Predictors of disease recurrence in high-risk non-metastatic renal cell carcinoma patients post-surgical resection A single-center, retrospective study.

INTRODUCTION: Approximately 20-40% of kidney cancer patients treated for localized disease experience post-surgical recurrence. Several prognostic models exist to help clinicians determine the risk of distant recurrence, but these models vary in criteria and endpoints. We aimed to examine the recurrence rate and clinicopathologic factors as predictors of recurrence in high-risk renal cell carcinoma (RCC) patients. METHODS: We conducted a single-center, retrospective chart review of pT3 RCC patients who underwent a nephrectomy between January 2000 and December 2015. Patients registered in clinical trials for adjuvant therapy and those with fewer than three years of followup were excluded. Kaplan-Meier survival analysis and univariate and multivariate Cox regression were performed to identify the rate and predictors of disease recurrence. RESULTS: Eighty-eight pT3 RCC patients were included, and 39 patients had recurrence with a median of 23.5 months (range 1.6-127.5). Nine patients had disease recurrence beyond 58 months. Kaplan-Meier log-rank tests identified patients with negative surgical margins and low Fuhrman nuclear grades had greater recurrence-free survival. Univariate Cox regression revealed positive surgical margins, high Fuhrman nuclear grade, and large tumor sizes were significant predictors. In the multivariate Cox regression model, high Fuhrman nuclear grade and positive surgical margins were significant predictors of recurrence. CONCLUSIONS: Disease recurrence occurred in 44% of pT3-staged patients. High Fuhrman nuclear grade and positive surgical margins were associated with time to recurrence. Physicians should use prognostic models to facilitate conversations about disease recurrence and continue to monitor high-risk patients beyond the recommended five-year followup period. We recommend monitoring pT3 resected patients for up to 10 years post-surgery.

A systematic review of postoperative outcomes of kidney stone surgery and meta-analysis of outcomes of percutaneous nephrolithotomy in individuals with spinal cord injury.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: To evaluate outcomes of surgical treatment for nephrolithiasis in individuals with spinal cord injury (SCI). METHODS: We systematically reviewed the Ovid MEDLINE, Embase, CENTRAL, and Web of Science databases for studies examining outcomes of kidney stone procedures in individuals with SCI. Our primary outcomes were stone-free rate (SFR) and complications as categorized by Clavien-Dindo classification. A meta-analysis of comparative studies was performed to assess differences in SFR and complication rate between individuals with and without SCI following PCNL. RESULTS: A total of 27 retrospective and observational articles were included. Interventions for kidney stones included PCNL, shockwave lithotripsy (SWL), and ureteroscopy. Pooled SFR in individuals with SCI was 54%, for SWL, 74% for PCNL, and 36% for ureteroscopy. Meta-analyses found that there was higher rate of grades I (OR 9.54; 95% CI, 3.06 to 29.79), II (OR 3.38; 95% CI, 1.85 to 6.18), and III-V (OR 2.38; 95% CI, 1.35 to 4.19) complications in individuals with SCI compared to non-SCI individuals following PCNL. The rate of infectious complications was also higher in individuals with SCI (OR 6.15; 95% CI, 1.86 to 20.39). However, there was no difference in SFR (OR 0.64; 95% CI, 0.15 to 2.64) between groups. CONCLUSIONS: Individuals with SCI are at higher risk of minor, major, and infectious complications following PCNL compared to non-SCI individuals. There was no significant difference between groups in SFR following PCNL, suggesting that PCNL is an effective surgery for kidney stones in individuals with SCI.

The impact of tranexamic acid on perioperative outcomes in urological surgeries A systematic review and meta-analysis.

INTRODUCTION: Tranexamic acid (TXA) is an antifibrinolytic agent widely used in surgery to decrease bleeding and reduce the need for blood product transfusion. The role of TXA in urology is not well-summarized. We conducted a systematic review of studies reporting outcomes of TXA use in urological surgery. METHODS: A comprehensive search was conducted from the following databases: PubMed, Embase, Cochrane Library, and Web of Science. Two reviewers performed title and abstract screening, full-text review, and data collection. Primary outcomes included estimated blood loss (EBL), decrease in hemoglobin, decrease in hematocrit, and blood transfusion rates. Secondary outcomes included TXA administration characteristics, length of stay, operative time, and postoperative thromboembolic events. RESULTS: A total of 26 studies consisting of 3261 patients were included in the final analysis. These included 11 studies on percutaneous nephrolithotomy, 10 on transurethral resection of prostate, three on prostatectomy, and one on cystectomy. EBL, transfusion rate, hemoglobin drop, operative time, and length of stay were significantly improved with TXA administration. In addition, the use of TXA was not associated with an increased risk of venous thromboembolism (VTE ). The route, dosage, and timing of TXA administration varied considerably between included studies. CONCLUSIONS: TXA use may improve blood loss, transfusion rates, and perioperative parameters in urological procedures. In addition, there is no increased risk of VTE associated with TXA use in urological surgery; however, there is still a need to determine the most effective TXA administration route and dose. This review provides evidence-based data for decision-making in urological surgery.

Visceral adipose tissue loss and 24-hour urinary profile changes post-bariatric surgery.

INTRODUCTION: The relationship between obesity and nephrolithiasis is a well-documented phenomenon. Visceral adipose tissue (VAT) has been proposed to be an accurate indicator of metabolic derangement. We present a study that investigates the relationship between computed tomography (CT) delineated VAT measurements and 24-hour urine (24 HU) profiles in the context of profound weight loss. MATERIALS AND METHODS: A total of 86 patients with a history of nephrolithiasis who underwent bariatric surgery were reviewed. All patients had pre and postoperative 24 HU analysis and CT kidney and urinary bladder performed. CT-based fat delineation program, AnalyzePro, was used to measure VAT at levels L4-L5 (VAT 1) and L1-L2 (VAT2). Univariate and multivariate analysis was utilized to examine associations between VAT measurements and comorbidities, 24 HU values, and postoperative urinary changes. RESULTS: Preoperative VAT2 was correlated with preoperative serum creatinine and all 24 HU (R2: 0.23-0.43, p = < 0.001-0.030). Only VAT1 and VAT2 had relationships with hypertension, dyslipidemia, and metabolic syndrome (R2: 0.25-0.30, p = 0.004-0.015). The percent change in VAT1 and VAT2 was a significant predictor of change in 24 HU uric acid (respectively, R2: 0.14, beta: -0.03, p = 0.002 and R2: 0.13, beta: -0.03, p = 0.003). CONCLUSIONS: This study found VAT to have strong correlations with urinary outcomes in obese patients, especially in the excretion of uric acid. These findings support a potential use of CT delineated measurements of fat as a surrogate measure for urinary metabolites, and may be used as a marker for patient counseling in stone prevention.

Extraperitoneal versus transperitoneal approach for robot-assisted radical prostatectomy: a contemporary systematic review and meta-analysis.

We aim to evaluate the differences in peri-operative characteristics, surgical complications, and oncological and functional control between the extraperitoneal RARP (EP-RARP) and transperitoneal RARP (TP-RARP). A comprehensive database search was performed up to March 2021 for eligible studies comparing outcomes between EP-RARP versus TP-RARP. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with PROSPERO. A leave-one-out sensitivity analysis was performed to control for heterogeneity and risk of bias. A total of 16 studies were included with 3897 patients, including 2201 (56.5%) EP-RARPs and 1696 (43.5%) TP-RARPs. When compared to TP-RARP, EP-RARP offers faster operative time (MD - 14.4 min; 95% CI - 26.3, - 2.3), decreased length of post-operative stay (MD - 0.9 days, 95% CI - 1.3, - 0.4), and decreased rates of post-operative ileus (RR 0.2, 95% CI 0.1, 0.7) and inguinal hernia formation (RR 0.2, 95% CI 0.1, 0.5). There were no significant differences in total complications, estimated blood loss, positive surgical margins, or continence at 6 months. In this review, EP-RARP delivered similar oncological and functional outcomes, while also offering faster operative time, decreased length of post-operative stay, and decreased rates of post-operative ileus and inguinal hernia formation when compared to TP-RARP. These findings provide evidence-based data for surgical approach optimization and prompts future research to examine whether these findings hold true with recent advances in single-port RARP and outpatient RARP.

Management of adult tuberous sclerosis complex-related angiomyolipoma: A single-center experience.

INTRODUCTION: Tuberous sclerosis complex (TSC) is a rare, multi-system, genetic disease. A significant cause of TSC-related morbidity is potential bleeding from renal angiomyolipoma (AML). To pre-emptively decrease AML bleeding, mTOR inhibitors can be used; however, thresholds for initiating and maintaining everolimus therapy remain uncertain. Recent literature suggests not triggering active treatment of AMLs based on size thresholds alone. We evaluated the appropriateness of initiating everolimus therapy in asymptomatic patients after considering AML size, rate of growth, and other factors. METHODS: Diagnostic criteria developed by the 2012 International TSC Consensus Group and presence of AML were used as inclusion criteria. Medical and imaging reports of 11/20 TSC patients from a single center were reviewed. RESULTS: Mean age was 40.55 (±16.27) and 11 patients were female. Eight asymptomatic patients at high risk for complications underwent everolimus therapy, of which seven (88%) demonstrated decreased AML size, but multiple side effects were reported. Four high-risk asymptomatic patients did not undergo therapy due to side effect concerns, while four low-risk asymptomatic patients had stable AMLs under active surveillance. Four patients had reduced AMLs through local therapy. CONCLUSIONS: Everolimus treatment was effective for managing AML size in most high-risk, asymptomatic patients with tolerable side effects. AML size can remain relatively stable for asymptomatic, low-risk patients despite not receiving intervention(s). Patients with TSC-related AML can be safely managed with mTOR inhibitors like everolimus with shared decision-making, including factors such as bleeding risk, AML growth rate, and number and absolute size of AMLs.

Trigger videos: a novel application of a tool for surgical faculty development.

BACKGROUND: Trigger videos have occasionally been used in medical education; however, their application to surgical faculty development is novel. We assessed participants' attitudes towards workshops on intraoperative teaching (IOT) that were anchored by trigger videos, and studied whether they could generate discussion-for-learning among surgeons in this workshop setting. METHODS: Surgeons from multiple specialties attended one of six faculty development workshops where IOT trigger videos were shown and discussed during break-out sessions. Participants completed questionnaires to (1) evaluate videos via survey and feedback, and (2) identify adoptable and discardable IOT techniques. Teaching techniques were collated to identify planned IOT changes and survey data and feedback were analyzed. RESULTS: A total of 135 surgeons identified 292 adoptable and 202 discardable IOT techniques based on trigger videos and discussions, and 94% of participants reported that the trigger videos were useful and encouraged them to discuss and consider new IOT techniques in their own practice. CONCLUSIONS: Participants reported that the trigger videos were useful and motivating. Surgeons critically reflected on IOT during the sessions, identifying numerous adoptable and discardable techniques relevant to their own teaching styles. Trigger videos can be a valuable tool for surgical faculty development and can be tailored to other medical specialties.

Use of cannabis in urological cancer patients: A review to evaluate risk for cancer development, therapeutic use, and symptom management.

INTRODUCTION: Recent recreational legalization of cannabis has resulted in an increased interest in the therapeutic effects of cannabis use in cancer patients, with reports of its use in symptom management and as a risk factor for cancer development. The objective of this review was to evaluate the literature on the association of cannabis use with the risk of cancer development, symptom management, and therapeutic management in the urological cancer (UC) patient population. METHODS: A systematic search of databases and trial registries for papers published from January 1947 to March 2020 on cannabis, symptom and therapeutic management, and cancer development in UC patients was conducted. After screening of full-text articles, data were extracted for evaluation. Studies were eligible if they were in the clinical setting, included ≥5 UC patients, reported use of any cannabis variant, and were written in English. RESULTS: The search retrieved 2456 abstracts, of which 48 full-text articles were reviewed and 21 included in the review. Low-level evidence suggested a correlation between cannabis use and risk for development of testicular cancer. Some support existed for using cannabis for cancer pain and chemotherapy-induced nausea. There was inadequate evidence to substantiate cannabis use as a therapeutic agent for management of UCs. A lack of high-level evidence and robust methodology of the studies limited evaluation of the findings. CONCLUSIONS: Given the paucity of data on cannabis use for therapeutic purposes in UC, large, prospective trials with adequate followup times to observe the effect of cannabis use on UCs are warranted to improve the evidence base.

Bariatric Surgery in Patients with a History of Nephrolithiasis: 24-h Urine Profiles and Radiographic Changes After Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy.

BACKGROUND: To evaluate the differences in 24-h urine profiles, radiographic imaging, and stone events post-Roux-en-Y gastric bypass versus sleeve gastrectomy in patients with a history of nephrolithiasis. METHODS: A retrospective review was conducted on 102 patients with a history of nephrolithiasis who then underwent bariatric surgery at our tertiary academic center. Computed tomography imaging and 24-h urine profile values were performed pre-operatively and at 1-year follow-up. RESULTS: A total of 60 patients underwent Roux-en-Y gastric bypass and 42 had sleeve gastrectomy. The Roux-en-Y gastric bypass group had significant increases in oxalate and decreases in citrate (p = 0.009 and 0.003, respectively), while the sleeve gastrectomy group had decreases in oxalate and stable citrate (p = 0.013 and 0.906, respectively). Roux-en-Y gastric bypass was the only significant predictor of post-operative hyperoxaluria (OR 7.1 [95% CI 2.3-21.3], p = 0.001). Radiographically, 38.3% of the Roux-en-Y gastric bypass group and 26.2% of the sleeve gastrectomy group had an increase in stone burden, and post-operative stone procedure rate was 10.0% and 7.1%, respectively. CONCLUSIONS: At 1-year post-bariatric surgery, patients who underwent Roux-en-Y gastric bypass had exacerbated lithogenic urinary profiles, while those in sleeve gastrectomy patients improved. Although not statistically significant, stone burden increase and stone procedure rate were higher post-Roux-en-Y gastric bypass and will likely worsen at a longer follow-up due to the group's lithogenic 24-h urine profiles. These findings support pre-bariatric counseling and urinary monitoring in patients with a history of kidney stones who undergo RYGB, with a multi-disciplinary approach between urologists and general surgeons.

Comparison of a magnetic retrieval device vs. flexible cystoscopy for removal of ureteral stents in renal transplant patients: A randomized controlled trial.

INTRODUCTION: Placement of a ureteral stent at the time of renal transplantation can reduce complications when compared to non-stented anastomoses. Removal by flexible cystoscopy can be associated with discomfort, risk for infection, and high costs. New magnetic stents offer a means of bypassing cystoscopy by use of a magnetic retrieval device. Our objective was to compare clinical and cost-related outcomes of conventional and magnetic stents in patients undergoing deceased donor renal transplantation. METHODS: Patients were randomized to receive either a conventional or a Black-Star® magnetic stent. Clinical, procedural, and cost outcomes were assessed, and the Ureteral Stent Symptom Questionnaire (USSQ) was administered with the stent in situ and after stent removal. All variables were compared between groups. RESULTS: Forty-one patients were randomized to conventional (n=19) or Black-Star (n=22) stent. The total time for stent removal under cystoscopy was significantly longer compared to Black-Star removal (6.67±2.47 and 4.80±2.21 minutes, respectively, p=0.019). No differences were found in the USSQ domains between groups. Rates of urinary tract infections and surgical complications between groups were similar. Stent removal was well-tolerated in both groups. Black-Star stent use resulted in a cost savings of $304.02 Canadian dollars (CAD) per case. CONCLUSIONS: USSQ scores suggest that stent removal with the Black-Star magnetic stent is as equally well-tolerated as flexible cystoscopy by renal transplant patients. Black-Star stent removal was significantly faster than conventional stents. No differences in discomfort, infection rate, or complication rate were found. Use of the Black-Star stent resulted in an estimated annual savings of $27 360 CAD at our centre.

Evolving Role of Urologists in the Management of Advanced Renal Cell Carcinoma.

Advanced renal cell carcinoma is not uncommon, but necessitates a multidisciplinary approach for optimal treatment. Targeted therapy has increased the likelihood of urologists managing patients in all disease stages. Neoadjuvant therapy is currently experimental. Systemic therapy for metastatic disease demonstrates survival benefits. The role of cytoreductive nephrectomy and adjuvant therapy is dependent on patient selection. Management of advanced renal cell carcinoma involves continued optimization of available agents and biomarker development. This article reviews the role of the urologist in medical and surgical therapies, including prognostication, management of locally advanced and metastatic disease, and provides the most recent clinical trial data.

Economic evaluation of robot-assisted radical prostatectomy compared to open radical prostatectomy for prostate cancer treatment in Ontario, Canada.

INTRODUCTION: Recent health technology assessments (HTAs) of robot-assisted radical prostatectomy (RARP) in Ontario and Alberta, Canada, resulted in opposite recommendations, calling into question whether benefits of RARP offset the upfront investment. Therefore, the study objectives were to conduct a cost-utility analysis from a Canadian public payer perspective to determine the cost-effectiveness of RARP. METHODS: Using a 10-year time horizon, a five-state Markov model was developed to compare RARP to open radical prostatectomy (ORP). Clinical parameters were derived from Canadian observational studies and a recently published systematic review. Costs, resource utilization, and utility values from recent Canadian sources were used to populate the model. Results were presented in terms of increment costs per quality-adjusted life years (QALYs) gained. A probabilistic analysis was conducted, and uncertainty was represented using cost-effectiveness acceptability curves (CEACs). One-way sensitivity analyses were also conducted. Future costs and QALYs were discounted at 1.5%. RESULTS: Total cost of RARP and ORP were $47 033 and $45 332, respectively. Total estimated QALYs were 7.2047 and 7.1385 for RARP and ORP, respectively. The estimated incremental cost-utility ratio (ICUR) was $25 704 in the base-case analysis. At a willingness-to-pay threshold of $50 000 and $100 000 per QALY gained, the probability of RARP being cost-effective was 0.65 and 0.85, respectively. The model was most sensitive to the time horizon. CONCLUSIONS: The results of this analysis suggest that RARP is likely to be cost-effective in this Canadian patient population. The results are consistent with Alberta's HTA recommendation and other economic evaluations, but challenges Ontario's reimbursement decision.

High-Intensity Focused Ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: predictors of disease response

ABSTRACT Background Some men with localized radio-recurrent prostate cancer may benefit from salvage high-intensity focused ultrasound (HIFU). Herein, we describe oncologic outcomes and predictors of disease response after salvage whole gland HIFU from our prospective cohort. Materials and Methods Patients with localized radio-recurrent prostate cancer were prospectively enrolled from January 2005 to December 2014. Participants had to meet both biochemical and histological definitions of recurrence. Exclusion criteria included the receipt of prior salvage therapy, presence of metastatic disease, and administration of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the AblathermTM device (EDAP, France). The primary endpoint was recurrence-free survival (RFS), defined as a composite endpoint of PSA progression (Phoenix criteria), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (TRUS biopsy grade, number of study entry TRUS biopsy cores positive, palpable disease at study enrollment, pre-HIFU PSA, an undetectable post-HIFU PSA nadir, and receipt of prior hormone therapy). Survival analysis was performed on participants with a minimum of 1-year follow-up. Results Twenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04ng/ml. Median 2-year and 5-year RFS was 66.3% and 51.6% respectively. Of our 6 prespecified predictors, an undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). One participant underwent an intervention for a urethral stricture. No participants developed osteitis pubis or rectourethral fistulae. Conclusions Salvage HIFU allows for disease control in selected patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response.

Compliance of the recurrent renal stone former with current best practice guidelines.

INTRODUCTION: Patient compliance to best practice guidelines is a significant factor in preventing renal stone recurrence. While patient compliance has been historically poor, there remains a paucity of data in the renal stone setting. We evaluated compliance of the recurrent renal stone former with current Canadian Urological Association (CUA) best practice guidelines. METHODS: A prospective, cross-sectional study design was used to evaluate patient compliance. Recurrent renal stone former patients were consecutively recruited from McMaster's Institute of Urology and completed a one-time questionnaire developed in accordance with CUA best practice guidelines. Questionnaire sections included: 1) demographics; 2) interaction(s) and satisfaction with their healthcare provider; and 3) knowledge, attitudes, and compliance with best practices. RESULTS: A total of 300 patients were enrolled in the study; 55.3% were men, 69.5% had a history of stone surgery, while 23.7% had a positive family history. Participants perceived satisfactory education from their urologist and primary care physician 82.7% and 59.7% of the time, respectively (p<0.05). Nearly a quarter of patients (22.8%) perceived their stone disease to be severe and 67.1% of patients believed in the efficacy of preventative stone measures. Overall, 45.8% of patients were compliant with CUA best practice guidelines. The majority of patients (72.6%) complied with high fluid intake, the most critical stone preventative practice. CONCLUSIONS: Consistent with previous studies, compliance to dietary recommendations in this evaluation of recurrent stone formers was low. Study findings may be attributed to insufficient knowledge translation, lack of perceived disease severity, and/or patient uncertainty in the importance of preventative stone practices.

A Randomized Comparison of 2 Robotic Virtual Reality Simulators and Evaluation of Trainees' Skills Transfer to a Simulated Robotic Urethrovesical Anastomosis Task.

OBJECTIVE: To determine, via a randomized comparison study, whether robotic simulator-acquired skills transfer to performance of a urethrovesical anastomosis (UVA) on a 3-dimensional-printed bladder model using the da Vinci Robot. MATERIALS AND METHODS: Medical students, surgical residents, and fellows were recruited and divided into 2 groups: Group 1 (G1) (junior trainees) and Group 2 (G2) (senior trainees). Participants were randomized to identical simulator training curricula on the dV-Trainer (dV-T) or da Vinci Surgical Skills Simulator (dVSSS). Participants then completed a UVA task on a 3-dimensional-printed bladder model using the da Vinci robot. Three blinded expert robotic surgeons rated videotaped performances of the UVA task using validated assessment tools, namely, the Global Evaluative Assessment of Robotic Skills (GEARS; overall procedure) and Robotic Anastomosis Competence Evaluation (RACE; specific to UVA). RESULTS: Thirty-nine participants (G1 = 23 and G2 = 16) completed the study. Participants in G2 had significantly more simulation and surgical experience compared with G1 (P <.05). UVA scores of the dVSSS group were higher compared with dV-T (GEARS: P = .09; RACE: P = .01). In the G1 cohort, dVSSS scores were significantly higher than dV-T (GEARS: P = .01; RACE: P <.01). In the G2 cohort, scores were statistically similar (GEARS: P = .32; RACE: P = .91). CONCLUSION: Compared with the dV-T, the dVSSS training led to superior GEARS and RACE scores for performance of the UVA task in junior trainees, but not in senior trainees. The dVSSS can be used to improve surgical skills acquisition in less experienced trainees in a safe and effective manner.

High-intensity Focused Ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: predictors of disease response.

BACKGROUND: Some men with localized radio-recurrent prostate cancer may benefit from salvage high-intensity focused ultrasound (HIFU). Herein, we describe oncologic outcomes and predictors of disease response after salvage whole gland HIFU from our prospective cohort. MATERIALS AND METHODS: Patients with localized radio-recurrent prostate cancer were prospectively enrolled from January 2005 to December 2014. Participants had to meet both biochemical and histological definitions of recurrence. Exclusion criteria included the receipt of prior salvage therapy, presence of metastatic disease, and administration of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the AblathermTM device (EDAP, France). The primary endpoint was recurrence-free survival (RFS), defined as a composite endpoint of PSA progression (Phoenix criteria), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (TRUS biopsy grade, number of study entry TRUS biopsy cores positive, palpable disease at study enrollment, pre-HIFU PSA, an undetectable post-HIFU PSA nadir, and receipt of prior hormone therapy). Survival analysis was performed on participants with a minimum of 1-year follow-up. RESULTS: Twenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04ng/ ml. Median 2-year and 5-year RFS was 66.3% and 51.6% respectively. Of our 6 pre-specified predictors, an undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). One participant underwent an intervention for a urethral stricture. No participants developed osteitis pubis or rectourethral fistulae. CONCLUSIONS: Salvage HIFU allows for disease control in selected patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response.

Positive surgical margin rates during the robot-assisted laparoscopic radical prostatectomy learning curve of an experienced laparoscopic surgeon.

INTRODUCTION: Since its introduction, robot-assisted laparoscopic radical prostatectomy (RARP) has gained widespread popularity, but is associated with a variable learning curve. Herein, we report the positive surgical margin (PSM) rates during the RARP learning curve of a single surgeon with significant previous laparoscopic radical prostatectomy (LRP) experience. METHODS: We performed a prospective cohort study of the first 400 men with prostate cancer treated with RARP by a single surgeon (BS) with significant LRP experience. Our primary outcome was the impact of case timing in the learning curve on margin status. Our analysis was conducted by dividing the case numbers into quartiles (Q1-Q4) and determining if a case falling into an earlier quartile had an impact on margin status relative to the most recent quartile (Q4). RESULTS: The Q1 cases had an odds ratio for margin positivity of 1.74 compared to Q4 (p=0.1). Multivariate logistic regression did not demonstrate case number to be a significant predictor of PSM. The mean Q1 operative time was 207.4 minutes, decreasing to 179.2 by Q4 (p<0.0001). The mean Q1 estimated blood loss was 255.1 ml, decreasing to 213.6 by Q4 (p=0.0064). There was no change in length of hospitalization within the study period. CONCLUSIONS: Even when controlling for copredictors, a statistically significant learning curve for PSM rate of a surgeon with significant previous LRP experience was not detected during the first 400 RARP cases. We hypothesize that previous LRP experience may reduce the RARP PSM learning curve.

Autoantibodies against the cell surface-associated chaperone GRP78 stimulate tumor growth via tissue factor.

Tumor cells display on their surface several molecular chaperones that normally reside in the endoplasmic reticulum. Because this display is unique to cancer cells, these chaperones are attractive targets for drug development. Previous epitope-mapping of autoantibodies (AutoAbs) from prostate cancer patients identified the 78-kDa glucose-regulated protein (GRP78) as one such target. Although we previously showed that anti-GRP78 AutoAbs increase tissue factor (TF) procoagulant activity on the surface of tumor cells, the direct effect of TF activation on tumor growth was not examined. In this study, we explore the interplay between the AutoAbs against cell surface-associated GRP78, TF expression/activity, and prostate cancer progression. First, we show that tumor GRP78 expression correlates with disease stage and that anti-GRP78 AutoAb levels parallel prostate-specific antigen concentrations in patient-derived serum samples. Second, we demonstrate that these anti-GRP78 AutoAbs target cell-surface GRP78, activating the unfolded protein response and inducing tumor cell proliferation through a TF-dependent mechanism, a specific effect reversed by neutralization or immunodepletion of the AutoAb pool. Finally, these AutoAbs enhance tumor growth in mice bearing human prostate cancer xenografts, and heparin derivatives specifically abrogate this effect by blocking AutoAb binding to cell-surface GRP78 and decreasing TF expression/activity. Together, these results establish a molecular mechanism in which AutoAbs against cell-surface GRP78 drive TF-mediated tumor progression in an experimental model of prostate cancer. Heparin derivatives counteract this mechanism and, as such, represent potentially appealing compounds to be evaluated in well-designed translational clinical trials.

Towards development and validation of an intraoperative assessment tool for robot-assisted radical prostatectomy training: results of a Delphi study

ABSTRACT Introduction As urology training shifts toward competency-based frameworks, the need for tools for high stakes assessment of trainees is crucial. Validated assessment metrics are lacking for many robot-assisted radical prostatectomy (RARP). As it is quickly becoming the gold standard for treatment of localized prostate cancer, the development and validation of a RARP assessment tool for training is timely. Materials and methods We recruited 13 expert RARP surgeons from the United States and Canada to serve as our Delphi panel. Using an initial inventory developed via a modified Delphi process with urology residents, fellows, and staff at our institution, panelists iteratively rated each step and sub-step on a 5-point Likert scale of agreement for inclusion in the final assessment tool. Qualitative feedback was elicited for each item to determine proper step placement, wording, and suggestions. Results Panelist's responses were compiled and the inventory was edited through three iterations, after which 100% consensus was achieved. The initial inventory steps were decreased by 13% and a skip pattern was incorporated. The final RARP stepwise inventory was comprised of 13 critical steps with 52 sub-steps. There was no attrition throughout the Delphi process. Conclusions Our Delphi study resulted in a comprehensive inventory of intraoperative RARP steps with excellent consensus. This final inventory will be used to develop a valid and psychometrically sound intraoperative assessment tool for use during RARP training and evaluation, with the aim of increasing competency of all trainees.

Utility of preoperative 3 Tesla pelvic phased-array multiparametric magnetic resonance imaging in prediction of extracapsular extension and seminal vesicle invasion of prostate cancer and its impact on surgical margin status: Experience at a Canadian academic tertiary care centre.

INTRODUCTION: To evaluate the utility of 3 Tesla (3T) pelvic phased-array (PPA) multiparametric magnetic resonance imaging (mpMRI) to predict extracapsular extension (ECE) and seminal vesicle invasion (SVI) and its subsequent effect on radical prostatectomy (RP) surgical margin status. METHODS: A retrospective evaluation was conducted of RP patients who underwent preoperative 3T PPA mpMRI (without endorectal coil) based on clinical probability of adverse pathological features. Frequencies, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI in predicting the status of ECE and SVI were calculated. RESULTS: Forty-eight consecutive patients were included. Sensitivity, specificity, PPV, and NPV for 3T PPA mpMRI using T2-weighted sequences with diffusion-weighted imaging (DWI) and dynamic contrast enhanced (DCE) imaging to predict ECE was 39%, 56%, 45%, and 50%, respectively, while SVI prediction was 33%, 95%, 50%, and 91%, respectively. Twelve of the 28 cases predicted as being negative for ECE had positive margins, while two of the 20 cases predicted to be positive for ECE had positive margins. Imaging predicted four cases would have SVI, yet two had positive margins, while of the 44 cases predicted as being negative for SVI, four had positive margins. CONCLUSIONS: These findings at our centre suggest that the use of 3T PPA mpMRI using T2-weighted sequences with DWI and DCE in predicting pathological ECE and SVI is of questionable benefit. These mpMRI reports may result in closer dissection of neurovascular bundles and subsequent positive surgical margins. Caution should be exercised when basing intraoperative decisions on mpMRI findings.