The word cancer refers to a group of diseases or genetic disorders that cause cells in the body to mutate and grow incorrectly. Many types of cancer cells form a mass called a tumor. Malignant cancer cells may invade the blood or lymphatic vessels, and spread to other parts of the body where they continue to grow and inhibit normal body functions.
There are two types of cancers found in the liver: primary liver cancer which originates from the liver and metastatic (or secondary) liver cancer which originates from other parts of the body and spreads to the liver.
Hepatocellular Carcinoma
HCC, also called hepatoma, is the most common type of malignant primary liver tumor. While HCC is fairly uncommon in the United States and Europe, it is among the top 3 causes of cancer deaths in many Asian and some African countries. The World Health Organization (WHO) states that at least 550,000 people die yearly from HCC, 75% (approximately 400,000) of these deaths are people in countries in Southeast Asia and the Pacific Rim. Chronic hepatitis B infection from birth and early childhood (as often the case in most chronically infected API) causes 80% of the liver cancer, with the hepatitis C virus accounting for most of the remaining cases. The Centers for Disease Control and Prevention found that the greatest health disparity between Asian Americans and Caucasian Americans is liver cancer. Preventing hepatitis B infection through vaccination can prevent 80% of the cases of liver cancer in Asian Americans and worldwide.
Symptoms
Liver cancer is called a silent killer because the majority of the patients appear to be perfectly healthy and have no any early signs or symptoms. Small tumorous lumps are impossible to feel due to the shielded location of the liver underneath the ribs. Pain is uncommon until the tumor is quite large, and even some large tumors do not cause pain or other symptoms. Later stages of liver cancer when the cancer is very large or when it impairs the functions of the liver can produce more obvious symptoms such as pain over the right upper abdomen, weight loss, lack of appetite, and finally the development of yellow discoloration of the eyes and skin (jaundice) and abdominal swelling. Late diagnosis explains why the average survival after diagnosis is often quoted as 3-6 months. Early diagnosis through screening for liver cancer in high-risk API hepatitis B carriers and in patients with cirrhosis due to hepatitis B or C is the only effective way of improving the outcome of treatment.Liver Cancer Screening
It is important to recognize that API chronically infected with hepatitis B who became infected early in childhood have a high risk of developing liver cancer. The risk is greater for men and those with a family history of liver cancer. Regular liver cancer screening in API hepatitis B carriers, although the role in Caucasian carriers who become infected later in life is controversial. Although API carriers may develop liver cancer early in their teens, data from the US shows that the incidence of liver cancer begins to rise around the age of 30 years. A reasonable approach is to begin regular liver cancer screening for the API hepatitis B carriers starting at 30-40 years of age. This generally consists of a blood test for alpha-fetoprotein (AFP) level every 6 months and an ultrasound of the liver once a year (In Taiwan, ultrasound is recommended twice a year). Either test alone can miss the diagnosis. Alpha-fetoprotein is elevated in only 60-70% of liver cancer so blood testing alone will miss 30-40% of the liver cancers. Ultrasound can miss 20% of liver cancers measuring less than 2 cm, especially when the images are difficult to interpret in cirrhotic livers. Once the patient develops cirrhosis, more frequent screening is generally recommended.Evaluation of Liver Cancer
A liver ultrasound and conventional CT scan are regularly used in the diagnostic evaluation of HCC, but these diagnostic techniques are sometimes too insensitive. Thorough assessment with a biphasic spiral CT scan of the abdomen is essential. The fast spiral scanner allows scanning of the liver at the arterial phase shortly after the patient is given an intravenous bolus of contrast. Tumors typically take up the contrast-compound so even small HCC can be detected, which are often missed with conventional CT techniques and slower scanners. A hypervascular lesion that enhances at the arterial phase and fades at the venous phase of scanning is characteristic of HCC. A liver tumor with these characteristics in an API hepatitis B carrier, or a patient with cirrhosis associated with rising serial AFP levels (or a level over 500), is virtually diagnostic of HCC and biopsy confirmation is unnecessary. Percutaneous fine needle biopsy may be indicated in cases when the diagnosis of primary versus metastatic liver tumor is uncertain, providing that it can be safely performed. Post biopsy bleeding can be life threatening in cirrhotic patients with low platelet count, prolonged clotting time, and enlarged blood vessels which are under high pressure (portal hypertension). In general, metastatic liver lesions are rare in patients with cirrhosis.Treatment of HCC
Treatment of liver cancer is particularly challenging when compared with other types of cancer because in addition to the cancer itself, many patients have livers that have sustained damaged from hepatitis resulting in cirrhosis and various degrees of liver failure. Treatment of the liver cancer without regard for the precarious state of the liver itself may harm the patient more than help. Some patients have such poor liver function that they are more likely to die from liver failure than from the cancer itself. For each individual patient, the potential benefits of the various treatment options must be balanced with the risk of liver failure and how it affects the patient's quality of life. At Stanford University, a multidisciplinary approach has been adopted where patients with liver tumors are presented and evaluated at the Multidisciplinary Liver Tumor Clinic/Tumor Board by a team of specialists to address both the treatment of the tumor and the underlying liver disease or hepatitis. Potential new treatments are also evaluated. Surgical Treatment: When the tumor is small or deemed surgically resectable, and the patient's liver condition is deemed fit for the extent of the planned resection, surgical removal offers the best chance for long-term survival. Improved surgical and anesthetic management has led to improved survival and dropped the risk of perioperative mortality to less than 2-5% in experienced hands and most patients can be discharged from the hospital after 3-4 days. Despite complete removal of the tumor, patients are still at risk for recurrent disease, and they need to be followed closely long-term, especially during the first year when the risk of recurrence is greatest.
Nonsurgical Treatment: For patients who are not resection candidates for anatomic or medical reasons, a number of alternative treatment options are available in an attempt to control the disease long-term and with the aim of maintaining quality of life. The management of these patients again has to be individualized based on the general condition of the patient, the condition of the liver, and the extent of the disease. Traditional chemotherapy is generally ineffective, causes many side effects that may severely impair the patient's quality of life, and often does not prolong survival. HCC are hypervascular tumors and the ability of experienced interventional radiologists to navigate these vessels and selectively cannulate the feeding tributaries provides us with a unique opportunity to target the therapy directly into the tumor. Intrahepatic arterial chemoembolization or chemo infusion (TACE or TAC) is performed frequently by interventional radiologists in Asia and has been adopted by the Stanford Multidisciplinary Liver Tumor Clinic for the last four years in the treatment of selected patients with unresectable lesions. Despite a superselective and staged treatment approach to minimize the risk of damaging the non-tumor bearing part of the liver, this treatment is not suitable for patients who already have signs of moderate liver failure (serum albumin less than 3 gm/dL, bilirubin over 1.5 mg/dL, fluid in the abdomen also called ascites) and in patients with blockage of the portal vein. In patients who respond well, the treatment is usually repeated every 4 months if necessary until the AFP levels have returned to normal or until no new hypervascular lesions are seen. The treatment only requires an overnight stay for observation and is often well tolerated if the above approach is followed. Long-term treatments with TACE or TAC have been associated with prolonged patient survival, and those who have good control or shrinkage of the tumor may even become suitable candidates for surgical resection or transplantation.
Liver Transplantation: Liver transplant is a treatment option for HCC that are surgically or medically unresectable, provided that the tumor is small (less than 5 cm or fewer than 4 lesions), confined to the liver, and without invasion into the blood vessels. A report from a study by the Asian Liver Center at Stanford University shows that patients who had good tumor response to TACE or TAC also had excellent survival rates after transplantation. More extensive tumors have a high risk for early recurrence and death after liver transplantation. After transplantation, the patient must receive either hepatitis B immunoglobulin (HBIG) or lamivudine, or both, to prevent HBV reinfection of the new liver.
Liver cancer treatment remains difficult and requires a good understanding of many disciplines including cancer, diagnostic radiology, surgery, transplantation, and liver disease. Early diagnosis of small tumors is the only effective way of improving the outcome of liver cancer treatment, and that is only possible through screening of the high-risk population.
Last Updated: May 9, 2008
