Diverticulosis is one of the most common morphologic changes of the colon observed in citizens of highly-developed countries. So far, in spite of numerous observational and experimental trials, not all etiopathogenetic factors of diverticulosis have been defined. It is assumed that one of the most common reasons of colonic diverticulosis is the increase in intracolonic pressure, mainly in the sigmoid colon, resulting from disturbance of colonic motility. One of the important factors responsible for gastrointestinal tract motor function are interstitial cells of Cajal (ICCs). It was confirmed, that in such gastrointestinal tract disorders as infantile hypertrophic pyloric stenosis, slow transit constipation, megacolon, diabetic gastro- and gastroenteroparesis, internal anal sphincter achalasia and Hirschprung’s disease there is a marked decrease of the interstitial cells of Cajal number. On the basis of published observations, the following aims of the study were established:
1. Assessment of the quantity and distribution of interstitial cells of Cajal in a transverse section of the sigmoid colon wall of patients with colonic diverticular disease, and in the control group (patients with non-obturative colon cancer).
2. Determination of the relationship between the number and distribution of interstitial cells of Cajal in the sigmoid colon in patients with diverticulosis, and age, duration of disease, type of symptoms and concomitant diseases.
3. Determination of the correlation between the number and distribution of the interstitial cells of Cajal in the sigmoid colon, and anorectal functions as recorded using anorectal manometry.
A total of 101 patients, operated in IIIrd Department of the General Surgery, Jagiellonian University Medical College between 2001 and 2006, were enrolled into the study. 34 patients operated for colonic diverticular disease were enrolled into the study group. The control group consisted of 67 patients operated electively for non-obturative colorectal cancer. The study has been conducted, with the Jagiellonian University Bioethical Committee’s consent, according to the Declaration of Helsinki guidelines.The primary goal of this study was to assess the quantity and determine the localization of the interstitial cells of Cajal in the transverse sections of the sigmoid colon wall in patients with diverticular disease, and in patients from the control group. The secondary goals were to determine the correlations between the number and distribution of the ICCs in the sigmoid colon of patients with diverticulosis, and age, duration of disease, diverticular disease symptoms, concomitant disorders and anorectal manometry results.
The distribution and the quantity of the ICCs constituting particular subpopulations were assessed, after performing immunohistochemical assay using anti c-kit antibody (DAKO), using the light microscope conjoined with an image analysis system (Image Analysis System; ProGres C 12 Plus camera (Jenoptik)).
The cells with positive reaction to anti c-kit antibody were identified using the method described above. Positive reaction revealed interstitial cells of Cajal as well as mast cells. Interstitial cells of Cajal had a characteristic fusiform shape, and in some preparations its branches were also visualized. Mast cells observed in the preparations had round and oval shape, and round, centrally located nucleus. Cajal cells, present in the circular and longitudinal muscle layer of sigmoid colon, were oriented parallel to the smooth muscle cells.
The following subpopulations of interstitial cells of Cajal were identified and assessed: ICC-SM – interstitial cells of Cajal, localized on the submucosal and circular muscle border of the sigmoid colon and in the region of the submucosal plexus, ICC-CM – interstitial cells localized in the sigmoid colon circular muscle layer, ICC-MP – interstitial cells localized between the circular and longitudinal muscle layers of the sigmoid colon and in the neighbourhood of the Auerbach’s plexus and ICC-LM – interstitial cells localized in the longitudinal sigmoid colon muscle layer. The quantity and distribution of particular ICCs subpopulations were assessed.
The number of interstitial cells was statistically significantly lower in patients with diverticulosis as compared to patients from the control group (15.53 vs 19.45 / breadth of 1 visual field respectively; p<0.001). The decrease of interstitial cells number was significantly higher in the neighbourhood of the Auerbach's plexus and in the area between the circular and longitudinal sigmoid colon wall muscle layers (ICC-MP). The mean number of interstitial cells observed in 1 visual field of 0,2756 mm2 in area in patients from the studied and control groups, divided into particular subpopulation, amounted respectively: ICC-SM 1.28 vs 1.67, ICC-CM 3.94 vs 4.69, ICC-MP 6.71 vs 10.08 and for ICC-LM subpopulation 2.85 vs 4.09.No differences in size, morphology and distribution of interstitial cells of Cajal in the previously described sigmoid colon wall layers were found between the control and study groups.
Moreover a positive correlation between the number of ICC-MP interstitial cells of Cajal and the presence of flatulence as well as mucous in the stool was demonstrated. A negative correlation between the number of ICC-LM cells of Cajal and the presence of pain, as reported by patients prior to the surgery, was also determined. The analysis of correlation between the number of interstitial cells of Cajal in the sigmoid colon obtained from patients with diverticulosis, and the presence of selected concomitant diseases, revealed a relationship between the quantity of the ICC-SM cells and the presence of the neurologic and thyroid gland disorders.
The analysis also revealed a correlation between interstitial cells of Cajal (ICC-CM subpopulation), and the presence of the thyroid gland diseases (nodular goiter, hyperthyreosis).
A correlation was also found between the number of interstitial cells of Cajal localized in the sigmoid colon circular muscle layer (ICC-CM) and the presence of the normal anorectal reflexes, as well as between the quantity of ICC-MP cells and the anorectal manometry values (BAP and MVSP).Obtained results confirm the observations, published in other publications, concerning the decrease in number of interstitial cells of Cajal in patients with colonic diverticulosis.
In summary, the number of the interstitial cells of Cajal is decreased in the sigmoid colon of patients with diverticulosis. It is particularly distinct in the ICC-MP, ICC-CM and ICC-LM groups. Taking into consideration the role of interstitial cells of Cajal in the regulation of gastrointestinal motility, it appears that a reduction of their number may be an important etiopathogenetic factor of colonic diverticulosis. These cells may also play a role in the pathophysiology of the symptoms of diverticular disease by modulating enteric nervous system (ENS) impulsation. The study revealed the negative correlation between the number of ICC-MP subpopulation cells and some subjective symptoms, as well as the relationship between abdominal pain and the decrease in the number of ICC-LM cells. Obtained results do not allow an unambiguous determination of the order and sequence of events leading to diverticula formation. There is no positive correlation between the duration of disease and its stage of advancement, and the number of the particular interstitial cell subpopulations. It seems that the number of Cajal cells may be influenced by the stage of local diverticular disease advancement, for example the increased quantity of collagen in the colonic wall, and not by the duration of symptoms. Diverticular disease is in most cases asymptomatic, and only patients operated with a high stage of local advancement of the disease following inefficacious conservative treatment and dietary modifications were enrolled into the study. The results of this study may contribute to the practical application of interstitial cells of Cajal detection methods in preoperative and intraoperative diagnostics, decision making regarding the extent of operative procedures, and reduction of recurrence after operative treatment. Progress concerning the role of interstitial cells of Cajal in the sigmoid colon of patients with diverticulosis may also contribute to the indications for modification of elective operative treatment, allowing more objective qualification of patients than currently possible.
Wydział Lekarski , 2007.