The Prevalence and Clinical Impact of Transition Zone Anastomosis in Hirschsprung Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Hirschsprung disease (HD) is characterized by absent neuronal innervation of the distal colonic bowel wall and is surgically treated by removing the affected bowel segment via pull-through surgery (PT). Incomplete removal of the affected segment is called transition zone anastomosis (TZA). The current systematic review aims to provide a comprehensive overview of the prevalence and clinical impact of TZA. METHODS: Pubmed, Embase, Cinahl, and Web of Sciences were searched (last search: October 2020), and studies describing histopathological examination for TZA in patients with HD were included. Data were synthesized into aggregated Event Rates (ER) of TZA using random-effects meta-analysis. The clinical impact was defined in terms of obstructive defecation problems, enterocolitis, soiling, incontinence, and the need for additional surgical procedures. The quality of studies was assessed using the Newcastle-Ottawa Scale. KEY RESULTS: This systematic review included 34 studies, representing 2207 patients. After excluding series composed of only patients undergoing redo PT, the prevalence was 9% (ER = 0.09, 95% CI = 0.05-0.14, p < 0.001, I2 = 86%). TZA occurred more often after operation techniques other than Duhamel (X2 = 19.21, p = <0.001). Patients with TZA often had obstructive defecation problems (62%), enterocolitis (38%), soiling (28%), and fecal incontinence (24%) in follow-up periods ranging from 6 months to 13 years. Patients with TZA more often had persistent obstructive symptoms (X2 = 7.26, p = 0.007). CONCLUSIONS AND INFERENCES: TZA is associated with obstructive defecation problems and redo PT and is thus necessary to prevent.

Did Age at Surgery Influence Outcome in Patients With Hirschsprung Disease? A Nationwide Cohort Study in the Netherlands.

OBJECTIVES: Hirschsprung disease (HD) requires surgical resection of affected bowel, but the current evidence is inconclusive regarding the optimal age for resection. The aim of this study was to assess whether age at resection of the aganglionic segment is a determinant for surgical outcomes. METHODS: A cross-sectional cohort study was done including all consecutive patients with HD between 1957 and 2015, aged 8 years or older (n = 830), who were treated in 1 of the 6 pediatric surgical centers in the Netherlands. Outcome measures were mortality, postoperative complications, stoma rate and redo surgery rate, retrieved from the medical records. Additionally, constipation and fecal incontinence rate in long term were assessed with the Defecation and Continence Questionnaire (DeFeC and P-DeFeC). RESULTS: The medical records of 830 patients were reviewed, and 346 of the 619 eligible patients responded to the follow-up questionnaires (56%). There was a small increase in the risk of a permanent stoma [odds ratio (OR) 1.01 (95% confidence interval {CI}: 1.00-1.02); P = 0.019] and a temporary stoma [OR 1.01 (95% CI: 1.00-1.01); P = 0.022] with increasing age at surgery, regardless of the length of the aganglionic segment and operation technique. Both adjusted and unadjusted for operation technique, length of disease, and temporary stoma, age at surgery was not associated with the probability and the severity of constipation and fecal incontinence in long term. CONCLUSIONS: In this study, we found no evidence that the age at surgery influences surgical outcomes, thus no optimal timing for surgery for HD could be determined.

Generic and disease-specific health-related quality of life in patients with Hirschsprung disease: A systematic review and meta-analysis.

BACKGROUND: Patients with Hirschsprung disease (HD) are at risk of persistent constipation, fecal incontinence or recurrent enterocolitis after surgical treatment, which in turn may impact physical and psychosocial functioning. Generic health-related quality of life (HRQoL) and disease-specific health-related quality of life are relevant outcome measures to assess the impact of HD on the QoL of these patients. AIM: To summarize all available evidence on HRQoL of patients with HD after surgery and the impact of possible moderating factors. METHODS: Pubmed, Web of Sciences, PsycInfo and Embase were searched with search terms related to 'Hirschsprung disease', 'Pediatrics' and 'Quality of life'. Mean and standard deviation of generic HRQoL overall and domain scores were extracted from each study, as well as data describing potential factors associated with QoL. Random effect models were used for meta-analytic aggregation of generic HRQoL scores. Meta-regression was used to assess the relationship between patient and clinical characteristics and generic HRQoL. Disease-specific HRQoL outcomes of patients with HD were systematically reviewed. RESULTS: Seventeen articles were included in the systematic review (n = 1137 patients) and 15 in the quantitative meta-analysis (n = 1024 patients). Four studies reported disease-specific HRQoL. Patient's age ranged between 0 and 21 years. Meta-analytic aggregation showed a non-significantly impaired generic HRQoL (d = -0.168 [95%CI: -0.481; 0.145], P = 0.293, I 2 = 94.9) in patients with HD compared to healthy controls. Physical (d = -0.042 [95%CI: -0.419; 0.335], P = 0.829, I 2 = 95.1), psychosocial (d = -0.159 [95%CI: -0.458; 0.141], P = 0.299, I 2 = 93.6) and social HRQoL (d = -0.092 [95%CI: -0.642; 0.457], P = 0.742, I² = 92.3) were also not significantly lower compared to healthy controls. There was no relation between health-related outcomes and the sex of the patients and whether generic HRQoL was measured by parental proxy or self-report. Disease-specific complaints of patients with HD impaired physical HRQoL, but not psychosocial and social HRQoL. CONCLUSION: In this systematic review and meta-analysis, no evidence was found for impaired generic HRQoL in patients with HD compared to healthy controls, neither for moderating effects of sex, parental proxy or self-report.

Implementing structured follow-up of neonatal and paediatric patients: an evaluation of three university hospital case studies using the functional resonance analysis method.

BACKGROUND: In complex critical neonatal and paediatric clinical practice, little is known about long-term patient outcomes and what follow-up care is most valuable for patients. Emma Children's Hospital, Amsterdam UMC (Netherlands), implemented a follow-up programme called Follow Me for neonatal and paediatric patient groups, to gain more insight into long-term outcomes and to use such outcomes to implement a learning cycle for clinical practice, improve follow-up care and facilitate research. Three departments initiated re-engineering and change processes. Each introduced multidisciplinary approaches to long-term follow-up, including regular standardised check-ups for defined age groups, based on medical indicators, developmental progress, and psychosocial outcomes in patients and their families. This research evaluates the implementation of the three follow-up programmes, comparing predefined procedures (work-as-imagined) with how the programmes were implemented in practice (work-as-done). METHODS: This study was conducted in 2019-2020 in the outpatient settings of the neonatal intensive care, paediatric intensive care and paediatric surgery departments of Emma Children's Hospital. It focused on the organisational structure of the follow-up care. The functional resonance analysis method (FRAM) was applied, using documentary analysis, semi-structured interviews, observations and feedback sessions. RESULTS: One work-as-imagined model and four work-as-done models were described. The results showed vast data collection on medical, developmental and psychosocial indicators in all work-as-done models; however, process indicators for programme effectiveness and performance were missing. In practice there was a diverse allocation of roles and responsibilities and their interrelations to create a multidisciplinary team; there was no one-size-fits-all across the different departments. Although control and feedback loops for long-term outcomes were specified with respect to the follow-up groups within the programmes, they were found to overlap and misalign with other internal and external long-term outcome monitoring practices. CONCLUSION: Implementing structured long-term follow-up may provide insights for improving daily practice and follow-up care, with the precondition of standardised measurements. Lessons learned from practice are (1) to address fragmentation in data collection and storage, (2) to incorporate the diverse ways to create a multidisciplinary team in practice, and (3) to include timely actionable indicators on programme effectiveness and performance, alongside medical, developmental and psychosocial indicators.

Risk factors for short-term complications graded by Clavien-Dindo after transanal endorectal pull-through in patients with Hirschsprung disease.

BACKGROUND: Transanal endorectal pull-through (TERPT) is a common surgical procedure in Hirschsprung disease (HD). Aim of this study was to gain insight in the prevalence and severity of postoperative complications within 30-days after TERPT and to identify patient and perioperative characteristics, associated with the development of short-term postoperative complications. METHODS: This study retrospectively analyzed data of children with HD and treated with TERPT in our center between 2005 and 2020. Complications emerging within 30-days after surgery were assessed using Clavien-Dindo (CD). Patient and perioperative characteristic as predictor of a complication were tested using (multivariable) logistic regression analysis. RESULTS: Twenty-two of 106 (21%) included patients (17 transanal only; 77 laparoscopic-assisted; 12 laparotomy-assisted) developed 35 complications, including two patients (1.8%) that deceased. We suspect postoperative rectal irrigation leading to perforation as cause of death in both patients. Six patients (6%) had a minor (CD<3) and 16 patients (15%) a major (CD≥3) complication. Anastomotic leakage (n = 4, 11%), abdominal abscess (n = 3, 9%) and anastomotic stricture (n = 3,9%) occurred most frequently. Predictive factors for developing a complication were older age at time of surgery (OR 1.03 1.00-1.01, p = 0.041), laparotomy-assisted surgery (OR 12.65, CI 1.712-93.07, p = 0.013) and long-segment HD (OR 4.09 CI 1.09-15.39, p = 0.037). CONCLUSIONS: We found a CD-graded short-term postoperative complication rate of 21% following TERPT, reporting anastomotic complications most frequently. In patients at risk a diverting stoma should be considered. We suspect postoperative rectal irrigation being the cause of two lethal perforations. Therefore, we recommend to place a rectal transanastomotic tube in all patients receiving TERPT. LEVEL OF EVIDENCE: Level III.

Neurodevelopmental outcome of patients with congenital gastrointestinal malformations: a systematic review and meta-analysis.

AIM: Children with congenital gastrointestinal malformations may be at risk of neurodevelopmental impairment due to challenges to the developing brain, including perioperative haemodynamic changes, exposure to anaesthetics and postoperative inflammatory influences. This study aggregates existing evidence on neurodevelopmental outcome in these patients using meta-analysis. METHOD: PubMed, Embase and Web of Science were searched for peer-reviewed articles published until October 2019. Out of the 5316 unique articles that were identified, 47 studies met the inclusion criteria and were included. Standardised mean differences (Cohen's d) between cognitive, motor and language outcome of patients with congenital gastrointestinal malformations and normative data (39 studies) or the studies' control group (8 studies) were aggregated across studies using random-effects meta-analysis. The value of (clinical) moderators was studied using meta-regression and diagnostic subgroups were compared. RESULTS: The 47 included studies encompassed 62 cohorts, representing 2312 patients. Children with congenital gastrointestinal malformations had small-sized cognitive impairment (d=-0.435, p<0.001; 95% CI -0.567 to -0.302), medium-sized motor impairment (d=-0.610, p<0.001; 95% CI -0.769 to -0.451) and medium-sized language impairment (d=-0.670, p<0.001; 95% CI -0.914 to -0.425). Patients with short bowel syndrome had worse motor outcome. Neurodevelopmental outcome was related to the number of surgeries and length of total hospital stay, while no relations were observed with gestational age, birth weight, age and sex. INTERPRETATION: This study shows that children with congenital gastrointestinal malformations exhibit impairments in neurodevelopmental outcome, highlighting the need for routine screening of neurodevelopment during follow-up.

Risk factors for enterocolitis in patients with Hirschsprung disease: A retrospective observational study.

INTRODUCTION: Hirschsprung-associated enterocolitis (HAEC) accounts for substantial morbidity and mortality in patients with Hirschsprung disease (HD). The aim of this study was to identify incidence of pre- and postoperative HAEC in our consecutive cohort and to identify patient and clinical characteristics that are associated with developing postoperative HAEC and HAEC-free interval. MATERIAL AND METHODS: A retrospective cohort study was performed with all 146 HD patients treated between 2000 and 2017. Data were retrieved from the medical records. HAEC was defined as presence of clinical signs of bowel inflammation, that required treatment with intravenous antibiotics and admittance to the hospital during at least two days. To identify risk factor for HAEC, patients with and without a history of postoperative HAEC were compared. Kaplan-Meier and Cox-regression were used to assess HAEC free intervals before and after surgery. RESULTS: Out of 146 patients, 12 patients had pre-operative HAEC (8%) and 31 patients had postoperative HAEC (21%). Median preoperative HAEC free interval was 112 days (IQR 182 days). Length of hospital stay due to readmissions was longer for patients with a history of postoperative HAEC compared to patients without a history of postoperative HAEC (9.5 vs 16 days, U = 1872.5, p = 0.047). Median postoperative HAEC free interval was 226 days. Of the patients who had postoperative HAEC, 66% had their first episode within the first year after surgery and that the incidence of HAEC declined over follow-up. CONCLUSIONS: HAEC incidence was relatively low in our population. No patient or clinical characteristics were associated with the risk of postoperative HAEC.

Intrasphincteric botulinum toxin injections for post-operative obstructive defecation problems in Hirschsprung disease: A retrospective observational study.

BACKGROUND: Patients with Hirschsprung disease may have obstructive symptoms after resection of the aganglionic segment. Botulinum toxin (BT) injections can help improve faecal passage by relaxing the internal anal sphincter. This study assess effect of BT injections and aims to identify factors associated with receiving BT injections and favourable response to the first BT injection. METHODS: A retrospective study was performed in a cohort of consecutive patients treated for Hirschsprung disease in our centre between 2003 and 2017. The indication for BT injections was obstructive defecation problems that were non-responsive to high-dose laxatives or rectal irrigation, or an episode of Hirschsprung-associated enterocolitis (HAEC). Effectiveness of BT injections was measured in terms of clinical improvement. Relationships between factors associated with receiving BT injections and with response to the first BT injection were tested with group comparison and logistic regression. RESULTS: Forty-one out of 131 patients received BT injections (31%) with a median of two injections (range 1-11). All patients had obstructive defecation problems non-responsive to high-dose laxatives or rectal irrigation, two patient also had an episode of HAEC. Twenty-five out of 41 patients (61%) had clinical improvement after first injection. In 29 of the 41 patients (71%) spontaneous defecation or treatment with laxatives only was achieved. Adverse effects were seen in 12 out of 41 patients (29%) after 14 injections (16%), and consisted of anal pain, temporary loss of stools and dermatitis. Patients who received BT injections more often had long segment disease, more often required laxatives or rectal irrigation and had longer length of hospital stay, both after corrective surgery and in follow-up. None of the tested factors was associated with clinical improvement after first BT injection. CONCLUSION: Our findings show that BT injections effectively treat obstructive defecation problems in the majority of patients with Hirschsprung disease with mild adverse effects. LEVEL OF EVIDENCE: Level III.

Redo surgery with longitudinal resection for dilated bowel in Hirschsprung disease: an illustrative case series.

PURPOSE: Patients with Hirschsprung disease (HD) can have persistent obstructive symptoms after resection of the aganglionic segment. If obstructive symptoms are treated inadequately, this may lead to recurrent faecal stasis and impaction, and may result in severe distension of the bowel. A permanently distended bowel which not responds to conservative treatment may be an indication for redo surgery. The aim of this study is to describe our experiences and the short-term results of a novel technique: longitudinal antimesenteric resection with a longitudinal anastomosis. METHODS: We reviewed the medical records of our three patients who underwent longitudinal resection of severe distended bowel. This technique aims to improve defecation by improving faecal passage and is characterized by resection of the antimesenteric side of the distended intestinal segment, followed by plication with a longitudinal anastomosis. In this paper, this novel technique is described in detail, as well as short-term outcomes. RESULTS: All patients had an uneventful recovery after longitudinal antimesenteric resection. During follow-up, the functional outcomes were excellent, with a large improvement of bowel function. All patients were continent for faeces, and treated with low-dose laxatives or occasional preventive irrigation in one patient. There were no more complaints of persistent constipation or soiling. CONCLUSION: Longitudinal resection is a surgical redo-procedure offering large benefits for patients with Hirschsprung disease with distended bowel after primary surgery.

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

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, I 2 = 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, I 2 = 71.0, n = 52 patients). There were adverse effects in on average 17% of patients (ER = 0.17, P < 0.001, I 2 = 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.