Influence of postoperative acute-phase response on angiogenesis and tumor growth: Open vs. laparoscopic-assisted surgery in mice

Inflammatory responses and tumor growth are increased after laparotomy compared with laparoscopy in some animal models. Proinflammatory cytokines interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) upregulate the expression of vascular endothelial growth factor (VEGF). Our aim was to investigate the influence of postoperative inflammatory responses on angiogenesis and tumor growth. 5 Χ 10⁶ B51LiM cells were injected into the cecal wall of Balb/c mice. After 2 weeks, the animals were randomized into the following three groups: open cecectomy (OC), CO₂-laparoscopic-assisted cecectomy (LC), and helium-laparoscopic-assisted cecectomy (LH). On postoperative day 12, the mice were killed. Tumor load scores and weight were significantly greater after laparotomy than after laparoscopy. Serum IL-6 levels 6 hours after surgery (OC: 4157 ± 1297 pg/ml vs. LC: 2514 ± 1417 pg/ml vs. LH: 2255 ± 1714 pg/ml) and VEGF levels on postoperative day 12 (OC: 231 ± 125 pg/ml vs. LC: 45 ± 9 pg/ml vs. LH: 49 ± 8 pg/ml), measured by enzyme-linked immunosorbent assay, were significantly higher in the laparotomy group. Microvessel density was also significantly higher in the OC group (OC: 34.3 ± 11.5 vs. LC: 15.5 ± 12.5 vs. LH: 18.5 ± 11.9). There was a positive correlation between IL-6 and VEGF postoperative serum levels (rho = 0.67; P < 0.001). We concluded that increased systemic levels of proinflammatory cytokines and VEGF are associated with increased angiogenesis and tumor growth after laparotomy compared to laparoscopy in mice. Presented at the Fifty-Seventh Annual Sessions of the Owen H. Wangensteen Surgical Forum, The American College of Surgeons Clinical Congress, San Francisco, California, October 6–10, 2002; and published as an abstract in Journal ofthe American College of Surgeons 2002; 195:S69. Supported by an International Fellowship Grant from the American Society of Colon and Rectal Surgeons (M.P.) and by a Postdoctoral Grant (EX2001-35105008) from the Ministry of Education and Culture of Spain.