Despite having a technically satisfactory pull-through operation for Hirschsprung’s disease (HSCR) (complete resection of all aganglionic or hypoganglionic colon with hypertrophic nerve trunks while avoiding injury to the sphincter mechanism), a substantial proportion of patients continue to experience symptoms such as intractable constipation, soiling, or recurrent Hirschsprung-associated enterocolitis. Some of these patients are later found to have a retained segment of aganglionic or transition zone colon. This may be avoided with more rigorous definition of what constitutes transition zone colon and by ensuring that a margin, the recommended length of which has yet to be determined, of colon above the normally ganglionated intraoperative biopsy is also resected.
The ostensibly normal ganglionic colon in children with HSCR exhibits a range of abnormalities when compared to healthy colon from children without HSCR. Excitatory and inhibitory innervation is imbalanced, with excessive nitrergic innervation and deficient cholinergic innervation (the opposite of what is seen in aganglionic colon). Neuronal serotonin, which has an anti-inflammatory role, is deficient in the ganglionic colon, especially of those who have been treated for enterocolitis.
The support cells responsible for intercellular communication in the electrical syncytium composed of the colonic smooth muscle and the enteric nervous system is also deficient, with less dense networks of interstitial cells of Cajal (ICC) (the pacemaker cells of the colon) and PDGFRα+ cells (mediate smooth muscle relaxation) being observed.
Finally, the colonic microbiome in children with HSCR is less diverse than that seen in healthy children, with expansions of pathogenic organisms and Candida species. This occurs in association with deficiency of mucus-producing goblet cells and other abnormalities of innate immunity and may contribute toward the increased susceptibility for Hirschsprung-associated enterocolitis seen in some patients after pull-through surgery.
Hirschsprung’s disease Transition zone pull-through
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