DOES PREOPERATIVE CHEMOTHERAPY FOR HEPATIC-TUMORS HAVE AN ADVERSE EFFECT ON HEPATIC PROLIFERATION AFTER DELAYED LIVER RESECTION

The authors evaluate the effect of preoperative cisplatin and Adriamycin on hepatic proliferation after delayed partial hepatectomy. Sprague-Dawley rats were placed into five experimental groups. Group I received 0.9% saline intraperitoneally (IP). Group II received 2 mg/kg of cisplatin IP. Group III received 4 mg/kg of cisplatin IP. Group IV received 6 mg/kg of Adriamycin intravenously. Group V received 0.9% saline IP. Groups I through IV underwent 70% partial hepatectomy 2 and 10 days after chemotherapy. They were killed 24 hours later, and analyses were performed. Group V animals underwent celiotomy and were killed. Hepatic proliferation was evaluated by tritiated thymidine (3H-TdR) incorporation into DNA, quantitative image analysis (QIA), and proliferating cell nuclear antigen immunostained hepatic nuclei (PCNA). 3H-TdR incorporation values in animals treated 2 days before partial hepatectomy in treatment groups II through IV were similar to those of the hepatectomized controls. Although among the animals treated 10 days before partial hepatectomy there was inhibition of 3H-TdR DNA incorporation in the Adriamycin group, no significant differences were noted between all treatment groups. QIA of the S-phase nuclei (an indicator of proliferation) indicated that the animals treated with 2 mg/kg of cisplatin had significantly more nuclei than those treated with Adriamycin. PCNA labeling showed a decrease in proliferating nuclei in all treatment groups compared with the control hepatectomized animals. These data indicate that (1) preoperative cisplatin (2 and 4 mg/kg) is safe when measured by 3H-TdR, (2) preoperative Adriamycin had an adverse effect on hepatic proliferation, (3) PCNA may be a more sensitive indicator of proliferation than 3H-TdR, and (4) cisplatin may be the drug of choice for patients with hepatic tumors who are being considered preoperative chemotherapy. © 1994.