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Table of Contents Purpose of This PDQ Summary
General Information
Cellular Classification
Stage Information
Localized Extrahepatic Bile Duct Cancer
Unresectable Extrahepatic Bile Duct Cancer
Recurrent Extrahepatic Bile Duct Cancer
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Changes to This Summary (05/16/2008)
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Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of extrahepatic bile duct cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Cellular classification.
- Staging.
- Treatment options by cancer stage.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
Back to Top General Information
Cancer arising in the extrahepatic bile duct is an uncommon disease, curable by
surgery in fewer than 10% of all cases.[1] Prognosis depends in part on the
tumor’s anatomic location, which affects its resectability. Total resection is
possible in 25% to 30% of lesions that originate in the distal bile duct, a
resectability rate that is clearly better than for lesions that occur in more
proximal sites.[2]
Bile duct cancer may occur more frequently in patients with
a history of primary sclerosing cholangitis, chronic ulcerative colitis,
choledochal cysts, or infections with the fluke, Clonorchis sinensis.[3] The
most common symptoms caused by bile duct cancer are jaundice, pain, fever, and
pruritus.
In most patients, the tumor cannot be completely removed by surgery
and is incurable. Palliative resections or other palliative measures such as
radiation therapy (e.g., brachytherapy or external-beam radiation therapy) or
stenting procedures may maintain adequate biliary drainage and allow for
improved survival. Many bile duct cancers are multifocal. Perineural invasion
has a negative impact on survival.[4]
References
-
Henson DE, Albores-Saavedra J, Corle D: Carcinoma of the extrahepatic bile ducts. Histologic types, stage of disease, grade, and survival rates. Cancer 70 (6): 1498-501, 1992.
[PUBMED Abstract]
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Stain SC, Baer HU, Dennison AR, et al.: Current management of hilar cholangiocarcinoma. Surg Gynecol Obstet 175 (6): 579-88, 1992.
[PUBMED Abstract]
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de Groen PC, Gores GJ, LaRusso NF, et al.: Biliary tract cancers. N Engl J Med 341 (18): 1368-78, 1999.
[PUBMED Abstract]
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Bhuiya MR, Nimura Y, Kamiya J, et al.: Clinicopathologic studies on perineural invasion of bile duct carcinoma. Ann Surg 215 (4): 344-9, 1992.
[PUBMED Abstract]
Back to Top Cellular Classification
The term, cholangiocarcinoma, is sometimes used to refer to any primary cancer
of the biliary system; however, its use is often restricted to intrahepatic
tumors and, therefore, it is not included in this summary. Adenocarcinomas are
the most common type of extrahepatic bile duct cancers. The histologic types
are listed below:[1]
- Carcinoma in situ.
- Adenocarcinoma, not otherwise specified (NOS).
- Adenocarcinoma, intestinal type.
- Mucinous adenocarcinoma.
- Clear cell adenocarcinoma.
- Signet-ring cell carcinoma.
- Adenosquamous carcinoma.
- Squamous cell carcinoma.
- Small cell (oat cell) carcinoma.
- Undifferentiated carcinoma.
- Spindle and giant cell types.
- Small cell types.
- Papillomatosis.
- Papillary carcinoma, noninvasive.
- Papillary carcinoma, invasive.
- Carcinoma, NOS.
Malignant mesenchymal tumors, although rare, include the following:
- Embryonal rhabdomyosarcoma.
- Leiomyosarcoma.
- Malignant fibrous histiocytoma.
References
-
Extrahepatic bile ducts. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 145-150.
Back to Top Stage Information
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
From a clinical and practical point of view, extrahepatic bile duct cancers can
be considered to be localized (resectable) or unresectable. This has obvious
prognostic importance.
Localized extrahepatic bile duct cancer
Patients with localized extrahepatic bile duct cancer have cancer that
can be completely removed by the surgeon. These patients represent a
very small minority of cases of bile duct cancer and usually are those with a
lesion of the distal common bile duct where 5-year survival rate of 25% may be
achieved. Extended resections of hepatic duct bifurcation tumors (Klatskin
tumors) to include adjacent liver, either by lobectomy or removal of portions
of segments 4 and 5 of the liver, may be performed. There has been no
randomized trial of adjuvant therapy for patients with localized disease.
Radiation therapy (external-beam radiation with or without
brachytherapy), however, has been reported to improve local control.[1,2][Level of evidence: 3iiiDiii]
Unresectable extrahepatic bile duct cancer
Patients with unresectable extrahepatic bile duct cancer have cancer that cannot be completely removed by the surgeon.
These patients represent the majority of patients with bile duct cancer. Often the
cancer invades directly into the portal vein, the adjacent liver or along the
common bile duct, and to adjacent lymph nodes. Spread to distant parts of the
body is uncommon but intra-abdominal metastases, particularly peritoneal
metastases, do occur. At this stage patient management is directed at
palliation.
The TNM staging system should be used when staging the disease of a patient
with extrahepatic bile duct cancer. Most cancers are staged following surgery
and pathologic examination of the resected specimen. Evaluation of the extent
of disease at laparotomy is most important for staging.
Staging depends on imaging, which often defines the limits of the tumor, and
surgical exploration with pathologic examination of the resected specimen. In
many cases, it may be difficult to completely resect the primary tumor.
The American Joint Committee on Cancer (AJCC) has designated staging by TNM
classification.[3] Stages defined by TNM classification apply to all primary
carcinomas arising in the extrahepatic bile duct or in the cystic duct and do
not apply to intrahepatic cholangiocarcinomas, sarcomas, or carcinoid
tumors.[3]
TNM definitions
Primary tumor (T)
- TX: Primary tumor cannot be assessed
- T0: No evidence of primary tumor
- Tis: Carcinoma in situ
- T1: Tumor confined to the bile duct histologically
- T2: Tumor invades beyond the wall of the bile duct
- T3: Tumor invades the liver, gallbladder, pancreas, and/or unilateral branches of the portal vein (right or left) or hepatic artery (right or left)
- T4: Tumor invades any of the following: main portal vein or its branches bilaterally, common hepatic artery, or other adjacent structures, such as the colon, stomach, duodenum, or abdominal wall
Regional lymph nodes (N)
- NX: Regional lymph nodes cannot be assessed
- N0: No regional lymph node metastasis
- N1: Regional lymph node metastasis
Distant metastasis (M)
- MX: Distant metastasis cannot be assessed
- M0: No distant metastasis
- M1: Distant metastasis
AJCC stage groupings
Stage 0
Stage IA
Stage IB
Stage IIA
Stage IIB
- T1, N1, M0
- T2, N1, M0
- T3, N1, M0
Stage III
Stage IV
References
-
Kopelson G, Galdabini J, Warshaw AL, et al.: Patterns of failure after curative surgery for extra-hepatic biliary tract carcinoma: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 7 (3): 413-7, 1981.
[PUBMED Abstract]
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Minsky BD, Wesson MF, Armstrong JG, et al.: Combined modality therapy of extrahepatic biliary system cancer. Int J Radiat Oncol Biol Phys 18 (5): 1157-63, 1990.
[PUBMED Abstract]
-
Extrahepatic bile ducts. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 145-150.
Back to Top Localized Extrahepatic Bile Duct Cancer
In a minority of cases, proximal bile duct cancer can be completely resected.
Cures are not often achieved in these patients, in contrast to patients with
tumors arising in the distal bile duct, for whom a 5-year survival may be
achieved in as many as 25% of patients.
Standard treatment options:
- Surgery. The optimum surgical procedure for carcinoma of the extrahepatic
bile duct will vary according to its location along the biliary tree, the
extent of hepatic parenchymal involvement, and the proximity of the tumor to
major blood vessels in this region. It is important to assess the state of the
regional lymph nodes at the time of surgery because proven nodal involvement
may preclude potentially curative resection. It should be fully recognized
that operations for bile duct cancer are usually extensive and have a high
operative mortality (5%–10%) and low curability. Cases with cancer of the
lower end of the duct and regional lymph node involvement may warrant an
extensive resection (Whipple procedure), but bypass operations or endoluminal
stents are alternatives if lymph nodes are clinically involved by the
cancer.[1]
In jaundiced patients, percutaneous transhepatic catheter drainage or endoscopic placement of a stent
for relief of biliary obstruction should be considered before surgery, particularly if jaundice is severe or an
element of azotemia is present. An understanding of both the normal and varied
vascular and ductal anatomy of the porta hepatis has increased the number of
hepatic duct bifurcation tumors (Klatskin tumors) that can be resected.[1-3]
- External-beam radiation (EBRT). EBRT has been used in
conjunction with surgical resection.[4]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with localized extrahepatic bile duct cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Shutze WP, Sack J, Aldrete JS: Long-term follow-up of 24 patients undergoing radical resection for ampullary carcinoma, 1953 to 1988. Cancer 66 (8): 1717-20, 1990.
[PUBMED Abstract]
-
Bismuth H, Nakache R, Diamond T: Management strategies in resection for hilar cholangiocarcinoma. Ann Surg 215 (1): 31-8, 1992.
[PUBMED Abstract]
-
Pinson CW, Rossi RL: Extended right hepatic lobectomy, left hepatic lobectomy, and skeletonization resection for proximal bile duct cancer. World J Surg 12 (1): 52-9, 1988.
[PUBMED Abstract]
-
Cameron JL, Pitt HA, Zinner MJ, et al.: Management of proximal cholangiocarcinomas by surgical resection and radiotherapy. Am J Surg 159 (1): 91-7; discussion 97-8, 1990.
[PUBMED Abstract]
Back to Top Unresectable Extrahepatic Bile Duct Cancer
Patients with unresectable extrahepatic bile duct cancer have cancer that
cannot be completely removed by the surgeon. These patients represent the
majority of cases of bile duct cancer. Often a proximal bile duct cancer
invades directly into the adjacent liver or into the hepatic artery or portal
vein. Portal hypertension may result. Spread to distant parts of the body is
uncommon, though transperitoneal and hematogenous hepatic metastases do occur
with bile duct cancers of all sites. Invasion along the biliary tree and into
the liver is common.
Standard treatment options:
- These patients cannot be cured, but relief of bile duct obstruction is
warranted when symptoms such as pruritus and hepatic dysfunction outweigh other
symptoms from the cancer. Such palliation can be achieved by anastomosis of
the bile duct to the bowel or by the placement of bile duct stents by
operative, endoscopic, or percutaneous techniques.[1,2] Palliative radiation
therapy after biliary bypass or intubation may be beneficial for some patients.
If a percutaneous catheter has been placed, it can be used as a conduit for
placement of sources for brachytherapy.[3,4] Patients with unresectable tumors
should be considered for inclusion in clinical trials whenever possible.
Treatment options under clinical evaluation:
- Patients with unresectable disease can be considered candidates for
inclusion in clinical trials that explore ways to improve the effects of
radiation therapy with various radiation sensitizers such as hyperthermia,
radiosensitizer drugs, or cytotoxic chemotherapeutic agents.
- Patients with unresectable disease can be considered candidates for phase I
and II studies of chemotherapeutic agents or biologics. Fluorouracil,
doxorubicin, and mitomycin have been reported to produce transient partial
remissions in a small proportion of patients. Other drugs and drug
combinations await evaluation.[5]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with unresectable extrahepatic bile duct cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Nordback IH, Pitt HA, Coleman J, et al.: Unresectable hilar cholangiocarcinoma: percutaneous versus operative palliation. Surgery 115 (5): 597-603, 1994.
[PUBMED Abstract]
-
Levy MJ, Baron TH, Gostout CJ, et al.: Palliation of malignant extrahepatic biliary obstruction with plastic versus expandable metal stents: An evidence-based approach. Clin Gastroenterol Hepatol 2 (4): 273-85, 2004.
[PUBMED Abstract]
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Fritz P, Brambs HJ, Schraube P, et al.: Combined external beam radiotherapy and intraluminal high dose rate brachytherapy on bile duct carcinomas. Int J Radiat Oncol Biol Phys 29 (4): 855-61, 1994.
[PUBMED Abstract]
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Shin HS, Seong J, Kim WC, et al.: Combination of external beam irradiation and high-dose-rate intraluminal brachytherapy for inoperable carcinoma of the extrahepatic bile ducts. Int J Radiat Oncol Biol Phys 57 (1): 105-12, 2003.
[PUBMED Abstract]
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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 34 (7): 977-86, 1998.
[PUBMED Abstract]
Back to Top Recurrent Extrahepatic Bile Duct Cancer
The prognosis for any treated cancer patient with progressing, recurring, or
relapsing extrahepatic bile duct cancer is poor. Deciding on further treatment
depends on many factors, including prior treatment and site of recurrence, as
well as individual patient considerations. Relief of recurrent jaundice will
usually improve quality of life. Clinical trials are appropriate and should be
considered when possible.[1,2]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent extrahepatic bile duct cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Bartlett DL, Ramanathan RK, Deutsch M: Cancer of the biliary tree. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1009-31.
-
Nordback IH, Pitt HA, Coleman J, et al.: Unresectable hilar cholangiocarcinoma: percutaneous versus operative palliation. Surgery 115 (5): 597-603, 1994.
[PUBMED Abstract]
Back to Top Get More Information From NCI
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Back to Top Changes to This Summary (05/16/2008)
The PDQ cancer information summaries are reviewed regularly and updated as
new information becomes available. This section describes the latest
changes made to this summary as of the date above.
Editorial changes were made to this summary.
Back to Top More Information
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