Effects Of Propofol And Isoflurane On Perioperative Tumor Immune Function In Patients With Breast Cancer Undergoing Elective Radical Mastectomy

Objective: Breast cancer is the most common malignancy in women. Surgery isof paramount importance in the management of solid tumors such as breast cancer,but the immunosuppression induced by surgery and anesthesia during theperioperative period may cause immune escape of the tumor cells and even metastaticrecurrences. Although studies have shown that some anesthetics have regulatoryeffects on the immune system, there were few clinical researches concerning theinfluences of various anesthetic techniques on the cellular immune function in cancerpatients. Therefore, the aim of this prospective study was to investigate the impact ofdifferent anesthetic techniques based on propofol and/or isoflurane on theperioperative level of cytokines IL-17A, IFN-γ, IL-10and regulatory T cells inpatients with invasive breast cancer undergoing surgery.Methods: Twenty seven ASA I~II patients aged35~75yr, TNM I~II with aweigh index<30kg/m2undergoing elective radical mastectomy for invasive breastcancer were prospectively randomized into three groups: Group-Ppf, Group-Iso andGroup-PI, with nine cases in each group respectively. Routine monitoring includednoninvasive arterial blood pressure, ECG, SpO2and Nacrotrend index. For patients inGroup-Ppf and Group-PI, anesthesia was induced with intravenous midazolam4g/kg,fentanyl2g/kg, propofol1.5~2mg/kg, cisatracurium besylate0.15mg/kg, and forthose in Group-Iso, the induction agents were the same as in the the Group-Ppf and Group-PI except that etomidate0.3mg/kg was used instead of propofol. Afterintubation, the lungs were mechanically ventilated with settings aimed at achievingnormocapnia. Anesthesia was maintained with3~4g/ml propofol in TCI modethough infusion pumps in Group-Ppf, and with1.5%~2%isoflurane in Group-Iso. Asfor Group-PI,1%~1.5%isoflurane combined with background infusion of propofol at1g/ml in TCI mode was used for maintenance of anesthesia. During surgery, theconcentration of propofol and isoflurane were adjusted according to the Nacrotrendindex. Fentanyl50~100g and cisatracurium besylate3~4mg were givenintermittently to maintain hemodynamic stability and neuromuscular blockade. On theday of surgery (D0), and the first (D1) and seventh day (D7) after the operation, bloodsamples were collected. The CD4+CD25+Foxp3+regulatory T cells were evaluated byflow cytometry and reported as a percentage of total CD4+cells. The plasmaconcentration of IL-17A、IFN-γ and IL-10were determined by the technique ofcytometric bead array.Results: In all three groups, the percentage of CD4+CD25+Foxp3+regulatory Tcells and the plasma concentration of IFN-γ did not change significantly at differenttime points (p>0.05). Compared with D0, the concentration of IL-17A in patients inGroup-Ppf was decreased significantly at D1(p<0.001). Comparison among thegroups showed that, at D1, the concentration of IL-17A in Group-Ppf is significantlylower than that in Group-Iso and Group-PI (p=0.002), but no significant differenceswere observed regarding the level of IL-17A among three groups at D7(p>0.05). Theplasma concentration of IL-10in Group-Iso increased markedly at D1(p=0.01), ascompared with the baseline level. Among three groups, the concentration of IL-10issignificantly higher in Group-Iso than that in Group-Ppf (p=0.016) and Group-PI(p=0.043) at D1. Till D7, the level of IL-10in patients in Group-PI and Group-Isowas still notably higher than that in Group-Ppf (p=0.027). As for the ratio of IFN-γ/IL-10, a obvious decrease was observed in Group-Iso at D1as compared withD0(p=0.007). At D1, the IFN-γ/IL-10ratio decreased more significantly in Group-Isothan that in Group-Ppf (p=0.024), and at D7, this ratio remains markedly lower inGroup-Iso when compared to Group-Ppf (p=0.007).Conclusion:1. Different anesthetic techniques based on propofol and/orisoflurane have no obvious effects on the percentage of circulating CD4+CD25+Foxp3+regulatory T cells in patients undergoing elective radical mastectomy forinvasive breast cancer.2. Anesthetics could change the secretion pattern of several cytokines. Comparedwith isoflurane, propofol may contribute to the inhibition of IL-17A production, acytokine who has pro-tumorigenic characteristics. Propofol may also inhibit theexcessive expression of IL-10, and shift the Th1/Th2balance toward Th1. Theseeffects of propofol may therefore be immunoprotective for cancer patients and mayindirectly reduce the incidence of metastasis.