Is there a relationship between testosterone and androgen receptor with prostatectomy outcomes?

INTRODUCTION:   Prostate cancer has a variable natural history and, despite the existence of biochemical recurrence (BCR) predictors, they are still limited in predicting outcomes.  The role of testosterone in advanced prostate cancer is well known, however its role in localized prostate cancer is still uncertain.  In the present study, we evaluated the relationship of testosterone levels and androgen receptor (AR) expression with oncological and functional outcomes, in patients undergoing radical retropubic prostatectomy (RRP). MATERIALS AND METHODS:   Through a retrospective study, patients who underwent RRP, who had at least two preoperative total testosterone dosages, were analyzed and compared according to testosterone levels, oncological and functional outcomes.  After analyzing data, tissue samples were selected in a biorepository to carry out the AR and the AR-V7 expression. RESULTS:   After applying exclusion criteria, 212 patients were included in the analysis.  Thirty-two patients (15.1%) had low testosterone levels and, in this group, a lower rates of erectile function recovery were observed at 24 months (53.1% vs. 71.7%; p = 0.037), a higher rate of BCR (21.9% vs. 9.4%; p = 0.041) and higher International Society of Urological Pathology (ISUP) grade in biopsy products.  The AR expression was higher in patients with low testosterone, but there was no difference in relapse rates. CONCLUSIONS:   Lower levels of testosterone were related to lower rates of erectile function recovery at the end of 24 months after RRP, in addition to conferring higher rates of BCR and higher ISUP grades in biopsy.  Furthermore, patients with total testosterone < 300 ng/dL had higher expression of AR, but no difference in BCR rates.

The landscape of biomedical research funding in Brazil: a current overview.

OBJECTIVE: The objective of this narrative review is to discuss the current state of research funding in Brazil. MATERIALS AND METHODS: This study is based on the most recent edition of the course Funding for Research and Innovation in the University of Sao Paulo School of Medicine which was a three-day course with 12 hours of instruction. The course brought together leading experts in the field to comprehensively discuss the current state of research funding in Brazil. Each speaker provided a presentation on a specific topic related to research funding. After the workshop, speakers assembled relevant topics in this manuscript. RESULTS: collaborative research is critical for securing research funding. It optimizes proposal competitiveness, amplifies societal impact, and manages risks effectively. As such, fostering and supporting these collaborations is paramount for both researchers and funding agencies. To maintain the highest integrity in research, investigators involved in these collaborations must disclose any relationships that could potentially influence the outcomes or interpretation of their projects. CONCLUSIONS: In Brazil, the mainstay of research funding stems from public entities, with agencies such as CNPq, CAPES, and state bodies like FAPESP, FAPERJ, FAPEMIG and others at the forefront. Concurrently, industry funding offers viable pathways, especially through industry-sponsored studies, investigator-led projects, and collaborative initiatives. The Brazilian funding landscape is further enriched by innovative platforms, including crowdfunding and the contributions of institutions like the Serrapilheira Institute. Internationally, esteemed organizations such as the National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation stand out as potential funders.

The Complexity and Dynamics of the Tissue Glycoproteome Associated With Prostate Cancer Progression.

The complexity and dynamics of the immensely heterogeneous glycoproteome of the prostate cancer (PCa) tumor microenvironment remain incompletely mapped, a knowledge gap that impedes our molecular-level understanding of the disease. To this end, we have used sensitive glycomics and glycoproteomics to map the protein-, cell-, and tumor grade-specific N- and O-glycosylation in surgically removed PCa tissues spanning five histological grades (n = 10/grade) and tissues from patients with benign prostatic hyperplasia (n = 5). Quantitative glycomics revealed PCa grade-specific alterations of the oligomannosidic-, paucimannosidic-, and branched sialylated complex-type N-glycans, and dynamic remodeling of the sialylated core 1- and core 2-type O-glycome. Deep quantitative glycoproteomics identified ∼7400 unique N-glycopeptides from 500 N-glycoproteins and ∼500 unique O-glycopeptides from nearly 200 O-glycoproteins. With reference to a recent Tissue and Blood Atlas, our data indicate that paucimannosidic glycans of the PCa tissues arise mainly from immune cell-derived glycoproteins. Furthermore, the grade-specific PCa glycosylation arises primarily from dynamics in the cellular makeup of the PCa tumor microenvironment across grades involving increased oligomannosylation of prostate-derived glycoproteins and decreased bisecting GlcNAcylation of N-glycans carried by the extracellular matrix proteins. Furthermore, elevated expression of several oligosaccharyltransferase subunits and enhanced N-glycoprotein site occupancy were observed associated with PCa progression. Finally, correlations between the protein-specific glycosylation and PCa progression were observed including increased site-specific core 2-type O-glycosylation of collagen VI. In conclusion, integrated glycomics and glycoproteomics have enabled new insight into the complexity and dynamics of the tissue glycoproteome associated with PCa progression generating an important resource to explore the underpinning disease mechanisms.

The Effect of Gene Editing by CRISPR-Cas9 of miR-21 and the Indirect Target MMP9 in Metastatic Prostate Cancer.

Prostate cancer (PCa) has a high prevalence and represents an important health problem, with an increased risk of metastasis. With the advance of CRISPR-Cas9 genome editing, new possibilities have been created for investigating PCa. The technique is effective in knockout oncogenes, reducing tumor resistance. MMP9 and miR-21 target genes are associated with PCa progression; therefore, we evaluated the MMP-9 and miR-21 targets in PCa using the CRISPR-Cas9 system. Single guide RNAs (sgRNAs) of MMP9 and miR-21 sequences were inserted into a PX-330 plasmid, and transfected in DU145 and PC-3 PCa cell lines. MMP9 and RECK expression was assessed by qPCR, WB, and IF. The miR-21 targets, integrins, BAX and mTOR, were evaluated by qPCR. Flow cytometry was performed with Annexin5, 7-AAD and Ki67 markers. Invasion assays were performed with Matrigel. The miR-21 CRISPR-Cas9-edited cells upregulated RECK, MARCKS, BTG2, and PDCD4. CDH1, ITGB3 and ITGB1 were increased in MMP9 and miR-21 CRISPR-Cas9-edited cells. Increased BAX and decreased mTOR were observed in MMP9 and miR-21 CRISPR-Cas9-edited cells. Reduced cell proliferation, increased apoptosis and low invasion in MMP9 and miR-21 edited cells was observed, compared to Scramble. CRISPR-Cas9-edited cells of miR-21 and MMP9 attenuate cell proliferation, invasion and stimulate apoptosis, impeding PCa evolution.

Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer.

MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 µg weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals' serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.

Cholesterol Triggers Nuclear Co-Association of Androgen Receptor, p160 Steroid Coactivators, and p300/CBP-Associated Factor Leading to Androgenic Axis Transactivation in Castration-Resistant Prostate Cancer.

BACKGROUND/AIMS: Cholesterol modulates intratumoral androgenic signaling in prostate cancer; however, the molecular mechanisms underlying these changes in castration-resistant prostate cancer (CRPC) are not fully elucidated. Herein, we investigated the effect of cholesterol on androgen receptor (AR) coactivators expression and tumorigenesis in vitro and in vivo. METHODS: Herein, we monitored the expression of AR coactivators (SRC-1, 2, 3 and PCAF) genes in PC-3 cells exposed to 2µg/mL of cholesterol for 8 hours by qPCR. We also performed cell migration at 0, 8, 24, 48 and 72h and flow cytometry assays (viability, apoptosis, and cell cycle) after a 24h exposure. Immunofluorescence assay was performed to evaluate the protein expression of the AR coactivators. Additionally, in vivo experiments were conducted using 22 male NOD/SCID mice. Mice were fed a standard (Control) or hypercholesterolemic (HCOL) diet for 21 days and then subcutaneously implanted with PC-3 cells. The tumor volume was calculated every two days, and after four weeks, the tumors were resected, weighed, and the serum lipid profile was measured. We also measured the intratumoral lipid profile and AR coactivators gene and protein expression by qPCR and Western Blot, respectively. Intratumor testosterone and dihydrotestosterone (DHT) concentrations were determined using ELISA. RESULTS: Cholesterol up-regulated the gene expression of coactivators SRC-1, SRC-2, SRC-3and PCAF, increasing AR expression in PC-3 cells. Next, cholesterol-supplemented PC-3 cells exhibited increased cell migration and altered cell cycle phases, leading to changes in proliferation and reduced apoptosis. We found that SRC-1, SRC-2, SRC-3 and PCAF proteins co-localized in the nucleus of cholesterol-supplemented cells and co-associate with AR. In the in vivo model, the hypercholesterolemic (HCOL) group displayed higher serum total and intratumoral cholesterol levels, increased testosterone and dihydrotestosterone concentrations, and up-regulated AR coactivator expression. The tumor volume of the HCOL group was significantly higher than the control group. CONCLUSION: Our findings revealed that increased nuclear translocation of the coactivators leads to up-regulated AR gene and protein expression, potentially influencing tumor progression. Studies targeting cholesterol-modulated changes in AR coactivator expression may provide insights into the molecular mechanisms associated with the CRPC phenotype.

A Prospective, Randomized Trial Comparing the Outcomes of Open vs Laparoscopic Partial Nephrectomy.

PURPOSE: Partial nephrectomy is the standard treatment for renal tumors <7 cm, and the trend toward minimally invasive surgery has increased. However, data that could support its use and benefits are still lacking. MATERIALS AND METHODS: We conducted a prospective, randomized controlled trial comparing surgical, functional and oncologic outcomes in patients undergoing open partial nephrectomy (OPN) or laparoscopic partial nephrectomy (LPN). Randomization was 1:1 to OPN or LPN for the treatment of renal tumors <7 cm. The primary endpoint was surgical complications up to 90 days after surgery. Secondary outcomes were comparison of surgical, oncologic and functional results. RESULTS: We randomized 208 patients between 2012 and 2020 (110 with OPN vs 98 with LPN). Operative data showed no differences in operative time, warm ischemia time, estimated blood loss, transfusions or length of hospital stay. Zero ischemia was more frequent in the OPN (35.4% vs 15.5%, p=0.02). OPN was associated with more abdominal wall complications (31.2% vs 13.1%, p=0.004). Regarding oncologic outcomes, no differences were noted. The LPN group had less kidney function reduction at 3 (-5.2% vs -10%, p=0.04; CI 0.09 to 9.46) and 12 months after surgery (-0.8% vs -6.3%, p=0.02; CI 1.18 to 12.95), and a lower rate of downstaging on the chronic kidney disease classification at 12 months (14.1% vs 32.6%, p=0.006). CONCLUSIONS: Surgical and oncologic outcomes of LPN were similar to OPN. Minimally invasive surgery may provide better preservation of kidney function. More studies, especially those involving robotic surgery, are necessary to confirm our findings.

Supine versus Prone Percutaneous Nephrolithotomy for Complex Stones: A Multicenter Randomized Controlled Trial.

PURPOSE: High-quality evidence comparing supine to prone percutaneous nephrolithotomy (PCNL) for the treatment of complex stones is lacking. This study aimed to compare the outcomes of supine position (SUP) and prone position (PRO) PCNL. MATERIALS AND METHODS: A noninferior randomized controlled trial was performed according to the CONSORT (Consolidated Standards for Reporting Trials) criteria. The inclusion criteria were patients over 18 years of age with complex stones. SUP was performed in the Barts flank-free modified position. Except for positioning, all the surgical parameters were identical. The primary outcome was the difference in the success rate on the first postoperative day (POD1) between groups. The secondary outcome was the difference in the stone-free rate (SFR) on the 90th postoperative day (final SFR). A noninferiority margin of 15% was used. Demographic, operative, and safety variables were compared between the groups. Statistical significance was set at p <0.05. RESULTS: Overall, 112 patients were randomized and their demographic characteristics were comparable. The success rates on POD1 were similar (SUP: 62.5% vs PRO: 57.1%, p=0.563). The difference observed (-5.4%) was lower than the predefined limit. The final SFRs were also similar (SUP: 55.4% vs PRO: 50.0%, p=0.571). SUP had a shorter operative time (mean±SD 117.9±39.1 minutes vs 147.6±38.8 minutes, p <0.001) and PRO had a higher rate of Clavien ≥3 complications (14.3% vs 3.6%, p=0.045). CONCLUSIONS: Positioning during PCNL for complex kidney stones did not impact the success rates; consequently, both positions may be suitable. However, SUP might be associated with a lower high-grade complication rate.

Tranexamic acid in patients with complex stones undergoing percutaneous nephrolithotomy: a randomised, double-blinded, placebo-controlled trial.

OBJECTIVES: To assess the efficacy and safety of single-dose tranexamic acid on the blood transfusion rate and outcomes of patients with complex kidney stones undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: In a randomised, double-blinded, placebo-controlled trial, 192 patients with complex kidney stone (Guy's Stone Scores III-IV) were prospectively enrolled and randomised (1:1 ratio) to receive either one dose of tranexamic acid (1 g) or a placebo at the time of anaesthetic induction for PCNL. The primary outcome measure was the occurrence rate of perioperative blood transfusion. The secondary outcome measures included blood loss, operative time, stone-free rate (SFR), and complications. ClinicalTrials.gov identifier: NCT02966236. RESULTS: The overall risk of receiving a blood transfusion was reduced in the tranexamic acid group (2.2% vs 10.4%; relative risk, 0.21, 95% confidence interval [CI] 0.03-0.76, P = 0.033; number-needed-to-treat: 12). Patients randomised to the tranexamic acid group had a higher immediate and 3-month SFR compared with those in the placebo group (29% vs 14.7%, odds ratio [OR] 2.37, 95% CI 1.15-4.87, P = 0.019, and 46.2% vs 28.1%, OR 2.20, 95% CI 1.20-4.02, P = 0.011, respectively). Faster haemoglobin recovery occurred in patients in the tranexamic acid group (mean, 21.3 days; P = 0.001). No statistical differences were found in operative time and complications between groups. CONCLUSIONS: Tranexamic acid administration is safe and reduces the need for blood transfusion by five-times in patients with complex kidney stones undergoing PCNL. Moreover, tranexamic acid may contribute to better stone clearance rate and faster haemoglobin recovery without increasing complications. A single dose of tranexamic acid at the time of anaesthetic induction could be considered standard clinical practice for patients with complex kidney stones undergoing PCNL.

Grafting Area Reduction in Peyronie's Disease Surgery: Comparative Assessment Between Double Y Vs iGrafter APP Using 3D-Printed Penile Models.

BACKGROUND: The use of plaque incision and graft techniques (PIG) for the treatment of severe Peyronie's disease (PD), may lead to erectile dysfunction (ED); graft size is 1 of the contributing factors for post-PIG ED. Recently the iGrafter software APP was introduced using a mathematical algorithm to distribute the incisions along the penile length resulting in a smaller grafting area. AIM: Compare 2 PIG techniques, the Double-Y(DY) and iGrafter, in 3 main aspects: (i) Total grafting area; (ii) The variation in calculating the grafting to be used; (iii) time to perform the PIG. METHODS: Six urologists with expertise in sexual medicine performed both techniques twice using four 3-D validated training models for PD with a standard 60° uniplanar dorsal curvature. OUTCOMES: The graft areas and operative partial and total time for each step of the operation were recorded for each procedure. Unpaired t-test and the coefficient of variation for graft area across surgeons was calculated comparing both techniques. RESULTS: For all surgeons, the use of iGrafter resulted in 2 grafts, for the DY technique in 1 graft. Overall, TT for the iGrafter was significantly longer than for DY technique (49.4 ± 11 vs 40.7 ± 5.7 minute; P = .02), The iGrafter grafting area was significantly smaller (11.6 ± 1.2 vs 23.3 ± 5.4 cm2; P: .01), representing a 50.2% area reduction when compared to the DY. The variation of graft area, using the iGrafter also yielded a more consistent graft across all surgeons (CV = 10.56% vs 23.28%). CLINICAL SIGNIFICANCE: The iGrafter, when compared to DY technique, reduced the graft area by 50%, which potentially means less erectile dysfunction. STRENGTHS AND LIMITATIONS: Our study eliminates anatomical variations found in a real clinical case making it possible to compare surgical techniques with the same penile anatomy. However, the 3D-printed model cannot replicate the living human tissue property preventing a simulation close to actual surgery. CONCLUSION: The use of the iGrafter software for PIG surgery has shown to be a promising technique for severe PD management resulting in smaller graft size (about 50% smaller when compared to the DY), although it might be more time-consuming. Tourchi A, Nascimento B, de Freita Miranda A, et al. Grafting Area Reduction in Peyronie's Disease Surgery: Comparative Assessment Between Double Y Vs iGrafter APP Using 3D-Printed Penile Models. J Sex Med 2022;19:669-675.

Single-use flexible ureteroscopes: update and perspective in developing countries. A narrative review.

Flexible ureteroscopy is a well-established method for treatment of urinary stones but flexible ureteroscopes are expensive and fragile devices with a very limited lifetime. Since 2006 with the advent of digital flexible ureteroscopes a great evolution has occurred. The first single-use flexible ureteroscope was launched in 2011 and new models are coming to the market. The aim of this article is to review the characteristics of these devices, compare their results with the reusable devices and evaluate the cost-benefits of adopting single-use flexible ureteroscopes in developing countries. MATERIALS AND METHODS: an extensive review of articles listed at PubMed and published between 2000 and 2021 was performed. RESULTS: Single-use flexible ureteroscopes have a shaft with 65 to 68cm length and weight between 119 and 277g. Their deflection goes up to 300 degrees. Their stone-free rates vary between 60 and 95% which is comparable to reusable scopes and operative times ranges from 54 to 86 minutes which are lower when compared to reusable flexible scopes. Their costs vary between 800 and 3180 US dollars. CONCLUSION: single-use flexible ureteroscopes are lighter and have superior quality of image when compared to fiberoptic ones. There are no definite data showing a higher stone-free rate or less complications with the use of single-use flexible ureteroscopes. Each institution must perform a cost-benefit analysis before making the decision of adopting or not such devices depending on the local circumstances.

MCT1 expression is independently related to shorter cancer-specific survival in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) has been considered a metabolic disease, with loss of von Hippel-Lindau (VHL) gene and consequent overexpression of hypoxia-inducible factor 1 alpha (HIF-1α), which is central for tumor development and progression. Among other effects, HIF-1α is involved in the metabolic reprogramming of cancer cells towards the Warburg effect involved in tumor cell proliferation, migration and survival. In this context, several proteins are expressed by cancer cells, including glucose and lactate transporters as well as different pH regulators. Among them, monocarboxylate transporters (MCTs) can be highlighted. Our aim is to comprehensively analyze the immunoexpression of MCT1, MCT2, MCT4, CD147, CD44, HIF-1α, GLUT1 and CAIX in ccRCC surgical specimens correlating with classical prognostic factors and survival of patients with long follow-up. Surgical specimens from 207 patients with ccRCC who underwent radical or partial nephrectomy were used to build a tissue microarray. Immunostaining was categorized into absent/weak or moderate/strong and related to all classic ccRCC prognostic parameters. Kaplan-Meier curves were generated to assess overall and cancer-specific survival, and multivariate analysis was performed to identify independent prognostic factors of survival. Multivariate analysis showed that MCT1 together with tumor size and TNM staging, were independently related to cancer-specific survival. MCT1, CD147, CD44 and GLUT1 expression were significantly associated with poor prognostic factors. We show that MCT1 is an independent prognostic factor for cancer-specific survival in ccRCC justifying the use of new target therapies already being tested in clinical trials.

Longitudinal Improvement of Lower Urinary Tract Symptoms in Williams-Beuren Syndrome.

PURPOSE: Williams-Beuren syndrome is a chromosomal disorder caused by a deletion at region 7q11.23. Lower urinary tract symptoms are highly prevalent and significantly affect quality of life. We assessed the long-term outcomes of lower urinary tract symptoms in children with Williams-Beuren syndrome. MATERIALS AND METHODS: From February 2001 to July 2016, 90 patients with Williams-Beuren syndrome were evaluated in our hospital, of whom 31 (20 boys) had at least 5 years of followup. Baseline evaluation included a history of lower urinary tract symptoms, frequency-volume chart and the impact on quality of life measured on a scale of 0 (delighted) to 6 (terrible). Pharmacological therapy with oxybutynin or doxazosin was offered to symptomatic patients. We present the outcome of lower urinary tract symptoms after 5 and 10 years of followup. RESULTS: At baseline 27 (87.1%) patients were symptomatic. Median duration of followup was 10 (range 6-13) years. Pharmacological therapy was started for 25 (92.6%) symptomatic patients at baseline, including oxybutynin for 19 (76.0%), doxazosin for 1 (4.0%) and a combination of the 2 agents for 5 (20.0%). Medical therapy was still in use by 61.2% after 5 years and 52.9% after 10 years (p=0.043). Median duration of pharmacological treatment was 7 (range 6-11) years. A significant improvement of lower urinary tract symptoms was observed over time, with 35.5% and 29.5% patients considered symptomatic after 5 years and 10 years, respectively (p <0.001). Quality of life was also markedly improved over time (p <0.001). CONCLUSIONS: This long-term study showed significant improvement of lower urinary tract symptoms in children and adolescents with Williams-Beuren syndrome over time. Long-term pharmacological treatment was needed in most patients.

Prospective evaluation of a urinary biomarker panel to detect and predict recurrence of non-muscle-invasive bladder cancer.

PURPOSE: To perform a feasibility phase study of a panel of putative protein biomarkers and determine whether it can identify and predict tumor recurrence in patients with non-muscle-invasive bladder cancer (NMIBC) on follow-up. METHODS: We prospectively analyzed the urine of 152 patients previously treated for NMIBC. Quantitative expression of plasminogen activator inhibitor-1 (PAI-1), DJ-1, apolipoprotein A-I (apoA-1), matrix metallopeptidase-9 (MMP-9), and interleukin-8 (IL-8) was assessed by enzyme-linked immunosorbent assay and compared amongst patients with and without bladder cancer recurrence at urine collection and during 3 years of follow-up. Tumor recurrence was confirmed by pathologic analysis. We performed a prediction analysis, excluding patients with recurrence at the start of the study, and assessed the influence of previous use of intravesical BCG on the level of biomarkers. RESULTS: Median follow-up time was 47 months (interquartile range 39-50 months). Sixteen patients (10.5%) were diagnosed with recurrence at the start of the study, and 21 (15.4%) were diagnosed during the study. Three biomarker proteins (apoA-1, MMP-9, and IL-8) appear to hold diagnostic potential [odds ratio (OR) = 12.9; 95% CI 3.5-47.4]; while, PAI-1 and IL-8 predict recurrence (OR = 4.1; 95% CI 1.4-11.4). Previous use of intravesical BCG did not affect biomarker levels. CONCLUSION: In the feasibility phase, the panel of urine biomarkers analyzed detected and predicted recurrence of NMIBC and provided reliable results in patients who had previously used intravesical BCG. Validation studies are required to confirm the panel clinical utility.

Understanding urologic scientific publication patterns and general public interests on stone disease: lessons learned from big data platforms.

PURPOSE: To analyse patterns of stone disease online information-seeking behaviours in the United States and to correlate with urological literature publication aspects. METHODS: To compare Relative Search Volume (RSV) among different twelve preselected urologic keywords we chose "United States" as country and "01/01/2009-31/12/2018" as time range on Google Trends (GT). We defined "ureteroscopy" as a reference and compared RSV against it for each term. RSV was adjusted and normalized in a scale 0-100. Trend presence was evaluated by Mann-Kendall Test and magnitude by Sen's Slope Estimator (SS). Weather influence on RSV was also investigated by comparison of the ten hottest versus ten coldest states. Pearson correlation analysis was performed between number of Pubmed publications and RSV for each term over time. RESULTS: We found an upward tendency (p < 0.01) for most terms. Higher temporal trends were seen for "kidney stone" (SS = 0.36), "kidney pain" (SS = 0.39) and "tamsulosin" (SS = 0.21). Technical treatment terms had little search volumes and no increasing trend. States with hotter weather showed higher mean RSV for "kidney stone" than colder ones. There was little correlation between GT and Pubmed for most terms, with the exception of "kidney stone" (R = 0.89; p < 0.01), "URS" (R = 0.81; p < 0.01), and "laser lithotripsy" (R = 0.74; p = 0.01). CONCLUSION: There was a significant increase in online search for medical information related to stone disease. Citizens tend to look for generic terms related to symptoms or the disease itself. States with hotter weather show higher RSV than colder states. There is a discrepancy between public and medical community medical terms.

Percutaneous nephrolithotomy in patients with spinal cord injury: should all these patients be automatically assigned a Guy's stone score of 4?

PURPOSE: To assess the complication and stone-free rates of PCNL in patients with spinal cord injury (SCI) and to evaluate whether this population should be assigned a Guy's stone score (GSS) of 4. METHODS: A case-control study was conducted, and electronic charts were reviewed to search for patients with SCI, bladder dysfunction, and kidney stones who had undergone PCNL. Control cases were randomly selected from among patients with complete staghorn calculus (GSS = 4). RESULTS: One hundred and seventeen patients were included. Patients with SCI had a significant shorter operative time (119 vs. 141 min; p = 0.018). There were no significant differences between the groups in terms of the patients' position, number of renal tracts, bleeding or transfusion rate; however, there was a significantly higher complication rate (23.1% vs. 7.8%; p = 0.009) and a longer hospital stay (5.8 vs. 3.1 days; p = 0.002) among patients with SCI. With regards to the stone-free rate in patients with different grades of GSS patients with SCI who had a GSS of 1 had a stone-free rate of 85.7%, while those with a GSS of 2, 3, or 4 had 50%, 50%, and 31.5%, respectively (p = 0.024). Only patients with a GSS of 4 in the SCI group had outcomes that were similar to those of control patients (31.5% vs. 31.6%). CONCLUSION: Patients with SCI should not be automatically assigned GSS 4. Stone-free rate is related to stone burden in these patients, although they do show a higher complication rate and a longer hospital stay than non-neurological patients.

Percutaneous thermoablation of small renal masses (T1a) in surgical candidate patients: oncologic outcomes.

OBJECTIVE: To evaluate the local tumour progression-free survival (LTPFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) of healthy surgical candidates who underwent percutaneous thermoablation (TA) as a first-line therapy for small renal masses (T1a). METHODS: The institutional review board approved this bi-institutional retrospective study of 85 consecutive surgical candidates with 97 biopsy-proven malignant renal masses (T1a) treated with percutaneous TA from 2008 to 2016. The LTPFS, MFS, CSS and OS rates were calculated using the Kaplan-Meier method. Descriptive analysis was also performed. RESULTS: The median tumour size was 2.3 cm (range, 0.7-3.9 cm). The minimal and mean follow-up periods were 24 and 56 months, respectively. Local recurrence was detected in four patients (4.7%) at 8.5, 13.8, 58.0 and 64.0 months of follow-up and retreated successfully with percutaneous TA. No patient developed metastatic renal cell carcinoma, and none died due to renal oncologic complications. One patient died of heart attack. The 5-year LTPFS, OS, MFS and CSS rates were 93.0%, 98.4%, 100% and 100%, respectively. Only two patients (2.3%) had major complications (Clavien-Dindo grade > II), including ureteropelvic junction stenosis and urinary obstruction due to ureteral blood clots. CONCLUSIONS: Our study demonstrates that percutaneous TA is a feasible and effective first-line therapy for healthy surgical candidates with small renal masses (T1a). The 5-year LTPFS, OS, CSS and MFS rates were 93.0%, 98.4%, 100% and 100%, respectively, with a major complication rate of only 2.3%. KEY POINTS: • Image-guided percutaneous thermoablation of small renal malignancies was effective in 95.3% of the healthy surgical candidates. • Major complications were detected in 2.3% of the patients. • The local tumour progression-free survival rate was 97.6% and 93.0% at 3 and 5 years, respectively.

Role of Ultrasound Elastography in Patient Selection for Prostatic Artery Embolization.

PURPOSE: To determine the effects of prostatic artery embolization (PAE) on prostate elasticity as assessed using ultrasound elastography (US-E) and to describe baseline US-E's potential role in patient selection. MATERIALS AND METHODS: This was a prospective investigation that included 20 patients undergoing PAE to treat lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH). US-E with measurement of the prostatic elastic modulus (EM) and shear wave velocity (SWV) was performed before PAE and at 1-month follow-up. Baseline, 3-month, and 1-year follow-up evaluations included prostate-specific antigen, uroflowmetry, pelvic magnetic resonance imaging, and clinical assessment using the International Prostate Symptom Score (IPSS) and quality of life (QoL) metrics. RESULTS: Seventeen patients entered statistical analysis. US-E showed a significant reduction in mean prostatic EM (34.4 kPa vs 46.3 kPa, -24.7%, P < .0001) and SWV (3.55 m/s vs 4.46 m/s, -20.0%, P < .0001) after PAE. There were moderate positive correlations between baseline EM and 1-year IPSS (R = 0.62, P = .007) and between baseline SWV and 1-year IPSS (R = 0.68, P = .002). Baseline SWV ≥ 5.59 m/s and baseline EM ≥ 50.14 kPa were associated with suboptimal IPSS and QoL outcomes after PAE with high degrees of sensitivity (100%) and specificity (69-100%). CONCLUSIONS: PAE led to a positive effect on the BPH dynamic component related to prostatic elasticity. There was a moderate positive correlation between baseline prostatic elastographic parameters and 12-month IPSS. Measurement of baseline elastographic characteristics may become useful for the evaluation and selection of patients for PAE.

Intravesical Prostatic Protrusion Does Not Influence the Efficacy of Prostatic Artery Embolization.

PURPOSE: To compare the outcomes of prostatic artery embolization (PAE) in patients with different intravesical prostatic protrusion (IPP) grades. MATERIALS AND METHODS: This retrospective single-center study included 128 patients (aged 50-86 years) who underwent PAE from 2013 to 2017. IPP grades were classified as follows: grade I (<10 mm), grade II (10-19 mm), and grade III (≥20 mm). Nineteen patients (14.8%) had grade I [mean IPP 7.8 mm, prostatic volume (PV) 64.1 cm3], 77 (60.2%) had grade II (mean IPP 14.9 mm, PV 87.0 cm3), and 32 (25%) had grade III (mean IPP 26.2 mm, PV 132.6 cm3), P < .01. The outcomes, including PV, international prostate symptom score (IPSS), and quality of life (QoL), were compared between the IPP grades at the 12-month follow-up. Clinical failure was defined as IPSS >7 or QoL >2. RESULTS: IPP decreased (I: -8.2%, II: -27.3%, and III: -38.7%, P = .01), and all other endpoints improved (P < .01). Adjusted covariance analysis, considering baseline PV as a confounding factor, showed no correlation between the 12-month outcomes and baseline IPP. Clinical failure was observed in 17/128 patients (13.3%) and was similar in prevalence among the IPP groups (P = .20). Minor complications occurred in 43 patients (33.6%) and major in 3 (2.3%). There were statistical differences in the complications between IPP grades II and III (P < .01). CONCLUSIONS: PAE was similarly effective in all the IPP grades at the 12-month follow-up, and there was no difference in the clinical failure between the groups. Complications in IPP grade III were more frequent than those in IPP grade II.

Can increased expression of miR-Let-7c reduce the transition potential of high-grade urothelial carcinoma?

BACKGROUND: Bladder cancer is the leading transitional cell carcinoma affecting men and women with high morbidity and mortality rates, justifying the need to develop new molecular target therapies using microRNAs. This study aimed to evaluate the behavior of the T24 cell line after transfection with miR-Let-7c precursor mimic through invasion, migration, apoptosis, and cell cycle assays. METHODS AND RESULTS: T24 cell was transfected with the Let-7c mimic and its respective control and evaluated after 24 h. The expression levels of miR-Let-7c were analyzed by qPCR. We performed wound healing, Matrigel and flow cytometry, apoptosis, and cell cycle assays to determine its effect on cellular processes. Cells transfected with miR-Let-7c showed increased apoptosis rates (p = 0.019), decreased migration 24 h (p = 0.031) and 48 h (p = 0.0006), invasion potential (p = 0.0007), and cell proliferation (p = 0.002). CONCLUSIONS: Our results demonstrate that miR-Let-7c can act in different pathways of the carcinogenic cellular processes of muscle-invasive urothelial carcinoma cells, inhibiting cell proliferation and increasing apoptosis levels, consequently limiting their invasion potential. However, further studies should be carried out better to elucidate this microRNA's role in high-grade urothelial carcinomas and unveil which targets this microRNA may present, which are intrinsically related to the cancer survival pathways.