The role of single nucleotide polymorphisms of miRNAs 100 and 146a as prognostic factors for prostate cancer.

INTRODUCTION: Prostate cancer has a high incidence in men and is the second cause of cancer death among americans male. microRNA (miR) is becoming a potential new prognostic factor for prostate cancer. Single nucleotide polymorphisms (SNPs) are common polymorphisms, characterized by a single exchange of nitrogen based in the DNA. This polymorphism is present in the miRs, altering their function. OBJECTIVE: To evaluate the role of SNP rs1834306 of miR100 and rs2910164 of miR146a in the development and prognosis of prostate cancer. METHODS: One hundred patients diagnosed with prostate cancer and 68 controls were selected. The identification of SNP was rated by quantitative polymerase chain reaction from blood samples, and the analysis was performed within the presence of SNP and the prognostic variables. RESULTS: In the SNP rs1834306 (miR100), a smaller presence of the polymorphic homozygous genotype was identified in patients with PSA >10 ng/mL, (P=0.03); when evaluating only the presence of the polymorphic allele G (P=0.09) it was compared to the presence of the wild type allele A. Among the patients with prostate cancer, SNP rs2910164 (miR146A), the polymorphic allele was more frequent in patients with a Gleason score ⩾7 than in patients with a Gleason score <7, (P=0.043). In patients with prostate cancer, miR100 was overexpressed in those with pT3 staging compared to pT2 and among those who had biochemical recurrence (P = 0.004 and P = 0.011, respectively). CONCLUSIONS: SNP of miR146a acts as a poor prognostic factor (Gleason ⩾7), and the SNP of miR100 is linked to better prognostic data (PSA <10). MiR100 was overexpressed in prostate cancer with worse prognostic factors.

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.

Impact of 5-Alpha-Reductase Inhibitors Use at the Time of Prostatic Artery Embolization for Treatment of Benign Prostatic Obstruction.

PURPOSE: To compare the 12-month post-prostatic artery embolization (PAE) clinical outcomes of patients who were and were not taking 5-alpha-reductase inhibitors (5ARIs) at the time of PAE. MATERIALS AND METHODS: A retrospective review was conducted of patients who underwent PAE from 2010 to 2017 due to lower urinary tract symptoms, secondary to benign prostatic hyperplasia (BPH). One hundred fifty-five patients were included and divided in 2 groups; these groups did not present statistically significant differences in their baseline characteristics-those taking 5ARIs (Y-5ARIs, n = 40) and those not taking 5ARIs (N-5ARIs, n = 115). International Prostate Symptom Score (IPSS), the sub-item Quality of Life (QoL), and the incidence of clinical failure were used as primary endpoints. Secondary endpoints included mean prostate volume reduction and mean peak flow rate (Qmax) improvement. Clinical failure or recurrence was defined as absence of symptomatic improvement (IPSS ≥ 8 or QoL ≥ 3) or the need for invasive BPH treatment (PAE or transurethral resection of the prostate) during the 12-month follow-up period. RESULTS: After 12-month follow-up, IPSS, QoL, and prostatic volume were significantly lower compared to baseline in both groups, and Qmax showed a significant increase. No statistically significant differences were observed in outcomes between N-5ARIs and Y-5ARIs, and the clinical failure rate for both groups was approximately 20%. CONCLUSIONS: The use of 5ARIs did not show a detrimental effect on clinical outcomes of PAE, in either subjective (IPSS, QoL, and clinical failure) or objective (prostatic volume and Qmax) parameters.

Holmium Laser Enucleation of the Prostate Simulation: Analysis of Realism and Level of Difficulty by Holmium Laser Enucleation of the Prostate-naïve Urologists.

OBJECTIVE: To evaluate the opinion of Holmium laser enucleation of the prostate (HoLEP)-naïve urologists about a surgical simulator and the level of difficulty at each step. MATERIALS AND METHODS: We evaluated 40 HoLEP-naïve urologists in a course involving 4 steps: lecture introducing Holmium laser basics and technique; live surgery; video explaining prostate enucleation using simulators; and simulator trial. A survey was applied to evaluate content validity and face validity of the simulator. Subjects also ranked the level of difficulty of each surgical step. RESULTS: All urologists agreed on the importance of a validated HoLEP simulator in training; 95% agreed that simulation-based training is essential for patient safety. The mean rate of face validity of all analyzed components was 8.4 (8.1-9.0). Instrumentation was considered the most realistic component, followed by laser-tissue interaction. Positioning the fiber and bladder neck incisions (BNIs) at 5 and 7-o'clock were the easiest steps. Detaching the median lobe from the bladder neck, BNI at 12, dividing the mucosal bridge distally, and joining the upper and lower incisions were the most difficult steps. Residents found more difficulty in joining the BNIs distally (3.6 vs 2.4, P = .006) and in dividing the mucosal bridge distally (4.0 vs 3.0, P = .038) when compared to specialists. CONCLUSION: HoLEP-naïve urologists found this simulator useful and important for patient safety. Most components were considered realistic. Simulation was able to reproduce the levels of difficulty usually found in real life cases. The level of expertise may influence the learning process of some steps.

Benign prostatic hyperplasia.

The minimally invasive procedures (mips) for the treatment of symptoms of benign prostatic hyperplasia (bph) are presented as attractive techniques due to their ease of accomplishment and the possibility of outpatient treatment. This guideline aims to present recommendations that may assist in decision making in patients with benign prostatic hyperplasia and indication of the different minimally invasive therapies. For this, a systematic review of the literature was performed, with the descriptors according to the pico: patient with benign prostatic hyperplasia, minimally invasive therapy, clinical outcome and adverse events. With no time restriction, in medline, cochrane central and lilacs databases via vhl, 1,007 papers were retrieved, of which 16 were selected to respond to clinical doubt. Details of the methodology and results of this guideline are set out in annex I.

Benign prostatic hyperplasia

SUMMARY The minimally invasive procedures (mips) for the treatment of symptoms of benign prostatic hyperplasia (bph) are presented as attractive techniques due to their ease of accomplishment and the possibility of outpatient treatment. This guideline aims to present recommendations that may assist in decision making in patients with benign prostatic hyperplasia and indication of the different minimally invasive therapies. For this, a systematic review of the literature was performed, with the descriptors according to the pico: patient with benign prostatic hyperplasia, minimally invasive therapy, clinical outcome and adverse events. With no time restriction, in medline, cochrane central and lilacs databases via vhl, 1,007 papers were retrieved, of which 16 were selected to respond to clinical doubt. Details of the methodology and results of this guideline are set out in annex I

Increased detrusor collagen is associated with detrusor overactivity and decreased bladder compliance in men with benign prostatic obstruction.

BACKGROUND: This study aimed to investigate the relationship between detrusor collagen content and urodynamic parameters in men with benign prostatic obstruction. MATERIAL AND METHODS: Nineteen consecutive patients undergoing open prostatectomy for bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) were evaluated. Urodynamic tests were performed in all patients. BOO and detrusor contractility were assessed with the BOO index (BOOI) and the bladder contractility index (BCI), respectively. A bladder fragment was obtained during prostatectomy. Eight cadaveric organ donors composed the control group. Bladder sections were stained with picrosirius red and hematoxylin-eosin. The collagen to smooth muscle ratio (C/M) in the detrusor was measured and its relationship with urodynamic parameters was investigated. RESULTS: Seven (36.8%) patients were operated on due to lower urinary tract symptoms and 12 (63.2%) had urinary retention. The mean prostate volume was 128.6 cm3 ± 32.3 cm3, the mean BOOI was 76.4 ± 33.0, and the mean BCI was 116.1 ± 33.7. The mean C/M in BPH patients and controls were 0.43 ± 0.13 and 0.33 ± 0.09, respectively (P = 0.042). A negative correlation was shown between C/M and bladder compliance (r = -0.488, P = 0.043). The C/M was increased in BPH patients with detrusor overactivity (DO) compared to those without DO (0.490 ± 0.110 and 0.360 ± 0.130, respectively; P = 0.030) and also in patients with urinary retention (P = 0.002). No correlation was shown between C/M and maximum cystometric capacity, BOOI, or BCI. CONCLUSION: Men with BOO/BPH have increased detrusor collagen content which is associated with decreased bladder compliance, detrusor overactivity, and urinary retention.

The Obstructed Bladder: Expression of Collagen, Matrix Metalloproteinases, Muscarinic Receptors, and Angiogenic and Neurotrophic Factors in Patients With Benign Prostatic Hyperplasia.

OBJECTIVE: To evaluate the gene expression of collagen, matrix metalloproteinases (MMPs) and inhibitors, cholinergic muscarinic receptors (CHRMs), and angiogenic and nerve growth factors (NGFs) in the bladder of patients with bladder outlet obstruction caused by benign prostatic hyperplasia (BPH). METHODS: We analyzed bladder specimens from 43 patients with obstructive BPH undergoing transurethral resection of the prostate as compared to 10 age-matched controls with an International Prostatic Symptom Score of <8 and a prostate volume of <30 g. A bladder biopsy was performed for relative gene expression analysis with quantitative real-time polymerase chain reaction of collagens I and III, MMP-1, MMP-2, and MMP-9; tissue inhibitors of metalloproteinases (TIMPs) TIMP-1, TIMP-2, and reversion-inducing cysteine-rich protein with kazal motifs (RECK); CHRM2 and CHRM3; VEGF and CD105; and NGF and nerve growth factor receptor (NGFr). RESULTS: Patients with bladder outlet obstruction presented a statistically significant overexpression of collagens I and III, VEGF, CHRM2, and CHRM3. CD105, MMP-9, and TIMP-1 were underexpressed. Expressions of NGF, NGFr, MMP-1, MMP-2, TIMP-2, and RECK were heterogeneous. CHRM2 and CHRM3 were overexpressed in patients with persistent detrusor overactivity. Smokers presented an upregulation of NGFr and VEGF; dyslipidemic patients had an overexpression of NGFr. CONCLUSION: Bladder upregulation of collagens I and III on transcriptional level appears to be relevant in BPH. Muscarinic receptors CHRM2 and CHRM3 are also overexpressed, more so in patients with persistent detrusor overactivity. Upregulation of VEGF and NGFr, particularly in subjects with risk factors for atherosclerosis, reinforces the role of ischemia in BPH-induced modifications of the bladder.

Role of Genetic Polymorphisms in the Development and Prognosis of Sporadic and Familial Prostate Cancer.

BACKGROUNDS: Our aim was to evaluate the role of 20 genetic polymorphisms in the development and prognosis of sporadic and familial PC. A case-control study of 185 patients who underwent radical prostatectomy from 1997 to 2011. These patients were divided into two groups based on their family history. Gleason grade, PSA value and pathological TNM 2002 stage were used as prognostic factors. Blood samples from 70 men without PC were used as controls. The SNPs were genotyped using a TaqMan® SNP Genotyping Assay Kit. RESULTS: Considering susceptibility, the polymorphic allele in the SNP rs2660753 on chromosome 3 was significantly more prevalent in controls (p = 0.01). For familial clustering, the polymorphic homozygote genotype of the SNP rs7931342 was five times more frequent in patients with familial PC compared to sporadic PC (p = 0.01). Regarding the SNP 1447295, the polymorphic homozygote genotype was more prevalent in patients with organ-confined PC (p = 0.05), and most importantly, the polymorphic allele occurred more frequently in patients without biochemical recurrence (p = 0.01). Kaplan-Meier analysis showed a median biochemical recurrence free survival of 124.2 compared to 85.6 months for patients with the wild-type allele (p = 0.007). CONCLUSION: Our findings provide the evidence for the association of 20 recently highlighted SNPs and their susceptibility, familial clustering, staging, Gleason score and biochemical recurrence of PC. We believe that the association between these SNPs and PC may contribute to the development of alternative tools that can facilitate the early detection and prognosis of this disease.

Transurethral Resection of the Prostate (TURP) Versus Original and PErFecTED Prostate Artery Embolization (PAE) Due to Benign Prostatic Hyperplasia (BPH): Preliminary Results of a Single Center, Prospective, Urodynamic-Controlled Analysis.

PURPOSE: To compare clinical and urodynamic results of transurethral resection of the prostate (TURP) to original and PErFecTED prostate artery embolization (PAE) methods for benign prostatic hyperplasia. METHODS: We prospectively randomized 30 patients to receive TURP or original PAE (oPAE) and compared them to a cohort of patients treated by PErFecTED PAE, with a minimum of 1-year follow-up. Patients were assessed for urodynamic parameters, prostate volume, international prostate symptom score (IPSS), and quality of life (QoL). RESULTS: All groups were comparable for all pre-treatment parameters except bladder contractility and peak urine flow rate (Q max), both of which were significantly better in the TURP group, and IIEF score, which was significantly higher among PErFecTED PAE patients than TURP patients. All groups experienced significant improvement in IPSS, QoL, prostate volume, and Q max. TURP and PErFecTED PAE both resulted in significantly lower IPSS than oPAE but were not significantly different from one another. TURP resulted in significantly higher Q max and significantly smaller prostate volume than either original or PErFecTED PAE but required spinal anesthesia and hospitalization. Two patients in the oPAE group with hypocontractile bladders experienced recurrence of symptoms and were treated with TURP. In the TURP group, urinary incontinence occurred in 4/15 patients (26.7 %), rupture of the prostatic capsule in 1/15 (6.7 %), retrograde ejaculation in all patients (100 %), and one patient was readmitted for temporary bladder irrigation due to hematuria. CONCLUSIONS: TURP and PAE are both safe and effective treatments. TURP and PErFecTED PAE yield similar symptom improvement, but TURP is associated with both better urodynamic results and more adverse events.

Probability of extraprostatic disease according to the percentage of positive biopsy cores in clinically localized prostate cancer.

OBJECTIVE: Prediction of extraprostatic disease in clinically localized prostate cancer is relevant for treatment planning of the disease. The purpose of this study was to explore the usefulness of the percentage of positive biopsy cores to predict the chance of extraprostatic cancer. MATERIALS AND METHODS: We evaluated 1787 patients with localized prostate cancer submitted to radical prostatectomy. The percentage of positive cores in prostate biopsy was correlated with the pathologic outcome of the surgical specimen. In the final analysis, a correlation was made between categorical ranges of positive cores (10% intervals) and the risk of extraprostatic extension and/or bladder neck invasion, seminal vesicles involvement or metastasis to iliac lymph nodes. Student's t test was used for statistical analysis. RESULTS: For each 10% of positive cores we observed a progressive higher prevalence of extraprostatic disease. The risk of cancer beyond the prostate capsule for <10% positive biopsy cores was 7.4% and it increased to 76.2% at the category 90-100% positive cores. In patients with Gleason grade 4 or 5, the risk of extraprostatic cancer prostate was higher than in those without any component 4 or 5. CONCLUSION: The percentage of positive cores in prostate biopsy can predict the risk of cancer outside the prostate. Our study shows that the percentage of positive prostate biopsy fragments helps predict the chance of extraprostatic cancer and may have a relevant role in the patient's management.

Probability of Extraprostatic Disease According to the Percentage of Positive Biopsy Cores in Clinically Localized Prostate Cancer

Prediction of extraprostatic disease in clinically localized prostate cancer is relevant for treatment planning of the disease. The purpose of this study was to explore the usefulness of the percentage of positive biopsy cores to predict the chance of extraprostatic cancer.

MRI findings after prostatic artery embolization for treatment of benign hyperplasia.

OBJECTIVE: The purpose of this article is to assess and describe the MRI findings after prostatic artery embolization for treatment of benign prostatic hyperplasia. MATERIALS AND METHODS: We retrospectively evaluated 17 patients who underwent prostatic artery embolization as part of different prospective studies to evaluate this alternative treatment of benign prostatic hyperplasia. Clinical results were evaluated by assessment of urinary catheterization and International Prostate Symptom Score (IPSS). Serial MRI examinations were performed, and the prostatic central gland and peripheral zone were evaluated for signal intensity changes and the presence and characteristics of infarcted areas. Statistical analysis was performed with ANOVA for repeated measures and Student t test. RESULTS: All patients had clinical success, as defined by the removal of indwelling urinary catheter or decreased IPSS after embolization. Infarcts were seen in 70.6% of the subjects, exclusively in the central gland, were almost always characterized by hyperintensity on T1-weighted images and predominant hypointensity on T2-weighted images, and became smaller (mean reduction, p < 0.001) and isointense to the remaining of the central gland over time. Volume reduction of the prostate after embolization was significant (averaging 32.0% after 12-18 months; p < 0.001) only in patients with infarcts. No statistically significant association was seen between the development of infarcts and IPSS. CONCLUSION: MRI can be used for assessing the development of infarcts and volume reduction in the prostate after embolization. Further studies are needed to correlate these findings to clinical outcome.

The "PErFecTED technique": proximal embolization first, then embolize distal for benign prostatic hyperplasia.

Prostatic artery embolization requires a refined technique to achieve good imaging and clinical success. The PErFecTED (Proximal Embolization First, Then Embolize Distal) technique has produced greater prostate ischemia and infarction than previously described methods with clinical improvement of lower urinary symptoms and lower recurrence rates. The microcatheter should cross any collateral branch to the bladder, rectum, corpus cavernosum, gonad, or penis and be placed distally into the prostatic artery before its branching to the central gland and peripheral zone. This technique allows better distribution of embolic material in the intraprostatic arteries and reduces risk of spasm or thrombus. Because benign prostatic hyperplasia develops primarily in the periurethral region of the prostate, the urethral group of arteries should be embolized first. Subsequent distal investigation and embolization completes occlusion and stasis of blood flow to the prostatic parenchyma. Since we added the second step to the PErFecTED technique, we have observed infarcts in all patients submitted to prostatic artery embolization.

Biochemical recurrence rates are similar for pT2-positive surgical margins and pT3a.

OBJECTIVE: Histological details of positive surgical margins in radical prostatectomy specimens have been related to outcome after surgery in rare studies recently published. Our objective is to assess whether the status of surgical margins, the extent and the Gleason score of positive margins, and the extent of the extraprostatic extension are predictive of biochemical recurrence post-radical prostatectomy. MATERIALS AND METHODS: Three hundred sixty-five radical prostatectomy specimens were analyzed. The length of the positive surgical margin and extraprostatic extension and the Gleason score of the margin were recorded. Statistical analyses examined the predictive value of these variables for biochemical recurrence. RESULTS: 236 patients were stage pT2R0, 58 pT2R1, 25 pT3R0 and 46 pT3R1. Biochemical recurrence occurred in 11%, 31%, 20% and 45.7% of pT2R0, pT2R1, pT3R0 and pT3R1, respectively. The extent of the positive surgical margins and the Gleason score of the positive surgical margins were not associated with biochemical recurrence in univariate analysis in a mean follow up period of 35.9 months. In multivariate analyses, only the status of the surgical margins and the global Gleason score were associated with biochemical recurrence, with a risk of recurrence of 3.1 for positive surgical margins and of 3.8 for a Gleason score > 7. CONCLUSION: Positive surgical margin and the global Gleason score are significant risk factors for biochemical recurrence post-radical prostatectomy, regardless of the extent of the surgical margin, the extent of the extraprostatic extension, or the local Gleason score of the positive surgical margin or extraprostatic tissue. pT2R1 disease behaves as pT3R0 and should be treated similarly.

Obesity may influence the relationship between sex hormones and lower urinary tract symptoms.

PURPOSE: The effects of serum testosterone in the lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) are not well established. The objective of the study is to evaluate the association of sex hormones with LUTS and control the results by patient weight. MATERIALS AND METHODS: The study comprised a cross-sectional analysis of 725 men included in a prostate cancer screening program at University of Sao Paulo Medical School. The serum concentrations of total testosterone (TT), free testosterone (FT) and sex hormone binding globulin (SHBG) were measured. Variables analyzed were age, American Urological Association (AUA) symptom score, storage symptoms, voiding symptoms, quality of life score, prostate specific antigen levels and prostate volume. Obesity was measured through the calculation of body mass index (BMI). A regression analysis model was performed. RESULTS: Median patient age was 65 years (48 to 94). A higher TT level was significantly associated with a severe AUA symptom score only among patients with a BMI ≥ 25. Median TT was 371, 370 and 427ng/dL (p = 0.017) in patients with mild, moderate and severe LUTS respectively. The multivariate regression analysis in patients with BMI ≥ 25 showed that only age, TT and sex score were related to LUTS. CONCLUSIONS: A higher TT is associated with a severe AUA score symptom index only in obese patients. Further analysis are necessary to evaluate the mechanisms through which testosterone may influence LUTS in these patients.

Biochemical recurrence rates are similar for pT2-positive surgical margins and pT3a

Objective Histological details of positive surgical margins in radical prostatectomy specimens have been related to outcome after surgery in rare studies recently published. Our objective is to assess whether the status of surgical margins, the extent and the Gleason score of positive margins, and the extent of the extraprostatic extension are predictive of biochemical recurrence post-radical prostatectomy.Materials and Methods Three hundred sixty-five radical prostatectomy specimens were analyzed. The length of the positive surgical margin and extraprostatic extension and the Gleason score of the margin were recorded. Statistical analyses examined the predictive value of these variables for biochemical recurrence.Results 236 patients were stage pT2R0, 58 pT2R1, 25 pT3R0 and 46 pT3R1. Biochemical recurrence occurred in 11%, 31%, 20% and 45.7% of pT2R0, pT2R1, pT3R0 and pT3R1, respectively. The extent of the positive surgical margins and the Gleason score of the positive surgical margins were not associated with biochemical recurrence in univariate analysis in a mean follow up period of 35.9 months. In multivariate analyses, only the status of the surgical margins and the global Gleason score were associated with biochemical recurrence, with a risk of recurrence of 3.1 for positive surgical margins and of 3.8 for a Gleason score > 7.Conclusion Positive surgical margin and the global Gleason score are significant risk factors for biochemical recurrence post-radical prostatectomy, regardless of the extent of the surgical margin, the extent of the extraprostatic extension, or the local Gleason score of the positive surgical margin or extraprostatic tissue. pT2R1 disease behaves as pT3R0 and should be treated similarly.