Evaluation of HNF1B, KLK3, ELAC2, TMPRSS2-ERG, and CTNNB1 polymorphisms associated with prostate cancer in samples of patients from HUPE-UERJ.

PURPOSE: Prostate cancer (PCa) is the leading cause of death among men in 48 countries. Genetic alterations play a significant role in PCa carcinogenesis. For the hypothesis of this research, five unique polymorphisms (SNP) were investigated in different genes that showed to be associated in different ways with PCa: rs4430796, rs2735839, rs4792311, rs12329760, and rs28931588, respectively for the genes HNF1B, KLK3, ELAC2, TMPRSS2-ERG, and CTNNB1. PATIENTS AND METHODS: Blood samples from 426 subjects were evaluated: 290 controls (161 females and 129 males) and 136 PCa patients. SNP were determined by real-time polymerase chain reaction. TaqMan SNP genotyping assay. In the control samples, the SNPs were defined in association with the self-reported ethnicity, and in 218 control samples with markers with ancestry indicators. The genes were in Hardy-Weinberg equilibrium. One hundred and seventy control samples were matched by ethnicity for comparison with the PCa samples. RESULTS: The G allele at rs28931588 was monomorphic in both patients and controls studied. Significant differences were observed in allelic and genotypic frequencies between the control and Pca samples in rs2735839 (KLK3; p = 0.002 and χ2 = 8.73 and p = 0.01, respectively), by the global frequency and in the dominant model rs2735839_GG (odds ratio [OR] = 0.51, p = 0.02). AA and GA genotypes at rs4792311 (ELAC2) were more frequent in patients with Gleason 7(4 + 3), 8, and 9 (n = 37%-59.7%) compared to patients with Gleason 6 and 7(3 + 4) (n = 26%-40.0%) conferring a protective effect on the GG genotype (OR = 0.45, p = 0.02). The same genotype showed an OR = 2.71 (p = 0.01) for patients with low severity. The HNF1B-KLK3-ELAC2-TMPRSS2-ERG haplotypes: GAAT, AAAT, GAGT, and AAGT were more frequent in patients with Pca with OR ranging from 4.65 to 2.48. CONCLUSIONS: Higher frequencies of risk alleles were confirmed in the SNPs, KLK3 rs2735839_A, ELAC2 rs4792311_A, and TMPRSS2 rs12329760_T in patients with Pca. Rs2735839_A was associated with risk of Pca and rs4792311_A with severity and Gleason score of 7(4 + 3) or greater. There is a need for careful observation of rs2735839 and rs4792311 in association with the prostatic biopsy due to the increased risk of Pca.

Practical evaluation of the R.E.N.A.L. score system in 150 laparoscopic nephron sparing surgeries.

INTRODUCTION: Nephrometric scores play an interesting role in nephron sparring surgery (NSS) planning. The aim of this study is to evaluate if R.E.N.A.L. score (RS) is capable to predict the occurrence of adverse events in laparoscopic NSS. MATERIALS AND METHODS: We prospectively studied 150 laparoscopic NSS between 2015 and 2018 to evaluate the relationship between RS and incidence of adverse events. Clavien 3 or superior complications, warm ischemia time (WIT) over 30 minutes, tumor violation, positive surgical margins (PSM) and necessity of amplification of renal parenchyma during the resection of the masses to obtain free margins were considered as adverse events. We compared each item of the RS isolated and divided the patients between low risk and high risk. RESULTS: Adverse results occurred in 48 cases (32%). Amplification of the margin of resection was observed in 28 cases (19%). WIT exceeded 30 minutes in 9 cases (6.1%), complications Clavien 3 or superior occurred in 13 cases (9%) and PSM were detected en 6 cases (4%). Comparing the patients with adverse outcomes and each item of the RS we did not find any statistical difference, but when divided into high risk and low risk, we found that patients in the high risk group had a higher tendency to present ad-verse results - 25.84% vs. 44.26% (p=0.03). CONCLUSIONS: RS system is a good way to predict adverse outcomes in NSS, especially in cases over 7. Further studies should focus on robotic approach and patient's characteristics other than the masses' aspects.

A universal mathematical model applied to the congenital ventral penile curvature.

INTRODUCTION: The macroscopic dynamic of fetal penis development presents a pattern resembling the unfolding of a spiral, so congenital ventral penile curvature could indicate that this natural sequence has been interrupted. Our aim in this article is to offer a mathematical model of congenital ventral curvature of the penis. MATERIALS AND METHODS: Five individuals who presented with congenital ventral penile curvature and three who presented with acquired penile ventral curvature due to Peyronie's disease were evaluated. The penises were photographed during an induced erection test and the penile curvature patterns were compared with an equiangular spiral. When an association was found, a potential relationship to the golden spiral-a type of equiangular spiral-was also assessed. The mathematical spiral relationships were analyzed using Wolfram CDF Player® (Logarithmic Spiral) and PhiMatrix® software. The Wolfram software generated logarithmic spirals equivalent to the penile curvature with appropriate mathematical values. The PhiMatrix software, which builds any golden spirals from golden rectangles, was used to check whether the spiral was golden as well as equiangular. RESULTS: An equiangular spiral that was also golden was found in all cases of congenital ventral penile curvature. In contrast, none of the acquired penile ventral curvature cases showed a specific pattern. CONCLUSION: Congenital ventral penile curvature has the mathematical pattern of a golden spiral. Our results offer a mathematical algorithm for potential use in surgical reconstruction procedures, regenerative medicine, tissue engineering, robotics, and body-machine interfaces.

Open anterograde anatomic radical retropubic prostatectomy technique: description of the first fiftyfive procedures.

INTRODUCTION: Robotic-assisted radical prostatectomy is the leading surgical technique and was discussed in Pasadena Consensus Panel (1). The goal of this study is to present the results of the first fifty-five patients submitted to Anterograde Anatomic Radical Retropubic Prostatectomy technique (R2PA2), without adding complexity or cost. MATERIALS AND METHODS: Fifty-five eligible men with localized prostate cancer underwent R2PA2 from January, 2016 to December, 2017. The technique was previously described (2): the main surgical steps were anterograde dissection, ligation of the dorsal vascular complex without dividing, preservation of the bladder neck, nerve sparing, preservation of Denonvilliers' fascia and confection of the running suture anastomosis. All patients were operated on by second-year residents. RESULTS: All procedures were completed as planned, but one converted to retrograde prostatectomy (mean duration, 163.40 minutes; hospital stay, 4 days with 4.20 days of drainage; indwelling vesical catheterization of 9.80 days). Positive surgical margin was found in six T2 staging patient (10.90%) and five T3 (9.10%). Biochemical PSA recurrence occurred in three patients (5.50%). Twenty-four (43.60%) were continent immediately after indwelling catheter removal, seventeen (30.90%) did not wear a pad at one postoperative month while eighteen (30%) used only one safety pad. Five minor complications occurred. CONCLUSION: We were able to perform R2PA2 allowing men who do not have access to this new technology to be operated on with the same technique used in robotic surgery. This method was reproducible by low-volume prostate cancer surgeons; help inexperienced surgeons to develop skills valuable to future training with robotic techniques. ACKNOWLEDGEMENTS This work was supported by the FAPERJ - Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro. Secretaria de Estado de Ciência, Tecnologia e Inovação do Governo do Estado do Rio de Janeiro, Brazil, and Pedro Ernesto University Hospital of the State University of Rio de Janeiro, Brazil. Available at: http://www.intbrazjurol.com.br/video-section/20180421_Carrerette_et_al.

Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial.

BACKGROUND: In the LATITUDE trial, addition of abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) improved overall survival compared with placebos plus ADT in patients with newly diagnosed, high-risk, metastatic castration-naive prostate cancer. Understanding the effects of treatments on patient-reported outcomes (PROs) and health-related quality of life (HRQOL) is important for treatment decisions; therefore we aimed to analyse the effects of ADT plus abiraterone acetate and prednisone versus ADT plus placebos on PROs and HRQOL in patients in the LATITUDE study. METHODS: In the multicentre, international, randomised, phase 3 LATITUDE trial, eligible patients were aged 18 years or older, had newly diagnosed, high-risk, metastatic castration-naive prostate cancer confirmed by bone scan (bone metastases) or by CT or MRI (visceral, soft tissue, or nodal metastases), and an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less. Patients from 235 clinical sites in 34 countries were randomly assigned (1:1) following a country-by-country scheme done by permuted block randomisation (with two blocks) and stratified by the presence of visceral metastasis and ECOG performance status to receive ADT plus 1000 mg oral abiraterone acetate and 5 mg oral prednisone once daily or ADT plus placebos. Selection of ADT, chemical or surgical, was at the investigator's discretion. The co-primary endpoints of the trial, overall survival and radiographic progression-free survival, have been published. PRO data were collected directly on electronic tablet devices at the clinical sites during screening and before any other visit procedure on day 1 of cycles 1-3, monthly during cycles 4-13, and then every 2 months until the end of treatment, by use of the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy Prostate scale (FACT-P), and the EuroQol (EQ-5D-5L) questionnaires. PRO analyses were an exploratory endpoint. Analyses were by intention-to-treat. Results from the first pre-planned interim analysis (Oct 31, 2016), are presented here. This ongoing study is registered with Clinicaltrials.gov, number NCT01715285. FINDINGS: Between Feb 12, 2013, and Dec 11, 2014, 1199 patients were randomly assigned: 597 to ADT plus abiraterone acetate and prednisone and 602 to ADT plus placebos. Median follow-up was 30·9 months (IQR 21·2-33·2) in the ADT plus abiraterone acetate and prednisone group versus 29·7 months (1·4-43·5; 16·1-31·3) in the ADT plus placebos group. Median time to worst pain intensity progression assessed by the BPI-SF score was not reached in either group (ADT plus abiraterone acetate and prednisone, not reached [95% CI not reached to not reached]; 25th percentile 11·07 months [95% CI 9·23-18·43]; ADT plus placebos group, not reached [95% CI not reached to not reached]; 25th percentile 5·62 [95% CI 4·63-7·39]; hazard ratio [HR] 0·63 [95% CI 0·52-0·77]; p<0·0001). Median time to worst fatigue intensity was not reached in either the ADT plus abiraterone acetate and prednisone group (not reached [95% CI not reached to not reached]; 25th percentile 18·4 months [95% CI 12·9-27·7]) or the ADT plus placebos group (not reached [95% CI not reached to not reached]; 25th percentile 6·5 months [95% CI 5·6-9·2]; HR 0·65 [95% CI 0·53-0·81], p=0·0001). Median time to deterioration of functional status assessed by the FACT-P total score scale was 12·9 months (95% CI 9·0-16·6) in the ADT plus abiraterone acetate and prednisone group versus 8·3 months (7·4-11·1) in the ADT plus placebos group (HR 0·85 [95% CI 0·74-0·99]; p=0·032). INTERPRETATION: The addition of abiraterone acetate plus prednisone to ADT in patients with newly diagnosed, high-risk metastatic castration-naive prostate cancer improved overall PROs by consistently showing a clinical benefit in the progression of pain, prostate cancer symptoms, fatigue, functional decline, and overall HRQOL. FUNDING: Janssen Research & Development.

Minilaparoscopy in urology: initial results after 32 cases.

PURPOSE: The use of minilaparoscopic instruments has gained interest in recent years, permitting a less invasive treatment for many surgical procedures. Its application in urological surgeries has not been established yet. METHODS: Between November 2012 and December 2014, 32 patients underwent minilaparoscopic surgeries, using 3.5-mm instruments. The procedures performed included pyeloplasties (16 cases), radical nephrectomies (2), simple nephrectomies (4), renal cyst decortication (5), ureterolithotomy (2) ureteral reimplantation (2) and partial ureterectomy (1). RESULTS: All the procedures were performed minilaparoscopically, except for one simple nephrectomy and one renal cyst decortication that were converted to a standard laparoscopic approach, due to intensive perioperative bleeding. One pyeloplasty had to be reoperated for a urinary fistula repair. All the patients had good-to-excellent cosmetic outcomes, except for one patient who developed keloids at her scars. Functional results were comparable to the ones described in the literature. CONCLUSION: Minilaparoscopy is a feasible option for patients and physicians searching for a even less invasive procedure compared with the laparoscopic approach, with better cosmetic and the same functional and oncologic outcomes.

Association between the bladder wall thickness and urodynamic findings in patients with spinal cord injury.

PURPOSE: To investigate whether ultrasonographic bladder wall thickness (BWT) correlates with urodynamic parameters in patients with spinal cord injury (SCI). METHODS: Two hundred and seventy-two patients with SCI were enrolled in the study. All of the patients underwent bladder ultrasonography and urodynamic study. The anterior bladder wall was measured and compared to urodynamic data. RESULTS: The mean age of the patients was 37.4 years. The mean BWT was 3.9 mm. BWT was significantly higher in the patients with neurogenic detrusor overactivity associated with detrusor sphincter dyssynergia (NDO/DSD) compared to those without sphincter dyssynergia (4.2 vs. 3.6 mm, respectively, p < 0.001) and in those with compliance <20 ml/cm H2O. Nevertheless, ROC curve analysis [ROC = 0.624, 95 % CI (0.530, 0.718), p = 0.011] showed that no meaningful BWT measurement cutoff could be made to predict an elevated detrusor pressure in the storage phase. CONCLUSIONS: Increased BWT was present in patients with low bladder compliance and NDO/DSD. No BWT cutoff value to predict an elevated detrusor pressure was found. Therefore, the measurement of BWT has no clinical role in patients with SCI and cannot replace urodynamic evaluation.

From palmistry to anthropometry: can 2nd to 4th digit length (2D:4D) predict the risk of prostate cancer?

OBJECTIVE: The 2nd to 4th digit length (2D:4D) is inversely related to androgen exposure during the fetal period, which may represent a risk factor for several steroid-related diseases. We aimed to evaluate the relationship between 2D:4D ratio and the risk of developing prostate cancer (PCa). SUBJECTS AND METHODS: We assessed the 2D:4D ratio of 474 men >40 years old, stratified into three groups: group 1 (n = 222) patients with PCa, group 2 (n = 82) subjects with high risk of PCa, and group 3 (n = 170) men with low risk of PCa. Subjects were submitted to a digital picture of the ventral surface of the right hand and 2nd and 4th fingers measurements were determined by the distance from the proximal crease to the tip using computer-assisted analysis. RESULTS: The mean serum prostate-specific antigen level was 7.5 ng/ml in the high-risk group and 0.92 ng/ml in the low-risk group (p < 0.05). The mean 2D:4D ratios were 0.96 ± 0.04, 0.97 ± 0.04 and 0.96 ± 0.04 for the PCa, high-risk and low-risk groups, respectively, and no difference was found among the three groups (p = 0.12). CONCLUSION: Anthropometry of the hand using the 2D:4D ratio is not a predictor of PCa.

Role of penile biometric characteristics on surgical outcome of hypospadias repair.

PURPOSE: To assess influence of penile biometric characteristics on surgical outcome of tubularized incised plate (TIP) repair for hypospadias. METHODS: We prospectively studied 42 boys with distal hypospadias that underwent TIP urethroplasty. Biometric assessment prior to surgery consisted of classifying glans shape, urethral plate (UP) length and width, prepuce vascularization and penile size, using a caliper rule, according to previous definitions. Surgical outcome was assessed according to the occurrence of dehiscence, fistula or urethral stricture. RESULTS: There was no statistical difference among groups concerning postoperative complications. Glans shape: grooved (24/57 %), shallow (9/21 %) and conical (9/21 %). UP width: <10 mm (26/62 %) and ≥10 mm (16/38 %). UP length was evaluated in 29 patients: <10 mm in (12/41 %) and ≥10 mm (17/59 %). Prepuce vascularization: one predominant blood vessel (17/41 %), two predominant blood vessels (8/19 %), H-like form with communication between two well-developed blood vessels (6/14 %) and net-like form with no predominant blood vessels (11/26 %). Penile size was measured in 28 patients under 50th percentile (25/89 %). CONCLUSION: Glans shape, UP width, UP length, prepuce vascularization and penile size do not significantly affect the complication rate of TIP repair in distal hypospadias. Most of the patients with distal hypospadias presented with penile size under mean length for age suggesting some form of mild hypogonadism.

Parameters of two-dimensional perineal ultrasonography for evaluation of urinary incontinence after Radical Prostatectomy.

INTRODUCTION: Urinary incontinence remains a major concern for patients undergoing radical prostatectomy. Its prevalence can reach 20% in the late postoperative period. MATERIALS AND METHODS: This clinical study investigated the differences of a dynamic evaluation of the urethra and pelvic floor contraction using perineal ultrasound in men without prostate surgery and in men submitted to radical prostatectomy with and without stress urinary incontinence. Ninety two male patients were included, which 70% of them underwent radical prostatectomy (RP) for more than one year. Thirty one men with clinically post prostatectomy incontinence were compared by two-dimensional (2D) perineal ultrasound to 34 patients without post prostatectomy incontinence and to 27 men without surgery in two centers in Brazil. RESULTS: Our results showed that the continent group presented the urethral angle at rest significantly lower than the prostate group (p = 0.0002). We also observed that the incontinent group showed the displacement of the anterior bladder neck during contraction significantly lower than the continent group (p = 0.008). CONCLUSIONS: We found that the continent group presented the urethral angle at rest significantly lower than the prostate group. The incontinent group also showed the anterior bladder neck displacement during contraction significantly lower than the continent group. It was more evident when the severe incontinent group and the continent group were compared.

Same-day Catheter Removal and Hospital Discharge After Holmium Laser Enucleation of the Prostate: A Prospective Study.

OBJECTIVE: To assess the feasibility, safety, and predictive factors for the success of holmium laser enucleation of the prostate (HoLEP) with catheter removal and hospital discharge on the same day of the procedure. METHODS: This prospective study included 34 patients who underwent HoLEP using a 60-W holmium laser device and the Wolf Piranha morcellation system. Surgeries began at 10:30 am and the patients were expected to be discharged by 5 pm on the same day. The patients underwent a voiding trial to remove the urinary catheter before hospital discharge. Functional outcomes were assessed 90 days after the procedure. RESULTS: Mean (range) age, prostate-specific antigen value, and prostate weight were as follows: 63.4 (50-80) years, 4.81 (0.19-14) ng/mL, and 89.3 (33-258) g, respectively. The mean (range) enucleation and morcellation times were 56.2 (29-91) minutes and 14.67 (3-45) minutes, respectively. Thirty-one patients (91.1%) were discharged on the same day of the procedure after urinary catheter removal. CONCLUSION: The performance of HoLEP is safe on an outpatient basis. Same-day catheter removal is feasible and does not affect hospital discharge.

Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial.

BACKGROUND: Bone metastases are a major cause of morbidity and mortality in men with prostate cancer. Preclinical studies suggest that osteoclast inhibition might prevent bone metastases. We assessed denosumab, a fully human anti-RANKL monoclonal antibody, for prevention of bone metastasis or death in non-metastatic castration-resistant prostate cancer. METHODS: In this phase 3, double-blind, randomised, placebo-controlled study, men with non-metastatic castration-resistant prostate cancer at high risk of bone metastasis (prostate-specific antigen [PSA] ≥8·0 µg/L or PSA doubling time ≤10·0 months, or both) were enrolled at 319 centres from 30 countries. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous denosumab 120 mg or subcutaneous placebo every 4 weeks. Randomisation was stratified by PSA eligibility criteria and previous or ongoing chemotherapy for prostate cancer. Patients, investigators, and all people involved in study conduct were masked to treatment allocation. The primary endpoint was bone-metastasis-free survival, a composite endpoint determined by time to first occurrence of bone metastasis (symptomatic or asymptomatic) or death from any cause. Efficacy analysis was by intention to treat. The masked treatment phase of the trial has been completed. This trial was registered at ClinicalTrials.gov, number NCT00286091. FINDINGS: 1432 patients were randomly assigned to treatment groups (716 denosumab, 716 placebo). Denosumab significantly increased bone-metastasis-free survival by a median of 4·2 months compared with placebo (median 29·5 [95% CI 25·4-33·3] vs 25·2 [22·2-29·5] months; hazard ratio [HR] 0·85, 95% CI 0·73-0·98, p=0·028). Denosumab also significantly delayed time to first bone metastasis (33·2 [95% CI 29·5-38·0] vs 29·5 [22·4-33·1] months; HR 0·84, 95% CI 0·71-0·98, p=0·032). Overall survival did not differ between groups (denosumab, 43·9 [95% CI 40·1-not estimable] months vs placebo, 44·8 [40·1-not estimable] months; HR 1·01, 95% CI 0·85-1·20, p=0·91). Rates of adverse events and serious adverse events were similar in both groups, except for osteonecrosis of the jaw and hypocalcaemia. 33 (5%) patients on denosumab developed osteonecrosis of the jaw versus none on placebo. Hypocalcaemia occurred in 12 (2%) patients on denosumab and two (<1%) on placebo. INTERPRETATION: This large randomised study shows that targeting of the bone microenvironment can delay bone metastasis in men with prostate cancer. FUNDING: Amgen Inc.

Randomized controlled trial comparing open anterograde anatomic radical retropubic prostatectomy with retrograde technique.

Objective: Radical prostatectomy is the recommended treatment for localized prostate cancer; however, it is an invasive procedure that can leave serious morbidity. Robot-assisted radical prostatectomy was introduced with the aim of reducing postoperative morbidity and facilitating rapid recovery compared to the traditional Walsh's open radical retropubic prostatectomy. Therefore, a protocol was developed to perform an open prostatectomy comparable to that performed by robotics, but without involving novel instrumentation. Methods: A total of 220 patients diagnosed with localized prostate cancer underwent radical prostatectomy. They were divided into two groups: anterograde technique (115 patients) and the retrograde method (105 patients). The study outcomes were observed 3 months after surgery. Results: No differences were found in terms of surgical time, hospital stay, and suction drainage. However, reduced bleeding was observed in the anterograde technique (p=0.0003), with rapid anastomosis duration (p=0.005). Among the patients, 60.9% undergoing the anterograde technique were continent 3 months after surgery compared to 42.9% treated by the retrograde method (p=0.007). Additionally, fewer complications in terms of the number (p=0.007) and severity (p=0.0006) were observed in the anterograde technique. Conclusion: The anterograde method displayed increased efficiency in reducing complications, compared to the retrograde technique.

Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study.

BACKGROUND: Bone metastases are a major burden in men with advanced prostate cancer. We compared denosumab, a human monoclonal antibody against RANKL, with zoledronic acid for prevention of skeletal-related events in men with bone metastases from castration-resistant prostate cancer. METHODS: In this phase 3 study, men with castration-resistant prostate cancer and no previous exposure to intravenous bisphosphonate were enrolled from 342 centres in 39 countries. An interactive voice response system was used to assign patients (1:1 ratio), according to a computer-generated randomisation sequence, to receive 120 mg subcutaneous denosumab plus intravenous placebo, or 4 mg intravenous zoledronic acid plus subcutaneous placebo, every 4 weeks until the primary analysis cutoff date. Randomisation was stratified by previous skeletal-related event, prostate-specific antigen concentration, and chemotherapy for prostate cancer within 6 weeks before randomisation. Supplemental calcium and vitamin D were strongly recommended. Patients, study staff, and investigators were masked to treatment assignment. The primary endpoint was time to first on-study skeletal-related event (pathological fracture, radiation therapy, surgery to bone, or spinal cord compression), and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. Efficacy analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00321620, and has been completed. FINDINGS: 1904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive zoledronic acid were eligible for the efficacy analysis. Median duration on study at primary analysis cutoff date was 12·2 months (IQR 5·9-18·5) for patients on denosumab and 11·2 months (IQR 5·6-17·4) for those on zoledronic acid. Median time to first on-study skeletal-related event was 20·7 months (95% CI 18·8-24·9) with denosumab compared with 17·1 months (15·0-19·4) with zoledronic acid (hazard ratio 0·82, 95% CI 0·71-0·95; p = 0·0002 for non-inferiority; p = 0·008 for superiority). Adverse events were recorded in 916 patients (97%) on denosumab and 918 patients (97%) on zoledronic acid, and serious adverse events were recorded in 594 patients (63%) on denosumab and 568 patients (60%) on zoledronic acid. More events of hypocalcaemia occurred in the denosumab group (121 [13%]) than in the zoledronic acid group (55 [6%]; p<0·0001). Osteonecrosis of the jaw occurred infrequently (22 [2%] vs 12 [1%]; p = 0·09). INTERPRETATION: Denosumab was better than zoledronic acid for prevention of skeletal-related events, and potentially represents a novel treatment option in men with bone metastases from castration-resistant prostate cancer. FUNDING: Amgen.

Nephrometry scoring systems: their importance for the planning of nephron-sparing surgery and the relationships among them.

In recent years, the development of new imaging techniques and scoring systems have improved the diagnosis and management of small renal masses. Imaging-based nephrometry scoring systems play an interesting role in the planning of nephron-sparing surgery, providing surgeons with the information necessary to determine the complexity of the renal mass, to deliver the appropriate postoperative care, and to predict adverse outcomes. The aim of this study was to review nephrometry scoring systems, evaluating their characteristics and the relationships among them. The urology and radiology communities should decide which nephrometry scoring system will prevail and be used in daily practice.

O diagnóstico e o manejo das pequenas massas renais têm sido aprimorados nos últimos anos com o desenvolvimento de técnicas de imagem e escores que desempenham papel interessante no planejamento da nefrectomia parcial, fornecendo informações importantes ao cirurgião para determinar o tipo de tratamento em relação a complexidade da massa renal, cuidados pós-operatórios e previsão de complicações após as cirurgias. O objetivo deste estudo é revisar os escores de nefrometria, suas características e relações entre eles no cenário da cirurgia. Os serviços de urologia e radiologia devem decidir qual é o melhor escore de nefrometria para ser utilizado na prática diária.

Human acellular matrix graft of tunica albuginea for penile reconstruction.

INTRODUCTION: Penile curvature is one of the most common male conditions, affecting nearly 10% of men, and can impair sexual intercourse. Tunica albuginea (hTA) plays a key role in penile curvature, and reconstructive procedures may be necessary for its substitution. Although several grafts have been proposed for hTA repair, the ideal graft is not yet available. AIM: The aim of this article is to evaluate a new human tunica albuginea acellular matrix (hTAAM) as potential graft for penile reconstructive procedures. METHODS: Twelve penises were obtained during sex reassignment surgeries from male-to-female transsexual patients. After dissection, hTAs were assigned into two groups according to the decellularization methods: polyethylene glycol (PEG) 1000 method following ultraviolet-C radiation, and Triton X-100 modified method. MAIN OUTCOME MEASURES: Structural analyses were assessed by hematoxilin and eosin, Masson's trichrome, Weigert's, and picrosirius-polarization staining methods. Total protein, total glycosaminoglycan (GAG), and nucleic acid (DNA and RNA) concentrations were assessed by specific biochemical analyses. Uniaxial strength tests were performed to evaluate biomechanical properties. RESULTS: All hTAAMs presented no nuclear or cellular remnants. Total protein concentration was significantly higher in PEG 1000 hTAAM. Despite GAG concentration decreased significantly in hTAAM, Triton X-100 hTAAM retained the highest GAG concentration (1.0 ± 0.42 µg HexUr/mg dry tissue, P > 0.05). All decellularization methods were efficacious to remove nucleic acids. The maximal break point presented no difference between hTA and hTAAM groups (P > 0.05). CONCLUSIONS: PEG 1000 and Triton X-100 decellularization methods provide equally successful hTAAMs, preserving original structural and biochemical properties.

Comparative study between trimetazidine and ice slush hypothermia in protection against renal ischemia/reperfusion injury in a porcine model.

PURPOSE: The aim of the study was to compare the effects of renal ice slush hypothermia and the use of trimetazidine in the protection against ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: Fifteen farm pigs were submitted to left kidney ischemia and right nephrectomy during the same procedure. Animals were divided into three groups. Group 1 was submitted to warm ischemia; Group 2 was submitted to cold ischemia with ice slush; and Group 3 received trimetazidine 20 mg one day and 4 hours before surgery. Ischemia time was 120 minutes in all three groups. Serum creatinine (SCr) and plasma iohexol clearance (CLioh) were measured before surgery and on postoperative days (PODs) 1,3,7, and 14. Semi-quantitative analyses of histological alterations were performed by a pathologist. A p value of < 0.05 was considered significant. RESULTS: All groups showed elevation of serum creatinine in the first week. Serum creatinine was higher in Group 3 in the first and third postoperative days (Mean Cr: 5.5 and 8.1 respectively). Group 2 showed a lower increase in creatinine and a lower decrease in iohexol clearance than the others. Renal function stabilized in the fourteenth POD in all three groups. Analyses of histological alterations did not reach statistical significance between groups. CONCLUSION: Trimetazidine did not show protection against renal I/R injury in comparison to warm ischemia or hypothermia in a porcine model submitted to 120 minutes of renal ischemia.

Efficacy and safety of parecoxib in the treatment of acute renal colic: a randomized clinical trial.

PURPOSE: Although non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) and opioids are effective treatments for acute renal colic, they are associated with adverse events (AEs). As cyclooxygenase-2 selective NSAIDs may provide a safer alternative, we compared the efficacy and safety of parecoxib versus an nsNSAID in subjects with acute renal colic. MATERIALS AND METHODS: Phase IV., multicenter, double-blind, noninferiority, active-controlled study: 338 subjects with acute renal colic were randomized to parecoxib 40 mg i.v. plus placebo (n = 174) or ketoprofen 100 mg IV plus placebo (n = 164). 338 subjects with acute renal colic were randomized to parecoxib 40 mg IV (n = 174) or ketoprofen 100 mg IV(n = 164) plus placebo. Subjects were evaluated 15, 30, 45, 60, 90 and 120 minutes after treatment start and 24 hours after discharge. Primary endpoint was the mean pain intensity difference (PID) at 30 minutes by visual analog scale (VAS) (per-protocol population). An ANCOVA model was used with treatment group, country, and baseline score as covariates. Non-inferiority of parecoxib to ketoprofen was declared if the lower bound of the 95% confidence interval (CI) for the difference between the two groups excluded the pre-established margin of 10 mm for the primary endpoint. RESULTS: Baseline demographics were similar. The mean (SD) mPID30 min was 33.84 (24.61) and 35.16 (26.01) for parecoxib and ketoprofen, respectively. For treatment difference (parecoxib-ketoprofen) the lower bound of the 95% CI was 6.53. The mean change from baseline in VAS 30 minutes after study medication was ~43 mm; AEs were comparable between treatments. CONCLUSIONS: Parecoxib is as effective as ketoprofen in the treatment of pain due to acute renal colic, is well tolerated, and has a comparable safety profile.

Efficacy and tolerability of lodenafil carbonate for oral therapy of erectile dysfunction: a phase III clinical trial.

INTRODUCTION: This is a phase III, prospective, randomized, double-blind, placebo-controlled clinical trial on lodenafil carbonate (LC), a novel phosphodiesterase 5 inhibitor developed in Brazil. AIM: Expanding information on LC efficacy and safety. MAIN OUTCOME MEASURES: International Index of Erectile Function (IIEF) erectile domain, positive answers to the sexual encounter profile (SEP)-2 and SEP-3 questions and incidence of adverse events (AEs). METHODS: A total of 350 men with erectile dysfunction (ED) of all degrees were randomized to placebo, LC 40 mg or LC 80 mg and followed for 4 weeks. They completed the IIEF and answered the SEP questions 2 and 3 after each intercourse without and with the use of LC. RESULTS: IIEF Erectile Domain scores without and with the use of medication were the following (mean [M] +/- standard deviation [SD]): placebo = 13.9 +/- 5.2 and 14.8 +/- 7.8; LC 40 mg = 13.6 +/- 5.3 and 18.6 +/- 8.0; LC 80 mg = 13.4 +/- 4.9 and 20.6 +/- 7.7 (analysis of variance [ANOVA] P < 0.01). Positive answers to SEP-2 without and with the use of medication were the following (M +/- SD): placebo = 55.3 +/- 43.2% and 52.1 +/- 41.4%; LC 40 mg = 46.4 +/- 44.3% and 63.5 +/- 42.0%; LC 80 mg = 50.2 +/- 40.9% and 80.8 +/- 32.3% (ANOVA P < 0.01). Positive answers to SEP-3 were the following: placebo = 20.2 +/- 32.3% and 29.7 +/- 38.1%; LC 40 mg = 19.6 +/- 34.3% and 50.8 +/- 44.4%; LC 80 mg = 20.8 +/- 33.2% and 66.0 +/- 39.3% (ANOVA P < 0.01). The patients with at least one AE were placebo = 28.7%, LC 40 mg = 40.9%, and LC 80 mg = 49.5%. AEs whose incidence was significantly higher with LC than with placebo included rhinitis, headache, flushing, visual disorder, and dizziness. CONCLUSIONS: LC showed a satisfactory efficacy-safety profile for oral therapy of ED.