Metastasis and Recurrence After Surgical Resection of Hepatocellular Carcinoma: Recent Progress in Clinical and Related Basic Aspects

Metastasis and recurrence, which is caused either by intrahepatic metastasis (IM) or by metachronously multicentric carcinogenesis, has become one major obstacle for further improving the survival and prognosis of HCC patients. Many factors, such as the patient's general conditions (age, sex, co-existing hepatitis, liver function, AFP level), macroscopic tumor morphology (tumor size, number, capsule status, intra or extra-hepatic spreading, vessel invasion), and tumor pathohistological features, as well as treatment-related factors (surgical techniques, blood transfusion), have been determined as risk factors, and proven of predicting significance for HCC recurrence. In recent years, with the understanding of tumor biology and the development of molecular biology techniques, many molecular factors (biomarkers) have been developed. Various neoadjuvant or adjuvant therapeutic approaches including pre-operative transcatheter arterial chemoembolization (TACE), post-operative TACE, systemic or locoregional chemotherapy, immunotherapy, interferon, and acyclic retinoic acid have been hoped to decrease or eliminate recurrence of HCC. However, there is no evidence demonstrate benefit from the various neoadjuvant and adjuvant therapies investigated. Most of them deserve further evaluation by randomized control trial (RCT), and among them, biotherapy could be an ideal strategy. Many kinds of treatment strategies, including surgical treatment (repeat resection and salvage transplantation), TACE, regional cancer therapies such as radiofrequency ablation (RFA), chemotherapy have been tried and proven to be potentially helpful for the control of HCC recurrence and metastasis. However, there are few RCT to evaluate the effect of these modalities on the recurrence and metastasis of HCC.