학술논문
Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung's disease.
Document Type
Article
Author
Dariel, Anne; Grynberg, Lucie; Auger, Marie; Lefèvre, Chloé; Durand, Tony; Aubert, Philippe; Le Berre-Scoul, Catherine; Venara, Aurélien; Suply, Etienne; Leclair, Marc-David; de Vries, Philine; Levard, Guillaume; Parmentier, Benoit; Podevin, Guillaume; Schmitt, Françoise; Couvrat, Véronique; Irtan, Sabine; Hervieux, Erik; Villemagne, Thierry; Lardy, Hubert
Source
Subject
*ENTERIC nervous system
*HIRSCHSPRUNG'S disease
*SURGICAL complications
*ENTEROCOLITIS
*DIARRHEA
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Language
ISSN
2045-2322
Abstract
In Hirschsprung's disease (HSCR), postoperative course remains unpredictable. Our aim was to define predictive factors of the main postoperative complications: obstructive symptoms (OS) and Hirschsprung-associated enterocolitis (HAEC). In this prospective multicentre cohort study, samples of resected bowel were collected at time of surgery in 18 neonates with short-segment HSCR in tertiary care hospitals. OS and HAEC were noted during postoperative follow-up. We assessed the enteric nervous system and the intestinal epithelial barrier (IEB) in ganglionic segments by combining immunohistochemical, proteomic and transcriptomic approaches, with functional ex vivo analysis of motility and para/transcellular permeability. Ten HSCR patients presented postoperative complications (median follow-up 23.5 months): 6 OS, 4 HAEC (2 with OS), 2 diarrhoea (without OS/HAEC). Immunohistochemical analysis showed a significant 41% and 60% decrease in median number of nNOS-IR myenteric neurons per ganglion in HSCR with OS as compared to HSCR with HAEC/diarrhoea (without OS) and HSCR without complications (p = 0.0095; p = 0.002, respectively). Paracellular and transcellular permeability was significantly increased in HSCR with HAEC as compared to HSCR with OS/diarrhoea without HAEC (p = 0.016; p = 0.009) and HSCR without complications (p = 0.029; p = 0.017). This pilot study supports the hypothesis that modulating neuronal phenotype and enhancing IEB permeability may treat or prevent postoperative complications in HSCR. [ABSTRACT FROM AUTHOR]