Colorectal resection is associated with persistent proangiogenic plasma protein changes: postoperative plasma stimulates in vitro endothelial cell growth, migration, and invasion

Ann Surg. 2009 Jun;249(6):973-7. doi: 10.1097/SLA.0b013e3181a6cd72.


Introduction: Plasma vascular endothelial growth factor (VEGF) levels are elevated for weeks after minimally invasive colorectal resection (MICR). Decreased plasma angiopoietin-(Ang) 1 and increased Ang-2 levels have been noted on postoperative days (POD) 1 and 3. These proangiogenic changes may stimulate tumor growth postoperatively (postop). This study's purpose was to track plasma VEGF, Ang-1, and Ang-2 levels for 4 to 8 weeks after MICR for cancer and to assess the impact of preoperative (preop) and postop plasma on in vitro endothelial cell (EC) behavior.

Methods: Blood samples from 105 MICR patients were taken preop, on POD 5 and at varying time points for 2 months. Samples from 7 day time blocks after POD 5 were bundled to permit statistical analysis. Plasma protein levels were measured via enzyme-linked immunosorbent assay. In vitro EC branch point formation, EC invasion, and EC migration assays were carried out with preop, POD 7 to 13 and 14 to 20 plasma. The t test and Bonferonni correction was used.

Results: VEGF levels were significantly elevated on POD 5 and 7 to 13; lesser increases were noted on POD 14 to 20 and 21 to 27. Ang-2 levels were significantly increased at all time points postop. No significant Ang-1 changes were noted. When compared to preop EC culture results, there was significantly more EC branch point formation, EC invasion, and EC migration assays noted with POD 7 to 13 and POD 14 to 20 plasma.

Conclusions: MICR is associated with proangiogenic plasma changes for 2 to 4 weeks and plasma from POD 7 to 13 and 14 to 20 stimulated EC growth, invasion, and migration. Postop plasma may stimulate the growth of residual tumor.

Publication types

  • Multicenter Study

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery*
  • Aged
  • Aged, 80 and over
  • Angiopoietin-1 / blood*
  • Angiopoietin-2 / blood*
  • Cell Movement
  • Cell Proliferation
  • Cohort Studies
  • Colectomy
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery*
  • Endothelial Cells / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Minimally Invasive Surgical Procedures
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / blood*


  • ANGPT1 protein, human
  • Angiopoietin-1
  • Angiopoietin-2
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A