Non-surgical treatment of hepatocellular carcinoma

A decade ago, surgery was the only satisfactory treatment modality for hepatocellular carcinoma (HCC), but it was limited only to selected cases. For the majority of cases of HCC, systemic chemotherapy was one of the few treatment alternatives, but provided only marginal benefit. In the past 20 years, diagnostic methods have improved to an extent that small HCC less than 1 cm can be detected. Moreover, non-surgical treatment is available, of which regional therapy has been shown to prolong patients' survival, and may even replace surgical resection in some cases. Regional therapy is indicated for the treatment of HCC when there is no extrahepatic metastasis and the patient has adequate liver function reserve, thus permitting repeated therapy. Transcatheter hepatic arterial embolization (TAE) using various embolizers has been well documented to include controlled studies. However, it is not indicated for patients with thrombosed main portal veins. Its therapeutic effect is also doubtful when the tumour is infiltrative in nature or is hypovascular, too large or too small. Additional chemotherapeutic agents mixed into the embolizer with lipiodol and degraded starch microspheres or styrene-maleic acid-neocarzinostatin in which chemotherapeutic agents are embedded, are used with a better response, but the survival rate has not shown significant improvement. Ultrasound-guided local injection therapy is another new method of treatment of HCC. Of these techniques, percutaneous ethanol injection therapy (PEIT) is widely used with excellent results for small, encapsulated tumours in livers with less than three HCC. Percutaneous ethanol injection therapy can also be used in cases with portal vein thrombosis, but it is not suitable for patients having coagulopathy or ascites. Using acetic acid, OK-432, interferon or anti-cancer drugs in the injection therapy shows no further benefit over ethanol alone. Transcatheter echoguided thermotherapy or cryotherapy has been reported in small series of patients, as has target therapy with immune or radiotherapy and conformal radiotherapy. Preliminary studies show encouraging results. Systemic therapy with either single drug or multidrugs is ineffective, with a response rate of less than 20%. Immunotherapy, such as with interferon or other cytokines, is not beneficial. Hormone therapy has not been promising, except for treatment with tamoxifen, which has been reported to show some beneficial effect. Gene therapy is still in its infancy. In summary, recent progress in non-surgical treatment of HCC has resulted in a breakthrough of regional therapy looking quite promising. Moreover, a combination of different types of regional therapies may yield better outcomes in selected individuals.