Introduction: High plasma VEGF levels are associated with advanced stage and a poor prognosis in colorectal cancer patients (pts). It has been shown that VEGF levels are significantly increased, over baseline, on postoperative day (POD) 3 after cancer resection (CR). Such increases may stimulate the growth of residual micrometastases. This study's purpose was to assess the duration of the plasma VEGF increase after colorectal CR.
Methods: Cancer pts from 3 IRB approved prospective studies for whom late postoperative blood samples were available make up the study population. Demographic, pathologic, operative, and short term outcome data was collected. Plasma samples were obtained preoperatively (PO), on POD1, and at various other time points during the first month after surgery and beyond. VEGF levels were measured via ELISA and compared using Wilcoxon's Matched Pairs Test. Because the later sampling times varied widely and since there were limited numbers of late specimens, from POD5 onward results from 7 day time blocks were bundled and averaged to permit statistical analysis.
Results: 70 pts undergoing minimally invasive CR comprise the study population. 49 pts (70%) had laparoscopic assisted resections (mean incision 4.8 cm) while 21 (30%) had hand-assisted operations (mean incision 10.7 cm). The mean age was 68.2 (33 males and 37 females). The cancer locations were: right, 30 (43%): sigmoid, 17 (24%); rectal, 14 (20%); left, 6 (9%); and transverse, 3 (4%). The mean length of stay was 7.0 days and 10 % of pts were transfused. The mean plasma VEGF values in pg/ml (standard deviation) for each time point or sampling block were: Preop, 191.2 ±158.7; POD1, 216.6 ± 178.7; POD3, 243.3 ± 243.0; POD5, 407.1 ± 281.3; POD 7-13, 571.7 ± 496.9; POD 14-20, 491.4 ± 444.0, POD 21-27, 383.5 ± 385.6 ; POD 28-52, 166.2 ± 175.8. Significant increases over the PO baseline were noted at the following time points: POD3, POD 5, POD 7-13, POD 14-20, and POD 21-27. VEGF levels peaked during the 2nd and 3rd weeks after surgery. Values returned to baseline or below during the second month.
Conclusions: Surgery is associated with significant elevations of VEGF that start on POD 3 and persist for 4 weeks. Although not proven, this increase is likely related to wound healing. This persistent plasma VEGF increase may promote the growth of surviving tumor cells and microfoci. The first month after resection may be a dangerous time for cancer patients; the development of neoadjuvant and immediate adjuvant therapies is warranted.