Liver and gallbladder cancer is a common and aggressive malignancy of the hepatic biliary system. Liver cancer is the fourth leading cause of cancer mortality and is ranked the sixth most diagnosed cancer worldwide. However, gallbladder cancer is rare and accounts for 1.2% of all cancer diagnoses globally. The incidence of these cancers is increasing and there is a higher prevalence in developing countries.
The liver and gallbladder are two accessory organs of the gastrointestinal tract. The liver is located under the diaphragm in the upper right portion of the abdomen. It aids in digestion and hemostasis. The liver secretes bile - a yellowish-green fluid that emulsifies fats. The excess bile is stored in a small sac-shaped organ – the gallbladder which is located below the liver. The liver and gallbladder are interconnected by ducts. When the cells in the liver or gallbladder undergo DNA changes (mutations), it may cause abnormal cell growth, leading to cancers.
Liver cancer (or hepatic cancer) arises when the healthy cells in the liver undergo mutations in their DNA and grow out of control to form a mass or sheet of cells called a tumor. These tumors can be malignant (cancerous, spread to other parts of the body) or benign (non-cancerous, do not spread to nearby tissues).
Liver cancer can be classified into two:
Liver cancer in the early stage generally has no signs or symptoms. As cancer grows and spreads to nearby tissue the following symptoms can be observed:
The precise cause of liver cancer is not known. However, certain factors can increase the risk of developing liver cancer. These include:
If a person experiences any signs or symptoms of liver cancer, the following tests may be recommended:
A Blood tests: These tests help to diagnose liver function abnormalities.
Imaging tests: Tests such as ultrasound, computerized tomography (CT) scan, and magnetic resonance imaging (MRI) provide detailed information about the size and spread of cancer. An angiogram is performed to examine the blood vessels that supply blood to the tumor.
Biopsy: It involves the removal of tumor tissues using specialized needles for detailed examination. It is the most reliable way to determine cancer.
The liver cancer staging is done using the TNM staging system. It provides detailed information about:
Based on this system, liver cancer stages are as follows:
Once liver cancer is diagnosed, a customized treatment plan is created based on the stage of cancer at the time of diagnosis and the overall health of the liver. Treatments for liver cancer include:
Surgery: The tumor and some surrounding healthy tissue are removed by surgical procedures. Surgery improves the chance of recovery for patients with early-stage liver cancer. Surgical approaches include:
Possible side effects are bleeding, infections, blood clots, and rejection of new liver.
Ablation therapy: This therapy involves non-surgical methods to destroy the tumors without removing them and is recommended for the elderly or patients with serious conditions, where surgery cannot be considered. The procedure involves placing a needle or probe directly into the liver tumor to destroy them. Based on the methods used to destroy the cancer cells, it is classified into:
Embolization Therapy: Embolization is a procedure in which certain substances are injected directly into the blood vessels in the liver to block or reduce the blood flow to a tumor in the liver. Sometimes, the procedure is combined with chemotherapy (called chemoembolization) or radiation (radioembolization) for better outcomes.
Possible complications after the procedure are abdominal pain, fever, nausea, liver infections, and blood clots in the main blood vessels.
Targeted therapy: This therapy uses drugs that interfere with genes or proteins that contribute to the growth and survival of cancer, and thereby destroy the cancer cells. These are different from chemo drugs and have minimal side effects.
Chemotherapy: It involves the use of specific oral or intravenous drugs to kill cancer cells. It is recommended for patients who cannot undergo surgery or have not responded to local therapies or targeted therapy. Chemotherapy is usually given in cycles and the patient may receive a single or a combination of drugs.
Common side effects include fatigue, nausea, vomiting, loss of appetite, hair loss, and diarrhea.4
Radiation therapy: High-energy radiations like X-rays are used to destroy tumor cells. It is not considered for patients with severe liver damage due to hepatitis or cirrhosis.
For liver cancer, stereotactic body radiation therapy is used. This method delivers high doses of radiation to a tumor while limiting the amount of radiation to nearby healthy tissue.
Major side effects may include mild skin reactions, fatigue, loss of appetite, nausea and vomiting, diarrhea, and weight loss.
Immunotherapy: This uses drugs that direct the body’s immune system to kill cancer cells. For liver cancer, drugs like atezolizumab, pembrolizumab, nivolumab, and ipilimumab are used to attack cancer cells by boosting the natural defense of the immune system.
Gallbladder cancer occurs when healthy cells in the gallbladder undergo change and start to grow out of control, which slowly forms a tissue mass or lump called a tumor. The tumors can be benign (non-cancerous, do not spread to nearby tissues) or malignant (cancerous, spread to other parts of the body).
The majority of gallbladder cancers are adenocarcinomas - cancer that starts in the tissue on the inside wall of the gallbladder. Less common types of gallbladder cancer are adenosquamous carcinomas, squamous cell carcinomas, and carcinosarcomas.
There are no specific symptoms for gallbladder cancer in its early stage. Symptoms usually appear in the advanced stage when the tumor is large and/or has spread.
Common symptoms of gallbladder cancer include:
Like other cancers, the exact cause of gallbladder cancer is not clear. Some factors that may increase the risk of gallbladder cancer are:
There are no early screening tests used for gallbladder cancer. If a person experiences any signs or symptoms of gallbladder cancer, the following tests are recommended.
Liver and gallbladder function test: Elevated levels of bilirubin in the blood indicate gallbladder cancer due to blockage of the common bile duct by a tumor.
Tumor marker: Tumor markers are proteins secreted by cancer cells, whose presence in the blood indicates cancer. Gallbladder cancer patients have high CA19-9 or carcinoembryonic antigen (CEA) levels in their blood.
Gallbladder cancer is also staged based on the TNM staging system. Based on this system, cancer has the following stages:
Treatment approaches for gallbladder cancer depend on the stage of cancer at the time of diagnosis, possible side effects, and the overall health of the patient. The main types of treatments for gallbladder cancer are:
Surgery: It involves the surgical removal of the entire tumor. Surgery is the mainstay of early and advanced cancers for easing the symptoms of advanced cancer.
Radiation therapy: Radiation therapy may be used before surgery (neoadjuvant therapy) to shrink the tumor or after surgery (adjuvant therapy) to destroy any remaining cancer cells. For advanced cancers, it is also used to ease the symptoms (palliative therapy).
For gallbladder cancer, high-energy beams are delivered to the site of the tumor through an external source (external beam therapy). It is an outpatient procedure that is usually given over several weeks.
Side effects from radiation therapy may include mild skin reactions, fatigue, loss of appetite, nausea and vomiting, diarrhea, and weight loss.
Chemotherapy: It involves the use of specific anticancer drugs to destroy the cancer cells. In gallbladder cancer, chemo drugs are used as:
Common side effects of chemotherapy are fatigue, nausea and vomiting, loss of appetite, hair loss, and diarrhea.
Immunotherapy: It involves the use of medications that boost the patient’s immune system to recognize the cancer cells and destroy them. Most of the immunotherapy drugs for gallbladder cancer are in clinical trials.
Although there is no way to prevent liver and gallbladder cancers, early diagnosis and prompt treatment may reduce the risk of cancer. Patients with early-stage tumors have the best chance of long-term survival. Unfortunately, most liver and gallbladder cancers are diagnosed in the advanced stages. Follow-up care and staying positive throughout the treatment will help obtain better outcomes.
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