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Abstract Background Clear cell renal cell cancer (ccRCC), the 8th leading cause of cancer-related death in the US, is challenging to treat due to high level intratumoral heterogeneity (ITH) and the paucity of druggable driver mutations. CcRCC is unusual for its high frequency of epigenetic regulator mutations, such as the SETD2 histone H3 lysine 36 trimethylase (H3K36me3), and low frequency of traditional cancer driver mutations. In this work, we examined epigenetic level ITH and defined its relationships with pathologic features, aspects of tumor biology, and SETD2 mutations. Results A multi-region sampling approach coupled with EPIC DNA methylation arrays was conducted on a cohort of normal kidney and ccRCC. ITH was assessed using DNA methylation (5mC) and CNV-based entropy and Euclidian distances. We found elevated 5mC heterogeneity and entropy in ccRCC relative to normal kidney. Variable CpGs are highly enriched in enhancer regions. Using intra-class correlation coefficient analysis, we identified CpGs that segregate tumor regions according to clinical phenotypes related to tumor aggressiveness. SETD2 wild-type tumors overall possess greater 5mC and copy number ITH than SETD2 mutant tumor regions, suggesting SETD2 loss contributes to a distinct epigenome. Finally, coupling our regional data with TCGA, we identified a 5mC signature that links regions within a primary tumor with metastatic potential. Conclusion Taken together, our results reveal marked levels of epigenetic ITH in ccRCC that are linked to clinically relevant tumor phenotypes and could translate into novel epigenetic biomarkers.

Abstract Purpose/Objectives Holmium laser enucleation of the prostate (HoLEP) is commonly performed in patients with significant bladder outlet obstruction. However, there are few reports on the toxicity of external beam irradiation (RT) for prostate cancer in patients after prior HoLEP. In this study, we evaluate the side effects and treatment outcomes of RT after HoLEP. Materials/Methods Eighteen patients who had HoLEP and subsequently received RT for prostate cancer were included. Data collected included patient and disease characteristics, urinary function, and radiation dose. Acute and late urinary (GU) and gastrointestinal (GI) side effects were evaluated. Disease control and survival rates were calculated using Kaplan–Meier method. Results Median follow‐up was 18 months (range: 4–46 months). Median prostate volume was 107 ml before HoLEP and 24 ml after HoLEP. Median International Prostate Symptom Score (IPSS) was 17 (range: 5–32) before HoLEP. Median decline in IPSS score after HoLEP was 7 (range: −2–21). On uroflow study, peak flow rate, and post‐void residual were significantly improved after HoLEP. After radiation, peak flow rate and average flow rate showed a decline but remained significantly improved compared to pre‐HoLEP measurements. Maximum acute Common Terminology Criteria for Adverse Events (CTCAE) adverse events were 12 grade 1 and 3 grade 2 for GU, and 3 grade 1 for GI, respectively. Maximum late adverse events were 13 grade 1 and 2 grade 2 for GU, and all grade 0 for GI, respectively. At last follow‐up, there were 8 grade 1 and 1 grade 2 late GU, and 3 grade 1 late GI adverse events, respectively. There was no significant increase in urinary incontinence after RT compared to before RT. The 18‐month biochemical control, local control, distant control rates were 78%, 94%, and 80%, respectively. Conclusions Patients who received RT as definitive treatment for prostate cancer after prior HoLEP had low risk of serious acute and late side effects. HoLEP can be safely performed and should be considered in patients with significant bladder outlet obstruction and large prostate volume before RT.

Purpose: To assess the efficacy of placing a polyethylene glycol (PEG) spacing hydrogel in patients undergoing proton beam radiation therapy for prostate cancer. This study also aims to assess the effect on rectal radiation dose of prostate–rectum separation in various anatomic planes. Methods and Materials: Seventy-two consecutive prostate cancer patients undergoing conventionally fractionated pencil beam scanning proton radiation therapy with and without hydrogel placement were compared. Magnetic resonance images taken after hydrogel placement measured prostate–rectum separation and were correlated to rectal dosing and rectal toxicity. Univariate analysis of clinical variables and radiation dosing was conducted using nonparametric Wilcoxon rank-sum test with continuity correction between groups (hydrogel spacer vs controls). Spearman's rank correlation coefficient assessed relationships between the various anatomic dimensions of perirectal space and rectal radiation dosing. Results: Fifty-one patients had hydrogel placement before therapy and 21 did not. There was a 42.2% reduction in rectal dosing (mL3 rectum) in hydrogel patients (P

Purpose To compare the inter-observer variability of apparent diffusion coefficient (ADC) values of prostate lesions measured by 2D-region of interest (ROI) with and without specific measurement instruction. Methods Forty lesions in 40 patients who underwent prostate MR followed by targeted prostate biopsy were evaluated. A multi-reader study (10 readers) was performed to assess the agreement of ADC values between 2D-ROI without specific instruction and 2D-ROI with specific instruction to place a 9-pixel size 2D-ROI covering the lowest ADC area. The computer script generated multiple overlapping 9-pixel 2D-ROIs within a 3D-ROI encompassing the entire lesion placed by a single reader. The lowest mean ADC values from each 2D-small-ROI were used as reference values. Inter-observer agreement was assessed using the Bland-Altman plot. Intraclass correlation coefficient (ICC) was assessed between ADC values measured by 10 readers and the computer-calculated reference values. Results Ten lesions were benign, 6 were Gleason score 6 prostate carcinoma (PCa), and 24 were clinically significant PCa. The mean±SD ADC reference value by 9-pixel-ROI was 733 ± 186 (10−6 mm2/s). The 95% limits of agreement of ADC values among readers were better with specific instruction (±112) than those without (±205). ICC between reader-measured ADC values and computer-calculated reference values ranged from 0.736–0.949 with specific instruction and 0.349–0.919 without specific instruction. Conclusion Interobserver agreement of ADC values can be improved by indicating a measurement method (use of a specific ROI size covering the lowest ADC area).

Objective: To identify factors that predict kidney stone patient's ability to produce 2.5 L urine volume per day on metabolic evaluation. Patients and Methods: In a retrospective chart review, the first analysis evaluated initial 24-hour urine collections with respect to those who achieved or did not achieve a urine volume of 2.5 L/day. The second analysis evaluated those who achieved or did not achieve a daily urine volume of 2.5 L on their subsequent collection. Several variables were assessed. Results: Patients’ initial collections (n=1100) that achieved 2.5 L/day (n=274) were of younger age and had a higher body mass index, increased urine sodium, phosphorus, calcium levels, increased protein catabolic rate, and decreased supersaturation of calcium oxalate. In the second analysis (n=273), decreased supersaturation of calcium oxalate, increased urine urea nitrogen level, and increased protein catabolic rate were observed in subsequent collections with a urine volume of 2.5 L/day or more. Patients with a diagnosis of hyponatremia were less likely to achieve 2.5 L/day urine volume. Collection date, other comorbidities, and diuretic use were not associated with achieving 2.5 L/day urine volume. Patients’ mean creatinine per kilogram for all study cohorts were within the range of adequate collection. Conclusion: Predictive factors for a urine volume of 2.5 L/day or more include increased fluid intake, higher salt and animal protein diet, elevated body mass index, and male sex. Patients with these factors may require interventions other than hydration recommendations to optimize their prevention of future kidney.

The last two decades witnessed the inception and exponential implementation of key technological advancements in laparoscopic urology. While some of these technologies thrived and became part of daily practice, others are still hindered by major challenges. This review was conducted through a comprehensive literature search in order to highlight some of the most promising technologies in laparoscopic visualization, augmented reality, and insufflation. Additionally, this review will provide an update regarding the current status of single-site and natural orifice surgery in urology.

The purpose of this publication is to document the evolution of a new surgical procedure for the treatment of carefully selected patients with organ confined localized prostate cancer. Natural orifice surgery represents a paradigm shift in the surgical approach to disease, although its adoption into clinical practice has been limited to date. This manuscript describes the development of natural orifice translumenal endoscopic surgical radical prostatectomy (NOTES RP). The laboratory, animal, preclinical and early clinical experiences are described and detailed. While the early experiences with this approach are promising and encouraging, more information is required. Despite the early successes with the procedure, long-term oncological and functional outcomes are essential and more work needs to be done to facilitate the teaching and ease of the NOTES RP.

AbstractPurpose:The goal of this study is to demonstrate the feasibility of transurethral radical prostatectomy in the canine model. We describe the surgical procedure for natural orifice translumenal endoscopic surgery-radical prostatectomy (NOTES-RP).Materials and Methods:NOTES-RP was performed on six nonsurvival male canines. The 100 watt holmium:yttrium-aluminum-garne laser, 550 μm end-firing fiber, 28F laser resectoscope, 7F stabilizing catheter, and continuous irrigation were used to radically resect the prostate. A Vest vesicourethral anastomosis was performed using a laparoscopic suture device that was delivered through the nephroscope. In the initial cases, the prostate was removed manually; for the last two cases, the prostate was removed endoscopically with a tissue morcellator.Results:NOTES-RP was successfully executed in all canines. Visualization was not obscured by bleeding. Dissection times ranged from 40 to 120 minutes. Fluid absorption was problematic in cases lasting more than 1 hour, because of the intraperitoneal location of the canine prostate and bladder.Conclusions:The feasibility and technique of NOTES-RP was successfully demonstrated in the living canine model. [ABSTRACT FROM AUTHOR]

AbstractBackground and Purpose:Innovations in minimally invasive surgery have led to the proposal of incision-free natural orifice translumenal endoscopic surgery (NOTES™). The purpose of this manuscript is to describe the initial technique of natural orifice translumenal endoscopic surgical radical prostatectomy (NOTES-RP).Materials and Methods:NOTES-RP was performed on four male cadavers in a surgical simulation laboratory setting. The 100 W holmium:yttrium-aluminum-garnet laser, 550 μm end-firing laser fiber, 26F resectoscope, 7F laser stabilizing catheter, and continuous irrigation were used to radically resect and deliver the prostate of each cadaver into the bladder. The neurovascular bundles were preserved bilaterally, as well as the dorsal venous complex, bladder neck, and external sphincter. The entire resection was performed with the laser, while a rigid offset 27F nephroscope was used to perform the vesicourethral anastomosis using a laparoscopic suture device and knot pusher in an interrupted fashion. The prostate tissue was removed endoscopically with a tissue morcellator. After the initial NOTES-RP, a pelvic exploration with biopsy of neurovascular bundles, bladder, and urethral margins was performed.Results:NOTES-RP was successfully executed in the cadaveric model. Pathologic evaluation of tissue demonstrates complete removal of all prostate tissue with preservation of the neurovascular bundles bilaterally as well as the external urinary sphincter.Conclusion:The present work demonstrates the feasibility of NOTES-RP in the cadaver model. While further testing and instrument modification are necessary before clinical application, this concept demonstrates the evolving nature of minimally invasive surgery and what could be possible for patients. [ABSTRACT FROM AUTHOR]

Background and PurposeThe role of laparoscopic radical nephrectomy (LRN) for very large renal tumors remains to be defined. We review our experience with LRN for very large (≥10 cm) renal malignancies.Patients and MethodsA retrospective analysis of 360 consecutive patients who underwent LRN for renal tumors between October 1999 and May 2007 in a tertiary academic center identified 11 patients with malignancies ≥10 cm.ResultsMedian age was 67 years (range 48–80 y), operative time was 170 minutes (range 80–240 min), estimated blood loss was 150 mL (range 50–300 mL), and length of stay was 2 days (range 1–6 d). There were two minor postoperative complications (acute renal insufficiency and ileus). Median tumor size was 12 cm (range 10–21 cm). Pathologic stage for patients with renal cell carcinoma was T2, T3a, T3b, and T4, in five, three, two, and one patient(s), respectively. One patient died after brain metastasis developed. Two patients in whom pulmonary metastases developed were still alive at last follow-up.ConclusionsLRN was successfully performed in patients with renal tumors up to 21 cm. Important considerations when performing LRN include the individual clinical picture, surgeon experience, tumor location, and patient well-being. LRN for very large tumors is feasible in properly selected patients and can have significant benefits in the palliative setting. [ABSTRACT FROM AUTHOR]

Background and PurposeMicroporous polysaccharide hemospheres (MPH) are hemostatic beads engineered from purified plant starch. MPH accelerates the natural clotting cascade by concentrating clotting factors and proteins on their surface while absorbing aqueous and low molecular weight components from blood. The purpose of this study was to determine the efficacy of MPH in achieving hemostasis in the setting of laparoscopic renal injury.Materials and MethodsIn four domestic pigs, 16 laparoscopic renal trocar injuries were created (8 each of 12 and 5 mm). A standard hand-assisted laparoscopic approach was used to each kidney so that two lesions per kidney were randomly created. MPH was applied to each treatment lesion with light pressure maintained for 60 seconds. Four of the 16 lesions, two each of 12 and 5 mm, were allowed to bleed as controls. Hemostasis was defined as no active bleeding or oozing. The animals were sacrificed at the conclusion of the procedure.ResultsThe mean time to hemostasis for the 12-mm MPH and control lesions was 196.2 ± 53.3 and 372.0 ± 225.6 seconds, while the average blood loss was 8.3 ± 3.7 and 12.0 ± 4.9 g, respectively. For the 5-mm MPH and control lesions, the average time to hemostasis was 100.2 ± 24.8 and 247.0 ± 134.4 seconds, while the average blood loss was 8.3 ± 3.8 and 9.0 ± 0.7 g, respectively. The median number of applications of the MPH for the 5- and 12-mm injuries was 1 and 2, respectively.ConclusionsMPH provided a rapid and effective means of hemostasis for laparoscopic renal parenchymal injuries in this model. Additional evaluation is warranted, however, before general application is advisable. [ABSTRACT FROM AUTHOR]

Purpose Advances in the field of surgery have recently developed a number of devices and materials to improve surgical hemostasis. The effects of one such device, saline-cooled monopolar radiofrequency electrocautery, has been well scrutinized in splenic and hepatic applications. Despite the utilization of this device in urologic surgery, the classification of the thermal effects has been poorly characterized to date. The purpose of this study was to discern the thermal characteristics of the device in the laparoscopic environment when used on renal parenchyma.Materials and Methods After institutional approval, four domestic swine were randomized to receive laparoscopic renal lesions randomly generated by either saline-cooled (25 W with saline flow rate of 4 mLmin) or standard monopolar radiofrequency electrocautery. The energy source was applied for between 1 and 11 seconds for each device in order to create a total of 64 renal lesions. Each kidney was harvested and examined by a genitourinary pathologist blinded to the treatment interval.Results The saline-cooled device provided a greater depth of coagulation effect compared to standard monopolar electrocautery at all points in time (P< 0.05). The diameter of the lesions created using saline-cooled monopolar electrocautery was greater than those created with standard electrocautery (P< 0.05).Conclusions The saline-cooled monopolar electrocautery provided an improved coagulation effect compared to standard electrocautery in the laparoscopic setting. Recognition of the time and resultant thermal consequences can help the laparoscopic surgeon plan surgical approaches for renal lesions and improve hemostasis. [ABSTRACT FROM AUTHOR]

Introduction: The objective was to analyze the diagnostic value of multiparametric magnetic resonance imaging (MRI) prostate lesion volume (PLV) and its correlation with the subsequent MRI–ultrasound (MRI-US) fusion biopsy results. Materials and Methods: Between March 2014 and July 2016, 150 men underwent MRI-US fusion biopsies at our institution. All suspicious prostate lesions were graded according to the Prostate Imaging Reporting and Data System (PIRADS) and their volumes were measured. These lesions were subsequently biopsied. All data were prospectively collected and retrospectively analyzed. The PLV of all suspicious lesions was correlated with the presence of cancer on the final MRI-US fusion biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results: There were 206 suspicious lesions identified in 150 men. The overall cancer detection rate was 102/206 (49.5%). The mean PLV for benign lesions was 0.63 ± 0.94 cm3 versus 1.44 ± 1.76 cm3 for cancerous lesions (P < 0.01). There was a statistically significant difference between the PLV of PIRADS 5 lesions when compared to PIRADS 4, 3, and 2 lesions (P < 0.0001, < 0.0001, and 0.006, respectively). The area under the curve for volume in predicting prostate cancer (PCa) was 0.66. The optimal volume for predicting PCa was 0.26 cm3 with a sensitivity, specificity, PPV, and NPV of 80.7%, 42.7%, 41.2%, and 74.6%, respectively. Conclusion: PLV may serve as a useful measure to triage patients prior to MRI-US fusion biopsy and help better understand the limits of this technology for individual patients.

Xp11.2 translocation tumor is a rare but aggressive form of renal cell carcinoma that predominantly occurs in children but also may be found in young adults. Because this type of cancer is diagnosed via histologic and chromosomal analysis, clinicians should consider translocation tumor in the differential diagnosis of patients with renal lesions and gross hematuria.