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The goal of this study was to determine if transplantation of enteric neural stem cells (ENSCs) can rescue the enteric nervous system, restore gut motility, reduce colonic inflammation, and improve survival in the Ednrb-KO mouse model of Hirschsprung disease (HSCR). ENSCs were isolated from mouse intestine, expanded to form neurospheres, and microinjected into the colons of recipient Ednrb-KO mice. Transplanted ENSCs were identified in recipient colons as cell clusters in neo-ganglia. Immunohistochemical evaluation demonstrated extensive cell migration away from the sites of cell delivery and across the muscle layers. Electrical field stimulation and optogenetics showed significantly enhanced contractile activity of aganglionic colonic smooth muscle following ENSC transplantation and confirmed functional neuromuscular integration of the transplanted ENSC-derived neurons. ENSC injection also partially restored the colonic migrating motor complex. Histological examination revealed a significant reduction in inflammation in ENSC-transplanted aganglionic recipient colon compared with that of sham-operated mice. Interestingly, mice that received cell transplant also had prolonged survival compared with controls. This study demonstrates that ENSC transplantation can improve outcomes in HSCR by restoring gut motility and reducing the severity of Hirschsprung-associated enterocolitis, the leading cause of death in human HSCR.

Regenerative cell therapy to replenish the missing neurons and glia in the aganglionic segment of Hirschsprung disease represents a promising treatment option. However, the success of cell therapies for this condition are hindered by poor migration of the transplanted cells. This limitation is in part due to a markedly less permissive extracellular environment in the postnatal gut than that of the embryo. Coordinated interactions between enteric neural crest-derived cells (ENCDCs) and their local environment drive migration along the embryonic gut during development of the enteric nervous system. Modifying transplanted cells, or the postnatal extracellular environment, to better recapitulate embryonic ENCDC migration could be leveraged to improve the engraftment and coverage of stem cell transplants. We compared the transcriptomes of ENCDCs from the embryonic intestine to that of postnatal-derived neurospheres and identified 89 extracellular matrix (ECM)-associated genes that are differentially expressed. Agrin, a heparin sulfate proteoglycan with a known inhibitory effect on ENCDC migration, was highly over-expressed by postnatal-derived neurospheres. Using a function-blocking antibody and a shRNA-expressing lentivirus, we show that inhibiting agrin promotes ENCDC migration in vitro and following cell transplantation ex vivo and in vivo. This enhanced migration is associated with an increased proportion of GFAP + cells, whose migration is especially enhanced.

Neurointestinal diseases cause significant morbidity and effective treatments are lacking. This study aimes to test the feasibility of transplanting autologous enteric neural stem cells (ENSCs) to rescue the enteric nervous system (ENS) in a model of colonic aganglionosis. ENSCs are isolated from a segment of small intestine from Wnt1::Cre;R26iDTR mice in which focal colonic aganglionosis is simultaneously created by diphtheria toxin injection. Autologous ENSCs are isolated, expanded, labeled with lentiviral-GFP, and transplanted into the aganglionic segment in vivo. ENSCs differentiate into neurons and glia, cluster to form neo-ganglia, and restore colonic contractile activity as shown by electrical field stimulation and optogenetics. Using a non-lethal model of colonic aganglionosis, our results demonstrate the potential of autologous ENSC therapy to improve functional outcomes in neurointestinal disease, laying the groundwork for clinical application of this regenerative cell-based approach.

Purpose: This study investigated the prevalence of bowel dysfunction and associated factors after pull-through surgery. Methods: The medical records of children under 18 years old diagnosed with Hirschsprung disease (HD) based on histopathology between 2004 and 2022 were reviewed. Bowel dysfunction after pull-through surgery was categorized into Hirschsprung-associated enterocolitis (HAEC), constipation, and fecal incontinence. Results: Among 97 children diagnosed with HD, the median age at presentation was 3 (2-15) days (84.54% male). The clinical manifestations included abdominal distension (58.76%), constipation (17.52%), bilious vomiting (17.52%), nonbilious vomiting (14.43%), and enterocolitis (12.37%). HDs were classified by the location of aganglionosis: short segments (74.23%), long segments (8.25%), total colonic (12.37%), and small intestinal (5.15%). Excluding surgical complications, the prevalence of bowel dysfunction was 64.95% during an average follow-up of 8.33 years. HAEC was the most common issue (46.39%), followed by nonretentive incontinence (22.68%), constipation (20.62%), and retentive incontinence (15.46%). Preoperative HAEC was significantly associated with post-surgery HAEC (adjusted odds ratio [aOR] 18.31; 95% confidence interval [CI], 1.30-257.73; p=0.031). The Duhamel operation was associated with constipation and retentive incontinence (aOR 62.15; 95% CI, 1.64-2,349.13; p=0.026). Age under 6 months at pull-through surgery was associated with nonretentive fecal incontinence after 4 years (aOR 8.83; 95% CI, 1.11-70.39; p=0.040). Conclusion: The prevalence of bowel dysfunction in children with HD remains high despite successful surgical correction. Preoperative HAEC, Duhamel operation, and pull-through surgery before the age of 6 months were found to be independent factors associated with bowel dysfunction after pull-through surgery. [ABSTRACT FROM AUTHOR]

Aim: Extended total colonic aganglionosis (ETCA) represents uncommon forms of Hirschsprung disease (HD), with aganglionosis extending into the proximal small bowel. ETCA management is challenging and associated with poor outcomes and high mortality. This study compares management and outcomes of ETCA to more common HD forms. Methods: A retrospective cohort of HD patients (2012–2023) from two institutions. Three HD forms were compared: short‐segment HD (SSHD, n = 19), long‐segment HD or total colonic aganglionosis (LS/TCA, n = 9) and ETCA (n = 7). Results: Normally innervated segments in ETCA patients ranged 0–70 cm. Median times to first surgery were; ETCA = 3 days versus TCA = 21 days (p = 0.017) and SSHD = 95 days (p < 0.001), respectively. Median number of surgeries were; ETCA = 4, versus TCA = 2 (p = 0.17) and SSHD = 1 (p = 0.002), respectively. All the patients underwent a definitive pull‐through procedure, except four ETCA patients with a permanent jejunostomy and residual aganglionic segment of 57–130 cm. ETCA patients had 92% lower odds of enterocolitis (14%) compared to TCA patients (67%, p = 0.054), and comparable odds to SSHD patients (16%, p = 0.92). ETCA mortality was 14%. Conclusion: Extended total colonic aganglionosis patients require earlier and multiple interventions. Leaving an aganglionic segment may be advantageous, without increasing risk for enterocolitis. Tailored surgical treatment and rehabilitation programmes may prevent mortality and need for transplantation. [ABSTRACT FROM AUTHOR]

A growing number of patients with Hirschsprung disease are reaching adulthood, of whom a significant minority will require ongoing input from healthcare providers. In order to ensure patients receive the best care possible, it is essential to transition patients appropriately to adult services. This article describes the unmet need and some of the obstacles to this process and explores potential solutions, drawing on model examples for transitional care. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the differences in postoperative complications and long-term bowel function outcomes between patients with rectosigmoid Hirschsprung disease (HD) who underwent transanal endorectal pull-through (TEPT) beyond infancy (age> 1 year of age) and those during infancy (≤ 1 year of age). Methods: All patients with rectosigmoid HD at Beijing Children's Hospital between January 2011 and December 2020 were analyzed retrospectively. They were divided into two groups based on age at TEPT: group A was defined as patients who performed TEPT beyond infancy (age>1 year of age), and group B as patients who performed TEPT during infancy (age ≤ 1 year of age). Clinical details were collected from medical records. Bowel function outcomes were assessed by the Rintala questionnaire (age ≥ 4 years). Results: A total of 339 patients were included: 216 (63.7%) who operated with TEPT beyond infancy (group A) and 123 (36.3%) during infancy (group B). Regarding postoperative complications, all patients suffering anastomosis leakage following TEPT (7/216, 3.2%) occurred in group A, and the rate of anastomosis leakage in group A was significantly higher than in group B (3.2% vs. 0.0%, p = 0.044). 228 patients (228/327, 69.7%) completed the Rintala questionnaire. There was no significant difference in long-term bowel function outcomes between the two groups. Conclusion: Compared with patients who performed TEPT during infancy, those beyond infancy are more likely to suffer anastomosis leakage. however, the long-term bowel function outcomes seem comparable. Type of Study: A retrospective single-center study. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Hirschsprung disease (HSCR) and its associated disorders (AD-HSCR) often result in severe hypoperistalsis caused by enteric neuropathy, mesenchymopathy, and myopathy. Notably, HSCR involving the small intestine, isolated hypoganglionosis, chronic idiopathic intestinal pseudo-obstruction, and megacystis-microcolon-intestinal hypoperistalsis syndrome carry a poor prognosis. Ultimately, small-bowel transplantation (SBTx) is necessary for refractory cases, but it is highly invasive and outcomes are less than optimal, despite advances in surgical techniques and management. Thus, regenerative therapy has come to light as a potential form of treatment involving regeneration of the enteric nervous system, mesenchyme, and smooth muscle in affected areas. We review the cutting-edge regenerative therapeutic approaches for managing HSCR and AD-HSCR, including the use of enteric nervous system progenitor cells, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells as cell sources, the recipient intestine's microenvironment, and transplantation methods. Perspectives on the future of these treatments are also discussed. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to understand the influence of diet and nutrition items on gastrointestinal symptoms in patients with Hirschsprung Disease (HD). Method: An online questionnaire was created to obtain patient-reported outcomes using the multinational Holistic Care in Hirschsprung Disease Network. This was distributed in Dutch, English, German, Italian, Polish, and Swedish via patient associations. Information on demographics, the extension of disease, current diet, and the influence of food ingredients on bowel function were obtained. Results: In total, 563 questionnaires were answered by parents or patients themselves. The length of the aganglionic segment was short in 33%, long in 45%, total colonic aganglionosis (TCA) in 11%, and involved the small intestine in 10%. Overall, 90% reported following a mixed diet, and 31% reported taking probiotics, with twice as many patients taking probiotics in the TCA group compared to standard HD. Mealtimes and behaviours around eating were affected by 61%, while 77% had established food items that worsened symptoms, and of these, 80% stated that they had worked these items out themselves. A high-fibre diet was followed by 24% and 18% a low-fibre diet. Symptoms were reported, particularly from dairy in 30%, fruits in 39%, pulses in 54%, and sugar in 48%. Conclusions: This first multinational survey on diet and bowel function in HD reports an association between certain dietary items with gastrointestinal symptoms. This study can support an improved understanding of the interaction between food items and bowel function in children with HD. We suggest a multidisciplinary approach to balance dietary exclusions and support adequate growth, preventing nutrition deficiencies and enhancing quality of life. [ABSTRACT FROM AUTHOR]

The diagnosis of adult Hirschsprung disease (HD) is rare, furthermore there are only 3 or 4 cases of adult ultrashort segment HD (USHD) reported previously in English literature to our knowledge. Herein, we present a case of a 22-year-old female presented with long standing history of constipation and abdominal distension secondary to USHD. Imaging modalities included plain abdominal X-ray, ultrasound (USG) and computed tomography (CT) scan which collectively aided in establishing the diagnosis. Through this case report, we aim to emphasize that HD should be suspected in every adult population with chronic constipation. Also, it highlights the role of CT scan as how it should be the preferred diagnostic tool for suspected adult HD, as, not only it helps correctly identify the transition zone but rule out other possible causes of chronic obstruction.

Abstract Purpose This study aimed to compare the differences in postoperative complications and long-term bowel function outcomes between patients with rectosigmoid Hirschsprung disease (HD) who underwent transanal endorectal pull-through (TEPT) beyond infancy (age> 1 year of age) and those during infancy (≤ 1 year of age). Methods All patients with rectosigmoid HD at Beijing Children’s Hospital between January 2011 and December 2020 were analyzed retrospectively. They were divided into two groups based on age at TEPT: group A was defined as patients who performed TEPT beyond infancy (age>1 year of age), and group B as patients who performed TEPT during infancy (age ≤ 1 year of age). Clinical details were collected from medical records. Bowel function outcomes were assessed by the Rintala questionnaire (age ≥ 4 years). Results A total of 339 patients were included: 216 (63.7%) who operated with TEPT beyond infancy (group A) and 123 (36.3%) during infancy (group B). Regarding postoperative complications, all patients suffering anastomosis leakage following TEPT (7/216, 3.2%) occurred in group A, and the rate of anastomosis leakage in group A was significantly higher than in group B (3.2% vs. 0.0%, p = 0.044). 228 patients (228/327, 69.7%) completed the Rintala questionnaire. There was no significant difference in long-term bowel function outcomes between the two groups. Conclusion Compared with patients who performed TEPT during infancy, those beyond infancy are more likely to suffer anastomosis leakage. however, the long-term bowel function outcomes seem comparable. Type of Study A retrospective single-center study. Level of evidence III.

The enteric nervous system (ENS) is principally derived from vagal neural crest cells that migrate caudally along the entire length of the gastrointestinal tract, giving rise to neurons and glial cells in two ganglionated plexuses. Incomplete migration of enteric neural crest-derived cells (ENCDC) leads to Hirschsprung disease, a congenital disorder characterized by the absence of enteric ganglia along variable lengths of the colorectum. Our previous work strongly supported the essential role of the avian ceca, present at the junction of the midgut and hindgut, in hindgut ENS development, since ablation of the cecal buds led to incomplete ENCDC colonization of the hindgut. In situ hybridization shows bone morphogenetic protein-4 (BMP4) is highly expressed in the cecal mesenchyme, leading us to hypothesize that cecal BMP4 is required for hindgut ENS development. To test this, we modulated BMP4 activity using embryonic intestinal organ culture techniques and retroviral infection. We show that overexpression or inhibition of BMP4 in the ceca disrupts hindgut ENS development, with GDNF playing an important regulatory role. Our results suggest that these two important signaling pathways are required for normal ENCDC migration and enteric ganglion formation in the developing hindgut ENS.

Objective To discuss the clinical features, differential diagnosis and complication treatment of a patient with genetic visceral myopathy. Methods Medical history, physical examination and laboratory results of the patient were collected in detail. The pathology of previous surgery was reviewed. The patient's peripheral blood DNA was extracted and submitted for whole-exome sequencing. Subsequent Sanger sequencing was used to complete the pedigree verification of the mutation site. Results The patient was a young female presented with repeated incomplete intestinal obstruction since early childhood. She used to be misdiagnosed as Hirschsprung's disease for a long period and underwent multiple gastrointestinal segment resections. Her intestinal obstruction symptoms were temporarily relieved by surgeries, but severe diarrhea, mucus and bloody stools and malnutrition gradually occurred after the last operation. The patient had bacterial overgrowth in small intestinal tract and followed by intestinal opportunistic infections secondary to chronic intestinal pseudo-obstruction. The symptoms improved after anti-infection and enteral element diet treatment. Further pathological consultation and whole-exome gene sequencing confirmed the diagnosis of visceral myopathy related to ATCG2 R148L mutation. Conclusions Patients with early onset of chronic intestinal pseudo-obstruction and have poor response to conventional treatment are recommended to perform genetic test. The patients with hereditary visceral myopathy are susceptible to opportunistic intestinal infection. Attentions should also be paid to the prevention and treatment of complications to avoid unnecessary surgery.

Purpose: Early post-operative fever (< 48 h) is common in adults and children and seldom indicative of an infection. Guidance to limit excessive evaluation in adults is well-characterized but similar studies for the pediatric population is scarce. This study was performed to better clarify which infants should undergo investigation for post-operative fever after colorectal reconstructive surgical procedures. Methods: We performed a retrospective chart review of all infants under one year of age who underwent elective reconstruction for anorectal malformations (ARM) and Hirschsprung Disease (HD) between June 2018 and April 2020 at a single institution. Patient and perioperative characteristics were analyzed to evaluate for possible factors associated with infection. Results: Sixty-eight infants met study criteria – 38 (55.9%) had HD and 30 (44.1%) had ARM. Twenty-two infants (32.4%) had early post-operative fever. A definitive infectious cause was identified in only two infants. The presence of a colostomy pre-operatively and longer operative times were associated with increased risk of post-operative fever (62.5% vs. 22.7% and 175 min vs. 150 min respectively, p < 0.05). Conclusion: Early post-operative fever in infants after colorectal surgery is common and rarely associated with an infection. Further research is needed to determine which infants require further work-up and which can be safely observed. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of intestinal microecological agents in enhancing gastrointestinal function in perioperative period of Hirschsprung disease. Methods: 30 cases with surgically managed Hirschsprung in The Affiliated Hospital of Guizhou Medical University, China between March 2020 and March 2022, were randomized into control and study groups comprising 15 patients each. Both groups underwent laparoscopic-assisted megacolon-modified Swenson radical surgery. Control group received preoperative oral cefaclor suspension for three days, while the study group received Bacillus subtilis diphtheriae granules in addition to preoperative oral cefaclor suspension for four days prior to surgery, and continued from day 10 to day 24 after surgery. Symptoms, efficacy, safety, intestinal microecology, gastrointestinal function, inflammation, and nutrition were assessed upon admission, and 10 days after surgery. Postoperative complications were compared. Results: Bacterial counts in both groups increased significantly on Day 10 after surgery compared to the counts at admission (p < 0.05). The study group exhibited significantly higher counts compared to the control group (p < 0.05). The bacilli-to-cocci ratio in the study group did not change significantly (p > 0.05). Nutritional status was significantly higher in the study group compared to control group 10 days after surgery (p < 0.05). Furthermore, the incidence of small bowel colitis was lower in the study group compared to control group. There was no significant difference in the incidence of complications in both groups (p > 0.05). Conclusion: Perioperative use of intestinal microecological agents effectively corrects dysbiosis, improves gastrointestinal function, regulates nutritional indices, and reduces postoperative complications in patients with Hirschsprung disease. Future studies involving a larger number of participants from different ethnic extractions would be required to improve the quality of results obtained from this investigation. [ABSTRACT FROM AUTHOR]

Introduction: The Duhamel procedure is a widely utilized surgical approach for addressing Hirschsprung Disease, a congenital condition affecting colonic innervation. The elimination of the septum between the rectum and ganglionic bowel is fundamental in this procedure and can be accomplished using either a stapling device or LigaSure. This study aims to compare the outcomes of septum elimination in the Duhamel procedure when employing these distinct devices. Methods: Retrospective analysis of patient databases and medical records was conducted for individuals undergoing Duhamel pull through surgery at our institutions between 2021 and 2023. The study focused on evaluating postoperative outcomes, specifically obstructive symptoms, Hirschsprung-associated enterocolitis (HAEC), and mortality rates. Results: The study included 96 patients, with a gender distribution of 36 males and 60 females. The majority of patients (90%) presented with the short type of Hirschsprung Disease, while long-type and total colon aganglionosis accounted for 5% each. Analysis revealed a significant association between stapler usage and an increased risk of HAEC (Relative Risk [RR] = 9.545, 95% Confidence Interval [CI] = 1.1 – 78.3; p = 0.017). However, no significant correlations were observed between device usage and post-pull through obstructive symptoms (p = 0.329). Notably, there were no reported mortalities during the study period. Conclusion: LigaSure emerges as a safe and applicable alternative to stapling devices in the Duhamel procedure. This study emphasizes the importance of device selection in achieving favourable outcomes for patients with Hirschsprung Disease undergoing the Duhamel procedure. [ABSTRACT FROM AUTHOR]

Introduction: The standard diagnosing Hirschsprung disease is obtained by pathologic evaluation. There are several techniques to acquire pathologic sample included Full Thickness Biopsy, Rectal Suction Biopsy, Punch Biopsy, and Endoscopic Biopsy. Currently, the endoscopic device is widely available and its utility is more frequent in pediatric population. This study conducted to compare the effectiveness in diagnosing Hirschsprung disease using the Colonoscopy Forceps Biopsy (CFB) and full thickness biopsy (FTB) method as a gold standard. Method: A preliminary study of the pathologic evaluation in 10 children clinically Hirschsprung disease who underwent two types of biopsy procedures: full-thickness biopsy and colonoscopy forceps biopsy. This study aimed to compare the diagnostic result of these two methods. Results: The biopsy results indicate that 10 FTB samples were aganglionic, while 9 samples taken using CFB were aganglionic. Conclusion: Colonoscopy with forceps biopsy may be used as an alternative for the diagnosis of Hirschsprung’s disease in children, further studies are needed to assess the diagnostic accuracy of colonoscopy with forceps biopsy. [ABSTRACT FROM AUTHOR]

Constipation is common in childhood, and most patients can be successfully managed by their primary care provider. However, some patients will require more specialized management either due to an underlying congenital colorectal disorder such as Hirschsprung disease or anorectal malformation or due to severe functional constipation that is refractory to medical management. [ABSTRACT FROM AUTHOR]

As pediatric patients with colorectal diseases grow, it is important to address transition to adult practice. We aim to describe our center's transition process and early outcomes. We developed a standardized process for transition to adult practice. An annual survey is given to parents and caregivers starting at age 12 that assesses knowledge of disease, independence with healthcare tasks, and confidence and interest regarding transition. After multidisciplinary review, those eligible are recommended for transition. Those not referred are provided with tools to help with areas of weakness. Outcomes were analyzed with descriptive and regression analyses (significance at p ≤ 0.05). A total of 116 patients were evaluated, with 80 patients (69.0%) recommended for transition. Median age at survey was 15.5 years [IQR: 13.7–18.1], and those recommended were older (16.6 years [IQR: 14.7–19.4] vs 13.5 years [IQR: 12.5–14.9], p < 0.001)). Primary diagnosis and gender were not associated with recommendation for transition. Overall, a minority (18.1%) were able to complete healthcare tasks; this correlated strongly with transition recommendation (26.3% vs 0.0%, p < 0.0001). On regression controlling for age, diagnosis, knowledge, and confidence, age (aOR 1.98, 95% CI 1.44–2.71) and confidence (aOR 3.78, 95% CI 1.29–11.11) independently predicted transition recommendation. A standardized approach may be effective in transitioning patients from pediatric to adult colorectal surgery practice. Patients who transition are more confident and can perform healthcare tasks independently; however, these skills are not essential prior to a recommendation of transition. III. • A standardized approach to transition to adult practice can be useful in identifying pediatric patients ready for transition to adult practice and successfully transitioning these patients. • Factors that aligned with successful transition recommendation in this sample included older age, ability to perform healthcare tasks independently, and confidence with transition to adult practice. [ABSTRACT FROM AUTHOR]

Antegrade colonic enemas (ACE) can be an effective management option for defecation disorders and improve quality of life. Best practice regarding channel placement is unclear and variation may exist around preferred initial type of channel, age at placement, and underlying diagnoses. We aimed to describe practice patterns and patient characteristics around ACE channel placement. We conducted a multicenter retrospective study of children with an ACE channel cared for at sites participating in the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) from 2017 to 2022. Kruskal–Wallis test was utilized to test the age at surgery by site with significance level of 0.05. 500 patients with ACE channel were included. 293 (58.6%) patients had their ACE procedure at a PCPLC center. The median age at surgery was 7.6 [IQR 5.3–11.0] years for the overall cohort and 8.1 [IQR 5.3–11.5] years for placement at PCPLC centers. For PCPLC centers, median age at placement varied significantly across centers (p = 0.009). 371 (74.2%) patients received Malone appendicostomy, 116 (23.2%) received cecostomy, and 13 (2.6%) received Neo-Malone appendicostomy. Median age of patients by channel type was 7.7 [IQR 5.3–11.0], 7.5 [IQR 5.7–11.0], and 9.8 [IQR 4.2–11.6] years, respectively. The most common indication for cecostomy was idiopathic/refractory constipation (52.6%), whereas anorectal malformation was the most common indication for Malone (47.2%) and Neo-Malone (61.5%). Among ACE channels placed at PCPLC centers, there was variation across institutions in preferred initial channel type. The 4 highest volume centers favored Malone appendicostomy over cecostomy. There is variation in practice of ACE channel placement. At specialty pediatric colorectal centers, age at time of placement and type of channel placed varied across institutions. Further work is needed to better characterize diagnosis- and age-focused patient centered outcomes to clarify recommendations for our patients who benefit from these procedures. Retrospective comparative study. Level III. [ABSTRACT FROM AUTHOR]

Background: Constipation and outlet obstruction may persist after successful pull-through in Hirschsprung Disease (HD). The radiographic assessment of the faecal load is widely used but exposes the child to radiation. This study aims to evaluate whether the transrectal diameter (TRD) assessed with ultrasound correlates with symptoms of faecal load and whether the TRD normalises when symptoms disappear. Method: Children with HD after pullthrough and functional constipation presenting to our colorectal clinic between 4/23 and 4/24 were assessed for symptoms of constipation, smearing and outlet obstruction, as well as healthy controls. Ultrasound measurement of the TRD was conducted. Bowel management was initiated according to our institutional pathway using Peristeen© irrigation after an orthograde disimpaction regime. Results: A total of 193 children underwent TRD assessment. Of 60 children with HD, 26 (43.3%) presented with obstructive symptoms, and 34 (56.7%) were asymptomatic. In asymptomatic patients with HD, the mean TRD of 2.26 cm (SD 0.61) was significantly (p < 0.001) lower than in HD with symptoms, with a mean TRD of 3.35 cm (SD 1.03). Individuals without colorectal pathology had a mean TRD of 2.04 cm (SD 0.37), and children with functional constipation and symptoms showed a mean TRD of 4.36 cm (SD 1.32). The mean TRD after symptom resolution was 2.37 cm. Conclusions: Children with HD without obstructive symptoms have a TRD < 3 cm, as do controls. The transrectal diameter allows the clinician to sonographically assess the faecal load in children with HD at the bedside without radiation. The TRD is useful for monitoring a bowel management program in children with HD. [ABSTRACT FROM AUTHOR]

Background: Total colonic aganglionosis, as a rare variant of Hirschsprung Disease, still poses challenges to surgeons in terms of diagnosis and management. The optimal preparation for pullthrough is crucial for reconstructive surgery. This study aims to explore our surgical pathway for children with total colonic aganglionosis (TCA) and to describe the prehabilitation necessary to prepare for successful reconstructive pullthrough surgery. Methods: A prospective review of children with TCA receiving an abdominal surgical intervention between 1/22 and 4/24. The cohort included children receiving mapping +/− primary ileoanal pullthrough. An analysis of preoperative, perioperative, and postoperative data, and a short-term follow-up were performed. Results: A total of 18 children with TCA and no prior pullthrough received an abdominal intervention during the 29-month study period, and 5/18 (27.8%) were female. The children had a median of 4 (range 2–7) prior external surgeries; all had a stoma; 6 (33%) children received parental nutrition; 12 children underwent a mapping of the ganglia distribution and bowel length at a median age of 11 months (range 3–54), and in 10 of them, we relocated the stoma. There was a mean involvement of 15 (5–93) cm small bowel aganglionosis, with the remaining mean ganglionic small bowel having a length of 178 cm (110–254). A total of 11 children underwent straight primary ileoanal pullthrough of the stoma site at a median age of 16.7 months (10–133). Conclusions: The timely diagnosis of TCA still challenges the care team, and most children have a rough journey involving several surgeries until their diagnosis is established. The ensure bowel function with an adequate working stoma is the key to enabling enteral nutrition and growth, which are the baseline requirements to undertake a successful pullthrough procedure and restore continuity. Careful perioperative bowel management and parents' active involvement supports children with Hirschsprung Disease achieving the best possible quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Women born with anorectal malformation (ARM) or Hirschsprung disease (HD) may have impaired urologic function resulting in sequelae in adulthood. This study assessed and compared self-reported urinary outcomes in adult females born with ARM or HD to a reference population. Methods: This was an IRB approved, cross-sectional study of female-born patients with ARM or HD, who completed surveys between November 2021 and August 2022. Female patients between the ages of 18 and 80 years were included. Lower Urinary Tract Symptom Questionnaires were administered through REDCap and the responses were compared to a reference population using Chi-squared or Fisher's exact tests. Results: Sixty-six born female patients answered the questionnaires, two of them identified as non-binary. The response rate was 76%. Median age was 31.6 years. The majority were born with cloaca (56.3%), followed by other type of ARMs (28.1%), complex malformation (9.4%), and HD (6.3%). A history of bladder reconstruction was present for 26.6%. Catheterization through a channel or native urethra was present in 18.8%. Two had ureterostomies and were excluded from the analysis. Seven had chronic kidney disease or end-stage renal disease, three with a history of kidney transplantation. Patients with cloaca had significantly higher rates of urinary incontinence, urinary tract infection, and social problems due to impaired urological functioning, when compared to an age-matched reference population (Table 3). Conclusion: This study emphasizes the need for a multi-disciplinary team that includes urology and nephrology following patients with ARM long term, especially within the subgroup of cloaca. Level of Evidence: III. [ABSTRACT FROM AUTHOR]

Objective To investigate the role and mechanism of miR-103a3p in the development of Hirschsprung disease (HSCR). Methods The expression levels of miR-103a3p in the constricted and dilated segments of colon tissue from HSCR patients were analyzed using RT-PCR. The effects of miR-103a3p on cell proliferation and migration were assessed using CCK-8 and Transwell assays. Potential target genes were predicted using KEGG, GO, and protein protein interaction network analyses. The target gene PIK3R1 of miR-103a-3p was validated at both cellular and tissue levels using RT-PCR, Western blot, and dual- luciferase reporter assays. Results miR-103a-3p was significantly upregulated in the constricted segments of colon tissues from HSCR patients. miR-103a-3p inhibited cell proliferation and migration. Bioinformatics analysis suggested that PIK3R1 is a potential target gene of miR103a3p in HSCR. Dual-luciferase reporter assays confirmed that miR-103a-3p binds to the 3'UTR of PIK3R1 and affects its mRNA and protein expression levels. In tissue samples, PIK3R1 expression was significantly reduced in the constricted segments, showing a negative correlation with miR-103a3p expression. Conclusion miR-103a3p is differentially expressed in the pathological intestinal segments of HSCR and plays a crucial role in the disease by targeting PIK3RI, influencing cell proliferation and migration. [ABSTRACT FROM AUTHOR]

The number of patients with congenital disease living to adulthood continues to grow. Often undergoing surgical correction in infancy, they continue to require lifelong care. Their numbers are largely unknown. We sought to evaluate hospital admissions of adult patients with esophageal atresia with tracheoesophageal fistula (EA/TEF), congenital diaphragmatic hernia (CDH), and Hirschsprung disease (HD). The Florida Agency for Healthcare Administration inpatient database was merged with the Distressed Communities Index and Centers for Medicare and Medicaid Services Hospital and Physician Compare datasets. The dataset was queried for adult patients (≥18 y, born after 1970) with EA/TEF, CDH, and HD in their problem list from 2010 to 2020. Patient demographics, hospitalization characteristics, and discharge information were obtained. In total, 1140 admissions were identified (266 EA/TEF, 135 CDH, 739 HD). Patients were mostly female (53%), had a mean age of 31.6 y, and often admitted to an adult internist in a general hospital under emergency. Principal diagnoses and procedures (when performed) varied with diagnosis and age at admission. EA patients were admitted with dysphagia and foregut symptoms and often underwent upper endoscopy with dilation. CDH patients were often admitted for diaphragmatic hernias and underwent adult diaphragm repair. Hirschsprung patients were often admitted for intestinal obstructive issues and frequently underwent colonoscopy but trended toward operative intervention with increasing age. Adults with congenital disease continue to require hospital admission and invasive procedures. As age increases, diagnoses and performed procedures for each diagnoses evolve. These data could guide the formulation of multispecialty disease-specific follow-up programs for these patients. [ABSTRACT FROM AUTHOR]

Hirschsprung Disease (HD) is a rare cause of functional bowel obstruction in children. Patients are typically diagnosed in the neonatal period and undergo pull-through (PT) soon after diagnosis. The optimal management and post-operative outcomes of children who present in a delayed fashion are unknown. A multi-center retrospective review of children with HD was performed at participating Pediatric Colorectal and Pelvic Learning Consortium sites. Children were stratified by age at diagnosis (neonates <29 days; infants 29 days–12 months; toddler 1 year–5 years and child >5 years). 679 patients with HD from 14 sites were included; Most (69%) were diagnosed in the neonatal period. Age at diagnosis was not associated with differences in 30-day complication rates or need for PT revision. Older age at diagnosis was associated with a greater likelihood of undergoing fecal diversion after PT (neonate 10%, infant 12%, toddler 26%, child 28%, P < 0.001) and a greater need for intervention for constipation or incontinence postoperatively (neonate 56%, infant 62%, toddler 78%, child 69%, P < 0.001). Delayed diagnosis of HD does not impact 30-day post-operative outcomes or need for revision surgery but, delayed diagnosis is associated with increased need for fecal diversion after pull-through. III [ABSTRACT FROM AUTHOR]

Purpose: To characterise the investigations, management and ultimate diagnosis of neonates with distal intestinal obstruction. Methods: Retrospective review of term (> 37 weeks) neonates with admission diagnosis of distal intestinal obstruction over 10 years (2012–2022). Patient pathways were identified and associations between presentations, response to treatments and outcome investigated. Results: A total of 124 neonates were identified and all included. Initial management was colonic irrigation in 108, contrast enema in 4, and laparotomy in 12. Of those responding to irrigations none underwent contrast enema. Ultimately, 22 neonates proceeded to laparotomy. Overall, 106 had a suction rectal biopsy and 41 had genetic testing for cystic fibrosis. Final diagnosis was Hirschsprung disease (HD) in 67, meconium ileus with cystic fibrosis (CF) in 9, meconium plug syndrome in 19 (including 3 with CF), intestinal atresia in 10 and no formal diagnosis in 17. Median length of neonatal unit stay was 11 days (7–19). Conclusions: Initial management of neonates with distal bowel obstruction should be colonic irrigation since this is therapeutic in the majority and significantly reduces the need for contrast enema. These infants should all have suction rectal biopsy to investigate for HD unless another diagnosis is evident. If a meconium plug is passed, testing for CF is recommended. Evaluation and therapy are multimodal and time consuming, placing burden on resources and families. [ABSTRACT FROM AUTHOR]

Objective To discuss the clinical features, differential diagnosis and complication treatment of a patient with genetic visceral myopathy. Methods Medical history, physical examination and laboratory results of the patient were collected in detail. The pathology of previous surgery was reviewed. The patient's peripheral blood DNA was extracted and submitted for whole-exome sequencing. Subsequent Sanger sequencing was used to complete the pedigree verification of the mutation site. Results The patient was a young female presented with repeated incomplete intestinal obstruction since early childhood. She used to be misdiagnosed as Hirschsprung's disease for a long period and underwent multiple gastrointestinal segment resections. Her intestinal obstruction symptoms were temporarily relieved by surgeries, but severe diarrhea, mucus and bloody stools and malnutrition gradually occurred after the last operation. The patient had bacterial overgrowth in small intestinal tract and followed by intestinal opportunistic infections secondary to chronic intestinal pseudo-obstruction. The symptoms improved after anti-infection and enteral element diet treatment. Further pathological consultation and whole-exome gene sequencing confirmed the diagnosis of visceral myopathy related to ATCG2 R148L mutation. Conclusions Patients with early onset of chronic intestinal pseudo-obstruction and have poor response to conventional treatment are recommended to perform genetic test. The patients with hereditary visceral myopathy are susceptible to opportunistic intestinal infection. Attentions should also be paid to the prevention and treatment of complications to avoid unnecessary surgery. [ABSTRACT FROM AUTHOR]

Despite surgical advances for complex congenital colorectal conditions, such as anorectal malformation (ARM) and Hirschsprung disease (HD), many adolescents require transfer from specialist pediatric to adult providers for ongoing care. A systematic review of PubMed, MEDLINE and Embase was conducted to identify what is known about the transitional care of patients with ARM and HD (PROSPERO # CRD42022281558). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework guided our reporting of studies that focused on the transition care of 10–30-year-olds with ARM and HD. Eight studies were identified that included patient and parent (n = 188), and/or clinician perspectives (n = 334). Patients and clinicians agreed that transitional care should commence early in adolescence to support transfer to adult care when a suitable level of maturation is reached. There was little evidence from patients that transfer happened in a timely or coordinated manner. Patients felt that clinicians did not always understand the significance of transfer to adult services. No models of transition care were identified. Surgeons ranked ARM and HD as the most common conditions to experience delayed transfer to adult care. Beyond pediatric surgeons, patients also highlighted the importance of general practitioners, transitional care coordinators and peer support groups for successful transition. There is little research focused on transitional care for patients with ARM and HD. Given evidence of delayed transfer and poor experiences, the development of models of transitional care appears essential. • The nature of health issues faced by adolescents with congenital colorectal conditions, and the health professionals who care for them, is complex, but poorly described in the literature. We did not identify any successful models of transitional care for this surgical cohort. [ABSTRACT FROM AUTHOR]

Studies of mental health in adolescents with Hirschsprung disease (HD) are scarce. This cross-sectional study investigates mental health, psychosocial functioning and quality of life in HD adolescents. Adolescents (12–18 years) treated at the Department of pediatric surgery at Oslo University Hospital were invited for participation. Mental health was assessed by interview; Child Assessment Schedule (CAS) and questionnaires; parental Child Behavior Checklist (CBCL) and adolescent Youth Self-Report (YSR). Psychosocial functioning was rated by Child Global Assessment Scale (cGAS). Adolescent Quality of Life was assessed by Pediatric Quality of Life inventory (PedsQL) and chronic family difficulties (CFD) by interview. Medical records were reviewed for somatic history. Thirty-seven adolescents, 28 males, median age 14.3 years, participated. By CAS interview, 8 of 37 (44% of females and 14% of males) fulfilled criteria for psychiatric diagnosis all within emotional and related disorders. Twenty-seven percent had CBCL internalizing scores and 16% had YSR internalizing scores in clinical range indicating emotional problems. By interviewer rated cGAS, 27% were scored in clinical range. By PedsQL 16% reported reduced psychosocial health score. Increased CFD, lower psychosocial functioning and reduced QoL as well as less paternal education were significantly associated with psychiatric diagnosis. Twice as many (4/8) adolescents who either had a stoma or bowel management had a psychiatric diagnosis compared to those who had neither stoma nor bowel management (7/28). Nearly one in four adolescents with HD fulfilled criteria for psychiatric diagnosis. Mental health problems were associated with reduced psychosocial function and reduced QoL. III. [ABSTRACT FROM AUTHOR]

Background: Pediatric colorectal specialists care for patients with a variety of defecation disorders. Anorectal (AR) manometry testing is a valuable tool in the diagnosis and management of these children. This paper provides a summary of AR manometry techniques and applications as well as a review of AR manometry findings in pediatric patients with severe defecation disorders referred to a pediatric colorectal center. This is the first study describing multi-year experience using a portable AR manometry device in pediatric patients. Methods: An electronic medical record review was performed (1/2018 to 12/2023) of pediatric patients with defecation disorders who had AR manometry testing. Demographics, diagnostic findings, and outcomes are described. Key Results: A total of 297 unique patients (56.9% male, n = 169) had AR manometry testing. Of these, 72% (n = 188) had dyssynergic defecation patterns, of which 67.6% (n = 127) had fecal soiling prior to treatment. Pelvic rehabilitation (PR) was administered to 35.4% (n = 105) of all patients. A total of 79.5% (n = 58) of the 73 patients that had fecal soiling at initial presentation and completed PR with physical therapy and a bowel management program were continent after therapy. AR manometry was well tolerated, with no major complications. Conclusions: AR manometry is a simple test that can help guide the management of pediatric colorectal surgical patients with defecation disorders. As a secondary finding, PR is a useful treatment for patients with dyssynergic stooling. [ABSTRACT FROM AUTHOR]