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Liver Cancer Overview
What is Liver Cancer?
The liver is the largest internal organ of the body. It weighs about 3 pounds and accounts for about 2% of a person's body weight. It is sheltered by the lower right ribs and it is found underneath the right lung, separated from it by a muscle known as the diaphragm. It is shaped like a pyramid and divided into right and left lobes. Each of these lobes is further divided into segments. The liver, unlike most other organs, receives blood form two sources. The hepatic artery supplies the liver with blood that is rich in oxygen. The portal vein carries nutrient-rich blood from the intestines to the liver.
Because the liver is involved in many important metabolic functions, a person cannot survive without a liver. Some nutrients and vitamins absorbed by the intestines are stored in the liver until other organs need them. Other nutrients must be metabolized (chemically changed) in the liver before they can be used by the body for energy or to build and repair tissues.
Carbohydrate, protein, and lipid metabolism all depend on proper liver function. Blood levels of glucose and controlled by the liver. Glucose is a type of sugar that serves as the main source of energy for most tissues and organs in the body. The lover produces albumin. Albumin is a blood protein with several essential functions that include keeping a proper balance of fluid between tissues and the bloodstream, and transporting many hormones and drugs through the bloodstream. Several clotting factors are made in the liver. Without these factors to plug up damaged blood vessels, even small cuts or scrapes would cause life-threatening bleeding. Without amino acid metabolism by the liver, other tissues of the body could not produce the structural proteins of our bones and connective tissues or enzymes (proteins that regulate nearly all chemical processes of the body). The lover also plays a part on the metabolism of lipids (fats) and makes cholesterol, which is an essential part of the membranes that surround all cells and divide the cells into organelles (specific parts of cells). The liver also inactivates many drugs and toxic chemicals. If the liver is not working well, these substances can build up and interfere with many of the body's functions. The liver also produces bile, which is needed for the intestines to absorb certain nutrients.
Types of Liver Tumors
There are several types of malignant (cancerous) and benign (non-cancerous) tumors that con form in the liver. Because these tumors have different causes, are treated differently, and have a different prognosis (outlook for survival), it is important to briefly review their names. Several different types of cells form the liver. Different tumors can start in any of these cell types. The most common type of benign liver tumor starts in blood vessels. It is called a hemangoima. Most hemangiomas of the liver cause no symptoms. Some may cause blood loss. This type of tumor can be cured by surgical removal. Hepaticadenomas are benign tumors that start from hepatocytes (the main type of liver cell). Most cause no symptoms but some cause abdominal (stomach area) pain, an increased by long-term use of oral contraceptives (birth control pills). This type of tumor can be cured by surgical removal. Hepaticadenomas are benign tumors that start from hepatocytes (the main type of liver cell). Most cause no symptoms but some cause abdominal (stomach area) pain, a mass in the abdomen, or blood loss. The risk of having a hepatic adenoma is increased by ling-term use of oral contraceptives ( birth control pills). This type of tumor can be cured by surgical removal. Focal nodular hyperplasia (FNH) is a tumor-like growth of several cell types (hepatocytes, bile duct cells, and connective tissues.). FNH is also cured by surgical removal. Both FNH and hepatic adenomas are more common in women that in men.
There are four main types of malignant liver tumors: Angiosarcomas or hemangiosarcomas begin from blood vessels of the liver. The risk of developing an angiosarcoma is greatly increased by exposure to vinyl chloride or to thorium dioxide (Thorotrast). Vinyl chloride is a chemical used in manufacturing some kinds of plastics. In the past, Thorotrast was a chemical injected into some patients as part of a certain x-ray test. Once the cancer-causing properties of these chemicals were recognized, steps were taken to eliminate or reduce the risk. Workers exposed to vinyl chloride are strictly regulated, and plastics manufacturing processes have been changed to lower exposure. Medical use of Thorotrast was stopped about 50 years ago. Angiosarcomas of the liver are rare, accounting for about 1% of liver cancers. Unfortunately, they grow rapidly and are usually too widespread to be removed surgically by the time they are found. Chemotherapy and radiation therapy does not help much. The typical patient survives less than 6 months after diagnosis. Cholangiocarcinoma is a type of adenocarcinoma (malignant glandular tumor) that starts in small bile ducts within the liver. About 13% of primary liver cancers are cholangiosarcomas. People with gallstones are gallbladder inflammation, chronic ulcerative colitis (a longstanding inflammation of the large bowel), or chronic infection with Clonorchis sinensis (a parasitic worm found in parts of Asia) has an increased risk of developing this cancer. Signs and symptoms may include abdominal pain, liver enlargement, or jaundice (green-yellow coloration of the skin and eyes). Joundice without abdominal pain is most typical of cholangiocarcinomas that start near the hilum to the liver (the area where bile ducts exit the liver on their way to the gallbladder). Cholangiocarcinomas in that area also known as Klatskin tumors. Most cholangiocarcinomas cannot be completely removed by surgery, due to their size and location within the liver. Chemotherapy and radiation therapy is also not effective. For these reasons, their prognosis is poor, with an average survival after diagnosis of about 6 months. When possible, complete surgical removal is attempted. Surgery to bypass bile ducts blocked by cancer can temporarily relieve some symptoms. Hepatoblastoma is a rare type of liver cancer that is usually found in children less that 4 years old. Under the microscope, the cells of hepatoblastoma resemble embryonic or fetal liver cells. About 70% of children with this disease are treated successfully and the survival rate is over 90% for early stage hepatoblastomas. In contrast with most adult liver cancers, hepatoblastomas usually respond well to chemotherapy.
Hepatocellular carcinoma (also known as hepatoma or HCC) develops from hepatocytes (the main type of liver cell). It is the most common type of primary liver cancer (cancer beginning within the liver). HCC accounts for about 84% of primary liver cancers. For this reason, the remaining sections of this document refer only to HCC. There are several subtypes of HCC which appear slightly different when viewed under a microscope. The fibrolamellar subtype of HCC is the most significant of these. Patients with fibrolamellar HCC are usually younger than those with other subtypes. They are usually women and do not have diseases of their non-cancerous liver tissue. Most importantly this subtype is associated with a much better prognosis that other forms of HCC.
In contrast to primary liver cancers that form in the liver, metastatic or secondary liver tumors are those that develop in other organs (such as the pancreas, colon, stomach, breast, lung, etc.) and secondary metastasize (spread) to the liver. In the United States and Europe, secondary liver tumors are more common than primary liver cancer. The opposite is true for many areas of Asia and Africa.
Do We Know What Causes Liver Cancer?
Although several risk factors for HCC are known, the exact way in which these factors cause normal liver cells to become cancerous is only partially understood. Scientists believe that cancers develop in two steps: The first step requires damage to the DNA cells. DNA contains the instructions for nearly every chemical process in our bodies. Some of these instructions help cells to grow at a proper rate. If these instructions are altered, the cells may grow too much and form a tumor. Fortunately, our cells have the ability to repair our DNA, so that most DNA damage does not cause a cancer.
The second step in cancer formation requires cells to grow and divide. When cells divide shortly after their DNA is damaged, two new "daughter cells" may be formed before the original cell has time to repair its DNA damage. Both daughter cells will have the same DNA error. Once this happens, it is too late to repair the damage, which may eventually cause a cancer.
Certain chemicals that cause liver cancer, such as aflatoxins, are known to damage liver cells' DNA. Recent studies have shown that aflatoxins can damage the p53 gene. The DNA of these genes normally works to prevent cells from growing too much. Damage to the p53 DNA can lead to increased growth of cells and formation of cancers. Infection of liver cells with hepatitis viruses can also cause DNA damage. These viruses have their own DNA, which carries instructions on how to infect cells and produce more viruses. In some patients this viral DNA can become inserted into the liver cell's DNA. An insertion of virus DNA can cause confusion in the DNA instructions of a liver cell. If the virus interrupts instruction related to cell growth control, a cancer may be formed.
Cells of certain tissues such as blood, skin, and the intestinal lining constantly wear out and must be replaced. Under normal conditions, adult liver cells rarely wear out and rarely divide. Only a small fraction of liver cells undergo cell division in response to minor cell loss due to natural aging. However, if hepatitis viral infection, alcohol abuse, or iron accumulation damages the liver, cells can die. This leads the remaining liver cells to grow and divide.
This growth and division can pass damaged liver cell DNA (due to virus insertion, aflatoxin, or other causes) on to the new "daughter" liver cells before it can be repaired. The result is that cell instructions for growth control can be permanently altered, and a cancer may form.
Although scientists are making progress in understanding this process, there are still some points that are not completely understood. It is hoped that a more complete understanding will help in developing ways to better prevent and treat liver cancers.