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Eur J Pediatr Surg 2023; 33(04): 299-309
DOI: 10.1055/a-1889-6355
Original Article

Associations of Mucosal Nerve Fiber Innervation Density with Hirschsprung-Associated Enterocolitis: A Retrospective Three-Center Cohort Study

Michèle Moesch
1   Department of Pediatric Surgery, University Children's Hospital Basel, Basel, BS, Switzerland
,
Jakob Usemann
2   Department of Pediatric Pulmonology, UKBB Ringgold Standard Institution, Basel, BS, Switzerland
,
Elisabeth Bruder
3   Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
,
Philipp Romero
4   Division of Pediatric Surgery, University of Heidelberg, Heidelberg, Baden-Württemberg, Germany
,
Constantin Schwab
5   Institute of Pathology, University Hospital Heidelberg Institute of Pathology Ringgold Standard Institution, Heidelberg, Baden-Württemberg, Germany
,
Beate Niesler
6   Department of Human Molecular Genetics, University Hospital Heidelberg Institute of Human Genetics Ringgold Standard Institution, Heidelberg, Baden-Württemberg, Germany
,
Maria Angeles Tapia-Laliena
7   Department of Pediatric Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
,
Rasul Khasanov
7   Department of Pediatric Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
,
Tauseef Nisar
7   Department of Pediatric Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
,
Study Group NIG Retro,
Stefan Holland-Cunz
1   Department of Pediatric Surgery, University Children's Hospital Basel, Basel, BS, Switzerland
,
Simone Keck
1   Department of Pediatric Surgery, University Children's Hospital Basel, Basel, BS, Switzerland
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Abstract

Objective Hirschsprung's disease (HSCR) is a congenital intestinal neurodevelopmental disorder characterized by the absence of enteric ganglion cells in the distal colon. Although Hirschsprung-associated enterocolitis (HAEC) is the most frequent life-threatening complication in HSCR, to date reliable biomarkers predicting the likelihood of HAEC are yet to be established. We established a three-center retrospective study including 104 HSCR patients surgically treated between 1998 and 2019.

Materials and Methods Patient-derived cryopreserved or paraffin-preserved colonic tissue at surgery was analyzed via βIII-tubulin immunohistochemistry. We subsequently determined extrinsic mucosal nerve fiber density in resected rectosigmoid specimens and classified HSCR patients accordingly into nerve fiber-high or fiber-low groups. We compared the distribution of clinical parameters obtained from medical records between the fiber-high (n = 36) and fiber-low (n = 68) patient groups. We assessed the association between fiber phenotype and enterocolitis using univariate and multivariate logistic regression adjusted for age at operation.

Results Enterocolitis was more prevalent in patients with sparse mucosal nerve fiber innervation (fiber-low phenotype, 87%) compared with the fiber-high phenotype (13%; p = 0.002). In addition, patients developing enterocolitis had a younger age at surgery (3 vs. 7 months; p = 0.016). In the univariate analysis, the odds for enterocolitis development in the fiber-low phenotype was 5.26 (95% confidence interval [CI], 1.67–16.59; p = 0.005) and 4.01 (95% CI, 1.22–13.17; p = 0.022) when adjusted for age.

Conclusion Here, we showed that HSCR patients with a low mucosal nerve fiber innervation grade in the distal aganglionic colon have a higher risk of developing HAEC. Consequently, histopathologic analysis of the nerve fiber innervation grade could serve as a novel sensitive prognostic marker associated with the development of enterocolitis in HSCR patients.

Keywords

Hirschsprung-associated enterocolitis - prognostic marker - extrinsic nerve fibers


Publikationsverlauf

Eingereicht: 21. November 2021

Angenommen: 23. Juni 2022

Accepted Manuscript online:
01. Juli 2022

Artikel online veröffentlicht:
14. Oktober 2022

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