Floxuridine

Definition

Liver cancer is a form of cancer with a high mortality rate. Liver cancers are classified into two types. They are either primary, when the cancer starts in the liver itself; or metastatic, when the cancer has metastasized (spread) to the liver from some other part of the body.

Description

Primary liver cancer

Primary liver cancer is a relatively rare disease in the United States, representing about 2% of all malignancies. It is much more common in other parts of the world, representing from 10-50% of malignancies in Africa and parts of Asia. According to the American Cancer Society, in the United States during 1998, more than 14,000 new cases of primary liver cancer were diagnosed, and approximately 13,000 deaths were attributable to it.

Types of primary liver cancer

In adults, most primary liver cancers belong to one of two types: hepatomas, also known as hepatocellular carcinomas, which start in the liver tissue itself; and cholangiocarcinomas, which are cancers that develop in the bile ducts inside the liver. About 90% of primary liver cancers are hepatomas. In the United States, about one person in every 40,000 will develop a hepatoma; in Africa and Asia, over 8 persons in 40,000 will develop this form of cancer. Two rare types of primary liver cancer are mixed-cell tumors and Kupffer cell sarcomas.

There is one type of primary liver cancer that usually occurs in children younger than four years of age and between the ages of 12-15. This type of childhood liver cancer is called a hepatoblastoma. Unlike liver cancers in adults, hepatoblastomas have a good chance of being treated successfully. Approximately 70% of children with hepatoblastomas experience complete cures. When 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 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. Second only to cirrhosis, metastatic liver cancer is the most common cause of fatal liver disease.

Causes and symptoms

Risk factors for primary liver cancer

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:

• Gender. The male/female ratio for hepatoma is 4:1.

• Age over 60 years.

• Environmental exposure to carcinogens (cancer causing substances). Examples of environmental carcinogens are aflatoxin, substance produced by a mold that grows on rice and peanuts; thorium dioxide, used at one time as a contrast dye for x rays of the liver; and vinyl chloride, used in manufacturing plastics.

• Use of oral estrogens for contraception (birth control).

• Hereditary hemochromatosis. Hemochromatosis is a disorder characterized by abnormally high levels of iron storage in the body. It often progresses to cirrhosis.

• Cirrhosis. Hepatomas appear to be a frequent complication of cirrhosis of the liver. Between 30-70% 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. Cirrhosis usually results from alcohol abuse or chronic viral hepatitis.

• Exposure to hepatitis B (HBV) or hepatitis C (HBC) viruses. 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 associated with a higher risk of developing liver cancer. In the United States, nearly 25% of patients with liver cancer have evidence of HBV infection. Hepatitis B and C are commonly found among intravenous drug abusers.

Symptoms of liver cancer

The early symptoms of primary, as well as metastatic, liver cancer are often vague and not specific to liver disorders. The long delay between the beginning of the tumor's growth and signs of illness is the major reason the disease has such a high mortality rate. At the time of diagnosis, patients are often tired, with fever, abdominal pain, and loss of appetite. They may look emaciated and generally ill. As the tumor grows bigger, 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 ascites (a collection of fluid) in the abdominal cavity. Others may have gastrointestinal bleeding. 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.

Diagnosis

Physical examination

When a diagnosis of primary liver cancer is suspected, the physician will scrutinize the patient's history for risk factors and pay close attention to the condition of the 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 physician presses on it. In some cases, the patient's spleen is also enlarged. The physician may be able to hear a bruit (an abnormal sound) or friction rub when a stethoscope is used to listen to the blood vessels that lie near the liver. These abnormal sounds are caused by the pressure of the tumor on the blood vessels.

Laboratory tests

Blood tests, performed by a laboratory technologist or technician, may be used to evaluate liver function or to confirm risk factors, such as hepatitis B or C infection. About 75% of patients with liver cancer show evidence of hepatitis infection. Between 50-75% of primary liver cancer patients have abnormally high blood serum levels of alpha-fetoprotein (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. Though useful, abnormal liver function test results can not alone establish the diagnosis of liver cancer.

Imaging studies

Imaging studies are used to locate specific areas of abnormal tissue in the liver. Liver tumors as small as an inch across can 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 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 may be used to guide the physician 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. Imaging studies, including chest x rays, are usually performed by a radiology technician.

Liver biopsy

Liver biopsy provides the definite diagnosis of liver cancer. A sample of the liver or tissue fluid is removed with a fine needle and is examined by a pathologist, 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.

Laparoscopy

The physician also may perform a laparoscopy to assist in the diagnosis of liver cancer. A laparoscope is a small tube-shaped instrument with a light at one end that is inserted into the patient's abdomen. A small piece of liver tissue is removed and sent for biopsy (microscopic examination for the presence of cancer cells).

Treatment

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; 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; it aims to relieve symptoms but not to cure the disease.

Surgery

Few liver cancers in adults can be cured surgically 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 cirrhosis, jaundice, or ascites, then surgery is the best treatment option. Patients who can have their entire tumors removed have the best chances 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 surgical procedure 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).

Chemotherapy

Some patients with metastatic cancer of the liver may have their lives prolonged for a few months by chemotherapy, although cure is not possible. If the tumor cannot be removed by surgery, then a catheter may be placed in the main artery (hepatic artery) of the liver and an implantable infusion pump can be installed. The pump allows much higher concentrations of the anticancer drug to be carried to the tumor than is possible with chemotherapy carried through the bloodstream. The drug used for infusion pump therapy is usually floxuridine (FUDR), given for 14-day periods alternating with 14-day rests.

Systemic chemotherapy, given through a peripheral vein, can also be used to treat liver cancer. The drugs usually used are 5-fluorouracil (Adrucil, Efudex) or methotrexate (MTX, Mexate). Systemic chemotherapy does not, however, significantly increase survival time.

Radiation therapy

Radiation therapy may be used to relieve some symptoms of the disease. In general, radiation therapy will not prolong survival. Radioimmunotherapy is an experimental form of radiation therapy used to treat some types of liver cancer. A radioactive isotope is given intravenously and concentrates in the liver, where it radiates the tumor internally.

Liver transplantation

Since 1998, removal of the entire liver (total hepatectomy) and liver transplantation have very rarely been used to treat liver cancer. This is because very few patients are eligible for this procedure, either because the cancer has spread beyond the liver or because there are no suitable donors. Further research in the field of transplant immunology may make liver transplantation a viable treatment modality.

Prognosis

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 several months of diagnosis. 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.

Health care team roles

Like other cancer patients, patients with liver cancer are usually cared for by a multidisciplinary team of health professionals. The patient's family physician or primary care physician collaborates with other physician specialists, such as surgeons and oncologists. Radiologic technicians perform x ray, CT and MRI scans and nurses and laboratory technicians may obtain samples of blood, urine and other laboratory tests. Nurses also perform patient and family education.

Before and after any surgical procedures, including biopsies, nurses explain the procedures and help to prepare patients and families. Patients may also benefit from counseling from social workers, other mental health professionals or pastoral counselors.

Prevention

Presently, there are no useful strategies for preventing metastatic cancers of the liver. Primary liver cancers, however, are 75-80% 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 may be modified in order to prevent liver cancer include avoidance of exposure to environmental carcinogens, toxic chemicals, and foods harboring molds that produce aflatoxin. Most important, however, is avoidance of alcohol and drug abuse. Alcohol abuse is responsible for 60-75% 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.

Key Terms

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.

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.