Botulinum toxin injections after surgery for Hirschsprung disease: Systematic review and meta-analysis

Table 1 Study characteristics of included studies

Study	Study design	Inclusion period	Sample size, n	Male (%)	Syndromal patients (%)	Total follow-up in months	Number of BT injections needed per patient	Age at first BT injection (yr)	Type BT	Mean dose (IU/injection)	Guidance at BT injection	Definition of outcomes	Improvement in obstructive symptoms < 1 mo	Prolonged improvement in obstructive symtpoms	Improvement of enterocolitis	Complications/adverse effects	Decrease in mean resting pressure on anorectal manometry (mmHG)
Basson (2014)	Retrospective	2010-2014	11	67	NR	12-72	1pt: 1BTI5pt: 2BTI4pt: 3BTI1pt: 4BTI	5	Dysport	200	Palpation	Successful-Improvement-FailedFavorable: successful/improvement	10/11 (91%)	5/11 (45%)	NR	1 (transient soiling)	NR
Chumpitazi (2008)	Retrospective	1998-2007	30	80	10	41.2 ± 4.9	2.7 ± 0.2	5	Botox	NR	Palpation	Poor-Fair-Good-Excellent Favorable: Excellent/good	27/30 (90%)	11/30 (37%)	NR	8 (7 transients soiling, 1 anal pain)	NR
Chumpitazi (2011)	Retrospective	1998-2016	37	80	23	41.4 ± 4.5	2.8 ± 0.3	NR	Botox	100	NR	Poor-Fair-Good-Excellent Favorable: Excellent/good	33/37 (90%)	NA	NR	NR	NR
Church (2016)	Retrospective	2010-2015	30	NR	NR	20	87% in total:With US: 2Without US: 1	3.1	NR	40	US-guided	Improvement of symptoms	NA	NR	3/4 (75%)	NR	NR
Han-Geurts (2014)	Retrospective	2002-2013	33	79	0	7.3 yr (1-24)	2 (1-5)	3.6	Dysport	200	NR	Poor-Fair-Good-Excellent Favorable: Excellent/good	25/33 (76%)	17/33 (52%)	7/19 (37%)	2	NR
Hemanshoo Thakkar (2017)	Retrospective	2002-2014	6	NR	NR	6 yr (1-12)		3	Dysport	200	US-guided	Short-term: postoperative complications < 30 dLong-term: Rintala Bowel Function Score (BFS)	1/6 (17%)	NR	NR	NR	NR
Hosseini (2008)	Prospective	2002-2006	16	62	NR		8 pt: 1-3	NR	Dysport	NR	NR	Improvement in Constipation score (good/recurrence/non-responders)	14/16 (88%)	8/16 (50%)	NR	NR	NR
Jiang (2009)	Prospective	2000-2008	23	65	NR	12		NR	Botox	120	Palpation	Poor-Moderate-Excellent Favorable: Moderate/Excellent	NR	21/23 (91%)	NR	9 (anal pain)	8-30
Koisuvalo (2009)	Retrospective	2005-2008	16 *	62	12.5	19 (3-43)	2 (1-4)	4	NR	100	NR	No effect-Little effect-Significant effect-Symptoms dissapearedFavorable: Significant effect/symptoms dissapeared	10/16 (63%)	3/8 (38%)	1/4 (25%)	4 (increased soiling)	28-31 (2 w); 8-24 (8 m)
Langer (1997)	Prospective	NR	4	50	25		3 pt: 1, 1 pt 2	6	Botox	NR	Palpation	Improvement of obstructive symptoms, presence of incontinence	3/4 (75%)	1/4 (25%)	NR	1 (transient incontinence)	NR
Langer (2004)	Retrospective	NR	14	NR	NR	24	4 pt: 1, 9pt: 1-4	4	NR	150	NR	Improvement of obstructive symptoms, presence of incontinence	9/14 (64%)	4/14 (29%)	NR	NR	NR
Minkes (2000)	Prospective	NR	18	78	NR		8: 1; 10: 2-6	NR	Botox	60	Palpation	No response-Significant response	12/18 (67%)	5/18 (28%)	NR	4 (transient incontinence)	35-37
Patrus (2010)	Retrospective	1998-2008	22	78	5	5.0 ± 2.9 yr (0-10)	2 (1-23)	8.4	NR	120	NR	Improvement of obstructive symptoms, presence of incontinence	18/22 (81%)	6/22 (27%)	NR	0	NR
Wester (2015)	Retrospective	2007-2014	18	83	33	3, 8 yr (0, 1-8, 3)	3 (1-13)	2.4	Botox	100	Palpation	Good-Insufficient	NR	13/18 (72%)	NR	NR	NR

NR: Not reported; BT: Botulinum toxin.