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- Can epigenetic and inflammatory biomarkers identify clinically aggressive prostate cancer?Publication . Santos, PB; Patel, H; Henrique, R; Félix, AProstate cancer (PCa) is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. It emerges through the acquisition of genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications and microRNA deregulation. These generate heritable transformations in the expression of genes but do not change the DNA sequence. Alterations in DNA methylation (hypo and hypermethylation) are the most characterized in PCa. They lead to genomic instability and inadequate gene expression. Major and minor-specific modifications in chromatin recasting are involved in PCa, with signs suggesting a dysfunction of enzymes modified by histones. MicroRNA deregulation also contributes to the initiation of PCa, including involvement in androgen receptor signalization and apoptosis. The influence of inflammation on prostate tumor carcinogenesis is currently much better known. Recent discoveries about microbial species resident in the urinary tract suggest that these are the initiators of chronic inflammation, promoting prostate inflammatory atrophy and eventually leading to PCa. Complete characterization of the relationship between the urinary microbiome and prostatic chronic inflammation will be crucial to develop plans for the prevention of PCa. The prevalent nature of epigenetic and inflammatory alterations may provide potential biomarkers for PCa diagnosis, treatment decisions, evaluation of prognosis and posttreatment surveillance.
- Urethral leak: an unusual symptom of pudendal nerve entrapmentPublication . Ramos, SA; Guimarães, T; Bollens, RPudendal nerve (PN) entrapment is one of the most misunderstood and underdiagnosed medical conditions. It is recognized as a cause of chronic pelvic pain syndrome. However, due to the pudendal nerve's mixed composition and complex anatomy, the presenting symptoms are varied and go beyond pain, depending on the entrapment's nature, location and duration. We report a unique case of a young patient presenting with a urethral leak refractory to antibiotics. Patient evaluation highlighted findings suspicious of pudendal nerve entrapment. The patient was submitted to a laparoscopic transperitoneal PN neurolysis, resulting in major symptoms improvement.
- L-cysteine/hydrogen Sulfide Pathway Induces cGMP-dependent Relaxation of Corpus Cavernosum and Penile Arteries From Patients With Erectile Dysfunction and Improves Arterial Vasodilation Induced by PDE5 InhibitionPublication . La Fuente, J; Fernández, A; Pepe-Cardoso, A; Martínez-Salamanca 4, J Nuno Louro 1, Javier Angulo 5; Louro, N; Angulo, JThe aim was to evaluate and characterize H2S-induced relaxation of human corpus cavernosum (HCC) and penile resistance arteries (HPRA) from patients with erectile dysfunction (ED). HCC and HPRA were obtained from men with ED at the time of penile prosthesis insertion. H2S-mediated relaxations were evaluated by exposing these tissues to the stable analogue, NaHS, and to the precursor of H2S, L-cysteine (CYS). The effects of NaHS and CYS were also evaluated on cGMP accumulation in HCC and on acetylcholine- and sildenafil-mediated relaxations in HCC and HPRA. NaHS consistently relaxed HPRA and HCC and more potently than human prostate and bladder. NaHS-induced relaxations in HCC and HPRA were unaffected by the ATP-sensitive K+-channel blocker, glibenclamide or the NO synthase inhibitor, L-NAME, slightly reduced by the Ca2+-activated K+-channel blocker, tetraethylammonium, and markedly inhibited by the soluble guanylyl cyclase inhibitor, ODQ. NaHS caused a cGMP increase in HCC that was inhibited by ODQ. CYS produced relaxations of HCC and HPRA that were sensitive to ODQ and to inhibition of the H2S synthesizing enzymes, cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS). CYS also increased cGMP in HCC. In contrast to NaHS, CYS-induced relaxations were prevented by endothelium removal in HPRA. Only in HPRA, treatment with CYS (30 μM) potentiated acetylcholine- and sildenafil-induced relaxations. This effect was prevented by CSE/CBS inhibition and by removing the endothelium. Exogenous and endogenous H2S relaxes HCC and HPRA from ED patients through cGMP accumulation and potentiates vasodilatory capacity of PDE5 inhibition, supporting the therapeutic potential of modulating H2S pathway.
- Are we all doing it wrong? Influence of stripping and cleaving methods of laser fibers on laser lithotripsy performance.Publication . Kronenberg, P; Traxer, OPURPOSE: We assessed whether stripping and cleaving the laser fiber tip with specialized tools, namely laser fiber strippers, or ceramic or metal scissors, would influence lithotripsy performance. MATERIALS AND METHODS: Laser fiber tips were stripped with a specialized laser fiber stripper or remained coated. The tips were then cleaved with metal or ceramic scissors. Laser lithotripsy experiments were performed with the 4 fiber tip combinations using an automated laser fragmentation testing system with artificial stones made of plaster of Paris or BegoStone Plus (Bego, Lincoln, Rhode Island). High frequency-low pulse energy (20 Hz and 0.5 J) and low frequency-high pulse energy (5 Hz and 2.0 J) settings were used for 30 seconds. Fissure width, depth and volume, and laser fiber tip photos were analyzed. RESULTS: Coated laser fiber tips always achieved significantly higher ablation volumes (sometimes greater than 50%) than stripped laser fiber tips (p <0.00001) regardless of cleaving scissor type, stone material or lithotripter setting. Coated fiber tips cleaved with metal scissors ablated as well as those cleaved with ceramic scissors (p = 0.16). However, stripped fibers were much less ablative when they were cut with metal scissors compared to ceramic scissors (p <0.00001). Harder stone material decreased ablation volume (p <0.00001). Low frequency-high pulse energy settings were an average of 3 times more ablative than high frequency-low pulse energy settings (p <0.00001). Stripping the fibers, a harder stone material and low frequency-high pulse energy settings were associated with increased fiber tip degradation. CONCLUSIONS: Coated laser fibers provided better lithotripsy performance and metal scissors were as good as ceramic scissors to cleave coated fibers. This knowledge may improve and simplify the way that laser lithotripsy procedures are done worldwide.
- Update on lasers in urology 2014: current assessment on holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripter settings and laser fibers.Publication . Kronenberg, P; Traxer, OPURPOSE: The purpose of the study was to review the existing literature on holmium:yttrium-aluminum-garnet laser lithotripsy regarding lithotripter settings and laser fibers. METHODS: An online search of current and past peer-reviewed literature on holmium laser lithotripsy was performed on several databases, including PubMed, SciElo, and Google Scholar. Relevant studies and original articles about lithotripter settings and laser fibers were examined, and the most important information is summarized and presented here. RESULTS: We examine how the choice of lithotripter settings and laser fibers influences the performance of holmium laser lithotripsy. Traditional laser lithotripter settings are analyzed, including pulse energy, pulse frequency, and power levels, as well as newly developed long-pulse modes. The impact of these settings on ablation volume, fragment size, and retropulsion is also examined. Advantages of small- and large-diameter laser fibers are discussed, and controversies are highlighted. Additionally, the influence of the laser fiber is examined, specifically the fiber tip preparation and the lithotripter settings' influence on tip degradation. CONCLUSIONS: Many technical factors influence the performance of holmium laser lithotripsy. Knowing and understanding these controllable parameters allows the urologist to perform a laser lithotripsy procedure safely, efficiently, and with few complications.
- Color Doppler ultrasonographic scanning in acute bacterial prostatitisPublication . Palmas, A; Coelho, M; Fonseca, JOBJECTIVES: The purpose of this study was to reveal parenchymal and vascular changes in acute prostatitis and to determine the role of color Doppler sonography in monitoring patients with this pathology. MATERIAL AND METHODS: Twenty five patients with a clinical diagnosis of acute bacterial prostatitis (NIH 1) admitted to our institution were studied prospectively. Clinical, analytical and microbiological data were recorded. Color Doppler and transrectal ultrasonography (TRUS) were performed 1 week after antibiotic therapy and afterwards at 6 weeks, 3 and 6 month visits. The findings were recorded and scored using standardized criteria to characterize the degree and distribution of prostatic vascularity. RESULTS: Blood flow was observed to the entire prostate capsule (grade 2) in 23 (92%) patients at first visit (1 week) and were present in 11 (44%), 6 (24%) and 2 (8%) at 6 weeks, 3 and 6 month visits respectively. The amount and distribution of blood flow within the prostatic parenchyma were evaluated using several criteria. Using the 2-point scale flow were classified as grade 2 22 (88%), 18 (72%), 12 (48%) and 3 (12%) patients at first, second, third and fourth visit respectively. Similar findings were noted using the Doppler spot scale which revealed that flow was grade 2 (15 spots or more) in 23 (92%), 19 (76%), 11 (44%) and 3 (12%) patients respectively. Mean number of Doppler spots in the prostate parenchyma was 23.1 +/- 11.1 at first visit, 10.3 +/- 9.5 after the end of therapy and 8.3 +/- 5.4 and 7.9 +/- 5.1 at 3 and 6 monthly respectively. CONCLUSIONS: Patients with acute prostatitis require prolonged treatment and subsequent follow up for at least 6 months. Color Doppler sonography is a useful tool in monitoring response to treatment and in predicting clinical outcome.
- Prostate stem cell antigen - novel biomarker and therapeutic target?Publication . Santos, PB; Patel, HRProstate stem cell antigen gene was originally identified through an analysis of genes upregulated in the human prostate cancer LAPC-4 xenograft model. PSCA was named inaccurately since it is not a marker for a stem cell population nor is it exclusively expressed in the prostate. The function of PSCA in normal cellular processes or carcinogenesis is currently unknown.
- Impacto da terapêutica conservadora de órgão do carcinoma do pénis na função sexual e erétilPublication . Santos-Lopes, S; Ferreira, C; Morais, C; Oliveira, JPenile carcinoma is one of the less frequent tumors of the genitourinary system, however its effect on the patients' sex life and quality of life is of great impact. Studies about the influence on patients' sex life are scarce. OBJECTIVES: To characterize sexual activity with penetration of patients with penile carcinoma who underwent different conservative therapeutic approaches and to evaluate pre and post treatment erectile function. Secondarily, to compare the results between the patients who underwent partial penectomy to those subjected to other conservative therapies. MATERIAL AND METHODS: Review of patients' records diagnosed with penile carcinoma and observed at the Portuguese Institute of Oncology of Oporto between 2005 and 2015, to obtain demographic, clinical and histopathological data. Telephone interviews for the completion of the International Index of Erectile Function-5 (IIEF-5) questionnaire to patients undergoing treatment in that period. RESULTS: 16 out of the 107 patients met the inclusion criteria (n=16), with an average IIEF-5 score of 23.44 (10-25), lowering this value to 16.56 (5-25) after therapy, p<0,05. Fifteen out of the 16 patients kept sexual activity (93.8%) and one (6.25%) suspended due to erectile dysfunction. IIEF-5 score after treatment in the subgroup that underwent partial penectomy was lower when compared to the other subgroup of patients subjected to others conservative therapies, without statistical significance. CONCLUSION: Although penile carcinoma treatment has an impact in erectile function with statistical significance, the majority of patients keeps an active sexual life with penetration after treatment. It's not possible to conclude that less invasive therapies are associated with better erectile function.
- Advances in Lasers for the Treatment of Stones-a Systematic ReviewPublication . Kronenberg, P; Somani, BPURPOSE OF REVIEW: Laser lithotripsy is increasingly used worldwide and is a continuously evolving field with new and extensive research being published every year. RECENT FINDINGS: Variable pulse length Ho:YAG lithotripters allow new lithotripsy parameters to be manipulated, and there is an effort to integrate new technologies into lithotripters. Pulsed thulium lasers seem to be a viable alternative to holmium lasers. The performance of similar laser fibers varies from manufacturer to manufacturer. Special laser fibers and "cleaving only" fiber tip preparation can be beneficial for the lithotripsy procedure. Different laser settings and the surgical technique employed can have significant impact on the success of laser lithotripsy. When safely done, complications of laser lithotripsy are rare and concern the endoscopic nature of procedure, not the technology itself, making laser lithotripsy one of the safest tools in urology. Laser lithotripsy has had several new developments and more insight has been gained in recent years with many more advances expected in the future.