In patients with Helicobacter pylori gastritis and functional dyspepsia, a biopsy from the incisura angularis provides useful diagnostic information

The aim of this study was to assess whether the taking of an additional biopsy from the incisura angularis increases the chance of detecting maximal degrees of atrophy and intestinal metaplasia (IM) in patients with Helicobacter pylori gastritis and functional dyspepsia. At entry into a randomised trial, biopsies were taken from 328 patients (mean age 48 years), two from both the gastric antrum and corpus, and one from the incisura angularis, and comparative grading of gastritis variables was carried out. Biopsy material from the gastric antrum, corpus, and the incisura angularis revealed no notable differences in atrophy or an incidence of IM and mucosa-associated lymphatic tissue. However, when the incisura biopsies were classified histologically, 58% contained antral mucosa (AM), 18% corpus mucosa (CM), and 24% intermediate zone mucosa. AM at the incisura was associated with considerably more severe gastritis in both the incisura and antrum (14% atrophy, 20% IM) than in CM of incisura (2% atrophy, 6% IM). Corpus atrophy and IM were rare in the AM group and absent from the CM group. Incisura angularis biopsy in patients with H. pylori gastritis and functional dyspepsia does give additional information regarding the severity of gastritis expected in the corpus and antrum. Antral-type mucosa in the incisura angularis region seems to indicate an increased risk for the development of atrophy and/or IM.     

Incidence of duodenal ulcer healing after 1 week of proton pump inhibitor triple therapy for eradication of Helicobacter pylori

Background:

A number of clinical studies have assessed the efficacy of short-term twice-daily Helicobacter pylori eradication regimens but few have investigated the proportion of patients in whom duodenal ulcer disease was healed with these regimens.

Aim:

To compare the safety and efficacy of four 1-week H. pylori eradication regimens in the healing of H. pylori associated duodenal ulcer disease.

Methods:

Following endoscopic confirmation of duodenal ulcer disease and a positive CLO test, patients underwent a ¹³C-urea breath test to confirm H. pylori status. Treatment with one of four regimens: LAC, LAM, LCM or OAM, where L is lansoprazole 30 mg b.d., A is amoxycillin 1 g b.d., M is metronidazole 400 mg b.d., C is clarithromycin 250 mg b.d., and O is omeprazole 20 mg b.d., was assigned randomly to those patients who were H. pylori positive, with 62 (LAC), 64 (LAM), 61 (LCM) and 75 (OAM) patients in each treatment group. Follow-up breath tests and endoscopies were performed at least 28 days after the end of treatment.

Results:

Duodenal ulcer disease was healed 28 days after treatment in 53/62 (85.5%) patients who were treated with LAC, 52/64 (81.3%) of patients treated with LAM, 49/61 (80.3%) of patients treated with LCM and 60/75 (80.0%) of patients treated with OAM (intention-to-treat analysis, n=262, assumed unhealed if no follow-up endoscopy was performed). All the treatments were of similar efficacy (P=0.85, chi-squared test) with regard to the healing of duodenal ulcer disease.

Conclusions:

The four 1-week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.

     

Effect of eradication ofHelicobacter pylori infection on gastric epithelial cell proliferation

Helicobacter pylori infection has been linked with gastric carcinoma. Epithelial cell proliferation is an indicator of cancer risk. The aim of this study was to assess gastric epithelial cell proliferation before and after eradication therapy and to assess the efficacy of treatment ofH. pylori infection using lanzoprazole and clarithromycin. Twenty-three patients withH. pylori-associated gastritis were treated with lanzoprazole 30 mg daily for four weeks and clarithromycin 500 mg three times a day for two weeks. Antral mucosal biopsies were taken for gastric epithelial cell proliferation analysis using thein vitro bromodeoxyuridine (BrdU) immunohistochemical technique before and four weeks after eradication therapy. Labeling index percent (LI%) was calculated as the percent ratio of proliferating cells to the total number of cells in the gastric pit. Efficacy of treatment was assessed in 16 subjects. Eight were negative forH. pylori infection 28 days after therapy and in eight patientsH. pylori infection was not eradicated. The eradication rate for the regimen was 50%. Cell kinetics were assessed in 19 subjects who completed treatment. Patients withH. pylori infection had a significantly higher LI% compared to normal (N=19, LI%: 5.01±0.3 vs 3.2±0.2,N=29). Eradication ofH. pylori infection significantly reduced epithelial cell proliferation (N=9, LI%:5.2±0.4 to 3.2 ±0.8,P<0.001), whereas it was unaltered in those whose infection was not eradicated (N=10, LI%: 4.8±0.4 to 5.5±0.5,P=0.18). Eradication ofH. pylori reduces gastric epithelial cell proliferation to normal levels and may reduce the long-term the risk of gastric carcinoma.We wish to thankLederle for their support with this trial.     

Haplotypes in the CTLA4 region are associated with coeliac disease in the Irish population

Chromosomal region 2q33 encodes the immune regulatory genes, CTLA4, ICOS and CD28, which are involved in regulation of T-cell activity and has been studied as a candidate gene locus in autoimmune diseases, including coeliac disease (CD). We have investigated whether an association exists between this region and CD in the Irish population using a comprehensive analysis for genetic variation. Using a haplotype-tagging approach, this gene cluster was investigated for disease association in a case-control study comprising 394 CD patients and 421 ethnically matched healthy controls. Several SNPs, including CTLA4_CT60, showed association with disease; however, after correction for multiple-testing, CTLA4-658C/T was the only polymorphism found to show significant association with disease when allele, genotype, or carrier status frequency were analysed (carrier status (Allele C), P = 0.0016). Haplotype analysis revealed a haplotype incorporating the CD28/CTLA4 and two 5' ICOS polymorphisms to be significantly associated with disease (patients 24.1%; controls 31.5%; P = 0.035), as was a shorter haplotype composed of the CTLA4 markers only (30.9 vs 34.9%; P = 0.042). The extended haplotype incorporating CD28/CTLA4 and 5' ICOS is more strongly associated with disease than haplotypes of individual genes. This suggests a causal variant associated with this haplotype may be associated with disease in this population.     

Cost analysis and cost determinants in a European inflammatory bowel disease inception cohort with 10 years of follow-up evaluation

BACKGROUND & AIMS: Economic analysis in chronic diseases is a prerequisite for planning a proper distribution of health care resources. We aimed to determine the cost of inflammatory bowel disease, a lifetime illness with considerable morbidity. METHODS: We studied 1321 patients from an inception cohort in 8 European countries and Israel over 10 years. Data on consumption of resources were obtained retrospectively. The cost of health care was calculated from the use of resources and their median prices. Data were analyzed using regression models based on the generalized estimating equations approach. RESULTS: The mean annual total expenditure on health care was 1871 Euro/patient-year for inflammatory bowel disease, 1524 Euro/patient-year for ulcerative colitis, and 2548 Euro/patient-year for Crohn's disease (P < .001). The most expensive resources were medical and surgical hospitalizations, together accounting for 63% of the cost in Crohn's disease and 45% in ulcerative colitis. Total and hospitalization costs were much higher in the first year after diagnosis than in subsequent years. Differences in medical and surgical hospitalizations were the primary cause of substantial intercountry variations of cost; the mean cost of health care was 3705 Euro/patient-year in Denmark and 888 Euro/patient-year in Norway. The outlay for mesalamine, a costly medication with extensive use, was greater than for all other drugs combined. Patient age at diagnosis and sex did not affect costs. CONCLUSIONS: In this multinational, population-based, time-dependent characterization of the health care cost of inflammatory bowel disease, increased expenditure was driven largely by country, diagnosis, hospitalization, and follow-up year.     

Screening for Helicobacter pylori in young dyspeptic patients referred for investigation—endoscopy for those who test negative

Background:

Studies in young dyspeptic patients have suggested that screening strategies based on non-invasive H. pylori testing can reduce endoscopy workload by 25–40%. Such strategies usually propose that only H. pylori-positive individuals should undergo endoscopy. This approach may fail to diagnose idiopathic ulcers, ulcers in patients whose screening test is falsely negative and reflux disease.

Aim:

To investigate a hypothetical screening strategy in which endoscopy is initially performed only in H. pylori-negative dyspeptics.

Methods:

Seventy-two consecutive patients under 45 years of age undergoing investigation for ‘ulcer-like’ dyspepsia had invasive and non-invasive determination of H. pylori status. Individuals found to be H. pylori-positive at endoscopy received 1 week of proton pump inhibitor-based triple therapy. H. pylori-negative individuals received therapy tailored to their diagnosis. Endoscopy was repeated in the positive group to confirm successful eradication. Results were analysed according to our strategy, i.e. serologically-positive patients would have received eradication therapy without endoscopy, but patients found to be negative would have been referred for endoscopy.

Results:

According to the serology test there were 39 positive and 33 negative results. Symptoms failed to resolve during follow-up in nine of the serological positives despite successful eradication. There were also five false positives who were deemed likely treatment failures. Thus according to our strategy, these 14 serologically-positive patients would ultimately have required an endoscopy and the other 25 serologically-positive patients would have avoided an endoscopy, resulting in a 35% reduction in endoscopy usage in this population. In the serologically-negative group there were three cases of peptic ulcer disease where the test was falsely negative, but they were detected by the strategy. No cases of gastric malignancy were detected at endoscopy. Thus our strategy would have reduced initial endoscopy referrals by 35% in this selected population.

Conclusion:

A strategy of empirical H. pylori eradication therapy can safely reduce the requirement for endoscopy in young dyspeptic patients without sinister symptoms.