Adult Primary Liver Cancer

Adult primary liver cancer is a disease in which malignant (cancer) cells form in the tissues of the liver.

Types

There are two types of adult primary liver cancer. The two types of adult primary liver cancer are:

• Hepatocellular carcinoma.
• Cholangiocarcinoma (bile duct cancer). (

The most common type of adult primary liver cancer is hepatocellular carcinoma. This type of liver cancer is the third leading cause of cancer-related deaths worldwide. Primary liver cancer can occur in both adults and children. However, treatment for children is different than treatment for adults

Risk factors

Risk factors for liver cancer include the following:

• Having hepatitis B or hepatitis C infection. Having both hepatitis B and hepatitis C increases the risk even more.
• Having cirrhosis.
• Heavy alcohol use. Heavy alcohol use and having hepatitis B infection increases the risk even more.
• Eating foods tainted with aflatoxin (poison from a fungus that can grow on foods, such as grains and nuts, that have not been stored properly).
• Having nonalcoholic steatohepatitis (NASH), a condition in which fat builds up in the liver and may progress to inflammation of the liver and liver cell damage.
• Using tobacco, such as cigarette smoking.
• Having certain inherited or rare disorders that damage the liver, including the following:
• Hereditary hemochromatosis, an inherited disorder in which the body stores more iron than it needs. The extra iron is mostly stored in the liver, heart, pancreas, skin, and joints.
• Alpha-1 antitrypsin deficiency, an inherited disorder that can cause liver and lung disease.
• Glycogen storage disease, an inherited disorder in which there are problems with how a form of glucose (sugar) called glycogen is stored and used in the body.
• Porphyria cutanea tarda, a rare disorder that affects the skin and causes painful blisters on parts of the body that are exposed to the sun, such as the hands, arms, and face. Liver problems can also occur.
• Wilson disease, a rare inherited disorder in which the body stores more copper than it needs. The extra copper is stored in the liver, brain, eyes, and other organs.
• Older age is the main risk factor for most cancers. The chance of getting cancer increases as you get older.

Signs and symptoms

These and other signs and symptoms may be caused by adult primary liver cancer or by other conditions. Check with your doctor if you have any of the following:

• A hard lump on the right side just below the rib cage.
• Discomfort in the upper abdomen on the right side.
• A swollen abdomen.
• Pain near the right shoulder blade or in the back.
• Jaundice (yellowing of the skin and whites of the eyes).
• Easy bruising or bleeding.
• Unusual tiredness or weakness.
• Nausea and vomiting.
• Loss of appetite or feelings of fullness after eating a small meal.
• Weight loss for no known reason.
• Pale, chalky bowel movements and dark urine.
• Fever.

Diagnosis

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.

Serum tumor marker test

A procedure in which a sample of blood is examined to measure the amounts of certain substances released into the blood by organs, tissues, or tumor cells in the body. Certain substances are linked to specific types of cancer when found in increased levels in the blood. These are called tumor markers. An increased level of alpha-fetoprotein (AFP) in the blood may be a sign of liver cancer. Other cancers and certain noncancerous conditions, including cirrhosis and hepatitis, may also increase AFP levels. Sometimes the AFP level is normal even when there is liver 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 cancer.

CT scan (CAT scan)

A procedure that makes a series of detailed pictures of areas inside the body, such as the abdomen, 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. Images may be taken at three different times after the dye is injected, to get the best picture of abnormal areas in the liver. This is called triple-phase CT. A spiral or helical CT scan makes a series of very detailed pictures of areas inside the body using an x-ray machine that scans the body in a spiral path.

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, such as the liver. This procedure is also called nuclear magnetic resonance imaging (NMRI). To create detailed pictures of blood vessels in and near the liver, dye is injected into a vein. This procedure is called MRA (magnetic resonance angiography). Images may be taken at three different times after the dye is injected, to get the best picture of abnormal areas in the liver. This is called triple-phase MRI.

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. The picture can be printed to be looked at later.

Biopsy

The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. Procedures used to collect the sample of cells or tissues include the following: Fine-needle aspiration biopsy: The removal of cells, tissue or fluid using a thin needle. Core needle biopsy: The removal of cells or tissue using a slightly wider needle.

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. Another instrument is inserted through the same or another incision to remove the tissue samples. A biopsy is not always needed to diagnose adult primary liver cancer.

Treatment

Eight types of standard treatment are used: Surveillance Surveillance for lesions smaller than 1 centimeter found during screening. Follow-up every three months is common.

Surgery

A partial hepatectomy (surgery to remove the part of the liver where cancer is found) may be done. A wedge of tissue, an entire lobe, or a larger part of the liver, along with some of the healthy tissue around it is removed. The remaining liver tissue takes over the functions of the liver and may regrow.

Liver transplant

In a liver transplant, the entire liver is removed and replaced with a healthy donated liver. A liver transplant may be done when the disease is in the liver only and a donated liver can be found. If the patient has to wait for a donated liver, other treatment is given as needed.

Ablation therapy

Ablation therapy removes or destroys tissue. Different types of ablation therapy are used for liver cancer:

Radiofrequency ablation: The use of special needles that are inserted directly through the skin or through an incision in the abdomen to reach the tumor. High-energy radio waves heat the needles and tumor which kills cancer cells.

Microwave therapy

A type of treatment in which the tumor is exposed to high temperatures created by microwaves. This can damage and kill cancer cells or make them more sensitive to the effects of radiation and certain anticancer drugs.

Percutaneous ethanol injection

A cancer treatment in which a small needle is used to inject ethanol (pure alcohol) directly into a tumor to kill cancer cells. Several treatments may be needed. Usually local anesthesia is used, but if the patient has many tumors in the liver, general anesthesia may be used.

Cryoablation

A treatment that uses an instrument to freeze and destroy cancer cells. This type of treatment is also called cryotherapy and cryosurgery. The doctor may use ultrasound to guide the instrument.

Electroporation therapy

A treatment that sends electrical pulses through an electrode placed in a tumor to kill cancer cells. Electroporation therapy is being studied in clinical trials.

Embolization therapy

Embolization therapy is the use of substances to block or decrease the flow of blood through the hepatic artery to the tumor. When the tumor does not get the oxygen and nutrients it needs, it will not continue to grow. Embolization therapy is used for patients who cannot have surgery to remove the tumor or ablation therapy and whose tumor has not spread outside the liver.

The liver receives blood from the hepatic portal vein and the hepatic artery. Blood that comes into the liver from the hepatic portal vein usually goes to the healthy liver tissue. Blood that comes from the hepatic artery usually goes to the tumor. When the hepatic artery is blocked during embolization therapy, the healthy liver tissue continues to receive blood from the hepatic portal vein.

There are two main types of embolization therapy:

Transarterial embolization (TAE): A small incision (cut) is made in the inner thigh and a catheter (thin, flexible tube) is inserted and threaded up into the hepatic artery. Once the catheter is in place, a substance that blocks the hepatic artery and stops blood flow to the tumor is injected. Transarterial chemoembolization (TACE): This procedure is like TAE except an anticancer drug is also given. The procedure can be done by attaching the anticancer drug to small beads that are injected into the hepatic artery or by injecting the anticancer drug through the catheter into the hepatic artery and then injecting the substance to block the hepatic artery. Most of the anticancer drug is trapped near the tumor and only a small amount of the drug reaches other parts of the body. This type of treatment is also called chemoembolization.

Targeted therapy

Targeted therapy is a treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Tyrosine kinase inhibitors are a type of targeted therapy used in the treatment of adult primary liver cancer.

Tyrosine kinase inhibitors are small-molecule drugs that go through the cell membrane and work inside cancer cells to block signals that cancer cells need to grow and divide. Some tyrosine kinase inhibitors also have angiogenesis inhibitor effects. Sorafenib, lenvatinib, and regorafenib are types of tyrosine kinase inhibitors.

Immunotherapy

Immunotherapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or biologic therapy.

Immune checkpoint inhibitor therapy is a type of immunotherapy.

Immune checkpoint inhibitor therapy: PD-1 is a protein on the surface of T cells that helps keep the body’s immune responses in check. When PD-1 attaches to another protein called PDL-1 on a cancer cell, it stops the T cell from killing the cancer cell. PD-1 inhibitors attach to PDL-1 and allow the T cells to kill cancer cells. Nivolumab is a type of immune checkpoint inhibitor.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Cabozantinib (Brand name: Cabometyx)cabozantinib (Cabometyx) was approved for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
• Lenvatinib (Brand name: Lenvima) lenvatimib (Lenvima) was approved for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).
• Ethiodized oil injection (Brand name: Lipiodol)ethiodized oil injection (Lipiodol) was approved for selective hepatic intra-arterial use for imaging tumors in adults with known hepatocellular carcinoma (HCC).
• Sorafenib (Brand name: Nexavar) sorafenib (Nexavar) was approved for the treatment of unresectable hepatocellular carcinoma.
• Regorafenib (Brand name: Stivarga)regorafenib (Stivarga) was approved for the treatment of patients with hepatocellular carcinoma (HCC or liver cancer) who have been previously treated with the drug sorafenib.