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Abnormal colonic interstitial cells of Cajal in children with anorectal malformations
S E Kenny1, M G Connell, R J Rintala
1Department of Paediatric Surgery, Alder Hey Children's Hospital, Liverpool, England.
Insights
Defects in interstitial cells of Cajal (ICC), the intestinal pacemaker cells, may cause colonic hypomotility in children with high anorectal malformations, leading to constipation.
Area of Science:
- Pediatric Surgery
- Gastroenterology
- Developmental Biology
Background:
- Constipation is a common functional issue in children post-anorectal malformation surgery.
- Colonic hypomotility is observed in these patients, but its cause remains unclear.
- Interstitial cells of Cajal (ICC) are identified as key intestinal pacemaker cells.
Purpose of the Study:
- To investigate if defects in ICC distribution or density cause colonic hypomotility in anorectal malformation patients.
- To understand the underlying pathology of functional gastrointestinal disorders post-ARM surgery.
Main Methods:
- Immunohistochemical analysis of colostomy specimens from 12 high anorectal malformation (ARM) patients and 5 controls.
- Utilized antibodies for PGP9.5 (neural marker) and c-kit (ICC marker).
Main Results:
- All specimens showed ganglion cells.
- 7 of 12 ARM patients exhibited abnormal c-kit-positive ICC distribution or density.
- Two ARM patients lacked ICC; five had significantly reduced ICC density.
Conclusions:
- Abnormalities in interstitial cells of Cajal populations may explain colonic hypomotility in high anorectal malformations.
- These ICC defects could contribute to refractory constipation in affected children.
Background/Purpose:
Constipation is a frequent functional problem in children after operation for all types of anorectal malformations. Although this has been assumed to be caused by hypomotility of the rectosigmoid colon, recent studies have demonstrated generalized colonic hypomotility in children with high or intermediate anomalies. The cause of this disorder is unknown. The aim of this study was to determine whether the observed colonic hypomotility seen in patients with anorectal malformations was caused by defects in distribution or density of interstitial cells of Cajal (ICC), recently identified as 'intestinal pacemaker cells'.
Methods:
Colostomy specimens from 12 patients with high anorectal anomalies (ARM group; age 0 to 14 months) were compared with colostomy specimens from five control patients with nonmotility-related gastrointestinal pathology (age, 1 to 4 months). Specimens were immunohistochemically labelled with antibodies to PGP9.5, a marker for neural tissue, and antibodies to c-kit, a recently characterized marker for interstitial cells of Cajal (ICC).
Results:
Ganglion cells were present in all histological specimens. Abnormalities in distribution and density of c-kit-positive ICC were present in 7 of 12 ARM patients. In two ARM patients, ICC were completely absent, and in five patients, ICC density was markedly reduced in circular muscle and at the submucosal border of circular muscle. Only five ARM patients had a distribution of ICC similar to that of control patients.
Conclusion:
Defects in the population of intestinal pacemaker cells may underlie the colonic hypomotility seen in high anorectal malformations and hence may contribute to refractory constipation.