Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon

Wedel, Thilo; Spiegler, Juliane; Soellner, Stefan; Roblick, Uwe J.; Schiedeck, Thomas; Bruch, Hans–Peter; Krammer, Heinz-Jürgen

doi:10.1053/gast.2002.36600

Cited by 286 publications

(238 citation statements)

References 40 publications

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“…There is evidence from two studies regarding significant reduction in ICC density in Chagasic megacolons compared to non-Chagasic colons 8,11 . Similar results have been reported by Wedel et al 30 for patients with constipation and megacolon of other etiologies. However, it remains unknown whether these findings are primary or secondary in the physiopathology of Chagasic megacolon 8 .…”

supporting

confidence: 91%

Depopulation of interstitial cells of cajal in chagasic megacolon: towards tailored surgery?

Araújo

Dumarco

Rawet

et al. 2010

ABCD, arq. bras. cir. dig.

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-Background -The mechanism of constipation in patients with Chagasic megacolon remains partially explained. In these patients, it was recently demonstrated a reduction in the population of interstitial cells of Cajal. Aim -To evaluate density of Cajal cells in the surgically resected colon of Chagasic patients in comparison to control patients, and to verify possible association between preoperative and postoperative bowel function of Chagasic patients and colonic cell count. Method -Sixteen patients with Chagasic megacolon were operated on. Clinical pre-and postoperative evaluation using the Cleveland Clinic Constipation Score was undertaken.Resected colons were examined. Cajal cells were identified by immunohistochemistry using anti-CD117 antibody. The mean cell number was compared to resected colons from 16 patients with non-obstructive sigmoid cancer. Association between preand post-operative constipation scores and cell count for megacolon patients was evaluated using the Pearson coefficient correlation test (r).

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supporting

confidence: 91%

Depopulation of interstitial cells of cajal in chagasic megacolon: towards tailored surgery?

Araújo

Dumarco

Rawet

et al. 2010

ABCD, arq. bras. cir. dig.

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“…To determine the changes to the frequencies of ICCs and ganglion cells, an adaptation of the methodology described by Wedel et al 10 was used. In this, cell counts were obtained within the areas that had been measured using the Samsung CCD color video camera coupled to the optical microscope, and the number …”

Section: Methodsmentioning

confidence: 99%

Abnormalities of digestive tract innervation in rat fetus treated with ethylenethiourea

et al. 2012

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PURPOSE: The pathophysiology of abnormalities associated with myenteric plexus lesions remains imperfectly understood. Such abnormalities have been correlated with subocclusive intestinal conditions in children with Hirschsprung's disease, cases of chronic constipation and, postoperatively, in cases of anorectal anomalies. This study evaluated abnormalities of the myenteric plexus in fetus from female rats that received ethylenethiourea. METHODS: Female rats were exposed to ethylenethiourea on the 11th day of pregnancy (experimental group) or to 0.9% physiological solution (control group). Abnormalities were only found in the experimental group. The digestive tract muscle layer was analyzed morphometrically and changes to the frequencies of nerve plexus cells and interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100 protein, neuron-specific enolase and C-Kit, respectively. RESULTS: Muscle and skeletal abnormalities were observed in 100%, anorectal anomalies in 86%, absent tail in 71%, short tail in 29%, duodenal atresia in 5%, esophageal atresia in 5% and persistent omphalomesenteric duct in 5%. Histopathological analysis showed a thinner muscle layer associated with lower frequencies of ganglion cells and interstitial cells of Cajal, in all gastrointestinal tract. CONCLUSION: Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.

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“…Only a few specific histopathological abnormalities have been found and described to date [12] . Concerning ICCs, there have been two studies of patients with idiopathic megabowl [5,13] and four studies of patients with idiopathic constipation with decreased ICC density [6,[14][15][16] . By contrast, another study of 63 patients with megacolon has shown no consistent alterations in colonic ICC histology [17] .…”

Section: Discussionmentioning

confidence: 99%

“…Clinical symptoms can include low stool frequency, lack of urge to defecate, abdominal distention, bloating, and abdominal discomfort [1] . Although the pathophysiology has not yet been fully understood, visceral neuropathies [2] , dysregulation of neurotransmitters [3] , degeneration of enteric neurons [4] , and alterations of interstitial cells of Cajal (ICCs) [5] are possible etiological mechanisms that have been discussed in the literature [6] . ICCs form a network that is widely distributed in all layers of the gastrointestinal tract.…”

Section: Introductionmentioning

confidence: 99%

Therapy-refractory gastrointestinal motility disorder in a child with c-kit mutations

Breuer

Oh²,

Molderings³

et al. 2010

WJG

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Constipation and fecal impaction are frequent and distressing complaints in pediatric gastroenterology. Especially in neurologically handicapped children, treatment of severe forms of slow-transit constipation (STC) can be difficult. In the majority of cases, STC is of unknown etiology. However, in recent years, there is growing evidence that interstitial cells of Cajal (ICCs), which serve as electrical pacemakers and generate spontaneous electrical slow waves in the gastrointestinal tract, might play an important role in the pathophysiology of STC. It remains unclear whether morphological ICC alterations seen in affected patients are based on congenital developmental anomalies, or whether they are a consequence of long-term constipation with secondary damage of the gastrointestinal nervous system. To the best of our knowledge, we present the first case of a patient with histological alterations in ICC morphology who displayed multiple alterations of c-kit at the level of mRNA. The protein encoded by c-kit is the receptor tyrosine kinase Kit (CD117), which is crucial for development and function of ICCs. Therefore, these findings provide a new explanation for congenital alterations of ICC development that result in gastrointestinal motility disorders.

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Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon

Cited by 286 publications

References 40 publications

Depopulation of interstitial cells of cajal in chagasic megacolon: towards tailored surgery?

Depopulation of interstitial cells of cajal in chagasic megacolon: towards tailored surgery?

Abnormalities of digestive tract innervation in rat fetus treated with ethylenethiourea

Therapy-refractory gastrointestinal motility disorder in a child with c-kit mutations

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