Department of Pediatric Surgery, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Reproduction and Development, Amsterdam 1105 AZ, Netherlands.
Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Emma Neuroscience Group, Amsterdam Reproduction and Development, Amsterdam 1105 AZ, Netherlands.
World J Gastroenterol. 2019 Jul 7;25(25):3268-3280. doi: 10.3748/wjg.v25.i25.3268.
A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery. Persistent obstructive symptoms may result in faecal stasis that can develop into Hirschsprung-associated enterocolitis, a potential life-threatening condition. Important treatment to improve faecal passage is internal anal sphincter relaxation using botulinum toxin injections.
To give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease.
A systematic review and meta-analysis was done by searching PubMed, EMBASE and the Cochrane Library, using entry terms related to: (1) Hirschsprung disease; and (2) Botulinum toxin injections. 14 studies representing 278 patients met eligibility criteria. Data that were extracted were proportion of patients with improvement of obstructive symptoms or less enterocolitis after injection, proportion of patients with adverse effects and data on type botulinum toxin, mean dose, average age at first injection and patients with associated syndromes. Random-effects meta-analysis was used to aggregate effects and random-effects meta-regression was used to test for possible confounding factors.
Botulinum toxin injections are effective in treating obstructive symptoms in on average 66% of patients [event rate (ER) = 0.66, = 0.004, = 49.5, = 278 patients]. Type of botulinum toxin, average dose, average age at first injections and proportion of patients with associated syndromes were not predictive for this effect. Mean 7 duration of improvement after one botulinum toxin injections was 6.4 mo and patients needed on average 2.6 procedures. There was a significant higher response rate within one month after botulinum toxin injections compared to more than one month after Botulinum toxin injections (ER = 0.79, ER = 0.46, Q = 19.37, < 0.001). Botulinum toxin injections were not effective in treating enterocolitis (ER 0.58, = 0.65, = 71.0, = 52 patients). There were adverse effects in on average 17% of patients (ER = 0.17, < 0.001, = 52.1, = 187 patients), varying from temporary incontinence to mild anal pain.
Findings from this systematic review and meta-analysis indicate that botulinum toxin injections are effective in treating obstructive symptoms and that adverse effects were present, but mild and temporary.
很大一部分先天性巨结肠症患者在矫正手术后仍存在持续性梗阻症状。持续性梗阻症状可能导致粪便淤滞，进而发展为先天性巨结肠相关性结肠炎，这是一种潜在的危及生命的疾病。改善粪便通过的重要治疗方法是使用肉毒杆菌毒素注射来放松内括约肌。
概述肉毒杆菌毒素注射治疗先天性巨结肠症患者的所有经验证据。
通过检索 PubMed、EMBASE 和 Cochrane 图书馆，使用与以下内容相关的条目进行了系统评价和荟萃分析：（1）先天性巨结肠症；和（2）肉毒杆菌毒素注射。14 项研究代表了 278 名符合条件的患者。提取的数据包括注射后梗阻症状改善或结肠炎减轻的患者比例、不良反应患者比例以及肉毒杆菌毒素类型、平均剂量、首次注射时的平均年龄和伴有综合征的患者的数据。使用随机效应荟萃分析汇总效应，使用随机效应荟萃回归检验可能的混杂因素。
肉毒杆菌毒素注射在平均 66%的患者中有效治疗梗阻症状[事件发生率（ER）=0.66， = 0.004， = 49.5， = 278 名患者]。肉毒杆菌毒素类型、平均剂量、首次注射时的平均年龄和伴有综合征的患者比例对这种效果没有预测性。单次肉毒杆菌毒素注射后平均 7 个月的持续改善时间，患者平均需要 2.6 次治疗。与肉毒杆菌毒素注射后一个月以上相比，肉毒杆菌毒素注射后一个月内的反应率显著更高（ER=0.79，ER=0.46，Q=19.37， < 0.001）。肉毒杆菌毒素注射在治疗结肠炎方面无效（ER=0.58， = 0.65， = 71.0， = 52 名患者）。平均有 17%的患者出现不良反应（ER=0.17， < 0.001， = 52.1， = 187 名患者），从暂时失禁到轻度肛门疼痛不等，不良反应均为轻度且暂时的。
本系统评价和荟萃分析的结果表明，肉毒杆菌毒素注射治疗梗阻症状有效，且不良反应存在，但为轻度且暂时。
