Effects of propofol/remifentanil-based total intravenous anesthesia versus sevoflurane-based inhalational anesthesia on the release of VEGF-C and TGF-β and prognosis after breast cancer surgery: a prospective, randomized and controlled study

Abstract

Background: Vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) have been involved in tumor growth and metastasis. Sevoflurane may promote angiogenesis, whereas propofol can present an anti-angiogenic effect. In this study, we compared the effects of propofol/remifentanil-based total intravenous anesthesia (TIVA) and sevoflurane-based inhalational anesthesia on the release of VEGF-C and TGF-β, as well as recurrence- free survival (RFS) rates in the patients undergoing breast cancer surgery.

Methods: Eighty female patients undergoing breast cancer resection were enrolled and randomized to receive either sevoflurane-based inhalational anesthesia (SEV group) or propofol/remifentanil-based TIVA (TIVA group). The serum concentrations of VEGF-C and TGF-β before and 24 h after surgery were measured and RFS rates over a two-year follow-up were analyzed in both groups. The postoperative pain scores assessed using a visual analogue scale (VAS) and the use of perioperative opioids were also evaluated.

Results: Although VAS scores at 2 h and 24 h after surgery were comparable between the two groups, there were more patients receiving postoperative fentanyl in the TIVA group (16[40%]) compared with the SEV group (6[15%], p = 0.023). VEGF-C serum concentrations increased after surgery from 105 (87-193) pg/ml to174 (111-281) pg/ml in the SEV group (P = 0.009), but remained almost unchanged in the TIVA group with 134 (80-205) pg/ml vs.140(92-250) pg/ml(P = 0.402). The preoperative to postoperative change for VEGF-C of the SEV group (50 pg/ml) was significantly higher than that of the TIVA group (12 pg/ml) with a difference of 46 (- 11-113) pg/ml (P = 0.008). There were also no significant differences in the preoperative and postoperative TGF-β concentrations between the two groups. The two-year RFS rates were 78% and 95% in the SEV and TIVA groups (P = 0.221), respectively.

Conclusion: In comparison with sevoflurane-based inhalational anesthesia, propofol/remifentanil -based total intravenous anesthesia can effectively inhibit the release of VEGF-C induced by breast surgery, but didn't seem to be beneficial in the short-term recurrence rate of breast cancer.

Trial registration: Chictr.org.cn ChiCTR1800017910 . Retrospectively Registered (Date of registration: August 20, 2018).

Keywords: Angiogenesis; Breast cancer; Propofol; Sevoflurane; Total intravenous anesthesia.

Fig. 1

CONSORT flow diagram of participants allocation. SEV sevoflurane, TIVA total intravenous anesthesia, MRM modified radical mastectomy, BCS breast conserving surgery

Fig. 2

Median preoperative and postoperative VEGF-C concentrations in both groups. *P = 0.009,higher postoperative values versus preoperative values in the SEV group. SEV-pre preoperative values in the SEV group, SEV-post postoperative values in the SEV group, TIVA-pre preoperative values in the SEV group, TIVA-post postoperative values in the TIVA group. Horizontal line denotes median values, box borders refer to interquartile range, whiskers indicate range of values

Fig. 3

Median preoperative to postoperative changes of TGF-β concentrations of the patients with early stage cancer in both groups. There were13 and 14 patients with early stage cancer in the SEV and TIVA groups, respectively. SEV-pre preoperative values in the SEV group, SEV-post postoperative values in the SEV group, TIVA-pre preoperative values in the SEV group, TIVA-post postoperative values in the TIVA group. Horizontal line denotes median values, box borders refer to interquartile range, whiskers indicate range of values.

Fig. 4

Kaplan-Meier recurrence-free survival estimated for 80 patients in both groups. Univariate analysis by log-rank test (P = 0.221)