ABSTRACT
To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature.
ABSTRACT
BACKGROUND: Digestive damage due to Chagas disease (CD) occurs in 15-20% of patients diagnosed as a result of peristaltic dysfunction in some endemic areas. The symptoms of chronic digestive CD are non-specific, and there are numerous confounders. Diagnosis of CD may easily be missed if symptoms are not evaluated by a well trained physician. Regular tests, as barium contrast examinations, probably lack the necessary sensitivity to detect early digestive damage. METHODS: 71 individuals with T. cruzi infection (G1) and 18 without (G2) coming from Latin American countries were analyzed. They were asked for clinical and epidemiological data, changes in dietary habits, and history targeting digestive and cardiac CD symptoms. Serological tests for T. cruzi, barium swallow, barium enema, an urea breath test, and esophageal manometry were requested for all patients. PRINCIPAL FINDINGS: G1 and G2 patients did not show differences in lifestyle and past history. Fifteen (21.1%) of G1 had digestive involvement. Following Rezende criteria, esophagopathy was observed in 8 patients in G1 (11.3%) and in none of those in G2. Manometry disorders were recorded in 34 G1 patients and in six in G2. Isolated hypotensive lower esophageal sphincter (LES) was found in sixteen G1 patients (23.9%) and four G2 patients (28.8%). Achalasia was observed in two G1 patients. Among G1 patients, ineffective esophageal motility was seen in six (five with symptoms), diffuse esophageal spasm in two (one with dysphagia and regurgitation), and nutcracker esophagus in three (all with symptoms). There were six patients with hypertonic upper esophageal sphincter (UES) among G1. Following Ximenes criteria, megacolon was found in ten G1 patients (13.9%), and in none of the G2 patients. CONCLUSIONS: The prevalence of digestive chronic CD in our series was 21.1%. Dysphagia is a non-pathognomonic symptom of CD, but a good marker of early esophageal involvement. Manometry could be a useful diagnostic test in selected cases, mainly in patients with T. cruzi infection and dysphagia in whose situation barium swallow does not evidence alterations. Constipation is a common but non-specific symptom that can be easily managed. Testing for CD is mandatory in a patient from Latin America with constipation or dysphagia, and if diagnosis is confirmed, megacolon and esophageal involvement should be investigated.
Subject(s)
Chagas Disease , Esophageal Diseases , Adult , Chagas Disease/complications , Chagas Disease/epidemiology , Chagas Disease/physiopathology , Chronic Disease , Esophageal Diseases/epidemiology , Esophageal Diseases/etiology , Esophageal Diseases/physiopathology , Female , Humans , Male , Middle Aged , Spain/epidemiologyABSTRACT
La infección por Trypanosoma cruzi (T. cruzi), agente responsable de la enfermedad de Chagas, ha estado tradicionalmente ligada a las zonas rurales de América Latina, donde es transmitido por diversas especies de chinches. Esta situación epidemiológica ha ido cambiando en el transcurso de las últimas décadas, de forma que en la actualidad la enfermedad de Chagas es una patología importada diagnosticada a nivel urbano y un problema de salud pública en países no endémicos con gran número de población inmigrante, dónde la transmisión se puede producir durante el embarazo/parto, por transfusión sanguínea o por transplante de órganos. Se estima que hasta un 20% de los pacientes con infección por T. cruzi presentan afectación del aparato digestivo, que causa importante morbilidad y que requiere un manejo y tratamiento adecuado. En el presente documento se aborda el diagnóstico, manejo y tratamiento de las manifestaciones digestivas de pacientes con infección por T. cruzi en nuestro medio (AU)
Trypanosoma cruzi (T. cruzi) infection, causal agent of Chagas disease, has been traditionally limited to rural areas of Latinamerica, where it is transmitted by insects belonging to different species of bugs. Due to recent trends in migration, Chagas disease is now a public health problem in urban areas of endemic countries and in non endemic countries as well, where the transmission via blood products, transplantation of infected organs, or vertical transmission is possible. It is estimated that 20% of individuals infected with T. cruzi might develop symptomatic gastrointestinal disease, which causes important morbidity and needs an adequate management and treatment. The aim of this document is to improve patient care by increasing understanding among physicians and other healthcare professionals who may be involved in the management of patients infected by T. cruzi who present with gastrointestinal symptoms (AU)
