Allelic variation of the matrix metalloproteinase-9 gene is associated with collagenous colitis.

BACKGROUND: Collagenous colitis is a chronic inflammatory bowel disease of unknown origin characterized by a thickened subepithelial collagen layer. Differential expression of matrix-metalloproteinases (MMPs) have been implicated in the pathogenesis of collagenous colitis. The aim was to assess genetic polymorphisms of MMP-1, -7, and -9 in a case-control setting for susceptibility to collagenous colitis. METHODS: Seventy-five patients with symptomatic collagenous colitis and 334 healthy blood donors were genotyped for single nucleotide polymorphisms (SNPs) in MMP-1-1607, MMP-7-153, MMP-7-181, and MMP-9 exon 6 using TaqMan technology. Susceptibility to collagenous colitis was tested by comparison of the carrier status of the rare allele. RESULTS: The carrier frequency of the allele GG of the coding SNP MMP-9 in exon 6 was 24% in patients with collagenous colitis and 14.3% in healthy blood donors (P = 0.039). The carriage of the allele GG significantly increased the risk for collagenous colitis with an odds ratio of 1.9 (95% confidence interval: 1.0-3.5). None of the other SNPs of MMP-1, MMP-7-153, and MMP-7-181 were associated with collagenous colitis. CONCLUSIONS: Allelic variation in the MMP-9 gene may be part of a complex genetic risk profile for collagenous colitis. Further studies are needed to confirm this observation and to explore the functional role of this gene polymorphism in collagenous colitis.

Oral budesonide for maintenance treatment of collagenous colitis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Oral budesonide effectively induces clinical remission in patients with collagenous colitis, a debilitating illness characterized by chronic watery/loose diarrhea, but there is a high rate of relapse after treatment cessation. METHODS: This randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of long-term therapy with oral budesonide (Entocort CIR capsules) for maintenance of clinical remission of collagenous colitis. Patients were aged >18 years with histologically proven collagenous colitis and >3 watery/loose stools per day on >or=4 of the prior 7 days. Open-label oral budesonide 9 mg/d was administered to all patients for 6 weeks. Patients in clinical remission (3 stools per day on >or=4 consecutive days (and included patients withdrawn because of adverse events). RESULTS: Of 48 enrolled patients, 46 (96%) achieved clinical remission at week 6 and were randomized to maintenance budesonide or placebo. There were 21 relapses during maintenance therapy, and almost all occurred during the first 2 months. Budesonide therapy was associated with a significantly lower cumulative rate of relapse compared with placebo (6/23 [26%] and 15/23 [65%], respectively; P = .022), and high correlation between clinical remission and histologic improvement was observed. Budesonide was well tolerated with no serious adverse events. CONCLUSIONS: Oral budesonide 6 mg/d is efficacious and well tolerated for long-term maintenance of clinical remission in patients with collagenous colitis.

Human intestinal spirochetosis: analysis of the symptoms of 209 patients.

OBJECTIVE: Colonization of the colorectal mucosa with spirochetes is very rare. Owing to the small number of cases, it is not clear from the currently available publications whether spirochetes colonizing the colorectal mucosa are harmless commensals or pathogenic organisms. Furthermore, the reported complaints of these patients cannot be pooled to identify a characteristic complex of symptoms. The aim of the present work was to describe the symptoms associated with intestinal spirochetosis in a population of 209 patients, and to elucidate the effect of antibiotic treatment on these symptoms. MATERIAL AND METHODS: A total of 209 carefully processed questionnaires providing information on the symptoms, treatment and post-treatment symptoms of patients with spirochetosis were evaluated statistically and descriptively with the aid of the SPSS program, and the results were compared with those reported in the currently available literature. RESULTS: Of the 209 patients 168 (80.4%) were males, and the average age of the entire population at establishment of the diagnosis was 50.75 years. The most common symptoms reported were abdominal pain (46%), diarrhoea (51%) and alternating diarrhoea and constipation (13%). In this population, homosexuality and HIV infection played only a small role (6.5% homosexual patients, 3.8% HIV infected). In 72 of the 84 patients who received treatment (86%), the antibiotic employed was metronidazole, and the symptoms improved in 44 of the 84 patients (5%). Twenty-six of the 84 patients (30.9%) were investigated by colonoscopy/biopsy after receiving medical treatment. Biopsies in 20 of these patients no longer revealed infection with spirochetes, and symptoms were found to have improved in 11 of the 20 patients (55%). CONCLUSIONS: If intestinal spirochetosis is diagnosed to be the sole intestinal pathology in symptomatic patients, the bacteria should be eradicated with metronidazole and a colonoscopy/biopsy follow-up performed, where indicated, in patients with persisting symptoms. Significant results regarding symptoms and treatment of intestinal spirochetosis can be achieved only in a prospective, placebo-controlled, randomized, crossover study. In view of the low prevalence of this condition, such a study is difficult to implement.

Boswellia serrata extract for the treatment of collagenous colitis. A double-blind, randomized, placebo-controlled, multicenter trial.

BACKGROUND AND AIMS: The objective of this study was to investigate the effect of Boswellia serrata extract (BSE) on symptoms, quality of life, and histology in patients with collagenous colitis. MATERIALS AND METHODS: Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral BSE 400 mg three times daily for 6 weeks or placebo. Complete colonoscopy and histology were performed before and after treatment. Clinical symptoms and quality of life were assessed by standardized questionnaires and SF-36. The primary endpoint was the percentage of patients with clinical remission after 6 weeks (stool frequency

NOD2/CARD15 gene polymorphisms are not associated with collagenous colitis.

BACKGROUND: Collagenous colitis is a chronic inflammatory bowel disease of unknown origin. In some cases of collagenous colitis, histomorphological features are comparable to other inflammatory bowel diseases. AIM: To assess functional NOD2/CARD15 polymorphisms for the susceptibility to collagenous colitis in a case-control study. MATERIALS AND METHODS: Seventy-five patients with symptomatic collagenous colitis and 534 healthy blood donors were genotyped for SNP 8, 12, and 13 of the NOD2/CARD15 gene using TaqMan technology. Susceptibility to collagenous colitis was tested using Chi(2)-test comparing the carrier status of the rare allele. RESULTS: The carrier frequency of the rare allele in SNP 8, 12, and 13 was 9.5, 1.3, and 8.1% in patients with collagenous colitis and 8.9, 1.1, and 8.4% in healthy blood donors, respectively. There were no significant differences in allele-, genotype, and carrier frequency (p>0.05). CONCLUSION: Our data suggest that functional polymorphisms in the NOD2/CARD15 gene might not be involved in the susceptibility to collagenous colitis.

Strictures, diaphragms, erosions or ulcerations of ischemic type in the colon should always prompt consideration of nonsteroidal anti-inflammatory drug-induced lesions.

AIM: To investigate whether NSAIDs/ASA lesions in the colon can histologically be diagnosed on the basis of ischemic necrosis similar to biopsy-based diagnosis of NSAIDs/ASA-induced erosions and ulcers of the stomach. METHODS: In the period between 1997 and 2002, we investigated biopsy materials obtained from 611 patients (415 women, 196 men, average age 60.5 years) with endoscopic focal erosions, ulcerations, strictures or diaphragms in the colon. In the biopsies obtained from these lesions, we always established the suspected diagnosis of NSAID-induced lesions whenever necroses of the ischemic type were found. Together with the histological report, we enclosed a questionnaire to investigate the use of medication. The data provided by the questionnaire were then correlated with the endoscopic findings, the location, number and nature of the lesions, and the histological findings. RESULTS: At the time of their colonoscopy, 86.1% of the patients had indeed been taking NSAID/ASA medication for years (43.9%) or months (29.5%). The most common indication for the use of these drugs was pain (64.3%), and the most common indication for colonoscopy was bleeding (55.5%). Endoscopic inspection revealed multiple erosions and/or ulcers in 60.6%, strictures in 15.8%, and diaphragms in 3.0% of the patients. The lesions were located mainly in the right colon including the transverse colon (79.9%). A separate analysis of age and sex distribution, endoscopic and histological findings for NSAIDs alone, ASA alone, combined NSAID/ASA, and for patients denying the use of such drugs, revealed no significant differences among the groups. CONCLUSION: This uncontrolled retrospective study based on the histological finding of an ischemic necrosis shows that the histologically suspected diagnosis of NSAID-induced lesions in the colon is often correct. The true diagnostic validity of this finding and the differentiation from ischemic colitis should, however, be investigated in a prospective controlled study.

Oral budesonide therapy improves quality of life in patients with collagenous colitis.

INTRODUCTION: Collagenous colitis is an idiopathic microscopic colitis characterised by watery diarrhoea. The impact of collagenous colitis on quality of life has not been assessed. Our aim was to assess quality of life in patients with this condition and compare the effect of treatment with budesonide capsules or placebo on this parameter. METHODS: Patients with chronic diarrhoea and histologically-proven collagenous colitis were randomised to receive either budesonide controlled-release capsules (Entocort capsules, AstraZeneca, Lund, Sweden), 9 mg/day, or placebo for 6 weeks. Quality of life was measured using the validated Gastrointestinal Quality of Life Index (GIQLI) at baseline and after 6 weeks. With the GIQLI, scores range from 0 to 144, with higher scores representing better quality of life. RESULTS: Complete quality of life assessment was available in 29 patients (budesonide: n=17; placebo: n=12). At baseline, quality of life was low in patients with collagenous colitis (mean 76). After 6 weeks of treatment, the mean GIQLI score increased significantly in the budesonide group (from 67 to 92, p<0.001), but remained unchanged in the placebo group (86-88). The mean score of the dimensions symptoms (p=0.001), emotional functioning (p=0.003) and physical functioning (p=0.017) increased significantly in the budesonide group compared with the placebo group. A significantly larger proportion of patients in the budesonide group experienced improved stool consistency (p<0.01) and a significant reduction in the mean stool frequency compared with those in the placebo group (p<0.01). CONCLUSION: Quality of life is seriously reduced in patients with collagenous colitis. Six-week treatment with oral budesonide controlled-release capsules significantly improves quality of life and clinical symptoms compared with placebo in these patients.

Budesonide treatment for collagenous colitis: a randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND & AIMS: Collagenous colitis is an idiopathic microscopic colitis characterized by chronic watery diarrhea, a typical subepithelial collagen layer, and lymphoplasmacellular infiltration. We investigated the effect of budesonide on symptoms and histology in patients with collagenous colitis in a randomized, double-blind, placebo-controlled multicenter trial. METHODS: Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral budesonide (Entocort capsules; AstraZeneca, Sodertalje, Sweden) 9 mg/day for 6 weeks or placebo. Complete colonoscopy was performed before and after treatment. Histopathology was assessed by a single pathologist blinded to the patients' treatment. Clinical symptoms were assessed by standardized questionnaires. RESULTS: Fifty-one patients were randomized; 45 patients were available for per protocol analysis. The rate of clinical remission was significantly higher (P < 0.001) in the budesonide group than in the placebo group (per protocol 86.9% vs. 13.6%, respectively; intention-to-treat 76.9% vs. 12.0%, respectively). Histologic improvement was observed in 14 patients of the budesonide group (60.9%) and in 1 patient of the placebo group (4.5%; P < 0.001). Two patients in the budesonide group (7.7%) and 1 patient in the placebo group (4.0%) discontinued treatment prematurely because of side effects. CONCLUSIONS: Oral budesonide (Entocort capsules) is an effective and safe treatment modality for patients with collagenous colitis. Long-term follow-up of these patients is necessary to investigate whether clinical and histologic remission is sustained.

Colorectal de novo carcinoma: a review of its diagnosis, histopathology, molecular biology, and clinical relevance.

The effort to reduce colorectal adenocarcinoma mortality increasingly depends on detection and removal of precancerous adenomas by colonoscopy. Sporadic reports have described small, aggressive carcinomas that do not appear to develop from adenomas and have been called "de novo" carcinomas. These lesions seem to challenge the basis of colorectal surveillance and are therefore a controversial topic. This review presents the history of the de novo concept, the problems concerned with the histopathologic diagnosis of these lesions and what is presently known about their clinical and molecular biologic features in comparison with the more common ex adenoma type of colorectal carcinomas. This information will show that, despite their rarity, it is important for both pathologists and gastroenterologists to be aware of these lesions.