Division of Surgical Oncology, Department of Cancer Anaesthesia, Perioperative and Pain Medicine, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia.
Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
Clin Exp Metastasis. 2018 Apr;35(4):347-358. doi: 10.1007/s10585-017-9862-x. Epub 2017 Sep 11.
Cancer, currently the leading cause of death in the population aged less than 85 years, poses a significant global disease burden and is anticipated to continue to increase in incidence in both developed and developing nations. A substantial proportion of cancers are amenable to surgery, with more than 60% of patients undergoing tumour resection. Up to 80% of patients will receive anaesthesia for diagnostic, therapeutic or palliative intervention. Alarmingly, retrospective studies have implicated surgical stress in disease progression that is predominantly characterised by metastatic disease-the primary cause of cancer-associated mortality. Our understanding of the mechanisms of surgical stress and impact of perioperative interventions is, however, far from complete. Accumulating evidence from preclinical studies suggests that adrenergic-inflammatory pathways may contribute to cancer progression. Importantly, these pathways are amenable to modulation by adapting surgical (e.g. minimally invasive surgery) and anaesthetic technique (e.g. general vs. neuraxial anaesthesia). Disturbingly, drugs used for general anaesthesia (e.g. inhalational vs. intravenous anaesthesia and potentially opioid analgesia) may also affect behaviour of tumour cells and immune cells, suggesting that choice of anaesthetic agent may also be linked to adverse long-term cancer outcomes. Critically, current clinical practice guidelines on the use of anaesthetic techniques, anaesthetic agents and perioperative adjuvants (e.g. anti-inflammatory drugs) during cancer surgery do not take into account their potential effect on cancer outcomes due to a lack of robust prospective data. To help address this gap, we provide an up-to-date review of current clinical evidence supporting or refuting the role of perioperative stress, anaesthetic techniques and anaesthetic agents in cancer progression and review pre-clinical studies that provide insights into biological mechanisms.
癌症是目前 85 岁以下人群的主要死亡原因，对全球疾病负担构成了重大威胁，预计在发达国家和发展中国家的发病率都将继续上升。相当一部分癌症可以通过手术治疗，超过 60%的患者接受肿瘤切除术。多达 80%的患者将接受麻醉以进行诊断、治疗或姑息干预。令人震惊的是，回顾性研究表明手术应激与疾病进展有关，主要表现为转移性疾病——这是癌症相关死亡的主要原因。然而，我们对手术应激的机制和围手术期干预的影响的理解还远远不够。越来越多的临床前研究证据表明，肾上腺素能-炎症途径可能与癌症进展有关。重要的是，这些途径可以通过调整手术（例如微创手术）和麻醉技术（例如全身麻醉与椎管内麻醉）来调节。令人不安的是，用于全身麻醉的药物（例如吸入性麻醉与静脉性麻醉和潜在的阿片类镇痛药）也可能影响肿瘤细胞和免疫细胞的行为，这表明麻醉药物的选择也可能与不良的长期癌症结局有关。关键的是，目前关于癌症手术中使用麻醉技术、麻醉药物和围手术期辅助药物（例如抗炎药物）的临床实践指南并没有考虑到它们对癌症结局的潜在影响，因为缺乏强有力的前瞻性数据。为了帮助解决这一差距，我们提供了一份关于围手术期应激、麻醉技术和麻醉药物在癌症进展中的作用的最新临床证据综述，并回顾了提供生物学机制见解的临床前研究。
