{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:35:19Z","timestamp":1790897719100,"version":"4.1.0"},"reference-count":19,"publisher":"Georg Thieme Verlag KG","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr Surg"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Introduction\u2003Diagnosis of very short-segment Hirschsprung's disease (vsHD) by rectal suction biopsy is challenging as its aganglionic zone (AZ) overlaps with physiologic hypoganglionic zone and calretinin-positive mucosal nerves may extend from the transition zone (TZ) into AZ. We studied whether an increasing trend\/gradient of calretinin-positive mucosal nerves along the distance from AZ toward TZ aids in diagnosis of HD.<\/jats:p><jats:p>\n          Materials and Methods\u2003In this study, 46 rectal suction biopsies from non-HD and HD, and 15 pull-through specimens from short-segment HD were evaluated by mucosal calretinin immunostain (CI) and image processing and analysis (IPA) to measure pixel count (PC, the percentage of calretinin stained pixels in the mucosa). Consecutive longitudinal sections of proximal AZ toward distal TZ in HD pull-through specimens were utilized as a vsHD surrogate model. First, we studied variability of mucosal CI in non-HD biopsies along the distance from dentate line. Second, we determined a cutoff point of mucosal CI by IPA that separated non-HD versus HD and applied this cutoff to longitudinal sections from proximal AZ to distal TZ segments in HD pull-through specimens. Third, we studied whether an increasing trend of mucosal CI was universally observed in HD pull-through.<\/jats:p><jats:p>\n          Results\u2003Our findings included a significant variability in PC along the biopsy distance in non-HD cases. Positive mucosal CI was found in proximal AZ in 6 (43%) of 14 HD pull-through, among which 1 case lacked submucosal nerve hypertrophy in the proximal AZ. All 14 HD pull-through cases showed an increasing trend\/gradient of PC from AZ toward TZ.<\/jats:p><jats:p>\n          Conclusion\u2003Based on our findings, the presence or absence of mucosal CI positivity and submucosal nerve hypertrophy may not reliably diagnose vsHD in rectal suction biopsy. While we acknowledge that the density of mucosal innervation in variable contexts and anatomical locations is unknown and yet to be explored, our study suggests that an increasing trend of positive mucosal CI from AZ toward TZ by IPA might prove to be a useful tool for the diagnosis of vsHD in the future.<\/jats:p>","DOI":"10.1055\/s-0041-1722859","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T23:51:07Z","timestamp":1611964267000},"page":"191-197","source":"Crossref","is-referenced-by-count":4,"title":["Increasing Trend of Calretinin-Positive Mucosal Innervation from Aganglionic Zone toward Transition Zone in Hirschsprung's Disease"],"prefix":"10.1055","volume":"32","author":[{"given":"Saleh","family":"Najjar","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangtae","family":"Ahn","sequence":"additional","affiliation":[{"name":"GE Global Research, Niskayuna, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Umrau","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0683-7421","authenticated-orcid":false,"given":"Mustafa","family":"Erdem Arslan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Jennings","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Whyte","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Albany Medical College, Albany, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7005-6278","authenticated-orcid":false,"given":"Hwajeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,1,29]]},"reference":[{"issue":"04","key":"ref1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1053\/j.sempedsurg.2009.07.003","article-title":"Practical pathology and genetics of Hirschsprung's disease","volume":"18","author":"R P Kapur","year":"2009","journal-title":"Semin Pediatr Surg"},{"issue":"04","key":"ref2","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1097\/00000658-198404000-00005","article-title":"Diagnosis and treatment of Hirschsprung's disease in Japan. An analysis of 1628 patients","volume":"199","author":"K Ikeda","year":"1984","journal-title":"Ann Surg"},{"issue":"06","key":"ref3","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1007\/s100249900167","article-title":"Diagnosis of Hirschsprung disease using the rectal biopsy: multi-institutional survey","volume":"2","author":"S J Qualman","year":"1999","journal-title":"Pediatr Dev Pathol"},{"issue":"01","key":"ref4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.2350\/08-02-0424.1","article-title":"Calretinin immunohistochemistry versus acetylcholinesterase histochemistry in the evaluation of suction rectal biopsies for Hirschsprung disease","volume":"12","author":"R P Kapur","year":"2009","journal-title":"Pediatr Dev Pathol"},{"issue":"05","key":"ref5","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.jpedsurg.2013.02.026","article-title":"A study of calretinin in Hirschsprung pathology, particularly in total colonic aganglionosis","volume":"48","author":"M I Morris","year":"2013","journal-title":"J Pediatr Surg"},{"issue":"08","key":"ref6","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.5858\/arpa.2012-0220-OA","article-title":"Hirschsprung disease and use of calretinin in inadequate rectal suction biopsies","volume":"137","author":"D H Gonzalo","year":"2013","journal-title":"Arch Pathol Lab Med"},{"issue":"10","key":"ref7","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1038\/modpathol.2009.110","article-title":"Calretinin immunohistochemistry: a simple and efficient tool to diagnose Hirschsprung disease","volume":"22","author":"V Guinard-Samuel","year":"2009","journal-title":"Mod Pathol"},{"issue":"02","key":"ref8","doi-asserted-by":"crossref","first-page":"66","DOI":"10.4103\/0971-9261.109355","article-title":"Calretinin immunohistochemistry: a new cost-effective and easy method for diagnosis of Hirschsprung's disease","volume":"18","author":"L Kannaiyan","year":"2013","journal-title":"J Indian Assoc Pediatr Surg"},{"issue":"03","key":"ref9","doi-asserted-by":"crossref","first-page":"226","DOI":"10.4318\/tjg.2012.0337","article-title":"Calretinin immunohistochemistry in Hirschsprung's disease: an adjunct to formalin-based diagnosis","volume":"23","author":"A Ka\u00e7ar","year":"2012","journal-title":"Turk J Gastroenterol"},{"issue":"01","key":"ref10","doi-asserted-by":"crossref","first-page":"28","DOI":"10.2350\/13-10-1387-OA.1","article-title":"Calretinin-immunoreactive mucosal innervation in very short-segment Hirschsprung disease: a potentially misleading observation","volume":"17","author":"R P Kapur","year":"2014","journal-title":"Pediatr Dev Pathol"},{"issue":"03","key":"ref11","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1055\/s-2005-837601","article-title":"Topographic peculiarities of the submucous plexus in the human anorectum--consequences for histopathologic evaluation of rectal biopsies","volume":"15","author":"K Tafazzoli","year":"2005","journal-title":"Eur J Pediatr Surg"},{"issue":"02","key":"ref12","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1055\/s-0037-1618594","article-title":"Image processing and analysis of mucosal calretinin staining to define the transition zone in Hirschsprung disease: a pilot study","volume":"29","author":"S Najjar","year":"2019","journal-title":"Eur J Pediatr Surg"},{"issue":"02","key":"ref13","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1177\/1093526619864225","article-title":"Transition zone in total colonic aganglionosis and colorectal Hirschsprung's disease shows a similar trend of mucosal innervation: image processing and analysis study","volume":"23","author":"F Cordeiro-Rudnisky","year":"2020","journal-title":"Pediatr Dev Pathol"},{"issue":"04","key":"ref14","doi-asserted-by":"crossref","first-page":"252","DOI":"10.2350\/12-12-1282-OA.1","article-title":"Histopathologic delineation of the transition zone in short-segment Hirschsprung disease","volume":"16","author":"R P Kapur","year":"2013","journal-title":"Pediatr Dev Pathol"},{"issue":"11","key":"ref15","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/0022-3468(90)90748-X","article-title":"Ultrashort Hirschsprung's disease: myth or reality","volume":"25","author":"I R Neilson","year":"1990","journal-title":"J Pediatr Surg"},{"issue":"04","key":"ref16","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/0022-3468(68)90670-2","article-title":"Ganglion cell distribution in the normal rectum and anal canal. A basis for the diagnosis of Hirschsprung's disease by anorectal biopsy","volume":"3","author":"R T Aldridge","year":"1968","journal-title":"J Pediatr Surg"},{"issue":"01","key":"ref17","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jpedsurg.2013.09.034","article-title":"The problematic Soave cuff in Hirschsprung disease: manifestations and treatment","volume":"49","author":"B H Dickie","year":"2014","journal-title":"J Pediatr Surg"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3389\/fncel.2018.00467","article-title":"Spinal afferent innervation of the colon and rectum","volume":"12","author":"S M Brierley","year":"2018","journal-title":"Front Cell Neurosci"},{"issue":"07","key":"ref19","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1136\/jcp.2004.016030","article-title":"The loss of calretinin expression indicates aganglionosis in Hirschsprung's disease","volume":"57","author":"I Barshack","year":"2004","journal-title":"J Clin Pathol"}],"container-title":["European Journal of Pediatric Surgery"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0041-1722859.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T23:52:54Z","timestamp":1650412374000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0041-1722859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,29]]},"references-count":19,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2022,4,19]]},"published-print":{"date-parts":[[2022,4]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0041-1722859","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0939-7248","1439-359X"],"issn-type":[{"value":"0939-7248","type":"print"},{"value":"1439-359X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,29]]}}}