Symptoms

Some of the symptoms that manifest in a patient suffering from gallbladder cancer are:

• Steady pain in the upper right abdomen
• Weakness
• Loss of appetite
• Weight loss
• Jaundice and vomiting due to obstruction
• A swollen abdomen (tummy)
• Gallbladder enlargement

Early symptoms mimic gallbladder inflammation due to gallstones. Later, the symptoms may be that of biliary and stomach obstruction.

Causes

The exact causes of gallbladder cancer are as yet unclear. What we do know is that most gallbladder cancer begins in the glandular cells that line the inner surface of the gallbladder. Gallbladder cancer that begins in this type of cell is called adenocarcinoma. Some of the risk factors that increase the probability of getting gallbladder cancer are:

• Gender of the patient: Gallbladder disease as such is more common in women. Similarly, gallbladder cancer affects women more commonly than men.
• Cholecystitis: Gallstones and inflammation of the gallbladder is also known as cholecystitis. This is by far the most common risk factor that predisposes one to gallbladder cancer. Gallstones are hard stones that are formed within the gallbladder due to deposition of cholesterol and minerals from bile. About eight out of ten people with gallbladder cancer (80%) have gallstones or an inflamed gallbladder at diagnosis. However, most people with an inflamed gallbladder or gallstones do not get gallbladder cancer.
• Family history of gallstones and gallbladder cancer: Those with a family history of gallstones have double the chance of gallbladder cancer. In addition, those with a family history of gallstones who also have gallstones themselves have almost 60 times the normal risk of gallbladder cancer. Those with a first degree relative with gallbladder cancer are five times more likely to develop gallbladder cancer than people who do not have a relative with it. The risk, however, still remains very small as the cancer is rare.
• Genetics: Some races and ethnicities are more at risk of gall bladder cancer than others. The basis could be a family history of gallstones and gallbladder cancer: genetics. For example, north India has the highest rate of gallbladder cancer in the world.
• Smoking and exposure to chemicals: Cigarettes and some industrial chemicals containing nitrosamines can damage the DNA and lead to genetic mutations and raise the risk of gallbladder and other cancers. Workers in the metal or rubber industry are more likely to develop gallbladder cancer
• Porcelain gallbladder: This is a condition where calcium deposits build up on the inside wall of the gallbladder hardening the walls. This is usually seen in individuals who have repeated cholecystitis or inflammation of the gallbladder.
• Defects of the pancreas and bile ducts: Defects of the pancreas and bile ducts raise gallbladder cancer risk. Abnormalities in the connection between the bile duct and the pancreas and outgrowths in the bile duct (choledochal cysts) may also be risk factors for gall bladder cancer. These conditions may affect a baby since birth but symptoms may appear much later.
• Obesity: Being obese or overweight raises the risk of gallstones and cholecystitis. This is mainly because they change the hormonal balances of the body, particularly in women. Studies show that more than one in ten cases of gallbladder cancer in men and almost a third of cases in women are due to being overweight.
• Diet: Diet high in carbohydrates and low in fibre may increase the risk of gallbladder cancer. A diet rich in fresh fruit and vegetables seems to reduce the risk of many cancers, including gallbladder cancer. Inclusion of vitamins A, C, E and antioxidant chemicals in diet is also important for cancer prevention.
• Diabetes: Diabetes may also raise the risk of gallbladder cancer
• Exposure to female hormones in hormone replacement therapy: Women who have increased exposure to the hormone oestrogen may have an increased risk of gallbladder cancer. With longer use of hormone replacement therapy, the risk of gallbladder cancer seems to rise

Diagnosis

In order to treat gallbladder cancer, it is necessary to diagnose the stage of the cancer. In order to do that, the doctor adopts any one of the following procedures:

• Physical examination: During the exam, signs of gallbladder cancer and other health problems are looked for. The exam will focus mostly on the abdomen (belly) to check for any lumps, tenderness, or fluid build-up. The skin and the white part of the eyes will be checked for jaundice (a yellowish colour). Sometimes, cancer of the gallbladder spreads to lymph nodes, causing a lump that can be felt beneath the skin. Lymph nodes above the collarbone and in several other locations may be checked.

If symptoms and/or the physical exam suggest you might have gallbladder cancer, tests will be done. These might include lab tests, imaging tests, and other procedures.

• Blood Tests: Lab tests might be done to find out how much bilirubin is in the blood. Bilirubin is the chemical that causes jaundice. Problems in the gallbladder, bile ducts, or liver can raise the blood level of bilirubin. Tests for albumin, liver enzymes (alkaline phosphatase, AST, ALT, and GGT), and certain other substances in your blood may also be done. These tests are often called liver function tests. They help diagnose liver, bile duct, or gallbladder diseases.
• Tumour Markers: Tumour markers are substances made by cancer cells that can sometimes be found in the blood. People with gallbladder cancer may have high blood levels of the markers called CEA and CA 19-9. Usually the blood levels of these markers are high only when the cancer is in an advanced stage. While these markers are not specific for gallbladder cancer these tests can sometimes be useful after a person is diagnosed with gallbladder cancer. If the levels of these markers are found to be high, they can be followed over time to help tell how well treatment is working.
• Imaging Tests:
  • Ultrasound exam: This is a procedure in which high energy sound waves are bounced off internal tissues or organs to produce echoes. The echoes form a picture of body tissues called a sonogram. An abdominal ultrasound or endoscopic/laparoscopic ultrasound is done to diagnose gallbladder cancer.
  • CT scan: It is 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, Computerised Tomography, or Computerized Axial Tomography.
  • Chest x-ray: This involves 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, creating an image of areas inside the body.
  • MRI: MRI is 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.
  • Cholangiography: A cholangiogram is an imaging test that looks at the bile ducts to see if they are blocked, narrowed, or dilated (widened). This can help show if someone might have a tumour that’s blocking a duct. It can also be used to help plan surgery. There are several types of cholangiograms, each of which has different pros and cons:
    • Magnetic resonance cholangiopancreatography (MRCP):
    • Endoscopic retrograde cholangiopancreatography (ERCP):
    • Percutaneous transhepatic cholangiography (PTC):

Biopsy: Biopsy involves 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 tumour. If the tumour clearly cannot be removed by surgery, the biopsy may be done using a fine needle to remove cells from the tumour.
The tests help diagnose the cancer and also ascertain its stage. The earliest stage gallbladder cancers (called carcinoma in situ) are stage 0. Stages then range from stages I (1) through IV (4). As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV, means cancer has spread more. And within a stage, an earlier letter means a lower stage.

Treatment

There are different types of treatment for patients with gallbladder cancer. Three types of standard treatment that are used are:

Surgery

Gallbladder cancer may be treated with a cholecystectomy, a surgery performed to remove the gallbladder and some of the tissues around it. Nearby lymph nodes may be removed. A laparoscope is sometimes used to guide gallbladder surgery. The laparoscope is attached to a video camera and inserted through an incision (port) in the abdomen. Surgical instruments are inserted through other ports to perform the surgery. Because there is a risk that gallbladder cancer cells may spread to these ports, tissue surrounding the port sites may also be removed.

If the cancer has spread and cannot be removed, the following types of palliative surgery may relieve symptoms:

• Surgical biliary bypass: If the tumour is blocking the small intestine and bile is building up in the gallbladder, a biliary bypass may be done. During this operation, the gallbladder or bile duct will be cut and sewn to the small intestine to create a new pathway around the blocked area
• Endoscopic stent placement: If the tumour is blocking the bile duct, surgery may be done to put in a stent (a thin, flexible tube) to drain bile that has built up in the area. The stent may be placed through a catheter that drains to the outside of the body or the stent may go around the blocked area and drain the bile into the small intestine
• Percutaneous transhepatic biliary drainage: A procedure done to drain bile when there is a blockage and endoscopic stent placement is not possible. An x-ray of the liver and bile ducts is done to locate the blockage. Images made by ultrasound are used to guide placement of a stent, which is left in the liver to drain bile into the small intestine or a collection bag outside the body. This procedure may be done to relieve jaundice before surgery

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation towards the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). Chemotherapy is typically administered after (adjuvant) surgery to people with gall bladder cancer. For people with advanced cancers which may have spread to other organs beyond the Gall bladder, chemotherapy may be used alone to help relieve signs and symptoms caused by the cancer; and to improve survival to some extent.