Showing papers on "Ulcerative colitis published in 2004"

Inflammation and Cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation

Abstract: Patients with ulcerative colitis and Crohn's disease are at increased risk for developing colorectal cancer. To date, no known genetic basis has been identified to explain colorectal cancer predisp...

Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine

Abstract: Background and aim: Evidence exists for the pathogenic role of the enteric flora in inflammatory bowel disease. Probiotics contain living microorganisms which exert health effects on the host. We compared the efficacy in maintaining remission of the probiotic preparation Escherichia coli Nissle 1917 and established therapy with mesalazine in patients with ulcerative colitis. Patients and methods: In total, 327 patients were recruited and assigned to a double blind, double dummy trial to receive either the probiotic drug 200 mg once daily (n = 162) or mesalazine 500 mg three times daily (n = 165). The study lasted for 12 months and patients were assessed by clinical and endoscopic activity indices (Rachmilewitz) as well as by histology. The primary aim of the study was to confirm equivalent efficacy of the two drugs in the prevention of relapses. Results: The per protocol analysis revealed relapses in 40/110 (36.4%) patients in the E coli Nissle 1917 group and 38/112 (33.9%) in the mesalazine group (significant equivalence p = 0.003). Subgroup analyses showed no differences between the treatment groups in terms of duration and localisation of disease or pretrial treatment. Safety profile and tolerability were very good for both groups and were not different. Conclusions: The probiotic drug E coli Nissle 1917 shows efficacy and safety in maintaining remission equivalent to the gold standard mesalazine in patients with ulcerative colitis. The effectiveness of probiotic treatment further underlines the pathogenetic significance of the enteric flora.

Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism

Abstract: Background: Patients with inflammatory bowel disease (IBD) are thought to be at increased risk of venous thromboembolism (TE). However, the extent of this risk is not known. Furthermore, it is not known if this risk is specific for IBD or if it is shared by other chronic inflammatory diseases or other chronic bowel diseases. Aims: To compare the risk of TE in patients with IBD, rheumatoid arthritis, and coeliac disease with matched control subjects. Patients and methods: Study subjects answered a questionnaire assessing the history of TE, any cases of which had to be confirmed radiologically. A total of 618 patients with IBD, 243 with rheumatoid arthritis, 207 with coeliac disease, and 707 control subjects were consecutively included. All three patient groups were compared with control subjects matched to the respective group by age and sex. Results: Thirty eight IBD patients (6.2%) had suffered TE. This was significantly higher compared with the matched control population with only 10 cases reported (1.6%) (p Conclusions: IBD is a risk factor for TE. It seems that TE is a specific feature of IBD as neither rheumatoid arthritis, another chronic inflammatory disease, nor coeliac disease, another chronic bowel disease, had an increased risk of TE.

C-reactive protein as a marker for inflammatory bowel disease.

Abstract: The production of CRP occurs almost exclusively in the liver by the hepatocytes as part of the acute phase response upon stimulation by IL-6, TNF-alphaand IL-1-betaoriginating at the site of inflammation. Its short half-life makes CRP a valuable marker to detect and follow up disease activity in Crohn's disease (CD). In contrast, ulcerative colitis has only a modest to absent CRP response despite active inflammation, and the reason for this is unknown. In CD, serum levels of CRP correlate well with disease activity and with other markers of inflammation as the CDAI, serum amyloid, IL-6 and faecal calprotectin. CRP is a valuable marker for predicting the outcome of certain diseases as coronary heart disease and haematological malignancies. An increased CRP (>45 mg/L) in patients with IBD predicts with a high certainty the need for colectomy and this by reflecting severe ongoing and uncontrollable inflammation in the gut. Finally, trials with anti-TNF and anti-adhesion molecules have shown that a high CRP predicts better response to these drugs. However, whether we need to include CRP as an inclusion criterion for future trials with biologicals is still a matter of debate.

Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk

Abstract: Background and aims: The risk of colorectal cancer is increased in ulcerative colitis (UC). Patients with UC have diverse colonoscopic appearances. Determining colonoscopic markers for cancer risk could allow patient risk stratification. Patients and methods: Following on from an earlier study which demonstrated a correlation between inflammation severity and neoplasia risk, a case control study was performed to look for colonoscopic markers of colorectal neoplasia risk in UC. Each patient with neoplasia detected between 1988 and 2002 was matched with two non-dysplastic colitic controls. Data were collected on post-inflammatory polyps, scarring, strictures, backwash ileitis, a shortened, tubular, or featureless colon, severe inflammation, and normal looking surveillance colonoscopies. Results: Cases (n = 68) and controls (n = 136) were well matched. On univariate analysis, cases were significantly more likely to have post-inflammatory polyps (odds ratio (OR) 2.14 (95% confidence interval 1.24–3.70)), strictures (OR 4.22; 1.08–15.54), shortened colons (OR 10.0; 1.17–85.6), tubular colons (OR 2.03; 1.00–4.08), or segments of severe inflammation (OR 3.38; 1.41–10.13), and less likely to have had a macroscopically normal looking colonoscopy (OR 0.40; 0.21–0.74). After multivariate analysis, a macroscopically normal looking colonoscopy (OR 0.38; 0.19–0.73), post-inflammatory polyps (2.29; 1.28–4.11), and strictures (4.62; 1.03–20.8) remained significant. The five year risk of colorectal cancer following a normal looking colonoscopy was no different from that of matched general population controls. Conclusions: Macroscopic colonoscopic features help predict neoplasia risk in UC. Features of previous/ongoing inflammation signify an increased risk. A macroscopically normal looking colonoscopy returns the cancer risk to that of the general population: it should be possible to reduce surveillance frequency to five years in this cohort.

Specificities of inflammatory bowel disease in childhood.

Abstract: In parallel with overall population trends, the incidence of paediatric ulcerative colitis (UC) has remained stable, whereas that of paediatric Crohn's disease (CD) has increased in recent decades. Still rare among preschool children, the incidence of both UC and CD rises steadily from middle childhood through adolescence. There is an unexplained preponderance of males with early-onset CD, and an equal gender distribution in paediatric UC. Observations on the familiality of paediatric inflammatory bowel disease (IBD) suggest that genetic susceptibility is particularly important to disease pathogenesis in young patients. In comparison to adult-onset disease, childhood UC is usually extensive but the anatomic localization of paediatric CD varies, as in adults. UC manifests uniformly as bloody diarrhea whereas the symptomatology of paediatric CD is much more diverse. Linear growth impairment frequently complicates chronic intestinal inflammation in paediatric CD. Key contributing factors have been defined; better immunomodulatory therapy and emerging biologic agents will potentially reduce its prevalence.

Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis.

Abstract: Summary Background : Probiotics are efficacious for treating and maintaining remission of ulcerative colitis. Aim : To conduct a randomized placebo-controlled trial of bifidobacteria-fermented milk supplementation as a dietary adjunct in treating active ulcerative colitis. Methods : Twenty patients with mild to moderate, active, ulcerative colitis randomly received 100 mL/day of bifidobacteria-fermented milk or placebo for 12 weeks with conventional treatment. Results : Clinical and endoscopic activity indices and histological scores were similar in the two groups before treatment. Although improvements were significant in both groups, the clinical activity index was significantly lower in the bifidobacteria-fermented milk than in the placebo group after treatment. The post-treatment endoscopic activity index and histological score were significantly reduced in the bifidobacteria-fermented milk, but not the placebo group. Increases in faecal butyrate, propionate and short-chain fatty acid concentrations were significant in the bifidobacteria-fermented milk, but not the placebo group. No adverse effects were observed in either group. Conclusion : Supplementation with this bifidobacteria-fermented milk product is safe and more effective than conventional treatment alone, suggesting possible beneficial effects in managing active ulcerative colitis. This is a pilot study and further larger studies are required to confirm the result these preliminary results.

Lactobacillus GG in inducing and maintaining remission of Crohn's disease

Abstract: Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders such as Crohn's disease and ulcerative colitis. Alteration of the intestinal microflora by antibiotic or probiotic therapy may induce and maintain remission. The aim of this randomized, placebo-controlled trial was to determine the effect of oral Lactobacillus GG (L. GG) to induce or maintain medically induced remission. Eleven patients with moderate to active Crohn's disease were enrolled in this trial to receive either L. GG (2 × 109 CFU/day) or placebo for six months. All patients were started on a tapering steroid regime and received antibiotics for the week before the probiotic/placebo medication was initiated. The primary end point was sustained remission, defined as freedom from relapse at the 6 months follow-up visit. Relapse was defined as an increase in CDAI of >100 points. 5/11 patients finished the study, with 2 patients in each group in sustained remission. The median time to relapse was 16 ± 4 weeks in the L. GG group and 12 ± 4.3 weeks in the placebo group (p = 0.5). In this study we could not demonstrate a benefit of L. GG in inducing or maintaining medically induced remission in CD.

Infliximab in inflammatory bowel disease: clinical outcome in a population based cohort from Stockholm County

Abstract: Background: Several placebo controlled studies have demonstrated the efficacy of infliximab in inflammatory bowel disease (IBD) but the potential toxicity of this new biological compound has been less studied. Aim: To assess the use of infliximab in IBD in a population based cohort, with special emphasis on the occurrence of severe adverse events and mortality. Patients: All patients with IBD treated with infliximab between 1999 and 2001 in Stockholm County were evaluated. Methods: Prospective registration of clinical data was carried out. Retrospective analyses were made of possible adverse events occurring in relation to infliximab treatment. Adverse events requiring pharmacological treatment or hospitalisation were defined as severe. Clinical response was assessed as remission, response, or failure. Results: A cohort comprising 217 patients was assembled: 191 patients had Crohn’s disease (CD), and infliximab was used off label for ulcerative colitis (UC) in 22 patients. Four patients were treated for indeterminate colitis (IC). Mean age was 37.6 (0.9) years (range 8–79). The mean number of infliximab infusions was 2.6 (0.1) (range 1–11). Forty two severe adverse events were registered in 41 patients (CD, n = 35). Eleven of the severe adverse events occurred postoperatively (CD, n = 6). Three patients with CD developed lymphoma (of which two were fatal), opportunistic infections occurred in two patients (one with UC, fatal), and two patients with severe attacks of IBD died due to sepsis (one with CD, one postoperatively with UC). One additional patient with UC died from pulmonary embolism after colectomy. Mean age in the group with fatal outcome was 62.7 years (range 25–79). The overall response rate was 75% and did not differ between the patient groups. Conclusions: Infliximab was efficacious as an anti-inflammatory treatment when assessed in a population based cohort of patients with IBD. However, there appear to be a significant risk of deleterious and fatal adverse events, particularly in elderly patients with severe attacks of IBD. Off label use of infliximab in UC and IC should be avoided until efficacy is proven in randomised controlled trials. The underlying risk of developing malignancies among patients with severe or chronically active CD in need of infliximab treatment is not known but the finding of a 1.5% annual incidence of lymphoma emphasises the need for vigilant surveillance with respect to this malignant complication.

Inflammatory bowel disease and smoking. A review of epidemiology, pathophysiology, and therapeutic implications

Abstract: The relationship between smoking behavior and inflammatory bowel disease (IBD) is complex. While Crohn's disease (CD) is associated with smoking and smoking has detrimental effects on the clinical course of the disease, ulcerative colitis (UC) is largely a disease of nonsmokers and former smokers. Furthermore, cigarette smoking may even result in a beneficial influence on the course of ulcerative colitis. The potential mechanisms involved in this dual relationship include changes in humoral and cellular immunity, cytokine and eicosanoid levels, gut motility, permeability, and blood flow, colonic mucus, and oxygen free radicals. Nicotine is assumed to be the active moiety. The differential therapeutic consequences comprise the cessation of smoking in CD and, so far, clinical trials using nicotine in different forms of application for UC. In this article, we review the relationship between cigarette smoking and IBD, considering epidemiological, pathogenetic, and clinical aspects.

Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Örebro, Sweden, 1993–1998

Abstract: Background: Microscopic colitis, including collagenous colitis and lymphocytic colitis, mainly affects middle aged and older subjects, with a female predominance in collagenous colitis. The diseases have previously been regarded as rare. We present an epidemiological study of microscopic colitis in a well defined Swedish population. Methods: Patients were retrospectively searched for in colonoscopy reports of those who had a colonoscopy in the period 1993–1998 for non-bloody diarrhoea. All colonic mucosal biopsies were reassessed using strict diagnostic criteria. Results: Biopsies from 1018 patients were reassessed. Fifty one (45 female) collagenous colitis patients and 46 (31 female) lymphocytic colitis patients were diagnosed. Median age at diagnosis was 64 years in collagenous colitis and 59 years in lymphocytic colitis. The mean annual incidence of collagenous colitis was 4.9/105 inhabitants (95% confidence interval (CI) 3.6–6.2/105) and of lymphocytic colitis 4.4/105 inhabitants (95% CI 3.1–5.7/105). The annual incidence of collagenous colitis increased from 3.7/105 in 1993–1995 to 6.1/105 in 1996–1998 (difference 2.4/105 (95% CI −0.3–5.1/105)) whereas the incidence of lymphocytic colitis increased from 3.1/105 to 5.7/105 (difference 2.6/105 (95% CI 0.1–5.2/105)). Conclusions: The annual incidences of collagenous colitis and lymphocytic colitis are higher than considered previously and are now equal to the incidence of Crohn’s disease in Sweden, and combined rates approach the incidence of ulcerative colitis. Microscopic colitis was diagnosed in 10% of all patients with non-bloody diarrhoea referred for colonoscopy and in almost 20% of those older than 70 years.

Normalization of faecal calprotectin: a predictor of mucosal healing in patients with inflammatory bowel disease.

Abstract: (2004). Normalization of faecal calprotectin: a predictor of mucosal healing in patients with inflammatory bowel disease. Scandinavian Journal of Gastroenterology: Vol. 39, No. 10, pp. 1017-1020.

Tobacco and IBD: relevance in the understanding of disease mechanisms and clinical practice.

Abstract: Current smoking protects against ulcerative colitis and, after onset of the disease, improves its course, decreasing the need for colectomy. However, smoking increases the risk of developing Crohn's disease and worsens its course, increasing the need for steroids, immunosuppressants and reoperations. Smoking cessation aggravates ulcerative colitis and improves Crohn's disease. The effects of smoking are the sum of contradictory effects of various substances, including nicotine and carbon monoxide, and are modulated by gender, genetic background, disease location and activity, cigarette dose and nicotine concentration. Smokers with ulcerative colitis should not be discouraged from stopping smoking but encouraged to stop, to reduce their risk of cardiopulmonary tobacco-related diseases. In Crohn's disease, smoking cessation has become a major therapeutic goal, particularly in young women and in patients with ileal involvement. A large amount of supportive information, use of nicotine-replacement therapies and antidepressants, and individual counselling might aid the patient in quitting.

Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second-line medical therapy or surgery

Abstract: Summary Background : The failure rate of medical therapy in severe ulcerative colitis is high. A risk index, to aid the identification of patients of not responding at an early stage to intravenous corticosteroid therapy, would be useful to facilitate second-line treatment or surgery. Methods : We recruited 167 consecutive patients with severe ulcerative colitis between January 1995 and March 2002; and employed multiple logistic regression to analyse parameters within the first 3 days of medical therapy. We applied statistical modelling to formulate a risk score according to the likelihood of medical failure. Results : Sixty-seven (40%) patients failed to respond to medical therapy. Multiple logistic regression analysis identified mean stool frequency and colonic dilatation within the first 3 days and hypoalbuminaemia as independent predictors of outcome (P < 0.001, 0.001 and 0.002 respectively). A numerical risk score was formulated based on these variables. Patients with scores of 0–1, 2–3 and ≥4 had a medical therapy failure rate of 11%, 43% and 85% respectively. Receiver–operator characteristic analysis of this score yielded area under curve of 0.88, with a sensitivity of 85% and specificity of 75% using score ≥4 in predicting non-response. Conclusion : This risk score allows the early identification of patients with severe ulcerative colitis who would be suitable for second-line medical therapy or surgery.

IBS-like symptoms in patients with inflammatory bowel disease in remission; relationships with quality of life and coping behavior.

Abstract: The aim of this study was to assess the prevalence of irritable bowel syndrome-like symptoms in healthy controls and inflammatory bowel disease patients in remission using the Rome II criteria. Furthermore, the possible relation of irritable bowel syndrome-like symptoms with the quality of life and coping behavior was studied. Seventy-three ulcerative colitis patients in remission, 34 Crohn's disease patients in remission, and 66 healthy controls completed questionnaires on irritable bowel syndrome, quality of life, and coping. Using the Rome II criteria, irritable bowel syndrome-like symptoms were found in one-third of ulcerative colitis patients and in 42% of Crohn's disease patients in remission. The presence of irritable bowel syndrome-like symptoms impaired the quality of life of patients, while no relation was found between the presence of symptoms and coping strategies.