PPI联合瑞巴派特促进内镜黏膜下剥离术术后溃疡愈合的疗效分析

The efficacy and safety of PPI plus Rebamipide for endoscopic submucosal dissection-induced ulcers: a Meta-analysis

目的系统评价质子泵抑制剂（proton pump inhibitors,PPI）联合瑞巴派特治疗内镜黏膜下剥离术（endoscopic submucosal dissection,ESD）术后溃疡的有效性和安全性。方法计算机检索Pub Med、Web of Science、Medline、Embase、Cochrane Central Register of Controlled Trials、CENTRAL、CJFD、CBM、CNKI、VIP及Wan Fang Data,检索时间截至2015年8月1日,查找所有比较PPI联合瑞巴派特预防ESD术后溃疡出血作用的随机对照试验（RCTs）。由2名评价者按照纳入和排除标准独立选择文献、提取资料、评价质量,采用Rev Man 5.2和Stata 12.0软件进行Meta分析。结果共纳入6项RCTs,共724例患者。合并结果显示：与单用PPI相比,应用PPI联合瑞巴派特后溃疡愈合率明显升高（OR=2.40,95%CI：1.68~3.44）;根据疗程长短（4周和8周）进行亚组分析显示：联合用药组溃疡愈合率均高于单用PPI组（4周：OR=2.22,95%CI：1.53~3.24;8周：OR=3.19,95%CI：1.22~8.31）。对于直径〉2 cm溃疡,联合用药组疗效更明显（OR=4.77,95%CI：2.22~10.26）。而对于溃疡部位、是否合并H.pylori感染,两者疗效无明显差异。用药过程中两组均无明显不良反应。结论 PPI联合瑞巴派特疗效优于单用PPI,尤其对于直径〉2 cm的溃疡。受纳入研究数量和质量限制,需要开展更多高质量、大样本、多中心的RCTs进一步论证其安全性。

Objective To compare the efficacy and safety of proton pump inhibitors（ PPI） plus Rebamipide and PPI alone for the healing of ulcer after endoscopic submucosal dissection（ ESD）. Methods Pub Med,Web of Science,Medline,Embase,Cochrane Central Register of Controlled Trials,CENTRAL,CJFD,CBM,CNKI,VIP and Wan Fang Data were researched up to the end of Aug. 2015 to identify all randomized controlled trials（ RCTs） that reported the effect of PPI plus Rebamipide for the healing of ulcer after ESD. Outcome measures were ulcer healing. Results Six studies involving 724 patients were included. Pooled data suggested a significantly higher ulcer healing rate after endoscopic therapies in PPI plus Rebamipide group than that in the PPI alone group（ OR = 2. 40,95% CI： 1. 68- 3. 44）.Subgroup analysis showed PPI plus Rebamipide was more effective in the healing of ESD-induced ulcer than PPI in both4-week（ OR = 2. 22,95% CI： 1. 53- 3. 24） and 8-week duration of medication（ OR = 3. 19,95% CI： 1. 22-8. 31）. The combination therapy was significantly more effective than the PPI alone for every size of ESD ulcer larger than 2 cm（ OR = 4. 77,95% CI： 2. 22- 10. 26）. There was no significantly difference in ulcer location（ low,middle,or upper stomach） and H. pylori infection or not between combination therapy and PPI alone groups. No serious adverse events occurred in the two groups. Conclusion PPI plus Rebamipide is superior to PPI alone for the healing of ulcer after ESD,especially for large-sized ulcers. However,more well-designed trials are needed to confirm the findings.