Gallbladder carcinoma is diagnosed most frequently in individuals between ages 70 and 75 and shows a 3:1 predilection for women over men. Worldwide, the highest prevalence of gallbladder cancer is seen in Israel, Mexico, Chile, Japan, and among Native American women, particularly those living in New Mexico.The greatest risk factor for the development of gallbladder cancer is the presence of gallstones, in particular those associated with chronic cholecystitis. Other risks include the presence of a calcified gallbladder (porcelain gallbladder), gallbladder polyps, typhoid carriers, and carcinogens (eg, azotoluene, nitrosamines). Unfortunately, most gallbladder cancers are diagnosed at advanced stages when the tumor is unresectable. Patients often present with nonspecific symptoms, such as abdominal pain, weight loss, anorexia, nausea, acute cholecystitis, and jaundice. Up to 20% of cancers are diagnosed incidentally at the time of gallbladder surgery. No specific laboratory or marker tests are available to assist in making the diagnosis. A suspicious mass detected on ultrasound should warrant further evaluation, including CT or MRI, liver function tests, chest radiograph, and staging laparoscopy. Laparoscopy can be done in conjunction with surgery if no distant metastasis is found. If a polypoid mass is seen on ultrasound, the cholecystectomy should be performed by a surgeon who is prepared to do a cancer operation. For patients presenting with jaundice, additional workup should include endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography, or magnetic resonance (MR) cholangiography.

Management

Surgical Assessment and Evaluation.

As is true for all hepatobiliary cancers, surgery remains the only curative modality for gallbladder cancer. The guidelines distinguish between patients 1) in whom cancer is found incidentally at surgery or on pathologic review and 2) those who exhibit a mass on ultrasound or present with jaundice. Within these groups the algorithm differentiates between those with resectable disease and those with unresectable disease. Patients who present with an incidental finding of cancer at surgery may be treated with cholecystectomy and resection of gallbladder fossa and lymphadenectomy with or without partial hepatic resection and with or without bile duct excision. This approach may improve overall survival. A similar approach is appropriate for patients who present with a mass on ultrasound or with jaundice, for whom surgery is considered after more extensive evaluation, including staging laparoscopy, CT or MRI, liver function tests, chest radiograph and surgical consultation.

Among patients in whom gallbladder cancer is diagnosed as an incidental finding on pathologic review, those with T1 lesions may be observed. Patients with T2 or greater lesions should be considered for surgery, after CT/MRI confirms the absence of metastatic disease. In addition, for those who undergo laparoscopic operations, resection of port sites with or without bile duct excision should be considered because of the risk of local recurrence at these sites.

Postoperative therapy for resectable patients, except those with T1, N0 disease, should include adjuvant 5-fluororacil (5-FU)--based chemotherapy and radiation. Unfortunately, because of the relatively small numbers of patients with gallbladder cancer, no randomized trials have been conducted to determine definitive therapeutic approaches.

Patients With Unresectable Tumor Without Obvious Metastatic Disease

Patients with unresectable tumor but without jaundice and who do not have obvious metastatic disease may benefit from a regimen of 5-FU--based chemotherapy and radiation similar to the regimen used adjuvantly. However, overall survival of such patients remains poor. Because there is no definitive treatment with proven survival benefit, best supportive care or enrollment in a clinical trial are considered appropriate options for patients with unresectable disease. For jaundiced patients whose disease is considered unresectable after preoperative evaluation, a biopsy should be performed to confirm the diagnosis. In such patients, biliary decompression would be an appropriate palliative procedure. Participation in a clinical trial, supportive care, or consideration of gemcitabine and/or 5-FU-- based chemotherapy or best supportive care is also appropriate.