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

BackgroundVascular 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.MethodsEighty 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.ResultsAlthough 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.ConclusionIn 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 registrationChictr.org.cn ChiCTR1800017910. Retrospectively Registered (Date of registration: August 20, 2018).

Anesthetic technique and cancer outcomes: a meta-analysis of total intravenous versus volatile anesthesia

“…Patients receiving a propofol infusion only, or a propofol and remifentanil infusion during their surgery were categorized into the TIVA group; patients receiving sevoflurane, isoflurane, desflurane or enflurane were categorized into the volatile group. All studies except Yan et al 19 adjusted for at least one of the following variables in their multivariate analyses: age, body mass index, comorbidities, preoperative therapy, pathologic stage or grade of cancer, and intraoperative anesthetic interventions such as epidural or blood transfusion. [12][13][14][15][16][17][18]20,21…”

“…The pooled results from this meta-analysis suggest that TIVA use (compared with volatile anesthesia) during cancer surgery is associated with improved recurrence-free survival and overall survival across numerous cancer types. Breast cancer was the most often examined tumour type with five studies reporting on outcomes after breast cancer surgery 12,14,15,19,20 ; in this population, TIVA use was associated with an improvement in recurrence-free survival but not overall survival.…”

“…[12][13][14][15][16][17][18]20,21 The single prospective RCT included in this meta-analysis had a low risk of bias for each domain. 19…”

“…Six studies (five retrospective [13][14][15][16]20 and one RCT) 19 examined the effects of TIVA and volatile agents on recurrence-free survival in breast, esophageal, and nonsmall cell lung cancer (Fig. 2).…”

“…Eight studies (seven retrospective 12,13,[16][17][18]20,21 and one RCT), 19 that included a total of 18,778 patients, provided ten HRs for this analysis (Fig. 3) in breast, colorectal, gastric, esophageal, and non-small cell lung cancer, and mixed cancer types.…”