ABSTRACT
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited channelopathy. In this review, we summarize the epidemiology, pathophysiology, clinical characteristics, diagnostics, genetic mutations, standard treatment, and the emergence of potential gene therapy. This inherited cardiac arrhythmia presents in a bimodal distribution with no association between sex or ethnicity. Six different CPVT genes have been identified, however, most of the cases are related to a heterozygous, gain-of-function mutation on the ryanodine receptor-2 gene (RyR2) and calsequestrin-2 gene (CASQ2) that causes delayed after-depolarization. The diagnosis is clinically based, seen in patients presenting with syncope after exercise or stress-related emotions, as well as cardiac arrest with full recovery or even sudden cardiac death. Standard treatment relies on beta-blockers, with add-on therapy, flecainide, and cardiac sympathetic denervation as second-line treatments. An implantable cardioverter-defibrillator is indicated for patients who have suffered a cardiac arrest. Potential gene therapy has emerged in the last 20 years and accelerated because of associated viral vector application in increasing the efficiency of prolonged cardiac gene expression. Nevertheless, human trials for gene therapy for CPVT have been limited as the population is rare, and an excessive amount of funding is required.
ABSTRACT
O status dos linfonodos axilares permanece fundamental na decisão do estadiamento, prognóstico e tratamento no câncer de mama. A biópsia do linfonodo sentinela já está incorporada ao manejo cirúrgico, conseguindo predizer com boa acurácia o risco do envolvimento axilar. Essa técnica permitiu qualificar a análise histopatológica do sentinela e, cada vez mais, depósitos tumorais nesse linfonodo, identificados como micrometástases (dimensões de 0,2 a 2 mm), são valorizados na terapêutica do câncer de mama. São controversos o real significado clínico e o tratamento cirúrgico ideal das micrometástases no linfonodo sentinela. A tendência atual é de se proceder ao esvaziamento axilar e indicar tratamento sistêmico adjuvante nos casos em que houver micrometástases no gânglio sentinela, porém não nas situações em que são encontradas apenas células tumorais isoladas. O nomograma do Memorial Hospital pode ser uma ferramenta útil neste cenário para a tomada de decisões individuais. Esta questão provavelmente terá uma resposta após os resultados de grandes ensaios clínicos em andamento.
Axillary modal status remains as the most important parametermin breast cancer staging, prognosis and treatment. Sentinel node biopsy is now a standard procedure in the surgical management and an excellent risk predictor of axillary involvement. The detailed sentinel node histopathological analysis has lead to the increasing discovery of tumoral deposits defined as micrometastases. The real biological significance of these micrometastases and their treatment are controversial in the literature. The current trend is to proceed with full axillary dissection and prescribe adjuvant treatment when micrometastases are found. However, isolated tumor cells are detected these treatments are unnecessary. The Memorial Hospital nomogram could be an useful tool for individual decisions in the clinical setting. Answers to this question will probably be provided after the results of large ongoing randomized clinical
