Horowitz Maya, Neeman Elad, Sharon Eran, Ben-Eliyahu Shamgar
School of Psychological Sciences, Sharet Building, Tel Aviv University, Tel Aviv 6997801, Israel.
Department of Surgery, Rabin Medical Center, Beilinson Hospital, Petach-Tikva 49100, Israel.
Nat Rev Clin Oncol. 2015 Apr;12(4):213-26. doi: 10.1038/nrclinonc.2014.224. Epub 2015 Jan 20.
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.
有证据表明，围手术期和原发性肿瘤的切除可促进转移灶的形成，而转移是癌症相关死亡的主要原因。本综述首先提出这样一种观点，即围手术期在决定癌症长期预后方面起着关键作用，其时间跨度虽短（数天至数周），却有着不成比例的重要性。然后，我们分析手术的各个方面及其随之产生的旁分泌和神经内分泌反应，这些反应可能通过直接影响恶性组织和/或通过间接途径（如免疫紊乱）来促进转移过程。我们探讨手术相关焦虑和压力、营养状况、麻醉剂和镇痛药、体温过低、输血、组织损伤以及性激素水平的影响，并指出其中一些可能是有害因素。通过了解这些过程并回顾实证证据，我们为潜在的新围手术期方法和干预措施提供建议，旨在减轻有害过程并最终改善治疗结果。具体而言，我们强调围手术期儿茶酚胺和前列腺素的过度释放是手术的关键有害介质，并建议在围手术期阻断这些反应以及其他低风险、低成本的干预措施。本综述中描述的措施可能会将围手术期从转移进展的主要促进因素转变为阻止和/或消除残留疾病的机会窗口，有可能提高癌症患者的长期生存率。
