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.(ABSTRACT TRUNCATED AT 250 WORDS)
Engum
S A
SA
Indiana University School of Medicine, James Whitcomb Riley Hospital for Children, Indianapolis 46202-5200.
Sidner
R A
RA
Miller
G A
GA
Grosfeld
J L
JL
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004247:DNA / Q000096:biosynthesis; D004317:Doxorubicin / Q000008:administration & dosage*; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D011300:Preoperative Care; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D004317:Doxorubicin; D004247:DNA; D002945:Cisplatin; D013936:Thymidine