Altered expression pattern of molecular factors involved in colonic smooth muscle functions: an immunohistochemical study in patients with diverticular disease.

BACKGROUND: The pathogenesis of diverticular disease (DD) is thought to result from complex interactions among dietary habits, genetic factors and coexistence of other bowel abnormalities. These conditions lead to alterations in colonic pressure and motility, facilitating the formation of diverticula. Although electrophysiological studies on smooth muscle cells (SMCs) have investigated colonic motor dysfunctions, scarce attention has been paid to their molecular abnormalities, and data on SMCs in DD are lacking. Accordingly, the main purpose of this study was to evaluate the expression patterns of molecular factors involved in the contractile functions of SMCs in the tunica muscularis of colonic specimens from patients with DD. METHODS AND FINDINGS: By means of immunohistochemistry and image analysis, we examined the expression of Cx26 and Cx43, which are prominent components of gap junctions in human colonic SMCs, as well as pS368-Cx43, PKCps, RhoA and αSMA, all known to regulate the functions of gap junctions and the contractile activity of SMCs. The immunohistochemical analysis revealed significant abnormalities in DD samples, concerning both the expression and distribution patterns of most of the investigated molecular factors. CONCLUSION: This study demonstrates, for the first time, that an altered pattern of factors involved in SMC contractility is present at level of the tunica muscularis of DD patients. Moreover, considering that our analysis was conducted on colonic tissues not directly affected by diverticular lesions or inflammatory reactions, it is conceivable that these molecular alterations may precede and predispose to the formation of diverticula, rather than being mere consequences of the disease.

Review article: uncomplicated diverticular disease of the colon.

Diverticular disease of the colon is the fifth most important gastrointestinal disease in terms of direct and indirect health care costs in western countries. Uncomplicated diverticular disease is defined as the presence of diverticula in the absence of complications such as perforation, fistula, obstruction and/or bleeding. The distribution of diverticula along the colon varies worldwide being almost always left-sided and directly related to age in western countries and right-sided where diet is rich in fibre. The pathophysiology of diverticular disease is complex and relates to abnormal colonic motility, changes in the colonic wall, chronic mucosal low-grade inflammation, imbalance in colonic microflora and visceral hypersensitivity. Moreover, there can be genetic factors involved in the development of colonic diverticula. The use of non-absorbable antibiotics is the mainstay of therapy in patients with mild to moderate symptoms, and the effect of fibre-supplementation alone does not appear to be significantly different from placebo, although no definite data are available. More recently, alternative treatments have been reported. Mesalazine acts as a local mucosal immunomodulator and has been shown to improve symptoms and prevent recurrence of diverticulitis. In addition, probiotics have also been shown to be beneficial by re-establishing a normal gut microflora. In this study, the current literature on uncomplicated diverticular disease of the colon is reviewed.

Significant increase of colonic mutated crypts correlates with age in sporadic cancer and diverticulosis cases, with higher frequency in the left- than right-side colorectum.

Mild periodic acid-Schiff (mPAS) staining can discriminate non-O-acetylated (mPAS-positive) from O-acetylated (mPAS-negative) epithelial sialoglycoproteins in human colonic mucosa, allowing the three haplotypes expressed from a single polymorphic autosomal gene (oat) to be distinguished. In heterozygotes, we previously demonstrated wholly mPAS-positive (stem cell mutated) crypts and clusters of two or more mPAS-positive crypts to be significantly increased with duration of ulcerative colitis. To establish whether such an increase in the number of mutated crypts with age also occurs in normal individuals or in cases with diverticulosis, the O-acetylation phenotype in the non-cancerous colonic mucosa of 47 sporadic colorectal cancer patients who were heterozygotes for oat was tested with mild-PAS staining. PAS-positive crypts were assessed histologically in relation to age and compared between the left (sigmoid colon and rectum) and right (cecum and ascending colon) sides of the colorectum. Wholly mPAS-positive (stem cell mutated) crypts and foci in heterozygotes were found to be increased significantly (P < 0.0001) in the left side with aging (r = 0.598 and 0.643, respectively). Such a positive correlation with aging was also confirmed in 19 diverticulosis cases without cancer (r = 0.797 and 0.793, respectively). The frequency of mutated crypts and foci on the right side was significantly lower than on the left side in both spontaneous colorectal cancer and diverticulosis cases. The results provide support for an intimate relationship between accumulation of mutated crypts with aging, possibly with significance for colorectal cancer development. Furthermore, the environment in the right side of the colon may be different from that in the left side in this regard.

Evaluation of colonic diverticular disease in autosomal dominant polycystic kidney disease without end-stage renal disease.

A previous study had shown an increased prevalence (83%) of diverticula among patients with autosomal dominant polycystic kidney disease (ADPKD) with end-stage renal disease (ESRD) compared with other ESRD patients without ADPKD (32%). Others have also suggested an increased risk for diverticular complications in renal transplant recipients with ADPKD. To determine whether there was an increased occurrence of diverticula among non-ESRD patients with ADPKD, we studied 55 patients with ADPKD who were not receiving renal replacement therapy compared with 12 unaffected family members (non-ADPKD) and 59 random patients who had undergone barium enemas (control [C]). No study patient had a history of diverticular disease. All patients underwent a double-contrast barium enema after administration of glucagon. The occurrence, number, location, and size of diverticula were noted. There was no significant difference among the three groups in regard to sex (men: ADPKD, 42% versus non-ADPKD, 42% versus C, 37%) or age (ADPKD, 49.3 +/- 0.7 versus non-ADPKD, 51.2 +/- 2.1 versus C, 49 +/- 1 years). There was no significant difference in the percentage of patients with diverticula (ADPKD, 47% versus non-ADPKD, 58% versus C, 59%), the percentage with only right-colon diverticula (ADPKD, 5% versus non-ADPKD, 17% versus C, 5%), the mean number of diverticula in patients with diverticulosis (ADPKD, 13.8 versus non-ADPKD, 7.9 versus C, 9.9 diverticula), or the size of the largest diverticula (ADPKD, 9.5 versus non-ADPKD, 10.4 versus C, 10.5 mm). There was no significant difference in these variables between the patients with ADPKD with a creatinine clearance greater than 70 mL/min/1.73 m(2) (n = 25) or less than 70 mL/min/1.73 m(2). This study does not show the greater prevalence of diverticular disease in non-ESRD patients with ADPKD compared with the general population. Thus, patients with ADPKD need not be considered at greater risk for diverticular disease than the general population.

Diverticula of the colon in three Nigerian siblings.

This is a report of diverticular disease of the colon in three Nigerian adult siblings. Diverticular disease of the colon is known to be rare in Nigerians. Presence of this disease in a large number of a particular family raises the possibility of a familial tendency or some other undefined underlying abnormality. The three siblings have spent some years in the industrialized world. Our anecdotal experience however shows that the prevalence of diverticular disease of the colon may be on the increase in Nigeria.

[Diverticulosis and diverticular disease (reference to a case of diverticular disease observed in 3 sisters)]. / Diverticolosi e malattia diverticolare (riferimento a un caso di malattia diverticolare osservato in 3 sorelle).

We started from this frequent and important intestinal pathology to emphasize the above mentioned observation of three cases where it was possible to apply three different medico-surgical techniques with excellent results.

An inherited form of large bowel cancer: Muir's syndrome.

Three inherited types of large bowel cancer not associated with polyposis were previously proposed. A fourth should also be added to the list, namely, Torre's or Muir's syndrome. This report summarizes the clinical and genetic features of that syndrome in one family. The principle features of the syndrome comprise multiple skin tumors, i.e., sebaceous adenomas, keratoacanthomas, and basal and squamous cell carcinomas occurring with polyps and adenocarcinomas, mainly of the large bowel and also of the small intestine and stomach. Other malignancies occurring with the multiple skin tumors, with or without the involvement of intestinal malignancies, included adenocarcinoma of the uterus, transitional cell carcinoma of the bladder or ureter, squamous cell carcinoma of the larynx, esophagus, or vulva, and cancer of the breast. The syndrome followed a dominant mode of inheritance with high penetrance and variable expressivity, perhaps more variable in females than in males.