ABSTRACT
ABSTRACT Background: Non-metastatic castration resistant prostate cancer (M0 CRPC) has seen important developments in drugs and diagnostic tools in the last two years. New hormonal agents have demonstrated improvement in metastasis free survival in M0 CRPC patients and have been approved by regulatory agencies in Brazil. Additionally, newer and more sensitive imaging tools are able to detect metastasis earlier than before, which will impact the percentage of patients staged as M0 CRPC. Based on the available international guidelines, a group of Brazilian urology and medical oncology experts developed and completed a survey on the diagnosis and treatment of M0 CRPC in Brazil. These results are reviewed and summarized and associated recommendations are provided. Objective: To present survey results on management of M0 CRPC in Brazil. Design, setting, and participants: A panel of six Brazilian prostate cancer experts determined 64 questions concerning the main areas of interest: 1) staging tools, 2) treatments, 3) side effects of systemic treatment/s, and 4) osteoclast-targeted therapy. A larger panel of 28 Brazilian prostate cancer experts answered these questions in order to create country-specific recommendations discussed in this manuscript. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on the predefined questions. These answers are the panelists' opinions, not a literature review or meta-analysis. Therapies not yet approved in Brazil were excluded from answer options. Each question had five to seven relevant answers including two non-answers. Results were tabulated in real time. Conclusions: The results and recommendations presented can be used by Brazilian physicians to support the management of M0 CRPC patients. Individual clinical decision making should be supported by available data, however, for Brazil, guidelines for diagnosis and management of M0 CRPC patients have not been developed. This document will serve as a point of reference when confronting this disease stage.
Subject(s)
Humans , Male , Physicians , Prostatic Neoplasms, Castration-Resistant/diagnosis , Prostatic Neoplasms, Castration-Resistant/drug therapy , Perception , Brazil , Treatment Outcome , Patient Selection , ConsensusABSTRACT
Dengue virus is the most important mosquito-borne viral disease in the world. Co-circulation of the four types of dengue viruses and expansion of dengue epidemic gave rise to infection enhancement and a big expansion of clinical aspects of the disease. Herein we report a case of a 25-year-old white woman with dengue fever and numerous associated autoimmune features. Our patient had proteinuria, an extensive right pleural effusion, a thin pericardial effusion and ascites. She had a low C3 level and positive antinuclear antibody; cryoglobulins were also positive. The numerous autoimmune features of this patient were a diagnostic challenge, since she was a young woman and could be easily mistaken for a rheumatologic patient in a newly open disease. Dengue infection probably was a triggering event causing an abnormal immune response. Therefore, dengue should be suspected in patients with hematological disorders and autoimmune features in endemic regions or those who have travelled to those regions.
Subject(s)
Adult , Female , Humans , Autoimmune Diseases/immunology , Dengue/immunology , Autoimmune Diseases/virology , Dengue/diagnosisABSTRACT
O tamoxifeno (TMX),consagrado como terapia padrão no tratamento de pacientes portadoras de câncer de mama com receptores hormonais positivos, é convertido por metabolização primária e secundária no metabólito endoxifeno, que apresenta afinidade muito maior pelos receptores hormonais e é o maior responsável pelos efeitos antitumorais desta droga. A biotransformação do TMX em endoxifeno é dependente da subunidade 2D6 do citocromo P-450 (CYP2D6), cujo gene apresenta inúmeros polimorfismos que reduzem a atividade metabólica dessa via biológica, resultando em menores níveis de seu produto ativo e, possivelmente, da resposta terapêutica ao uso do TMX. Objetivo: O objetivo deste estudo foi determinar a frequência dos polimorfismos CYP2D6*3, *4, *5, *6 e *10 e dos fenótipos de metabolização da droga TMX em pacientes portadoras de câncer de mama atendidas pelos autores no Centro de Oncologia do Hospital Sírio Libanês (HSL), além de revisar os dados sobre este tema disponíveis na literatura. Métodos: Amostras de sangue periférico de 30 pacientes foram enviadas a laboratório de referência para pesquisa dos polimorfismos descritos de CYP2D6 pela técnica de reação em cadeia da polimerase e digestão por enzimas de restrição (PCR-RFLP). Resultados: Os resultados mostraram heterozigose para polimorfismo CYP2D6*4 e *10 em 33 e 38% das mulheres, respectivamente. Utilizando a classificação de fenótipos de metabolização de TMX previamente descrita determinamos que 27% das mulheres avaliadas foram categorizadas com perfil de metabolização intermediária da droga, e 3% como metabolizadoras pobres, as quais, segundo dados atuais, parecem estar duas vezes mais sujeitas a desenvolverem recorrência de câncer de mama durante tratamento com TMX. Foi documentada uma elevada e inesperada prevalência de heterozigose do polimorfismo *10 na população estudada. Conclusões: Estudos prospectivos estão em andamento, visando definir o papel do perfil dos polimorfismos de CYP2D6 na escolha...
Tamoxifen (TMX), established as standard therapy in treating patients with breast cancer with hormone receptor positive, is converted by metabolism in primary and secondary metabolite endoxifeno, which has much higher affinity for hormone receptors and is most responsible the antitumor effects of this drug. Biotransformation of TMX in endoxifeno 2D6 is dependent on the subunit of cytochrome P-450 (CYP2D6), whose gene has many polymorphisms that reduce the metabolic activity of this biological pathway, resulting in lower levels of its active product, and possibly therapeutic response to use of TMX. Objective: The objective of this study was to determine the frequency of CYP2D6 polymorphisms * 3, * 4, * 5, * 6 and * 10 and phenotypes of drug metabolizing TMX in patients with breast cancer treated by the authors at the Centre for Oncology Syrian Lebanese Hospital (HSL), and review the data on this subject available in the literature. Methods: Blood samples from 30 patients were sent to reference laboratory for research of CYP2D6 polymorphisms described the technique of polymerase chain reaction and restriction enzyme digestion (PCR-RFLP). Results: Results showed heterozygosity for polymorphic CYP2D6 * 4 and * 10 in 33 women and 38% respectively. Using the classification of phenotypes of metabolism of TMX described previously determined that 27% of the women studied were categorized with a profile of intermediate metabolites of the drug, and 3% as poor metabolizers, which, according to current data seem to be two times more likely to develop recurrence of breast cancer during treatment with TMX. It was documented and an unexpected high prevalence of heterozygous * 10 polymorphism in the population. Conclusions: Prospective studies are underway, aimed at defining the role of the profile of CYP2D6 polymorphisms on the choice of strategy hormonal therapy in women with breast cancer.