Retzius-sparing vs. posterior urethral suspension: similar early-phase post-robotic radical prostatectomy continence outcomes.

Stress urinary incontinence (SUI) is a risk of robotic-assisted radical prostatectomy (RP) which can be a frustrating problem for both surgeons and patients. We aim to compare short-term continence outcomes between patients undergoing Retzius Sparing RP (RS-RP) and those undergoing standard RP with the inclusion of a PUS suture technique and suprapubic tube (PUS-RP). A retrospective review of 105 consecutive patients who underwent RP was performed, comparing patients who underwent RS-RP and PUS-RP. Our main outcome was pad usage as a surrogate for SUI. Patients were evaluated 4 weeks following RP and again at approximately 3 months. Continence was defined as no pad usage or up to one safety pad per day. Risk factors associated with not being continent were identified using univariate and multivariate analyses. In our cohort, 52 patients underwent RS-RP and 53 patients underwent PUS-RP. The two groups had similar patient demographics. Although not statistically significant, there was a higher rate of a positive surgical margin in the RS-RP compared to PUS-RP (25% vs 15%, p = 0.204). At one month follow-up for PUS-RP and RS-RP, there was no significant difference in the frequency of continent men (69.2% vs. 76.9%, p = 0.302). At 3-month follow-up for the two groups of patients, again, there was no significant difference in the frequency of continence for PUS-RP and RS-RP (86.2% vs 88%, p = 0.824). Patients who underwent RS-RP had similar rates of continence to those patients undergoing PUS-RP in the short-term post-operative period.

Mapping Cellular Interactions from Spatially Resolved Transcriptomics Data.

Cell-cell communication (CCC) is essential to how life forms and functions. However, accurate, high-throughput mapping of how expression of all genes in one cell affects expression of all genes in another cell is made possible only recently, through the introduction of spatially resolved transcriptomics technologies (SRTs), especially those that achieve single cell resolution. However, significant challenges remain to analyze such highly complex data properly. Here, we introduce a Bayesian multi-instance learning framework, spacia, to detect CCCs from data generated by SRTs, by uniquely exploiting their spatial modality. We highlight spacia's power to overcome fundamental limitations of popular analytical tools for inference of CCCs, including losing single-cell resolution, limited to ligand-receptor relationships and prior interaction databases, high false positive rates, and most importantly the lack of consideration of the multiple-sender-to-one-receiver paradigm. We evaluated the fitness of spacia for all three commercialized single cell resolution ST technologies: MERSCOPE/Vizgen, CosMx/Nanostring, and Xenium/10X. Spacia unveiled how endothelial cells, fibroblasts and B cells in the tumor microenvironment contribute to Epithelial-Mesenchymal Transition and lineage plasticity in prostate cancer cells. We deployed spacia in a set of pan-cancer datasets and showed that B cells also participate in PDL1/PD1 signaling in tumors. We demonstrated that a CD8+ T cell/PDL1 effectiveness signature derived from spacia analyses is associated with patient survival and response to immune checkpoint inhibitor treatments in 3,354 patients. We revealed differential spatial interaction patterns between γδ T cells and liver hepatocytes in healthy and cancerous contexts. Overall, spacia represents a notable step in advancing quantitative theories of cellular communications.

Optimal Prostate Cancer Diagnostic Pathways for Men With Prostatomegaly in the MRI Era.

OBJECTIVE: To evaluate utilities of multiparametric MRI and targeted biopsy to detect clinically significant prostate cancer in men with prostatomegaly. MATERIALS AND METHODS: We conducted a retrospective review of multiparametric MRI obtained for elevated PSA between 2017 and 2020. We selected patients with prostates ≥80 g who had undergone biopsy. Clinically significant prostate cancer was defined as grade group ≥2. Predictive and logistic regression analyses quantified impacts of diagnostic components. RESULTS: A total of 338 patients met inclusion criteria: 89 (26.3%) had clinically significant prostate cancer. On MRI, positive predictive value for clinically significant prostate cancer was 26.5% for PIRADS 4% and 73.5% for PIRADS 5; negative predictive value for MRI without suspicious lesions was 98.8%. Applying PSA density to MRI yielded a negative predictive value of 78.9% for PIRADS 4 lesions at PSA density <0.05 and a positive predictive value of 90.5% for PIRADS 5 lesions at PSA density ≥0.15. Targeted (versus standard) biopsy reduced likelihood of missing clinically significant prostate cancer by >50% (12.2% vs 28.3%). MRI in-bore biopsies trended towards better accuracy versus MRI-transrectal ultrasound fusion biopsies (75% versus 52%). On logistic regression analyses, MRI improved predictive accuracy (area under the curve 0.91), and PIRADS score demonstrated the strongest association with clinically significant prostate cancer (odds ratio 6.42, P < .001). CONCLUSION: For large prostates, MRI is less predictive of clinically significant prostate cancer but effectively rules out malignancy. PSA density better informs biopsy decisions for PIRADS 4 and 5 lesions. There may be a pronounced role for targeted biopsy, specifically in-bore, in prostatomegaly.

Evaluating Surgical Outcomes of Robot Assisted Simple Prostatectomy in the Retreatment Setting.

OBJECTIVE: To report perioperative and postoperative outcomes in men who undergo salvage RASP (sRASP) following some other endoscopic outlet procedure for benign prostate enlargement (BPE) compared to those undergoing RASP for primary treatment (pRASP). METHODS: A prospectively maintained database consisting of all RASP surgeries (December 2014-October 2019) performed at our institution by 3 different urologists was used. Patients who had received an endoscopic procedure for BPE prior to their RASP (sRASP) were compared to those who had not had a prior outlet procedure (pRASP). RESULTS: In total, 310 men underwent RASP during the study period. Of those, 30 (9.7%) had undergone an endoscopic procedure prior to surgery. There were no significant differences in age, race, ASA, BMI, prostate volume, PSA or rates of preoperative retention (P> .05 for all). Men who were treatment-naive had significantly higher preoperative International Prostate Symptom Scores (IPSS) than men who had a prior procedure (18.3 ± 7.7 vs 13.6 ± 6.2, P = .008). However, there were no significant differences in functional or quality of life outcomes between the 2 groups (P > .05 for all). There were no significant differences in perioperative or post-operative outcomes between the 2 groups. Furthermore, rates of post-operative complications and incontinence were similar between groups (11% vs 10%, P = .9 and 2% vs 0%, P = 1 respectively). CONCLUSION: Performing a RASP after prior endoscopic procedure for BPE was found to be safe and effective. Success and complication rates were similar to patients with no prior procedures.

PSA density is associated with BPH cellular composition.

BACKGROUND: Current AUA guidelines recommend 5 alpha reductase inhibitor (5ARI) treatment for patients with obstructive benign prostatic hyperplasia (BPH) that display prostate volume ≥30 cc and total prostate specific antigen (PSA) ≥1.5 ng/ml. However, BPH is highly pleomorphic and response to 5ARIs is highly variable. An understanding of cellular composition based on a noninvasive PSA density test could lead to improved clinical decision making. METHODS: The histological composition of 307 BPH specimens was scored by a pathologist for stromo-glandular content and associated with total PSA, prostate volume, PSA density and other clinical variables using univariate and multivariate linear regression. RESULTS: The percentage of glandular composition in prostates of 5ARI-naïve men was positively and independently associated with PSA and PSA density. It was determined through statistical modeling that a PSA density ≤0.05 ng/ml2 associated with a glandular composition of ≤30% with 76% sensitivity. CONCLUSIONS: PSA density could provide a decisive variable for estimating BPH cellular content and may eventually improve selection of patients for 5ARI treatment. Further work is needed to demonstrate that patients with higher glandular content are more responsive to 5ARI treatment.

Safety and Feasibility of Telehealth Only Preoperative Evaluation Before Minimally Invasive Robotic Urologic Surgery.

Purpose: Telehealth utilization has increased dramatically over the past few years due to improvement in technology and the COVID-19 pandemic. To date, no study has examined whether a telehealth visit alone for preoperative evaluation is safe and sufficient before surgery. We examined the safety and feasibility of preoperative telehealth visits alone before minimally invasive urologic surgery. Materials and Methods: Single institution retrospective review of robotic prostate, kidney, and cystectomy procedures between April and December 2020. Cases were dichotomized into those who underwent preoperative evaluation by telehealth only vs traditional in-person visits. Outcomes included complications, blood loss, conversion to open surgery rates, and operative times. We assessed efficiency of care by measuring time from preoperative visit to surgery. Results: Three hundred fourteen patients were included in the study, with 14% of cases (n = 45) being performed after a preoperative telehealth visit. The majority of cases included in analysis were robotic surgeries of the prostate (56.1% of all cases, n = 176) and the kidney (35.0% of all cases, n = 110). Patients seen via telehealth alone preoperatively had no significant differences in any grade of complications, perioperative outcomes, blood loss, operative time, and length of stay. There was no difference in change in anticipated procedure between the groups, and there was no case of conversion to open surgery in the telehealth only group. Time from preoperative visit to surgery was significantly shorter for the telehealth group by 13 days. Conclusions: Our study is the first to analyze the safety of telehealth only preoperative visits before minimally invasive urologic surgery. We found no difference in perioperative outcomes including conversion to open surgery or change in planned procedure. Furthermore, telehealth preoperative visits appeared to facilitate shorter time to surgery. This study has important implications for expediting patient care and medicolegal considerations.

Identifying predictors of antispasmodic use following robotic assisted simple prostatectomy.

INTRODUCTION: Anticholinergic or ß-3 agonist use following robotic simple prostatectomy (RASP) is not well described. We describe rates of antispasmodic use following RASP and identify potential predictors of medication use. MATERIALS AND METHODS: A retrospective review of all RASP patients from 2/2016 - 1/2020 was conducted. Patients with no preoperative International Prostate Symptom Score (IPSS) were excluded. Demographics, clinical data, and postoperative medication use were collected by electronic medical record review. Multivariable logistic regression analysis using a priori variables was performed to identify independent factors associated with antispasmodic use. RESULTS: A total of 255 patients underwent RASP at a mean age of 70.0 years ± 7.3 and mean body mass index (BMI) of 28.6 kg/m2 ± 5.0. Median preoperative prostate volume was 132.3 cc ± 45.0. Rates of preoperative diabetes, obstructive sleep apnea (OSA), smoking and alcohol use were 19.6%, 6.3%, 3.1%, and 11.8% respectively; 8.6% of patients (n = 22) initiated antispasmodics at a median of 2.5 months (IQR 1.3-4.2) postoperatively. Median duration of antispasmodic use was 6.5 months (IQR 1.7-14.7). Mirabegron was most commonly prescribed (31.8%). On multivariable logistic regression analysis, OSA was independently associated with postoperative antispasmodic use (OR 8.13, 95% CI 2.02-32.67, p = 0.003); 68.8% of OSA patients were treated with continuous positive airway pressure (CPAP). Treatment was not significantly associated with postoperative antispasmodic use (p = 0.61). CONCLUSION: Patients with OSA are over 8 times more likely to require antispasmodic medications following RASP in the short term. These patients may benefit from more tailored preoperative counseling.

5-Alpha reductase inhibitors induce a prostate luminal to club cell transition in human benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a progressive expansion of peri-urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with 5-alpha reductase inhibitors (5ARIs) to shrink prostate volume by blocking the conversion of testosterone to dihydrotestosterone (DHT). A reduction in DHT levels can elicit atrophy and apoptosis of prostate secretory luminal cells, which results in a favorable clinical response characterized by improved lower urinary tract symptoms. However, the histologic response to 5ARI treatment is often heterogeneous across prostate acini and lower urinary tract symptoms can persist to require surgical intervention. We used two spatial profiling approaches to characterize gene expression changes across histologically normal and atrophied regions in prostates from 5ARI-treated men. Objective transcriptomic profiling using the Visium spatial gene expression platform showed that 5ARI-induced atrophy of prostate luminal cells correlated with reduced androgen receptor signaling and increased expression of urethral club cell genes including LTF, PIGR, OLFM4, SCGB1A1, and SCGB3A1. Prostate luminal cells within atrophied acini adapted to decreased DHT conditions by increasing NF-κB signaling and anti-apoptotic BCL2 expression, which may explain their survival. Using GeoMx digital spatial profiling with a probe set to assess ~18 000 RNA targets, we confirmed that atrophied acini expressing SCGB3A1 displayed higher levels of club cell markers compared with histologically normal acini with NKX3-1 expression. In addition, club-like cells within regions of 5ARI-induced atrophy closely resembled true club cells from the prostatic urethra. A comparison of histologically normal regions from 5ARI-treated men and histologically normal regions from untreated men revealed few transcriptional differences. Taken together, our results describe a heterogeneous response to 5ARI treatment where cells in atrophied acini undergo an adaptation from a prostate secretory luminal to a club cell-like state in response to 5ARI treatment. © 2021 The Pathological Society of Great Britain and Ireland.

Single-port robotic-assisted simple prostatectomy is associated with decreased post-operative narcotic use in a propensity score matched analysis.

Robotic-assisted simple prostatectomy (RASP) has proven to be an effective minimally invasive option for benign prostatic enlargement (BPE) in recent years. Single-site surgery is theorized to reduce post-operative pain beyond traditional minimally invasive approaches. We sought to assess whether use of a single-port robotic platform decreases post-operative opioid use in patients undergoing robotic-assisted simple prostatectomy (RASP). A retrospective review was performed of all patients undergoing RASP our institution from November 2017 to July 2019. Demographic, intraoperative, and post-operative data, including morphine equivalent (ME) use, were collected. Patients were stratified by robotic platform utilized. Propensity score matching using nearest neighbor method was performed using prostate volume, Charlson comorbidity index (CCI), and post-op ketorolac use in 4:1 fashion. Chi-squared analysis and Kruskal-Wallis analyses were utilized. Two-hundred-and-seven men underwent RASP. After matching, 80 patients (64 multi-port, 16 single-port) were included in the analysis. Groups were comparable for age, body mass index, CCI, prostate volume, prior opioid use, and use of scheduled ketorolac post op. The single-port approach was associated with a reduction in MEs once admitted to the floor (5 vs. 11 mg, p = 0.025) and an increase in the proportion of patients who did not require any narcotics post-operatively (44 vs. 19%, p = 0.036). In a propensity matched cohort of patients undergoing RASP at a single institution, use of the single-port robotic system conferred a significant decrease in post-operative narcotic use by approximately 50%.

MRI Features Associated with Histology of Benign Prostatic Hyperplasia Nodules: Generation of a Predictive Model.

Background: Histologic phenotypic variation of benign prostatic hyperplasia (BPH) has been hypothesized to underlie response to medical therapy. We evaluate preoperative MRI of robot-assisted simple prostatectomy (RASP) specimens and determine imaging features associated with histologic phenotype. Materials and Methods: All patients undergoing RASP from November 2015 to November 2019 with a multiparametric MRI ≤1 year before RASP were included. Patients without identifiable BPH nodules on histologic specimens were excluded. Histology slides were obtained from whole mount adenoma specimens and corresponding MRI were reviewed and graded independently by a blinded expert in BPH histopathology (D.W.S.) and an experienced radiologist specializing in prostate imaging (D.N.C.), respectively. Each nodule was assigned a phenotypic score on a 5-point Likert scale (1 = predominantly glandular; 5 = predominantly stromal) by each reviewer. Scores were compared using the sign test and univariate analysis. Signal intensity relative to background transition zone and nodule texture were noted on T2, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) imaging sequences. Univariate and multivariate stepwise linear regression analysis were conducted to identify MRI features associated with histology score. All analyses were performed using Statistical Analysis System (version 9.4). Results: A total of 99 prostate nodules in 29 patients were included. Median phenotypic scores by histology and MRI were comparable (2, interquartile range [IQR] 2-3 vs 2, IQR 2-4, respectively; p = 0.63). Histology scores were positively correlated with MRI scores (Pearson's correlation 0.84, p < 0.0001). Multivariate stepwise linear regression analysis showed that low apparent diffusion coefficient (ADC) signal intensity (p < 0.001) and DCE wash-in (p = 0.03) were positively associated with more stromal histology, whereas ADC standard deviation (p = 0.03), DCE wash-out (p = 0.001), and heterogeneous T2 texture (p = 0.003) were associated with more glandular histology. Conclusion: There is a strong correlation between MRI features and the histologic phenotype of BPH nodules. MRI may provide a noninvasive method to determine underlying BPH nodule histology.

Clinical and radiographic outcomes following salvage intervention for ureteropelvic junction obstruction

ABSTRACT Purpose: We aimed to assess failure rates of salvage interventions and changes in split kidney function (SKF) following failed primary repair of ureteropelvic junction obstruction (UPJO). Materials and Methods: A retrospective review of adult patients at an academic medical center who underwent salvage intervention following primary treatment for UPJO was performed. Symptomatic failure was defined as significant flank pain. Radiographic failure was defined as no improvement in drainage or a decrease in SKF by ≥7%. Overall failure, the primary outcome, was defined as symptomatic failure, radiographic failure, or both. Results: Between 2008-2017, 34 patients (median age 38 years, 50% men) met study criteria. UPJO management was primary pyeloplasty/secondary endopyelotomy for 21/34 (62%), primary pyeloplasty/secondary pyeloplasty for 6/34 (18%), and primary endopyelotomy/secondary pyeloplasty for 7/34 (21%). Median follow-up was 3.3 years following secondary intervention. Patients undergoing primary pyeloplasty/secondary endopyelotomy had significantly higher overall failure than those undergoing primary pyeloplasty/secondary pyeloplasty (16/21 [76%] vs. 1/6 [17%], p=0.015). Among patients undergoing secondary endopyelotomy, presence of a stricture on retrograde pyelogram, stricture length, and SKF were not associated with symptomatic, radiographic, or overall failure. Serial renography was performed for 28/34 (82%) patients and 2/28 (7%) had a significant decline in SKF. Conclusions: Following failed primary pyeloplasty, secondary endopyelotomy had a greater overall failure rate than secondary pyeloplasty. No radiographic features assessed were associated with secondary endopyelotomy failure. Secondary intervention overall failure rates were higher than reported in the literature. Unique to this study, serial renography demonstrated that significant functional loss was overall infrequent.

Clinical and radiographic outcomes following salvage intervention for ureteropelvic junction obstruction.

PURPOSE: We aimed to assess failure rates of salvage interventions and changes in split kidney function (SKF) following failed primary repair of ureteropelvic junction obstruction (UPJO). MATERIALS AND METHODS: A retrospective review of adult patients at an academic medical center who underwent salvage intervention following primary treatment for UPJO was performed. Symptomatic failure was defined as significant flank pain. Radiographic failure was defined as no improvement in drainage or a decrease in SKF by ≥7%. Overall failure, the primary outcome, was defined as symptomatic failure, radiographic failure, or both. RESULTS: Between 2008-2017, 34 patients (median age 38 years, 50% men) met study criteria. UPJO management was primary pyeloplasty/secondary endopyelotomy for 21/34 (62%), primary pyeloplasty/secondary pyeloplasty for 6/34 (18%), and primary endopyelotomy/secondary pyeloplasty for 7/34 (21%). Median follow-up was 3.3 years following secondary intervention. Patients undergoing primary pyeloplasty/secondary endopyelotomy had significantly higher overall failure than those undergoing primary pyeloplasty/secondary pyeloplasty (16/21 [76%] vs. 1/6 [17%], p=0.015). Among patients undergoing secondary endopyelotomy, presence of a stricture on retrograde pyelogram, stricture length, and SKF were not associated with symptomatic, radiographic, or overall failure. Serial renography was performed for 28/34 (82%) patients and 2/28 (7%) had a significant decline in SKF. CONCLUSIONS: Following failed primary pyeloplasty, secondary endopyelotomy had a greater overall failure rate than secondary pyeloplasty. No radiographic features assessed were associated with secondary endopyelotomy failure. Secondary intervention overall failure rates were higher than reported in the literature. Unique to this study, serial renography demonstrated that significant functional loss was overall infrequent.

Single-cell analysis of mouse and human prostate reveals novel fibroblasts with specialized distribution and microenvironment interactions.

Stromal-epithelial interactions are critical to the morphogenesis, differentiation, and homeostasis of the prostate, but the molecular identity and anatomy of discrete stromal cell types is poorly understood. Using single-cell RNA sequencing, we identified and validated the in situ localization of three smooth muscle subtypes (prostate smooth muscle, pericytes, and vascular smooth muscle) and two novel fibroblast subtypes in human prostate. Peri-epithelial fibroblasts (APOD+) wrap around epithelial structures, whereas interstitial fibroblasts (C7+) are interspersed in extracellular matrix. In contrast, the mouse displayed three fibroblast subtypes with distinct proximal-distal and lobe-specific distribution patterns. Statistical analysis of mouse and human fibroblasts showed transcriptional correlation between mouse prostate (C3+) and urethral (Lgr5+) fibroblasts and the human interstitial fibroblast subtype. Both urethral fibroblasts (Lgr5+) and ductal fibroblasts (Wnt2+) in the mouse contribute to a proximal Wnt/Tgfb signaling niche that is absent in human prostate. Instead, human peri-epithelial fibroblasts express secreted WNT inhibitors SFRPs and DKK1, which could serve as a buffer against stromal WNT ligands by creating a localized signaling niche around individual prostate glands. We also identified proximal-distal fibroblast density differences in human prostate that could amplify stromal signaling around proximal prostate ducts. In human benign prostatic hyperplasia, fibroblast subtypes upregulate critical immunoregulatory pathways and show distinct distributions in stromal and glandular phenotypes. A detailed taxonomy of leukocytes in benign prostatic hyperplasia reveals an influx of myeloid dendritic cells, T cells and B cells, resembling a mucosal inflammatory disorder. A receptor-ligand interaction analysis of all cell types revealed a central role for fibroblasts in growth factor, morphogen, and chemokine signaling to endothelia, epithelia, and leukocytes. These data are foundational to the development of new therapeutic targets in benign prostatic hyperplasia. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Use of Pre-operative Pharmacologic Venous Thromboembolism Prophylaxis for Robotic Partial Nephrectomy.

OBJECTIVE: To determine whether a single dose of preoperative enoxaparin for venous thromboembolism (VTE) prophylaxis impacts rates of thrombotic and bleeding events after robotic partial nephrectomy (RPNx). METHODS: A retrospective cohort study of RPNx patients from 2009 to 2020 was performed. Clinical characteristics and perioperative outcomes were compared between patients receiving a single dose of preoperative enoxaparin and those who did not. The primary outcome was 30-day hemorrhagic complications (transfusion ≥2 units, embolization, or reoperation for bleeding). Secondary outcomes were 30-day VTE events. Multivariable logistic regression was performed to control for significant differences between groups and to identify predictors of hemorrhagic complications among patients. RESULTS: Among 945 RPNx procedures, 794 (84%) received preoperative enoxaparin (PPx) and 151 (16%) did not (NPPx). The PPx cohort was older (P = .004), had lower BMI (P = .03), lower ASA class (P = .049), and fewer smokers (P = .03). Warm ischemia time was longer for PPx patients (P < .001). 4.9% and 2.6% of the PPx and NPPx cohorts, respectively, developed postoperative hemorrhagic complications (P = .29). After adjustment for potential covariates, pharmacologic prophylaxis was not associated with 30-day hemorrhagic complications (P = .39). On multivariable regression, longer warm ischemia time (OR 1.05, 95% CI 1.01-1.10, P = .02) and greater tumor size (OR 1.27, 95% CI 1.03-1.56, P = .02) were predictors of hemorrhagic complications. 30-day readmissions, VTE events, and mortality were similar between groups (all P> 0.05). CONCLUSION: Similar rates of thrombotic and bleeding events occurred between patients receiving pharmacologic prophylaxis and those who did not. Single dose of preoperative enoxaparin did not significantly alter perioperative outcomes after RPNx.

Experienced bedside-assistants improve operative outcomes for surgeons early in their learning curve for robot assisted laparoscopic radical prostatectomy.

Robot-assisted laparoscopic radical prostatectomy (RALP) relies heavily on the bedside assistant (BA). Currently, the relationship between BA experience and surgical outcomes in robotic surgery is not clear. We examined whether bedside assistant experience can significantly affect positive margin rate and peri-operative outcomes for RALP for surgeons within their learning curve. A retrospective cohort study of a single surgeon's peri-operative outcomes during RALP was examined and compared with and without an experienced bedside assistant. Patient demographic data and peri-operative data, margin rate, and length of stay (LOS), were collected and analyzed. Univariate and multivariable analyses were performed to determine if expert BA was a predictor of post-operative outcomes. In total, 170 consecutive cases over three years were analyzed. 111 (65%) were performed without an expert BA. The two groups were not significantly different with regards patient demographics (p > 0.05). On univariate analysis, having an expert BA was associated with a significantly lower LOS (31 h ± 21 vs. 42 h ± 26, p = 0.004), EBL (296 ml ± 180 vs. 441 ml ± 305, p < 0.0001) and positive margin rate (20% vs. 37%, p = 0.03). Other surgical outcomes were comparable between groups. On multivariable analysis, expert BA remained a predictor of, EBL (B stat = - 146, 95% CI - 240 to - 52, p = 0.003) and positive margin rate (OR 0.4, 95% CI 0.2-0.96, p = 0.04). Our results demonstrate that the use of an expert BA may result in improved patient outcomes early in the learning curve of RALP, most notably, positive margin rate and estimated blood loss.

Urethral luminal epithelia are castration-insensitive cells of the proximal prostate.

BACKGROUND: Castration-insensitive epithelial progenitors capable of regenerating the prostate have been proposed to be concentrated in the proximal region based on facultative assays. Functional characterization of prostate epithelial populations isolated with individual cell surface markers has failed to provide a consensus on the anatomical and transcriptional identity of proximal prostate progenitors. METHODS: Here, we use single-cell RNA sequencing to obtain a complete transcriptomic profile of all epithelial cells in the mouse prostate and urethra to objectively identify cellular subtypes. Pan-transcriptomic comparison to human prostate cell types identified a mouse equivalent of human urethral luminal cells, which highly expressed putative prostate progenitor markers. Validation of the urethral luminal cell cluster was performed using immunostaining and flow cytometry. RESULTS: Our data reveal that previously identified facultative progenitors marked by Trop2, Sca-1, KRT4, and PSCA are actually luminal epithelial cells of the urethra that extend into the proximal region of the prostate, and are resistant to castration-induced androgen deprivation. Mouse urethral luminal cells were identified to be the equivalent of previously identified human club and hillock cells that similarly extend into proximal prostate ducts. Benign prostatic hyperplasia (BPH) has long been considered an "embryonic reawakening," but the cellular origin of the hyperplastic growth concentrated in the periurethral region is unclear. We demonstrate an increase in urethral luminal cells within glandular nodules from BPH patients. Urethral luminal cells are further increased in patients treated with a 5-α reductase inhibitor. CONCLUSIONS: Our data demonstrate that cells of the proximal prostate that express putative progenitor markers, and are enriched by castration in the proximal prostate, are urethral luminal cells and that these cells may play an important role in the etiology of human BPH.

Initial experience with extraperitoneal robotic-assisted simple prostatectomy using the da Vinci SP surgical system.

Robotic-assisted simple prostatectomy (RASP) has emerged as a safe and effective treatment option for symptomatic patients with lower urinary tract symptoms related to significant benign prostatic enlargement (BPE) above 80 g. The recent release of the da Vinci SP robotic system (Intuitive, Sunnyvale, CA, USA) continues to advance the minimally invasive nature of robotic surgical technology. We now report our institution's initial experience performing RASP using the da Vinci SP robotic system. An IRB-approved, retrospective chart review was performed of all patients undergoing robotic-assisted simple prostatectomy using the da Vinci SP surgical system in the treatment of benign prostatic enlargement by a single surgeon from March to June 2019. Pre-operative, intraoperative, and post-operative data were collected for descriptive analysis. A total of 10 men, mean age of 69 ± 4 years, with mean prostate volume of 104 ± 11 g underwent surgery. The robotic cannula and a single assistant port were utilized in all cases. No cases required conversion to a multi-port robotic platform or open approach, nor required the placement of additional assistant ports. No intraoperative or immediate post-operative complications were noted. Mean estimated blood loss was 141 ± 98 mL and operative time was 172 ± 19 min. Mean catheter time was 1.9 ± 1.8 days. One patient reported transient de novo stress urinary incontinence. Single-port RASP is a safe and effective intervention for BPE. The smaller surgical footprint from the device appears to make earlier catheter removal possible. Comparative evaluation with multi-port RASP and other modalities is warranted.

Pathologic response and surgical outcomes in patients undergoing nephrectomy following receipt of immune checkpoint inhibitors for renal cell carcinoma.

OBJECTIVE: To evaluate the pathologic response, safety, and feasibility of nephrectomy following receipt of immune checkpoint inhibition (ICI) for renal cell carcinoma (RCC). METHODS: Patients who underwent nephrectomy for RCC after exposure to nivolumab monotherapy or combination ipilimumab/nivolumab were reviewed. Primary surgical outcomes included operative time (OT), estimated blood loss (EBL), length of stay (LOS), readmission rates, and complication rates. Pathologic response in the primary and metastatic sites constituted secondary outcomes. RESULTS: Eleven nephrectomies (10 radical, 1 partial) were performed in 10 patients after ICI with median postoperative follow-up 180 days. Six patients received 1 to 4 cycles of ipilimumab/nivolumab, while 5 received 2 to 12 infusions of nivolumab preoperatively. Five surgeries were performed laparoscopically, and 4 patients underwent concomitant thrombectomy. One patient exhibited complete response (pT0) to ICI, and 3/4 patients who underwent metastasectomy for hepatic, pulmonary, or adrenal lesions exhibited no detectable malignancy in any of the metastases resected. No patients experienced any major intraoperative complications, and all surgical margins were negative. Median OT, EBL, and LOS were 180 minutes, 100 ml, and 4 days, respectively. Four patients experienced a complication, including 3 that were addressed with interventional radiology procedures. One patient died of progressive disease >3 months after surgery, and 1 patient succumbed to pulmonary embolism complicated by sepsis. No complications or readmissions were noted in 6 patients. CONCLUSION: Nephrectomy following ICI for RCC is safe and technically feasible with favorable surgical outcomes and pathologic response. Timing of the nephrectomy relative to checkpoint dosing did not seem to impact outcome. Biopsies of lesions responding radiographically to ICI may warrant attention prior to surgical excision.

Design and Validation of a Low-Cost, High-Fidelity Model for Urethrovesical Anastomosis in Radical Prostatectomy.

OBJECTIVE: We sought to develop and validate a low-cost, high-fidelity robotic surgical model for the urethrovesical anastomosis component of the robot-assisted laparoscopic radical prostatectomy. MATERIALS AND METHODS: A novel simulation model was constructed using a 3D-printed model of the male bony pelvis from CT scan data and silicone molds to recreate the soft tissue aspects. Using a da Vinci Si surgical robot, urology faculty and trainees performed simulated urethrovesical anastomosis. Each participant was given 12 minutes to complete the simulation. A survey established face validity, content validity, and acceptability. Simulation runs were evaluated by three blinded reviewers. The anastomosis was graded by two reviewers for suture placement accuracy and anastomosis quality. These factors were compared with robotic experience to establish construct validity. RESULTS: Twenty participants took part in the initial validation of this model. Groups were defined as experts (surgical faculty), intermediate (fellows and chief residents), and novices (junior residents). Likert scores (1-5 scale, top score 5) examining face validity, content validity, and acceptability were 3.49 ± 0.43, 4.15 ± 0.23, and 4.02 ± 0.19, respectively. Construct validity was excellent based on the model's ability to stratify groups. All evaluated metrics were statistically different between the three levels of training. Total material cost was $2.50 per model. CONCLUSIONS: We developed a novel low-cost robotic simulation of the urethrovesical anastomosis for robot-assisted radical prostatectomy. The model discerns robotic skill level across all levels of training and was found favorable by participants showing excellent face, content, and construct validities.

A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra.

A comprehensive cellular anatomy of normal human prostate is essential for solving the cellular origins of benign prostatic hyperplasia and prostate cancer. The tools used to analyze the contribution of individual cell types are not robust. We provide a cellular atlas of the young adult human prostate and prostatic urethra using an iterative process of single-cell RNA sequencing (scRNA-seq) and flow cytometry on ∼98,000 cells taken from different anatomical regions. Immunohistochemistry with newly derived cell type-specific markers revealed the distribution of each epithelial and stromal cell type on whole mounts, revising our understanding of zonal anatomy. Based on discovered cell surface markers, flow cytometry antibody panels were designed to improve the purification of each cell type, with each gate confirmed by scRNA-seq. The molecular classification, anatomical distribution, and purification tools for each cell type in the human prostate create a powerful resource for experimental design in human prostate disease.