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Cancer Epidemiol Biomarkers Prev ; Updated version. A ccess the most recent version of this article at:. Cited Articles. T his article cites by 27 articles, 12 of which you can access for free at:. Citing articles. T his article has been cited by 15 HighWire-hosted articles. Access the articles at:.

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To request perm ission to re-use all or pa rt of this article, contact the AACR Publications Department at perm i ss i ons aacr. DownloadedDownloaded fromfrom cebp. Helicobacter pylori Eradication and Gastric Preneoplastic Conditions:. Abstract Helicobacter pylori causes gastric adenocarcinoma; whether treatment of H.

In a randomized, double-blind, placebo-controlled trial of H. Endoscopy was performed at baseline and at 6 weeks and 1 year. Seven biopsies from each endoscopy were reviewed by two pathologists using the revised Sydney classification.

We compared change in these outcomes over time between the two treatment groups. Change in index score was favorably greater in treatment compared with placebo subjects intention-to-treat analysis, P 0. The costs of publication of this article were defrayed in part by the payment of page charges.

This article must therefore be hereby marked advertisement in accordance with 18 U. Section solely to indicate this fact. Notes: D. Halperin is deceased; None of the authors has a conflict of interest with this study or its results. Requests for reprints: J. Such incomplete regression suggests but does not prove that eradication of H.

Introduction Gastric adenocarcinoma remains among the leading causes of death worldwide 1. Intestinal-type gastric adenocarcinoma, the most common type, is preceded by well-defined conditions, starting with superficial gastritis, followed by chronic atrophic gastritis AG , intestinal metaplasia IM , and dysplasia 2, 3. Infection with the bacterium Helicobacter pylori fosters the development of gastric adenocarcinoma, with organisms con- taining the Cag pathogenicity island engendering highest risk 4.

By contrast, diets rich in fruits and vegetables and low in nitrates and salts are considered protective 5. Randomized clinical trials directly examining gastric adenocarcinoma pre- vention through H. These studies will take years, great expense, and providence to attain sufficient power. Meanwhile, many people will die from a disease for which a prevention strategy—screening and treatment for H. Investigations using intermediate biomarkers as endpoints are cost-effective alternatives to cancer prevention trials, al- though less definitive 8.

Several randomized trials examining H. Inherent problems include sampling error in obtaining biopsies and misclassification of histological diagnoses. The optimal follow-up time required to assess clinically significant effects is unknown. To determine whether H. Subjects were healthy volunteers at high risk of preneoplasia. Endpoints included both change in the consensus worst biopsy diagnosis and change in a new stomach index score. Designed to minimize effects of misclas- sification and sampling error, this index used data from seven biopsies read by two pathologists.

Materials and Methods Study Participants. Healthy volunteers were recruited in Chiapas, Mexico. An interviewer-administered questionnaire obtained information regarding demographics, family cancer history, and exclusion criteria age 40 years; current preg- nancy; known alcoholism; allergic reactions to study medica- tion; history of malignancy, gastrectomy or debilitating illness; recent antibiotic use; previous H.

Downloaded from cebp. CagA antibodies are markers of H. Blood samples were tested for antibodies to the CagA protein as reported previously Ref. Eligible subjects were randomized to receive anti- microbial therapy 20 mg of omeprazole twice a day, 1 g of amoxicillin twice a day, g of clarythromycin twice a day or matched placebo for 1 week the standard treatment time at trial onset in Masked active therapy and placebo vials had been randomly assigned a number and delivered in bulk to Chiapas.

Once a patient was randomized, a single unmasked investigator at Stanford e-mailed to Chiapas the appropriate vial number to be used. Patient randomization followed the biased- coin method with blocking by age 60 years and gender Written informed con- sent was obtained at the time of initial screening and again before randomization. A data safety and monitoring board at Stanford University regularly reviewed recruitment and pro- gress of the study. Upper endoscopy was performed before treatment and at 6 weeks and 1 year after treatment.

Seven biopsies three each from the antrum and body and one from the incisura angularis were systematically collected from prespecified locations for histological examination using jumbo forceps. Subjects with ulcers or gastric masses were excluded and referred for treat- ment.

Immunohistochemistry for H. Histological parameters, including AG, were evaluated using the updated Sydney system 16 ; IM was defined as the presence of goblet cells. Each biopsy was read independently by two general sur- gical pathologists.

Summary consensus diagnoses were then derived for each subject based on a joint review of all biopsies by both pathologists. Subjects with severe dysplasia were ex- cluded and referred for treatment. Pathologists were blinded to treatment arm and endoscopy stage baseline, 6 weeks, 1 year. Using the consensus diagnoses and assuming an ascending scale of preneoplastic conditions normal AG IM dysplasia , we defined a worst biopsy diagnosis for each subject at each time point.

Because diagnoses of mild AG or dysplasia are prone to misclassification 17, 18 , these diagnoses were ignored, e. We therefore constructed an index to incorporate these characteristics from all biopsies. On the basis of a liter-. The index score was calculated for each subject at each time point, using all biopsies.

Statistical Analysis. Changes in worst biopsy diagnosis defined as worsening, no change, or improvement and in index scores were examined for each subject for each time interval baseline to 6 weeks, 6 weeks to 1 year, baseline to 1 year.

The index score was examined as a mean across pathologists and for each patholo- gist independently. We used the Spearman coefficient to assess correlations in score within and between pathologists and to assess correlation in change in score over time between pathol- ogists.

We used the Wilcoxon rank-sum test to assess associ- ations between worst biopsy diagnosis and index score. Because a change in index score before and after treatment could be confounded by marked concurrent changes in inflam- mation attributable to H. A priori , we therefore chose the interval from 6 weeks to 1 year to be the primary interval for comparing change in the two study arms. Changes observed from 6 weeks to 1 year in the placebo group were considered as the natural history of gastric histopathology time effect.

Changes in index score from 6 weeks to 1 year in the treatment group were thus considered to reflect time effect plus treatment effect. For the intention-to-treat analysis, we compared placebo and treatment groups based on initial randomization. For the per-eradication-protocol analysis, we compared placebo sub- jects who remained H. Subanalyses evaluated changes in the antrum and body separately. All statistical tests were conducted with SAS ver- sion 8.

Role of the Funding Source. Abbott Laboratories provided all antimicrobial therapy for the clinical trial free of charge; the company was not involved in study design, data management, data analysis, or interpretation of results. Results Recruitment, Retention, and H.

A total of subjects were screened for enrollment. Of the The remaining eligible subjects were sequentially invited to participate until a mini- mum calculated sample size of was achieved. A total of The remaining Enrollment and follow-up occurred over the period August to March Demographic characteristics and medical histories were similar between enrolled subjects and subjects who did not.

Demographic charac- teristics were also similar between placebo and treatment sub- jects Table 1. No serious adverse effects of treatment were reported. Minor side effects were common Among subjects who completed the study, treatment and placebo subjects were equally compliant Among enrolled subjects, 68 One subject with an early gastric carcinoma was withdrawn by investigators.

Other than having a greater prevalence of non- atrophic gastritis, treatment subjects were similar to placebo subjects with respect to consensus histological diagnoses at baseline Table 2. Median index scores at baseline were low.


Conditions: A Randomized, Double-Blind, Eradication and Gastric Preneoplastic

Cancer Epidemiol Biomarkers Prev ; Updated version. A ccess the most recent version of this article at:. Cited Articles. T his article cites by 27 articles, 12 of which you can access for free at:. Citing articles. T his article has been cited by 15 HighWire-hosted articles.


Enfermedades Exantematicas En Pediatria.ppt

Haemorrhagic exanthema due to dengue virus induced by acetylsalicylic acid. Valerio 1 , X. Pedro-Botet 4. Servicio de Medicina Intensiva. Unidad de Enfermedades Infecciosas.

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