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Background: Children with total colonic Hirschsprung disease (TCHD) are a unique group of patients with pre- and postoperative management challenges. This review provides a rational, expert-based approach to diagnosing and managing TCHD., Methods: The guidelines were developed by the Hirschsprung Disease Interest Group members established by the American Pediatric Surgical Association (APSA) Board of Governors. Group discussions, literature review, and expert consensus were used to summarize the current knowledge regarding diagnosis, staged approach, the timing of pull-through, and pre-and postoperative management in children with TCHD., Results: This paper presents recommendations for managing TCHD before and after reconstruction, including diagnostic criteria, surgical approaches, bowel management, diet, antibiotic prophylaxis, colonic irrigations, and post-surgical considerations., Conclusions: A clear understanding of the unique challenges posed by TCHD and consensus on its treatment are lacking in the literature. This review standardizes this patient group's pre- and postoperative management., Level of Evidence: V., Competing Interests: Conflict of interest The authors report no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: 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., Methods: 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., Results: 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)., Conclusions: Software-assisted machine-learning analysis of AChE staining is suitable to improve the diagnostic accuracy of HD., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose: Rectal 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., Methods: We 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)., Results: A 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%)., Conclusions: We 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., (© 2024. The Author(s).)

Background: Mowat-Wilson syndrome (MWS) is a rare genetic condition resulting in multiple congenital anomalies, including facial dysmorphism, structural anomalies of the internal organs, functional disorders, and, although less commonly, ocular abnormalities. To present a child with MWS and eye abnormalities., Methods: A 3-year-old boy was born at 37 weeks of pregnancy with dysmorphic features, neurodevelopmental disorders, genetically confirmed MWS, nystagmus, strabismus, and suspicion of congenital glaucoma. Ophthalmic examination was carried out under general anesthesia; eyeball ultrasound and electrophysiological examination (flash visual evoked potentials) were also performed., Results: The examinations revealed nystagmus, a normal response of pupils to light in both eyes, and normal intraocular pressure, that is, 17 and 18 mm Hg in the right and left eye, respectively. Corneal thickness was 606 µm in the right eye and 588 µm in the left eye. Gonioscopy revealed displacement of Schwalbe line anterior to the limbus of the cornea (posterior embryotoxon). Fundus examination revealed a pink optic disk with a cup-to-disc ratio of 0.5, macular pigment regrouping, and normal blood vessels. Flash visual evoked potentials: P2 latency was normal. P2 amplitude from the left hemisphere was reduced to 50%, and P2 amplitude over the right hemisphere was normal., Conclusion: Children with genetically determined congenital anomalies need regular ophthalmic checkups to accurately assess the eye and determine the prospects of vision function development., Competing Interests: The authors have no conflict of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Faecal incontinence is a highly prevalent and very distressing condition that occurs throughout the entire paediatric age., Aim: To summarise advances in the understanding of the epidemiology, pathophysiology, evaluation and treatment of children with faecal incontinence due to either disorders of gut-brain interaction or organic diseases., Methods: Literature review on prevalence, impact, diagnosis and treatment options for children with faecal incontinence, interspersed with observations from the author's lifelong career focused on evaluation of children with motility disorders., Results: Faecal incontinence in children is most commonly due to unrecognised or insufficiently treated functional constipation with overflow incontinence. Non-retentive faecal incontinence (NRFI) is probably more common than previously thought and is particularly challenging to treat. Organic diseases such as anorectal malformations (ARMs), Hirschsprung disease and spinal defects are often associated with faecal incontinence; in these conditions, faecal incontinence has a profound impact on quality of life. Recognition of the different pathophysiologic mechanisms causing the incontinence is essential for a successful treatment plan. A thorough physical examination and history is all that is needed in the diagnosis of the causes of faecal incontinence related to disorders of gut-brain interaction. Colonic transit studies or x-rays may help to differentiate retentive from NRFI. Manometry tests are helpful in determining the mechanisms underlying the incontinence in children operated on for ARMs or Hirschsprung diseases. Multiple behavioural, medical and surgical interventions are available to lessen the severity of faecal incontinence and its impact on the daily life of affected individuals., Conclusions: Recent advances offer hope for children with faecal incontinence., (© 2023 John Wiley & Sons Ltd.)

Background: 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., Methods: 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)., Results: 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)., Conclusion: 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., Level of Evidence: III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mowat-Wilson syndrome (MOWS) is a rare congenital disease caused by haploinsufficiency of ZEB2, encoding a transcription factor required for neurodevelopment. MOWS is characterized by intellectual disability, epilepsy, typical facial phenotype and other anomalies, such as short stature, Hirschsprung disease, brain and heart defects. Despite some recognizable features, MOWS rarity and phenotypic variability may complicate its diagnosis, particularly in the neonatal period. In order to define a novel diagnostic biomarker for MOWS, we determined the genome-wide DNA methylation profile of DNA samples from 29 individuals with confirmed clinical and molecular diagnosis. Through multidimensional scaling and hierarchical clustering analysis, we identified and validated a DNA methylation signature involving 296 differentially methylated probes as part of the broader MOWS DNA methylation profile. The prevalence of hypomethylated CpG sites agrees with the main role of ZEB2 as a transcriptional repressor, while differential methylation within the ZEB2 locus supports the previously proposed autoregulation ability. Correlation studies compared the MOWS cohort with 56 previously described DNA methylation profiles of other neurodevelopmental disorders, further validating the specificity of this biomarker. In conclusion, MOWS DNA methylation signature is highly sensitive and reproducible, providing a useful tool to facilitate diagnosis., (© 2024. The Author(s).)

Biallelic pathogenic variants in RMRP, the gene encoding the RNA component of RNase mitochondrial RNA processing enzyme complex, have been reported in individuals with cartilage hair hypoplasia (CHH). CHH is prevalent in Finnish and Amish populations due to a founder pathogenic variant, n.71A > G. Based on the manifestations in the Finnish and Amish individuals, the hallmarks of CHH are prenatal-onset growth failure, metaphyseal dysplasia, hair hypoplasia, immunodeficiency, and other extraskeletal manifestations. Herein, we report six Japanese individuals with CHH from four families. All probands presented with moderate short stature with mild metaphyseal dysplasia or brachydactyly. One of them had hair hypoplasia and the other immunodeficiency. By contrast, the affected siblings of two families showed only mild short stature. We also reviewed all previously reported 13 Japanese individuals. No n.71A > G allele was detected. The proportions of Japanese versus Finnish individuals were 0% versus 70% for birth length < -2.0 SD, 84% versus 100% for metaphyseal dysplasia and 26% versus 88% for hair hypoplasia. Milder manifestations in the Japanese individuals may be related to the difference of genotypes. The mildest form of CHH phenotypes is mild short stature without overt skeletal alteration or extraskeletal manifestation and can be termed "RMRP-related short stature"., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Introduction:  A biopsy protocol for diagnosing Hirschsprung's disease (HD) in children using the anorectal line (ARL)., Materials and Methods:  The ARL was adopted for diagnosing HD in 2016 using two excisional submucosal rectal biopsies performed at different levels, sequentially; the first just above the ARL and the second, further proximal (2-ARL). Currently, only the first-level biopsy is performed (1-ARL) and examined intraoperatively. Management was observation if normoganglionic, pull-through if aganglionic, and a second-level biopsy if hypoganglionic. Hypoganglionosis was considered physiologic if the second-level biopsy was normoganglionic and pathologic if hypoganglionic. Colon caliber change and bowel obstructive symptoms reflect the severity of hypoganglionosis., Results:  For 2-ARL ( n  = 54), results were: normoganglionosis ( n  = 31/54; 57.4%), aganglionosis ( n  = 19/54; 35.2%), and hypoganglionosis ( n  = 4/54; 7.4%); physiologic ( n  = 3/54; 5.6%) and pathologic ( n  = 1/54; 1.9%). Normoganglionosis and aganglionosis were always duplicated in 2-ARL (kappa = 1.0). For 1-ARL ( n  = 36), results were: normoganglionosis ( n  = 17/36; 47.2%), aganglionosis ( n  = 17/36; 47.2%), and hypoganglionosis ( n  = 2/36; 5.6%). Second-level biopsies were normoganglionic (physiologic: n  = 1) and hypoganglionic (pathologic: n  = 1). All normoganglionic cases, except one, resolved conservatively. All aganglionic cases had pull-through with HD confirmed on histopathology. Both pathologic hypoganglionic cases had caliber change and severe obstructive symptoms as definitive indications for pull-through with hypoganglionosis of the entire rectum confirmed on histopathology. Physiologic hypoganglionic cases were observed and currently have regular defecation., Conclusion:  Because the ARL is an objective functional, neurologic, and anatomic demarcation, normoganglionosis and aganglionosis can be diagnosed accurately with a single excisional biopsy. Only hypoganglionosis requires a second-level biopsy., Competing Interests: None declared., (Thieme. All rights reserved.)

Rationale: Cartilage-hair hypoplasia (CHH, OMIM # 250250) is a rare autosomal recessive disorder, which includes cartilage-hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders. CHH-AD is caused by homozygous or compound heterozygous mutations in the RNA component of the mitochondrial RNA-processing Endoribonuclease (RMRP) gene., Patient Concerns: Here, we report 2 cases of Korean children with CHH-AD., Diagnoses: In the first case, the patient had metaphyseal dysplasia without hypotrichosis, diagnosed by whole exome sequencing (WES), and exhibited only skeletal dysplasia and lacked extraskeletal manifestations, such as hair hypoplasia and immunodeficiency. In the second case, the patient had skeletal dysplasia, hair hypoplasia, and immunodeficiency, which were identified by WES., Interventions: The second case is the first CHH reported in Korea. The patients in both cases received regular immune and lung function checkups., Outcomes: Our cases suggest that children with extremely short stature from birth, with or without extraskeletal manifestations, should include CHH-AD as a differential diagnosis., Lessons Subsections: Clinical suspicion is the most important and RMRP sequencing should be considered for the diagnosis of CHH-AD., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Paired-like homeobox 2B ( PHOX2B ) is a gene essential in the development of the autonomic nervous system. PHOX2B mutations are associated with neurocristopathies-Hirschsprung disease (HSCR) and congenital central hypoventilation syndrome (CCHS)-and peripheral neuroblastic tumours. PHOXB2 plays an important role in the diagnostics of these conditions.Genotyping of a PHOX2B pathogenic variant is required to establish a diagnosis of CCHS. In HSCR patients, PHOX2B immunohistochemical staining has proven to be a valuable tool in identifying this disease. Furthermore, PHOXB2 is a predisposition gene for neuroblastoma, in which PHOX2B immunohistochemical staining can be used as a highly sensitive and specific diagnostic marker. The utility of PHOX2B immunohistochemistry in pheochromocytoma and paraganglioma has also been studied but yields conflicting results.In this review, an overview is given of PHOX2B , its associated diseases and the usefulness of PHOX2B immunohistochemistry as a diagnostic tool., Competing Interests: Competing interests: One of the coauthors (DC) is an editor for the Journal of Clinical Pathology. The other authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Cartilage hypoplasia syndrome is a primary immunodeficiency disease characterized by short stature, hypoplastic hair and a variable degree of immunodeficiency. Noninfectious cutaneous granulomas represent an uncommon yet well-recognized manifestation within the spectrum of primary immunodeficiency diseases. However, cutaneous granulomas as a manifestation of cartilage-hair hypoplasia syndrome, are extremely rare. We present a case of a middle-aged man with cartilage hypoplasia syndrome featuring cutaneous granulomas, manifesting as chronic, extensive and deep cutaneous ulcers. The patient was treated with anti-TNF-alpha adalimumab with partial improvement. Our case underscores the broad spectrum of clinical manifestations associated with cartilage hypoplasia syndrome and adds new evidence to the potential therapeutic efficacy of anti-TNF-alpha drugs in its treatment., (© 2024 Australasian College of Dermatologists.)

Introduction: Diagnostic delay in Hirschsprung disease is uncommon. Different definitions have been proposed but that of a diagnosis achieved after 12 months of age seems to be the most reliable and resorted to. Some authors reported a worse outcome in case of delay. Our study aims at providing the most relevant features of a series of patients who received a delayed diagnosis of Hirschsprung disease., Materials and Methods: All consecutive patients admitted to our Center with a delayed diagnosis of Hirschsprung diseases between January 2017 and July 2023 have been retrospectively enrolled. Demographic data, phenotype, genotype, surgical complications, and outcome were assessed and compared to those of literature. A number of variables were also compared to those of a series of patients admitted during the same study period without a delayed diagnosis., Results: A total of 45 patients were included (16.4% out of a series of 346 patients with data regarding age at diagnosis). Male to female ratio was 3.1:1. Median age at diagnosis was 41 months with a wide variation (range between 17 months and 58 years). All patients but 2 suffered from classic rectosigmoid aganglionosis. Normal meconium passage (58%) was reported in a significantly higher number of patients compared to what observed in a series without diagnostic delay (p = 0.0140). All other variables (associated anomalies, preoperative enterocolitis, complications, and functional outcome) proved not to have statistically significant differences compared to a series of patients without a diagnostic delay., Conclusions: The results of our study underline that a significant percentage of patients are basically missed in the neonatal period mostly due to mild symptoms. Overall outcome does not differ from that of patients without diagnostic delay. Nonetheless, we underline the importance of a throughout investigation of all patients with meconium delay/failure and that of adopting a low threshold for performing rectal suction biopsies in constipated children to avoid misdiagnosis to serve the best for our patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Current diagnostics in Hirschsprung's disease are often challenging and invasive. This study aims to investigate whether surface electroenterography can non-invasively discern healthy subjects from subjects suffering from Hirschsprung's disease. Nine healthy subjects (seven children, two adults) and eleven subjects suffering from surgically untreated Hirschsprung's disease (nine children, two adults) underwent an electroenterography procedure. This procedure consisted of ultrasound-guided placement of surface electrodes on the abdomen covering all parts of the colon, fasting and two 20-min electroenterography measurements separated by a meal. The dominant frequency, magnitude and relative increase (pre- to postprandial) of colonic activity were compared between both groups. The results showed that in the pediatric group, no significant differences in dominant frequency, colonic activity and relative power increase were observed between controls and patients. The adult patients showed decreased colonic motility and relative power increase in the electrodes closest to the distal colon, both when compared to the same electrodes in controls and to the more proximal electrodes of themselves. To conclude, electroenterography measurements in young children is challenging, but the results in adults demonstrate that these measurements can possibly distinguish between controls and Hirschsprung's patients. Therefore, optimization of electroenterography measurements in young children is necessary., (© 2024. The Author(s).)

Purpose: Hirschsprung Disease (HD) is typically diagnosed in the neonatal period. A small subset of patients have a prolonged course of abdominal distention and constipation prior to diagnosis. Late HD is defined as having been diagnosed at greater than or equal to one year of age. The literature is limited and offers conflicting data on the implications of a late diagnosis. We aim to investigate the presentation, operative approach, and functional outcomes of a large cohort of patients with a late HD diagnosis., Methods: All patients with a late diagnosis of HD (after 1 year of age) at our institution between 1997 and 2021 were included., Results: Twenty-eight patients were diagnosed with HD at a median age of 3.4 years. Chronic constipation, failure to thrive, and enterocolitis occurred in 100 %, 31 %, and 14 %, respectively. All patients underwent contrast enema and biopsies during their workup, identifying primarily rectosigmoid disease (n = 27) and total colonic aganglionosis (n = 1). Surgical intervention was performed in 27 patients, with 4 patients (15 %) needing a stoma (3 with plan for staged pull-through, 1 long-term stoma) and 23 patients (85 %) undergoing a single-stage pull-through. Postoperative complications included Hirschsprung-associated enterocolitis (n = 5), ostomy prolapse and revision (n = 2), abdominal distention requiring ileostomy creation (n = 2), redo pull-through (n = 2), retroperitoneal hematoma (n = 1), and cecostomy tube placement (n = 1). At a median follow-up of 5.4 years, 83 % of eligible patients achieved fecal continence with 43 % needing laxatives for persistent constipation., Conclusion: Recognizing a late presentation of HD requires a high index of suspicion. Patients with a late diagnosis did not experience an increased rate of permanent stoma, complications, or redo surgery compared to rates reported for the larger HD population. Similar long-term functional outcomes were achieved compared to the larger HD population., Level of Evidence: IV., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Inflammation on diagnostic rectal biopsy for children with suspected Hirschsprung disease (HSCR) is reported on pathology, and its significance is unknown. We describe the management and outcomes of a cohort with inflammation on rectal biopsy compared to those without. Specifically, to address the hypothesis that inflammation on diagnostic biopsy is associated with increased complication rates irrespective of intervention type and timing., Methods: A single institution retrospective review of children with HSCR who underwent biopsy and endorectal pull-through (ERPT) from 2010 to 2020 was performed. The primary outcome was overall complications at 30-days following ERPT. Secondary outcomes included timing and type of operative intervention as well as postoperative enterocolitis diagnosed within 6-months of ERPT., Results: Forty-nine children were identified; inflammation was present on diagnostic biopsy for 17 children. Those with inflammation were more likely to have clinical evidence of enterocolitis at the time of biopsy (p = 0.001) and were more likely to undergo leveling colostomy before ERPT (p = 0.01). Children with inflammation had a higher anastomotic leak rate (p = 0.04). Subgroup analysis of patients with inflammation undergoing primary ERPT versus leveling colostomy demonstrated no significant difference in outcomes following definitive ERPT., Conclusions: Our study suggests inflammation on diagnostic rectal biopsy for HSCR is associated with increased anastomotic leak rates. While additional prospective studies are indicated, attention to methods of mitigating inflammation and confirming its resolution before definitive pull-through may be of benefit for improving clinical outcomes in patients found with inflammation on diagnostic rectal biopsy., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: The authors report their experience of the transanal endorectal pull through technique as described by De la Torre Mondragon in the treatment of Hirschsprung's disease (HD)., Materials and Methods: It was a retro prospective, observational and descriptive hospital based study involving all proven cases of HD managed within a time frame of 8 years., Results: Fifty two patients with a mean age of 18 months at the time of surgery. The male pre dominance was remarkable. The mean duration of the surgery was 2 h and a half hours. The surgical indication was based on the history, clinical findings and on the contrast enema (transition zone) with a 24 h film (prolonged contrast evacuation) and calculation of the rectosigmoid index (<1). With a mean follow up of 16 months, the morbidity was dominated by soiling, anastomotic strictures and enterocolitis. The mortality in one case was related to a post operative enterocolitis that was not amenable to resuscitation., Conclusion: Soiling, anastomotic strictures and enterocolitis are the main post operative complications of TEPT in the treatment of HD in our practice., (Copyright © 2023 Copyright: © 2023 African Journal of Paediatric Surgery.)

The purpose of the work - to investigate the peculiarities of the clinical course of Hirschsprung's disease in children of the first year of life and to determine the significance of symptoms in the verification of the disease. From 1980 to 2021, at the pediatric surgery clinic of the National Medical University named after O.O. Bogomolets on the basis of the National Children's Specialized Hospital "OKHMATDYT" and in the pediatric surgery clinic of the Ivano-Frankivsk National Medical University on the basis of the Ivano-Frankivsk Regional Children's Clinical Hospital, 483 children of the first year of life suffering from Hirschsprung's disease were examined and treated. The clinical manifestation and course of aganglionosis varied in length at the time of hospitalization and depended on the time after birth. During the first month of life, 97 (20.08%) patients were hospitalized, of which 39 (8.07%) hadatypical clinical picture due to: colonic atresia in 15 (3.10%), colonic atresia + gastroschisis in 3 (0.62%), ileal atresia in 9 (1.86%), esophageal atresia in 3 (0 .62%), clefts of the hard and soft palate in 9 (1.86%). Depending on the age, there were 280 (57.97%) patients under 6 months, and 203 (42.03%) patients between 6 months and 1 year. The classic typical clinical picture was in 444 (91.93%) patients, which was characterized by the absence of meconium excretion, abdominal distension in 444 (91.93%), delayed physiological weight gain against the background of nutritional insufficiency with the development of hypotrophy in 327 (67.70%) , vomiting of stagnant gastric and intestinal contents in 417 (86.34%). On the other hand, enterocolitis in 315 (65.22%), toxic megacolon in 16 (3.31%), and anemia of various degrees occurred in 241 (49.89%) patients among the complications that arose during the examination of patients with Hirschsprung's disease. According to the results of a comprehensive examination, the following extent of aganglionosis was established: rectal in 100 (20.70%), rectosigmoid in 192 (39.75%), subtotal in 150 (31.06%) and total in 41 (8.49%) patients. Concomitant malformations were found in 98 (20.29%) patients: renal malformations were diagnosed in 7 (1.45%) patients, concomitant heart malformations in 18 (3.73%) patients. Associated intraoperative findings were Meckel's diverticulum in 5 (1.03%) and congenital cyst of the right ovary in 1 (0.21%) patient. The clinical course was affected by concomitant malformations: incomplete bowel rotation in 10 (2.07%) and internal abdominal hernia in 2 (0.42%). The clinical manifestations and course of Hirschsprung's disease primarily depend on the presence of accompanying developmental defects, which may prevail during the examination due to vital disorders. In the clinical course of Hirschsprung's disease, it is necessary to distinguish between typical and atypical forms. Typical clinical symptoms were in 444 (91.93%), and atypical in 39 (8.07%).

Aim of the Study: The coexistence of Hirschsprung's disease (HD) with anorectal malformation (ARM) is rare but many surgeons still ask pathologists to look for ganglia in the terminal rectum or fistula. In this study, we aimed to highlight the rarity of this association and question the necessity of histological evaluation., Methods: After obtaining board review approval, rectal specimens of ARM patients who underwent corrective surgery in the last 8 years were re-analyzed by two blinded pathologists for the presence and structure of ganglia. Clinical and radiological data of patients retrieved from center records and correlated with histopathologic findings., Main Results: 67 patients with ARM were identified, distal rectal specimen was obtained in 47. The median age at the time of surgery was 11 months (2 days-59 months). A normal pattern of ganglia was present in 51.1% (24/47), 29.7% (14/47) had aganglionosis and 19.1% (9/47) were inconclusive due to insufficient material. None of the aganglionic specimens showed other histological findings of HD. Patients were followed up regularly in the outpatient colorectal clinic for a median of 87 months (42-117 m). Only 6 experienced severe constipation (3 ganglionic, 2 no biopsy, 1 aganglionic), all of whom responded to a bowel management program, and none developed other manifestations of HD (abdominal distension, failure to thrive or enterocolitis) or required additional surgery., Conclusions: Our results strongly suggest that the association of ARM and HD is extremely rare and the practice of searching for ganglia in the distal rectum or fistula of ARM patients should be discouraged to avoid potential misdiagnosis and overtreatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hirschsprung's Disease (HD) is a congenital disorder causing severe constipation in infants and children. Suction rectal biopsy (SRB) is the preferred technique for obtaining tissue samples for histopathological evaluation. In low-resource settings like Malaysia, cost-effective diagnostic approaches are necessary, making single sample SRB valuable. This study evaluates the diagnostic accuracy and sufficiency of a single macroscopically adequate sample in suction rectal biopsies for the histopathological confirmation of HD. We conducted a retrospective study of children who underwent suction rectal biopsies for the diagnosis of HD at Hospital Raja Perempuan Zainab II (HRPZII), Kota Bharu, Kelantan. A total of 68 patients were included in the study. The inadequacy rate for bedside SRB was 14%, comparable to current literature. Our study found no statistically significant association between sample inadequacy and gestational age, gender, birth weight, or weight at biopsy. Complication rates were 0%, consistent with literature reports. Calretinin staining, an additional technique, was performed in 23 biopsy episodes, with a 4.3% inadequacy rate, compared to 20% in specimens not subjected to calretinin staining. The cost of SRB almost doubled with each additional sample taken, significant in low-resource environments. In conclusion, single sample SRBs can be adequately diagnostic and cost-effective in low-resource settings, providing valuable insights for healthcare facilities in Malaysia and other developing countries. The use of adjunctive techniques such as calretinin staining may improve diagnostic accuracy while maintaining cost-effectiveness. Further prospective studies with larger sample sizes are needed to validate these findings.

Purpose: Accurate histological diagnosis in Hirschsprung disease (HD) is challenging, due to its complexity and potential for errors. In this study, we present an artificial intelligence (AI)-based method designed to identify ganglionic cells and hypertrophic nerves in HD histology., Methods: Formalin-fixed samples were used and an expert pathologist and a surgeon annotated these slides on a web-based platform, identifying ganglionic cells and nerves. Images were partitioned into square sections, augmented through data manipulation techniques and used to develop two distinct U-net models: one for detecting ganglionic cells and normal nerves; the other to recognise hypertrophic nerves., Results: The study included 108 annotated samples, resulting in 19,600 images after data augmentation and manually segmentation. Subsequently, 17,655 slides without target elements were excluded. The algorithm was trained using 1945 slides (930 for model 1 and 1015 for model 2) with 1556 slides used for training the supervised network and 389 for validation. The accuracy of model 1 was found to be 92.32%, while model 2 achieved an accuracy of 91.5%., Conclusion: The AI-based U-net technique demonstrates robustness in detecting ganglion cells and nerves in HD. The deep learning approach has the potential to standardise and streamline HD diagnosis, benefiting patients and aiding in training of pathologists., (© 2023. The Author(s).)

Hirschsprung disease (HSCR) is a rare congenital intestinal disease that occurs in 1 in 5,000 live births. HSCR is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. Most patients present during the neonatal period with the first meconium passage delayed beyond 24 h, abdominal distension and vomiting. Syndromes associated with HSCR include trisomy 21, Mowat-Wilson syndrome, congenital central hypoventilation syndrome, Shah-Waardenburg syndrome and cartilage-hair hypoplasia. Multiple putative genes are involved in familial and isolated HSCR, of which the most common are the RET proto-oncogene and EDNRB. Diagnosis consists of visualization of a transition zone on contrast enema and confirmation via rectal biopsy. HSCR is typically managed by surgical removal of the aganglionic bowel and reconstruction of the intestinal tract by connecting the normally innervated bowel down to the anus while preserving normal sphincter function. Several procedures, namely Swenson, Soave and Duhamel procedures, can be undertaken and may include a laparoscopically assisted approach. Short-term and long-term comorbidities include persistent obstructive symptoms, enterocolitis and soiling. Continued research and innovation to better understand disease mechanisms holds promise for developing novel techniques for diagnosis and therapy, and improving outcomes in patients., (© 2023. Springer Nature Limited.)

Background:  The gold standard for diagnosing Hirschsprung disease (HD) in patients younger than 6 months is pathological examination of rectal suction biopsy (RSB). The aim of this study was to gain insight into the following: (1) complications following RSB, (2) final diagnosis of patients referred for RSB, and (3) factors associated with HD., Methods:  Patients suspected of HD referred for RSB at our center were analyzed retrospectively. Severity of complications of RSB was assessed using Clavien-Dindo (CD) grading. Factors associated with HD were tested using multivariate logistic regression analysis., Results:  From 2000 to 2021, 371 patients underwent RSB because of infrequent defecation, at a median age of 44 days. Three patients developed ongoing rectal bleeding (0.8%) graded CD1. Most frequent final diagnoses were: HD (n = 151, 40.7%), functional constipation (n = 113, 31%), idiopathic meconium ileus (n = 11, 3%), and food intolerance (n = 11, 3%). Associated factors for HD were male sex (odds ratio [OR], 3.19; confidence interval [CI], 1.56-6.53), presence of syndrome (OR, 7.18; CI, 1.63-31.69), younger age at time of RSB (OR, 0.98; CI, 0.85-0.98), meconium passage for more than 48 hours (OR, 3.15; CI, 1.51-6.56), distended abdomen (OR, 2.09; CI, 1.07-4.07), bilious vomiting (OR, 6.39; CI, 3.28-12.47), and failure to thrive (OR, 8.46; CI, 2.11-34.02) (model R 2  = 0.566)., Conclusion:  RSB is a safe procedure with few and only minor complications. In the majority of patients referred for RSB under the age of 6 months, HD was found followed by a functional cause for the defecation problems. RSB should be obtained on a low threshold in all patients under the age of 6 months with the suspicion of HD., Competing Interests: None declared., (Thieme. All rights reserved.)

Congenital colonic stenosis (CCS) is an extremely rare cause of large bowel obstruction in early infancy. Only 35 cases of CCS have been reported in literature to date. CCS often causes a diagnostic quandary as it is difficult to distinguish it clinically from Hirschsprung's disease. We report a case of an infant with CCS who was managed with resection of the diseased colonic segment with critical stenosis at two sites and colo-colonic anastomosis. In our report, we discuss the challenges faced in the diagnosis and surgical management of this unusual case., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Contiguous gene gain syndrome including entire ZEB2 may be a novel syndrome. In the past, there were no easily distinct and recognizable features as a guide for precise clinical and genetic diagnosis of the syndrome., Case Presentation: We report a novel case with the syndrome with a novel de novo 22.16 Mb duplication at 2q21.2-q24.1. The syndrome is characterized by multiple anomalies including the same typical craniofacial phenotype that is entirely different from Mowat-Wilson syndrome (MWS), and other quite similar features of MWS consisting of development delay, congenital heart disease, abdominal abnormalities, urogenital abnormalities, behavioral problems and so on, in which the distinctive craniofacial features can be more easily recognized., Conclusions: Contiguous gene gain syndrome including entire ZEB2 characterized with similar multiple congenital anomalies of MWS and the distinctive craniofacial features is mainly caused by large 2q22 repeats including ZEB2 leading to dominant singe ZEB2 gene gain mutation, which is recommended to be named "Liu-Liang-Chung" syndrome. We diagnose this novel syndrome to distinguish it from MWS. Some variable additional features in the syndrome including remarkable growth and development retardation and protruding ears were recognized for the first time., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The discovery of low-coverage (i.e. uncovered) regions containing clinically significant variants, especially when they are related to the patient's clinical phenotype, is critical for whole-exome sequencing (WES) based clinical diagnosis. Therefore, it is essential to develop tools to identify the existence of clinically important variants in low-coverage regions. Here, we introduce a desktop application, namely DEVOUR (DEleterious Variants On Uncovered Regions), that analyzes read alignments for WES experiments, identifies genomic regions with no or low-coverage (read depth < 5) and then annotates known variants in the low-coverage regions using clinical variant annotation databases. As a proof of concept, DEVOUR was used to analyze a total of 28 samples from a publicly available Hirschsprung disease-related WES project (NCBI Bioproject: https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJEB19327), revealing the potential existence of 98 disease-associated variants in low-coverage regions. DEVOUR is available from https://github.com/projectDevour/DEVOUR under the MIT license., Competing Interests: The authors declare there are no competing interests., (©2023 Türk et al.)

Introduction: The gene-environment interaction of the REarranged during Transfection ( RET ) gene with vitamin A in the etiopathogenesis of Hirschsprung disease (HSCR) has been suggested in rodents. The aim of this study was to evaluate vitamin A status in mothers of children with HSCR and to assess its association with pathogenic variants of the RET gene in affected children., Methods: This was a case-control study of stable isotope-based vitamin A measurement stores of mothers of children diagnosed with HSCR (within 8 months from birth, n = 7) and age-matched mothers of normal children (n = 6). Next-generation sequencing of RET exons, along with their upstream promoter region, was performed in the 7 HSCR proband-parent triads to evaluate pathogenic variants., Results: Maternal vitamin A stores in the HSCR group was almost 50% that of those in controls, tending toward significance (0.50 ± 0.17 vs 0.89 ± 0.51 μmol/g respectively, P = 0.079). Two novel pathogenic de novo mutations were identified in 2 cases, and a rare single-nucleotide deletion was detected in the 3.5-kb RET upstream region, in a heterozygous state, in all 7 proband-parent triads. Low-penetrance RET haplotypes associated with HSCR were detected in 5 cases., Discussion: Mothers with children with HSCR had lower vitamin A liver stores than mothers with normal children, and the children who were affected had HSCR despite having no established pathogenic RET variants. Lower maternal vitamin A status may increase the penetrance of genetic mutations in RET , and vitamin-A mediated gene-environment interactions may underpin some of the etiology of HSCR., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Hirschsprung's disease is an important cause of pediatric constipation with high risk of bacterial enterocolitis. Its diagnosis is histological and the suction biopsy is the gold standard. In resource-limited countries, the main diagnostic exam is the contrast enema and mini-invasive surgery lacks. We present the management of a cohort of patients with megacolon in Haiti, a low-resource country., Methods: Children with megacolon and fecal impaction admitted at St Damien Children Hospital in Port-Au-Prince in June, August and December 2017 were included. We considered only patients with an evident transition zone on contrast enema who underwent endorectal pull-through (ERPT). Short term complications were recorded., Results: Twenty children with clinical megacolon were admitted, eleven were included in the study. No suction rectal biopsy and intraoperative histological evaluation were performed. In ten children a Soave ERPT with anastomosis at 5POD was performed, in the other case a Boley primary anastomosis was preferred. One patient complicated with a peritonitis. No major complications were recorded. Colostomy was not considered a good option., Conclusions: In developing countries, Soave ERPT with definitive anastomosis after few days could be considered a valid option. Colostomy is suggested only in case of scant general conditions or bad colon appearance.

Purpose: To assess the quality of life and disease-specific functioning of adults with anorectal malformations (ARM) or Hirschsprung disease (HD) compared to healthy reference scores., Methods: Patients with the diagnosis of ARM or HD from the Adult Colorectal Research Registry completed the Short Form 36 Health Survey (SF-36), the Gastrointestinal Quality of Life Index (GIQoLI), and the Bowel Function Score (BFS) between October 2019 and August 2022. One-sample Wilcoxon test compared the results to reported healthy references with a significance level of < 0.05., Results: The response rate was 67%. All three surveys were completed by 133 adults with a slight preponderance of males (51%). Median age was 31 years, 117 were born with ARM and 16 with HD. All subgroups had significantly lower BFS than healthy references. ARM patients scored significantly lower than the healthy reference population when assessed for GIQoL. All showed significant impairment with the mental component summary (MCS) of SF-36. Patients with a successful bowel management had significantly higher scores on all three questionnaires than those with fecal accidents., Conclusion: Our results emphasize the importance of a successful bowel management and its impact on the quality of life and bowel function. Long-term follow-up is recommended with attention to mental health., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hirschsprung's disease is a congenital disorder identified by the absence of ganglion cells at the Meissner's plexus of the submucosa and Auerbach's plexus of the muscularis. This disease can be found in approximately 1 in 5000 live births. It is a congenital disorder that is rarely diagnosed in adults, where 95% of cases are diagnosed in infants aged under 1 year old. Here we present a rare case of adult Hirschsprung's disease to enrich the body of knowledge  in diagnosing adult patients with chronic refractory constipation symptoms., Case Report: An 18-year-old Indonesian woman came to the general surgery department of Unggul Karsa Medika Teaching Hospital with a defecating problem (constipation) since childhood. There was no history of her passage of meconium. A contrast enema study showed that the sigmoid colon was dilated and the rectum was narrowed, with rectosigmoid index < 1. With these findings, it was suspected that the patient may have ultra-short segment Hirschsprung's disease. The patient was then referred to the digestive surgery department of referral hospital for surgical treatment., Conclusion: In adult patients presenting with history of constipation since childhood, it is necessary to consider the possibility of Hirschsprung's disease that was not diagnosed in early childhood. Hirschsprung's disease in adults is usually a short or ultra-short aganglionic segment because it shows relatively mild symptoms. Surgical removal of the aganglionic segment of the gut is the definitive treatment for Hirschsprung's disease., (© 2023. The Author(s).)

Background: Colon atresia is one of the rarest congenital anomalies of the gastrointestinal tract, with an incident range of between 1 in 10,000 and 66,000 live births. Type I colonic atresia affects only the mucosal layer of the intestine and spares the intestinal wall and mesentery. Hirschsprung Disease is a rare association of Colon atresia and is usually diagnosed as a complication of atresia treatment., Case Presentation: This study reports a 14-h term white middle-eastern female infant with type I transverse colonic atresia complicated by the association of Hirschsprung disease and provides a brief literature review of the topic. She presented with poor feeding, weakness, and failure to pass meconium, and her abdominal X-ray showed complete distal bowel obstruction. The presence of Hirschsprung disease was realized after complications of atresia surgery. The infant underwent a total of three surgeries involving an end-to-end anastomosis of the atresia, colostomy formation following anastomosis leakage, and Hirschsprung surgery. The patient ultimately expired., Conclusions: The association between colonic atresia and Hirschsprung disease poses a diagnostic and therapeutic challenge. Considering Hirschsprung disease as a possible association in colon atresia patients can facilitate proper decision-making in the course of treating colon atresia cases and achieving better outcomes., (© 2023. The Author(s).)

Background: The diagnosis of Hirschsprung's disease (HD) by rectal suction biopsy (RSB) has cost implications that could be reduced by ascertaining the optimal number of specimens required. The aim was to audit our experience to optimise cost-effectiveness., Methods: Medical records of all patients who underwent an RSB between January 2018 and December 2021 were reviewed. In 2020, we transitioned from using the Solo-RBT to the rbi2 system (requiring single-use cartridges). Descriptive statistics were reported and a comparative analysis of the diagnostic efficacy of the Solo-RBT versus the rbi2 system was performed. The cost of consumables was calculated according to the number of specimens submitted., Results: Of 218 RSBs, 181 were first and 37 were repeat. The mean age at biopsy was 62 days (IQR 22-65). An average of two tissue specimens were obtained per biopsy. Of the 181 first biopsies, 151 were optimal and 30 suboptimal. HD was confirmed in 19 (10.5%) of the patients. Amongst biopsies where a single specimen was obtained, 16% were inconclusive, compared to 14% with two specimens and 5% with three specimens. The cartridges for the rbi2 system cost R530. If two cartridges are used at initial biopsy the total cost is double of a single tissue specimen sent for initial biopsy, and two specimens sent for repeat biopsies., Conclusion: In a low-resource setting, selecting the appropriate RSB system and obtaining a single specimen is sufficient to diagnose HD. Patients with inconclusive results should undergo a repeat biopsy where two specimens are obtained., (Copyright© Authors.)

Background: Optimizing rectal suction biopsy (RSB) diagnostics in Hirschsprung's disease (HD) may shorten diagnostic time and prevent need for repeated biopsies., Aim: To explore whether systematic orientation of fresh RSB specimens increased biopsy quality, diagnostic times, diagnostic efficacy, and histopathologic workload, and to explore these outcome measures for aganglionic specimens., Materials/methods: This was an observational case-control study conducted at a national referral center for HD on data collected from the local HD-diagnostic register. From 2019 each fresh RSB was oriented by the collector in a notch in a foam cushion, placed in a separate cassette, and sent in formalin for pathological analysis. Outcome measures of oriented RSB samples collected 2019-2021 were compared to those of non-oriented RSB samples collected 2015-2018. Staining/immunohistochemistry consisted of hematoxylin eosin, S-100 and calretinin., Results: 78 children with 81 RSBs and 242 biopsy analyzes were included. The frequency of high-quality RSB specimens was higher in oriented: 40% (42/106) versus non-oriented 25% (34/136) (p = 0.018), the diagnostic turnaround time was shorter: 2 days (1-5) versus 3 days (2-8) (p = 0.015), and the number of additional sectioning/leveling/re-orientation per biopsy was lower: 7 (3-26) versus 16 (7-72) (p = 0.011). Specifically for aganglionic specimens, the frequency of high-quality biopsies was generally higher in oriented than in non-oriented RSB specimens: 47% (28/59) versus 14% (7/50) (p < 0.001); the diagnostic efficacy was higher 95% (19/20) versus 60% (9/15) (p = 0.027) and the diagnostic turnaround time shorter: 2 days (2-3) versus 3 days (2-8) (p = 0.036)., Conclusions: Systematic orientation of fresh RSB specimens improves HD diagnostics. Improvement was consistent in aganglionic specimens., (© 2023. The Author(s).)

Background/purpose: A small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients., Methods: Retrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale., Results: There were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD., Conclusion: More than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment., Level of Evidence: Level 4., (Copyright © 2023. Published by Elsevier Inc.)

Background: Hirschsprung disease (HD) is an aganglionosis of variable length starting at the rectosigmoid colon with surgery as sole therapeutic option. The length of the resected bowel segment is a crucial information for the treating surgeons and influences the prognosis of the patient. It is often artificially altered due to post operative tissue shrinkage. The objective of this study is to quantify the extent tissue shrinkage of HD specimens., Material and Methods: Colorectal HD specimens were measured at the time of surgery and at the time of cut-up, either fresh or after formalin fixation and statistically analyzed., Results: Sixteen colorectal specimens were included. Following formalin fixation the specimen length decreased by 22.7% ( P  < .001). Without formalin fixation the specimens shrank by an average of 24.9% ( P  = .05). There was no significant difference in the extent of tissue shrinkage with or without formalin fixation ( P  = .76)., Conclusion: This study showed that there is significant tissue shrinkage in HD specimens. The 2 different cohorts revealed that tissue shrinkage is mostly caused by tissue retraction/alteration after organ removal but also to a lesser extent by fixation with formalin. Surgeons and (neuro-)pathologists should be aware of the sizeable shrinking artifact to avoid unnecessary confusion.

Hirschsprung's disease (HD) is one of the most well-known gastrointestinal motility disorders. Diagnosis and management of other lesser-known motility disorders are often challenging and tedious. We describe a teenager who was severely constipated from birth and needed intensive care admissions for life-threatening enterocolitis. She also had concomitant anal stenosis. Several rectal biopsies were unable to yield a conclusive diagnosis. Surgical level of resection had to be identified based on the motility of the bowel as determined by transit studies using oral ingestion of a milk feed labelled with Technetium-99m colloid. After completion of all operative stages, histopathological examination of the excised specimens concluded that she had short-segment HD associated with reduced interstitial cells of Cajal in the large bowel. She is currently continent, evacuating voluntarily approximately four times a day and is relieved of all her symptoms., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hirschsprung's Disease (HD) is characterized by intestinal sub-occlusion and the absence of enteric ganglion cells. A rectal biopsy examination is performed to confirm the diagnosis. In a recent study, we demonstrated that the analysis of 60 sections of rectal mucosa and submucosa stained by H&E may ensure a 90% diagnostic accuracy. Although the need to analyze so many sections makes the process of reading the slides more time-consuming, this encouraged us to study their distribution in the healthy rectal submucosa, to simplify the diagnosis., Objectives: To develop a method that facilitates HD diagnosis by studying the distribution of ganglion cells in the submucosal plexus., Methods: Using the calretinin technique, we studied the distribution of plexuses in 60 fragments of rectal submucosa from 19 cadavers. After the study, the reading method created was used for diagnosis in 47 cases of suspected HD, using H&E staining. The accuracy was verified by comparing the results obtained with H&E to those obtained with the acetylcholinesterase technique, the golden standard in our laboratory., Results: The study of submucosal plexus distribution showed that just by examining the submucosal region every 20 µm, approximately, it is possible to locate a ganglionic plexus, and we have already been able to diagnose HD with 93% accuracy., Conclusion: The study of ganglion cell distribution enabled the creation of a simplified method for reading the slides. The method applied achieved good accuracy and it can be used as an alternative method in HD diagnosis., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Total colonic aganglionosis is an extremely rare variant of Hirschsprung's disease, which is predominant in males and can be seen in 1:50,000 live births. The presented case not only depicts a rare case, but also unusual clinical, laboratory, and instrumental data., Case Presentation: A 2-day-old Caucasian female newborn was transferred to our hospital from maternity. The initial presentation was reverse peristalsis, abdominal distention, and inability to pass stool. Fever had started before the patient was transferred. Hirschsprung's disease was suspected, and tests such as contrast enema and rectal suction biopsy were done. Before enterostomy, the management of the disease included fluid resuscitation, colonic irrigation, antibiotic administration, enteral feeding, and supportive therapy. During ileostomy operation, no transition zone was visualized and full-thickness biopsy samples were retrieved from the rectum and descending colon. After surgical intervention, status significantly improved-defervescence and weight gain most importantly improved., Conclusion: It is well known that diagnosis of total colonic aganglionosis may be delayed for months or even years since the transition zone may not be visible and rectal suction biopsy, unlike full-thickness biopsy, is not always reliable. It might be more prudent not to be derailed because of negative radiography and rectal suction biopsy. Also, doctors should be more suspicious of the disease if signs and symptoms are starting to be consistent with Hirschsprung-associated enterocolitis, despite biopsy and radiology results., (© 2023. The Author(s).)

Objectives: Hirschsprung disease (HD) is a congenital condition defined by the absence of ganglion cells in the distal-most portion of the gastrointestinal tract. Biopsies and resections for HD can be adrenaline inducing for the general surgical pathologist because specimens are infrequent; HD is 1 of only a few neuroanatomic diseases that general surgical pathologists diagnose; numerous preanalytic factors (eg, biopsy adequacy, surgeon sampling protocol, processing artifacts) can affect histologic interpretation; and most importantly, the diagnosis has high stakes., Methods: We provide a comprehensive overview of the background, relevant clinical procedures, and pathologic assessment of HD. Grossing and frozen section protocols, an algorithmic approach to diagnosis, and histologic pearls and pitfalls are also discussed., Results: Evaluation and recognition of the features of HD have evolved significantly in the past 2 decades with the discovery of the value of calretinin immunohistochemistry in the late 2000s and the recent development of straightforward and reproducible histologic criteria for identification of the HD transition zone., Conclusions: These advancements have substantially improved the pathologist's ability to reliably evaluate for HD. Nonetheless, as with any high-stakes surgical pathology specimen, clear communication with the clinical team is essential., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Surgeons create a neorectum to repair patients with Hirschsprung's disease (HD), which should be formed from a normoganglionic bowel. However, the neorectum is occasionally created with a transition zone (TZ) bowel. A neorectum created with a TZ has been postulated as a cause of postoperative enterocolitis or constipation. This study compares the incidence of enterocolitis and constipation in patients with TZ neorectum and normoganglionic bowel., Methods: We conducted a retrospective review of patients with rectosigmoid HD who underwent primary pull-through. Patients were divided into normoganglionic neorectum (NNR) and TZ neorectum. The diagnosis was based on the final histopathologic report of the proximal margin. The incidence of enterocolitis and constipation was compared between these two groups., Results: A total of 98 HD patients were analyzed. Seventy-one patients fulfilled the inclusion criteria. 65 (92%) had a NNR, and six patients (8%) had a TZ neorectum. From these patients, 42 (59%) presented with enterocolitis or constipation. However, there was no significant difference between both groups., Conclusion: The present study showed no difference in the incidence of enterocolitis or postoperative constipation in HD patients with normoganglionic or TZ neorectum. These results suggest that TZ neorectum does not cause postoperative obstructive symptoms., (Copyright: © 2023 Permanyer.)