Gastroenterology

Gastroenterology

Volume 118, Issue 1, January 2000, Pages 14-21
Gastroenterology

Alimentary Tract
Decreased interstitial cell of Cajal volume in patients with slow-transit constipation,☆☆

https://doi.org/10.1016/S0016-5085(00)70409-4Get rights and content

Abstract

Background & Aims: The cause of slow-transit constipation is incompletely understood. Recent observations suggest a central role for interstitial cells of Cajal in the control of intestinal motility. The aim of this study was to determine the volume of interstitial cells of Cajal in the normal sigmoid colon and in the sigmoid colon from patients with slow transit constipation. Methods: Sigmoid colonic samples were stained with antibodies to protein gene product 9.5, c-Kit, and α–smooth muscle actin. Three-dimensional reconstruction of regions of interest was performed using consecutive images collected on a laser scanning confocal microscope and ANALYZE software. Results: Volume of interstitial cells of Cajal was significantly decreased in all layers of sigmoid colonic specimens from patients with slow-transit constipation compared with normal controls. Neuronal structures within the colonic circular smooth muscle layer were also decreased. Conclusions: A decrease in the volume of interstitial cells of Cajal may play an important role in the pathophysiology of slow-transit constipation.

GASTROENTEROLGY 2000;118:14-21

Section snippets

Materials and methods

Procurement of human tissue was approved by the Institutional Review Board of the Mayo Clinic. All tissues were immediately snap-frozen after procurement and stored at −70°C until use. The investigator performing the data analysis was blinded to the clinical diagnosis (control vs. slow-transit constipation).

Demographics

The demographics of the patients with slow-transit constipation are shown in Table 1, and the demographics of the controls are shown in Table 2.

. Patient demographics

PatientAge (yr)SexColonic transit (GC at 24 h; n = 1.6-3.8)Duration of constipation (yr)Pathology report
171F1.1LifelongColon mildly dilated, more so proximally; no microscopic abnormality
237F1.6>20Histologically unremarkable colon, ileum, and appendix
342F1.3>15Colon, ileum, and appendix without diagnostic abnormality
423F1.310

Discussion

The cause of constipation, even in patients with severe slow-transit constipation requiring surgery, is often elusive. The data presented in this report suggest that in addition to a previously described defect in innervation,59 which the present study confirms, there is also a decrease in ICC volume. It is now established that ICC are required for generation of the smooth muscle electrical slow wave.11, 12 The electrical slow wave determines smooth muscle contractile activity. In the absence

Acknowledgements

The authors thank Gary Stoltz and Adrian Holm for technical assistance and Kristy Zodrow for secretarial assistance.

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    Address request for reprint to: Gianrico Farrugia, M.D., Mayo Clinic, Guggenheim 8, 200 First Street Southwest, Rochester, Minnesota 55905. e-mail: [email protected]; fax: (507) 284-0266.

    ☆☆

    Supported by National Institutes of Health grants DK 52766 and 17238.

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