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Author: search.filters.author.Alberto BustamanteSubject: search.filters.subject.female

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    Comparative Analysis of Very Reduced vs Full Dose BCG Treatment for High-Risk Non-Muscle Invasive Bladder Cancer: A Contemporary Experience from Chile
    (2023)
    Valentina Grajales
    ;
    Roberto Contieri
    ;
    Wei Shen Tan
    ;
    Marta Flores
    ;
    Marcela Schultz
    <jats:p>BACKGROUND: Adjuvant bacillus Calmette-Guérin (BCG) is recommended for high-risk (HR) non-muscle invasive bladder cancer (NMIBC), but BCG shortages have led to exploration of reduced-dose regimens and shortened maintenance durations out of necessity, with limited data on treatment efficacy in Latin America. OBJECTIVE: Oncological outcomes of HR-NMIBC patients treated with reduced (RD,1/4th dose) vs full dose (FD) BCG instillations of Danish Strain 1331 BCG. METHODS: We performed a retrospective study of HR-NMIBC patients treated with BCG between 2003 and 2022 at our center in Santiago Chile. We stratified patients according to either RD (1/4th dose) or FD BCG. Univariate and multivariable Cox regression models were used to predict recurrence. Kaplan-Meier method was used to calculate survival estimates. RESULTS: Of a total of 200 patients, 116 (58%) had RD and 84 (42%) FD BCG. Median follow-up was 57 months (IQR: 29–100). Patients who received FD BCG had a lower risk of recurrence (HR: 0.41, 95% CI 0.22–0.74) and high-grade (HG)-recurrence (HR: 0.30, 95% CI 0.15–0.61; p = 0.001). More patients in the RD vs FD group progressed to MIBC (10/84 vs 2/116; p = 0.18). Additionally, patients were less likely to stop BCG treatment in the RD group compared to the FD group due to toxicity (5% vs 11%, p = 0.14). CONCLUSIONS: A 1/4th dose of Danish Strain 1331 BCG treatment was associated with worse recurrence free rate and HG-recurrence rate in our cohort. Patients with RD had lower discontinuation treatment rates due to a reduced toxicity profile. These findings would suggest that RD BCG would compromise oncological outcomes in HR-NMIBC patients.</jats:p>
      7Scopus© Citations 2
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    Scopus© Citations 8  2
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    Adaptation to Extreme Environments in an Admixed Human Population from the Atacama Desert
    (2019)
    Lucas Vicuña
    ;
    FERNANDEZ ARANCIBIA, MARIO  
    ;
    VIAL COX, MARIA CECILIA  
    ;
    Patricio Valdebenito
    ;
    Eduardo Chaparro
    <jats:title>Abstract</jats:title><jats:p>Inorganic arsenic (As) is a toxic xenobiotic and carcinogen associated with severe health conditions. The urban population from the Atacama Desert in northern Chile was exposed to extremely high As levels (up to 600 µg/l) in drinking water between 1958 and 1971, leading to increased incidence of urinary bladder cancer (BC), skin cancer, kidney cancer, and coronary thrombosis decades later. Besides, the Andean Native-American ancestors of the Atacama population were previously exposed for millennia to elevated As levels in water (∼120 µg/l) for at least 5,000 years, suggesting adaptation to this selective pressure. Here, we performed two genome-wide selection tests—PBSn1 and an ancestry-enrichment test—in an admixed population from Atacama, to identify adaptation signatures to As exposure acquired before and after admixture with Europeans, respectively. The top second variant selected by PBSn1 was associated with LCE4A-C1orf68, a gene that may be involved in the immune barrier of the epithelium during BC. We performed association tests between the top PBSn1 hits and BC occurrence in our population. The strongest association (P = 0.012) was achieved by the LCE4A-C1orf68 variant. The ancestry-enrichment test detected highly significant signals (P = 1.3 × 10−9) mapping MAK16, a gene with important roles in ribosome biogenesis during the G1 phase of the cell cycle. Our results contribute to a better understanding of the genetic factors involved in adaptation to the pathophysiological consequences of As exposure.</jats:p>
    Scopus© Citations 15  1
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    Scopus© Citations 10  1  3