Hepatocellular carcinoma (HCC) is the ninth leading cause of cancer death in the USA, the third leading cause worldwide, and the fifth most common solid tumor cancer. It begins in the cells of the liver and is usually not detected at an early stage, often resulting in a poor patient prognosis. The incidence of primary liver cancer in the USA is approximately 20,000 cases per year and is rapidly growing worldwide. In a report published in the May 7, 2010 issue of Morbidity and Mortality Weekly Report (MMWR), the average annual incidence rate of hepatocellular carcinoma in the U.S. increased significantly, from 2.7 per 100,000 people in 2001 to 3.2 per 100,000 people in 2006, with an average annual percentage change in incidence rate of 3.5%.
Globally there are approximately 660,000 cases per year. More than 80% of these cases occur in developing countries, with China alone accounting for over 55% of the total. Rates are more than twice as high in men as in women. Liver cancer rates are the highest in West and Central Africa and in Asia. In contrast, incidence rates are lowest in developed countries, with the exception of Japan. Among primary liver cancers occurring worldwide, hepatocellular carcinoma represents the major histologic type and likely accounts for 70-85% of cases.
Unfortunately, most cases could have been prevented. Chronic hepatitis B and C virus infections, which are highly prevalent in developing countries, account for 78% of all hepatocellular cancer in the USA. Prevention of virus transmission and progression of chronic viral disease has been shown to decrease the incidence of this cancer.
Current and Emerging Treatment Trends.
Liver cancer has one of the highest fatality rates of all cancers, with five-year relative survival rates less than 11% even in developed countries. There are few non-surgical therapeutic treatment options available. Treatment may include surgery, chemotherapy, radiation therapy, or percutaneous ethanol injection, but radiation and chemotherapy are largely ineffective in the treatment of primary liver cancer. The standard first line treatment for liver cancer is surgery, either resection or liver transplantation, but surgery is confined to those patients whose tumors are confined to the liver, are no larger than 5 cm, and where the cancer has not invaded the adjacent blood vessels, organs or lymph nodes. Approximately 70% to 80% of patients are ineligible for surgery.
Applicable Ablation Technologies: Rationale for Use and Effect on Tissues.
Radio frequency ablation (RFA), with limitations, has shown to be effective and has increasingly become the standard of care for non-resectable liver disease. Radiofrequency ablation devices work by sending alternating current through the tissue. This creates increased intracellular temperatures and localized interstitial heat. When temperatures exceed 60°C, cell proteins rapidly denature and coagulate, killing the cells and producing a lesion. The lesion can be used to resect and remove the tissue or to simply destroy the tissue, leaving the ablated tissue in place.
Laser-induced interstitial thermotherapy (LITT) and microwave have also been utilized for the ablation of HCC tumors, although these two treatments do not seem to work as well on large tumors as other treatments. Interstitial laser photocoagulation uses a thin optical fiber (which is inserted into the center of the tumor) and a laser. When the laser light is emitted, the cancerous cells undergo thermal necrosis. Interstitial microwave kills the tumor cells by heating them to a high temperature (50 degrees C) for an extended period of time.
Minimally invasive irreversible electroporation is another treatment for HCC tumors. Electroporation increases the permeability of the cell membrane by exposing the cell to electric pulses. Irreversible electroporation opens the cell membrane in such a way that the cell cannot reverse the process and close the membrane. This open membrane causes the cell’s death. Irreversible electroporation is felt by some researchers to be comparable to cryosurgery, nonselective chemical ablation and high temperature thermal ablation.
Other ablation technologies are under development for use in treatment of liver cancer at various stages. (See link.)