title: Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon.
abstract: OBJECTIVE
  A variety of gastrointestinal motility disorders have been attributed to alterations of interstitial cells of Cajal and malformations of the enteric nervous system. This study evaluates both the distribution of interstitial cells of Cajal and the pathohistology of the enteric nervous system in 2 severe human colorectal motility disorders.
  
  
  METHODS
  Colonic specimens obtained from patients with slow-transit constipation (n = 11), patients with megacolon (n = 6), and a control group (n = 13, nonobstructing neoplasia) were stained with antibodies against c-kit (marker for interstitial cells of Cajal) and protein gene product 9.5 (neuronal marker). The morphometric analysis of interstitial cells of Cajal included the separate registration of the number and process length within the different regions of the muscularis propria. The structural architecture of the enteric nervous system was assessed on microdissected whole-mount preparations.
  
  
  RESULTS
  In patients with slow-transit constipation, the number of interstitial cells of Cajal was significantly decreased in all layers except the outer longitudinal muscle layer. The myenteric plexus showed a reduced ganglionic density and size (moderate hypoganglionosis) compared with the control group. Patients with megacolon were characterized by a substantial decrease in both the number and the process length of interstitial cells of Cajal. The myenteric plexus exhibited either complete aganglionosis or severe hypoganglionosis.
  
  
  CONCLUSIONS
  The enteric nervous system and interstitial cells of Cajal are altered concomitantly in slow-transit constipation and megacolon and may play a crucial role in the pathophysiology of colorectal motility disorders.
authors.affiliation: Department of Anatomy, Medical Universitiy of Luebeck, Luebeck, Germany. wedel@anat.mu-luebeck.de
authors.forename: Thilo
authors.initials: T
authors.lastname: Wedel
authors.forename: Juliane
authors.initials: J
authors.lastname: Spiegler
authors.forename: Stefan
authors.initials: S
authors.lastname: Soellner
authors.forename: Uwe J
authors.initials: UJ
authors.lastname: Roblick
authors.forename: Thomas H K
authors.initials: TH
authors.lastname: Schiedeck
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Bruch
authors.forename: Heinz-Juergen
authors.initials: HJ
authors.lastname: Krammer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D003106:Colon / Q000473:pathology*; D003248:Constipation / Q000473:pathology* / Q000503:physiopathology*; D035061:Control Groups; D017615:Enteric Nervous System / Q000473:pathology*; D005260:Female; D005772:Gastrointestinal Transit; D006801:Humans; D008297:Male; D008531:Megacolon / Q000473:pathology* / Q000503:physiopathology*; D008875:Middle Aged; D009197:Myenteric Plexus / Q000473:pathology