Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s disease

Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s disease

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 o...

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Autores principales: Anne Dariel, Lucie Grynberg, Marie Auger, Chloé Lefèvre, Tony Durand, Philippe Aubert, Catherine Le Berre-Scoul, Aurélien Venara, Etienne Suply, Marc-David Leclair, Philine de Vries, Guillaume Levard, Benoit Parmentier, Guillaume Podevin, Françoise Schmitt, Véronique Couvrat, Sabine Irtan, Erik Hervieux, Thierry Villemagne, Hubert Lardy, Carmen Capito, Cécile Muller, Sabine Sarnacki, Jean-François Mosnier, Louise Galmiche, Pascal Derkinderen, Hélène Boudin, Charlène Brochard, Michel Neunlist
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2020
Materias:
Medicine
R
Science
Q
Acceso en línea:https://doaj.org/article/3110da24af8843d099fb67bca2e44e21
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Sumario: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.

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