Oines Mari Nanna, Krarup Peter-Martin, Jorgensen Lars Nannestad, Agren Magnus Sven
Mari Nanna Øines, Peter-Martin Krarup, Lars Nannestad Jorgensen, Magnus Sven Ågren, Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark.
World J Gastroenterol. 2014 Sep 21;20(35):12637-48. doi: 10.3748/wjg.v20.i35.12637.
To identify pharmaceuticals for the prophylaxis of anastomotic leakage (AL), we systematically reviewed studies on anastomosis repair after colorectal surgery.
We searched PubMed and EMBASE for articles published between January 1975 and December 2012. We included studies in English with the primary purpose of promoting healing of anastomoses made in the colon or rectum under uncomplicated conditions. We excluded studies on adverse events from interventions, nutritional interventions or in situ physical supporting biomaterials. The primary outcome was biomechanical strength or AL. We performed meta-analyses on therapeutic agents investigated by three or more independent research groups using the same outcome. The DerSimonian-Laird method for random effects was applied with P < 0.05.
Of the 56 different therapeutic agents assessed, 7 met our inclusion criteria for the meta-analysis. The prostacyclin analog iloprost increased the weighted mean of the early bursting pressure of colonic anastomoses in male rats by 60 mmHg (95%CI: 30-89) vs the controls, and the immunosuppressant tacrolimus increased this value by 29 mmHg (95%CI: 4-53) vs the controls. Erythropoietin showed an enhancement of bursting pressure by 45 mmHg (95%CI: 14-76). The anabolic compound growth hormone augmented the anastomotic strength by 21 mmHg (95%CI: 7-35), possibly via the up-regulation of insulin-like growth factor-1, as this growth factor increased the bursting pressure by 61 mmHg (95%CI: 43-79) via increased collagen deposition. Hyperbaric oxygen therapy increased the bursting pressure by 24 mmHg (95%CI: 13-34). Broad-spectrum matrix metalloproteinase inhibitors increased the bursting pressure by 48 mmHg (95%CI: 31-66) on postoperative days 3-4. In the only human study, the AL incidence was not significantly reduced in the 103 colorectal patients treated with aprotinin (11.7%) compared with the 113 placebo-treated patients (9.7%).
This systematic review identified only one randomized clinical trial and seven therapeutic agents from pre-clinical models that could be explored further for the prophylaxis of AL after colorectal surgery.
为确定预防吻合口漏（AL）的药物，我们系统回顾了关于结直肠手术后吻合口修复的研究。
我们检索了1975年1月至2012年12月期间发表在PubMed和EMBASE上的文章。我们纳入了以促进在无并发症情况下结肠或直肠吻合口愈合为主要目的的英文研究。我们排除了关于干预措施不良事件、营养干预或原位物理支持生物材料的研究。主要结局是生物力学强度或吻合口漏。我们对由三个或更多独立研究组使用相同结局研究的治疗药物进行了荟萃分析。采用DerSimonian-Laird随机效应方法，P<0.05。
在评估的56种不同治疗药物中，7种符合我们荟萃分析的纳入标准。与对照组相比，前列环素类似物伊洛前列素使雄性大鼠结肠吻合口早期破裂压力的加权平均值增加了60 mmHg（95%CI：30-89），免疫抑制剂他克莫司使该值增加了29 mmHg（95%CI：4-53）。促红细胞生成素使破裂压力提高了45 mmHg（95%CI：14-76）。合成代谢化合物生长激素使吻合口强度提高了21 mmHg（95%CI：7-35），可能是通过上调胰岛素样生长因子-1，因为该生长因子通过增加胶原蛋白沉积使破裂压力提高了61 mmHg（95%CI：43-79）。高压氧治疗使破裂压力提高了24 mmHg（95%CI：13-34）。广谱基质金属蛋白酶抑制剂在术后第3-4天使破裂压力提高了48 mmHg（95%CI：31-66）。在唯一一项人体研究中，与113例接受安慰剂治疗的患者（9.7%）相比，103例接受抑肽酶治疗的结直肠患者的吻合口漏发生率未显著降低（11.7%）。
本系统评价仅确定了一项随机临床试验和七种来自临床前模型的治疗药物，可进一步探索其预防结直肠手术后吻合口漏的作用。
