The Colombian Chemoprevention Trial: 20-Year Follow-Up of a Cohort of Patients With Gastric Precancerous Lesions.

BACKGROUND & AIMS: Helicobacter pylori eradication and endoscopic surveillance of gastric precancerous lesions are strategies to reduce gastric cancer (GC) risk. To our knowledge, this study is the longest prospective cohort of an H pylori eradication trial in a Hispanic population. METHODS: A total of 800 adults with precancerous lesions were randomized to anti-H pylori treatment or placebo. Gastric biopsy samples taken at baseline and 3, 6, 12, 16, and 20 years were assessed by our Correa histopathology score. A generalized linear mixed model with a participant-level random intercept was used to estimate the effect of H pylori status on the score over time. Logistic regression models were used to estimate progression by baseline diagnosis and to estimate GC risk by intestinal metaplasia (IM) subtype and anatomic location. RESULTS: Overall, 356 individuals completed 20 years of follow-up. Anti-H pylori therapy (intention-to-treat) reduced progression of the Correa score (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.38-0.93). H pylori-negative status had a beneficial effect on the score over time (P = .036). Among individuals with IM (including indefinite for dysplasia) at baseline, incidence rates per 100 person-years were 1.09 (95% CI, 0.85-1.33) for low-grade/high-grade dysplasia and 0.14 (95% CI, 0.06-0.22) for GC. Incomplete-type (vs complete-type) IM at baseline presented higher GC risk (OR, 13.4; 95% CI, 1.8-103.8). Individuals with corpus (vs antrum-restricted) IM showed an OR of 2.1 (95% CI, 0.7-6.6) for GC. CONCLUSIONS: In a high-GC-risk Hispanic population, anti-H pylori therapy had a long-term beneficial effect against histologic progression. Incomplete IM is a strong predictor of GC risk.

Duodenal microbiome in patients with or without Helicobacter pylori infection.

BACKGROUND: Intestinal microbiota are recognized as an organ with important physiological functions whose alterations have been associated with common diseases including inflammatory intestinal conditions, malnutrition, type-2 diabetes, and cardiovascular diseases. The composition and function of the microbiota in the distal part of the intestine has been mainly described, while there is limited information on the small intestine microbiota. The objective of the present study was to describe the duodenal microbiome in individuals with dyspepsia in the presence or absence of Helicobacter pylori gastric infection. MATERIALS AND METHODS: Thirty-eight biopsies from the proximal duodenum of uninfected and 37 from H pylori-infected individuals were analyzed. Microbiota composition was assessed by PCR amplification and sequencing of 16S rRNA and ITS genes; sequences were analyzed with QIIME2. RESULTS AND CONCLUSIONS: At the phyla level, Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, and Fusobacteria were predominant in the mucosal associated duodenal microbiota (MAM); at the genera level, we observed the predominance of Ralstonia, Streptococcus, Pseudomonas, Haemophilus, Herbaspirillum, Neisseria, and Veillonella. Microbiota α-diversity was higher in H pylori-infected individuals than in non-infected ones. In terms of ß-diversity metrics, there was a statistically significant difference between groups. Also, relative abundance of Haemophilus, Neisseria, Prevotella pallens, Prevotella 7, and Streptococcus was greater in H pylori-infected patients. In infected patients, several types of H pylori were present in duodenal MAM. Finally, the majority of duodenal samples had fungi sequences; the most common taxa observed were Recurvomyces followed by Ascomycota and Basidiomycota.

Análisis molecular de Helicobacter pylori (genes de patogenicidad) en biopsias gástricas de pacientes de la Sierra y Oriente Ecuatorianos / Molecular analysis of Helicobacter pylori (pathogenicity genes) in gastric biopsies of patients from the Ecuadorian Sierra and Oriente

Antecedentes: Helicobacter pylori es una bacteria Gram negativa, reconocida como la causa de la úlcera péptica (UP) y cáncer el gástrico (CG). Se han identificado genes de virulencia asociados con la patogenicidad del H. pylori incluyendo la isla de patogenicidad cagA y la citotoxina vacuolizante A (vacA). La frecuencia de los genes de patogenicidad se ha asociado con la localización geográfica y condiciones de vida de las personas. Pocos estudios en el Ecuador, han demostrado la relación entre los genes de patogenicidad de H. pylori y regiones geográficas de diferente altitud. Este estudio analizó los genes de patogenicidad de biopsias gástricas dos parroquias del Ecuador: una ubicada en la altura, Zumbahua (Sierra Central) y otra a nivel del mar, Shushufindi (Amazonía). Métodos: Se obtuvieron 127 muestras de biopsias gástricas embebidas en parafina de sujetos provenientes de Zumbahua (n = 90) y Shushufindi (n = 37). Mediante un análisis histopatológico se determinó la presencia de la infección y alteraciones patológicas tisulares. Se seleccionaron las muestras de los pacientes con mayor índice de infección por H. pylori (++ y +++ en el examen histopatológico) para el análisis molecular del H. pylori; se aisló su ADN y se evaluaron los genes de patogenicidad por PCR. Resultados: Se determinó la presencia de 5 casos de cáncer gástrico en la parroquia de Zumbahua, con mayor frecuencia en hombres que en mujeres. En la parroquia de Sushufindi hubo mayor prevalencia de infección por H. pylori comparada con Zumbahua. El análisis molecular de los genes de patogenicidad determinó que hubo una mayor expresión de estos en las muestras provenientes de la parroquia de Zumbahua; el 20% de las muestras amplificaron para vacAm1, 8.57% para vacAs1 y el 20% para vacAs2; mientras que para Shushufindi, únicamente el 8.0% amplificó para el gen vacAm1. Conclusiones: La prevalencia de infección por H. pylori en las muestras de las parroquias estudiadas es alta. Los genes de patogenicidad asociados con mayor virulencia provinieron de Zumbahua así como también las muestras con cáncer. Por otro lado, en las muestras de Shushufindi los genes de patogenicidad fueron menos virulentos y no hubo casos de malignidad. Es necesario establecer sistemas de tamizaje tanto para detectar cepas de H. pylori con genes de virulencia como para la detección temprana del cáncer gástrico.

Dynamics of Helicobacter pylori infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial.

OBJECTIVE: To evaluate the long-term effect of cumulative time exposed to Helicobacter pylori infection on the progression of gastric lesions. DESIGN: 795 adults with precancerous gastric lesions were randomised to receive anti-H. pylori treatment at baseline. Gastric biopsies were obtained at baseline and at 3, 6, 12 and 16 years. A total of 456 individuals attended the 16-year visit. Cumulative time of H. pylori exposure was calculated as the number of years infected during follow-up. Multivariable logistic regression models were used to estimate the risk of progression to a more advanced diagnosis (versus no change/regression) as well as gastric cancer risk by intestinal metaplasia (IM) subtype. For a more detailed analysis of progression, we also used a histopathology score assessing both severity and extension of the gastric lesions (range 1-6). The score difference between baseline and 16 years was modelled by generalised linear models. RESULTS: Individuals who were continuously infected with H. pylori for 16 years had a higher probability of progression to a more advanced diagnosis than those who cleared the infection and remained negative after baseline (p=0.001). Incomplete-type IM was associated with higher risk of progression to cancer than complete-type (OR, 11.3; 95% CI 1.4 to 91.4). The average histopathology score increased by 0.20 units/year (95% CI 0.12 to 0.28) among individuals continuously infected with H. pylori. The effect of cumulative time of infection on progression in the histopathology score was significantly higher for individuals with atrophy (without IM) than for individuals with IM (p<0.001). CONCLUSIONS: Long-term exposure to H. pylori infection was associated with progression of precancerous lesions. Individuals infected with H. pylori with these lesions may benefit from eradication, particularly those with atrophic gastritis without IM. Incomplete-type IM may be a useful marker for the identification of individuals at higher risk for cancer.

Fuentes de variabilidad en el diagnóstico de gastritis atrófica multifocal asociada con la infección por Helicobacter pylori / Source of variation in the diagnosis of Helicobacter pylori-associated multifocal atrophic gastritis

Introducción: El mapeo de las diferentes regiones del estómago y el número de fragmentos de mucosa gßstrica disponibles para evaluación histopatológica son fuentes importantes de variación en el momento de clasificar y hacer la gradación de la gastritis crónica. Objetivos: Estimar la sensibilidad del número de fragmentos de mucosa gßstrica necesarios para establecer los diagnósticos de gastritis atrófica con metaplasia intestinal (MI), displasia y estado de infección por Helicobacter pylori. Ademßs evaluar la variabilidad intra-observador en la clasificación de estas lesiones precursoras del cancer gastrico. Materiales y métodos: En una cohorte de 6 a±os de seguimiento se evaluaron 1,958 procedimientos de endoscopia realizados por dos gastroenterólogos. En cada procedimiento y de cada participante se obtuvieron 5 biopsias de mucosa gßstrica que representaban antro, incisura angularis y cuerpo. Un único patólogo hizo la interpretación histológica de las 5 biopsias y proporcionó un diagnóstico definitivo global que se utilizó como patrón de referencia. Cada fragmento de mucosa gßstrica examinado condujo a un diagnóstico individual para cada biopsia que se comparó con el patrón de referencia. La variabilidad intra-observador se evaluó en 127 personas que corresponden a una muestra aleatoria de 20% del total de endoscopias hechas a los 72 meses de seguimiento. Resultados: La sensibilidad del diagnóstico de MI y displasia gßstrica aumentó de manera significativa con el número de fragmentos de mucosa gßstrica evaluados El sitio anatómico de mayor sensibilidad para el diagnóstico de MI y displasia fue la incisura angularis. Para descubrir H. pylori se logró alta sensibilidad con el estudio de un solo fragmento de mucosa gastrica (95.9%) y fue independiente del sitio de obtención de la biopsia. El acuerdo intra-observador para el diagnóstico de gastritis crónica fue 86.1% con valor kappa de 0.79 IC 95% (0.76-0.85).

Introduction: Multiple sampling from different sites of the stomach as well as the number of fragments of gastric mucosa available for histopathologic evaluation are important sources of variation when classifying and grading chronic gastritis. Objective: To estimate the sensitivity of the number of fragments of gastric mucosa necessary to establish the diagnosis of atrophic gastritis with intestinal metaplasia, gastric dysplasia and H. pylori infection. In addition, this study will attempt to assess the intra-observer variability in the classification of these premalignant gastric lesions. Methods: This is a 6 year-cohort study, wherein 1958 gastric endoscopic procedures performed by two gastroenterologists were reviewed. Five gastric biopsy samples were obtained from the antrum, body and lesser curvature during each procedure. One pathologist was in charge of reviewing the five histopathology samples for each subject and providing a definitive diagnosis which was used as the gold standard. Each gastric mucosa sample reviewed led to an individual diagnosis for that sample which was compared with the gold standard. Intra-observer variability was assessed in 127 individuals who correspond to a random sample of 20% of the total endoscopic procedures performed during the 72 month-follow-up. Results: The sensitivity of the diagnosis of intestinal metaplasia (IM) and gastric dysplasia increased proportionally with the number of gastric mucosa samples reviewed. The lesser curvature of the stomach had the highest sensitivity for the diagnosis of IM and dysplasia, among all the stomach regions studied. Just one sample of gastric mucosa attained a sensitivity of 95.9% for the detection of H. pylori infection. The intra-observer agreement for the diagnosis of multifocal atrophic gastritis was 86.1% and the kappa value was 0.79 (95% CI 0.76-0.85). Alcohol-fixed biopsy specimens were inadequate to diagnose H. pylori infection and to assess dysplasia.

[Source of variation in the diagnosis of Helicobacter pylori-associated multifocal atrophic gastritis.] / Fuentes de variabilidad en el diagnóstico de gastritis atrófica multifocal asociada con la infección por Helicobacter pylori.

INTRODUCTION: Multiple sampling from different sites of the stomach as well as the number of fragments of gastric mucosa available for histopathologic evaluation are important sources of variation when classifying and grading chronic gastritis. OBJECTIVE: To estimate the sensitivity of the number of fragments of gastric mucosa necessary to establish the diagnosis of atrophic gastritis with intestinal metaplasia, gastric dysplasia and H. pylori infection. In addition, this study will attempt to assess the intra-observer variability in the classification of these premalignant gastric lesions. METHODS: This is a 6 year-cohort study, wherein 1958 gastric endoscopic procedures performed by two gastroenterologists were reviewed. Five gastric biopsy samples were obtained from the antrum, body and lesser curvature during each procedure. One pathologist was in charge of reviewing the five histopathology samples for each subject and providing a definitive diagnosis which was used as the gold standard. Each gastric mucosa sample reviewed led to an individual diagnosis for that sample which was compared with the gold standard. Intra-observer variability was assessed in 127 individuals who correspond to a random sample of 20% of the total endoscopic procedures performed during the 72 month-follow-up. RESULTS: The sensitivity of the diagnosis of intestinal metaplasia (IM) and gastric dysplasia increased proportionally with the number of gastric mucosa samples reviewed. The lesser curvature of the stomach had the highest sensitivity for the diagnosis of IM and dysplasia, among all the stomach regions studied. Just one sample of gastric mucosa attained a sensitivity of 95.9% for the detection of H. pylori infection. The intra-observer agreement for the diagnosis of multifocal atrophic gastritis was 86.1% and the kappa value was 0.79 (95% CI 0.76-0.85). Alcohol-fixed biopsy specimens were inadequate to diagnose H. pylori infection and to assess dysplasia. CONCLUSION: The number of mucosa gastric fragments reviewed, the fixation method used, and the biopsy site are all important factors in order to ensure a correct classification of chronic gastritis.