title: Exploiting the critical perioperative period to improve long-term cancer outcomes.
abstract: Evidence suggests that the perioperative period and the excision of the primary tumour can promote the development of metastases—the main cause of cancer-related mortality. This Review first presents the assertion that the perioperative timeframe is pivotal in determining long-term cancer outcomes, disproportionally to its short duration (days to weeks). We then analyse the various aspects of surgery, and their consequent paracrine and neuroendocrine responses, which could facilitate the metastatic process by directly affecting malignant tissues, and/or through indirect pathways, such as immunological perturbations. We address the influences of surgery-related anxiety and stress, nutritional status, anaesthetics and analgesics, hypothermia, blood transfusion, tissue damage, and levels of sex hormones, and point at some as probable deleterious factors. Through understanding these processes and reviewing empirical evidence, we provide suggestions for potential new perioperative approaches and interventions aimed at attenuating deleterious processes and ultimately improving treatment outcomes. Specifically, we highlight excess perioperative release of catecholamines and prostaglandins as key deleterious mediators of surgery, and we recommend blockade of these responses during the perioperative period, as well as other low-risk, low-cost interventions. The measures described in this Review could transform the perioperative timeframe from a prominent facilitator of metastatic progression, to a window of opportunity for arresting and/or eliminating residual disease, potentially improving long-term survival rates in patients with cancer.
authors.affiliation: School of Psychological Sciences, Sharet Building, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Horowitz
authors.affiliation: School of Psychological Sciences, Sharet Building, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Neeman
authors.affiliation: Department of Surgery, Rabin Medical Center, Beilinson Hospital, Petach-Tikva 49100, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Sharon
authors.affiliation: School of Psychological Sciences, Sharet Building, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Shamgar
authors.initials: S
authors.lastname: Ben-Eliyahu
mesh_terms: D006801:Humans; D007108:Immune Tolerance; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology / Q000503:physiopathology / Q000601:surgery*; D009752:Nutritional Status; D019990:Perioperative Care / Q000379:methods*; D059035:Perioperative Period; D011379:Prognosis; D012008:Recurrence; D013312:Stress, Physiological; D013315:Stress, Psychological; D016896:Treatment Outcome