Prostate Benign Prostatic Hyperplasia Research Articles

Activation of the cGMP/PKG/ERK signaling pathway associated with PDE5Is inhibits fibroblast activation by downregulating autophagy in early progressive benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is one of the most prevalent diseases affecting aging males. However, approximately, 8% of the BPH patients under 50-year-old experience remarkably early progression, for reasons that remain elusive. Among the various factors implicated in promoting BPH advancement, the activation of fibroblasts and autophagy hold particular importance. Our research endeavors to explore the mechanisms behind the accelerated progression in these patients. Immunohistochemistry and immunofluorescence were performed to detect the expression levels of LC3, p62, PDE5, and α-SMA in diverse BPH tissues and prostate stromal cells. The autophagy activator rapamycin, the autophagy suppressor chloroquine, and siRNA transfection were used to identify the impact of autophagy on fibroblast activation. Prostatic stromal fibroblasts in early progressive BPH tissues displayed activation of autophagy with an upregulation of LC3 and a concurrent downregulation of p62. After starvation or rapamycin treatment to a heightened level of autophagy, fibroblasts exhibited activation. Conversely, chloroquine treatment and ATG-7-knockdown effectively suppressed the level of autophagy and fibroblast activation. High expression of PDE5 was found in early progressive BPH stromal cells. The administration of PDE5 inhibitors (PDE5Is) hindered fibroblast activation through suppressing autophagy by inhibiting the ERK signaling pathway. Our findings suggest that autophagy plays a pivotal role in promoting BPH progression through fibroblast activation, while PDE5Is effectively suppress autophagy and fibroblast activation via the ERK signaling pathway. Nevertheless, further investigations are warranted to comprehensively elucidate the role of autophagy in BPH progression.

Perioperative changes in ganglioside monosialodihexosylganglioside (GM3) molecular species for benign prostatic hyperplasia: a preliminary report.

Benign prostatic hyperplasia (BPH) progresses with age and is associated with chronic inflammation. We focused on the relationship between BPH and ganglioside monosialodihexosylganglioside (GM3), a sialic acid-containing glycosphingolipid that is involved in chronic inflammation. GM3 molecular species would have a significant role in regulating inflammatory processes. In this prospective study, preoperative and postoperative serum samples were obtained from patients who underwent holmium laser enucleation of the prostate (HoLEP) for BPH. Preoperative and postoperative measurements of serum GM3 species were performed one month before and three months after HoLEP. Twenty-three patients were included in the study. The average patient age was 75 years, and the average prostate volume was 66 mL. The average weight of the surgically resected prostate tissue was 42 g. At three months after HoLEP, the serum concentration of GM3 species was found to have decreased after HoLEP compared with the preoperative concentration of GM3 species. Six GM3 species such as d18:1-17:0 [C17 acyl chain (-17:0) linked to a C18 sphingosine base with a double bond (d18:1-) by an amide linkage], were significantly reduced. The sample size was small; therefore, this study showed only preliminary results and could not evaluate prostate tissue inflammation. This study showed that the serum concentrations of several GM3 species, which indicate chronic inflammation, may be significantly reduced after BPH surgery.

Computerized metric assessment of glandular tissue volume within the peripheral zone of the prostate using combined magnetic resonance imaging and histopathology: Possible pathophysiological implications on prostate cancer development.

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are prevalent urological ailments in elderly males. Numerous clinical studies have revealed an invert association between BPH/prostate size and PCa growth. This study investigates the association between prostate size and total glandular tissue volume of the peripheral zone (GVPZ) using a unique blend of magnetic resonance imaging (MRI) and histo-anatomical imaging technique. Patients were selected who underwent both radical prostatectomy and preoperative MRI scans. MRI scans provided quantitative measurements of prostatic zone dimensions, while histo-anatomical slides yielded quantitative data on glandular density of the peripheral zone (PZ) using imaging software. Integration of MRI and histopathology enabled the assessment of the GVPZ. Statistical analysis identified relationships between total prostate volume (TPV) and GVPZ. Seventy-two patients were selected and 40 cc was determined to be the optimal cutoff for small-to-moderate versus large prostates. Once the two subgroups in TPV were formed, the relationship between TPV and GVPZ was found to be highly significant (p<0.001). The combination of MRI and histopathology offers a novel approach for precise quantification of glandular tissue within the prostatic PZ. This study corroborates the hypothesis of PZ compression via an enlarging transition zone in larger BPH prostates, resulting in PZ glandular atrophy. Given that most PCa originates in the PZ, these results shed light on the potential protective role of larger BPH prostates against PCa growth.

Endogenous Zinc-Ion-Triggered In Situ Gelation Enables Zn Capture to Reprogram Benign Hyperplastic Prostate Microenvironment and Shrink Prostate.

Benign prostatic hyperplasia (BPH) as the leading cause of urination disorder is still a refractory disease, and there have no satisfied drugs or treatment protocols yet. With identifying excessive Zn2+ , inflammation, and oxidative stress as the etiology of aberrant hyperplasia, an injectable sodium alginate (SA) and glycyrrhizic acid (GA)-interconnected hydrogels (SAGA) featuring Zn2+ -triggered in situ gelation are developed to load lonidamine for reprogramming prostate microenvironment and treating BPH. Herein, SAGA hydrogels can crosslink with Zn2+ in BPH via coordination chelation and switch free Zn2+ to bound ones, consequently alleviating Zn2+ -arisen inflammation and glycolysis. Beyond capturing Zn2+ , GA with intrinsic immunoregulatory property can also alleviate local inflammation and scavenge reactive oxygen species (ROS). Intriguingly, Zn2+ chelation-bridged interconnection in SAGA enhances its mechanical property and regulates the degradation rate to enable continuous lonidamine release, favoring hyperplastic acini apoptosis and further inhibiting glycolysis. These multiple actions cooperatively reprogram BPH microenvironment to alleviate characteristic symptoms of BPH and shrink prostate. RNA sequencing reveals that chemotaxis, glycolysis, and tumor necrosis factor (TNF) inflammation-related pathways associated with M1-like phenotype polarization are discerned as the action rationales of such endogenous Zn2+ -triggered in situ hydrogels, providing a candidate avenue to treat BPH.

Inhibiting CBP Decreases AR Expression and Inhibits Proliferation in Benign Prostate Epithelial Cells.

(1) Background: CREB-binding protein (CBP) is a key transcriptional coactivator of androgen receptors (AR). We conducted this study to investigate the effects of CBP on AR expression and proliferation in benign prostatic hyperplasia (BPH) prostate epithelial cells. (2) Methods: By analyzing a published data set, we found that CBP was closely related to the gene expression of AR in prostate cells. We enrolled 20 BPH patients who underwent transurethral resection of the prostate (TURP) in Peking University First Hospital in 2022, and analyzed the expressions of CBP and AR in BPH prostate tissues. Then, we used ICG-001 and shRNA to inhibit CBP in prostate epithelial cells (BPH-1 cells and RWPE-1 cells), and conducted immunofluorescence, cell viability assay, flow cytometry analysis, and Western blot to analyze the effects of CBP on AR expression and proliferation in prostate epithelial cells. We also studied the interaction between CBP and AR through a co-immunoprecipitation assay. (3) Results: CBP is consistent with AR in expression intensity in prostate tissues. Inhibiting CBP decreases AR expression, and induces proliferation inhibition, apoptosis, and cell cycle arrest in BPH prostate epithelial cells. The co-immunoprecipitation assay showed that CBP binds with AR to form transcription complexes in prostate epithelial cells. (4) Conclusions: Inhibiting CBP decreases AR expression and inhibits proliferation in benign prostate epithelial cells. CBP may be a potential target to affect AR expression and the proliferation of prostate epithelial cells in BPH.

Five-alpha reductase inhibitors and risk of prostate cancer among men with benign prostatic hyperplasia: A historical cohort study using primary care data

Background: Five-alpha reductase inhibitors (5ARIs) are used in the management of benign prostatic hyperplasia (BPH). 5ARIs prevent the conversion of testosterone to dihydrotestosterone, which is important in prostate development. It has been suggested that 5ARIs can be used a chemopreventative agent for prostate cancer. The aim of this study was to assess the risk of prostate cancer associated with 5ARI use among men with BPH. Methods: Using Clinical Practice Research Datalink (CPRD) from 1992 to 2011 in UK, prostate cancer risk was retrospectively compared in men with a new diagnosis of BPH, with no history of prostate cancer who were treated with 5ARIs, to men treated with alpha blockers (ABs) and those given no pharmacological treatment. Incidence rate of prostate cancer was calculated by treatment group; the association between BPH treatment group and prostate cancer was estimated by a multivariate Cox model. Results: 77,494 men with newly diagnosed BPH were included. The crude incidence rate of prostate cancer was 892.4 cases per 100,000 person-years amongst those treated with 5ARIs, compared with 1209.0 and 1542.9 in those treated with ABs and untreated individuals, respectively. The HR adjusted for potential confounders was 0.79 (0.72-0.86) for 5ARI vs ABs and 0.72 (0.66-0.79) for 5ARI vs untreated. After excluding the first year after BPH diagnosis, adjusted HRs attenuated to 0.87 (0.79-0.97) for 5ARI vs ABs and 0.97 (0.87-1.08) for 5ARI vs untreated. Conclusion: Among men diagnosed with BPH, we found evidence of lower risks of subsequent prostate cancer in those treated with 5ARIs, but this appeared to be driven by cases diagnosed within a year of BPH, possibly reflecting prevalent prostate cancers that were initially misdiagnosed. After excluding the first year after BPH diagnosis, there was little evidence of a reduced prostate cancer risk in those taking 5ARIs.

LBA01-01 UROPATHOGENS IN THE PROSTATE ARE ASSOCIATED WITH PROSTATE SIZE, INDEPENDENT OF AGE EFFECTS

You have accessJournal of UrologyCME1 Apr 2023LBA01-01 UROPATHOGENS IN THE PROSTATE ARE ASSOCIATED WITH PROSTATE SIZE, INDEPENDENT OF AGE EFFECTS Alec Sun, Prajit Khooblall, Juan Sebastian Rodriguez-Alvarez, Smita De, and Aaron Miller Alec SunAlec Sun More articles by this author , Prajit KhooblallPrajit Khooblall More articles by this author , Juan Sebastian Rodriguez-AlvarezJuan Sebastian Rodriguez-Alvarez More articles by this author , Smita DeSmita De More articles by this author , and Aaron MillerAaron Miller More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003360.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) affects an estimated 70% of men between the ages of 60-69, yet the etiology is not well understood. Recently, the human urinary tract microbiome has been associated with a variety of urologic diseases, especially those mediated by an inflammatory pathway. Here, we sought to determine associations between age-independent prostate size and microbiome. METHODS: Men over 18 years old undergoing Holmium Laser Enucleation of the Prostate (HoLEP) for BPH with no history of prostate cancer, prostate surgery, or pelvic radiation were recruited. Patients were excluded if they had a positive preprocedural urine culture, recent UTI requiring antibiotics, bladder stones, or if they were catheter-dependent due to obstruction. From each patient, prostate tissue, midstream urine, and urethral and specimen container swabs were collected. All non-prostate samples were used as contamination controls. Patient data such as age, prostate-specific antigen (PSA) level, BPH symptoms, and prostate size were recorded. All samples underwent DNA extraction, 16S sequencing, and analysis in R statistical software. After quality control, reads associated with the controls were removed. High-quality, decontaminated data were assessed for diversity (alpha, beta, taxonomy). The correlation between amplicon sequence variants (ASVs) and patient metrics were quantified through Sparcc correlations, which was designed for count matrix correlations. RESULTS: 20 patients qualified, consented, and were analyzed in this study. Mean age was 68.6 years, mean PSA was 3.4 ng/mL, and mean prostate size was 107.9 g. After bioinformatic decontamination of samples with the negative controls, diversity analyses showed site-specific differences between the urine, urethral swab, and prostate microbiomes were greater than inter-individual variability, indicative of distinct microbiomes. Common uropathogens were positively associated with prostate size. These included five ASVs belonging to Enterobacter cloaceae (p=0.02-0.03), four Planococcaceae ASVs (p=0.008-0.03), and four Acinetobacter (p=0.014-0.026). Only one ASV in the Ralstonia genus exhibited a significant association with age (p=0.015). CONCLUSIONS: This study is the first to characterize the prostatic microbiome in BPH and to link prostate size to specific common bacterial uropathogens while controlling for age and contamination. Further research with a larger sample size and culturomics will provide insight into the mechanisms of how the prostate microbiome contributes to enlarged size. Source of Funding: Endourology Society Summer Student Scholarship © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1176 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alec Sun More articles by this author Prajit Khooblall More articles by this author Juan Sebastian Rodriguez-Alvarez More articles by this author Smita De More articles by this author Aaron Miller More articles by this author Expand All Advertisement PDF downloadLoading ...

MP13-06 AQUABLATION FOR BENIGN PROSTATIC HYPERPLASIA IN LARGE PROSTATES (80-150 ML): FINAL 5-YEAR RESULTS

You have accessJournal of UrologyCME1 Apr 2023MP13-06 AQUABLATION FOR BENIGN PROSTATIC HYPERPLASIA IN LARGE PROSTATES (80-150 ML): FINAL 5-YEAR RESULTS Naeem Bhojani and Mitchell R. Humphreys Naeem BhojaniNaeem Bhojani More articles by this author and Mitchell R. HumphreysMitchell R. Humphreys More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003233.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To report 5-year safety and efficacy outcomes of the Aquablation procedure for the treatment of men with symptomatic benign prostatic hyperplasia (BPH) and large-volume prostate glands. METHODS: 101 men with moderate-to-severe BPH symptoms and prostate volumes between 80-150 mL underwent a robotic-assisted Aquablation procedure in a prospective multicenter international trial. Herein we report the final 5-year results. RESULTS: The study successfully met its safety and efficacy performance goal, which was based upon TURP outcomes typically done in smaller prostates, at three months. Mean prostate volume was 107 mL (range 80-150 mL). Mean operative time (TRUS in to catheter in), was 55 minutes (range 24-111 minutes) and mean Aquablation resection time was 8 minutes (range 2.5-17 minutes). Most (89%) adverse events were low grade defined as either non-procedure related or Clavien-Dindo grade 2 or less. There was no reported de novo erectile dysfunction and 15% of patients developed ejaculatory dysfunction. The TRUS results showed a 42% reduction in prostate volume at 3 months, which aligned to the 44% reduction in serum PSA at 6 months. At 5-years, IPSS scores improved from 23.2 at baseline to 6.9 and Qmax improved from 8.7 cc/sec at baseline to 18.6 cc/sec. Improvements in both IPSS, IPSS Quality of Life, Qmax, and PVR were immediate (p<.0001) and sustained (p<.0001) throughout the follow-up period, Figure 1. The annualized retreatment rate was less than 1% per year. CONCLUSIONS: At 5-year of prospective follow-up, the Aquablation procedure was shown to be safe and effective in men with large prostates (80-150 mL). ClinicalTrials.gov number, NCT03123250. Source of Funding: Procept BioRobotics © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e175 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Naeem Bhojani More articles by this author Mitchell R. Humphreys More articles by this author Expand All Advertisement PDF downloadLoading ...

MP76-06 WATER VAPOR THERMAL THERAPY FOR BPH: IS LESS MORE?

You have accessJournal of UrologyCME1 Apr 2023MP76-06 WATER VAPOR THERMAL THERAPY FOR BPH: IS LESS MORE? Michelle C. Leach, Vi Nguyen, Clara Cerrato, Mimi V. Nguyen, and Seth K. Bechis Michelle C. LeachMichelle C. Leach More articles by this author , Vi NguyenVi Nguyen More articles by this author , Clara CerratoClara Cerrato More articles by this author , Mimi V. NguyenMimi V. Nguyen More articles by this author , and Seth K. BechisSeth K. Bechis More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003350.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Water vapor thermal therapy is an effective treatment for lower urinary tract symptoms (LUTS) from benign prostatic hyperplasia (BPH) but can be associated with short term post-procedural irritative voiding symptoms. We sought to evaluate the effect of a minimal approach of water vapor thermal therapy (Rezum, Boston Scientific, Marlborough, MA, USA), defined as 1 vapor treatment per prostate lobe, on urinary symptoms and quality of life (QOL) compared to patients who received multiple treatments per lobe. METHODS: We performed a single-institution retrospective review of patients who underwent water vapor therapy for the treatment of symptomatic BPH from February 2017 to September 2022. Propensity score matching was utilized to generate patient cohorts based on the number of treatments per lobe (1 per lobe including median lobe if present vs ≥2 per lobe) matched for age, BMI, and pre-operative prostate volume (cc). Primary outcome of interest was post-operative complications and irritative symptoms. Secondary outcomes included differences in International Prostate Symptom Score (IPSS) and QOL sub score at baseline and at 1, 3, 6, and 12 months after the procedure. RESULTS: 146 patients were included in the PSM with 73 patients who received one vapor treatment per lobe and 73 patients receiving 2 or more treatments per lobe. DEMOGRAPHICS TABLE (Table 1a). On MVA, an increasing number of treatments (HR 1.3, p=0.039) and treatment of the median lobe (HR 4.7, p=0.008) were significant risk factors for adverse events after REZUM. On MVA looking at risk of post-op urinary retention, only increasing number of treatments (HR 1.6, p=0.005) was an independent risk factor while use of BPH medications, prostate volume, and median lobe treatment were not (p=0.3-0.72). Patient’s with minimal treatment had improved IPSS total and voiding sub-score at 1 month and non-inferior IPSS scores at 3-, 6-, and 12- month follow-up. CONCLUSIONS: Minimal Rezum treatment approach with a single water vapor injection per lobe is a safe and effective option for patients undergoing long-term treatment for BPH and is associated with improved postoperative complications and irritative voiding symptoms. Further studies are needed to investigate the effect of this minimal approach on longer-term outcomes. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1092 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michelle C. Leach More articles by this author Vi Nguyen More articles by this author Clara Cerrato More articles by this author Mimi V. Nguyen More articles by this author Seth K. Bechis More articles by this author Expand All Advertisement PDF downloadLoading ...

Association between prostate size and glandular tissue volume of the peripheral zone via novel combined MRI and histopathology: possible pathophysiological implications on prostate cancer development.

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most prevalent urologic diseases affecting elderly men. An inverse relationship between BPH/prostate size and PCa incidence is well documented in the current literature, but the precise mechanism is poorly understood. This study aims to investigate the effect of total prostate volume on total glandular tissue volume of the peripheral zone via a novel combination of magnetic resonance imaging (MRI) and histo-anatomical imaging. 42 male patients between ages 53-79 years underwent both radical prostatectomy and pre-operative MRI scans. Prostate sizes ranged from 14.8-133.3cc. Quantitative measurements of surgical capsule thickness and glandular epithelial cell density within the peripheral zone (PZ) were obtained on histo-anatomical slides using computer-based imaging software. Quantitative prostatic zonal measurements were obtained from MRI scans. Combining MRI- and histopathology-obtained parameters allowed measurement of the total glandular tissue volume of the PZ (GVPZ). Statistical analysis was performed to identify associations between total prostate volume (TPV) and GVPZ. The Mann-Whitney U-test showed significant decreases in GVPZ in larger prostates when compared to smaller prostates. Combined MRI and histopathology techniques provide a novel method for accurate measuring of glandular tissue content within the prostatic PZ. The findings of this pilot study support the hypothesis of PZ compression by an expanding transition zone in large BPH prostates, leading to atrophy of PZ glandular tissue. As the majority of PCa originates in the PZ, this dynamic process may explain the protective effect of large BPH prostates against PCa development.

Upregulation of mir-1199-5p is associated with reduced type 2 5-α reductase expression in benign prostatic hyperplasia

Background5-α reductase inhibitors (5-ARIs) are first-line drugs for managing benign prostatic hyperplasia (BPH). Unfortunately, some patients do not respond to 5-ARI therapy and may even show worsening symptoms. The decreased expression of steroid 5-α reductase type 2(SRD5A2) in BPH tissues may explain the failure of 5-ARI therapy, however, the mechanisms underlying SRD5A2 decreased remained unelucidated.ObjectivesTo investigate microRNA-mediated regulation of the expression of SRD5A2 resulting in 5-ARI therapy failure.Materials and methodsThe expression of SRD5A2 and microRNAs in BPH tissues and prostate cells were detected by immunohistochemistry, western blotting, and quantitative real-time PCR. Dual-luciferase reporter assay was performed to confirm that microRNA directly combine to SRD5A2 mRNA. The apoptosis of prostatic cells was detected by flow cytometry.ResultsSRD5A2 expression was variable; it was negative, weak, and strong in 13.6%, 28.8%, and 57.6% of BPH tissues respectively. The normal human prostatic epithelial cell line RWPE-1 strongly expressed SRD5A2, whereas the immortalized human prostatic epithelial cell line BPH-1 weakly expressed SRD5A2. miR-1199-5p expression was remarkably higher in BPH-1 than in RWPE-1 cells(P<0.001), and miR-1199-5p expression was significantly upregulated in BPH tissues with negative SRD5A2 expression than those with positive SRD5A2 expression. Transfection of miR-1199-5p mimics in RWPE-1 cells led to a marked decrease in SRD5A2 expression, whereas miR-1199-5p inhibitor increased SRD5A2 expression in BPH-1 cells. Dual-luciferase reporter assay showed that miR-1199-5p could bind the 3′untranslated region of SRD5A2 mRNA. miR-1199-5p also decreased the RWPE-1 sensibility to finasteride, an inhibitor of SRD5A2.ConclusionOur results show that SRD5A2 expression varies in BPH tissues and miR-1199-5p might be one of the several factors contributing to differential SRD5A2 expression in BPH patients.

RNA sequencing and integrative analysis reveal pathways and hub genes associated with TGFβ1 stimulation on prostatic stromal cells.

Objective: Benign prostatic hyperplasia (BPH) is the most common urological disease in elderly men. The transforming growth factor beta 1 (TGFβ1) plays an important role in the proliferation and differentiation of BPH stroma. However, it is not clear yet which important pathways and key genes are the downstream of TGFβ1 acting on prostatic stromal cells. Methods: GSE132714 is currently the newer, available, and best high-throughput sequencing data set for BPH disease and includes the largest number of BPH cases. We examined the TGFβ1 expression level in BPH and normal prostate (NP) by analyzing the GSE132714 data set as well as carrying out immunohistochemistry of 15 BPH and 15 NP samples. Primary prostatic stromal cells (PrSCs) were isolated from five fresh BPH tissues. RNA sequencing and bioinformatics analysis were used to reveal important pathways and hub genes associated with TGFβ1 stimulation on PrSCs. Results: TGFβ1 was upregulated in BPH stroma compared to NP stroma. A total of 497 genes (244 upregulated and 253 downregulated) were differentially expressed in PrSCs with and without TGFβ1 stimulation. The Gene Ontology revealed that differentially expressed genes (DEGs) were mainly enriched in progesterone secretion, interleukin-7 receptor binding, and CSF1-CSF1R complex. The Wnt signaling pathway, PI3K−Akt signaling pathway, JAK−STAT signaling pathway, and Hippo signaling pathway were screened based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. FN1, SMAD3, CXCL12, VCAM1, and ICAM1 were selected as hub genes according to the degree of connection from the protein–protein interaction (PPI) network. Conclusion: This study sheds some new insights into the role of TGFβ1 in BPH stroma and provides some clues for the identification of potential downstream mechanisms and targets.

Association Between Prostate Size and MRI Determined Quantitative Prostate Zonal Measurements.

PurposeBenign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most prevalent and common urologic diseases impacting elderly men. The current literature has well documented an inverse relationship between prostate/BPH-size and incidence of PCa, but the exact interaction between these two disease entities is not well understood. The purpose of this study is to analyze prostatic zonal measurements with magnetic resonance imaging (MRI) in order to investigate the dynamic changes of the transition zone (TZ) and peripheral zone (PZ) in response to prostate/BPH growth.MethodsMultiparametric magnetic resonance imaging (mpMRI) scans of 430 consecutive male patients aged 18–89 years were obtained to measure the different zonal areas of the prostate. The data were statistically analyzed to identify specific associations between the different measurement parameters and total prostate volume (TPV).ResultsThe Mann–Whitney U-test showed a significant decline of the average peripheral zone thickness (PZT) (z = −4.5665, p < 0.0001) in larger prostates when compared to smaller prostates. The Spearman correlation between TPV and PZT demonstrated a significant negative correlation (−0.20, p < 0.0001).ConclusionThe data revealed that PZT was significantly smaller in the subgroup of patients with higher TPV. This supports the hypothesis of PZ compression and thinning caused by the growing and expanding TZ in BPH prostates. This dynamic growth-related process in the different prostatic zones may explain the protective effect of BPH against PCa.

Evolving Hypothesis that Prostate/BPH Size Matters in Protection against Prostate Cancer

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two predominant urologic diseases affecting aging men. As a matter of fact, 95–98% of elderly men with prostate as their “primary organ disease” for consulting urologists have either the clinical diagnosis of BPH, PCa or both. Other primary diagnoses of the prostate such as sarcoma, lymphoma or isolated bacterial prostatitis (not in the context of a systemic urinary tract infection) are rare entities. Although BPH and PCa are very common, their interaction is currently not well understood. Numerous clinical studies and meta-analysis reviews have demonstrated a negative correlation between prostate BPH size and the probability of PCa presence, but little is known to explain this clinical phenomenon. Recent histo-anatomical and magnetic resonance imaging studies have revealed data leading to a hypothesis indicating the expanding transition zone (TZ) in a growing BPH prostate causes mechanical stress within the peripheral zone (PZ) with secondary fibrosis and atrophy of the glands within the PZ. This dynamic interaction of the TZ against the PZ in a growing BPH-prostate could explain the negative correlation between BPH size and PCa incidence. The purpose of this review is to present and discuss the evolving hypothesis that prostate size may matter and be protective against prostate cancer.

MP29-08 AQUABLATION FOR BENIGN PROSTATIC HYPERPLASIA IN LARGE PROSTATES (80-150CC): 4-YEAR RESULTS

You have accessJournal of UrologyCME1 May 2022MP29-08 AQUABLATION FOR BENIGN PROSTATIC HYPERPLASIA IN LARGE PROSTATES (80-150CC): 4-YEAR RESULTS Naeem Bhojani Naeem BhojaniNaeem Bhojani More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002572.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To report 4-year safety and efficacy outcomes of the Aquablation procedure for the treatment of men with symptomatic benign prostatic hyperplasia (BPH) and large-volume prostates. METHODS: 101 men with moderate-to-severe BPH symptoms and prostate volumes between 80-150cc underwent robotically executed Aquablation in a prospective multicenter international clinical trial with scheduled follow-up at 5 years. Herein we report the 4 year data. RESULTS: Mean prostate volume was 107cc (range 80-150). Mean operative time, TRUS in to catheter in, was 55 minutes and mean Aquablation resection time was 8 minutes. IPSS scores improved from 23.2 at baseline to 5.6 at 4 years (change of -16.6 points, p<.0001). Qmax improved from 8.7 cc/sec at baseline to 18.2 cc/sec at 4 years. Improvements in both IPSS, IPSS Quality of Life, Qmax, and PVR were immediate and sustained throughout follow-up (Figure 1). At 4 years the retreatment rate was less than 1% per year. CONCLUSIONS: At 4-year prospective follow-up, the Aquablation procedure was shown to be safe and effective in men with large prostates (80-150cc). ClinicalTrials.gov number, NCT03123250.*Submitted on behave of the Water II investigators. Source of Funding: Procept Biorobotics © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e472 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Naeem Bhojani More articles by this author Expand All Advertisement PDF DownloadLoading ...

PD16-11 TRANS-ETHNIC GENOME-WIDE ASSOCIATION STUDY REVEALS NEW THERAPEUTIC TARGETS FOR BENIGN PROSTATIC HYPERPLASIA

You have accessJournal of UrologyCME1 May 2022PD16-11 TRANS-ETHNIC GENOME-WIDE ASSOCIATION STUDY REVEALS NEW THERAPEUTIC TARGETS FOR BENIGN PROSTATIC HYPERPLASIA Michael Ng, Koichi Matsuda, Chizu Tanikawa, Chikashi Terao, Yoichiro Kamatani, Wei Wang, Adam Auton, 23andme Research Team, Benjamin Turney, Richard Bryant, and Dominic Furniss Michael NgMichael Ng More articles by this author , Koichi MatsudaKoichi Matsuda More articles by this author , Chizu TanikawaChizu Tanikawa More articles by this author , Chikashi TeraoChikashi Terao More articles by this author , Yoichiro KamataniYoichiro Kamatani More articles by this author , Wei WangWei Wang More articles by this author , Adam AutonAdam Auton More articles by this author , 23andme Research Team More articles by this author , Benjamin TurneyBenjamin Turney More articles by this author , Richard BryantRichard Bryant More articles by this author , and Dominic FurnissDominic Furniss More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002548.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is a common condition affecting men in and beyond middle age, causing significant morbidity. Medical treatments comprise a small number of pharmacological agents, and patients often progress to require surgery. There is an unmet clinical need to identify genomic drivers of BPH progression requiring surgery, and to identify novel targets for pharmacological intervention. METHODS: We performed a large genome-wide association study of BPH in 126,082 subjects from UK Biobank, with replication in 44,093 subjects from the RIKEN Japanese biobank, and 756,878 subjects from 23andMe (total 110,916 BPH cases and 816,137 controls). We investigated candidate genes using differential expression between single cell subtypes in samples from BPH versus normal prostate. A genetic risk score for BPH was constructed to assess its use for prognostication. Therapeutic targets were identified from the Open Targets platform. RESULTS: We identified 17 BPH-associated loci. Two loci were only associated with this condition in men of Western European or Japanese origin, and represent ethnicity-specific risk alleles. We demonstrated differential expression of associated genes in cells derived from BPH compared to normal prostate. For example, we provide evidence that the homeobox gene NKX3.1 specifically plays a role in BPH in basal epithelial cells. Patients with BPH managed with surgery had a higher genetic risk score than those managed conservatively or with non-surgical treatment. Several genes implicated in our genetic analysis are tractable to therapeutic targeting or drug repurposing, and represent attractive targets for new therapeutic development. CONCLUSIONS: These results point to important genes driving the pathophysiology of BPH, and reveal promising candidates for future therapeutic development. Our proof-of-principle that the genetic risk score correlates with the severity of BPH, and the need for surgery, provides a first step towards personalised medicine in the management of this common condition. Source of Funding: This work was co-funded by co-funded by the John Black Foundation and the Rosetrees Trust, with funding administered by The Urology Foundation. The BioBank Japan project was supported by the Ministry of Education, Culture, Sports, Sciences and Technology Japan and the Japan Agency for Medical Research and Development. The funders had no role in the design of the study, the collection, analysis or interpretation of data, the writing of the manuscript, or the decision to publish the results. We would like to thank the research participants and employees of 23andMe for making this work possible © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e272 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Ng More articles by this author Koichi Matsuda More articles by this author Chizu Tanikawa More articles by this author Chikashi Terao More articles by this author Yoichiro Kamatani More articles by this author Wei Wang More articles by this author Adam Auton More articles by this author 23andme Research Team More articles by this author Benjamin Turney More articles by this author Richard Bryant More articles by this author Dominic Furniss More articles by this author Expand All Advertisement PDF DownloadLoading ...

Association of prostate size with capsule thickness and glandular epithelial cell density: The possible clinical implications on prostate cancer development

Objective: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most common urologic diseases in aging males. The negative association between prostate/BPH size and incidence of PCa is well documented in the literature. However, the exact mechanism is not well understood. This study aims to further investigate the possible effect of prostate volume on prostate capsule thickness and glandular cell density in the prostatic peripheral zone (PZ). Materials and Methods: A total of 100 patients were selected that had undergone radical prostatectomy with prostate sizes ranging from 20 to 160 mL. Quantitative measurements of capsule thickness and density of epithelial glands within the peripheral zone not affected by cancer were analysed and calculated on histo-anatomical slides using computer-based imaging software. Associations between the different variables were calculated using Spearman correlation with 95% confidence intervals (CIs). Results: In the non-cancerous areas of the PZ, prostate volume and average capsule thickness are positively associated ( rs = +0.6526, 95% CI +0.5233 to +0.7526, p &lt; 0.0001), while prostate volume and average glandular epithelial cell density of the PZ are negatively associated ( rs = −0.6011, 95% CI −0.7133 to −0.4589, p &lt; 0.0001). These associations remain consistent on subgroup analysis. Conclusion: The findings of this study support the hypothesis that transition zone (TZ) growth in large BPH prostates may cause pressure on the outer PZ, leading to fibrosis and atrophy of the glandular tissue. This may provide a protective effect against PCa, as most PCa originates in the PZ of the prostate. Level of evidence: Not applicable

Clinicopathological correlation of p53 expression in benign prostatic hyperplasia and prostate adenocarcinoma

Prostate adenocarcinoma is the 6 most common carcinoma in men worldwide. It is usually a cancer of the elderly age group. Benign prostatic hyperplasia is a common cause of urinary incontinence and urine flow symptoms, usually seen in the middle along with elderly age group. In this study we have evaluated the expression of p53 immunohistochemistry (IHC) in prostate adenocarcinoma with benign prostatic hyperplasia along with its diagnostic, treatment and prognostic implications.: 1. Assessment of clinical and biochemical parameters in patients with benign prostatic hyperplasia (BPH) and prostate adenocarcinoma. 2. To assess p53(IHC) expression in benign prostatic hyperplasia and prostate adenocarcinoma : The study population comprised of a subset of patients who came to Ramaiah hospital, Bangalore from May 2018 till June 2019, for treatment regarding prostate related symptoms. The clinicodemographic data was collected and prostate biopsies were taken for which histopathological assessment was done. A total of 60 cases comprising of 30 cases of BPH and 30 cases of prostatic adenocarcinoma was subjected to p53 immunohistochemistry. The results were tabulated and statistically analyzed for significance.The present prospective study was conducted on 60 patients with 30 cases (50%) of BPH and 30 cases (50%) of prostatic adenocarcinoma. Based on the tumor differentiation there was 1 case (3.3%) of well differentiated carcinoma, 18 cases(60%) of moderately differentiated carcinoma and 11cases (36.6%) of poorly differentiated carcinomas. We observed an inverse relationship between p53 expression and histological grade. All poorly differentiated carcinoma had higher p53(&amp;#62;50% expression). There was statistically significant difference in expression of p53 between cases of BPH and carcinoma prostate, indicated by P value of &amp;#60;0.05. Among prostate carcinomas p53 had higher expression on those cases with Gleason score 9 and 10.: P53 expression directly correlates with Gleason score, while inversely correlating with tumor differentiation of prostate carcinoma cases. The expression of p53 is low in BPH as compared to that of prostate cancers. Hence it can be used as a good diagnostic and prognostic marker in prostate carcinoma.

A0891 - Aquablation for benign prostatic hyperplasia in large prostates (80-150cc): 4-year results

Abstract OBJECTIVE To report 12-month safety and effectiveness outcomes of the Aquablation procedure for the treatment of men with symptomatic benign prostatic hyperplasia (BPH) and large-volume prostates. METHODS One hundred and one men with moderate-to-severe BPH symptoms and prostate volumes of 80-150 cc underwent a robotic-assisted Aquablation procedure in a prospective multicenter international clinical trial. Functional and safety outcomes were assessed at 12 months postoperatively. RESULTS Mean prostate volume was 107 cc (range 80-150). Mean operative time was 37 minutes and mean Aquablation resection time was 8 minutes. The average length of hospital stay following the procedure was 1.6 days. Mean International Prostate Symptom Score improved from 23.2 at baseline to 6.2 at 12 months (P 100 at baseline). Antegrade ejaculation was maintained in 81% of sexually active men. No patient underwent a repeat procedure for BPH symptoms. There was a 2% de novo incontinence rate at 12 months, and 10 patients did require a transfusion postoperatively while 5 required take back fulgurations. At 12 months, prostate-specific antigen reduced from 7.1 ± 5.9 ng/mL at baseline to 4.4 ± 4.3 ng/mL. CONCLUSION The Aquablation procedure is demonstrated to be safe and effective in treating men with large prostates (80-150 cc) after 1 year of follow-up, with an acceptable complication rate and without a significant increase in procedure or resection time compared to smaller sized glands. ClinicalTrials.gov number, NCT03123250.

SIGNIFICANCE OF DETECTION OF FREE/TOTAL PSA RATIO AND OTHER BIOCHEMICAL PARAMETERS IN PATIENTS WITH BPH, CARCINOMA PROSTATE AND ITS CLINICOPATHOLOGIC CORRELATION

Background. Benign prostatic hyperplasia (BPH) can raise prostate-specific antigen (PSA) levels two to three times higher than the normal level. An increased PSA level does not indicate Prostate Cancer (PCa), but the higher the PSA level, the higher the chance of having PCa. Detection and treatment have been profoundly affected by the advent of Free/Total PSA ratio testing. Objectives. The aim of the study was to estimate free, total PSA levels and its ratio for serum levels of calcium, acid phosphatase and alkaline phosphatase in patients with BPH and PCa; to correlate clinical, biochemical and histopathological findings in the above patients. Methods. PSA levels were detected by Chemiluminescent assay; serum calcium – by Modified Arsenazo method; serum acid phosphatase – by Doumas et al method; and Alkaline phosphatase – by Lowry et al method. Results. Present study found high levels of total PSA in BPH and PCa. Levels of free PSA were high in BPH as compared to PCa rate. Free/Total PSA ratio is reduced considerably in PCa as compared to BPH. Serum acid phosphatase and alkaline phosphatase were considerably higher in PCa as compared to BPH. Serum calcium levels did not show significant difference in control and study groups. Conclusions. It was established that patients with PCa have a greater fraction of bound PSA and a lower percentage of free PSA than in those without PCa. Therefore, in clinical practice Free/Total PSA ratio helps clinicians to decide if a biopsy is necessary. Objectives: The study was carried out with the following objectives: to estimate free, total PSA levels and calculate Free/Total PSA ratio in patients with BPH and Carcinoma Prostate, to study the serum levels of calcium, acid phosphates, and alkaline phosphatase in patients with BPH and PCa. and to correlate clinical, biochemical and histopathological findings in the above patients. Methods. Free and total PSA levels were detected by Chemiluminescent assay; Serum Calcium was detected by Modified Arsenazo method. Serum acid phosphatase was detected by Doumas et al method and Alkaline phosphatase were detected by Lowry et al method Results: Present study found high levels of Total PSA in BPH and PCa. Levels of free PSA were high in BPH as compared to PCa ate. Free /Total PSA ratio is reduced considerably in PCa as compared to BPH. Serum acid phosphatase and alkaline phosphatase were slightly raised in PCa as compared to BPH. Serum calcium levels did not show a significant difference in control and study groups. Conclusion: We concluded that patients with PCa have a greater fraction of bound PSA and a lower percentage of free PSA than in men without PCa. There was a negative correlation found between the free/total PSA ratio and the histopathologic findings. The lower the ratio higher is the grade of malignancy. Therefore in clinical practice Free/Total PSA ratio helps clinicians to decide if a biopsy is necessary