Different ureteral access sheaths sizes for retrograde intrarenal surgery.

PURPOSE: There is a trend toward miniaturization in endourological stone therapy. Good visibility, intrarenal pressures and temperature control should be ensured by ureteral sheaths. In the context of the present study, 10/12 Charr. sheaths and 12/14 Charr. sheaths for flexible ureterorenoscopy were investigated regarding stone-free rate, complication rate and efficacy for laser lithotripsy. METHODS: From January 2020 to January 2022, 100 patients each with kidney stone up to 1.5 cm in diameter were included in the study. Use of a 12/14 Charr. vs. 10/12 Charr. ureteral sheath for flexible ureterorenoscopy was compared. Perioperative data, stone size, volume and density, laser energy, laser duration, stone-free rates and complications based on Clavien-Dindo classification were retrospectively analyzed. RESULTS: For both groups of ureteral access sheaths, there were no differences in median surgery duration (10/12 Charr: 29 min (7-105 min) vs. 12/14 Charr: 34 min (9-95 min); p = 0.33), overall complication rate (p = 0.61) and hospitalization (p = 0.155). There were no differences in stone-free rates (97.9% vs. 92.7%, p = 0.37). Laser lithotripsy duration usingholmium laser was 1.9 min (0.1-10.8 min) vs. 3.8 min (0.2-20.7 min) (p < 0.01) and applied laser energy was 3.1 J (0.15 J-10.29 J) vs. 6.8 J (1.07 J-26.77 J) (p < 0.01) for 12/14 Charr. sheaths and 10/12 Charr. sheaths, respectively. CONCLUSION: In terms of stone-free rates, there are no differences between the 10/12 and 12/14 Charr. ureteral access sheaths. The laser duration and energy was increased with 10/12 Charr. sheaths without showing increased risk for clinical complications like trauma or inflammation.

Salvage Radiotherapy for Recurrent Prostate Cancer after High-Intensity Focused Ultrasound Therapy: Quality of Life and Functional Outcome.

INTRODUCTION: The aim of this study was to evaluate toxicity, oncological and functional outcome, and quality of life after salvage radiotherapy for recurrent prostate cancer after high-intensity focused ultrasound (HIFU) therapy. METHODS: A total of 13 patients undergoing salvage radiotherapy for biopsy-proven prostate cancer recurrence after HIFU therapy were included and followed up every 3 months. Oncological outcome (by PSA measurements), toxicity (according to CTCAE criteria), and functional outcome were evaluated. Quality of life was assessed by standardized questionnaires (QLQ-C30 and QLQ-PR25) at baseline, 3 months, and 12 months after salvage treatment. RESULTS: Median age of patients was 80 years (interquartile range [IQR] 75-82). Patients underwent normofractionated salvage radiotherapy with median 73.6 Gy. PSA nadir was reached at 6 months and was 0.2 ng/mL. Median follow-up was 76 months (IQR 55-96). Biochemical recurrence occurred in 3 patients (23.1%) at a median of 36.4 months. No gastrointestinal (GI) or genitourinary (GU) toxicity ≥ grade 3 was noted during follow-up. Early and late grade II GI toxicity occurred in 1 patient (7.7%), respectively. GU toxicity grade II was noted in up to 53.8% at 3 months and 61.5% at 12 months. In terms of health-related quality of life, there was no statistically significant difference at 3 and 12 months compared to the baseline. Only differences were seen in sexual functioning (3 and 12 months) and in diarrhea (3 months), affecting patients' wellbeing. DISCUSSION/CONCLUSION: Salvage radiotherapy after HIFU treatment can be performed safely, thereby providing acceptable recurrence-free survival without severe impact on post-interventional quality of life.

A Forgotten Ureteral Stent: Potential Risks for the Urinary Function.

A 32-year-old man presented with painless macrohaematuria. An endoscopic stone removal of the upper moiety of a left double kidney with ureter duplex was performed 4 years ago. The inserted ureteral catheter (DJ) was not removed although it was communicated to the patient and written in the discharge report. The DJ led to a large bladder stone, a total incrustation of the DJ, and a staghorn calculus of the upper moiety. Furthermore, renal function scintigraphy showed no clinically significant function of the upper moiety. Therefore, a heminephrectomy was performed with corresponding ureterectomy and sectio alta for bladder stone removal.

Magnetic resonance imaging-guided transurethral ultrasound ablation in patients with localised prostate cancer: 3-year outcomes of a prospective Phase I study.

OBJECTIVES: To report the 3-year follow-up of a Phase I study of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) in 30 men with localised prostate cancer. Favourable 12-month safety and ablation precision were previously described. PATIENTS AND METHODS: As a mandated safety criterion, TULSA was delivered as near whole-gland ablation, applying 3-mm margins sparing 10% of peripheral prostate tissue in 30 men. After 12-month biopsy and MRI, biannual follow-up included prostate-specific antigen (PSA), adverse events (AEs), and functional quality-of-life assessment, with repeat systematic biopsy at 3 years. RESULTS: A 3-year follow-up was completed by 22 patients. Between 1 and 3 years, there were no new serious or severe AEs. Urinary and bowel function remained stable. Erectile function recovered by 1 year and was stable at 3 years. The PSA level decreased 95% to a median (interquartile range) nadir of 0.33 (0.1-0.4) ng/mL, stable to 0.8 (0.4-1.6) ng/mL at 3 years. Serial biopsies identified clinically significant disease in 10/29 men (34%) and any cancer in 17/29 (59%). By 3 years, seven men had recurrence (four histological, three biochemical) and had undergone salvage therapy without complications (including six prostatectomies). At 3 years, three of 22 men refused biopsy, and two of the 22 (9%) had clinically significant disease (one new, one persistent). Predictors of salvage therapy requirement included less extensive ablation coverage and higher PSA nadir. CONCLUSION: With 3-year Phase I follow-up, TULSA demonstrates safe and precise ablation for men with localised prostate cancer, providing predictable PSA and biopsy outcomes, without affecting functional abilities or precluding salvage therapy.

External validation of two MRI-based risk calculators in prostate cancer diagnosis.

BACKGROUND: The diagnosis of (significant) prostate cancer ((s)PC) is impeded by overdiagnosis and unnecessary biopsy. Risk calculators (RC) have been developed to mitigate these issues. Contemporary RCs integrate clinical characteristics with mpMRI findings. OBJECTIVE: To validate two of these models-the MRI-ERSPC-RC-3/4 and the risk model of van Leeuwen. METHODS: 265 men with clinical suspicion of PC were enrolled. Every patient received a prebiopsy mpMRI, which was reported according to PI-RADS v2.1, followed by MRI/TRUS fusion-biopsy. Cancers with ISUP grade ≥ 2 were classified as sPC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statistical analysis was performed by comparing discrimination, calibration, and clinical utility RESULTS: There was no significant difference in discrimination between the RCs. The MRI-ERSPC-RC-3/4-RC showed a nearly ideal calibration-slope (0.94; 95% CI 0.68-1.20) than the van Leeuwen model (0.70; 95% CI 0.52-0.88). Within a threshold range up to 9% for a sPC, the MRI-ERSPC-RC-3/4-RC shows a greater net benefit than the van Leeuwen model. From 10 to 15%, the van Leeuwen model showed a higher net benefit compared to the MRI-ERSP-3/4-RC. For a risk threshold of 15%, the van Leeuwen model would avoid 24% vs. 14% compared to the MRI-ERSPC-RC-3/4 model; 6% vs. 5% sPC would be overlooked, respectively. CONCLUSION: Both risk models supply accurate results and reduce the number of biopsies and basically no sPC were overlooked. The van Leeuwen model suggests a better balance between unnecessary biopsies and overlooked sPC at thresholds range of 10-15%. The MRI-ERSPC-RC-3/4 risk model provides better overall calibration.

Combination of Robotic Pyeloplasty and Percutaneous Renal Surgery for Simultaneous Treatment of Ureteropelvic Junction Obstruction and Calyx Stones.

INTRODUCTION: Ureteropelvic junction obstruction (UPJO) and the simultaneous presence of kidney calyx stones represent a challenge for renal surgery. We present a novel technique for the simultaneous treatment of UPJO by robotic pyeloplasty in combination with the percutaneous endoscopic treatment of kidney calyx stones by flexible nephroscopy. PATIENTS AND METHODS: Between January 2018 and February 2020, 4 patients were diagnosed with UPJO and simultaneous pelvic or calyceal stones. UPJO was treated by conventional robotic pyeloplasty. After opening the renal pelvis, a flexible 16-French cystoscope was introduced via the 12-mm assistant trocar into the renal pelvis. The kidney calyx stones (n = 1-15) were removed endoscopically through a flexible nephroscope using a Dormia helical basket. Before suturing the anastomosis of the renal pelvis, a ureter stent was inserted. RESULTS: After the procedure, all patients were stone free. Using the Clavien-Dindo classification, no complications were noted. The mean size of the calculi was 6.69 mm (range: 1-25). Up to 15 calyx stones (mean 3.46) were removed per patient. A complete stone clearance confirmed by postoperative X-ray imaging was achieved in all patients. The mean operative time was 149 min (range: 130-178). Mean hospital stay was 7 days (7-8). The urethral stent was removed after 4-6 weeks. CONCLUSIONS: Robotic management of UPJO and simultaneous flexible nephroscopy for removal of calyceal stones is an effective treatment in 1 session. Combining robotic surgery with flexible percutaneous renal surgery is a feasible, safe, and effective method of the treatment of UPJO and concomitant calyceal stones.

External validation of novel magnetic resonance imaging-based models for prostate cancer prediction.

OBJECTIVES: To validate, in an external cohort, three novel risk models, including the recently updated European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator, that combine multiparametric magnetic resonance imaging (mpMRI) and clinical variables to predict clinically significant prostate cancer (PCa). PATIENTS AND METHODS: We retrospectively analysed 307 men who underwent mpMRI prior to transperineal ultrasound fusion biopsy between October 2015 and July 2018 at two German centres. mpMRI was rated by Prostate Imaging Reporting and Data System (PI-RADS) v2.0 and clinically significant PCa was defined as International Society of Urological Pathology Gleason grade group ≥2. The prediction performance of the three models (MRI-ERSPC-3/4, and two risk models published by Radtke et al. and Distler et al., ModRad and ModDis) were compared using receiver-operating characteristic (ROC) curve analyses, with area under the ROC curve (AUC), calibration curve analyses and decision curves used to assess net benefit. RESULTS: The AUCs of the three novel models (MRI-ERSPC-3/4, ModRad and ModDis) were 0.82, 0.85 and 0.83, respectively. Calibration curve analyses showed the best intercept for MRI-ERSPC-3 and -4 of 0.35 and 0.76. Net benefit analyses indicated clear benefit of the MRI-ERSPC-3/4 risk models compared with the other two validated models. The MRI-ERSPC-3/4 risk models demonstrated a discrimination benefit for a risk threshold of up to 15% for clinically significant PCa as compared to the other risk models. CONCLUSION: In our external validation of three novel prostate cancer risk models, which incorporate mpMRI findings, a head-to-head comparison indicated that the MRI-ERSPC-3/4 risk model in particular could help to reduce unnecessary biopsies.

Ablation energies for focal treatment of prostate cancer.

CONTEXT: In recent years, focal therapy has emerged as a treatment option for a selected group of men with localized prostate cancer. Cryotherapy and high-intensity focused ultrasound (HIFU) are the most investigated types of focal treatment with other options currently under evaluation. OBJECTIVE: The objective of the study was to give a comprehensive overview of six available focal treatment options for prostate cancer with their rationale, delivery mechanism, and outcomes. INFORMATION ACQUISITION: The SIU ICUD chapter on available Energies to Treat Prostate Cancer was used as a guide to describe the different technologies. For outcomes, a literature search was conducted using PubMed key words including focal therapy, HIFU, cryotherapy, irreversible electroporation, vascular-targeted photodynamic therapy, laser interstitial therapy, radiofrequency ablation, microwave therapy, and their synonyms in MeSH terms. CONCLUSION: Focal therapy appears to have encouraging outcomes on quality of life and urinary and erectile function. For oncological outcomes, it is challenging to fully interpret the outcomes due to heterogeneity in patient selection and short-term follow-up.

Prospective Multicenter Phase II Study on Focal Therapy (Hemiablation) of the Prostate with High Intensity Focused Ultrasound.

PURPOSE: We evaluated focal therapy with high intensity focused ultrasound hemiablation in a prospective trial. MATERIALS AND METHODS: We performed a prospective, multicenter, single arm study in patients with unilateral low/intermediate risk prostate cancer who were treated from April 2013 through March 2016 in Germany in AUO (Arbeitsgemeinschaft Urologische Onkologie) Study Protocol AP 68/11. Unilateral prostate cancer was assessed by transrectal ultrasound guided biopsy and multiparametric magnetic resonance imaging. Hemiablation was done using the Ablatherm® or the Focal One® device. The oncologic outcome was assessed by the salvage treatment rate, multiparametric magnetic resonance imaging and rebiopsy at 12 months. Functional outcome, quality of life, anxiety and depression were measured by validated questionnaires at baseline and every 3 months. RESULTS: Of the 54 recruited patients 51 completed 12-month or greater visits. Mean ± SD followup was 17.4 ± 4.5 months. Mean prostate specific antigen decreased from 6.2 ± 2.0 to 2.9 ± 1.9 ng/ml at 12 months (p <0.001). Biopsy at 12 months was positive for any prostate cancer and for clinically significant prostate cancer in 13 (26.5%) and 4 (8.2%) of the 49 patients, respectively. Posttreatment multiparametric magnetic resonance imaging had limited 25% sensitivity for clinically significant prostate cancer. Ten patients (19.6%) underwent salvage treatment. Potency was maintained in 21 of the 30 men who were potent preoperatively. There was no increase in incontinence. Quality of life, anxiety and depression did not change postoperatively. The study was limited by a short followup and the lack of a control arm. CONCLUSIONS: Focal therapy hemiablation is safe with little alteration of functional outcome. The oncologic outcome is acceptable on short-term followup. Followup multiparametric magnetic resonance imaging performed poorly and should not replace repeat biopsy. Focal therapy has no impact on posttreatment anxiety and depression.

Complete bladder neck preservation promotes long-term post-prostatectomy continence without compromising midterm oncological outcome: analysis of a randomised controlled cohort.

PURPOSE: The only RCT available on complete bladder neck preservation (cBNP) during radical prostatectomy reported superior continence and QoL outcomes in the first 12 months after cBNP. We provide the first data on long-term urinary continence, QoL and biochemical recurrence (BCR) after complete bladder neck preservation in a randomised controlled cohort. METHODS: After approval by IRB, 199 men recruited for the randomised, controlled single-blind Heidelberger cBNP Study had prostatectomy performed with (cBNP) or without (noBNP) complete bladder neck preservation. Only men with renewed consent for this follow-up were evaluated for continence, QoL outcomes and BCR by ICIQ-SF self-assessment questionnaire, Pad-use/day and PSA levels. Students-t test, Pearson´s Chi-square, Fishers exact test and multiple logistic regression analyses were applied. RESULTS: Mean follow-up was approx. 4 years. There were no significant differences in baseline characteristics between responders/non-responders or between study groups. We noted significantly higher continence rates (p = 0.004), less pad-use (p < 0.001), reduced frequency (p = 0.023) and amount (p = 0.009) of urine loss, and higher QoL outcomes (p = 0.012) after cBNP. A younger age positively influenced continence (OR = 0.91), but the multivariate analysis found cBNP to be the only independent predictor of continence (p = 0.008; OR = 8.1). pT stage was the only predictor for positive surgical margins (PSM; p < 0.001). There was no significant difference in pT stage (p = 0.23) or BCR (p = 0.63) between study groups and also no significant correlation between BCR and presence (p = 0.26) or localisation (p = 0.11) of PSM, nerve sparing (p = 0.70), surgeon (p = 0.41), preoperative PSA (p = 0.53) or pT stage (p = 0.17). No cancer-related death was noted. CONCLUSIONS: Results of this first follow-up on a prospective randomised controlled cohort demonstrate that cBNP is associated with significantly higher continence and QoL outcomes without compromising cancer control making cBNP a novel objective during radical prostatectomy.

The Value of PSA Density in Combination with PI-RADS™ for the Accuracy of Prostate Cancer Prediction.

PURPOSE: Multiparametric magnetic resonance imaging has an emerging role in prostate cancer diagnostics. In addition, clinical information is a reliable predictor of significant prostate cancer. We analyzed whether the negative predictive value of multiparametric magnetic resonance imaging to rule out significant prostate cancer could be improved using clinical factors, especially prostate specific antigen density. MATERIALS AND METHODS: A total of 1,040 consecutive men with suspicion of prostate cancer underwent multiparametric magnetic resonance imaging first, followed by transperineal systematic and magnetic resonance imaging-transrectal ultrasound fusion guided biopsy. Logistic regression analyses were performed to test different clinical factors as predictors of significant prostate cancer and build nomograms. To simplify these nomograms for clinical use patients were stratified into 3 prostate specific antigen density groups, including group 1-less than 0.07, group 2-0.07 to 0.15 and group 3-greater than 0.15 ng/ml/ml. After stratification we calculated the negative predictive value of a PI-RADS (Prostate Imaging Reporting and Data System) Likert score of less than 3. Significant prostate cancer was defined as a Gleason score of 3 + 4 or greater. High grade prostate cancer was defined as a Gleason score of 4 + 3 or greater. RESULTS: Overall 451 men were diagnosed with significant prostate cancer, including 187 with a Gleason score of 4 + 3 or greater. On ROC curve analyses the predictive power of the developed nomogram for significant prostate cancer showed a higher AUC than that of PI-RADS alone (0.79 vs 0.75, p <0.001). The negative predictive value of harboring significant prostate cancer increased in men with unsuspicious magnetic resonance imaging from 79% up to 89% when prostate specific antigen density was 0.15 ng/ml/ml or less. In the repeat biopsy setting the negative predictive value of significant prostate cancer increased from 83% to 93%. The negative predictive value to harbor high grade prostate cancer increased from 92% up to 98% in the entire cohort. CONCLUSIONS: Using prostate specific antigen density combined with multiparametric magnetic resonance imaging improved the negative predictive value of PI-RADS scoring. By increasing the probability of ruling out significant prostate cancer approximately 20% of unnecessary biopsies could be avoided safely.

Ureterocystoneostomy in complex oncological cases with an "Uebelhoer" modified Boari bladder flap.

PURPOSE: The study aims to describe the technique and analyze the outcome of an arcuated bladder incision with building of a triangular flap, first described by Uebelhoer (UBBF), as a modification of the classical rectangular Boari bladder flap (BBF), that is often viable, but can present difficulties, such as reduced flap vascularization and mobility in pretreated patients. METHODS: Twelve consecutive patients with distal or mid ureteral leakage or stenosis, that underwent UBBF, were retrospectively analyzed. We assessed postoperative morbidity using Clavien-Dindo classification. Short- and long-term functional outcomes were assessed using glomerular filtration rate (GFR), ultrasound, and renal scintigraphy. RESULTS: Patients underwent UBBF during initial oncological surgery in five cases and due to ureteral defects following oncological surgery or radiotherapy in seven cases. Median patient age was 57 (interquartile range (IQR) 46-72), defect length was 7.5 cm (IQR 5-8 cm), and median follow-up period was 41 (IQR 36-48) months. In short-term follow-up, 11/13 postoperative morbidities were Clavien-Dindo level I-II complications, mostly infections. Two level IIIa complications occurred. One anastomotic leakage was treated sufficiently with temporarily ureteral stenting and one voiding disorder needed intervention. In the long-term follow-up, 84% of patients had improved or constant GFR. In the one-year renal scintigraphy, no urodynamically relevant voiding disorder occurred. CONCLUSIONS: The UBBF is a reliable procedure to reconstruct ureteral trauma even in complex oncological, pretreated patients suffering from distal or mid ureteral defects. It can be performed easily by a modified arcuate incision and provides good long-term functional outcomes.

Effective downsizing but enhanced intratumoral heterogeneity following neoadjuvant sorafenib in patients with non-metastatic renal cell carcinoma.

OBJECTIVES: To evaluate the safety and feasibility of sorafenib prior to surgery for downsizing tumors in patients with non-metastatic cT1-3 renal tumors together with a characterization of functional intratumoral heterogeneity (ITH). MATERIALS AND METHODS: The effects of 4-week sorafenib prior to curative surgery were assessed in a prospective, single-center, randomized, placebo-controlled, double-blinded, pilot trial in patients with T1-3N0M0 renal cell carcinoma (RCC). Patients received sorafenib or placebo for 28 days prior to surgery. MRI was performed at baseline and prior to surgery to calculate tumor volume. The clinical responses were further characterized on the molecular level by immunohistochemical stainings for Ki-67, cleaved caspase-3, and CD31. RESULTS: After enrolling 20 patients into the study, 14 patients were randomized, of which 12 patients were available for analysis. While no significant change in tumor volume was seen for placebo (range = -24.2-0.2%) a reduction of 29.0% (range = -4.9-61.1%) was detected for sorafenib (p < 0.05). Primary renal tumor diameter changed from 10.6 cm (range = 6.5-10.8) to 10.7 cm (range = 6.7-11.1) in the placebo group, and from 5.4 cm (range = 4.3-7.3) to 4.4 cm (range = 3.5-6.8) for the sorafenib group, at baseline vs. 28 days of treatment. Correlative assessment of proliferation, apoptosis, and microvessel density revealed an enhanced degree of functional ITH in treated patients suggesting adaptive and/or regenerative processes with potential relevance for the development of drug resistance. CONCLUSIONS: Sorafenib in standard dosage, given preoperatively for 28 days, was clinically active in downsizing tumors in patients with locally confined, non-metastatic RCC together but led to an enhanced functional ITH in the residual tumor tissue.

Results of a Patient Survey for Assessment Services in Renal Transplant Patients With a History of Cancer.

Patients with cancer who require a kidney transplant often face a prolonged time on the waiting list to ensure a sufficient relapse-free time. Patients and relatives were invited to the patient assessment service where they get an individualized risk assessment and a recommendation for transplantation and waiting period directly from an expert panel. We investigated in 31 patients who filled out questionnaires concerning depression, anxiety, distress, and quality of life and were interviewed for their satisfaction, experiences, and circumstances of the counseling. In 12 (39%) of the 31 patients, a recommendation for transplantation could be made, although the regular waiting period was not yet achieved. The assessment service was received as very good or good by 22 (79%) of 28 patients. We found no relevant differences in patients with regular and shortened waiting time. An interdisciplinary assessment service is a valuable instrument to help with a decision-making between 2 life-threatening conditions.

Impact of resection and systemic therapy on the survival of patients with brain metastasis of metastatic renal cell carcinoma.

Patients with brain metastasis (BM) from renal cell carcinoma (RCC) are associated with poor prognosis. Between 1990 and 2015, data of consecutive RCC patients with BM were retrospectively analyzed from a urologic oncologic database. The treatment outcome was evaluated by overall survival (OS), which was defined as interval from initial diagnosis of BM to death or last follow-up. Statistical analyses of clinical and pathological variables were performed using Cox regression and the Kaplan-Meier method. A total of 116 RCC patients with BM were included. Median time from initial diagnosis of RCC to BM was 15.8 months (95 % CI 11.6-20.0). Median OS after diagnosis of brain metastases of the whole cohort was 5.8 months (95 % CI 4.3-7.2). On multivariate Cox regression analysis, age and histology of non-clear cell RCC were associated with poorer outcome, while targeted therapy (n = 26) (OS 9.9 months, 95 % CI 3.3-16.5) and BM resection (n = 33) (OS 24.7 months, 95 % CI 4-40) were associated with better survival. Furthermore, patients who underwent both targeted therapy and BM resection (n = 5) had the best outcome with median OS of 52.4 months. In conclusion, BM from RCC is associated with a poor oncological outcome. Furthermore, age and histology of non-clear cell RCC are risk factors for poor prognosis. Patients with resectable BM may comprise a better prognostic group. Here, a better OS for resected than unresected patients was observed, which warrants BM resection. A combined modality approach of resection and targeted therapy appears to further improve the outcome of these patients while additional radiation seems to add no benefit.

Renal cell carcinoma with inferior vena cava involvement: Prognostic effect of tumor thrombus consistency on cancer specific survival.

BACKGROUND: Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort. METHODS: The records of 413 patients collected by the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan-Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors. RESULTS: VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS. CONCLUSIONS: In the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. 2016;114:764-768. © 2016 Wiley Periodicals, Inc.

PBRM1 (BAF180) protein is functionally regulated by p53-induced protein degradation in renal cell carcinomas.

About 40% of clear-cell renal cell carcinomas (ccRCC) harbour mutations in Polybromo-1 (PBRM1), encoding the BAF180 subunit of a SWI/SNF chromatin remodelling complex. This qualifies PBRM1 as a major cancer gene in ccRCC. The PBRM1 protein alters chromatin structure and its known functions include transcriptional regulation by controlling the accessibility of DNA and influencing p53 transcriptional activity. Since little is known about the regulation of PBRM1, we studied possible mechanisms and interaction partners involved in the regulation of PBRM1 expression. Activation of p53 in RCC cells resulted in a marked decrease of PBRM1 protein levels. This effect was abolished by siRNA-mediated down-regulation of p53, and transcriptional activity was not crucial for p53-dependent PBRM1 regulation. Pulse-chase experiments determined post-translational protein degradation to be the underlying mechanism for p53-dependent PBRM1 regulation, which was accordingly inhibited by proteasome inhibitors. The effects of p53 activation on PBRM1 expression were confirmed in RCC tissue ex vivo. Our results demonstrate that PBRM1 is a target of p53-induced proteasomal protein degradation and provide further evidence for the influence of PBRM1 on p53 function in RCC tumour cells. Considering the paramount role of p53 in carcinogenesis and the presumptive impact of PBRM1 in RCC development, this novel regulation mechanism might be therapeutically exploited in the future.

Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy.

Diabetic nephropathy is a growing health concern with characteristic sterile inflammation. As the underlying mechanisms of this inflammation remain poorly defined, specific therapies targeting sterile inflammation in diabetic nephropathy are lacking. Intriguingly, an association of diabetic nephropathy with inflammasome activation has recently been shown, but the pathophysiological relevance of this finding remains unknown. Within glomeruli, inflammasome activation was detected in endothelial cells and podocytes in diabetic humans and mice and in glucose-stressed glomerular endothelial cells and podocytes in vitro. Abolishing Nlrp3 or caspase-1 expression in bone marrow-derived cells fails to protect mice against diabetic nephropathy. Conversely, Nlrp3-deficient mice are protected against diabetic nephropathy despite transplantation of wild-type bone marrow. Pharmacological IL-1R antagonism prevented or even reversed diabetic nephropathy in mice. Mitochondrial reactive oxygen species (ROS) activate the Nlrp3 inflammasome in glucose or advanced glycation end product stressed podocytes. Inhibition of mitochondrial ROS prevents glomerular inflammasome activation and nephropathy in diabetic mice. Thus, mitochondrial ROS and Nlrp3-inflammasome activation in non-myeloid-derived cells aggravate diabetic nephropathy. Targeting the inflammasome may be a potential therapeutic approach to diabetic nephropathy.

A European multicenter randomized noninferiority trial comparing 180 W GreenLight XPS laser vaporization and transurethral resection of the prostate for the treatment of benign prostatic obstruction: 12-month results of the GOLIATH study.

PURPOSE: We present the 1-year results of the GOLIATH prospective randomized controlled trial comparing transurethral resection of the prostate to GreenLight XPS for the treatment of men with nonneurogenic lower urinary tract symptoms due to prostate enlargement. The updated results at 1 year show that transurethral resection of the prostate and GreenLight XPS remain equivalent, and confirm the therapeutic durability of both procedures. We also report 1-year followup data from several functional questionnaires (OABq-SF, ICIQ-SF and IIEF-5) and objective assessments. MATERIALS AND METHODS: A total of 291 patients were enrolled at 29 sites in 9 European countries. Patients were randomized 1:1 to undergo GreenLight XPS or transurethral resection of the prostate. The trial was designed to evaluate the hypothesis that GreenLight XPS is noninferior to transurethral resection of the prostate on the International Prostate Symptom Score at 6 months. Several objective parameters were assessed, including maximum urinary flow rate, post-void residual urine volume, prostate volume and prostate specific antigen, in addition to functional questionnaires and adverse events at each followup. RESULTS: Of the 291 enrolled patients 281 were randomized and 269 received treatment. Noninferiority of GreenLight XPS was maintained at 12 months. Maximum urinary flow rate, post-void residual urine volume, prostate volume and prostate specific antigen were not statistically different between the treatment arms at 12 months. The complication-free rate at 1 year was 84.6% after GreenLight XPS vs 80.5% after transurethral resection of the prostate. At 12 months 4 patients treated with GreenLight XPS and 4 who underwent transurethral resection of the prostate had unresolved urinary incontinence. CONCLUSIONS: Followup at 1 year demonstrated that photoselective vaporization of the prostate produced efficacy outcomes similar to those of transurethral resection of the prostate. The complication-free rates and overall reintervention rates were comparable between the treatment groups.

Impact of synchronous metastasis distribution on cancer specific survival in renal cell carcinoma after radical nephrectomy with tumor thrombectomy.

PURPOSE: Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival. MATERIALS AND METHODS: The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates. RESULTS: Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival. CONCLUSIONS: In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease.