The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Prem Puri - One of the best experts on this subject based on the ideXlab platform.
-
classification and diagnostic criteria of variants of hirschsprung s disease
Pediatric Surgery International, 2013Co-Authors: Florian Friedmacher, Prem PuriAbstract:“Variants of Hirschsprung’s disease” are conditions that clinically resemble Hirschsprung’s disease (HD), despite the presence of ganglion cells in rectal suction biopsies. The diagnosis and management of these patients can be challenging. Specific histological, immunohistochemical and electron microscopic investigations are required to characterize this heterogeneous group of functional bowel disorders. Variants of HD include Intestinal Neuronal Dysplasia, Intestinal ganglioneuromatosis, isolated hypoganglionosis, immature ganglia, absence of the argyrophil plexus, internal anal sphincter achalasia and congenital smooth muscle cell disorders such as megacystis microcolon Intestinal hypoperistalsis syndrome. This review article systematically classifies variants of HD based on current diagnostic criteria with an additional focus on pathogenesis, epidemiology, clinical presentation, management and outcome.
-
variants of hirschsprung disease
Seminars in Pediatric Surgery, 2012Co-Authors: Prem Puri, Janhendrik GosemannAbstract:Variants of Hirschsprung disease are conditions that clinically resemble Hirschsprung disease, despite the presence of ganglion cells in rectal suction biopsies. The characterization and differentiation of various entities are mainly based on histologic, immunohistochemical, and electron microscopy findings of biopsies from patients with functional Intestinal obstruction. Intestinal Neuronal Dysplasia is histologically characterized by hyperganglionosis, giant ganglia, and ectopic ganglion cells. In most Intestinal Neuronal Dysplasia cases, conservative treatments such as laxatives and enema are sufficient. Some patients may require internal sphincter myectomy. Patients with the diagnosis of isolated hypoganglionosis show decreased numbers of nerve cells, decreased plexus area, as well as increased distance between ganglia in rectal biopsies, and resection of the affected segment has been the treatment of choice. The diagnosis of internal anal sphincter achalasia is based on abnormal rectal manometry findings, whereas rectal suction biopsies display presence of ganglion cells as well as normal acetylcholinesterase activity. Internal anal sphincter achalasia is either treated by internal sphincter myectomy or botulinum toxin injection. Megacystis microcolon Intestinal hypoperistalsis is a rare condition, and the most severe form of functional Intestinal obstruction in the newborn. Megacystis microcolon Intestinal hypoperistalsis is characterized by massive abdominal distension caused by a largely dilated nonobstructed bladder, microcolon, and decreased or absent Intestinal peristalsis. Although the outcome has improved in recent years, survivors have to be either maintained by total parenteral nutrition or have undergone multivisceral transplant. This review article summarizes the current knowledge of the aforementioned entities of variant HD.
-
abnormal vasculature in Intestinal Neuronal Dysplasia
Pediatric Surgery International, 2003Co-Authors: Udo Rolle, Anna Piaseczna Piotrowska, Prem PuriAbstract:Intestinal Neuronal Dysplasia (IND) is an Intestinal motility disorder, which clinically resembles Hirschsprung's disease (HD). Adventitial fibromuscular Dysplasia (AFMD) consists of proliferation of smooth muscle cells and collagen fibers in the adventitia of blood vessels. The purpose of this study was to investigate vascular abnormalities in large bowel biopsies from patients with isolated HD, IND associated with HD and isolated IND. Large bowel biopsies from patients presenting with isolated HD ( n =23), IND associated with HD ( n =11), isolated IND ( n =16) and normal bowel as controls ( n =6) were investigated using acetylcholinesterase (AChE) histochemistry, van Gieson staining and α-smooth muscle actin (α-SMA) immunohistochemistry. Increased AChE activity around submucosal vessels was found in 9/16 (56%) cases with isolated IND, 3/11 (27%) cases of IND associated with HD, 5/23 (21%) isolated HD cases and 0/6 controls. AFMD was found in 10/16 (62%) of the isolated IND cases, 4/11 (362) of the cases with IND associated with HD and 4/23 (17%) cases of HD without IND using van Gieson staining. None of the control specimens revealed AFMD. Increased α-SMA immunoreactivity filaments were demonstrated in the submucosal vessel wall in 9/16 (56%) of isolated IND and 2/11(18%) of IND associated with HD cases. Normal α-SMA immunoreactivity around submucosal vessels was seen in isolated HD and controls. Abnormal submucosal vasculature is a common histological finding in isolated IND and IND associated with HD and may be a useful additional diagnostic feature in these patients.
-
Intestinal Neuronal Dysplasia results of treatment in 33 patients
Journal of Pediatric Surgery, 2001Co-Authors: John Gillick, H Tazawa, Prem PuriAbstract:Abstract Purpose: Intestinal Neuronal Dysplasia (IND) is a disease of the enteric nervous system, which clinically resembles Hirschsprung's disease. The authors reviewed their experience of IND over an 8-year period. Methods: Between 1992 and 1999, 418 patients underwent rectal suction biopsy for persistent constipation. Thirty-three (7.8%) patients had histologic evidence of IND. There were 26 boys and 7 girls (age range, 1 week to 10 years). The diagnosis of IND was based on the presence of hyperganglionosis of the submucous plexus and giant ganglia and at least one of the following features in rectal biopsies: (1) ectopic ganglia, (2) increased acetylcholinesterase (AChE) activity in the lamina propria, and (3) increased AChE nerve fibers around the submucosal blood vessels. All patients were started on laxatives with or without enemas after the diagnosis was made. Patients have been followed up from 1 to 8 years (mean, 2.4 years). Results: Twenty-one (64%) patients had a good response to conservative management and currently have normal bowel habits. Twelve patients (36%) underwent internal sphincter myectomy after failed conservative management. Seven of these patients now have normal bowel habits. Two patients are able to stay clean with regular enemas. Three patients who continued to have persistent constipation after myectomy and underwent resection of redundant and dilated sigmoid colon now have normal bowel habits. Conclusion: The majority of patients with IND can be treated successfully with conservative treatment. J Pediatr Surg 36:777-779. Copyright © 2001 by W.B. Saunders Company.
-
Intestinal Neuronal Dysplasia
Seminars in Pediatric Surgery, 1998Co-Authors: Prem Puri, Tomas WesterAbstract:Intestinal Neuronal Dysplasia (IND) is a disorder of the enteric nervous system that was first described by Meier-Ruge in 1971. IND may be associated with Hirschsprung's disease or may occur as an isolated disorder. The incidence of isolated IND varies from 0.3% to 40% of suction rectal biopsies. The uncertainty regarding the incidence of IND has resulted from considerable confusion concerning essential diagnostic criteria. The diagnostic difficulties reflect the wide variability in the literature in terms of diagnostic criteria, biopsy procedures, staining techniques, and patient age. The recent application of histochemical and immunohistochemical techniques indicates that IND is a distinct histopathologic entity. The majority of patients with IND can be treated conservatively with laxatives and enemas. If bowel symptoms persist after at least 6 months of conservative treatment, internal sphincter myectomy should be considered.
Hiroyuki Kobayashi - One of the best experts on this subject based on the ideXlab platform.
-
Intestinal Neuronal Dysplasia ind
2019Co-Authors: Fumi Alicia Ishida, Hiroyuki KobayashiAbstract:Intestinal Neuronal Dysplasia (IND) is a pathological condition in which hyperplasia of the submucosal and myenteric plexuses occurs, causing clinical symptoms resembling that of Hirschsprung’s disease despite distinct histological differences. Reports of IND occurring independently, or isolated IND, vary between 0.3% and 62% of all suction rectal biopsies worldwide [1]. In addition, IND can occur in conjunction with other gastroIntestinal neuropathies. This condition in which IND coexists with another gastroIntestinal disorder is referred to as associated IND. IND is typically associated with Hirschsprung’s disease (HD), and the reported incidence varies from 20% to 66% [2]. Moreover, Fadda et al. further separated IND into two distinct subtypes based on both clinical and histological conditions. These subtypes are referred to as IND Type A and IND Type B [1].
-
isolated Intestinal Neuronal Dysplasia type b ind b in japan results from a nationwide survey
Pediatric Surgery International, 2014Co-Authors: Tomoaki Taguchi, Hiroyuki Kobayashi, Atsuyuki Yamataka, Yutaka Kanamori, Osamu Segawa, Masahiko Sugiyama, Tadashi Iwanaka, Naoki Shimojima, Tatsuo Kuroda, Atsuko NakazawaAbstract:Intestinal Neuronal Dysplasia Type B (IND-B) has been proposed to be an allied disorder of Hirschsprung’s disease (ADHD). The original histological criteria included hyperganglionosis, giant ganglia, ectopic ganglion cells and an increased AChE activity in the lamina propria. The criteria for IND-B have been gradually revised. The present diagnostic criteria are [1] more than 20 % of the submucosal ganglia contain nine or more ganglion cells and [2] the patient is older than 1 year. To clarify the current status of IND-B in Japan, a nationwide retrospective cohort study was performed. Questionnaires were sent to 161 major institutes of pediatric surgery and gastroenterology in Japan. A total of 355 cases of ADHD were collected, including 18 cases of IND-B (5 %). Based on original criteria, 13 out of 18 cases were diagnosed as IND-B. However, only four cases met the current criteria. Three of the four patients (75 %) required pull-through operation. All of the patients exhibited giant ganglia and ganglioneuromatosis-like hyperplasia of the myenteric plexus. IND-B cases matching the current criteria are thought to be quite rare and they are associated with marked hyperplasia of the myenteric plexus. “True” IND-B is a rare and intractable disease.
-
inflammatory changes secondary to postoperative complications of hirschsprung s disease as a cause of histopathologic changes typical of Intestinal Neuronal Dysplasia
Journal of Pediatric Surgery, 2004Co-Authors: Hiroyuki Kobayashi, Geoffrey J Lane, Atsuyuki Yamataka, Takeshi MiyanoAbstract:Abstract Purpose The aim of this study was to clarify the pathogenesis of Intestinal Neuronal Dysplasia (IND). Methods The bowel habits of 36 postoperative HD patients were assessed retrospectively. Twenty-five had no complaints. Seven had persistent enterocolitis and were the focus of our study. They were divided into group A (n = 2) if they were severe and had associated postoperative surgical complications, and group B (n = 5) if they were mild. The histological changes were assessed. Results The 7 patients who had persistent enterocolitis postoperatively had no AchE activity in the mucosa, and there was normal distribution of submucosal and myenteric ganglia in the proximal resection margin. Rectal biopsies performed postoperatively for investigation of persistent enterocolitis in group A showed inflammatory changes and typical histopathologic features of IND such as abundant acetylcholinesterase (AchE)-positive nerve fibers in the lamina propria associated with giant submucosal ganglia and hyperganglionosis, and in group B there was increased AchE activity without hyperganglionosis or giant ganglia. Conclusions This is the first report of histopathologic changes typical of IND occurring in response to persistent enterocolitis related to postoperative complications of surgery for HD.
-
Intestinal Neuronal Dysplasia like pathology in ncx hox11l 1 gene deficient mice
Journal of Pediatric Surgery, 2001Co-Authors: Atsuyuki Yamataka, Hiroyuki Kobayashi, Katsumi Miyahara, Masahiko Hatano, Kun Wang, Noriyoshi Sueyoshi, Takeshi MiyanoAbstract:Abstract Background/Purpose: Ncx/Hox11L.1 -deficient (Ncx-/-) mice specifically created by the authors had mega-ileo-ceco-colon (mega-ICC) with a caliber change in the proximal colon. The authors studied the nerve distribution in the bowel of these Ncx-/- mice to determine the cause of their bowel dysmotility. Methods: Four-week-old Ncx-/- mice (n = 10; 5 with mega-ICC, 5 without mega-ICC) were killed and the bowel harvested. Half of each specimen was snap frozen for AchE and NADPH-diaphorase histochemistry, and the other half were fixed with 10% formalin for H&E staining and immunohistochemistry using PGP9.5 antibody (a marker for neurons), C-kit antibody (a marker for Intestinal pacemaker cells), and stem cell factor antibody (a marker for C-kit ligand). Age-matched wild-type normal mice (n = 5) served as controls. Results: In the ileum, cecum, and proximal colon from all Ncx-/- mice (irrespective of the association of mega-ICC), typical findings of human Intestinal Neuronal Dysplasia (IND) ie, obvious hyperganglionosis in Neuronal plexuses on PGP9.5 immunohistochemistry, ectopic ganglia in the mucosal and muscular layers on AchE histochemistry, and ghostlike ganglia on NADPH-diaphorase histochemistry were found. Likewise, in normal caliber distal colon from these mice, the distribution of ganglion cells, C-kit, and stem cell factor was normal. In control specimens, there was no ectopic ganglia or hyperganglionosis. Conclusions: These findings suggest that the Ncx/Hox11L.1 gene is required for the proper innervation of the enteric nervous system in mice, and our deficient strain may be useful as a model for studying IND in humans. J Pediatr Surg 36:1293-1296. Copyright © 2001 by W.B. Saunders Company.
-
mast cells and gut nerve development implications for hirschsprung s disease and Intestinal Neuronal Dysplasia
Journal of Pediatric Surgery, 1999Co-Authors: Hiroyuki Kobayashi, Geoffrey J Lane, Atsuyuki Yamataka, Takao Fujimoto, Takeshi MiyanoAbstract:Abstract Background/Purpose: In Hirschsprung's disease (HD), the aganglionic bowel is characterized by the presence of hypertrophic nerve trunks and increased numbers of adrenergic and cholinergic nerve fibers. Intestinal Neuronal Dysplasia (IND), if associated with HD, occurs proximal to the aganglionic segment in HD, and is characterized by Dysplasia of parasympathetic nerves, hyperganglionosis, and giant ganglia. However, the cause of such abnormalities in HD and IND is unclear. Recent reports that mast cells (MC) have been observed in direct contact with nerve fibers generally, suggest that MC are essential for nerve growth and repair. MC synthesize, store, and release nerve growth factor (NGF). NGF supports the development and functional maintenance of sympathetic and cholinergic neurons. The aim of this study was to examine the colonic distribution of MC with respect to nerves in HD and HD associated with IND. Methods: MC and NGF were examined immunohistochemically in ganglionic, transitional, and aganglionic segments of colon from 20 patients with HD (five patients associated with IND) and 15 age-matched controls. MC were counted in each of five random fields using light microscopy (x100). Results : Interestingly, aganglionic and IND segments had large numbers of MC in all layers compared with ganglionic segments in HD patients and controls ( P P Conclusions : MC may cause hypertrophic nerve trunks and giant ganglia by releasing NGF and also may be an important factor in the excessive development of cholinergic and adrenergic nerve fibers in HD and IND.
Zhi Gang Feng - One of the best experts on this subject based on the ideXlab platform.
-
Mutation of RET proto-oncogene in Hirschsprung's disease and Intestinal Neuronal Dysplasia.
World Journal of Gastroenterology, 2006Co-Authors: Min-ju Li, Tao Guan, Ji-cheng Li, Zhi Gang FengAbstract:AIM: To investigate the genetic relationship between Hirschsprung’s disease (HD) and Intestinal Neuronal Dysplasia (IND) in Chinese population. METHODS: Peripheral blood samples were obtained from 30 HD patients, 20 IND patients, 18 HD/IND combined patients and 20 normal individuals as control. Genomic DNA was extracted according to standard procedure. Exons 11,13,15,17 of RET proto-oncogene were amplified by polymerase chain reaction (PCR). The mutations of RET proto-oncogene were analyzed by single strand conformational polymorphism (SSCP) and sequencing of the positive amplified products was performed. RESULTS: Eight germline sequence variants were detected. In HD patients, 2 missense mutations in exon 11 at nucleotide 15165 G→A (G667S), 2 frameshift mutations in exon 13 at nucleotide 18974 (18974insG), 1 missense mutation in exon 13 at nucleotide 18919 A→G (K756E) and 1 silent mutation in exon 15 at nucleotide 20692 G→A(Q916Q) were detected. In HD/IND combined patients, 1 missense mutation in exon 11 at nucleotide 15165 G→A and 1 silent mutation in exon 13 at nucleotide 18888 T→G (L745L) were detected. No mutation was found in IND patients and controls. CONCLUSION: Mutation of RET proto-oncogene is involved in the etiopathogenesis of HD. The frequency of RET proto-oncogene mutation is quite different between IND and HD in Chinese population. IND is a distinct clinical entity genetically different from HD.
Sibylle Koletzko - One of the best experts on this subject based on the ideXlab platform.
-
analysis of the ret gdnf edn3 and ednrb genes in patients with Intestinal Neuronal Dysplasia and hirschsprung disease
Gut, 2001Co-Authors: R Gath, A Goessling, K M Keller, Sibylle Koletzko, W Coerdt, H Muntefering, Stefan Wirth, Robert M W Hofstra, Lois M Mulligan, Charis EngAbstract:BACKGROUND—Hirschsprung disease (HSCR) is a frequent congenital disorder with an incidence of 1 in 5000 live births, characterised by the absence of parasympathetic intramural ganglion cells in the hindgut resulting in Intestinal obstruction in neonates and severe constipation in infants and adults. Intestinal Neuronal Dysplasia (IND) shares clinical features with HSCR but the submucosal parasympathetic plexus is affected. IND has been proposed as one of the most frequent causes of chronic constipation and is often associated with HSCR. METHODS—We examined 29 patients diagnosed with sporadic HSCR, 20 patients with IND, and 12 patients with mixed HSCR/IND for mutations in the coding regions of the RET, GDNF, EDNRB, and EDN3 genes. The entire coding regions were analysed by single strand conformational polymorphism and DNA sequencing. RESULTS—Only three RET mutations were detected in patients with HSCR. In patients with IND or a mixed HSCR/IND phenotype, no mutations in these genes were observed. While HSCR and HSCR/IND showed over representation of a specific RET polymorphism in exon 2, IND exhibited a significantly lower frequency comparable with that of controls. CONCLUSIONS—The mutation frequency found in our sporadic HSCR patients (10%) and the allelic distribution of RET polymorphisms are comparable with earlier published data. A significantly different allelic distribution in an established HSCR associated polymorphism argues against common genetic pathways for HSCR and IND. Keywords: Hirschsprung disease; Intestinal Neuronal Dysplasia; RET; GDNF; EDNRB; EDN3
-
rectal biopsy for diagnosis of Intestinal Neuronal Dysplasia in children a prospective multicentre study on interobserver variation and clinical outcome
Gut, 1999Co-Authors: Sibylle Koletzko, K M Keller, W Coerdt, H Muntefering, I Jesch, T Fauskessler, J Briner, W Meierruge, Lucas Wessel, W NutzenadelAbstract:BACKGROUND Intestinal Neuronal Dysplasia (IND) of the colonic submucous plexus is considered to be a congenital malformation of the enteric nervous system causing symptoms resembling those of Hirschsprung’s disease. In contrast with the established diagnosis of aganglionosis using enzyme histochemistry, controversy exists over the diagnostic criteria of IND on rectal biopsies previously defined by a consensus report and the causal relation between morphological findings and clinical symptoms. AIMS The interobserver variability was prospectively investigated with respect to final diagnoses and several histological features in rectal biopsy specimens from children suspected of having colonic motility disturbances. METHODS 377 biopsy specimens from 108 children aged 4 days to 15 years were independently coded without knowledge of clinical symptoms by three experienced pathologists for 20 histological features, and a final diagnosis was given for every case. Interobserver variation for the different items and the final diagnosis were analysed using Cohen’s κ statistic. Clinical data at biopsy and outcome after 12 months were related to morphological findings. RESULTS The three pathologists agreed completely with respect to the diagnosis Hirschsprung’s disease (κ = 1), but in only 14% of the children without aganglionosis. In 15 (17%) of the 87 children without aganglionosis, at least one pathologist judged the case as normal, while another diagnosed IND. κ values were close to the zero value expected by chance for the diagnoses normal and IND. Young age was related to the presence of several morphological features—for example, acetylcholine esterase staining and presence of giant ganglia. Children with chronic constipation diagnosed as having IND, given no other specific diagnosis by any of the pathologists, were significantly younger (median 8.8 months) and had a higher cure rate after one year (60%) than constipated patients considered by all observers to have no histological abnormalities (median 6.1 years, cure rate 23%). CONCLUSIONS In contrast with Hirschsprung’s disease, there is a high interobserver variation with regard to the different morphological features and final diagnosis of IND, based on the criteria and conditions of the previous consensus report. The high frequency of histological “abnormalities” in young infants suggests that some of the features may represent a normal variant of postnatal development rather than a pathological process. Investigations using more refined and morphometric methods in rectal specimens from infants and children without bowel disease are needed to define the normal range of morphological appearance at different ages. These preliminary data indicate that, with current knowledge, rectal biopsy for diagnostic purposes should only be performed in constipated children for diagnosis of Hirschsprung’s disease.
K M Keller - One of the best experts on this subject based on the ideXlab platform.
-
analysis of the ret gdnf edn3 and ednrb genes in patients with Intestinal Neuronal Dysplasia and hirschsprung disease
Gut, 2001Co-Authors: R Gath, A Goessling, K M Keller, Sibylle Koletzko, W Coerdt, H Muntefering, Stefan Wirth, Robert M W Hofstra, Lois M Mulligan, Charis EngAbstract:BACKGROUND—Hirschsprung disease (HSCR) is a frequent congenital disorder with an incidence of 1 in 5000 live births, characterised by the absence of parasympathetic intramural ganglion cells in the hindgut resulting in Intestinal obstruction in neonates and severe constipation in infants and adults. Intestinal Neuronal Dysplasia (IND) shares clinical features with HSCR but the submucosal parasympathetic plexus is affected. IND has been proposed as one of the most frequent causes of chronic constipation and is often associated with HSCR. METHODS—We examined 29 patients diagnosed with sporadic HSCR, 20 patients with IND, and 12 patients with mixed HSCR/IND for mutations in the coding regions of the RET, GDNF, EDNRB, and EDN3 genes. The entire coding regions were analysed by single strand conformational polymorphism and DNA sequencing. RESULTS—Only three RET mutations were detected in patients with HSCR. In patients with IND or a mixed HSCR/IND phenotype, no mutations in these genes were observed. While HSCR and HSCR/IND showed over representation of a specific RET polymorphism in exon 2, IND exhibited a significantly lower frequency comparable with that of controls. CONCLUSIONS—The mutation frequency found in our sporadic HSCR patients (10%) and the allelic distribution of RET polymorphisms are comparable with earlier published data. A significantly different allelic distribution in an established HSCR associated polymorphism argues against common genetic pathways for HSCR and IND. Keywords: Hirschsprung disease; Intestinal Neuronal Dysplasia; RET; GDNF; EDNRB; EDN3
-
Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with Intestinal Neuronal Dysplasia and Hirschsprung disease
2001Co-Authors: Gath R, K M Keller, Koletzko S, Muntefering H, Coerdt W, Goessling A, Wirth S, Hofstra Rmw, Mulligan L, Eng CAbstract:Background-Hirschsprung disease (HSCR) is a frequent congenital disorder with an incidence of 1 in 5000 live births, characterised by the absence of parasympathetic intramural ganglion cells in the hindgut resulting in Intestinal obstruction in neonates and severe constipation in infants and adults. Intestinal Neuronal Dysplasia (IND) shares clinical features with HSCR but the submucosal parasympathetic plexus is affected. IND has been proposed as one of the most frequent causes of chronic constipation and is often associated with HSCR. Methods-We examined 29 patients diagnosed with sporadic HSCR, 20 patients with IND, and 12 patients with mixed HSCR/IND for mutations in the coding regions of the RET, GDNF, EDNRB, and EDN3 genes. The entire coding regions were analysed by single strand conformational polymorphism and DNA sequencing. Results-Only three RET mutations were detected in patients with HSCR. In patients with IND or a mixed HSCR/IND phenotype, no mutations in these genes were observed. While HSCR and HSCR/ IND showed over representation of a specific RET polymorphism in exon 2, IND exhibited a significantly lower frequency comparable with that of controls. Conclusions-The mutation frequency found in our sporadic HSCR patients (10%) and the allelic distribution of RET polymorphisms are comparable with earlier published data. A significantly different allelic distribution in an established HSCR associated polymorphism argues against common genetic pathways for HSCR and IND
-
rectal biopsy for diagnosis of Intestinal Neuronal Dysplasia in children a prospective multicentre study on interobserver variation and clinical outcome
Gut, 1999Co-Authors: Sibylle Koletzko, K M Keller, W Coerdt, H Muntefering, I Jesch, T Fauskessler, J Briner, W Meierruge, Lucas Wessel, W NutzenadelAbstract:BACKGROUND Intestinal Neuronal Dysplasia (IND) of the colonic submucous plexus is considered to be a congenital malformation of the enteric nervous system causing symptoms resembling those of Hirschsprung’s disease. In contrast with the established diagnosis of aganglionosis using enzyme histochemistry, controversy exists over the diagnostic criteria of IND on rectal biopsies previously defined by a consensus report and the causal relation between morphological findings and clinical symptoms. AIMS The interobserver variability was prospectively investigated with respect to final diagnoses and several histological features in rectal biopsy specimens from children suspected of having colonic motility disturbances. METHODS 377 biopsy specimens from 108 children aged 4 days to 15 years were independently coded without knowledge of clinical symptoms by three experienced pathologists for 20 histological features, and a final diagnosis was given for every case. Interobserver variation for the different items and the final diagnosis were analysed using Cohen’s κ statistic. Clinical data at biopsy and outcome after 12 months were related to morphological findings. RESULTS The three pathologists agreed completely with respect to the diagnosis Hirschsprung’s disease (κ = 1), but in only 14% of the children without aganglionosis. In 15 (17%) of the 87 children without aganglionosis, at least one pathologist judged the case as normal, while another diagnosed IND. κ values were close to the zero value expected by chance for the diagnoses normal and IND. Young age was related to the presence of several morphological features—for example, acetylcholine esterase staining and presence of giant ganglia. Children with chronic constipation diagnosed as having IND, given no other specific diagnosis by any of the pathologists, were significantly younger (median 8.8 months) and had a higher cure rate after one year (60%) than constipated patients considered by all observers to have no histological abnormalities (median 6.1 years, cure rate 23%). CONCLUSIONS In contrast with Hirschsprung’s disease, there is a high interobserver variation with regard to the different morphological features and final diagnosis of IND, based on the criteria and conditions of the previous consensus report. The high frequency of histological “abnormalities” in young infants suggests that some of the features may represent a normal variant of postnatal development rather than a pathological process. Investigations using more refined and morphometric methods in rectal specimens from infants and children without bowel disease are needed to define the normal range of morphological appearance at different ages. These preliminary data indicate that, with current knowledge, rectal biopsy for diagnostic purposes should only be performed in constipated children for diagnosis of Hirschsprung’s disease.
