Systemic Effects of Surgery: Quantitative Analysis of Circulating Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF) and Transforming Growth Factor Beta (TGF-β) in Patients with Breast Cancer Who Underwent Limited or Extended Surgery

Abstract

Angiogenic cytokines perioperative levels could be increased on 5th day (D(+5)) by extent of surgery and should induce perioperative stimulation of residual cancer cells. A better understanding of the time interval during which the sequelae of events in wound healing occur may be the basis for defining new therapeutic strategies that can interfere with tumor outgrowth sparing wound healing processes.

Neoadjuvant Treatment of Colorectal Cancer with Bevacizumab: The Perioperative Angiogenic Balance Is Sensitive to Systemic Thrombospondin-1 Levels

“…Other groups have reported an additional peak or plateau of plasma VEGF around postoperative days 8 to 10, which we have not observed (19,40). The difference may relate to the extent and type of surgery in the respective studies (16) or -as suggested by one of the authors-may be due to variations in plasma preparation (19). The latter argument seems highly feasible because different methods of plasma preparation were shown to be prone to platelet contamination and degranulation (41,42), and the extended postoperative increase in plasma VEGF correlated with an increase in platelet counts and serum VEGF levels in this particular study (19).…”

“…A significant ''spillover'' to circulation is shown in an increase of plasma VEGF concentrations on postoperative days 1 to 2, which provides a limited time window for systemic investigations on the wound healing process (14). Serum measurements primarily reflect VEGF stored in and released by platelets upon serum preparation and have thus been found to mimic the initial decrease of platelet counts in hemostatic plug formation rather than the local VEGF surge in wound tissue (14,16,17). Detectable increases in serum VEGF levels have only been reported for major surgery (16,18,19), which argues for plasma analyses to investigate changes in the systemic angiogenic balance during wound healing.…”

“…Serum measurements primarily reflect VEGF stored in and released by platelets upon serum preparation and have thus been found to mimic the initial decrease of platelet counts in hemostatic plug formation rather than the local VEGF surge in wound tissue (14,16,17). Detectable increases in serum VEGF levels have only been reported for major surgery (16,18,19), which argues for plasma analyses to investigate changes in the systemic angiogenic balance during wound healing. A change in balance involving the increase of proangiogenic factors and a concomitant decrease of antiangiogenic molecules is required to promote vessel growth (15,20).…”

Persistent elevation of plasma vascular endothelial growth factor levels during the first month after minimally invasive colorectal resection

“…A number of investigators have noted increased serum or plasma VEGF levels during the first 8 days after resection of gastric, breast, and large bowel malignancies [14,[19][20][21][22]. A recent study assessed plasma VEGF levels preoperatively and on days 1 and 3 after open and minimally invasive colorectal resection for both benign and malignant indications as well as after gastric bypass in morbidly obese patients.…”

“…Other investigators also have noted increased postoperative blood VEGF levels during the first 8 days after surgical resection of colorectal, gastric, and breast cancers as well as after hip surgery [14,[19][20][21][22]. It is possible, although currently unproven, that increased plasma VEGF levels after surgery might encourage the growth of tumor micrometastases that persist after resection of the primary lesion.…”