手术联合多种干预措施治疗耳部瘢痕疙瘩疗效的网状meta分析

EndNote教程 | 2019-01-10 04:42

手术联合多种干预措施治疗耳部瘢痕疙瘩疗效的网状meta分析

李晓庆 刘文军 段建兴 王欣 王迪 张高飞 魏亚婷

本文来源:《中华整形外科杂志》201年12期

DOI:10.3760/cma.j.issn.1009-4598.2018.12.006

作者单位:昆明医科大学第二附属医院烧伤科

通信作者:

【摘要】

目的 采用网状meta分析方法,以手术治疗耳部瘢痕疙瘩为共同参照,比较手术联合多种干预措施治疗耳部瘢痕疙瘩的有效性。

方法 以“(((((((((((Ear, External[MeSH Terms])) OR (Ears, Exernal)) OR (Outer Ear)) OR (Ear, Outer)) OR (Ears, Outer)) OR (External Ear))) AND (((keloid[Mesh Terms])) OR (keloids))) AND ((((((surgery[MeSH Terms])) OR (operative therapy)) OR (operative procedures)) OR (invasive procedures)) OR (operations)))) AND (randomized controlled trial [pt])”为检索词,检索“PubMed”、“Cochrane Library”数据库,以((‘external ear’/exp) OR(‘auricle’/exp) OR (‘ear lobe’/exp)) AND ((‘surgery’/exp) OR (‘ear surgery’/exp)) AND (‘keloid’/exp) AND (‘randomized controlled trial’/exp) 检索“Embase”数据库,以“耳瘢痕疙瘩,手术”为检索词检索“中国期刊全文数据库”、“中国生物医学文献数据库”、 “维普数据库”、“万方数据库”,检索自数据库建库以来至2018年 6月公开发表的有关手术联合多种干预措施治疗耳部瘢痕疙瘩的随机对照试验。结局指标为治疗的有效性。采用EndNote X7、Revman5.3、STATA14.0、GeMTC14.3统计软件进行文献筛选数据提取、文献质量评估、绘制网络图、发表偏倚分析、传统meta分析及异质性检验、一致性检验、相似性检验、网状meta分析。

结果 共纳入18篇文献,涉及8项治疗措施,共纳入1 425例耳部瘢痕疙瘩患者,纳入的18篇文献的偏倚风险均偏高。网络图显示8项治疗措施可形成28个不同的两两比较,其中纳入的18篇文献存在10个直接比较,剩余18个比较无直接证据,其比较将由网状meta分析间接比较产生。绘制漏斗图中各点基本对称,Beggs检验及Eggers检验P值均大于0.05,说明存在发表偏倚的可能性较小。传统meta分析显示手术+激素、手术+压力、手术+放疗和手术+激素+放疗的有效率均高于单纯手术,且差异具有统计学意义(P<0.05);手术+激素+放疗的有效率优于手术+激素,差异具有统计学意义(P=0.001);手术+激素+氟尿嘧啶及手术+激素+放疗的有效率均高于手术+放疗,差异均具有统计学意义(P<0.05),其余直接比较均不具有统计学意义。异质性检验结果中所有P值均大于0.1,I2均小于50%,故纳入研究不存在明显异质性。8项治疗措施直接共形成4个闭环,各个闭环的一致性均较好。纳入18篇文献相似性较好。网状meta分析结果显示:7种联合治疗方式与单纯手术相比疗效均有统计学意义(95%CI不含1),且均优于单纯手术治疗。7种联合治疗方式之间的比较,手术+激素+氟尿嘧啶的疗效优于手术+激素;手术+激素+放疗的疗效优于手术+激素;手术+激素+放疗的疗效优于手术+压力;手术+激素+放疗的疗效优于手术+放疗,均具有统计学意义(95%CI不含1)。其余联合治疗方式之间的疗效差异无统计学意义。根据网状meta分析结果绘制SUCRA曲线图, 各治疗措施的有效性排序及SUCRA值为:手术+激素+放疗(98.4%)>手术+激素+氟尿嘧啶(76.4%)>手术+咪喹莫特(53.3%)>手术+压力(52.2%)>手术+氟尿嘧啶(51.6%)>手术+放疗(34.6%)>手术+激素(33.0%)>手术(0.4%)。

结论 对于耳部瘢痕疙瘩的治疗,手术联合多种治疗方式疗效均优于单纯的手术治疗,其中手术+激素+放疗的疗效最佳。

【关键词】耳,瘢痕疙瘩;外科;meta分析

基金项目:国家卫生计生委公益性行业科研专项();国家自然科学基金(81660319)

Network meta analysis of the effectiveness of surgery combined with multiple interventions in treating patients with ear keloids

Li Xiaoqing, Liu Wenjun, Duan Jianxing, Wang Xin, Wang Di, Zhang Gaofei, Wei Yating.

Department of Burns, Second Affiliated Hospital of Kunming Medical University, Kunming, China

Corresponding author:

【Abstract】

Objective To evaluate the effectiveness of surgery combined with multiple interventions in treating patients with ear keloid by network meta-analysis.

Methods Databases including "PubMed", "Cochrane Library" were searched using key words "(((((((((((Ear, External[MeSH Terms]]] OR (Ears, Exernal]] OR (Outer Ear]] OR (Ear, Outer]] OR (Ears, Outer]] OR (External Ear]]] AND (((keloid[Mesh Terms]]] OR (keloids]]] AND ((((((surgery[MeSH Terms]]] OR (operative therapy]] OR (operative procedures]] OR (invasive procedures]] OR (operations]]]] AND (randomized controlled trial[pt]]", database "Embase" was searched using key words ((′external ear′/exp] OR(′auricle′/exp] OR (′ear lobe′/exp]] AND ((′surgery′/exp] OR (′ear surgery′/exp]] AND (′keloid′/exp] AND (′randomized controlled trial′/exp] and Chineses journals full-text database, China biology medicine disc, VIP database, and Wanfang database were searched using key words in chinese version "耳瘢痕疙瘩,手术" to obtain the randomized controlled trails about surgery combined with multiple interventions in the treatment of ear keloid from the establishment of each database to June 2018. EndNote X7, Revman 5.3, STATA 14.0, GeMTC 14.3 statistical software were used to extract data from studies, study quality assessment, drawing network figure, publication bias analysis, traditional meta-analysis, heterogeneity test, consistency test, similarity test, network meta-analysis.

Results A total of 18 trails involving 8 therapeutic measures were included, and 1 425 patients with ear keloid were included. All of the 18 trails had high risk of bias. The network figure shows that there are 28 different pairwise comparisons among the eight treatments. Of the 18 studies included, 10 were directly compared, and the remaining 18 were not directly evidenced, those comparisons will be made indirectly by the network meta-analysis. The basic symmetry of each point in the funnel plot and the P values of Beggs test and Eggers test were all greater than 0.05, shows that the existence of publication bias is less likely. Traditional meta-analysis showed that the efficiency of surgery + hormone, surgery + pressure, surgery + radiotherapy and surgery + hormone + radiotherapy were better than that of simple surgery, and the difference was statistically significant(P<0.05); the efficiency of surgery + hormone + radiotherapy was better than that of surgery + hormone, the difference was statistically significant(P=0.001); surgery + hormone + fluorouracil and surgery + hormone + radiotherapy had statistical significance(P<0.05). Efficiency is higher than surgery + radiotherapy, the difference is statistically significant. The rest of the direct comparisons are not statistically significant. All P values in the heterogeneity test were greater than 0.1 and I2 was less than 50%, so there was no significant heterogeneity in the study. 8 treatments formed 4 closed loops, the inconsistency factor IF ranged from 0.06 to 0.23, and the lower limit of 95% CI was 0, it means than the consistency of those loops were good. The similarity test of the 18 studies was good. Based on Bayesian theory, the random effect model of MCMC method was analyzed by network meta analysis. The results of 7 combined therapies were statistically significant compared with those of simple operation, and were superior to those of simple operation. The results of the seven combined therapies were statistically significant as follows: surgery + hormone + fluorouracil VS surgery + radiotherapy (OR = 0.28, 95% CI 0.08-0.93], surgery + hormone + fluorouracil was better than surgery + hormone; surgery + hormone + radiotherapy + VS surgery + hormone (OR = 0.06, 95% CI 0.01-0.23], surgery + hormone + radiotherapy Surgery + hormone + radiotherapy VS surgery + pressure (OR = 0.07, 95% CI 0.01-0.37], surgery + hormone + radiotherapy is better than surgery + pressure; surgery + hormone + radiotherapy VS surgery + radiotherapy (OR = 0.06, 95% CI 0.01-0.30], surgery + hormone + radiotherapy is better than surgery + radiotherapy. There was no significant difference in the curative effect between the other combined treatments. The SUCRA curves were drawn according to the randomized effect model of MCMC. The SUCRA values of each treatment measure were as follows: surgery, 0.4%; surgery + hormone, 33.0%; surgery + pressure, 52.2%; surgery + radiotherapy, 34.6%; surgery + imiquimod 53.3%; surgery + fluorouracil 51.6%; surgery + hormone + fluorouracil, 76.4%; surgery + hormone + radiotherapy, 34.6%; surgery + hormone + fluorouracil, 53.3%; surgery + hormone Radiotherapy, 98.4%. According to the results of SUCRA chart, the effectiveness of each treatment measure was sorted as follows: operation + hormone + radiotherapy > operation + hormone + fluorouracil > operation + imiquimod > operation + pressure > operation + fluorouracil > operation + radiotherapy > operation + hormone > operation.

Conclusions Surgery combined with a variety of treatments for ear keloid were superior to simple surgical treatment, of which surgery + hormone + radiotherapy is the best.

【Key words】Ear, keloids;Surgery;Meta analysis

Fund program:National Health and Family Planning Commission (); National Natural Science Foundation of China (81660319)

Disclosure of Conflicts of Interest: The authors have no financial interest to declare in relation to the content of this article.

耳部瘢痕疙瘩发病率较高,多继发于穿耳洞、烧伤、外伤等,主要是由于损伤后成纤维细胞大量增生,胶原蛋白大量沉积而导致。耳部的瘢痕疙瘩不仅影响患者耳部外形的美观,常常还伴有一定程度的疼痛和瘙痒症状。目前,对于耳部瘢痕的治疗以手术切除为主,但是单纯的手术治疗复发率较高。许多研究者采取手术联合多种干预措施对其进行治疗,但是对于不同联合方案的有效性尚无大规模的临床试验进行验证。网状meta 分析(network meta\|analysis)可以实现对3个或3个以上的干预措施同时进行比较,并能够提供最佳干预措施的概率[1]。本研究拟采用网状meta 分析的方法,纳入联合治疗耳部瘢痕疙瘩的随机对照试验,为耳部瘢痕疙瘩的联合治疗提供一定的参考依据。

资料与方法

一、 文献来源与检索

以“(((((((((((Ear, External[MeSH Terms])) OR (Ears, Exernal)) OR (Outer Ear)) OR (Ear, Outer)) OR (Ears, Outer)) OR (External Ear))) AND (((keloid[Mesh Terms])) OR (keloids))) AND ((((((surgery[MeSH Terms])) OR (operative therapy)) OR (operative procedures)) OR (invasive procedures)) OR (operations)))) AND (randomized controlled trial [pt])”为检索词,检索“PubMed”、“Cochrane Library”数据库、以((‘external ear’/exp) OR (‘auricle’/exp) OR (‘ear lobe’/exp)) AND ((‘surgery’/exp) OR (‘ear surgery’/exp)) AND (‘keloid’/exp) AND (‘randomized controlled trial’/exp) 检索“Embase”数据库,以“耳瘢痕疙瘩,手术”为检索词检索“中国期刊全文数据库”、“中国生物医学文献数据库”、“维普数据库”、“万方数据库”,文献发表时间为自数据库建库以来至2018年6月。检索策略遵循《Cochrane 系统评价员手册》。

文献纳入标准①研究对象(P):耳部瘢痕疙瘩患者,其诊断标准为耳部肿块质地坚硬,突出于皮肤表面,范围超过原损伤边缘,并向周围组织浸润,呈持续性生长状态,无自愈倾向[2]。患者种族、性别和受伤原因不受限制。②干预措施(I):手术治疗耳部瘢痕疙瘩。③结局指标(O):手术联合不同治疗方式治疗耳部瘢痕疙瘩的有效率,且文献有明确的有效性评价标准。④研究类型(S):纳入文献均为随机对照试验(randomized controlled trials,RCT),文中提及“randomized”和“随机”。

排除标准①重复发表的文献;②综述等二次研究文献;③会议文献、学位论文;④研究类型不符。

二、 文献筛选与数据提取

使用文献管理软件(EndNote X7, Thomson ResearchSoft,Stanford USA)合并所有相关文献并剔除重复文献,对剩余文献阅读标题和摘要进行初步筛选,仍然无法确定的文献获取全文进一步阅读后筛选。均由本文的第1作者和第2作者根据文献纳入与排除标准完成筛选和数据提取,如果意见不一致,则交由第3作者协助共同商议解决。文献资料提取内容包括:纳入研究的基本信息,包括第1作者、发表年份;研究对象的基本特征,包括患者的病例数、性别、年龄、干预措施;研究结果为治疗的总有效率。总有效率=(治愈人数+有效人数)/总人数×100%

三、 纳入文献质量评估

纳入的随机对照试验采用Cochrane系统评价指南510推荐的“偏倚风险评价工具”进行评估,内容包括以下7个方面:①随机分配的方法是否正确。②是否分配隐藏。③干预过程中是否使用盲法,使用是否正确。④结果测量过程中是否使用盲法,使用是否正确。⑤资料是否完整。⑥是否完整地报告了各个结局指标,有无选择性报告。⑦其他偏倚风险。

四、 统计学分析

您可以通过以下方式获得全文的内容

直接订阅:

2018年每期15元,共12期,全年180元。

2019年每期28元,共12期,全年336元。

邮局订阅:可在全国各地邮政局订购,邮发代号18-95

网上订阅:中华医学会杂志社菁医汇商城

微信订阅:直接扫描下方二维码(手机端长按识别进入),订阅全年各期或选择性订阅某期《中华整形外科杂志》