eMedicine Specialties > Oncology > Carcinomas of the Gastrointestinal Tract

Cholangiocarcinoma: Treatment & Medication

Author: Peter E Darwin, MD, Associate Professor, Director of GI Endoscopy, Department of Medicine, Division of Gastroenterology, University of Maryland School of Medicine
Coauthor(s): Andrew Scott Kennedy, MD, Co-Medical Director, Wake Radiology Oncology; Jennifer Lynn Bonheur, MD, Attending Physician, Division of Gastroenterology, Lenox Hill Hospital
Contributor Information and Disclosures

Updated: Jan 8, 2009

Treatment

Medical Care

  • Stenting may relieve pruritus and improve quality of life.
    • Palliative plastic or metal stents can be placed by ERCP or PTC to relieve biliary obstruction. They usually are used if the tumor is unresectable or if the patient is not a surgical candidate. Debate exists about whether preoperative stenting is warranted, but most surgeons believe that preoperative biliary decompression does not alter the outcome of surgery.
    • Plastic stents usually occlude in 3 months and require replacement.
    • Metal stents are more expensive but expand to a larger diameter and tend to stay patent longer. Adequate biliary drainage can be achieved in a high percentage of cases.
  • Photodynamic therapy (PDT) is a new experimental local cancer therapy already in use for other GI malignancies.13,14
  • PDT is a 2-step process: the first step is intravenous (IV) administration of a photosensitizer; the second step is activation by light illumination at an appropriate wavelength.13,14
  • PDT is effective in restoring biliary drainage and improving quality of life in patients with nonresectable disseminated cholangiocarcinomas. Survival times may be longer than those reported previously. A prospective, multicenter study showed a significant survival benefit in the PDT treatment group.13 An additional multicenter study is being planned.
  • In addition, other endoscopic forms of palliation, such as brachytherapy, have been used.15
  • Most often, chemotherapy is given in low doses to act as a radiation sensitizer during a 4- to 5-week course of external-beam radiotherapy. Primary chemotherapy has been evaluated, as well including gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma.16,17
  • Adjuvant and preoperative radiation therapy has been used to reduce tumors in an effort to make them resectable. This therapy has been performed with and without concurrent chemotherapy as a radiation sensitizer.
  • The value of adjuvant radiotherapy has been to improve local control, with variable effect on overall survival rate after complete resection. Several series have shown an increase in median survival duration with postoperative radiation, from 8 months with surgery alone to more than 19 months.
  • Special radiation techniques have been used, such as intraluminal brachytherapy and external-beam therapy during surgery (ie, intraoperative radiotherapy [IORT]). See Image 3 for treatment planning technique.
  • Primary radiotherapy without surgery, with or without chemotherapy, has provided a survival advantage and significant palliation over stent placement or bypass surgery alone in patients with medially inoperable or unresectable tumors.
  • Chemotherapy agents used without radiotherapy or surgery do not appear to provide any local control or meaningful survival benefit.
  • The most used agent is 5-fluorouracil, which has a partial  response rate of about 12%. Gemcitabine has a similar response rate. Although fluoropyrimidines and doxorubicin have been reported to have response rates as high as 30-40%, partial responses lasting from weeks to months have been observed in only 10-35% of trials.16,17 Marimastat in early trials has been reported to be associated with a higher rate of response, but the number of patients treated with this agent is small. Overall, the duration of any response seen has been no better than 3-6 months, and median survival has been 11 months or less.
  • For palliative treatment, celiac-plexus block via regional injection of alcohol or other sclerosing agent can relieve pain in the mid back that is associated with retroperitoneal tumor growth.

Surgical Care

Complete surgical resection is the only therapy to afford a chance of cure. Unfortunately, only 10% of patients present with early stage disease and are considered for curative resection. Intrahepatic and Klatskin tumors6 require liver resection, which may not be an option for older patients with comorbid conditions. In one report, 15% of patients with proximal lesions were candidates for complete resections, with higher rates in patients with mid-ductal tumors (33%) or distal tumors (56%). The survival rate for patients with proximal tumors can be 40% if negative margins are obtained. The National Comprehensive Cancer Network suggests reresection, ablation, or chemotherapy for intrahepatic cholangiocarcinomas that are resected with microscopic margins or residual local disease.18 Those with no residual local disease after resection can be followed with imaging periodically.

  • Orthotopic liver transplantation is considered for some patients with proximal tumors who are not candidates for resection because of the extent of tumor spread in the liver. The largest series reports a 53% 5-year survival rate and a 38% complete pathologic response rate with preoperative radiation therapy and chemotherapy. Liver transplantation may have a survival benefit over palliative treatments, especially for patients with tumors in the initial stages. One study has demonstrated a 5-year survival rate greater than 80% in select patients.19
  • Distal tumors are resected via Whipple procedure; periampullary region tumors have a uniformly better prognosis, with a long-term survival rate of 30-40%.
  • Patterns of treatment failure after curative surgery show disappointingly high rates of tumor bed and regional nodal recurrence. This finding may be due in part to the narrow pathologic margins; however, the regional node failure rate is approximately 50%, and the distal metastases rate is 30-40%. Failures are correlated with TNM stage.
  • Palliative procedures are required if internal stenting cannot be accomplished and/or external stenting is not desirable or cannot be obtained; surgical bypass, particularly for tumors in the common bile duct, should be performed.

Consultations

Gastroenterologists, interventional radiologists, and transplant/biliary surgeons play a key role in diagnosis and management. Radiation oncology and medical oncology specialists are part of the multidisciplinary team taking part in the treatment of both patients with curatively resected tumors and those with unresectable tumors. Radiation oncologists have taken a more significant role in therapy for cholangiocarcinomas since the early 1980s.

More on Cholangiocarcinoma

Overview: Cholangiocarcinoma
Differential Diagnoses & Workup: Cholangiocarcinoma
Treatment & Medication: Cholangiocarcinoma
Follow-up: Cholangiocarcinoma
Multimedia: Cholangiocarcinoma
References
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References

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  2. Lake JR. Benign and malignant neoplasms of the gallbladder, bile ducts and ampulla. In: Sleisinger MH, Fordtran JS, eds. Gastrointestinal Disease. 5th ed. Vol 2. Philadelphia, Pa: WB Saunders. 1993:1891-1902.

  3. Lotze MT, Flickinger JC, Carr BI. Hepatobiliary neoplasms. In: Devita V, Hellman S, Rosenberg S. Cancer: Principles and Practice of Oncology. 4th. Philadelphia, Pa: Lippincott; 1993:883-907.

  4. de Groen PC, Gores GJ, LaRusso NF, et al. Biliary tract cancers. N Engl J Med. Oct 28 1999;341(18):1368-78. [Medline].

  5. 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. Feb 1965;38:241-56. [Medline].

  6. Clary B, Jarnigan W, Pitt H, et al. Hilar cholangiocarcinoma. J Gastrointest Surg. Mar-Apr 2004;8(3):298-302. [Medline].

  7. American Cancer Society Statistics. Estimated New Cancer Cases and Deaths, 2007. Available at http://www.cancer.org/downloads/stt/CFF2007EstCsDths07.pdf. Accessed April 11, 2008.

  8. Biliary Tract Cancer. In: Schottenfeld D, Fraumeni J. Cancer. Epidemiology and Prevention. 3rd Edition. Oxford University Press; 2006:787-800.

  9. Chalasani N, Baluyut A, Ismail A, et al. Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study. Hepatology. Jan 2000;31(1):7-11. [Medline].

  10. Keiding S, Hansen SB, Rasmussen HH, et al. Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography. Hepatology. Sep 1998;28(3):700-6. [Medline].

  11. 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.

  12. 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. Jan 2004;99(1):45-51. [Medline].

  13. Ortner MA, Liebetruth J, Schreiber S, et al. Photodynamic therapy of nonresectable cholangiocarcinoma. Gastroenterology. Mar 1998;114(3):536-42. [Medline].

  14. Ortner ME, Caca K, Berr F, et al. Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. Gastroenterology. Nov 2003;125(5):1355-63. [Medline].

  15. 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.

  16. 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. Feb 2005;16(2):279-81. [Medline].

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Further Reading

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Keywords

cholangiocarcinoma, CCC, biliary duct system, perihilar tumors, Klatskin tumors, adenocarcinoma, primary sclerosing cholangitis, PSC

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Contributor Information and Disclosures

Author

Peter E Darwin, MD, Associate Professor, 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 College of Gastroenterology, American College of Physicians, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Coauthor(s)

Andrew Scott Kennedy, MD, Co-Medical Director, Wake Radiology Oncology
Andrew Scott Kennedy, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Hepato-Pancreato-Biliary Association, American Society for Therapeutic Radiology and Oncology, American Society of Clinical Oncology, and Radiological Society of North America
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 Academy of Sciences, New York Society for Gastrointestinal Endoscopy, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Michael Perry, MD, MS, MACP, Nellie B Smith Chair of Oncology Emeritus, Professor, Department of Internal Medicine, Division of Hematology and Oncology, University of Missouri/Ellis Fischel Cancer Center
Michael Perry, MD, MS, MACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, International Association for the Study of Lung Cancer, and Missouri State Medical Association
Disclosure: Bionumerik Consulting fee Consulting; Proactya Consulting fee Consulting; GSK Consulting fee Consulting; NovoNordisk Consulting fee Consulting; Amgen Honoraria Speaking and teaching; GSK Consulting fee Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Benjamin Movsas, MD, Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center
Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

 
 
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