R. W. M. Van Der Hulst

Prevalence of Vacuolating Cytotoxin Production and Distribution of Distinct vacA Alleles in Helicobacter pylori from China

Studies of Helicobacter pylori from the West have linked production of vacuolating cytotoxin and a particular signal sequence (s1a) allele of the underlying vacA gene to peptic ulcer disease (PUD). Among Chinese H. pylori, most isolates from both PUD and gastritis patients were toxigenic (35/46 and 29/35, respectively). Polymerase chain reaction and DNA sequencing showed that 95 of 96 isolates carried vacA s1a alleles. In the mid-region, 78 of 96 isolates carried m2; 14 were m1-like but only 87% identical (DNA-level) to classical m1 and were designated m1b; the other 4 were unusual hybrids (m1b-type proximal, m2-type distal). Isolates with m1b and m1b-m2 alleles produced higher levels of vacuolating activity than did isolates with m2 alleles (P < .01). There was no association between any vacA allele and disease. These results suggest that the composition of H. pylori gene pools varies geographically and that other as-yet-unknown polymorphic H. pylori genes are important in PUD.

H pylori colocalises with MUC5AC in the human stomach

BACKGROUND The bacterium Helicobacter pyloriis able to adhere to and to colonise the human gastric epithelium, yet the primary gene product responsible as a receptor for its adherence has not been identified. AIMS To investigate the expression of the gastric mucins MUC5AC and MUC6 in the gastric epithelium in relation to H pyloricolonisation in order to examine their possible roles in the binding of H pylori. PATIENTS Seventy two consecutive patients suspected of having H pylori infection. METHODS MUC5AC, MUC6, and H pylori were detected in single sections of antral biopsy specimens using immunohistochemical triple staining. RESULTS MUC5AC was expressed in the superficial epithelium and the upper part of the gastric pits. MUC6 expression was detected in the lower part of the gastric pits. The expression of both mucins in the epithelium was complementary. In each patient, there was a sharply delineated transition between MUC5AC and MUC6 producing cell populations. In allH pylori positive patients there was a striking colocalisation of H pylori and MUC5AC; more than 99% of the bacteria were associated with either extracellular MUC5AC or the apical domain of MUC5AC producing cells. CONCLUSIONS H pylori is very closely associated with extracellular MUC5AC and epithelial cells that produce MUC5AC. This indicates that MUC5AC, but not MUC6, plays a role in the adhesion ofH pylori to the gastric mucosa.

Colonic work-up after incomplete colonoscopy: significant new findings during follow-up

BACKGROUND AND STUDY AIMS Cecal intubation is not achieved in 2 - 23 % of colonoscopies. The efforts made by physicians to visualize the remaining colon and the number of missed significant lesions are unknown. This study evaluates 1) the reasons for incomplete colonoscopy, 2) the rates of complete colonic evaluation after incomplete colonoscopy, and 3) the number of (pre-) malignant lesions missed by incomplete colonoscopy. PATIENTS AND METHODS In this population-based cohort study index colonoscopies were performed between September and December 2005. Prospectively collected data from consecutive patients with an incomplete colonoscopy were analyzed. For up to 18 months after the index colonoscopy, any further examinations performed in these patients were identified retrospectively. These secondary examinations included: repeat colonoscopy, computed tomography (CT) colonography, barium enema, abdominal CT scan, and surgery involving the colorectum. RESULTS Of 5278 colonoscopies, 511 were incomplete (9.7 %). The most frequent causes of incomplete colonoscopy were looping of the scope (20.4 %), patient discomfort (15.3 %), and obstructing tumor (13.9 %). Secondary examination was performed in 278 patients (54.4 %) after incomplete colonoscopy. Patients undergoing surveillance after colorectal cancer (CRC) (78.9 %) and those with anemia (73.1 %) most frequently received a secondary examination. Incomplete colonoscopies due to stenosis (78.9 %), severe inflammation (77.8 %) or an obstructing tumor (74.6 %) were most frequently followed by a secondary examination. In all of the follow-up examinations, CRC was diagnosed in 18 patients (3.5 %) and advanced adenoma in four patients (0.8 %). CONCLUSIONS In 4.3 % of the patients, advanced neoplasia was missed by incomplete colonoscopy. Our data therefore suggest that additional imaging is obligatory to visualize the remaining colon adequately.

Interobserver variation in the histopathological scoring of Helicobacter pylori related gastritis.

AIM: To test the reproducibility between two histopathologists of features of Helicobacter pylori gastritis, using the updated Sydney classification. METHODS: 290 dyspeptic Dutch patients with biopsy proven H pylori infection were enrolled in the study. Gastric antral mucosal biopsy specimens were analysed before and after H pylori eradication treatment. The biopsies were scored semi-quantitatively by two histopathologists, according to the updated Sydney classification system. Variables analysed included the density of H pylori infection, the degree of chronic inflammation, inflammatory activity, atrophy, intestinal metaplasia, and surface epithelial damage. Before grading biopsy specimens, both pathologists reached a consensus on the scoring of gastritis through interactive sessions using a multiheaded microscope. Subsequently all biopsy specimens were graded. Interobserver variability was also analysed using weighted kappa scores. RESULTS: For interobserver agreement on scoring the various gastritis features a high degree of reproducibility was reached overall. Agreement on grading of atrophy was the lowest; however, moderate to good reproducibility was achieved, with weighted kappa values of 0.49 in the pretreatment biopsies and 0.52 in the post-treatment biopsies. Disagreement was most common in biopsy specimens with lesser degrees of atrophy. A high degree of agreement was obtained for intestinal metaplasia, with weighted kappa values of 0.72 in the pretreatment biopsies and 0.73 in the post-treatment biopsies. The best agreement was reached in the assessment of the density of H pylori both before and after H pylori eradication treatment, with excellent weighted kappa values of 0.76 and 0.95, respectively. The grade of reproducibility of inflammatory activity, superficial epithelial damage, and chronic inflammation was high, with weighted kappa values varying from 0.60 to 0.76 and 0.62 to 0.83 before and after eradication, respectively. CONCLUSIONS: Reproducibility of grading H pylori related gastritis is high using the updated Sydney system. Despite the novel criteria for scoring atrophy, there was imperfect agreement on this feature between two independent histopathologists.

Colonoscopy-controlled intra-individual comparisons to screen relevant neoplasia: faecal immunochemical test vs. guaiac-based faecal occult blood test.

Aliment Pharmacol Ther 31, 432–439

Reinfection versus recrudescence in Helicobacter pylori infection

Antimicrobial treatment of Helicobacter pylori is the proper management strategy in patients with ulcers. A high rate of H. pylori reinfection after successful eradication therapy however, may give rise to ulcer recurrence. The risk of reinfection, depending on the prevalence and the rate of acquisition of H. pylori infection, varies with socioeconomic status, age and geographical location. The rate of reinfection may vary in a similar way. The available data in the literature reveal that reinfection by H. pylori is low or absent in developed countries and may be lower than the initial rate of acquisition. In addition, reported cases of H. pylori reinfection are often cases of recrudescent H. pylori infection. Acquisition rate in developing countries is high, so the reinfection rate is expected to be higher than in developed countries. However, studies discriminating reinfection from recrudescence are lacking and therefore more data from developing regions are needed to settle if ‘cured once, cured forever’ holds true.

Higher Fecal Immunochemical Test Cutoff Levels: Lower Positivity Rates but Still Acceptable Detection Rates for Early-Stage Colorectal Cancers

Background: Adjusting the threshold for positivity of quantitative fecal immunochemical tests (FIT) allows for controlling the number of follow-up colonoscopies in a screening program. However, it is unknown to what extent higher cutoff levels affect detection rates of screen-relevant neoplasia. This study aimed to assess the effect of higher cutoff levels of a quantitative FIT on test positivity rate and detection rate of early-stage colorectal cancers (CRC). Methods: Subjects above 40 years old scheduled for colonoscopy in 5 hospitals were asked to sample a single FIT (OC sensor) before colonoscopy. Screen-relevant neoplasia were defined as advanced adenoma or early-stage cancer (stage I and II). Positivity rate, sensitivity, and specificity were evaluated at increasing cutoff levels of 50 to 200 ng/mL. Results: In 2,145 individuals who underwent total colonoscopy, 79 patients were diagnosed with CRC, 38 of which were with early-stage disease. Advanced adenomas were found in 236 patients. When varying cutoff levels from ≥50 to ≥200 ng/mL, positivity rates ranged from 16.5% to 10.2%. With increasing cutoff levels, sensitivity for early-stage CRCs and for screen-relevant neoplasia ranged from 84.2% to 78.9% and 47.1% to 37.2%, respectively. Conclusions: Higher FIT cutoff levels substantially decrease test positivity rates with only limited effects on detection rates of early-stage CRCs. However, spectrum bias resulting in higher estimates of sensitivity than would be expected in a screening population may be present. Impact: Higher cutoff levels can reduce strain on colonoscopy capacity with only a modest decrease in sensitivity for curable cancers. Cancer Epidemiol Biomarkers Prev; 20(2); 272–80. ©2010 AACR.

Treatment of Helicobacter pylori infection with low or high dose omeprazole combined with amoxycillin and the effect of early retreatment

Background: Cure rates of H. pylori infection, using dual therapy with omeprazole and amoxycillin, vary considerably and the efficacy of retreatment with this regimen in the case of initial failure is controversial. Therefore, we conducted a large prospective double‐blind randomized trial, studying the efficacy of low vs. high dose omeprazole in dual therapy and of early retreatment with the same regimens.

Randomized trial of omeprazole and clarithromycin combined with either metronidazole or amoxycillin in patients with metronidazole-resistant or -susceptible Helicobacter pylori strains

: The impact of metronidazole resistance on the efficacy of proton pump inhibitor based triple therapies remains unclear.

Arrest of chronic acid suppressant drug use after successful Helicobacter pylori eradication in patients with peptic ulcer disease: a six-month follow-up study

It remains controversial whether successful H. pylori eradication leads to relief of dyspepsia and the subsequent arrest or tapering of acid‐suppressant drug therapy, or to an aggravation of acid‐related dyspepsia requiring more acid‐suppressant drug intake.