Search

Background: The burden of common urologic diseases, including benign prostatic hyperplasia (BPH), urinary tract infections (UTI), urolithiasis, bladder cancer, kidney cancer, and prostate cancer, varies both geographically and within specific regions. It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases. Methods: We obtained data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for the aforementioned urologic diseases by age, sex, location, and year from the Global Burden of Disease (GBD) 2021. We analyzed the burden associated with urologic diseases based on socio-demographic index (SDI) and attributable risk factors. The trends in burden over time were assessed using estimated annual percentage changes (EAPC) along with a 95% confidence interval (CI). Results: In 2021, BPH and UTI were the leading causes of age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR), with rates of 5531.88 and 2782.59 per 100,000 persons, respectively. Prostate cancer was the leading cause of both age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR), with rates of 12.63 and 217.83 per 100,000 persons, respectively. From 1990 to 2021, there was an upward trend in ASIR, ASPR, ASMR, and ASDR for UTI, while urolithiasis showed a downward trend. The middle and low-middle SDI quintile levels exhibited higher incidence, prevalence, mortality, and DALYs related to UTI, urolithiasis, and BPH, while the high and high-middle SDI quintile levels showed higher rates for the three cancers. The burden of these six urologic diseases displayed diverse age and sex distribution patterns. In 2021, a high body mass index (BMI) contributed to 20.07% of kidney cancer deaths worldwide, while smoking accounted for 26.48% of bladder cancer deaths and 3.00% of prostate cancer deaths. Conclusions: The global burden of 6 urologic diseases presents a significant public health challenge. Urgent international collaboration is essential to advance the improvement of urologic disease management, encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Xiaojin Pill (XJP) is a traditional Chinese medicine prescribed for treating benign prostatic hyperplasia (BPH). It has been proven to have multiple effects, such as regulating sex hormone levels, exhibiting anti-tumor, anti-inflammatory, analgesic, and anti-platelet aggregation properties, and improving immunity. However, the material basis of XJP's therapeutic effect on BPH and its metabolic process in vivo remains to be clarified. At the same time, many microorganisms that exist in the urogenital tract, including those related to BPH, can also affect the health of the host. Methods: Using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), the chemical components of XJP were identified. A BPH model was created through bilateral testicular ablation and injections of testosterone propionate. A comprehensive evaluation of XJP efficacy was conducted using pathological ELISA, TUNEL, and immunohistochemical techniques. In addition, UPLC-MS metabolomics and 16S rRNA sequencing revealed the serum metabolic profile and intestinal microbiota composition. We performed a Spearman correlation coefficient analysis to highlight the interactions between "intestinal microbiota-serum factors" and "intestinal microbiota-metabolites." Results: XJP contains 91 compounds that alleviate pathologies of BPH in rats, decreasing prostate weight, index, and serum levels of Dihydrotestosterone (DHT), Prostate-Specific Antigen (PSA), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) levels. It inhibits prostatic epithelial cell apoptosis and downregulates Bax, TGF-β1, and IGF-1 proteins in the caspase-3 pathway. Metabolomics studies have revealed 10 upregulated and 10 downregulated metabolites in treated rats, with 5-methylcytosine, uracil, and cytosine enriched in pyrimidine metabolism. L-arginine plays a pivotal role in metabolic pathways encompassing pyrimidine metabolism, arginine biosynthesis, and the mammalian target of rapamycin (mTOR) signaling pathway. 16S rRNA sequencing revealed that XJP optimized the diversity and balance of intestinal flora in BPH rats by decreasing the Bacteroidetes/Firmicutes (B/F) ratio, enhancing the beneficial bacteria, such as Eggerthellaceae, Anaerovoracaceae, and Romboutsia, and suppressing the dysfunctional bacteria, such as Atopobiaceae, Prevotellaceae_NK3B31_group, Dorea, and Frisingicoccus. According to the Spearman correlation coefficient analysis, Lactobacillus was found to be most associated with serum factors, whereas Romboutsia showed the highest correlation with metabolites. This finding suggests that XJP modulates pyrimidine metabolism disorders in BPH rats, a regulation that aligns closely with Romboutsia, Prevotellaceae_NK3B31_group, Lactobacillus, Chujaibacter, and Enterorhabdus, thereby providing valuable biological insights. Conclusion: In summary, these findings indicate that XJP possesses a synergistic anti-BHP effect through its multi-component, multi-target, multi-gut microbiota, and multi-metabolic pathway properties. The effect involves the regulation of sex hormone levels, growth factors, and the anti-epithelial cell apoptosis process. The modulation of specific gut microbiota by the host and the involvement of multiple metabolic pathways are likely one of the significant mechanisms of XJP in treating BPH. Notably, pyrimidine metabolism and the intestinal microbial ecosystem are closely intertwined in this process. [ABSTRACT FROM AUTHOR]

Abstract Background The burden of common urologic diseases, including benign prostatic hyperplasia (BPH), urinary tract infections (UTI), urolithiasis, bladder cancer, kidney cancer, and prostate cancer, varies both geographically and within specific regions. It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases. Methods We obtained data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for the aforementioned urologic diseases by age, sex, location, and year from the Global Burden of Disease (GBD) 2021. We analyzed the burden associated with urologic diseases based on socio-demographic index (SDI) and attributable risk factors. The trends in burden over time were assessed using estimated annual percentage changes (EAPC) along with a 95% confidence interval (CI). Results In 2021, BPH and UTI were the leading causes of age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR), with rates of 5531.88 and 2782.59 per 100,000 persons, respectively. Prostate cancer was the leading cause of both age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR), with rates of 12.63 and 217.83 per 100,000 persons, respectively. From 1990 to 2021, there was an upward trend in ASIR, ASPR, ASMR, and ASDR for UTI, while urolithiasis showed a downward trend. The middle and low-middle SDI quintile levels exhibited higher incidence, prevalence, mortality, and DALYs related to UTI, urolithiasis, and BPH, while the high and high-middle SDI quintile levels showed higher rates for the three cancers. The burden of these six urologic diseases displayed diverse age and sex distribution patterns. In 2021, a high body mass index (BMI) contributed to 20.07% of kidney cancer deaths worldwide, while smoking accounted for 26.48% of bladder cancer deaths and 3.00% of prostate cancer deaths. Conclusions The global burden of 6 urologic diseases presents a significant public health challenge. Urgent international collaboration is essential to advance the improvement of urologic disease management, encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies.

Abstract Background Benign prostatic hyperplasia (BPH) is a prevalent condition in aging males, leading to bladder outlet obstruction (BOO) and associated urinary symptoms. With increasing life expectancy, the incidence of BPH and its co-morbidities, like inguinal hernia, has risen. This study explores the efficacy of combining transurethral resection of the prostate (TURP) and inguinal hernioplasty in a single surgical session to address both conditions, potentially reducing the need for multiple hospitalizations and surgical interventions. Methods This retrospective study at Chi Mei Medical Center included patients from 2014 to 2023 who underwent concurrent TURP and inguinal hernioplasty. A total of 85 patients met the criteria defined for this study. Preoperative, intraoperative, and postoperative characteristics were meticulously documented. Outcomes evaluated included the duration of the surgery, incidence of intraoperative and postoperative complications, duration of Foley catheterization, length of hospital stay, and treatment efficacy. Additionally, we conducted a comparative assessment of the surgical outcomes between two distinct techniques for inguinal hernia repair: open hernioplasty and laparoscopic hernioplasty (LH). Results In 85 patients who met the criteria, the mean age was 71.1 ± 7.8 years. The study reported no significant intraoperative complications, and postoperative care was focused on monitoring for blood loss, infection, and managing pain. The average postoperative hospital stay was 2.9 ± 1.0 days and the mean duration of catheterization was 51.6 ± 16.7 h, with a minimal complication rate observed during the one-year follow-up. A significant reduction in both operative duration and catheterization interval was observed in patients undergoing LH as opposed to those receiving open hernioplasty. Conclusion Concurrent TURP and inguinal hernioplasty effectively manage BOO due to BPH and inguinal hernias with minimal complications, suggesting a viable approach to reducing hospital stays and surgical interventions. Laparoscopic techniques, in particular, offer benefits in operative efficiency and recovery time, making combined surgery a feasible option for selected patients.

To evaluate the efficacy of Transurethral holmium laser enucleation of the prostate (HoLEP) with preservation of the urethral ridge in the treatment of benign prostatic hyperplasia (BPH) in patients aged 75 years or less. We conducted retrospective analysis of clinical data acquired from 80 patients aged 75 years or less with BPH. We also included 30 cases of HoLEP with preservation of the “urethral ridge” (the modified group) and 50 cases of HoLEP (the control group). Analysis showed that there were no significant differences in operation time (59.5 (55.0, 66.0) min vs. 57.0 (52.5, 64.3) min), the weight of prostate tissue removed (45.4 ± 13.5 vs. 47.7 ± 15.2 grams), hemoglobin drop (1.5 ± 0.4 grams per liter vs. 1.4 ± 0.3 grams per liter), the time of postoperative bladder irrigation (21.0 (19.8, 23.3) h vs. 21.0 (19.0, 23.2) h), postoperative indwelling catheter time (4.0 (3.0, 4.0) d vs. 4.0 (3.0, 4.0) d) and postoperative hospitalization time (5.0 (4.0, 5.0) d vs. 5.0 (4.0, 5.0) d) between the two groups (all p > 0.05). However, there was a significant difference in the immediate postoperative urinary control rate (93.3% (28/30) vs. 76% (38/50), p < 0.05) and the incidence of retrograde ejaculation (5 cases (16.7%) vs. 19 cases (38%), p < 0.05) between the two groups. In addition, we identified significant differences in the International Prostate Symptom Score (IPSS), quality-of-life score (QoL), maximum urinary flow rate (Qmax), International Index of Erectile Function score (IIEF-5), and postvoid residual volume (PVR) intragroup comparison (all p < 0.05). The efficacy of HoLEP with preservation of the “urethral ridge” in the treatment of BPH was found to be comparable to that of conventional two-lobe HoLEP but can improve the rate of immediate urinary control and reduce the incidence of retrograde ejaculation.

Background: Benign prostatic hyperplasia (BPH) is a prevalent condition in aging males, leading to bladder outlet obstruction (BOO) and associated urinary symptoms. With increasing life expectancy, the incidence of BPH and its co-morbidities, like inguinal hernia, has risen. This study explores the efficacy of combining transurethral resection of the prostate (TURP) and inguinal hernioplasty in a single surgical session to address both conditions, potentially reducing the need for multiple hospitalizations and surgical interventions. Methods: This retrospective study at Chi Mei Medical Center included patients from 2014 to 2023 who underwent concurrent TURP and inguinal hernioplasty. A total of 85 patients met the criteria defined for this study. Preoperative, intraoperative, and postoperative characteristics were meticulously documented. Outcomes evaluated included the duration of the surgery, incidence of intraoperative and postoperative complications, duration of Foley catheterization, length of hospital stay, and treatment efficacy. Additionally, we conducted a comparative assessment of the surgical outcomes between two distinct techniques for inguinal hernia repair: open hernioplasty and laparoscopic hernioplasty (LH). Results: In 85 patients who met the criteria, the mean age was 71.1 ± 7.8 years. The study reported no significant intraoperative complications, and postoperative care was focused on monitoring for blood loss, infection, and managing pain. The average postoperative hospital stay was 2.9 ± 1.0 days and the mean duration of catheterization was 51.6 ± 16.7 h, with a minimal complication rate observed during the one-year follow-up. A significant reduction in both operative duration and catheterization interval was observed in patients undergoing LH as opposed to those receiving open hernioplasty. Conclusion: Concurrent TURP and inguinal hernioplasty effectively manage BOO due to BPH and inguinal hernias with minimal complications, suggesting a viable approach to reducing hospital stays and surgical interventions. Laparoscopic techniques, in particular, offer benefits in operative efficiency and recovery time, making combined surgery a feasible option for selected patients. [ABSTRACT FROM AUTHOR]

The β3-adrenoceptor agonist mirabegron is available for the treatment of storage symptoms of overactive bladder, including frequency, urgency, and incontinence. The off-target effects of mirabegron include binding to α1-adrenoceptors, which are central in the treatment of voiding symptoms. Here, we examined the structure–function relationships in the binding of mirabegron to a cryo-electron microscopy structure of α1A. The binding was simulated by docking mirabegron to a 3D structure of a human α1A-adrenoceptor (7YMH) using Autodock Vina. The simulations identified two binding states: slope orientation involving 10 positions and horizontal binding to the receptor surface involving 4 positions. No interactions occurred with positions constituting the α1A binding pocket, including Asp-106, Ser-188, or Phe-312, despite the positioning of the phenylethanolamine moiety in transmembrane regions close to the binding pocket by contact with Phe-288, -289, and Val-107. Contact with the unique positions of α1A included the transmembrane Met-292 during slope binding and exosite Phe-86 during horizontal binding. Exosite binding in slope orientation involved contact of the anilino part, rather than the aminothiazol end, to Ile-178, Ala-103, and Asn-179. In conclusion, contact with Met-292 and Phe-86, which are unique positions of α1A, accounts for mirabegron binding to α1A. Because of its lack of interactions with the binding pocket, mirabegron has lower affinity compared to α1A-blockers and no effects on voiding symptoms. [ABSTRACT FROM AUTHOR]

Objectives: The relationship between cathepsins and prostate cancer (PCa) has been reported. However, there is a lack of research on cathepsins and benign prostate diseases (BPDs). This study investigated the potential genetic link between cathepsins and BPDs through the utilization of Mendelian randomization (MR) analysis to determine if a causal relationship exists. Methods: Publicly accessible summary statistics on BPDs were obtained from FinnGen Biobank. The data comprised 149,363 individuals, with 30,066 cases and 119,297 controls for BPH, and 123,057 individuals, with 3,760 cases and 119,297 controls for prostatitis. The IEU OpenGWAS provided the Genome-wide association data on ten cathepsins. To evaluate the causal relationship between BPDs and cathepsins, five distinct MR analyses were employed, with the primary method being the inverse variance weighted (IVW) approach. Additionally, sensitivity analyses were conducted to examine the horizontal pleiotropy and heterogeneity of the findings. Results: The examination of IVW MR findings showed that cathepsin O had a beneficial effect on BPH (IVW OR=0.94, 95% CI 0.89-0.98, P=0.0055), while cathepsin X posed a threat to prostatitis (IVW OR=1.08, 95% CI 1.00-1.16, P=0.047). Through reverse MR analysis, it was revealed that prostatitis had an adverse impact on cathepsin V (IVW OR=0.89, 95% CI 0.80-0.99, P=0.035), while no favorable association was observed between BPH and cathepsins. The results obtained from MR-Egger, weighted median, simple mode, and weighted mode methods were consistent with the findings of the IVW approach. Based on sensitivity analyses, heterogeneity, and horizontal pleiotropy are unlikely to distort the results. Conclusion: This study offers the initial evidence of a genetic causal link between cathepsins and BPDs. Our findings revealed that cathepsin O was beneficial in preventing BPH, whereas cathepsin X posed a potential threat to prostatitis. Additionally, prostatitis negatively affected cathepsin V level. These three cathepsins could be targets of diagnosis and treatment for BPDs, which need further research. [ABSTRACT FROM AUTHOR]

AbstractBackground Benign prostatic hyperplasia (BPH) affects 30% of men worldwide, folate is essential for life. However, few studies have investigated the relationship between folate levels and BPH. The present study aims to explore the relationship between red blood cell (RBC) folate, a better indicator of long-term folate intake, and BPH in United States (US) men.Methods We used statistics from four cycles of the “National Health and Nutrition Examination Survey” (NHANES2001-2008), RBC folate data come from laboratory data and BPH date come from questionnaire data. A multivariate conditional logistic regression model and subgroup analysis were using to assess the association between RBC folate and BPH.Results 647 males from four survey cycles in the NHANES2001-2008, of which, 574 men (88.7%) had BPH. After adjusting for potential confounders, a considerable correlation was observed between RBC folate and BPH; With the first quintiles of RBC folate as the reference, multivariable-adjusted odds ratios (ORs) and confidence intervals (95% CIs) of the second, third, fourth, and the highest quintiles were 1.19 (0.58 ∼ 2.44), 1.39 (0.65 ∼ 2.97), 2.27 (0.96 ∼ 5.39), 2.26 (1.35 ∼ 3.76) and 5.37 (1.85 ∼ 15.59), respectively.Conclusions Individuals with high levels of RBC folate were associated with an increased risk of self-reported benign prostatic hyperplasia of US men.

Introduction: Transurethral Resection of Prostate (TURP) is the most common treatment for Benign Prostatic Hyperplasia (BPH). Blood loss during and after transurethral resection of the prostate (TURP) is a potential cause of morbidity and clot retention. Usual practise is to apply traction in every case of TURP to reduce early postoperative hematuria and clot retention. There are very few studies in the literature and they have mainly concentrated on the effect of traction on reducing blood loss but there is scanty data regarding the morbidity associated with the use of traction. Various authors have described their method of traction application. So, in this study, we will compare the result of short term (10 min) traction with standard (4–6 h) traction. Materials and methods: It is a prospective comparative study with 50 participants, conducted at the department of Urology of a tertiary care hospital in eastern India after taking ethical clearance and consent from the patient. The patients attending urology O.P.D. with LUTS and diagnosed as BPH and planned for elective TURP and who had prolonged traction after TURP were excluded. Study period was one and the half year. Results: Post operatively 25 patients were managed with catheter traction while 25 patients were managed with short term traction of 10 min. Pain which is assessed by visual analog scale (VAS) at 2 and 4 h post operatively is statistically significant with p value of <0.05 and cut off of 65 g prostate volume is drawn below which the successful outcome of short term traction is feasible without any complications. Conclusion: If hemostatsis is done properly then short term traction is preferable, safe and had fewer complications for prostate volume <65 g in comparison to standard traction TURP comparing the overall factors. Although, VAS score at 2 and 4 h post operatively shows patient experienced less pain even in prostate volume >65 g. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Shenyang Pharmaceutical University is the property of Shenyang Pharmaceutical University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Cancer testis antigens (CTAs) are a family of proteins typically expressed in male testicles but overexpressed in various cancer cell types. Transmembrane Phosphatase with Tensin homology (TPTE) is expressed only in the testis of healthy individuals and is a member of the family of CTAs. The current study, for the first time, examined the significance of TPTE expression in prostate cancer (PCa) tissues by generating a novel antibody marker targeting TPTE protein. Methods: Polyclonal antibodies were prepared for TPTE-p1 and TPTE-p2 peptides, which are derived from the extracellular domains of TPTE. Anti-TPTE-p2 antibody was then used to study the extent and pattern of TPTE expression in 102 PCa and 48 benign prostatic hyperplasia (BPH) tissue samples by immunohistochemistry. The viability of cancer cell lines (PC-3 and MCF-7 cells) was also evaluated in the presence of anti-TPTE-p2 antibody using the MTT test. Results: The immunohistochemical analysis demonstrated a significant increase in cytoplasmic and membrane TPTE expression in the PCa samples compared to the BPH group (both P < 0.0001). Cytoplasmic TPTE expression was positively correlated with Gleason score and PSA levels (P = 0.03 and P = 0.001, respectively). Significant correlations were identified between the levels of PSA and perineural invasion and the membrane expression (P = 0.01, P = 0.04, respectively). Moreover, anti-TPTE-p2 antibody inhibited PC-3 and MCF-7 cells proliferation compared to the control group for 24 h (P < 0.001 and P = 0.001, respectively) as well as for 48 h (P = 0.001 and P = 0.001, respectively). Conclusion: Our findings indicate that increased TPTE expression is associated with progression of disease. The ability of anti-TPTE-p2 antibody to recognize and target the TPTE protein makes it a potential biomarker to assess and/or target the PCa. [ABSTRACT FROM AUTHOR]

Pyroptosis, a new mode of programmed cell death, is primarily characterized by persistent cellular swelling that culminates in cell rupture. This process results in the release of large amounts of inflammatory factors, subsequently triggering an inflammatory response. Benign prostatic hyperplasia (BPH) is the most frequent urological disease in old males and is closely associated with changes in hormones and inflammation response. In recent years, the role of pyroptosis in the occurrence and development of BPH has also received increasing attention. This article summarizes the mechanisms of pyroptosis, concludes the pathogenesis associated with BPH in old males, and outlines the role of pyroptosis in BPH, to provide new ideas for finding more effective therapeutic measures for BPH through pyroptosis.

Smooth muscle contraction by Pim kinases and ZIPK has been suggested, but evidence for lower urinary tract organs or using Pim-selective inhibitor concentrations is not yet available. Here, we assessed effects of the Pim inhibitors AZD1208 and TCS PIM-1 and the dual ZIPK/Pim inhibitor HS38 on contractions of human prostate and bladder tissues and of porcine interlobar arteries. Human tissues were obtained from radical prostatectomy and radical cystectomy and renal interlobar arteries from pigs. Contractions were studied in an organ bath. Noradrenaline-, phenylephrine- and methoxamine-induced contractions were reduced (up to > 50%) with 500-nM AZD1208 in prostate tissues and to lesser degree and not consistently with all agonists in interlobar arteries. A total of 100-nM AZD1208 or 500-nM TCS PIM-1 did not affect agonist-induced contractions in prostate tissues. Decreases in agonist-induced contractions with 3-µM HS38 in prostate tissues and interlobar arteries were of small extent and did not occur with each agonist. Carbachol-induced contractions in detrusor tissues were unchanged with AZD1208 (500 nM) or HS38. Electric field stimulation–induced contractions were not affected with AZD1208 or HS38 in any tissue, but slightly reduced with 500-nM TCS PIM-1 in prostate tissues. Concentration-dependent effects of Pim inhibitors suggest lacking Pim-driven smooth muscle contraction in the prostate, bladder, and interlobar arteries but point to organ-specific functions of off-targets. Procontractile functions of ZIPK in the prostate and interlobar arteries may be limited and are lacking in the detrusor. [ABSTRACT FROM AUTHOR]

Introduction This study aimed to compare the safety and efficacy of treatment using simple prostatectomy (SP) and using photoselective vaporization of the prostate (PVP) with a 180W GreenLight XPS laser in patients with high-volume prostate hypertrophy. Material and methods The study included 120 patients with LUTS symptoms caused by prostatic enlargement of more than 80 ml; 79 patients were treated with SP, while 41 were treated with PVP. The analysis included subjective the International Prostate Symptom Score (IPSS) and Quality of Life (QoL), and objective (Qmax), (Qave), and post-void residual volume (PVR) parameters before treatment and at an average of 38 months after surgical treatment. Early and late adverse effects and length of hospitalisation were assessed. Complication reports were performed according to the modified Clavien-Dindo system. Results The analysis independently showed the effectiveness of both methods. Subjective parameters (IPSS, QoL), showed no significant differences. Patients treated with SP scored slightly better on objective parameters (Qmax, Qave, and PVR). Analysis of adverse effects and hospitalisation time were more favourable after PVP. Conclusions SP and PVP were found to be comparable and highly effective in treating benign prostatic hyperplasia in terms of IPSS and QoL. Patients treated with the SP method obtained slightly better results of objective parameters such as Qmax, Qave, and PVR. Compared with SP, PVP has a more favourable safety profile. [ABSTRACT FROM AUTHOR]

Purpose: Prostate artery embolisation (PAE) is a key treatment for the management of symptomatic benign prostatic hyperplasia (BPH). Common cardiovascular risk factors might be associated with suboptimal outcomes and thus influence patient treatment selection. The aim of the study was to evaluate whether cardiovascular comorbidities affect PAE outcomes. Methods: Retrospective subset analysis of the UK Registry of Prostate Artery Embolisation (UK-ROPE) database was performed with patients who had a full documented past medical histories including hypertension, diabetes, coronary artery disease (CAD), diabetes and smoking status as well as international prostate symptom score (IPSS) at baseline and at 12 months. Multiple regression was performed to assess for any significant predictors. Results: Comorbidity data were available for 100/216 patients (mean age 65.8 ± 6.4 years), baseline IPSS 20.9 ± 7.0). Regression analysis revealed that the presence of hypertension (53.7% IPSS reduction vs. absence 51.4%, p = 0.94), diabetes (52.6% vs. absence 52.1%, p = 0.6), CAD (59.2% vs. absence 51.4%, p = 0.95), no comorbidities (49.8% vs. any comorbidity present 55.3%, p = 0.66), smoking status (non-smoker, 52.6%, current smoker, 61.5%, ex-smoker, 49.8%, p > 0.05), age (p = 0.52) and baseline Qmax (p = 0.41) did not significantly impact IPSS reduction at 12 months post-PAE. Baseline prostate volume significantly influenced IPSS reduction (≥ 80 cc prostates, 58.9% vs. < 80 cc prostates 43.2%, p < 0.05). Conclusion: The presence of cardiovascular comorbidities/smoking history does not appear to significantly impact PAE symptom score outcomes at 12 months post procedure. Our findings suggest that if the prostatic artery can be accessed, then clinical success is comparable to those without cardiovascular comorbidities. [ABSTRACT FROM AUTHOR]

Purpose: To identify the urodynamic parameters affecting the clinical outcomes of transurethral resection of the prostate(TURP) surgery for patients with benign prostatic hyperplasia(BPH) by multifactor analysis and establish a regression model with diagnostic values. Methods: The medical records of patients who underwent TURP surgery for BPH between December 2018 and September 2021 were collected from the urology department of the Second Affiliated Hospital of Kunming Medical University, Kunming, China. The patients' clinical data and urodynamic parameters were collected before surgery. The urodynamic parameters affecting surgical efficacy were identified by multifactor analysis, and a regression model with diagnostic values was established and evaluated. Results: A total of 201 patients underwent TURP, of whom 144 had complete preoperative urodynamic data. Each urodynamic factor was subjected to multifactor analysis, and the bladder contractility index (BCI), bladder outflow obstruction index (BOOI), bladder residual urine, and bladder compliance (BC) were found to be independent influence factors on the efficacy of TURP in patients with BPH. The diagnostic value of the regression model was analyzed by receiver operating characteristics (ROC) analysis, and it was found that the AUC = 0.939 (95% CI 0.886–0.972), for which the sensitivity and specificity were 95.19% and 80%, respectively. Conclusions: The regression model had high diagnostic sensitivity and specificity in predicting the efficacy of surgery, and the diagnostic value was higher than that of individual urodynamic factors. Therefore, BCI, BOOI, bladder residual urine, and BC should be considered as independent influence factors on the efficacy of TURP surgery for BPH. [ABSTRACT FROM AUTHOR]

Aim: This study explores the risk of diabetes-associated lower and upper urinary tract diseases among male older adults aged 45 and above in India. Methods: Longitudinal Ageing Study in India (LASI), 2017-2018 data was used in this study. The prevalence of various urinary tract problems and diabetes among male older adults was estimated by background characteristics using bivariate cross-tabulation. In addition, multivariate logistic regression was applied to examine the likelihood of urological disorders associated with diabetes. Result: The prevalence of incontinence was highest among male older adults with diabetes, followed by kidney stones, benign prostatic hyperplasia, and chronic renal failure. Multivariate logistic regression estimation showed that men diagnosed with diabetes were 80% more likely to experience chronic renal failure, 78% more likely to suffer from incontinence, and 37% more likely to suffer from kidney stones than those without diabetes when controlling for various socio-demographic, behavioral, and co-morbidity status of the older adults. Conclusions: The study findings suggest that diabetes is associated with multiple urinary complications among male older adults in India and needs more careful investigation of the phenomenon. Independent risk factors such as changes in lifestyle with regular monitoring and diagnosis may help to prevent the progression of diabetes and reduce the risk of diabetes-associated lower and upper urinary tract diseases among male older adults. [ABSTRACT FROM AUTHOR]

Pyroptosis, a new mode of programmed cell death, is primarily characterized by persistent cellular swelling that culminates in cell rupture. This process results in the release of large amounts of inflammatory factors, subsequently triggering an inflammatory response. Benign prostatic hyperplasia (BPH) is the most frequent urological disease in old males and is closely associated with changes in hormones and inflammation response. In recent years, the role of pyroptosis in the occurrence and development of BPH has also received increasing attention. This article summarizes the mechanisms of pyroptosis, concludes the pathogenesis associated with BPH in old males, and outlines the role of pyroptosis in BPH, to provide new ideas for finding more effective therapeutic measures for BPH through pyroptosis. [ABSTRACT FROM AUTHOR]

Tamsulosin is a first-line drug for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Despite its high ratings for efficacy and safety, these parameters may vary due to genetic polymorphisms of CYP2D6 enzyme, which is involved in the metabolism of the drug. This variability may have great impact on the therapy of LUTS associated with BPH and may require an individualized approach to drug selection. The aim of the study was to assess the impact of genetic polymorphisms in CYP2D6 on the efficacy and safety of tamsulosin therapy in patients with LUTS associated with BPH. The study included 106 patients with LUTS/BPH (N40 according to ICD-10). All patients received monotherapy with tamsulosin 0.4 mg/day for at least 8 weeks. Depending on the severity of symptoms, all patients were divided into 2 groups based on the IPSS score: the first group of patients had moderate symptoms (n=57), and the second group of patients had severe symptoms (n=49). The results of treatment were assessed using the IPSS questionnaire with determination of quality of life (QoL), transrectal ultrasound of the prostate with determination of prostate volume and postvoid residual urine volume, and uroflowmetry. The carriage of allelic variants of CYP2D6 (*3, *4, *9, *10, and *41) were determined by polymerase chain reaction in all patients. In patients with moderate symptoms who was classified as «intermediate» metabolizers by CYP2D6, a statistically significant greater reduction in symptoms according to the overall IPSS scale at 8 weeks (p=0.046) and the obstructive symptom subscale starting from 4 weeks of treatment (p<0.05) was shown. Allelic variants of the CYP2D6 gene did not affect the frequency of adverse reactions to tamsulosin. The results of the study show that in patients with moderate LUTS associated with BPH who are «intermediate» metabolizers by CYP2D6, there is a better therapeutic effect of tamsulosin. [ABSTRACT FROM AUTHOR]

Purpose: Laser enucleation of the prostate (LEP) and simple prostatectomy (SP) are surgical treatment options for large gland Benign Prostatic Hyperplasia. While multiple studies compare clinical outcomes of these procedures, there are limited data available comparing hospital charges in the United States. Here, we present current practice trends and a hospital charge analysis on a national level using an annual insurance claims data repository. Methods: The Healthcare Cost and Utilization Project National Inpatient Sample and Nationwide Ambulatory Surgery Sample databases for 2018 were queried. CPT and ICD-10PCS codes identified patients undergoing LEP or SP, who were then compared for practice setting, total hospital charges, and payor. Laser type for LEP and surgical approach for SP could not be differentiated. Results: The median hospital charge of 5782 LEPs and 973 SPs is $26,689 and $51,250 (p < 0.001), respectively. LEP independently predicts a decreased hospital charge of $16,464 (p < 0.001) per case. Medicare is the primary payor for both procedures. More LEP procedures are completed in the outpatient setting (87.8%) vs. SPs (5.7%, p < 0.001). Median length of stay is longer for SP (LEP: 0, IQR: 0; SP: 3, IQR: 2–4; p < 0.001). In the Western region, LEP is least commonly performed (184, p < 0.001), most expensive ($43,960; p < 0.001), and has longer length of stay (2, p < 0.001). Conclusions: LEP should be considered a cost-effective alternative to SP. Regions of the U.S. that perform more LEPs have shorter length of stay and lower hospital charges associated with the procedure. [ABSTRACT FROM AUTHOR]

The β3-adrenoceptor agonist mirabegron is available for the treatment of storage symptoms of overactive bladder, including frequency, urgency, and incontinence. The off-target effects of mirabegron include binding to α1-adrenoceptors, which are central in the treatment of voiding symptoms. Here, we examined the structure–function relationships in the binding of mirabegron to a cryo-electron microscopy structure of α1A. The binding was simulated by docking mirabegron to a 3D structure of a human α1A-adrenoceptor (7YMH) using Autodock Vina. The simulations identified two binding states: slope orientation involving 10 positions and horizontal binding to the receptor surface involving 4 positions. No interactions occurred with positions constituting the α1A binding pocket, including Asp-106, Ser-188, or Phe-312, despite the positioning of the phenylethanolamine moiety in transmembrane regions close to the binding pocket by contact with Phe-288, -289, and Val-107. Contact with the unique positions of α1A included the transmembrane Met-292 during slope binding and exosite Phe-86 during horizontal binding. Exosite binding in slope orientation involved contact of the anilino part, rather than the aminothiazol end, to Ile-178, Ala-103, and Asn-179. In conclusion, contact with Met-292 and Phe-86, which are unique positions of α1A, accounts for mirabegron binding to α1A. Because of its lack of interactions with the binding pocket, mirabegron has lower affinity compared to α1A-blockers and no effects on voiding symptoms.

Benign prostatic hyperplasia (BPH) is a common urinary disease among the elderly, characterized by abnormal prostatic cell proliferation. Neferine is a dibenzyl isoquinoline alkaloid extracted from Nelumbo nucifera and has antioxidant, anti-inflammatory and anti-prostate cancer effects. The beneficial therapeutic effects and mechanism of action of neferine in BPH remain unclear.A mouse model of BPH was generated by subcutaneous injection of 7.5 mg/kg testosterone propionate (TP) and 2 or 5 mg/kg neferine was given orally for 14 or 28 days. Pathological and morphological characteristics were evaluated. Prostate weight, prostate index (prostate/body weight ratio), expression of type Ⅱ 5α-reductase, androgen receptor (AR) and prostate specific antigen were all decreased in prostate tissue of BPH mice after administration of neferine. Neferine also downregulated the expression of pro-caspase-3, uncleaved PARP, TGF-β1, TGF-β receptor Ⅱ (TGFBR2), p-Smad2/3, N-cadherin and vimentin. Expression of E-cadherin, cleaved PARP and cleaved caspase-3 was increased by neferine treatment.1–100 μM neferine with 1 μM testosterone or 10 nM TGF-β1 were added to the culture medium of the normal human prostate stroma cell line, WPMY-1, for 24 h or 48 h. Neferine inhibited cell growth and production of reactive oxygen species (ROS) in testosterone-treated WPMY-1 cells and regulated the expression of androgen signaling pathway proteins and those related to epithelial-mesenchymal transition (EMT). Moreover, TGF-β1, TGFBR2 and p-Smad2/3, N-cadherin and vimentin expression were increased but E-cadherin was decreased after 24 h TGF-β1 treatment in WPMY-1 cells. Neferine reversed the effects of TGF-β1 treatment in WPMY-1 cells. Neferine appeared to suppress prostate growth by regulating the EMT, AR and TGF-β/Smad signaling pathways in the prostate and is suggested as a potential agent for BPH treatment.

AbstractAim This study explores the risk of diabetes-associated lower and upper urinary tract diseases among male older adults aged 45 and above in India.Methods Longitudinal Ageing Study in India (LASI), 2017–2018 data was used in this study. The prevalence of various urinary tract problems and diabetes among male older adults was estimated by background characteristics using bivariate cross-tabulation. In addition, multivariate logistic regression was applied to examine the likelihood of urological disorders associated with diabetes.Result The prevalence of incontinence was highest among male older adults with diabetes, followed by kidney stones, benign prostatic hyperplasia, and chronic renal failure. Multivariate logistic regression estimation showed that men diagnosed with diabetes were 80% more likely to experience chronic renal failure, 78% more likely to suffer from incontinence, and 37% more likely to suffer from kidney stones than those without diabetes when controlling for various socio-demographic, behavioral, and co-morbidity status of the older adults.Conclusions The study findings suggest that diabetes is associated with multiple urinary complications among male older adults in India and needs more careful investigation of the phenomenon. Independent risk factors such as changes in lifestyle with regular monitoring and diagnosis may help to prevent the progression of diabetes and reduce the risk of diabetes-associated lower and upper urinary tract diseases among male older adults.

Background: Phospholipases A2 (PLA2) may be involved in α1‐adrenergic contraction by formation of thromboxane A2 in different smooth muscle types. However, whether this mechanism occurs with α1‐adrenergic contractions of the prostate, is still unknown. While α1‐adrenoceptor antagonists are the first line option for medical treatment of voiding symptoms in benign prostatic hyperplasia (BPH), improvements are limited, probably by nonadrenergic contractions including thromboxane A2. Here, we examined effects of PLA2 inhibitors on contractions of human prostate tissues. Methods: Prostate tissues were obtained from radical prostatectomy. Contractions were induced by electric field stimulation (EFS) and by α1‐adrenergic agonists in an organ bath, after application of the cytosolic PLA2 inhibitors ASB14780 and AACOCF3, the secretory PLA2 inhibitor YM26734, the leukotriene receptor antagonist montelukast, or of solvent to controls. Results: Frequency‐dependent contractions of human prostate tissues induced by EFS were inhibited by 25% at 8 Hz, 38% at 16 Hz and 37% at 32 Hz by ASB14780 (1 µM), and by 32% at 16 Hz and 22% at 32 Hz by AACOCF3 (10 µM). None of both inhibitors affected contractions induced by noradrenaline, phenylephrine or methoxamine. YM26734 (3 µM) and montelukast (0.3 and 1 µM) neither affected EFS‐induced contractions, nor contractions by α1‐adrenergic agonists, while all contractions were substantially inhibited by silodosin (100 nM). Conclusions: Our findings suggest presynaptic PLA2 functions in prostate smooth muscle contraction, while contractions induced by α1‐adrenergic agonists occur PLA2‐independent. Lacking sensitivity to montelukast excludes an involvement of PLA2‐derived leukotrienes in promotion of contractile neurotransmission. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH), characterized by the enlargement of the prostate gland and subsequent lower urinary tract symptoms, poses a significant health concern for aging men with increasing prevalence. Extensive efforts encompassing in vitro and in vivo models are underway to identify novel and effective agents for the management and treatment of BPH. Research endeavors are primarily channeled toward assessing the potential of compounds to inhibit cell proliferation, curb inflammation, and display anti-androgenic activity. Notably, through screening aimed at inhibiting 5-alpha reductase type 2 (5αR2) in human prostatic cells, two acyl compounds (1 and 2) were isolated from a bioactive fraction sourced from an association of marine sponges Poecillastra sp. and Jaspis sp. The complete structure of 1 was determined as (Z)-dec-3-enony (2S, 3S)-capreomycidine, ascertained by JBCA and ECD comparison. While the absolute configurations of 2 remained unassigned, it was identified as a linkage of a 2, 7S*-dihydoxy-9R*-methyloctadecanoyl group with the 2-amino position of a tramiprosate moiety referred to as homotaurine. Evaluation of both compounds encompassed the assessment of their inhibitory effects on key biomarkers (5αR2, AR, PSA, and PCNA) associated with BPH in testosterone propionate (TP)-activated LNCap and RWPE-1 cells. [ABSTRACT FROM AUTHOR]

Transurethral resection of the prostate (TURP) cannot completely resect hyperplastic tissues and is often associated with high recurrence rate and short recurrence interval. Western and Chinese scholars have reported higher incidences of stress urinary incontinence (SUI) with traditional enucleations. This study investigated the potential applicability of Modified Plasmakinetic Enucleation and Resection of the Prostate by three glands (MPKERP) in treating benign prostatic hyperplasia (BPH). Between April 2020 and June 2021, 28 patients underwent MPKERP for BPH. The surgical procedures included (1) surgical capsule exploration; (2) moderate range enucleation; (3) middle gland enucleation; (4) sector resection at 12 o’clock in the lithotomy position; (5) cut residual distal urethral mucosa; (6) lateral hyperplastic glands enucleation. All 28 patients recovered well after the surgery, and the curative effect was satisfactory. The average operation time was 68.9 ± 21.8 min, the average weight of excised glands was 62.5 ± 19.1 g, the average indwelling catheter time was 4.6 ± 0.6 d, and the average bladder washing time was 28.6 ± 9.5 h. The average postoperative 1-day hemoglobin decrease was 10.2 ± 9.8 g/L. Only one severe hyperplasia patient had transient SUI (incidence rate: 3.6%). No complications, such as urethral stricture, dysuria, urinary incontinence and urinary retention, were reported during follow-up. International Prostate Symptoms Score (IPSS), quality of life (QOL), maximum urinary flow rate (Qmax) and post-void residual volume (PVR) significantly improved three months after surgery (p < 0.0001). The MPKERP can enucleate and resect the hyperplastic glands anatomically in an orderly manner and pay attention to expanding space, reducing resistance, reducing the damage of pushing and pulling, protecting the urethral sphincter complex (USC), and reducing the incidence of urinary incontinence. Altogether, our findings support MPKERP as an improved surgical technique worthy of promotion, and it is more suitable for grass-roots hospitals that lack hardware equipment.

Introduction: Benign Prostatic Hyperplasia (BPH) is one of the most frequent diseases in men. The laser treatment for BPH has challenged TURP due to advances in laser technology, a better understanding of tissue-laser interactions and rowing clinical experience. Objective: To evaluate the safety and efficacy of HoLEP, comparing it to Bipolar TURP. Material and methods: This was a prospective study to evaluate the outcomes in BPH patients undergoing surgery by HOLEP and Bipolar TURP done between January 2018 to December 2019. A total of 80 Patients were enrolled, 40 undergoing HoLEP and the other 40 Bipolar TURP for BPH. The procedures were performed by a single surgeon. All patients with symptomatic BPH and who were candidates for surgical treatment were included. Patients with previous prostate surgery, urethral surgery, history of prostate cancer or neurogenic bladder were excluded. Results: Baseline parameters were almost similar between both the groups in terms of age, IPSS, QOL, Q max, PVR, and gland size. Operative time and resected gland weight were more in HoLEP arm (p Conclusion: Both Bipolar TURP and HoLEP were effective in relieving BOO. HoLEP has equal efficacy compared to conventional bipolar TURP, with decreased hospital stay and catheter indwelling time. The learning curve of HoLEP is steep; however, it can be overcome gradually.

Benign prostatic hyperplasia (BPH) is a non-malignant disease of the prostate characterized by uncontrolled proliferation of the prostate gland. Inflammation and oxidative stress have been reported to play a role in the development of BPH. Kolaviron, a bioflavonoid complex of Garcinia kola seed, has been shown to possess anti-inflammatory effect. In this study, we investigated the effect of Kolaviron on testosterone propionate (TP)-induced BPH in rats. Fifty male rats were assigned in 5 groups. Groups 1 and 2 were orally exposed to corn oil (2 ml/kg) and Kolaviron (200 mg/kg/day, p.o) for 28 days. Group 3 rats received TP (3 mg/kg/day, s.c) for 14 days while Groups 4 and 6 were treated with Kolaviron (200 mg/kg/day, p.o) and Finasteride (5 mg/kg/day, p.o), respectively, for 14 days prior to TP (3 mg/kg, s.c) co-exposure for the remaining 14 days. Administration of Kolaviron to TP-treated rats reverted histological alteration and significantly decreased prostate weight, prostate index, 5α-reductase, dihydrotestosterone, androgen receptor expression, tumor necrosis factor α, interleukin-1β, cyclooxygenase-2, prostaglandin E2, 5-lipoxygenase leukotriene B4, inducible nitric oxide synthase and nitric oxide concentration. In addition, Kolaviron alleviated TP-induced oxidative stress and reduced the expression of Ki-67, VEGF, and FGF to almost control levels. Furthermore, Kolaviron promoted apoptosis in TP-treated rats through downregulation of BCL-2 and upregulation of P53 and Caspase 3 expressions. Overall, Kolaviron prevented BPH via regulation of androgen/androgen receptor signaling, anti-oxidative and anti-inflammatory mechanisms. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) is a common urinary disease among the elderly, characterized by abnormal prostatic cell proliferation. Neferine is a dibenzyl isoquinoline alkaloid extracted from Nelumbo nucifera and has antioxidant, anti-inflammatory and anti-prostate cancer effects. The beneficial therapeutic effects and mechanism of action of neferine in BPH remain unclear. A mouse model of BPH was generated by subcutaneous injection of 7.5 mg/kg testosterone propionate (TP) and 2 or 5 mg/kg neferine was given orally for 14 or 28 days. Pathological and morphological characteristics were evaluated. Prostate weight, prostate index (prostate/body weight ratio), expression of type Ⅱ 5α-reductase, androgen receptor (AR) and prostate specific antigen were all decreased in prostate tissue of BPH mice after administration of neferine. Neferine also downregulated the expression of pro-caspase-3, uncleaved PARP, TGF-β1, TGF-β receptor Ⅱ (TGFBR2), p-Smad2/3, N-cadherin and vimentin. Expression of E-cadherin, cleaved PARP and cleaved caspase-3 was increased by neferine treatment. 1–100 μM neferine with 1 μM testosterone or 10 nM TGF-β1 were added to the culture medium of the normal human prostate stroma cell line, WPMY-1, for 24 h or 48 h. Neferine inhibited cell growth and production of reactive oxygen species (ROS) in testosterone-treated WPMY-1 cells and regulated the expression of androgen signaling pathway proteins and those related to epithelial-mesenchymal transition (EMT). Moreover, TGF-β1, TGFBR2 and p-Smad2/3, N-cadherin and vimentin expression were increased but E-cadherin was decreased after 24 h TGF-β1 treatment in WPMY-1 cells. Neferine reversed the effects of TGF-β1 treatment in WPMY-1 cells. Neferine appeared to suppress prostate growth by regulating the EMT, AR and TGF-β/Smad signaling pathways in the prostate and is suggested as a potential agent for BPH treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear. Methods We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P

Abstract Background Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are the most common prostate disorders in the UK, which cause considerable ill health in older men. Transperineal template prostate biopsy (TTPB) has emerged as a reliable procedure for the histopathological diagnosis of PCa and BPH due to its higher cancer detection rates. Although antiseptic preparation and antibiotic prophylaxis are used to ensure safety in patients undergoing surgical intervention, post-operative complications, such as infection and bleeding are still unavoidable, resulting in re-admissions, with resource implications. Currently, there is no biomarker profile to predict outcomes or monitor patients during the post-operative course. The main aim of this single-centre observational clinical pilot-study was to investigate the role of inflammatory and infection biomarkers following TTPB and their association with post-operative complications. Methods Forty-five patients scheduled for elective TTPB were recruited after informed consent at the Wrexham Maelor and Glan Clwyd Hospitals, North Wales, UK (n = 45). Prior to surgery, venous blood samples were collected at baseline and subsequently at 30, 120, and 240 min post-operatively. Urine samples were collected before and 120 min after the procedure. Serum procalcitonin (PCT), serum ferritin, and urine B2MG analysis were done using enzyme-linked fluorescent assay (ELFA) and the magnetic Luminex® multiplex performance assay was used to analyse IL-6, IL-8, IL-10 and TNF-α plasma concentrations. Data on clinical outcomes were collected from patients’ medical records. Results Following TTPB, significant (p ≤ 0.05) increases were observed in uB2MG, IL-6, IL-8, IL-10 and TNF-α. Significant decreases were observed in ferritin (p ≤ 0.05). No significant change was observed in PCT concentration (p ≥ 0.05). One patient developed an infection and severe haematuria post-operatively following TTPB. Conclusion Although not confirmative, changes seen in biomarkers such as uB2MG, IL-10 and TNF-α in our observational clinical pilot-study may warrant further investigation, involving larger cohorts, to fully understand the role of these biomarkers and their potential association with post-operative complications such as infection and bleeding which can develop following TTPB for the diagnosis of PCa and BPH.

Background: NUAKs promote myosin light chain phosphorlyation, actin organization, proliferation and suppression of cell death in non-muscle cells, which are critical for smooth muscle contraction and growth. In benign prostatic hyperplasia (BPH), contraction and growth in the prostate drive urethral obstruction and voiding symptoms. However, a role of NUAKs in smooth muscle contraction or prostate functions are unknown. Here, we examined effects of NUAK silencing and the presumed NUAK inhibitors, HTH01-015 and WZ4003 on contraction and growth-related functions in prostate stromal cells (WPMY-1) and in human prostate tissues. Methods: Effects of NUAK1 and -2 silencing, HTH01-015 and WZ4003 on matrix plug contraction, proliferation (EdU assay, Ki-67 mRNA), apoptosis and cell death (flowcytometry), viability (CCK-8) and actin organization (phalloidin staining) were examined in cultured WPMY-1 cells. Effects of HTH01-015 and WZ4003 on smooth muscle contraction were assessed in organ bath experirments with human prostate tissues. Results: Effects of silencing were most pronounced on proliferation and cell death, resulting in decreases of proliferation rate by 60% and 70% by silencing of NUAK1 and NUAK2 (compared to scramble siRNA-transfected controls), decreases in Ki-67 by 75% and 77%, while numbers of dead cells after silencing of NUAK1 and NUAK2 amounted to 2.8 and 4.9 fold of scramble-transfected controls. Silencing of each isoform was paralleled by reduced viability, breakdown in actin polymerization, and partial decreases in contractility (maximally 45% by NUAK1 silencing, 58% by NUAK2 silencing). Effects of silencing were mimicked by HTH01-015 and WZ4003, with numbers of dead cells amounting up to 16.1 fold or 7.8 fold with HTH01-015 or WZ4003, compared to solvent-treated controls. Using concentrations of 500 nM, neurogenic contractions of prostate tissues were inhibited partly by HTH01-015 and U46619-induced contractions were inhibited partly by HTH01-015 and WZ4003, while α1-adrenergic and endothelin-1-induced contractions remained unaffected. Using 10 μM, inhibition of endothelin-1-induced contractions by both inhibitors and inhibition of α1-adrenergic contractions by HTH01-015 added to effects seen by 500 nM. Conclusion: NUAK1 and -2 suppress cell death and promote proliferation in prostate stromal cells. A role in stromal hyperplasia appears possible in BPH. Effects of NUAK silencing are mimicked by HTH01-015 and WZ4003. [ABSTRACT FROM AUTHOR]

This review summarises the presentations during a workshop session entitled “The Use of Soluble Guanylate Cyclase Activators to Treat Benign Prostatic Hyperplasia, Obstruction and Fibrosis – Mechanistic Concepts and Clinical Implications” at the International Continence Society (ICS) 2021 Melbourne Virtual meeting. Benign prostatic hyperplasia (BPH) is a highly prevalent condition that can result in bladder outflow obstruction (BOO) and development of lower urinary tract symptoms (LUTS), and by 80 years of age is present in about 75% of men. Current pharmacological therapies include α-adrenoceptor antagonists, 5α-reductase inhibitors, and the phosphodiesterase type 5 (PDE5) inhibitor, tadalafil. The efficacy of tadalafil suggests a role for nitric oxide (NO•) through activation of soluble guanylate cyclase (sGC) and production of cyclic guanosine 3’5’-monophosphate (cGMP), a cyclic nucleotide that relaxes smooth muscle, reduces neurotransmitter release and also acts as an antifibrotic agent. Patient refractoriness to tadalafil may be, for example, due to sGC inactivation due to oxidative stress. The workshop discussed the superiority of cinaciguat, an sGC activator that functions even when the enzyme is oxidised, over PDE5 inhibitors, and potentially its use in combination with agents that reduce formation of reactive oxygen species.

Introduction: Although microwave thermotherapy is becoming an almost forgotten therapy, occasional reports confirm that transurethral microwave thermotherapy (TUMT) still seems to be a good alternative for benign prostate hyperplasia (BPH). The aim of this study was to re-evaluate the advantages and disadvantages of TUMT. Materials and methods: The non-randomized study included 4590 patients with BPH. All patients were on pharmacological treatment. Prior to the study, patients underwent digital rectal examination (DRE), ultrasound examination, uro-dynamic examination, and prostatic specific antigen (PSA) concentration. Exclusion criteria included suspected prostate cancer on DRE, an ambiguous result of the urodynamic examination, suggesting a neurological component in lower urinary tract symptoms (LUTS), and elevated PSA concentration. In the end, 3329 patients were enrolled for further analysis. Of this group 2159 patients elected to receive TUMT. The others decided to continue their pharmacotherapy. Two questionnaires were used to evaluate the effect of TUMT on the relief of urinary symptoms and erectile dysfunction (ED). The International Prostate Symptom Score (IPSS) was used for LUTS and the International Index of Erectile Function-5 (IIEF-5) for ED. Results: After 6 months from thermotherapy, more than 50% of patients experienced an improvement in their urination (p < 0.0018), while in the pharmacological group only 30% did (p < 0.031). Approximately 28% of all patients regained erection. Before thermotherapy, only 12% reported no erection problems. In contrast, a further deterioration of erectile function (EF) was observed in the reference group (differences with TUMT at p < 0.0001). Apart from transient fever or temporary urinary retention, no serious complications were observed. Conclusions: It appears that TUMT is still a valuable option for BPH, especially in outpatient practice and for those patients who wish to protect their EF. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa), as the fifth leading cause of death, is the second most common cancer diagnosis in men worldwide. Human papillomavirus (HPV) can potentially contribute to PCa development and chronic inflammation. HPV infection leads to malignant and benign lesions in the genital areas of men and women. The data on the role of HPV in PCa development is contradictory. Objective: This study aims to investigate the frequency of HPV in PCa samples in hospitals in Tabriz City, Iran. Methods: This study was conducted in a cross-sectional descriptive manner. Paraffin tissue blocks including 50 patients with primary prostate adenocarcinoma and 50 patients with benign prostatic hyperplasia (BPH) were selected from Tabriz hospitals. All samples were examined for the presence of HPV16/18 by the polymerase chain reaction (PCR) method. Findings: 3 out of 50 PCa patients are infected with HPV18. None of the benign and malignant prostate samples are infected with HPV 16. Therefore, in our study, no connection exists between HPV and PCa. The Mean±SD age of HPV positive samples was 61.33±11.50 years. Conclusion: The result of this research does not support the role of HPV in the development of PCa. Therefore, additional studies are necessary to clarify the possible role of HPV in prostate carcinogenesis.

We aimed to review the current evidence on surgical and functional outcomes of Transperineal Laser Ablation for LUTS due to BPH. A comprehensive review of the English-language literature was performed using the MEDLINE and Web of Science databases until 1 August 2022, aiming to select studies evaluating TPLA for the treatment of LUTS due to BPH. Additional records were found from Google Scholar. Data were extracted and summarized in Tables. An appropriate form was used for qualitative data synthesis. Seven studies were included in the review, with all being single arm, non-comparative studies. In all studies, functional outcomes were evaluated with uroflowmetry parameters and validated questionnaires, showing a promising effectiveness at short- and mid-term follow-up. There is a lack of standardized pathways for preoperative assessment of patients suitable for TPLA, and even the technique itself has been reported with a few nuances. A good safety profile has been reported by all the authors. Although promising results have been reported by different groups, selection criteria for TPLA and few technical nuances regarding the procedure were found to be heterogeneous across the published series that should be standardized in the future. Further research is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: To compare the safety and efficacy of holmium laser enucleation of the prostate (HoLEP) and bipolar palsmakinetic enucleation of the prostate (BPEP) for patients with benign prostatic hyperplasia (BPH) and prostate volumes 50-120 mL. Methods: a total of 52 patients were prospectively randomized and enrolled in this study at Zagazig university hospitals. All patients were preoperatively evaluated using prostate volume measurement, the International Prostate Symptom Scores (IPSS) questionnaire, a quality-of-life (QoL) questionnaire and international index for erectile function-5 (IIEF-5). Measurement of maximum urinary flow rate (Qmax), post-void residual urine volume (PVR) and blood sample analysis for determination of prostate-specific antigen (PSA) and haemoglobin concentration. Patients were evaluated peri-operatively and postoperatively at 1, 3, 6 and 12 months with documentation of any complication. Results: Of 52 patients enrolled in this study, 47 patients completed 12 months of follow-up. There were statistically insignificant differences between both groups regarding the preoperative and intraoperative data. Perioperatively, bleeding, need for blood transfusion and hemoglobin drop were higher in the HoLEP group. There were no statistically significant differences in the post-operative follow-up data between both groups. Conclusion: In terms of surgical safety and efficacy BPEP is comparable to HoLEP for moderately to markedly enlarged prostates, with indication for surgical intervention. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the leading causes of cancer-related deaths among men worldwide. Research has shown that genetic variations can increase an individual's risk of developing this disease. In this study, we investigated the potential role of two genetic variants, one within RFX6 and another within SLC22A3, in predisposition to prostate cancer. A genetic association study was conducted, involving a case-control design with 112 prostate cancer cases and 95 individuals affected by benign prostatic hyperplasia who served as controls and had no history of cancer. The genotypes of the two variants, rs339331 in RFX6 and rs9364554 in SLC22A3, were determined using tetra-primer ARMS-PCR. In this study, a multi-stage strategy was employed to analyze the data obtained from genotyping and to assess the association of these two variants with prostate cancer risk. For statistical analysis, Chi-squared, Fisher's exact test and logistic regression were performed to evaluate the association of variants with prostate cancer and Gleason score. The results suggest that the rs9364554 variant in SLC22A3 is not associated with prostate cancer risk under either additive or multiplicative genetic models, while the variant in RFX6 is significantly associated with prostate cancer susceptibility. The TT genotype of rs339331 indicated a possible protective effect against prostate adenocarcinoma (CI 95% = 0/009 - 0/725, P-value = 0/009, OR = 0/083). In conclusion, our study provides evidence that the genetic variant rs339331 within RFX6 is significantly associated with prostate cancer susceptibility and may have a potential protective effect against prostate adenocarcinoma. It should be mentioned that more research is needed to investigate the possible protective effect of the TT genotype of rs9364554 against prostate cancer risk in other populations and various ethnic groups and particularly larger sample sizes are required to confirm this association. [ABSTRACT FROM AUTHOR]

Isoflavone-rich legumes, including soy, are used for food production, as dietary supplements and in traditional medicine. Soy consumption correlates negatively with benign prostatic hyperplasia (BPH) and voiding symptoms. However, isoflavone effects on the prostate are hardly known. Here, we examined the effects on human prostate smooth muscle contractions and stromal cell growth, which are driving factors of voiding symptoms in BPH. Smooth muscle contractions were induced in prostate tissues from radical prostatectomy. Growth-related functions were studied in cultured stromal cells (WPMY-1). Neurogenic, α1-adrenergic and non-adrenergic contractions were strongly inhibited with 50 µM and by around 50% with 10 µM genistein. Daidzein inhibited neurogenic contractions using 10 and 100 µM. Agonist-induced contractions were inhibited by 100 µM but not 10 µM daidzein. A combination of 6 µM genistein with 5 µM daidzein still inhibited neurogenic and agonist-induced contractions. Proliferation of WPMY-1 cells was inhibited by genistein (>50%) and daidzein (<50%). Genistein induced apoptosis and cell death (by seven-fold relative to controls), while daidzein induced cell death (6.4-fold) without apoptosis. Viability was reduced by genistein (maximum: 87%) and daidzein (62%). In conclusion, soy isoflavones exert sustained effects on prostate smooth muscle contractions and stromal cell growth, which may explain the inverse relationships between soy-rich nutrition, BPH and voiding symptoms. [ABSTRACT FROM AUTHOR]

Abstract Background Crinum latifolium L. (Amaryllidaceae) has been used in Southeast Asian traditional medicine to alleviate the symptoms of benign prostatic hyperplasia (BPH). The pathological mechanism of BPH is associated with the induction of prostate stromal cell proliferation through transforming growth factor-beta (TGF-β). Standardization as well as investigation of the potential anti-BPH activity of C. latifolium extract could benefit the further development of BPH-related analyses and provide evidence to support the application of this extract for BPH treatment. This study aimed to standardize and investigate the antiproliferative activity of the ethanolic extract of C. latifolium leaves. The major alkaloids isolated from C. latifolium were also explored for their potential use as bioactive markers. Methods Two major alkaloids were isolated from the ethanolic extract of C. latifolium leaves by chromatographic techniques, identified by NMR and MS, and quantified by a validated UHPLC method. Their antiproliferative activity was studied in human prostate stromal cells (WPMY-1) induced by TGF-β. The synergistic effect of combining the two major isolated alkaloids was analyzed by the zero interaction potency (ZIP) model. Results Two alkaloids, lycorine (1) and 6α-hydroxybuphanidrine (2), were isolated from the ethanolic leaf extract of C. latifolium. A UHPLC method for the quantification of (1) and (2) was developed and validated in terms of linearity, precision, and accuracy. The C. latifolium leaf extract contained 0.279 ± 0.003% (1) and 0.232 ± 0.004% (2). The crude extract was more potent than either (1) and (2) alone against TGF-β-treated WPMY-1 cell proliferation. The drug combination study revealed that the greatest synergistic effect of (1) and (2) was achieved at a 1:1 ratio. Conclusions The results of this study support the anti-BPH activity of C. latifolium in traditional medicine and suggest that these the two isolated alkaloids may promote the efficacy of the C. latifolium extract. Additionally, major alkaloids (1) and (2) can be used as bioactive markers for the standardization of C. latifolium extracts.

Purpose: To determine the potential effect of Chikusetsu saponin IVA (CS-IVA) on benign prostatic hyperplasia (BPH), as well as the mechanism of action. Methods: Benign prostatic hyperplasia epithelial cell response to treatment by CS-IVA was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation assay, and cell cycle analysis. Flow cytometry and immunoblot assay were used to assess the effect of CS-IVA on cell apoptosis. Mitochondrial damage was examined by JC-1 staining and immunoblot, while immunoblot assay was also performed to determine the effect of CS-IVA on JAK/STAT3 pathway. Results: CS-IVA inhibited the growth and cycle progression of BPH-1 cell but promoted cell apoptosis (p < 0.01). It also exacerbated mitochondrial damage in BPH-1 cell lines (p < 0.01). With regard to the mechanism of action, CS-IVA inhibited JAK/STAT3 pathway in BPH-1 cells (p < 0.01). Conclusion: CS-IVA induces apoptosis and mitochondrial dysfunction of BPH-1 cells by inhibiting JAK/STAT3 pathway, and thus it is a potential drug for the treatment of BPH. However, in vivo studies on the effect of CS-IVA are are required to validate these results. [ABSTRACT FROM AUTHOR]