Castration Levels of Testosterone Results in Atrophy of Androgen-Sensitive Perineal Muscles: A Potential Biomarker for Male Hypogonadism.

OBJECTIVES: To evaluate MRI-based measurements of androgen-sensitive perineal/pelvic muscles in men with prostate cancer before and after androgen deprivation therapy (ADT) as a novel imaging marker for end-organ effects of hypogonadism. Diagnosing hypogonadism or testosterone deficiency (TD) requires both low serum testosterone and clinical symptoms, such as erectile dysfunction and reduced libido. However, the non-specific nature of many TD symptoms makes it challenging to initiate therapy. Objective markers of TD help to better identify patients who may benefit from testosterone supplementation; however, current markers, such as low bone mineral density, lack sensitivity. Previous studies suggest that decreased bulbocavernosus-muscle (BCM) thickness may be associated with TD, although it remains unclear if this is a correlative relationship. METHODS: Data was prospectively collected for patients with intermediate/high-risk localized prostate cancer enrolled in a phase II trial (NCT02430480). Patients received ADT before prostatectomy and underwent prostate MRI pre-/post-ADT. BCM, ischiocavernosus-muscle (ICM), and levator-ani-muscle (LAM) measurements were made using T2W-MRI. Paired t-tests evaluated changes in BCM/ICM/LAM width, and linear regression analyses evaluated relationships between changes in testosterone and muscle width. RESULTS: Thirty-eight consecutive patients with pre-/post-ADT MRIs were analyzed. Baseline testosterone was 286.5ng/dl, and 36/38 patients had post-ADT testosterone <50ng/dL. Pre-ADT and post-ADT measurements of the bilateral BCM/ICM/LAM width were 7.16mm/7.95mm/5.53mm and 5.68mm/6.71mm/4.89mm, respectively (p<0.001). Decreases in testosterone predicted reduction in combined perineal muscle (BCM+ICM) width (p=0.032). CONCLUSIONS: Androgen deprivation led to significant and relatively rapid decreases in BCM/ICM/LAM thickness. This objective biomarker of low testosterone states may help identify patients who will potentially benefit from testosterone replacement.

Predicting post-surgical complications using renal scoring systems.

Current surgical approaches for renal malignancies primarily rely on qualitative factors such as patient preferences, surgeon experience, and hospital capabilities. Applying a quantitative method for consistent and reliable assessment of renal lesions would significantly enhance surgical decision-making and facilitate data comparison. Nephrometry scoring (NS) systems systematically evaluate and describe renal tumors based on their anatomical features. These scoring systems, including R.E.N.A.L., PADUA, MAP scores, C-index, CSA, and T-index, aim to predict surgical complications by evaluating anatomical and patient-specific factors. In this review paper, we explore the components and methodologies of these scoring systems, compare their effectiveness and limitations, and discuss their application in advancing patient care and optimizing surgical outcomes.

Evaluating Diagnostic Accuracy and Inter-reader Agreement of the Prostate Imaging After Focal Ablation Scoring System.

Background and objective: Focal therapy (FT) is increasingly recognized as a promising approach for managing localized prostate cancer (PCa), notably reducing treatment-related morbidities. However, post-treatment anatomical changes present significant challenges for surveillance using current imaging techniques. This study aimed to evaluate the inter-reader agreement and efficacy of the Prostate Imaging after Focal Ablation (PI-FAB) scoring system in detecting clinically significant prostate cancer (csPCa) on post-FT multiparametric magnetic resonance imaging (mpMRI). Methods: A retrospective cohort study was conducted involving patients who underwent primary FT for localized csPCa between 2013 and 2023, followed by post-FT mpMRI and a prostate biopsy. Two expert genitourinary radiologists retrospectively evaluated post-FT mpMRI using PI-FAB. The key measures included inter-reader agreement of PI-FAB scores, assessed by quadratic weighted Cohen's kappa (κ), and the system's efficacy in predicting in-field recurrence of csPCa, with a PI-FAB score cutoff of 3. Additional diagnostic metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were also evaluated. Key findings and limitations: Scans from 38 patients were analyzed, revealing a moderate level of agreement in PI-FAB scoring (κ = 0.56). Both radiologists achieved sensitivity of 93% in detecting csPCa, although specificity, PPVs, NPVs, and accuracy varied. Conclusions and clinical implications: The PI-FAB scoring system exhibited high sensitivity with moderate inter-reader agreement in detecting in-field recurrence of csPCa. Despite promising results, its low specificity and PPV necessitate further refinement. These findings underscore the need for larger studies to validate the clinical utility of PI-FAB, potentially aiding in standardizing post-treatment surveillance. Patient summary: Focal therapy has emerged as a promising approach for managing localized prostate cancer, but limitations in current imaging techniques present significant challenges for post-treatment surveillance. The Prostate Imaging after Focal Ablation (PI-FAB) scoring system showed high sensitivity for detecting in-field recurrence of clinically significant prostate cancer. However, its low specificity and positive predictive value necessitate further refinement. Larger, more comprehensive studies are needed to fully validate its clinical utility.

Feasibility and Impact of Immunohistochemistry-based Molecular Subtyping for Muscle-invasive Bladder Cancer in Patients Treated with Radiation-based Therapy.

Background: Distinct molecular subtypes of muscle-invasive bladder cancer (MIBC) have been identified via gene expression profiling. Objective: We investigated the feasibility of a simple immunohistochemistry (IHC)-based Lund subtyping method and the association of MIBC subtypes with oncological outcomes for patients after bladder-preserving radiation-based therapy. Design setting and participants: Transurethral resected tumor tissues from 104 patients treated with radiation-based therapy were sampled on tissue microarray blocks. Outcome measurements and statistical analysis: The expression of KRT5, GATA3, and p16 proteins was scored via digital image analysis. Hierarchical clustering was used to classify tumors as the basal subtype or one of two luminal subtypes: genomically unstable (GU) or urothelial-like (URO). Subtypes were evaluated for association with complete response (CR), recurrence-free survival (RFS), and overall survival (OS). Results and limitations: The median OS was 43 mo (95% confidence interval 19-77) and median follow-up was 55 mo (interquartile range 39-75). Age and clinical stage had a significant impact on OS (p < 0.05). IHC-based subtype classification was feasible in most patients (89%). The subtype was basal in 23.6%, GU in 14.0%, URO in 31.2%, and unclassified in 31.2% of patients. No significant differences in CR, RFS, or OS were observed between the molecular subtypes. Limitations include the retrospective design and relatively small sample size. Conclusions: IHC-based molecular MIBC subtyping using a three-antibody algorithm is feasible in most patients treated with radiation-based therapy. MIBC subtype was not associated with response or survival. Further prospective studies are warranted to confirm the lack of association between molecular subtype and survival in patients treated with trimodal therapy. Patient summary: For patients with invasive bladder cancer treated with radiation-based therapy, we classified tumors into different subtypes using just three molecular stains. This method is cheaper and more widely available than the usual approach. However, we did not find an association between different cancer subtypes and survival.

Identifying risk factors for development of nephrolithiasis in end-stage renal disease patients.

INTRODUCTION: We sought to assess the incidence and risk factors for stone development in patients with end-stage renal disease (ESRD) on hemodialysis (HD). METHODS: Medical records of patients receiving HD between 2007 and 2017 were retrospectively reviewed. Patients who had been on HD for at least three months and had imaging studies (computed tomography [CT] scans or ultrasound [US]) pre- and post-initiation of HD were included. Exclusion criterion was presence of stones pre-HD. De novo stones were defined as renal stones found on followup imaging. Demographics, laboratory data, comorbidities, and dialysis characteristics were compared between non-stone-formers and stone-formers using propensity score matching. RESULTS: A total of 133 patients met the inclusion criteria. Their median age was 68.5 years, median body mass index 28.7 kg/m2, and median dialysis duration 59.5 months. After HD, 14 (10.5%) patients developed de novo stones and their median dialysis-to-stone duration was 23.5 months. When compared with non-stone-formers, stone-formers had significantly lower incidence of hypertension (48.2% vs. 14.3%; p=0.03), lower serum ionized calcium (1.16 vs. 1.07 mmol/L; p=0.01) and magnesium (0.95 vs. 0.81 mmol/L; p=0.01), and significantly higher serum uric acid (281.5 vs. 319.0 µmol/L; p=0.03). Multivariate analysis demonstrated that lower serum ionized calcium (adjusted odds ratio [OR] 0.00001; 95% confidence interval [CI] 0-0.18) and magnesium (adjusted OR 0.0003; 95% CI 0-0.59) were significantly associated with stone-formation. CONCLUSIONS: The incidence of de novo nephrolithiasis in ESRD patients on HD was 10.5%. Increased serum uric acid, decreased serum magnesium and ionized calcium, and absence of hypertension were associated with increased stone-formation in ESRD patients on HD.

Combined vitamin D and calcium supplementation in vitamin D inadequate patients with urolithiasis: Impact on hypercalciuria and de novo stone formation.

INTRODUCTION: We examined the effect of combined vitamin D and calcium supplementation (VDCS) on urinary calcium excretion and de novo stone formation in vitamin D inadequate (VDI) urolithiasis patients. METHODS: We retrospectively reviewed the data of VDI patients (serum 25-hydroxyvitamin D <75 nmol/L) followed at a tertiary stone centre between September 2009 and December 2014. VDI patients with history of urolithiasis, who were placed on VDCS for abnormal bone mineral density or hyperoxaluria, were included. Hypercalciuric patients and patients on thiazide diuretics were excluded. Metabolic stone workup and two 24-hour urine collections were performed before and after VDCS. RESULTS: In total, we included 34 patients, with a mean age of 54.8 years and a mean body mass index of 25.7 kg/m(2). After VDCS, there was a significant increase in the mean serum 25-hydroxyvitamin D (52.0 vs. 66.4 nmol/L, p < 0.001) and the mean urinary calcium excretion (3.80 vs. 5.64 mmol/d, p < 0.001). Eight (23.5%) patients developed de novo hypercalciuria. After a median follow-up of 39 (range: 7-60) months, 50% of hypercalciuric patients developed stones compared with 11.5% of non-hypercalciuric patients (p = 0.038). CONCLUSION: This study showed a significant effect of combined VDCS on mean urinary calcium excretion, de novo hypercalciuria, and stone development in VDI patients with history of urolithiasis. Therefore, VDI urolithiasis patients receiving VDCS are advised to have monitoring with 24-hour urine collections and imaging studies. Although small, our sample size was good enough to validate the statistical outcomes. Prospective studies are needed to confirm these results.