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There is a growing list of cancer immunotherapeutics approved for use in a population with an increasing number of aged individuals. Cancer immunotherapy (CIT) mediates tumor destruction by activating anti-tumor immune responses that have been silenced through the oncogenic process. However, in an aging individual, immune deregulation is positively correlated with age. In this context, it is vital to examine the age-related changes in the tumor microenvironment (TME) and specifically, those directly affecting critical players to ensure CIT efficacy. Effector T cells, regulatory T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and tumor-associated neutrophils play important roles in promoting or inhibiting the inflammatory response, while cancer-associated fibroblasts are key mediators of the extracellular matrix (ECM). Immune checkpoint inhibitors function optimally in inflamed tumors heavily invaded by CD4 and CD8 T cells. However, immunosenescence curtails the effector T cell response within the TME and causes ECM deregulation, creating a biophysical barrier impeding both effective drug delivery and pro-inflammatory responses. The ability of the chimeric antigen receptor T (CAR-T) cell to artificially induce an adaptive immune response can be modified to degrade essential components of the ECM and alleviate the age-related changes to the TME. This review will focus on the age-related alterations in ECM and immune-stroma interactions within the TME. We will discuss strategies to overcome the barriers of immunosenescence and matrix deregulation to ameliorate the efficacy of CIT in aged subjects.

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The flow rates of irrigation produced by the HP and the E.A.S.I. pump are similar at pressures of 150 and 200 mm Hg irrespective of the occupancy of a ureteroscope's working channel during the first 5-minutes of irrigation. Irrigation pressure at the entry site of the ureteroscope is subject to significant variability with use of the HP compared to the E.A.S.I. pump irrigation system.

Purpose: In urolithiasis patients, preoperative non-contrast computed tomography (NCCT) commonly fails to provide sufficient distention of the renal collecting system to allow reliable preoperative planning for how best to approach a stone. Our objective was to evaluate the effect of a novel protocol, including oral hydration and an oral diuretic, on the distention of the renal collecting system. Patients and Methods: Twenty patients with a prior NCCT, who were scheduled to undergo a subsequent NCCT for urolithiasis assessment, were enrolled. Each patient was instructed to ingest 1 L of water and 20 mg of oral furosemide 30 to 60 minutes before their scan (DRINK [DiuResIs Enhanced Non-contrast Computed Tomography for Kidney Stones] protocol). Patients' prior NCCT scan (non-DRINK) was used for comparison. Three-dimensional (3D) reconstruction of DRINK and non-DRINK NCCT studies was performed to determine the volume and surface area of the collecting system. In addition, three faculty endourologists measured the width of the upper and lower pole infundibula and renal pelvis in the axial, coronal, and sagittal views. Results: Among the 20 patients, 13 completed the DRINK protocol as specified. For these 13 patients, 3D reconstruction of the DRINK study collecting systems showed a 63% and a 36% increase in collecting system volume and surface area, respectively (p = 0.02 and p < 0.01, respectively). Also, measurements of the CT images demonstrated a significant (p < 0.05) increase in the collecting system widths in 67% of measurements. Conclusion: The DRINK protocol significantly increased the visible collecting system volume and surface area; in the majority of cases, the upper and lower pole infundibular widths and the width of the renal pelvis were also expanded.

Introduction: Currently, there exists no serum biomarker to predict patients likely to benefit from varicocelectomy. The purpose of this study was to assess the association between baseline follicle-stimulating hormone (FSH) and semen parameter changes after subinguinal microscopic varicocelectomy. Methods: We retrospectively reviewed all men who underwent microscopic subinguinal varicocelectomy between August 2015 and October 2018. Pre- and postoperative semen analyses were stratified per total motile sperm count (TMSC): TMSC <5, 5–9, and >9 million (based on TMSC required for in vitro fertilization, intrauterine insemination (IUI), and natural conception, respectively). Then, variables were analyzed to determine the correlation with postoperative TMSC values and upgrade in TMSC category. Results: Among the 66 men analyzed, 55 (83.3%) and 11 (16.7%) had a preoperative TMSC of <5 million and 5–9 million, respectively. A total of 33 (50%) patients upgraded in TMSC category, 26 of them achieving levels corresponding to natural conception and seven achieving those of IUI. Additionally, a significant correlation was observed between postoperative TMSC and preoperative TMSC (r=0.528; p<0.001), and preoperative FSH (r=-0.314; p=0.010). A lower preoperative FSH (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.68–0.98; p=0.028) and a higher preoperative TMSC (OR 1.37; 95% CI 1.06–1.76; p=0.015) were associated with upgrade in TMSC category. Conclusions: Lower preoperative FSH and higher TMSC are associated with improvement in TMSC category after varicocelectomy, although small sample size limited the study. FSH can be useful to identify men who are most likely to benefit from varicocele repair.

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