Role Of Interstitial Cells Of Cajal In The Bowel Of Hirschsprung's Disease

Background:The pathogenesis of Hirschsprung's Disease(HD)is unclear.Some studies show that the symptoms in HD is not related to the length of the aganglionic segment but to the total length of the aganglionic segment and transitional segment.So the absence of ganglion cells is not the only pathogenesis of HD.Recently many scientists have recognized that interstitial cells of Cajal (ICCs)are pacemaker cells between gastrointestinal smooth muscles;which generate spontaneous slow waves of the smooth muscle layers and mediate the neurotransmission.The cellular network of ICCs is connected by Gap junctions to each other and to the smooth muscle cells.This study examined the distribution of interstitial cells of Cajal in the aganglionic and transitional segments and aimed to explore the role of ICCs in the pathogenesis of Hirschsprung's disease.Subjects:Thirty three children with HD were enrolled and all of them had been performed radical operation from July 2006 to January 2008 in the department of general surgery,children's hospital of Zhejiang University.All clinical materials were achieved via the clinical history,physical examinations,barium enema,and pathology.There were twenty three boys and ten girls,aging from 1 month to 45 months.Of which,long segment type was in 5 cases,common type in 21,short segment in 7.Method:Full-thickness bowel specimens were obtained from aganglionic segment,transitional segment and proximal segment of thirty three children with HD and 9 normal controls.The distribution of ICCs in bowel from HD patients and normal controls was studied by c-kit immunohistochemistry.Results:1.At aganglionic segment of HD patients,there were no ganglion cells in Auerbach plexus(AP),and abnormal hypertrophic never trunks were observed. At transitional segment,immature or mature ganglion cells and reduction of abnormal hypertrophic never trunks showed in AP.The number of ganglion cells and intramuscular nerve fibers in the proximal segment of HD patients were almost the same as that at normal controls.2.In bowel from normal controls and the proximal segment of HD patients, large amount of ICCs were observed around the myenteric plexus and the submuscular nerve plexus.And there were moderate to large amount of ICCs at the circular muscle layer.ICCs in both the muscle layers and around the myenteric plexus appeared as a network structure.There was no significant difference in the number of ICCs between the proximal segment of HD patients and that of normal controls(P±0.05).3.In bowel from the transitional segment of HD patients,moderate amount of ICCs were observed around the myenteric plexus and circular muscle layer. And the network structure had been destroyed partially.Statistics showed the significant difference of the amounts of ICCs between the transitional segment of HD patients and that of normal controls(P±0.05).4.In bowel from the aganglionic segment of HD patients,the number of ICCs was remarkably reduced or even disappeared around the myenteric Plexus.It was very difficult to find ICCs at longitudinal muscle layer.Statistics showed the significant difference of the amount of ICCs between the aganglionicsegment of HD patients and that of normal controls(P＜0.05).Conclusion:Lack of ICCs and destruction of the network of ICCs in the aganglionic and transitional segments of bowel maybe one of the pathological changes in HD.