Serum Testosterone and Dihydrotestosterone and Incidence and Progression of Lower Urinary Tract Symptoms: Results From the REDUCE Study.

PURPOSE: Though the pathogenesis of benign prostatic hyperplasia is unclear, it was previously believed that increasing androgen levels contributed, though not all data support this idea. We tested if elevated serum testosterone or dihydrotestosterone were risk factors for lower urinary tract symptoms incidence in asymptomatic men and for lower urinary tract symptoms progression in symptomatic men. MATERIALS AND METHODS: A post hoc analysis of REDUCE was performed in 3009 asymptomatic men and in 2145 symptomatic men. REDUCE was a randomized trial of dutasteride for prostate cancer prevention in men with an elevated prostate-specific antigen and negative prestudy biopsy. We estimated multivariable adjusted hazard ratios and 95% confidence intervals using Cox models to test the association between quintiles of serum testosterone and dihydrotestosterone at baseline and lower urinary tract symptoms incidence and progression and tested for interaction by treatment arm (dutasteride vs placebo). RESULTS: In asymptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms incidence (P = .9, P = .4). In symptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms progression (P = .9, P = .7). Results were similar in both placebo and dutasteride arms (all P interaction ≥ .3). CONCLUSIONS: In REDUCE, higher serum testosterone and higher serum dihydrotestosterone were not associated with either lower urinary tract symptoms incidence in asymptomatic men or lower urinary tract symptoms progression in symptomatic men. These data do not support the hypothesis that serum androgens in middle-aged men are associated with lower urinary tract symptoms.

Investigating trends in interest for benign prostatic hyperplasia surgery options using Google Trends.

Understanding patient interest among surgical options is challenging. We used Google Trends to analyze interest in benign prostatic hyperplasia (BPH) surgeries recommended for prostate volumes <80 cc. Google Trends was queried with five BPH surgeries. Final rank of search terms was TURP, UroLift, Rezum, Aquablation, and Greenlight. Google Trends can be an effective tool for evaluating public interest trends in BPH surgery.

27-hydroxycholesterol and DNA damage repair: implication in prostate cancer.

Introduction: We previously reported that cholesterol homeostasis in prostate cancer (PC) is regulated by 27-hydroxycholesterol (27HC) and that CYP27A1, the enzyme that converts cholesterol to 27HC, is frequently lost in PCs. We observed that restoring the CYP27A1/27HC axis inhibited PC growth. In this study, we investigated the mechanism of 27HC-mediated anti-PC effects. Methods: We employed in vitro models and human transcriptomics data to investigate 27HC mechanism of action in PC. LNCaP (AR+) and DU145 (AR-) cells were treated with 27HC or vehicle. Transcriptome profiling was performed using the Affymetrix GeneChip™ microarray system. Differential expression was determined, and gene set enrichment analysis was done using the GSEA software with hallmark gene sets from MSigDB. Key changes were validated at mRNA and protein levels. Human PC transcriptomes from six datasets were analyzed to determine the correlation between CYP27A1 and DNA repair gene expression signatures. DNA damage was assessed via comet assays. Results: Transcriptome analysis revealed 27HC treatment downregulated Hallmark pathways related to DNA damage repair, decreased expression of FEN1 and RAD51, and induced "BRCAness" by downregulating genes involved in homologous recombination regulation in LNCaP cells. Consistently, we found a correlation between higher CYP27A1 expression (i.e., higher intracellular 27HC) and decreased expression of DNA repair gene signatures in castration-sensitive PC (CSPC) in human PC datasets. However, such correlation was less clear in metastatic castration-resistant PC (mCRPC). 27HC increased expression of DNA damage repair markers in PC cells, notably in AR+ cells, but no consistent effects in AR- cells and decreased expression in non-neoplastic prostate epithelial cells. While testing the clinical implications of this, we noted that 27HC treatment increased DNA damage in LNCaP cells via comet assays. Effects were reversible by adding back cholesterol, but not androgens. Finally, in combination with olaparib, a PARP inhibitor, we showed additive DNA damage effects. Discussion: These results suggest 27HC induces "BRCAness", a functional state thought to increase sensitivity to PARP inhibitors, and leads to increased DNA damage, especially in CSPC. Given the emerging appreciation that defective DNA damage repair can drive PC growth, future studies are needed to test whether 27HC creates a synthetic lethality to PARP inhibitors and DNA damaging agents in CSPC.

Higher Component Malposition Rates with Patient-Specific Cruciate Retaining TKA than Contemporary Posterior Stabilized TKA.

Customized individually manufactured total knee arthroplasty (CIM-TKA) was developed to improve kinematic total knee arthroplasty (TKA) performance. Component placement accuracy may influence the success of CIM-TKA designs. We performed this study to compare radiographic component alignment and revision rates of a cruciate retaining (CR) CIM-TKA and a contemporary posterior stabilized TKA (PS-TKA). After obtaining Institutional Review Board approval, we identified 94 CR CIM-TKAs (76 patients) and 91 PS-TKAs (82 patients) performed between July 1, 2013 and December 31, 2014 with a minimum 2-year follow-up (mean 41.1 months, range 24-59 months). We performed a retrospective electronic medical record review to identify patient demographic characteristics and revision procedures performed. Postoperative plain radiographs were reviewed to assess component alignment including cruciate ligament imbalance, femoral overhang, and femoral notching. Demographic characteristics, component malalignment, and revision surgery rates were assessed using a student's t-test or two-tailed Fisher's exact test, with a p-value < 0.05 designating significance. Technical errors were more commonly identified with CR CIM-TKA (29.8 vs. 9.9%, p < 0.001), including higher rates of tibiofemoral instability (13.8 vs. 1.1%, p < 0.01), femoral notching (12.8 vs. 3.3%, p = 0.03), and patellofemoral malalignment (20.2 vs. 7.7%, p = 0.02). CR CIM-TKA had more frequent coronal plane malposition (26.6 vs. 9.9%, p < 0.01) or sagittal plane reconstruction > 3 degrees outside of an optimized range (20.2 vs. 9.9%, p = 0.06). Aseptic revisions occurred more frequently with the CR CIM-TKA design (9.6 vs. 3.3%, p = 0.13). Demographic characteristics were not significantly different between the treatment groups. CR CIM-TKA may improve kinematic performance for patients undergoing knee replacement surgery. However, our study observations suggest that careful attention to surgical technique is important for optimizing implant survivorship with the CR CIM-TKA design. Additional study is needed to determine whether higher revision rates identified during this study are related to patient selection, surgical technique, or implant design.