The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease.

Background: There is a paucity of literature on racial differences across a full total joint arthroplasty (TJA) “episode of care” and beyond. Given various incentives, the Comprehensive Care for Joint Replacement (CJR) program in the U.S. may have impacted preexisting racial differences across this care continuum. The purposes of the present study were (1) to assess trends in racial differences in care/outcome characteristics before, during, and after TJA surgery and (2) to assess if the CJR program coincided with reductions in these racial differences. Methods: This retrospective cohort study includes data on 1,483,221 TJAs (based on Medicare claims data, 2013 to 2018). Racial differences between Black and White patients were assessed for (1) preoperative characteristics (Deyo-Charlson comorbidity index, patient sex, and age), (2) characteristics during hospitalization (length of stay, blood transfusions, and combined complications), and (3) postoperative characteristics (90 and 180-day readmission rates and institutional post-acute care). Additionally, Medicare payments for each period were assessed. Racial differences (Black versus White patients) were expressed in terms of odds ratios (ORs) and 95% confidence intervals (CIs) per year. A “difference-in-differences” analysis (comparing before and after CJR implementation, with non-CJR hospitals being used as controls) estimated the association of the CJR program with changes in racial differences. Results: In both 2013 and 2018, Black patients (n = 74,390; 5.0%) were more likely than White patients to have a higher Deyo-Charlson comorbidity index (score of >0) (OR = 1.32 [95% CI = 1.28 to 1.36] and OR = 1.32 [95% CI = 1.28 to 1.37]), to require more transfusions (OR = 1.55 [95% CI = 1.49 to 1.62] and OR = 1.77 [95% CI = 1.56 to 2.01]), to be discharged to institutional post-acute care (OR = 1.40 [95% CI = 1.36 to 1.44] and OR = 1.49 [95% CI = 1.43 to 1.56]), and to be readmitted within 90 days (OR = 1.38 [95% CI = 1.32 to 1.44] and OR = 1.21 [95% CI = 1.13 to 1.29]) (p < 0.05 for all). Adjusted difference-in-differences analyses demonstrated that the CJR program coincided with reductions in racial differences in 90-day readmission (−1.24%; 95% CI, −2.46% to −0.03%) and 180-day readmission (−1.28%; 95% CI, −2.52% to −0.03%) (p = 0.044 for both). Conclusions: Racial differences persist among patients managed with TJA. The CJR program coincided with reductions in some racial differences, thus identifying bundle design as a potential novel strategy to target racial disparities. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Extracellular vesicles (EVs)—including apoptotic bodies, microvesicles, and exosomes—are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.

Malignant pleural mesothelioma (MPM) is an aggressive tumor and the prognosis is still dismal despite the various proposed multimodal treatment plans. Currently, new palliative treatments, such as talc pleurodesis, are being explored besides traditional surgery. This review reports survival rates after talc pleurodesis in comparison to surgery in patients with malignant pleural mesothelioma. A systematic literature search yielded 49 articles eligible for this review. The mean survival in the talc pleurodesis group was 14 months compared to 17 and 24 months for the pleurectomy decortication (P/D) group and extrapleural pneumonectomy (EPP) group, respectively. Few studies reported on the 1-, 2-year overall survival for the talc pleurodesis group and the results were very heterogeneous. The pooled 1-year overall survival for the P/D and EPP groups were 55% [credibility limits (CL): 21–87%] and 67% (CL: 3–89%), the pooled 2-year overall survival were 32% (CL: 8–63%) and 36% (CL: 8–54%), respectively. The pooled 1- and 2-year survival for surgery independently from the type of surgery were 62% (CL: 38–84%) and 34% (CL: 16–54%). There was significant heterogeneity in all the analyses. This review shows that there is limited research on the survival rate after talc pleurodesis compared to surgery in the treatment of malignant pleural mesothelioma. A comparison study is necessary to accurately assess the best way to treat MPM patients, including assessment of the quality of life after treatment as an outcome measure.

Renal cancer ranks twelfth in incidence among cancers worldwide. Despite improving outcomes due to better therapeutic options and strategies, prognosis for those with metastatic disease remains poor. Current systemic therapeutic approaches include inhibiting pathways of angiogenesis, immune checkpoint blockade, and mTOR inhibition, but inevitably resistance develops for those with metastatic disease, and novel treatment strategies are urgently needed. Emerging molecular and epidemiological evidence suggests that quinazoline-based α1-adrenoceptor-antagonists may have both chemopreventive and direct therapeutic actions in the treatment of urological cancers, including renal cancer. In human renal cancer cell models, quinazoline-based α1-adrenoceptor antagonists were shown to significantly reduce the invasion and metastatic potential of renal tumors by targeting focal adhesion survival signaling to induce anoikis. Mechanistically these drugs overcome anoikis resistance in tumor cells by targeting cell survival regulators AKT and FAK, disrupting integrin adhesion (α5β1 and α2β1) and engaging extracellular matrix (ECM)-associated tumor suppressors. In this review, we discuss the current evidence for the use of quinazoline-based α1-adrenoceptor antagonists as novel therapies for renal cell carcinoma (RCC) and highlight their potential therapeutic action through overcoming anoikis resistance of tumor epithelial and endothelial cells in metastatic RCC. These findings provide a platform for future studies that will retrospectively and prospectively test repurposing of quinazoline-based α1-adrenoceptor-antagonists for the treatment of advanced RCC and the prevention of metastasis in neoadjuvant, adjuvant, salvage and metastatic settings.