R. Freitas

MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors

BackgroundContemporary challenges of prostate cancer (PCa) include overdiagnosis and overtreatment, entailing the need for novel clinical tools to improve risk stratification and therapy selection. PCa diagnosis and prognostication might be perfected using epigenetic biomarkers, among which aberrant DNA methylation of microRNA promoters has not been systematically explored. Herein, we identified aberrantly methylated microRNAs promoters in PCa and assessed its diagnostic and prognostic biomarker potential.MethodsUsing HumanMethylation450 BeadChip-based analysis differentially methylated CpGs in microRNA promoters were identified. Promoter methylation of six microRNAs (miR-34b/c, miR-129-2, miR-152, miR-193b, miR-663a and miR-1258) was analyzed by qMSP in three sets (180 prostatectomies, 95 urine sediments and 74 prostate biopsies). Biomarkers’ diagnostic (validity estimates) and prognostic [disease-free (DFS) and disease-specific survival (DSS)] performance was assessed.ResultsSignificantly higher promoter methylation levels in PCa were confirmed for six candidate microRNAs. Except for miR-152, all displayed AUC values higher than 0.90, with miR-1258 and miR-193b disclosing the best performance (AUC = 0.99 and AUC = 0.96, respectively). In urine samples, miR-193b showed the best performance (91.6% sensitivity, 95.7% specificity, AUC = 0.96). Moreover, higher miR-129-2 independently predicted for shorter DSS and miR−34b/c methylation levels independently predicted for shorter DFS and DSS.ConclusionsQuantitative miR-193b, miR-129-2 and miR-34b/c promoter methylation might be clinically useful PCa biomarkers for non-invasive detection/diagnosis and prognostication, both in tissue and urine samples.

Adult circumcision and male sexual health: a retrospective analysis

We aimed to evaluate possible associations of circumcision with several sexual dysfunctions and to identify predictors for the development of these outcomes post‐operatively. Telephone surveys about sexual habits and dysfunctions before and after intervention were conducted post‐operatively to patients that underwent circumcision in Centro Hospitalar Vila Nova de Gaia/Espinho during 2011. McNemar test was used for a matched‐pairs analysis of pre‐ and post‐operative data. Odds ratios, adjusted in a multivariate analysis, explored predictors of de novo sexual dysfunctions after circumcision. With intervention, there was an increase in frequency of erectile dysfunction (9.7% versus 25.8%, P = 0.002) and delayed orgasm (11.3% versus 48.4%, P < 0.001), and a significant symptomatic improvement in patients with pain with intercourse (50.0% versus 6.5%, P < 0.001). Significant predictors for de novo erectile dysfunction were diabetes mellitus (OR 9.81, P = 0.048) and lack of sexual desire (OR 8.76, P = 0.028). Less than three sex partners (OR 7.04, P = 0.007) and low sexual desire (OR 7.49, P = 0.029) were significant predictors for de novo delayed orgasm.

Biopsy sampling and histopathological markers for diagnosis of prostate cancer

Prostate cancer is one of the most common malignant tumors and a leading cause of cancer-related morbidity and mortality. Irrespective of the method that allows for risk stratification of prostate cancer suspects, diagnosis relies on tissue sampling through prostate biopsy and subsequent histopathological evaluation. This provides critical information about disease aggressiveness, which is required for adequate patient management. Prostate biopsy methods have significantly evolved over the years, including the definition of indications, sampling schemes and use of imaging techniques (ultrasound and MRI) that allow for more accurate tissue sampling. In response to the challenges emerging from more precise collection of minute prostate tissue samples for analysis, histopathological assessment should include not only the observation of routinely stained sections, but also, and increasingly so, a series of ancillary techniques, especially immunohistochemistry, which increment the accuracy of prostate cancer diagnosis and may provide relevant information to guide patient management.

Cistectomia radical / experiência de um centro oncológico

Resumo Objectivos Apresentar a nossa experiencia clinica e cirurgica da cistectomia radical no carcinoma da bexiga, avaliar as complicacoes pos-operatorias e a sobrevida global dos doentes. Material e metodos Foi efectuada uma analise retrospectiva de todos os doentes submetidos a cistectomia radical por carcinoma da bexiga entre 2006 e 2010. As caracteristicas patologicas foram descritas com base na classificacao TNM de 2009. Foram avaliadas as complicacoes pos-operatorias nos primeiros 30 dias apos a cirurgia, segundo a escala de Clavien-Dindo e calculada a sobrevida global. Resultados Foram analisados os dados de 195 doentes com uma idade media de 67,8 anos (28–87 anos). 82,6% eram do sexo masculino. A mediana do tempo de seguimento foi de 2,5 anos. Foi diagnosticado carcinoma urotelial em 93,8% dos casos. A maioria dos doentes apresentava doenca extravesical, com estadio patologico T3 em 28,7% e T4 em 22,1%. Em 32,8% dos doentes submetidos a linfadenectomia foram detectadas metastases ganglionares. A derivacao urinaria mais frequente foi a uretero-ileostomia cutânea realizada em 79% dos casos, seguida pela neobexiga em 10,3%. Foram registadas complicacoes pos-operatorias em 40,5% dos doentes, sendo 28,2% grau I/II e 12,3% grau III-V, com uma taxa de mortalidade de 3,6%. A sobrevida global aos 3 anos foi de 54% e aos 5 anos foi de 48%. Os casos com doenca localizada a bexiga (≤ pT2N0) apresentaram uma sobrevida aos 3 anos de 89%. A presenca de doenca extravesical (≥ pT3) e a metastizacao ganglionar confirmaram ser factores de mau prognostico, com sobrevidas globais aos 3 anos de 46% e de 22%, respectivamente. Conclusoes Os resultados desta serie mostram que a cistectomia radical e uma cirurgia complexa mas com morbilidade e mortalidade pos-operatoria precoce razoaveis. A cirurgia deve ser efectuada numa fase inicial da doenca de forma a oferecer os melhores resultados de sobrevida.