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    Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer
    (MDPI AG, 2025-04-03)
    María José Maturana
    ;
    Oslando Padilla
    ;
    Pablo M. Santoro
    ;
    Maria Alejandra Alarcón
    ;
    Wilda Olivares
    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 a 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.
      1Scopus© Citations 4
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    Cáncer de vesícula: ¿Es momento de modificar el GES?
    (SciELO Agencia Nacional de Investigacion y Desarrollo (ANID), 2024-10)
    Camila P. Samaniego
    ;
    Xabier de Aretxabala
    ;
    Felipe Castillo
    ;
    Álvaro Paredes
    ;
    M. Trinidad González
      14
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    Prenatal presentation of pleuropulmonary blastoma associated to DICER1 syndrome: differential diagnosis of congenital pulmonary malformation
    (2023)
    Valenzuela, Catalina Catán
    ;
    Paula Vargas Innocenti
    ;
    Gutierrez, Aquiles Hachim
    ;
    Pinto, Pablo Jorquera
    ;
    Ramos, Ximena Claverie
      3Scopus© Citations 2
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    The Global Otolaryngology–Head and Neck Surgery Workforce
    (2023)
    Beatriz Petrucci
    ;
    Samuel Okerosi
    ;
    Rolvix H. Patterson
    ;
    Sara B. Hobday
    ;
    Valerie Salano
    <jats:sec id="ab-ooi230053-4"><jats:title>Importance</jats:title><jats:p>A core component of delivering care of head and neck diseases is an adequate workforce. The World Health Organization report, <jats:italic>Multi-Country Assessment of National Capacity to Provide Hearing Care</jats:italic>, captured primary workforce estimates from 68 member states in 2012, noting that response rates were a limitation and that updated more comprehensive data are needed.</jats:p></jats:sec><jats:sec id="ab-ooi230053-5"><jats:title>Objective</jats:title><jats:p>To establish comprehensive workforce metrics for global otolaryngology–head and neck surgery (OHNS) with updated data from more countries/territories.</jats:p></jats:sec><jats:sec id="ab-ooi230053-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>A cross-sectional electronic survey characterizing the OHNS workforce was disseminated from February 10 to June 22, 2022, to professional society leaders, medical licensing boards, public health officials, and practicing OHNS clinicians.</jats:p></jats:sec><jats:sec id="ab-ooi230053-7"><jats:title>Main Outcome</jats:title><jats:p>The OHNS workforce per capita, stratified by income and region.</jats:p></jats:sec><jats:sec id="ab-ooi230053-8"><jats:title>Results</jats:title><jats:p>Responses were collected from 121 of 195 countries/territories (62%). Survey responses specifically reported on OHNS workforce from 114 countries/territories representing 84% of the world’s population. The global OHNS clinician density was 2.19 (range, 0-61.7) OHNS clinicians per 100 000 population. The OHNS clinician density varied by World Bank income group with higher-income countries associated with a higher density of clinicians. Regionally, Europe had the highest clinician density (5.70 clinicians per 100 000 population) whereas Africa (0.18 clinicians per 100 000 population) and Southeast Asia (1.12 clinicians per 100 000 population) had the lowest. The OHNS clinicians deliver most of the surgical management of ear diseases and hearing care, rhinologic and sinus diseases, laryngeal disorders, and upper aerodigestive mucosal cancer globally.</jats:p></jats:sec><jats:sec id="ab-ooi230053-9"><jats:title>Conclusion and Relevance</jats:title><jats:p>This cross-sectional survey study provides a comprehensive assessment of the global OHNS workforce. These results can guide focused investment in training and policy development to address disparities in the availability of OHNS clinicians.</jats:p></jats:sec>
    Scopus© Citations 6  14
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    ASO Author Reflections: Precision in Gallbladder Cancer Care: Present Challenges and Future Directions
    (2023)
    Sebastian Mellado
    ;
    Ariana M. Chirban
    ;
    Belen Rivera
    ;
    Elena Panettieri
    ;
    Eduardo A. Vega
      1Scopus© Citations 1
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      1Scopus© Citations 3  1
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      10Scopus© Citations 1
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    Incidence of occult uterine sarcoma and other unexpected pathologies in patients having surgery for presumed myomas: A retrospective observational study
    (2021)
    Mariane Von Mühlenbrock
    ;
    Paz Navarrete-Rey
    ;
    Elias Kovoor
    ;
    Rodrigo Guzman-Rojas
    ;
    Fernando Troncoso
      5Scopus© Citations 4
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    Angiomiolipoma hepático epitelioide: reporte de un caso
    (2022)
    Oscar Ahumada Espinoza
    ;
    Juan Hepp Kuschel
    ;
    Marcela Gallegos Angulo
    ;
    Giancarlo Schiappacasse Faundes
      1Scopus© Citations 2
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      1Scopus© Citations 1  1