BACKGROUND: Surgical treatment of Hirschsprung\'s disease (HSCR) in Sweden was centralized to two tertiary pediatric surgery centers 1st of July 2018. Although complex surgical care in adults seems to benefit from centralization there is little evidence to support centralization of pediatric surgical care. The aim of this study was to assess centralization of HSCR in Sweden, with special consideration to preoperative management and outcomes in this group of patients.
METHODS: This study retrospectively analyzed data of patients with HSCR that had undergone or were planned to undergo pull-through at our center, from 1st of July 2013 to 30th of June 2023. Patients managed from 1st of July 2013 to 30th of June 2018 were compared with patients managed from 1st of July 2018 to 30th of June 2023 regarding diagnostic procedures, preoperative treatment, complications and time to definitive surgery.
RESULTS: Thirty-six patients were managed during the first five-year period compared to 57 during the second period. There was an increased number of patients referred from other Swedish regions to our center following the centralization. Time from diagnosis to pull-through increased from 33 to 55 days after centralization. There were no significant differences in pre-operative management or complications, general or related to stoma.
CONCLUSIONS: Despite increasing patient volumes and longer time from diagnosis to pull through, centralization of care for HSCR does not seem to change the preoperative management and risk of complications. With access to support from the specialist center, transanal irrigations remain a safe mode of at home management until surgery, regardless of distance to index hospital.
METHODS: Level III.

OBJECTIVE: Hirschsprung disease (HSCR) is a severe congenital disorder affecting 1:5000 live births. HSCR results from the failure of enteric nervous system (ENS) progenitors to fully colonise the gastrointestinal tract during embryonic development. This leads to aganglionosis in the distal bowel, resulting in disrupted motor activity and impaired peristalsis. Currently, the only viable treatment option is surgical resection of the aganglionic bowel. However, patients frequently suffer debilitating, lifelong symptoms, with multiple surgical procedures often necessary. Hence, alternative treatment options are crucial. An attractive strategy involves the transplantation of ENS progenitors generated from human pluripotent stem cells (hPSCs).
METHODS: ENS progenitors were generated from hPSCs using an accelerated protocol and characterised, in detail, through a combination of single-cell RNA sequencing, protein expression analysis and calcium imaging. We tested ENS progenitors\' capacity to integrate and affect functional responses in HSCR colon, after ex vivo transplantation to organotypically cultured patient-derived colonic tissue, using organ bath contractility.
RESULTS: We found that our protocol consistently gives rise to high yields of a cell population exhibiting transcriptional and functional hallmarks of early ENS progenitors. Following transplantation, hPSC-derived ENS progenitors integrate, migrate and form neurons/glia within explanted human HSCR colon samples. Importantly, the transplanted HSCR tissue displayed significantly increased basal contractile activity and increased responses to electrical stimulation compared with control tissue.
CONCLUSIONS: Our findings demonstrate, for the first time, the potential of hPSC-derived ENS progenitors to repopulate and increase functional responses in human HSCR patient colonic tissue.

BACKGROUND: Hirschsprung\'s disease (HD) is a rare and complex malformation. The corrective operation is challenging and schedulable. The complete care situation for the corrective surgery for HD in Germany is uninvestigated.
METHODS: For the years 2016-2022, the microdata of the diagnosis-related groups (DRG) -statistics provided by the Research Data Center of the German Federal Statistical Office were accessed. All hospital stays for corrective surgery of HD in patients aged 0-17 were analyzed for patient\'s comorbidities, treatment characteristics and hospital structures. The occurrence of severe early postoperative complications during the hospital stay were documented.
RESULTS: The care structure for HD in Germany is decentralized with 109 hospitals performing 1199 corrective surgeries in 7 years. 75% of the participating hospitals performed three or less cases per year and 55 participating hospitals did not perform corrective surgery for HD each year. Early postoperative complications were common with at least one severe early complication in 18.6% of the cases. With an overall low case load per hospital, a volume outcome relationship cannot be established within Germany. Compared to international high volume centers the quality of outcomes for some of the investigated parameters was reduced. Despite the establishing of centers of expertise by the European reference network ERNICA for the treatment of HD no trend towards centralization occurred in Germany.
CONCLUSIONS: The corrective surgery for HD in Germany is decentralized and results in an overall high rate of early complications. The comparison with international studies from high-volume centers indicates potential for improvement for the corrective surgery of HD. Centralization remains essential for the improvement of care for patients with HD.

BACKGROUND: Anorectal malformation (ARM) or Hirschsprung\'s disease (HD) in children impact on parents\' burden of care and quality of life (QoL). The aim of this study was to investigate the relationship between caregiver burden and QoL in parents of children with ARM or HD.
METHODS: This cross-sectional study was conducted with 51 parents who completed the Zarit Burden Inventory (ZBI) and World Health Organization Quality of Life Scale-Short Form Turkish Version (WHOQOL-BREF-TR).
RESULTS: The mean (±SD) ZBI score was 33.6 (±12.7), and 47.1% of parents (n = 24) perceived their caregiver burden as mild, 31.4% (n = 16) as moderate, and 3.9% (n = 2) as severe. According to the multivariate linear regression, associated anomalies (β1 = 5.912), family income (β1 = -6.007), stoma care (β1 = 8.287), and diagnosis were identified to be significant determinants of caregiver burden. A negative, moderate, and significant relationship was identified between the ZBI scores and the physical domain (r = -0.417, p < .01), psychological domain (r = -0.421, p < .01), social relations domain (r = -0.398, p < .01), and environmental domain (r = -0.495, p < .01) scores of the WHOQOL-BREF-TR.
CONCLUSIONS: The mothers perceived their caregiver burden as mild. However, a significant number of parents suffer from moderate to heavy caregiver burden. An increase in the caregiver burden of parents reduces their quality of life.
CONCLUSIONS: Heightened awareness of the potential for caregiver burden and its association with quality of life among parents of children with ARM and HD may contribute to improved.

BACKGROUND: Hirschsprung\'s disease is a rare congenital anomaly of the colon with absence of the ganglionic nerve cells. The treatment of the anomaly is surgical.
METHODS: This population-based data-linkage cohort study was part of the EUROlinkCAT project and investigated mortality and morbidity for the first 5 years of life for European children diagnosed with Hirschsprung\'s disease. Nine population-based registries in five countries from the European surveillance of congenital anomalies network (EUROCAT) participated. Data on children born 1995-2014 and diagnosed with Hirschsprung\'s disease were linked to hospital databases. All analyses were adjusted for region and length of follow-up, which differed by registry.
RESULTS: The study included 680 children with Hirschsprung\'s disease. One-year survival was 97.7% (95% CI: 96.4-98.7). Overall, 85% (82-87) had a code for a specified intestinal surgery within the first year increasing to 92% (90-94) before age 5 years. The median age at the first intestinal surgery up to 5 years was 28 days (11-46) and the median number of intestinal surgical procedures was 3.5 (3.1-3.9). Thirty days mortality after neonatal surgery (within 28 days after birth) was 0.9% (0.2-2.5) for children with a code for intestinal surgery within the first 28 days after birth and there were no deaths for children with a code for stoma surgery in the neonatal period.
CONCLUSIONS: Children with Hirschsprung\'s disease have a high morbidity in the first 5 years of life requiring more surgical procedures in addition to the initial surgery. Mortality after neonatal surgery is low.

BACKGROUND: Even if understanding of neuronal enteropathies, such as Hirschsprung\'s disease and functional constipation, has been improved, specialized therapies are still missing. Sacral neuromodulation (SNM) has been established in the treatment of defecation disorders in adults. The aim of the study was to investigate effects of SNM in children and adolescents with refractory symptoms of chronic constipation.
METHODS: A two-centered, prospective trial has been conducted between 2019 and 2022. SNM was applied continuously at individually set stimulation intensity. Evaluation of clinical outcomes was conducted at 3, 6, and 12 months after surgery based on the developed questionnaires and quality of life analysis (KINDLR). Primary outcome was assessed based on predefined variables of fecal incontinence and defecation frequency.
RESULTS: Fifteen patients enrolled in the study and underwent SNM (median age 8.0 years (range 4-17 years)): eight patients were diagnosed with Hirschsprung\'s disease (53%). Improvement of defecation frequency was seen in 8/15 participants (53%) and an improvement of fecal incontinence in 9/12 patients (75%). We observed stable outcome after 1 year of treatment. Surgical revision was necessary in one patient after electrode breakage. Urinary incontinence was observed as singular side effect of treatment in two patients (13%), which was manageable with the reduction of stimulation intensity.
CONCLUSIONS: SNM shows promising clinical results in children and adolescents presenting with chronic constipation refractory to conservative therapy. Indications for patients with enteral neuropathies deserve further confirmation.

During enteric nervous system (ENS) development, pioneering wavefront enteric neural crest cells (ENCCs) initiate gut colonization. However, the molecular mechanisms guiding their specification and niche interaction are not fully understood. We used single-cell RNA sequencing and spatial transcriptomics to map the spatiotemporal dynamics and molecular landscape of wavefront ENCCs in mouse embryos. Our analysis shows a progressive decline in wavefront ENCC potency during migration and identifies transcription factors governing their specification and differentiation. We further delineate key signaling pathways (ephrin-Eph, Wnt-Frizzled, and Sema3a-Nrp1) utilized by wavefront ENCCs to interact with their surrounding cells. Disruptions in these pathways are observed in human Hirschsprung\'s disease gut tissue, linking them to ENS malformations. Additionally, we observed region-specific and cell-type-specific transcriptional changes in surrounding gut tissues upon wavefront ENCC arrival, suggesting their role in shaping the gut microenvironment. This work offers a roadmap of ENS development, with implications for understanding ENS disorders.

Hirschsprung\'s disease (HSCR) is a congenital disorder characterized by the absence of ganglion cells in the colon, leading to various intestinal complications. The etiology of HSCR stems from complex genetic and environmental interactions, of which the intricate roles of non-coding RNAs (ncRNAs) are a key area of research. However, the roles of ncRNAs in the pathogenesis of HSCR have not been fully elucidated. In order to understand the variety of symptoms caused by HSCR and develop new therapeutic approaches, it is essential to understand the underlying biological genetic basis of HSCR. This review presents a comprehensive overview of the current understanding regarding the involvement of ncRNAs in HSCR, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Additionally, it provides a summary of the molecular mechanisms through which ncRNAs regulate the expression of genes related to the proliferation, migration, and differentiation of intestinal neural crest cells, thereby contributing to the advancement of HSCR research.

The enteric nervous system (ENS) controls gastrointestinal (GI) motility, and defects in ENS development underlie pediatric GI motility disorders. In disorders such as Hirschsprung\'s disease (HSCR), pediatric intestinal pseudo-obstruction (PIPO), and intestinal neuronal dysplasia type B (INDB), ENS structure is altered with noted decreased neuronal density in HSCR and reports of increased neuronal density in PIPO and INDB. The developmental origin of these structural deficits is not fully understood. Here, we review the current understanding of ENS development and pediatric GI motility disorders incorporating new data on ENS structure. In particular, emerging evidence demonstrates that enteric neurons are patterned into circumferential stripes along the longitudinal axis of the intestine during mouse and human development. This novel understanding of ENS structure proposes new questions about the pathophysiology of pediatric GI motility disorders. If the ENS is organized into stripes, could the observed changes in enteric neuron density in HSCR, PIPO, and INDB represent differences in the distribution of enteric neuronal stripes? We review mechanisms of striped patterning from other biological systems and propose how defects in striped ENS patterning could explain structural deficits observed in pediatric GI motility disorders.

Background: Surgical correction is the main line of treatment for the congenital disorder Hirschsprung\'s disease (HD). Laparoscopic techniques proved their safety and efficacy in previous studies. LigaSure™ is the gold standard for colorectal dissection. However, other sealing methods could be used during the unavailability of LigaSure. Purpose: This study aimed to assess the safety profile of the hook diathermy technique compared to LigaSure in colorectal dissection during laparoscopic-assisted pull-through for HD. Materials and Methods: This case-control study was held in the pediatric surgery department at Assiut University Hospitals between September 2017 and January 2023. The study included 57 HD patients who were surgically operated on during a laparoscopic-assisted pull-through. They were divided into 2 groups according to the sealing methods: the ligasure group included 25 patients, and the hook diathermy group included 32 patients. Results: Both groups had no statistically significant differences regarding age, sex, or weight. The transition zone was present in all patients, and most transition zones were rectosigmoid. No cases reported intraoperative blood transfusion or conversion to an open or transanal approach. Minimum intraoperative blood loss was reported in both groups, with no significant differences. As regards postoperative complications, including bleeding, leakage, perianal excoriation, and enterocolitis, no significant differences between both groups were found. Conclusion: The LigaSure and hook diathermy techniques are safe and effective sealing methods for colorectal dissection during laparoscopic-assisted pull-through for HD.