EARLY USE OF CISPLATIN IS SAFE AFTER PARTIAL-HEPATECTOMY

Although cisplatin is widely used in the treatment of liver tumors, little information is available concerning its effect on liver regeneration. This report evaluates the effect of cisplatin on liver regeneration after hepatectomy (HPx). One hundred sixty male Sprague-Dawley rats were placed into five experimental groups following 70% hepatectomy. Group I (untreated controls, n = 32) received 0.9% saline intraperitoneally (IP); group II (n = 31), cisplatin 4 mg/kg IP; group III (n = 36), cisplatin 10 mg/kg IP; group IV (n = 34), cisplatin 20 mg/kg IP; and group V (n = 27), doxorubicin 6 mg/kg intravenously (IV). Five additional sham groups underwent celiotomy without hepatectomy (n = 106) followed by the above treatment protocols. Liver regeneration was evaluated by liver weight, DNA incorporation measured by tritiated thymidine (3H-TdR), and quantitative image analysis (QIA) of hepatic nuclei at 18, 24, 36, 48, and 72 hours, and 5 days postoperatively. 3H-TdR incorporation peaked at 36 hours and was similar in hepatectomized controls group I (404 ± 110 counts per minute [CPM]/mg liver weight) and cisplatin-treated rats (groups II to IV) (ifP > .05, ANOVA). All sham groups were similar to controls. QIA of feulgen-stained touch preps identified polyploid, stem line, and proliferating nuclei in both controls and treated groups. At 36 hours, QIA showed differences in mitotic status of sham, control, and adriamycin-treated HPx rats, consistent with 3H-TdR incorporation. In contrast, although cisplatin-treated rats receiving 4 mg/kg showed proliferating nuclei, QIA demonstrated decreasing hepatocyte proliferation with higher doses of cisplatin (10 mg/kg, and 20 mg/kg). These data indicate that 3H-TdR DNA incorporation is not inhibited by cisplatin. QIA, however, shows a dose-dependent inhibition with 4 mg/kg, 10 mg/kg, and 20 mg/kg cisplatin administration. Early use of cisplatin (4 mg/kg = 2 times the human dose) following hepatic resection is feasible and may reduce the risk of local recurrence and/or metastatic spread. QIA may represent a more sensitive indicator of hepatocyte toxicity not detected by 3H-TdR incorporation. © 1993.