Localization and potential role of prostate microbiota.

Introduction: We aimed to clarify the presence and localization of the prostate microbiota and examine its association with benign prostate enlargement (BPE). Methods: The microbiota of prostate tissues and catheterized urine from 15 patients were analyzed by 16S metagenomic analysis and compared to show that the prostate microbiota was not a contaminant of the urinary microbiota. Fluorescence in situ hybridization (FISH) and in situ hybridization (ISH) using the specific probe for eubacteria was performed on prostate tissue to show the localization of bacteria in the prostate. The BPE group was defined as prostate volume ≥30 mL, and the non-BPE group as prostate volume <30 mL. The microbiota of the two groups were compared to clarify the association between prostate microbiota and BPE. Results: Faith's phylogenetic diversity index of prostate tissue was significantly higher than that of urine (42.3±3.8 vs 25.5±5.6, P=0.01). Principal coordinate analysis showed a significant difference between the microbiota of prostate tissue and catheterized urine (P<0.01). FISH and ISH showed the presence of bacteria in the prostatic duct. Comparison of prostate microbiota between the BPE and non-BPE groups showed that the Chao1 index of the BPE group was significantly lower than that of the latter [142 (50-316) vs 169 (97-665), P=0.047] and the abundance of Burkholderia was significantly higher in the BPE group than in the latter. Conclusions: We demonstrated that the prostate microbiota was located in the prostatic duct and reduced diversity of prostate microbiota was associated with BPE, suggesting that prostate microbiota plays a role in BPE.

Robot-assisted Bladder Diverticulectomy Using a Transperitoneal Extravesical Approach.

Background: Acquired bladder diverticula (BD) are a possible complication of bladder outlet obstruction (BOO) due to benign prostate enlargement (BPE). Robot-assisted bladder diverticulectomy (RABD) has been proposed as an alternative to open removal; however, only a few small series have been published. Objective: To describe our surgical technique for RABD and to assess perioperative results and functional outcomes at 6-mo follow-up. Design setting and participants: A prospective single-centre, single-surgeon cohort of 16 consecutive men with posterior or posterolateral BD due to BOO/BPE undergoing RABD between May 2017 and December 2021 was analysed. Surgical procedure: RABD was performed with a four-arm robotic system via a transperitoneal approach. BD were identified intraoperatively via bladder distension with saline solution through an indwelling catheter with or without concomitant illumination using flexible cystoscopy and fluorescence imaging. Extravesical BD dissection and removal were performed. Outcome measurements and statistical analysis: Operating room time, estimated blood loss, intraoperative and postoperative complications, indwelling catheter time, and timing of associated procedures for BOO/BPE were assessed. The International Prostate Symptom Score (IPSS) and postvoid residual volume (PVR) were compared between baseline and 6 mo after surgery. Results and limitations: Median age and maximum BD diameter were 68 yr (interquartile range [IQR] 54-74) and 69 mm (IQR 51-82), respectively. The median operative time was 126 min (IQR 92-167) and the median estimated blood loss was 20 ml (IQR 15-40). No intraoperative complications were recorded. The urethral catheter was removed on median postoperative day 5 (IQR 5-7). Two men experienced 90-d postoperative complications (persistent urinary infection requiring prolonged antimicrobial therapy). Bipolar transurethral resection of the prostate was performed 3 wk before RABD in seven men and concomitant to RABD in nine men. Median IPSS significantly decreased from 25 (IQR 21-30) to 5 (IQR 5-6), and median PVR from 195 ml (IQR 140-210 ml) to 30 (IQR 28-40) ml (both p < 0.001) at 6-mo follow-up in comparison to baseline. A limitation is the rather small cohort with no control group. Conclusions: RABD is a safe and effective minimally invasive option for treatment of acquired BD in men with BOO/BPE. Validation of our results in larger series with longer follow-up is warranted. Patient summary: We describe our surgical technique for robot-assisted removal of pouches in the bladder wall (called diverticula) in men with bladder outlet obstruction caused by benign prostate enlargement, and report functional results at 6 months after the operation. This minimally invasive technique was found to be safe and effective.

Complications and functional outcomes of endoscopic enucleation of the prostate: a systematic review and meta-analysis of randomised-controlled studies.

Introduction: There are several endoscopic enucleation procedures (EEP) using different energy sources: holmium laser enucleation of the prostate (HoLEP), thulium laser enucleation of the prostate (ThuLEP), Greenlight® (GreenVEP) and diode (DiLEP) lasers, and plasma kinetic enucleation of the prostate (PKEP). The comparative outcomes among these EEPs are unclear. We aimed to compare the peri-operative and post-operative outcomes, complications and functional outcomes among different EEPs. Material and methods: A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. Only randomised-controlled trials (RCT) comparing EEPs were included. The risk of bias was assessed using the Cochrane tool for RCTs. Results: The search identified 1153 articles and 12 RCTs were included. The number of RCTs for each comparison was, HoLEP vs ThuLEP; n = 3, HoLEP vs PKEP; n = 3, PKEP vs DiLEP; n = 3, HoLEP vs GreenVEP; n = 1, HoLEP vs DiLEP; n = 1, ThuLEP vs PKEP; n = 1. Operative time was shorter and blood loss was lower with ThuLEP compared with HoLEP, whereas operative time was shorter for HoLEP compared with PKEP. Blood loss was lower with HoLEP and DiLEP compared with PKEP. There were no Clavien-Dindo IV-V complications, and the incidence of Clavien-Dindo I complications was lower with ThuLEP compared with HoLEP. No significant differences were detected among EEPs regarding urinary retention, stress urinary incontinence, bladder neck contracture or urethral stricture. Lower International Prostate Symptom Score (IPSS) and higher quality of life (QoL) scores were in favour of ThuLEP compared with HoLEP at 1 month. Conclusions: EEP improves symptoms and uroflowmetry parameters with a low incidence of high-grade complications. ThuLEP was associated with shorter operative time, lower blood loss, and lower incidence of low-grade complications compared with HoLEP.

Association between hyperlipidemia and prostatic enlargement: A case-control study.

OBJECTIVE: A high-fat diet is associated with the development of benign prostatic enlargement (BPE), but whether hyperlipidemia is associated with BPE remains unclear. This study aimed to evaluate whether hyperlipidemia is a risk factor for the development of BPE. MATERIAL AND METHODS: This study included 265 BPE patients with lower urinary tract symptoms (LUTS) and 248 age-matched healthy individuals without LUTS. The patient and control groups included in the study were compared in terms of fasting serum glucose, serum lipid values, prostate specific antigen (PSA), and prostate size measured by abdominal ultrasonography. RESULTS: The prostate sizes of the patient and healthy control group were 59.4 ± 12.6 and 41.8 ± 11.1 ml, respectively (p = 0.007). It was observed that the mean PSA value of the patient group (2.33 ± 1.69) was statistically higher than that of the control group (1.21 ± 1.05) (p = 0.002). Total cholesterol and LDL-cholesterol were significantly higher and HDL-cholesterol was significantly lower among the patients compared to the controls. Prostate size had a negative correlation with HDL-cholesterol and a positive correlation with LDL-cholesterol and total cholesterol. Additionally, LDL-cholesterol and total cholesterol were independent risk factors for prostate enlargement. CONCLUSION: This study indicates that increased levels of LDL-cholesterol and total cholesterol are significantly associated with the enlargement of the prostate. Hyperlipidemia may be one of the risk factors in the processes of prostatic growth and progression.

Focus on Silodosin: Pros and Cons of Uroselectivity.

Medical management of lower urinary tract symptoms related to benign prostatic obstruction engages healthcare professionals worldwide. Currently, alpha-1 adrenergic antagonists are strongly recommended as first-line therapy for patients with moderate to severe symptoms because of their safety, efficacy and good tolerability. These agents are highly heterogeneous in terms of pharmacological selectivity for the adrenergic receptor subtypes with silodosin being the agent characterized by the highest α1A/α1B affinity ratio. This property has been proposed to confer to silodosin advantages in terms of bladder outlet obstruction improvement and lower incidence of cardiovascular side effects at the cost of a higher incidence of ejaculatory dysfunction. These aspects should be carefully taken in consideration when personalizing medical therapy for lower urinary tract symptoms related to benign prostatic obstruction.

Zinc Deficiency in Men Over 50 and Its Implications in Prostate Disorders.

Research has been consistently showing the role of zinc (Zn) in prostate function. In this article, we review the current literature on the anatomy and main functions of the prostate, highlighting the role of zinc. In particular, we will review the etiology of benign prostate enlargement (BPH), its prevalence in men over 50, the likelihood of BPH becoming prostate cancer (PCa), and explain the relationship of zinc and apoptosis in the prostate cells and the implications for BPH and PCa. We present a model that explains how endogenous factors provoke excretion of zinc or limit zinc absorption, and how exogenous factors like nutrition and drugs regularly used in men over 50 can significantly decrease zinc status and thereby increase the risk of BPH. Finally, we explain how Zn amino acid (AA) complexes may be capable of avoiding antagonists and inhibitors of zinc absorption, thereby increasing the bioavailability of zinc for the necessary biological processes in the prostate.

Sexual outcomes of endoscopic enucleation of prostate.

The emergence of various endoscopic enucleation techniques in the past decade has provided surgeons with more options and opportunities in performing enucleation. With the same surgical principle as holmium laser enucleation of prostate, the early results of different techniques were comparable. However, sexual outcomes of endoscopic enucleation of the prostate (EEP) were less commonly reported than the voiding and urodynamic outcomes. In this review, the sexual outcomes including erectile function, ejaculatory and orgasmic function of various endoscopic enucleation technique would be studied. The overall sexual outcomes were heterogeneous and inconclusive. Outcomes measurement, sample size calculation, hypothesis generation and selection criteria were not specifically designed for sexual outcomes or even available. There were also limitations in the individual sexual assessment tools. Nonetheless, most studies showed no significant deterioration of erectile function after EEP, and ejaculation dysfunction was common. Looking forward in the field of benign prostatic enlargement surgery, the 'one size fits all' notion should be abandoned. Treatment should be tailor-made according to the prostate size, co-morbidities and sexual needs. The sexual outcomes of enucleation have to be better studied and defined. More prospective controlled studies focusing primarily on sexual functions are needed. For enucleation surgeons, exploring different ejaculatory-sparing technique could be the golden opportunities in further consolidating the role and expanding the indication of enucleation surgery.

Unmet Medical Needs of Patients with Benign Prostate Enlargement.

This study aimed to analyze the factors affecting the unmet medical needs of patients with benign prostate enlargement (BPE) based on Andersen's behavioral model. The data were taken from the 2009-2016 Korea Health Panel Study and 3003 participants were used for analysis. "Unmet medical needs" was used as a dependent variable. Independent variables were predisposing variables: age, educational attainment, and marital status; enabling factors: income, job type, and insurance type; and need factors: lying in a sickbed, activity limitation, subjective health status, and having chronic diseases. Results showed that younger patients experienced a higher probability of unmet medical needs. Those with higher educational attainment had a lower chance of experiencing unmet medical needs. Patients with national health insurance were less likely to experience unmet medical needs. In addition, patients who experienced lying in a sickbed had a higher probability of experiencing unmet medical needs. Therefore, in order to reduce the unmet medical needs of patients with BPE, it is necessary to allow patients to be treated early and give them accurate information about the disease. In addition, access to medical care should be strengthened through continuous care focused on primary care.

Value-based care for the treatment and evaluation of benign prostatic hyperplasia: an analysis of a metropolitan service area claims database.

PURPOSE: With an aging population, cost containment and improved outcomes will be crucial for a sustainable healthcare ecosystem. Current data demonstrate great variation in payments for procedures and diagnostic workup of benign prostatic hyperplasia (BPH). To help determine the best financial value in BPH care, we sought to analyze the major drivers of total payments in BPH. MATERIALS AND METHODS: Commercial and Medicare claims from the Truven Health Analytics Markestscan® database for the Austin, Texas Metropolitan Service Area from 2012 to 2014 were queried for encounters with diagnosis and procedural codes related to BPH. Linear regression was utilized to assess factors related to BPH-related payments. Payments were then compared between surgical patients and patients managed with medication alone. RESULTS: Major drivers of total payments in BPH care were operative, namely transurethral resection of prostate (TURP) [$2778, 95% CI ($2385-$3171), p < 0.001) and photoselective vaporization (PVP) ($3315, 95% CI ($2781-$3849) p < 0.001). Most office procedures were also associated with significantly higher payments, including cystoscopy [$708, 95% CI ($417-$999), p < 0.001], uroflometry [$446, 95% CI ($225-668), p < 0.001], urinalysis [$167, 95% CI ($32-$302), p = 0.02], postvoid residual (PVR) [$245, 95% CI ($83-$407), p < 0.001], and urodynamics [$1251, 95% CI ($405-2097), p < 0.001]. Patients who had surgery had lower payments for their medications compared to patients who had no surgery [$120 (IQR: $0, $550) vs. $532 (IQR: $231, $1852), respectively, p < 0.001]. CONCLUSION: Surgery and office-based procedures are associated with increased payments for BPH treatment. Although payments for surgery were more in total, surgical patients paid significantly less for BPH medications.

Super early detailed assessment of lower urinary tract symptoms after holmium laser enucleation of the prostate (HoLEP): a prospective study.

PURPOSE: To prospectively investigate early and consecutive changes of lower urinary tract symptoms (LUTS), specifically storage symptoms after holmium laser enucleation of the prostate (HoLEP). METHODS: Patients referred for HoLEP completed the International Prostatic Symptom Score (IPSS) the day before, at discharge, and 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, and 52 weeks after HoLEP. Total IPSS was stratified into mild (score 0-7), moderate (8-19), and severe (20-35) LUTS. Storage symptoms were sub-stratified into storage "negative" and "positive". IPSS changes served as the main postoperative outcome. Mixed linear models identified risk factors affecting postoperative recovery of LUTS. RESULTS: Between December 2010 and 2012, 144 consecutive HoLEP patients were prospectively included in the study. Preoperatively 57.6% of the cohort reported severe storage symptoms (mean total IPSS: 22.6 ± 5.0). Total IPSS decreased significantly immediately after surgery (p < 0.001). Patients with severe LUTS, storage-positive sub-score, and high maximum urinary flow rate were affected by a rebound of mainly storage symptoms 6-8 weeks after HoLEP and prolonged recovery from LUTS. Of these, about 7.4% presented persisting urge complaints. Finally, 12 weeks following HoLEP, the vast majority of patients were symptom-free. Limitations of this study include missing urodynamic workup and a comparative patient cohort. CONCLUSION: Immediately after HoLEP, patients experience a significant decrease of LUTS. Continuous symptom recovery seems to be hampered in patients with severe and storage-positive baseline symptoms. (De-novo) storage symptoms slightly affect postoperative recovery. Quality of life is restored to a stable and significantly improved status 3 months after surgery.

Hyperlipidemia patients with long-term statin treatment are associated with a reduced risk of progression of benign prostatic enlargement.

OBJECTIVE: To evaluate the impacts of statin treatment on the risk of benign prostatic enlargement (BPE) progression in hyperlipidemia patients. METHODS: Newly diagnosed hyperlipidemia patients (n = 7961), identified from Taiwan's National Health Insurance Research Database, were divided into four statin cohorts (statin use >365 days, n = 1604; statin use 181-365 days, n = 813; statin use 91-180 days, n = 739; and statin use 31-90 days, n = 713) and one control cohort (cohort that used no statins, n = 4092). Study endpoint was occurrence of BPE progression (BPE diagnosis plus receiving BPE-related medications or surgery). Relative risks of BPE progression in the statin cohorts compared to the control cohort were analyzed. RESULTS: Multivariable Cox proportional hazards regression analyses demonstrated that BPE progression risk in the cohort used statins for >365 days was significantly lower than the control cohort (adjusted hazard ratio: 0.70, 95% confidence interval: 0.58 ∼ 0.85, p < .001). However, BPE progression risks of the other three statin cohorts did not significantly differ from the control cohort. Trend analysis revealed that the effects of statin treatment on decreasing BPE progression risk were significantly related to statin treatment duration (p = .001). CONCLUSIONS: Hyperlipidemia patients with long-term statin treatment (more than 365 days) are associated with a reduced risk of BPE progression.

Preoperative multiparametric prostate magnetic resonance imaging: a safe clinical practice to reduce incidental prostate cancer in Holmium laser enucleation of the prostate.

INTRODUCTION: Purpose of the study was to investigate the correlation of a preoperative multiparametric magnetic resonance imaging of the prostate (mpMRI) in patients with a suspicion of prostate cancer and eligible for Holmium Laser Enucleation of the Prostate (HoLEP). MATERIAL AND METHODS: Data of 228 patients who had undergone HoLEP was selected and retrospectively analyzed from a multicentric database. All patients presented with a raised serum PSA and/or an abnormal digital rectal examination (DRE). Prostate cancer (PCa) was excluded either with a negative mpMRI (group 'NEGATIVE MRI' n = 113) or a standard biopsy (group 'NO MRI' n = 115). Preoperative characteristic surgical and histological outcomes were confronted. A univariate and multivariate logistic regression model was performed to investigate independent predictors of incidental Prostate Cancer (iPCa). RESULTS: Both groups presented with no statistical differences in preoperative characteristics besides previous acute urinary retention rates and post-voided residual volume, found to be higher (27.8% vs. 14.2% and median 120cc vs. 80cc) in NO MRI and NEGATIVE MRI respectively.No differences were registered in surgical time, removed tissue, catheterization time, hospital stay and complications rate.Statistically lower rate of iPCa (p = 0.03) was detected in the NEGATIVE MRI group (6.2%) in comparison with NO MRI group (14.8%). In multivariate logistic regression only presence of a preoperative negative mpMRI correlated (p = 0.04) as an independent predictive factor (OR 2.63; 95% CI: 1.02-6.75). CONCLUSIONS: A negative mpMRI might be a useful tool to be included in a novel preoperative assessment to patients eligible for HoLEP with a suspicion of PCa in order to avoid an incidental PCa.

Economic Value of the Transurethral Resection in Saline System for Treatment of Benign Prostatic Hyperplasia in England and Wales: Systematic Review, Meta-analysis, and Cost-Consequence Model.

CONTEXT: Monopolar transurethral resection of the prostate (M-TURP) is the current UK surgical standard of care for benign prostatic hyperplasia, a condition estimated to affect >2 million men in the United Kingdom. Although M-TURP efficacy in prostate resection is established, potential perioperative complications and associated costs remain a concern. OBJECTIVE: To present up-to-date and robust evidence in support of bipolar transurethral resection in saline (TURis) as an alternative surgical option to M-TURP. EVIDENCE ACQUISITION: A systematic review (SR) of electronic databases (up to 2015) for randomised controlled trials (RCTs) comparing TURis with M-TURP was conducted, followed by evidence synthesis in the form of a meta-analysis of hospital stay, catheterisation time and procedure duration, transurethral resection (TUR) syndrome, blood transfusion, clot retention, and urethral strictures. An economic analysis was subsequently undertaken from the UK National Health Service hospital perspective with costs and resource use data from published sources. EVIDENCE SYNTHESIS: The SR identified 15 good-quality RCTs, of which 11 were used to inform the meta-analysis. TURis was associated with improved safety versus M-TURP, eliminating the risk of TUR syndrome and reducing the risk of blood transfusion and clot retention (relative risks: 0.34 and 0.43, respectively; p<0.05). TURis also reduced hospital stay (mean difference: 0.56 d; p<0.0001). The economic analysis indicated potential cost savings with TURis versus M-TURP of up to £204 per patient, with incremental equipment costs offset by savings from reduced hospital stay and fewer complications. CONCLUSIONS: The TURis system is associated with significant improvements in perioperative safety compared with M-TURP while ensuring equivalent clinical outcomes of prostate resection. The safety benefits identified may translate into cost savings for UK health services. PATIENT SUMMARY: Our review of bipolar transurethral resection in saline, the new prostate resection technique, indicates that it offers equal efficacy while reducing complications and length of hospital stay.

Pathophysiology of benign prostate enlargement and lower urinary tract symptoms: Current concepts.

Lower urinary tract symptoms (LUTS) are highly prevalent in the aging population, particularly in men. Historically, prostate enlargement was thought to be responsible for most cases of male LUTS. Several risk factors for the development of benign prostate enlargement/hyperplasia (BPE/BPH) have been identified, including age, genetics, hormones, growth factors, inflammation, and lifestyle factors. However, as our knowledge continues to evolve, male LUTS are no longer managed entirely in a prostate-centric fashion. In this article, we review current concepts in the epidemiology, etiology, and pathophysiology of BPE/BPH and male LUTS.

The Use of Urodynamics Assessment Before the Surgical Treatment of BPH.

Lower urinary tract symptoms (LUTS) are a common problem in men especially with aging. The International Continence Society (ICS) revealed an overall prevalence of LUTS of about two-thirds of men age 40 years and above. The treatment approach depends on accurate determination of the underlying etiology. LUTS is not unique to benign prostate enlargement (BPE) and can be secondary to other causes. In the era where quality of care is important, accurate diagnosis and counseling to meet patients' expectations is of extreme paramount. Thus, proper assessment of patients who present with BPE and LUTS should be an important part of the work up process. Accurate diagnosis and identification of the cause will help to improve quality of treatment, optimize counseling, and improve treatment outcomes. Pressure flow urodynamic studies (PFUDs) are not only important tools that help to identify the underlying causes of LUTS; it is considered the "gold standard" for diagnosis of bladder outlet obstruction (BOO) in patients with enlarged prostate [1, 2]. However, there is a continuous debate on the value of using PFUDs and its association with improved outcomes.

Cooperative effects of EGF, FGF, and TGF-ß1 in prostate stromal cells are different from responses to single growth factors.

AIMS: Stromal growth is critical for prostate enlargement during benign prostatic hyperplasia (BPH). While responses of prostate cells to single growth factors have been well characterized, responses to multiple growth factors at once are poorly understood. Here, we examined the effects of combinations between epidermal growth factor (EGF), fibroblast growth factor (FGF), and transforming growth factor-ß1 (TGF-ß1) in human prostate stromal cells. MAIN METHODS: EGF, FGF, and TGF-ß1 were applied to WPMY-1 cells, an immortalized, non-malignant line of stromal cells from the human prostate. Hypertrophic responses were assessed by protein/DNA ratio, and cyclin D1 mRNA by RT-PCR. Expression of EGF, FGF, and TGF-ß1 and their receptors in human prostate tissue was analyzed by RT-PCR, Western blot, and fluorescence staining. KEY FINDINGS: Hypertrophic responses to single growth factors and combinations were similar. Combinations showed additive effects on cyclin D1 mRNA. Combination of EGF with TGF-ß1, but not EGF or TGF-ß1 alone, caused assembly of cells to a new two-dimensional structure, being characterized by dense aggregates connected by branches of few cells. EGF and TGF-ß1 were detected together in human prostates. Receptors for EGF and TGF-ß colocalized on stromal cells in human prostates. SIGNIFICANCE: Responses of prostate stromal cells to combinations of EGF, FGF, and TGF-ß1 may be quantitatively different, qualitatively different, or similar to responses to single growth factors. The combination of EGF and TGF-ß1, but not EGF or TGF-ß1 alone, induces aggregation of prostate stromal cells, which may be relevant for morphogenesis.

Management of large prostatic adenoma: Lasers versus bipolar transurethral resection of prostate.

Transurethral resection of prostate (TURP) has long been the most commonly performed surgical procedure for the management of benign prostate enlargement (BPE), but has several associated limitations. Over the years, laser techniques have developed as major contenders as alternative therapies for BPE. However, simultaneously, TURP has also flourished and with relatively recent development of resection in saline (bipolar TURP), the tussle between laser techniques and TURP has further gained momentum. A systematic search was performed on Medline using the various Medical subject headings related to the surgical management of BPE including TURP, bipolar, lasers, holmium laser enucleation of prostate (HoLEP), photo-selective vaporization of prostate (PVP), etc., All articles types including meta-analysis randomized controlled trials, review articles, guidelines from various urological associations, single center studies from 2002 onward were considered for review. Bipolar TURP, HoLEP, and PVP provide equivalent outcomes for large prostate adenoma (<60 g). For extremely large glands (<150 g), HoLEP is a very efficacious endoscopic alternative to open prostatectomy and has proven long-term results over more than a decade. Bipolar TURP and PVP are attractive with a minimal learning curves and equivalent short term durability. Surgical management of large prostate should be individualized based upon patient's comorbidities and surgeon's expertise.