Tumor proliferative index is higher in mice undergoing laparotomy vs. CO2 pneumoperitoneum

PURPOSE: Our laboratory has previously shown that tumors are more easily es tablished and grow larger after laparotomy vs, laparoscopy. The purpose of this study was to better characterize these differences in tumor growth by assessing tumor cell proliferation via the proliferating cell nuclear antig en assay, which has been shown to be a reliable marker of cellular prolifer ation. METHODS: Female C3H/He mice (N = 40) were inoculated intradermally i n the dorsal skin with 10(6) cultured mouse mammary carcinoma cells <1 hour before interventions. Anesthesia control mice underwent no procedure. Lapa rotomy group mice had a midline incision from xiphoid to pubis that was clo sed after 20 minutes. Insufflation group mice underwent CO2 pneumoperitoneu m (4-6 mmHg) for 20 minutes. On postoperative Day 6, tumors were excised fr om one-third of the mice in each group, and from the remaining mice on post operative Day 12. Sections were made and stained immunohistochemically for proliferating cell nuclear antigen, and the proliferative index of each tum or was determined by taking the average of proliferating cell nuclear antig en-positive cells in five high-power fields (X450), counted in a blinded fa shion with the aid of an optical grid. RESULTS: On postoperative Day 6, the mean proliferative index for the laparotomy group was significantly higher than those for both the insufflation (P < 0.04) and the control (P < 0.001 ) groups. Of note, the proliferative index of the insufflation group was si gnificantly higher than that of the control (P < 0.01) group. Similarly, on postoperative Day 12, the mean proliferative index for the laparotomy grou p was significantly higher than for both the insufflation (P < 0.05) and th e control (P < 0.005)groups. The proliferative index in the insufflation gr oup was also significantly higher than that of the control (P < 0.04) group . CONCLUSIONS: We have demonstrated that there is a significantly higher ra te of tumor cell proliferation with the mouse mammary carcinoma cell tumor line after laparotomy than after pneumoperitoneum or anesthesia alone at tw o postoperative times. Additionally, insufflation alone increases postopera tive tumor cell proliferation but to a lesser extent than laparotomy. The m echanism underlying these findings is unclear.