Isoform-independent promotion of contractility and proliferation, and suppression of survival by with no lysine/K kinases in prostate stromal cells.

With no lysine/K kinases (WNKs) promote vasocontraction and vascular smooth muscle cell proliferation. In the prostate, smooth muscle contraction and growth may be critical for the development and medical treatment of voiding symptoms in benign prostatic hyperplasia. Here, we examined the effects of isoform-specific WNK silencing and of the WNK inhibitor WNK463 on growth-related functions and contraction in prostate stromal cells, and in human prostate tissues. Impacts of WNK silencing by transfection of cultured stromal cells with isoform-specific siRNAs were qualitatively and quantitatively similar for each WNK isoform. Effects of silencing were largest on cell death (3-5 fold increase in annexin V-positive/7-AAD-positive cells), on proliferation rate, Ki-67 mRNA expression and actin organization (reduced around two-thirds). Contraction in matrix contraction assays and viability were reduced to a lower degree (approximately half), but again to a similar extent for each WNK isoform. Effects of silencing were quantitatively and qualitatively reproduced by 10 µM WNK463, while 1 µM still induced cell death and breakdown in actin organization, without affecting proliferation or viability. Using 500 nM and 10 µM, WNK463 partly inhibited neurogenic and U46619-induced contractions of human prostate tissues (around half), while inhibition of α1-adrenergic contractions (around half) was limited to 10 µM. All four WNK isoforms suppress cell death and promote proliferation in prostate stromal cells. WNK-driven contraction of stromal cells appears possible, even though to a limited extent. Outcomes of isoform-specific WNK silencing can be fully reproduced by WNK463, including inhibition of smooth muscle contraction in human prostate tissues, but require high concentrations.

Transcriptomic analysis of benign prostatic hyperplasia identifies critical pathways in prostatic overgrowth and 5-alpha reductase inhibitor resistance.

BACKGROUND: The medical therapy of prostatic symptoms (MTOPS) trial randomized men with symptoms of benign prostatic hyperplasia (BPH) and followed response of treatment with a 5α-reductase inhibitor (5ARI), an alpha-adrenergic receptor antagonist (α-blocker), the combination of 5ARI and α-blocker or no medical therapy (none). Medical therapy reduced risk of clinical progression by 66% but the reasons for nonresponse or loss of therapeutic response in some patients remains unresolved. Our previous work showed that prostatic glucocorticoid levels are increased in 5ARI-treated patients and that glucocorticoids can increased branching of prostate epithelia in vitro. To understand the transcriptomic changes associated with 5ARI treatment, we performed bulk RNA sequencing of BPH and control samples from patients who received 5ARI versus those that did not. Deconvolution analysis was performed to estimate cellular composition. Bulk RNA sequencing was also performed on control versus glucocorticoid-treated prostate epithelia in 3D culture to determine underlying transcriptomic changes associated with branching morphogenesis. METHOD: Surgical BPH (S-BPH) tissue was defined as benign prostatic tissue collected from the transition zone (TZ) of patients who failed medical therapy while control tissue termed Incidental BPH (I-BPH) was obtained from the TZ of men undergoing radical prostatectomy for low-volume/grade prostatic adenocarcinoma confined to the peripheral zone. S-BPH patients were divided into four subgroups: men on no medical therapy (none: n = 7), α-blocker alone (n = 10), 5ARI alone (n = 6) or combination therapy (α-blocker and 5ARI: n = 7). Control I-BPH tissue was from men on no medical therapy (none: n = 8) or on α-blocker (n = 6). A human prostatic cell line in 3D culture that buds and branches was used to identify genes involved in early prostatic growth. Snap-frozen prostatic tissue taken at the time of surgery and 3D organoids were used for RNA-seq analysis. Bulk RNAseq data were deconvoluted using CIBERSORTx. Differentially expressed genes (DEG) that were statistically significant among S-BPH, I-BPH, and during budding and branching of organoids were used for pathway analysis. RESULTS: Transcriptomic analysis between S-BPH (n = 30) and I-BPH (n = 14) using a twofold cutoff (p < 0.05) identified 377 DEG (termed BPH377) and a cutoff < 0.05 identified 3377 DEG (termed BPH3377). Within the S-BPH, the subgroups none and α-blocker were compared to patients on 5ARI to reveal 361 DEG (termed 5ARI361) that were significantly changed. Deconvolution analysis of bulk RNA seq data with a human prostate single cell data set demonstrated increased levels of mast cells, NK cells, interstitial fibroblasts, and prostate luminal cells in S-BPH versus I-BPH. Glucocorticoid (GC)-induced budding and branching of benign prostatic cells in 3D culture was compared to control organoids to identify early events in prostatic morphogenesis. GC induced 369 DEG (termed GC359) in 3D culture. STRING analysis divided the large datasets into 20-80 genes centered around a hub. In general, biological processes induced in BPH supported growth and differentiation such as chromatin modification and DNA repair, transcription, cytoskeleton, mitochondrial electron transport, ubiquitination, protein folding, and cholesterol synthesis. Identified signaling pathways were pooled to create a list of DEG that fell into seven hubs/clusters. The hub gene centrality was used to name the network including AP-1, interleukin (IL)-6, NOTCH1 and NOTCH3, NEO1, IL-13, and HDAC/KDM. All hubs showed connections to inflammation, chromatin structure, and development. The same approach was applied to 5ARI361 giving multiple networks, but the EGF and sonic hedgehog (SHH) hub was of particular interest as a developmental pathway. The BPH3377, 5ARI363, and GC359 lists were compared and 67 significantly changed DEG were identified. Common genes to the 3D culture included an IL-6 hub that connected to genes identified in BPH hubs that defined AP1, IL-6, NOTCH, NEO1, IL-13, and HDAC/KDM. CONCLUSIONS: Reduction analysis of BPH and 3D organoid culture uncovered networks previously identified in prostatic development as being reinitiated in BPH. Identification of these pathways provides insight into the failure of medical therapy for BPH and new therapeutic targets for BPH/LUTS.

The yeast LYST homolog Bph1 is a Rab5 effector and prevents Atg8 lipidation at endosomes.

Lysosomes mediate degradation of macromolecules to their precursors for cellular recycling. Additionally, lysosome-related organelles mediate cell type-specific functions. Chédiak-Higashi syndrome is an autosomal, recessive disease, in which loss of the protein LYST causes defects in lysosomes and lysosome-related organelles. The molecular function of LYST, however, is largely unknown. Here, we dissected the function of the yeast LYST homolog, Bph1. We show that Bph1 is an endosomal protein and an effector of the minor Rab5 isoform Ypt52. Strikingly, bph1Δ mutant cells have lipidated Atg8 on their endosomes, which is sorted via late endosomes into the vacuole lumen under non-autophagy-inducing conditions. In agreement with this, proteomic analysis of bph1Δ vacuoles reveals an accumulation of Atg8, reduced flux via selective autophagy, and defective endocytosis. Additionally, bph1Δ cells have reduced autophagic flux under starvation conditions. Our observations suggest that Bph1 is a novel Rab5 effector that maintains endosomal functioning. When Bph1 is lost, Atg8 is lipidated at endosomes even during normal growth and ends up in the vacuole lumen. Thus, our results contribute to the understanding of the role of LYST-related proteins and associated diseases.

Development of the UroARC Surgical Calculator: A Novel Risk Calculator for Older Adults Undergoing Surgery for Bladder Outlet Obstruction.

PURPOSE: Bladder outlet obstruction (BOO) is common in older adults. Many older adults who pursue surgery have additional vulnerabilities affecting surgical risk, including frailty. A clinical tool that builds on frailty to predict surgical outcomes for the spectrum of BOO procedures would be helpful to aid in surgical decision-making but does not currently exist. MATERIALS AND METHODS: Medicare beneficiaries undergoing BOO surgery from 2014 to 2016 were identified and analyzed using the Medicare MedPAR, Outpatient, and Carrier files. Eight different BOO surgery categories were created. Baseline frailty was calculated for each beneficiary using the Claims-Based Frailty Index (CFI). All 93 variables in the CFI and the 17 variables in the Charlson Comorbidity Index were individually entered into stepwise logistic regression models to determine variables most highly predictive of complications. Similar and duplicative variables were combined into categories. Calibration curves and tests of model fit, including C statistics, Brier scores, and Spiegelhalter P values, were calculated to ensure the prognostic accuracy for postoperative complications. RESULTS: In total, 212,543 beneficiaries were identified. Approximately 42.5% were prefrail (0.15 ≤ CFI < 0.25), 8.7% were mildly frail (0.25 ≤ CFI < 0.35), and 1.2% were moderately-to-severely frail (CFI ≥0.35). Using stepwise logistic regression, 13 distinct prognostic variable categories were identified as the most reliable predictors of postoperative outcomes. Most models demonstrated excellent model discrimination and calibration with high C statistic and Spiegelhalter P values, respectively, and high accuracy with low Brier scores. Calibration curves for each outcome demonstrated excellent model fit. CONCLUSIONS: This novel risk assessment tool may help guide surgical prognostication among this vulnerable population.

Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia (BPH): AUA Guideline Amendment 2023.

PURPOSE: The purpose of this American Urological Association (AUA) Guideline amendment is to provide a useful reference on the effective evidence-based management of male lower urinary tract symptoms secondary/attributed to BPH (LUTS/BPH). MATERIALS AND METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, the Cochrane Library, and the Agency for Healthcare Research and Quality (AHRQ) database to identify studies relevant to the management of BPH. The guideline was updated in 2023 to capture eligible literature published between September 2020 and October 2022. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: The BPH amendment resulted in changes to statements/supporting text on combination therapy, photoselective vaporization of the prostate (PVP), water vapor thermal therapy (WVTT), laser enucleation, and prostate artery embolization (PAE). A new statement on temporary implanted prostatic devices (TIPD) was added. In addition, statements on transurethral needle ablation (TUNA) and transurethral microwave thermotherapy (TUMT) were removed and information regarding these legacy technologies was added to the background section. References and the accompanying treatment algorithms were updated to align with the updated text. CONCLUSION: This guideline seeks to improve clinicians' ability to evaluate and treat patients with BPH/LUTS based on currently available evidence. Future studies will be essential to further support these statements to improve patient care.

Trends in day-case bladder outflow obstruction surgery: a study using Hospital Episode Statistics.

OBJECTIVES: To describe the contemporary evolution of day-case bladder outflow obstruction (BOO) surgery in England and to profile day-case BOO surgery practices across England in terms of the types of operation performed and their safety profiles. MATERIALS AND METHODS: This was a retrospective observational analysis of Hospital Episode Statistics and UK Office for National Statistics data. All 111 043 recorded operations across 117 hospital trusts over 66 months, from 1 January 2017 to 30 June 2022, were obtained. Operations were identified as one of: transurethral resection of prostate (TURP); laser ablation or enucleation; vapour therapy; prostatic urethral lift (PUL); or bladder neck incision. Monthly day-case rate trends were plotted across the study period. Descriptive data, day-case rates and 30-day hospital readmissions were analysed for each operation type. Multilevel regression modelling with mixed effects was performed to determine whether day-case surgery was associated with higher 30-day hospital readmissions. RESULTS: Day-case patients were younger, with fewer comorbidities. Time series analysis showed a linear day-case rate increase from 8.3% (January 2017) to 21.0% (June 2022). Day-case rates improved for 92/117 trusts in 2021/2022 compared with 2017. Three of the six trusts with the highest day-case rates performed predominantly day-case TURP, and the other three laser surgery. Nationally, PUL and vapour surgery had the highest day-case rates (80.9% and 38.1%). Most inpatient operations were TURP. Multilevel regression modelling found reduced odds of 30-day readmission after day-case BOO surgery (all operations pooled), no difference for day-case vs inpatient TURP, and reduced odds following day-case LASER operations. CONCLUSIONS: The day-case rates for BOO surgery have linearly increased. Minimally invasive surgical technologies are commonly performed as day cases, whereas high day-case rates for TURP and for laser ablation operations are seen in a minority of hospitals. Day-case pathways to treat BOO can be safely developed irrespective of operative modality.

Salvage holmium laser enucleation of the prostate after previous interventions: a systematic review.

OBJECTIVE: To investigate the feasibility, safety and efficacy of holmium laser enucleation of the prostate (HoLEP) in the re-treatment setting (salvage HoLEP) and compare it to the primary HoLEP procedure that is commonly used for the treatment of benign prostate hyperplasia (BPH). MATERIALS AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, PubMed, Scopus, and Cochrane databases were systematically screened, from inception to 8 August 2022. Other potentially eligible studies were retrieved using the reference lists of the included studies. Retrospective and prospective studies, both comparative and non-comparative, were included. RESULTS: A total of 12 studies met the inclusion criteria and were included in the final qualitative synthesis. One study was prospective comparative (non-randomised), seven studies were retrospective comparative, and four studies were retrospective non-comparative or case series. In total, 831 patients were treated with salvage HoLEP in the above studies. Previous intervention before salvage HoLEP ranged among studies. The most commonly performed was transurethral resection of the prostate. Intraoperative parameters of salvage HoLEP were comparable with those reported during primary HoLEP, while all postoperative outcomes were significantly improved after salvage HoLEP and were similar with those observed after primary HoLEP. No major complications were noted after salvage HoLEP according to Clavien-Dindo classification. CONCLUSIONS: Salvage HoLEP after previous interventions for treating recurrent or residual BPH is a feasible, safe, and efficient procedure. Data presented in selected studies, along with the holmium laser's physical properties to resect more tissue and to dissect along the true anatomical plane of BPH, render HoLEP an ideal salvage treatment modality for recurrent or residual BPH symptoms.

Inheritance patterns of lower urinary tract symptoms in adults: a systematic review.

OBJECTIVE: To compile and evaluate the heritability and inheritance patterns of lower urinary tract symptoms (LUTS) in adult cohorts. METHODS: Searches of five databases (PubMed, Embase, APA PsycInfo, Global Health, and OVID Medline) commenced on 6 July 2024, resulting in 736 articles retrieved after deduplication. Studies evaluating heritability patterns, gene frequencies, and familial aggregation of symptoms were included for review. Screening and predefined eligibility criteria produced 34 studies for final review. A descriptive analysis of synthesised data was performed, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Cochrane Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool and the Johanna Briggs Institute checklist were used to evaluate these studies. RESULTS: Ten of the 34 studies (29%) described general LUTS, 14 (41%) described symptoms due to benign prostatic enlargement (BPE), nine (26%) described urinary incontinence (UI; urge UI [UUI], stress UI [SUI] and mixed UI [MUI]), four (12%) described nocturia alone, two (6%) described overactive bladder (OAB), and four (13%) described other specific symptoms (frequency, postvoid residual urine volume). BPE symptoms, UI (MUI and UUI), nocturia alone, and frequency alone were associated with genetic predisposition, whilst OAB and SUI had more modest inheritance. CONCLUSION: The pathogenetic and pharmacological mechanisms fundamental to LUTS manifestation are highly heterogeneous. Further work is required to evaluate the inheritance patterns of LUTS more extensively.

Emerging drugs for the treatment of benign prostatic hyperplasia: a 2023 update.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a condition that affects over 50% of men as they enter their fifth decade of life, often leading to lower urinary tract symptoms (LUTS). Primary treatment options include alpha blockers, 5-alpha reductase inhibitors, and phosphodiesterase-5 inhibitors. However, these medications can have some side effects, and there is a noticeable dearth of information addressing the long-term use of these medications. Thus, the exploration of all treatment modalities helps ensure patients receive personalized and effective care. Consequently, the primary objective of this review is to identify potential emerging medications for the treatment of BPH. AREAS COVERED: We conducted an extensive review of articles discussing pharmacotherapy for BPH spanning the last 15 years. Our information gathering process involved Scopus, PubMed-MEDLINE, Cochrane, Wiley Online Library Google Scholar, ClinicalTrials.gov, and the PharmaProjects database. This approach ensures that readers gain an in-depth knowledge of the existing therapeutic agents as well as promising avenues for managing BPH. EXPERT OPINION: BPH treatment targets a patient's specific constellation of symptoms. Therefore, a broad knowledge base encompassing various treatment options is paramount in ensuring optimal treatment. Looking forward, the emphasis on personalization promises to reshape the landscape of BPH treatment and improve patient outcomes.

Evaluation of the learning curve for Thulium fiber laser enucleation of prostate (ThuFLEP): retrospective study of a single-surgeon experience in real-world settings.

PURPOSE: To assess the learning curve of Thulium Fiber Laser Enucleation of prostate (ThuFLEP) of a single surgeon inexperienced in laser endoscopic enucleation of prostate (EEP). METHODS: We retrospectively analyzed all patients with benign prostate hyperplasia undergoing ThuFLEP at our center between January 2022 and August 2023 by one surgeon. Inclusion criteria were International Prostate Symptom Score > 7, prostate volume < 200 g, and maximal urinary flow rate < 15 mL/s. The surgeon was inexperienced in laser EEP and trained by watching educational videos of ThuFLEP before starting to perform the procedure under mentoring during the first 4 cases. Procedural data (enucleation and morcellation efficiency, complications) and functional results up to 3 months were evaluated. Patients were divided into 4 cohorts of 20 consecutive cases to evaluate outcomes evolution throughout time. RESULTS: The mean age of the patients was 69.9 years (SD 7.8) and mean prostate volume was 89.9 g (SD 25.8). Preoperative functional parameters were comparable between the groups. Mean enucleation efficiency (EE) ratio and morcellation efficiency (ME) ratio reached respectively 0.78 g/min (SD 0.55) and 2.49 g/min (SD 1.03) and both variables significantly increased from group 1 to group 3 (p < 0,001). Perioperative complications remained low throughout the caseload with similar significant 3-month functional improvements between all groups. CONCLUSION: This is the first study to evaluate ThuFLEP learning curve for a single surgeon inexperienced in laser EEP with limited mentoring. Under these real-world conditions, nearly 60 cases were needed to complete the learning curve with a complications rate remaining low throughout the training process.

Tamsulosin 0.8 mg daily dose in management of BPH patients with failed tamsulosin 0.4 mg monotherapy and unfit for surgical intervention.

AIM: This study aims to evaluate the effectiveness and safety of administering double-dose tamsulosin (0.8 mg) for treating patients with benign prostatic hyperplasia (BPH) who have not responded to the standard single dose of tamsulosin (0.4 mg) and are deemed unsuitable for transurethral resection (TUR) intervention. MATERIALS AND METHODS: Between November 2022 and July 2023, we prospectively analyzed 111 patients who were experiencing severe BPH symptoms. These patients received a double dose of tamsulosin for one month. We collected baseline characteristics such as age, body mass index, and underlying medical conditions. Various parameters including the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, prostate volume, peak urinary flow rate (Qmax), voided volume, and post-void residual volume were evaluated before and after treatment. RESULTS: All 111 patients completed the study. The mean age, PSA level, and prostate volume were 63.12 ± 4.83 years, 3.42 ± 0.93 ng/ml, and 50.37 ± 19.23 ml, respectively. Of these patients, 93 showed improvement in Qmax, post-void residual volume, and IPSS score (p-value = 0.001). The total IPSS score and total Qmax improved from 24.03 ± 2.49 and 7.72 ± 1.64 ml/sec to 16.41 ± 3.84 and 12.08 ± 2.37 ml/sec, respectively. CONCLUSION: Double-dose 0.8mg tamsulosin as an alpha-blocker therapy appears to be a viable temporary management option for BPH patients who have not responded to the standard single dose 0.4mg tamsulosin and are not suitable candidates for TUR intervention.

Tadalafil versus tamsulosin as combination therapy with 5-alpha reductase inhibitors in benign prostatic hyperplasia, urinary and sexual outcomes.

PURPOSE: To compare the urological and sexual outcomes of using either tamsulosin/finateride or tadalafil/finasteride as combination therapies in patients with large prostate. PATIENTS AND METHODS: Selection criteria included prostate volume > 40 ml and IPSS > 7. Patients with severe erectile dysfunction (IIEF-erectile functions ≤ 10) were excluded. Patients were randomized into group I (tamsulosin/finasteride) and group II (tadalafil/finasteride). The primary endpoint was to define urinary and sexual function changes (IPSS, IPSS-quality of life, urinary flow rates and IIEF domains) within each group. The secondary endpoint was to compare the treatment induced changes between both groups. RESULTS: At 4th and 12th weeks, 131 and 127 patients were available in both groups, respectively. Both groups showed significant LUTS improvement (IPSS changes: - 4.9 ± 2.7 and - 4.3 ± 2.9 at 4th week and - 6.1 ± 3 and - 5.4 ± 2.8 points by the 12th week in both groups, respectively). Group I had better average flow rates at both follow-up visits. Meanwhile, maximum flow rates were comparable in both groups at 12th week (13.5 ± 3.9vs. 12.6 ± 3.7, p > 0.05). In group I, all IIEF domains were significantly lowered at both visits (p < 0.05). Group II showed significant increase in IIEF-erectile function scores (1.3 ± 1.1 and 1.8 ± 1.2 at the 4th and 12th weeks) with a transient significant reduction of IIEF-orgasm and sexual desire noted only by the 4th week (- 0.8 ± 0.4 and - 0.6 ± 0.4, respectively). CONCLUSION: Within three months, both combinations are comparably effective in improving BPH related LUTS. Tamsulosin/finasteride provided significantly better Qmax only at 4th week. Tadalafil/finasteride had the advantage of improving sexual performance over the other combination.

Revisiting the issue of "beach balls" in holmium laser enucleation of prostate: clinical and histological characterization.

PURPOSE: To clinically and histologically characterize prostatic nodules resistant to morcellation ("beach balls," BBs). PATIENTS AND METHODS: We reviewed a consecutive cohort of 559 holmium laser enucleation of the prostate (HoLEP) procedures performed between January 2020 and November 2023. The BBs group comprised 55 men (10%) and the control group comprised 504 men (90%). The clinical, intraoperative, outcome, and histologic data were statistically processed for the prediction of the presence of BBs and their influence on the perioperative course and outcome. RESULTS: The BBs group in comparison to the controls was older (75 vs 73 years, respectively, p = 0.009) and had higher rates of chronic retention (51 vs 29%, p = 0.001), larger prostates on preoperative abdominal ultrasound (AUS) (140 vs 80 cc, p = 0.006E-16), longer operating time (120 vs 80 min, p = 0.001), higher weights of removed tissue (101 vs 60 gr, p = 0.008E-10), higher complication rates (5 vs 1%, p = 0.03), and longer hospitalization (p = 0.014). A multivariate analysis revealed that larger prostates on preoperative AUS and older age independently predicted the presence of BBs which would prolong operating time. ROC analyses revealed that a threshold of 103 cc on AUS predicted BBs with 94% sensitivity and 84% specificity. BBs were mostly characterized histologically by stromal component (p = 0.005). CONCLUSIONS: BBs are expected in older patients and cases of chronic retention. Prostatic volume is the most reliable predictor of their presence. They contribute to prolonged operating time and increased risk of complications. The predominantly stromal composition of the BBs apparently confers their resistance to morcellation.

UroLift to preserve seminal parameters in young male with LUTS from BPH.

PURPOSE: Prostatic urethral lift has been an effective ejaculation sparing treatment for benign prostatic hypertrophy. The aim of this study was to evaluate the effect on male semen parameters. METHODS: Between July 2014 and January 2022, 20 young men with urinary symptoms of BPH, unresponsive to drug treatment and motivated to preserve ejaculation for eventual paternity, underwent UroLift. Semen analysis was performed before and 6 month after surgery with evaluation of pH, volume, sperm concentration, total motility, vitality and morphology according to WHO 2011. All underwent digital rectal examination, transrectal prostate ultrasound to measure prostate volume, PSA, uroflowmetry, cystoscopy and urodynamics test if necessary. Objective and subjective urinary function was scheduled at 1, 3, 6, 12 month than yearly with UFM, IPSS, IIEF-5, and MSHQ-EjD-SF. RESULTS: At a mean follow-up of 36 month (range 12 to 63), no retroejaculation or changes in seminal parameters occurred. Mean age was 44.5 (range 36.5 to 48) years. Mean operative time was 15 (range 10 to 20) min and 2.5 (range 2 to 4) implants per patients were used. At 6 month there were no difference in terms of total sperm count, volume, pH, motility, vitality, morphology, liquefaction, leucocytes (p = 0.9; p = 0.8; p = 0.7; p = 1; p = 1; p = 1; p = 0,2; p = 0.5). At last, Q-max increased by 64.4% (p = 0.001), post-void residual volume decreased by 66.6% (p = 0.016), and IPSS decreased by 60% (p < 0.001). IIEF and MSHQ-EjD-SF were preserved (p = 0.14, p = 0.4). CONCLUSIONS: UroLift appears safe technique to correct LUTS from BPH in young men desirous to preserve seminal analysis.

The early learning curve of the bipolar enucleation of the prostate: a multicenter cohort study.

OBJECTIVES: To evaluate the early learning curve of BipolEP (Bipolar Enucleation of the Prostate). SUBJECTS/PATIENTS AND METHODS: We conducted a retrospective, multicenter analysis of surgical and functional outcomes of patients treated with BipolEp for BPO (benign prostatic obstruction). We evaluated the first 20 cases of BipolEp performed by four different surgeons in three different countries. The following baseline parameters were obtained: age, IPSS, indwelling catheter, transrectal measured prostate volume, post void residual volume (PVR) and uroflowmetry. The learning curve was analysed based on perioperative parameters and the influence of perioperative parameters was correlated with the sequence of BipolEp cases. RESULTS: 84 BipolEp operations performed by 4 different surgeons in their early learning curve were studied. Mean prostate volume was 75 ml, 39% of cases had an indwelling catheter and the average operating time was 101 min. Three out of four surgeons performed at least 50% of successful operations according to Trifecta (complete enucleation and morcellation < 90 min., no conversion to TUR-P). Conversion rate to TURP was 11.9% in total which however was driven by a single surgeon with an almost 50% conversion rate. Mean enucleated prostate was 33.3 gr (18-54.5). Intraoperative complications and reported stress incontinence ranged from 0 to 38.1%. At six-weeks review, the IPPS improved by 12.5 (8-16) points and Qmax by 208% (109.8-266.7). Uroflowmetry outcomes correlated with the sequence of cases with a linear improvement during 20 consecutive cases (p = 0.018) in all centres. Major complications (Clavien Dindo ≥ 3) were rare (4.8%) and comparable between the groups. CONCLUSION: Surgeons starting to learn BipolEp can expect to be able to achieve a linear improvement in Uroflow at the six-week postoperative evaluation after 20 consecutive cases. BipolEp can be successfully performed during the early learning curve with an acceptable rate of conversion to standard TUR-P.

Refining surgical strategies in ThuLEP for BPH: a propensity score matched comparison of En-bloc, three lobes, and two lobes techniques.

PURPOSE: This study compares the peri-operative and functional outcomes of three distinct surgical techniques in Thulium Laser Enucleation of the Prostate (ThuLEP) for benign prostatic hyperplasia (BPH). The main aim is to assess whether the En-bloc, Three-lobe, and Two-lobe techniques have differential effects on surgical efficacy and patient outcomes. METHODS: A retrospective analysis was conducted on patients undergoing ThuLEP for BPH between January 2019 and January 2024 at two tertiary centers. Propensity score matching was utilized to balance baseline characteristics among patients undergoing the different techniques. Surgical parameters, including operative time, enucleation time, morcellation time, energy consumption, and postoperative outcomes, were compared among the groups. RESULTS: Following propensity score matching, 213 patients were included in the analysis. Intraoperative analysis revealed significantly shorter enucleation, laser enucleation, morcellation and operative times and total energy delivered in the En-bloc and Two-lobe groups compared to the Three-lobe group. No significant differences were observed among the groups in terms of intraoperative and postoperative complications. There were no significant differences in functional outcomes at the 3-month follow-up among the groups. CONCLUSION: The findings of this study suggest that while the En-bloc and Two-lobe techniques may offer efficiency benefits and could be considered safe alternatives in ThuLEP procedures, the reduction in laser enucleation time and energy delivered did not necessarily translate into improvements in post operative storage symptoms or other functional outcomes for the patients. Surgeon preference and proficiency may play a crucial role in selecting the most suitable technique for individual patients. Future research should focus on larger-scale prospective studies to further validate these findings and explore potential factors influencing surgical outcomes.

Prevalence and potential predictors of incidental prostate Cancer in patients undergoing surgery for Benign Prostatic obstruction: a retrospective study in the MRI era.

PURPOSE: Despite advancements in prostate multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy (FB), the management of incidental prostate cancer (IPCa) after surgery for benign prostatic obstruction (BPO) remains unclear. The aim of this retrospective study is to determine the prevalence of IPCa in our cohort and identify potential predictors for its occurrence. METHODS: We enrolled patients underwent TURP or simple prostatectomy for BPO at our high-volume center between January 2020-December 2022. Data on age, pre-operative total PSA (tPSA) and PSA density (PSAd) levels, prostate volume, previous MRI, biopsies, specimen weight, rates of positive tissue slices, ISUP score and three-month tPSA were collected. RESULTS: Of 454 patients with negative digital rectal examination who underwent BPO surgery, 74 patients (16.3%) were found to have IPCa. Of these, 33 patients (44.6%) had undergone previous mpMRI. Among the patients who had mpMRI, 23 had negative mpMRI results for suspected prostate cancer, while 10 had positive mpMRI findings (PIRADS ≥ 3) but no evidence of tumor upon FB. KW analysis indicates that PSAd was statistically associated with higher ISUP score, while at univariable regression analysis negative mpMRI (p = 0.03) was the only potential predictor for IPCa. CONCLUSIONS: Among the ISUP groups, PSAd showed a correlation with the tumor, while negative mpMRI was protective against clinically significant PCa. In the era of mpMRI and FB, the IPCa rates found at our center is higher than reported in existing literature and if it were confirmed with further studies, maybe there is a need for expansion in urology guidelines.

Impact of kidney disease on perioperative outcomes of endoscopic BPH surgery: a propensity score matched analysis from the NSQIP database.

INTRODUCTION: To assess the impact of kidney function in patients with BPH undergoing surgery prior to Transurethral resection of prostate (TURP), Laser enucleation of the prostate (LEP), and Laser Vaporization of the prostate (LVP) on operative and post-operative outcomes using the ACS-NSQIP database. METHODS: The ACS-NSQIP database was reviewed for patients that underwent TURP, LEP and LVP for treatment of patients with BPH between the years of 2008 and 2021. Demographics, comorbidities, bleeding disorders, operative time, and surgical procedure performed were collected for comparison between Kidney function groups: G1, normal/high function; G2-G3, mild/moderate kidney disease; and G4-G5, severe kidney disease. The 30-day peri-operative complications were measured and a multivariate logistic regression analysis was performed while adjusting for all confounding variables. Propensity score matching was performed between the G1 and G4-G5 cohorts. RESULTS: A total of 83,020 patients were included. On multivariable regression, in the G2-G3 cohort, patients were at significantly increased risk for renal complications with OR = 2.43[1.56-3.79]. After propensity score matching, the G4-G5 cohort showed increased odds of pneumonia OR = 4.02[1.343-12.056], renal complications with OR = 7.62[2.283-25.411], cardiac complications OR = 4.53[1.531-13.411], and sepsis/septic shock OR = 1.76[1.091-2.834]. They also had a higher need for blood transfusion OR = 3.58[2.242-5.714], and prolonged hospital stay with OR = 1.49[1.296-1.723]. CONCLUSION: Pre-operative kidney disease may pose an increased risk of complications for patients undergoing endoscopic BPH surgery. The literature lacks information on the effect of pre-operative kidney disease on endoscopic BPH surgeries. Further studies are required to compare post-operative outcomes of LEP and LVP as compared to TURP across kidney function status.

Pulse modulation in En-Bloc HoLEP: does it really matter? A propensity score matched analysis.

INTRODUCTION: Holmium laser enucleation of the prostate (HoLEP) is an established option in the surgical treatment of benign prostatic hyperplasia. Pulse modulation, such as MOSES® technology, has recently been introduced and may offer potential advantages in HoLEP. METHODS: Perioperative data from 117 patients who underwent MOSES® laser enucleation of the prostate (MoLEP) were collected. Propensity score matching using prostate volume, age, body mass index (BMI), and anticoagulant intake was performed using a database of 237 patients treated with HoLEP. In total, 234 patients were included in the analysis. RESULTS: Prostate volume (104 vs. 102 ml), age (70 vs. 71 years), BMI (27 vs. 27), and anticoagulant intake (34 vs. 35%) did not differ significantly between the groups. There were no significant differences in operation time (61.5 vs. 58.1 min, p = 0.42), enucleation efficiency (2.5 vs. 2.6 g/min, p = 0.74), hemostasis time (7.8 vs. 8 min, p = 0.75) and hemoglobin drop (0.9 vs. 0.7 mg/dl, p = 0.48). The complication rates were low in both groups (16.2% for HoLEP and 17.1% for MoLEP). No differences were noted in the Clavien-Dindo Classification (p = 0.63) and the Comprehensive Complication Index (p = 0.24). The rate of complications > CDC IIIa was 0.9% for HoLEP (endoscopic coagulation) and 1.7% for MoLEP (2 cases of endoscopic coagulation). No transfusions were administered. CONCLUSION: Overall, the enucleation efficiency was high in both groups and the procedure time was short. HoLEP is an efficient and safe treatment option in experienced hands, regardless of the use of pulse modulation technology.

Real-world experience with the new pulsed solid-state Thulium: YAG laser (Thulio) for endoscopic enucleation of the prostate.

PURPOSE: The solid-state Thulium laser (Tm: YAG) is a novel alternative to the widely used Holmium laser for endoscopic enucleation of the prostate (EEP) due to its relatively high peak power. The aim of this study was to examine the efficacy and safety of a new pulsed Tm: YAG laser in its first application in humans. METHODS: Data were retrospectively collected for the first 103 patients who underwent EEP with a new pulsed solid-state Tm: YAG laser (Thulio®, Dornier MedTech Systems GmbH, Weßling, Germany). Peri- and postoperative data were assessed. Procedure-specific complications were graded using Clavien-Dindo Classifications (CDC). Patients were interviewed 15 months after the surgery to evaluate functional and long-term outcomes. Statistical analysis was performed with Statistical Package for the Social Sciences (SPSS®). RESULTS: The mean preoperative prostate volume was 105.6 ± 55.0 ml. Median enucleation speed was 4.1 g per minute (range 1.1-9.7). Short-term postoperative complications occurred in 21 patients (20.4%), but no high-grade complications (CDC ≥ IV) were observed. Five patients suffered gross haematuria and required reintervention (CDC IIIb; 4.9%). After 15 months, 76 patients (73.8%) participated in the follow-up interview, where seven patients (9.2%) reported complications, including two reinterventions for urethral strictures (CDC IIIb; 2.6%). Most patients reported an improvement in continence (54.0%) and urine stream (93.4%), but no difference in erectile function (81.6%). No persistent dysuria was reported. Patient satisfaction with the surgery results was very high (96.1%). CONCLUSION: Endoscopic enucleation of the prostate with the new pulsed solid-state Tm: YAG laser is a safe and effective option for surgical BPH treatment. TRIAL REGISTRATION: German Clinical Trials Register number: DRKS00031676. Registration date: 10 May 2023, retrospectively registered.