Meta-Analysis
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2019; 25(25): 3268-3280
Published online Jul 7, 2019. doi: 10.3748/wjg.v25.i25.3268
Botulinum toxin injections after surgery for Hirschsprung disease: Systematic review and meta-analysis
Daniëlle Roorda, Zarah AM Abeln, Jaap Oosterlaan, Lodewijk WE van Heurn, Joep PM Derikx
Daniëlle Roorda, Zarah AM Abeln, Lodewijk WE van Heurn, Joep PM Derikx, 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
Jaap Oosterlaan, Department of Pediatrics, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Emma Neuroscience Group, Amsterdam Reproduction and Development, Amsterdam 1105 AZ, Netherlands
Lodewijk WE van Heurn, Joep PM Derikx, Department of Pediatric Surgery, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Gastroenterology and Metabolism, Amsterdam 1105 AZ, Netherlands
Author contributions: Roorda D, van Heurn LWE and Derikx JPM designed the research; Roorda D and Abeln ZAM performed the systematic review and data-extraction; Roorda D and Derikx JPM analysed the data; Roorda D, Abeln ZAM, Oosterlaan J, van Heurn LWE and Derikx JPM wrote and revised the paper.
Conflict-of-interest statement: All authors have no conflicts of interest to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Daniëlle Roorda, MD, BSc, MD, Research Associate, PhD Student, Department of Pediatric Surgery, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Reproduction and Development, Meibergdreef 9, Amsterdam 1105 AZ, Netherlands. d.roorda@amc.uva.nl
Telephone: +31-20-5665693 Fax: +31-20-5669683
Received: March 14, 2019
Peer-review started: March 14, 2019
First decision: April 11, 2019
Revised: May 5, 2019
Accepted: May 31, 2019
Article in press: June 1, 2019
Published online: July 7, 2019
Processing time: 115 Days and 16.3 Hours
Abstract
BACKGROUND

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.

AIM

To give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease.

METHODS

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.

RESULTS

Botulinum toxin injections are effective in treating obstructive symptoms in on average 66% of patients [event rate (ER) = 0.66, P = 0.004, I2 = 49.5, n = 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, vs ER = 0.46, Q = 19.37, P < 0.001). Botulinum toxin injections were not effective in treating enterocolitis (ER 0.58, P = 0.65, I2 = 71.0, n = 52 patients). There were adverse effects in on average 17% of patients (ER = 0.17, P < 0.001, I2 = 52.1, n = 187 patients), varying from temporary incontinence to mild anal pain.

CONCLUSION

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.

Keywords: Hirschsprung disease; Botulinum toxin; Internal anal sphincter; Obstructive symptoms; Enterocolitis; Adverse effects

Core tip: Patients with obstructive symptoms after surgery for Hirschsprung disease can benefit from intra-sphincteric botulinum toxin injections. This study indicates that Botulinum toxin injections are effective in treating obstructive symptoms after surgery for Hirschsprung disease and were associated with mild and temporary adverse effects. The proportion of patients that benefited from botulinum toxin injections was significantly higher within one month after administration (79%) compared to longer follow-up (46%). Beneficial effect was temporary and lasted on average 6 months, therefore requiring on average 2-3 injections per patient before satisfactory clinical improvement was achieved.