Hirschsprung's Disease Research Articles

Diagnosis of Hirschsprung disease by analyzing acetylcholinesterase staining using artificial intelligence.

Classical Hirschsprung disease (HD) is defined by the absence of ganglion cells in the rectosigmoid colon. The diagnosis is made from rectal biopsy, which reveals the aganglionosis and the presence of cholinergic hyperinnervation. However, depending on the method of rectal biopsy, the quality of the specimens and the related diagnostic accuracy varies substantially. To facilitate and objectify the diagnosis of HD, we investigated whether software-based identification of cholinergic hyperinnervation in digitalized histopathology slides is suitable for distinguishing healthy individuals from affected individuals. N = 190 samples of 112 patients who underwent open surgical rectal biopsy at our pediatric surgery center between 2009 and 2019 were included in this study. Acetylcholinesterase (AChE) stained slides of these samples were collected and digitalized via slide scanning and analyzed using two digital imaging software programs (HALO, QuPath). The AChE-positive staining area in the mucosal layers of the intestinal wall was determined. In the next step machine learning was employed to identify patterns of cholinergic hyperinnervation. The area of AChE-positive staining was greater in HD patients compared to healthy individuals (p < 0.0001). Artificial intelligence-based assessment of parasympathetic hyperinnervation identified HD with a high precision (area under the curve [AUC] 0.96). The accuracy of the prediction model increased when nonrectal samples were excluded (AUC 0.993). Software-assisted machine-learning analysis of AChE staining is suitable to improve the diagnostic accuracy of HD.

Flowmetry and spectrophotometry can detect reduced intestinal microperfusion in nonsurvivors during equine colic surgery for large intestinal strangulation.

To evaluate the use of laser Doppler flowmetry and spectrophotometry (LDFS) for large intestinal viability assessment in horses with naturally occurring large intestinal strangulations. By use of LDFS, intestinal microperfusion was quantified as tissue oxygen saturation (tSo2), hemoglobin (tHB), and blood flow (tBF) in cases with large colon volvulus and small colon strangulations undergoing colic surgery (n = 17). Intestinal biopsies were taken from the pelvic flexure in all large colon cases and in small colon cases that underwent intraoperative euthanasia. Measurements were compared between survivors and nonsurvivors, and the correlation between LDFS and (immuno)histology was tested (P < .05). The tSo2 and tBF were clearly lower and tHB was higher than previously reported in healthy horses. Following correction of the lesion, pelvic flexure tBF was significantly lower than that of the left ventral colon. Prior to correction of the lesion, microperfusion did not differ between survivors and nonsurvivors, but following release of the strangulation the survivors had a significantly higher tSo2 and tBF compared to the nonsurvivors. There was a negative correlation between tBF and interstitium-to-crypt ratio and a positive correlation between tHB and the histological hemorrhage score. There were no significant correlations between LDFS measurements and inflammatory cell counts or hypoxia-inducible factor-1α immunoreactivity. Large intestinal microperfusion was decreased in nonsurvivors compared to survivors and was correlated with histological injury, suggesting that LDFS has the potential to predict tissue injury and postoperative survival. The use of LDFS as an ancillary diagnostic aid may improve intraoperative viability assessment during colic surgery.

Human enteric nervous system progenitor transplantation improves functional responses in Hirschsprung disease patient-derived tissue

ObjectiveHirschsprung 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...

H3K36 methyltransferase SMYD2 affects cell proliferation and migration in Hirschsprung's disease by regulating METTL3.

The pathogenesis of Hirschsprung's disease (HSCR) is complex. Recently, it has been found that histone modifications can alter genetic susceptibility and play important roles in the proliferation, differentiation and migration of neural crest cells. H3K36 methylation plays a significant role in gene transcriptional activation and expression, but its pathogenic mechanism in HSCR has not yet been studied. This study aimed to elucidate its role and molecular mechanism in HSCR. Western blot analysis, immunohistochemistry (IHC) and reverse transcription-quantitative PCR (RT‒qPCR) were used to investigate H3K36 methylation and methyltransferase levels in dilated and stenotic colon tissue sections from children with. We confirm that SMYD2 is the primary cause of differential H3K36 methylation and influences cell proliferation and migration in HSCR. Subsequently, quantitative detection of m6A RNA methylation revealed that SMYD2 can alter m6A methylation levels. Western blot analysis, RT-qPCR, co-immunoprecipitation (co-IP), and immunofluorescence colocalization were utilized to confirm that SMYD2 can regulate METTL3 expression and affect m6A methylation, affecting cell proliferation and migration. These results confirm that the H3K36 methyltransferase SMYD2 can affect cell proliferation and migration in Hirschsprung's disease by regulating METTL3. Our study suggested that H3K36 methylation plays an important role in HSCR, confirming that the methyltransferase SMYD2 can affect m6A methylation levels and intestinal nervous system development by regulating METTL3 expression.

Applications of Indocyanine Green (ICG) fluorescence in pediatric colorectal conditions

Postoperative success in pediatric colorectal surgery hinges on achieving adequate perfusion during complex reconstructive procedures. This review synthesizes findings from recent publications regarding the application of Indocyanine Green (ICG) in various surgical interventions for conditions such as Hirschsprung disease, anorectal malformations, cloacal reconstructions, and others.Preliminary evidence suggests that ICG fluorescence enhances intraoperative decision-making by improving vascular visualization and assessing tissue perfusion. Compared to conventional methods, ICG may offer superior evaluation of intestinal perfusion.While initial reports indicate a favorable safety profile for ICG use in pediatric patients, further prospective studies are needed to confirm these observations, quantify benefits, and assess its impact on surgical outcomes. By providing real-time perfusion data, ICG holds promise for enhancing surgical precision and improving patient outcomes in pediatric colorectal surgery.

Peutz-Jeghers syndrome: A case series

IntroductionPeutz-Jeghers syndrome (PJS) is a rare hereditary disorder characterized by gastrointestinal hamartomatous polyps, due to mutation of the STK11/LKB1 gene located on chromosome 19p. The polyps are most commonly found in the small bowel followed by colon. Case presentationOur case series includes 4 patients, three being male and one female. Each of them either presented with abdominal pain and other associated symptoms. Oral cavity and lip melanin pigmentation were common. CT abdomen revealed multiple large jejunal, ileal, gastric and colon polyps. Cancer was found in one patient. Different surgical approaches were adopted. All recovered well. DiscussionPJS is an autosomal dominant disorder with an estimated incidence of 1:50,000 to 1:200,000 cases with a significant family history. Mostly found in small bowel followed by colon, it can also occur in a rare organ like gall bladder as evident in our case. PJS carries a substantial risk for gastrointestinal cancer. The treatment modality depends on the site of polyp, mode of presentation and availability of the expertise. ConclusionPJS is a common disease in our part which is usually observed in teen age groups male. They have a varied presentation, from intestinal obstruction (due to intussusception) to GI bleeding. Colonic malignancy at young age may be the first presentation of the disease. Observation of melanin pigmentations on lips helps diagnose the disease; and one should always look at this findings in a young patient with pain abdomen or in intestinal obstruction to confirm/exclude the disease.

Intradyadic Correlation Between Parent-reported and Child-reported Quality of Life in Patients With Anorectal Malformation and Hirschsprung's Disease in Comparison to Healthy Controls

BackgroundQuality of life (QOL) is an important clinical endpoint in paediatric chronic conditions. How parent-proxy reports differ from child self-reported QOL in patients with anorectal malformation (ARM) and Hirschsprung's disease (HD) has not been well examined to date. This study evaluates agreement between parent-proxy and child-reported QOL scores in ARM and HD patients compared to healthy controls. MethodsWe recruited ARM and HD patients aged 5–17 years and their parents at four tertiary referral centres between December 2020 to February 2023 who had corrective surgery done >12 months prior. Healthy controls were age-matched and gender-matched. They completed the Pediatric Quality of Life Inventory™ (PedsQL™) Generic Core Scales and General Well-Being (GWB) Scale. The questionnaires were administered in parallel parent-proxy-report and child self-report formats. Appropriate statistical analysis was performed with p < 0.05 significance. Data are reported as median (interquartile range). Ethical approval was obtained. ResultsThere were 65 ARM, 54 HD and 83 controls. There were no significant differences between parent-reported scores and child-reported scores overall in the Total, Psychosocial Health and Physical Health components of Core Scales for ARM, HD and controls. However, parent-reported scores were significantly higher than child-reported scores overall in ARM, HD and controls in the GWB Scale. ConclusionOur findings show that parent-rated and child-rated overall QOL was similar in Core Scales for ARM, HD, and controls. However, parents overestimated child's overall GWB for ARM, HD and controls. This highlights the importance of capturing the perspectives of both parents and children to inform strategies to improve patient care. Level of EvidenceLevel III.

Minimally Invasive Surgery for Hirschsprung Disease: Current Practices and Future Directions.

Hirschsprung disease (HD) is a congenital disorder characterized by the absence of ganglion cells in the distal colon and rectum, leading to functional obstruction and severe constipation. Over the past decades, the surgical management of HD has significantly evolved, with minimally invasive surgery (MIS) techniques revolutionizing treatment approaches. This review explores recent innovations in MIS for HD, focusing on laparoscopic, transanal endorectal pull-through (TERPT), and robotic-assisted techniques. These approaches offer numerous advantages over traditional open procedures, including reduced surgical trauma, improved cosmesis, faster recovery times, and potentially lower complication rates. Laparoscopic surgery has become widely adopted, providing excellent visualization and precise dissection. TERPT has gained popularity for short-segment disease, offering a completely transanal approach with minimal scarring. Robotic-assisted surgery represents the cutting edge, enhancing surgical precision and dexterity. The review also examines emerging technologies and future directions, such as advanced imaging techniques, artificial intelligence applications, and potential developments in tissue engineering. While MIS techniques have shown promising outcomes, challenges remain in standardizing approaches, addressing long-segment disease, and optimizing long-term functional results. The future of HD surgery lies in personalized approaches that integrate genetic and molecular profiling with advanced surgical technologies. As the field continues to evolve, comprehensive long-term studies and efforts to improve access to specialized care will be crucial to further enhancing outcomes for patients with HD.

Development of Prediction Model for Hirschsprung-Associated Enterocolitis (HAEC) in Postoperative Hirschsprung Patients

BackgroundDespite identifying numerous risk factors for postoperative Hirschsprung-associated enterocolitis (HAEC), predicting individual risk remains challenging. This study aimed to develop a clinical prediction model for predicting the probability of postoperative HAEC within 5 years after surgery in Hirschsprung individuals. MethodsThe study included all children with Hirschsprung disease who underwent definitive surgery at Chiang Mai University Hospital from 2006 to 2021. Concomitant anorectal abnormalities and incomplete data were excluded. A multivariable logistic regression analysis, adjusted for correlated data, was utilized to develop the prediction model. ResultsOf the included 274 patients, 75 patients (27.4%) experienced postoperative HAEC within 5 years, totaling 121 episodes. Based on statistical and theoretical significance, eight parameters were utilized as predictors, which included male (OR1.23,95%CI:0.53–2.86), trisomy21(OR1.34,95%CI:0.21–8.45), weight at the time of surgery (OR0.86,95%CI:0.73–1.02), absence of exclusive breastfeeding (OR1.51,95%CI:0.65–3.51), length of the aganglionic segment (rectosigmoid (OR1.32,95%CI:0.48–3.62), long segment (OR41.39,95%CI:3.00–570.37), and total colonic aganglionosis (OR710.20,95%CI:23.55–21420.72)), preoperative stoma (OR1.72,95%CI:0.34–8.58), surgical approach (Duhamel (OR0.06,95%CI:0.01–0.81) and abdominal assisted trans anal endorectal pull-through (OR0.04,95%CI:0.002–0.65)), and early HAEC before two weeks following surgery (OR1.98,95%CI:0.67–5.82). The derived predictive model exhibited acceptable discriminative performance (AuROC:0.749,95%CI:0.679–0.816). Risk groups were categorized into low and high-risk, with positive likelihood ratios of 0.65 and 10.70, respectively. Recommendations for management and follow-up were generated based on these risk groups. An online application has been developed for calculating individual risk of postoperative HAEC and offering management suggestions with follow-up schedule: [https://w1.med.cmu.ac.th/surgery/personnel/pedsurgerycmu/#HAEC-Calculator]. ConclusionsThis risk predictive model accurately estimates the probability of postoperative HAEC within 5 years after surgery in Hirschsprung patients. It facilitates risk stratification and provides personalized recommendations to parents for the prevention and early detection of postoperative HAEC. Levels of EvidenceLevel II Retrospective cohort study (Prognosis study).

Is the Transrectal Diameter (TRD) Suitable for Assessing Faecal Loads and Monitoring Bowel Management in Children with Hirschsprung Disease-ReKiSo Study: Prospective Study.

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. 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. 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. 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.

Hirschsprung's disease: a review

Hirschsprung disease (HD) is a congenital condition that affects intestinal function due to the absence of ganglion cells in the myenteric and submucosal plexus of the colon. This absence causes difficulty in intestinal relaxation and, consequently, normal intestinal evacuation, resulting in severe constipation from birth or early childhood. At the genetic level, mutations have been identified in genes such as RET, involved in the migration and differentiation of neural crest cells. The diagnosis is based on rectal biopsies that show the absence of ganglion cells. The main treatment is surgical, with techniques such as rectosigmoidectomy or pull-through to restore intestinal function. Despite advances, patients can experience complications such as fecal incontinence. Multidisciplinary management is crucial to improve the patient's quality of life.

Surgical Strategies in Total Colonic Aganglionosis: Primary Pullthrough-Pathway of Care.

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.

A multi-center cross-sectional comparison of parent-reported quality of life and bowel function between anorectal malformation and Hirschsprung's disease patients with versus those without Down syndrome.

Down syndrome (DS) is a common abnormality associated with anorectal malformation (ARM) and Hirschsprung's disease (HD). However, quality of life (QOL) in ARM and HD patients with DS is under-researched. This study compares parent-reported QOL and bowel function in ARM and HD patients with DS to those without. Between December 2020 to February 2023, parents of ARM and HD patients with and without DS aged 3-17 years who had undergone surgery > 12 months prior at four tertiary referral centers were recruited. We used the Pediatric Quality of Life Inventory™ (PedsQL™) Generic Core Scales, General Well-Being (GWB) Scale and Family Impact (FI) Module questionnaires, and the Rintala bowel function score (BFS). There were 101 ARM, 9 (8.9%) of whom had DS; and 87 HD, of whom 6 (6.9%) had DS. Parent-reported Core scores in ARM and HD with DS were comparable to those without DS. However, ARM and HD with DS had worse scores in the FI Module and bowel function than those without DS. Although parent-reported QOL in ARM and HD with DS is similar to those without DS, family impact and BFS are worse. Our findings are limited by small sample size in proportion of DS patients.

Major stoma complications in pediatric patients in a tertiary hospital in a low-middle-income country: a retrospective cohort study.

Intestinal stomas are one of the most common parts of pediatric surgical care,and complications arising from it have significant impact on overall patient outcomes. However, data on major complications in low-middle-income countries remain limited. This pilot retrospective cohort study aimed to investigate the prevalence, types, and management of major stoma complications in pediatric patients at a tertiary government hospital in the Philippines. Medical records of pediatric patients with major stoma complications classified as Clavien-Dindo III-V from June 2018 to June 2023 were reviewed. Patient-related factors (age, sex, diagnosis) and surgery-related factors (stoma type and location, surgeon expertise) were analyzed. Descriptive statistics characterized demographic profiles, while Chi-square and t tests analyzed categorical and continuous variables, respectively. Multivariable logistic regression evaluated independent associations with major stoma complications. Out of 1041 pediatric patients with stomas, 102 cases had major complications, representing a prevalence rate of 9.8%. Mortality directly attributed to stoma complications accounted for 1.3% of the total cases, or 14 deaths in 5years. Neonates comprised a significant portion, primarily diagnosed with congenital conditions like anorectal malformation and Hirschsprung's disease. Ileostomies exhibited a higher incidence of major complications compared to other stoma types. Stomal prolapse and adhesive bowel obstruction are the most common reported stoma complications requiring surgical intervention while stoma revision is the most frequent corrective procedure. The median time from stoma creation to presentation of major complication was 14months, with nearly half of the complications occurring within the first year. Only the presence of ileostomy had significant association with the development of major complications among the risk factors analyzed. This study provides useful insights into stoma complications in pediatric patients in a low-middle income country. Despite the lack of significant associations between the patient-related and surgeon-related factors, and major stoma complications, further investigation into other contributing factors is warranted. Improvements in data collection methods and prospective studies with larger sample sizes are recommended to enhance understanding and optimize care of major stoma complications. Addressing the challenges identified in this study could lead to a comprehensive and tailored approach to pediatric stoma care and their complications.

Enteric neural stem cell transplant restores gut motility in mice with Hirschsprung disease.

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.

Enough is enough: how many rectal suction biopsies do you need to diagnose Hirschsprung’s disease?

PurposeRectal suction biopsy (RSB) is the gold standard for diagnosing Hirschsprung’s disease (HD) in infants. Despite being a common procedure, no standard exists on the number of biopsy specimens and their respective level within the rectum.MethodsWe conducted a retrospective review of epidemiological and pathological data of patients who underwent RSB at our institution between January 2011 and May 2022. During RSB we obtain 4 specimens: at 1 cm, 3 cm and 5 cm above the dentate line, besides one specimen at the dentate line. We used a logistic regression model for statistical analysis and included control variables (e.g. underlying disease, weight at first biopsy, gestational age).ResultsA total of 92 patients underwent 115 biopsies, with an average of 3.77 specimens per session. Of the specimens taken at 1 cm above the dentate line 73.9% were conclusive, at 3 cm 75.9% and at 5 cm 79.2%. Specimens taken at the dentate line were squamous or transitional epithelia in 31.5% and therefore of no use for HD diagnostics. The specimen at 3 cm shows the highest discriminative power whether the biopsy session was diagnostic (p-value < 1%).ConclusionsWe propose that a total of three specimens, namely one at 1 cm, one at 3 cm and one at 5 cm above the dentate line, is enough to diagnose or exclude HD.

Technical evaluation and fecal continence of laparoscopic-assisted procedures for total colonic aganglionosis

Total colonic aganglionosis (TCA), defined as aganglionosis extending from the anus up to the distal ileum, is a rare variant of Hirschsprung's disease. Surgery for TCA aims to remove the aganglionic colon and reconstruct the intestinal tract by bringing the normally innervated ileum down to the anus while preserving normal sphincter function. Laparoscopy with surgeries including laparoscopic-assisted Duhamel-like and Soave-like pull-through procedures have been progressively applied to the treatment of TCA over the past two decades and may become the dominant treatment for TCA in the future. Postoperative fecal continence, involving issues such as normal defecation, Hirschsprung-associated enterocolitis (HAEC), frequent stool and perianal erosion (perineal rash), soiling/fecal incontinence and constipation/obstructive symptoms, is very important to patients. These complications require nutritional support and comprehensive postoperative gastroenterological care and even require permanent ileostomy and redo pull-through. Some patients have previously seen a psychologist for frequent complaints of diarrhea and other physical symptoms. Patients with TCA postoperatively must be evaluated regularly by pediatric surgeons, enterostoma therapists, gastroenterologists, dieticians and psychologists to achieve a good nutritional status and psychological health.

Assessing fecal load with ultrasound in children with colorectal pathology: ReKiSo study

PurposeTo evaluate bowel management for children with colorectal pathology by measuring transverse rectal diameter (TRD) and assessing fecal load with transabdominal rectal ultrasound (TRU).MethodsProspective case–control study of children receiving bowel management (BM) between 04/2023 and 04/2024 was done. There was inclusion of patients with Hirschsprung disease (HD), anorectal malformation (ARM) and functional constipation (FC). Patients with other congenital or neurological conditions were excluded. Control group consisted of inpatients and outpatients without abdominal complaints. FC was diagnosed according to ROM-IV-criteria. For HD and ARM, we followed a list of symptoms. To assess fecal load, we visualized the TRD using the Klijn (Klijn et al. in J Urol 172:1986–1988, 2004) method. The bladder was moderately full. The fecal load was assessed retrograde from the rectum. Follow-up was at 1/3/6 months. Secondary data were collected from medical records. Sample size calculated a priori and follow-up group with new gathered data.Resultsp value for TRD in all groups significant with p < 0.05 and in grouped follow-up.ConclusionUltrasound is a useful tool for assessing fecal load and helps diagnose constipation and monitor BM. Irrespective of colorectal pathology, a cut-off of 3 cm seems to discriminate between children without constipation/overload symptoms and asymptomatic patients. We present a radiation-free method for monitoring bowel management.

A protocol for neoWONDER: Neonatal whole population data linkage to improve long-term health and wellbeing of preterm and sick babies.

Early-life medical and surgical interventions in babies born preterm and/or with surgical conditions influence later life health and educational outcomes. Obtaining long-term outcomes post-discharge to evaluate the impact of interventions is complex, expensive, and burdensome to families. Linkage of routinely collected data offers a feasible and cost-effective solution. The NeoWONDER research programme aims to describe the short and long-term health and educational outcomes for babies born preterm and/or with surgical conditions and evaluate the impact of neonatal care and interventions on later health and educational outcomes. We will include babies who received care in neonatal units in England and Wales, born between 2007-2020 with a gestational age below 32 weeks (approximately 100,000), and/or born between 2012-2020 (all gestations) with any of six surgical conditions: necrotising enterocolitis, Hirschsprung's disease, gastroschisis, oesophageal atresia, congenital diaphragmatic hernia, and posterior urethral valves (approximately 8,000). A detailed list of surgical condition codes is shown in S3 File. We will obtain long-term health and education outcomes through linkage of the National Neonatal Research Database, which contains routine data for all babies admitted to NHS neonatal units, to other existing health and educational datasets. For England, these are: Hospital Episode Statistics, the Office for National Statistics, Mental Health Services Dataset, Paediatric Intensive Care Audit Network, National Pupil Database; and for Wales, the Secure Anonymised Information Linkage databank. Analysis will be undertaken on de-identified linked datasets. Outcomes of interest for health include mortality, hospital admissions, diagnoses indicative of neurodisability and/or chronic illness, health care utilisation; and for education are attainment (using national curriculum assessments), school absence and special educational needs status.

The Pathologist's Role in the Diagnosis of Hirschsprung's Disease.

The possibilities, recent advances, and pitfalls in the histopathologic workup of specimens submitted for the diagnosis of Hirschsprung's disease (HSCR) are presented. A literature research was performed in the database PubMed including the years 2000 to 2024. The pathologist is involved in the diagnosis of HSCR in three scenarios: (1) the primary diagnosis in a child with the typical clinical symptoms, (2) the intra-operative guidance of surgery in a case where the diagnosis is already established, and (3) the confirmation of the diagnosis and the documentation of the extent of the disease in the resected specimen. Identification of ganglion cells in the enteric neural plexuses excludes HSCR, and the histological confirmation of a complete absence of these ganglion cells is the gold standard for its diagnosis. However, difficulties in the detection of ganglion cells with standard stains and/or a limited amount of tissue in the specimen submitted for diagnosis make supportive histologic stains and techniques, e.g., calretinin immunohistochemistry or acetylcholinesterase histochemistry necessary for an unequivocal diagnosis of HSCR. Improving the diagnostic accuracy of this life-threating disease is an interdisciplinary task. A good communication between pathologist and clinician, as well as mutual knowledge of skills and challenges of the other discipline, is necessary for a successful diagnostic teamwork.