Effect of Anesthetic Technique on Serum Vascular Endothelial Growth Factor C and Transforming Growth Factor β in Women Undergoing Anesthesia and Surgery for Breast Cancer

Abstract

Background:In breast cancer, vascular endothelial growth factor C, transforming growth factor ␤, placental growth factor, and fibroblast growth factor (acidic and basic) promote angiogenesis and metastases. We tested the hypothesis that a propofol-paravertebral anesthetic (PPA) technique would attenuate postoperative changes in these angiogenic factors to a greater extent than balanced general anesthesia (GA) and morphine analgesia in women undergoing surgery for primary breast cancer. Method: Forty women with primary breast cancer undergoing surgical excision were randomized to receive either standard GA or PPA technique. Venous blood was sampled before and at 24 h after surgery and serum analyzed. The primary endpoint was a preoperative versus postoperative change in vascular endothelial growth factor C and transforming growth factor ␤ concentrations. Results: Using a visual analog scale (median [25-75% interquartile range]), PPA patients (1 [0 -2]) had less pain at 2 h (P ϭ 0.02) than did GA patients (3 [2-5]). The mean postoperative change in vascular endothelial growth factor C concentrations among GA patients was 733 versus 27 pg/ml for PPA patients (difference, 706 [97.5% CI,130] pg/ml, P ϭ 0.001). In contrast, the mean postoperative change in transforming growth factor ␤ concentration among GA patients was Ϫ163 versus 146 pg/ml for PPA patients (difference, 309 [97.5% CI, Ϫ474 to Ϫ143] pg/ml, P ϭ 0.005). Concentrations of placental growth factor and fibroblast growth factor, both acidic and basic, were undetectable in serum. Conclusion:Anesthetic technique influences serum concentrations of factors associated with angiogenesis in primary breast cancer surgery. BREAST cancer remains a leading cause of death among women and is second only to lung cancer as a cause of cancer mortality in western countries, most of which is attributable to recurrence and metastasis. Breast cancer also accounts for more new cases of cancer among women than any other cancer.1 Initial treatment almost invariably involves surgical excision. However, tumor recurrence occurs in a significant number of patients. Even when the most experienced operator performs surgical resection, it is unavoidable that tumor cells are dispersed into the blood and lymphatic circulations. 2 The fate of this small burden of tumor cells depends on the balance between antimetastatic factors and the ability of the tumor to invade, propagate, and metastasize.3

Morphine and tumor growth and metastasis

“…RAA was confirmed to inhibit the surgical stress response, as indicated by lower plasma glucose, cortisol, and C-reactive protein in RAA patients compared to general anesthesia/morphine analgesia-but RAA did not seem to affect the postoperative percent change in pro-angiogenic factors VEGF and prostaglandin E2 [93]. In contrast, regional anesthesia/analgesia decreased circulating TGF-β and IL-1β and attenuated the postoperative increase in lymphangiogenic VEGF-C and in pro-invasion, pro-metastatic, and pro-angiogenic MMP-9 [94,95]. Lastly, in an ex vivo experiment, the serum from general anesthesia/morphine analgesia patients was shown to promote cancer cell proliferation without affecting cancer cell migration when compared to the serum of patients undergoing RAA [96].…”

Perioperative Interventions During Cancer Surgery: Can Anesthetic and Analgesic Techniques Influence Outcome?

“…The results showed a mean post-operative change in VEGF concentrations among GA patients of 733 versus 27 pg/ml for paravertebral and TIVA patients [difference, 706 (97.5 % CI 280-1130) pg/ml, P = 0.001]. In contrast, the mean post-operative change in transforming growth factor b concentration among GA patients was -163 versus 146 pg/ml for paravertebral and TIVA patients [difference 309 (97.5 % CI -474 to -143) pg/ml, P = 0.005] [17]. Both VEGF and transforming growth factor b are important for the proliferation of tumor cells and angiogenesis.…”

Can Regional Anesthesia and Analgesia Prolong Cancer Survival After Orthopaedic Oncologic Surgery?

“…In another series of clinical studies, the authors randomized patients with breast cancer undergoing mastectomy to general anesthesia with sevoflurane-opioid versus propofol-paravertebral block. They found that the serum of those patients who received propofol-paravertebral block inhibited in vitro breast cancer cell proliferation but not migration and had better control of stress response markers, metalloproteinases, and transforming growth factor b but higher levels of vascular endothelial growth factor C [9,10,26,31].…”