Browsing by Author "De Aretxabala, Xabier"

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    Cáncer de vesícula: ¿Es momento de modificar el GES?
    (2024) Samaniego, Camila; De Aretxabala, Xabier; Castillo, Felipe; Paredes, Álvaro; González, María
    Chile presenta en la actualidad una de las más altas tasas de mortalidad por cáncer de vesícula en el mundo. En 2006 el Ministerio de Salud Chileno incluyó la colelitiasis (pacientes 35-49 años) y el tratamiento con colecistectomía dentro del programa de Garantías Explícitas de Salud (GES). Objetivo: Evaluar los resultados del programa GES "Colecistectomía preventiva del cáncer de vesícula biliar" con la intención de proponer cambios en el programa. Método: Estudio retrospectivo de datos oficiales obtenidos de fuentes abiertas y mediante solicitud por transparencia desde el Ministerio de Salud e Instituto Nacional de Estadísticas. Resultados: Desde su inicio el año 2006, se han efectuado un total de 284.139 notificaciones de pacientes portadores de colelitiasis pertenecientes al rango etario entre 35 y 49 años. Lo anterior puede correlacionarse al número de colecistectomías practicadas como parte del programa. De estos, 229.546 fueron a pacientes mujeres. Durante los últimos 20 años, la mortalidad ajustada de la enfermedad ha mostrado una caída desde 15.16 muertes/100.000 habitantes hasta 6.72/100.000 habitantes el año 2021. La disminución en la tasa de mortalidad comenzó antes de la implementación del programa. A lo largo del país, se observan áreas claramente identificadas como de alta incidencia, especialmente en la zona centro sur. Mientras se identifican otras de baja incidencia en el norte". En cuanto a notificaciones GES existen regiones con alta notificación que no siempre se correlacionan con la incidencia. Existiendo áreas de alta incidencia y baja notificación. Conclusión: La disminución en la mortalidad del cáncer de vesícula en Chile, requiere que el programa de colecistectomía preventiva del cáncer de vesícula biliar sea modificado. Los recursos existentes debieran focalizarse en pacientes portadores de colelitiasis de áreas de alta incidencia además de portadores de factores de riesgo. Chile currently has one of the highest mortality rates from gallbladder cancer in the world. In 2006, the Chilean Ministry of Health included cholelithiasis (patients aged 35-49) and treatment with cholecystectomy within the Explicit Health Guarantees (GES) program. Aim: To evaluate the results of the GES Preventive Cholecystectomy Program for Gallbladder Cancer as to consider the need to propose changes to the model. Methods: retrospective analysis of official data from the Chile Ministry of Health and National Statistics Institute. Results: Since the program's inception in 2006, 284.139 notifications have been issued to patients aged between 35 and 49 with gallstones. Notifications can be correlated with the number of cholecystectomies performed under the program. Gallbladder cancer standardized mortality has shown a decrease over the last two decades, even before the program was implemented. High and low incidences are observed throughout the country. Regarding notifications, there are areas with a high incidence that are not always correlated with the areas with high notifications. Conclusion: The decrease in the standardized mortality of GBC in Chile requires modifying the present GES Preventive Cholecystectomy program for Gallbladder Cancer. Resources should be oriented to patients living in high-incidence areas with known risk factors.
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    ERCC1 (Excision repair cross-complementing 1) expression in pT2 gallbladder cancer is a prognostic factor
    (2011) Roa, Iván; De Aretxabala, Xabier; Lantadilla, Soledad; Muñoz, Sergio
    Gallbladder cancer (GBC) is the main cause of death by malignant tumour in women in Chile. There is no information regarding the role of excision repair cross-complementing group 1 (ERCC1) in GBC. Our aim is to determine the expression and significance of ERCC1 as a prognostic factor in GBC. Tissue microarrays were prepared using 200 surgically resected GBCs and 50 non-malignant gallbladders as controls. In 190 cases, ERCC1 was determined by immunohistochemistry. The correlation between ERCC1 expression and GBC pathological characteristics and patient survival were analysed. Ninety-five percent of the non-malignant gallbladder epithelia showed intense and diffuse ERCC1 expression. GBC cases showed ERCC1 expression in the tumour cells in 100/190 (53%) cases. The best differentiated tumours showed significantly greater expression than the less differentiated (p<0.05). Patients with ERCC1-positive status with subserosal carcinomas (pT2) had significantly better survival than ERCC1-negative patients at 20 and 60 months of follow-up (p=0.005), and the probability of dying was 6 times lower for ERCC1-positive than for ERCC1-negative patients. Our preliminary results show that cholecystectomised patients with GBC in stage pT2 and with ERCC1 expression have significantly better survival than patients at the same stage that did not present ERCC1 expression.
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    ¿Es posible utilizar las muestras de colecistectomías con cáncer en investigación?: Calidad del ADN de muestras obtenidas del sistema público y privado de salud
    (Sociedad Médica de Santiago, 2013) Roa, Iván; De Toro, Gonzalo; Sánchez, Tamara; Slater, Jeannie; Ziegler, Anne Marie; Game, Anakaren; Arellano, Leonardo; Schalper, Kurt; De Aretxabala, Xabier
    Background: The quality of the archival samples stored at pathology services could be a limiting factor for molecular biology studies. Aim: To determine the quality of DNA extracted from gallbladder cancer samples at different institutions. Material and Methods: One hundred ninety four samples coming from five medical centers in Chile, were analyzed. DNA extraction was quantified determining genomic DNA concentration. The integrity of DNA was determined by polymerase chain reaction amplification of different length fragments of a constitutive gene (β-globin products of 110, 268 and 501 base pairs). Results: The mean DNA concentration obtained in 194 gallbladder cancer samples was 48 ± 43.1 ng/µl. In 22% of samples, no amplification was achieved despite obtaining a mean DNA concentration of 58.3 ng/ul. In 81, 67 and 22% of samples, a DNA amplification of at least 110, 268 or 501 base pairs was obtained, respectively. No differences in DNA concentration according to the source of the samples were demonstrated. However, there were marked differences in DNA integrity among participating centers. Samples from public hospitals were of lower quality than those from private clinics. Conclusions: Despite some limitations, in 80% of cases, the integrity of DNA in archival samples from pathology services in our country would allow the use of molecular biology techniques.
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    Expresión y amplificación del gen HER2 en el cáncer gástrico avanzado
    (Sociedad Médica de Santiago, 2013) Roa, Iván; Slatter, Jeannie; Carvajal, Daniel; Schalper, Kurt; De Toro, Gonzalo; Ares, Raúl; Game, Anakaren; León, Jorge; De Aretxabala, Xabier
    Background: Overexpression/amplification of the HER2 gene in advanced gastric cancer is a predictor of response to adjuvant therapy with monoclonal antibodies. Aim: To determine the frequency of HER2 gene overexpression and amplification in advanced gastric cancer. Material and Methods: One hundred nine advanced gastric cancer biopsy specimens, from 76 men and 33 women aged 67 ± 14 and 62 ± 12 years respectively, were selected. Three histological patterns (diffuse, intestinal and mixed) were recognized. Automated immunohistochemistry was performed with monoclonal c-erbB-2 (NCL-356) Novocastra. Fluorescent in situ hybridization (FISH) for HER2 was performed in positive cases. Results: In 39% of cases, immunohistochemical staining was negative. It was 1+, 2+ and 3+ positive in 15, 36 and 11% of cases, respectively. It was positive in 16% and 3% of intestinal type and mixed carcinomas, respectively. It was negative in all diffuse carcinomas. FISH was performed in 39 (2 +) cases and in 11 (3 +) cases. The gene amplification was positive in two (2 +) and 11 (3 +) cases (11.9%). The overall concordance between immunohistochemical staining and in situ hybridization was 85%. Conclusions: In advanced gastric cancer, HER2 gene overexpression or amplification was observed in 11% and 12% of cases, respectively.
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    Inactivation of tumor suppressor gene pten in early and advanced gallbladder cancer
    (Biomed Central Ltd., 2015) Roa, Iván; De Toro, Gonzalo; Fernández, Fernanda; Game, Anakaren; Muñoz, Sergio; De Aretxabala, Xabier; Javle, Milind
    BACKGROUND: PTEN is a tumor suppressor gene that regulates the PTEN/PI3k/AKT/mTOR pathway, which is frequently altered in human cancers including gallbladder cancer (GBC). To determine the frequency of PTEN expression in GBC and to establish its relation to clinical and morphological parameters and survival in GBC. METHODS: The immunohistochemical expression of PTEN was studied in 108 GBC. All the cases included areas of non-tumor mucosa adjacent to the tumor. RESULTS: The group was comprised of 108 patients, 91 women (84.3%) and 17 men (15.7%) with an average age of 65.2 years (SD ± 12.3 years). Thirty-five cases (33%) were early carcinomas (EC) and the remaining 73 (67%) were advanced cases (AC). All the internal controls were positive (moderate or intense in 96.3%). Only in three AC (4.1%) was there a complete absence of PTEN immunohistochemical expression. There were no significant differences in relation between PTEN expression and tumor infiltration or degree of differentiation. The three patients with PTEN inactivation died before 10 months; however, the other patients with AC had a survival of 53% at 10 months. DISCUSSION: Loss of PTEN expression was observed in 4.1% of the advanced GBC. All the patients with this alteration died before 10 months. PTEN inactivation could be a rare event, but with a poor prognosis in advanced GBC.
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    Somatic Mutations of PI3K in Early and Advanced Gallbladder Cancer: Additional Options for an Orphan Cancer
    (American Society for Investigative Pathology and the Association for Molecular Pathology by Elsevier, 2016) Roa, Iván; Gracía, Hernán; Game, Anakaren; De Toro, Gonzalo; De Aretxabala, Xabier; Javle, Milind
    Gallbladder cancer (GBC) is the second-leading cause of death from malignant tumors in Chilean women. The phosphatidylinositol 3-kinase (PI3K) pathway is involved in proliferation, cell survival, and growth. We investigated mutations in exons 9 and 20 of the PI3K gene in GBC. Mutations in exons 9 (E542K, E545G, E545K) and 20 (H1047L and H1047R) of PI3K were determined by direct sequencing in 130 cases of GBC. The patient group consisted of 110 women and 20 men, and mutations were found in 22 cases (16.9%). Of these, 14 cases had mutations in exon 9 (63.6%) (E542K, 64%; E545K, 29%; and E545G, 7%) and 8 in exon 20 (37.4%; H1047L, 50%; H1047R, 50%). No differences were noted in the frequency and type of mutations analyzed by sex, age, or histologic features. We observed mutations in 22% of the early-stage GBC and 14.6% of the advanced cases. In this series of GBC, 17% of cases were noted as having mutations in either exons 9 or 20 of PI3K. These results suggest that therapeutic testing of inhibitors of the PI3K/AKT pathway may be of benefit in advanced GBC patients

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