Deptartment of Anesthesiology, Centre for Cancer and Organ Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Deptartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Scand J Immunol. 2020 Sep;92(3):e12930. doi: 10.1111/sji.12930. Epub 2020 Jul 22.
Major surgery is associated with substantial morbidity and mortality with early post-operative adverse events (POAE) occurring in 30% of patients within the first 30 days. The underlying pathogenesis is multifactorial, including immune dysfunction and increased inflammatory response to surgery. We investigated preoperative immune function by the TruCulture® whole blood technique in a cohort of patients undergoing pancreaticoduodenectomy (PD), hypothesizing that patients developing inflammatory POAE defined as leucocytosis, fever or high (above median) area under the curve (AUC) C-reactive protein (CRP) the first post-operative week would display perturbed preoperative immune function. Sixty-two adult patients were screened, 30 included and 11 excluded post-inclusion due to other surgical procedures than PD and post-operative complications directly attributed to surgery, leaving 19 patients for analysis of preoperative immune function. Patients developing leucocytosis (n = 5, 26%) had lower Toll-like receptor (TLR)-3-stimulated IL-12p40 and higher Candida Albicans (TLR1/2/4/6, Dectin-1)-stimulated TNF-α, compared to patients without leucocytosis (all P < .05). Patients developing fever (n = 7, 37%) had lower TLR7/8-stimulated IFN-γ and patients with high AUC CRP (n = 9, 47%) had lower TLR3-stimulated IFN-γ and IL-6 and lower TLR7/8-stimulated IL-10 (all P < .05), compared to patients without fever or low CRP, respectively. In conclusion, patients with inflammatory POAE displayed lower preoperative stimulated IL-12p40, IFN-γ, IL-6 and IL-10 and higher TNF-α response, compared to patients without inflammatory POAE. This finding suggests that TruCulture is a feasible immunologic screening tool in surgical patients, with a potential for preoperative identification of patients at increased risk for inflammatory POAE, allowing for risk-based intervention trials.
大手术与大量发病率和死亡率相关，术后早期不良事件（POAE）在术后 30 天内发生在 30%的患者中。潜在的发病机制是多因素的，包括免疫功能障碍和对手术的炎症反应增加。我们通过 TruCulture®全血技术调查了胰腺十二指肠切除术（PD）患者的术前免疫功能，假设在术后第一周白细胞增多、发热或高（高于中位数）C 反应蛋白（CRP）曲线下面积（AUC）的患者会出现炎症性 POAE，他们的术前免疫功能会受到干扰。对 62 名成年患者进行了筛选，纳入 30 名患者，11 名患者因 PD 以外的其他手术程序和直接归因于手术的术后并发症而被排除在外，因此有 19 名患者用于分析术前免疫功能。发生白细胞增多（n=5，26%）的患者，与没有白细胞增多的患者相比，Toll 样受体（TLR）-3 刺激的白细胞介素-12p40 水平较低，而白色念珠菌（TLR1/2/4/6、Dectin-1）刺激的肿瘤坏死因子-α水平较高（均 P<.05）。发生发热（n=7，37%）的患者，TLR7/8 刺激的干扰素-γ水平较低，而 CRP AUC 较高（n=9，47%）的患者，TLR3 刺激的干扰素-γ、白细胞介素-6 和白细胞介素-10 水平较低（均 P<.05），与没有发热或 CRP 较低的患者相比。总之，与没有炎症性 POAE 的患者相比，发生炎症性 POAE 的患者的术前刺激白细胞介素-12p40、干扰素-γ、白细胞介素-6 和白细胞介素-10 水平较低，而肿瘤坏死因子-α水平较高。这一发现表明，TruCulture 是一种可行的手术患者免疫筛选工具，具有术前识别炎症性 POAE 风险增加患者的潜力，从而可以进行基于风险的干预试验。
