围手术期使用非甾体抗炎药可降低结直肠切除术后癌症复发的风险：一项基于前瞻性数据的队列研究。

Perioperative Use of Nonsteroidal Anti-inflammatory Drugs Decreases the Risk of Recurrence of Cancer After Colorectal Resection: A Cohort Study Based on Prospective Data.

机构信息

Department of Surgery, Center for Surgical Science (CSS), Enhanced Perioperative Oncology Consortium, Zealand University Hospital and University of Copenhagen, Copenhagen, Denmark.

Department of Surgery, Center for Robotics and Minimally Invasive Surgery, Copenhagen University Hospital Herlev, Copenhagen, Denmark.

出版信息

Ann Surg Oncol. 2019 Nov;26(12):3826-3837. doi: 10.1245/s10434-019-07600-8. Epub 2019 Jul 16.

DOI:10.1245/s10434-019-07600-8

PMID:31313040

Abstract

BACKGROUND

Perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to reduce inflammatory response in relation to surgery. Inflammation may promote recurrence of cancer, thus inhibition by use of NSAIDs could reduce recurrence after surgery.

OBJECTIVE

The aim of this study was to examine the association between perioperative use of NSAIDs and cancer recurrence, as well as disease-free survival (DFS) and mortality after colorectal cancer surgery.

METHODS

This was a cohort study based on data from a prospective clinical database, electronic medical records, and nationwide registers, and included patients from six major colorectal centers in Denmark. The primary outcome was cancer recurrence, while secondary outcomes included 5-year mortality and DFS.

RESULTS

Overall, 2308 patients undergoing colorectal cancer surgery between 1 January 2006 and 31 December 2009 were included. A total of 909 patients received at least 2 days of treatment with NSAIDs, of whom 702 (77.2%) received ibuprofen and 204 (22.4%) received diclofenac. Cox regression analysis adjusting for NSAIDs resulted in decreased recurrence risk (adjusted hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.72-0.99; p = 0.042). Competing risk analysis confirmed the finding, with an HR of 0.76 (95% CI 0.60-0.97; p = 0.026). There was no significant effect on mortality or DFS. Sensitivity analysis of the effect of ibuprofen reported an HR of 0.83 (95% CI 0.70-1.00; p = 0.047). In restricted analyses of localized disease only (Union for International Cancer Control [UICC] I-II) and elective surgery only, no effect was found (localized: HR 0.81, 95% CI 0.62-1.06, p = 0.12; elective: HR 0.85, 95% CI 0.72-1.01, p = 0.063).

CONCLUSIONS

Perioperative use of NSAIDs was associated with a reduced risk of cancer recurrence after resection for colorectal cancer. No effect on 5-year mortality or DFS was found.

摘要

背景

围手术期使用非甾体抗炎药（NSAIDs）可降低与手术相关的炎症反应。炎症可能会促进癌症复发，因此使用 NSAIDs 抑制炎症可能会降低手术后的复发率。

目的

本研究旨在探讨围手术期使用 NSAIDs 与结直肠癌手术后癌症复发、无病生存率（DFS）和死亡率之间的关系。

方法

这是一项基于前瞻性临床数据库、电子病历和全国登记处的数据的队列研究，纳入了丹麦六个主要结直肠中心的患者。主要结局是癌症复发，次要结局包括 5 年死亡率和 DFS。

结果

共有 2308 例 2006 年 1 月 1 日至 2009 年 12 月 31 日期间接受结直肠癌手术的患者纳入研究。共有 909 例患者接受了至少 2 天的 NSAIDs 治疗，其中 702 例（77.2%）接受了布洛芬治疗，204 例（22.4%）接受了双氯芬酸治疗。调整 NSAIDs 后，Cox 回归分析显示复发风险降低（调整后的危险比 [HR]0.84，95%置信区间 [CI]0.72-0.99；p=0.042）。竞争风险分析证实了这一发现，HR 为 0.76（95% CI 0.60-0.97；p=0.026）。对死亡率或 DFS 无显著影响。对布洛芬影响的敏感性分析报告 HR 为 0.83（95% CI 0.70-1.00；p=0.047）。仅在局部疾病（国际抗癌联盟 [UICC]I-II 期）和选择性手术中进行的受限分析中未发现效果（局部疾病：HR 0.81，95% CI 0.62-1.06，p=0.12；选择性手术：HR 0.85，95% CI 0.72-1.01，p=0.063）。