Holmium laser enucleation of the prostate in men on active surveillance for prostate cancer with refractory lower urinary tract symptoms secondary to enlarged prostates.

INTRODUCTION: The surgical treatment of men with lower urinary tract symptoms (LUTS) and significantly enlarged symptomatic prostates on active surveillance (AS) for low-risk prostate cancer (PCa) is not well defined. We report our single-institution initial experience with holmium laser enucleation of the prostate (HoLEP) for LUTS in men with low-risk PCa being managed with AS. MATERIALS AND METHODS: Men on AS who underwent HoLEP between 2013 and 2019 were identified. Data regarding preoperative cancer workup, prostate-specific antigen (PSA), perioperative outcomes, and voiding parameters were analyzed. Postoperative surveillance for PCa including PSA nadir, prostate magnetic resonance imaging, prostate biopsy (PBx), and PSA at last follow-up were evaluated. RESULTS: Twenty men met the inclusion criteria. Preoperative mean max flow 7.9 ml/s, median postvoid residual 101 cc, and mean transrectal ultrasound prostate size 99 cc. Patients had a median adjusted preoperative PSA of 8.5 (interquartile range [IQR]: 4.8-13.2) ng/ml. Mean resected tissue weight was 65.5 g with improved postoperative flow rate and significantly decreased residual. A total of 5/20 men had PCa in the specimen (all Gleason Grade Group 1). The median postoperative PSA nadir was 1.2 (IQR: 0.5-1.8) ng/ml at median of 5 months. At the last follow-up (median 18.5 months, IQR: 10.5-37.8), the median postoperative PSA was 1.4 (IQR: 0.63-2.48) ng/ml. Nine men underwent postoperative multiparametric magnetic resonance imaging (mpMRI) with the identification of a new prostate imaging reporting and data system 5 lesion in one patient who underwent negative fusion biopsy. Five men underwent post-HoLEP PBx with progression in two patients, who both successfully underwent radical prostatectomy. CONCLUSIONS: Men on AS for low-risk PCa can safely undergo HoLEP with significantly improved voiding parameters. Postoperative monitoring with PSA, mpMRI, and PBx can detect disease progression requiring definitive treatment. Further research is needed to optimize surveillance strategies and long-term cancer-specific outcomes.

MicroRNA-155-5p Targets JADE-1, Promoting Proliferation, Migration, and Invasion in Clear Cell Renal Cell Carcinoma Cells.

Clear cell renal cell carcinoma (ccRCC) incidence has been rising in recent years, with strong association between differential microRNA (miRNA) expression and neoplastic progression. Specifically, overexpression of miR-155-5p has been associated with promoting aggressive cancer in ccRCC and other cancers. In this study, we further investigate the role of this miRNA and one of its protein targets, Jade-1, to better understand the mechanism behind aggressive forms of ccRCC. Jade-1, a tumor suppressor, is stabilized by Von-Hippel Lindau (VHL), which is frequently mutated in ccRCC. Experiments featuring downregulation of miR-155-5p in two ccRCC cell lines (786-O and Caki-1) attenuated their oncogenic potential and led to increased levels of Jade-1. Conversely, knockdown experiments with an anti-Jade-1 shRNA in 786-O and Caki-1 cells showed increased metastatic potential through elevated proliferation, migration, and invasion rates. In a mouse xenograft model, downregulation of miR-155 decreased the rate of tumor implantation and proliferation. Direct interaction between miR-155-5p and Jade-1 was confirmed through a 3'UTR luciferase reporter assay. These findings further elucidate the mechanism of action of miR-155-5p in driving an aggressive phenotype in ccRCC through its role in regulating Jade-1.

Preoperative MRI PI-RADS scores are associated with prostate cancer upstaging on surgical pathology.

INTRODUCTION: Prostate Imaging Reporting and Data System (PI-RADS) scores can help identify clinically significant prostate cancer and improve patient selection for prostate biopsies. However, the role of PI-RADS scores in patients already diagnosed with prostate cancer remains unclear. The purpose of this study was to evaluate the association of PI-RADS scores with prostate cancer upstaging. Upstaging on final pathology harbors a higher risk for biochemical recurrence with important implications for additional treatments, morbidity, and mortality. METHODS: All patients from a single high-volume institution who underwent a prostate multiparametric magnetic resonance imaging and radical prostatectomy between 2016 and 2020 were included in this retrospective analysis. Univariable and multivariable analyses were conducted to investigate potential associations with upstaging events, defined by pT3, pT4, or N1 on final pathology. A logistic regression model was constructed for the prediction of upstaging events based on PI-RADS score, prostate-specific antigen density (PSA-D), and biopsy Gleason grade groups. We built receiver operative characteristic (ROC) curves to measure the area under the curve of different predictive models. RESULTS: Two hundred and ninety-four patients were included in the final analysis. Upstaging events occurred in 137 (46.5%) of patients. On univariable analysis, patients who were upstaged on final pathology had significantly higher PI-RADS scores (odds ratio [OR] 2.34 95% confidence interval [CI] 1.64-3.40, p < 0.001) but similar PSA-D (OR 2.70 95% 0.94-8.43, p = 0.188) compared with patients who remained pT1 or pT2 on final pathology. On multivariable analysis, PI-RADS remained independently significantly associated with upstaging, suggesting it is an independent risk predictor for upstaging. Lymph node metastasis only occurred in patients with PI-RADS 4 or 5 lesions (n = 15). Our model using PSA-D, biopsy Gleason grade, and PI-RADS had a predictive AUC of 0.69 for upstaging events, an improvement from 0.59 using biopsy Gleason grade alone. CONCLUSION: PI-RADS scores are independent predictors for upstaging events and may play an important role in forecasting biochemical recurrence and lymph node metastasis. Modern nomograms should be updated to include PI-RADS to predict lymph node metastases and the likelihood of biochemical recurrence more accurately.

Initial transperineal prostate biopsy experience at a high-volume center.

INTRODUCTION: Transperineal prostate biopsy (TPBx) allows for prostate cancer detection with fewer infectious complications when compared to transrectal prostate biopsy (TRUSBx). We evaluated the initial experience of a single physician with no prior TPBx exposure, compared to TRUSBx and MRI/US fusion biopsy (MRIBx) performed by experienced physicians. MATERIALS AND METHODS: All consecutive patients undergoing prostate biopsy (June 2019-March 2020) were included. Patient discomfort, procedural time, clinically significant cancer detection rates (csCDR) and 30-day complications were compared between TPBx, TRUSBx and MRIBx. RESULTS: A total of 303 patients underwent biopsy. Comparing TPBx to TRUSBx to MRIBx, median pain scores during the anesthetic block were 4 versus 2 versus 3 (p = 0.007) respectively, and not statistically different during the rest of the procedure. Median time of biopsy was 11, 7.5 and 12 minutes respectively. csCDR were 38%, 29.8%, and 43.6% (p = 0.12) respectively. The combined transrectal groups (n = 211) had nine complications including two sepsis events. The TPBx group (n = 92) had no 30-day complications. CONCLUSIONS: TPBx was well tolerated in the office setting with similar levels of discomfort for all aspects of the procedure compared to transrectal approach. Learning curve for TPBx showed rapid improvement in procedural time within the first 15 cases with an average procedure time of 9 minutes thereafter. Similar rates of csCDR were found between the groups and TPBx had significantly fewer infectious complications than standard transrectal technique.

Reducing postoperative opioid pill prescribing via a quality improvement approach.

BACKGROUND: The opioid epidemic has been fueled by prescribing unnecessary quantities of opioid pills for postoperative use. While evidence mounts that postoperative opioids can be reduced or eliminated, implementing such changes within various institutions can be met with many barriers to adoption. OBJECTIVE: To address excess opioid prescribing within our institutions, we applied a plan-do-study-act (PDSA)-like quality improvement strategy to assess local opioid prescribing and use, modify our institutional protocols, and assess the impacts of the change. The opioid epidemic has been fueled by prescribing unnecessary quantities of opioid pills for postoperative use. While evidence mounts that postoperative opioids can be reduced or eliminated, implementing such changes within various institutions can be met with many barriers to adoption. We describe our approach, findings, and lessons learned from our quality improvement approach. METHODS: We prospectively recorded home pain pill usage after robotic-assisted laparoscopic prostatectomy (RALP) and robotic-assisted partial nephrectomy (RAPN) at two academic institutions from July 2016 to July 2019. Patients prospectively recorded their home pain pill use on a take-home log. Other factors, including numeric pain rating scale on the day of discharge, were extracted from patient records. We analyzed our data and modified opioid prescription protocols to meet the reported use data of 80% of patients. We continued collecting data after the protocol change. We also used our prospectively collected data to assess the accuracy of a retrospective phone survey designed to measure postdischarge opioid use. Our primary outcomes were the proportion of patients taking zero opioid pills postdischarge, median pills taken after discharge and the number of excess pills prescribed but not taken. We compared these outcomes before and after protocol change. RESULTS: A total of 266 patients (193 RALP, 73 RAPN) were included. Reducing the standard number of prescribed pills did not increase the percentage of patients taking zero pills postdischarge in either group (RALP: 47% vs. 41%; RAPN 48% vs. 34%). The patients in either group reporting postoperative Day 1 pain score of 0 or 1 were much more likely to use zero postdischarge opioid pills. Our reduction in prescribing protocol resulted in an estimated reduction in excess pills from 1555 excess pills in the prior protocol to just 155 excess pills in the new protocol. CONCLUSION: Our PDSA-like approach led to an acceptable protocol revision resulting in significant reductions in excess pills released into the community. Reducing the quantity of opioids prescribed postoperatively does not increase the percentage of patients taking zero pills postdischarge. To eliminate opioid use may require no-opioid pathways. Our approach can be used in implementing zero opioid discharge plans and can be applied to opioid reduction interventions at other institutions where barriers to reduced prescribing exist.

Underutilization of immediate intravesical chemotherapy following TURBT: results from NSQIP.

INTRODUCTION: A single perioperative dose of intravesical chemotherapy (IVC) following transurethral resection of bladder tumors (TURBT) for non-muscle invasive bladder cancer has demonstrated a reduction in tumor recurrence. In this study, we investigate the contemporary (2010) utilization of IVC following TURBT using a prospective national database. MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, we identified patients with bladder cancer using ICD-9 codes. From this group, patients undergoing TURBT based on Current Procedural Terminology (CPT) codes were analyzed. We then identified those patients who underwent TURBT and also received intravesical therapy. Operative time, length of hospital stay, and perioperative complications were evaluated. RESULTS: From January 1 to December 31, 2010, 1273 patients at participating ACS-NSQIP sites underwent TURBT for bladder cancer. There were 417 (33%) small, 486 (38%) medium, and 370 (29%) large tumors treated. In total, 33 (2.6%) patients received IVC. When comparing patients who received perioperative IVC to those who did not, there was no difference in median operative times (27 mins versus 28 mins, p = 0.899). There was one urinary tract infection in the IVC group. CONCLUSIONS: IVC remains greatly underutilized despite current data documenting its efficacy in reducing tumor recurrence for TaT1 bladder cancer. Instillation of IVC following TURBT does not increase morbidity. Our findings support the continued need to explore ways of improving rates of perioperative IVC administration following TURBT.

Use of Droplet Digital Polymerase Chain Reaction to Identify Biomarkers for Differentiation of Benign and Malignant Renal Masses.

Several microRNAs (miRNAs) have been identified as cell-free biomarkers for detecting renal cell carcinoma (RCC). Droplet digital polymerase chain reaction (ddPCR) is a unique technology for nucleic acid quantification. It has the potential for superior precision, reproducibility, and diagnostic performance in identifying circulating miRNA biomarkers compared to conventional quantitative real-time PCR (qRT-PCR). This study aims to evaluate the performance of ddPCR compared to qRT- PCR in identifying miRNA biomarkers that differentiate malignant from benign renal masses. Potential biomarkers of RCC were identified from a literature review. RNA was extracted from the plasma of 56 patients. All the samples underwent analysis via ddPCR as well as qRT-PCR, and expression levels were recorded for the following miRNAs: miR-93, -144, -210, -221, and -222. Tumors were grouped into low-grade ccRCC, high-grade ccRCC, papillary RCC, and benign masses (primarily angiomyolipoma). The miRNA miR-210 (p = 0.034) and the combination of miRs-210 and miR-222 (p = 0.003) were expressed at significantly higher rates among those with RCC than those with benign masses, as measured by ddPCR. Using the combination of miR-210 and miR-222, ddPCR identified significant differences between the subgroups: papillary RCC versus benign (p = 0.03), low-grade ccRCC versus benign (p = 0.026), and high-grade ccRCC versus benign (p = 0.002). The only significant difference between these subgroups using qRT-PCR was between high-grade ccRCC and benign (p = 0.045). All the AUCs were significant when comparing each RCC subgroup with benign for both PCR technologies. Using a combination of miR-210 and miR-222, ddPCR identified significant differences between benign and malignant renal masses that were not identified as significant by conventional qRT-PCR.

Comparison of positive surgical margin rates in high risk prostate cancer: open versus minimally invasive radical prostatectomy.

OBJECTIVE: We compared positive surgical margin (PSM) rates for patients with high risk prostate cancer (HRCaP) who underwent open radical retropubic (RRP), robotic (RALP), and laparoscopic (LRP) prostatectomy at a single institution. MATERIALS AND METHODS: We performed a retrospective review of our prospectively maintained IRB approved database identifying prostate cancer patients who underwent RRP, RALP, or LRP between January 2000 and March 2010. Patients were considered to have HRCaP if they had biopsy or final pathologic Gleason score ≥ 8, or preoperative PSA ≥ 20, or pathologic stage ≥ T3a. A positive surgical margin (PSM) was defined by the presence of tumor at the inked surface of the specimen. Patients who received neoadjuvant hormonal therapy and those who underwent a perineal prostatectomy were excluded from the study. RESULTS: Of the 445 patients in this study, surgical technique for prostatectomy included RRP (n = 153), RALP (n = 152), and LRP (n = 140). PSM rate for the three groups were not different: 52.9% RRP, 50% RALP, and 41.4% LRP, (p = 0.13). The PSM rate did not differ when comparing RRP to a combined group of RALP and LRP (p = 0.16). Among patients with a PSM, there was no statistical difference between the three groups in terms of the number of patients with a pathologic stage of T3 or higher (p = 0.83). On univariate analysis, a higher preoperative PSA value was associated with a positive margin (p = 0.04). CONCLUSION: In this HRCaP series, the PSM rate did not differ based on the surgical approach. On univariate analysis, patients with a higher preoperative PSA value were more likely to have a PSM.

Temporary targeted renal blood flow interruption using a reverse thermosensitive polymer to facilitate bloodless partial nephrectomy: a swine survival study.

UNLABELLED: What's known on the subject? and What does the study add? Lumagel™ is a reverse thermosensitive polymer (RTP) that has previously been described in the literature as providing temporary vascular occlusion to allow for bloodless partial nephrectomy (PN) while maintaining blood flow to the untargeted portion of the kidney. At body temperature, Lumagel™ has the consistency of a viscous gel but upon cooling rapidly converts to a liquid state and does not reconstitute thereafter. This property has allowed for it to be used in situations requiring temporary vascular occlusion. Previous experience with similar RTPs in coronary arteries proved successful, with no detectable adverse events. We have previously described our technique for temporary vascular occlusion of the main renal artery, as well as segmental and sub-segmental renal branches, to allow for bloodless PN in either an open or minimally invasive approach. These experiments were performed in the acute setting. This study is a two-armed survival trial to assess whether this RTP is as safe as hilar clamping for bloodless PN. Surviving animals showed normal growth after using the RTP, absence of toxicity, no organ dysfunction, and no pathological changes attributable to the RTP. We conclude that Lumagel™ is as safe as conventional PN with hilar clamping, while adding the advantage of uninterrupted perfusion during renal resection. OBJECTIVE: To examine whether randomly selected regions of the kidney could undergo temporary flow interruption with a reverse thermosensitive polymer (RTP), Lumagel™ (Pluromed, Inc., Woburn, MA, USA), followed by partial nephrectomy (PN), without adding risks beyond those encountered in the same procedure with the use of hilar clamping. MATERIALS AND METHODS: A two-armed (RTP vs hilar clamp), 6-week swine survival study was performed. Four swine underwent PN using hilar clamps, while six underwent PN with flow interruption using the RTP. The RTP, administered angiographically, was used for intraluminal occlusion of segmental or subsegmental arteries and was compared with main renal artery clamping with hilar clamps. The resection site was randomized for each swine. Laboratory studies were performed preoperatively, and at weeks 1, 3 and 6. Before killing the swine, repeat angiography was performed with emphasis on the site of previous flow interruption. Gross and microscopic examination of kidney, liver, lung, heart, skeletal muscle was later performed, and the vessel that had supported the previous plug was examined. RESULTS: All animals survived. No abnormal chemistry or haematology results were encountered over the 6 weeks. There were no surgical complications in either group. Using angiography we found 100% patency of vessels that had been occluded with the polymer 6 weeks previously for PN. The only gross or microscopic abnormalities were related to the renal resection and scar formation, and were similar in the two groups. CONCLUSION: Targeted flow interruption with the RTP added no additional risk to PN while allowing bloodless resection and uninterrupted flow to untargeted renal tissue.

Unidirectional barbed suture versus standard monofilament for urethrovesical anastomosis during robotic assisted laparoscopic radical prostatectomy.

PURPOSE: V-Loc™180 (Covidien Healthcare, Mansfield, MA) is a new unidirectional barbed suture that may reduce loss of tension during a running closure. We evaluated the use of the barbed suture for urethrovesical anastomosis (UVA) during robotic assisted laparoscopic prostatectomy (RALP). Time to completion of UVA, post-operative anastomotic leak rate, and urinary incontinence were compared in patients undergoing UVA with 3-0 unidirectional-barbed suture vs. 3-0 Monocryl™ (Ethicon, Somerville, NJ). MATERIALS AND METHODS: Data were prospectively collected for 70 consecutive patients undergoing RALP for prostate cancer between November 2009 and October 2010. In the first 35 patients, the UVA was performed using a modified running van Velthoven anastomosis technique using two separate 3-0 monofilament sutures. In the subsequent 35 patients, the UVA was performed using two running novel unidirectional barbed sutures. At 7-12 days postoperatively, all patients were evaluated with a cystogram to determine anastomotic integrity. Urinary incontinence was assessed at two months and five months by total daily pad usage. Clinical symptoms suggestive of bladder neck contracture were elicited. RESULTS: Age, PSA, Gleason score, prostate size, estimated blood loss, body mass index, and clinical and pathologic stage between the 2 groups were similar. Comparing the monofilament group and V-Loc™180 cohorts, average time to complete the anastomosis was similar (27.4 vs. 26.4 minutes, p = 0.73) as was the rate of urinary extravasation on cystogram (5.7 % vs. 8.6%, p = 0.65). There were no symptomatic bladder neck contractures noted at 5 months of follow-up. At 2 months, the percentage of patients using 2 or more pads per day was lower in the V-Loc™180 cohort (24% vs. 44%, p < 0.02). At 5 months, this difference was no longer evident. CONCLUSIONS: Time to complete the UVA was similar in the intervention and control groups. Rates of urine leak were also comparable. While the V-Loc™180 was associated with improved early continence, this difference was transient.

MicroRNA Associated with the Invasive Phenotype in Clear Cell Renal Cell Carcinoma: Let-7c-5p Inhibits Proliferation, Migration, and Invasion by Targeting Insulin-like Growth Factor 1 Receptor.

Differential microRNA (miRNA) expression can portend clear cell renal cell carcinoma (ccRCC) progression. In a previous study, we identified a subset of dysregulated miRNA in small renal masses, pT1 ccRCC (≤5 cm) that are associated with an aggressive phenotype. The present study investigated miRNA expression in clinical stage I (cT1) tumors (≤5 cm), comparing pathologic stage I (pT1) tumors to those upstaged to pathologic stage 3 (pT3) after surgery following identification of renal vein invasion or invasion into adjacent fat tissue within Gerota's fascia. Twenty cT1 tumors were examined in an miRNA screening, 10 pT1 and 10 pT3 tumors. The ccRCC cell lines 786-O and Caki-1 were used to assess the impact of let-7c-5p and its protein target insulin-like growth factor 1 receptor (IGF1R). Cells were transfected with pre-let-7c-5p and assessed through cell proliferation, migration, and invasion assays. IGF1R expression was evaluated through Simple Western, and interaction between let-7c-5p and IGF1R was confirmed via luciferase reporter assay. Screening identified 20 miRNA, including let-7c-5p, that were dysregulated between pT1 and pT3 upstaged tumors. This miRNA was also downregulated in our previous study of pT1 tumors that progressed to metastatic disease. Transfection of ccRCC cells with pre-let-7c-5p significantly inhibited proliferation, migration, invasion, and IGF1R expression. These findings suggest that miRNA dysregulation is involved in ccRCC progression, specifically through invasion, and that let-7c-5p downregulation contributes to the aggressiveness of small ccRCC tumors, in part, through its regulation of IGF1R.

Robotic approach to Giant multiloculated cystadenoma of the prostate: Initial experience.

Giant multiloculated cystadenoma of the prostate (GMPC) is a rare, massive and benign tumor. Recurrence rates after resection are low but have been recorded. An open approach is most common, with few laparoscopic and no robotic cases reported. We report on a case of a 65-year-old man with a new presentation of a 400 cc cystic prostatic mass thought to be GMPC. This patient underwent what is, to our knowledge, the first reported case of RARP in the treatment of GMPC. A robotic approach to massive GMPC was safe and efficacious in our initial experience.

MicroRNAs MiR-15a and MiR-26a cooperatively regulate O-GlcNAc-transferase to control proliferation in clear cell renal cell carcinoma.

BACKGROUND: MicroRNAs (miRNAs), a group of non-coding post-transcriptional regulators of gene expression, are dysregulated in clear cell renal cell carcinoma (ccRCC) and play an important role in carcinogenesis. Our prior work identified a subset of miRNAs in pT1 ccRCC tumors associated with progression to metastatic disease. OBJECTIVE: To investigate the impact of two of these dysregulated miRNA, miR-15a-5p and -26a-5p, in an effort to elucidate the mechanisms underpinning aggressive forms of stage I ccRCC. METHODS: The ccRCC cell line 786-O was transfected with pre-miRs-15a-5p and -26a-5p to rescue expression. Cell proliferation was measured via MT Cell Viability Assay. O-GlcNAc-transferase (OGT), a known protein in ccRCC proliferation, was identified by bioinformatics analysis as a target of both miRNA and validated via luciferase reporter assay to confirm binding of each miR to the 3' untranslated region (UTR). OGT protein expression was evaluated via western blotting. RESULTS: Luciferase assay confirmed specificity of miR-15a-5p and -26a-5p for the OGT UTR. Western blot analysis for OGT showed reduced expression following co-transfection of both miRNAs compared to negative control or individual transfection. Co-transfection of these miRNAs greatly reduced proliferation when compared to negative control or the individual transfections. CONCLUSION: Our results indicate that the dysregulation of miR-15a-5p and -26a-5p contribute cooperatively to the proliferation of ccRCC through their regulation of OGT. These results give insight into the pathogenesis of aggressive early stage ccRCC and suggest potential therapeutic targets for future research.

MiRNA-424-5p Suppresses Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma and Attenuates Expression of O-GlcNAc-Transferase.

MicroRNAs (miRNAs) are non-coding post-transcriptional regulators of gene expression that are dysregulated in clear cell renal cell carcinoma (ccRCC) and play an important role in tumor progression. Our prior work identified a subset of miRNAs in pT1 ccRCC tumors, including miR-424-5p, that are associated with an aggressive phenotype. We investigate the impact of this dysregulated miRNA and its protein target O-GlcNAc-transferase (OGT) to better understand the mechanisms behind aggressive stage I ccRCC. The ccRCC cell lines 786-O and Caki-1 were used to assess the impact of miR-424-5p and OGT. Cells were transfected with pre-miR-424-5p, a lentiviral anti-OGT shRNA, or were treated with the demethylating agent 5-Aza-2'-deoxycytidine. Cell proliferation was measured via MT cell viability assay. Cell migration and invasion were analyzed using Transwell assays. The expression of miR-424-5p was determined through qRT-PCR, while OGT protein expression was evaluated through Western blotting. The interaction between miR-424-5p and OGT was confirmed via luciferase reporter assay. The transfection of ccRCC cells with pre-miR-424-5p or anti-OGT shRNA significantly inhibited cell proliferation, migration, and OGT expression, while miR-424-5p also attenuated cell invasion. Addition of the demethylating agent significantly reduced cell proliferation, migration, invasion, and OGT expression, while significantly increasing the expression of miR-424-5p. Altogether, these findings suggest that epigenetic downregulation of miR-424-5p, which in turn augments OGT expression, contributes to the creation of aggressive forms of stage I ccRCC.

Estimating the rate and reasons of clinical trial failure in urologic oncology.

OBJECTIVES: Clinical trials are pillars of modern clinical evidence generation. However, the clinical trial enterprise can be inefficient, and trials often fail before their planned endpoint is reached. We sought to estimate how often urologic oncology trials fail, why trials fail, and associations with trial failure. METHODS: We queried phase 2/3 urologic clinical trial data from ClinicalTrials.gov registered between 2007 and 2019, with status marked as active, completed, or terminated. We extracted relevant trial data, including anticipated and actual accrual, from trial records and ClinicalTrials.gov archives. We manually coded reasons given in the "why stopped" free text field for trial failure into categories (poor accrual, interim results, toxicity/adverse events, study agent unavailable, canceled by the sponsor, inadequate budget, logistics, trial no longer needed, principal investigator left, no reason given, or other). We considered trials terminated for safety or efficacy to be completed trials. Trials marked as terminated for other reasons were considered failed trials. We then estimated the rate of trial failure using competing risks methods. Finally, we assessed associations with trial failure using a Cox proportional hazards model. RESULTS: A total of 1,869 urologic oncology trials were included. Of these, 225 (12.0%) failed, and 51 (2.7%) were terminated for "good" reasons (e.g., toxicity, efficacy). Of the 225 failed trials, 122 (54%) failed due to poor accrual. Failed trials had a lower anticipated accrual than successfully completed trials (55 vs. 63 patients, P<0.001). A total of 6,832 patients were actually accrued to failed trials. The 10-year estimated risk of trial failure was 17% (95% CI 15%-22%). Single center trials, phase 3 trials, drug trials, and trials with exclusively USA sites were more likely to fail. CONCLUSION: We estimate that 17%, or roughly 1 in 6, of urologic oncology trials fail, most frequently for poor accrual. Further investigations are needed into systemic, trial, and site-specific factors that may impact accrual and successful trial completion.

"Robotic fatigue?" - The impact of case order on positive surgical margins in robotic-assisted laparoscopic prostatectomy.

PURPOSE: Multiple robotic-assisted surgeries are often performed within a single operating day; however, the impact of this practice on patient outcomes has not been examined. We aim to determine whether outcomes for robotic-assisted laparoscopic prostatectomy (RALP) differed when performed sequentially. MATERIALS AND METHODS: A multi-institutional, retrospective cohort study was conducted involving a total of 8 academic centers between years 2015 and 2018. Participants were adult males undergoing RALP for localized prostate cancer on operative days in which 2 RALP cases were performed sequentially by the same resident-attending team. The primary outcome of the study was presence of positive surgical margin (PSM). Secondary outcomes were lymph node yield, operative time, and estimated blood loss. The primary analysis was a random effects meta-analysis model for PSM. RESULTS: Overall, 898 RALP cases (449 sequential pairs) were included in the study. There was no significant difference in PSM rate (27.2% vs. 30.3%, P= 0.338) between first and second case groups, respectively. Utilizing random effects meta-analysis, the second case cohort had no increased risk of PSM (OR 0.761.231.97, P= 0.40). Higher blood loss was noted in the second case cohort (186.7 ml vs. 221.7 ml, P = 0.002). Additionally, factors associated with PSM were increasing prostate specific antigen, higher percent tumor involvement, extraprostatic extension, and seminal vesicle invasion. CONCLUSION: Case sequence was not associated with PSM, lymph node yield, or operative time for RALP. Disease specific factors and institutional experience are associated with increased risk for positive surgical margin which can aid providers in scheduling of patients.

Comparison of laparoscopic versus robotic assisted partial nephrectomy: one surgeon's initial experience.

INTRODUCTION/OBJECTIVE: Partial nephrectomy is an effective surgical treatment for small renal masses. We compare a single surgeon's experience with consecutive laparoscopic and robotic partial nephrectomy to assess potential perioperative outcomes. A review of the literature is provided. MATERIALS AND METHODS: A retrospective review was performed comparing 15 consecutive patients undergoing laparoscopic partial nephrectomy to the subsequent consecutive 13 patients undergoing robotic assisted partial nephrectomy for small renal tumors. All patients had normal contralateral kidney appearance on cross sectional imaging. A similar transperitoneal technique was employed for both cohorts. A 4-arm technique was used for the robotic cases using the da Vinci (Intuitive Surgical, Sunnyvale, USA) surgical system. Patient demographics, tumor characteristics, intraoperative, and postoperative data including tumor size, warm ischemia time, and estimated blood loss (EBL) were compared using Student t-test, Wilcoxon rank-sum, or Chi square test as appropriate. RESULTS: All cases were completed laparoscopically or with robotic assistance without conversion to open surgery. Demographic data were not statistically different between the two groups. Warm ischemia time (WIT) was shorter in the robotic group: 29.7 minutes versus 39.9 minutes for the laparoscopic group (p < 0.0001). Operative time was longer in the robotic group: 253 versus 352 minutes (p < 0.0001). Mean hospital stay and postoperative complication rates were not statistically different. Two (13%) of patients in the laparoscopic group required conversion of partial nephrectomy to radical nephrectomy while none did in the robotic group. Final pathology revealed negative margins in all cases. CONCLUSIONS: Robotic partial nephrectomy resulted in decreased WIT as compared to the conventional laparoscopic approach. Total operating time was increased in the robotic group.

Symptomatic Ureteral Metastasis from Colon Adenocarcinoma.

Background: Symptomatic ureteral obstruction from a nonurologic metachronous metastatic malignancy is an unusual phenomenon that is underreported in the literature. This potential etiology for ureteral obstruction warrants consideration by the practicing urologist during a comprehensive evaluation as it may alter prognosis and management options for the afflicted patient. Case Presentation: An 80-year-old Caucasian man with a remote history of prostate cancer and colon cancer presented with new unilateral ureteral obstruction characterized by hydronephrosis, acute kidney injury, and right-sided abdominal pain. A high clinical index of suspicion ultimately leads to the diagnosis of metastatic colon cancer on ureteral biopsy specimen. Conclusion: Evaluation of symptomatic ureteral obstruction in a patient with a significant cancer history should include nonurologic malignant obstruction. Diligence in evaluation of the etiology of the ureteral stricture with repeat biopsies should be undertaken if there is clinical concern. Nephroureterectomy should be part of patient counseling for management of long segment malignant ureteral stricture disease.

A Novel Technique of Ureteral Stricture Measurement: Impact on Diagnosis and Subsequent Management.

Background: Appropriate surgical management of ureteral strictures is dependent on not only the etiology of the stricture but also its location and characteristics. Stricture length and location play a significant role in potential surgical options, yet accurate evaluation of these features is limited. We present a case of a complex ureteral stricture where employment of an endoscopic tool in a novel manner helped to better evaluate the patient and provide more precise counseling in the preoperative setting. Case Presentation: A 65-year-old Caucasian man with a history of nephrolithiasis developed a complex ureteral stricture secondary to his calculus disease and prior instrumentation. His stricture was causing obstruction of his left collecting system and the patient was interested in a reconstructive procedure. We present a novel use for a pre-existing endoscopic tool that helped to more accurately delineate the characteristics of his ureteral stricture and improved preoperative planning. Conclusion: Determination of precise stricture length and location is of utmost importance for preoperative patient counseling and surgical planning. Where more sophisticated calibration technology is not available, use of an angiographic catheter during diagnostic endoscopy can improve preoperative assessment and surgical planning for complex ureteral reconstructive procedures.