New Immunotherapy for hepatocellular carcinoma after hepatectomy

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Experimental study : The influence of IL-2 on liver regeneration was examined using mitotic index (MI) and the bromodeoxyuridine (BrdU) labeling index (LI) in 70% hepatectomized Donryu rats. IL-2 (45,000 JRU/day) or saline was administered continuously via the portal vein immediately after hepatectomy using an infusion pump. No difference in the weight of the liver, serum Alb, GPT,or Bil was observed in any groups at 1,2, or 4 days after hepatectomy. Gap junctions began to disappear after hepatectomy and reached a minimum on day 2 in all groups. Four days after hepatectomy, the density of the reappearing gap junctions was markedly lower in groups treated with IL-2 than in those receiving saline. However, the density returned to close to preoperative levels 6 days after hepatectomy in all groups. Continuous portal infusion of LI-2 transiently disturbed gap junction reappearance during liver regeneration. However, no other parameters of liver regeneration or liver functions differed. The … More se results suggest that intrahepatic IL-2 administration can be performed without serious complications after hepatectomy.Clinical Study : We performed intraarterial combined immunotherapy (ACIT) for 12 paticnts with hepatocellular carcinoma (HCC) 14 days after hepatectomy. ACIT consists of IL-2, OK-432, adriamycin, cyclophosphamide, and famotidine. The 3-year survial rate of treated patients was 100%, while, that of 38 untreated patiens was 60%. Thus, intraarterial combined immunotherapy following hepatectomy significantly improved the survival rate in patients with HCC.Three patients with HCC were treated with ACIT.Histological analysis using the resected specimen revealed massive invasion of lymphocytes around HCC lesions. Immunohistochemical analysis demonstrated that the major invaded lymphocytes were the CD8 positive and HLA-DR positive lymphocytes.Furthermore, in the lymphocyte infiltrating area, the Fas antigen in tumor cells were strongly expressed. In conclusion, the antitumor effect of ACIT may be related with the activation of tumor infiltrating lymphocytes. These lymphocytes may kill tumor cells in an apoptotic fashion. Less