Recurrence is a major concern for oncologic patients. However, a solution has not yet been found to this problem. There is cumulative evidence that anesthesia and analgesia techniques may influence outcomes after cancer surgery. This effect is mediated by induced changes in the immune system and by other mechanisms including the mitigation of surgical stress response.
A prospective study was conducted in patients with infiltrating bladder cancer, who underwent radical cystectomy and received combined anesthesia with propofol as hypnotic and a local anesthetic for analgesia. A comparison was performed of disease-free survival (in days) associated with combined anesthesia versus opioid-based analgesia.
A range of retrospective studies have been published on the influence of the anesthetic technique and cancer outcomes.4-8 A relationship has been suggested between anesthesia and impaired anti-tumor immune cell function as it is the case of NK cells, lymphocytes, and macrophages. The use of opioids and the stimulation of the mu opioid (mu) receptor have been associated with an increased risk for recurrence, as these agents reduce cellular and humoral immunity.9,10
Regional anesthesia seems to improve anti-tumor immunity through lower use of volatile anesthetics and opioids, the reduction of a surgical stress response, and an anti-inflammatory effect mediated by a direct local anesthetic. The anesthetic agent with the strongest association with cancer outcomes is non-muscle invasive bladder cancer (NMIBC), with regional anesthesia being associated with lower recurrence rates and higher disease-free survival.11,12
Pain management with local anesthetics instead of opioids has also been associated with an anti-tumor effect. The use of neuraxial anesthesia stimulates NK function and hinders tumor dissemination. The mechanism by which local anesthetics and neuraxial anesthesia reduce the risk for recurrence and increase disease-free survival may be a reduction of surgical stress response, a lower use of opioids, and its effect on endogenous endorphins.
Pain suppresses NK cell activity. Adequate management of postoperative pain has been documented to preserve the anti-tumor activity of NK cells in animals. Pain activates the hypothalamic-pituitary-adrenal axis (HPA) and activates the sympathetic nerve system, thereby favoring immunosuppression via beta-adrenergic receptors. The sympathetic system blockade attenuates surgery-induced immunosuppression. Therefore, spinal anesthesia preserves NK and TH1 / TH2 cell function.13
As to hypnotics, volatile anesthetics seem to favor mechanisms such as mitogenesis and angiogenesis, which favors the development of metastasis and tumors.15 Isoflurane has been suggested to stimulate tumor proliferation and oncologic angiogenesis, as compared to propofol as a hypnotic. One of the mechanisms by which halogenated agents exert protective effects is the increase in hypoxia-inducible factors (HIFs), which stimulates tumor dissemination.16
Written by: Aida Raigon-Ponferrada, MD, Institute of Biomedical Research in Malaga [IBIMA], Malaga, Spain and Department of Anaesthesiology, Virgen de la Victoria University Hospital, Malaga, Spain; Alfredo Malo Manso, MD, Institute of Biomedical Research in Malaga [IBIMA], Malaga, Spain and Department of Anaesthesiology, Virgen de la Victoria University Hospital, Malaga, Spain; Jose Luis Guerrero Orriach, MD, Institute of Biomedical Research in Malaga [IBIMA], Malaga, Spain and Department of Anaesthesiology, Virgen de la Victoria University Hospital, Malaga, Spain, Department of Pharmacology and Pediatrics, School of Medicine, University of Malaga, Malaga, Spain, Member of COST Action 15204
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