Search Results (880)

Background: Prostate cancer (PCa) trends have evolved due to changing screening practices. This study assessed long-term trends in PCa incidence and survival according to Gleason score (GS) in Friuli Venezia Giulia, northeastern Italy. Methods: A population-based study was conducted, encompassing 21,571 PCa cases from the regional Cancer Registry, diagnosed between 2000 and 2020. Age-standardized incidence rates and 5-year overall (OS) and net survival (NS) were assessed by GS (2–6, 7, 8–10) and age group (<65, 65–74, ≥75). Trends were analyzed using Joinpoint regression. Results: PCa incidence increased from 2000 to 2007 (Annual Percent Change, APC = +1.8%), then declined sharply until 2010 (APC = −7.6%) and remained stable thereafter. Incidence of low-grade cancers (GS 2–6) decreased across all age groups, especially in men aged ≥ 75 years (APC = −8.1%). The incidence of GS 7 rose until 2007 and then stabilized. High-grade cancers (GS 8–10) showed a stable incidence, but their proportion increased from 20% to 29%, mainly in older men. Survival improved across all GS groups. For GS 2–6, OS increased from 81.4% to 88.2%; for GS 7, from 78.1% to 88.1%. GS 8–10 had smaller gains, but NS reached 82% in recent years. Among men aged ≥ 75 years, OS for GS 7 rose from 51.9% to 78.1%, and for GS 8–10, from 43.9% to 54.4%. NS remained high for GS ≤ 7. Conclusions: While overall outcomes improved, the increasing proportion of high-grade PCa, despite a stable incidence, raises concerns, particularly in older men, and calls for tailored clinical strategies. Full article

Benign prostatic hyperplasia (BPH) is a multifactorial condition that is highly prevalent and affects aging males. It frequently results in lower urinary tract symptoms (LUTS) and a reduced quality of life. While hormonal dysregulation and chronic inflammation have long been implicated in BPH pathogenesis, recent evidence highlights the role of physical activity in modulating prostate health. In this narrative review, evidence from quantitative studies examining the effect of exercise on BPH risk and symptom severity was first synthesized. Collectively, these studies suggest that regular physical activity is associated with a lower incidence and reduced progression of BPH. The potential mechanisms through which exercise may exert protective effects on the prostate were then explored. These include modulation of sympathetic nervous system activity, alterations in hormonal profiles (e.g., testosterone and insulin), suppression of chronic inflammation and oxidative stress, and the promotion of autophagy within prostatic tissue. Central to these mechanisms is the role of myokines—signaling molecules secreted by skeletal muscle during exercise. Key myokines, such as irisin, interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and myostatin, are reviewed in the context of prostate health. These molecules regulate inflammatory pathways, metabolic processes, and tissue remodeling. For instance, exercise-induced reductions in myostatin are linked to improved insulin sensitivity and decreased fat accumulation, while elevated irisin and BDNF levels may exert anti-inflammatory and metabolic benefits relevant to BPH pathophysiology. Although direct causal evidence linking myokines to BPH is still emerging, their biological plausibility and observed systemic effects suggest a promising avenue for non-pharmacological intervention. Future research should focus on identifying the specific myokines involved, elucidating their molecular mechanisms within the prostate, and evaluating their therapeutic potential in clinical trials. Full article

Background/Objectives: The Pleth Variability Index (PVI) is a non-invasive parameter used to guide fluid management by reflecting respiratory-induced variations in the plethysmographic waveform. While PVI’s reliability in various positions has been studied, data on its behavior in geriatric patients undergoing transurethral resection of the prostate (TUR-P) in the lithotomy position remain limited. This study aimed to evaluate the effect of the lithotomy position on PVI in geriatric versus non-geriatric patients under spinal anesthesia. Methods: This prospective observational study included 90 patients undergoing elective TUR-P in the lithotomy position under spinal anesthesia. Patients were divided into geriatric (≥65 years, n = 48) and non-geriatric (<65 years, n = 42) groups. PVI and Perfusion Index (PI) were recorded at baseline, in the supine position, and in the lithotomy position. Fluid and vasopressor requirements, along with hemodynamic parameters, were also analyzed. Results: PVI values at the 5th minute in the lithotomy position were significantly higher in the geriatric group compared to the non-geriatric group (p = 0.019). No significant differences were observed in PI values or intraoperative hypotension rates between the groups. Neurological comorbidities were more prevalent in the geriatric group (p = 0.025). Conclusions: PVI appears to be a more sensitive indicator of fluid responsiveness in elderly patients under spinal anesthesia in the lithotomy position. Its age-dependent variability suggests clinical utility in guiding fluid management in geriatric populations, while the stable hypotension rates support the effectiveness of PVI-guided goal-directed therapy. Full article

Background: Diabetes and cancer are two of the most life-threatening disorders affecting individuals of all ages worldwide. This study aimed to develop a novel Acrocomia aculeata (bocaiuva) fruit pulp oil-loaded nanoemulsion and evaluate its inhibitory effects on α-glucosidase and pancreatic lipase, as well as its antiglycant activity and cytotoxicity against cancer cells. Additionally, this study assessed the impact of both the oil and the nanoemulsion on blood cells. Methods: The pulp oil was extracted by cold pressing. The oil’s physicochemical properties were determined according to the AOAC and the Brazilian Pharmacopeia. The lipid profile was performed by GC-MS. The nanoemulsion was prepared by the phase inversion method using ultrasonic stirring for particle size reduction and for homogenization. Response Surface Methodology was used for optimizing nanoemulsion preparation. Enzyme inhibition tests were conducted using assay kits. Cytotoxicity in cancer cells was evaluated using the Sulforhodamine B assay. Results: Comprehensive physicochemical and chemical characterization of bocaiuva oil was performed, identifying oleic acid (71.25%) as the main component. The oil contains 23.04% saturated fatty acids, 73.79% monounsaturated acids, and 3.0% polyunsaturated fatty acids. The nanoemulsion (particle size 173.6 nm; zeta potential −14.10 mV) inhibited α-glucosidase (IC₅₀: 43.21 µg/mL) and pancreatic lipase (IC₅₀: 41.99 µg/mL), and revealed a potent antiglycation effect (oxidative IC₅0: 18.36 µg/mL; non-oxidative pathway IC₅₀: 16.33 µg/mL). The nanoemulsion demonstrated good cytotoxicity and selectivity against prostate cancer cells (IC₅₀: 19.13 µg/mL) and breast cancer cells (IC₅₀: 27.22 µg/mL), without inducing hemolysis, platelet aggregation, or anticoagulant effects. Conclusions: In this study, a comprehensive physical and chemical characterization of bocaiuva fruit pulp oil was conducted for the first time as a preliminary step toward its future standardization as an active ingredient in cosmetic and pharmaceutical formulations. The resulting nanoemulsion represents a novel alternative for managing diabetes and cancer. Although the nanoemulsion exhibited lower cytotoxicity compared to doxorubicin, it remains promising due to its composition of essential fatty acids, phenols, and carotenoids, which offer multiple health benefits. Further studies are needed to validate its efficacy and safety in clinical applications. Full article

Background: Circadian rhythms regulate critical cellular processes, including DNA repair and cell cycle dynamics, potentially influencing the effectiveness of radiotherapy (RT). This study evaluated whether RT timing impacts clinical outcomes and symptom burden in prostate cancer patients. Patients/Methods: This retrospective study (n = 336, median follow-up 55 months) included men who received curative intent external beam RT between 2010 and 2019 (median age 69, 69% black, median PSA 11.3, 40% with Gleason 8–10). Treatment times (TTs) were averaged and analyzed by quartile/median. Outcomes included freedom from biochemical failure (FFBF) and distant metastasis (FFDM), GI and GU toxicity, and quality of life (QOL). Subgroup analyses by race and hormone therapy status were performed. Results: Across the overall cohort, TT was not associated with FFBF or FFDM. However, in white men, earlier TTs were significantly associated with higher 5-year FFBF (89% vs. 67%, p = 0.0139) and FFDM (93% vs. 72%, p = 0.0268). In the multivariate analysis (MVA), TT was not associated with FFBF or FFDM for all men, but in white men, earlier TT was associated with improved FFBF (HR 2.8, p = 0.06) in a model also including risk category (p = 0.21). Overall, no significant differences were observed for grade 2–3+ toxicity and TT. Trends for inferior QOL, and worse grade 2+ (p = 0.2) and 3+ GU toxicity (p = 0.1) were observed for later TTs. In white men, bowel, urinary continence, and irritative/obstructive urinary QOL were worse with later TTs (p < 0.05). Conclusions: TT may influence clinical outcomes and symptom burden, particularly in white men. These findings underscore the potential of chronoradiotherapy as a personalized treatment strategy and highlight the need for prospective trials. Full article

Purpose: The identification of cardiovascular risk factors in metastatic prostate cancer (PCa) patients prior to the initiation of androgen receptor pathway inhibitors (ARPIs) is important yet challenging. Methods and Results: A nationwide cohort study was conducted utilizing data from the National Health Insurance Research Database containing the Taiwan Cancer Registry. The study population comprised 4739 PCa patients who received abiraterone or enzalutamide between 1 January 2014, and 28 February 2022. The cohort was divided into a training set (n = 3318) and a validation set (n = 1421). Machine learning techniques with random survival forest (RSF) model incorporating 16 variables was developed to predict major adverse cardiovascular events (MACEs). Over a mean follow-up period of 2.1 years, MACEs occurred in 10.9% and 11.3% of the training and validation cohorts, respectively. The RSF model identified five key predictive indicators: age < 65 or ≥75 years, heart failure, stroke, hypertension, and myocardial infarction. The model exhibited robust performance, achieving an area under the curve (AUC) of 85.1% in the training set and demonstrating strong external validity with an AUC of 85.5% in the validation cohort. A positive correlation was observed between the number of risk factors and the incidence of MACEs. Conclusions: This machine learning approach identified five predictors of MACEs in PCa patients receiving ARPIs. These findings highlight the need for comprehensive cardiovascular risk assessment and vigilant monitoring in this patient population. Full article

Background/Objectives: Prostate cancer (PCa) is diagnosed at an earlier median age, more advanced stage, and has worse clinical outcomes in African American (AA) men compared to European Americans (EA). Methods: To investigate the role of aberrant DNA methylation in tumor-adjacent stroma (TAS), methyl binding domain sequencing (MBD-seq) was performed on AA (n = 17) and EA (n = 15) PCa patients. This was independently confirmed using the long interspersed nuclear element-1 (LINE-1) assay. Pathway analysis was performed on statistically significantly differentially methylated genes for AA and EA TAS. DNA methylation profiles of primary cultured AA and EA carcinoma-associated fibroblasts (CAFs) were compared with AA and EA TAS. AA and EA CAFs were treated with demethylating agent 5-Azacytidine (5-AzaC). Results: AA TAS exhibited higher global DNA methylation than EA TAS (p-value < 0.001). Of the 3268 differentially methylated regions identified (DMRs, p-value < 0.05), 85% (2787 DMRs) showed increased DNA methylation in AA TAS, comprising 1648 genes, of which 1379 were protein-coding genes. Based on DNA methylation levels, two AA subgroups were identified. Notably, AA patients with higher DNA methylation were predominantly those with higher Gleason scores. Pathway analysis linked methylated genes in AA TAS to several key signaling pathways (p-value < 0.05), including immune response (e.g., IL-1, IL-15, IL-7, IL-8, IL-3, and chemokine), Wnt/β-catenin, androgen, PTEN, p53, TGF-β, and circadian clock regulation. A total of 168 concordantly methylated genes were identified, with 109 genes (65%) showing increased methylation in AA CAFs and TAS (p-value < 0.05). Treatment with 5-AzaC significantly reduced DNA methylation of concordant genes in AA CAFs (p-value < 0.001). Conclusions: These findings suggest a distinct stromal methylome in AA, providing a foundation for integrating demethylating agents into standard therapies. This approach targets the tumor microenvironment, potentially addressing PCa disparities in AA men. Full article

Background and Objective: Benign prostatic hyperplasia (BPH) and urethral stricture (US) are common causes of lower urinary tract symptoms in ageing men, often requiring repeated interventions. Conventional treatments of US, such as urethrotomy and mechanical dilation, have high recurrence rates. The Optilume drug-coated balloon catheter system, which combines mechanical dilation with paclitaxel delivery, has emerged as a minimally invasive alternative. This systematic review assesses its efficacy and safety in the management of BPH and US. Methods: A systematic search of PubMed was conducted for studies published between August 2020 and October 2023. Eligible studies included randomised controlled trials (RCTs), cohort studies, and case reports evaluating Optilume’s therapeutic effects. Key outcomes analysed included symptom relief, urinary flow improvement, recurrence rates, and adverse events. Results: Seven studies met the inclusion criteria, including five on US and two on BPH. The ROBUST trial series demonstrated sustained improvements in urinary flow rates and symptom scores in US patients over follow-up periods of up to four years. The EVEREST-1 and PINNACLE trials reported significant symptom relief and preserved sexual function in BPH patients, with a favourable safety profile and minimal complications. Conclusions: Optilume appears to be a promising alternative to conventional endoscopic treatments for US and BPH, offering durable symptom relief with a low complication rate. Further long-term studies are required to confirm its efficacy and cost-effectiveness in routine clinical practice. Full article

Objective: To test for in-hospital mortality and complication rates in a population-based group of patients with vs. without a history of heart valve replacement undergoing radical prostatectomy (RP). Methods: Relying on the National Inpatient Sample (2000–2019), prostate cancer patients undergoing RP were stratified according to the presence or absence of heart-valve replacement. Multivariable logistics and Poisson regression models addressed adverse hospital outcomes. Results: Within the NIS, 220,358 patients underwent RP. Of those, 694 (0.3%) had a history of heart valve replacement. The patients undergoing heart valve replacement were older (median age 66 vs. 62 years). The proportion of patients with a history of heart valve replacement increases with the Charlson Comorbidity Index (CCI): CCI 0–0.3%, CCI 1–0.4%, and CCI ≥ 2–0.7%. Patients with a history of heart valve replacement exhibited higher rates of postoperative bleeding (<1.5% vs. <0.1%; odds ratio (OR) 16.2; p < 0.001), cardiac complications (7.5% vs. 1.2%; OR 3.9; p < 0.001), infections (<1.5% vs. 0.1%; OR 3.7; p = 0.01), critical care therapy (CCT) use (<1.5% vs. 0.4%; OR 2.5; p = 0.003), intraoperative complications (8.8% vs. 4.1%; OR 1.9; p < 0.001), transfusions (11% vs. 7.2%; OR 1.5; p < 0.001), longer hospital stay (mean 3.39 vs. 2.37 days; rates ratio [RR] 1.4; p < 0.001), and higher estimated hospital cost (median 33,539 vs. 30,716 $USD; RR 1.1; p < 0.001). Conversely, no statistically significant differences were observed in vascular complications (p = 0.3) or concerning in-hospital mortality (p = 0.1). Conclusions: After RP, patients with a history of heart valve replacement exhibited a higher rate of eight out of nine adverse in-hospital outcomes. However, these differences did not translate into higher in-hospital mortality. Full article

Background/Objectives: The HOX genes encode a family of homeodomain-containing transcription factors that have important roles in defining cell and tissue identity in embryonic development, but which also show deregulated expression in many cancers and have been shown to have pro-oncogenic roles. Due to their functionally redundant nature, strategies to target HOX protein function in cancer have focused on their interaction with their PBX cofactor using competitive peptides such as HXR9. HOX/PBX inhibition triggers apoptosis through a sudden increase in target gene expression, including Fos, DUSP1, and ATF3, which are otherwise repressed by HOX/PBX binding. Methods: We analyzed publicly available transcriptomic data in the R2 platform. Results: We show that a specific subgroup of HOX genes is negatively correlated with Fos, DUSP1, and ATF3 expression in prostate cancer, and that this subgroup also shows a strong positive corelation with pathways that support tumour growth, most notably DNA repair and aminoacyl tRNA biosynthesis, and a negative correlation with genes that promote cell adhesion and prevent motility. In addition, this set of HOX genes strongly correlates with patient age, reflecting a previously identified progressive loss of regulation of HOX expression in normal peripheral blood cells. Conclusions: Our findings indicate these HOX genes may have pro-oncogenic functions in prostate cancer. Full article

Introduction: Ureteral stents are widely used in the specialty of urology to preserve renal function and provide ureteral patency in cases of urolithiasis, strictures, malignancy, and trauma. This paper presents a novel application of prophylactic ureteral stents deployed under MRI-guidance for ureteral protection in the setting of in-bore salvage cryoablation therapy for recurrent and metastatic prostate cancer. This is the first known case series of ureteral stent placement using near real-time MRI. Materials and Methods: A retrospective chart review was performed for all patients who underwent MRI-guided ureteral stent placement prior to in-bore cryoablation therapy from 2021 to 2022. Each case was managed by an interdisciplinary team of urologists and interventional radiologists. Preoperative and postoperative data were collected for descriptive analysis. Physics safety testing was conducted on the cystoscope and viewing apparatus prior to its implementation for stent deployment. Results: A total of seven males, mean age 73.4 years (range 65–81), underwent successful prophylactic, cystoscopic MRI-guided ureteral stent placement prior to cryoablation therapy of their prostate cancer. No intraoperative complications occurred. A Grade 2 postoperative complication of pyelonephritis and gross hematuria following stent removal occurred in one case. The majority of patients were discharged the same day as their procedure. Conclusions: This case series demonstrates the feasibility of in-bore cystoscopic aided MRI guidance for ureteral stent placement. Ureteral stents can be used to increase the safety margin of complex cryoablation treatments close to the ureter. Furthermore, by following the meticulous MRI safety protocols established by MRI facility safety design guidelines, MRI conditional tools can aid therapy in the burgeoning interventional MRI space. Full article

Prostate cancer, a malignancy of significant prevalence, affects approximately half a million men in Europe, with one in twelve males receiving a diagnosis before reaching the age of 75. Radiotheranostics represents a paradigm shift in prostate cancer treatment, leveraging radionuclides for diagnostic and therapeutic applications, with PSMA emerging as the primary molecular target. Regulatory bodies have approved various PSMA-targeted radiodiagnostic agents, such as [¹⁸F]DCFPyL (PYLARIFY^®, Lantheus Holdings), [¹⁸F]rhPSMA-7.3 (POSLUMA^®, Blue Earth Diagnostics), and [⁶⁸Ga]Ga-PSMA-11 (LOCAMETZ^®, Novartis/ILLUCCIX^®, Telix Pharmaceuticals), as well as therapeutic agents like [¹⁷⁷Lu]Lu-PSMA-617 (PLUVICTO^®, 15 Novartis). The approval of PLUVICTO^® in March 2022 for patients with metastatic castration-resistant prostate cancer who have undergone prior treatments, including androgen receptor pathway-targeting agents and taxane-based chemotherapy, represents a significant advancement. Other radionuclides like ¹⁶¹Tb, ¹⁴⁹Tb, ²²⁵Ac, ²²⁷Th, ²²³Ra, ²¹¹At, ²¹³ Bi, ²¹²Pb, ⁸⁹Zr, and ¹²⁵I are presented, emphasizing their clinical implementation or the stage of clinical trial they are in in the flow to biomedical implementation. Three clinically wise used radionuclides ¹⁷⁷Lu, ²²⁵Ac, ²²³Ra are shown along with their characteristics. This review aims to elucidate the molecular mechanisms underpinning PSMA, explore the clinical applications of PSMA-targeted radiotheranostics, and critically examine the diverse challenges these therapies encounter in the treatment of prostate cancer. Full article

Temporal changes in testicular traits have been reported in both humans and dogs. Analysis of % living sperm and motility from semen collections from 186 Labrador Retrievers and 113 Golden Retrievers between 2006 and 2023, and of incidents of cryptorchidism in over 15,000 dogs of the same breeds and crosses born between 1994 and 2023 was undertaken to determine influential factors. A general temporal increase in incidence of cryptorchidism masked significant differences in the trend between breeds, which persisted after accounting for genetic and litter effects. The incidence in the F1 cross was significantly lower than in either pure breed, implying hybrid vigour. The semen traits were both moderately repeatable within individuals, but this belied breed differences in its composition; for both traits, only the heritability was significantly greater than zero in the Golden Retriever, while only the permanent environment effect was present in Labrador Retrievers. There were significant negative temporal trends in Golden Retrievers for both semen traits, but not in Labrador Retrievers; significant negative effects of age (except on % motility in Labrador Retrievers); and significant negative effects of a diagnosis of benign prostatic hyperplasia on both traits in both breeds. These results reveal complex breed by environment interactions in traits related to testicular form and function. Full article

Background/Objectives: Prostate cancer ranks as the second-most prevalent cancer globally, and is the fifth-ranking cause of cancer-related mortality. Radical prostatectomy presents a significant risk of postoperative sequelae, including erectile dysfunction. Postoperative erectile dysfunction adversely affects the patient’s quality of life and can severely impact total treatment satisfaction. Nomograms have demonstrated efficacy in forecasting diverse outcomes in urology. We sought to create a nomogram to facilitate a more precise, evidence-based, and individualized prediction of erectile function outcomes following radical prostatectomy. Between January 2018 and January 2022, one hundred and eleven prostate cancer patients had robot-assisted radical prostatectomy, excluding those who had undergone prior transurethral prostatectomy, radiotherapy, or hormone therapy. Demographics, medical records, preoperative and postoperative erectile function statuses, and IIEF scores (≥17 indicating retained erections, <17 indicating full erectile dysfunction) were evaluated. Outcomes: Patients’ ages ranged from 45 to 76 years, with an average of 61.18 ± 6.72 years. Patients in the emergency department were considerably older (p = 0.004; p < 0.01) and exhibited elevated Charlson Comorbidity Indices (3.63 ± 0.85; p = 0.004; p < 0.01). Preoperative IIEF scores in ED patients were lower (14.29 ± 5.34), although obturator internus thickness (20.61 ± 2.91) and intraprostatic urethra length (36.48 ± 9.3) were considerably elevated. Altered surgical techniques were linked to maintained erections (p = 0.002; p < 0.01), but traditional approaches were connected with erectile dysfunction (p = 0.007; p < 0.01). Bilateral nerve-sparing procedures were more prevalent among patients preserving erectile function (p = 0.003; p < 0.01). Conclusions: The nomogram, which includes age, Charlson Comorbidity Index, preoperative IIEF, obturator internus thickness, intraprostatic urethra length, surgical technique, and degree of nerve preservation, provides clinicians with a pragmatic instrument for forecasting postoperative erectile dysfunction in prostate cancer patients. Full article

Background: Accurate upfront risk stratification in suspected clinically significant prostate cancer (csPCa) may reduce unnecessary prostate biopsies. Integrating clinical and Magnetic Resonance Imaging (MRI) variables using deep learning could improve prediction. Methods: We retrospectively analysed 538 men who underwent MRI and biopsy between April 2019-September 2024. A fully connected neural network was trained using 5-fold cross-validation. Model 1 included clinical features (age, prostate-specific antigen [PSA], PSA density, digital rectal examination, family history, prior negative biopsy, and ongoing therapy). Model 2 used MRI-derived Prostate Imaging Reporting and Data System (PI-RADS) categories. Model 3 used all previous variables as well as lesion size, location, and prostate volume as determined on MRI. Results: Model 3 achieved the highest area under the receiver operating characteristic curve (AUC = 0.822), followed by Model 2 (AUC = 0.778) and Model 1 (AUC = 0.716). Sensitivities for detecting clinically significant prostate cancer (csPCa) were 87.4%, 91.6%, and 86.8% for Models 1, 2, and 3, respectively. Although Model 3 had slightly lower sensitivity than Model 2, it showed higher specificity, reducing false positives and avoiding 43.4% and 21.2% more biopsies compared to Models 1 and 2. Decision curve analysis showed M2 had the highest net benefit at risk thresholds ≤ 20%, while M3 was superior above 20%. Conclusions: Model 3 improved csPCa risk stratification, particularly in biopsy-averse settings, while Model 2 was more effective in cancer-averse scenarios. These models support personalized, context-sensitive biopsy decisions. Full article