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Important: This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Gallbladder cancer


Table of Contents

GENERAL INFORMATION
CELLULAR CLASSIFICATION
STAGE INFORMATION
AJCC Stage Groupings
Stage 0
Stage I
Stage II
Stage III
Stage IVA
Stage IVB
Localized (Stage I-II)
Unresectable (Stage III-IV)
TREATMENT OPTION OVERVIEW
LOCALIZED GALLBLADDER CANCER
UNRESECTABLE GALLBLADDER CANCER
RECURRENT GALLBLADDER CANCER

GENERAL INFORMATION

Cancer that arises in the gallbladder is uncommon. In patients whose superficial cancer is discovered on pathological examination of tissue after gallbladder removal for other reasons, the disease is often cured without further therapy. Even in patients who present with symptoms, the tumor is rarely diagnosed preoperatively.[1] In such cases, the tumor often cannot be removed completely by surgery and is incurable, although palliative measures may benefit these patients. Cholelithiasis is an associated finding in the majority of cases, but fewer than 1% of patients with cholelithiasis develop this cancer. The most common symptoms caused by gallbladder cancers are jaundice, pain, and fever.

References:

  1. Chao T, Greager JA: Primary carcinoma of the gallbladder. Journal of Surgical Oncology 46(4): 215-221, 1991.


CELLULAR CLASSIFICATION

The histologic types of gallbladder cancer include the following. Some histologic types have a better prognosis than others; papillary carcinomas have the best prognosis.

carcinoma in situ
adenocarcinoma
papillary adenocarcinoma
adenocarcinoma, intestinal type
mucinous adenocarcinoma
clear cell adenocarcinoma
signet-ring cell
adenosquamous carcinoma
squamous cell carcinoma
small cell (oat cell) carcinoma
undifferentiated carcinoma
carcinoma, NOS
carcinosarcoma


STAGE INFORMATION

The American Joint Committee on Cancer (AJCC) has designated staging by the TNM classification as follows:[1]


-- TNM definitions --
Primary tumor (T)
  TX:  Primary tumor cannot be assessed
  T0:  No evidence of primary tumor
  Tis: Carcinoma in situ
  T1:  Tumor invades lamina propria or muscle layer
    T1a:  Tumor invades lamina propria
    T1b:  Tumor invades the muscle layer
  T2:  Tumor invades the perimuscular connective tissue; no extension beyond
       the serosa or into the liver
  T3:  Tumor perforates the serosa (visceral peritoneum) or directly invades
       one adjacent organ, or both (extension 2 cm or less into the
       liver)
  T4:  Tumor extends more than 2 cm into the liver, and/or into two or more
       adjacent organs (stomach, duodenum, colon, pancreas, omentum,
       extrahepatic bile ducts, any involvement of the liver)

Regional lymph nodes (N)
  NX:  Regional lymph nodes cannot be assessed
  N0:  No regional lymph node metastasis
  N1:  Metastasis in cystic duct, pericholedochal, and/or hilar lymph nodes
       (i.e., in the hepatoduodenal ligament)
  N2:  Metastasis in peripancreatic (head only), periduodenal, periportal,
       celiac, and/or superior mesenteric lymph nodes

Distant metastasis (M)
  MX:  Distant metastasis cannot be assessed
  M0:  No distant metastasis
  M1:  Distant metastasis


AJCC Stage Groupings


Stage 0

Tis, N0, M0


Stage I

T1, N0, M0


Stage II

T2, N0, M0


Stage III

T1, N1, M0
T2, N1, M0
T3, N0, M0
T3, N1, M0


Stage IVA

T4, N0, M0
T4, N1, M0


Stage IVB

Any T, N2, M0
Any T, Any N, M1


Localized (Stage I-II)

These patients have cancer confined to the gallbladder wall that can be completely resected. They represent a minority of cases of gallbladder cancer. Patients with muscular invasion or beyond have a survival of less than 15%. Regional lymphatics and lymph nodes should be removed along with the gallbladder.


Unresectable (Stage III-IV)

With the exception of patients with T1 N1 M0 or T2 N2 M0 disease, these patients have cancer that cannot be completely resected. They represent the majority of cases of gallbladder cancer. Often the cancer invades directly into adjacent liver or biliary lymph nodes or has disseminated throughout the peritoneal cavity. Spread to distant parts of the body is uncommon. At this stage, standard therapy is directed at palliation. Because of its rarity, no specific clinical trials exist; however, such patients can be included in trials aimed at improving local control by combining radiation therapy with radiosensitizer drugs.

References:

  1. Gallbladder. In: American Joint Committee on Cancer: AJCC Cancer Staging Manual. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 103-108.


TREATMENT OPTION OVERVIEW

The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.


LOCALIZED GALLBLADDER CANCER

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 levels of evidence summary for more information.

(Tis, T1a or b, selected T2, rare T3; N0; M0)

When gallbladder cancer is previously unsuspected and is discovered in the mucosa of the gallbladder at pathologic examination, it is curable in more than 80% of cases. However, gallbladder cancer suspected before surgery because of symptoms usually penetrates the muscularis and serosa and is curable in fewer than 5% of patients.

Tsukada et al. have reported on patterns of lymph node spread from gallbladder cancer and outcomes of patients with metastases to lymph nodes in 111 consecutive surgical patients in a single institution from 1981-1995.[1][Level of evidence: 3iiiA] The standard surgical procedure was removal of the gallbladder, a wedge resection of the liver, resection of the extrahepatic bile duct, and resection of the regional (N1 and N2) lymph nodes. Kaplan-Meier estimates of the 5-year survival for node negative tumors pathologically staged as T2-T4 were 42.5% plus or minus 6.5% and for similar node positive tumors, 31% plus or minus 6.2%.

Treatment options:

Standard:

1. Surgery: In previously unsuspected gallbladder cancer, discovered in the surgical specimen following a routine gallbladder operation and confined to mucosa or muscle layer (T1), the majority of patients are cured and require no further surgical intervention.[2] Re-exploration to resect liver tissue near the gallbladder bed and lymphadenectomy including N1 and N2 lymph node basins may be associated with delayed recurrences in patients with stage I or II gallbladder cancer.[3,4] Apparently localized cancers that are suspected before or during the operation can be surgically removed with a wedge of liver and lymph nodes and lymphatic tissue anterior to the portal triad and along the hepatic artery, behind the pancreas and around the superior mesenteric artery. Cure will occasionally be achieved. In jaundiced patients (stage III or stage IV), there should be consideration of preoperative percutaneous transhepatic biliary drainage for relief of biliary obstruction.

Implantation of the carcinoma at all port sites (including the camera site) after laparoscopic removal of an unsuspected cancer is a problem. Even for stage I cancers, the port sites must be excised completely.[5]

2. External-beam irradiation: The use of external-beam irradiation with or without chemotherapy as a primary treatment has been reported in small groups of patients to produce short-term control. Similar benefits have been reported for radiation therapy with or without chemotherapy administered following resection.[6,7]

Under clinical evaluation:
Clinical trials are exploring ways of improving local control with
radiation therapy combined with radiosensitizer drugs. When possible, such
patients are appropriately considered candidates for these studies.

References:

  1. Tsukada K, Kurosaki I, Uchida K, et al.: Lymph node spread from carcinoma of the gallbladder. Cancer 80(4): 661-667, 1997.

  2. Chijiiwa K, Tanaka M: Carcinoma of the gallbladder: an appraisal of surgical resection. Surgery 115(6): 751-756, 1994.

  3. Shirai Y, Yoshida K, Tsukada K, et al.: Inapparent carcinoma of the gallbladder: an appraisal of a radical second operation after simple cholecystectomy. Annals of Surgery 215(4): 326-331, 1992.

  4. Yamaguchi K, Chijiiwa K, Saiki S, et al.: Retrospective analysis of 70 operations for gallbladder carcinoma. British Journal of Surgery 84(2): 200-204, 1997.

  5. Wibbenmeyer LA, Wade TP, Chen RC, et al.: Laparoscopic cholecystectomy can disseminate in situ carcinoma of the gallbladder. Journal of the American College of Surgeons 181(6): 504-510, 1995.

  6. Smoron GL: Radiation therapy of carcinoma of gallbladder and biliary tract. Cancer 40(4): 1422-1424, 1977.

  7. Hejna M, Pruckmayer M, Raderer M: The role of chemotherapy and radiation in the management of biliary cancer: a review of the literature. European Journal of Cancer 34(7): 977-986, 1998.


UNRESECTABLE GALLBLADDER CANCER

(any T, N1, M0; any T, N0 or N1, M1; most T3, N0, M0; T4, N0, M0)

These patients are not curable. Significant symptomatic benefit can often be achieved with relief of biliary obstruction. A few patients have very slow-growing tumors and may live several years.

Treatment options:

Standard:

Palliative treatment options may include the following:

1. Palliative surgery will often relieve bile duct obstruction and is warranted when symptoms produced by biliary blockade (pruritus, hepatic dysfunction, cholangitis) outweigh other symptoms from the cancer.

2. An alternative approach to biliary obstruction is percutaneous transhepatic radiologic catheter bypass or endoscopically placed stents.

3. Standard external-beam radiation therapy can, on occasion, alleviate biliary obstruction in some patients and may supplement bypass procedures.

4. Standard chemotherapy is usually not effective although occasional patients may be palliated. Clinical trials should be considered as a first option for most patients.[1,2]

Under clinical evaluation:
Clinical trials are in progress to improve local control rates by radiation
therapy using brachytherapy and/or radiosensitizer drugs or to discover more
effective forms of chemotherapy. When possible, patients should be
considered for these clinical trials.

References:

  1. Pitt HA, Grochow LB, Abrams RA: Hepatobiliary cancers: cancers of the biliary tree. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 1114-1128.

  2. Hejna M, Pruckmayer M, Raderer M: The role of chemotherapy and radiation in the management of biliary cancer: a review of the literature. European Journal of Cancer 34(7): 977-986, 1998.


RECURRENT GALLBLADDER CANCER

The prognosis for any treated cancer patient with progressing or recurrent gallbladder cancer is poor. The question and selection of further treatment depends on many factors: tumor burden, prior treatment, site of recurrence, and individual patient considerations. Patients may have portal hypertension caused by portal vein compression by the tumor. Transperitoneal and intrahepatic metastases are not uncommon. Clinical trials are appropriate and should be considered when possible.

Date Last Modified: 05/1999



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