Gallbladder Cancer

Usually, signs and symptoms of gallbladder cancer do not appear until the disease has become fairly advanced. Owing to this inconspicuous nature of gallbladder cancer, most cases are detected with the appearance of clinical features at later stages, when the disease has spread to surrounding tissues, lymph nodes or even to farther sites in the body, resulting in poorer treatment outcomes. If present, clinical features can include but may not be limited to:

• Pain: The gallbladder is located in a region medically termed as the right hypochondrium of the abdominal area. Pain arising in the right upper portion of the abdomen can raise suspicion of gallbladder cancer.
• Lumps: They can be present in the right upper portion of the abdomen sometimes, noticed visibly or on touching, due to the enlargement of the gallbladder. When the liver gets involved with the infiltration of the cancer, lumps may appear over the abdominal liver area as well.
• Jaundice: Yellow discolouration of the skin and whites of the eye (sclera) can be perceived by the patient due to the rising bilirubin levels in the blood, owing to the blockade of bile ducts by the cancer.
• Itching: Jaundice can also be accompanied by widespread itching due to bilirubin deposits.
• Nausea and vomiting
• Bloating
• Indigestion
• Dyspepsia
• Flatulence
• Unintentional weight loss
• Loss of appetite
• Fever
  
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As with all types of cancer, genetic mutations, inherited or acquired, arise in the cells of the organ that cause them to rapidly proliferate and form a mass or tumour. This tumour mass grows in size and invades through various layers of the gallbladder and eventually the adjacent and distant organs and lymph nodes.

Certain factors increase the risk of developing gallbladder cancer:

• Gallstones and cholecystitis: When the patient’s blood cholesterol levels are unduly raised or due to other disorders that cause increased levels of bilirubin (a product of hemoglobin breakdown), stones may form in the gallbladder. The stone can irritate the lining of the gallbladder wall, block the bile duct and cause chronic inflammation called cholecystitis. While it is the most significant risk factor for gallbladder cancer, most people with gallstones do not develop cancer.
• Porcelain gallbladder: A stiff white gallbladder can develop due to excessive calcium deposits and is another cause of chronic inflammation that can lead to cancer.
• Gallbladder polyps: A very small percentage of polypoid growths in the gallbladder hold the potential to become cancerous.
• Primary sclerosing cholangitis: Chronic inflammation of the bile duct can also lead to cancer of the biliary tract.
• Other factors that can increase the risk of gallbladder cancer are:
  • Sex: Women are at a higher risk of both gallstones and gallbladder cancer.
  • Age: The risk of gallbladder cancer increases with age, significantly so after 65.
  • Dietary habits: Excessive mustard oil consumption has been implicated in increasing the risk of gallbladder cancer. The incidence of gallbladder cancer is higher in geographical regions where mustard is consumed as part of the local traditional diet.
  • Genetics: Family history of gallbladder cancer.
  • Previous typhoid infection: The bacteria that causes typhoid or enteric fever, Salmonella typhi, can sometimes establish chronic long term infection, with or without symptoms. This can increase the risk of gallbladder cancer.

Gallbladder cancer is staged using the TNM classification system, where T stands for tumour (extent of primary cancer tumour spread), N for nodes (involvement of lymph nodes), and M for metastasis (spread of cancer to distant organs). Cancer is staged by radiological imaging investigations like CT scans. A simplified staging of gallbladder cancer is as follows:

• Stage 0 (carcinoma in situ): The cancerous tumour has not grown beyond the innermost layer of the gallbladder wall. Carcinoma in situ implies that the cancer is located in its site of origin and hasn’t spread. In this stage, no lymph nodes are infiltrated by the disease.
• Stage 1: The cancer has spread into the muscular layer of the gallbladder wall in this stage but has not gone beyond it. Lymph nodes have not been invaded by the cancer in this stage.
• Stage 2; The cancer extends beyond the muscular wall of the gallbladder and spreads into the fibrous tissue surrounding the organ. Depending on the direction of spread - towards the abdominal wall lining or the liver - the cancer is staged as stage 2A or stage 2B, respectively. No lymph nodes are involved in this stage.
• Stage 3: The cancer extends through the outermost layers of the gallbladder wall and invades surrounding organs like the liver and the bile ducts. If upto three lymph nodes have been infiltrated by the cancer, it is stage 3B.
• Stage 4: The cancer has either invaded one of the main vessels of the liver or has spread to at least two other organs besides the liver. No more than three lymph nodes may be involved in this stage but metastasis, or distant spread, has not occurred. If four or more lymph nodes have been invaded or metastasis due to the dissemination of cancer to distant sites in the body has occurred, the cancer has advanced to stage 4B.

(Read more: Difference between a tumour and cancer)

A definitive clinical diagnosis is reached after comprehensive assessment by taking a medical history, followed by a physical examination and aided by laboratory tests and special radiological imaging. It is important to rule out other possible differential diagnoses that may present similar symptoms to arrive at an accurate diagnosis and formulate an effective treatment plan.

History: The doctor begins by taking a thorough medical history of the patient that focuses on their presenting complaints of signs and symptoms. Furthermore, they’re asked about their past and their family’s medical history. A history of preexisting lifestyle diseases and medications is also taken.

Examination: Following the medical history, the physician conducts a thorough medical examination of the patient. The process begins with a general physical examination in which signs of jaundice are sought. Upon abdominal examination, lumps and tenderness can be noted. A systemic examination is done next.

Clinical suspicion is cemented as a diagnosis only after conducting laboratory and special radiological imaging investigations.

• Blood tests:
  • Liver function tests: Elevated bilirubin levels due to blockage of bile ducts by the tumour or due to other causes, leading to the formation of pigment gallstones, can be detected.
  • Lipid profile: Deranged cholesterol levels can result in cholesterol gallstones to form and a blood test can help diagnose blood cholesterol levels.
  • Carcinoembryonic antigen (CEA) assay: Assessment of levels can be useful in diagnosis.
  • CA 19-9 assay: Can play a role in the detection of gallbladder cancer.
• Radiological imaging:
  • Abdominal ultrasound: All cases of right upper abdominal pain are generally subjected to ultrasound.
  • CT scan: It provides a more comprehensive picture of the gallbladder and possible metastasis elsewhere in the body. It is used to stage gallbladder cancer.
  • Percutaneous transhepatic cholangiography (PTC): X-ray images are taken if the gallbladder after injection of a special dye that can show blockage in the bile ducts.
  • Endoscopic retrograde cholangiography (ERCP): A special tube with a camera is inserted through the mouth, into the intestines and finally the bile duct. A dye is then injected and the gallbladder visualised.

Gallbladder cancer is managed by the formulation of a healthcare plan that involves the following components:

• Surgical management: Depending on whether the cancer is resectable or unresectable (i.e. has invaded into adjoining organs and other distant sites), the surgical treatment varies. Curative surgery is done before the cancer reaches an advanced stage. The entire gallbladder is removed along with a margin of tissue to prevent a recurrence. This procedure is called an extended cholecystectomy. Palliative surgery is done in unresectable cases to alleviate symptoms brought about by bile duct blockage.
• Radiation therapy: Following surgical treatment radiation therapy may be used as an add-on measure to reduce the chances of recurrence.
• Chemotherapy: Chemotherapeutic drugs can be used as an adjuvant following radical surgery but may also be considered as primary treatment if surgery is not possible.
• Palliative care: Besides surgical management to alleviate symptoms in advanced cancer other therapeutic measures are also taken to make the patient more comfortable. These can include, but may not be limited to:
  • Analgesics (Pain medication)
  • Antiemetics (Nausea medication)
  • Oxygen therapy
  • Placement of a stent in the bile duct to overcome blockage and allow drainage of bile

(Read more: Diet for cancer patients)

Although not all risk factors for gallbladder cancer are modifiable, some measures that can be taken to minimise chances include:

• Healthy diet: Limiting mustard and fatty foods
• Exercising: Maintaining an ideal weight and BMI

The prognostic outcome of gallbladder cancer is defined in terms of the likelihood of survival up to five years after diagnosis. The five-year survival rate or the percentage of people surviving up to five years after diagnosis, for gallbladder cancer is fairly dismal, with an overall average of only 19%. However, the five-year survival rates vary widely with the stage of the disease. If the cancer is diagnosed and treated while limited to the gallbladder, the five-year survival rate is as high as 62%; however, due to the insidious nature of the disease, only 1 in 5 cases are detected at this stage. The outlook dips to 27% with the involvement of surrounding organs and lymph nodes and to 2% after metastasis (spread to distant body parts) occurs.