Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon.
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.
Wedel
Thilo
T
Department of Anatomy, Medical Universitiy of Luebeck, Luebeck, Germany. wedel@anat.mu-luebeck.de
Spiegler
Juliane
J
Soellner
Stefan
S
Roblick
Uwe J
UJ
Schiedeck
Thomas H K
TH
Bruch
Hans-Peter
HP
Krammer
Heinz-Juergen
HJ
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