Gastroenterology

Gastroenterology

Volume 123, Issue 5, November 2002, Pages 1459-1467
Gastroenterology

Clinical–Alimentary Tract
Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon*,**

https://doi.org/10.1053/gast.2002.36600Get rights and content

Abstract

Background & Aims: 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.

GASTROENTEROLOGY 2002;123:1459-1467

Section snippets

Control group

Patients in the control group (n = 13; mean age, 61.1 years; range, 23–83 years; 7 women and 6 men) underwent partial colectomy for nonobstructive carcinoma (T1–T2) or adenoma not suitable for endoscopic resection. All control patients reported normal bowel habits with stool frequencies at regular intervals. Radiographic studies showed normal anatomy of the colon and rectum. Rectal manometry did not show any abnormalities.

Patients with STC

All patients (n = 11, mean age, 49.8 years; range, 19–70 years; all

Control group

ICC were readily discernible throughout the entire smooth muscle coat. ICC processes running within the circular and longitudinal muscle layer were orientated preferably parallel to the axis of the smooth muscle cells (Figure 2A).

. Distribution of ICC. (A) Control group: ICC are densely distributed within the muscularis propria. Intramuscular ICC are shaped ovally and have bipolar processes that are orientated preferably parallel to the axis of the smooth muscle cells. (B) STC: Compared with the

Alterations of ICC

It has been established that, apart from the ENS, ICC are actively involved in the mediation of intestinal motility. The scientific “renaissance” of ICC, originally described about 100 years ago,25 is based on the observations that ICC generate electrical slow-wave activity13, 14 and are capable of mediating neuronal input.15, 16, 22 Evidence of these 2 main roles has mostly been derived from animal experiments in which ICC have been removed mechanically26 or damaged chemically27 or in which

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    *

    Address requests for reprints to: Thilo Wedel, M.D., Department of Anatomy, University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany. e-mail: [email protected]; fax: (49) 451-500-4034.

    **

    Supported by grants from the Deutsche Forschungsgemeinschaft (DFG Kr 1257/2-2) and the Research Foundation of the Medical University of Luebeck (1599/J-25).

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