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Testis-sparing surgery (TSS) is a guideline-recommended treatment option for men with synchronous or metachronous bilateral testicular germ-cell tumor (GCT) or GCT in a solitary testicle. The tumor volume should not exceed 50% of the total testicular volume and serum concentrations of both testosterone and luteinizing hormone should be within the normal ranges. After tumor enucleation, patients should undergo adjuvant radiation of the testicle in case of germ cell neoplasia in situ. The local relapse rate is approximately 4% if TSS is performed properly. Physiological serum testosterone concentrations are achieved in more than 85% of patients, and approximately 50% of men with intact spermatogenesis can achieve paternity. The risk of systemic metastases is not increased by TSS. Patient summary: Testis-sparing surgery is the treatment of choice for men with testicular cancer in both testes or in men who have just one testis. In more than 85% of patients this approach results in maintenance of normal testosterone levels.

Introduction & Objectives: Kidney-sparing surgery (KSS) seems inferior to radical nephroureterectomy (RNU) in recurrence-free survival (RFS). However, there is limited data regarding the potential influence of the location of the upper tract urothelial carcinoma (UTUC). The current study aims to provide further evidence by the largest UTUC registry.

Objective: To compare the effectiveness and safety of standard percutaneous nephrolithotomy (sPCNL) and super-mini PCNL (SMP). Patients and Methods: A total of 150 patients presenting with renal calculi of

Objective To study the incidence of postoperative systemic inflammatory response syndrome (SIRS) following different antibiotic prophylaxis (ABP) regimens in retrograde intrarenal surgery (RIRS). Patients and methods Single-centre, randomised, controlled trial (August 2014-September 2017) including 426 patients with renal stones with preoperative sterile urine managed by RIRS (ClinicalTrials.gov NCT02304822). Different ciprofloxacin-based ABP regimens were used and included a zero dose, single dose (30 min before surgery) or two doses (first dose at 30 min before RIRS and additional dose within 6 h after RIRS). The incidence of SIRS was compared using intention-to-treat (ITT) and per-protocol (PP) analyses. Results Each group enrolled 142 patients. In the ITT analysis, a zero dose of ABP was statistically similar to the two ABP regimes for the incidence of SIRS (9.9% vs single dose 4.9%, P = 0.112; vs two doses 4.2%, P = 0.062). There were also no relevant differences across groups in the PP analysis; no urosepsis was recorded. In subgroup analysis with stratification by stone area, the three regimens all had a low and similar incidence of SIRS for stones of ≤200 mm2 in the ITT analysis with a sufficient power value (5.4% vs 6.2% vs 3.6%, P = 0.945 vs single dose and P = 0.553 vs two doses). However, there was a greater chance of SIRS in patients who received no ABP with stones of >200 mm2 (18% vs single dose 4.3%, P = 0.036; vs two doses 5.5%, P = 0.044). Similar trends were seen in the PP analysis. Conclusions For patients with preoperative sterile urine, ABP is not strongly recommended in patients with stones of ≤200 mm2 , but for stones >200 mm2 single-dose ABP is still required.

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.

This systematic review was conducted to assess the diagnostic accuracy of chronic kidney disease screening tests in the general population. MEDLINE, EMBASE, Web of Science, Scopus, The Cochrane Library and ProQuest databases were searched for English-language publications up to November 2016. Two reviewers independently screened studies and extracted study data in standardized tables. Methodological quality was assessed using the QUADAS-2 tool. Sensitivity and specificity of all available screening methods were identified through included studies. Ten out of 1349 screened records included for final analysis. Sensitivities of the dipstick test with a cutoff value of trace were ranged from 37.1% to 69.4% and specificities from 93.7% to 97.3% for the detection of ACR>30 mg/g. The diagnostic sensitivities of the UAC>10 mg/dL testing was shown to vary from 40% to 87%, and specificities ranged from 75% to 96%. While the sensitivities of ACR were fluctuating between 74% and 90%, likewise the specificities were between 77% and 88%. Sensitivities for C-G, Grubb and Larsson equations were 98.9%, 86.2%, and 70.1% respectively. In the meantime the study showed specificities of 84.8%, 84.2% and 90.5% respectively for these equations. Individual studies were highly heterogeneous in terms of target populations, type of screening tests, thresholds used to detect CKD and variations in design. Results pointed to the superiority of UAC and dipstick over the other tests in terms of all parameters involved. The diversity of methods and thresholds for detection of CKD, necessitate considering the cost parameter along with the effectiveness of tests to scale-up an efficient strategy. [GMJ.2020;9:e1573]

Technological advances in minimally invasive treatment of stone disease and its integration with concomitant clinical practice are amongst the most important achievements in urology. Despite the wealth of information accumulated over the years and the richness of existing literature, the knowledge about the definition, treatment and outcomes of residual stone fragments after percutaneous nephrolithotomy (PNL) is still insufficient. Due to the high stone load a lot of patients with staghorn stones have residual fragments (RFs) after treatment with PNL, which depends on the size of tract, definition of stone free rate (SFR), timing of evaluation and the imaging used. No consensus exists on the imaging modality or their timing in the evaluation of possible RFs. The treatment of residual stones is apparently different depending on the facilities of the department and the preference of the surgeon, which includes active surveillance, shock wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS) or a second look PNL. Keywords: Urolithiasis, Stone management, Staghorn, Percutaneous nephrolithotomy, Residual fragments, Staghorn stones

Optical coherence tomography (OCT) is being investigated in urologic oncology for optical diagnosis. This comprehensive review analyzes the current state of development of OCT for bladder, upper urinary tract, kidney, prostate, testis, and penis cancer. Also, the potential role of OCT with regard to the current diagnostic pathways is critically appraised to guide future developments. Embase and Pubmed were systematically searched for English and German articles on OCT in humans up to December 2017. Reviews were excluded. Case reports were excluded, unless they presented a landmark in the development of OCT. Out of 878 articles, 17 relevant articles on bladder, seven on kidney, five on upper urinary tract, four on prostate, and two on penile cancer were included. In these organs, in vivo OCT imaging is feasible with potential for qualitative and quantitative diagnosis, grading and staging in specific organs. The development of OCT has reached IDEAL stage 2b with 2b level of evidence. Relevant articles on testis cancer were lacking. OCT allows for non- or minimally invasive cancer diagnosis in the bladder, upper urinary tract, kidney, prostate, and penis. In some organs, OCT also may enable histologic grade and stage prediction. However, the current evidence is still at an exploratory level. With regard to the potential additional value of OCT in comparison to the current diagnostic pathways, OCT could become a diagnostic replacement or add-on test for urothelial carcinoma, penile carcinoma, and renal masses. Further research in these conditions should be encouraged.

Objective To determine factors associated with performance and quality of lymph node dissection during radical nephrectomy. Materials and Methods Using an International Data Registry, we performed multilevel logistic regression to determine the association of surgical approach (open surgery vs minimally invasive surgery), institutional experience (low, moderate, and high tertiles), and institutional preference (minimally invasive surgery, balanced, and open surgery tertiles) with the performance of lymph node dissection in subgroups by clinical stage and nodal status. Results Among 1,742 patients undergoing radical nephrectomy, 312 (18%) underwent lymph node dissection, which was associated with stage (28% for ≥cT2 vs 9.3% for cT1), and nodal status (68% for ≥cN1 vs 13% for cN0). Open surgery was significantly associated with performing lymph node dissection in all subgroups. Institutional experience and institutional preference had no association with performing lymph node dissection in the ≥cN1 group. The number of nodes removed was greater for open surgery (mean 5.9) vs minimally invasive surgery (mean 3.4); this held true even when stratified by stage and nodal status. Conclusion In this large dataset, open surgical radical nephrectomy is associated with more frequent performance and higher quality of lymph node dissection, which may owe to selection bias but also could reflect technical concerns. In the patient population in whom lymph node dissection is recommended (≥cN1), this is not explained by institutional experience or preference. Lymph node dissection may be under-utilized for ≥cN1 disease and over-utilized for cN0 disease, at least according to practice guidelines.

Objective: To study the incidence of postoperative systemic inflammatory response syndrome (SIRS) following different antibiotic prophylaxis (ABP) regimens in retrograde intrarenal surgery (RIRS). Patients and Methods: Single-centre, randomised, controlled trial (August 2014–September 2017) including 426 patients with renal stones with preoperative sterile urine managed by RIRS (ClinicalTrials.gov NCT02304822). Different ciprofloxacin-based ABP regimens were used and included a zero dose, single dose (30 min before surgery) or two doses (first dose at 30 min before RIRS and additional dose within 6 h after RIRS). The incidence of SIRS was compared using intention-to-treat (ITT) and per-protocol (PP) analyses. Results: Each group enrolled 142 patients. In the ITT analysis, a zero dose of ABP was statistically similar to the two ABP regimes for the incidence of SIRS (9.9% vs single dose 4.9%, P = 0.112; vs two doses 4.2%, P = 0.062). There were also no relevant differences across groups in the PP analysis; no urosepsis was recorded. In subgroup analysis with stratification by stone area, the three regimens all had a low and similar incidence of SIRS for stones of ?200 mm2 in the ITT analysis with a sufficient power value (5.4% vs 6.2% vs 3.6%, P = 0.945 vs single dose and P = 0.553 vs two doses). However, there was a greater chance of SIRS in patients who received no ABP with stones of >200 mm2 (18% vs single dose 4.3%, P = 0.036; vs two doses 5.5%, P = 0.044). Similar trends were seen in the PP analysis. Conclusions: For patients with preoperative sterile urine, ABP is not strongly recommended in patients with stones of ?200 mm2, but for stones >200 mm2 single-dose ABP is still required.

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_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_search.nsf/fABRpop?readform&unids=D27C9C3E5755CFECC12581690016779F (Archived by WebCite at http://www.webcitation.org/6wvy8R44C).

Minimal invasive endoscopic treatment for upper urinary tract urothelial carcinoma (UUT-UC) is advocated in patients with low-risk disease and limited tumor volume. Diagnostic ureterorenoscopy combined with biopsy is the diagnostic standard. This study aims to evaluate two alternative diagnostic techniques for UUT-UC: optical coherence tomography (OCT) and endoluminal ultrasound (ELUS). Following nephroureterectomy, OCT, ELUS, and computed tomography (CT) were performed of the complete nephroureterectomy specimen. Visualization software (AMIRA®) was used for reconstruction and coregistration of CT, OCT, and ELUS. Finally, CT was used to obtain exact probe localization. Coregistered OCT and ELUS datasets were compared with histology. Coregistration with three-dimensional CT makes exact data matching possible in this ex-vivo setting to compare histology with OCT and ELUS. In OCT images of normal-appearing renal pelvis and ureter, urothelium, lamina propria, and muscularis were visible. With ELUS, all anatomical layers of the ureter could be distinguished, besides the urothelial layer. ELUS identified suspect lesions, although exact staging and differentiation between noninvasive and invasive lesions were not possible. OCT provides high-resolution imaging of normal ureter and ureter lesions. ELUS, however, is of limited value as it cannot differentiate between noninvasive and invasive tumors.

Developments in optical diagnostics have potential for less invasive diagnosis of upper urinary tract urothelial carcinoma (UUT-UC). This systematic review provides an overview of technology, applications, and limitations of recently developed optical diagnostics in the upper urinary tract and outlines their potential for future clinical applications. In addition, current evidence was evaluated. A PubMed literature search was performed and articles on narrow band imaging (NBI), photodynamic diagnosis (PDD), Storz professional imaging enhancement system (SPIES), optical coherence tomography (OCT), and confocal laser endomicroscopy (CLE) regarding UUT-UC were reviewed for data extraction. Study quality was reviewed according to Quality Assessment of Diagnostic Accuracy Studies and Innovation, Development, Exploration, Assessment, and Long-term follow-up (IDEAL) standards. Four articles available for quality assessment, demonstrated high level of evidence, but low level of IDEAL stage. NBI and SPIES enhance contrast of mucosal surface and vascular structures, improving tumor detection rate. A first in vivo study showed promising results. PDD uses fluorescence to improve tumor detection rate. However, due to the acute angle of the ureterorenoscopes there is an increased risk of false positives. OCT produces cross-sectional high-resolution images, providing information on tumor grade and stage. A pilot study showed promising diagnostic accuracy. CLE allows ultrahigh-resolution microscopy of tissue resulting in images of the cellular structure. CLE cannot be applied in vivo in the upper urinary tract yet, due to technical limitations. NBI, SPIES, and PDD aim at improving visualization of UUT-UC through contrast enhancement. OCT and CLE aim at providing real-time predictions of histopathological diagnosis. For all techniques, more research has to be conducted before these techniques can be implemented in the routine management of UUT-UC. All techniques might be of value in specific clinical scenarios and allow for integration, for example, OCT with NBI, and could therefore improve tumor detection and staging and help in selecting the optimal treatment for the individual patient

A significant number of patients with intermediate- or high-risk bladder cancer treated with intravesical Bacillus Calmette–Guérin (BCG) immunotherapy are non-responders to this treatment. Since we cannot predict in which patients BCG therapy will fail, markers for responders are needed. UroVysion® is a multitarget fluorescence in situ hybridization (FISH) test for bladder cancer detection. The aim of this study was to evaluate whether FISH can be used to early identify recurrence during treatment with BCG. In a multicenter, prospective study, three bladder washouts at different time points during treatment (t 0 = week 0, pre-BCG, t 1 = 6 weeks following TURB, t 2 = 3 months following TURB) were collected for FISH from patients with bladder cancer treated with BCG between 2008 and 2013. Data on bladder cancer recurrence and duration of BCG maintenance therapy were recorded. Thirty-six (31.6%) out of 114 patients developed a recurrence after a median of 6 months (range 2–32). No significant association was found between a positive FISH test at t 0 or t 1 and risk of recurrence (p = 0.79 and p = 0.29). A positive t 2 FISH test was associated with a higher risk of recurrence (p = 0.001). Patients with a positive FISH test 3 months following TURB had a 4.0–4.6 times greater risk of developing a recurrence compared to patients with a negative FISH. Patients with a positive FISH test 3 months following TURB and induction BCG therapy have a higher risk of developing tumor recurrence. FISH can therefore be a useful additional tool for physicians when determining a treatment strategy. Electronic supplementary material The online version of this article (doi:10.1007/s12032-017-1033-z) contains supplementary material, which is available to authorized users.

Background Lack of accuracy in preoperative imaging leads to overtreatment of benign renal masses (RMs) or indolent renal cell carcinomas (RCCs). Optical coherence tomography (OCT) is real time and high resolution, enabling quantitative analysis through attenuation coefficient (μ OCT , mm −1 ). Objective To determine the accuracy and diagnostic yield of OCT and renal mass biopsy (RMB) for the differentiation of benign RMs versus RCC and oncocytoma versus RCC. Design, setting, and participants From October 2013 to June 2016, 95 patients with solid enhancing RMs on cross-sectional imaging were prospectively included. All patients underwent subsequent excision or ablation. Intervention Percutaneous, image-guided, needle-based OCT followed by RMB in an outpatient setting under local anaesthesia. Outcome measurements and statistical analysis Accuracy and diagnostic yield, μ OCT correlated to resection pathology or second biopsy during ablation. Tables (2×2) for RMB, receiver operating characteristic curve for OCT. Mann-Whitney test to differentiate μ OCT of RMs. Results and limitations RMB diagnostic yield was 79% with sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 100%, 89%, 99%, and 100%, respectively. Diagnostic yield and added value of OCT to differentiate RCC from benign was 99% and 15%, respectively. Significant difference was observed in median μ OCT between benign RMs (3.2mm −1 , interquartile range [IQR]: 2.65–4.35) and RCCs (4.3mm −1 , IQR: 3.70–5.00), p =0.0171, and oncocytomas (3.38mm −1 , IQR: 2.68–3.95) and RCCs (4.3mm −1 , IQR: 3.70–5.00), p =0.0031. OCT showed sensitivity, specificity, positive predictive value. and NPV of 91%, 56%, 91%, and 56%, respectively, to differentiate benign RMs from RCCs and 92%, 67%, 95%, and 55%, respectively, to differentiate oncocytoma from RCC. Limitations include two reference standards and heterogeneity benign RMs. Conclusions Compared with RMB, OCT has a higher diagnostic yield. OCT accurately distinguishes benign RMs from RCCs, and oncocytoma from RCCs, although specificity and NPV are lower. Patient summary Optical coherence tomography, a new optical scan, exhibits similar sensitivity and positive predictive value than renal mass biopsy, although lower specificity and negative predictive value. Optical coherence tomography has a higher diagnostic yield for diagnosing renal cell carcinoma.

Context Patients with clinical stage I (CS I) seminoma testis with large primary tumours and/or rete testis invasion (RTI) might have an increased risk of relapse. In recent years, these risk factors have frequently been employed to decide on adjuvant treatment. Objective To systematically review the literature on tumour size and RTI as risk factors for relapse in CS I seminoma testis patients under surveillance. Evidence acquisition Relevant databases including Medline, Embase, and the Cochrane Library were searched up to November 2016. Randomised controlled trials (RCTs) or quasi-RCTs, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The primary outcome was the rate of relapse and relapse-free survival (RFS). The risk of bias was assessed by the Quality in Prognosis Studies tool. Evidence synthesis After assessing 3068 abstracts and 80 full-text articles, 20 studies met the inclusion criteria. Although evidence to justify a cut-off of 4cm for size was lacking, it was the most frequently studied. The reported hazard ratio (HR) for the RFS for tumours >4cm was 1.59–2.8. Accordingly, the reported 5-yr RFS ranged from 86.6% to 95.5% and from 73.0% to 82.6% for patients having tumours ≤4 and >4cm, respectively. For tumours with RTI present, the reported HR was 1.4–1.7. The 5-yr RFS ranged from 86.0% to 92.0% and 74.9% to 79.5% for patients without versus those with RTI present, respectively. A meta-analysis was considered inappropriate due to data heterogeneity. Conclusions Primary tumour size and RTI are associated with the risk of relapse in CS I seminoma testis patients during surveillance. However, in the presence of either risk factor, the vast majority of patients are cured by orchiectomy alone and will not relapse. Furthermore, the evidence on the prognostic value of size and RTI has significant limitations, so prudency is warranted on their routine use in clinical practice. Patient summary Primary testicular tumour size and rete testis invasion are considered to be important prognostic factors for the risk of relapse in patients with clinical stage I seminoma testis. We systematically reviewed all the literature on the prognostic value of these two postulated risk factors. The outcome is that the prognostic power of these factors in the published literature is too low to advocate their routine use in clinical practice and to drive the choice on adjuvant treatment in clinical stage I seminoma testis patients.

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. 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. 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. Using an automated technique of measurement, CAIX and vimentin are independent predictors of clinical outcomes in ccRCC.

Purpose The purposes of this paper were to present the current status of contrast-enhanced transrectal ultrasound imaging and to discuss the latest achievements and techniques now under preclinical testing. Objective Although grayscale transrectal ultrasound is the standard method for prostate imaging, it lacks accuracy in the detection and localization of prostate cancer. With the introduction of contrast-enhanced ultrasound (CEUS), perfusion imaging of the microvascularization became available. By this, cancer-induced neovascularisation can be visualized with the potential to improve ultrasound imaging for prostate cancer detection and localization significantly. For example, several studies have shown that CEUS-guided biopsies have the same or higher PCa detection rate compared with systematic biopsies with less biopsies needed. Materials and methods This paper describes the current status of CEUS and discusses novel quantification techniques that can improve the accuracy even further. Furthermore, quantification might decrease the user-dependency, opening the door to use in the routine clinical environment. A new generation of targeted microbubbles is now under pre-clinical testing and showed avidly binding to VEGFR-2, a receptor up-regulated in prostate cancer due to angiogenesis. The first publications regarding a targeted microbubble ready for human use will be discussed. Conclusion Ultrasound-assisted drug delivery gives rise to a whole new set of therapeutic options, also for prostate cancer. A major breakthrough in the future can be expected from the clinical use of targeted microbubbles for drug delivery for prostate cancer diagnosis as well as treatment.

Purpose: Injury to blood microvessels has a crucial role in effective cryoablation for renal masses. We visualized vascular injury induced by a clinically applied cryoablation instrument and established a microvascular diameter threshold for vascular damage. Materials and Methods: In 5 anesthetized pigs 1 kidney each was exposed and 3, 17 gauge cryoneedles were inserted in 1 pole. Tissue was exposed to freezing for 2 x 10 minutes with a 10-minute thaw between freezes. After nephrectomy the arteries were injected with fluorescence dyed casting material and the kidney was frozen to -20C and cut in 40 to 60 mu slices in the imaging cryomicrotome, where fluorescent images of the cutting plane of the bulk were obtained. This resulted in a 3-dimensional image of the arterial tree that was segmented, resulting in unbranched vessel segments. Histograms were constructed with the total segment length per diameter bin plotted as function of diameter. Results: The ablated zone was sharply demarcated on fluorescent and normal light images. Mean SD diameter at the peak of the histogram from control areas was 152.4 +/- 5.3 mu. Compared to control areas the peak diameter of ablated areas was shifted to a larger diameter by an average of 25.4 +/- 2.6 mu. Conclusions: Immediate renal cryoablation injury destroys arteries smaller than 180 mu. Branching structures of larger arteries remain anatomically intact and connected to vascular structures in surrounding tissue

Life expectancy gradually increases in the Western part of the world. Older patients may present with small, localized tumours and/or advanced or metastatic disease and still, potentially, have a considerable life expectancy. The consequence of the increased life span is that in older patients all potential treatments have to be discussed. A critical review of the literature regarding the treatment of different stages of renal cell cancer (RCC) in the elderly patient group was conducted. Elderly people with small renal masses are up to 3.5 times more likely to have a benign lesion. The oncological outcome from nephron sparing surgery (NSS), whether by means of laparoscopy or by means of open surgery, seems not to be different between young and old patients. No relationship between local recurrence and metastatic progression rates and patient age has been demonstrated. The outcome from systemic treatments in advanced/metastatic disease has been studied, no differences were observed between age groups, although toxicity profiles might differ between the younger and older patient groups. (C) 2009 Elsevier Ireland Ltd. All rights reserved

Aim: To evaluate the diagnostic feasibility and reproducibility of immediate postcryoablation biopsies of small renal masses. Materials and Methods: Between December 2006 and July 2007, 21 intraoperative pre- and postcryoablation (18-gauge core) biopsies of renal masses were obtained. Evaluation of the biopsies by the institutional uropathologist was followed by a blind assessment by two other uropathologists. Tumor subtype and Fuhrman grade were determined by the three pathologists, while biopsy timing (before or after cryoablation) was only assessed by the two blinded pathologists. The diagnostic yield of the pre- and postcryoablation biopsies and interobserver agreement were calculated. Results: The mean size of the 21 cryoablated tumors was 2.8 cm. No significant bleeding occurred after any biopsy. Of the precryoablation biopsies 75-81% was correctly labeled as precryo, and 48% of the postcryoablation biopsies as postcryo. The diagnostic yield of the three pathologists for precryo biopsies ranged between 67% and 71%, and for postcryo biopsies between 48% and 71% (not statistically different). When combining both types of biopsies, the overall diagnostic yield was 81% for all pathologists. The interobserver agreement was "almost perfect'' (kappa = 0.902) for precryo biopsies and "substantial'' (kappa = 0.514) for postcryo biopsies. Conclusion: This study shows that it is feasible to obtain histopathological diagnoses from postcryoablation biopsies with a diagnostic yield and interobserver agreement similar to precryoablation biopsies

Purpose of review Testicular microlithiasis becomes a greater interdisciplinary issue among urologists, andrologists, gynecologists dedicated to reproductive medicine, pediatricians, radiologists and pathologists. Proposed management ranges from benign neglect, instructing self-examination over follow-up once, regular biannual follow-up including ultrasonography to bilateral testicular biopsy to rule out possible concomitant unclassified intratubular germ cell neoplasia (ITGCN) or future development of testicular cancer. The aim of this review is to present an overview of the current dilemma and summarize management trends based on the most recent data. Recent findings Testicular microlithiasis is not a premalignant condition but may accompany ITGCN or testicular cancer. The importance of ruling out ITGCN with testicular biopsy in high-risk men, such as in those with bilateral testicular microlithiasis, infertility, cryptorchidism, atrophic testes or contralateral testicular cancer, has been recently advocated. Summary Despite greater awareness of testicular microlithiasis, a clear definition is currently missing and the etiology is still obscure. This causes confusion in management and follow-up. Self-examination alone or in combination with testicular ultrasonography has been advised. Recently, a single set of biopsies in selected, high-risk groups has been proposed to rule out ITGCN without a need for further investigations apart from self-examination. However, the cost-effectiveness of such a strategy needs to be evaluated.

Objective To examine the ability of preoperative clinical characteristics to predict histological features of renal masses (RMs). Patients and Methods Data from consecutive patients with clinical stage I RMs treated surgically between 2010 and 2011 in the Clinical Research Office of Endourology Society (CROES) Renal Mass Registry were collected. Based on surgical histology, tumours were categorised as benign, low- or high-aggressiveness cancer. Multivariate logistic regression was used to estimate the probability of the histological group by clinical and radiographic features in the entire cohort and a subcohort of cT1a tumours. The performance of the models was studied by calibration, Nagelkerke's R2, and discrimination (area under the receiver operating characteristic curve). Results The study cohort included 2 224 patients with a clinical stage I RM, of which 1 367 (61%) were cT1a. Benign lesions were found in 369 (16.6%), low-aggressiveness tumours in 1 156 (52%) and high-aggressiveness tumours in 699 (31.4%). Male gender, smoking history, increased tumour size, and lower exophytic rate were associated with malignancy and high-aggressiveness features (all P < 0.05). Models developed based on these characteristics had the ability to discriminate benign from malignant (bootstrap corrected c-index of 0.64) and high-aggressiveness tumours from benign and low-aggressiveness tumours (bootstrap corrected c-index of 0.66). Similar results were achieved in the cT1a subgroup. The c-index of tumour diameter as a single predictor of malignancy and high-aggressiveness tumours in the entire cohort was 0.6 and 0.63, respectively. Conclusion Although older age, male gender, smoking history, increased tumour diameter, and reduced exophytic rate are associated with malignancy and high aggressiveness of clinical stage I RMs, models incorporating these characteristics have modest discriminating power, being only slightly better than the predictive ability of tumour size alone.

Laparoscopic partial nephrectomy (LPN) is increasingly performed all over the world. However, as in its open counterpart, achieving a satisfactory haemostasis may be challenging. Our goal is to describe the different methods employed to control bleeding during LPN. We performed a non-structured review of the literature on the different haemostatic methods used during LPN. The techniques and materials used are divided into two main groups: LPN with ischemia and LPN without ischemia. The techniques to achieve warm, cold and regional ischemia are described. Energy sources and sealants are discussed in the section on LPN without ischemia. Case selection is of capital importance in the choice the appropriate haemostatic tools for LPN. Some refinements, related to the nature of the laparoscopic procedure, are still required to reach an effective cold ischemia. A broad variety of energy sources have been tested in animal models and in human setting. Major disadvantages are tissue scarring, smoke creation and low progression speed. To date none has been demonstrated to be superior to the conventional suturing. Fibrin and thrombin promoters as bio-glues are an important adjuvant method during LPN. Bipolar current devices together with fibrin sealants or coagulation promoters are used in small peripheral tumors. In bigger or central tumors, additionally suturing over Surgicel bolsters, the most popular technique is to secure the suture by means of clips. The level of the recommendations is based on comparative cohorts. We conclude that haemostasis is achieved during LPN adapting the protocols used in open nephron sparing surgery to the laparoscopic approach. Renal ischemia and bolster sutures are still mandatory in complicated LPN while in case of small exophytic tumors a satisfactory haemostasis may be achieved by using only a sealant product.

We determine the ability of percutaneous needle based optical coherence tomography to differentiate renal masses by using the attenuation coefficient (μOCT, mm(-1)) as a quantitative measure. Percutaneous needle based optical coherence tomography of the kidney was performed in patients presenting with a solid renal mass. A pathology specimen was acquired in the form of biopsies and/or a resection specimen. Optical coherence tomography results of 40 patients were correlated to pathology results of the resected specimens in order to derive μOCT values corresponding with oncocytoma and renal cell carcinoma, and with the 3 main subgroups of renal cell carcinoma. The sensitivity and specificity of optical coherence tomography in differentiating between oncocytoma and renal cell carcinoma were assessed through ROC analysis. The median μOCT of oncocytoma (3.38 mm(-1)) was significantly lower (p=0.043) than the median μOCT of renal cell carcinoma (4.37 mm(-1)). ROC analysis showed a μOCT cutoff value of greater than 3.8 mm(-1) to yield a sensitivity, specificity, positive predictive value and negative predictive value of 86%, 75%, 97% and 37%, respectively, to differentiate between oncocytoma and renal cell carcinoma. The area under the ROC curve was 0.81. Median μOCT was significantly lower for oncocytoma vs clear cell renal cell carcinoma (3.38 vs 4.36 mm(-1), p=0.049) and for oncocytoma vs papillary renal cell carcinoma (3.38 vs 4.79 mm(-1), p=0.027). We demonstrated that the μOCT is significantly higher in renal cell carcinoma vs oncocytoma, with ROC analysis showing promising results for their differentiation. This demonstrates the potential of percutaneous needle based optical coherence tomography to help in the differentiation of renal masses, thus warranting ongoing research

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

Background: Stenting of the ureterovesical anastomosis reduces the incidence of urological complications (UCs) after renal transplantation, but there are multiple stenting techniques, and there is no consensus regarding which technique is preferred. The aim of this study was to compare an internal versus an external stenting technique on the incidence of UCs. Methods: This is a retrospective analysis of 419 deceased donor renal transplantations performed between January 2008 and December 2013. Until 2011, 183 patients received an external stent through the ureterovesical anastomosis placed by suprapubic bladder puncture (SP stent). From 2011, 236 recipients received an internal double-J (JJ) stent. Results: The rate of UC was 3.8% in JJ stents, compared to 9.3% in SP stents (p = 0.021). No difference in surgical ureter revision rate was observed between the groups (2.1 vs. 5.5%; p = 0.068). Urinary tract infection (UTI) rate and graft function were comparable between both groups. Conclusions: Internal JJ stenting significantly decreased the incidence of UC compared to an external SP stent. There was no difference in surgical ureter revision rate, UTI or graft function.

Optical coherence tomography (OCT) is the optical equivalent of ultrasound imaging, based on the backscattering of near infrared light. OCT provides real time images with a 15 µm axial resolution at an effective tissue penetration of 2-3 mm. Within the OCT images the loss of signal intensity per millimeter of tissue penetration, the attenuation coefficient, is calculated. The attenuation coefficient is a tissue specific property, providing a quantitative parameter for tissue differentiation. Until now, renal mass treatment decisions have been made primarily on the basis of MRI and CT imaging characteristics, age and comorbidity. However these parameters and diagnostic methods lack the finesse to truly detect the malignant potential of a renal mass. A successful core biopsy or fine needle aspiration provides objective tumor differentiation with both sensitivity and specificity in the range of 95-100%. However, a non-diagnostic rate of 10-20% overall, and even up to 30% in SRMs, is to be expected, delaying the diagnostic process due to the frequent necessity for additional biopsy procedures. We aim to develop OCT into an optical biopsy, providing real-time imaging combined with on-the-spot tumor differentiation. This publication provides a detailed step-by-step approach for percutaneous, needle based, OCT of renal masses.

BACKGROUND: Electroporation is a novel treatment technique utilizing electric pulses, traveling between two or more electrodes, to ablate targeted tissue. The first in human studies have proven the safety of IRE for the ablation of renal masses. However the efficacy of IRE through histopathological examination of an ablated renal tumour has not yet been studied. Before progressing to a long-term IRE follow-up study it is vital to have pathological confirmation of the efficacy of the technique. Furthermore, follow-up after IRE ablation requires a validated imaging modality. The primary objectives of this study are the safety and the efficacy of IRE ablation of renal masses. The secondary objectives are the efficacy of MRI and CEUS in the imaging of ablation result.METHODS/DESIGN: 10 patients, age ≥ 18 years, presenting with a solid enhancing mass, who are candidates for radical nephrectomy will undergo IRE ablation 4 weeks prior to radical nephrectomy. MRI and CEUS imaging will be performed at baseline, one week and four weeks post IRE. After radical nephrectomy, pathological examination will be performed to evaluate IRE ablation success.DISCUSSION: The only way to truly assess short-term (4 weeks) ablation success is by histopathology of a resection specimen. In our opinion this trial will provide essential knowledge on the safety and efficacy of IRE of renal masses, guiding future research of this promising ablative technique.TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT02298608 . Dutch Central Committee on Research Involving Human Subjects registration number NL44785.018.13.

The objective of this study is to demonstrate the feasibility of needle-based optical coherence tomography (OCT) and functional analysis of OCT data along the full pullback trajectory of the OCT measurement in the prostate, correlated with pathology. OCT images were recorded using a commercially available C7-XR(TM) OCT Intravascular Imaging System interfaced to a C7 Dragonfly(TM) intravascular 0.9-mm-diameter imaging probe. A computer program was constructed for automated image attenuation analysis. First, calibration of the OCT system for both the point spread function and the system roll-off was achieved by measurement of the OCT signal attenuation from an extremely weakly scattering medium (Intralipid(R) 0.0005 volume%). Second, the data were arranged in 31 radial wedges (pie slices) per circular segments consisting of 16 A-scans per wedge and 5 axial B-scans, resulting in an average A-scan per wedge. Third, the decay of the OCT signal is analyzed over 50 pixels (500 mu m) in depth, starting from the first found maximum data point. Fourth, for visualization, the data were grouped with a corresponding color representing a specific mu(oct) range according to their attenuation coefficient. Finally, the analyses were compared to histopathology. To ensure that each single use sterile imaging probe is comparable to the measurements of the other imaging probes, the probe-to-probe variations were analyzed by measuring attenuation coefficients of 0.03, 6.5, 11.4, 17, and 22.7 volume% Intralipid(R). Experiments were repeated five times per probe for four probes. Inter-and intraprobe variation in the measured attenuation of Intralipid samples with scattering properties similar to that of the prostate was

Objective: Although tissue ablation by irreversible electroporation (IRE) has been characterized as nonthermal, the application of frequent repetitive high-intensity electric pulses has the potential of substantially heating the targeted tissue and causing thermal damage. This study evaluates the risk of possible thermal damage by measuring temperature development and distribution during IRE of porcine kidney tissue. Methods: The animal procedures were conducted following an approved Institutional Animal Ethics Committee protocol. IRE ablation was performed in 8 porcine kidneys. Of them, 4 kidneys were treated with a 3-needle configuration and the remaining 4 with a 4-needle configuration. All IRE ablations consisted of 70 pulses with a length 90 mu s. The pulse frequency was set at 90 pulses/min, and the pulse intensity at 1,500 V/cm with a spacing of 15 rum between the needles. The temperature was measured internally using 4 fiber-optic temperature probes and at the surface using a thermal camera. Results: For the 3-needle configuration, a peak temperature of 57 degrees C (mean = 49 +/- 10 degrees C, n = 3) was measured in the core of the ablation zone and 40 degrees C (mean = 36 +/- 3 degrees C, n = 3) at 1 cm outside of the ablation zone, from a baseline temperature of 33 +/- 1 degrees C. For the 4-needle configuration, a peak temperature of 79 degrees C (mean = 62 +/- 16 degrees C, n = 3) was measured in the core of the ablation zone and 42 degrees C (mean = 39 +/- 3 degrees C, n = 3) at 1 cm outside of the ablation zone, from a baseline of 35 +/- 1 degrees C. The thermal camera recorded the peak surface temperatures in the center of the ablation zone, reaching 31 degrees C and 35 degrees C for the 3- and 4-needle configuration IRE (baseline 22 degrees C). Conclusions: The application of repetitive high-intensity electric pulses during IRE ablation in porcine kidney causes a lethal rise in temperature within the ablation zone. Temperature monitoring should be considered when performing IRE ablation near vital structures. C) 2015 Elsevier Inc. All rights reserved

Ninety-five percent of all urothelial carcinomas are located in the bladder and 5% in the upper urinary tract. Therefore, upper urinary tract urothelial carcinoma is relatively rare, with an incidence of 2.1-2.4 per 100,000 persons per year. Diagnosis is based on imaging, endoscopy, urine cytology and histology. Histopathological diagnosis of upper urinary tract tumours is essential for choice of therapy and follow-up, as both tumour grade and stage are important prognostic factors. Radical nephroureterectomy is the standard treatment, but has a direct effect on kidney function. For this reason, an increasing number of patients with low-risk tumours undergo kidney-sparing surgery to maintain kidney function. After kidney-sparing surgery intensive follow-up of the ipsilateral upper urinary tract is mandatory because of a five-year recurrence-free survival rate of 17-63%, depending on tumour grade. Current diagnostics all have their limitations. Nowadays, research focuses on improving diagnosis in order to be able to offer better individual treatment.

To discuss the use of renal mass biopsy (RMB) for small renal masses (SRMs), formulate technical aspects, outline potential pitfalls and provide recommendations for the practicing clinician. The meeting was conducted as an informal consensus process and no scoring system was used to measure the levels of agreement on the different topics. A moderated general discussion was used as the basis for consensus and arising issues were resolved at this point. A consensus was established and lack of agreement to topics or specific items was noted at this point. Recommended biopsy technique: at least two cores, sampling different tumour regions with ultrasonography being the preferred method of image guidance. Pathological interpretation: 'non-diagnostic samples' should refer to insufficient material, inconclusive and normal renal parenchyma. For non-diagnostic samples, a repeat biopsy is recommended. Fine-needle aspiration may provide additional information but cannot substitute for core biopsy. Indications for RMB: biopsy is recommended in most cases except in patients with imaging or clinical characteristics indicative of pathology (syndromes, imaging characteristics) and cases whereby conservative management is not contemplated. RMB is recommended for active surveillance but not for watchful-waiting candidates. We report the results of an international consensus meeting on the use of RMB for SRMs, defining the technique, pathological interpretation and indications.

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.

With overall cure rates superior to 95% for early stages and to 89% for metastatic disease Testicular Germ Cell Tumors (TGCT) are unique among solid tumors. Early diagnosis, accurate staging, tailored treatment and strict follow up contribute to this high cure rate. Prompt detection and the existence of and efficient treatment of the recurrences are major reasons to institute a follow-up schedule. Currently there is no universally accepted standard follow-up protocol after primary treatment with curative intention. Diagnostic test should be performed with a frequency and duration consistent with the recurrence risk and should ideally include test with high positive and negative predictive value. Furthermore follow-up schedules should be adapted to the tumor type and the treatment policy chosen. Currently follow-up schedules not only aim to detect systemic or contralateral recurrences but include monitoring of fertility, secondary and long term effects as well as detection of second cancers chemo or radiation induced.