21st Century Adult Cancer Sourcebook: Liver Cancer, Hepatocellular Carcinoma (HCC) - Clinical Data for Patients, Families, and Physicians
Edition 1.0 - October 2011
National Cancer Institute
Smashwords Edition
Copyright 2011 Progressive Management
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PART ONE
Chapter 1A: Liver Cancer Patient Information
Chapter 2A: Liver Cancer Health Professional Information
Chapter 3A: Liver Cancer NCI Drugs
Chapter 4A: Liver Cancer Background Information
Chapter 5A: Liver Cancer Clinical Trials
PART TWO
Chapter 1B: Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (NCI)
Chapter 2B: Glossary of Clinical Trial Terms
Chapter 3B: Clinical Trials Background Information
Chapter 4B: Cancer Clinical Trials -The Basic Workbook
Chapter 5B: Cancer Clinical Trials - The In-Depth Program
Chapter 6B: Clinical Trials at NIH
Chapter 7B: How To Find A Cancer Treatment Trial: A Ten Step Guide
Chapter 8B: Taking Part in Cancer Treatment Research Studies
Chapter 9B: Cancer Clinical Trials
Chapter 10B: Access to Investigational Drugs
Chapter 12B: Taking Time: Support for People with Cancer
Chapter 13B: Facing Forward - Life After Cancer Treatment
Chapter 14B: Chemotherapy and You
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PART ONE
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Chapter 1A: Liver Cancer Patient Information
Adult Primary Liver Cancer Treatment
Patient Version
Last Modified: 03/30/2011
General Information About Adult Primary Liver Cancer
Key Points for This Section
* Adult primary liver cancer is a disease in which malignant (cancer) cells form in the tissues of the liver.
* Having hepatitis or cirrhosis can affect the risk of developing adult primary liver cancer.
* Possible signs of adult primary liver cancer include a lump or pain on the right side.
* Tests that examine the liver and the blood are used to detect (find) and diagnose adult primary liver cancer.
* Certain factors affect prognosis (chance of recovery) and treatment options.
Adult primary liver cancer is a disease in which malignant (cancer) cells form in the tissues of the liver.
The liver is one of the largest organs in the body. It has four lobes and fills the upper right side of the abdomen inside the rib cage. The liver has many important functions, including:
* Filtering harmful substances from the blood so they can be passed from the body in stools and urine.
* Making bile to help digest fats from food.
* Storing glycogen (sugar), which the body uses for energy.
Anatomy of the liver. The liver is in the upper abdomen near the stomach, intestines, gallbladder, and pancreas. The liver has four lobes. Two lobes are on the front and two small lobes (not shown) are on the back of the liver.
This summary refers to the treatment of primary liver cancer (cancer that begins in the liver). Treatment of metastatic liver cancer, which is cancer that begins in other parts of the body and spreads to the liver, is not discussed in this summary. Primary liver cancer can occur in both adults and children. Treatment for children, however, is different than treatment for adults
Having hepatitis or cirrhosis can affect the risk of developing adult primary liver cancer.
Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. The following are possible risk factors for adult primary liver cancer:
* Having hepatitis B and/or hepatitis C.
* Having a close relative with both hepatitis and liver cancer.
* Having cirrhosis.
* 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).
Possible signs of adult primary liver cancer include a lump or pain on the right side.
These symptoms may be caused by swelling of the liver. These and other symptoms may be caused by adult primary liver cancer or by other conditions. A doctor should be consulted if any of the following problems occur:
* A hard lump on the right side just below the rib cage.
* Discomfort in the upper abdomen on the right side.
* Pain around the right shoulder blade.
* Unexplained weight loss.
* Jaundice (yellowing of the skin and whites of the eyes).
* Unusual tiredness.
* Nausea.
* Loss of appetite.
Tests that examine the liver and the blood are used to detect (find) and diagnose adult primary liver cancer.
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.
* 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, 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. 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. 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).
* 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.
* Angiogram: A procedure to look at blood vessels and the flow of blood. A contrast dye is injected into the blood vessel. As the contrast dye moves through the blood vessel, x-rays are taken to see if there are any blockages in or near the liver.
* 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. Other instruments may be inserted through the same or other incisions to perform procedures such as removing organs or taking tissue samples for biopsy.
* Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. The sample may be taken using a thin needle inserted into the liver during an x-ray or ultrasound. This is called a fine-needle aspiration (FNA) biopsy. The biopsy may be done during a laparoscopy.
Certain factors affect prognosis (chance of recovery) and treatment options.
The prognosis (chance of recovery) and treatment options depend on the following:
* The stage of the cancer (the size of the tumor, whether it affects part or all of the liver, or has spread to other places in the body).
* How well the liver is working.
* The patient’s general health, including whether there is cirrhosis of the liver.
Prognosis is also affected by alpha-fetoprotein (AFP) levels.
Glossary Terms
abdomen (AB-doh-men)
* The area of the body that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs.
aflatoxin (A-fluh-TOK-sin)
* A harmful substance made by certain types of mold (Aspergillus flavus and Aspergillus parasiticus) that is often found on poorly stored grains and nuts. Consumption of foods contaminated with aflatoxin is a risk factor for primary liver cancer.
alpha-fetoprotein (AL-fuh-FEE-toh-PROH-teen)
* A protein normally produced by a fetus. AFP levels are usually undetectable in the blood of healthy adult men or women (who are not pregnant). An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. Also called AFP.
angiogram (AN-jee-oh-gram)
* An x-ray of blood vessels. The person receives an injection of dye to outline the vessels on the x-ray.
angiography (an-jee-AH-gruh-fee)
* A procedure to x-ray blood vessels. The blood vessels can be seen because of an injection of a dye that shows up in the x-ray.
appetite (A-peh-tite)
* A desire to satisfy a physical or mental need, such as for food, sex, or adventure.
bile (bile)
* A fluid made by the liver and stored in the gallbladder. Bile is excreted into the small intestine, where it helps digest fat.
biopsy (BY-op-see)
* The removal of cells or tissues for examination by a pathologist. The pathologist may study the tissue under a microscope or perform other tests on the cells or tissue. There are many different types of biopsy procedures. The most common types include: (1) incisional biopsy, in which only a sample of tissue is removed; (2) excisional biopsy, in which an entire lump or suspicious area is removed; and (3) needle biopsy, in which a sample of tissue or fluid is removed with a needle. When a wide needle is used, the procedure is called a core biopsy. When a thin needle is used, the procedure is called a fine-needle aspiration biopsy.
blood (blud)
* A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
blood vessel (blud VEH-sel)
* A tube through which the blood circulates in the body. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins.
cancer (KAN-ser)
* A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.
cell (sel)
* The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
cirrhosis (seh-ROH-sis)
* A type of chronic, progressive liver disease in which liver cells are replaced by scar tissue.
contrast material (KON-trast muh-TEER-ee-ul)
* A dye or other substance that helps show abnormal areas inside the body. It is given by injection into a vein, by enema, or by mouth. Contrast material may be used with x-rays, CT scans, MRI, or other imaging tests.
CT scan (… skan)
* A series of detailed pictures of areas inside the body taken from different angles. The pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography scan, computerized axial tomography scan, and computerized tomography.
digestion (dy-JES-chun)
* The process of breaking down food into substances the body can use for energy, tissue growth, and repair.
fine-needle aspiration biopsy (... NEE-dul AS-pih-RAY-shun BY-op-see)
* The removal of tissue or fluid with a thin needle for examination under a microscope. Also called FNA biopsy.
fungus (FUN-gus)
* A plant-like organism that does not make chlorophyll. Mushrooms, yeasts, and molds are examples. The plural is fungi.
helical computed tomography (HEE-lih-kul kum-PYOO-ted toh-MAH-gruh-fee)
* A detailed picture of areas inside the body. The pictures are created by a computer linked to an x-ray machine that scans the body in a spiral path. Also called spiral CT scan.
hepatitis B virus (HEH-puh-TY-tis ... VY-rus)
* A virus that causes hepatitis (inflammation of the liver). It is carried and passed to others through the blood and other body fluids. Different ways the virus is spread include sharing needles with an infected person and being stuck accidentally by a needle contaminated with the virus. Infants born to infected mothers may also become infected with the virus. Although many patients who are infected with hepatitis B virus may not have symptoms, long-term infection may lead to cirrhosis (scarring of the liver) and liver cancer. Also called HBV.
hepatitis C virus (HEH-puh-TY-tis ... VY-rus)
* A virus that causes hepatitis (inflammation of the liver). It is carried and passed to others through the blood and other body fluids. Different ways the virus is spread include sharing needles with an infected person and being stuck accidentally by a needle contaminated with the virus. Infants born to infected mothers may also become infected with the virus. Although patients who are infected with hepatitis C virus may not have symptoms, long-term infection may lead to cirrhosis (scarring of the liver) and liver cancer. These patients may also have an increased risk for certain types of non-Hodgkin lymphoma. Also called HCV.
incision (in-SIH-zhun)
* A cut made in the body to perform surgery.
injection (in-JEK-shun)
* Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."
jaundice (JAWN-dis)
* A condition in which the skin and the whites of the eyes become yellow, urine darkens, and the color of stool becomes lighter than normal. Jaundice occurs when the liver is not working properly or when a bile duct is blocked.
laparoscope (LA-puh-ruh-SKOPE)
* A thin, tube-like instrument used to look at tissues and organs inside the abdomen. A laparoscope has a light and a lens for viewing and may have a tool to remove tissue.
laparoscopy (LA-puh-ROS-koh-pee)
* A procedure that uses a laparoscope, inserted through the abdominal wall, to examine the inside of the abdomen. A laparoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue to be checked under a microscope for signs of disease.
liver (LIH-ver)
* A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.
liver cancer (LIH-ver KAN-ser)
* Primary liver cancer is cancer that forms in the tissues of the liver. Secondary liver cancer is cancer that spreads to the liver from another part of the body.
liver function test (LIH-ver FUNK-shun ...)
* A blood test to measure the blood levels of certain substances released by the liver. A high or low level of certain substances can be a sign of liver disease.
lobe
* A portion of an organ, such as the liver, lung, breast, thyroid, or brain.
metastatic (meh-tuh-STA-tik)
* Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.
microscope (MY-kroh-SKOPE)
* An instrument that is used to look at cells and other small objects that cannot be seen with the eye alone.
MRI
* A procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. MRI makes better images of organs and soft tissue than other scanning techniques, such as computed tomography (CT) or x-ray. MRI is especially useful for imaging the brain, the spine, the soft tissue of joints, and the inside of bones. Also called magnetic resonance imaging, NMRI, and nuclear magnetic resonance imaging.
nausea
* A feeling of sickness or discomfort in the stomach that may come with an urge to vomit. Nausea is a side effect of some types of cancer therapy.
organ (OR-gun)
* A part of the body that performs a specific function. For example, the heart is an organ.
pathologist (puh-THAH-loh-jist)
* A doctor who identifies diseases by studying cells and tissues under a microscope.
personal medical history (PER-suh-nul MEH-dih-kul HIH-stuh-ree)
* A collection of information about a person’s health. It may include information about allergies, illnesses and surgeries, and dates and results of physical exams, tests, screenings, and immunizations. It may also include information about medicines taken and about diet and exercise. Also called personal health record and personal history.
physical examination (FIH-zih-kul eg-ZA-mih-NAY-shun)
* An exam of the body to check for general signs of disease.
primary tumor (PRY-mayr-ee TOO-mer)
* The original tumor.
prognosis (prog-NO-sis)
* The likely outcome or course of a disease; the chance of recovery or recurrence.
risk factor (... FAK-ter)
* Something that increases the chance of developing a disease. Some examples of risk factors for cancer are age, a family history of certain cancers, use of tobacco products, being exposed to radiation or certain chemicals, infection with certain viruses or bacteria, and certain genetic changes.
serum tumor marker test (SEER-um TOO-mer MAR-ker ...)
* A blood test that measures the amount of substances called tumor markers (or biomarkers). Tumor markers are released into the blood by tumor cells or by other cells in response to tumor cells. A high level of a tumor marker may be a sign of cancer.
shoulder blade (SHOLE-der …)
* One of a pair of triangular bones at the back of the shoulder. The shoulder blade connects the collarbone with the upper arm bone. Also called scapula.
sonogram (SAH-noh-gram)
* A computer picture of areas inside the body created by bouncing high-energy sound waves (ultrasound) off internal tissues or organs. Also called ultrasonogram.
spiral CT scan (SPY-rul … skan)
* A detailed picture of areas inside the body. The pictures are created by a computer linked to an x-ray machine that scans the body in a spiral path. Also called helical computed tomography.
stage
* The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.
stool (stool)
* The material in a bowel movement. Stool is made up of undigested food, bacteria, mucus, and cells from the lining of the intestines. Also called feces.
surgery (SER-juh-ree)
* A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.
symptom (SIMP-tum)
* An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.
tissue (TIH-shoo)
* A group or layer of cells that work together to perform a specific function.
tumor (TOO-mer)
* An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.
tumor marker (TOO-mer ...)
* A substance that may be found in tumor tissue or released from a tumor into the blood or other body fluids. A high level of a tumor marker may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (in ovarian cancer), CA 15-3 (in breast cancer), CEA (in ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (in prostate cancer).
ultrasound (UL-truh-SOWND)
* A procedure in which high-energy sound waves are bounced off internal tissues or organs and make echoes. The echo patterns are shown on the screen of an ultrasound machine, forming a picture of body tissues called a sonogram. Also called ultrasonography.
urine (YOOR-in)
* Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra.
vein (vayn)
* A blood vessel that carries blood to the heart from tissues and organs in the body.
x-ray (EX-ray)
* A type of high-energy radiation. In low doses, x-rays are used to diagnose diseases by making pictures of the inside of the body. In high doses, x-rays are used to treat cancer.
Table of Links
1 http://www.cancer.gov/cancertopics/pdq/treatment/childliver/Patient
Stages of Adult Primary Liver Cancer
Key Points for This Section
* After adult primary liver cancer has been diagnosed, tests are done to find out if cancer cells have spread within the liver or to other parts of the body.
* There are three ways that cancer spreads in the body.
* The following stages are used for adult primary liver cancer:
* Stage I
* Stage II
* Stage III
* Stage IV
* For adult primary liver cancer, stages are also grouped according to how the cancer may be treated. There are 3 treatment groups:
* Localized resectable
* Localized and locally advanced unresectable
* Advanced
After adult primary liver cancer has been diagnosed, tests are done to find out if cancer cells have spread within the liver or to other parts of the body.
The process used to find out if cancer has spread within the liver or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:
* Chest x-ray: 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, making a picture of areas inside the body.
* CT scan (CAT scan): 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, computerized tomography, or computerized axial tomography.
* 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. This procedure is also called nuclear magnetic resonance imaging (NMRI).
* Bone scan: A procedure to check if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones and is detected by a scanner.
There are three ways that cancer spreads in the body.
The three ways that cancer spreads in the body are:
* Through tissue. Cancer invades the surrounding normal tissue.
* Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
* Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.
When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.
The following stages are used for adult primary liver cancer:
Stage I
In stage I, there is one tumor and it has not spread to nearby blood vessels.
Pea, peanut, walnut, and lime show tumor sizes.
Stage II
In stage II, one of the following is found:
* one tumor that has spread to nearby blood vessels; or
* more than one tumor, none of which is larger than 5 centimeters.
Stage III
Stage III is divided into Stage IIIA, IIIB, and IIIC.
* In stage IIIA, one of the following is found:
* more than one tumor larger than 5 centimeters; or
* one tumor that has spread to a major branch of blood vessels near the liver.
* In stage IIIB, there are one or more tumors of any size that have either:
* spread to nearby organs other than the gallbladder; or
* broken through the lining of the peritoneal cavity.
* In stage IIIC, the cancer has spread to nearby lymph nodes.
Stage IV
In stage IV, cancer has spread beyond the liver to other places in the body, such as the bones or lungs. The tumors may be of any size and may also have spread to nearby blood vessels and/or lymph nodes.
For adult primary liver cancer, stages are also grouped according to how the cancer may be treated. There are 3 treatment groups:
Localized resectable
The cancer is found in the liver only, has not spread, and can be completely removed by surgery.
Localized and locally advanced unresectable
The cancer is found in the liver only and has not spread, but cannot be completely removed by surgery.
Advanced
Cancer has spread throughout the liver or has spread to other parts of the body, such as the lungs and bone.
Glossary Terms
blood (blud)
* A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
blood vessel (blud VEH-sel)
* A tube through which the blood circulates in the body. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins.
bone cancer (bone KAN-ser)
* Primary bone cancer is cancer that forms in cells of the bone. Some types of primary bone cancer are osteosarcoma, Ewing sarcoma, malignant fibrous histiocytoma, and chondrosarcoma. Secondary bone cancer is cancer that spreads to the bone from another part of the body (such as the prostate, breast, or lung).
bone scan (bone skan)
* A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner.
breast cancer (brest KAN-ser)
* Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.
cancer (KAN-ser)
* A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.
capillary (KA-pih-layr-ee)
* The smallest type of blood vessel. A capillary connects an arteriole (small artery) to a venule (small vein) to form a network of blood vessels in almost all parts of the body. The wall of a capillary is thin and leaky, and capillaries are involved in the exchange of fluids and gases between tissues and the blood.
cell (sel)
* The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
centimeter (SEN-tih-MEE-ter)
* A measure of length in the metric system. There are 100 centimeters in a meter and 2½ centimeters in an inch.
chest x-ray (chest EX-ray)
* An x-ray of the structures inside the chest. An x-ray is a type of high-energy radiation that can go through the body and onto film, making pictures of areas inside the chest, which can be used to diagnose disease.
contrast material (KON-trast muh-TEER-ee-ul)
* A dye or other substance that helps show abnormal areas inside the body. It is given by injection into a vein, by enema, or by mouth. Contrast material may be used with x-rays, CT scans, MRI, or other imaging tests.
CT scan (… skan)
* A series of detailed pictures of areas inside the body taken from different angles. The pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography scan, computerized axial tomography scan, and computerized tomography.
gallbladder (GAWL-bla-der)
* The pear-shaped organ found below the liver. Bile is concentrated and stored in the gallbladder.
injection (in-JEK-shun)
* Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."
invasive cancer (in-VAY-siv KAN-ser)
* Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues. Also called infiltrating cancer.
liver (LIH-ver)
* A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.
lung
* One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.
lymph (limf)
* The clear fluid that travels through the lymphatic system and carries cells that help fight infections and other diseases. Also called lymphatic fluid.
lymph node (limf node)
* A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Lymph nodes filter lymph (lymphatic fluid), and they store lymphocytes (white blood cells). They are located along lymphatic vessels. Also called lymph gland.
lymph vessel (limf ...)
* A thin tube that carries lymph (lymphatic fluid) and white blood cells through the lymphatic system. Also called lymphatic vessel.
lymphatic system (lim-FA-tik SIS-tem)
* The tissues and organs that produce, store, and carry white blood cells that fight infections and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes, and lymphatic vessels (a network of thin tubes that carry lymph and white blood cells). Lymphatic vessels branch, like blood vessels, into all the tissues of the body.
metastasis (meh-TAS-tuh-sis)
* The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).
MRI
* A procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. MRI makes better images of organs and soft tissue than other scanning techniques, such as computed tomography (CT) or x-ray. MRI is especially useful for imaging the brain, the spine, the soft tissue of joints, and the inside of bones. Also called magnetic resonance imaging, NMRI, and nuclear magnetic resonance imaging.
organ (OR-gun)
* A part of the body that performs a specific function. For example, the heart is an organ.
peritoneal cavity (PAYR-ih-toh-NEE-ul KA-vuh-tee)
* The space within the abdomen that contains the intestines, the stomach, and the liver. It is bound by thin membranes.
primary tumor (PRY-mayr-ee TOO-mer)
* The original tumor.
radioactive (RAY-dee-oh-AK-tiv)
* Giving off radiation.
stage
* The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.
stage I adult primary liver cancer (... uh-DULT PRY-mayr-ee LIH-ver KAN-ser)
* There is one tumor and it has not spread to nearby blood vessels.
stage II adult primary liver cancer (... uh-DULT PRY-mayr-ee LIH-ver KAN-ser)
* There is either (1) one tumor that has spread to nearby blood vessels; or (2) there is more than one tumor, none of which is larger than 5 centimeters.
stage IIIA adult primary liver cancer (... uh-DULT PRY-mayr-ee LIH-ver KAN-ser)
* Stage III adult primary liver cancer is divided into stages IIIA, IIIB, and IIIC. In stage IIIA there is either (1) more than one tumor larger than 5 centimeters; or (2) one tumor that has spread to a major branch of blood vessels near the liver.
stage IIIB adult primary liver cancer (... uh-DULT PRY-mayr-ee LIH-ver KAN-ser)
* Stage III adult primary liver cancer is divided into stages IIIA, IIIB, and IIIC. In stage IIIB, there are one or more tumors of any size that have either (1) spread to nearby organs other than the gallbladder; or (2) broken through the lining of the peritoneal cavity.
stage IIIC adult primary liver cancer (... uh-DULT PRY-mayr-ee LIH-ver KAN-ser)
* Stage III adult primary liver cancer is divided into stages IIIA, IIIB, and IIIC. In stage IIIC, the cancer has spread to nearby lymph nodes.
stage IV adult primary liver cancer (... uh-DULT PRY-mayr-ee LIH-ver KAN-ser)
* Cancer has spread beyond the liver to other places in the body, such as the bones or lungs. The tumors may be of any size and may also have spread to nearby blood vessels and/or lymph nodes.
staging (STAY-jing)
* Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. It is important to know the stage of the disease in order to plan the best treatment.
surgery (SER-juh-ree)
* A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.
tissue (TIH-shoo)
* A group or layer of cells that work together to perform a specific function.
tumor (TOO-mer)
* An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.
vein (vayn)
* A blood vessel that carries blood to the heart from tissues and organs in the body.
x-ray (EX-ray)
* A type of high-energy radiation. In low doses, x-rays are used to diagnose diseases by making pictures of the inside of the body. In high doses, x-rays are used to treat cancer.
Recurrent Adult Primary Liver Cancer
Recurrent adult primary liver cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the liver or in other parts of the body.
Treatment Option Overview
Key Points for This Section
* There are different types of treatment for patients with adult primary liver cancer.
* Four types of standard treatment are used:
* Surgery
* Radiation therapy
* Chemotherapy
* Percutaneous ethanol injection
* New types of treatment are being tested in clinical trials.
* Hyperthermia therapy
* Biologic therapy
* Patients may want to think about taking part in a clinical trial.
* Patients can enter clinical trials before, during, or after starting their cancer treatment.
* Follow-up tests may be needed.
There are different types of treatment for patients with adult primary liver cancer.
Different types of treatments are available for patients with adult primary liver cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
Four types of standard treatment are used:
Surgery
The following types of surgery may be used to treat liver cancer:
* Cryosurgery: A treatment that uses an instrument to freeze and destroy abnormal tissue, such as carcinoma in situ. This type of treatment is also called cryotherapy. The doctor may use ultrasound to guide the instrument.
* Partial hepatectomy: Removal of the part of the liver where cancer is found. The part removed may be a wedge of tissue, an entire lobe, or a larger portion of the liver, along with some of the healthy tissue around it. The remaining liver tissue takes over the functions of the liver.
* Total hepatectomy and liver transplant: Removal of the entire liver and replacement 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.
* Radiofrequency ablation: The use of a special probe with tiny electrodes that kill cancer cells. Sometimes the probe is inserted directly through the skin and only local anesthesia is needed. In other cases, the probe is inserted through an incision in the abdomen. This is done in the hospital with general anesthesia.
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. Radiation therapy is given in different ways:
* External radiation therapy uses a machine outside the body to send radiation toward 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.
* Drugs called radiosensitizers may be given with the radiation therapy to make the cancer cells more sensitive to radiation therapy.
* Radiation may be delivered to the tumor using radiolabeled antibodies. Radioactive substances are attached to antibodies made in the laboratory. These antibodies, which target tumor cells, are injected into the body and the tumor cells are killed by the radioactive substance.
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 them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy).
Regional chemotherapy is usually used to treat liver cancer. A small pump containing anticancer drugs may be placed in the body. The pump puts the drugs directly into the blood vessels that go to the tumor.
Another type of regional chemotherapy is chemoembolization of the hepatic artery. The anticancer drug is injected into the hepatic artery through a catheter (thin tube). The drug is mixed with a substance that blocks the artery, cutting off blood flow to the tumor. Most of the anticancer drug is trapped near the tumor and only a small amount of the drug reaches other parts of the body. The blockage may be temporary or permanent, depending on the substance used to block the artery. The tumor is prevented from getting the oxygen and nutrients it needs to grow. The liver continues to receive blood from the hepatic portal vein, which carries blood from the stomach and intestine.
The way the chemotherapy is given depends on the type and stage of the cancer being treated.
Percutaneous ethanol injection
Percutaneous ethanol injection is a cancer treatment in which a small needle is used to inject ethanol (alcohol) directly into a tumor to kill cancer cells. The procedure may be done once or twice a week. Usually local anesthesia is used, but if the patient has many tumors in the liver, general anesthesia may be needed.
New types of treatment are being tested in clinical trials.
This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site 1.
Hyperthermia therapy
Hyperthermia therapy is a type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. Because some cancer cells are more sensitive to heat than normal cells are, the cancer cells die and the tumor shrinks.
Biologic therapy
Biologic therapy 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 immunotherapy.
Patients may want to think about taking part in a clinical trial.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.
Follow-up tests may be needed.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
Treatment Options for Adult Primary Liver Cancer
Localized Resectable Adult Primary Liver Cancer
Treatment of localized resectable adult primary liver cancer may include the following:
* Surgery (partial hepatectomy).
* Surgery (total hepatectomy) and liver transplant.
* A clinical trial of regional or systemic chemotherapy or biologic therapy following surgery.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with localized resectable adult primary liver cancer 1. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site 2.
Localized and Locally Advanced Unresectable Adult Primary Liver Cancer
Treatment of localized and locally advanced unresectable adult primary liver cancer may include the following:
* Surgery (cryosurgery or radiofrequency ablation).
* Chemotherapy (chemoembolization, regional chemotherapy, or systemic chemotherapy).
* Percutaneous ethanol injection.
* Surgery (total hepatectomy) and liver transplant.
* Radiation therapy with radiosensitizers.
* A clinical trial of a combination of surgery, chemotherapy, and radiation therapy. Hyperthermia therapy may also be used. Chemotherapy and radiation therapy may be used to shrink the tumor before surgery.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with localized unresectable adult primary liver cancer 3. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site 2.
Advanced Adult Primary Liver Cancer
There is no standard treatment for advanced adult primary liver cancer. Patients may consider taking part in a clinical trial. Treatment may be a clinical trial of biologic therapy, chemotherapy, and/or radiation therapy with or without radiosensitizers. These treatments may be given as palliative therapy to help relieve symptoms and improve the quality of life.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with advanced adult primary liver cancer 4. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site 2.
Recurrent Adult Primary Liver Cancer
Treatment of recurrent adult primary liver cancer may include the following:
* Surgery (partial hepatectomy).
* Surgery (total hepatectomy) and liver transplant.
* Chemotherapy (chemoembolization or systemic chemotherapy).
* Percutaneous ethanol injection.
* A clinical trial of a new therapy.
* * * * * * * * * * * *
Chapter 2A: Liver Cancer Health Professional Information
Adult Primary Liver Cancer Treatment
General Information
Note: Estimated new cases and deaths from liver and intrahepatic bile duct cancer in the United States in 2010:[1]
• New cases: 24,120.
• Deaths: 18,910.
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy.
Hepatocellular carcinoma is a tumor that is relatively uncommon in the United States, although its incidence is rising, principally in relation to the spread of hepatitis C infection.[2] It is the most common cancer in some parts of the world, with more than 1 million new cases diagnosed each year. Hepatocellular carcinoma is potentially curable by surgical resection, but surgery is the treatment of choice for only the small fraction of patients with localized disease.[3] Prognosis depends on the degree of local tumor replacement and the extent of liver function impairment. Therapy other than surgical resection is best administered as part of a clinical trial. Such trials evaluate the efficacy of systemic or infusional chemotherapy, hepatic artery ligation or embolization, percutaneous ethanol injection, radiofrequency ablation, cryotherapy, and radiolabeled antibodies, often in conjunction with surgical resection and/or radiation therapy. In some studies of these approaches, long remissions have been reported.[3] A few patients may be candidates for liver transplantation, but the limited availability of livers for transplantation restricts the use of this approach.[4] Hepatocellular carcinoma can coexist with bile duct cancer (cholangiocarcinoma).[5]
Risk factors
Hepatocellular carcinoma is associated with cirrhosis in 50% to 80% of patients; 5% of cirrhotic patients eventually develop hepatocellular cancer, which is often multifocal.
Hepatitis B infection [3,6] and hepatitis C infection [7] appear to be the most significant causes of hepatocellular carcinoma worldwide, particularly in patients with continuing antigenemia and in those who have chronic active hepatitis. A series found that male patients older than 50 years who have both hepatitis B and hepatitis C infection may be at particularly high risk for hepatocellular cancer.[8][Level of evidence: 3iiiDiv] There is evidence that patients with both hepatitis B and hepatitis C infection who consume more than 80 grams of alcohol per day have an increased risk of developing cancer (odds ratio [OR] = 7.3) when compared to patients who abstain from alcohol.[9] Additionally, having a first-degree relative with hepatitis B plus hepatocellular carcinoma is associated with an increased risk (OR = 2.41) for family members who are hepatitis B carriers.[10]
Aflatoxin has also been implicated as a factor in the etiology of primary liver cancer in parts of the world where this mycotoxin occurs in high levels in ingested food.[6,H] Workers who were exposed to vinyl chloride before controls on vinyl chloride dust were instituted developed sarcomas in the liver, most commonly angiosarcomas. Other sarcomas of smooth muscular and vascular origin are also found.
The primary symptoms of hepatocellular carcinoma are those of a hepatic mass. Among patients with underlying cirrhotic disease, a progressive increase in alpha-fetoprotein (AFP) and/or in alkaline phosphatase or a rapid deterioration of hepatic function may be the only clue to the presence of the neoplasm. Infrequently, patients with this disease have polycythemia, hypoglycemia, hypercalcemia, or dysfibrinogenemia. (For more information on Hypercalcemia, refer to the PDQ summary of the same name.)
Prognostic factors
The biologic marker AFP is useful for the diagnosis of this neoplasm. By a radioimmunoassay technique, 50% to 70% of patients in the United States who have hepatocellular carcinoma have elevated levels of AFP. However, patients with other malignancies (germ cell carcinoma and, rarely, pancreatic and gastric carcinoma) also demonstrate elevated serum levels of this protein. AFP levels have been shown in studies such as RTOG-8301 to be prognostically important, with the median survival of AFP-negative patients significantly longer than that of AFP-positive patients.[12,13] Other prognostic variables include performance status, liver functions,[14] and the presence or absence of cirrhosis and its severity in relation to the Child-Pugh classification.[15]
Patients scheduled for possible resection require preoperative assessment with angiography in conjunction with helical computed tomographic (CT) scan or magnetic resonance imaging (MRI) with magnetic resonance angiography; these scans have obviated the need for angiography in most patients. Information on the arterial anatomy is helpful for the operating surgeon and may eliminate some patients from consideration for resection. The presence of tumor thrombi in the hepatic veins, the inferior vena cava, or the portal vein can significantly alter treatment approaches. Dynamic CT and MRI scans can document the relationship of the tumor to the hepatic and portal veins (and, on occasion, involvement of these structures), delineating tumors for which the chances for surgical cure are remote.[16] Laparoscopic evaluation may detect metastatic disease, bilobar disease, or inadequate liver remnant, and therefore obviate the need for open surgical exploration.[17]
References
1. American Cancer Society.: Cancer Facts and Figures 2010. Atlanta, Ga: American Cancer Society, 2010. Also available online. Last accessed June 16, 2011.
2. El-Serag HB, Mason AC: Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 340 (10): 745-50, 1999.
3. Mor E, Kaspa RT, Sheiner P, et al.: Treatment of hepatocellular carcinoma associated with cirrhosis in the era of liver transplantation. Ann Intern Med 129 (8): 643-53, 1998.
4. Klintmalm GB: Liver transplantation for hepatocellular carcinoma: a registry report of the impact of tumor characteristics on outcome. Ann Surg 228 (4): 479-90, 1998.
5. Jarnagin WR, Weber S, Tickoo SK, et al.: Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer 94 (7): 2040-6, 2002.
6. Blumberg BS, Larouze B, London WT, et al.: The relation of infection with the hepatitis B agent to primary hepatic carcinoma. Am J Pathol 81 (3): 669-82, 1975.
7. Tsukuma H, Hiyama T, Tanaka S, et al.: Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 328 (25): 1797-801, 1993.
8. Chiaramonte M, Stroffolini T, Vian A, et al.: Rate of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis. Cancer 85 (10): 2132-7, 1999.
9. Tagger A, Donato F, Ribero ML, et al.: Case-control study on hepatitis C virus (HCV) as a risk factor for hepatocellular carcinoma: the role of HCV genotypes and the synergism with hepatitis B virus and alcohol. Brescia HCC Study. Int J Cancer 81 (5): 695-9, 1999.
10. Yu MW, Chang HC, Liaw YF, et al.: Familial risk of hepatocellular carcinoma among chronic hepatitis B carriers and their relatives. J Natl Cancer Inst 92 (14): 1159-64, 2000.
11. Alpert ME, Hutt MS, Wogan GN, et al.: Association between aflatoxin content of food and hepatoma frequency in Uganda. Cancer 28 (1): 253-60, 1971.
12. Stillwagon GB, Order SE, Guse C, et al.: Prognostic factors in unresectable hepatocellular cancer: Radiation Therapy Oncology Group Study 83-01. Int J Radiat Oncol Biol Phys 20 (1): 65-71, 1991.
13. Izumi R, Shimizu K, Kiriyama M, et al.: Alpha-fetoprotein production by hepatocellular carcinoma is prognostic of poor patient survival. J Surg Oncol 49 (3): 151-5, 1992.
14. Yamashita Y, Takahashi M, Koga Y, et al.: Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion. Cancer 67 (2): 385-91, 1991.
15. Nakakura EK, Choti MA: Management of hepatocellular carcinoma. Oncology (Huntingt) 14 (7): 1085-98; discussion 1098-102, 2000.
16. Karl RC, Morse SS, Halpert RD, et al.: Preoperative evaluation of patients for liver resection. Appropriate CT imaging. Ann Surg 217 (3): 226-32, 1993.
17. Lo CM, Lai EC, Liu CL, et al.: Laparoscopy and laparoscopic ultrasonography avoid exploratory laparotomy in patients with hepatocellular carcinoma. Ann Surg 227 (4): 527-32, 1998.
Cellular Classification
Malignant tumors of the liver are primarily adenocarcinomas, with two major cell types: hepatocellular and cholangiocarcinoma.
Histologic classification is as follows:
• Hepatocellular carcinoma (liver cell carcinoma).
• Hepatocellular carcinoma (fibrolamellar variant). [Note: The fibrolamellar variant is important because an increased proportion of these patients may be cured if the tumor can be resected. It is more frequent in young women. It also generally exhibits a slower clinical course than the more common hepatocellular carcinoma.]
• Cholangiocarcinoma (intrahepatic bile duct carcinoma).
• Mixed hepatocellular cholangiocarcinoma.
• Undifferentiated.
Hepatoblastoma rarely occurs in adults.
Stage Information
Note: The American Joint Committee on Cancer has recently published a new edition of the AJCC Cancer Staging Manual, which includes revisions to the staging for this disease. The PDQ Adult Treatment Editorial Board, which is responsible for maintaining this summary, is currently reviewing the new staging to determine the changes that need to be made in the summary. In addition to updating this Stage Information section, additional changes may need to be made to other parts of this summary to ensure that it is up-to-date. The changes will be made as soon as possible.
TNM Definitions
Primary tumor (T)
• TX: Primary tumor cannot be assessed
• T0: No evidence of primary tumor
• T1: Solitary tumor without vascular invasion
• T2: Solitary tumor with vascular invasion or multiple tumors none more than 5 cm
• T3: Multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s)
• T4: Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of the visceral peritoneum
Regional lymph nodes (N)
• NX: Regional lymph nodes cannot be assessed
• N0: No regional lymph node metastasis
• N1: Regional lymph node metastasis
[Note: The regional lymph nodes are the hilar (i.e., those in the hepatoduodenal ligament, hepatic, and periportal nodes). Regional lymph nodes also include those along the inferior vena cava, hepatic artery, and portal vein. Any lymph node involvement beyond these nodes is considered distant metastasis and should be coded as M1. Involvement of the inferior phrenic lymph nodes should also be considered M1.]
Distant metastasis (M)