Hiller Jonathan G, Sampurno Shienny, Millen Rosemary, Kuruvilla Niketh, Ho Kwok M, Ramsay Rob, Riedel Bernhard
Division of Surgical Oncology, Department of Cancer Anaesthesia, Perioperative and Pain Medicine, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne, 3000, VIC, Australia.
Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia.
Can J Anaesth. 2017 May;64(5):497-505. doi: 10.1007/s12630-017-0818-z. Epub 2017 Jan 13.
During cancer surgery, prostaglandin-mediated inflammation may promote and activate micrometastatic disease with a consequent increase in long-term cancer recurrence. Cyclooxygenase-2 inhibitors, known to have anti-proliferative properties, may offset such perioperative perturbation. We investigated the effectiveness of these agents to minimize inflammatory changes during cancer surgery.
Following ethics approval, 32 patients who were to undergo major intracavity cancer surgery were enrolled in this prospective, randomized, clinical trial. The treatment group received 400 mg celecoxib preoperatively followed by five 200 mg 12-hourly doses. The control group received no anti-inflammatory agents. Inflammatory and immunomodulatory end points were measured serially. The primary end points were the measured plasma and urinary prostaglandin E metabolite (PGE) levels 48 hours following surgery. Secondary endpoints included interleukin levels, leucocyte profile, and clinical end points.
No differences in the 48-hr plasma or urinary PGE levels were observed between the celecoxib and control groups. Linear mixed modeling, used to accommodate differences in baseline PGE levels, showed that celecoxib (cf. control) administration lowered plasma PGE over the entire 48-hr period following surgery (β-coefficient = -0.38 pg.ml; 95% confidence interval: -0.69 to -0.06; P = 0.021). Celecoxib administration also lowered postoperative pain scores.
Standard dosing of the cyclooxygenase-2 inhibitor celecoxib slightly reduced perioperative cyclooxygenase activity during cancer surgery. Given cyclooxygenase's role in cancer pathways, we recommend dose-finding studies be undertaken before prospective clinical trials are conducted testing the currently unsubstantiated hypothesis that perioperative anti-inflammatory administration improves long-term cancer outcomes. This trial was registered at: Australian New Zealand Clinical Trial Registry: ACTRN12615000041550; www.anzctr.org.au.
在癌症手术期间，前列腺素介导的炎症可能会促进并激活微转移病灶，从而导致长期癌症复发率增加。已知具有抗增殖特性的环氧合酶-2抑制剂可能会抵消这种围手术期的干扰。我们研究了这些药物在癌症手术期间将炎症变化降至最低的有效性。
在获得伦理批准后，32例即将接受大型腔内癌症手术的患者被纳入这项前瞻性、随机临床试验。治疗组在术前服用400毫克塞来昔布，随后每12小时服用5次200毫克剂量。对照组未接受抗炎药物治疗。连续测量炎症和免疫调节终点指标。主要终点指标是术后48小时测量的血浆和尿液中前列腺素E代谢物（PGE）水平。次要终点指标包括白细胞介素水平、白细胞谱和临床终点指标。
塞来昔布组和对照组在术后48小时的血浆或尿液PGE水平上没有差异。用于适应基线PGE水平差异的线性混合模型显示，服用塞来昔布（与对照组相比）在术后整个48小时期间降低了血浆PGE水平（β系数=-0.38 pg/ml；95%置信区间：-0.69至-0.06；P=0.021）。服用塞来昔布还降低了术后疼痛评分。
环氧合酶-2抑制剂塞来昔布的标准剂量在癌症手术期间略微降低了围手术期环氧合酶活性。鉴于环氧合酶在癌症途径中的作用，我们建议在进行前瞻性临床试验之前进行剂量探索研究，以检验目前未经证实的假设，即围手术期抗炎给药可改善长期癌症结局。该试验已在澳大利亚新西兰临床试验注册中心注册：ACTRN12615000041550；www.anzctr.org.au。
