Gallbladder Cancer

Introduction
Your gallbladder is a small pouch-shaped organ, about 3 inches long and 1 inch wide, located beneath your liver. Its function is to store bile, a fluid produced by your liver. After being stored in the gallbladder, bile is released into the small intestine to aid in digestion.

Gallbladder cancer is rare. According to the American Cancer Society (ACS):

• In 2019, more than 12,000 people in the United States were diagnosed with the disease.

• It is most often adenocarcinoma, a type of cancer that begins in the glandular cells lining the organ.

Causes of Gallbladder Cancer
Doctors do not know exactly what causes gallbladder cancer. However, like all cancers, it begins with an error or mutation in a person’s DNA that causes uncontrolled rapid cell growth.

As the number of cells grows quickly, a lump or tumor forms. If left untreated, these cells can spread to nearby tissues and distant parts of the body.

Certain risk factors increase the likelihood of developing gallbladder cancer, most of which are linked to long-term inflammation of the gallbladder.

Having these risk factors does not guarantee cancer, but it may increase the chances compared to the general population.

Risk Factors

• Gallstones: Small, hard, stone-like particles that form when there is too much cholesterol or bilirubin in bile. Bilirubin is a pigment formed when red blood cells break down.
  If gallstones or stones in the bile duct inside the liver block the flow of bile, inflammation of the gallbladder (cholecystitis) occurs. This may happen suddenly or be long-term (chronic).
  Chronic inflammation is the biggest risk factor for gallbladder cancer. According to the American Society of Clinical Oncology (ASCO), 75–90% of people with gallbladder cancer have gallstones.
  However, gallstones are very common, and most people with them never develop cancer. ASCO reports that more than 99% of people with gallstones never get gallbladder cancer.

• Other risk factors:

  • Porcelain gallbladder: Thickening and calcification of the gallbladder wall due to chronic cholecystitis, making it appear white like porcelain.

  • Gallbladder polyps: Only about 5% become cancerous.

  • Gender: Women are four times more likely than men to develop gallbladder cancer.

  • Age: Most common in those over 65; average age is 72.

  • Ethnicity: Higher risk among Latin Americans, Native Americans, and Mexicans in the U.S.

  • Bile duct problems: Blockage can cause bile to build up in the gallbladder, increasing inflammation and cancer risk.

  • Primary sclerosing cholangitis: Scarring from inflammation of the bile ducts increases cancer risk.

  • Typhoid: Chronic Salmonella infection increases risk.

  • Family history: Having a close relative with gallbladder cancer slightly raises the risk.

Symptoms and Signs of Gallbladder Cancer
Gallbladder cancer symptoms often appear only in advanced stages, when it has usually spread to nearby organs, lymph nodes, or other parts of the body.

Possible symptoms include:

• Pain in the upper right side of the abdomen

• Jaundice (yellowing of the skin and eyes)

• Abdominal lump or swelling from gallbladder enlargement or spread to the liver

• Nausea and vomiting

• Unexplained weight loss

• Fever

• Abdominal bloating

• Dark-colored stools (black or dark yellow)

Diagnosis and Staging of Gallbladder Cancer
Sometimes gallbladder cancer is found accidentally during surgery for cholecystitis or another reason. More often, doctors order tests when symptoms appear.

Tests used for diagnosis, staging, and treatment planning include:

• Blood tests: Check liver function and detect issues in the liver, gallbladder, or bile ducts.

• Ultrasound: Uses sound waves to create images of the gallbladder and liver; often done first.

• CT scan: Produces detailed images of the gallbladder and nearby organs.

• MRI scan: Provides more detailed images than other tests.

• Percutaneous transhepatic cholangiography (PTC): X-ray with dye to detect bile duct or liver blockages.

• Endoscopic retrograde cholangiopancreatography (ERCP): A lighted tube is passed through the mouth to the small intestine; dye is injected into the bile ducts for X-rays.

• Biopsy: A small tumor sample is examined under a microscope to confirm cancer.

Staging
Gallbladder cancer staging determines how far the cancer has spread beyond the gallbladder. Doctors use this to decide the best treatment and predict outcomes.

The American Joint Committee on Cancer (AJCC) TNM system is used:

• Stage 0: Cancer cells are confined to the innermost layer (carcinoma in situ).

• Stage 4: Large tumors have spread to nearby organs or distant parts of the body.

TNM stands for:

• T (Tumor): How deeply the tumor has invaded the gallbladder wall.

• N (Nodes): Whether cancer has spread to nearby lymph nodes.

• M (Metastasis): Whether cancer has spread to distant parts of the body.

Treatment for Gallbladder Cancer
Surgery is a possible treatment to completely remove gallbladder cancer, but only if it is detected early and has not spread to nearby organs or distant sites.

Unfortunately, according to the ACS, only about 20% of people are diagnosed before it spreads.

Additional treatments:

• Radiation therapy and chemotherapy may be used after surgery to eliminate remaining cancer cells.

• If the cancer cannot be removed, chemotherapy and radiation may extend life and reduce symptoms but will not cure the disease.

Palliative care for advanced cancer:
When cancer has spread too far, surgery may be done to relieve symptoms. Other supportive treatments include:

• Pain-relief medications

• Anti-nausea drugs

• Oxygen therapy

• Stent or tube placement in blocked bile ducts to restore bile flow

These treatments are used when overall health is poor or surgery is not possible.

Prognosis
The outlook depends on the stage of the cancer. Early-stage gallbladder cancer has a much better prognosis than advanced-stage disease.

Five-year survival rates:

• All stages combined: 19%

• Stage 0 (carcinoma in situ): 80%

• Stage 1 (confined to gallbladder): 50%

• Stage 3 (spread to lymph nodes): 8%

• Stage 4 (spread to distant organs): Less than 4%

Prevention
Many risk factors such as age or ethnicity cannot be changed, so gallbladder cancer cannot be completely prevented. However, healthy habits may reduce risk.

Tips include:

• Maintain a healthy weight: Reduces the risk of cancer and other diseases.

• Eat a healthy diet: Fruits and vegetables boost immunity; whole grains and limited processed foods help.

• Exercise regularly: Helps maintain a healthy weight and strengthen immunity.