We performed a meta-analysis of studies of the association between excess body weight and risk of gallbladder cancer identified from MEDLINE and EMBASE databases from 1966 to February 2007 and the references of retrieved articles. A random-effects model was used to combine results from eight cohort studies and three casecontrol studies, with a total of 3288 cases. Compared with individuals of ‘normal weight’, the summary relative risk of gallbladder cancer for those who were overweight or obese was 1.15 (95% CI, 1.011.30) and 1.66 (95% CI, 1.471.88) respectively. The association with obesity was stronger for women (relative risk, 1.88; 95% CI, 1.662.13) than for men (relative risk, 1.35; 95% CI, 1.091.68). There was no statistically significant heterogeneity among the results of individual studies. This meta-analysis confirms the association between excess body weight and risk of gallbladder cancer.

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There are four ways to make an appointment at the Vanderbilt-Ingram Cancer Center

1. Phone a specific department or call the Henry-Joyce Cancer Clinic at 615-322-6053. To see a complete listing of VICC physicians who treat Cancer, visit the VICC.ORG Directory of Doctors.
2. Call 1-800-811-8480. This is our Cancer Information Program, available from 9:00AM to 4:00PM Central Time Monday through Thursday and 9:00AM to 12:00PM Friday.
3. Fill out our online self referral form. This form is on a secure server to ensure confidentiality.
4. Fax a referral form to the VICC. This form is a PDF document; download the free Acrobat Reader software if needed to access this form.

For more information about a specific cancer, call 1-800-4CANCER or see Cancer Information on this web site.

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Background

The long-term prognosis of laparoscopic cholecystectomy (LC) for patients with unsuspected gallbladder carcinoma (GBC) remains unclear. We investigated retrospectively the role of examination of frozen sections and the prognosis of patients with unsuspected GBC detected during or after LC.

Methods

LC was performed on 1,793 consecutive patients. If a suspicious lesion was found, intraoperative frozen section examination was performed.

Results

Of all these patients, 38 (2.1%) were histopathologically diagnosed as having a GBC during (28) or after LC (10). The tumor stages of the 28 diagnosed during LC were: pT1a (17), pT1b (2), pT2 (8), and pT3 (1). The sensitivity and specificity of intraoperative frozen section examination were 90 and 100%, respectively. On the other hand, those 10 cases diagnosed after LC had pT1a (1) and pT2 (9) tumors. Survival rates were not significantly affected by whether the patient was diagnosed with GBC during or after LC.

Conclusions

The survival with unsuspected GBC was related to stage and it was confirmed that a carefully performed LC is adequate treatment for Stage 1A and B cancer. The LC procedure does not adversely affect the prognosis of unsuspected GBC, regardless of whether it is detected during or after LC. J. Surg. Oncol. © 2007 Wiley-Liss, Inc.

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Doctors and scientists are always looking for better ways to treat patients with gallbladder cancer. A clinical trial is a way to test a new treatment in order to prove that it is safe, effective, and possibly better than a standard treatment. Patients who participate in clinical trials are among the first to receive new treatments, such as new chemotherapy drugs, before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.

Patients decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that this is the only way to make progress in treating gallbladder cancer, such as finding new drugs. Even if they do not benefit directly from the clinical trial, their participation may benefit future patients with gallbladder cancer.

To join a clinical trial, patients must complete a learning process known as informed consent. During informed consent, the doctor should list all of the patient’s options, so the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different than the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment. Learn more about clinical trials, including patient safety, phases of a clinical trial, deciding to participate in a clinical trial, questions to ask the research team, and links to find cancer clinical trials.

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Cancer is found in the lining of the chest wall and may also be found in the lining of the lung, the lining of the diaphragm (the thin muscle below the lungs and heart that separates the chest from the abdomen), or the lining of the sac that covers the heart on the same side of the chest. Also called stage I malignant mesothelioma.

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Cancer of the gallbladder, an uncommon cancer, is a disease in which cancer (malignant) cells are found in the tissues of the gallbladder. The gallbladder is a pear-shaped organ that lies just under the liver in the upper abdomen. Bile, a fluid made by the liver, is stored in the gallbladder. When food is being broken down (digested) in the stomach and the intestines, bile is released from the gallbladder through a tube called the bile duct that connects the gallbladder and liver to the first part of the small intestine. The bile helps to digest fat.

Cancer of the gallbladder is more common in women than in men. It is also more common in people who have hard clusters of material in their gallbladder (gallstones).

Cancer of the gallbladder is hard to find (diagnose) because the gallbladder is hidden behind other organs in the abdomen. Cancer of the gallbladder is sometimes found after the gallbladder is removed for other reasons. The symptoms of cancer of the gallbladder may be like other diseases of the gallbladder, such as gallstones or infection, and there may be no symptoms in the early stages. You should see your doctor if you have pain above the stomach, you lose weight without trying to, you have a fever that won’t go away, or your skin turns yellow (jaundice).

If you have such symptoms, your doctor may order x-rays and other tests to see what is wrong. However, usually the cancer cannot be found unless you have surgery. During surgery, a cut is made in your abdomen so that the gallbladder and other nearby organs and tissues can be examined.

Your chance of recovery (prognosis) and choice of treatment depend on the stage of cancer (whether it is just in the gallbladder or has spread to other places) and on your general health.

Stages Of Cancer Of The Gallbladder

Once cancer of the gallbladder is found, more tests will be done to find out if cancer cells have spread to other parts of the body. Your doctor needs to know the stage to plan treatment. The following stages are used for cancer of the gallbladder:

Localized Cancer is found only in the tissues that make up the wall of the gallbladder, and it can be removed completely in an operation. Unresectable All of the cancer cannot be removed in an operation. Cancer has spread to the tissues around the gallbladder, such as the liver, stomach, pancreas, or intestine and/or to lymph nodes in the area. (Lymph nodes are small, bean-shaped structures that are found throughout the body. They produce and store infection-fighting cells.)

Recurrent Recurrent disease means that the cancer has come back (recurred) after it has been treated. It may come back in the gallbladder or in another part of the body.

How Cancer Of The Gallbladder Is Treated

There are treatments for all patients with cancer of the gallbladder. Three treatments are used: surgery (taking out the cancer or relieving symptoms of the cancer in an operation) radiation therapy (using high-dose x-rays to kill cancer cells) chemotherapy (using drugs to kill cancer).

Surgery is a common treatment for cancer of the gallbladder if it has not spread to surrounding tissues. Your doctor may take out the gallbladder in an operation called a cholecystectomy. Part of the liver around the gallbladder and lymph nodes in the abdomen may also be removed.

If your cancer has spread and cannot be removed, your doctor may do surgery to relieve symptoms. If the cancer is blocking the bile ducts and bile builds up in the gallbladder, your doctor may do surgery to go around (bypass) the cancer. During this operation, your doctor will cut the gallbladder or bile duct and sew it to the small intestine. This is called biliary bypass. Surgery or other procedures may also be done to put in a tube (catheter) to drain bile that has built up in the area. During these procedures, your doctor may place the catheter so that it drains through a tube to the outside of your body or so that it goes around the blocked area and drains the bile into the small intestine.

Radiation therapy is the use of high-energy x-rays to kill cancer cells and shrink tumors. Radiation for gallbladder cancer usually comes from a machine outside the body (external-beam radiation therapy). Radiation may be used alone or in addition to surgery.

Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy for cancer of the gallbladder is usually put into the body by a needle inserted into a vein. Chemotherapy is called a systemic treatment because the drug enters the bloodstream, travels through the body, and can kill cancer cells outside the gallbladder. Chemotherapy or other drugs may be given with radiation therapy to make cancer cells more sensitive to radiation (radiosensitizers).

Treatment By Stage

Treatments for cancer of the gallbladder depend on the stage of the disease and your general health.

You may receive treatment that is considered standard based on its effectiveness in a number of patients in past studies, or you may choose to go into a clinical trial. Most patients with gallbladder cancer are not cured with standard therapy and some standard treatments may have more side effects than are desired. For these reasons, clinical trials are designed to find better ways to treat cancer patients and are based on the most up-to-date information. Clinical trials are going on in many parts of the country for patients with cancer of the gallbladder. If you want more information, call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237); TTY at 1-800-332-8615.

LOCALIZED GALLBLADDER CANCER

Your treatment may be one of the following: 1. Surgery to remove the gallbladder and some of the tissues around it (cholecystectomy). 2. External-beam radiation therapy. 3. Surgery followed by external-beam radiation therapy. 4. Clinical trials of radiation therapy plus chemotherapy or drugs to make the cancer cells more sensitive to radiation (radiosensitizers).

UNRESECTABLE GALLBLADDER CANCER

Your treatment may be one of the following: 1. Surgery or other procedures to relieve symptoms. 2. External-beam radiation therapy with or without surgery or other procedures to relieve symptoms. 3. Chemotherapy to relieve symptoms. Clinical trials are testing new chemotherapy drugs. 4. Clinical trials of radiation therapy plus chemotherapy or drugs to make the cancer cells more sensitive to radiation (radiosensitizers).

RECURRENT GALLBLADDER CANCER

Treatment for recurrent cancer of the gallbladder depends on the type of treatment you received before, the place where the cancer has recurred, and other facts about your cancer and your general health. You may wish to consider taking part in a clinical trial.

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This information represents the views of the doctors and nurses serving on the American Cancer Society’s Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don’t hesitate to ask him or her questions about your treatment options.

After the cancer is found and staged, your cancer care team will discuss treatment choices with you. It is important for you to take time and think about all of the choices. In choosing a treatment plan, factors to consider include your overall physical health, the type and stage of the cancer, likely side effects of the treatment, and the probability of curing the disease, extending life, or relieving symptoms.

It is often a good idea to seek a second opinion, particularly for an uncommon cancer such as gallbladder cancer. A second opinion can provide more information and help you feel more confident about your chosen treatment plan.

Nearly all doctors agree that surgery offers the only hope for curing people with gallbladder cancer. But at this time, there are differences of opinion about how advanced a gallbladder cancer may be and still be curable. Therefore, it may be especially important for people diagnosed with gallbladder cancer to seek a second opinion when considering treatment options. In addition, while survival statistics show significantly better 5-year survival rates for most patients treated with extended or radical surgeries, such operations are most often done at major cancer centers and may not be available in every community.

In general, spread of the cancer beyond the gallbladder does not make it incurable by surgery unless the cancer has spread too far or into major blood vessels. For instance, if the cancer has invaded the liver — but only in one area and not too deeply — it may be possible to remove all of the cancer by surgery. If the cancer has spread to both sides of the liver, to the lining of the abdominal cavity, to organs farther away from the gallbladder than the liver, or if it surrounds the vein bringing blood to the liver from the stomach and intestines, surgery may not be able to remove it all.

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Deaths from Gall Bladder Cancer: 3,540 estimated deaths for gall bladder/biliary cancer in the US 2004 (Cancer Facts and Figures, American Cancer Society, 2004)

Estimated mortality rate for Gall Bladder Cancer from incidence and deaths statistics:

                        Deaths: 3,539 (USA annual deaths calculated from this data: 3,540 estimated deaths for gall bladder/biliary cancer in the US 2004 (Cancer Facts and Figures, American Cancer Society, 2004))

                        Incidence: 7,100 (USA annual incidence calculated from this data: 7,100 annual cases (SEER 2002 estimate: gallbladder and other biliary)

49.9% (ratio of deaths to incidence).

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Procedures that create pictures of the gallbladder and the area around it help diagnose gallbladder cancer and show how far the cancer has spread. The process used to find out if cancer cells have spread within and around the gallbladder is called staging.

In order to plan treatment, it is important to know if the gallbladder cancer can be removed by surgery. Tests and procedures to detect, diagnose, and stage gallbladder cancer are usually done at the same time. The following tests and procedures may be used:

—      Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.

—      Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. An abdominal ultrasound is done to diagnose gallbladder cancer.

—      Liver function tests: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by the liver. A higher than normal amount of a substance can be a sign of liver disease that may be caused by gallbladder cancer.

—      Carcinoembryonic antigen (CEA) assay: A test that measures the level of CEA in the blood. CEA is released into the bloodstream from both cancer cells and normal cells. When found in higher than normal amounts, it can be a sign of gallbladder cancer or other conditions.

—      CA 19-9 assay: A test that measures the level of CA 19-9 in the blood. CA 19-9 is released into the bloodstream from both cancer cells and normal cells. When found in higher than normal amounts, it can be a sign of gallbladder cancer or other conditions.

—      CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

—      Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that produces it.

—      Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

—      MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI). A dye may be injected into the gallbladder area so the ducts (tubes) that carry bile from the liver to the gallbladder and from the gallbladder to the small intestine will show up better in the image. This procedure is called MRCP (magnetic resonance cholangiopancreatography). To create detailed pictures of blood vessels near the gallbladder, the dye is injected into a vein. This procedure is called MRA (magnetic resonance angiography).

—      ERCP (endoscopic retrograde cholangiopancreatography): A procedure used to x-ray the ducts (tubes) that carry bile from the liver to the gallbladder and from the gallbladder to the small intestine. Sometimes gallbladder cancer causes these ducts to narrow and block or slow the flow of bile, causing jaundice. An endoscope (a thin, lighted tube) is passed through the mouth, esophagus, and stomach into the first part of the small intestine. A catheter (a smaller tube) is then inserted through the endoscope into the bile ducts. A dye is injected through the catheter into the ducts and an x-ray is taken. If the ducts are blocked by a tumor, a fine tube may be inserted into the duct to unblock it. This tube (or stent) may be left in place to keep the duct open. Tissue samples may also be taken.

—      Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. The biopsy may be done after surgery to remove the tumor. If the tumor clearly cannot be removed by surgery, the biopsy may be done using a fine needle to remove cells from the tumor.

—      Laparoscopy: A surgical procedure to look at the organs inside the abdomen to check for signs of disease. Small incisions (cuts) are made in the wall of the abdomen and a laparoscope (a thin, lighted tube) is inserted into one of the incisions. Other instruments may be inserted through the same or other incisions to perform procedures such as removing organs or taking tissue samples for biopsy. The laparoscopy helps to determine if the cancer is within the gallbladder only or has spread to nearby tissues and if it can be removed by surgery.

PTC (percutaneous transhepatic cholangiography): A procedure used to x-ray the liver and bile ducts. A thin needle is inserted through the skin below the ribs and into the liver. Dye is injected into the liver or bile ducts and an x-ray is taken. If a blockage is found, a thin, flexible tube called a stent is sometimes left in the liver to drain bile into the small intestine or a collection bag outside the body.

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A risk factor is anything that increases a person’s chance of getting a disease such as cancer. Different cancers have different risk factors. For example, unprotected exposure to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for cancers of the lung, mouth, larynx, colon, bladder, kidney, and several other organs. But having a risk factor, or even several risk factors, does not necessarily mean that a person will get the disease. Scientists have found several risk factors that make a person more likely to develop gallbladder cancer.

Gallstones and inflammation of the gallbladder: Gallstones are the most common risk factor for gallbladder cancer. Gallstones are hard, rock-like formations of cholesterol and other substances in the gallbladder. Between 75% and 90% of persons with gallbladder cancer have gallstones and chronically inflamed gallbladders when they are diagnosed. People with one or several large (3 cm or 1.2 inches) gallstones are 10 times more likely to develop gallbladder cancer than those with small (1 cm or 0.4 inches) gallstones. However, gallstones are a very common condition and gallbladder cancer is quite rare, especially in the United States. The vast majority of people with gallstones never develop gallbladder cancer.

Porcelain gallbladder: Porcelain gallbladder is a condition in which the wall of the gallbladder becomes covered with calcium deposits. It sometimes occurs after the gallbladder has been severely inflamed. People with this condition may have a high risk of developing gallbladder cancer, although recent studies have tended to cast doubt on this. Doctors may recommend surgery to remove a porcelain gallbladder.

Typhoid: People chronically infected with salmonella (the bacterium that causes typhoid) and those who are carriers of the disease are 6 times as likely to develop gallbladder cancer as those not infected. Typhoid is rare in the United States, with fewer than 600 cases each year.

Choledochal cysts: Choledochal means having to do with the common bile duct, the passageway that carries bile from the liver and gallbladder to the first part of the small intestine. Choledochal cysts are bile-filled sacs that are connected to the common bile duct. They can grow over time and may contain as much as 1 to 2 quarts of bile. The cells lining the sac often have areas of precancerous changes, which increase the patient’s risk for developing gallbladder cancer.

Industrial and environmental chemicals: Animal studies indicate that an industrial chemical known as azotoluene and chemical compounds called nitrosamines may cause gallbladder cancer. Workers in rubber plants and metal-fabricating industries have more gallbladder cancers than the general public.

Anomalous pancreatobiliary duct junction and other abnormalities of the bile ducts: The pancreatobiliary junction is the area where the bile duct (passageway carrying fluids from the liver and gallbladder) and the pancreatic duct (passageway carrying digestive juices from the pancreas) join together. An anomalous junction is one that is connected differently than a normal junction. A higher risk is found among people with this abnormality and others that allow very acidic juice from the pancreas to reflux (flow back “upstream”) into the ducts. That backward flow also prevents the bile from being emptied through the bile ducts into the intestines as quickly as normal. Scientists are not sure whether the increased risk is due to the action of the pancreatic juice or possibly due to the ducts being exposed longer to carcinogens in the concentrated bile.

Age: The highest proportion of patients with this cancer are in their 70s.

Family history: Gallbladder cancer can run in families. A history of gallbladder cancer in the family increases a person’s chances of developing this cancer. The risk, however, is still low because this is a rare disease.

Gender: In the United States, gallbladder cancer occurs nearly twice as often in women. Gallstones and gallbladder inflammation, 2 important risk factors for gallbladder cancer, are much more common among women than men.

Gallbladder polyps: A gallbladder polyp is a growth that bulges outward from the surface level of the inner gallbladder wall. Some polyps are formed by a small gallstone embedded in the gallbladder wall. Others may be small tumors (either cancerous or benign) or may be caused by inflammation. Polyps larger than 1 centimeter (a little less than half an inch) are more likely to be malignant, so doctors commonly recommend removal of the gallbladder in patients with gallbladder polyps that size or larger.

Obesity: Patients with gallbladder cancer are more often overweight or obese than people without this disease.

Ethnicity: Native Americans, particularly in the southwestern United States, and Mexican Americans have a high rate of gallbladder cancer. They are also more likely to have gallstones than members of other ethnic and racial groups.

Diet: A high-carbohydrate and low-fiber diet may increase a person’s susceptibility to gallbladder cancer.

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