Neuroanatomical Techniques: Insect Nervous System. ns: p > 0.05, paired t-test for all. 8600 Rockville Pike and M.M.H. Hirschsprung disease (HSCR) is a congenital disorder characterized by failure of the enteric nervous system to develop in the distal part of the intestine. Kapur R.P. Informed consent was obtained from all subjects involved in the study. Contrast enema used for the diagnosis of Hirschsprung's disease (HD) has a reported false-negative rate of between 20 and 25%, and false-positive identification of a transition zone reported as high as 43% [1-3].At our institution, clinical evaluation, a stooling history, abdominal radiographs, and rectal biopsy help achieve the diagnosis of HD. LAS and MMH are fellows of the Australian Research Council (ARC DECRA: DE180100261 and DE190101209, respectively). Archives of Disease in Childhood. FOIA However, in 3-4% of cases, colonic perforation complicates presentation 2, and this and its sequelae significantly increase mortality and morbidity. histopathologic features of the transition zone in hematoxylin and eosin-stained sections in order to interpret intraoperative frozen sections and ensure adequate resection. Accessibility Gold standard was pathological examination of resection specimen. This is in part due to the lack of formal protocols for surgical reporting and pathological evaluation, with recommendations from the American Pediatric Surgery Association (APSA) Hirschsprung Disease Interest Group only being published in 2019 [34]. (C) Quantification of the size of ganglia (#DAPI+ cells/ganglion, left), the proportion of neurons per ganglion (%Hu+/DAPI+, middle), and the ratio of glia/neurons per ganglion (right) in four long-segment and four short-segment HSCR patients. In the transition zone of long-segment HSCR patients, this ratio was significantly increased, indicating a reduction in the ganglia density. The median age at surgery was 13.5 days in Group 1 and 22.5 days in Group 2. Objective: 2013 Jul-Aug;16(4):252-66. doi: 10.2350/12-12-1282-OA.1. Hence, functional obstruction develops due to a spasm in the denervated colon. Muller P.A., Koscso B., Rajani G.M., Stevanovic K., Berres M.-L., Hashimoto D., Mortha A., Leboeuf M., Li X.-M., Mucida D., et al. Yang W., Chen S.-C., Lai J.-Y., Ming Y.-C., Chen J.-C., Chen P.-L. A radiograph of the abdomen showed dilated colonic loops.. Karim A., Tang C.S.-M., Tam P.K.-H. Comparison of ganglia from the proximal normoganglionic tissue in non-HAEC and HAEC patients. Gershon M.D., Margolis K.G. Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study. Surgical removal of the aganglionic segment is the only treatment currently for HSCR, but outcomes are often unsatisfactory. However, routine intraoperative frozen section examination of the proximal resection margin to exclude the 3 primary forms of hematoxylin and eosin neuropathology described in this study is strongly advised. Therefore, a two . Benign Anorectal Diseases: Diagnosis with Endoanal and Endorectal Ultrasonography and New Treatment Options. [38]. Epub 2013 Mar 15. Lawal TA, Chatoorgoon K, Collins MH, Coe A, Pea A, Levitt MA. It is thought to either occur from a failure of neuroblasts in neural crest cells to migrate into bowel segments or degeneration of already migrated neuroblasts. The proportion of Hu+ neurons (out of DAPI+ cells in the ganglion) was not significantly different between the two regions (NZ: 29.8 2.1%; TZ: 28.0 4.0%; p = 0.64, paired t-test), and the ratio of glia to neurons was also not different between the regions (NZ: 2.8 0.6; TZ: 3.2 0.8; p = 0.56, paired t-test). Ganglia are more sparsely located in the transition zone, and no ganglia are visible in the aganglionic zone, although individual glial cells are present (some highlighted by arrowheads). The condition typically presents in term neonates with failure to pass meconium in the first 1-2 days after birth, although later presentation is also common. In children with long-segment disease, a longer transition zone is possible. Recent data shows that enteric glia also play important roles in this exchange [53,54]. Keywords: Althoughmostpatientsmarkedlyimprovepostoperatively, some continue to experience obstruction and require reoperation. Secondary antibodies were donkey anti-mouse Alexa 594 (1:500, Molecular Probes), donkey anti-rabbit Alexa 488 (1:800, Molecular Probes), and DAPI. Surgery, Surgical Pathology, and Postoperative Management of Patients With Hirschsprung Disease. Altered fecal short chain fatty acid composition in children with a history of Hirschsprung-associated enterocolitis. Patients with short-segment HSCR were also investigated, however, the muscle unit to ganglion ratio was not significantly different in these patients. Additionally, delayed evacuation of the administered contrast medium. (2006) ISBN: 8847003369. Many studies have also investigated the components of ganglia, reporting on differences between enteric neuron to glia ratios [31,32,33]. Overview of the distribution of myenteric ganglia in relation to circular muscle units in the proximal normal zone (A, NZ), the transition zone (B, TZ), and the aganglionic zone (C) in longitudinal sections of HSCR patient tissue following immunohistochemistry against HuC/D (Hu), S100B and DAPI. Phenotypes of HSCR depend on the length of affected bowel. Clinically, the uncoordinated and tonic muscle contraction of the gut in HSCR results in functional obstruction of a variable length of colon, which may be fatal if left untreated [7]. Guidelines for the management of postoperative obstructive symptoms in children with Hirschsprung disease. Pediatr Dev Pathol. The median age at pull-through for Hirschsprung's disease was 5 months (3-14 months). Routine resection of at least 5 cm of ganglionic bowel proximal to the aganglionic segment may reduce the incidence of transition zone pull-through. Management and outcomes for long-segment Hirschsprung disease: A systematic review from the APSA Outcomes and Evidence Based Practice Committee. This project was funded by a grant from the Medical Research Future Fund (MRFF: APP2009049) from the National Health and Medical Research Council, Australia (NHMRC) (to LAS, SKK and MMH) and REACHirschsprung Foundation Research Grant (to LAS, MMH and SKK). The transition zone was defined as ganglionic bowel exhibiting ganglion hypoplasia, hypertrophic nerve trunks, or partial circumference aganglionosis. Three other neuroanatomic phenotypes (gangliosclerosis, ectopic myenteric ganglia, and eosinophilic ganglionitis) of uncertain clinical significance were distributed more irregularly and often over much longer distances. Guidelines for synoptic reporting of surgery and pathology in Hirschsprung disease. DOI: 10.1056/NEJMicm2007613. A ganglion was defined as a cluster of at least two Hu+/DAPI+ neurons. The https:// ensures that you are connecting to the 2. Seven patients also had either an ileostomy or colostomy prior to pull-through surgery (64%, Table 1). Would you like email updates of new search results? Interestingly, our study identified that HAEC patients had smaller ganglion size in their normoganglionated region compared to control patients. NCI CPTC Antibody Characterization Program. Immunohistochemical examination of individual ganglia showed that there were no differences in the proportions of either enteric neurons or glial cells through the different regions of the resected colon. It was first described in 1888 by the Danish pediatrician Harald Hirschsprung(1830-1916)6-8. A radiograph of the abdomen showed dilated colonic loops. HHS Vulnerability Disclosure, Help All underwent Swenson pull-through (100%), with the average age at operation being 8.5 months (range 327 months). Murthi GVS, Townley OG, Lindley RM, Cohen MC. Hirschsprung disease affects approximately 1:5000-8000 live births. Copyright 2019 Elsevier Inc. All rights reserved. Whilst initial studies have linked HAEC with infection of Clostridium difficile and rotavirus, more recent studies have suggested an altered microbial community may result in impaired gut homeostasis and barrier function [18,19]. 2021 Mar-Apr;26(2):111-116. doi: 10.4103/jiaps.JIAPS_43_20. Our study shows that comparison of ganglia density using the muscle unit to ganglion ratios in the proximal regions of resected gut of patients experiencing post-operative enterocolitis to those who did not reveal any significant difference between patient cohorts. Moore S.W. Tomuschat C, Mietzsch S, Dwertmann-Rico S, Clauditz T, Schaefer H, Reinshagen K. Children (Basel). Diagnosis of Hirschsprung's Disease. A 3-day-old boy presented with vomiting and inability to pass stools. Increased submucosal nerve trunk caliber in aganglionosis: a "positive" and objective finding in suction biopsies and segmental resections in Hirschsprung's disease. Altman J.S. For glianeuron ratio analysis, ganglia were imaged using a 40 objective. Methods For patients with long-segment HSCR (n = 7), we identified a significant difference between the normoganglionated colon and transition zone; however, the two regions were not statistically different for short-segment patients (n = 4). However, if the most proximal biopsy did not have any enteric ganglia, further biopsies proximal to this site would be taken. 13:10-3. through for Hirschsprung's disease in infants and children. Surgical management of Hirschsprung . 2008;247(2):428-34. Further investigation examining the longitudinal muscle using transverse sections will help build strict parameters for adopting the muscle unit as a tool for quantifying ganglia density. National Library of Medicine It is now recognised that the ENS communicates with the gut immune system and has an important role in immune activation and suppression [48,49,50]. Two of these patients were syndromic as shown in Table 1. sharing sensitive information, make sure youre on a federal Interestingly, further analysis of individual ganglia in our study revealed that while the density of ganglia in the transition zone was sparser, the composition of ganglia was remarkably similar to that of ganglia in the proximal, normal region. Coe A, Collins MH, Lawal T, et al. Transition zone pull-through occurred in eight children (16%). The median length of the transition zone across the population was 8 cm (4-22 cm). Once the ganglionated region of gut was established, a circumferential doughnut of tissue was taken 2 cm proximal to this site, and the bowel resected at this location. Ghosh DN, Liu Y, Cass DT, Soundappan SSV. McGraw-Hill Professional. We aimed to evaluate the extent of the histological transition zone in patients with Hirschsprung's disease. However, there were no significant differences between the proportion of neurons or the glia to neuron ratio (Figure 4). Transition Zone in Hirschsprung's Disease Shouptik Basu, M.S. Ippolito C., Segnani C., De Giorgio R., Blandizzi C., Mattii L., Castagna M., Moscato S., Dolfi A., Bernardini N. Quantitative evaluation of myenteric ganglion cells in normal human left colon: Implications for histopathological analysis. However, our study is currently limited by sample size with only one control specimen, and further investigation is required before this can be integrated into intraoperative analysis for transition zone identification. However, there appears to be much variability in tissue handling and measurement of various parameters. Burns A.J., Champeval D., Le Douarin N.M. Sacral Neural Crest Cells Colonise Aganglionic Hindgut in Vivo but Fail to Compensate for Lack of Enteric Ganglia. World J Gastrointest Surg. In short segment disease, there is a significant predilection for males (M:F of ~3.5:1), which reduces with the increasing length of involvement 4,6. PEDIATRICS. Clipboard, Search History, and several other advanced features are temporarily unavailable. For each patient, serial biopsies (a minimum of 3) were first taken to determine the location for anastomosis, one as the bowels calibre changes at the site of the megacolon, one 2 cm proximal to this, and one 2 cm distal to this site. and transmitted securely. Kata kunci: Morbus Hirschsprung; zona transisi Background: Transition zone (TZ) pullthrough is a leading cause of obstructive symptoms after pullthrough procedure in Hirschsprung disease (HD). Design: All data from this study can be made available upon request. Learn more Knowles C.H., Veress B., Kapur R.P., Wedel T., Farrugia G., Vanderwinden J.M., Geboes K., Smith V.V., Martin J.E., Lindberg G., et al. Careers. Background: HHS Vulnerability Disclosure, Help and transmitted securely. MeSH Accessibility Elsherbeny M., Abdelhay S. Obstructive complications after pull-through for Hirschsprungs disease: Different causes and tailored management. A range of Hirschsprung phenotypes were treated, with four patients (36.3%) suffering from short-segment disease and seven patients (63.6%) with long-segment disease. in their systematic review, which revealed an incidence of 10% to 45% [45,46]. The muscle unit to ganglion ratio in the transition zone was found to be 1.9 0.2, which was significantly higher compared to the proximal, normal tissue segment (n = 11, Figure 2D). Keck S., Galati-Fournier V., Kym U., Moesch M., Usemann J., Mller I., Subotic U., Tharakan S.J., Krebs T., Stathopoulos E., et al. In conventional HSCR, a transition zone (TZ) is present between the aganglionic segment and histologically euganglionic bowel. Correctly and quickly identifying the transition zone during HSCR pull-through surgery is important for reducing post-operative complications. Takeda Pharmaceuticals had no role in the design, execution, interpretation, or writing of the study. Epub 2016 Aug 31. Adult patients with allied disorders of Hirschsprung's disease in emergency department: An 11-year retrospective study. Histology of the Transition Zone in Hirschsprung Disease. Radiological Imaging of the Digestive Tract in Infants and Children (Medical Radiology / Diagnostic Imaging). Changes in ENS structure and innervation have also recently been implicated [21,22]. Patients 10 and 13 were excluded from tissue analysis. This could be due to clinicopathological differences between the two phenotypes. This site needs JavaScript to work properly. Clear and reliable distinction of the normoganglionated bowel from the transition zone is key for successful resection of the entire defective bowel, and the avoidance of subsequent postoperative complications. A transition point is seen at the junction between sigmoid and descending colon. An official website of the United States government. Our primary aim was to evaluate the lengths of the TZ in a cohort of consecutive patients with HD. Cholinergic Signaling Attenuates Pro-Inflammatory Interleukin-8 Response in Colonic Epithelial Cells. A definitive diagnosis requires a full-thickness rectal biopsy (2 cm above the dentate line as the region below the dentate line usually is aganglionic). Previous studies have described decreasing numbers of ganglia with increasing density of TNBs within the transition zone (TZ) between . Whether loss of other subtypes of neurons or specific enteric glial cells contribute to HAEC remains to be investigated further. Please contact the corresponding authors. Get access now with a free NEJM.org account. This was only identified after investigation of resected tissue using immunohistochemistry. Please enable it to take advantage of the complete set of features! The affected segment is of small caliber with proximal dilatation. If the most proximal biopsy was identified to be ganglionated and with an absence of hypertrophic nerve bundles, then no further biopsies would be taken. Mortality rates can be as high as 30% due to enterocolitis. Background Over the past few decades, surgery for Hirschsprung's disease (HD) has evolved into a minimally invasive, single-stage procedure with excellent outcomes. sharing sensitive information, make sure youre on a federal Short-segment disease, defined as aganglionosis to the junction of the descending colon and sigmoid colon, accounts for 6085% of patients; long-segment disease (10% of patients) is characterised by aganglionosis proximal to the sigmoid colon with ganglion cells present in the colon; and total colonic aganglionosis is defined as aganglionosis of the entire colon extending into the terminal ileum (312%) [8,9,10,11]. Unable to load your collection due to an error, Unable to load your delegates due to an error. Transition zone pullthrough in Hirschsprung's disease: a tertiary hospital experience - Ghosh - 2017 - ANZ Journal of Surgery - Wiley Online Library an intestinal perforation occurred in utero and 55 Patients with Hirschsprung's disease are treated with spontaneously sealed; if not, the extruded meconium a colostomy near to the transition zone (level of is walled off by adjacent intestine to form pseudocysts. Contrast enema post evacuation phase demonstrating the transition zone ( arrows ). # Patient with Down syndrome. have demonstrated a lack of interstitial cells of Cajal and markedly reduced NADPH-positive nerve trunks in smooth muscle layers of total colonic aganglionosis patients. 1998 Aug;122(8):721-5. Intestinal Neuronal Dysplasia-Like Submucosal Ganglion Cell Hyperplasia at the Proximal Margins of Hirschsprung Disease Resections. A range of Hirschsprung phenotypes were treated, with four patients (36.3%) suffering from short-segment disease and seven patients (63.6%) with long-segment disease. Hirschsprung disease-integrating basic science and clinical medicine to improve outcomes. Tomuschat C, Mietzsch S, Dwertmann-Rico S, Clauditz T, Schaefer H, Reinshagen K. Children (Basel). After deparaffinization, the specimens were immersed in 0.1 M trisodium citrate (pH 6.0) antigen retrieval solution at 60 C overnight. Neuvonen M.I., Kyrklund K., Rintala R.J., Pakarinen M.P. Crossref. Seguella L., Gulbransen B.D. Toluidine Blue as a Rapid Stain for Nerve Cell Bodies in Intact Ganglia. Gosain A. A stoma was made at that time and when the stoma was closed, we found a segmental stricture secondary to neonatal necrotizing enterocolitis located at sigmoid colon. This site needs JavaScript to work properly. Swenson O. Hirschsprung's Disease: A Review. (B) shows a hypertrophic nerve bundle, which could be identified using S100B immunohistochemistry, but lacked neuronal cell bodies. While changes in immune function and microbial dysbiosis are important, recently, changes in ENS structure and function have also been implicated in HAEC [21,22]. Current gold standard treatment involves the surgical resection of the defective, aganglionic bowel. Although most studies have investigated submucosal nerve hypertrophy [23,29], and have previously stipulated the identification of two hypertrophic submucous nerves within a single 400 magnification field of view, we used the more stringent criteria of a single hypertrophic nerve bundle identified in the myenteric plexus, which has also been previously described [38]. Thus far, we have assessed the muscle unit to ganglion ratio for the circular muscle, as the tissue was sectioned along the longitudinal axis of the gut in order to capture data from the entire length of the resected bowel segment. For all patients, intraoperative frozen sections were used to identify the ganglionated bowel. 1996;167(2):517-20. The follow-up period of this study ended in May 2021, with a mean follow-up time of 10 months (range 217 months) from the date of their final surgery (stoma closure if an ostomy was performed). The Emerging Genetic Landscape of Hirschsprung Disease and Its Potential Clinical Applications. Results: The median age at pull-through for Hirschsprung's disease was 5 months (3-14 months). Cell therapy offers the potential to restore colorectal function. Monforte-Muoz H, Gonzalez-Gomez I, Rowland JM, Landing BH. It can be anatomically divided into four types according to the length of the aganglionic segment: It is postulated that hypoganglionosis (reduced number of ganglion cells) handles intestinal pseudo-obstruction 4. In our longitudinal colon sections, the presence of a myenteric hypertrophic nerve bundle (>40 m) was used to identify the transition zone, as described by Subramanian et al. An official website of the United States government. It affects cells both in the myenteric and submucosal plexuses 4. It is thought to either occur from a failure of neuroblasts in neural crest cells to migrate into bowel segments or degeneration of already migrated neuroblasts. Federal government websites often end in .gov or .mil. 2012 Nov;21(4):291-301. doi: 10.1053/j.sempedsurg.2012.07.003. Pediatr Surg Int. 9. The size of ganglia was significantly smaller in HAEC patients when compared with non-HAEC patients (Figure 4), and again, this is likely to be an under-representation as many ganglia were not completely captured by the field of view. Previous studies have reported that the ratio of enteric glia to neurons is disrupted in the transition zone [31,32,33]. We examined the size and proportions of neurons and glia within each ganglion. At the conclusion of the follow-up period, one patient was unable to be evaluated as she still had an ileostomy (Patient 11). The strip was divided into sections for ease of rolling, with the proximal end of the tissue rolled into the centre. Bowel Function and Quality of Life After Transanal Endorectal Pull-through for Hirschsprung Disease: Controlled Outcomes up to Adulthood. 40 m was previously described as the upper limit of the thickness of a normal myenteric nerve bundle in longitudinal gut resections [38]. Reference article, Radiopaedia.org. Aganglionosis; Constipation; Hirschsprung; Hypertrophic nerve trunk; Hypoganglionosis; Pull-through; Transition zone. A "transition zone" (the point where the normal bowel becomes aganglionic) may be visible on a contrast enema radiograph; however, the aganglionic colon will extend beyond this point in about.
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