Search

Background: Many individuals consider nocturia a significant nuisance, leading to a reduced health-related quality of life (HRQOL). However, there has been a lack of psychometrically sound patient-reported outcome measures to assess the impact of nocturia on patients in Chinese contexts. This study aimed to translate, culturally adapt, and validate the International Consultation on Incontinence Questionnaire Nocturia Quality of Life Module (ICIQ-NQOL) for use among primary care patients in Hong Kong, China. Additionally, it sought to investigate the mechanisms that link nocturia and sleep quality with HRQOL by employing moderated mediation analysis. Methods: The traditional Chinese version of the ICIQ-NQOL was developed through iterative translations, cognitive debriefing interviews, and panel reviews. The psychometric evaluation included assessments of factor structure, convergent validity, concurrent validity, known-group validity, internal consistency, test-retest reliability and responsiveness. Study instruments included the ICIQ-NQOL, International Prostate Symptom Score (IPSS), Pittsburgh Sleep Quality Index (PSQI), and a modified Incontinence Impact Questionnaire-Short Form (IIQ-7). Results: A total of 419 primary care patients were recruited from general outpatient clinics, among whom 228 experiencing an average of two or more nocturia episodes per night over the past four weeks. Confirmatory factor analysis supported the two-factor structure of the ICIQ-NQOL. Concurrent validity was confirmed by moderate correlations between the IIQ-7 total score and the total score as well as two domain scores of the ICIQ-NQOL (r ranging from 0.43 to 0.49, all p < 0.001). The ICIQ-NQOL also had moderate correlations with the IPSS total symptom score (r ranging from 0.40 to 0.48, all p < 0.001). Convergent validity was supported by moderate correlations between the global PSQI score and the total score as well as two domain scores of the ICIQ-NQOL (r ranging from 0.42 to 0.52, all p < 0.001). Known-group comparisons showed that the ICIQ-NQOL could differentiate between patients with and without nocturia in terms of sleep/energy domain score (p < 0.001), bother/concern domain score (p < 0.001), and total score (p < 0.001), each demonstrating a moderate Cohen's d effect size. Item-total correlations corrected for overlap exceeded 0.4, and Cronbach's alpha coefficients were greater than 0.7. Test-retest reliability was confirmed with intraclass correlation coefficients exceeding 0.7 among patients reporting no change in their nocturia symptoms at a 2-week follow-up. Regarding responsiveness, the Cohen's d effect sizes for differences in domain and total scores between the baseline and 2-week follow-up assessments were greater than 0.3 among patients showing improvement in nocturia. Our moderated mediation analysis indicated that sleep quality significantly moderated the impact of nocturia on HRQOL, with a notably stronger indirect effect among females compared to males. Conclusions: The ICIQ-NQOL is a reliable and valid instrument for assessing the HRQOL in primary care patients suffering from nocturia. The findings advocate for gender-specific approaches in the management and treatment of nocturia to optimize HRQOL. [ABSTRACT FROM AUTHOR]

Simple Summary: Medical gas plasma is a new modality in cancer treatment showing favorable results in preclinical and clinical trials; however, the cascade of molecular events underlying selective killing of cancer cells has not been fully elucidated. This study examines the hypothesis that cell death induced by gas plasma is mediated by a universal molecular mechanism. Using high-throughput data from eight transcriptomic studies on patient-derived prostate cultures, melanoma, breast, lymphoma, and lung cancer cells, we implemented two computational methodologies for re-analysis of single cohorts as well as meta-analysis of multi-cohort gene expression data. The results provide converging insights into the induction of immunogenic cell death in human tumors, reinforcing the potential of plasma treatment as an emerging immunotherapeutic approach in oncology. The therapeutic potential of cold physical gas plasma operated at atmospheric pressure in oncology has been thoroughly demonstrated in numerous preclinical studies. The cytotoxic effect on malignant cells has been attributed mainly to biologically active plasma-generated compounds, namely, reactive oxygen and nitrogen species. The intracellular accumulation of reactive oxygen and nitrogen species interferes strongly with the antioxidant defense system of malignant cells, activating multiple signaling cascades and inevitably leading to oxidative stress-induced cell death. This study aims to determine whether plasma-induced cancer cell death operates through a universal molecular mechanism that is independent of the cancer cell type. Using whole transcriptome data, we sought to investigate the activation mechanism of plasma-treated samples in patient-derived prostate cell cultures, melanoma, breast, lymphoma, and lung cancer cells. The results from the standardized single-cohort gene expression analysis and parallel multi-cohort meta-analysis strongly indicate that plasma treatment globally induces cancer cell death through immune-mediated mechanisms, such as interleukin signaling, Toll-like receptor cascades, and MyD88 activation leading to pro-inflammatory cytokine release and tumor antigen presentation. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is a common and challenging disease among men, driving researchers to find better ways to understand and manage it. The understanding of two specific types, cribriform and intraductal prostate cancer (IDC-P), has evolved significantly over the years. This review aims to help pathologists differentiate between cribriform prostate cancer and IDC-P, and addresses current recommendations. Recent studies show that including these features in decision-making tools enhances predictions of cancer recurrence, spread, and patient outcomes. Future research should further focus on their pathological and molecular aspects to improve risk stratification, treatment approaches, and patient care. Over the years, our understanding of cribriform and intraductal prostate cancer (PCa) has evolved significantly, leading to substantial changes in their classification and clinical management. This review discusses the histopathological disparities between intraductal and cribriform PCa from a diagnostic perspective, aiming to aid pathologists in achieving accurate diagnoses. Furthermore, it discusses the ongoing debate surrounding the different recommendations between ISUP and GUPS, which pose challenges for practicing pathologists and complicates consensus among them. Recent studies have shown promising results in integrating these pathological features into clinical decision-making tools, improving predictions of PCa recurrence, cancer spread, and mortality. Future research efforts should focus on further unraveling the biological backgrounds of these entities and their implications for clinical management to ultimately improve PCa patient outcomes. [ABSTRACT FROM AUTHOR]

Herbal supplements containing several types of plant sterols, vitamins, and minerals, are marketed for prostate health. In the majority of these supplements, the most abundant plant sterol is saw palmetto extract or its' principal component, beta-sitosterol. In terms of prostate health, previous work almost exclusively focused on the effects of beta-sitosterol on prostatic epithelium, with little attention paid to the effects on prostatic stroma. This omission is a concern, as the abnormal accumulation of collagen, or fibrosis, of the prostatic stroma has been identified as a factor contributing to lower urinary tract symptoms and dysfunction in aging men. To address whether beta-sitosterol may be promoting prostatic fibrosis, immortalized and primary prostate stromal fibroblasts were subjected to immunoblotting, immunofluorescence, qRT-PCR, ELISA, and image quantitation and analysis techniques to elucidate the effects of beta-sitosterol on cell viability and collagen expression and cellular localization. The results of these studies show that beta-sitosterol is nontoxic to prostatic fibroblasts and does not stimulate collagen production by these cells. However, beta-sitosterol alters collagen distribution and sequesters collagen within prostatic fibroblasts, likely in an age-dependent manner. This is a significant finding as prostate health supplements are used predominantly by middle aged and older men who may, then, be affected disproportionately by these effects. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) is a common urological condition affecting aging men worldwide. Among the treatment options available for BPH, transurethral resection of the prostate (TURP) is the gold-standard invasive intervention. To reduce the TURP-related non-negligible morbidity, loss-of-ejaculation rate, hospitalization, blood loss and catheterization time several laser techniques have been developed, such as the Thulium Laser Enucleation of the Prostate (ThuLEP). To investigate the efficacy outcomes of the ThuLEP as a treatment option for benign prostatic hyperplasia (BPH) we performed a retrospective observational study at Moriggia Pelascini Hospital (Como, Italy) between January 2015 and September 2018. We included 265 patients who underwent ThuLEP at a specific hospital between defined dates. Data on various parameters, including post-void residue volume, peak urinary flow rate (Qmax), International Prostate Symptom Score (IPSS) for urinary symptoms, IPSS Quality of Life (QoL) score, and International Index of Erectile Function (IIEF) score for erectile dysfunction, were collected at baseline and follow-up. The analysis revealed significant improvements in voiding efficiency, urinary flow, urinary symptoms, quality of life, and erectile function following ThuLEP. Furthermore, certain baseline characteristics, such as post-void residue, peak urinary flow rate, age, prostate volume, and aspirin usage, were found to influence treatment outcomes. Despite the study's limitations, these findings contribute to understanding ThuLEP's effectiveness in managing BPH and can aid in making informed clinical decisions for patient care. Prospective studies with longer follow-up periods are recommended to validate and extend these results. [ABSTRACT FROM AUTHOR]

Background: Prostate brachytherapy (BT) techniques have evolved over the past century. This paper aimed to preserve our collective memory of history and the early development of its technique. We searched articles in PubMed and Google Scholar using keywords referring to authors, dates, and BT technical details, including different radioactive sources and country-specific publications. We reviewed the work published by Holm and Aronowitz. The digital library Internet Archives was used to retrieve original journal articles, science newspaper printings, and government reports, which allowed us to situate the development of BT in its sociopolitical context in Europe and the USA. Our search was conducted in English, French, and German languages. Summary: Early BT methods were developed by European physicians with early access to radium. Technical advancements were made by HH Young, who brought this practice to the USA, where Barringer pioneered the use of radon seeds and low-dose interstitial brachytherapy. While centralized radiotherapy centers, such as Memorial Hospital in New York, emerged for training and research, the high cost of radium and opposing interests made brachytherapy harder to implement in Germany. After World War II, the introduction of man-made radioisotopes allowed experiments with colloidal solutions and new seeds, including I-125. In the 1980s, transrectal ultrasound allowed for more accurate radioactive seed insertion and replaced the transrectal finger guidance. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of the International Society of Urological Pathology (ISUP) grade group 4 (GG4) and ISUP GG5 subgroups according to prostate biopsy on biochemical recurrence (BCR). Materials and Methods: Patients who underwent radical prostatectomy (RP) after being diagnosed with GG4 and GG5 prostate cancer according to prostate biopsy and who had follow-up data were retrospectively evaluated. Patient data were obtained from the Urologic Cancer Database-Prostate of the Turkish Urooncology Association. GG4 and GG5 pathologies were evaluated using Gleason subgroups. The effect of clinicopathological parameters on BCR after RP was investigated separately in the GG4 and GG5 patient groups. Results: In GG4, 73 of 188 patients developed BCR. When GG4 patients were evaluated for BCR, only lymphovascular invasion was significant for BCR (p=0.004). In addition, seminal vesicle invasion (SVI) and high ISUP grade according to RP pathology were significant in patients with BCR (p=0.004 and p=0.005). In the follow-up of 145 patients with GG5, 80 patients developed BCR. When GG5 patients were evaluated for BCR, no predictive factor was found for developing BCR. However, surgical margin positivity, extraprostatic extension, and SVI after RP were found to be significant in patients with BCR (p=0.031, p=0.011 and p=0.007). Conclusion: According to our results, the ISUP GG system, which does not include Gleason subgroups, is an appropriate classification system for GG4 and GG5 patients for the prediction of BCR in the Turkish patient population, in parallel with the current literature. [ABSTRACT FROM AUTHOR]

Copyright of Die Urologie is the property of Springer Nature 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.)

Patients with prostate cancer (PCa) have a lower docetaxel exposure for both intravenous (1.8‐fold) and oral administration (2.4‐fold) than patients with other solid cancers, which could influence efficacy and toxicity. An altered metabolism by cytochrome P450 3A (CYP3A) due to castration status might explain the observed difference in docetaxel pharmacokinetics. In this in vivo phenotyping, pharmacokinetic study, CYP3A activity defined by midazolam clearance (CL) was compared between patients with PCa and male patients with other solid tumors. All patients with solid tumors who did not use CYP3A‐modulating drugs were eligible for participation. Patients received 2 mg midazolam orally and 1 mg midazolam intravenously on 2 consecutive days. Plasma concentrations were measured with a validated liquid chromatography–tandem mass spectrometry method. Genotyping was performed for CYP3A4 and CYP3A5. Nine patients were included in each group. Oral midazolam CL was 1.26‐fold higher in patients with PCa compared to patients with other solid tumors (geometric mean [coefficient of variation], 94.1 [33.5%] L/h vs 74.4 [39.1%] L/h, respectively; P =.08). Intravenous midazolam CL did not significantly differ between the 2 groups (P =.93). Moreover, the metabolic ratio of midazolam to 1′‐hydroxy midazolam did not differ between the 2 groups for both oral administration (P =.67) and intravenous administration (P =.26). CYP3A4 and CYP3A5 genotypes did not influence midazolam pharmacokinetics. The observed difference in docetaxel pharmacokinetics between both patient groups therefore appears to be explained neither by a difference in midazolam CL nor by a difference in metabolic conversion rate of midazolam. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Radiation therapy for prostate cancer is associated with a 15-20% five-year recurrence rate. Patients with recurrence in the prostate only are candidates for salvage local therapies; however, there is no consensus on modality. This study uses registries at Memorial Sloan Kettering Cancer Center (MSKCC) and University of Western Ontario (UWO) to compare the oncologic outcomes of salvage radical prostatectomy (SRP) and salvage ablation (SA). METHODS: A total of 444 patients were available for analysis. Due to intergroup differences, propensity score methodology was used and identified 378 patients with more comparable pre-salvage prostate-specific antigen (PSA), Gleason score, and primary radiation treatment. Patients underwent SRP at MSKCC and SA at UWO. RESULTS: Of the 378 patients, 48 died of disease, with a 6.0-year median (interquartile range [IQR] 3.0, 9.7) followup among survivors; 88 developed metastases, with a median 4.6-year (IQR 2.3, 7.9) followup among metastasis-free survivors. There was a non-significantly higher rate of cancer-specific (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.51, 2.06, p=0.9) and improved metastasis-free survival (HR 0.71, 95% CI 0.44, 1.13, p=0.15) among patients undergoing SA compared to patients undergoing SRP. There were 143 patients who received hormonal therapy, with higher rates of androgen deprivation therapy (ADT) in SA (HR 1.42, 95% CI 0.97, 2.08, p=0.068), although this did not meet conventional levels of significance. CONCLUSIONS: This propensity score analysis of salvage therapy for radio-recurrent prostate cancer identified no statistically significant differences in oncologic outcome between SRP and SA; however, there was evidence of a lower risk of ADT in the cohort undergoing SRP. Given they are both potentially curative therapies, these treatments are viable options for men with clinically localized, radio-recurrent prostate cancer rather than ADT alone. Future research may further elucidate subpopulations that may be more amenable to either SRP or SA. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic body radiation therapy (SBRT) can be safely delivered for the treatment of localized prostate cancer. High-dose-per-fraction treatments require precise and rapid delivery of the radiation dose to the tumor, and any potential margin expansion must be balanced against the risk of increased toxicity. Since significant intrafraction prostate displacement can have a relevant impact on an extreme-hypofractionated regimen, real-time monitoring has emerged as a strategy to avoid the excessive exposure of healthy tissue or insufficient target coverage, but it requires continuous investment of resources and time. In real-world clinical practice, the utilization of organ motion management devices is not always feasible for all patients. Thus, our strategy has often been to mitigate the impact of intrafraction motion by shortening the delivery time without compromising the quality of the treatment. This was achieved through optimal patient preparation, flattening filter-free (FFF) beams, adequate margins, and a reduction in the number of arcs in the VMAT technique. This study aimed to comprehensively present data on treatment optimization in linac-based SBRT for localized prostate cancer at a single institution. Moreover, the dosimetric quality and treatment efficiency of single-arc (SA) versus dual-arc (DA) VMAT planning and delivery approaches were compared. Re-optimization was performed on twenty low-to-intermediate-risk- (36.25 Gy in 5 fractions) and twenty high-risk (42.7 Gy in 7 fractions) prostate plans initially administered with the DA FFF-VMAT technique in 2021. An SA approach was adopted, incorporating new optimization parameters based on increased planning and clinical experience. Analysis included target coverage, organ-at-risk (OAR) sparing, treatment delivery time, and the pre-treatment verification's gamma analysis-passing ratio. The SA optimization technique has consistently produced superior plans. Rectum and bladder mean doses were significantly reduced, and comparable target coverage and homogeneity were achieved in order to maintain a urethra protection strategy. The mean SA treatment delivery time was reduced by 22%; the mean monitor units increased due to higher plan complexity; and dose measurements demonstrated optimal agreement with calculations. The substantial reduction in treatment delivery time decreased the probability of prostate motion beyond the applied margins, suggesting potential decrease in treatment-related toxicity and improved target coverage in prostate SBRT. Further investigations are warranted to assess the long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: This is a prospective randomized study with the aim of comparing (thulium laser enucleation of the prostate (ThuLEP) and transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH) treatment. Methods: Patients are assessed preoperatively and up to 6 months postoperatively. International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rates (Qmax), international index of erectile function-5 (IIEF-5) and post-void residual volume (PVR) are collected on each follow-up. Results: In comparison to TURP, the ThuLEP group has significantly less need for catheter traction and less need for postoperative irrigation. The operative time is significantly higher in ThuLEP compared to TURP. ThuLEP is significantly superior to TURP in terms of early catheter removal, less drop in haemoglobin, less fall in serum sodium level, and early hospital discharge. ThuLEP and TURP resulted in a significant improvement from baseline in terms of IPSS, PVR, Qmax, and QoL, but there was no significant difference between the 2 groups. The IIEF-5 is the same as the baseline in both groups. Early and late complications are also comparable. Conclusion: The ThuLEP outperforms TURP in terms of blood loss, significantly less need for postoperative catheter traction, bladder irrigations, early catheter removal, and less hospital stay. Transurethral resection of the prostate takes longer operative time in the early stages of experience. The results of both surgeries are comparable in terms of PVR, Qmax, and subjective scoring systems (IPSS, QoL). Transurethral resection of the prostate is a safe and efficient BPH treatment method comparable to the monopolar TURP. [ABSTRACT FROM AUTHOR]

Background. Although prostate cancer patients initially respond to androgen deprivation therapy, most patients progress to a resistant phenotype. Castration resistance is due, in part, to intratumoral and/or adrenal synthesis of androgens, overexpression or mutation of the androgen receptor (AR), stabilization of AR by chaperones, and ligand-independent activation of AR. Increasing evidence also links disruption of calcium homeostasis to progression of prostate cancer. Our previous study shows that heavy metal cadmium activates the AR through a ligand-independent mechanism. Cadmium mimics calcium in biological systems due to their similar ionic charge and radius. This study determines whether calcium activates AR and whether first- and second-generation antiandrogens block the ability of calcium to activate the receptor. Methods. The expression of androgen-responsive genes and calcium channels was measured in prostate cells using a quantitative real-time polymerase chain reaction assay. Cell growth was measured. Results. To ask whether calcium activates AR, prostate cells were treated with calcium in the absence and presence of the first-generation antiandrogens hydroxyflutamide and bicalutamide and the second-generation antiandrogen enzalutamide, and the expression of androgen-responsive genes and cell growth was measured. In the normal PWR-1E cells and HEK293T cells transiently expressing AR, treatment with calcium increased the expression of androgen-responsive genes by approximately 3-fold. The increase was blocked by enzalutamide but was not consistently blocked by the first-generation antiandrogens. In LNCaP cells which contain a mutant AR, treatment with calcium also increased the expression of androgen-responsive genes by approximately 3-fold, and the increase was more effectively blocked by enzalutamide than by hydroxyflutamide or bicalutamide. Treatment with calcium also increased cell growth that was blocked by enzalutamide. To ask whether dysregulation of calcium channels is associated with castration resistance, calcium channels were measured in the normal PWR-1E prostate cells, the hormone-responsive LNCaP cells, and the castration-resistant VCaP and 22RV1 cells. Compared to normal prostate cells, the hormone-responsive and hormone-resistant cells overexpressed several calcium channels. Conclusions. The results of this study show that calcium activates AR and increases cell growth and that calcium channels are overexpressed in hormone-responsive and hormone-resistant prostate cancer cells. Taken together, the results suggest a novel role of calcium in the castration-resistant phenotype. [ABSTRACT FROM AUTHOR]

Simple Summary: Auto contouring driven by artificial intelligence can improve the workflow of radiotherapy by accelerating the contouring process. However, quality assurance of artificial intelligence-based tools is necessary for ensuring safety and efficacy in a clinical practice. In this study investigated the geometric accuracy of structural contours created by a commercial software for autocontouring based on artificial intelligence using well established metrics. In particular, the impact on the radiotherapy treatment plan quality from the adoption of artificial intelligence generated contours was investigated. Our results show that the combination of automatically generated contours and careful review by a clinical radiation oncologist results in time saving without affecting the quality of treatment plan. In conclusion, after quality checks that involve both geometric accuracy as well as dosimetric impact, contouring based on AI can be safely adopted in clinical practice. Purpose: When autocontouring based on artificial intelligence (AI) is used in the radiotherapy (RT) workflow, the contours are reviewed and eventually adjusted by a radiation oncologist before an RT treatment plan is generated, with the purpose of improving dosimetry and reducing both interobserver variability and time for contouring. The purpose of this study was to evaluate the results of application of a commercial AI-based autocontouring for RT, assessing both geometric accuracies and the influence on optimized dose from automatically generated contours after review by human operator. Materials and Methods: A commercial autocontouring system was applied to a retrospective database of 40 patients, of which 20 were treated with radiotherapy for prostate cancer (PCa) and 20 for head and neck cancer (HNC). Contours resulting from AI were compared against AI contours reviewed by human operator and human-only contours using Dice similarity coefficient (DSC), Hausdorff distance (HD), and relative volume difference (RVD). Dosimetric indices such as Dmean, D0.03cc, and normalized plan quality metrics were used to compare dose distributions from RT plans generated from structure sets contoured by humans assisted by AI against plans from manual contours. The reduction in contouring time obtained by using automated tools was also assessed. A Wilcoxon rank sum test was computed to assess the significance of differences. Interobserver variability of the comparison of manual vs. AI-assisted contours was also assessed among two radiation oncologists for PCa. Results: For PCa, AI-assisted segmentation showed good agreement with expert radiation oncologist structures with average DSC among patients ≥ 0.7 for all structures, and minimal radiation oncology adjustment of structures (DSC of adjusted versus AI structures ≥ 0.91). For HNC, results of comparison between manual and AI contouring varied considerably e.g., 0.77 for oral cavity and 0.11–0.13 for brachial plexus, but again, adjustment was generally minimal (DSC of adjusted against AI contours 0.97 for oral cavity, 0.92–0.93 for brachial plexus). The difference in dose for the target and organs at risk were not statistically significant between human and AI-assisted, with the only exceptions of D0.03cc to the anal canal and Dmean to the brachial plexus. The observed average differences in plan quality for PCa and HNC cases were 8% and 6.7%, respectively. The dose parameter changes due to interobserver variability in PCa were small, with the exception of the anal canal, where large dose variations were observed. The reduction in time required for contouring was 72% for PCa and 84% for HNC. Conclusions: When an autocontouring system is used in combination with human review, the time of the RT workflow is significantly reduced without affecting dose distribution and plan quality. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is a serious health problem for men around the world, and it is often caused by inflammation in the prostate gland. The authors of this article explore how a group of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs) can help prevent and treat this disease by reducing inflammation and interfering with the growth and survival of cancer cells. We describe the various mechanisms by which NSAIDs can affect prostate cancer, such as triggering cell death, halting cell division, and cutting off blood supply. We also discuss the evidence from previous studies that support the use of NSAIDs as anti-cancer agents, either alone or in combination with other treatments. NSAIDs have a lot of promise as potential drugs for prostate cancer, but more research to understand their optimal dosage, timing, and safety is needed. Prostate cancer (PC) is the second most common type of cancer and the leading cause of death among men worldwide. Preventing the progression of cancer after treatments such as radical prostatectomy, radiation therapy, and hormone therapy is a major concern faced by prostate cancer patients. Inflammation, which can be caused by various factors such as infections, the microbiome, obesity and a high-fat diet, is considered to be the main cause of PC. Inflammatory cells are believed to play a crucial role in tumor progression. Therefore, nonsteroidal anti-inflammatory drugs along with their effects on the treatment of inflammation-related diseases, can prevent cancer and its progression by suppressing various inflammatory pathways. Recent evidence shows that nonsteroidal anti-inflammatory drugs are effective in the prevention and treatment of prostate cancer. In this review, we discuss the different pathways through which these drugs exert their potential preventive and therapeutic effects on prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study provides an overview of the current state of artificial intelligence applications in urooncology and explores potential future advancements in this field. With remarkable progress already achieved, artificial intelligence has revolutionized urooncology by facilitating image analysis, grading, biomarker research, and treatment planning. We also discuss types of artificial intelligence and their possible applications in the management of cancers such as prostate, kidney, bladder, and testicular. As artificial intelligence technology continues to evolve, it holds immense promise for further advancing urooncology and enhancing the care of patients with cancer. Introduction: Artificial intelligence is transforming healthcare by driving innovation, automation, and optimization across various fields of medicine. The aim of this study was to determine whether artificial intelligence (AI) techniques can be used in the diagnosis, treatment planning, and monitoring of urological cancers. Methodology: We conducted a thorough search for original and review articles published until 31 May 2022 in the PUBMED/Scopus database. Our search included several terms related to AI and urooncology. Articles were selected with the consensus of all authors. Results: Several types of AI can be used in the medical field. The most common forms of AI are machine learning (ML), deep learning (DL), neural networks (NNs), natural language processing (NLP) systems, and computer vision. AI can improve various domains related to the management of urologic cancers, such as imaging, grading, and nodal staging. AI can also help identify appropriate diagnoses, treatment options, and even biomarkers. In the majority of these instances, AI is as accurate as or sometimes even superior to medical doctors. Conclusions: AI techniques have the potential to revolutionize the diagnosis, treatment, and monitoring of urologic cancers. The use of AI in urooncology care is expected to increase in the future, leading to improved patient outcomes and better overall management of these tumors. [ABSTRACT FROM AUTHOR]

Background: There is limited real-world evidence on how increasing use of treatment intensification in metastatic castration-sensitive prostate cancer (mCSPC) has influenced treatment decisions in metastatic castration-resistant prostate cancer (mCRPC). The study objective was to evaluate the impact of novel hormonal therapy (NHT) and docetaxel use in mCSPC on first-line treatment patterns among patients with mCRPC in 5 European countries and the United States (US). Methods: Physician-reported data on patients with mCRPC from the Adelphi Prostate Cancer Disease Specific Program were descriptively analyzed. Results: A total of 215 physicians provided data on 722 patients with mCRPC. Across 5 European countries and the US, 65% and 75% of patients, respectively, received NHT, and 28% and 9% of patients, respectively, received taxane chemotherapy as first-line mCRPC treatment. In Europe, patients who had received NHT in mCSPC (n = 76) mostly received taxane chemotherapy in mCRPC (55%). Patients who had received taxane chemotherapy, or who did not receive taxane chemotherapy or NHT in mCSPC (n = 98 and 434, respectively) mostly received NHT in mCRPC (62% and 73%, respectively). In the US, patients who had received NHT, taxane chemotherapy, or neither in mCSPC (n = 32, 12, and 72, respectively) mostly received NHT in mCRPC (53%, 83%, and 83%, respectively). Two patients in Europe were rechallenged with the same NHT. Conclusions: These findings suggest that physicians consider mCSPC treatment history when making first-line treatment decisions in mCRPC. Further studies are needed to better understand optimal treatment sequencing, especially as new treatments emerge. This study evaluated whether treatments used in the metastatic castration-sensitive prostate cancer (mCSPC) setting influence choice of first-line treatment of metastatic castration-resistant prostate cancer (mCRPC) across a diverse, real-world patient population in five European countries and the US. [ABSTRACT FROM AUTHOR]

Simple Summary: The imaging of prostate cancer has evolved over the last few decades with molecular imaging, especially Positron Emission Tomography (PET) replacing conventional CT and MRI in patients with prostate cancer recurrence. These recent advances in PET imaging have allowed for a better localization of disease recurrence, and a better characterization of disease extent. Beyond localization and characterization, new uses for PET imaging have emerged, with PET agents now playing a role in assessing the response to treatment at the receptor level, and also helping to determine patient prognosis and survival. Prostate cancer is the most common non-dermatologic cancer in men, and one of the leading causes of cancer-related mortality. The incidence of prostate cancer increases precipitously after the age of 65 and demonstrates variable aggressiveness, depending on its grade and stage at diagnosis. Despite recent advancements in prostate cancer treatment, recurrence is seen in 25% of patients. Advancements in prostate cancer Positron Emission Tomography (PET) molecular imaging and recent United States Food and Drug Administration (FDA) approvals have led to several new options for evaluating prostate cancer. This manuscript will review the commonly used molecular imaging agents, with an emphasis on Fluorine-18 fluciclovine (Axumin) and PSMA-ligand agents, including their protocols, imaging interpretation, and pitfalls. [ABSTRACT FROM AUTHOR]

Modifiable lifestyle factors, such as following a healthy dietary pattern may delay or prevent prostate cancer (PCa) progression. However, few studies have evaluated whether following specific dietary patterns after PCa diagnosis impacts risk of disease progression among men with localized PCa managed by active surveillance (AS). 564 men enrolled in the Canary Prostate Active Surveillance Study, a protocol-driven AS study utilizing a pre-specified prostate-specific antigen monitoring and surveillance biopsy regimen, completed a food frequency questionnaire (FFQ) at enrollment and had ≥ 1 surveillance biopsy during follow-up. FFQs were used to evaluate adherence to the Dietary Guidelines for Americans (Healthy Eating index (HEI))-2015, alternative Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) dietary patterns. Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals were estimated using Cox proportional hazards models. During a median follow-up of 7.8 years, 237 men experienced an increase in Gleason score on subsequent biopsy (grade reclassification). Higher HEI-2015, aMED or DASH diet scores after diagnosis were not associated with significant reductions in the risk of grade reclassification during AS. However, these dietary patterns have well-established protective effects on chronic diseases and mortality and remain a prudent choice for men with prostate cancer managed by AS. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells and mesenchymal stem cells (MSCs) secrete C-C motif chemokine ligand 2 (CCL2), a small protein that attracts tumor-associated macrophages (TAMs), which promotes malignant progression, such as drug resistance and metastasis. In addition, MSCs can also be recruited by CCL2; thus, a local milieu consisting of tumor cells, MSCs, and TAMs can promote tumor progression via a CCL2-dependent paracrine. The aim of the current study was to examine the functions of endogenous CCL2 of MSCs in cancer biology. Using a genetic engineering technique, we blocked the CCL2 expression in murine bone marrow-derived MSCs (CCL2 KO MSCs) and analyzed the effects on cancer progression. We found that CCL2 KO MSCs showed anti-tumor function when injected with murine prostate cancer cells into mice. The inhibitory effect was associated with an increase of CD45+CD11b+ mononuclear myeloid cells in tumors. Background: MSCs are known to secrete abundant CCL2, which plays a crucial role in recruiting TAMs, promoting tumor progression. It is important to know whether disrupting MSC-derived CCL2 affects tumor growth. Methods: Murine bone marrow-derived MSCs were characterized by their surface markers and differentiation abilities. Proliferation and migration assays were performed in order to evaluate the functions of MSCs on cancer cells. CCL2 expression in MSCs was reduced by small interfering RNA (siRNA) or completely disrupted by CRISPR/Cas9 knockout (KO) approaches. An immune-competent syngeneic murine model of prostate cancer was applied in order to assess the role of tumor cell- and MSC-derived CCL2. The tumor microenvironment was analyzed to monitor the immune profile. Results: We confirmed that tumor cell-derived CCL2 was crucial for tumor growth and MSCs migration. CCL2 KO MSCs inhibited the migration of the monocyte/macrophage but not the proliferation of tumor cells in vitro. However, the mice co-injected with tumor cells and CCL2 KO MSCs exhibited anti-tumor effects when compared with those given tumor cell alone and with control MSCs, partly due to increased infiltration of CD45+CD11b+Ly6G− mononuclear myeloid cells. Conclusions: Disruption of MSC-derived CCL2 enhances anti-tumor functions in an immune-competent syngeneic mouse model for prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Kangquan Recipe (康泉方, KQR) on bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) expression and its mechanism in rats with benign prostatic hyperplasia (BPH). Methods: Forty-eight male Sprague-Dawley rats were divided into 6 groups using a random number table, with 8 in each group: the normal group (normal saline 10 mL/kg), the model group (normal saline 10 mL/kg), the finasteride group (0.5 mg/kg), the low-dose KQR group (3.5 g/kg), the middle-dose KQR group (7 g/kg), and the high-dose KQR group (14 g/kg). The 40 rats were subcutaneously injected with testosterone propionate after castration for 30 days to establish the BPH rat model except for those in the normal group. At the same time, the corresponding drugs were administered by gavage for 30 consecutive days. The effects of different doses of KQR on the protate wet weight, prostate volume and prostate index (PI) were observed. The changes in histopathology were monitored with hematoxylin-eosin staining. BAMBI protein and mRNA expression contents were determined by Western blot and quantitative real-time polymerase chain reaction, respectively. Results: All doses of KQR could decrease prostatic epithelial tissue proliferation. Compared to the model group, the high and middle-dose KQR significantly reduced prostate wet weight, prostate volume and PI; increased BAMBI protein expression in the hypothalamus, pituitary and prostate tissue; all doses of KQR up-regulated BAMBI mRNA expression in serum, prostatic fluid and prostate tissue (P<0.05 or P<0.01). Conclusions: KQR could inhibit the proliferation of rat prostatic tissue, promote BAMBI protein expression in the hypothalamic-pituitary-prostate of rats with BPH; and increase BAMBI mRNA expression in the blood, prostatic fluid and prostate tissue of rats with BPH, showing a dose-effect relationship. KQR can be used as a potential drug for the treatment of BPH. [ABSTRACT FROM AUTHOR]

People often experience high level of distress during invasive interventions, which may exceed their coping abilities. This may be in particular evident when confronted with the suspicion of cancer. Taking the example of prostate biopsy sampling, we aimed at investigating the impact of an MRI guided prostate biopsy on the acute stress response and its mechanistic basis. We recruited 20 men with a clinical suspicion of prostate cancer. Immediately before an MRI guided biopsy procedure, we conducted fMRI in the same scanner to assess resting-state brain connectivity. Physiological and hormonal stress measures were taken during the procedure and associated with questionnaires, hair cortisol levels and brain measures to elucidate mechanistic factors for elevated stress. As expected, patients reported a stress-related change in affect. Decreased positive affect was associated with higher hair but not saliva cortisol concentration. Stronger use of maladaptive emotion regulation techniques, elevated depression scores and higher within-salience-network connectivity was associated with stronger increase in negative affect and/or decrease of positive affect during the procedure. While being limited in its generalization due to age, sample size and gender, our proof of concept study demonstrates the utility of real-life stressors and large-scale brain network measures in stress regulation research with potential impact in clinical practice. [ABSTRACT FROM AUTHOR]

Up to date, screening for prostate cancer (PCa) remains one of the most appealing but also a very controversial topics in the urological community. PCa is the second most common cancer in men worldwide and it is universally acknowledged as a complex disease, with a multi-factorial etiology. The pathway of PCa diagnosis has changed dramatically in the last few years, with the multiparametric magnetic resonance (mpMRI) playing a starring role with the introduction of the "MRI Pathway". In this scenario the basic tenet of network medicine (NM) that sees the disease as perturbation of a network of interconnected molecules and pathways, seems to fit perfectly with the challenges that PCa early detection must face to advance towards a more reliable technique. Integration of tests on body fluids, tissue samples, grading/staging classification, physiological parameters, MR multiparametric imaging and molecular profiling technologies must be integrated in a broader vision of "disease" and its complexity with a focus on early signs. PCa screening research can greatly benefit from NM vision since it provides a sound interpretation of data and a common language, facilitating exchange of ideas between clinicians and data analysts for exploring new research pathways in a rational, highly reliable, and reproducible way. [ABSTRACT FROM AUTHOR]

Environmental and nutritional factors, including fatty acids (FA), are associated with prostatitis, benign prostate hyperplasia and prostate cancer. We hypothesized that different FA in normolipidic diets (7%) affect prostate physiology, increasing the susceptibility to prostate disorders. Thus, we fed male C57/BL6 mice with normolipidic diets based on linseed oil, soybean oil or lard (varying saturated and unsaturated FA contents and ω-3/ω-6 ratios) for 12 or 32 weeks after weaning and examined structural and functional parameters of the ventral prostate (VP) in the systemic metabolic context. Mongolian gerbils were included because they present a metabolic detour for low water consumption (i.e., oxidize FA to produce metabolic water). A linseed oil-based diet (LO, 67.4% PUFAs, ω-3/ω-6 = 3.70) resulted in a thermogenic profile, while a soybean oil-based diet (SO, 52.7% PUFAs, ω-3/ω-6 = 0.11) increased body growth and adiposity. Mice fed lard (PF, 13.1% PUFA, ω-3/ω-6 = 0.07) depicted a biphasic growth, resulting in decreased adiposity in adulthood. SO and PF resulted in hepatic steatosis and steatohepatitis, respectively. PF and SO increased prostate epithelial volume, and lard resulted in epithelial hyperplasia. Animals in the LO group had smaller prostates with predominant atrophic epithelia and inflammatory loci. Inflammatory cells were frequent in the VP of PF mice (predominantly stromal) and LO mice (predominantly luminal). RNAseq after 12 weeks revealed good predictors of a later-onset inflammation. The transcriptome unveiled ontologies related to ER stress after 32 weeks on PF diets. In conclusion, different FA qualities result in different metabolic phenotypes and differentially impact prostate size, epithelial volume, inflammation and gene expression. [ABSTRACT FROM AUTHOR]

The article discusses the superiority of prostatespecific membrane antigen (PSMA) positron emission tomography (PET) imaging over bone scans in detecting prostate cancer bone metastases. It emphasizes its use in initial staging, recurrence detection, and treatment response assessment. It reports that PSMA PET in evaluating treatment response for bone metastases impacted by androgen-axis targeted agents remains uncertain, despite its effectiveness in initial diagnosis and recurrence detection.

Introduction: This study aims to assess whether cryosurgery is a feasible local therapy for bone metastatic prostate cancer (bmPCa).Methods: A total of 23 patients with bmPCa who received cryosurgery and adjuvant androgen deprivation therapy (ADT) were included in the cryosurgery group (Group 1). Another 23 matched patients who received only ADT served as the control (Group 2). Prostate-specific antigen (PSA) nadir level, time to PSA nadir, time to castration-resistant prostate cancer (CRPC), progression-free survival and therapy response of bone metastases were compared between the groups.Results: The median follow-up time in Group 1 and Group 2 patients was 37 (range 19-53) months and 42 (range 24-56) months, respectively. Patients in Group 1 had fewer local complications, lower PSA nadir level (0.23 ng/mL vs. 4.01 ng/mL; p = 0.024), shorter median time to PSA nadir (3 months vs. 7 months; p < 0.001), longer median time to CRPC (36 months vs. 27 months; p = 0.002) and longer progression-free survival (35 months vs. 26 months; p = 0.003) compared to those in Group 2. Therapy responses of bone metastases were similar in the two treatment groups (p = 0.689).Conclusion: Cryosurgery is a feasible local therapy for bmPCa patients with prostate volume less than 50 mL and without bulk tumours outside the prostate capsula. Cryosurgery may decrease PSA nadir level, local complications and time to PSA nadir, delay time to CRPC and improve progression-free survival. [ABSTRACT FROM AUTHOR]

Background: Phospholipases A 2 (PLA 2 ) may be involved in α 1 -adrenergic contraction by formation of thromboxane A 2 in different smooth muscle types. However, whether this mechanism occurs with α 1 -adrenergic contractions of the prostate, is still unknown. While α 1 -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 A 2 . Here, we examined effects of PLA 2 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 α 1 -adrenergic agonists in an organ bath, after application of the cytosolic PLA 2 inhibitors ASB14780 and AACOCF3, the secretory PLA 2 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 α 1 -adrenergic agonists, while all contractions were substantially inhibited by silodosin (100 nM)., Conclusions: Our findings suggest presynaptic PLA 2 functions in prostate smooth muscle contraction, while contractions induced by α 1 -adrenergic agonists occur PLA 2 -independent. Lacking sensitivity to montelukast excludes an involvement of PLA 2 -derived leukotrienes in promotion of contractile neurotransmission., (© 2023 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Highlights • Toxicants exposure is associated with the occurrence of male reproductive disorders. • Prostate is highly sensible to hormonal unbalance caused by EDCs during its development. • EDCs are able to disrupt cell-cell adhesion in different experimental models and in different pathologic conditions. • Some EDCs can accelerate the epithelial-mesenchymal transition during oncogenic process and metastasis in the prostate. Abstract Throughout the last decades, increasing exposure to environmental Endocrine Disruptors Chemicals (EDCs) has been associated with the occurrence of male reproductive disorders, such as impairment of prostate development and function, increase of susceptibility to oncogenesis, Epithelial-Mesenchymal Transition and the metastatic invasive potential. Nevertheless, few studies address the mechanisms involved in these alterations, especially those related to cell junctions, which are hormonally regulated and, therefore, possible EDCs targets. The cellular mechanisms discussed in this review are addressed to EDCs actions on tight, gap and adherent junctions and its related genes and proteins, such as claudin-1, -3, -4 and -8, connexin-32 and -43, E-cadherin and β-catenin, respectively. The impairment of cell junction function, mainly due EDCs exposure during the prostate's critical window of development, can corroborate to acquire a mesenchymal phenotype by epithelial cells and the prostate microenvironment becomes susceptible to development of lesions in the latter stages of life. [ABSTRACT FROM AUTHOR]

Highlights • Flutamide during development affects cell junctions in adult male reproductive tract. • Flutamide exerts short-term effects on cell-cell junctions in adult testis and epididymis. • Hydroxyflutamide may act either as androgen agonist or antagonist in cell cultures. • Hydroxyflutamide acts on cell-cell junctions in prostate cancer cells. Abstract In this review, we summarize recent findings on the effect of the anti-androgen flutamide on cell-cell junctions in the male reproductive system. We outline developmental aspects of flutamide action on the testis, epididymis, and prostate, and describe changes in junction protein expression and organization of junctional complexes in the adult boar following prenatal and postnatal exposure. We also discuss findings on the mechanisms by which flutamide induces alterations in cell-cell junctions in reproductive tissues of adult males, with special emphasis on cytoplasmic effects. Based on the results from in vivo and in vitro studies in the rat, we propose that flutamide affects the expression of junction proteins and junction complex structure not only by inhibiting androgen receptor activity, but equally important by modulating protein kinase-dependent signaling in testicular cells. Additionally, results from studies on prostate cancer cell lines point to a role for the cellular molecular outfit in response to flutamide. [ABSTRACT FROM AUTHOR]

Aim: To validate the diagnostic accuracy of Prostate Imaging-Reporting and Data System (PI-RADS) version 2 in detecting clinically significant prostate cancer (csPCa, Gleason score ≥7) on prebiopsy biparametric MRI (bpMRI) in patients with different prostate-specific antigen (PSA) levels.Materials and Methods: This retrospective study included 184 patients who underwent prebiopsy bpMRI followed by transrectal ultrasonography-guided biopsy between June 2015 and February 2017. Reader 1 performed a combination of systematic and targeted biopsy with cognitive fusion after reviewing bpMRI and reader 2 reviewed the bpMRIs retrospectively. PI-RADS categories 4 and 5 were considered positive, and the results of the biopsy were considered the reference standard. Diagnostic performance of PI-RADS of bpMRI was evaluated in two PSA groups with a PSA cut-off level of 10 ng/ml and compared to PSA and the PSA density using receiver operating characteristics (ROC) curve analysis.Results: csPCa was diagnosed in 24 of 123 patients (19.5%) and 26 of 61 patients (42.6%) in the low and high PSA groups, respectively. A PI-RADS v2 category by either readers 1 or 2 had a significantly better performance to detect csPCa than PSA in both PSA groups. In the high PSA group, only one csPCa was missed by reader 2, but none by reader 1. In the low PSA group, readers 1 and 2 were unable to detect seven and five of the 24 csPCas, respectively.Conclusion: Prebiopsy bpMRI has good performance for detecting csPCa in the high PSA group but may miss small-volume csPCa in the low PSA group. [ABSTRACT FROM AUTHOR]

Abstract: Morphological characterisation of the genital organs of primates may bring significant contributions to the understanding of different reproductive behaviours and support new conservation strategies. However, relevant or detailed descriptions of genital morphology of several primate species are still lacking. This study describes the gross and microscopic anatomy of the internal and external genitalia of Marca's marmoset (Mico marcai). The same organs described in other primate species were identified here, but some anatomical particularities were detected, such as absence of a dartos tunic, presence of a vas deferens ampulla, absence of spongious erectile tissue in the pelvic urethra, separation of prostate gland lobes by a longitudinal sulcus and lack of septation in the corpus cavernosus and spongiosus at the level of the shaft and free portion of the penis. Keratinised type 1 spicules arising from epidermal or dermal projections were found in the free portion of the penis. Microscopic analysis revealed a small bone (baculum) consisting of peripheral compact bone and a central, non‐ossified area filled with vascular tissue at the distal end of this portion of the penis. Results of this study may support further comparative studies of primates' reproductive ecology. [ABSTRACT FROM AUTHOR]

Purpose. Triple-negative breast cancer refers to breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (Her2). This study aimed to identify the key pathways and genes and find the potential initiation and progression mechanism of triple-negative breast cancer (TNBC). Methods. We downloaded the gene expression profiles of GSE76275 from Gene Expression Omnibus (GEO) datasets. This microarray Super-Series sets are composed of gene expression data from 265 samples which included 67 non-TNBC and 198 TNBC. Next, all the differentially expressed genes (DEGs) with p<0.01 and fold change ≥1.5 or ≤-1.5 were identified. Result. 56 upregulated and 151 downregulated genes were listed and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis was performed. These significantly changed genes were mainly involved in the biological process termed prostate gland morphogenesis, inner ear morphogenesis, cell maturation, digestive tract morphogenesis, autonomic nervous system development, monovalent inorganic anion homeostasis, neural crest cell development, regulation of dendrite extension and glial cell proliferation, immune system process termed T cell differentiation, regulation of immune response, and macrophage activation. Genes are mainly involved in the KEGG pathway termed Oocyte meiosis. All DEGs underwent survival analysis using datasets from The Cancer Genome Atlas (TCGA) integrated by cBioPortal, of which amplification of SRY-related HMG-box 8 (SOX8), androgen receptor (AR), and Chromosome 9 Open Reading Frame 152 (C9orf152) were significantly negative while Nik Related Kinase (NRK) and RAS oncogene family 30 (RAB30) were positively correlated to the life expectancy (p<0.05). Conclusions. In conclusion, these pathways and genes identified could help understanding the mechanism of development of TNBC. Besides, SOX8, AR, C9orf152, NRK and RAB30, and other key genes and pathways might be promising targets for the TNBC treatment. [ABSTRACT FROM AUTHOR]

Aims: To assess the feasibility, findings and potential value of early post-interventional, contrast-enhanced ultrasonographic (CEUS) study of prostate artery embolization (PAE).Material and Methods: Fourteen patients treated with PAE for symptomatic benign prostatic hyperplasia were prospectively included in the study. Sonographic evaluation of the prostate included: 1) baseline transabdominal and transrectal CEUS (ta-CEUS and tr-CEUS, respectively) 1-3 days prior to PAE; 2) early post PAE CEUS, with ta-CEUS immediately post PAE and tr-CEUS 3 days post PAE; and 3) follow-up with ta-CEUS and tr-CEUS 3 months post PAE. A brief unenhanced US study preceded each CEUS. Post-therapeutic changes in size, echogenicity and enhancement of the prostate were recorded and were correlated with clinical outcomes.Results: PAE resulted in clinical success in 11/14 patients (78.5%). All sonographic studies were technically adequate, with the exception of ta-CEUS immediately post PAE in 2/14 (14.2%) patients. CEUS studies immediately post PAE and 3 days post PAE showed non-enhancing, welldefined infarctions of the prostate in 10/14 patients (71.4%). There was a strong correlation between ta-CEUS immediately post PAE and tr-CEUS 3 days post PAE regarding the measurements of prostatic infarctions (r =0.98, p< 0.01). The presence of infarctions on early post PAE CEUS was associated with clinical success (p=0.01) and their extent correlated with the degree of prostate shrinkage on 3-month follow-up (r=0.84, p<0.05). The 3 cases of failed PAE showed no infarctions and no prostate shrinkage.Conclusions: Early post-interventional CEUS of PAE is feasible and may have clinical and prognostic value. [ABSTRACT FROM AUTHOR]

The impact of bisphenol A (BPA) on the prostate gland has taken center stage, with a special focus placed on understanding how BPA affects prostate physiopathology. In this study, we evaluated the ability of lower doses of BPA to induce alterations in 5α-R isozymes and aromatase, in the prostate of juvenile rats exposed during developmental stage. Gestating Wistar rats were treated s.c with either vehicle or BPA (2.4 and 10 μg/kg b.w./day) from gestational day 12 to parturition. Then, male pups were s.c treated from postnatal day 1 through day 21, when they were euthanized and qRT-PCR, western blot and hormone levels determination were performed. We found that BPA at dose of 2.4 and 10 μg/kg b.w./day significantly decreased the mRNA and protein levels of 5α-R2. However, neither 5α-R1 nor 5α-R3 was affected by this exposure. BPA at dose of 10 μg/kg b.w./day significantly increased the mRNA and protein levels of aromatase. BPA also decreased plasma levels of both testosterone and dihydrotestosterone and increased estradiol. These data lend support that low-dose BPA during fetal and neonatal prostate development interfere with in situ estrogen and androgen production in the prostate gland of juvenile rats through the enzymes aromatase and 5α-Reductase. [ABSTRACT FROM AUTHOR]

Isosamidin is a pharmacologically active compound extracted from Peucedanum japonicum which is used as a health food in East Asia. Our preliminary animal data suggested that isosamidin may have sufficient potency to treat patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia or overactive bladder. However, the efficacy of isosamidin in humans is unknown. Here, we examined whether isosamidin inhibits agonist-stimulated contractions in isolated human bladder and prostate tissue strips in vitro. Human bladder and prostate strips obtained from 9 to 10 male patients, respectively, were suspended in organ baths. After administration of isosamidin (10, 30, and 100 μM), concentration-response curves to agonists (acetylcholine or phenylephrine) were constructed by cumulatively increasing agonist concentration. Isosamidin inhibited phenylephrine-stimulated contractions of isolated human prostate tissue strips in a concentration-dependent manner, with significant differences observed between control and 100 μM isosamidin. In contrast, isosamidin had no effect on acetylcholine-stimulated contractions of isolated human bladder tissue strips. Isosamidin may have pharmacological potency in the treatment of male patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Clinical studies are needed to confirm the efficacy and safety of isosamidin in humans. [ABSTRACT FROM AUTHOR]

Objective: To assess cardiovascular risk factors and carotid intima-media thickness in patients with benign prostatic hyperplasia.Materials and Methods: One hundred and twenty-three patients who were evaluated for the presence of benign prostatic hyperplasia with accompanying symptoms were included in the study. Patients were also examined by cardiology department to assess and measure cardiovascular risk factors, left ventricular functions, and carotid intima-media thickness.Results: Cardiovascular risk factors adjusted carotid intima-media thickness was found to be different between 3 groups, being highest in the severely symptomatic group and lowest in the mildly symptomatic group. Significant correlation of prostatic volume was shown with carotid intima-media thickness after adjusting prostatic volume for body mass index and age, and carotid intima-media thickness for cardiovascular risk factors (r = 0.75 P = .01). Linear regression analysis revealed that carotid intima-media thickness significantly associated with prostatic volume (beta coefficient: 0.628; confidence interval: 37.02-60.1; P = .001).Conclusion: We have demonstrated that prostatic tissue has significant association with carotid intima-media thickness in patients with benign prostatic hyperplasia. [ABSTRACT FROM AUTHOR]

Supplementation is a strategy to potentiate physical training through hypertrophy of skeletal muscles, but other tissues such as the prostate may also be affected. Changes in prostate size and function are associated with the behavior of individuals, but evidence for an association with supplementation is scarce. Therefore, the aim of our study was to evaluate the effect of b-hydroxy bmethylbutyrate (HMB) supplementation and concurrent training on the prostate. Wistar rats were divided randomly into four groups with 10 animals each: control group (C), supplemented group (S), training group (T), and supplemented plus training group (TS). The supplemented groups (S and TS) received 76 mg·kg/day of HMB and the concurrent training groups (T and TS) performed exercise three times per week for eight weeks. HMB increased body composition, total weight of the prostate, and altered the histology of prostatic compartments. The lateral prostate of animals in the supplemented group had an increase in mast cells per mm2 (28.0 ± 3.9) compared to the control and exercise group (6.1 ± 3.0; 2.3 ± 0.9) There was also an increase in inflammation in the stroma and lumen of the prostate, and increased expression of androgen receptor (AR) in the supplemented and trained supplemented group (79.8 ± 2.1; 76.8 ± 11.4) in relation to the trained group (61.5 ± 7.0). We concluded that HMB alters hormone receptors that induce morphological changes and inflammation, and animals in the concurrent training group had normal inflammatory and hormonal profiles, and favorable prostatic histology. [ABSTRACT FROM AUTHOR]

Purpose: To date, the parameters for evaluating enucleation efficiency have only considered enucleation time, although operators simultaneously consume both time and energy during holmium laser enucleation of the prostate. This study was undertaken to find a better way of assessing enucleation skills, considering both enucleation time and consumed energy. Materials and Methods: One hundred (n=100) consecutive patients who underwent holmium laser enucleation of the prostate from April 2012 to April 2014 by a single surgeon were enrolled. Ten groups of 10 consecutive cases were used to analyze the parameters of enucleation efficiency. Results: The mean enucleation time, consumed energy, and enucleated weight were 41.3±19.2 minutes, 66.2±36.0 kJ, and 26.6±21.8 g, respectively. Concerning learning curves, like enucleation time-efficacy (=enucleated weight/enucleation time), enucleation energy-efficacy (=enucleated weight/consumed energy) also had an increasing tendency. Enucleation ratio efficacy (=enucleated weight/transitional zone volume/enucleation time) plateaued after 30 cases. However, enucleation time-energyefficacy (=enucleated weight/enucleation time/consumed energy) continued to increase after 30 cases and plateaued at 61 to 70 cases. Furthermore, one-way analysis of variance showed that group means for enucleation time-energy-efficacy (F=3.560, p=0.001) were significantly different, but that those of enucleation ratio efficacy (F=1.931, p=0.057) were not. Conclusions: When both time and energy were considered, enucleation skills continued to improve even after 30 cases and plateaued at 61 to 70 cases. Therefore, we propose that enucleation time-energy-efficacy should be used as a more appropriate parameter than enucleation ratio efficacy for evaluating enucleation skills. [ABSTRACT FROM AUTHOR]

Proteinases secreted by the prostate gland have a reproductive function in cleaving proteins in the ejaculate and in the female reproductive tract, but some may have a fundamental role in disease and pathological processes including cancer. The purpose of this study was to determine if there were differences in proteinase activities in urine samples collected following prostate massage of men positive (CaP) or negative (no evidence of malignancy, NEM) for biopsy determined prostate cancer. Matrix metalloproteinase (MMP) and serine proteinase activities were detected using protein substrate zymography. There were no differences in activities of MMP-2, proMMP-9, and MMP-9/NGAL (neutrophil gelatinase associated lipocalin) complex (gelatin substrate) in men with detected prostate cancer, although the latter two were somewhat diminished. A caseinolytic activity of about 75 kDa inhibited by calcium did not differ between the NEM and CaP groups. Heparin stimulated calcium sensitive gelatinolytic activities of approximately 22, 42, and 60 kDa, but did not affect activities of MMP-2, MMP-9, or the 75 kDa caseinolytic activity. The 22, 42, and 60 kDa activities appear to be serine proteinases since they were inhibited by benzamidine. There was a significant decrease in the 22 kDa heparin-stimulated serine proteinase activity in urines of men with cancer. Proteinase expression and activities, perhaps in combination with other potential markers, may prove useful in urine for detection and evaluation of prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: To prospectively investigate the longitudinal effect of ejaculatory abstinence on MRI-measured seminal vesicle (SV) volume and whole-prostate ADC over consecutive days.Methods: 15 healthy male volunteers (mean 35.9 years, range 27-53) underwent 3-T MRI at baseline and 1, 2 and 3 days post-ejaculation. Prostate and SV volumes were derived by volume segmentation and whole-gland apparent diffusion coefficient (ADC) values calculated. A mixed-effects linear regression compared ADC values and prostate/seminal vesicle volumes in each volunteer between studies in a pairwise manner.Results: All subjects completed the four MRIs. Mean prostate volume was 22.45 cm3 (range 13.04-31.21 cm3), with no change between the four studies (p = 0.89-0.99). 13/15 subjects showed SV volume reduction from baseline to day 1, with group-mean decreasing from 6.45 to 4.80 cm3 (-25.6%, p < 0.001), and a significant reduction from baseline to day 2 (-18.1%, p = 0.002). There was a significant volume increase from both day 1 (+21.3%, p = 0.006) and day 2 (+10.2%, p = 0.022) to day 3 post-ejaculation. There was a significant reduction in ADC from 1.105 at baseline to 1.056 × 10-3 mm2/s at day 1 (mean -4.3%, p = 0.009).Conclusion: The longitudinal effect of ejaculation on SV volume was demonstrated. Significant reductions in SV volume and whole-gland ADC were observed post-ejaculation, supporting a 3-day period of abstinence before prostate MRI.Key Points: • Seminal vesicle volume significantly reduced 24 h post-ejaculation remaining reduced at day 2 • Seminal vesicle fluid volume significantly increased from day 1 to day 3 post-ejaculation • There was a significant reduction in whole-gland prostate ADC values day 1 post-ejaculation • 3-day abstinence from ejaculation is required to ensure maximal seminal vesicle distension. [ABSTRACT FROM AUTHOR]

Telocytes are CD34-positive interstitial cells, known to exert several functions, one of which is a role in tissue organisation, previously demonstrated by telocytes in the myocardium. The existence of telocytes in the prostate has recently been reported, however, there is a lack of information regarding the function of these cells in prostate tissue, and information regarding the possible role of these cells in prostatic development. This study used immunofluorescence techniques in prostate tissue and prostatic telocytes in culture to determine the relationship between telocytes and prostate morphogenesis. Furthermore, immunofluorescent labelling of telocytes was performed on prostate tissue at different stages of early postnatal development. Initially, CD34-positive cells are found at the periphery of the developing alveoli, later in the same region, c-kit-positive cells and cells positive for both factors are verified and CD34-positive cells were predominantly observed in the interalveolar stroma and the region surrounding the periductal smooth muscle. Fluorescence assays also demonstrated that telocytes secrete TGF-β1 and are ER-Beta (ERβ) positive. The results suggest that telocytes play a changing role during development, initially supporting the differentiation of periductal and perialveolar smooth muscle, and later, producing dense networks that separate alveoli groups and form a barrier between the interalveolar region and periurethral smooth muscle. We conclude that telocytes play a relevant role in prostate tissue organisation during postnatal development. [ABSTRACT FROM AUTHOR]

The prostate gland is a strictly androgen-dependent organ which is also the main target of infectious and inflammatory diseases in the male reproductive tract. Host defenses and immunity of the gland have unique features to maintain a constant balance between response and tolerance to diverse antigens. In this context, the effects of reproductive hormones on the male tract are thus complex and have just started to be defined. From the classical description of 'the prostatic antibacterial factor,' many host defense proteins with potent microbicidal and anti-tumoral activities have been described in the organ. Indeed, it has been proposed a central role for resident cells, that is, epithelial and smooth muscle cells, in the prostatic response against injuries. However, these cells also represent the target of the inflammatory damage, leading to the development of a Proliferative Inflammatory Atrophy-like process in the epithelium and a myofibroblastic-like reactive stroma. Available data on androgen regulation of inflammation led to a model of the complex control, in which the final effect will depend on the tissue microenvironment, the cause of inflammation, and the levels of androgens among other factors. In this paper, we review the current scientific literature about the inflammatory process in the gland, the modulation of host defense proteins, and the influence of testosterone on the resolution of prostatitis. [ABSTRACT FROM AUTHOR]

Zinc is important for cell physiology and alteration of its levels during development can modulate a series of biological events. The aim of this study was to investigate whether dietary zinc deficiency or supplementation during morphogenesis and early postnatal development could interfere in prostate maturation. Pregnant rats were exposed to a standard diet (NZ:35 mg Zn/kg chow), low-zinc diet (LZ:3 mg of Zn/kg chow) and zinc-supplemented diet (HZ:180 mg/Kg chow) from gestational day 10 (GD10) through postnatal day 21 (PND21). After weaning, male offspring were divided into three groups that were submitted to the same food conditions as their mothers until PND53. The animals were euthanized at PND53 and PND115. The ventral prostate was removed, weighed and its fragments were subjected to histological, western blot and zymography analysis. PND53: body and prostate weight were lower in LZ compared to NZ; the epithelial compartment was reduced while the stromal compartment was increased in LZ compared to NZ; there was an increase in the amount of collagen and reduction in AR and SIRT1 expression in LZ compared to NZ. PND115: body weight was lower in LZ compared to NZ and prostate weight was similar among the groups; peripheral physiological hyperplasia was observed, as well as an increased epithelial proliferation index and reduced PAR4 expression in LZ and HZ compared to NZ. Zinc deficiency during prostate morphogenesis and differentiation is potentially harmful to its morphology, however, by restoring the standard dietary environment, the gland responds to the new microenvironment independent of the previous dietary condition. [ABSTRACT FROM AUTHOR]

The female prostate was first described by Reijnier de Graaf in 1672, and even after several years this gland is still a matter of controversy. Part of this is because the biological function of this female gland is unclear. Moreover, when compared with the male prostate, the existence of this organ in females does not make sense, mainly when we consider that the major function of this gland is to produce a secretion that is responsible for guarantee the sperm survival and assure the reproductive success. However, even under a controversy field, we now have a lot of scientific information which enhances our knowledge of several important biological aspects of this gland. It is clear that this gland is found in some female mammals including humans, rodents, rabbits, bats, and dogs. Several studies with rodents showed that the female prostate is homolog of the male prostate, showing strong macroscopic and microscopic similarities with the ventral lobe of males. Besides these aspects, there are several studies reporting that diseases such as cysts, hyperplasia, and carcinoma may affect the female prostate. Therefore, although diseases involving the female prostate are rare, the susceptibility of this organ to develop lesions must be considered, especially in our recent years in which the exposure to endocrine-disrupting chemicals has greatly increased. Finally, further studies will be necessary to enhance our understanding about this gland, mainly of the developmental, evolutionary, and biological functions. [ABSTRACT FROM AUTHOR]

The effects of intrauterine exposure to 17β-oestradiol (E2) are well studied for the male prostate and there are accumulating evidences that the exposure to high dosages leads to a hypomorphic development. However, there is a lack of information about the effects of intrauterine exposure to E2 in the prostate of rodent females, and such research becomes relevant in view of the presence of functional prostate in a proportion of women, and the morphophysiological similarities between the prostate of female rodents and the prostate of women. This study uses histochemical, immunohistochemical, immunofluorescence and three-dimensional (3D) reconstruction techniques to evaluate the effects of intrauterine exposure to E2 (500 BW/d) on neonatal prostate development in both male and female gerbils. It was verified that intrauterine exposure to E2 promotes epithelial proliferation and growth of prostatic budding in females, whereas in males the prostatic budding shows hypomorphic growth in the VMP (Ventral Mesenchymal Pad) as well as reduced epithelial proliferation. Together, the data demonstrate that intrauterine exposure to E2 causes different effects on male and female prostates of the gerbil even at the early postnatal development of the gland. [ABSTRACT FROM AUTHOR]

The prostate is a compound exocrine gland of the male reproductive tract universally present in mammals. It is highly responsive to androgen and can be committed by a variety of pathological complications as prostatitis, benign, and malignant proliferative changes, which may be intensified by aging. Prostate intensively turnover its extracellular matrix (ECM) either at homeostasis or disease which includes a dynamically change of glycosaminoglycan composition during the life of an individual. Among the different enzymes playing a role in such changes, heparanase-1 is responsible for cleaving heparan sulfate (HS) at a limited number of sites, clearly involved in tissue remodeling. Its activity has been strongly implicated in cell invasion associated with cancer metastasis, a consequence of the structural modification that loosens the ECM barrier. In the present review we focuses in some aspects of the prostate physiology and diseases, particular prostate cancer, evidencing how the HPSE-1 activity encompasses the relationship of both processes. [ABSTRACT FROM AUTHOR]