Characterization of intracalyceal pressure during ureteroscopy.

PURPOSE: To provide the first report of measuring intracalyceal pressures during ureteroscopy (URS). METHODS: A prospective single-center clinical study using a cardiac pressure guidewire to measure intracalyceal pressure during flexible URS was performed. Eight patients (45 calyces) undergoing URS for nephrolithiasis were included. A Verrata® pressure guide wire was passed through the working channel of a dual lumen flexible ureteroscope and into the calyces while irrigation was maintained at 150 mmHg. Pressure was measured in the renal pelvis, upper pole, interpolar, and lower pole calyces both with and without a ureteral access sheath (UAS). The pressure in each location with and without a UAS was compared. The correlation between calyceal pressure and infundibular dimensions (width, length) was determined. RESULTS: Intracalyceal pressure was significantly lower in each region when a UAS was used. Compared to patients with a 12/14Fr UAS, those with a 14/16Fr UAS had significantly lower pressure in the interpolar (25.3 ± 13.1 vs. 44.0 ± 27.5 mmHg, p = 0.03) and lower pole (16.2 ± 3.5 vs. 49.2 ± 40.3 mmHg, p = 0.004) calyces. Interpolar calyceal pressure in the presence of a UAS was significantly higher than the renal pelvis pressure (RPP) (30.8 ± 19.6 vs. 17.9 ± 11.0 mmHg, p = 0.004). CONCLUSIONS: During flexible URS, RPP strongly correlates with, but does not uniformly represent, the intracalyceal pressure. With a 14/16Fr UAS and an inflow pressure of 150 mmHg, RPP and intracalyceal pressure never exceed the threshold for renal backflow.

Preoperative follicle-stimulating hormone: A factor associated with semen parameter improvement after microscopic subinguinal varicocelectomy.

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.

Evaluation of a Diuresis Enhanced Non-Contrast Computed Tomography for Kidney Stones Protocol to Maximize Collecting System Distention.

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.

Impact of Surgical Technique on Surgical Margin Status Following Partial Cystectomy.

INTRODUCTION: We assessed the impact of open or minimally-invasive partial cystectomy on surgical margin status in a nationwide hospital-based cohort. MATERIALS AND METHODS: Patients who underwent partial cystectomy from 2010 to 2014 were identified in the National Cancer Data Base. The primary outcome was surgical margin status. A multivariable logistic regression model was fitted to identify patient, hospital, and surgical factors associated with positive surgical margins (PSMs). RESULTS: Partial cystectomy was performed in 1,118 patients via open (n = 715, 64%), laparoscopic (n = 209, 19%), and robotic (n = 194, 17%) approaches. Overall, 220 (19.7%) patients had PSMs. The PSM rate by surgical approach was 19.6% for open, 18.2% for laparoscopic, and 21.6% for robotic (P = 0.678). Compared to open partial cystectomy, the laparoscopic (aOR 1.06, 95%CI 0.70-1.60, P = 0.782), and robotic (aOR 1.28, 95%CI 0.85-1.91, P = 0.235) approaches were not significantly different in terms of PSM rate. There were higher odds of PSMs in non-Hispanic blacks (aOR 1.93, 95%CI 1.09-3.39, P = 0.023) compared to non-Hispanic whites, and in patients with muscle invasive bladder cancer (aOR 3.28, 95%CI 2.00-5.37, P < 0.001) or tumor size ≥ 3 cm (aOR 1.67, 95%CI 1.21-2.30, P = 0.002). Tumors in a dome/urachal location had lower odds of a PSM compared to tumors in a nondome/urachal location (aOR 0.67, 95%CI 0.47-0.94, P = 0.022). CONCLUSIONS: Our results suggest that partial cystectomy using a laparoscopic or robotic-assisted approach is not associated with an increased risk of PSMs compared to open partial cystectomy.

Expression and prognostic utility of PD-L1 in patients with squamous cell carcinoma of the bladder.

OBJECTIVES: Checkpoint inhibitors are approved for the treatment of urothelial bladder cancer. However, there have been no reports on the prognostic value of programmed-death receptor ligand 1 (PD-L1) expression in squamous cell carcinoma (SCC) of the bladder. We assessed the relationship between PD-L1 expression, clinicopathological features, and oncologic outcomes in bladder SCC. METHODS AND MATERIALS: Immunohistochemistry of PD-L1 was performed on 151 radical cystectomy specimens with pure SCC treated in Mansoura, Egypt from 1997 to 2004. RESULTS: Median patient age was 52 years (range: 36-74 years) and median length of follow up was 63 months (range: 1-100 months). Schistosomiasis was present in 81% of the specimens and 93% had muscle-invasive disease on pathologic staging. PD-L1 expression was negative in 50 (33%) of the specimens. Negative PD-L1 expression was associated with higher pathologic tumor stage (P = 0.04), higher grade lesions (P = 0.01), and the presence of lymphovascular invasion (P < 0.01). Kaplan-Meier analyses showed that negative PD-L1 expression is associated with worse recurrence-free (P = 0.01) and worse cancer-specific survival (P = 0.01). Multivariable Cox regression analyses showed negative PD-L1 expression was an independent predictor of disease recurrence (hazards ratio 2.05, 95% confidence interval 1.06-3.96, P = 0.03) and cancer-specific mortality (hazards ratio 2.89, 95% confidence interval 1.22-6.82, P = 0.02). CONCLUSIONS: Negative PD-L1 expression is associated with higher pathologic tumor stage, higher grade lesions, presence of lymphovascular invasion, and worse oncologic outcomes after radical cystectomy for SCC. These findings support the need for the inclusion of patients with bladder SCC into immunotherapy clinical trials.

Pilot Assessment of Immersive Virtual Reality Renal Models as an Educational and Preoperative Planning Tool for Percutaneous Nephrolithotomy.

BACKGROUND: Percutaneous nephrolithotomy (PCNL) requires the urologist to have detailed knowledge of the stone and its relationship with the renal anatomy. Immersive virtual reality (iVR) provides patient-specific three-dimensional models that might be beneficial in this regard. Our objective is to present the initial experience with iVR in surgeon planning and patient preoperative education for PCNL. MATERIALS AND METHODS: From 2017 to 2018 four surgeons, each of whom had varying expertise in PCNL, used iVR models to acquaint themselves with the renal anatomy before PCNL among 25 patients. iVR renderings were also viewed by patients using the same head-mounted Oculus rift display. Surgeons rated their understanding of the anatomy with CT alone and then after CT+iVR; patients also recorded their experience with iVR. To assess the impact on outcomes, the 25 iVR study patients were compared with 25 retrospective matched-paired non-iVR patients. Student's t-test was used to analyze collected data. RESULTS: iVR improved surgeons' understanding of the optimal calix of entry and the stone's location, size, and orientation (p < 0.01). iVR altered the surgical approach in 10 (40%) cases. Patients strongly agreed that iVR improved their understanding of their stone disease and reduced their preoperative anxiety. In the retrospective matched-paired analysis, the iVR group had a statistically significant decrease in fluoroscopy time and blood loss as well as a trend toward fewer nephrostomy tracts and a higher stone-free rate. CONCLUSIONS: iVR improved urologists' understanding of the renal anatomy and altered the operative approach in 40% of cases. In addition, iVR improved patient comprehension of their surgery. Clinically, iVR had benefits with regard to decreased fluoroscopy time and less blood loss along with a trend toward fewer access tracts and higher stone-free rates.

Overcoming Barriers of Age to Enhance Efficacy of Cancer Immunotherapy: The Clout of the Extracellular Matrix.

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.

Fluid Dynamic Analysis of Hand-Pump Infuser and UROMAT Endoscopic Automatic System for Irrigation Through a Flexible Ureteroscope.

INTRODUCTION: To evaluate the flow characteristics produced by a manual and automated-pump irrigation system connected to a flexible ureteroscope. MATERIALS AND METHODS: An in vitro analysis of a manual hand-pump infuser (HP) and the UROMAT Endoscopic Automatic System for Irrigation® (E.A.S.I.) pump was performed. Standard irrigation tubing was used to connect a three-way valve to a flexible ureteroscope, the irrigation system, and a digital manometer. Flow rate and irrigation pressure measurements were recorded over a 15-minute period using pressure settings of 150 and 200 mm Hg for both irrigation pump systems. Once the HP was inflated to the initial pressure, it was not reinflated over the course of the trial. Data were collected with the working channel unoccupied and with placement of a 200 µm (0.6F) holmium laser fiber, 1.7F nitinol stone retrieval basket, or 2.67F guidewire. RESULTS: The difference in pressure measured at the site of inflow of irrigation to the ureteroscope was significantly greater using the HP compared to the E.A.S.I. pump at pressure settings of 150 mm Hg with and without the use of ureteroscopic instrumentation (p < 0.001), and at 200 mm Hg with instrumentation in the working channel (p < 0.01). There was no significant difference in the flow rate of irrigation through the open-channel ureteroscope over the course of 5 minutes between the two pump systems. CONCLUSION: 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.