Giakomidi Despina, Bird Mark F, Lambert David G
Department of Cardiovascular Sciences (Anaesthesia, Critical Care and Pain Management), University of Leicester, Hodgkin Building, Leicester, UK.
BJA Open. 2022 May 11;2:100010. doi: 10.1016/j.bjao.2022.100010. eCollection 2022 Jun.
There is a controversial narrative in the anaesthetic literature suggesting that anaesthetic technique (including opioids) may be detrimental to survival after tumour resection. The initial observations were retrospective. Several prospective studies are ongoing; one in breast cancer has reported no adverse outcome. The evidence for an effect of opioids stems from three pieces of information: (1) opioids depress the immune system, (2) opioids potentially promote angiogenesis, and (3) opioids potentially support tumour growth. Although the evidence for (2)/(3) is unclear, combinations of these effects are beneficial to tumours and potentially promote metastatic reseeding. Accepted wisdom suggests that opioid effects are driven by opioid receptor activation but the presence of opioid receptors on immune cells for example is unlikely. Immune cells, vascular endothelium and a range of tumour cells express Toll-like receptor 4 (TLR4) receptors (for Gram-negative bacterial wall components), and there is growing evidence for opioids interacting with this alternative receptor; and for some there is paradoxical naloxone sensitivity. Is the focus on opioid receptors and cancer the wrong target? TLR4 receptor activation produces immune activation, stimulates angiogenesis, and supports tumour survival. We know that some opioids are more immune suppressive than others (there is no such comparative information for angiogenesis and tumour survival); this may correlate with TLR4 activation. If there are clusters of opioids that have more opioid than TLR4 profiles and , this may influence outcome. If this is the case, then evidence-based advice could be given for perioperative use in the oncology-anaesthesia setting.
麻醉学文献中存在一种有争议的说法，即麻醉技术（包括阿片类药物）可能对肿瘤切除后的生存有害。最初的观察是回顾性的。几项前瞻性研究正在进行；其中一项针对乳腺癌的研究报告没有不良结果。阿片类药物产生影响的证据来自三条信息：（1）阿片类药物会抑制免疫系统，（2）阿片类药物可能促进血管生成，（3）阿片类药物可能支持肿瘤生长。尽管（2）/（3）的证据尚不清楚，但这些作用的组合对肿瘤有益，并可能促进转移再植。公认的观点认为阿片类药物的作用是由阿片受体激活驱动的，但例如免疫细胞上存在阿片受体的可能性不大。免疫细胞、血管内皮细胞和一系列肿瘤细胞表达Toll样受体4（TLR4）受体（针对革兰氏阴性菌细胞壁成分），越来越多的证据表明阿片类药物与这种替代受体相互作用；而且对一些人来说存在矛盾的纳洛酮敏感性。将重点放在阿片受体和癌症上是不是错误的目标？TLR4受体激活会产生免疫激活、刺激血管生成并支持肿瘤存活。我们知道一些阿片类药物比其他药物更具免疫抑制作用（关于血管生成和肿瘤存活没有此类比较信息）；这可能与TLR4激活有关。如果存在阿片类药物簇，其阿片作用比TLR4作用更明显，这可能会影响结果。如果是这样，那么就可以在肿瘤麻醉环境中给出围手术期使用的循证建议。
