Browsing by Author "Calvo, Alfonso"

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    Diagnóstico precoz de cáncer gástrico. Propuesta de detección y seguimiento de lesiones premalignas gástricas: protocolo ACHED
    (Sociedad Médica de Santiago, 2014) Rollán, Antonio; Cortés, Pablo; Calvo, Alfonso; Araya, Raúl; Bufadel, María Ester; González, Robinson; Heredia, Carolina; Muñoz, Pablo; Squella, Freddy; Nazal, Roberto; Gatica, María de los Ángeles; Gobelet, Jaquelina; Estay, René; Pisano, Raúl; Contreras, Luis; Osorio, Ingrid; Estela, Ricardo; Fluxá, Fernando; Parra-Blanco, Adolfo
    An expert panel analyzed the available evidence and reached a consensus to release 24 recommendations for primary and secondary prevention of gastric cancer (CG) in symptomatic patients, with indication for upper GI endoscopy. The main recommendations include (1) Search for and eradicate H. pylori infection in all cases. (2) Systematic gastric biopsies (Sydney protocol) in all patients over 40 years of age or first grade relatives of patient with CG, to detect gastric atrophy, intestinal metaplasia or dysplasia. (3) Incorporate the OLGA system (Operative Link on Gastritis Assessment) to the pathological report, to categorize the individual risk of CG. (4) Schedule endoscopic follow-up according to the estimated risk of CG, namely annual for OLGA III- IV, every 3 years for OLGA I- II or persistent H. pylori infection, every 5 years for CG relatives without other risk factors and no follow-up for OLGA 0, H. pylori (-). (4) Establish basic human and material resources for endoscopic follow-up programs, including some essential administrative processes, and (5 ) Suggest the early CG/total CG diagnosis ratio of each institution and the proportion of systematic recording of endoscopic images, as quality indicators. These measures are applicable using currently available resources, they can complement any future screening programs for asymptomatic population and may contribute to improve the prognosis of CG in high-risk populations
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    Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer
    (2025) Maturana, María; Padilla, Oslando; Santoro, Pablo; Alarcón, Maria; Olivares, Wilda; Blanco, Alejandro; Armisen, Ricardo; Garrido, Marcelo; Aravena, Edmundo; Barrientos, Carlos; Calvo, Alfonso; Corvalán, Alejandro
    Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia/low-grade dysplasia [GIM/LGD]), 21 with high-grade dysplasia/early GC [HGD/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies/mL) was higher than that of the HD controls (139.00 copies/mL) (p < 0.0001). After dividing this cohort into training–validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683–0.845) in the training group. This resulted in a cut-off value of 87.37 copies/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM/LGD, HGD/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11–3.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53–9.93, p = 0.004) for the risk of developing GIM/LGD and HGD/eGC, respectively. The combined methylated RPRM cfDNA and PG-I/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response.

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