ADAR1-mediated RNA-editing of 3'UTRs in breast cancer

BACKGROUND: Whole transcriptome RNA variant analyses have shown that adenosine deaminases acting on RNA ( ADAR ) enzymes modify a large proportion of cellular RNAs, contributing to transcriptome diversity and cancer evolution. Despite the advances in the understanding of ADAR function in breast cancer, ADAR RNA editing functional consequences are not fully addressed. RESULTS: We characterized A to G(I) mRNA editing in 81 breast cell lines, showing increased editing at 3'UTR and exonic regions in breast cancer cells compared to immortalized non-malignant cell lines. In addition, tumors from the BRCA TCGA cohort show a 24% increase in editing over normal breast samples when looking at 571 well-characterized UTRs targeted by ADAR1. Basal-like subtype breast cancer patients with high level of ADAR1 mRNA expression shows a worse clinical outcome and increased editing in their 3'UTRs. Interestingly, editing was particularly increased in the 3'UTRs of ATM, GINS4 and POLH transcripts in tumors, which correlated with their mRNA expression. We confirmed the role of ADAR1 in this regulation using a shRNA in a breast cancer cell line (ZR-75-1). CONCLUSIONS: Altogether, these results revealed a significant association between the mRNA editing in genes related to cancer-relevant pathways and clinical outcomes, suggesting an important role of ADAR1 expression and function in breast cancer.

Recomendaciones sobre el manejo del cáncer de páncreas tipo adenocarcinoma en Latinoamérica: Reunión del Consenso del Simposio Latinoamericano de Gastroenterología Oncológica (SLAGO) y de la Asociación Ibero Latinoamericana de Terapia Radiante (ALATRO), Viña del Mar, Chile 2015 / Recommendations for the management of pancreatic cancer type adenocarcinoma: A consensus statement reached during the 2015 Latin American Symposium on Gastroenterological Oncology

Pancreatic cancer is a malignancy of great impact in developed countries and is having an increasing impact in Latin America. Incidence and mortality rates are similar for this cancer. This is an important reason to offer to the patients the best treatments available. During the Latin American Symposium of Gastroenterology Oncology (SLAGO) held in Viña del Mar, Chile, in April 2015, a multidisciplinary group of specialists in the field met to discuss about this disease. The main conclusions of this meeting, where practitioners from most of Latin American countries participated, are listed in this consensus that seek to serve as a guide for better decision making for patients with pancreatic cancer in Latin America.

Adjuvant chemoradiation for resected gallbladder cancer: Treatment strategies for one of the leading causes of cancer death in Chilean women.

BACKGROUND: Gallbladder cancer (GBC) is the second leading cause of cancer death in women in Chile. Even after curative surgery, prognosis is grim. To evaluate acute and late toxicity and efficacy of adjuvant chemoradiation (CRT) after curatively resected GBC. MATERIALS AND METHODS: We retrospectively analyzed the cohort of patients diagnosed between January 1999 and December 2009, treated with adjuvant CRT at our institution. Treatment protocol considered external beam radiation (RT) (45–54 Gy) to tumor bed and regional lymph nodes with or without concurrent 5-fluorouracil (5-FU) (500 mg/m2/day by 120-hours continuous infusion on days 1–5 and 29–33). Data was obtained from medical records, mortality from death certificates. Survival was estimated by Kaplan– Meier curves. RESULTS: 46 patients with curatively resected GBC received adjuvant CRT. Median age was 57 years (range 33–76); 39 patients were female. After diagnosis, a second surgery was performed in 42 patients. Cholecystectomy with hepatic segmentectomy and lymphadenectomy was the curative surgery in 41 patients. All patients received RT with a planned dose of 45 Gy in 25 fractions, 11 patients received a boost to the tumor bed up to 54 Gy and 34 patients had concurrent 5-FU. Therapy was well tolerated. Five patients experienced grade 3 toxicities. No grade 4 or 5 toxicity was observed. No grade >2 late toxicity was observed. Three- and 5-year overall survival (OS) were 57% and 51%, respectively. CONCLUSIONS: Adjuvant chemoradiation is well tolerated and might impact favorably on survival in patients with curatively resected GBC.

Osteosarcomas de la región de cabeza y cuello / Osteosarcoma of the head and neck area: analysis of 12 patients

Background: Less than 10 percent of osteosarcomas are located the head and neck region, mainly affecting the mandible and maxillary region. Aim: To analyze the therapeutic modality, types of reconstruction, surgical complications and survival of patients treated for osteosarcoma of the head and neck. Material and Methods: Review of medical records of 12 patients aged 17 to 34 years (6 women) treated for osteosarcoma of the head and neck between September 1998 and may 2009. Results: The localization of the tumor was maxillary in eight, mandibular three and ethmoidal in one patient. According to histologic grade, seven tumors were grade 1, four were grade 2 and one was grade 3. Adjuvant and neoadjuvant chemotherapy were administered to all and seven patients, respectively. The surgical treatment for maxillary tumors was maxillectomy. A reconstruction with rectum abdomini free flap was done in four patients and with dermoepidermic graft and an obturator prosthesis in three. In one patient, the defect was covered with a dental prosthesis. Treatment for mandibular tumors was mandibular excision. A reconstruction with peroneal free flap was performed in two patients and with an iliac crest graft in one. The ethmoidal tumor was resected and covered with local flaps. There were four complications. Two patients had a cutaneous fistula, one patient had a free flap partial atrophy and one patient had surgical site infection. Two patients who had positive margins died from local recurrence. Of the 10 patients with negative margins, seven are alive without recurrence, one died due to the disease, one has disseminated disease and one died from another cause. Conclusions: Our results in the treatment of head and neck osteosarcomas are consistent with published data.

Objetivos: Analizar la modalidad terapéutica, tipos de reconstrucción, complicaciones quirúrgicas y sobrevida de un grupo de pacientes tratados por esta patología. Métodos: Revisión de fichas clínicas de 12 pacientes portadores de osteosarcoma de cabeza y cuello entre septiembre de 1998 y mayo de 2009. Resultados: Edad promedio 30 años (17-34), 6 mujeres y 6 hombres. Localización fue 8 maxilar, 3 mandibular y 1 etmoidales. 7 tumores G1, 4 G2 y 1 G3. Siete pacientes recibieron quimioterapia neoadyuvante y todos adyuvante. El tratamiento de tumores maxilares fueron maxilectomías reconstruidas 4 con colgajo libre de recto abdominal, 3 con injerto dermoepidérmico más prótesis obturadora y una con prótesis dentaria. Se realizó mandibulectomía a los tumores mandibulares, 2 reconstruidos con colgajo libre de peroné y uno con injerto de cresta ilíaca. El tratamiento del tumor etmoidal fue resección craneofacial y se reparó con colgajos locales. Hubo 4 complicaciones; 2 fístulas cutáneas, una atrofia parcial de colgajo libre y una infección de herida operatoria. Dos pacientes tuvieron bordes comprometidos, quienes murieron por recidiva local. De los 10 pacientes con bordes libres, 7 se encuentran sin evidencia de recidiva, uno con enfermedad diseminada, uno fallecido por la enfermedad y uno fallecido por otra causa. Conclusiones: Nuestros resultados son consistentes con la literatura.

Registro de evaluación de tratamiento de cáncer gástrico en Chile (REGATE): características clínicas básales de 523 pacientes / Registry of gastric cancer evaluation in Chile (REGATE): basal clinical features of 523 patients

Background: Gastric cancer is one of the leading causes of cancer-related deaths in Chile and worldwide. No consensus exists for therapeutic management. Aim: To assess clinical features and practice patterns of patients with newly diagnosed gastric cancer in Chile. Method: Chilean patients > 18 years old with newly diagnosed primary gastric adenocarcinoma enrolled by thirteen centers from different regions of Chile. Target sample size calculated according to gastric cancer prevalence in Chile. Data collected from two visits within a 10-month timeframe: baseline (patients and tumor features, treatment plan) and end of study (completion of initial treatment). Herein, baseline visit data is presented. Results: Between 2005 and 2008, 523 patients enrolled. Median age 61.3 years. Diagnosis by endoscopy in 98.5 percent patients. Location: body 35.8 percent, proximal 35.4 percent, and antral 23.9 percent. Most frequently used histopathological classification was WHO classification, with tubular adenocarcinoma being most frequent finding (53.1 percent). AJCC/UICC clinical staging (available in 31.1 percent of patients) was: 0 and I - 23.3 percent, II - 18.3 percent, III- 20.8 percent, IV - 37.6 percent. Therapeutic choice based mainly on clinical staging (49.9 percent) and included surgery in 440 patients (84.1 percent). Therapy planned by surgeon (54.9 percent) or multidisciplinary team (42.3 percent). Conclusions: REGATE is the largest prospective multicenter registry study performed in Chile. Basal visit data report that diagnosis is established frequently at advanced stages. Surgery is the most frequent therapeutic choice, (neo-) adjuvant therapies are only planned in one out of four patients. End of study visit data will provide the full scope of diagnosis and treatment of these patients.

Introducción: El cáncer gástrico es una de las principales causas de muerte por cáncer en Chile. No existe consenso acerca del tratamiento. Objetivos: Conocer características clínicas y patrón de tratamiento de pacientes con cáncer gástrico recién diagnosticado. Material y Método: Pacientes chilenos mayores de 18 años con diagnóstico reciente de adenocarcinoma gástrico primario, enrolados en 13 centros de diferentes regiones de Chile. Datos obtenidos en dos visitas dentro de período de 10 meses: basal (características del tumor y paciente, plan de tratamiento) y fin de estudio (tratamiento inicial completado). Se presentan datos de visita basal. Resultados: Entre 2005 y 2008, 523 pacientes enrolados. Mediana edad 61,3 años. Diagnóstico por endoscopia en 98,5 por ciento pacientes. Localización: corporal 35,8 por ciento, proximal 35,4 por ciento y antral 23,9 por ciento. Clasificación histopatológica más usada fue clasificación OMS, y tipo histopatológico más frecuente fue tubular 53,1 por ciento. Etapificación clínica AJCC/UICC (disponible en 37,6 por ciento de pacientes) distribuida en: 0 y I - 23,3 por ciento, II -18,3 por ciento, III - 20,8 por ciento, IV - 37,6 por ciento. Principal característica clínica para elección de terapia planeada fue etapificación clínica (49,9 por ciento). Plan de tratamiento consideró cirugía en 440 pacientes (84,1 por ciento). En mayoría de casos, plan terapéutico decidido por cirujano (54,9 por ciento) o equipo multidisciplinario (42,3 por ciento). Conclusiones: REGATE es el estudio de registro prospectivo multicéntrico más grande desarrollado en Chile. Datos visita basal informan que diagnóstico se establece frecuentemente en etapas avanzadas. Cirugía es alternativa terapéutica más frecuentemente indicada; terapias (neo-) adyuvantes sólo son ofrecidas a uno de cuatro pacientes. Datos visita fin de estudio proveerá visión completa del diagnóstico y tratamiento de estos pacientes.

Manejo paliativo del cáncer de vesícula biliar irresecable o metastásico: Conclusiones del Consenso Latinoamericano de Manejo del Cáncer de Vesícula Biliar / Palliative treatment for locally advanced or metastatic gallbladder cancer: conclusions of the Latin American Consensus meeting for the management of gallbladder cancer

Gallbladder cancer is a rare disease in Western developed countries, but it is a highly prevalent and lethal disease in Chile and other countries in Latin America. No randomized controlled trials have been performed in gallbladder cancer to establish standard treatments. We therefore performed the first Latin American consensus meeting for the management of gallbladder cancer. In this article we present the conclusions of the panel of experts for the palliative treatment of unresectable or metastatic gallbladder cancer based on a review of the literature, the discussion of the participating experts and the opinion of the assistants. The topics reviewed included: 1.- Gallbladder Cancer and Cholangiocarcinoma -are they the same disease?; 2. - Palliative Chemotherapy: Indications, Drugs and Schedules; 3. - Palliative Radiotherapy; 4.- Palliative Surgery; 5.-Management of Malignant Biliary Obstruction.

Quimiorradioterapia adyuvante en el cáncer gástrico resecado con intención curativa: análisis de supervivencia y toxicidad de pacientes tratados entre 1995 y 2003 en el Instituto Nacional del Cáncer, Chile / Results of adjuvant chemoradiation after curative surgery for gastric cancer: a retrospective study

Background: Survival rates after curative surgery for gastric cancer are disappointing. Therefore adjuvant therapeutic strategies are required. Aim: To analyze survival and side effects of treatment among gastric cancer patients treated with adjuvant chemo radiotherapy after curative resection of gastric adenocarcinoma. Material and methods: Retrospective review of medical records of 74 patients aged 20 to 74 years, treated with complete resection of gastric adenocarcinoma followed by adjuvant chemo radiation. Survival analysis was based on the records and information from the National Mortality Registry. Results: Five years survival fluctuated from 50 percent among patients in stage IB to 25 percent among those is stage IV. Significant acute toxicity was observed in 23 patients (31 percent). No patients died due to acute toxicity. Eleven patients (16.4 percent) developed significant late toxicity, with two possible deaths related to treatment. Conclusions: Postoperative chemo radiotherapy is feasible in our experience. Continues infusion of 5-fluoruracil is recommended to reduce toxicity.