{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T04:57:17Z","timestamp":1778302637702,"version":"3.51.4"},"reference-count":46,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[1999,1,5]]},"published-print":{"date-parts":[[1999,6,1]]},"abstract":"<jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>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\u2019s 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>AIMS<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec sec-type=\"methods\">\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>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\u2019s \u03ba statistic. Clinical data at biopsy and outcome after 12 months were related to morphological findings.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>The three pathologists agreed completely with respect to the diagnosis Hirschsprung\u2019s disease (\u03ba = 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. \u03ba 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\u2014for 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%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>In contrast with Hirschsprung\u2019s 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 \u201cabnormalities\u201d 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\u2019s disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/gut.44.6.853","type":"journal-article","created":{"date-parts":[[2010,6,30]],"date-time":"2010-06-30T12:46:12Z","timestamp":1277901972000},"page":"853-861","source":"Crossref","is-referenced-by-count":98,"title":["Rectal biopsy for diagnosis of intestinal neuronal dysplasia in children: a prospective multicentre study on interobserver variation and clinical outcome"],"prefix":"10.1136","volume":"44","author":[{"given":"S","family":"Koletzko","sequence":"first","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Jesch","sequence":"additional","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Faus-Ke\u03b2ler","sequence":"additional","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Briner","sequence":"additional","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Meier-Ruge","sequence":"additional","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"M\u00fcntefering","sequence":"additional","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Coerdt","sequence":"additional","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Wessel","sequence":"additional","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K M","family":"Keller","sequence":"additional","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"N\u00fctzenadel","sequence":"additional","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Schmittenbecher","sequence":"additional","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Holschneider","sequence":"additional","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Sacher","sequence":"additional","affiliation":[{"name":"aKinderpoliklinik der Ludwig-Maximilians- Universit\u00e4t, M\u00fcnchen, Germany, \n\nbGSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, M\u00fcnchen, Germany, \n\ncPathologisches Institut der Universit\u00e4t Z\u00fcrich, Switzerland, \n\ndPathologisches Institut der Universit\u00e4t Basel, Switzerland, \n\nePathologisches Institut der Universit\u00e4t Mainz, Germany, \n\nfKinderchirurgische Klinik der Universit\u00e4t Mannheim, Germany, \n\ngKinderklinik der Universit\u00e4t Bonn, Germany, \n\nhKinderklinik der Universit\u00e4t Heidelberg, Germany, \n\niKinderchirurgi"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1999,6,1]]},"reference":[{"key":"2025090711414032000_44.6.853.1","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/S0022-3468(88)80366-X","article-title":"Diagnosis of allied functional bowel disorders using monoclonal antibodies and electronmicroscopy.","volume":"23","author":"Puri","year":"1988","journal-title":"J Pediatr Surg"},{"key":"2025090711414032000_44.6.853.2","first-page":"179","article-title":"Visceral neuropathies responsible for chronic intestinal pseudo-obstruction syndrome in pediatric practice: analysis of 26 cases.","volume":"11","author":"Navarro","year":"1990","journal-title":"J Pediatr Gastroenterol 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