The FGF/FGFR system in the physiopathology of the prostate gland.

Fibroblast growth factors (FGFs) are a family of proteins possessing paracrine, autocrine, or endocrine functions in a variety of biological processes, including embryonic development, angiogenesis, tissue homeostasis, wound repair, and cancer. Canonical FGFs bind and activate tyrosine kinase FGF receptors (FGFRs), triggering intracellular signaling cascades that mediate their biological activity. Experimental evidence indicates that FGFs play a complex role in the physiopathology of the prostate gland that ranges from essential functions during embryonic development to modulation of neoplastic transformation. The use of ligand- and receptor-deleted mouse models has highlighted the requirement for FGF signaling in the normal development of the prostate gland. In adult prostate, the maintenance of a functional FGF/FGFR signaling axis is critical for organ homeostasis and function, as its disruption leads to prostate hyperplasia and may contribute to cancer progression and metastatic dissemination. Dissection of the molecular landscape modulated by the FGF family will facilitate ongoing translational efforts directed toward prostate cancer therapy.

Estrogens in Male Physiology.

Estrogens have historically been associated with female reproduction, but work over the last two decades established that estrogens and their main nuclear receptors (ESR1 and ESR2) and G protein-coupled estrogen receptor (GPER) also regulate male reproductive and nonreproductive organs. 17ß-Estradiol (E2) is measureable in blood of men and males of other species, but in rete testis fluids, E2 reaches concentrations normally found only in females and in some species nanomolar concentrations of estrone sulfate are found in semen. Aromatase, which converts androgens to estrogens, is expressed in Leydig cells, seminiferous epithelium, and other male organs. Early studies showed E2 binding in numerous male tissues, and ESR1 and ESR2 each show unique distributions and actions in males. Exogenous estrogen treatment produced male reproductive pathologies in laboratory animals and men, especially during development, and studies with transgenic mice with compromised estrogen signaling demonstrated an E2 role in normal male physiology. Efferent ductules and epididymal functions are dependent on estrogen signaling through ESR1, whose loss impaired ion transport and water reabsorption, resulting in abnormal sperm. Loss of ESR1 or aromatase also produces effects on nonreproductive targets such as brain, adipose, skeletal muscle, bone, cardiovascular, and immune tissues. Expression of GPER is extensive in male tracts, suggesting a possible role for E2 signaling through this receptor in male reproduction. Recent evidence also indicates that membrane ESR1 has critical roles in male reproduction. Thus estrogens are important physiological regulators in males, and future studies may reveal additional roles for estrogen signaling in various target tissues.

Chronic inflammation in benign prostatic hyperplasia: Pathophysiology and treatment options.

Benign prostatic hyperplasia, a prevalent condition in aging men, is characterized by the proliferation of prostatic epithelial and stromal cells, which leads to bladder outlet obstruction and the exacerbation of lower urinary tract symptoms. There is increasing evidence that chronic prostatic inflammation contributes to the pathogenesis and progression of benign prostatic hyperplasia. This review explores the complex relationship between chronic inflammation and benign prostatic hyperplasia, focusing on the underlying mechanisms, clinical implications, and current therapeutic approaches. The pathophysiology of benign prostatic hyperplasia is multifaceted, involving factors such as hormonal changes, hypoxia, urine reflux into prostatic ducts and stroma, autoimmune responses, and infection-induced inflammation. Inflammatory cytokines, particularly interleukin-17 and interleukin-8, may play key roles in tissue remodeling and smooth muscle contraction within the prostate, thereby influencing benign prostatic hyperplasia progression. Current therapies for benign prostatic hyperplasia include α1-blockers, phosphodiesterase 5 inhibitors, 5α-reductase inhibitors, and plant-based treatments (e.g., pollen extract). These therapies aim to alleviate symptoms by reducing prostatic inflammation, improving blood flow, and inhibiting hormonal pathways involved in prostatic enlargement. However, patients with chronic prostatic inflammation often experience more severe lower urinary tract symptoms and may be resistant to conventional treatments. This resistance has prompted the exploration of alternative therapies targeting inflammation. Chronic prostatic inflammation plays a central role in the pathogenesis and severity of benign prostatic hyperplasia. An understanding of its mechanisms will enable the development of more effective treatments to improve the quality of life among patients with benign prostatic hyperplasia.

Cross-organ sensitization between the prostate and bladder in an experimental rat model of lipopolysaccharide (LPS)-induced chronic pelvic pain syndrome.

BACKGROUND: The aim of the current study was to investigate the effects of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on bladder function via prostate-to-bladder cross-sensitization in a rat model of lipopolysaccharide (LPS)-induced prostate inflammation. METHODS: Male rats were intraprostatically injected with LPS or saline, serving as control. Micturition parameters were examined in a metabolic cage 10 or 14 days later. Subsequently, to evaluate bladder function, cystometry was performed. Micturition cycles were induced by saline infusion and cholinergic and purinergic contractile responses were measured by intravenous injection with methacholine and ATP, respectively. Thereafter, the prostate and bladder were excised and assessed histopathologically for possible inflammatory changes. RESULTS: Metabolic cage experiments showed increased urinary frequency in rats with LPS-induced CP/CPPS. Cystometry showed a significant increase in the number of non-voiding contractions, longer voiding time and lower compliance in CP/CPPS animals compared to controls. Induction of CP/CPPS led to significantly reduced cholinergic and purinergic bladder contractile responses. Histopathological analysis demonstrated prostatic inflammation in CP/CPPS animals. There were no significant differences between the groups regarding the extent or the grade of bladder inflammation. Prostate weight was not significantly different between the groups. CONCLUSIONS: The present study shows that prostate-to-bladder cross-sensitization can be triggered by an infectious focus in the prostate, giving rise to bladder overactivity and alterations in both afferent and efferent signalling. Future studies are required to fully understand the underlying mechanisms.

An IKKα-E2F1-BMI1 cascade activated by infiltrating B cells controls prostate regeneration and tumor recurrence.

Androgen-deprived prostate cancer (PCa) is infiltrated by B lymphocytes that produce cytokines that activate IκB kinase α (IKKα) to accelerate the emergence of castration-resistant tumors. We now demonstrate that infiltrating B lymphocytes and IKKα are also required for androgen-dependent expansion of epithelial progenitors responsible for prostate regeneration. In these cells and in PCa cells, IKKα phosphorylates transcription factor E2F1 on a site that promotes its nuclear translocation, association with the coactivator CBP, and recruitment to critical genomic targets that include Bmi1, a key regulator of normal and cancerous prostate stem cell renewal. The IKKα-BMI1 pathway is also activated in human PCa.

Paying the price for standing tall: Fluid mechanics of prostate pathology.

BACKGROUND: Age-dependent increase in the incidence of benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are both related to cell proliferation and survival controlled by intraprostatic free testosterone (FT) concentration. Paradoxically, BPH and PCa occur as circulating testosterone levels decrease, so any possible relationship between testosterone levels and development of BPH and PCa remains obscure. RESULTS: In BPH the enlarging prostate is exposed to high testosterone levels arriving directly from the testes at concentrations about hundredfold higher than systemic FT. This occurs because venous blood from the testes is diverted into the prostate due to the elevated hydrostatic pressure of blood in the internal spermatic veins (ISVs). Elevated pressure is caused by the destruction of one-way valves (clinically detected as varicocele), a unique phenomenon related to human erect posture. While standing, human males are ISVs vertically oriented, resulting in high intraluminal hydrostatic pressures-a phenomenon not found in quadrupeds. In this communication, we demonstrate the fluid mechanics' phenomena at the basis of varicocele leading to prostate pathology. CONCLUSIONS: So far, varicocele has been studied mostly for its etiologic role in male infertility and, thus, for its effects on the testes. It is becoming clear that varicocele is a major etiologic factor in BPH and likely also in PCa. Restoring normal testicular venous pressure by treatment of the abnormal ISV's in varicocele has been shown to avert the flow from the prostate with the effect of reducing prostate volume, alleviating symptoms of BPH, and increasing concentrations of circulating FT.

The role of prostatic apex shape in voiding symptoms and urine flow: an exploratory and confirmatory study.

PURPOSE: Lower urinary tract symptoms in men have previously been attributed to obstruction from an enlarged prostate. However, several factors in addition to prostate volume have been identified as impacting urine flow. Prostatic apex shape is one factor that has not been evaluated. This study evaluates the relationship between prostatic apex shape and voiding symptoms and urine flow. METHODS: A retrospective, exploratory data review was conducted for 806 healthy men who underwent routine transrectal ultrasonography at our hospital, and data for 329 patients with uroflowmetric measurements were reviewed for the confirmatory study. Patients were categorized into four groups according to the prostatic apex shape on midsagittal ultrasonography. The association between prostatic apex shape and voiding symptoms was investigated. International Prostate Symptom Score (IPSS) and uroflowmetry were measured, and the associations between IPSS, uroflowmetry, and prostatic apex shape were analyzed. RESULTS: Patients in group 4 (356/806, 44.2%), whose prostatic apex did not overlap the membranous urethra anteriorly or posteriorly, had a significantly lower incidence of moderate and severe lower urinary tract symptoms compared to other groups. There was a significant relationship between prostatic apex shape and total International Prostate Symptom Score. Patients in group 3, whose prostatic apex overlapped posteriorly with the membranous urethra, had lower maximum flow rates on uroflowmetry. There were significant correlations between the maximum flow rate and independent factors including age, intravesicle prostatic protrusion, and prostatic apex shape. CONCLUSIONS: Prostatic apex shape is an independent risk factor for voiding symptom severity and low maximum flow rate.

Four-Year Impact of Voiding and Storage Symptoms in Patients with Benign Prostatic Hyperplasia Treated with Prostatic Artery Embolization.

PURPOSE: To study the subscore improvement in International Prostate Symptom Scores (IPSS) after prostatic artery embolization (PAE). MATERIALS AND METHODS: A single-center retrospective study was carried out with follow-up from December 2013 to July 2019 in 37 consecutive patients (66.0 ± 8.8 years old) who underwent PAE, comparing resultant scores before and after PAE. IPSS were divided into storage (IPSS-s) subscores and voiding (IPSS-v) subscores. The changes between IPSS-s and IPSS-v at 1, 3, 6, and 12 months' follow-up as well as the last follow-up were compared with baseline scores. The changes in percentages of IPSS-s and IPSS-v and the changes in average IPSS-s-to-total IPSS ratios (IPSS-s/IPSS-t) and IPSS-v-to-IPSS-t ratios (IPSS-v/IPSS-t) were also analyzed. RESULTS: In the study population, consisting of 37 patients, IPSS-t significantly decreased from 16.5 ± 7.2 at baseline to 8.3 ± 5.7 at the last follow-up (4 years later) (P < .0001). Additionally, the changes in IPSS-v symptoms were greater than the changes in IPSS-s symptoms at 1, 3, 6, and 12 months' follow-up, reaching a statistical significance at 6 months with a decrease of 72.9% ± 42.4% for IPSS-v and a decrease of 50.1% ± 52.2% for IPSS-s (P = .009). CONCLUSIONS: PAE can successfully reduce both IPSS-s and IPSS-v with predominant IPSS-v reduction. The improvements in both subscores were sustained for up to 4 years of follow-up.

Prostatic Artery Embolization Using 100-300-µm Trisacryl Gelatin Microspheres to Treat Lower Urinary Tract Symptoms Attributable to Benign Prostatic Hyperplasia: A Single-Center Outcomes Analysis with Medium-Term Follow-up.

PURPOSE: To report medium-term outcomes of prostatic artery embolization (PAE) using 100-300-µm trisacryl gelatin microspheres to treat lower urinary tract symptoms (LUTS) from benign prostatic hyperplasia (BPH) and to evaluate how cone-beam computed tomography-measured prostate gland volume (PGV), median lobe enlargement (MLE), age, and Charlson Comorbidity Index (CCI) affect these results. MATERIALS AND METHODS: Seventy-four consecutive patients who underwent PAE from April 2014 through August 2018 were retrospectively reviewed. Patients had International Prostate Symptom Score (IPSS) >12, Quality of Life (QoL) score >2, prostate gland volume (PGV) >40 mL, age older than 45 years, and medical therapy failure. Twelve patients were excluded for bladder pathology or prostate cancer. Patients (n = 62, age = 71.8 ± 9.3 years, CCI = 3.5 ± 1.7, PGV = 174 ± 110 mL) had pre-procedure IPSS = 22.4 ± 5.6, QoL score = 4.4 ± 0.9, and post-void residual (PVR) = 172 ± 144 mL. Post-procedure values were compared to baseline at 1, 3, 6, 12, and 24 months. Associations between outcomes and PGV, MLE, age, and CCI were evaluated. Adverse event recording used Clavien-Dindo classification. RESULTS: One month after PAE (n = 37), IPSS improved to 7.6 ± 5.2 (P < .0001) and QoL score improved to 1.7 ± 1.4 (P < .0001). At 3 months (n = 32), improvements continued, with IPSS = 6.4 ± 5.1 (P < .0001), QoL score = 1.2 ± 1.2 (P < .0001), PVR = 53 ± 41 mL (P < .001), and PGV = 73 ± 38 mL (P < .0001). Results were sustained at 6 months (n = 35): IPSS = 6.4 ± 4.1 (P < .0001), QoL score = 1.2 ± 1.2 (P < .0001), PVR = 68 ± 80 mL (P < .0001), PGV = 60 ± 19 mL (P < .001). At 12 months, patients (n = 26) had IPSS = 7.3 ± 5.5 (P < .0001), QoL score = 1.2 ± 0.8 (P <.0001), PVR = 89 ± 117 mL (P < .0001), PGV = 60 ± 48 mL (P < .01). At 24 months, patients (n = 8) had IPSS = 8.0 ± 5.4 (P < .0001), QoL score = 0.7 ± 0.5 (P < .0001), PVR = 91 ± 99mL (P = 0.17), and PGV = 30 ± 5mL (P = .11). Improvements were independent of PGV, MLE, age, and CCI. Two grade II urinary infections occurred. CONCLUSIONS: PAE with 100-300-µm microspheres produced sustained substantial improvements in LUTS, PGV, and PVR, which were independent of baseline PGV, MLE, age, or CCI.

[Ectopic seminal tract opening in enlarged prostatic utricle: A report of 22 cases].

OBJECTIVE: To explore the diagnosis, classification and treatment of ectopic seminal tract opening in enlarged prostatic utricle (EPU). METHODS: We retrospectively analyzed the clinical data on 22 cases of ectopic seminal tract opening in EPU confirmed by spermography, EPU open cannula angiography or intraoperative puncture of the vas deferens and treated by transurethral incision of EPU, cold-knife incision or electric incision of EPU, full drainage of the anteriorwal, and open or laparoscopic surgery from October 1985 to October 2017. RESULTS: Five of the patients were diagnosed with ectopic opening of the vas deferens and the other 17 with ectopic opening of the ejaculatory duct in EPU. During the 3－48 months of postoperative follow-up, symptoms disappeared in all the cases, semen quality was improved in those with infertility, and 2 of the infertile patients achieved pregnancy via ICSI. CONCLUSIONS: Ectopic seminal tract opening in EPU is rare clinically. Spermography is a reliable method for the diagnosis of the disease, and its treatment should be aimed at restoring the smooth flow of semen based on proper classification and typing of the disease.

Dopamine receptor antagonists induce differentiation of PC-3 human prostate cancer cell-derived cancer stem cell-like cells.

BACKGROUND: The objective of this study was to determine whether PC-3 human prostate cancer cell-derived cancer stem cells (CSC)-like cells grown in a regular cell culture plate not coated with a matrix molecule might be useful for finding differentiation-inducing agents that could alter properties of prostate CSC. METHODS: Monolayer cells prepared from sphere culture of PC-3 cells were characterized for the presence of pluripotency and tumorigenicity. They were then applied to screen a compound library to find compounds that could induce morphology changes of cells. Mechanisms of action of compounds selected from the chemical library that induced the loss of pluripotency of cells were also investigated. RESULTS: C5A cells prepared from PC-3 cell-derived sphere culture expressed pluripotency markers such as Oct4, Sox2, and Klf4. C5A cells were highly proliferative. They were invasive in vitro and tumorigenic in vivo. Some dopamine receptor antagonists such as thioridazine caused reduction of pluripotency markers and tumorigenicity. Thioridazine, unlike promazine, inhibited phosphorylation of AMPK in a dose dependent manner. BML-275, an AMPK inhibitor, also induced differentiation of C5A cells as seen with thioridazine whereas A769663, an AMPK activator, blocked its differentiation-inducing ability. Transfection of C5A cells with siRNAs of dopamine receptor subtypes revealed that knockdown of DRD2 or DRD4 induced morphology changes of C5A cells. CONCLUSIONS: Some dopamine receptor antagonists such as thioridazine can induce differentiation of CSC-like cells by inhibiting phosphorylation of AMPK. Binding to DRD2 or DRD4 might have mediated the action of thioridazine involved in the differentiation of CSC-like cells.

Patient-reported sexual quality of life after different types of radical prostatectomy and radiotherapy: Analysis of a population-based prospective cohort.

BACKGROUND: Although patients with prostate cancer face many treatment options, to the authors' knowledge the comparative effects of different surgical and radiotherapy (RT) options on sexual function are unclear. METHODS: In the current study, a population-based cohort of 835 men with newly diagnosed prostate cancer from 2011 through 2013 was recruited throughout North Carolina in collaboration with the Rapid Case Ascertainment system of the North Carolina Central Cancer Registry. All men were enrolled prior to treatment and followed prospectively using the validated Prostate Cancer Symptom Indices (PCSI) instrument. This analysis compares the sexual dysfunction scores of the PCSI among patients who received external-beam RT (EBRT), EBRT with androgen deprivation therapy (ADT), brachytherapy, nerve-sparing radical prostatectomy (RP), and non-nerve-sparing RP. Propensity scores were used to balance patient characteristics across groups, and multiple imputation was used for missing data. RESULTS: EBRT and brachytherapy resulted in similar PCSI scores through 24 months. Compared with those receiving EBRT, patients treated with EBRT with ADT and RP with or without nerve sparing were found to have worse PCSI scores at all posttreatment time points. Preservation of useful sexual function at 24 months was associated with treatment type, baseline score, and age. Predicted preservation rates were 14.1% to 70.7% for EBRT, 8.4% to 52.3% for EBRT with ADT, 4.7% to 45.3% for nerve-sparing RP, and 4.8% to 34.5% for non-nerve-sparing RP. CONCLUSIONS: The findings of the current study indicate that RT alone results in the best preservation of sexual function, and brachytherapy provides similar outcomes. RT with ADT and nerve-sparing RP yielded similar outcomes, whereas patients treated with non-nerve-sparing RP experienced the worst sexual function. These results help patients to make decisions among the specific types of surgery and RT they face based on each individual's diagnosis.

Effects of isocorynoxeine, from Uncaria, on lower urinary tract dysfunction caused by benign prostatic hyperplasia via antagonism of α1A-adrenoceptors.

Medical therapy of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) targets smooth muscle contraction in the prostate, for which α1A-adrenoceptor (α1A-AR) antagonists have been considered to be the primary therapeutic method. We investigated the effects and underlying mechanisms of isocorynoxeine (ICN), one of indole alkaloids from Uncaria, on the treatment of LUTS secondary to BPH via α1A-ARs in mice. The effect of ICN on prostatic contractility was studied via myographic measurements in the prostates of rabbits. The effects of ICN on bladder function, serum-hormone levels, bladder histology, and prostate histology were determined in testosterone propionate-induced prostatic hyperplasic wild-type (WT) and α1A-AR knockout (α1A-KO) mice. The cytotoxicity of ICN in cultured human prostatic stromal cells (WPMY-1) was assessed by the following: a cell-counting kit, measuring the relaxant effect on WPMY-1 by a collagen gel contraction assay, intracellular Ca2+ mobilization indicated by Fluo-4, cytoskeletal organization by phalloidin staining, and expressions of α1A-AR-mediated key messengers by western blot analyses. ICN non-competitively antagonized the contractions of prostates induced by α1A-AR agonists. ICN treatment improved bladder functions in prostatic hyperplasic WT mice, whereas it failed to ameliorate bladder functions in prostatic hyperplasic α1A-KO mice. In WPMY-1, ICN relaxed cell contractions on collagen gels, disrupted F-actin organization, inhibited α1A-AR agonist-stimulated Ca2+ mobilization, and antagonized α1A-ARs via the RhoA/ROCK2/MLC signaling pathway. Our results suggest that ICN may be a promising therapeutic drug for targeting α1A-ARs in the treatment of BPH/LUTS.

Comparison of Short-Term Outcomes between Button-Type Bipolar Plasma Vaporization and Transurethral Resection for the Prostate: A Systematic Review and Meta-Analysis.

Background: Previous meta-analysis evaluated a limited number of parameters regarding the comparison of BTPV and TURP for BPH. Method: PubMed, Embase and Cochrane Library were searched for literature comparing BTPV with TURP. Data of efficacy (IPSS, Qmax, PVR and QoL) and safety were extracted and evaluated using either SMD or OR with 95% CI. All analyses were performed by RevMan 5.3. Results: Eleven trials with 1690 patients were selected. Compare to BTPV, TURP had better 6-month IPSS (SMD=0.36, 95% CI 0.08 to 0.63), better 1- (SMD=-0.38, 95% CI -0.63 to -0.12), 6- (SMD=-0.73, 95% CI -0.99 to -0.46) and 12-month Qmax (SMD=-0.47, 95% CI -0.85 to -0.10), better 6-month PVR (SMD=1.18, 95% CI 0.87 to 1.48), as well as better 3- (SMD=-0.24, 95% CI -0.48 to -0.01) and 6-month QoL (SMD=-0.62, 95% CI -0.91 to -0.33). However, BTPV had shorter catheterization time (SMD=-0.96, 95% CI -1.12 to -0.79) and hospital stay (SMD=-0.71, 95% CI -0.89 to -0.53), less hemoglobin decrease (SMD=-1.09, 95% CI -1.27 to -0.91) and virtually shorter operation time (SMD=-0.15, 95% CI -0.31 to 0.01). Moreover, BTPV had fewer occurrence of overall complications (OR=0.52, 95% CI 0.40 to 0.69), Clavien III-IV complications (OR=0.61, 95% CI 0.37 to 1.02), blood transfusion (OR=0.25, 95% CI 0.09 to 0.69), hematuria (OR=0.27, 95% CI 0.13 to 0.56) and capsular perforation (OR=0.19, 95% CI 0.08 to 0.48). Subgroup analysis indicated BTPV and bipolar TURP had similar total complications (OR 1.08, 95% CI 0.40-2.88, P=0.88) and Clavien III-IV complications (OR 1.42, 95% CI 0.36-5.57, P=0.61) and blood transfusion rate (OR 0.28, 95% CI 0.04-1.73, P=0.17). Conclusion: Both TURP and BTPV could significantly improve IPPS, Qmax, PVR and QoL. TURP had slightly better short-term efficacy, while BTPV had better safety. However, subgroup analysis found bipolar TURP and BTPV had similar safety.

The ex vivo and in vivo Characteristics of New DrillCutTM Prostate Morcellator after Holmium Laser Enucleation of the Prostate: A Pilot Study.

INTRODUCTION: The DrillCutTM morcellator is marketed for its fast and highly efficient removal of prostatic tissue and a higher level of patient safety. However, a paucity of publications has looked into its actual efficacy and safety. The aim of our study was to evaluate its ex vivo and in vivo efficiency and to compare its results with other devices presented in the literature. PATIENTS AND METHODS: We conducted a prospective pilot study on patients who underwent holmium laser enucleation of the prostate (HoLEP) from 2017 to 2018 using the Top-Down technique. Enucleated adenomas were morcellated using the DrillCutTM morcellator. We collected both preoperative and operative data. Operative data included the enucleated adenoma weight and operative time. Various morcellator parameters were collected including morcellation time and efficiency. We recorded the encountered complications and device malfunction. Ex vivo characteristics were evaluated in terms of morcellation speed and aspiration power. RESULTS: Sixty consecutive patients with a median age of 72.8 years were included. The enucleated adenoma was retrieved in 12.5 min (4-58). The median resected prostatic weight was 90 g (44-242). The DrillCutTM efficiency was calculated as 6.46 g/min (2.7-15). Only one patient had a simple bladder mucosal injury. Device malfunction was encountered in 4 patients (6.6%) due to blockage of the morcellator blades. The ex vivo aspiration speed was 52 s/L, while the morcellation power was 14 g/2 min. CONCLUSION: Our results showed that the DrillCut morcellator was effective and safe in managing our patients post-HoLEP. The DrillCutTM has better ex vivo morcellation power but modest aspiration speed in comparison to other morcellators.

Prostatic stromal inflammation is associated with bladder outlet obstruction in patients with benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common urologic disease in older men. Prostatic inflammation research has focused on the magnitude of inflammation; its location has received little attention. We investigated whether the anatomic location of prostatic inflammation is related to the severity of lower urinary tract symptoms (LUTS), measured subjectively and objectively. METHODS: We retrospectively analyzed hematoxylin+eosin-stained tissue specimens from 179 BPH patients who underwent transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP). Chronic prostatic inflammation was assessed by the grade (lymphocyte density), extent (lymphocyte distribution), and location of inflammation. Each inflammation-finding type was evaluated in relation to these clinical parameters: age, prostate volume, prostate-specific antigen (PSA) value, body mass index (BMI), the frequency of acute urinary retention (AUR) episodes, the international prostatic symptom score (IPSS), and urodynamic study results. RESULTS: The magnitude and extent of inflammation were not associated with any clinical parameters. We classified the BPH patients into stromal (n = 72) versus non-stromal (n = 105) groups based on their inflammation's dominant location. The stromal group's prostatic volume was significantly larger than the non-stromal group's (63.8 vs 53.8 mL; P = 0.032). AUR episodes were more significantly frequent in the stromal group (36.1% vs 11.4%; P = 0.006). Between-group differences in storage parameters (ie, maximum cystometric capacity) in the urodynamic study were not significantly different. Voiding parameters differed significantly between the stromal and non-stromal groups: maximum detrusor pressure (maxPdet) (116.8 vs 94.5 cmH2 O, P = 0.014), Pdet at the maximum flow rate (Qmax) (95.8 vs 75.4 cmH2 O, P = 0.014), and the bladder outlet obstruction index (BOOI) (78.5 vs 56.3, P = 0.014). The stromal group's Qmax was significantly lower than the non-stromal group's (7.3 vs 9.8 mL/s, P = 0.004). CONCLUSIONS: The location of inflammation in the prostate might be an important factor affecting the severity of LUTS, especially voiding dysfunction.

Symptom and function profiles of men with localized prostate cancer.

BACKGROUND: Men diagnosed with localized prostate cancer seek information on how treatment options may impact their health-related quality of life (HRQOL). The authors used latent profile analysis (LPA) to group men according to their symptom burden and functional status and to identify patient characteristics associated with each HRQOL profile. METHODS: Patients completed the Patient-Reported Outcomes Measurement Information System and the Expanded Prostate Index Composite measures 3 months after treatment initiation. Anxiety, depression, fatigue, sleep disturbance, pain, diarrhea, urinary obstruction, urinary incontinence, erectile function, and sex satisfaction were modeled jointly using LPA, and the analysis was adjusted for covariates to examine associations between patient characteristics and profiles. RESULTS: One-third of the 373 men were not non-Hispanic white (26% were black). Four LPA profiles were identified. Men who experienced the "best HRQOL" were less likely to receive treatment, to be older, and to smoke. Men in the second best profile experienced symptoms similar to men in the best HRQOL group but reported poor sexual and urinary function, because they were more likely to receive therapy. The third profile included men with increased symptom burden and poor functioning who were likely to undergo prostatectomy and to have increased comorbidity. The "worst HRQOL" group experienced the worst symptoms and the poorest functioning, and these men were more likely to be younger, to have more comorbidities, and to smoke. CONCLUSIONS: LPA revealed that men who receive the same treatment can experience very different HRQOL impact. Understanding the factors most associated with poorer HRQOL allows clinicians to focus their care on individuals most in need of symptom management and support. Cancer 2018;124:2832-2840. © 2018 American Cancer Society.

Involvement of prostatic interstitial cells of Cajal in inflammatory cytokines-elicited catecholamines production: Implications for the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

In a previous work using guinea pig prostate, we have identified a novel interstitial cells of Cajal (ICCs) which possess close contacts between sympathetic nerve bundles and smooth muscle cells. The ability of prostatic ICCs in mediating excitatory neural inputs was therefore studied using isolated murine prostate ICCs by collagenase digestion combined with FACS method. RT-PCR and Western blotting analyses revealed that prostatic ICCs under a quiescent state expressed abundantly the rate-limiting enzymes essential for catecholamine synthesis. Moreover, distinct proinflammatory cytokines (e.g. IL-1ß, IL-8, ICAM-1 and TNF-α) could significantly stimulate the expression levels of the rate-limiting enzymes of catecholamine production in prostate ICCs. Mechanistically, the above-mentioned stimulatory effects of proinflammatory cytokines appeared to be mediated via activation of NF-κB, HIF-1α and HDACs signaling pathways. Considering that prostatic catecholamine overactivity serves as an essential etiology of pelvic pain by indirectly stimulating the smooth muscle cell proliferation, or by directly causing muscular spasm, our results collectively suggest that targeting the NF-κB, HIF-1α and HDACs pathways in prostate ICCs be considered as a new strategy for treatment of chronic pelvic pain syndrome (CPPS) induced by chronic prostatitis (CP). Overall, the current study should shed novel light on the biology of this unique prostate ICCs.

Functional Recovery, Oncologic Outcomes and Postoperative Complications after Robot-Assisted Radical Prostatectomy: An Evidence-Based Analysis Comparing the Retzius Sparing and Standard Approaches.

PURPOSE: We report a 1-year update of functional urinary and sexual recovery, oncologic outcomes and postoperative complications in patients who completed a randomized controlled trial comparing posterior (Retzius sparing) with anterior robot-assisted radical prostatectomy. MATERIALS AND METHODS: A total of 120 patients with clinically low-intermediate risk prostate cancer were randomized to undergo robot-assisted radical prostatectomy via the posterior and anterior approach in 60 each. Surgery was performed by a single surgical team at an academic institution. An independent third party ascertained urinary and sexual function outcomes preoperatively, and 3, 6 and 12 months after surgery. Oncologic outcomes consisted of positive surgical margins and biochemical recurrence-free survival. Biochemical recurrence was defined as 2 postoperative prostate specific antigen values of 0.2 ng/ml or greater. RESULTS: Median age of the cohort was 61 years and median followup was 12 months. At 12 months in the anterior vs posterior prostatectomy groups there were no statistically significant differences in the urinary continence rate (0 to 1 security pad per day in 93.3% vs 98.3%, p = 0.09), 24-hour pad weight (median 12 vs 7.5 gm, p = 0.3), erection sufficient for intercourse (69.2% vs 86.5%) or postoperative Sexual Health Inventory for Men score 17 or greater (44.6% vs 44.1%). In the posterior vs anterior prostatectomy groups a nonfocal positive surgical margin was found in 11.7% vs 8.3%, biochemical recurrence-free survival probability was 0.84 vs 0.93 and postoperative complications developed in 18.3% vs 11.7%. CONCLUSIONS: Among patients with clinically low-intermediate risk prostate cancer randomized to anterior (Menon) or posterior (Bocciardi) approach robot-assisted radical prostatectomy the differences in urinary continence seen at 3 months were muted at the 12-month followup. Sexual function recovery, postoperative complication and biochemical recurrence rates were comparable 1 year postoperatively.

Computer-Assisted Quantitative Assessment of Prostatic Calcifications in Patients with Chronic Prostatitis.

BACKGROUND: The aim of this study was the development of quantitative assessment of prostatic calcifications at prostatic ultrasound examination by the use of an image analyzer. MATERIALS AND METHODS: A group of 82 patients was evaluated by medical history, physical, and transrectal ultrasound examination. Patients had a urethral swab, a 4-specimen study and culture of the seminal fluid. Patients were classified according to National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health. Subjective symptoms were scored by Chronic Prostatitis Symptom Index (CPSI) questionnaire. Ultrasound images were analyzed by the digital processing software Image J to quantitatively assess the presence of calcifications. RESULTS: Computer-assessed calcified areas were significantly higher in chronic bacterial prostatitis (n = 18; group II; 6.76 ± 8.09%) than in the chronic pelvic pain syndrome group IIIa (n = 26; 2.07 ± 1.01%) and IIIb (n = 38; 2.31 ± 2.18%). The area of calcification of the prostate was significantly related to the CPSI score for domains of micturition (r = 0.278, p = 0.023), Prostatic Specific Antigen values (r = 0341, p = 0.005), postvoiding residual urine (r = 0.262, p = 0.032), total prostate volume (r = 0.592, p = 0.000), and adenoma volume (r = 0.593; p = 0.000). CONCLUSIONS: The presence of calcifications is more frequently observed in patients with chronic bacterial prostatitis and is related to urinary symptoms.