Influence of continuous interleukin-2 administration via the portal vein on liver regeneration following partial hepatectomy in rats
✍ Scribed by K Wadamori; M Oka; N Tokuda; Y Fujikura; S Hazama; T Fukumoto; T Suzuki
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 514 KB
- Volume
- 23
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
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 administered continuously via the portal vein immediately tients with HCC in the year following hepatic resecafter hepatectomy using an infusion pump. We also extion. 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. [2] weight of the liver, serum albumin, alanine transami-Since 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 juncable 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 2tectomy, the density of the reappearing gap junctions was markedly lower in groups treated with IL-2 than year survival rate of responders was 80%. Before this in those receiving saline with or without splenectomy. therapy is introduced to prevent intrahepatic recur-However, 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. Continube 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. Howcol. A previous experimental study reported that ILever, no other parameters of liver regeneration or liver 2 exerts inhibitory influence on liver regeneration in functions differed. These results suggest that the liver hepatectomized rats when given by intraperitoneal inregeneration after partial hepatectomy may be supjection at regular intervals. 5 However, the influence of pressed by the administration of IL-2, even though the continuous intrahepatic administration of IL-2 on liver regeneration has not been reported. To evaluate cell proliferation in the remnant liver, the bromodeoxyuri-Abbreviations: JRU, Japanese reference units; HCC, hepatocellular carcinoma; IL-2, interleukin-2; BrdU, bromodeoxyuridine; LI, labeling index; MI, dine (BrdU) labeling index (LI) and mitotic index (MI) mitotic index; TB, total bilirubin; FITC, fluorescein isothiocyanate.
have been a popular method for measuring cell kinetics