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Related to liver cancer: liver disease
Liver cancer is a relatively rare form of cancer but has a high mortality rate. Liver cancers can be classified into two types. They are either primary, when the cancer starts in the liver itself, or metastatic, when the cancer has spread to the liver from some other part of the body.
Primary liver cancer
Primary liver cancer is a relatively rare disease in the United States, representing about 2% of all malignancies and 4% of newly diagnosed cancers. Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world as of 2004. It is much more common outside the United States, representing 10% to 50% of malignancies in Africa and parts of Asia. Rates of HCC in men are at least two to three times higher than for women. In high-risk areas (East and Southeast Asia, sub-Saharan Africa), men are even more likely to have HCC than women.
According to the American Cancer Society, 18,920 people in the United States will be diagnosed with primary liver cancer in 2004, and 14,270 persons will die from the disease. The incidence of primary liver cancer has been rising in the United States and Canada since the mid-1990s, most likely as a result of the rising rate of hepatitis C infections.
TYPES OF PRIMARY LIVER CANCER. In adults, most primary liver cancers belong to one of two types: hepatomas, or hepatocellular carcinomas (HCC), which start in the liver tissue itself; and cholangiomas, or cholangiocarcinomas, which are cancers that develop in the bile ducts inside the liver. About 80% to 90% of primary liver cancers are hepatomas. In the United States, about five persons in every 200,000 will develop a hepatoma (70% to 75% of cases of primary liver cancers are HCC). In Africa and Asia, over 40 persons in 200,000 will develop this form of cancer (more than 90% of cases of primary liver are HCC). Two rare types of primary liver cancer are mixed-cell tumors and Kupffer cell sarcomas.
One type of primary liver cancer, called a hepatoblastoma, usually occurs in children younger than four years of age and between the ages of 12 and 15. Unlike liver cancers in adults, hepatoblastomas have a good chance of being treated successfully. Approximately 70% of children with hepatoblastomas experience complete cures. If the tumor is detected early, the survival rate is over 90%.
Metastatic liver cancer
The second major category of liver cancer, metastatic liver cancer, is about 20 times as common in the United States as primary liver cancer. Because blood from all parts of the body must pass through the liver for filtration, cancer cells from other organs and tissues easily reach the liver, where they can lodge and grow into secondary tumors. Primary cancers in the colon, stomach, pancreas, rectum, esophagus, breast, lung, or skin are the most likely to metastasize (spread) to the liver. It is not unusual for the metastatic cancer in the liver to be the first noticeable sign of a cancer that started in another organ. After cirrhosis, metastatic liver cancer is the most common cause of fatal liver disease.
Causes and symptoms
The exact cause of primary liver cancer is still unknown. In adults, however, certain factors are known to place some individuals at higher risk of developing liver cancer. These factors include:
- Male sex.
- Age over 60 years.
- Ethnicity. Asian Americans with cirrhosis have four times as great a chance of developing liver cancer as Caucasians with cirrhosis, and African Americans have twice the risk of Caucasians. In addition, Asians often develop liver cancer at much younger ages than either African Americans or Caucasians.
- Exposure to substances in the environment that tend to cause cancer (carcinogens). These include: a substance produced by a mold that grows on rice and peanuts (aflatoxin); thorium dioxide, which was once used as a contrast dye for x rays of the liver; vinyl chloride, used in manufacturing plastics; and cigarette smoking.
- Use of oral estrogens for birth control.
- Hereditary hemochromatosis. This is a disorder characterized by abnormally high levels of iron storage in the body. It often develops into cirrhosis.
- Cirrhosis. Hepatomas appear to be a frequent complication of cirrhosis of the liver. Between 30% and 70% of hepatoma patients also have cirrhosis. It is estimated that a patient with cirrhosis has 40 times the chance of developing a hepatoma than a person with a healthy liver.
- Exposure to hepatitis viruses: Hepatitis B (HBV), Hepatitis C (HCV), Hepatitis D (HDV), or Hepatitis G (HGV). It is estimated that 80% of worldwide HCC is associated with chronic HBV infection. In Africa and most of Asia, exposure to hepatitis B is an important factor; in Japan and some Western countries, exposure to hepatitis C is connected with a higher risk of developing liver cancer. In the United States, nearly 25% of patients with liver cancer show evidence of HBV infection. Hepatitis is commonly found among intravenous drug abusers. The 70% increase in HCC incidence in the United States is thought to be due to increasing rates of HBV and HCV infections due to increased sexual promiscuity and illicit drug needle sharing. The association between HDV and HGV and HCC is unclear at this time.
Symptoms of liver cancer
The early symptoms of primary, as well as metastatic, liver cancer are often vague and not unique to liver disorders. The long period between the beginning of the tumor's growth and the first signs of illness is the major reason why the disease has such a high mortality rate. At the time of diagnosis, patients are often fatigued, with fever, abdominal pain, and loss of appetite. They may look emaciated and generally ill. As the tumor enlarges, it stretches the membrane surrounding the liver (the capsule), causing pain in the upper abdomen on the right side. The pain may extend into the back and shoulder. Some patients develop a collection of fluid, known as ascites, in the abdominal cavity. Others may show signs of bleeding into the digestive tract. In addition, the tumor may block the ducts of the liver or the gall bladder, leading to jaundice. In patients with jaundice, the whites of the eyes and the skin may turn yellow, and the urine becomes dark-colored.
If the doctor suspects a diagnosis of liver cancer, he or she will check the patient's history for risk factors and pay close attention to the condition of the patient's abdomen during the physical examination. Masses or lumps in the liver and ascites can often be felt while the patient is lying flat on the examination table. The liver is usually swollen and hard in patients with liver cancer; it may be sore when the doctor presses on it. In some cases, the patient's spleen is also enlarged. The doctor may be able to hear an abnormal sound (bruit) or rubbing noise (friction rub) if he or she uses a stethoscope to listen to the blood vessels that lie near the liver. The noises are caused by the pressure of the tumor on the blood vessels.
Blood tests may be used to test liver function or to evaluate risk factors in the patient's history. Between 50% and 75% of primary liver cancer patients have abnormally high blood serum levels of a particular protein (alpha-fetoprotein or AFP). The AFP test, however, cannot be used by itself to confirm a diagnosis of liver cancer, because cirrhosis or chronic hepatitis can also produce high alpha-fetoprotein levels. Tests for alkaline phosphatase, bilirubin, lactic dehydrogenase, and other chemicals indicate that the liver is not functioning normally. About 75% of patients with liver cancer show evidence of hepatitis infection. Again, however, abnormal liver function test results are not specific for liver cancer.
Imaging studies are useful in locating specific areas of abnormal tissue in the liver. Liver tumors as small as an inch across can now be detected by ultrasound or computed tomography scan (CT scan). Imaging studies, however, cannot tell the difference between a hepatoma and other abnormal masses or lumps of tissue (nodules) in the liver. A sample of liver tissue for biopsy is needed to make the definitive diagnosis of a primary liver cancer. CT or ultrasound can be used to guide the doctor in selecting the best location for obtaining the biopsy sample.
Chest x rays may be used to see whether the liver tumor is primary or has metastasized from a primary tumor in the lungs.
Liver biopsy is considered to provide the definite diagnosis of liver cancer. A sample of the liver or tissue fluid is removed with a fine needle and is checked under a microscope for the presence of cancer cells. In about 70% of cases, the biopsy is positive for cancer. In most cases, there is little risk to the patient from the biopsy procedure. In about 0.4% of cases, however, the patient develops a fatal hemorrhage from the biopsy because some tumors are supplied with a large number of blood vessels and bleed very easily.
The doctor may also perform a laparoscopy to help in the diagnosis of liver cancer. First, the doctor makes a small cut in the patient's abdomen and inserts a small, lighted tube called a laparoscope to view the area. A small piece of liver tissue is removed and examined under a microscope for the presence of cancer cells.
Treatment of liver cancer is based on several factors, including the type of cancer (primary or metastatic); stage (early or advanced); the location of other primary cancers or metastases in the patient's body; the patient's age; and other coexisting diseases, including cirrhosis. For many patients, treatment of liver cancer is primarily intended to relieve the pain caused by the cancer but cannot cure it.
Few liver cancers in adults can be cured by surgery because they are usually too advanced by the time they are discovered. If the cancer is contained within one lobe of the liver, and if the patient does not have either cirrhosis, jaundice, or ascites, surgery is the best treatment option. Patients who can have their entire tumor removed have the best chance for survival. Unfortunately, only about 5% of patients with metastatic cancer (from primary tumors in the colon or rectum) fall into this group. If the entire visible tumor can be removed, about 25% of patients will be cured. The operation that is performed is called a partial hepatectomy, or partial removal of the liver. The surgeon will remove either an entire lobe of the liver (a lobectomy) or cut out the area around the tumor (a wedge resection).
A newer technique that is reported to be safe and effective is laparoscopic radiofrequency ablation (RFA). RFA is a technique in which the surgeon places a special needle electrode in the tumor under guidance from MRI or CT scanning. When the electrode has been properly placed, a radiofrequency current is passed through it, heating the tumor and killing the cancer cells. RFA can be used to treat tumors that are too small or too inaccessible for removal by conventional open surgery.
Some patients with metastatic cancer of the liver can have their lives prolonged for a few months by chemotherapy, although cure is not possible. If the tumor cannot be removed by surgery, a tube (catheter) can be placed in the main artery of the liver and an implantable infusion pump can be installed. The pump allows much higher concentrations of the cancer drug to be carried to the tumor than is possible with chemotherapy carried through the bloodstream. The drug that is used for infusion pump therapy is usually floxuridine (FUDR), given for 14-day periods alternating with 14-day rests. Systemic chemotherapy can also be used to treat liver cancer. The medications usually used are 5-fluorouracil (Adrucil, Efudex) or methotrexate (MTX, Mexate). Systemic chemotherapy does not, however, significantly lengthen the patient's survival time.
Radiation therapy is the use of high-energy rays or x rays to kill cancer cells or to shrink tumors. Its use in liver cancer, however, is only to give short-term relief from some of the symptoms. Liver cancers are not sensitive to radiation, and radiation therapy will not prolong the patient's life.
Removal of the entire liver (total hepatectomy) and liver transplantation can be used to treat liver cancer. However, there is a high risk of tumor recurrence and metastases after transplantation. In addition, most patients have cancer that is too far advanced at the time of diagnosis to benefit from liver transplantation.
Other therapeutic approaches include:
- Hepatic artery embolization with chemotherapy (chemoembolization).
- Alcohol ablation via ultrasound-guided percutaneous injection.
- Ultrasound-guided cryoablation.
- Immunotherapy with monoclonal antibodies tagged with cytotoxic agents.
- Gene therapy with retroviral vectors containing genes expressing cytotoxic agents.
Many patients find that alternative and complementary therapies help to reduce the stress associated with illness, improve immune function, and boost spirits. While there is no clinical evidence that these therapies specifically combat disease, activities such as biofeedback, relaxation, therapeutic touch, massage therapy and guided imagery have no side effects and have been reported to enhance well-being.
Several other healing therapies are sometimes used as supplemental or replacement cancer treatments, such as antineoplastons, cancell, cartilage (bovine and shark), laetrile, and mistletoe. Many of these therapies have not been the subject of safety and efficacy trials by the National Cancer Institute (NCI). The NCI has conducted trials on cancell, laetrile, and other alternative therapies and found no anticancer activity. These treatments have varying effectiveness and safety considerations. Patients using any alternative remedy should first consult their doctor in order to prevent harmful side effects or interactions with traditional cancer treatment.
Liver cancer has a very poor prognosis because it is often not diagnosed until it has metastasized. Fewer than 10% of patients survive three years after the initial diagnosis; the overall five-year survival rate for patients with hepatomas is around 4%. Most patients with primary liver cancer die within six months of diagnosis, usually from liver failure; fewer than 5% are cured of the disease. Patients with liver cancers that metastasized from cancers in the colon live slightly longer than those whose cancers spread from cancers in the stomach or pancreas.
As of 2004, African American and Hispanic patients have much lower 5-year survival rates than Caucasian patients. It is not yet known, however, whether cultural differences as well as biological factors may be partly responsible for the variation in survival rates.
There are no useful strategies at present for preventing metastatic cancers of the liver. Primary liver cancers, however, are 75% to 80% preventable. Current strategies focus on widespread vaccination for hepatitis B, early treatment of hereditary hemochromatosis, and screening of high-risk patients with alpha-fetoprotein testing and ultrasound examinations.
Lifestyle factors that can be modified in order to prevent liver cancer include avoidance of exposure to toxic chemicals and foods harboring molds that produce aflatoxin. Most important, however, is avoidance of alcohol and drug abuse. Alcohol abuse is responsible for 60% to 75% of cases of cirrhosis, which is a major risk factor for eventual development of primary liver cancer. Hepatitis is a widespread disease among persons who abuse intravenous drugs.
Aflatoxin — A substance produced by molds that grow on rice and peanuts. Exposure to aflatoxin is thought to explain the high rates of primary liver cancer in Africa and parts of Asia.
Alpha-fetoprotein — A protein in blood serum that is found in abnormally high concentrations in most patients with primary liver cancer.
Cirrhosis — A chronic degenerative disease of the liver, in which normal cells are replaced by fibrous tissue. Cirrhosis is a major risk factor for the later development of liver cancer.
Cryoablation — A technique for removing cancerous tissue by killing it with extreme cold.
Hepatitis — A viral disease characterized by inflammation of the liver cells (hepatocytes). People infected with hepatitis B or hepatitis C virus are at an increased risk for developing liver cancer.
Metastatic cancer — A cancer that has spread to an organ or tissue from a primary cancer located elsewhere in the body.
Radiofrequency ablation — A technique for removing a tumor by heating it with a radiofrequency current passed through a needle electrode.
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American Institute for Cancer Research (AICR). 1759 R St. NW, Washington, DC 20009. (800) 843-8114. http://www.aicr.org.
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a malignant neoplastic disease of the liver. Primary liver cancer is common in Africa and Southeast Asia. Primary tumors are 6 to 10 times more prevalent in men than in women, develop most often in the sixth decade of life, and are associated with cirrhosis of the liver in 70% of the cases. Other risk factors include hemochromatosis, hepatitis, schistosomiasis, exposure to vinyl chloride or arsenic, and possibly nutritional deficiencies. Alcoholism may be a predisposing factor, but nonalcoholic cirrhosis is a greater risk than alcoholic cirrhosis. Aflatoxins in moldy grain and peanuts appear to be linked to high rates of hepatocellular carcinoma in parts of Africa. Characteristics of liver cancer are abdominal bloating, anorexia, weakness, dull upper abdominal pain, ascites, mild jaundice, and a tender enlarged liver; in some cases tumor nodules are palpable on the liver surface. Diagnostic procedures include radioisotope scan, biopsy, and various laboratory studies of liver function. An elevated level of alkaline phosphatase, increased retention of sulfobromophthalein, and the presence of alpha-fetoprotein in the blood suggest liver cancer. Most primary liver tumors are adenocarcinomas, classified as hepatomas, when derived from hepatic cells, and cholangiomas, if they originate in cells of the bile duct. Systemic chemotherapy may result in temporary tumor regression; it may be administered with a surgically implanted infusion pump. Liver transplantation may also be used to treat eligible individuals. Irradiation is very destructive to liver cells and not very toxic to tumor cells in the liver. See also hepatoma.
hepatocellular carcinomaA primary liver cancer that arises in hepatocytes (liver cells).
Incidence increased (1.6/105 from 1980 to 4.9/105 from 2005), primarily in middle- to older-aged (age 40–60) patients; black patients are 2-fold more common than whites; male:female ratio is 3:1.
Abdominal pain, weight loss, weakness, anorexia, vomiting, jaundice, hepatomegaly, ascites, splenomegaly, wasting, fever; paraneoplastic changes include increased cholesterol, polycythaemia and sex-discordant changes in hormone levels.
• HBV+ carries a 7-fold increased risk; HCV-ness carries a 4-fold increased risk.
• Mycotoxin (e.g., aflatoxin B1 in stored grains, drinking water).
• 3-year risk for HCC is 12.5% in patients with cirrhosis; 4% in patients with chronic liver disease; others include alcohol consumption, autoimmune chronic active hepatitis and cryptogenic cirrhosis.
• Metabolic diseases—Haemochromatosis, glycogen storage diseases, Wilson’s disease, galactosemia.
• Environmental conditions, such as excessive exposure to thorotrast (an obsolete radiocontrast medium), androgenic steroids, PVC (polyvinylchloride).
AFP, HepPAR, PIVKA II (protein induced by the absence of vitamin K), biopsy, hepatitis serology, LFTs, CBC, coagulation profile.
5-year postoperative recurrence is 80%, reflects adequacy of surgical margins, detected by AFP.