Jan Y-Y, Tseng J-H, et al.: Malignant perihilar biliary obstruction: magnetic resonance cholangiopancreatographic findings. Am J Gastroenterol 2000, 95:432–440.

    Article  PubMed  CAS  Google Scholar 

  10. Zidi SH, Prat F, Le Guen O, et al.: Performance characteristics of magnetic resonance cholangiography in the staging of malignant hilar strictures. Gut 2000, 46:103–106. This study is a prospective comparison of the performance of MRCP relative to ERCP in staging of malignant hilar strictures. MRCP tended to undergrade tumor extension but appeared to provide information that might have implications for treatment choice and possible avoidance of unnecessary endoscopic procedures. Results should be confirmed in new prospective studies.

    Article  PubMed  CAS  Google Scholar 

  11. Lopera JE, Soto JA, M’ura F: Malignant hilar and perihilar biliary obstruction: use of MR cholangiography to define the extent of biliary ductal involvement and plan percutaneous interventions. Radiology 2001, 220:90–96. This prospective study comparing MRCP with ERCP shows principally the same results as those of Zidi et al. [10], including the power of MRCP to predict extent of cancer in a high proportion of patients and to guide planning of therapy.

    PubMed  CAS  Google Scholar 

  12. Braga HJV, Imam K, Bluemke DA: MR imaging of intrahepatic cholangiocarcinoma: use of ferumoxides for lesion localization and extension. AJR Am J Roentgenol 2001, 177:111–114.

    PubMed  CAS  Google Scholar 

  13. Fritscher-Ravens A, Broering DC, Sriram PVJ, et al.: EUS-guided fine-needle aspiration cytodiagnosis of hilar cholangiocarcinoma: a case series. Gastrointest Endosc 2000, 52:534–540.

    Article  PubMed  CAS  Google Scholar 

  14. Levy MJ, Vazquez-Sequeiros E, Wiersema MJ: Evaluation of the pancreaticobiliary ductal systems by intraductal US. Gastrointest Endosc 2002, 55:397–408.

    Article  PubMed  Google Scholar 

  15. Tamada K, Nagai H, Yasuda Y, et al.: Transpapillary intraductal US prior to biliary drainage in the assessment of longitudinal spread of extrahepatic bile duct carcinoma. Gastrointest Endosc 2001, 53:300–307.

    PubMed  CAS  Google Scholar 

  16. Kluge R, Schmidt F, Caca K, et al.: Positron emission tomography with [18F]fluoro-2-deoxy-D-glucose for diagnosis and staging of bile duct cancer. Hepatology 2001, 33:1029–1035.

    Article  PubMed  CAS  Google Scholar 

  17. Kato T, Tsukamoto E, Kuge Y, et al.: Clinical role of 18F-FDG PET for initial staging of patients with extrahepatic bile duct cancer. Eur J Nucl Med 2002, 29:1047–1054.

    Article  CAS  Google Scholar 

  18. Keiding S, Hansen SB, Rasmussen HH, et al.: Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography. Hepatology 1998, 28:700–706.

    Article  PubMed  CAS  Google Scholar 

  19. Ponsioen CY, Vrouenraets SME, van Milligen de Wit AWM, et al.: Value of brush cytology for dominant strictures in primary sclerosing cholangitis. Endoscopy 1999, 31:305–309.

    Article  PubMed  CAS  Google Scholar 

  20. Lindberg B, Arnelo U, Bergquist A, et al.: Diagnosis of biliary strictures in conjunction with endoscopic retrograde cholangiopancreaticography, with special reference to patients with primary sclerosing cholangitis. Endoscopy 2002, 34:909–916.

    Article  PubMed  CAS  Google Scholar 

  21. Boberg KM, Jebsen P, Clausen OP, et al.: Cholangiocarcinoma in situ in primary sclerosing cholangitis. J Hepatol 2002, 39:453.

    Article  Google Scholar 

  22. Ryan ME, Baldauf MC: Comparison of flow cytometry for DNA content and brush cytology for detection of malignancy in pancreaticobiliary strictures. Gastrointest Endosc 1994, 40:133–139.

    Article  PubMed  CAS  Google Scholar 

  23. Rumalla A, Baron TH, Leontovich O, et al.: Improved diagnostic yield of endoscopic biliary brush cytology by digital image analysis. Mayo Clin Proc 2001, 76:29–33.

    Article  PubMed  CAS  Google Scholar 

  24. Boberg KM, Schrumpf E, Bergquist A, et al.: Cholangiocarcinoma in primary sclerosing cholangitis: K-ras mutations and Tp53 dysfunction are implicated in the neoplastic development. J Hepatol 2000, 32:374–380.

    Article  PubMed  CAS  Google Scholar 

  25. Sturm PDJ, Rauws EAJ, Hruban RH, et al.: Clinical value of K-ras codon 12 analysis and endobiliary brush cytology for the diagnosis of malignant extrahepatic bile duct stenosis. Clin Cancer Res 1999, 5:629–635.

    PubMed  CAS  Google Scholar 

  26. Taniai M, Higuchi H, Burgart LJ, Gores GJ: p16INK4a promoter mutations are frequent in primary sclerosing cholangitis (PSC) and PSC-associated cholangiocarcinoma. Gastroenterology 2002, 123:1090–1098.

    Article  PubMed  CAS  Google Scholar 

  27. Morales CP, Burdick JS, Saboorian MH, et al.: In situ hybridization for telomerase RNA in routine cytologic brushings for the diagnosis of pancreaticobiliary malignancies. Gastrointest Endosc 1998, 48:402–405.

    Article  PubMed  CAS  Google Scholar 

  28. Kubicka S, Kühnel F, Flemming P, et al.: K-ras mutations in the bile from patients with primary sclerosing cholangitis. Gut 2001, 48:403–408.

    Article  PubMed  CAS  Google Scholar 

  29. Johnson PJ, Lo YMD: Plasma nucleic acids in the diagnosis and management of malignant disease. Clin Chem 2002, 48:1186–1193.

    PubMed  CAS  Google Scholar 

  30. Chamberlain RS, Blumgart LH: Hilar cholangiocarcinoma: a review and commentary. Ann Surg Oncol 2000, 7:55–66. This comprehensive review includes a list of 15 selected series of surgical resection for hilar cholangiocarcinoma published since 1990 and a discussion of strategies. The authors emphasize that the majority of groups now routinely do liver resections in 50% to 100% of cases and that an aggressive surgical approach can achieve 40% to 60% 3-year survival rates.

    Article  PubMed  CAS  Google Scholar 

  31. Ohtsuka M, Ito H, Kimura F, et al.: Results of surgical treatment for intrahepatic cholangiocarcinoma and clinicopathological factors influencing survival. Br J Surg 2002, 89:1525–1531.

    Article  PubMed  CAS  Google Scholar 

  32. Lillemoe KD, Cameron JL: Surgery for hilar cholangiocarcinoma: the Johns Hopkins approach. J Hepatobiliary Pancreat Surg 2000, 7:115–121.

    Article  PubMed  CAS  Google Scholar 

  33. Kitagawa Y, Nagino M, Kamiya J, et al.: Lymph node metastasis from hilar cholangiocarcinoma: audit of 110 patients who underwent regional and paraaortic node dissection. Ann Surg 2001, 233:385–392.

    Article  PubMed  CAS  Google Scholar 

  34. Jarnagin WR, Fong Y, DeMatteo RP, et al.: Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg 2001, 234:507–519. Results of experience with a large number (n=225) of patients are presented, based on prospectively collected clinical, radiologic, histopathologic, and survival data. Because existing staging systems are poor predictors of resectability and survival, the authors propose a preoperative staging system based on imaging data and demonstrate the applicability of this system.

    Article  PubMed  CAS  Google Scholar 

  35. Madariaga JR, Iwatsuki S, Todo S, et al.: Liver resection for hilar and perihilar cholangiocarcinomas: a study of 62 cases. Ann Surg 1998, 227:70–79.

    Article  PubMed  CAS  Google Scholar 

  36. Neuhaus P, Jonas S, Bechstein WO, et al.: Extended resections for hilar cholangiocarcinoma. Ann Surg 1999, 230:808–818.

    Article  PubMed  CAS  Google Scholar 

  37. Meyer CG, Penn I, James L: Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation 2000, 69:1633–1637.

    Article  PubMed  CAS  Google Scholar 

  38. Hassoun Z, Gores GJ, Rosen CB: Preliminary experience with liver transplantation in selected patients with unresectable hilar cholangiocarcinoma. Surg Oncol Clin N Am 2002, 11:909–921.

    Article  PubMed  Google Scholar 

  39. Sudan D, DeRoover A, Chinnakotla S, et al.: Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant 2002, 2:774–779.

    Article  PubMed  Google Scholar 

  40. Chang W-H, Kortan P, Haber GB: Outcome in patients with bifurcation tumors who undergo unilateral versus bilateral hepatic duct drainage. Gastrointest Endosc 1998, 47:354–362.

    Article  PubMed  CAS  Google Scholar 

  41. De Palma GD, Galloro G, Siciliano S, et al.: Unilateral versus bilateral endoscopic hepatic duct drainage in patients with malignant hilar biliary obstruction: results of a prospective, randomized, and controlled study. Gastrointest Endosc 2001, 53:547–553.

    Article  Google Scholar 

  42. Hintze RE, Abou-Rebyeh H, Adler A, et al.: Magnetic resonance cholangiopancreatography-guided unilateral endoscopic stent placement for Klatskin tumors. Gastrointest Endosc 2001, 53:40–46.

    Article  PubMed  CAS  Google Scholar 

  43. Flamm CR, Mark DH, Aronson N: Evidence-based assessment of ERCP approaches to managing pancreaticobiliary malignancies. Gastrointest Endosc 2002, 56 (Suppl):S218-S225.

    Article  PubMed  Google Scholar 

  44. Hejna M, Pruckmayer M, Raderer M: The role of chemotherapy and radiation in the management of biliary cancer: a review of the literature. Eur J Cancer 1998, 34:977–986.

    Article  PubMed  CAS  Google Scholar 

  45. Ortner M-A EJ, Liebetruth J, Schreiber S, et al.: Photodynamic therapy of nonresectable cholangiocarcinoma. Gastroenterology 1998, 114:536–542.

    Article  PubMed  CAS  Google Scholar 

  46. Berr F, Wiedmann M, Tannapfel A, et al.: Photodynamic therapy for advanced bile duct cancer: evidence for improved palliation and extended survival. Hepatology 2000, 31:291–298. This prospective phase II trial included 23 patients with nonresectable cholangiocarcinoma who were treated with photodynamic therapy and biliary endoprosthesis. The 6-month rate of survival from diagnosis was 91%, significantly longer than in historical control subjects. Bacterial cholangitis and prolonged hospital stays were major problems. This treatment is experimental and needs to be tested in controlled studies, but it represents an interesting principle of palliation.

    Article  PubMed  CAS  Google Scholar 

  47. Gjertsen MK, Buanes T, Rosseland AR, et al.: Intradermal ras peptide vaccination with granulocyte-macrophage colonystimulating factor as adjuvant: clinical and immunological responses in patients with pancreatic adenocarcinoma. Int J Cancer 2001, 92:441–450.

    Article  PubMed  CAS  Google Scholar 

  48. Sirica AE, Lai G-H, Endo K, et al.: Cyclooxygenase-2 and ERBB-2 in cholangiocarcinoma: potential therapeutic targets. Semin Liver Dis 2002, 22:303–313.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Department, 0027, Rikshospitalet, Oslo, Norway

    Kirsten Muri Boberg MD, PhD & Erik Schrumpf MD, PhD

Authors
  1. Kirsten Muri Boberg MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erik Schrumpf MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boberg, K.M., Schrumpf, E. Diagnosis and treatment of cholangiocarcinoma. Curr Gastroenterol Rep 6, 52–59 (2004). https://doi.org/10.1007/s11894-004-0026-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-004-0026-1

Keywords

Search

Navigation