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Background: Muscarinic receptor antagonists are the standard of care for patients with overactive bladder (OAB). However, they can increase heart rate, and this can be disadvantageous in patients with coronary heart disease (CHD) or congestive heart failure (CHF). Comedications frequently used in the treatment of cardiovascular disease can further increase the risk for elevation of heart rate.Objective: As such high-risk patients have not been well represented in most randomized trials of muscarinic receptor antagonists, we investigated whether the muscarinic receptor antagonist solifenacin alters heart rate or has other cardiovascular adverse effects during routine use in OAB patients. The study evaluated these effects both in the overall group and in pre-defined risk groups. The overall tolerability and safety of solifenacin were also explored.Methods: This open-label, post-marketing surveillance study was specifically designed to evaluate the cardiovascular safety of solifenacin 5-10 mg once daily during a 12-week treatment course without specific inclusion or exclusion criteria but with systematic documentation of heart rate-relevant co-morbidities and comedications. The study was conducted in 4450 patients with OAB under the care of office-based urologists. The primary outcome measurement was heart rate. Secondary outcome measures were blood pressure and overall adverse events, which were systematically recorded before, during (after 1 week) and at study end; in many cases, an ECG was also conducted.Results: CHD, previous myocardial infarction or CHF were reported by 11.9%, 1.6% and 7.0% of patients, respectively, and >60% were receiving at least one comedication. An ECG was conducted prior to solifenacin treatment in 915 patients and revealed abnormalities in 17.3%. At study end, 72.4% and 19.1% of patients were taking solifenacin 5 mg and 10 mg, respectively. No clinically relevant alterations in mean heart rate (75.2 +/- 8.2 beats/min pre-treatment vs 74.5 +/- 7.6 beats/min at study end) or mean blood pressure (137/82 mmHg pre-treatment vs 134/81 mmHg at study end) were observed. In the subgroup of patients who underwent ECG both before and during treatment, no increase in the prevalence of pathological findings was noted. Adverse effects were rare (affecting 4.8% of patients), and treatment discontinuations due to adverse effects occurred in only 1.4% of patients. Among various possible cofactors, only age >80 years and the presence of comedications significantly affected adverse event incidence.Conclusion: In real-life conditions, i.e. with inclusion of large numbers of patients with cardiovascular co-morbidities and taking comedications, therapeutically effective doses of solifenacin did not increase heart rate or blood pressure. [ABSTRACT FROM AUTHOR]

Peter GK Wagstaff,1 Mara Buijs,1 Willemien van den Bos,1 Daniel M de Bruin,2 Patricia J Zondervan,1 Jean JMCH de la Rosette,1 M Pilar Laguna Pes1 1Department of Urology, 2Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, the Netherlands Abstract: The field of focal ablative therapy for the treatment of cancer is characterized by abundance of thermal ablative techniques that provide a minimally invasive treatment option in selected tumors. However, the unselective destruction inflicted by thermal ablation modalities can result in damage to vital structures in the vicinity of the tumor. Furthermore, the efficacy of thermal ablation intensity can be impaired due to thermal sink caused by large blood vessels in the proximity of the tumor. Irreversible electroporation (IRE) is a novel ablation modality based on the principle of electroporation or electropermeabilization, in which electric pulses are used to create nanoscale defects in the cell membrane. In theory, IRE has the potential of overcoming the aforementioned limitations of thermal ablation techniques. This review provides a description of the principle of IRE, combined with an overview of in vivo research performed to date in the liver, pancreas, kidney, and prostate. Keywords: irreversible electroporation, IRE, tumor, ablation, focal therapy, cancer

The acronym EEP, coding for transurethral Endoscopic Enucleation of the Prostate, was introduced in 2016 by the European Association of Urology (EAU) guidelines panel on management of non-neurogenic male lower urinary tract symptoms (LUTS) and benign prostatic obstruction (BPO). Since then, a laser-based treatment, Holmium Laser Enucleation of the Prostate (HoLEP), and the current-based treatment of bipolar enucleation of the prostate (BipoLEP) are equally appreciated as valuable options for the management of benign prostatic obstruction (BPO). This was mainly inspired by the results of two meta-analyses on randomized controlled trials, comparing open prostatectomy with either Holmium Laser Enucleation of the Prostate (HoLEP) or bipolar enucleation of the prostate (BipoLEP). Prior to that, HoLEP was embraced as the only valid option for transurethral enucleation, although evidence for equivalence existed as early as 2006, but was not recognized due to a plethora of acronyms for bipolar energy-based treatments and practiced HoLEP-centrism. On the other hand, the academic discourse focused on different (other) laser approaches that came up, led by Thulium:Yttrium-Aluminum-Garnet (Tm:YAG) Vapoenucleation (ThuVEP) in 2009 and, finally, transurethral anatomical enucleation with Tm:YAG support (thulium laser enucleation of the prostate, ThuLEP) in 2010. Initially, the discourse on lasers focused on the different properties of lasers rather than technique or surgical anatomy, respectively. In and after 2016, the discussion ultimately moved towards surgical technique and accepting anatomical preparation as the common of all EEP techniques (AEEP). Since then, the unspoken question has been raised, whether lasers are still necessary to perform EEP in light of existing evidence, given the total cost of ownership (TCO) for these generators. This article weighs the current evidence and comes to the conclusion that no evidence of superiority of one modality over another exists with regard to any endpoint. Therefore, in the sense of critical importance, AEEP can be safely and effectively performed without laser technologies and without compromise.

Purpose: Longitudinal assessment of health-related quality of life (HRQoL) differences in patients with localized renal masses according to treatment strategy., Methods: Consecutive patients ≥ 18 years with localized renal masses treated with different approaches (open [O], laparoscopic [L], and percutaneous [P]) and modalities (radical nephrectomy [RN], nephron sparing surgery [NSS] and cryoablation [CA]). The SF-36, Functional Assessment of Cancer Therapy-Kidney Symptom Index-15 questionnaires and pain visual analog scale were completed pretreatment and at 1, 3, and 12 months posttreatment. Questionnaire results were stratified according to approach and treatment modality using a longitudinal multilevel linear regression model. Clinical patient and tumor characteristics, complications, and histopathology results were tested as confounders., Results: Ninety eight patients completed baseline and at least one follow-up questionnaires; 27.5%, 16.3%, 22.5%, 9.2%, 13.3%, and 11.2% patients received LNSS, ONSS, LRN, ORN, LCA, and PCA, respectively. Higher baseline SF-36 (3 domains) and Functional Assessment of Cancer Therapy-Kidney Symptom Index-15 scores were reported in L group compared with the O approach. Overall, HRQoL decreased at 1 month and gradually normalized to baseline level or higher at 1 year. For treatment modality at baseline, higher mean visual analog scale was observed in CA than RN group. A trend to decreased HRQoL was observed at 1 month for RN and NSS; thereafter, scores normalized to baseline levels or higher. Approach or treatment modality HRQoL did not change substantially when corrected for confounders., Conclusion: At short-term, HRQoL outcome favored minimally invasive treatment of RCC; at mid-term, these advantages were no longer apparent. This suggest that in selecting the best surgical treatment for the patient, oncological outcome should be the primary consideration as both approach and treatment modality result in similar HRQoL outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Flexible ureteroscopy is an established treatment modality for evaluating and treating abnormalities in the upper urinary tract. Reusable ureteroscope (USC) durability is a significant concern., Objective: To evaluate the durability of the latest generation of digital and fiber optic reusable flexible USCs and the factors affecting it., Design, Setting, Participants: Six new flexible USCs from Olympus and Karl Storz were included. The primary endpoint for each USC was its first repair. Data on patient and treatment characteristics, accessory device use, ureteroscopy time, image quality, USC handling, disinfection cycles, type of damage, and deflection loss were collected prospectively., Intervention: Ureteroscopy., Outcome Measurements and Statistical Analysis: USC durability was measured as the total number of uses and ureteroscopy time before repair. USC handling and image quality were scored. After every procedure, maximal ventral and dorsal USC deflection were documented on digital images., Results and Limitations: A total of 198 procedures were performed. The median number of procedures was 27 (IQR 16-48; 14h) for the six USCs overall, 27 (IQR 20-56; 14h) for the digital USCs, and 24 (range 10-37; 14h) for the fiber optic USCs. Image quality remained high throughout the study for all six USCs. USC handling and the range of deflection remained good under incremental use. Damage to the distal part of the shaft and shaft coating was the most frequent reason for repair, and was related to intraoperative manual forcing. A limitation of this study is its single-center design., Conclusions: The durability of the latest reusable flexible USCs in the current study was limited to 27 uses (14h). Damage to the flexible shaft was the most important limitation to the durability of the USCs evaluated. Prevention of intraoperative manual forcing of flexible USCs maximizes their overall durability., Patient Summary: Current flexible ureteroscopes proved to be durable. Shaft vulnerability was the most important limiting factor affecting durability., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: It is recommended to perform multiparametric magnetic resonance imaging (mpMRI) in the follow-up following focal therapy of prostate cancer (PCa)., Objective: To determine the diagnostic accuracy of mpMRI to detect residual PCa following focal therapy with irreversible electroporation., Design, Setting, and Participants: Seventy-six patients with biopsy-proven localized PCa consented for primary irreversible electroporation between February 2013 and March 2016. Final analysis was performed on 50 patients that received follow-up mpMRI at 6 mo, serial prostate-specific antigen (PSA) testing, and transperineal template-mapping biopsies at 12 mo., Outcome Measurements and Statistical Analysis: Outfield regions of interest (ROI) were reported using PI-RADS version 2. A binary outcome (suspicious vs nonsuspicious) was given for the infield ablation zone. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated for different definitions of significant PCa: (1) Gleason ≥4+3 or Gleason ≥3+3 with a maximum cancer core length ≥6mm, (2) Gleason ≥3+4 or Gleason ≥3+3 with a maximum cancer core length ≥4mm, for outfield and infield ROI. Multivariate linear regression analyses evaluated the additional value of nadir PSA., Results and Limitations: Sensitivity, specificity, positive predictive values, and negative predictive values of infield ROI was 43%, 86%, 33%, and 90% for definition 1 and 38%, 86%, 33%, and 88% for definition 2, respectively. For outfield ROI this was 33%, 82%, 20%, and 90% for definition 1 and 38%, 86%, 50%, and 80% for definition 2. PSA had no additional value in predicting residual significant PCa. Limitations include retrospective design, single reader, and low incidence of residual PCa., Conclusions: Our preliminary data suggest that mpMRI can rule out high-volume residual PCa. However, follow-up biopsies should still be performed to determine oncological control., Patient Summary: Multiparametric magnetic resonance imaging is able to detect high-volume significant prostate cancer following focal therapy. Prostate biopsies are still required in the follow-up of focal therapy as (low-volume) significant prostate cancer is being missed by multiparametric magnetic resonance imaging., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Despite improvements in early detection and advances in treatment, patients with prostate cancer continue to die from their disease. Minimal residual disease after primary definitive treatment can lead to relapse and distant metastases, and increasing evidence suggests that circulating tumour cells (CTCs) and bone marrow-derived disseminated tumour cells (BM-DTCs) can offer clinically relevant biological insights into prostate cancer dissemination and metastasis. Using epithelial markers to accurately detect CTCs and BM-DTCs is associated with difficulties, and prostate-specific markers are needed for the detection of these cells using rare cell assays. Putative prostate-specific markers have been identified, and an optimized strategy for staining rare cancer cells from liquid biopsies using these markers is required. The ideal prostate-specific marker will be expressed on every CTC or BM-DTC throughout disease progression (giving high sensitivity) and will not be expressed on non-prostate-cancer cells in the sample (giving high specificity). Some markers might not be specific enough to the prostate to be used as individual markers of prostate cancer cells, whereas others could be truly prostate-specific and would make ideal markers for use in rare cell assays. The goal of future studies is to use sensitive and specific prostate markers to consistently and reliably identify rare cancer cells.

Objectives: To compare the safety and effectiveness of super-mini-percutaneous nephrolithotomy (SMP) and retrograde intrarenal surgery (RIRS) for the treatment of 1-2 cm lower-pole renal calculi (LPC)., Patients and Methods: An international multicentre, prospective, randomised, unblinded controlled study was conducted at 10 academic medical centres in China, India, and Turkey, between August 2015 and June 2017. In all, 160 consecutive patients with 1-2 cm LPC were randomised to receive SMP or RIRS. The primary endpoint was stone-free rate (SFR). Stone-free status was defined as no residual fragments of ≥0.3 cm on plain abdominal radiograph of the kidneys, ureters and bladder, and ultrasonography at 1-day and on computed tomography at 3-months after operation. Secondary endpoints included blood loss, operating time, postoperative pain scores, auxiliary procedures, complications, and hospital stay. Postoperative follow-up was scheduled at 3 months. Analysis was by intention-to-treat. The trial was registered at http://clinicaltrials.gov/ (NCT02519634)., Results: The two groups had similar baseline characteristics. The mean (sd) stone diameters were comparable between the groups, at 1.50 (0.29) cm for the SMP group vs 1.43 (0.34) cm for the RIRS group (P = 0.214). SMP achieved a significantly better 1-day and 3-month SFR than RIRS (1-day SFR 91.2% vs 71.2%, P = 0.001; 3-months SFR 93.8% vs 82.5%, P = 0.028). The auxiliary procedure rate was lower in the SMP group. RIRS was found to be superior with lower haemoglobin drop and less postoperative pain. Blood transfusion was not required in either group. There was no significant difference in operating time, hospital stay, and complication rates, between the groups., Conclusions: SMP was more effective than RIRS for treating 1-2 cm LPC in terms of a better SFR and lesser auxiliary procedure rate. The complications and hospital stay were comparable. RIRS has the advantage of less postoperative pain., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Purpose: The design, conduct and completion of randomized trials for curative prostate cancer (PCa) treatments are challenging. To evaluate the effect of robot-assisted radical prostatectomy (RARP) versus focal irreversible electroporation (IRE) on patient-reported quality of life (QoL) and early oncological control using propensity-scored matching., Methods: Patients with T1c-cT2b significant PCa (high-volume ISUP 1 or any 2/3) who received unifocal IRE were pair-matched to patients who received nerve-sparing RARP. Patient-reported outcomes were prospectively assessed using the Expanded Prostate Cancer Index Composite (EPIC), AUA symptom score and Short Form of Health Survey (SF-12) physical and mental components. Oncological failure was defined as biochemical recurrence (RARP) or positive follow-up biopsies (IRE). Generalized mixed-effect models were used to compare IRE and RARP., Results: 50 IRE patients were matched to 50 RARP patients by propensity score. IRE was significantly superior to RARP in preserving pad-free continence (UC) and erections sufficient for intercourse (ESI). The absolute differences were 44, 21, 13, 14% for UC and 32, 46, 27, 22% for ESI at 1.5, 3, 6, and 12 months, respectively. The EPIC summary scores showed no statistically significant differences. Urinary symptoms were reduced for IRE and RARP patients at 12 months, although IRE patient initially had more complaints. IRE patients experienced more early oncological failure than RARP patients., Conclusions: These data demonstrated the superior preservation of UC and ESI with IRE compared to RARP up to 12 months after treatment. Long-term oncological data are warranted to provide ultimate proof for or against focal therapy.

Purpose: We aimed to evaluate the genitourinary function and quality of life (QoL) following the ablation of different prostate segments with irreversible electroporation (IRE) for localized prostate cancer (PCa)., Methods: Sixty patients who received primary focal IRE for organ-confined PCa were recruited for this study. Patients were evaluated for genitourinary function and QoL per prostate segment treated (anterior vs. posterior, apex vs. base vs. apex-to-base, unilateral vs. bilateral). IRE system settings and patient characteristics were compared between patients with preserved vs. those with impaired erectile function and urinary continence. Data were prospectively collected at baseline, 3, 6, and 12 months using the expanded prostate cancer index composite, American Urological Association symptom score, SF-12 physical and mental component summary surveys. Difference over time within segments per questionnaire was evaluated using the Wilcoxon's signed rank test. Outcome differences between segments were assessed using covariance models. Baseline measurements included questionnaire scores, age, and prostate volume., Results: There were no statistically significant changes over time for overall urinary (P = 0.07-0.89), bowel (P = 0.06-0.79), physical (P = 0.18-0.71) and mental (P = 0.45-0.94) QoL scores within each segment. Deterioration of sexual function scores was observed at 6 months within each segment (P = 0.001-0.16). There were no statistically significant differences in QoL scores between prostate segments (P = 0.08-0.97). Older patients or those with poor baseline sexual function at time of treatment were associated with a greater risk of developing erectile dysfunction., Conclusion: IRE is a feasible modality for all prostate segments without any significantly different effect on the QoL outcomes. Older patients and those with poor sexual function need to be counseled regarding the risk of erectile dysfunction.

Background: Focal therapy for prostate cancer has been proposed as an alternative treatment to whole-gland therapies in selected men to diminish side effects in localized prostate cancer. As nowadays imaging cannot offer complete prostate cancer disease characterization, multicore systematic biopsies are recommended (transrectal or transperineal). Optical imaging techniques such as confocal laser endomicroscopy and optical coherence tomography allow in vivo, high-resolution imaging. Moreover, they can provide real-time visualization and analysis of tissue and have the potential to offer additive diagnostic information., Objective: This study has 2 separate primary objectives. The first is to assess the technical feasibility and safety of in vivo focal imaging with confocal laser endomicroscopy and optical coherence tomography. The second is to identify and define characteristics of prostate cancer and normal prostate tissue in confocal laser endomicroscopy and optical coherence tomography imaging by comparing these images with the corresponding histopathology., Methods: In this prospective, in vivo feasibility study, needle-based confocal laser endomicroscopy and optical coherence tomography imaging will be performed before transperineal template mapping biopsy or radical prostatectomy. First, confocal laser endomicroscopy and optical coherence tomography will be performed in 4 patients (2 for each imaging modality) undergoing transperineal template mapping biopsy to assess the feasibility and safety of confocal laser endomicroscopy and optical coherence tomography. If proven to be safe and feasible, confocal laser endomicroscopy and optical coherence tomography will be performed in 10 patients (5 for each imaging modality) undergoing radical prostatectomy. Confocal laser endomicroscopy and optical coherence tomography images will be analyzed by independent, blinded observers. Confocal laser endomicroscopy- and optical coherence tomography-based qualitative and quantitative characteristics and histopathology will be compared. The study complies with the IDEAL (Idea, Development, Exploration, Assessment, Long-term study) stage 2a recommendations., Results: At present, the study is enrolling patients and results and outcomes are expected in 2019., Conclusions: Confocal laser endomicroscopy and optical coherence tomography are promising optical imaging techniques that can visualize and analyze tissue structure, possible tumor grade, and architecture in real time. They can potentially provide real-time, high-resolution microscopic imaging and tissue characteristics of prostate cancer in conjunction with magnetic resonance imaging or transrectal ultrasound fusion-guided biopsy procedures. This study will provide insight into the feasibility and tissue-specific characteristics of confocal laser endomicroscopy and optical coherence tomography for real-time optical analysis of prostate cancer., Trial Registration: ClinicalTrials.gov NCT03253458; https://clinicaltrials.gov/ct2/show/NCT03253458 (Archived by WebCite at http://www.webcitation.org/6z9owM66B)., Registered Report Identifier: RR1-10.2196/9813., (©Abel Swaan, Christophe K Mannaerts, Matthijs JV Scheltema, Jakko A Nieuwenhuijzen, C Dilara Savci-Heijink, Jean JMCH de la Rosette, R Jeroen A van Moorselaar, Ton G van Leeuwen, Theo M de Reijke, Daniel Martijn de Bruin. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 21.05.2018.)

Purpose: This study is a systematic analysis of the evidence regarding oncological, perioperative and postoperative outcomes and the cost of open retropubic radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP) and robotic-assisted laparoscopic radical prostatectomy (RALP)., Methods: Summary data was abstracted from 104 original research articles representing 227,400 patients. PubMed/Medline, Scopus, Google Scholar, EMBASE and the Cochrane Library were reviewed in December 2016. A total of 104 publications were selected for inclusion. The primary outcomes were positive surgical margin (PSM) and major complication rate according to Clavien classifications. Secondary outcomes were operative time, length of hospital stay, estimated blood loss, transfusions, conversions, rate of post-operative erectile dysfunction and incontinence and total cost of procedure., Results: ORP had a significantly higher rate than RALP for PSM (OR: 1.18; 95% CI 1.05-1.32; p = 0.004), but the rate of PSM was not significantly different between ORP versus LRP (OR: 1.37; 95% CI 0.88-2.14; p = 0.17) and RALP versus LRP (OR: 0.83; 95% CI 0.40-1.72; p = 0.62). The major Clavien complication rate was significantly different between ORP and RALP (OR: 2.14; 95% CI 1.24-3.68; p = 0.006). Estimated blood loss, transfusions and length of hospital stay were low for RALP, moderate for LRP and high for ORP. The rate of erectile dysfunction (OR: 2.58; 95% CI 1.77-3.75; p < 0.001) and incontinence (OR: 3.57; 95% CI 2.28-5.58; p < 0.001) were significantly lower after RALP than LRP and equivalent for other comparisons. Total cost was highest for RALP, followed by LRP and ORP., Conclusions: For PSM and peri- and post-operative complications, RALP showed better results than ORP and LRP. In the context of the biases between the studies, one should interpret the results with caution.

The number of patients on chronic anticoagulant or antiplatelet therapy requiring endoscopic urological surgery is increasing worldwide. Therefore, there is a strong demand to standardize the perioperative treatment of this cohort of patients, both from a surgical and cardiological point of view, balancing the risks of bleeding versus thrombosis, and the important possible clinical and medical legal repercussions therein. Although literature is scarce and the quality of evidence quite low, in line with other surgical specialties, guidelines and recommendations for the management of urological patients have begun to emerge. The aim of this review is to analyze current available literature and evidence on the most common endoscopic procedures performed in this high-risk group of patients, focusing on the perioperative management. In particular, to analyze the most frequently performed endoscopic procedures for the treatment of benign prostate enlargement (transurethral resection of the prostate, Thulium, Holmium and greenlight laser prostatectomy), bladder cancer (transurethral resection of the bladder), upper urinary tract urothelial cancer, and nephrolithiasis. Despite the lack of randomized studies, regardless of individual patient considerations, studies would support continuation of acetylsalicylic acid, which is recommended by cardiologists, in patients with intermediate/high risk of coronary thrombosis. In contrast, multiple studies found that bridging with light weight molecular weight heparin can potentially lead to more bleeding than continuation of the anticoagulant(s) and antiplatelet therapy, and caution with bridging is advised. All urologists should familiarize themselves with emerging guidelines and recommendations, and always be prepared to discuss specific cases or scenarios in a dedicated multidisciplinary team.

Background: Visual confirmation of a suspicious lesion in the urinary tract is a major corner stone in diagnosing urothelial carcinoma. However, during cystoscopy (for bladder tumors) and ureterorenoscopy (for tumors of the upper urinary tract) no real-time histopathologic information can be obtained. Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows for in vivo high-resolution imaging and may allow real-time tumor grading of urothelial lesions., Objective: The primary objective of both studies is to develop descriptive criteria for in vivo CLE images of urothelial carcinoma (low-grade, high-grade, carcinoma in situ) and normal urothelium by comparing CLE images with corresponding histopathology., Methods: In these two prospective clinical trials, CLE imaging will be performed of suspicious lesions and normal tissue in the urinary tract during surgery, prior to resection or biopsy. In the bladder study, CLE will be performed in 60 patients using the Cystoflex UHD-R probe. In the upper urinary tract study, CLE will be performed in 25 patients during ureterorenoscopy, who will undergo radical treatment (nephroureterectomy or segmental ureter resection) thereafter. All CLE images will be analyzed frame by frame by three independent, blinded observers. Histopathology and CLE-based diagnosis of the lesions will be evaluated. Both studies comply with the IDEAL stage 2b recommendations., Results: Presently, recruitment of patients is ongoing in both studies. Results and outcomes are expected in 2018., Conclusions: For development of CLE-based diagnosis of urothelial carcinoma in the bladder and the upper urinary tract, a structured conduct of research is required. This study will provide more insight in tissue-specific CLE criteria for real-time tumor grading of urothelial carcinoma., Trial Registration: Confocal Laser Endomicroscopy: ClinicalTrials.gov NCT03013894; https://clinicaltrials.gov /ct2/show/NCT03013894?term=NCT03013894&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPZ378I); and Dutch Central Committee on Research Involving Human Subjects NL55537.018.15; https://www.toetsingonline.nl /to/ccmo&#95;search.nsf/fABRpop?readform&unids=6B72AE6EB0FC3C2FC125821F001B45C6 (Archived by WebCite at http://www.webcitation.org/6wwJQvqWh). Confocal Laser Endomicroscopy in the upper urinary tract: ClinicalTrials.gov NCT03013920; https://clinicaltrials.gov/ct2/show/NCT03013920? term=NCT03013920&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPkjyt0); and Dutch Central Committee on Research Involving Human Subjects NL52989.018.16; https://www.toetsingonline.nl/to/ccmo&#95;search.nsf/fABRpop?readform&unids=D27C9C3E5755CFECC12581690016779F (Archived by WebCite at http://www.webcitation.org/6wvy8R44C)., (©Esmee IML Liem, Jan Erik Freund, Joyce Baard, D Martijn de Bruin, M Pilar Laguna Pes, C Dilara Savci-Heijink, Ton G van Leeuwen, Theo M de Reijke, Jean JMCH de la Rosette. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 07.02.2018.)

Purpose: To compare intra- and post-operative outcomes of endourological live surgical demonstrations (LSDs) and routine surgical practice (RSP) for urinary stones., Methods: Consecutive ureterorenoscopic (URS) and percutaneous (PNL) urinary stone procedures over a 5-year period were reviewed. Procedures were divided into LSDs and RSP. Differences between the groups were separately analysed for URS and PNL. Primary outcomes included intra- and post-operative complication rates and grades. Secondary outcomes were operation time, length of hospital stay, stone-free rate, and retreatment rate. Pearson's Chi-square analysis, Mann-Whitney U test, and logistic and linear regression were used to compare outcomes between LSDs and RSP., Results: During the study period, we performed 666 URSs and 182 PNLs, and 151 of these procedures were LSDs. Among URSs, the overall intra-operative complication rate was 3.2% for LSDs and 2.5% for RSP (p = 0.72) and the overall post-operative complication rate was 13.7% for LSDs and 8.8% for RSP (p = 0.13). Among PNLs, the overall intra-operative complication rate was 8.9% for LSDs and 5.6% for RSP (p = 0.52) and the overall post-operative complication rate was 28.6% for LSDs and 34.9% for RSP (p = 0.40). For both URSs and PNLs, no statistically significant differences in complication grade scores were observed between LSDs and RSP. Operation time was significantly longer for LSD-URS group, but there was no difference between the PNL groups. There were no significant differences in length of hospital stay and stone-free rate. The retreatment rate was higher in the LSD-URS group compared with RSP-URS group but similar between the PNL groups. Multiple logistic regression analyses, adjusting for confounders, revealed no association between LSD and more or less favourable outcomes as compared to RSP., Conclusion: Live surgical demonstrations do not seem to compromise patients' safety and outcomes when performed by specialised endourologists.

Objectives: To determine the stone-free rates and intra- and postoperative complication rates and grades of ureterorenoscopic stone treatment in patients with a solitary kidney. Methods: This study is a subanalysis of the Clinical Research Office of the Endourological Society (CROES) ureterorenoscopy (URS) study, which is a prospective international multicenter observational study. Over a 1-year period, consecutive patients treated with ureterorenoscopy for urinary stones were included. Patients entered in this analysis were those with a solitary functioning kidney. Descriptive data on patient characteristics, stone-free rates, complication rates, and grades were evaluated for three separate groups: patients treated with ureteroscopy for ureteral stones, for renal stones, and a combination of renal and ureteral stones. Results: A total of 301 patients were treated for stones in a solitary kidney; 219 were treated for ureteral stones. In this group, the stone-free rate was 88.6%, with an intraoperative complication rate of 7.4% and postoperative complication rate of 4.1%. Totally, 57 patients were treated for renal stones. In this group, the stone-free rate was 56.4%, with an intraoperative complication rate of 7.0% and postoperative complication rate of 10.5%. There were 25 patients who were treated for renal stones in combination with ureter stones. In this group, the stone-free rate was 60.0%, with an intraoperative complication rate of 12.0% and postoperative complication rate of 10.5%. Within the three groups, 72% of the postoperative complications were classified as Clavien I and II. Conclusions: Ureteroscopy is an effective and safe treatment modality for the removal of ureteral and renal stones in patients with a solitary kidney. Stone location as well as total stone burden seems to be important factors influencing the ability to render patients stone free. Moreover, single session ureteroscopic stone removal was less effective for the treatment of larger renal stones or renal stones in combination with ureteral stones.

Purpose: To describe stone-free rates and complications of ureteroscopic treatment for impacted compared with non-impacted ureteral stones and evaluate predictive variables for impaction., Methods: The Clinical Research Office of the Endourological Society prospectively collected 1 consecutive year of data from 114 centers worldwide. Patients eligible for inclusion were patients treated with ureteroscopy for ureteral stones. Patient characteristics, treatment details, and outcomes were compared with regard to stone impaction. Logistic regression analyses were conducted to explore predictive variables for ureteral stone impaction and to analyse the effect of impaction on outcomes., Results: Of the 8543 treated patients, 2650 (31%) had impacted and 5893 (69%) non-impacted stones. The stone-free rate was 87.1% for impacted stones, which is lower compared with 92.7% for non-impacted stones (p < 0.001). Intra-operative complication rates were higher for impacted stones (7.9 versus 3.0%, p < 0.001). Significantly higher ureteral perforation- and avulsion rates were reported in the impacted stone group compared with the non-impacted stone group. No association between stone impaction and post-operative complications could be shown. Female gender, ASA-score >1, prior stone treatment, positive pre-operative urine culture, and larger stones showed to be predictive variables for stone impaction., Conclusions: Ureteroscopic treatment for impacted stones is associated with lower stone-free rates and higher intra-operative complication rates compared with treatment for non-impacted stones. The predictive variables for the presence of stone impaction may contribute to the identification of stone impaction during the diagnostic process. Moreover, identification of stone impaction may aid the selection of the optimal treatment modality.

Purpose: This study presents a comparison of the international experience with ipsilateral and bilateral ureteroscopy for multiple, bilateral ureteral and renal stones vs single stone treatment. Patient and treatment characteristics and outcomes were compared., Materials and Methods: The CROES (Clinical Research Office of the Endourological Society) Ureteroscopy Global Study includes 114 centers in 32 countries. Patients undergoing bilateral ureteroscopy, ipsilateral ureteroscopy for multiple stones and ureteroscopy for a single stone were examined from January 2010 to October 2012. Intraoperative characteristics and postoperative outcomes were identified for each patient. Inverse probability weighted regression adjustment analyses were done to compare outcomes independent of differences among centers and patient characteristics., Results: The CROES Ureteroscopy Global Study consists of 11,885 patients. A total of 2,153 patients (18.7%) were treated for multiple stones, of whom 1,880 (87.3%) and 273 (12.7%) underwent ipsilateral and bilateral ureteroscopy, respectively. Inverse probability weighted regression adjustment models for bilateral vs ipsilateral ureteroscopy and multiple vs single stone treatments showed that patients with bilateral ureteroscopy and multiple stone treatments had lower stone-free rates, higher re-treatment rates and longer operative times compared to patients who underwent ipsilateral ureteroscopy and single stone treatment. There was no difference in complication rates among bilateral, ipsilateral and single stone ureteroscopy., Conclusions: This study presents a large series of patients who underwent bilateral and ipsilateral ureteroscopy. Our findings suggest a decrease in stone-free rates, increased re-treatment rates, increased operative times and longer hospital stay in patients treated for multiple stones. The treatment of multiple stones and bilateral ureteroscopy are safe compared to single stone treatment and ipsilateral ureteroscopy, respectively., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: To compare baseline characteristics and outcomes of patients undergoing GreenLight laser vaporization (GL) or transurethral resection of the prostate (TURP) in a real life setting., Methods: In this prospective observational cohort, the Clinical Research Office of the Endourological Society (CROES) collected data of consecutive GL or TURP treated patients. Treatment involved one of three GL laser powers (80 W, 120 W or 180 W) based on availability in each participating centre, or TURP. Data on baseline characteristics as well as functional measures were collected at three time points: 6-12 weeks, 6, and 12months after surgery. Functional measures included urinary flow parameters, perceived prostate function (IPSS), perceived erectile function (IIEF-5) and complications., Results: Seven hundred thirteen patients underwent GL, and 234 patients underwent TURP. Overall, patients treated with GL show higher BMI, IIEF and medication use, together with lower urinary function (voided volume, incontinence, urinary retention) at baseline. After the procedure, despite higher antibiotic and antimuscarinic use and shorter hospital stay, readmission rates, PVR, PSA were higher, but Qmax, and IIEF were lower in the GL group. The rate of post-operative complications was 10.3% and 5.2% for the TURP and GL group, respectively (P=0.006)., Conclusions: We were unable to categorically state which procedure is superior. This observational study confirms that treatment decision for either TURP or GL is not based on patient characteristics.

Background: The current standard for Prostate Cancer (PCa) detection in biopsy-naïve men consists of 10-12 systematic biopsies under ultrasound guidance. This approach leads to underdiagnosis and undergrading of significant PCa while insignificant PCa may be overdiagnosed. The recent developments in MRI and Contrast Enhanced Ultrasound (CEUS) imaging have sparked an increasing interest in PCa imaging with the ultimate goal of replacing these "blind" systematic biopsies with reliable imaging-based targeted biopsies., Methods/design: In this trial, we evaluate and compare the PCa detection rates of multiparametric (mp)MRI-targeted biopsies, CEUS-targeted biopsies and systematic biopsies under ultrasound guidance in the same patients. After informed consent, 299 biopsy-naïve men will undergo mpMRI scanning and CEUS imaging 1 week prior to the prostate biopsy procedure. During the biopsy procedure, a systematic transrectal 12-core biopsy will be performed by one operator blinded for the imaging results and targeted biopsy procedure. Subsequently a maximum of 4 CEUS-targeted biopsies and/or 4 mpMRI-targeted biopsies of predefined locations determined by an expert CEUS reader using quantification techniques and an expert radiologist, respectively, will be taken by a second operator using an MRI-US fusion device. The primary outcome is the detection rate of PCa (all grades) and clinically significant PCa (defined as Gleason score ≥7) compared between the three biopsy protocols., Discussion: This trial compares the detection rate of (clinically significant) PCa, between both traditional systematic biopsies and targeted biopsies based on predefined regions of interest identified by two promising imaging technologies. It follows published recommendations on study design for the evaluation of imaging guided prostate biopsy techniques, minimizing bias and allowing data pooling. It is the first trial to combine mpMRI imaging and advanced CEUS imaging with quantification., Trial Registration: The Dutch Central Committee on Research Involving Human Subjects registration number NL52851.018.15, registered on 3 Nov 2015. Clinicaltrials.gov database registration number NCT02831920 , retrospectively registered on 5 July 2016.

Background: The applicability of urinary biomarkers and optical diagnostics in upper urinary tract carcinoma (UUT-UC) are increasingly debated. To receive insight in the opinion of the urological community involved in this field, a survey was sent out to identify the most promising techniques and understand the need for new diagnostics. Primary objective of this study was to provide an overview of current diagnostics in upper urinary tract urothelial carcinoma. Secondary objectives of this study was to assess the need for additional diagnostic techniques in the current diagnostic work-up for UUT-UC and to assess knowledge of novel techniques., Methods: An electronic survey was distributed to all participants of the upper urinary tract tumor registration study by the Clinical Research Office of the Endourological Society. Additionally, based on publications, experts in the field were contacted. Analysis was performed on the results overviewed by the survey monkey website., Results: In total 81 of the 112 invited individuals responded resulting in a response rate of 72.3%. Most urologists involved in the treatment of upper urinary tract tumors follow the guidelines in their diagnostic work-up of patients suspected for UUT-UC. 61.4% of all responders consider current available diagnostic methods insufficient to select patient candidates for conservative renal sparing surgery. According to the responders, digital endoscopes for retrograde intrarenal surgery (RIRS) including narrow-band imaging (NBI) are best known and most likely to be beneficial compared to all evaluated diagnostic tools currently available., Conclusions: Urologists consider current diagnostic techniques for upper urinary tract tumors insufficient for optimal patient selection for conservative renal sparing surgery. Among the new techniques, NBI and digital RIRS are best known and considered to be beneficial in the diagnostic work-up.

Purpose of Review: Image enhancement techniques and optical diagnostic tools have emerged in the quest to improve diagnostics and treatment in patients with upper urinary tract carcinoma (UTUC). The aim of the present report is to describe their mechanisms of action and to assess the current evidence on applicability and utility in UTUC., Recent Findings: Image enhancement techniques including narrow band imaging, Image1 S, and photodynamic diagnosis aim at better visualization of malignant urothelium and especially flat tumours or carcinoma in situ which are often difficult to see with white light endoscopy. Conducted studies in the upper tract are scarce but first results show that tumour detection seems to be better for narrow band imaging and photodynamic diagnosis-guided inspection.Optical diagnostic tools as confocal laser endomicroscopy and optical coherence tomography aim at providing real time optical biopsies giving pathologic information. A pilot study of optical coherence tomography proved its feasibility to visualize, grade and stage low and high-grade UTUC., Summary: Better visualization of suspect lesions and optical diagnostic techniques providing real time optical biopsies aim to facilitate in higher diagnostic precision and optimal individualized treatment of our patients with UTUC. As the disease is rare, studies are scarce but indispensable for future implication of these techniques.

Background: Irreversible electroporation (IRE) is an emerging technique delivering electrical pulses to ablate tissue, with the theoretical advantage to overcome the main shortcomings of conventional thermal ablation. Recent short-term research showed that IRE for the ablation of renal masses is a safe and feasible treatment option. In an ablate and resect design, histopathological analysis 4 weeks after radical nephrectomy demonstrated that IRE-targeted renal tumors were completely covered by ablation zone. In order to develop a validated long-term IRE follow-up study, it is essential to obtain clinical confirmation of the efficacy of this novel technology. Additionally, follow-up after IRE ablation obliges verification of a suitable imaging modality., Objective: The objectives of this study are the clinical efficacy and safety of IRE ablation of renal masses and to evaluate the use of cross-sectional imaging modalities in the follow-up after IRE in renal tumors. This study conforms to the recommendations of the IDEAL Collaboration and can be categorized as a phase 2B exploration trial., Methods: In this prospective clinical trial, IRE will be performed in 20 patients aged 18 years and older presenting with a solid enhancing small renal mass (SRM) (≤4 cm) who are candidates for ablation. Magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) will be performed at 1 day pre-IRE, and 1 week post-IRE. Computed tomography (CT), CEUS, and MRI will be performed at 3 months, 6 months, and 12 months post-IRE., Results: Presently, recruitment of patients has started and the first inclusions are completed. Preliminary results and outcomes are expected in 2018., Conclusions: To establish the position of IRE ablation for treating renal tumors, a structured stepwise assessment in clinical practice is required. This study will offer fundamental knowledge on the clinical efficacy of IRE ablation for SRMs, potentially positioning IRE as ablative modality for renal tumors and accrediting future research with long-term follow-up., Trial Registration: Clinicaltrials.gov registration number NCT02828709; https://clinicaltrials.gov/ct2/show/NCT02828709 (archived by WebCite at http://www.webcitation.org/6nmWK7Uu9). Dutch Central Committee on Research Involving Human Subjects NL56935.018.16., (©Mara Buijs, Krijn P van Lienden, Peter GK Wagstaff, Matthijs JV Scheltema, Daniel M de Bruin, Patricia J Zondervan, Otto M van Delden, Ton G van Leeuwen, Jean JMCH de la Rosette, M Pilar Laguna. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 16.02.2017.)

Objective: To design and demonstrate a customized tool to generate histologic sections of the prostate that directly correlate with needle-based optical coherence tomography pullback measurements., Materials and Methods: A customized tool was created to hold the prostatectomy specimens during optical coherence tomography measurements and formalin fixation. Using the tool, the prostate could be sliced into slices of 4 mm thickness through the optical coherence tomography measurement trajectory. In this way, whole-mount pathology slides were produced in exactly the same location as the optical coherence tomography measurements were performed. Full 3-dimensional optical coherence tomography pullbacks were fused with the histopathology slides using the 3-dimensional imaging software AMIRA, and images were compared., Results: A radical prostatectomy was performed in a patient (age: 68 years, prostate-specific antigen: 6.0 ng/mL) with Gleason score 3 + 4 = 7 in 2/5 biopsy cores on the left side (15%) and Gleason score 3 + 4 = 7 in 1/5 biopsy cores on the right side (5%). Histopathology after radical prostatectomy showed an anterior located pT2cNx adenocarcinoma (Gleason score 3 + 4 = 7). Histopathological prostate slides were produced using the customized tool for optical coherence tomography measurements, fixation, and slicing of the prostate specimens. These slides correlated exactly with the optical coherence tomography images. Various structures, for example, Gleason 3 + 4 prostate cancer, stroma, healthy glands, and cystic atrophy with septae, could be identified both on optical coherence tomography and on the histopathological prostate slides., Conclusion: We successfully designed and applied a customized tool to process radical prostatectomy specimens to improve the coregistration of whole mount histology sections to fresh tissue optical coherence tomography pullback measurements. This technique will be crucial in validating the results of optical coherence tomography imaging studies with histology and can easily be applied in other solid tissues as well, for example, lung, kidney, breast, and liver. This will help improve the efficacy of optical coherence tomography in cancer detection and staging in solid organs.

The cancer community continues to search for an efficient and cost-effective technique to isolate and characterize circulating cells (CTCs) as a 'real-time liquid biopsy'. Existing methods to isolate and analyze CTCs require various transfer, wash, and staining steps that can be time consuming, expensive, and led to the loss of rare cells. To overcome the limitations of existing CTC isolation strategies, we have developed an inexpensive 'lab on a chip' device for the enrichment, staining, and analysis of rare cell populations. This device utilizes immunomagnetic positive selection of antibody-bound cells, isolation of cells through an immiscible interface, and filtration. The isolated cells can then be stained utilizing immunofluorescence or used for other downstream detection methods. We describe the construction and initial preclinical testing of the device. Initial tests suggest that the device may be well suited for the isolation of CTCs and could allow the monitoring of cancer progression and the response to therapy over time.

Prostate cancer (PCa) is the second-leading cause of cancer death in men; however, reliable tools for detection and localization are still lacking. Dynamic Contrast Enhanced UltraSound (DCE-US) is a diagnostic tool that is suitable for analysis of vascularization, by imaging an intravenously injected microbubble bolus. The localization of angiogenic vascularization associated with the development of tumors is of particular interest. Recently, methods for the analysis of the bolus convective dispersion process have shown promise to localize angiogenesis. However, independent estimation of dispersion was not possible due to the ambiguity between convection and dispersion. Therefore, in this study we propose a new method that considers the vascular network as a dynamic linear system, whose impulse response can be locally identified. To this end, model-based parameter estimation is employed, that permits extraction of the apparent dispersion coefficient (D), velocity (v), and Péclet number (Pe) of the system. Clinical evaluation using data recorded from 25 patients shows that the proposed method can be applied effectively to DCE-US, and is able to locally characterize the hemodynamics, yielding promising results (receiver-operating-characteristic curve area of 0.84) for prostate cancer localization., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: Clinical outcomes prognostic markers are awaited in clear-cell renal carcinoma (ccRCC) to improve patient-tailored management and to assess six different markers' influence on clinical outcomes from ccRCC specimen and their incremental value combined with TNM staging., Materials and Methods: This is a retrospective, multicenter study. One hundred and forty-three patients with pT1b-pT3N0M0 ccRCC were included. Pathology specimens from surgeries were centrally reviewed, mounted on a tissue micro-array and stained with six markers: CAIX, c-MYC, Ki67, p53, vimentin and PTEN. Images were captured through an Ultra Fast Scanner. Tumor expression was measured with Image Pro Plus. Cytoplasmic markers (PTEN, CAIX, vimentin, c-MYC) were expressed as surface percentage of expression. Nuclear markers (Ki67, p53) were expressed as number of cells/mm 2 . Clinical data and markers expression were compared with clinical outcomes. Each variable was included in the Cox proportional multivariate analyses if p < 0.10 on univariate analyses. Discrimination of the new marker was calculated with Harrell's concordance index., Results: At median follow-up of 63 months (IQR 35.0-91.8), on multivariate analysis, CAIX under-expression and vimentin over-expression were associated with worse survival (recurrence, specific and overall survival). A categorical marker CAIX-/Vimentin+ with cutoff points for CAIX and vimentin of 30 and 50 %, respectively, was designed. The new CAIX-/Vimentin+ marker presented a good concordance and comparable calibration to the reference model. Limitations are the retrospective design, the need for external validation and the large study period., Conclusion: Using an automated technique of measurement, CAIX and vimentin are independent predictors of clinical outcomes in ccRCC.

Purpose: To establish consensus on follow-up (FU) after focal therapy (FT) in renal masses. To formulate recommendations to aid in clinical practice and research., Methods: Key topics and questions for consensus were identified from a systematic literature research. A Web-based questionnaire was distributed among participants selected based on their contribution to the literature and/or known expertise. Three rounds according to the Delphi method were performed online. Final discussion was conducted during the "8th International Symposium on Focal Therapy and Imaging in Prostate and Kidney Cancer" among an international multidisciplinary expert panel., Results: Sixty-two participants completed all three rounds of the online questionnaire. The panel recommended a minimum follow-up of 5 years, preferably extended to 10 years. The first FU was recommended at 3 months, with at least two imaging studies in the first year. Imaging was recommended biannually during the second year and annually thereafter. The panel recommended FU by means of CT scan with slice thickness ≤3 mm (at least three phases with excretory phase if suspicion of collecting system involvement) or mpMRI. Annual checkup for pulmonary metastasis by CT thorax was advised. Outside study protocols, biopsy during follow-up should only be performed in case of suspicion of residual/persistent disease or radiological recurrence., Conclusions: The consensus led to clear FU recommendations after FT of renal masses supported by a multidisciplinary expert panel. In spite of the low level of evidence, these recommendations can guide clinicians and create uniformity in the follow-up practice and for clinical research purposes., Competing Interests: All authors of this manuscript declare no conflict of interest. Ethical standards All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Purpose: Biopsies and cytology are cornerstones in the diagnosis of upper urinary tract urothelial carcinoma. However, a high rate of nondiagnostic biopsies, tumor upgrading and tumor up staging after nephroureterectomy has been observed. In this prospective in vivo study we evaluated the diagnostic accuracy of optical coherence tomography for the grading and staging of upper tract urothelial carcinoma., Materials and Methods: A total of 26 patients underwent diagnostic ureterorenoscopy including biopsies and optical coherence tomography, followed by nephroureterectomy or segmental ureter resection. The sensitivity, specificity, negative predictive value and positive predictive value of upper tract urothelial carcinoma grading and staging by optical coherence tomography were evaluated according to the STARD (Standards for Reporting of Diagnostic Accuracy) initiative and the second stage (2a and 2b) of the IDEAL model. For tumor staging a 2×2 table for sensitivity and specificity was calculated. For tumor grading the Wilcoxon rank sum test was used to test μ oct in low and high grade lesions followed by ROC analysis for sensitivity and specificity., Results: In 83% the staging of lesions was in accordance with final histopathology. Sensitivity and specificity analysis for tumor invasion was 100% and 92%, respectively. Tumor size greater than 2 mm and inflammation were risks for false-positives. For low and high grade lesions median μ oct was 2.1 and 3.0 mm -1 , respectively (p <0.01). ROC analysis showed a sensitivity of 87% and a specificity of 90% using a μ oct cutoff of 2.4 mm -1 ., Conclusions: This report describes optical coherence tomography as a real-time, intraoperatively diagnostic modality in the diagnostic evaluation of upper tract urothelial carcinoma. We confirmed the ability of optical coherence tomography to visualize, grade and stage urothelial carcinoma in the upper urinary tract., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Cryoablation (CA) has been broadly used mostly in the treatment of small renal masses (SRMs). The present review aims to define the current role of CA in the treatment of SRMs by assessing clinical indications and outcomes., Method: A comprehensive review on patient selection, procedural details, perioperative complications, and short/long-term oncological and functional outcomes was conducted. For each section, a take-home message was formulated with level of evidence (LoE) according to Cochrane collaboration., Results: Age and comorbidity drive the choice of ablation in SRMs, although hospital setting also influences the decision. Technically in adequate CA or first post-CA control occurs in 3-5% of laparoscopic cryoablation (LCA) or percutaneous cryoablation (PCA) series. Meta-analysis does not evidence differences in the rate of residual tumor per person-year between the approaches (0.033 LCA vs. 0.046 PCA, p = 0.25). Perioperative complications (8-25%) are erratically reported. LCA has significantly lower likelihood of complications than minimally invasive partial nephrectomy (MIPN). Systematic reviews indicate 30-month local tumor progression rate of 8.5% for LCA in renal cell carcinoma but low metastatic progression (1-4.4%). Few LCA long-term follow-up series (mean/media 48-98 months) report recurrence-free survival (RFS) and cancer-specific survival (CSS) ranges of 80-100%. For PCA, Kaplan-Meier local disease-free survival (DFS) of 95.6% at 3-5 years [32] and 5-year overall survival and local RFS of 86.3% were reported. The decrease in renal function after CA is minimal, and the only risk factor associated is the basal estimated glomerular filtration rate (eGFR)., Conclusion: LoE 3a/b confirms lower CA perioperative complication rate and higher local progression rate than those for MIPN. CA preserves postoperative renal functional, without any evidence of differences in mid-/long-term follow-up compared to nephron sparing surgery., (Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa)., Methods: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated., Results: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text., Conclusion: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice., Competing Interests: Compliance with ethical standards This is a report of a Delphi consensus project among experts only. No human or animal subjects were involved; therefore, no informed consent was collected. Conflict of interest O.U reports being a consultant for Sonacare Medical. A.A. reports consulting for Steba Biotech. A.Bl., M.S., R.S. and S.C. report being consultants for EDAP TMS. S.E. reports being a consultant for NxThera and Profound Medical. J.J. reports being consultant for Endocare. C.K. reports being a consultant for Elekta and organizing educational internships sponsored by Elekta, Siemens, Philips, Medicom and Hitachi. T.P. reports performing a clinical trial with Angiodynamics and being a consultant for Healthtronics. The other authors report no conflicts of interest.

Purpose: Hyperthermia is an established (neo)adjuvant treatment modality for a number of pelvic malignancies. Optimal treatment of these tumors requires robust treatment planning, but up until now, the urinary bladder was not modeled accurately, making current simulations less reliable. The authors improved the dielectric and thermophysical model of the urinary bladder in their treatment planning system, and showed the improvements using phantom experiments., Methods: The authors suspended a porcine bladder in muscle tissue equivalent gel and filled it with 120 ml 0.9% saline. The authors heated the phantom during 15 min with their deep hyperthermia device, using clinical settings, and measured the temperature both inside and outside the bladder. The authors simulated the experiment, both using the clinically used treatment planning system, and using the improved model featuring correct dielectric properties for the bladder content and an enhanced thermophysical model, enabling the simulation of convection., Results: Although the dielectric changes have an impact throughout the phantom, the dominant effect is a higher net heat absorption in the bladder. The effects of changing the thermophysical model are limited to the bladder and its surroundings, but result in a very different temperature profile. The temperatures predicted by the simulations using the new bladder model were in much better agreement with the measurements than those predicted by currently used treatment planning system., Conclusions: Modeling convection in the urinary bladder is very important for accurate hyperthermia treatment planning in the pelvic area.

The aim of this study is to identify changes in scattering with optical coherence tomography (OCT) and relate these measurements with mitochondrial changes during the initiation of apoptosis. Human retinal pigment epithelial cells were cultured and apoptosis was induced using 10% alcohol. Using the attenuation coefficient and backscattering, changes were measured during cell death in a cell-pellet and monolayer respectively. To confirm apoptosis, fluorescent activated cell sorting was used. Mitochondrial activity during apoptosis was assessed using an oxidative stress assay and fluorescent confocal microscopy. Pelleted apoptotic cells measured with OCT showed a clear rise while untreated cells showed a very small increase in attenuation coefficient. Monolayered apoptotic cells displayed a distinct increase, while untreated cells showed a small increase in the backscattering. Apoptosis was confirmed by FACS experiments. Mitochondrial changes during the onset of apoptosis were also measured. The results demonstrate that apoptotic cell death could be monitored in real-time by OCT. Changes in the scattering after induction of apoptosis are likely to be related to changes in the intracellular morphology. Oxidative stress-induced mitochondrial swelling could be responsible for the initial increase, while cell blebbing and secondary necrosis subsequently for the observed decrease in scattering., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Irreversible electroporation is a tissue ablation modality that uses high voltage electric energy to induce an increase in cell membrane permeability. This causes destabilization of the existing cellular transmembrane potential leading to cell death, due to the inability to maintain cellular homeostasis. This phase I-II study was designed to evaluate the histopathological outcomes of irreversible electroporation to prostate and surrounding tissue in radical prostatectomy specimens., Materials and Methods: Sixteen patients with prostate cancer underwent an irreversible electroporation ablation without curative intent, followed by radical prostatectomy scheduled 4 weeks later. For histopathological examination of the prostate, whole mounted tissue slices were examined by dedicated genitourinary pathologists. The borders of the ablation zone and residual tumor were outlined on the slides., Results: The irreversible electroporation ablation zones were characterized as areas of fibrosis, necrosis and loss of epithelial tissue in terms of denudation in the glandular structures. The ablation zone was well demarcated, showing trenchant delineations between viable and nonviable tissue. The ablated tissue showed mild to moderate inflammation, with atrophic cells in 1 case. The area was surrounded by hemorrhage at the location of the electrodes. No skip lesions or viable tissue was seen in the ablation zone. Fibrinoid necrosis of the neurovascular bundle was observed in 13 patients and denudation of the urothelium of the prostatic urethra was seen in 9., Conclusions: Histopathological assessment of the prostate 4 weeks after irreversible electroporation ablation showed sharply demarcated fibrotic and necrotic tissue in the ablation zone. No viable tissue was observed in the irreversible electroporation ablation zone., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Irreversible electroporation (IRE) is an ablative therapy with a low side-effect profile in prostate cancer. The objective was: 1) To compare the volumetric IRE ablation zone on grey-scale transrectal ultrasound (TRUS), contrast-enhanced ultrasound (CEUS) and multiparametric MRI (mpMRI) with histopathology findings; 2) To determine a reliable imaging modality to visualize the IRE ablation effects accurately., Methods: A prospective phase I-II study was performed in 16 patients scheduled for radical prostatectomy (RP). IRE of the prostate was performed 4 weeks before RP. Prior to, and 4 weeks after the IRE treatment, imaging was performed by TRUS, CEUS, and mpMRI. 3D-analysis of the ablation volumes on imaging and on H&E-stained whole-mount sections was performed. The volumes were compared and the correlation was calculated., Results: Evaluation of the imaging demonstrated that with T2-weighted MRI, dynamic contrast enhanced (DCE) MRI, and CEUS, effects of IRE are visible. T2MRI and CEUS closely match the volumes on histopathology (Pearson correlation r = 0.88 resp. 0.80). However, IRE is not visible with TRUS., Conclusions: mpMRI and CEUS are appropriate for assessing IRE effects and are the most feasible imaging modalities to visualize IRE ablation zone. The imaging is concordant with results of histopathological examination., Key Points: • mpMRI and contrast-enhanced ultrasound are appropriate imaging modalities for assessing IRE effects • mpMRI and CEUS are the most feasible imaging modalities to visualize IRE ablation zone • The imaging is concordant with results of histopathological examination after IRE • Grey-scale US is insufficient for assessing IRE ablations.

Objective: Focal therapy (FT) is a tissuesparing treatment paradigm for localized prostate cancer (PCa) with the potential to improve functional outcomes while maintaining oncologic safety. This paper aims to provide an overview of important considerations and practical recommendations relating to the follow-up after FT., Methods: Literature review of papers related to FT in PCa derived from Medline/Pubmed database., Results: The recommended minimum follow-up period after FT is 5 years. Standard history taking should include: signs of disease progression, treatment-related complications and psychological aspects. Oncological outcome is based on serial prostate specific antigen monitoring, follow-up imaging (most commonly with multiparametric magnetic resonance imaging) and repeat biopsies (systematic from entire gland or targeted from treated zone). Significant PCa has been found at biopsy in up to 17% of patients after FT. Functional outcomes are evaluated using standardized questionnaires that relate to urinary function, erectile function and quality of life. A systematic review reports urinary continence in 83-100% of patients, erections sufficient for penetration in 54-100%. Outcomes differ between ablative energies and treatment templates. The most common side effects after FT are urinary retention (0-17%), urinary tract infection (UTI) (0-17%) and urinary stricture (0-5%). Rectal fistula is a rare complication occurring in up to 0.1-2% of patients. Clavien-Dindo Grade 3-4 complications are reported in 0-4% of patients. Type and rate vary with treatment modality. Complications should be reported using standardized reporting systems. Most data on FT outcomes come from small heterogeneous trials. Pooling of standardized data is necessary to advance the field of FT., Conclusion: Stringent follow-up after FT is required to confirm oncologic safety of the individual patient. Standardized data gathering and data pooling is necessary to evaluate whether FT can live up to its promise of improving functional outcomes while maintaining oncological safety.

The extensive use of prostate-specific antigen (PSA) testing and improved imaging technologies have resulted in an increased diagnosis of prostate cancer. Early diagnosis is often accompanied by an increased number of localized (i.e. unifocal or unilateral), small-volume and low-grade prostate cancers. Focal therapy is an emerging treatment option in prostate cancer, targeting individual cancer areas while sparing important functional and anatomical urological structures. Irreversible electroporation is an innovative treatment modality in focal therapy based on the process of cell membrane electroporation limiting damage to adjacent tissue and vital structures. The first phase I-II trials in humans have shown the safety of IRE for focal ablative therapy of prostate cancer and showed encouraging results considering functional preservation. Histological analysis after IRE showed fibrosis without glandular ducts and necrotic tissue with sharp demarcation between unaffected prostatic glandular tissue and the ablation zone. Short-term oncological results are promising; however more data on long-term oncological outcomes are necessary. New studies with IRE and other focal treatment modalities are initiated to explore opportunities for focal therapy in prostate cancer and to optimize current treatment protocols.

Non-muscle-invasive bladder cancer (NMIBC) is characterised by a high risk of recurrence for the present standard treatment of transurethral resection of the bladder (TURB) followed by intravesical instillation of Mitomycin-C (MMC) or bacillus Calmette-Guérin (BCG). To decrease this high recurrence rate, alternative treatments are studied. Intravesical MMC combined with hyperthermia could be an interesting alternative active treatment for intermediate- and high-risk NMIBC, and has been investigated in the past years. Hyperthermia, raising tumour temperatures to 40-44 °C, can be achieved with several hyperthermia systems, based on three different techniques: 1) intravesical microwave induced heating, 2) conductive heating, and 3) loco-regional, using external radiofrequency antennas. In this review an overview is given of the available hyperthermia systems and the reported outcomes. Future directions are discussed. Optimal implementation of a combined regimen of MMC and hyperthermia requires further clinical trials to identify patients who will benefit most from this treatment, to optimise treatment schedules and to compare the efficacy of different hyperthermia devices.

Background: Current surgical and ablative treatment options for prostate cancer (PCa) may result in a high incidence of (temporary) incontinence, erectile dysfunction and/or bowel damage. These side effects are due to procedure related effects on adjacent structures including blood vessels, bowel, urethra and/or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective and safe in destroying PCa cells and also has the potential advantage of sparing surrounding tissue and vital structures, resulting in less impaired functional outcomes and maintaining men's quality of life., Methods/design: In this randomized controlled trial (RCT) on IRE in localized PCa, 200 patients with organ-confined, unilateral (T1c-T2b) low- to intermediate-risk PCa (Gleason sum score 6 and 7) on transperineal template-mapping biopsies (TTMB) will be included. Patients will be randomized into focal or extended ablation of cancer foci with IRE. Oncological efficacy will be determined by multiparametric Magnetic Resonance Imaging, Contrast-Enhanced Ultrasound imaging if available, TTMP and Prostate Specific Antigen (PSA) follow-up. Patients will be evaluated up to 5 years on functional outcomes and quality of life with the use of standardized questionnaires., Discussion: There is critical need of larger, standardized RCTs evaluating long-term oncological and functional outcomes before introducing IRE and other focal therapy modalities as an accepted and safe therapeutic option for PCa. This RCT will provide important short- and long-term data and elucidates the differences between focal or extended ablation of localized, unilateral low- to intermediate-risk PCa with IRE., Trial Registration: Clinicaltrials.gov database registration number NCT01835977. The Dutch Central Committee on Research Involving Human Subjects registration number NL50791.018.14.

The diagnostic accuracy of Optical Coherence Tomography (OCT) based optical attenuation coefficient analysis is assessed for the detection of prostate cancer. Needle-based OCT-measurements were performed on the prostate specimens. Attenuation coefficients were determined by an earlier described in-house developed software package. The mean attenuation coefficients (benign OCT data; malignant OCT data; p-value Mann-Whitney U test) were: (3.56 mm(-1) ; 3.85 mm(-1) ; p < 0.0001) for all patients combined. The area under the ROC curve was 0.64. In order to circumvent the effect of histopathology mismatching, we performed a sub-analysis on only OCT data in which tumor was visible in two subsequent histopathological prostate slices. This analysis could be performed in 3 patients. The mean attenuation coefficients (benign OCT data; malignant OCT data; p-value Mann-Whitney U test) were: (3.23 mm(-1) ; 4.11 mm(-1) ; p < 0.0001) for all patients grouped together. The area under the ROC curve was 0.89. Functional OCT of the prostate has shown to differentiate between cancer and healthy prostate tissue. The optical attenuation coefficient in malignant tissue was significantly higher in malignant tissue compared to benign prostate tissue. Further studies are required to validate these initial results in a larger group of patients with a more tailored histopathology matching protocol., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Irreversible electroporation (IRE) is a novel minimally invasive therapy for prostate cancer using short electric pulses to ablate prostate tissue. The purpose of this study is to determine the IRE effects in prostate tissue and correlate electrode configuration with the histology of radical prostatectomy (RP) specimens. We hypothesize that the area within the electrode configuration is completely ablated and that the area within the electrode configuration is predictive for the ablated area after treatment., Methods: A prospective phase I/II study was conducted in 16 consecutive patients with histopathologically confirmed prostate cancer scheduled for RP. Focal or extended IRE treatment of the prostate was performed 4 weeks prior to RP. The locations of the electrodes were used to calculate the planned ablation zone. Following RP, the specimens were processed into whole-mount sections, histopathology (PA) was assessed and ablation zones were delineated. The area of the tissue alteration was determined by measuring the surface. The planned and the histological ablation zones were compared, analysed per individual patient and per protocol (focal vs. extended)., Results: All cells within the electrode configuration were completely ablated and consisted only of necrotic and fibrotic tissue without leaving any viable cells. The histological ablation zone was always larger than the electrodes configuration (2.9 times larger for the 3 electrodes configuration and 2.5 times larger for the ≥4 electrode configuration). These ablation effects extended beyond the prostatic capsule in the neurovascular bundle in 13 out of 15 cases., Conclusions: IRE in prostate cancer results in completely ablated, sharply demarcated lesions with a histological ablation zone beyond the electrode configuration. No skip lesions were observed within the electrode configuration., Clinical Trials: ClinicalTrials.gov Identifier: NCT01790451 https://clinicaltrials.gov/ct2/show/NCT01790451.