围术期高血糖与食管切除术后食管鳞癌不良预后相关性

Perioperative hyperglycemia predicts poorer prognosis of esophageal squamous cell carcinoma patients treated with esophagectomy

摘要

目的：基于大样本、多中心真实世界数据，系统评估围术期高血糖与食管鳞癌（esophageal squamous cell carcinoma，ESCC）患者术后预后之间的关联。方法：连续纳入河南省安阳市肿瘤医院（2012年1月至2017年12月）与广东省汕头大学医学院附属肿瘤医院（2009年8月至2018年12月）接受根治性食管切除术的 5952 例ESCC 患者的病例资料进行回顾性队列研究，围术期空腹血糖数据来源于医院信息系统。将围术期划分为术前和术后两个阶段，术前高血糖定义为术前第14天至第2天平均空腹血糖 ⩾7.0mmol/L ，术后高血糖定义为术后第2天至第14天平均空腹血糖 ⩾7.0mmol/L 。主要结局为总生存期，次要结局包括术后 30 d/90 d 死亡率及住院期间并发症。采用多因素 Cox 比例风险模型，评估围术期高血糖与总生存的关联，计算校正后的风险比（hazard ratio，HR）及其95％置信区间（confidence interval，CI）。结果：研究人群最长随访时间达12年。术前与术后高血糖发生率分别为 6.7% 和 18.3% 。术前高血糖患者的 5 年总生存率低于非高血糖患者（57.3% vs. 65.0%），校正后 HR 为1.41 （95%CI:1.19∼1.68）；术后高血糖患者的 5 年生存率亦较低（61.8% vs. 66.4%），校正后 HR 为 1.39 （95% CI:1.22∼1.58）。联合分析显示，与无高血糖者相比，仅在术前或术后单一阶段出现高血糖的患者死亡风险升高（HR=1.24,95\%CI:1.07∼1.43），而术前和术后均存在高血糖的患者死亡风险最高（$H R=1.86,95 % C I: 1.49 \sim$2.32）。分层分析显示，体重指数（body mass index，BMI）显著修饰了高血糖与不良预后的关联（交互作用 P= 0.010) ,  该关联在 BMI⩾24.0 kg/m² 的患者中尤为显著。此外，围术期高血糖亦与较差的术后短期结局相关。结论：围术期高血糖是接受根治性食管切除术的 ESCC 患者术后长期生存的独立危险因素，提示在 ESCC 围术期管理过程中加强常规血糖监测与控制，可能有助于改善患者的长期预后。

Abstract

Objective：To systematically evaluate the association between perioperative hyperglycemia and postoperative prognosis in esophageal squamous cell carcinoma（ESCC）patients using large-scale， multicenter real-world data. Methods：A total of 5952 patients with ESCC who underwent radical esophagectomy were consecutively included in this retrospective cohort study from the Anyang Cancer Hospital in Anyang，Henan Province（January 2012 to December 2017）and the Cancer Hospital of Shantou University Medical College in Shantou，Guangdong Province（August 2009 to December 2018）. Perioperative fasting glucose data were obtained from the hospital information system.The perioperative period was divided into preoperative and postoperative phases：Preoperative hyperglycemia was defined as a mean fasting glucose level ⩾7.0mmol/L from day 14 to day 2 before surgery，and postoperative hyper- glycemia was defined as a mean fasting glucose level ⩾7.0mmol/L from day 2 to day 14 after surgery. The primary outcome was overall survival（OS），and secondary outcomes included 30 d/90 d postopera- tive mortality and in-hospital complications.Multivariable Cox proportional hazards models were used to assess the association between perioperative hyperglycemia and OS，with adjusted hazard ratios（HR）and 95％confidence intervals（CI）calculated. Results：The maximum follow-up period was 12 years.The prevalence of preoperative and postoperative hyperglycemia was 6.7% and 18.3% ，respectively. Patients with preoperative hyperglycemia had a lower 5-year OS rate than those without（57.3％vs. 65.0%），with an adjusted HR of 1.41(95%CI:1.19-1.68).The patients with postoperative hyper- glycemia also had reduced 5-year survival（61.8％vs.66.4％），with an adjusted HR of 1.39 （95％CI： 1.22-1.58）.Joint analysis showed that compared with patients without hyperglycemia，those with hy- perglycemia in either the preoperative or postoperative phase alone had an elevated mortality risk（HR= 1.24,95\%CI:1.07-1.43），while the patients with hyperglycemia in both phases had the highest mor- tality risk $(\mathit{H}\mathit{R}=\mathrm{1.86,95}\mathrm{\%}\mathit{C}\mathit{I}:1.49-2.32)$.Stratified analysis revealed that BMI significantly modi- fied the association between hyperglycemia and adverse prognosis (P_interaction =0.010) ，with the associa- tion being particularly pronounced in patients with BMI ⩾24.0 kg/m².Additionally，perioperative hy- perglycemia was associated with poorer short-term postoperative outcomes. Conclusion：Perioperative hy- perglycemia is an independent risk factor for long-term survival in ESCC patients undergoing curative esophagectomy.These findings suggest that enhanced routine glucose monitoring and control during perioperative management of ESCC may help improve long-term patient outcomes.

关键词

围术期高血糖 / 糖尿病 / 预后 / 并发症 / 食管鳞癌

Key words

Perioperative hyperglycemia / Diabetes / Prognosis / Complications / Esophageal squamous cell carcinoma

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基金资助

国家重点研发计划项目资助(2021YFC2500405)