Browsing by Author "Marcelo Garrido"
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- ItemChanges in Clinical Presentation and Perioperative Management of Pheochromocytomas and Paragangliomas: A Four-Decade Experience in a Academic Center(2021) Thomas Uslar; Ignacio San Francisco; Roberto Ignacio Olmos; Stefano Pietro Macchiavello; Alvaro Zuñiga; Pablo Rojas; Marcelo Garrido; Alvaro Huete; Gonzalo Medez; Joaquin Cifuentes; Fernando Castro; Jose Tomas Zemelman; Daniela Olivari; Carlos E Fardella; Eugenio Arteaga; Jose Miguel Dominguez Ruiz-Tagle; Gloria Valdes; Rodrigo Tagle; Rene BaudrandObjective: Latin American reports on pheochromocytomas and paragangliomas (PPGL) are scarce. Recent studies have shown changes in both clinical presentation and management of these patients. We aimed to assess the main characteristics of PPGL patients in a single academic center over the last four decades. Experimental design: Cohort study. Patients and methods: Demographic, clinical, biochemical, genetic and perioperative data from 105 PPGL patients were retrospectively and prospectively collected over the 1980–2019 period. Patients were categorized into four groups (14 patients in the 1st, 25 patients in the 2nd, 27 patients in the 3th and 39 patients in the 4th decade) according to the date of diagnosis. Results: The mean age at diagnosis was 46±19 years, and the tumor size was 5.3±2.2 cm, female gender was 63%, bilateral tumor of 15%, paragangliomas 9% and metastatic disease in 15%. The aforementioned parameters remained stable across the four decades. During the study period we observed significant increases in doxazosin dosing (2.7±2.6 mg vs. 8.0±4.5 p<0.003) and laparoscopic procedures (28% vs. 84% p<0.001) along with a decrease in the length of hospital stay (10.0±8.9 vs. 3.8±1.7 days p=0.007). Among the 24 genetic tests performed, we identified 59% germline mutations. The most frequent mutations were RET (18%) and SDHX (18%), followed by VHL (14%), MAX (5%) and NF1 (4%). Notably, in the last decade we observed a dramatic increase in the proportion of incidental PPGL diagnosis (0% vs. 53% p<0.001) and genetic testing analyses (0 vs. 19 p<0.001). When comparing incidental diagnosis (n=25) versus clinically suspicious cases(n=50), incidentalomas had fewer adrenergic symptoms (38 vs. 62%; p<0.001), and lower rates of hypertension (64 vs. 80%; p=0.01), hypertension crises (28 vs. 44%; p=0.02), functionality (79 vs. 100%; p=0.01) and total catecholamines and/or metanephrine levels (8.4 vs. 12.5 fold above the upper normal limit; p=0.04). Conclusions: The implementation of a multidisciplinary program increased diagnosis and genetic testing and also optimized anesthesia and surgical procedure, translating into a notorious improvement in perioperative outcomes. In addition, we observed a change in the clinical presentation of PPGL in recent decades with a marked increase in incidental cases, which highlights the importance of early diagnosis and treatment.
- ItemHigh proportion of potential candidates for immunotherapy in a Chilean cohort of gastric cancer patients: results of the FORCE1 study(2019) Cordova-Delgado, Miguel; Mauricio P. Pinto; Ignacio N. Retamal; Matías Muñoz-Medel; María Loreto Bravo; María F. Fernández; Betzabé Cisternas; Sebastián Mondaca; César Sanchez; Hector Galindo; Bruno Nervi; Carolina Ibáñez; Francisco Acevedo; Jorge Madrid; José Peña; Erica Koch; Maria José Maturana; Diego Romero; Nathaly de la Jara; Javiera Torres; Manuel Espinoza; Carlos Balmaceda; Yuwei Liao; Zhiguang Li; Matías Freire; Valentina Gárate-Calderón; Javier Cáceres; Gonzalo Sepúlveda-Hermosilla; Rodrigo Lizana; Liliana Ramos; Rocío Artigas; Enrique Norero; Fernando Crovari; Ricardo Armisén; Alejandro H. Corvalán; Gareth I. Owen; Marcelo GarridoGastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53, NRAS, and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients.