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
ARTICLE HIGHLIGHTS
Research background

Patients with Hirschsprungs disease often suffer from persistent obstructive complaints after surgery. Improving faecal passage is important in these patients in order to prevent Hirsch-sprung-associated enterocolitis. Relaxation of the internal anal sphincter with botulinum toxin (BT) injections can be used to improve faecal passage.

Research motivation

BT injections are increasingly used to treat obstructive symptoms but an overview of the current evidence describing effectiveness of this treatment is lacking.

Research objectives

The objective of this study was to give a comprehensive overview of all evidence on effectiveness of intra-sphincteric BT injections to treat obstructive symptoms and enterocolitis in patients after surgery for Hirschsprungs disease, and to summarize evidence on its adverse effects.

Research methods

A systematic review and meta-analysis according to the PRISMA Guidelines was conducted, searching PubMed, EMBASE, Web of Science and Cochrane library using simple and hier-archical entry terms including “botulinum toxin injections” and “Hirschsprungs disease”. Predefined predictors of effectiveness that were analysed were age at injection, sex, associated syndromes, dosage and type of BT used.

Research results

Data of 14 studies representing 278 patients were analysed. BT injections were effective in treating obstructive symptoms in 66% of patients, ranging from 79% in the first month of follow-up to 46% in follow-up longer than month. This was regardless of age at injection, sex, associated syndromes, dosage and type of BT used. Enterocolitis incidence was reduced in 57%, but the meta-analysis lacked power to draw conclusions. Mild adverse effects were present in 17%, which mainly consisted of temporary faecal incontinence or anal pain.

Research conclusions

Our systematic review and meta-analysis shows that BT injections effectively treat obstructive symptoms in patients after surgery for Hirschsprungs disease, regardless of age at injection, sex, associated syndromes, dosage and type of BT used. Furthermore, the data suggests that BT injections are associated with mild adverse effects. Evidence on effectiveness of BT injections in treating enterocolitis is limited and lacked power to draw conclusions. Our findings show that BT injections are a useful treatment modality in clinical practice.

Research perspectives

Future studies should further elucidate what factors predict good response to BT injections and subsequently if we can predict which patients can and cannot benefit from BT injections.