Colorectal resection is associated with persistent proangiogenic plasma protein changes: postoperative plasma stimulates in vitro endothelial cell growth, migration, and invasion.
BACKGROUND
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.
Kumara
H M C Shantha
HM
Columbia University College of Physicians and Surgeons, New York, New York, USA.
Shantha Kumara
H M C
HM
Feingold
Daniel
D
Kalady
Matthew
M
Dujovny
Nadav
N
Senagore
Anthony
A
Hyman
Neil
N
Cekic
Vesna
V
Whelan
Richard L
RL
D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology / Q000601:surgery*; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D002465:Cell Movement; D049109:Cell Proliferation; D015331:Cohort Studies; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000097:blood / Q000473:pathology / Q000601:surgery*; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019060:Minimally Invasive Surgical Procedures; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A