Hirschsprung's Disease Research Articles

Enteric neural stem cell neurogenesis by glial cell-derived neurotrophic factor in experimental Hirschsprung's disease

Enteric neural stem cell neurogenesis by glial cell-derived neurotrophic factor in experimental Hirschsprung's disease

Atypical Presentation of Hirschsprung's Disease in an Infant: Challenges in Early Diagnosis and Management of Recurrent Enterocolitis

Atypical Presentation of Hirschsprung's Disease in an Infant: Challenges in Early Diagnosis and Management of Recurrent Enterocolitis

For short-segment Hirschsprung disease, daily trans-anal irrigation before pull-through surgery is necessary?

To explore the role of daily trans-anal irrigation (TAI) before pull-through surgery in preventing Hirschsprung disease-associated enterocolitis (HAEC) and improving other clinical outcomes in short-segment Hirschsprung disease (HSCR). We enrolled the children with short-segment HSCR who received primary pull-through surgery from February 2012 to August 2019 at our hospital. They were divided into two groups. Daily TAI group: daily TAI once diagnosed until undergoing surgery. Non-daily TAI group: anal dilation or glycerine enema, supplemented with TAI if these were noneffective. HAEC, nutritional status at surgery, postoperative rehabilitation, and long-term defecation function were compared. A total of 191 children were enrolled, 147 in the Daily TAI group and 44 others. 44 pairs of children were successfully matched by 1:1 propensity score matching. In all, 10 (11.36%) of the 88 children developed HAEC, 5 (5/44, 11.36%) in the Daily TAI group and 5 (5/44, 11.36%) in another, and the difference was not statistically significant (χ2 = 0.000, p = 1.000). Besides, there was no significant difference in the nutritional status at surgery, postoperative rehabilitation indicators, and the defecation function. For children with short-segment HSCR, preoperative daily TAI had no significant advantage over non-daily TAI in preventing HAEC and improving other clinical outcomes. For children with short-segment Hirschsprung disease, one or more times trans-anal irrigations (TAI) per day before pull-through surgery may not be necessary. Daily TAI had no significant advantage over non-daily TAI in preventing preoperative and postoperative HAEC. Whether to receive daily TAI before surgery did not affect postoperative recovery and long-term defecation function.

Acute presentation of short‑segment Hirschsprung's disease treated with Soave's procedure in a 20‑year‑old male: A case report and mini‑review of the literature

Acute presentation of short‑segment Hirschsprung's disease treated with Soave's procedure in a 20‑year‑old male: A case report and mini‑review of the literature

To the 60th anniversary of Igor Vitalievich Poddubny

Prof. Igor V. Poddubny, a member of the Editorial Board of the Russian Journal of Pediatric Surgery, Dr. Sci. (med), celebrated his 60th anniversary on September 25, 2024. The basic area of his interest and research is mini-invasive endoscopic surgeries in children and adolescents. He has developed and implemented into clinical practice modern surgical techniques for treating children with various emergency and elective surgeries in urology, coloproctology and gynecology. He was the first in Russia to perform endoscopic surgical interventions for varicocele, abdominal cryptorchidism, cysts of parenchymal organs of the abdominal cavity and retroperitoneal space, as well as laparoscopic nephrectomy, heminephroterectomy, adrenalectomy. He also operated patients with Hirschsprung's disease, ulcerative colitis, Crohn's disease, colon polyposis, complex malformations of the uterus and vagina, etc.

Is Butyrate Concentration in the Equine Gastrointestinal Tract Altered During and After Surgery for Treatment of Large Colon Obstruction?

A major cause of morbidity and mortality in horses with large colon obstructive lesions is injury to the colonic mucosal barrier from ischemic injury. Since butyrate has been shown to play a critical role in the maintenance of a healthy mucosal barrier, it may play a role in the recovery process. This study’s objective was to determine whether the differences in butyrate concentrations existed between horses with surgical large colon obstructive lesions and healthy horses both during and after surgery. Eleven horses presenting with surgical colic lesions were enrolled; colonic samples were acquired during surgery, and fecal samples were obtained 36 h later. Colonic and fecal samples were also obtained from control groups. Samples were analyzed for butyrate, acetate, and propionate concentrations. There was no significant difference in butyrate content between surgical colonic or fecal samples and controls; however, an alteration in the proportion of SCFAs in relation to one another was noted. These changes in the individual SCFA levels were not statistically significant. The study findings demonstrated that there were no significant differences in butyrate proportions when comparing samples from horses with surgical colic lesions to healthy control horses.

Congenital Anomalies of the Kidney and Urinary Tract in Patients with Hirschsprung Disease.

To determine the frequency and types of congenital anomalies of the kidney and urinary tract (CAKUT) in patients with Hirschsprung disease. An observational cross-sectional study. Place and Duration of the Study: Department of Paediatric Surgery, National Institute of Child Health, Karachi, Pakistan, from June to December 2022. All patients with biopsy-proven Hirschsprung disease were included. Ultrasound was done to find out the anatomical and structural anomalies of the kidney and urinary tract. Functional assessment was done by renal function tests and MAG3 radioisotope scan where indicated. Fisher's exact test was applied to find out the association. A p ≤0.05 was taken as significant. Out of a total of 83, 15 (18.0%) patients had CAKUT. The mean age of the study population was 5.5 ± 2.3 years. It included 61 (73.5%) males and 22 (26.5%) females. No significant association was found between the type of Hirschsprung disease and CAKUT (p = 0.7). The gender distribution between CAKUT patients was also insignificant (p = 0.7). Renal hypoplasia was the most common anomaly found in six patients followed by hydronephrosis due to pelvi-ureteric junction obstruction in four children. All of these children were asymptomatic. Five male patients had undescended testis. Nearly a fifth of the children with Hirschsprung disease had CAKUT of whom renal dysplasia was the most common anomaly. There was no gender predilection and patients were asymptomatic regarding the urinary system. A routine ultrasound abdomen is a good screening investigation for identifying CAKUT. Hirschsprung disease, Kidney and urinary tract, Congenital diseases of the urinary tract, Congenital anomalies.

Congenital Anomalies of the Kidney and Urinary Tract in Patients with Hirschsprung Disease.

To determine the frequency and types of congenital anomalies of the kidney and urinary tract (CAKUT) in patients with Hirschsprung disease. An observational cross-sectional study. Place and Duration of the Study: Department of Paediatric Surgery, National Institute of Child Health, Karachi, Pakistan, from June to December 2022. All patients with biopsy-proven Hirschsprung disease were included. Ultrasound was done to find out the anatomical and structural anomalies of the kidney and urinary tract. Functional assessment was done by renal function tests and MAG3 radioisotope scan where indicated. Fisher's exact test was applied to find out the association. A p ≤0.05 was taken as significant. Out of a total of 83, 15 (18.0%) patients had CAKUT. The mean age of the study population was 5.5 ± 2.3 years. It included 61 (73.5%) males and 22 (26.5%) females. No significant association was found between the type of Hirschsprung disease and CAKUT (p = 0.7). The gender distribution between CAKUT patients was also insignificant (p = 0.7). Renal hypoplasia was the most common anomaly found in six patients followed by hydronephrosis due to pelvi-ureteric junction obstruction in four children. All of these children were asymptomatic. Five male patients had undescended testis. Nearly a fifth of the children with Hirschsprung disease had CAKUT of whom renal dysplasia was the most common anomaly. There was no gender predilection and patients were asymptomatic regarding the urinary system. A routine ultrasound abdomen is a good screening investigation for identifying CAKUT. Hirschsprung disease, Kidney and urinary tract, Congenital diseases of the urinary tract, Congenital anomalies.

Diagnosing Hirschsprung disease in children older than six months of age: complications after rectal biopsy, insight in final diagnoses and factors associated with Hirschsprung disease

Diagnosing Hirschsprung disease in children older than six months of age: complications after rectal biopsy, insight in final diagnoses and factors associated with Hirschsprung disease

052. Surgical Management of a Tumor Adhering to Ileum and Posterior Stomach: A Case Report

Background: Tumors in the transverse colon that invade adjacent organs, such as the ileum and posterior stomach, present complex surgical challenges. Resection and reconstruction are often required to achieve optimal outcomes. We present a case of a large transverse colon tumor adherent to the ileum and posterior gastric wall, managed with extensive surgical resection and reconstruction. Case: A 54-year-old male presented with abdominal pain, bloating, and weight loss. Imaging studies revealed a large mass originating from the transverse colon, adherent to the ileum and posterior gastric wall. Intraoperative findings confirmed the tumor’s adherence to the ileum, approximately 220 cm distal to the ligament of Treitz, as well as its invasion of the posterior gastric wall. The surgical team performed a multi-organ resection. The segment of ileum involved, located 220 cm from the ligament of Treitz, was resected, and an ileo-ileal anastomosis was performed. The primary tumor, located in the middle of the transverse colon, necessitated a total resection of the transverse colon, with subsequent anastomosis between the ascending and descending colon. Additionally, the portion of the posterior stomach adherent to the tumor was removed through subtotal gastrectomy, followed by a Billroth I reconstruction. Postoperatively, the patient recovered well, with no significant complications. Histopathology confirmed the tumor to be a moderately differentiated adenocarcinoma. The patient is currently undergoing adjuvant chemotherapy. Conclusion: This case highlights the complexity of managing tumors with multi-organ involvement. Comprehensive surgical resection, combined with appropriate reconstruction techniques, can result in favorable outcomes. Early detection and aggressive surgical management are essential in cases involving locally advanced tumors with invasion into adjacent structures.

Identification and validation of autophagy-related genes in Hirschsprung's disease.

Hirschsprung's disease (HSCR) is a congenital disorder characterized by aganglionosis in the intermuscular and submucosal nerve plexuses of the gut, leading to impaired gastrointestinal function. Although the precise cause and pathophysiology of HSCR remain elusive, increasing evidence points to a significant role of autophagy in its development, warranting further investigation into its underlying mechanisms. This study utilized publicly available microarray expression profiling datasets, GSE96854 and GSE98502, from the Gene Expression Omnibus (GEO). The R software (version 4.2.0) was employed to identify autophagy-related genes potentially showing differential expression in HSCR. Subsequent analyses included correlation analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) network analysis using the STRING database (version 11.0) and Cytoscape software (version 3.8.2). Ultimately, HSCR samples were used to verify the mRNA levels of important genes by quantitative real-time polymerase chain reaction (qRT-PCR) in a laboratory setting. We have discovered 20 genes that are involved in autophagy and show variable expression. Among these genes, 15 are up-regulated and five are down-regulated. The enrichment analysis using the GO and KEGG pathways revealed a notable enrichment in pathways related to the control of autophagy. Nine hub genes were found via the investigation of the PPI network constructed from STRING database and module analysis using Cytoscape. Moreover, the concordance between SIRT1 expression in the HSCR model and the bioinformatics analysis of mRNA chip findings was validated using qRT-PCR. Utilizing bioinformatics analysis, we identified 20 potential genes associated with Hirschsprung's disease that play a role in autophagy. Notably, the upregulation of SIRT1 may profoundly influence the progression of HSCR by regulating autophagy-related pathways, offering a novel perspective on the disease's pathogenesis.

004. Confirming The Diagnosis of Hirschsprung Associated Enterocolitis Based on The Hirschsprung Associated Enterocolitis Guidelines: A Literature Review

Background: Hirschsprung's disease (HD) is one of the most common causes of intestinal obstruction in neonates. One of the most frequently encountered complications, and the leading cause of morbidity and mortality in HD patients, is Hirschsprung-associated enterocolitis (HAEC). In 2017, Gosain et al. developed a guideline to aid in the diagnosis of HAEC, but there are limited studies discussing this guideline and diagnosing HAEC remains unclear. The aim of this study is to establish the diagnosis of HAEC in patients using the HAEC guideline. Methods: The studies were selected from online databases such as Scopus, EBSCOhost, PubMed, ScienceDirect, and Medline. Searches were conducted using Boolean OR and AND. Literature selection was based on abstracts, titles, and keywords. The literature selected were based on predetermined inclusion and exclusion criteria. Results: A total of 1,610 studies were identified from the literature search conducted on five databases using appropriate keywords. The articles were then screened using the PRISMA flow diagram, resulting in the selection of three articles that met the inclusion and exclusion criteria. These three selected studies included two retrospective cohort studies and one literature review and expert consensus study for the diagnosis of HAEC. Conclusion: The HAEC guideline by Gosain et al. can be used to clinically establish HAEC; however, it has not been tested in the population and remains an expert consensus, so its validity as a diagnostic guideline cannot yet be compared to previous scoring methods that have been analyzed in the HAEC patient population.

Angiopoietin-1 attenuates lipopolysaccharide-induced endotoxemia in a Hirschsprung's disease murine model by improving intestinal vascular integrity: implications for treating postoperative Hirschsprung-associated enterocolitis.

Angiopoietin-1 (Ang1) mitigates inflammation as a proangiogenic growth factor. Action of Ang1 on lipopolysaccharide (LPS)-induced endotoxemic inflammation was investigated in endothelin receptor-B null Hirschsprung's disease mice (KO). LPS or saline was injected intraperitoneally in KO (KO-LPS; n = 9, KO-sal; n = 5) and wild-type (WT) (WT-LPS; n = 6, WT-sal; n = 6) pups obtained within 24h of birth. Normoganglionic terminal ileum harvested 6h after LPS was used for RNA extraction and histology. IL-1β, SELE, VEGFA, Ang1, Angiopoietin-2 (Ang2), and TIE2 expression analyzed by quantitative polymerase chain reaction (qPCR), vascular permeability assessed by the Miles assay, severity of inflammation, and immunofluorescence for phospho-TIE2 and VE-cadherin were used to assess endothelial cell contact integrity and compared with KO pups pretreated with intraperitoneal Ang1 [Ang1(KO-LPS); n = 5] or saline [sal(KO-LPS); n = 6] 2h before LPS. KO-LPS pups showed significantly increased inflammation (p < 0.05) and expression of IL-1β, SELE, VEGFA, and Ang2 (p = 0.019, 0.003, 0.008 and < 0.0001, respectively); expression of Ang1 and TIE2 remained unchanged when compared with KO-saline. In Ang1(KO-LPS) ileum, changes seen in sal(KO-LPS) were eliminated and phospho-TIE2 and VE-cadherin fluorescence increased. Ang1 successfully attenuated LPS-induced normoganglionic intestinal inflammation, downregulated pro-inflammatory genes, and improved vascular barrier integrity in KO pups.

Enhancement of enteric neural stem cell neurogenesis by glial cell-derived neurotrophic factor in experimental Hirschsprung's disease.

Stem cell therapy offers a promising solution for congenital diseases like Hirschsprung's disease (HSCR). Optimizing stem cell efficacy by modifying the cells and their environment is crucial, but in vitro culture conditions need to be further improved. Glial cell-derived neurotrophic factor (GDNF) plays an important role in neuronal survival, proliferation, migration and differentiation during enteric nervous system (ENS) development. In this study, the effects of GDNF on neurites derived from an Ednrb knockout model were investigated with the aim of enhancing the neurogenic potential of enteric neural crest cells (ENCCs). Neurospheres were generated form Ednrb+/+ (control) and Ednrb-/- mice at embryonic day13.5 (E13.5) with Sox10-green fluorescent protein (Venus) transgenic expression. These neurospheres were cultured in control media and neurospheres from Ednrb-/- were cultured with either control media or media supplemented with GDNF. ENCCs differentiation was assessed using immunofluorescence staining after 18days. GDNF-treated Ednrb-/- neurospheres showed increased size and higher density of Sox10-positive ENCCs compared to untreated Ednrb-/- neurospheres. GDNF also enhanced the distribution of both TUJ1-positive neurons and S100-positive glial cells. GDNF effectively enhanced the neurogenic potential of ENCCs from HSCR animal model. This finding is crucial for the development of cell therapy in HSCR.

Combined MRI, high-resolution manometry and a randomised trial of bisacodyl versus hyoscine show the significance of an enlarged colon in constipation: the RECLAIM study

BackgroundColonic motility in constipation can be assessed non-invasively using MRI.ObjectiveTo compare MRI with high-resolution colonic manometry (HRCM) for predicting treatment response.DesignPart 1: 44 healthy volunteers (HVs), 43 patients with irritable...

Clinical and functional outcome of total transanal endorectal pull-through procedure for the management of Hirschsprung’s disease

ObjectiveThe aim of the study is to evaluate the complications and long-term bowel function in Hirschsprung’s disease (HD) patients following total transanal endorectal pull-through (TERPT) surgery operated in a tertiary hospital in Oman.MethodsA retrospective data retrieval was done for patients diagnosed with Hirschsprung’s disease and underwent total transanal endorectal pull-through procedure during the period from December 2008 to June 2019 with concomitant prospective phone call questionnaire interview to assess the long-term functional outcome of children aged 3 years and older.ResultsTotal transanal endorectal pull-through was performed in 61 patients. The mean age at the time of operation was 7.71 ± 8.26 months. The most common late complication was anal excoriation (19.7%). Of the patients, 61.5% had a normal to fair score, and the remaining 38% had a poor score in their functional outcome questionnaire. The majority had no social problems (65.4%), while 15.4% had problems causing varying degrees of social restrictions.ConclusionThe short-term outcomes of total transanal endorectal pull-through are found to be acceptable. In addition, the long-term functional outcome post total transanal endorectal pull-through was found to be satisfactory; however, longer follow-up studies with larger sample sizes are needed for more accurate functional outcome evaluation.

Correction to “Reproductive success in thoroughbred broodmares post large colon resection or colopexy”

Correction to “Reproductive success in thoroughbred broodmares post large colon resection or colopexy”

Calretinin Staining Pattern is Variable in Hirschsprung Disease Occurring in Patients with Down Syndrome

Abstract Introduction/Objective Hirschsprung disease (HD), a congenital absence of enteric ganglion cells, affects 2-10% of patients with Down syndrome (DS). Submucosal nerve hypertrophy (SNH) and abnormal calretinin immunohistochemistry (IHC) support a diagnosis of HD, but the concordance of these findings can be variable in DS. Recognizing differences in HD occuring in DS can provide insight into the disease and help to improve outcomes and reduce delays in diagnosis for these patients. We sought to describe the histologic and calretinin staining patterns in HD occurring in patients with DS. Methods/Case Report From 2017-2023, 22 rectal biopsies from 20 patients with DS were retrospectively collected and reviewed. Subsequent pull-through (PT) resections were evaluated from 8 patients. Biopsies were evaluated for ganglion cells and SNH. Calretinin IHC was qualitatively evaluated for intensity (strong, weak) and density (many, partial, rare). Quantitative analysis used a calculation of the percent area above threshold (%AAT) function of the NIH ImageJ software version 2.1.0. Representative areas of the PT resections were also evaluated by ImageJ %AAT analysis. Results (if a Case Study enter NA) HD biopsies (12/22, 54.5%) were from male patients (age 3 days-6 weeks) and showed SNH in 11/12 (91.7%) with a mean nerve diameter of 57.3 microns (range 25-89 microns). Ganglionated biopsies (10/22, 45.5%) were collected from patients 3 days to 12 years old (M:F ratio 1:1.5) and showed SNH in 6/10 (60%) with a mean nerve diameter of 44.4 microns (range 10-70 microns). Strong normal calretinin staining was only seen in ganglionated biopsies (7/10 non-HD versus 0/12 HD). Negative calretinin staining was only seen in HD (0/10 non-HD vs 7/12 HD). Abnormal staining was seen in both non-HD (3/10, 30%) and HD (5/12, 41.7%) as partial strong positivity and rare weak positivity, respectively. ImageJ %AAT quantitative analysis revealed an average of 1.71 in biopsies with strong calretinin expression, 0.130 with weak staining, and 0.033 with negative staining. Evaluation of 8 PT resections (mean length of aganglionosis 7.1 cm) showed a mean nerve diameter in the aganglionic segment of 88.3 microns, 49.6 microns in the TZ, and 32.7 microns in the ganglionated segment. ImageJ %AAT quantitative analysis of calretinin revealed a mean of 0.044 in the aganglionic area, 0.66 in the TZ, and 1.56 in the ganglionated segment. Conclusion Recognition of the variable calretinin patterns seen in rectal biopsies from patients with DS can assist in accurate and timely diagnosis of HD.

Burden and mortality of congenital gastrointestinal anomalies: insights from a nationwide cohort study.

Improved perioperative care has enhanced survival in children with congenital gastrointestinal conditions and abdominal wall defects (AWD). However, epidemiological and surgical outcomes in developing nations are still scarce. Our aim was to assess the burden and mortality of common congenital gastrointestinal anomalies and AWD in Malaysia, and their influencing factors. Using the Global PaedSurg study protocol with permission, we performed a prospective cohort study on children presenting for the first time between October 2021 and April 2022 with these conditions: Esophageal atresia (EA), congenital diaphragmatic hernia (CDH), intestinal atresia, gastroschisis, exomphalos, anorectal malformation (ARM) and Hirschsprung's disease. We compared mortality and 30-day outcome data across different geographical regions in Malaysia. There were 228 patients with 242 study conditions (EA n = 28, CDH n = 36, intestinal atresia n = 49, gastroschisis n = 12, exomphalos n = 8, ARM n = 77, Hirschsprung's disease n = 32). Our mortality rate was 8.8%; 60% of these were CDH patients. Factors significantly associated with mortality were CDH diagnosis, central venous access requirement, higher American Society of Anesthesiologists (ASA) score, blood transfusion and ventilation requirement. Diagnosis of CDH is the most important predictor for sepsis on arrival and mortality, therefore measures should be taken for early recognition and aggressive management.

Obstacles to an Effective Transition to Adult Services for Patients with Hirschsprung Disease.

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.