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Accurate prostate volume estimation is crucial for effective prostate disease management. Ultrasound (US) imaging, particularly transrectal ultrasound, offers a cost-effective and rapid assessment. However, US images often suffer from artifacts and poor contrast, making prostate volume estimation challenging. This review explores recent advancements in deep learning (DL) techniques for automatic prostate segmentation in US images as a primary step toward prostate volume estimation. We examine various DL architectures, including traditional U-Net modifications and innovative designs incorporating residual connections, multi-directional image data, and attention mechanisms. Additionally, we discuss pre-processing methods to enhance image quality, the integration of shape information, and strategies to improve the consistency and robustness of DL models. The effectiveness of these techniques is evaluated through metrics such as the Dice Similarity Coefficient, Jaccard Index, and Hausdorff Distance. The review highlights the potential of DL in improving prostate volume estimation accuracy and reducing clinical workload while also identifying areas for future research to enhance model performance and generalizability. [ABSTRACT FROM AUTHOR]

The molecular mechanisms driving the onset and metastasis of prostate cancer remain poorly understood. Actin, under the control of actin-binding proteins (ABPs), plays a crucial role in shaping the cellular cytoskeleton, which in turn supports the morphological alterations in normal cells, as well as the invasive spread of tumor cells. Previous research indicates that ABPs of various types serve distinct functions, and any disruptions in their activities could predispose individuals to prostate cancer. These ABPs are intricately implicated in the initiation and advancement of prostate cancer through a complex array of intracellular processes, such as severing, linking, nucleating, inducing branching, assembling, facilitating actin filament elongation, terminating elongation, and promoting actin molecule aggregation. As such, this review synthesizes existing literature on several ABPs linked to prostate cancer, including cofilin, filamin A, and fascin, with the aim of shedding light on the molecular mechanisms through which ABPs influence prostate cancer development and identifying potential therapeutic targets. Ultimately, this comprehensive examination seeks to contribute to the understanding and management of prostate diseases. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate how a family history of prostate cancer influences the progression of the disease in individuals with prostate cancer undergoing active surveillance. Materials and Methods: We conducted a thorough literature search in PubMed/MEDLINE, Embase, and Cochrane Library up to June 2023. This systematic review was registered in PROSPERO (CRD42023441853). The study evaluated the effects of family history of prostate cancer (intervention) on disease progression (outcome) in prostate cancer patients undergoing active surveillance (population) and compared them to those without a family history (comparators). For time to disease progression outcomes, the extracted data were synthesized using the inverse variance method on the log hazard ratios scale. Results: A total of eight studies were incorporated into this systematic review and meta-analysis. The combined hazard ratio for unadjusted disease progression was 1.06 (95% confidential interval [CI] 0.66-1.69; p=0.82). The combined hazard ratio for adjusted disease progression was 1.31 (95% CI 1.16-1.48; p<0.0001). All the enlisted studies demonstrated high quality based on the Newcastle-Ottawa scale. The certainty of evidence for univariate and multivariate analysis of disease progression was very low and low, respectively. Publication bias for all studies was not significant. Conclusions: For individuals with prostate cancer opting for active surveillance, a family history of prostate cancer may serve as an independent risk factor associated with an elevated risk of disease progression. Clinicians should be counseled about the increased risk of disease progression in patients with a family history of prostate cancer undergoing active surveillance. [ABSTRACT FROM AUTHOR]

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Background: Although it is thought that prostatitis or benign prostatic hyperplasia (BPH) is related to prostate cancer (PCa), the underlying causal effects of these diseases are unclear. Methods: We assessed the causal relationship between prostatitis or BPH and PCa using a two-sample Mendelian randomization (MR) approach. The data utilized in this study were sourced from genome-wide association study. The association of genetic variants from cohorts of prostatitis or BPH and PCa patients was determined using inverse-variance weighted and MR Egger regression techniques. The direction of chance was determined using independent genetic variants with genome-wide significance (P < 5 × 10–6). The accuracy of the results was confirmed using sensitivity analyses. Results: MR analysis showed that BPH had a significant causal effect on PCa (Odds Ratio = 1.209, 95% Confidence Interval: 0.098–0.281, P = 5.079 × 10− 5) while prostatitis had no significant causal effect on PCa (P > 0.05). Additionally, the pleiotropic test and leave-one-out analysis showed the two-sample MR analyses were valid and reliable. Conclusions: This MR study supports that BPH has a positive causal effect on PCa, while genetically predicted prostatitis has no causal effect on PCa. Nonetheless, further studies should explore the underlying biochemical mechanism and potential therapeutic targets for the prevention of these diseases. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion To explore the topic of Prostate Imaging‐Reporting and Data System (PI‐RADS) interobserver variability, including a discussion of major sources, mitigation approaches, and future directions.A narrative review of PI‐RADS interobserver variability.PI‐RADS was developed in 2012 to set technical standards for prostate magnetic resonance imaging (MRI), reduce interobserver variability at interpretation, and improve diagnostic accuracy in the MRI‐directed diagnostic pathway for detection of clinically significant prostate cancer. While PI‐RADS has been validated in selected research cohorts with prostate cancer imaging experts, subsequent prospective studies in routine clinical practice demonstrate wide variability in diagnostic performance. Radiologist and biopsy operator experience are the most important contributing drivers of high‐quality care among multiple interrelated factors including variability in MRI hardware and technique, image quality, and population and patient‐specific factors such as prostate cancer disease prevalence. Iterative improvements in PI‐RADS have helped flatten the curve for novice readers and reduce variability. Innovations in image quality reporting, administrative and organisational workflows, and artificial intelligence hold promise in improving variability even further.Continued research into PI‐RADS is needed to facilitate benchmark creation, reader certification, and independent accreditation, which are systems‐level interventions needed to uphold and maintain high‐quality prostate MRI across entire populations. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) in urine are a promising source for developing non-invasive biomarkers. However, urine concentration and content are highly variable and dynamic, and actual urine collection and handling often is nonideal. Furthermore, patients such as those with prostate diseases have challenges in sample collection due to difficulties in holding urine at designated time points. Here, we simulated the actual situation of clinical sample collection to examine the stability of EVs in urine under different circumstances, including urine collection time and temporary storage temperature, as well as daily urine sampling under different diet conditions. EVs were isolated using functionalized EVtrap magnetic beads and characterized by nanoparticle tracking analysis (NTA), western blotting, electron microscopy, and mass spectrometry (MS). EVs in urine remained relatively stable during temporary storage for 6 hours at room temperature and for 12 hours at 4 °C, while significant fluctuations were observed in EV amounts from urine samples collected at different time points from the same individuals, especially under certain diets. Sample normalization with creatinine reduced the coefficient of variation (CV) values among EV samples from 17% to approximately 6% and facilitated downstream MS analyses. Finally, based on the results, we applied them to evaluate potential biomarker panels in prostate cancer by data-independent acquisition (DIA) MS, presenting the recommendation that can facilitate biomarker discovery with nonideal handling conditions. [ABSTRACT FROM AUTHOR]

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

Objectives: To investigate the diagnostic performance of the apparent diffusion coefficient (ADC) for low to intermediate-risk prostate cancer (PCa), as well as its correlation with the prognostic Gleason score (GS). Materials and methods: Retrospective analysis of MRI images and relevant clinical data from patients with prostate disease. The differences in ADC between different GS groups were compared, and the efficacy of ADC in PCa diagnosis were analyzed. Furthermore, the diagnostic performance of the mean ADC (ADCmean) and minimum ADC (ADCmin) values was compared. Results: There were 1414 patients with 1631 lesions. In terms of GS, both ADCmin and ADCmean values of the GS 4 + 3 group were significantly lower than those of the GS 3 + 4 group, GS 3 + 3 group, and the benign group, with all differences being statistically significant (p < 0.01). The AUC values for diagnosing PCa based on ADCmin and ADCmean were 0.914 and 0.944, respectively. The corresponding diagnostic thresholds were 0.703 × 10−3 mm2/s for ADCmin and 0.927 × 10−3 mm2/s for ADCmean. The magnitudes of ADCmin and ADCmean values exhibited a negative correlation with GS values (ρ = −0.750, p < 0.001; ρ = −0.752, p < 0.001). Conclusions: ADC values demonstrate an inverse relationship with the invasiveness of PCa, indicating that higher invasiveness is associated with lower ADC values. Additionally, ADC values exhibit high diagnostic potential, sensitivity, and specificity for distinguishing between GS 3 + 4 and GS 4 + 3 lesions. Moreover, the diagnostic value of ADCmean is even more significant, highlighting its crucial role in the diagnosis of low to intermediate-risk PCa. Critical relevance statement: ADC values are a valuable tool for distinguishing different levels of aggressiveness in PCa. They help in the preoperative assessment of the biological characteristics of PCa, allowing clinicians to develop personalized treatment strategies, effectively mitigating the risk of unnecessary interventions. Key Points: The preoperative GS is crucial for planning the clinical treatment of PCa. The invasiveness of PCa is inversely correlated with ADC values. ADC values play a crucial role in the accurate preoperative evaluation of low to intermediate-risk PCa, thus aiding clinicians in developing tailored treatment plans. [ABSTRACT FROM AUTHOR]

Secondary prostate cancer typically occurs from direct seeding of a renal or bladder tumor. Metastasis via hematogenous spread is exceedingly rare and is typically identified incidentally at autopsy. This report describes a 72-year-old male with lung adenocarcinoma initially staged as Stage IA2 who developed oligometastatic disease of the prostate. He was initially treated with radiation therapy and was found to have a hypermetabolic focus in the prostate gland during surveillance PET/CT imaging 6 months following treatment. Subsequent biopsy revealed metastatic lung adenocarcinoma in 6/6 core samples, leading to diagnosis of oligometastatic disease of the prostate. To our knowledge, this is the first report of isolated oligometastatic disease to the prostate from a primary lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is increasing worldwide, and previous work found that OA increases systemic cartilage oligomeric matrix protein (COMP), which has also been implicated in prostate cancer (PCa). As such, we sought to investigate whether OA augments PCa progression. Cellular proliferation and migration of RM1 murine PCa cells treated with interleukin (IL)-1α, COMP, IL-1α + COMP, or conditioned media from cartilage explants treated with IL-1α (representing OA media) and with inhibitors of COMP were assessed. A validated murine model was used for tumor growth and marker expression analysis. Both proliferation and migration were greater in PCa cells treated with OA media compared to controls (p < 0.001), which was not seen with direct application of the stimulants. Migration and proliferation were not negatively affected when OA media was mixed with downstream and COMP inhibitors compared to controls (p > 0.05 for all). Mice with OA developed tumors 100% of the time, whereas mice without OA only 83.4% (p = 0.478). Tumor weight correlated with OA severity (Pearson correlation = 0.813, p = 0.002). Moreover, tumors from mice with OA demonstrated increased Ki-67 expression compared to controls (mean 24.56% vs. 6.91%, p = 0.004) but no difference in CD31, PSMA, or COMP expression (p > 0.05). OA appears to promote prostate cancer in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Inflammation is pivotal in the pathogenesis and progression of the most challenging diseases and even cancer. Nanomedicine‐based strategy can be referred as a distinct solution to this complicated clinical obstacle by proposing an elaborated combination of effective therapeutic performances on inflammation and cancer. Herein, 2,2,6,6‐tetramethylpiperidine‐1‐oxyl doped polydopamine nanoparticles, termed as TPDA NPs, with the significantly improved reactive oxygen/nitrogen species (RO/NSs) scavenging performance and enhanced photothermal efficiency are designed and synthesized by constructing donor‐acceptor pairs, for prostate diseases treatment including anti‐inflammation and anti‐tumor. Benefiting from mimicking multi‐natural enzymes, including superoxide dismutase, catalase, peroxidase, and glutathione peroxidase, TPDA NPs can inhibit the NF‐κB signaling pathways by downregulating the CD36 expression for the treatment of oxidative stress‐induced prostatitis. Especially, TPDA NPs can improve the prostatitis‐associated impairment of sexual behavior. By virtue of the enhanced photothermal‐conversion efficiency, TPDA NPs ablate prostate cancer and simultaneously decrease inflammatory reaction. Therefore, this work provides a "three birds with one shot" paradigm to utilize rationally designed TPDA NPs for efficient management of prostate diseases. [ABSTRACT FROM AUTHOR]

The latest advancement in high-intensity focused ultrasound (HIFU) treatment technology integrates magnetic resonance imaging (MRI) guidance for precise treatment of prostate disease. As conventional electromagnetic motors are not applicable for utilization within MRI scanners, we have developed a prototype robotic system driven by pneumatic stepper motors to control the movement of the HIFU transducer within an intrarectal probe during MRI-guided HIFU treatment procedures. These pneumatic stepper motors were constructed entirely from MRI-compatible plastic materials. Assessment of the robotic system's MRI compatibility was conducted utilizing a 3.0T MRI scanner, revealing no discernible MRI image distortion with a minor decrease in the signal-to-noise ratio (2.8%) during the motor operation. The robotic system enabled the transducer to move inside the probe with two degrees of freedom, allowing both linear and rotational motion. The positional accuracy of the transducer movement was assessed, yielding ±0.20 and ±0.22 mm accuracies in the forward and backward linear movements, respectively, and ±0.79° and ±0.74° accuracies in the clockwise and counterclockwise rotational motions, respectively. Emulation of authentic HIFU procedures involved creating a two-dimensional array of thermal lesions in a tissue-mimicking phantom, achieving positional accuracy within ±1 mm for the generated HIFU focal spots. The prototype robotic system incorporating pneumatic stepper motors fabricated entirely from MRI-compatible plastic materials has demonstrated the requisite positional accuracy necessary for effective HIFU treatment of prostate disease, indicating substantial promise for future clinical application. [ABSTRACT FROM AUTHOR]

Population differences in risk of disease are common, but the potential genetic basis for these differences is not well understood. A standard approach is to compare genetic risk across populations by testing for mean differences in polygenic scores, but existing studies that use this approach do not account for statistical noise in effect estimates (i.e., the GWAS betas) that arise due to the finite sample size of GWAS training data. Here, we show using Bayesian polygenic score methods that the level of uncertainty in estimates of genetic risk differences across populations is highly dependent on the GWAS training sample size, the polygenicity (number of causal variants), and genetic distance (FST) between the populations considered. We derive a Wald test for formally assessing the difference in genetic risk across populations, which we show to have calibrated type 1 error rates under a simplified assumption that all SNPs are independent, which we achieve in practise using linkage disequilibrium (LD) pruning. We further provide closed-form expressions for assessing the uncertainty in estimates of relative genetic risk across populations under the special case of an infinitesimal genetic architecture. We suggest that for many complex traits and diseases, particularly those with more polygenic architectures, current GWAS sample sizes are insufficient to detect moderate differences in genetic risk across populations, though more substantial differences in relative genetic risk (relative risk > 1.5) can be detected. We show that conventional approaches that do not account for sampling error from the training sample, such as using a simple t-test, have very high type 1 error rates. When applying our approach to prostate cancer, we demonstrate a higher genetic risk in African Ancestry men, with lower risk in men of European followed by East Asian ancestry. Author summary: Many diseases and complex traits, such as prostate cancer, exhibit differences in incidence across populations. Yet the potential contribution of genetic factors towards such disparities is unclear. Polygenic scores summarise genetic effects across the genome and can in principle provide a valuable tool for assessing and comparing disease risk across populations. In practise, current approaches based on polygenic scores assume that such scores perfectly measure genetic risk of disease without measurement error, and thus do not account for uncertainty that arises in the construction of the score from a finite genome-wide association study (GWAS) training sample, which can be substantial. We introduce a Bayesian approach based on the LDpred2 polygenic score model that accounts fully for training sample uncertainty, and we propose a Wald test for formally testing such genetic risk differences across populations. Simulations show that the method properly controls for type 1 errors assuming independent SNPs (achieved by pruning), and that statistical power is sensitive to both the genetic architecture (heritability and polygenicity) and training sample size. In application to prostate cancer, this framework enables us to identify a higher genetic risk in African Ancestry men, with lower risk in men of European followed by East Asian ancestry. [ABSTRACT FROM AUTHOR]

Pleural metastasis of prostate cancer is an extremely rare manifestation of prostate metastatic disease. We report the first case reported in the literature of prostate pleural metastasis diagnosed with EBUS-TBNA. [ABSTRACT FROM AUTHOR]

Background: Previous observational researchers have found an inverse bidirectional link between Alzheimer's disease (AD) and prostate cancer (PCa); yet, the causative nature of this link remains unclear. To investigate the causal interactions between AD and PCa, a bidirectional Mendelian randomization (MR) analysis was conducted. Methods: This study comprised two Genome-Wide Association Study (GWAS) summary statistics for AD (17,008 cases and 37,154 controls) and PCa (79,148 cases and 61,106 controls) in individuals of European ancestry. The inverse-variance weighted (IVW) method was employed as the primary approach, while MR-Egger, weighted median, weighted mode, and simple mode served as supplementary methods for estimating the causal effect. To assess pleiotropy, the MR-PRESSO global test and MR-Egger regression were used. Cochran's Q test was adopted to check heterogeneity, MR Steiger test and the leave-one-out analysis was performed to confirm the robustness and reliability of the results. Results: The causal association genetically inferred of AD on PCa was found using IVW (OR = 0.974, 95% CI = 0.958-0.991, p = 0.003) in forward MR analysis and the causal association genetically inferred of PCa on AD was not found using IVW (OR = 1.000, 95% CI: 0.954-1.049, P = 0.988) in reverse MR analysis. The sensitivity analysis showed that no pleiotropy and heterogeneity was observed. The leave-one-out analysis showed that the findings were not inordinately affected by any instrumental variables. Conclusion: The results of this study demonstrated an absence of bidirectional causality between AD and PCa among the European population, suggested that a genetically predicted possibility of decreased PCa risk in AD patients, and no significant genetically predicted causal effect of PCa on AD. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has had, and still has, a profound impact on national health systems, altering trajectories of care and exacerbating existing inequalities in health. Postponement of surgeries and cancellation of elective surgical procedures have been reported worldwide. In Italy, the lock-down measures following the COVID-19 pandemic caused cancellations of surgical procedures and important backlogs; little is known about potential social inequalities in the recovery process that occurred during the post-lockdown period. This study aims at evaluating whether all population social strata benefited equally from the surgical volumes' recovery in four large Italian regions. Methods: This multicentre cohort study covers a population of approximately 11 million people. To assess if social inequalities exist in the recovery of eight indicators of elective and oncological surgery, we estimated Risk Ratios (RR) through Poisson models, comparing the incidence proportions of events recorded during COVID-19 (2020-21) with those in pre-pandemic years (2018-19) for each pandemic period and educational level. Results: Compared to 2018-19, volumes of elective surgery showed a U-shape with the most significant drops during the second wave or the vaccination phase. The recovery was socially unequal. At the end of 2021, incidence proportions among highly educated people generally exceeded the expected ones; RRs were 1.31 (95%CI 1.21–1.42), 1.24 (95%CI 1.17–1.23), 1.17 (95%CI 1.08–1.26) for knee and hip replacement and prostatic surgery, respectively. Among low educated patients, RR remained always < 1. Oncological surgery indicators showed a similar social gradient. Whereas volumes were preserved among the highly educated, the low educated were still lagging behind at the end of 2021. Conclusions: Surgical procedures generally returned to pre-pandemic levels but the low educated experienced the slowest recovery. An equity-oriented appraisal of trends in healthcare provision should be included in pandemic preparedness plans, to ensure that social inequalities are promptly recognised and tackled. [ABSTRACT FROM AUTHOR]

Objective: In the diagnosis of prostate cancer, only digital rectal examination and prostate-specific antigen (PSA) testing cause unnecessary prostate biopsies, excessive cost, and treatment burden. Therefore, PSA density (PSAD) and multiparametric magnetic resonance imaging (mp-MRI) of the prostate are becoming common. In this study, we aimed to investigate the predictiveness of PSAD and mp-MRI of the prostate in the diagnosis of prostate cancer, which are non-invasive diagnostic methods. Materials and Methods: The files of 193 patients who applied to the urology outpatient clinic for approximately 5 years were reviewed and evaluated retrospectively. Serum PSAD values and prostate imaging reporting and data system (PIRADS) scores were recorded. Prostate biopsies were performed. The cut-off value for PSAD was 0.15 ng/mL/cc. Patients with <0.15 were divided into group 1, and those with =0.15 were divided into group 2. Patients with a PIRADS score of 3 were divided into the suspicious group, and patients with a PIRADS score of 4 or 5 were divided into the risky group. Results: Prostate volume, PSA, and PSAD were significantly different between the benign and malignant groups. PSAD was positively correlated with the PIRADS score. Of the 123 patients with a PIRADS score of 3, 82.9% had benign prostatic enlargement (BPE) and 17.1% had prostate cancer. Of the 70 patients with a PIRADS score of 4 or 5, 45.7% had BPE and 54.3% had prostate cancer (p<0.001). Clinically significant prostate cancer rates were significantly different between the PSA score groups and were also different for PIRADS (p<0.001). The sensitivity and specificity of PSAD in the diagnosis of prostate cancer were 67.8% and 64.9%, respectively. The sensitivity and specificity of the PIRADS score in the diagnosis of prostate cancer were 64.4% and 76.1%, respectively. When these two parameters were used in combination, the specificity was 87.3% and the sensitivity was 81.4% in the presence of at least one. Conclusion: According to the data of the study, it was concluded that PSAD and PRIDAS scores are complementary diagnostic methods in the diagnosis of prostate cancer and are indispensable elements in the diagnosis. PSAD and PRIDAS scores are important diagnostic parameters in making the biopsy decision in the diagnosis of prostate cancer and help to prevent unnecessary prostate biopsies. [ABSTRACT FROM AUTHOR]

According to previous observational researches and clinical trials, the gut microbiota is related to prostate diseases. However, the potential association between gut microbiota and prostate disorders is still uncertain. We first identified groups of gut microbiota based on the phylum, class, order, family, and genus levels from consortium MiBioGen. And we acquired prostate diseases statistics from the FINNGEN study and PRACTICAL consortium. Next, two-sample Mendelian randomization was used to investigate the potential associations between three prevalent prostate disease and gut microbiota. In addition, we performed a reverse MR analysis and Benjamini-Hochberg (BH) test for further research. We investigated the connection between 196 gut microbiota and three prevalent prostate diseases. We identified 42 nominally significant associations and 2 robust causative links. Upon correction for multiple comparisons using the Benjamini–Hochberg procedure, our analysis revealed a positive correlation between the risk of prostatitis and the presence of the taxonomic order Gastranaerophilales. Conversely, the risk of prostate cancer exhibited an inverse correlation with the presence of the taxonomic class Alphaproteobacteria. Our study revealed the potential association between gut microbiota and prostate diseases. The results may be useful in providing new insights for further mechanistic and clinical studies of prostate diseases. [ABSTRACT FROM AUTHOR]

Background: To investigate the value of semi-quantitative and quantitative parameters (PI-RADS score, T2WI score, ADC, Ktrans, and Kep) based on multiparametric MRI (mpMRI) or biparametric MRI (bpMRI) combined with prostate specific antigen density (PSAD) in detecting clinically significant prostate cancer (csPCa). Methods: A total of 561 patients (276 with csPCa; 285 with non-csPCa) with biopsy-confirmed prostate diseases who underwent preoperative mpMRI were included. Prostate volume was measured for calculation of PSAD. Prostate index lesions were scored on a five-point scale on T2WI images (T2WI score) and mpMRI images (PI-RADS score) according to the PI-RADS v2.1 scoring standard. DWI and DCE-MRI images were processed to measure the quantitative parameters of the index lesion, including ADC, Kep, and Ktrans values. The predictors of csPCa were screened by logistics regression analysis. Predictive models of bpMRI and mpMRI were established. ROC curves were used to evaluate the efficacy of parameters and the model in diagnosing csPCa. Results: The independent diagnostic accuracy of PSA density, PI-RADS score, T2WI score, ADCrec, Ktrans, and Kep for csPCa were 80.2%, 89.5%, 88.3%, 84.6%, 58.5% and 61.6%, respectively. The diagnostic accuracy of bpMRI T2WI score and ADC value combined with PSAD was higher than that of PI-RADS score. The combination of mpMRI PI‑RADS score, ADC value with PSAD had the highest diagnostic accuracy. Conclusions: PI-RADS score according to the PI-RADS v2.1 scoring standard was the most accurate independent diagnostic index. The predictive value of bpMRI model for csPCa was slightly lower than that of mpMRI model, but higher than that of PI-RADS score. [ABSTRACT FROM AUTHOR]

To validate the performance of automated Prostate Cancer Molecular Imaging Standardized Evaluation (aPROMISE) in quantifying total prostate disease burden with 18F-DCFPyL PET/CT and to evaluate the interobserver and histopathologic concordance in the establishment of dominant and index tumor. Patients with a recent diagnosis of intermediate/high-risk prostate cancer underwent 18F-DCFPyL-PET/CT for staging purpose. In positive-18F-DCFPyL-PET/CT scans, automated prostate tumor segmentation was performed using aPROMISE software and compared to an in-house semiautomatic-manual guided segmentation procedure. SUV and volume related variables were obtained with two softwares. A blinded evaluation of dominant tumor (DT) and index tumor (IT) location was assessed by both groups of observers. In histopathological analysis, Gleason, International Society of Urological Pathology (ISUP) group, DT and IT location were obtained. We compared all the obtained variables by both software packages using intraclass correlation coefficient (ICC) and Cohen's kappa coefficient (k) for the concordance analysis. Fifty-four patients with a positive 18F-DCFPyL PET/CT were evaluated. The ICC for the SUVmax, SUVpeak, SUVmean, tumor volume (TV) and total lesion activity (TLA) was: 1, 0.833, 0.615, 0.494 and 0.950, respectively (p < 0.001 in all cases). For DT and IT detection, a high agreement was observed between both softwares (k = 0.733; p < 0.001 and k = 0.812; p < 0.001, respectively) although the concordances with histopathology were moderate (p < 0001). The analytical validation of aPROMISE showed a good performance for the SUVmax, TLA, DT and IT definition in comparison to our in-house method, although the concordance was moderate with histopathology for DT and IT. [ABSTRACT FROM AUTHOR]

Introduction: Mental disorders, smoking, or alcoholism and benign prostate disease are highly prevalent in men. Aims: To identify the relationship between mental disorders, smoking, or alcoholism and benign prostate disease. Methodology: A prospective multicenter study that evaluated prostate health status in 558 men from the community. Groups: GP—men who request a prostate health examination and whose medical history includes a mental disorder, smoking, or alcoholism prior to a diagnosis of benign prostate disease; GU—men who request a prostate health examination and whose medical history includes a benign prostate disease prior to a diagnosis of mental disorder, smoking, or alcoholism. Variables: age, body mass index (BMI), prostate specific antigen (PSA), follow-up of the mental disorder, smoking or alcoholism, time elapsed between urological diagnosis and the mental disorder, smoking or alcoholism diagnosis, status of the urological disease (cured or not cured), concomitant diseases, surgical history, and concomitant treatments. Descriptive statistics, Student's t-test, Chi2, multivariate analysis. Results: There were no mental disorders, smoking, or alcoholism in 51.97% of men. Anxiety, smoking, major depressive disorder, pathological insomnia, psychosis, and alcoholism were identified in 19.71%, 13.26%, 5.73%, 4.30%, 2.87%, and 2.15% of individuals, respectively. Nonbacterial prostatitis (31.54%), urinary tract infection (other than prostatitis, 24.37%), prostatic intraepithelial neoplasia (13.98%), and prostatodynia (1.43%) were prostate diseases. Unresolved symptomatic benign prostate disease was associated with anxiety, depression, and psychosis (p = 0.002). Smoking was the disorder that men managed to eliminate most frequently. The dominant disorder in patients with symptomatic benign prostatic disease was alcoholism (p = 0.006). Conclusions: Unresolved symptomatic benign prostatic disease is associated with anxiety, depression, and psychosis. Alcoholism is associated with a worse prognosis in the follow-up of symptomatic benign prostatic disease. [ABSTRACT FROM AUTHOR]

Non-metastatic castration-resistant prostate cancer (nmCRPC) represents a challenging disease state in prostate cancer care. nmCRPC patients with a high risk of progression to metastatic disease who are identified by a prostate-specific antigen doubling time (PSADT) =10 months are eligible for treatment with the novel androgen receptor inhibitors (ARIs), shown to delay disease progression and extend survival. However, nmCRPC is often unexploited in clinical practice due to a lack of standardization in the methodology and in the tools used for its identification. In this article, a group of Urology and Oncology specialists with acknowledged expertise in prostate cancer reviews the state of the art in the management of high-risk nmCRPC patients, identifies gaps and unmet needs, and proposes strategies to optimize the identification of this patient subgroup in the clinical practice and improve their health outcomes. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have found a potential link between prostate disease, particularly prostate cancer (PCa), and kidney disease, specifically chronic renal disease (CKD), in relation to erectile dysfunction (ED), yet the causal relationship between these factors remains uncertain. Aim: The study sought to explore the potential causal association between prostate diseases, renal diseases, renal function, and risk of ED. Methods: In this study, 5 analytical approaches were employed to explore the causal relationships between various prostate diseases (PCa and benign prostatic hyperplasia), renal diseases (CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, and kidney ureter calculi), as well as 8 renal function parameters, with regard to ED. All data pertaining to exposure and outcome factors were acquired from publicly accessible genome-wide association studies. The methods used encompassed inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode residual sum and outlier techniques. The MR-Egger intercept test was utilized to assess pleiotropy, while Cochran's Q statistic was employed to measure heterogeneity. Outcomes: We employed inverse variance weighting MR as the primary statistical method to assess the causal relationship between exposure factors and ED. Results: Genetically predicted PCa demonstrated a causal association with an elevated risk of ED (odds ratio, 1.125; 95% confidence interval, 1.066-1.186; P <.0001). However, no compelling evidence was found to support associations between genetically determined benign prostatic hyperplasia, CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, kidney ureter calculi, and the renal function parameters investigated, and the risk of ED. Clinical Implications: The risk of ED is considerably amplified in patients diagnosed with PCa, thereby highlighting the importance of addressing ED as a significant concern for clinicians treating individuals with PCa. Strengths and Limitations: This study's strength lies in validating the PCa-ED association using genetic analysis, while its limitation is the heterogeneity in study results. Conclusion: The results of this study suggest a potential link between PCa and a higher risk of ED. [ABSTRACT FROM AUTHOR]

The precise and automatic segmentation of prostatemagnetic resonance imaging (MRI) images is vital for assisting doctors in diagnosing prostate diseases. In recent years, many advanced methods have been applied to prostate segmentation, but due to the variability caused by prostate diseases, automatic segmentation of the prostate presents significant challenges. In this paper, we propose an attention-guided multi-scale feature fusion network (AGMSFNet) to segment prostateMRI images. We propose an attention mechanism for extracting multi-scale features, and introduce a 3D transformer module to enhance global feature representation by adding it during the transition phase from encoder to decoder. In the decoder stage, a feature fusion module is proposed to obtain global context information. We evaluate our model on MRI images of the prostate acquired from a local hospital. The relative volume difference (RVD) and dice similarity coefficient (DSC) between the results of automatic prostate segmentation and ground truth were 1.21% and 93.68%, respectively. To quantitatively evaluate prostate volume on MRI, which is of significant clinical significance, we propose a unique AGMSF-Net. The essential performance evaluation and validation experiments have demonstrated the effectiveness of our method in automatic prostate segmentation. [ABSTRACT FROM AUTHOR]

The steroid submetabolome, or steroidome, is of particular interest in prostate cancer (PCa) as the dependence of PCa growth on androgens is well known and has been routinely exploited in treatment for decades. Nevertheless, the community is still far from a comprehensive understanding of steroid involvement in PCa both at the tissue and at systemic level. In this study we used liquid chromatography/high resolution mass spectrometry (LC/HRMS) backed by a dynamic retention time database DynaSTI to obtain a readout on circulating steroids in a cohort reflecting a progression of the PCa. Hence, 60 relevant compounds were annotated in the resulting LC/HRMS data, including 22 unknown steroid isomers therein. Principal component analysis revealed only subtle alterations of the systemic steroidome in the study groups. Next, a supervised approach allowed for a differentiation between the healthy state and any of the stages of the disease. Subsequent clustering of steroid metabolites revealed two groups responsible for this outcome: one consisted primarily of the androgens, whereas another contained corticosterone and its metabolites. The androgen data supported the currently established involvement of a hypothalamic-pituitary–gonadal axis in the development of PCa, whereas biological role of corticosterone remained elusive. On top of that, current results suggested a need for improvement in the dynamic range of the analytical methods to better understand the role of low abundant steroids, as the analysis revealed an involvement of estrogen metabolites. In particular, 2-hydroxyestradiol-3-methylether, one of the compounds present in the disease phenotype, was annotated and reported for the first time in men. [ABSTRACT FROM AUTHOR]

Background: Numerous observational studies have investigated the risk of prostate cancer (PCa) in patients diagnosed with Parkinson's Disease (PD). However, the existence of a definitive association remains uncertain. Methods: Systematic searches were performed on PubMed, Web of Science, Scopus, and Google Scholar for studies published up to October 1, 2023. For Mendelian randomized (MR) causal inference, we employed pooled data from the IPDGC and PRACTICAL Consortium. The inverse variance weighted (IVW) method served as the principal technique for estimating odds ratios (ORs) and 95% confidence intervals (CIs) for the associations under investigation. Results: Cumulative analysis of nine studies revealed no significant association between patients diagnosed with PD and the subsequent incidence of PCa ([relative ratio] RR = 0.89, 95%CI = 0.73 to 1.08, P = 0.237). However, subgroup analyses indicated a reduced occurrence of PCa in Caucasian patients with PD (RR = 0.81, 95%CI = 0.69 to 0.95, P = 0.011). MR analyses failed to establish a significant link between increased genetic susceptibility to PD and the risk of PCa (IVW OR = 1.025, 95%CI = 0.997 to 1.054, P = 0.082). Sensitivity analyses further corroborated the robustness of these results. Conclusion: Both observational meta-analysis and MR analysis based on genetic variation do not support an association between PD patients and the subsequent risk of PCa. Further research is warranted to unravel the potential underlying mechanisms linking these two diseases. [ABSTRACT FROM AUTHOR]

Objective: To compare the safety and efficacy of the en bloc technique with the standard 2-lobe technique for holmium laser enucleation of the prostate (HoLEP). Methods: This prospective study included patients with benign prostatic hyperplasia (BPH) who underwent HoLEP from September 2020 to March 2022, by en bloc or 2-lobe technique. Patient demographics, prostate volume, enucleation, morcellation and operative time, and incidence of postoperative incontinence were compared between the 2 groups. Results: We included 64 patients (30 en bloc and 34 2-lobe techniques) who underwent HoLEP in this study. The mean age, prostate volume, creatinine, and PSA of patients were comparable in both groups [(68.53 vs. 67.55 years; P = .62), (79.43 vs. 79.88 g, P = .92), (1.08 mg/dL vs. 1.20 mg/dL, P = .35), (3.78 vs. 4.63 ng/mL; P = .376), respectively]. The enucleation time was significantly shorter in the en bloc group than in the 2-lobe group (54.2 vs. 61.67; P = .03). Additionally, the mean operative time was also comparatively shorter in the en bloc group than the 2-lobe group (72.36 vs. 80.50; P = .057). The improvement in the quality-of-life (QoL) score was significantly better with en bloc than the 2-lobe group (3.80 vs. 2.11; P = .01). There was a significant difference in stress urinary incontinence on days 1, 7, and 30 (P < .001) with en bloc compared to the two-lobe technique. Conclusion: Although the outcomes of en bloc and 2-lobe endoscopic enucleation of prostate techniques were comparable, the en bloc technique seems to be a better option in most patients undergoing HoLEP due to less enucleation and operative time and lowered stress urinary incontinence incidence. [ABSTRACT FROM AUTHOR]

Prostate Cancer Associated 3 (PCA3) as a promising biomarker to replace serum prostate-specific antigen (PSA) for differential diagnosis of benign and malignant prostate diseases. However, the detection of PCA3 in urine requires the collection of digital rectal examination (DRE) urine, which limits the application of PCA3 in screening prostate diseases. In the present study, a new reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) method was developed for PCA3 detection in non-DRE urine. The method uses the nanomaterial Graphene oxide (GO) to effectively prevent nonspecific amplification in qRT-PCR. GO-based qRT-PCR produced no nonspecific amplification. Receiver operating characteristic curve (ROC) results showed that the area under curve (AUC) of PCA3 to discriminate normal control subjects from prostate cancer (PCa) was 0.869 (95% confidence interval [CI], 0.689–1.000), and using 2.711 as the cutoff value of PCA3, the sensitivity was 81.8% and the specificity was as high as 88.9%. For prostatitis (PTIS) and PCa, the AUC value of PCA3 to distinguish them was 0.636 (95% CI, 0.396–0.877), with 81.8% sensitivity and 58.3% specificity. Compared with the 8.3% specificity of PAS, the specificity of PCA3 was improved by 50%, which suggested that PCA3, in non-DRE urine, has a significant potential application in the differential diagnosis of prostate diseases.

Abstract Background Red ginseng (RG) is a traditional herb commonly used in China, Korea, and other East Asian countries. Recently, it has demonstrated a better clinical value in men’s reproductive health (MRH). The present review aimed to examine the effects of RG treatment on MRH. Results Overall, 42 articles related to RG application in MRH were reviewed, of which 31 were animal experiments and 11 were clinical studies. Furthermore, this review analyzed the use of RG in some male reproductive diseases in clinical trials and determined the associated mechanisms of action. The mechanism of action of RG in MRH may be related to oxidative stress, regulation of sex hormones and spermatogenesis-related proteins, and anti-inflammation. Conclusions The application of RG for the treatment of male infertility, erectile dysfunction, and prostate diseases has the potential to contribute to MRH.

Background: Prostate disease represents about 0.7% of diseases in canines. The main diagnosed pathology is benign prostatic hyperplasia (BPH). However, the reports that study the association of a certain clinical sign with a specific prostate disease are scarce. Aim: The main objective of this study was to evaluate the clinical relevance of the most commonly observed clinical signs associated with the different prostatic disorders in canines admitted to the hospital of the Facultad de Veterinaria-Universidad de la República between 2011 and 2019. Methods: This retrospective study included 7,729 male canines treated at the hospital de la Facultad de Veterinaria-Universidad de la República (Montevideo, Uruguay) between 2011 and 2019. 289 canines with a presumptive/definitive diagnosis of prostate diseases were selected, recording the presence/absence of associated clinical signs. Results were reported in terms of odds ratios (ORs) using logistic regression (p < 0.05). Results: The five most frequently reported clinical signs were tenesmus (34%), anorexia (32%), lethargy (27%), prostatomegaly or pain during rectal examination (25%), and abdominal pain from palpation (22%). Diarrhea (3.39 vs. 0.33 OR), anorexia (2.07 vs. 0.39 OR), weight loss (2.27 vs. 0.27 OR), hematuria (3.25 vs. 0.44 OR), and urinary incontinence (2.96 vs. 0.33 OR) indicated a highest predictive value (p < 0.05) with prostatitis versus BPH, respectively. Being weight loss, the clinical sign is more frequently associated with neoplasia (20.2 OR, p = 0.002). Conclusion: This study shows that there are clinical signs with a higher degree of association for certain canine prostatic disorders than others. [ABSTRACT FROM AUTHOR]

Background: Ureaplasma species are common pathogens of the urogenital tract and can cause a range of diseases. Unfortunately, there is still a scarcity of large-scale and cross-sectional studies on the prevalence of Ureaplasma species in China to clarify their epidemic patterns. Methods: This study retrospectively analyzed the data of 18667 patients who visited Peking Union Medical College Hospital for showing various symptoms of (suspected) Ureaplasma species infection during the period 2013–2022. The overall prevalence of Ureaplasma species was calculated, and subgroup analyses were conducted in view of gender, age, specimen types, and diagnosis in every year within the period studied. Furthermore, previous literature that reported on the prevalence of Ureaplasma species in various regions of China was searched and summarized. Results: The overall positive rate of Ureaplasma species in this study reached 42.1% (7861/18667). Specifically, the prevalence of Ureaplasma species was significantly higher in female patients, while the highest detection rate was found in the 21–50 age group. From 2013 to 2022, there were no significant differences in positive rates of Ureaplasma species among years. However, the detection rate of Ureaplasma species was decreased in COVID-19 period (2020–2022) compared to pre-COVID-19 period (2017–2019). In view of the distribution of patients, outpatients predominated, but the detection rate was lower than inpatients. Urine was the most common specimen type, while cervical swabs had the highest detection rate of Ureaplasma species. When grouped by diagnosis, the highest positive rate of Ureaplasma species was seen in patients with adverse pregnancy outcomes and the lowest rate in patients with prostate disease. The previous literature, although heterogeneous, collectively suggested a high prevalence of Ureaplasma species in China. Conclusions: Our study has shown that Ureaplasma species have reached a significant prevalence in China and demands adequate attention. [ABSTRACT FROM AUTHOR]

Background: We report a case of diffuse large B-cell lymphoma that progressed rapidly after androgen deprivation therapy for prostate cancer in a patient with a history of IgG4-related disease. Estrogen has been reported to be a possible cause of acute exacerbations of malignant lymphoma only in mouse models. Therefore, its clinical significance has not been clarified. Case presentation: This case report describes a 75-year-old man with prostate cancer who had IgG4-related disease. Hormone therapy was initiated to treat prostate cancer, but he developed dyspnea and back pain. A diagnosis was made of diffuse large B-cell lymphoma. Immunohistochemistry was positive for estrogen receptor β, which led us to suspect rapid progression of diffuse large B-cell lymphoma due to estrogen suppression by gonadotropin-releasing hormone antagonists. Hormone therapy was discontinued, and the patient received R-CHOP therapy. Subsequently, the lymphoma masses shrunk, and the patient obtained remission. Conclusion: This case is the first report of clinical significance regarding the crucial role of estrogen and estrogen receptor β in malignant lymphoma in a patient with IgG4-related disease. Our report aims to raise awareness of the need to carefully select treatment options for prostate cancer patients with IgG4-related disease or lymphoma. [ABSTRACT FROM AUTHOR]

We show that the gene regulatory potential of the androgen receptor, the driver of prostate cancer disease, in low-risk grade group 1 lesions is very similar to that in higher-grade tumors and distinctly different from that in normal prostate epithelium, positioning grade group 1 lesions as bona fide cancers from an epigenetic perspective. Grade group 1 (GG1) primary prostate cancers with a pathologic Gleason score of 6 are considered indolent and generally not associated with fatal outcomes, so treatment is not indicated for most cases. These low-grade cancers have an overall negligible risk of locoregional progression and metastasis to distant organs, which is why there is an ongoing debate about whether these lesions should be reclassified as "noncancerous". However, the underlying molecular activity of key disease drivers, such as the androgen receptor (AR), have thus far not been thoroughly characterized in low-grade tumors. Therefore, we set out to delineate the AR chromatin-binding landscape in low-grade GG1 prostate cancers to gain insights into whether these AR-driven programs are actually tumor-specific or are normal prostate epithelium-like. These analyses showed that GG1 tumors do not harbor a distinct AR cistrome and, similar to higher-grade cancers, AR preferentially binds to tumor-defining cis-regulatory elements. Furthermore, the enhancer activity of these regions and the expression of their respective target genes were not significantly different in GG1 tumors. From an epigenetic perspective, this finding supports the cancer designation currently given to these low-grade tumors and clearly distinguishes them from noncancerous benign tissue. We characterized the molecular activity of the androgen receptor protein, which drives prostate cancer disease, in low-grade tumors. Our results show that these tumors are true cancers and are clearly separate from benign prostate tissue despite their low clinical aggressiveness. [ABSTRACT FROM AUTHOR]

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Prostate disorders are commonplace in medicine, especially in older men, with prostatitis, benign prostatic hyperplasia, and prostate cancer being the most abundant pathologies. The complexity of this organ, however, turns treatment into a challenge. In this review, we aim to provide insight into the efficacy of alternative treatments, which are not normally used in conventional medicine, with a particular focus on nutrients. In order to understand why and how nutrition can be beneficial in diseases of the prostate, we give an overview of the known characteristics and features of this organ. Then, we provide a summary of the most prevalent prostate illnesses. Finally, we propose nutrition-based treatment in each of these prostate problems, based on in-depth research concerning its effects in this context, with an emphasis on surgery. Overall, we plead for an upgrade of this form of alternative treatment to a fully recognized mode of therapy for the prostate. [ABSTRACT FROM AUTHOR]

Cistus albidus L. (Cistaceae) is a medicinal plant that has been used therapeutically since ancient times in the Mediterranean basin for its important pharmacological properties. The ability of C. albidus to produce large quantities of a wide range of natural metabolites makes it an attractive source of raw material. The main constituents with bioactive functions that exert pharmacological effects are terpenes and polyphenols, with more than 200 identified compounds. The purpose of this review is to offer a detailed account of the botanical, ethnological, phytochemical, and pharmacological characteristics of C. albidus with the aim of encouraging additional pharmaceutical investigations into the potential therapeutic benefits of this medicinal plant. This review was carried out using organized searches of the available literature up to July 2023. A detailed analysis of C. albidus confirms its traditional use as a medicinal plant. The outcome of several studies suggests a deeper involvement of certain polyphenols and terpenes in multiple mechanisms such as inflammation and pain, with a potential application focus on neurodegenerative diseases and disorders. Other diseases such as prostate cancer and leukemia have already been researched with promising results for this plant, for which no intoxication has been reported in humans. [ABSTRACT FROM AUTHOR]

Background: Oligometastatic disease in prostate cancer (PCa) is a challenging clinical scenario encountered more frequently with the widespread adoption of PSMA-PET. SBRT aims to defer androgen deprivation and may deliver sustained biochemical failure (BF) free survival in selected patients. Little long-term data is currently available regarding the effectiveness of this approach. Methods: A retrospective single institution study of PSMA-PET directed SBRT without initial ADT for oligo-metachronous PCa. Median dose/fractionation was 24 Gy in 2# to bones and 30 Gy in 3# to lymph nodes. The primary endpoint was time to BF (PSA + 0.2 ug/L above nadir). Secondary endpoints included time to ADT for relapse (i.e. palliative ADT), BF defined as PSA nadir + 2 ug/L, toxicity, patterns of failure and survival. Patients were excluded if they received ADT with their SBRT, had short disease-free interval, or > 3 metastases on PSMA-PET. Results: 103 patients treated from November-2014 to December-2019 were analysed from our prospective database. Median follow-up was 5 years. 64 patients were treated for nodal only disease, 35 bone only and 4 mixed. 15% were free of any BF at 5 years with median time to BF of 1.1 years. 32% (33/103) of patients had further curative-intent radiation treatment following their first BF after SBRT, including subsequent SBRT. Eight patients underwent potentially curative treatment for their second or third relapse. Allowing for salvage treatment, 29/103 (28%) were biochemically disease free at last follow up. At 5 years, 39% of patients had never received any ADT and 55% had not started ADT for relapse with a median time to ADT for relapse of 5.5 years. There were 2 grade 3 toxicities (rib fracture and lymphoedema), and no local failures. Conclusion: PSMA-PET guided SBRT for oligo-metachronous PCa recurrence in appropriately triaged patients results in excellent local control, low toxicity and over 50% ADT free at 5 years. [ABSTRACT FROM AUTHOR]

Prostate-Specific Membrane Antigen (PSMA)-based diagnostics and therapeutics are proving highly valuable in identifying disease sites and providing targeted radioligand therapy (RLT) for disseminated disease in prostate cancer (PC). With successful integration of these tools in limited PC presentations, there is a real need and excitement for trials testing PSMA-based approaches more broadly. We review the ongoing trials registered on ClinicalTrials.gov which aim to evaluate PSMA-PET or PSMA-RLT applications. We outline clinical contexts which have significant ongoing study and therefore may see imminent change, as well as contexts which are lacking in study in the hopes of guiding future research. Trials examining intensification strategies through targeted radiotherapy, combination systemic therapies, and RLTs have the potential to demonstrate improved clinical outcomes using PSMA-PET CT for guidance. We expect that PSMA-PET will become fundamental in the work-up of patients before targeted radiotherapy or surgery. The results of ongoing trials will likely clarify the benefits of PSMA-RLT in metastatic PC including in oligometastatic and hormone-sensitive disease; however, there is a sparsity of trials evaluating PSMA-RLT outside of metastatic PC. Clinical trials with PSMA PET/CT as an endpoint for disease control are emerging and standardized reporting and metrics for PSMA staging and response will facilitate the inclusion of PSMA PET endpoints into therapeutic trials. [ABSTRACT FROM AUTHOR]

The reactivation of developmental genes and pathways during adulthood may contribute to pathogenesis of diseases such as prostate cancer. Analysis of the mechanistic links between development and disease could be exploited to identify signalling pathways leading to disease in the prostate. However, themechanisms underpinning prostate development require further characterisation to interrogate fully the link between development and disease. Previously, our group developed methods to produce prostate organoids using induced pluripotent stem cells (iPSCs). Here, we show that human iPSCs can be differentiated into prostate organoids using neonatal rat seminal vesicle mesenchyme in vitro. The organoids can be used to study prostate development or modified to study prostate cancer. We also elucidated molecular drivers of prostate induction through RNAsequencing analyses of the rat urogenital sinus and neonatal seminal vesicles. We identified candidate drivers of prostate development evident in the inductive mesenchyme and epithelium involved with prostate specification. Our top candidates included Spx, Trib3, Snai1, Snai2, Nrg2 and Lrp4. This work lays the foundations for further interrogation of the reactivation of developmental genes in adulthood, leading to prostate disease. [ABSTRACT FROM AUTHOR]

Many health problems are seen due to aging. One of these is problems in the reproductive system. Reproductive system problems are caused by lower urinary system symptoms, prostate diseases, low fertility, testicular dysfunction. The aim of this study was to compare reproductive parameters of geriatric (3 years old) and young (3 months old) rats. A 3-year-old rat is equivalent to an average 90-95-year-old human. For this purpose, sperm analysis, testicular and prostate histopathology, testicular oxidative stress parameters were examined in geriatric (3 years old) and young (3 months old) rats. In the analysis results, it was determined that sperm motility ratio decreased (p<0.001), abnormal sperm ratio increased (p<0.001) and sperm density decreased (p<0.001) in the geriatric group. Statistically, oxidative stress parameters MDA, AOPP, T-SH levels increased (p<0.05) and CAT level decreased (p<0.05) in geriatric group. Histopathologically, degeneration, necrosis and irregular alignments were observed in the tubulus seminiferous contortus in the geriatric group. Hyperplasia and dilatation of the prostate gland were detected in the geriatric group. As a result of this study, it is thought that reproductive performance in geriatric male rats is very low, and the probability of reproduction is very difficult. [ABSTRACT FROM AUTHOR]

Prostate diseases often occur in men. For further clinical treatment and diagnosis, we need to do accurate segmentation on prostate. There are already many methods that concentrate on solving the problem of automatic prostate MR image segmentation. However, the design of some hyperparameters of these methods is migrated from the models that are used for nature images which do not consider the difference between medical image and nature image. Besides, there is trend that researchers are likely to use deeper and more complicated networks to achieve high accuracy. The improvement is limited with surging parameters, computations, training time, and inference time. In this paper, we propose an efficient attention residual U-Net to segment the prostate MR image. We analyze the property of prostate MR image and fine-tune the architecture of U-Net. To accelerate the convergence of our method, residual connection and channel attention are added to our network. A set of experiments suggest our method can achieve a similar accuracy of state of the art with less parameters, less computations, shorter training time, and shorter inference time. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is one of the most prevalent cancers worldwide. The clinical manifestations and molecular characteristics of PCa are highly variable. Aggressive types require radical treatment, whereas indolent ones may be suitable for active surveillance or organ-preserving focal therapies. Patient stratification by clinical or pathological risk categories still lacks sufficient precision. Incorporating molecular biomarkers, such as transcriptome-wide expression signatures, improves patient stratification but so far excludes chromosomal rearrangements. In this study, we investigated gene fusions in PCa, characterized potential novel candidates, and explored their role as prognostic markers for PCa progression. Methods: We analyzed 630 patients in four cohorts with varying traits regarding sequencing protocols, sample conservation, and PCa risk group. The datasets included transcriptome-wide expression and matched clinical follow-up data to detect and characterize gene fusions in PCa. With the fusion calling software Arriba, we computationally predicted gene fusions. Following detection, we annotated the gene fusions using published databases for gene fusions in cancer. To relate the occurrence of gene fusions to Gleason Grading Groups and disease prognosis, we performed survival analyses using the Kaplan–Meier estimator, log-rank test, and Cox regression. Results: Our analyses identified two potential novel gene fusions, MBTTPS2,L0XNC01::SMS and AMACR::AMACR. These fusions were detected in all four studied cohorts, providing compelling evidence for the validity of these fusions and their relevance in PCa. We also found that the number of gene fusions detected in a patient sample was significantly associated with the time to biochemical recurrence in two of the four cohorts (log-rank test, p-value < 0.05 for both cohorts). This was also confirmed after adjusting the prognostic model for Gleason Grading Groups (Cox regression, p-values < 0.05). Conclusions: Our gene fusion characterization workflow revealed two potential novel fusions specific for PCa. We found evidence that the number of gene fusions was associated with the prognosis of PCa. However, as the quantitative correlations were only moderately strong, further validation and assessment of clinical value is required before potential application. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review paper, we explore the role of chronic inflammation in the pathogenesis of prostatic diseases, such as chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Chronic inflammation is a significant risk factor for these diseases, but the molecular mechanisms behind it are not yet fully understood. Previous attempts to investigate, link, and target inflammatory signaling molecules in men with these conditions have been clinically ambiguous and inconclusive. As a result, we proposed a paradigm shift in which less-explored molecules in the inflammatory signaling cascade are investigated as possible therapeutic targets for prostate diseases. In addition, we comprehensively discuss how aberrant signaling of these molecules may cause prostate cancer stemness, neuroendocrine differentiation, castration resistance, metabolic reprogramming, and immunosuppression. In conclusion, we forecast that targeting the interleukin-1 receptor-associated kinases (IRAKs) signaling pathway may provide a far more effective therapeutic or prophylactic strategy for the management of chronic inflammation-driven prostatic diseases. Chronic inflammation is now recognized as one of the major risk factors and molecular hallmarks of chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate tumorigenesis. However, the molecular mechanisms by which chronic inflammation signaling contributes to the pathogenesis of these prostate diseases are poorly understood. Previous efforts to therapeutically target the upstream (e.g., TLRs and IL1-Rs) and downstream (e.g., NF-κB subunits and cytokines) inflammatory signaling molecules in people with these conditions have been clinically ambiguous and unsatisfactory, hence fostering the recent paradigm shift towards unraveling and understanding the functional roles and clinical significance of the novel and relatively underexplored inflammatory molecules and pathways that could become potential therapeutic targets in managing prostatic diseases. In this review article, we exclusively discuss the causal and molecular drivers of prostatitis, BPH, and prostate tumorigenesis, as well as the potential impacts of microbiome dysbiosis and chronic inflammation in promoting prostate pathologies. We specifically focus on the importance of some of the underexplored druggable inflammatory molecules, by discussing how their aberrant signaling could promote prostate cancer (PCa) stemness, neuroendocrine differentiation, castration resistance, metabolic reprogramming, and immunosuppression. The potential contribution of the IL1R-TLR-IRAK-NF-κBs signaling molecules and NLR/inflammasomes in prostate pathologies, as well as the prospective benefits of selectively targeting the midstream molecules in the various inflammatory cascades, are also discussed. Though this review concentrates more on PCa, we envision that the information could be applied to other prostate diseases. In conclusion, we have underlined the molecular mechanisms and signaling pathways that may need to be targeted and/or further investigated to better understand the association between chronic inflammation and prostate diseases. [ABSTRACT FROM AUTHOR]

Objective: To report the clinical results of patients who had metastatic prostate cancer (PC) at admission and underwent standard androgen deprivation therapy with radiotherapy (RT) and radical prostatectomy (RP) for the primary tumor. Materials and Methods: This study used the PC database from the Turkish Urooncology Association, to which participating institutions submit online data. The following clinical, radiological, and pathological findings were retrieved from the database: age, total prostate-specific antigen, clinical TNM stage, number of metastases, International Society of Urological Pathology grade group of biopsy, time to castration-resistant disease, type of local treatment, type of staging method, status of survival, type of systemic treatment, and follow-up time. Results: The median follow-up of the 18 included patients was 59.1 (19.9-180) months. RP and extended lymphadenectomy were performed in 12 patients. RT was performed in 6 patients. The median number of metastases was 2 (1-4) and 3 (1-4) in the RP and RT groups, respectively. In the RP group, 3 of 12 patients developed castration-resistant prostate cancer (CRPC) during the follow-up period. In the RT group, 2 of 6 patients developed CRPC in the follow-up period. The time to CRPC was 48.4 and 43.3 months, respectively. Conclusion: While primary tumor-directed RT is effective in selected patients, the results of prospective randomized controlled studies are required to demonstrate the effectiveness of RP. [ABSTRACT FROM AUTHOR]

Resveratrol is a polyphenol found naturally in fruits and plants. Recently, studies in humans and animal models have suggested beneficial properties of this polyphenol, such as improvements to metabolic and lipid profiles, along with antioxidant, anti-inflammatory and anti-proliferative effects. In the urogenital tract (UGT), resveratrol has also been tested clinically and experimentally as a therapeutic drug in several diseases; however, the translational efficacy of resveratrol, especially in UGT, is still a matter of debate. In the present review, we address the pre-clinical efficacy of resveratrol in UGT-related dysfunctions, focusing on lower urinary tract symptoms, non-cancerous prostatic disease (benign prostatic hyperplasia and prostatitis) and erectile dysfunction. In vitro studies indicate that resveratrol reduces inflammatory markers and oxidative stress, and improves endothelial function in UGT organs and cells isolated from humans and animals. Despite displaying low oral bioavailability, in vivo administration of resveratrol largely improves erectile dysfunction, benign prostatic hyperplasia, prostatitis and voiding impairments, as evidenced in different animal models. Resveratrol also acts as a microbiota modulator, which may explain some of its beneficial effects in vivo. In contrast to the large amount of pre-clinical data, there are insufficient clinical trials to establish resveratrol treatment efficacy in human UGT-related diseases. In summary, we provide an overview of the in vivo and in vitro efficacy of resveratrol in animal and human UGT dysfunctions, which may support future clinical trials. [ABSTRACT FROM AUTHOR]