What is the gallbladder, and what does it do?

It is a small pear-shaped organ that stores and concentrates a substance called bile. Bile is a substance that aids in digestion and is made in the liver. The gallbladder and liver are connected by the hepatic duct.

When you eat fatty food, the food passes from the stomach into the small intestine, and triggers the lining of the small bowel to release a hormone called CCK (cholecystokinin). CCK is then carried in the bloodstream to the gallbladder, where it causes the gallbladder to contract and send bile through the common bile duct and into the small bowel duodenum. Gallstones form when the substances contained in bile crystallize into small, hard rocks.

How common is gallbladder cancer?

Primary cancer of the gallbladder affects about 6000 adults in the US each year.

What are the types of gallbladder cancer?

The majority of these cancers are "adenocarcinomas", with subtypes such as papillary, nodular, and tubular, depending on the appearance of the tumor cells under the microscope. Less common subtypes include: squamous cell, signet ring cell, and adenosquamous (adenoacanthoma).

Who gets gallbladder cancer?

Gallbladder cancer is most often seen in older patients, with a median age at diagnosis of 62-66 years. It occurs more often in females, with a female-to-male ratio of about 3:1. The highest rates of gallbladder cancer occur among US Native Americans, as well as in Mexico, South America, Israel, and China. In fact, Israel has the highest worldwide incidence, with 7.5 cases per 100,000 men and 13.8 cases per 100,000 women. Low rates are seen in India, Nigeria, and Singapore.

What causes gallbladder cancer? What are the risk factors?

The cause of gallbladder cancer is unknown, although it has been associated with gallstones, high estrogen levels, cigarette smoking, alcohol, obesity, and the female gender. Also, patients with inflammatory bowel disease, (ulcerative colitis and Crohn's disease), are 10 times more likely to develop cancer of the extrahepatic biliary tract.

What are the signs and symptoms of gallbladder cancer?

Unfortunately, there are no specific, surefire symptoms that suggest a diagnosis of gallbladder cancer. Usually, patients present with problems resulting from blockage of the bile ducts, such as jaundice, loss of appetite and weight loss. There may be a mass and/or pain in the abdomen, especially on the right under the ribcage.

On patient examination, a healthcare provider (HCP) may detect ja undice of skin or the whites of the eyes, a mass in the right upper abdominal quadrant or around the belly button (periumbilical).

How is gallbladder cancer diagnosed?

First and foremost, a HCP should always perform a thorough history and physical examination. Laboratory work should include metabolic chemistry and liver function panels to look for abnormal levels of various substances in the blood that are suggestive of general hepatobiliary disease. A urinalysis is usually done to evaluate urinary levels of some of these substances as well.

*The role of tumor markers, [carbohydrate antigen 19-9 (CA 19-9), cancer antigen 125 (CA125), and carcinoembryonic antigen (CEA)] has not been established in gallbladder cancer.

Ultrasonography ( US) is the standard study done first in patients presenting with right upper quadrant pain. It allows HCPs to make a diagnosis of gallbladder cancer in about half of patients, and can also detect disease spread into the liver or bile ducts.

Computed tomography (CT) scans can also be helpful in patients with upper abdominal pain. They are better than US for detecting tumor invasion out of the gallbladder and disease spread to other sites in the abdomen or pelvis. About 70-80% of cases will have some degree of liver invasion, and so the combination of CT and US provides more accurate information.

Magnetic resonance imaging (MRI) has been useful in examining this region for disease spread into the liver or other tissues. This technology is particularly good for planning surgery, by evaluating surrounding blood vessels [magnetic resonance angiogram (MRA)] and bile duct passages [magnetic resonance cholangiogram (MRC)].

Cholangiography, either through the skin or the stomach, is a technique that allows HCPs to not only establish a diagnosis, but to locate the blockage and place a stent through the blockage to help alleviate the blockage.

How is gallbladder cancer staged?

The American Joint Committee on Cancer uses the TNM system to stage gallbladder cancer as follows: (Adapted from AJCC 6 th edition, 2002)

Primary tumor (T)

TX - Primary tumor cannot be assessed
T0 - No evidence of primary tumor
Tis - Carcinoma in situ
T1 - Tumor invades mucosa or muscle layer
T2 - Tumor invades perimuscular connective tissue
T3 - Tumor invades/perforates the serosa and/or directly invades the liver and/or one other adjacent organ or structure
T4 - Tumor invades main portal vein or hepatic artery or >2 adjacent organs

Regional lymph node (N)

NX - Regional lymph nodes cannot be assessed
N0 - No metastases in regional lymph nodes
N1 – Regional lymph node metastases

Metastases (M)

MX - Presence of metastases cannot be assessed
M0 - No distant metastases
M1 - Distant metastases

How is gallbladder cancer treated?

As with many tumor types, management is often a multidisciplinary approach involving a variety of treatments.

Total surgical removal of all known tumor is the only truly curative treatment. Unfortunately, only about 25% of patients with gallbladder cancer are able to undergo definitive surgery. Furthermore, such a procedure is typically quite extensive, and involves removal of the gallbladder, regional lymph nodes, and a portion of liver if there is concern of invasion. As you might expect, such a surgery carries a high risk of serious operative injury.

Even when surgery is possible, the surgeon is usually unable to take very large resection margins around the tumor, meaning that cancer cells may exist at, or very close to, the tissue edges where the surgeon cut. In such cases, external beam radiation therapy can be used in hopes of eradicating any microscopic cancer remaining in the surgical area and surrounding at-risk regions. Median survival in patients with advanced but operable disease treated with surgery alone is cited as roughly 6-7 months. This can sometimes be improved to over 16 months with postoperative radiation therapy.

For patients who are unable to undergo surgery, either because the disease is too advanced or because of other serious medical conditions, HCPs can use radiation therapy with or without concurrent chemotherapy in order to improve symptoms, and in some cases maybe even increase survival.

What are the outcomes of treatment?

Disease stage at presentation is the most important prognostic factor.

Stage I patients can have very good 5-year survival rates, on the order of 70-85% after a complete surgery. Perioperative mortality rates range from 2-15%, depending upon the extent of liver resection required or the need for pancreas and small bowel removal (pancreaticoduodenectomy).