An abnormal distribution of C-kit positive cells in the normoganglionic segment can predict a poor clinical outcome in patients with Hirschsprung's disease.
OBJECTIVE
The loss or decrease of interstitial cells of Cajal (ICCs) has been implicated in several disorders of human intestinal motility. We have encountered a few cases suffering from severe constipation or enterocolitis resulting in patient death after a definitive operation for HD, even though the normoganglionic intestine had been successfully pulled through. We investigated the distribution of ICCs using c-kit immunostaining in the normoganglionic segment and compared these findings with the clinical outcome after a definitive operation in each case.


METHODS
The distributions of ICCs were investigated by using c-kit immunostaining in the normoganglionic segment in the resected bowel in 15 cases with HD. The distributions of protein gene product 9.5 (PGP 9.5) as a general neuronal marker and those of NADPH-diaphorase (NADPH-d) as a marker of nitric-oxide neurons were also examined. The numbers of ICCs and neurons were evaluated quantitatively. The histopathological results were compared with the clinical outcome after definitive operation in each case.


RESULTS
C-kit immunoreactive cells showed a normal distribution in the normoganglionic segment in 13 cases, while they were markedly (less than 50% compared with the other cases) decreased in 2 cases. The distributions of PGP 9.5 and NADPH-d were almost the same in all cases. The bowel movements of 13 cases showing normal c-kit distribution were satisfactory. In contrast, the bowel movements were impaired in 2 cases with a decreased number of c-kit positive cells. One infant suffered from severe persistent constipation and thus had to undergo a resection of a dilated colon. The other infant died of sepsis due to postoperative enterocolitis and showed a markedly dilated colon.


CONCLUSIONS
A decreased number of c-kit positive cells in the normoganglionic segment can thus allow us to predict a poor clinical outcome after definitive surgery, probably due to poor intestinal motility. Therefore examining the c-kit distribution in a resected bowel specimen in patients with HD should be mandatory in order to select the optimal postoperative treatment regimen for each case.
Taguchi
T
T
Department of Pediatric Surgery, Reproductive and Developmental Medicine, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan. taguchi@pedsurg.med.kyuishu-u.ac.jp
Suita
S
S
Masumoto
K
K
Nagasaki
A
A
D002648:Child; D002675:Child, Preschool; D003106:Colon / Q000473:pathology; D004108:Dilatation, Pathologic / Q000473:pathology; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology; D006627:Hirschsprung Disease / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007422:Intestines / Q000166:cytology*; D008297:Male; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D016896:Treatment Outcome; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
C482860:UCHL1 protein, human; D019009:Proto-Oncogene Proteins c-kit; D043222:Ubiquitin Thiolesterase