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Background and aimDisease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC.MethodsUsing a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute.ResultsFor CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities.ConclusionsBased on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.

Background The natural history of ulcerative colitis requires continuous monitoring of medical treatment via frequent outpatient visits. The European health authorities9 focus on e-health is increasing. Lack of easy access to inflammatory bowel disease (IBD) clinics, patients9 education and understanding of the importance of early treatment at relapse is leading to poor compliance. To overcome these limitations a randomised control trial ‘Constant-care’ was undertaken in Denmark and Ireland. Methods 333 patients with mild/moderate ulcerative colitis and 5-aminosalicylate acid treatment were randomised to either a web-group receiving disease specific education and self-treatment via http://www.constant-care.dk or a control group continuing the usual care for 12 months. A historical control group was included to test the comparability with the control group. We investigated: feasibility of the approach, its influence on patients9 compliance, knowledge, quality of life (QoL), disease outcomes, safety and health care costs. Results 88% of the web patients preferred using the new approach. Adherence to 4 weeks of acute treatment was increased by 31% in Denmark and 44% in Ireland compared to the control groups. In Denmark IBD knowledge and QoL were significantly improved in web patients. Median relapse duration was 18 days (95% CI 10 to 21) in the web versus 77 days (95% CI 46 to 108) in the control group. The number of acute and routine visits to the outpatient clinic was lower in the web than in the control group, resulting in a saving of 189 euro/patient/year. No difference in the relapse frequency, hospitalisation, surgery or adverse events was observed. The historical control group was comparable with the control group. Conclusion The new web-guided approach on http://www.constant-care.dk is feasible, safe and cost effective. It empowers patients with ulcerative colitis without increasing their morbidity and depression. It has yet to be shown whether this strategy can change the natural disease course of ulcerative colitis in the long term.

Aims:Some patients with coeliac disease, despite strict adherence to a gluten-free diet, continue to have significant symptoms and/or a severe small intestinal histological lesion. The term “refractory coeliac disease” (rCD) is used to describe this condition. The purpose of this study was to investigate the value of tissue molecular markers reported to help in the diagnosis of rCD.Methods:Details on 61 patients with suspected rCD were collected. The clinical and laboratory findings in these patients were carefully evaluated, in part to determine whether patients were adhering to a strict gluten-free diet. The co-expression of CD3 and CD8 on intraepithelial lymphocytes was investigated by monoclonal antibody staining of small intestinal biopsy tissue; a finding of less than 50% CD3+ cells co-expressing CD8 was defined as an aberrant phenotype. T cell receptor gene rearrangement was assessed when a sufficient tissue sample was available.Results:A diagnosis of rCD was made in 38 patients based on clinical, laboratory and histological data. An aberrant intraepithelial lymphocyte population was found in 20 of these patients and in this group a clonal T cell population was found in five of seven patients tested. In the remaining 18 patients, the CD3/CD8 ratio was normal and two of seven tested had a clonal T cell population. After detailed monitoring, a diagnosis of rCD was excluded in the remaining 23 patients.Conclusions:This study supports the use of phenotypic and T cell clonality investigations in identifying patients with true rCD.

Background—Eradication ofHelicobacter pylori cures and prevents the relapse of duodenal ulceration and also results in histological resolution of chronic active gastritis. Aim—To compare four treatment regimens lasting seven days of a proton pump inhibitor and two antibiotics in the eradication of H pylori.Patients—Men or women with H pylori positive duodenal ulceration or gastritis, or both.Methods—A single blind, prospectively randomised, parallel group, comparative, multicentre study. After a positive CLO test, patients underwent histology, H pylori culture, and a 13C urea breath test to confirm H pyloristatus. Treatment with one of four regimens: LAC, LAM, LCM, or OAM, where L is 30 mg of lansoprazole twice daily, A is 1 g of amoxycillin twice daily, M is 400 mg of metronidazole twice daily, C is 250 mg of clarithromycin twice daily, and O is 20 mg of omeprazole twice daily, was assigned randomly. A follow up breath test was done at least 28 days after completing treatment.Results—H pylori eradication (intention to treat) was 104/121 (86.0%) with LAC, 87/131 (66.4%) with LAM, 103/118 (87.3%) with LCM, and 94/126 (74.6%) with OAM. There was a significant difference (p < 0.001) in the proportion of patients in whom eradication was successful between LAC and LCM when compared with LAM, but no significant difference (p = 0.15) between LAM and OAM. Metronidazole resistance before treatment was identified as a significant prognostic factor with regard to eradication of H pylori. The regimens which contained metronidazole were significantly less effective than those without metronidazole in the presence of pretreatment resistant H pylori. There was no difference among the treatment groups with regard to the incidence and severity of adverse events reported. Conclusions—All four treatment regimens were safe and effective in eradicating H pylori in the patient population studied. LAC was the most efficacious treatment in patients with pretreatment metronidazole resistant H pylori, and was significantly better than LAM and OAM in this group of patients.

Increased epithelial cell proliferation is associated with an increased risk of adenocarcinoma and is associated with Helicobacter pylori infection. The aim of this study was to assess both gastric epithelial cell proliferation and the influence of H pylori infection on cell kinetics in the progression from normal mucosa to gastric carcinoma. One hundred and forty four subjects were assigned to study groups based on diagnosis and H pylori status: microscopically normal mucosa and H pylori negative (n = 28); chronic active gastritis and H pylori positive (n = 83); atrophic gastritis (n = 9); intestinal metaplasia (n = 19); gastric carcinoma (n = 12). Gastric antral epithelial cell proliferation was assessed using the in vitro bromodeoxyuridine immunohistochemical technique and expressed as the labelling index per cent (LI%). Subjects with chronic atrophic gastritis, intestinal metaplasia or gastric cancer have increased gastric epithelial cell proliferation compared with normal mucosa (LI% mean (SEM): 5.14 (0.6), 4.68 (0.3), 6.50 (0.5) v 3.08 (0.2), p < 0.001). This increase in gastric epithelial cell proliferation was not influenced by H pylori status. Gastritis associated with H pylori had an increased LI% compared with normal controls or subjects with H pylori negative gastritis (4.98 (0.2) v 3.08 (0.2), 3.83 (0.2), p < 0.01). H pylori infection although associated with an increased epithelial cell proliferation in subjects with chronic gastritis, does not influence the increased epithelial cell proliferation seen in subjects with precancerous lesions or gastric carcinoma. This is further evidence that H pylori may be an initiating step in gastric carcinogenesis.

AIM--To evaluate the histological changes that occur in the antral mucosa of healthy male subjects before and after one week of naproxen administration, using a chemical gastritis score according to the Helicobacter pylori status. METHODS--Nineteen male subjects (mean age 31 years) underwent two endoscopies: one before and the other after one week of naproxen treatment (1 g daily). Antral biopsy specimens were assessed for the presence of H pylori infection and for chemical gastritis, defined as the presence of foveolar hyperplasia, muscle fibres in the lamina propria, oedema, and vasodilatation, in the absence of acute or chronic inflammatory cell infiltrate. RESULTS--Of the 19 subjects, eight had H pylori infection. After one week of naproxen treatment, none of those with H pylori infection developed chemical gastritis, while five of 11 (45%) of those without H pylori infection did. In the absence of H pylori infection there was no evidence of inflammation, either before or after naproxen administration. CONCLUSIONS--A different pattern of antral histological change occurs following naproxen administration. This pattern is related to the presence or absence of H pylori infection, suggesting that H pylori status should be determined in histological studies of subjects taking non-steroidal anti-inflammatory drugs.

Introduction Osteoporosis is one of the under diagnosed and undertreated conditions worldwide. It is estimated that 1 in 3 women and 1 in 5 men in Ireland are diagnosed with it above the age of 50 years and will be likely to become more common with the increased life expectancy. In our study, we aimed to assess the rate of screening with DEXA scans for this condition in a prospective IBD cohort and to evaluate the results. We also studied possible factors that may influence DEXA rates. Methods As part of two decades follow up study of a multi-centre Irish IBD prospective cohort from the early 1990’s that was part of European Collaborative Study on IBD (EC-IBD), patients were traced and interviewed. There were 126 IBD patients from the Greater Dublin area who consented and completed the study questionnaire, following Ethical committees’ approvals. In this questionnaire we evaluated DEXA frequency and possible factors that may influence it; including patient diagnosis, age, gender, family history of IBD, courses of steroids, social class, total years of education, attending gastroenterologist or a surgeon, years of loss to follow up (LTFU) and membership to the national IBD patient support group (Irish Society of Crohn’s Colitis ISCC). Results were analysed with logistic regression and forward stepwise analysis using R program 3.0.1 software, taking p value Results Of the total 126 patients only 58 (46.03%) patients had DEXA scans performed. Of those 67.44% had CD and 33.73% had UC. When evaluating DEXA results osteoporosis was diagnosed in 26.67 and 21.43% of CD and UC patients respectively. Osteopenia was diagnosed in 43.33% CD and 42.86% of UC patients. About 30% of remaining scanned patients had normal DEXA. Logistic regression analysis showed that patients with positive family history of IBD and longer years of education were more likely to have had a scan with P = 0.024 and 0.049 respectively. Other possible risk factors didn’t reach statistical significance. Patients who were less compliant and LTFU were less likely to get DEXA with p = 0.045 in CD and p = 0.0336 in UC group. Conclusion Osteoporosis is an increasingly recognised condition and recently has been considered as one of the extra intestinal manifestations of IBD. Patient and doctor awareness is paramount to screening and diagnosis. Our study showed that CD patients were more likely to have DEXA scans during their disease course. The rate of osteoporosis was higher in CD patients, despite their fewer numbers when compared to UC group. Over 40% of IBD patients had osteopenia. Early detection and appropriate management will help to reduce fracture risk, improve patient quality of life in a cost effective manner. Disclosure of Interest None Declared.

We read with interest the recent multicentre European study by Fritscher-Ravens et al on the feasibility of wireless capsule endoscopy (WCE) in a paediatric population.1 In this study a large proportion of the study population needed direct deployment of WCE using various devices. However, the authors encountered significant complications with the use of a polyp retrieval net. Complications included traumatic oesophageal intubation and the cumbersome nature of release of the capsule in the duodenum. While swallowing is not a major issue in adults, gastric retention of the capsule remains a noticeable complication in ∼5% of individuals.2 Various techniques including body position, motility medications, …

Introduction A significant proportion of Crohn9s disease (CD) patients have been treated with two biologic therapies. Follow-up from current published retrospective or prospective open-label studies on patients who have already received 2 biologics does not extend beyond 1 year (1-4). Methods Our aim was to collect “real-life”, long-term data on the tolerability and efficacy of the second biologic agent in (re)-capturing response, and to assess whether the reason for stopping the first agent impacted on the successful use of the second agent. We carried out secure data collection from three teaching IBD centres on CD patients currently on, or already failed a second biologic. We collected data on disease duration, distribution and behaviour, and report on the aetiology in the failure of the first biologic and the subsequent outcome of the second biologic agent. Response to biologics was assessed by Harvey Bradshaw Index or Physicians Global Assessment. Results We collected data on 66 patients (F 46%, mean age at diagnosis: 25). The disease distribution was characterised as L1: 11%, L2:32% L3:56% L4:1% and the behaviour as B1:41% B2:35% B3:24%. 17% had perianal involvement. 36 patients have had a total of 41 resectional operations. First biologic: 64/66 patients had infliximab (IFX) first-line, followed by adalimumab (ADA), and 2/66 patients had ADA followed by IFX. Reasons for swapping were failure in 23%, secondary-loss of response in 38%, intolerance to the first agent in 29%, and fear of hypersensitivity reaction due to previous episodic exposure to IFX in 10% (irrespective of efficacy or tolerance). Second biologic: 70% of patients remained on the second biologic after a median follow-up of 22 months. Reasons for discontinuing therapy were 1o failure in 35%, secondary loss of response in 25%, intolerance (or patient concerns regarding potential side-effects) in 25%, and achieving remission in 5%; no reason provided for the remainder 5%. Neither the demographics, disease characteristics nor the reason for failing the first biologic had a statistically significant bearing in predicting the initial response to and subsequent outcome of the second biologic. Conclusions (1) We report an overall 70% retention on the second biologic at 22 months following all-cause failure of the first agent in CD patients from England and Ireland. (2) Patients responded equally well to the second biologic, irrespective of the reason for the failure of the first biologic.

EDITOR—The audit by Bampton et al highlights the practical problems encountered in the area of Barrett's oesophagus surveillance.1 Our retrospective audit of 441 patients with Barrett's oesophagus in a university teaching hospital setting showed an alarmingly low compliance rate of 8.6%.2 The main area of concern was that quadrantic biopsies were not taken in a large proportion of …

We read with interest the study by Whiting and colleagues ( Gut 2002: 50 :378–81). The study has further highlighted the importance of early detection of gastric cancer and also given further emphasis on ways to prevent the multistep progression in gastric carcinogenesis. However, we would like to make the following comments. Firstly, one in five patients in this group had lesions which, according to Whiting et al , should be followed up by yearly …

Editor,—We read with interest the recent clinical @lert commentary by Rutgreerts ( (2001) Gut 48:452–53; [OpenUrl][1][CrossRef][2][PubMed][3] ) analysing the recently published study by Lochs and colleagues.1 Lochs et al concluded that compared with placebo, 18 months of treatment with high dose Pentasa (mesalazine 4 g/day) made no difference to postoperative recurrence rates in patients with Crohn's disease involving the small intestine and colon or colon alone (26.3% v 25.6% for mesalazine and placebo, respectively). We feel that the study raises many new questions with regards to the role of 5-aminosalicylate (5-ASA) formulations in the prevention of postoperative Crohn's relapse. Furthermore, … [1]: {openurl}?query=rft.jtitle%253DGastroenterology%26rft.stitle%253DGastroenterology%26rft.aulast%253DLOCHS%26rft.auinit1%253DH.%26rft.volume%253D118%26rft.issue%253D2%26rft.spage%253D264%26rft.epage%253D273%26rft.atitle%253DProphylaxis%2Bof%2BPostoperative%2BRelapse%2Bin%2BCrohn%2527s%2BDisease%2BWith%2BMesalamine%253A%2BEuropean%2BCooperative%2BCrohn%2527s%2BDisease%2BStudy%2BVI%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0016-5085%252800%252970208-3%26rft_id%253Dinfo%253Apmid%252F10648454%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0016-5085(00)70208-3&link_type=DOI [3]: /lookup/external-ref?access_num=10648454&link_type=MED&atom=%2Fgutjnl%2F49%2F6%2F873.1.atom

OBJECTIVE: To determine whether eradication of Helicobacter pylori infection reduces recurrence of benign gastric ulceration. DESIGN: Randomised, double blind, controlled study. Patients were randomised in a 1:2 ratio to either omeprazole 40 mg once daily for eight weeks or the same treatment plus amoxycillin 750 mg twice daily for weeks 7 and 8. A 12 month untreated follow up ensued. SETTING: Teaching and district general hospitals between 1991 and 1994. SUBJECTS: 107 patients with benign gastric ulcer associated with H pylori. MAIN OUTCOME MEASURES: Endoscopically confirmed relapse with gastric ulcer (analysed with life table methods), H pylori eradication, and healing of gastric ulcers (Mantel-Haenszel test). RESULTS: 172 patients were enrolled. Malignancy was diagnosed in 19; 24 were not infected with H pylori; four withdrew because of adverse events; and 18 failed to attend for start of treatment, leaving 107 patients eligible for analysis (35 omeprazole alone; 72 omeprazole plus amoxycillin). In the omeprazole/amoxycillin group 93% (67/72; 95% confidence interval 84% to 98%) of gastric ulcers healed and 83% (29/35; 66% to 94%) in the omeprazole group (P = 0.103). Eradication of H pylori was 58% (42/72; 46% to 70%) and 6% (2/35; 1% to 19%) (P < 0.001) and relapse after treatment was 22% (16/72) and 49% (17/35) (life table analysis, P < 0.001), in the two groups, respectively. The recurrence rates were 7% (3/44) after successful H pylori eradication and 48% (30/63) in those who continued to be infected (P < 0.001). CONCLUSIONS: Eradication of H pylori reduces relapse with gastric ulcer over one year. Eradication rates achieved with this regimen, however, are too low for it to be recommended for routine use.

Rectal biopsies were collected from control subjects, patients with ulcerative colitis both active and quiescent, and from patients with Crohn's disease, both with and without rectal involvement, as judged by histological assessment. Tissue homogenates were assayed for neutrophil (vitamin B12 binding protein, myeloperoxidase, lysozyme) and lymphocyte (5' nucleotidase) selective markers. Patients with acute but not those with quiescent colitis had striking increases of the neutrophil markers. Neither patient group with ulcerative colitis showed a change in the lymphocyte marker enzyme activity. Patients with Crohn's disease involving the rectum showed significant, but less marked, increases in the activity of the neutrophil markers that were found in active ulcerative colitis. Patients with Crohn's disease, not involving the rectum, showed normal or reduced levels of neutrophil markers. Patients with Crohn's disease, both those with and without rectal involvement, had increased activities of the lymphocyte selective marker. This distinguishes this inflammatory response from that of ulcerative colitis and provides further biochemical evidence of abnormalities in apparently uninvolved mucosa from Crohn's patients.

Rectal biopsy specimens from control subjects, patients with either active or quiescent ulcerative colitis, and patients with Crohn's colitis were examined histologically and assayed for marker enzymes associated with tissue organelles. They were catalase (peroxisome); neutral alpha-glucosidase (endoplasmic reticulum); alkaline phosphatase (plasma membrane); malate dehydrogenase (mitochondria); lactate dehydrogenase (cytosol). There was no significant change in these enzyme activities in patient samples compared with controls. Activities of three acid hydrolases (lysosomal enzymes), beta-glucuronidase, acid phosphatase, and N-acetyl-beta-glucosaminidase, were also assayed in the biopsy samples. Decreased activities of all three enzymes were noted in ulcerative colitis, particularly in active disease. Normal values were obtained in Crohn's colitis. Measurement of lysosomal integrity by assays of latent N-acetyl-beta-glucosaminidase activity revealed similar results in control and colitic subjects. It is suggested that the lysosomal changes reflect a specific tissue release of enzyme and may be implicated in the pathogenesis of the tissue damage.

49 malades ont suivi un traitement prolonge par dissolution (sels biliaires et terpene) plus des seances de lithotripsie piezoelectrique guidee par ultrasons. Dans 27 cas tous les calculs sont elimines, dans 10 cas plus de la moitie, dans 2 cas moins de la moitie et dans 10 il n'y a qu'une fragmentation peu significative. Beaucoup de ces cas n'auraient pas ete traites par lithotripsie (dont 16 sur les 27 meilleurs, si on s'etait tenu aux anciens criteres de selection)