New insights into the pathogenesis of Hirschsprung’s associated enterocolitis

Murphy, Fionnuala; Puri, Prem

doi:10.1007/s00383-005-1551-1

Cited by 72 publications

(20 citation statements)

References 57 publications

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“…Hirschsprung-associated enterocolitis can be associated with severe infections of the small bowel and colon, and these can lead to life-threatening sepsis and death. Hirschsprung-associated enterocolitis occurs independent of pull-through technique and is present worldwide [1–3]. In severe cases, or chronic recurrent episodes affecting a child’s growth, a diverting colostomy needs to be performed.…”

Section: Introductionmentioning

confidence: 99%

Murine model of Hirschsprung-associated enterocolitis. I: Phenotypic characterization with development of a histopathologic grading system

Cheng

Dhall

Zhao

et al. 2010

Journal of Pediatric Surgery

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Purpose The aim of the study was to characterize enterocolitis in the Ednrb-null (Ednrb−/−) mouse with aganglionosis of the colon and to develop and validate a semiquantitative histopathologic grading system to assess enterocolitis. Methods We isolated colon and ileal specimens of Ednrb−/− and control mice (Ednrb+/+) and performed histochemical staining (H&E) on tissue sections. After establishing inflammation grading criteria, 2 blinded pathologists independently assessed the severity and depth of inflammation of proximal colon segments on 2 separate occasions. Interclass correlations (ICCs) and coefficient of variation (CV) were calculated to determine interrater and intrarater agreement. We then prospectively applied the enterocolitis grading system to Ednrb−/− mice that became clinically ill. A cohort of Ednrb−/− mice were observed until they developed clinical illness, at which time they were euthanized and had multiple organ homogenates cultured for bacteria, and colon and small bowel were histopathologically graded for enterocolitis. Spearman’s rank correlations comparing enterocolitis scores with level of bacteremia were performed. Results Intra- and interrater ICCs of the histologic scoring system were satisfactory (0.61 and 0.94, respectively), as were intra- and interrater CVs (18% and 9%, respectively). Of the Ednrb−/− mice, 65% developed bacteremia. Those with bacteremia had significantly higher enterocolitis scores than those without bacteremia (P < .01). Ednrb−/− mice that developed bacteremia showed a strong positive correlation between total enterocolitis scores and number of bacterial colony forming units in peritoneal lavage, liver, kidney, and aerobic spleen. Conclusions The Ednrb−/− mouse with aganglionosis develops enterocolitis and has features similar to Hirschsprung-associated enterocolitis in humans. Our grading system is a reliable way to assess enterocolitis. By performing microsurgical pull-through, we can now perform controlled, hypothesis-driven, mechanistic studies to evaluate etiologic factors affecting enterocolitis in the Ednrb−/− mouse.

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Section: Introductionmentioning

confidence: 99%

Murine model of Hirschsprung-associated enterocolitis. I: Phenotypic characterization with development of a histopathologic grading system

Cheng

Dhall

Zhao

et al. 2010

Journal of Pediatric Surgery

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“…Enterocolitis and toxic megacolon with sudden onset of fever, abdominal distension, and explosive, at times bloody, diarrhea are the most feared complications of HD. Fecal stasis with proliferation of colonic bacteria may initiate enterocolitis (16) and therefore, a delayed diagnosis is thought to be a significant risk factor.…”

Section: Clinical Presentationmentioning

confidence: 99%

A Practical Guide for the Diagnosis of Primary Enteric Nervous System Disorders

Schäppi

Staiano

Milla

et al. 2013

J. pediatr. gastroenterol. nutr.

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Objective: Primary gastrointestinal neuropathies are a heterogeneous group of enteric nervous system (ENS) disorders that continue to cause difficulties in diagnosis and histological interpretation. Recently, an international working group published guidelines for histological techniques and reporting, along with a classification of gastrointestinal neuromuscular pathology. The aim of this article was to review and summarize the key issues for pediatric gastroenterologists on the diagnostic workup of congenital ENS disorders. In addition, we provide further commentary on the continuing controversies in the field. Results: Although the diagnostic criteria for Hirschsprung disease are well established, those for other forms of dysganglionosis remain ill-defined. Appropriate tissue sampling, handling, and expert interpretation are crucial to maximize diagnostic accuracy and reduce interobserver variability. The absence of validated age-related normal values for neuronal density, along with the lack of correlation between clinical and histological findings, result in significant diagnostic uncertainties while diagnosing quantitative aberrations such as hypoganglionosis or ultrashort Hirschsprung disease. Intestinal neuronal dysplasia remains a histological description of unclear significance. Conclusions:The evaluation of cellular quantitative or qualitative abnormalities of the ENS for clinical diagnosis remains complex. Such analysis should be carried out in laboratories that have the necessary expertise and access to their own validated reference values.

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“…Furthermore, patients who develop HEC are prone to recurrent episodes. The high recurrence rate may be attributed to the persistence of certain characteristics of the mucosa in these particular patients, even after a decompressive colostomy or a pull-through procedure has been performed [9][10][11][12][13]. Studies reporting that multiple crypt abscesses may predict the development of clinical HEC, support this latter hypothesis [1,2].…”

Section: Introductionmentioning

confidence: 73%