Adjuvant Therapy after Curative Treatment for Hepatocellular Carcinoma

Abstract

It is widely accepted that hepatocellular carcinoma (HCC) has an annual recurrence rate of approximately 15–20% even after potentially curative treatment, with the 5-year recurrence rate reaching 80–90%. This recurrence rate is also known to be similar after various curative treatments including resection, percutaneous ethanol injection therapy, and radiofrequency ablation. Generally, in treating patients with HCC associated with hepatitis C or liver cirrhosis, aggressive efforts to prevent secondary carcinogenesis are necessary rather than simply observing the clinical course after treatment. Presently, a combination of peg-interferon and ribavirin is known to be highly effective in patients with difficult-to-treat hepatitis C with a high viral load and genotype I virus. Therefore, indications of these treatments must be considered to prevent secondary carcinogenesis in patients with hepatitis C. Recently, long-term follow-up of low-dose, long-term maintenance therapy using pegylated interferon-α2a for cirrhotic patients clearly showed a preventive effect on HCC occurrence and recurrence. Preventing secondary carcinogenesis by suppressing inflammation employing the same treatment as that against primary carcinogenesis is also important. The molecular targeted agent sorafenib markedly suppresses the serine/threonine kinases of Raf in the MAP kinase cascade and inhibits the tyrosine kinases of angiogenesis factor receptors such as vascular endothelial growth factor and platelet-derived growth factor receptors. It thus simultaneously prevents the proliferation of tumors and inhibits angiogenesis. A clinical trial to examine the recurrence-preventing effect of sorafenib by administration of it after curative treatment such as resection or ablation is in progress (STORM trial: http://clinicaltrials.gov.com, NCT00692770). Treatments to prevent recurrence (including intrahepatic metastasis and multicentric carcinogenesis) as well as early detection and early curative treatment are extremely important to improve the prognosis of patients with HCC. Thus, further research on this issue should be carried out, especially in relation to molecular targeted therapy.

Activation of IL6/IGFIR Confers Poor Prognosis of HBV-Related Hepatocellular Carcinoma through Induction of OCT4/NANOG Expression

“…Effective strategies for the prevention of HCC recurrence are needed to improve the prognosis of patients with HCC (37). In this study, we demonstrated that the inflammatory cytokine IL6 stimulates the autocrine IGF loop to activate IGFIR, and initiates OCT4 (and/or NANOG) expression in HBV-HCC cells (Fig.…”

Oxidative stress and hepatocarcinogenesis

“…However, the high annual recurrence rate (approximately 20%) is still a huge hurdle before achieving long-term disease-free survival [74] . Neoadjuvant and adjuvant therapy for resectable HCC is still a difficult challenge.…”

Management of recurrent hepatocellular carcinoma after liver transplant

“…Activation of the Ras/mitogen-activated protein kinase pathway is a common finding in neoplastic processes (including in HCC) and is a determinant for promoting cell proliferation and the survival of tumor cells. This makes sorafenib an interesting drug; its use as a treatment for unresectable HCCs and as an adjuvant treatment before and after HCC recurrence is being investigated [50] . A study from Spain demonstrated that combination therapy resulted in an overall response (in accordance with the Response Evaluation Criteria in Solid Tumors) rate of 3.8% (1/26), and there was sustained stabilization of disease in 13 additional cases (50.0%) [42] .…”