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

J Gastrointest Surg. 2003 Sep-Oct;7(6):783-90. doi: 10.1016/s1091-255x(03)00111-2.

Abstract

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-1 beta) 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 x 10(6) 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), CO(2)-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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction / blood*
  • Acute-Phase Reaction / etiology
  • Animals
  • Cecal Neoplasms / blood
  • Cecal Neoplasms / pathology
  • Cecal Neoplasms / surgery*
  • Chi-Square Distribution
  • Enzyme-Linked Immunosorbent Assay
  • Immunohistochemistry
  • Interleukin-1 / blood
  • Interleukin-6 / blood
  • Laparoscopy* / adverse effects
  • Laparoscopy* / methods
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Neovascularization, Pathologic / blood*
  • Statistics, Nonparametric
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Interleukin-1
  • Interleukin-6
  • Vascular Endothelial Growth Factor A