Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma.

Molecular data generation and their combination in penile carcinomas (PeCa), a significant public health problem in poor and underdeveloped countries, remain virtually unexplored. An integrativemethodology combin ing genome-wide copy number alteration, DNA methylation, miRNA and mRNA expression analysis was performed in a set of 20 usual PeCa. The well-ranked 16 driver candidates harboring genomic alterations and regulated by a set of miRNAs, including hsa-miR-31, hsa-miR-34a and hsa-miR-130b, were significantly associated with over-represented pathways in cancer, such as immune-inflammatory system, apoptosis and cell cycle. Modules of co-expressed genes generated from expression matrix were associated with driver candidates and classified according to the over-representation of passengers, thus suggesting an alteration of the pathway dynamics during the carcinogenesis. This association resulted in 10 top driver candidates (AR, BIRC5, DNMT3B, ERBB4, FGFR1, PML, PPARG, RB1, TNFSF10 and STAT1) selected and confirmed as altered in an independent set of 33 PeCa samples. In addition to the potential driver genes herein described, shorter overall survival was associated with BIRC5 and DNMT3B overexpression (log-rank test, P = 0.026 and P = 0.002, respectively) highlighting its potential as novel prognostic marker for penile cancer.

Long-term follow-up of treatment of erectile dysfunction after radical prostatectomy using nerve grafts and end-to-side somatic-autonomic neurorraphy: a new technique.

OBJECTIVE: To study a novel penile reinnervation technique using four sural nerve grafts and end-to-side neurorraphies connecting bilaterally the femoral nerve and the cavernous corpus and the femoral nerve and the dorsal penile nerves. PATIENTS AND METHODS: Ten patients (mean [± sd; range] age 60.3 [± 4.8; 54-68] years), who had undergone radical prostatectomy (RP) at least 2 years previously, underwent penile reinnervation in the present study. Four patients had undergone radiotherapy after RP. All patients reported satisfactory sexual activity prior to RP. The surgery involved bridging of the femoral nerve to the dorsal nerve of the penis and the inner part of the corpus cavernosum with sural nerve grafts and end-to-side neurorraphies. Patients were evaluated using the International Index of Erectile Function (IIEF) questionnaire and pharmaco-penile Doppler ultrasonography (PPDU) preoperatively and at 6, 12 and 18 months postoperatively, and using a Clinical Evolution of Erectile Function (CEEF) questionnaire, administered after 36 months. RESULTS: The IIEF scores showed improvements with regard to erectile dysfunction (ED), satisfaction with intercourse and general satisfaction. Evaluation of PPDU velocities did not reveal any difference between the right and left sides or among the different time points. The introduction of nerve grafts neither caused fibrosis of the corpus cavernosum, nor reduced penile vascular flow. CEEF results showed that sexual intercourse began after a mean of 13.7 months with frequency of sexual intercourse varying from once daily to once monthly. Acute complications were minimal. The study was limited by the small number of cases. CONCLUSIONS: A total of 60% of patients were able to achieve full penetration, on average, 13 months after reinnervation surgery. Patients previously submitted to radiotherapy had slower return of erectile function. We conclude that penile reinnervation surgery is a viable technique, with effective results, and could offer a new treatment method for ED after RP.

Sedoanalgesia with midazolam and fentanyl citrate controls probe pain during prostate biopsy by transrectal ultrasound.

PURPOSE: To assess the pain intensity of patients administered midazolam and fentanyl citrate before undergoing transrectal ultrasound-guided prostate biopsy. MATERIALS AND METHODS: This was a study in patients with different indications for prostate biopsy in whom 5 mg of midazolam and 50 µg of fentanyl citrate was administered intravenously 3 minutes before the procedure. After biopsy, pain was assessed by use of a visual analogue scale (VAS) in three stages: VAS 1, during probe introduction; VAS 2, during needle penetration into prostate tissue; and VAS 3, in the weeks following the exam. Pain intensity at these different times was tested with stratification by age, race, education, prostate volume, rebiopsy, and anxiety before biopsy. Pain was ranked according to the following scores: 0 (no pain), 1-3 (mild pain), 4-7 (moderate pain), and 8-10 (severe pain). Statistical analysis was performed by using Kruskal-Wallis and Wilcoxon two-tailed tests with a significance of 5%. RESULTS: Pain intensity was not influenced by any risk factors. The mean VAS 1 score was 1.95±1.98, the mean VAS 2 score was 2.73±2.55, and the mean VAS 3 score was 0.3±0.9, showing greater pain at the time of needle penetration than in other situations (VAS 2>VAS 1>VAS 3, p=0.0013, p=0.0001, respectively). Seventy-five percent of patients reported a VAS pain scale of less than 3.1 or mild pain. CONCLUSIONS: Intravenous sedation and analgesia with midazolam and fentanyl citrate is a good method for reducing pain caused by prostate biopsy, even during probe insertion.

PSA and androgen-related gene (AR, CYP17, and CYP19) polymorphisms and the risk of adenocarcinoma at prostate biopsy.

The aim of the present study was to examine the impact of polymorphisms in prostate-specific antigen (PSA) and androgen-related genes (AR, CYP17, and CYP19) on prostate cancer (PCa) risk in selected high-risk patients who underwent prostate biopsy. Blood samples and prostate tissues were obtained for DNA analysis. Single-nucleotide polymorphisms in the 50-untranslated regions (UTRs) of the PSA (substitution A>G at position-158) and CYP17 (substitution T>C at 50-UTR) genes were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism assays. The CAG and TTTA repeats in the AR and CYP19 genes, respectively, were genotyped by PCR-based GeneScan analysis. Patients with the GG genotype of the PSA gene had a higher risk of PCa than those with the AG or AA genotype (OR=3.79, p=0.00138). The AA genotype was associated with lower PSA levels (6.44 +/- 1.64 ng=mL) compared with genotypes having at least one G allele (10.44 +/- 10.06 ng=mL) ( p=0.0687, 95% CI=0.3146 to 8.315, unpaired t-test). The multivariate analysis confirmed the association between PSA levels and PSA genotypes (AA vs. AG+ GG; chi2=0.0482) and CYP19 (short alleles homozygous vs. at least one long allele; chi2=0.0110) genotypes. Genetic instability at the AR locus leading to somatic mosaicism was detected in one PCa patient by comparing the length of AR CAG repeats in matched peripheral blood and prostate biopsy cores. Taken together, these findings suggest that the PSA genotype should be a clinically relevant biomarker to predict the PCa risk.

Pielonefrite pseudotuberculosa associada a nefrolitíase: relato de seis casos / Pseudotuberculous pyelonephritis associated with nephrolithiasis: report on six cases

Os autores apresentam seis casos de pacientes com história de litíase renal (cálculos coraliformes em quatro), infecçäo urinária de repetiçäo em todos, sem antecedentes ou clínica sugestiva de tuberculose pulmonar ou renal. Idade média de 47,5 anos, predomínio do sexo feminino (2:1). Todos foram submetidos a nefrectomia devido à presença de pielonefrite crônica complicada e apresentaram no exame anatomopatológico granulomas epitelióides similares à tuberculose renal. A pesquisa de bacilos álcool-ácido resistentes por meio de coloraçöes específicas e pelo estudo de DNA (Polimerase Chain Reaction - PCR) foi negativa. Acreditamos ser importante a divulgaçäo dessa forma peculiar de pielonefrite crônica, evitando diagnóstico incorreto de tuberculose renal e tratamento desnecessário

Oxibutinina intravesical / Intravesical oxybutynin

Os autores apresentam o caso de uma criança com bexiga neurogênica hiper-reflexa secundária a mielomeningocele, tratada inicialmente com oxibutinina por via oral e cateterismo intermitente, com bons resultados durante 18 meses. Após este período, a paciente desenvolveu náuseas e constipaçäo intestinal severa. A substituiçäo da medicaçäo oral pela via intravesical obteve bons resultados terapêuticos, com o desaparecimento dos efeitos colaterais