suppression may not be harmful for overall recovery of We have reported the efficacy of intraarterial-comthe resected liver. However, it seems that hepatic IL-2 bined immunochemotherapy including interleukin-2 administration can be performed without serious com-(IL-2) for unresectable hepatocellular carcinoma (HCC).plications after hepatectomy. (HEPATOLOGY 1996;23:1578-To further test this therapy for prevention of intrahe-1583.) patic recurrence after hepatectomy, the influence of IL-2 on liver regeneration was examined using mitotic index (MI) and the bromodeoxyuridine (BrdU) labeling index Although significant progress has been made in the (LI) in 70% hepatectomized Donryu rats. In addition, gap surgical treatment of human hepatocellular carcinoma junction appearance, which may change during liver re-(HCC), as well as in the detection of small HCC with generation, was analyzed using a monoclonal antibody diagnostic techniques such as ultrasonography and (HAM8). Serum albumin, alanine transaminase, and tocomputed tomography, cancer recurrence, including intal bilirubin (TB) levels were also evaluated. IL-2 (45,000 trahepatic recurrence, is observed in about 50% of pa- Japanese reference units [JRU]/d) or saline was admin-istered continuously via the portal vein immediately tients with HCC in the year following hepatic resecafter hepatectomy using an infusion pump. We also ex-tion. 1 Most of the recurrences involve the remnant amined the influence of IL-2 on liver regeneration after liver, with intrahepatic metastasis occurring via the hepatectomy with splenectomy. No difference in the portal tract. [1][2][3] weight of the liver, serum albumin, alanine transamiSince 1988, we have performed continuous intrahenase, or TB was observed in any groups at 1, 2, or 4 patic administration of interleukin-2 (IL-2) combined days after hepatectomy. Neither IL-2 nor splenectomy with anticancer agents for the treatment of unresectinfluenced MI and BrdU LI at all three points. Gap junc-able HCC with satisfactory response. The response rate tions began to disappear after hepatectomy and reached was 58.3%, including four cases of complete response. a minimum on day 2 in all groups. Four days after hepa-The overall 2-year survival rate was 52% and the 2-tectomy, the density of the reappearing gap junctions was markedly lower in groups treated with IL-2 than year survival rate of responders was 80%. 4 Before this in those receiving saline with or without splenectomy. therapy is introduced to prevent intrahepatic recurHowever, the density returned to close to preoperative rence, the influence of IL-2 on liver regeneration should levels 6 days after hepatectomy in all groups. Continu-be evaluated, although we experienced no severe side ous portal infusion of IL-2 transiently disturbed gap effects concerning hepatic function in our clinical protojunction reappearance during liver regeneration. How-col. A previous experimental study reported that ILever, no other parameters of liver regeneration or liver 2 exerts inhibitory influence ...