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Cancer of The Gall Bladder
Alan P. Venook, MD, Sabrina Selim, MD

The gall bladder stores bile, a produced of the liver that aids in the digestion of fat-containing foods. It is a non-essential organ and can be removed without significant consequences. Gall bladder cancer, also called carcinoma of the gall bladder, is extremely rare affecting only 7,100 people in the United States per year. Unless it is very small and found when the gall bladder is removed for other reasons, the treatment now available is not particularly effective.

Because it is so uncommon and because its symptoms mirror those of far more common ailments, cancer of the gall bladder is usually not found until it is at an advanced stage and cannot be surgically removed. In the advanced stages, pain relief and the restoration of normal bile flow from the liver into the intestines are the principal goals of therapy.

How It Spreads
Gall bladder cancer tends to spread to nearby organs and tissues such as the liver or small intestine. It also spreads through the lymph system to lymph nodes in the region of the liver (porta hepatis). Ultimately, other lymph nodes and organs can become involved.

What Causes It
No one factor has been clearly shown to cause gall bladder cancer. Although it occurs most often in people with porcelain gall bladders where repeated inflammation from passing gallstones leads to hardening (calcification) of the gall bladder, it is extremely rare even in such patients. Since the gallbladder isn't essential, people with a calcified gall bladder may consider having it removed as a preventative measure.

Common Signs and Symptoms
There are no clinical signs or symptoms characteristic of gall bladder cancer. Jaundice (the skin turning yellow), bloating, abdominal pain, weight loss, decreasing appetite, fever, nausea or an enlarging abdominal mass are all signs that may be attributable to gall bladder cancer. Even if the following are found, gall bladder cancer would still not be the prime suspect because it is so uncommon:

Frequently, jaundice is a late development and the other symptoms have been present for a long time. Itching may result from the buildup in the skin of a derivative of bile, bilirubin, which turns the skin yellow. This symptom usually reflects advanced disease.

Staging A TNM staging system exists for gall bladder cancer, but for the purposes of deciding on which therapeutic option to use there are only three stages - localized resectable, localized unresectable and advanced disease.

Stage Signs and Symptoms Diagnostic Procedures Treatments Survival

Localized Resectable

Cancer is confined to the superficial layers (mucosa and submucosa) of the gallbladder. Cancers at this limited stage are generally found when the gall bladder is removed because of other problems.

 Generally none

Diagnostic tests are notoriously inaccurate in their ability to pinpoint gall bladder cancer before surgery. A standard evaluation, however, includes: Blood test: ? hemoglobin (anemia); abnormal liver function tests; abnormal clotting time (PT and PTT)

Surgery: If there is no tumor spread, surgery (removal of the gall bladder and underlying liver tissue) is the only possible cure.
Radiation therapy: this is often advised after surgery to destroy any small or microscopic tumors remaining

5 year: approximately 80%. Those with cancers that are still very small but cause symptoms have a somewhat lower 5 year survival rate

Localized Unresectable

Despite being a localized mass, the tumor cannot be removed because of the particular way it has spread to local lymph nodes or adjacent liver tissue

Fever
Tender mass below the ribs on the right side of the abdomen
Enlarged, hard lymph nodes
Jaundice (skin turns yellow)
Swelling in legs (edema)
Decreased appetite
Nausea/vomiting
Itching

Ultrasound: Confirm that gall bladder wall has thickened, size and characteristics of mass
CT: Determine extent of tumor and possible other organ involvement
MRI: Determine if cancer can be surgically removed
Chest x-ray: Identify if cancer has spread to the lung (metastatic)
Biopsy: Positively identify the presence of characteristic tumor cells

There are no standard treatments. Clinical trials aimed at prolonging survival and relieving symptoms associated with the tumor should be considered.

Surgery: Even if a tumor cannot be fully removed, a drainage system for the bile from an obstructed duct may be necessary to reduce pain/symptoms. Surgery is not a cure.
Chemotherapy: The standard drugs, Mitomycin C and 5-FU may cause shrinkage in 20-25% of gall bladder cancers. Tumors, however, generally regrow and the treatments have many side-effects.
Radiation Therapy: Patients who are not candidates for surgery may benefit from radiation to the gall bladder area.

 2 year: less than 5%

Advanced Disease

The cancer has spread to distant sites (liver, lung, small intestine)

 Same as above Same as above

No standard therapy is known to prolong survival in patients with advanced gall bladder cancer. Single agent 5-FU or mitomhycin-C may help. An oral drug, capecitabine, also appears to be active against gall bladder cancer. Even if the tumor shrinks, however, patients may not benefit because of side effects and the tumor usually regrows quickly.

 2 year: less than 1%

Supportive Therapies
Symptoms associated with jaundice can include severe itching and a general sense of poor health. These symptoms can generally be managed with a drainage procedure to bypass the blockage in the biliary tract. This procedure may include placing of a tube through the skin or through the stomach. Surgery is rarely necessary to bypass an obstruction. If such drainage is ineffective, itching may be relieved by the use of Benadryl, Atarax or cholestyramine.
Pain relief may require large doses of medication. Narcotics must be used carefully, however, since they may have excessive side effects and are metabolized by the liver, which may not be working properly.
Non-steroidal anti-inflammatory drugs may be surprisingly effective even against the severe pain associated with gall bladder cancer.
Water pills (diuretics) to reduce fluid in the abdomen or legs may be helpful, but may cause significant imbalance in kidney function if not monitored carefully.
Nausea can be treated with standard medications, including suppositories.
Sleep disturbances are common, but sleeping pills should be used carefully since most are metabolized by the liver.
Frequent small meals may be necessary since an abdominal mass may reduce the size of the stomach.
Patients with the severe loss of appetite may be helped by an appetite-stimulating drug called Megace.

Important Questions to Ask Your Doctor
Should I see another physician to confirm that this tumor can or cannot be removed for cure?
Could I benefit from an investigational therapy available at another institution?
How sick will the proposed chemotherapy make me relative to its potential benefit?
Can anything be done to improve the quality of my life?

References
Everyone's Guide to Cancer Therapy by Malin Dollinger, Ernest H. Rosenbaum, Margaret Tempero and Sean Mulvihill. Andrews McMeel. 4th edition, 2002.
Jemal, Ahmedin et al. Cancer Statistics, 2002. Cancer J Clin 2002; 52:23-47.



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