Unveiling the challenges of UTUC biopsies and cytology: insights from a global real-world practice study.

PURPOSE: Diagnostic ureteroscopy (dURS) is optional in the assessment of patients with upper tract urothelial carcinoma (UTUC) and provides the possibility of obtaining histology. METHODS: To evaluate endoscopic biopsy techniques and outcomes, we assessed data from patients from the CROES-UTUC registry. The registry includes multicenter prospective collected data on diagnosis and management of patients suspected having UTUC. RESULTS: We assessed 2380 patients from 101 centers. dURS with biopsy was performed in 31.6% of patients. The quality of samples was sufficient for diagnosis in 83.5% of cases. There was no significant association between biopsy techniques and quality (p = 0.458). High-grade biopsy accurately predicted high-grade disease in 95.7% and high-risk stage disease in 86%. In ureteroscopic low-grade tumours, the prediction of subsequent low-grade disease was 66.9% and low-risk stage Ta-disease 35.8%. Ureteroscopic staging correctly predicted non-invasive Ta-disease and ≥ T1 disease in 48.9% and 47.9% of patients, respectively. Cytology outcomes did not provide additional value in predicting tumour grade. CONCLUSION: Biopsy results adequately predict high-grade and high-risk disease, but approximately one-third of patients are under-staged. Two-thirds of patients with low-grade URS-biopsy have high-risk stage disease, highlighting the need for improved diagnostics to better assess patient risk and guide treatment decisions. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ClinicalTrials.gov NCT02281188; https://clinicaltrials.gov/ct2/show/NCT02281188 ).

Experts' recommendations in laser use for the treatment of bladder cancer: a comprehensive guide by the European Section of Uro-Technology (ESUT) and Training and Research in Urological Surgery and Technology (TRUST)-Group.

PURPOSE: To identify laser settings and limits applied by experts during laser vaporization (vapBT) and laser en-bloc resection of bladder tumors (ERBT) and to identify preventive measures to reduce complications. METHODS: After a focused literature search to identify relevant questions, we conducted a survey (57 questions) which was sent to laser experts. The expert selection was based on clinical experience and scientific contribution. Participants were asked for used laser types, typical laser settings during specific scenarios, and preventive measures applied during surgery. Settings for a maximum of 2 different lasers for each scenario were possible. Responses and settings were compared among the reported laser types. RESULTS: Twenty-three of 29 (79.3%) invited experts completed the survey. Thulium fiber laser (TFL) is the most common laser (57%), followed by Holmium:Yttrium-Aluminium-Garnet (Ho:YAG) (48%), continuous wave (cw) Thulium:Yttrium-Aluminium-Garnet (Tm:YAG) (26%), and pulsed Tm:YAG (13%). Experts prefer ERBT (91.3%) to vapBT (8.7%); however, relevant limitations such as tumor size, number, and anatomical tumor location exist. Laser settings were generally comparable; however, we could find significant differences between the laser sources for lateral wall ERBT (p = 0.028) and standard ERBT (p = 0.033), with cwTm:YAG and pulsed Tm:YAG being operated in higher power modes when compared to TFL and Ho:YAG. Experts prefer long pulse modes for Ho:YAG and short pulse modes for TFL lasers. CONCLUSION: TFL seems to have replaced Ho:YAG and Tm:YAG. Most laser settings do not differ significantly among laser sources. For experts, continuous flow irrigation is the most commonly applied measure to reduce complications.

Longer is Better for Endoscopic Follow-up of Upper Tract Urothelial Carcinoma After Ureteroscopic Treatment: An Evaluation Spanning 10 Years of Data.

BACKGROUND: Tumour recurrences are frequent among patients with upper tract urothelial carcinoma (UTUC) treated with ureteroscopy (URS). Therefore, guidelines recommend a strict follow-up regimen, but there is little evidence on how to do this. OBJECTIVE: To analyse outcomes during our follow-up regimen and the impact on treatment in terms of ipsilateral UTUC recurrence, treatment conversion, and tumour upgrading, and to evaluate potential prognostic factors, including second-look URS outcomes. A secondary objective was to evaluate survival outcomes. DESIGN, SETTING, AND PARTICIPANTS: The single-centre cohort included all adult patients with nonmetastatic UTUC treated with URS from January 2010 to December 2020. Follow-up involved endoscopy at 3-mo intervals in the first year, then at 6-mo intervals up to year 3, and yearly thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive analyses were performed for the follow-up outcomes. The Andersen-Gill model for recurrent event analysis was used to analyse tumour recurrences, and multivariable Cox regression to analyse for predictors for treatment conversion in low-grade tumours. RESULTS AND LIMITATIONS: We analysed 71 patients with median follow-up of 49.5 mo. The overall 2-yr recurrence-free survival (RFS) rate was 22%. In low-grade disease, the 1-yr RFS rate was 50% and the 2-yr RFS rate was 29%. Treatment was converted to radical nephroureterectomy for 23 patients, at a median time to conversion of 9.9 mo. Upgrading was seen in 13 patients, at a median time to upgrading of 21.9 mo. No factors were prognostic for either tumour recurrence or treatment conversion. The 5-yr OS, CSS, and MFS rates were 82%, 86%, and 84%, respectively. CONCLUSIONS: Our data show that it is rational to extend endoscopic follow-up for UTUC treated with URS, as clinically relevant events (treatment conversion and tumour upgrading) occur beyond the current 6-mo guideline recommendation. Second-look URS outcomes were not prognostic for tumour recurrence or treatment conversion during follow-up. PATIENT SUMMARY: Our study results show that for patients with cancer of the upper urinary tract treated with kidney-sparing surgery through a small telescope called a ureteroscope (URS), most of the clinically relevant events (treatment conversion and tumour upgrading) occur outside the current recommended follow-up of 6 months. Therefore, URS follow-up should be extended for these patients.

Positioning the role of urine cytology within the diagnostic pathway for UTUC: supportive but inconclusive.

PURPOSE: With the introduction of kidney-sparing surgery (KSS) for low-risk Upper Tract Urothelial Carcinoma (UTUC), correct risk-stratification has become crucial. High-grade cytology is one of the decisive variables to stratify a tumor as high-risk. To position the role of urine cytology in the diagnostic pathway of UTUC patients, we evaluated the accuracy of urine cytology by comparing the outcomes with histopathology. METHOD: Patients with UTUC evaluated between 2010 and 2020, and diagnosed by imaging, cytology and histopathology were selected. Descriptive statistics were used to compare cytology with histopathological outcomes using crosstabs. Clinical performance characteristics of cytology were determined for the presence of a malignancy. RESULTS: This study included 176 patients with confirmed histopathological UTUC. Concordance between cytology and biopsy results was found in 14.8% of low-grade tumors and 16.8% of high-grade tumors. Comparing cytology with radical nephroureterectomy (RNU) specimens revealed concordance rates of 1.6% for low-grade tumors and 22.9% for high-grade tumors. Notably, 51.1% of urine cytology results were false negative. Sensitivity for detecting high-grade and low-grade tumors with a positive urine cytology was 56.6% and 52.6%, respectively, with specificities of 54.8% and 37.2%. CONCLUSION: In the current study, cytology appears to exhibit limited reliability when used as a sole diagnostic tool for assessing tumor grade and consequently risk stratification. It is imperative to recognize these limitations, optimize urine sampling techniques, and leverage a combination of diverse diagnostic methods for the most effective and individualized treatment decision-making.

Experts' recommendations in laser use for the treatment of upper tract urothelial carcinoma: a comprehensive guide by the European Section of Uro-Technology (ESUT) and Training Research in Urological Surgery and Technology (T.R.U.S.T.) group.

PURPOSE: To highlight and compare experts' laser settings during endoscopic laser treatment of upper tract urothelial carcinoma (UTUC), to identify measures to reduce complications, and to propose guidance for endourologists. METHODS: Following a focused literature search to identify relevant questions, a survey was sent to laser experts. We asked participants for typical settings during specific scenarios (ureteroscopy (URS), retrograde intrarenal surgery (RIRS), and percutaneous treatment). These settings were compared among the reported laser types to find common settings and limits. Additionally, we identified preventive measures commonly applied during surgery. RESULTS: Twenty experts completed the survey, needing a mean time of 12.7 min. Overall, most common laser type was Holmium-Yttrium-Aluminum-Garnet (Ho:YAG) (70%, 14/20) followed by Thulium fiber laser (TFL) (45%, 9/20), pulsed Thulium-Yttrium-Aluminum-Garnet (Tm:YAG) (3/20, 15%), and continuous wave (cw)Tm:YAG (1/20, 5%). Pulse energy for the treatment of distal ureteral tumors was significantly different with median settings of 0.9 J, 1 J and 0.45 J for Ho:YAG, TFL and pulsed Tm:YAG, respectively (p = 0.048). During URS and RIRS, pulse shapes were significantly different, with Ho:YAG being used in long pulse and TFL in short pulse mode (all p < 0.05). We did not find further disparities. CONCLUSION: Ho:YAG is used by most experts, while TFL is the most promising alternative. Laser settings largely do not vary significantly. However, further research with novel lasers is necessary to define the optimal approach. With the recent introduction of small caliber and more flexible scopes, minimal-invasive UTUC treatment is further undergoing an extension of applicability in appropriately selected patients.

Consultation on UTUC II Stockholm 2022: diagnostics, prognostication, and follow-up-where are we today?

PURPOSE: To summarise the current knowledge regarding diagnostics, prognostication and follow-up in upper tract urothelial carcinoma (UTUC). METHODS: A scoping review combined with expert opinion was applied to provide an overview of the current research field. Based on the published literature and the experts' own experience and opinions, consensus was reached through presentations and discussions at the meeting Consultation on UTUC II in Stockholm 2022. RESULTS: The strongest prognostic factors in UTUC are tumour grade and stage. They are correlated, and grade is used for indirect staging. The diagnostic examinations should include multiphase computed tomography urography (CTU) with corticomedullary phase, and urethrocystoscopy with cytology. If there is no clear diagnosis for clinical decision-making, ureterorenoscopy (URS) with focal cytology and biopsies should be performed. Both WHO classification systems (1973/1999 and 2004/2016) should be used. Novel biomarker tests are not yet widespread nor recommended for the detection of UTUC. Long-term, regular follow-up, including URS in patients who have had organ-sparing treatment, is important to check for tumour recurrences, intravesical recurrences, metastases and progression of the tumour. CONCLUSION: Proper diagnostics with correct grading of UTUC are necessary for appropriate treatment decisions. The diagnostics should include CTU with corticomedullary phase, urine or bladder cytology, URS with focal barbotage cytology, and biopsies when needed for proper diagnosis and risk stratification. Regular, long-term follow-ups are fundamental, due to the high rate of recurrence and risk of progression.

Is It the Load That Breaks You or the Way You Carry It: How Demanding Is Endourology?

Objective: Surgical outcomes are dependent on multiple factors. Besides patient-related or procedure-related factors, several surgeon-related factors contribute to surgical outcomes. The Surgery Task Load Index (SURG-TLX) questionnaire helps to assess the impact of several stressors on the perceived demands of surgeons during surgery. In this study, we evaluate the applicability of the SURG-TLX questionnaire for endourologic procedures and set a first point of reference. Materials and Methods: Between March and August 2022, 15 urologists and urology residents at a tertiary referral center for endourology completed the SURG-TLX questionnaire after endourologic procedures. After data acquisition, all participants were asked to evaluate the applicability of the questionnaire for endourologic procedures. Results: A total of 130 procedures were included between March and August 2022. Situational stress had the lowest median score (3.0/20; interquartile range [IQR] 2.0-7.0) and task complexity the highest (5.0/20; IQR 3.0-8.0). After weighing, the dimensions showed different proportions when compared with the nonweighted scores. Distractions received the highest score (15.0/100; IQR 7.5-32.8), temporal demands (6.0/100; IQR 3.0-12.5), and situational stress the lowest (6.0/100; IQR 2.0-21.0). This was caused by the higher weight that was attributed to distractions (3.4/5), as opposed to task complexity (2.6/5). In the questionnaire regarding applicability of the SURG-TLX, the overall satisfaction (6.0/10; IQR 5.0-7.0) and clarity (6.5/10; IQR 5.0-7.5) were moderate. The user-friendliness and applicability of the questionnaire were rated high (7.0/10; IQR 5.5-8.0 and 7.0/10; IQR 6.0-8.0, respectively) and task load (3.0/10; IQR 2.0-5.0) and time load (2.0/10; IQR 2.0-3.5) low. Conclusion: The SURG-TLX questionnaire is appropriate to assess the different dimensions of workload during endourologic procedures. Furthermore, the perceived workload during endourologic procedures is relatively low.

Donor kidney lithiasis and back-table endoscopy: a successful combination.

INTRODUCTION: Urolithiasis in renal allografts is relatively rare with an incidence of 0.17-4.40%. It is nonetheless an important issue, as there is a risk of obstruction, sepsis and even loss of the renal allograft. The management of stones in renal allografts remains challenging because of the anatomy, the renal denervation and the use of immunosuppressive medication. CASE PRESENTATION: This report discusses the ex-vivo treatment of asymptomatic nephrolithiasis in a living donor kidney allograft. A CT abdomen revealed a lower pole stone (5.9 × 5.5 × 5.0 mm; 920 HU) in the right kidney of the potential donor. After multidisciplinary discussion, it was decided to procure the right kidney despite the presence of a documented nephrolithiasis. After discussion with both donor and recipient, an ex-vivo flexible ureterorenoscopy for stone removal on the back table just before implantation of the allograft was planned. The stone was found in the lower pole covered by a thin film of the urothelium. The thin film of urothelium was opened with a laser and the stone fragments were retrieved with a basket. CT after one month showed no residual stones in the transplanted kidney. CONCLUSION: Back-table endoscopy in a renal allograft is a feasible technique and should be discussed as an option in case of urolithiasis in a kidney that is considered for transplantation. Furthermore, the appropriate treatment of donor kidney lithiasis is another, although rare, method to expand the living donor renal allograft pool.

Adherence to guideline recommendations in the management of upper tract urothelial carcinoma: an analysis of the CROES-UTUC registry.

BACKGROUND: The European Association of Urology provides Clinical Practice Guideline on upper tract urothelial carcinoma (UTUC). Due to the rarity of UTUC, guidelines are necessary to help guide decision-making based on the highest quality of care evidence available. OBJECTIVES: To evaluate guideline adherence in the management of UTUC by assessing recommendations on diagnostics needed for risk classification and subsequent treatment selection; to assess predictors for the latter. PARTICIPANTS: Data from the Clinical Research Office of the Endo Urology Society UTUC-registry were included for analysis. STATISTICAL ANALYSIS: Overall compliance were evaluated by cross-tables, differences in risk groups characteristics and treatment selection were assessed by Chi-square tests, predictors for treatment selection by logistic regression analysis. RESULTS: Data from 2380 patients were included. Imaging by CT-scan had highest adherence (85%) but was low for other diagnostics (17.7-49.7%). Multivariable regression analysis showed higher odds of receiving radical nephroureterectomy in patients with large tumours (OR 5.45, 95% CI 3.77-7.87, p < 0.001), signs of invasion (OR 3.07,CI 2.11-4.46, p < 0.001), high tumour grade (OR 2.05, CI 1.38-3.05, p < 0.001) and multifocality (OR 1.76,CI 1.05-2.97, p =0.032). CONCLUSIONS: CT-imaging is the most used and most impactful decision tool for risk-stratification and treatment selection in UTUC. Due to the low compliance in most of the diagnostic recommendations, proper risk stratification is not possible in a significant group of patients raising the question whether current stratification is deemed applicable in daily practice. Established prognostic factors on survival guides decision-making regarding radical versus kidney-sparing surgery. Tumour size was the most influencing factor on treatment decision. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ClinicalTrials.gov NCT02281188; https://clinicaltrials.gov/ct2/show/NCT02281188 ).

How Reliable Is Endoscopic Stone Recognition? A Comparison Between Visual Stone Identification and Formal Stone Analysis.

Objective: To assess the diagnostic accuracy and intra-observer agreement of endoscopic stone recognition (ESR) compared with formal stone analysis. Introduction: Stone analysis is a corner stone in the prevention of stone recurrence. Although X-ray diffraction (XRD) and infrared spectroscopy are the recommended techniques for reliable formal stone analysis, this is not always possible, and the process takes time and is costly. ESR could be an alternative, as it would give immediate information on stone composition. Materials and Methods: Fifteen endourologists predicted stone composition based on 100 videos from ureterorenoscopy. Diagnostic accuracy was evaluated by comparing the prediction from visual assessment with stone analysis by XRD. After 30 days, the videos were reviewed again in a random order to assess intra-observer agreement. Results: The median diagnostic accuracy for calcium oxalate monohydrate was 54% in questionnaire 1 (Q1) and 59% in questionnaire 2 (Q2), whereas calcium oxalate dihydrate had a median diagnostic accuracy of 75% in Q1 and 50% in Q2. The diagnostic accuracy for calcium hydroxyphosphate was 10% in Q1 and 13% in Q2. The median diagnostic accuracy for calcium hydrogen phosphate dihydrate and calcium magnesium phosphate was 0% in both questionnaires. The median diagnostic accuracy for magnesium ammonium phosphate was 20% in Q1 and 40% in Q2. The median diagnostic accuracy for uric acid was 22% in both questionnaires. Finally, there was a diagnostic accuracy of 60% in Q1 and 80% in Q2 for cystine. The intra-observer agreement ranged between 45% and 72%. Conclusion: Diagnostic accuracy of ESR is limited and intra-observer agreement is below the threshold of acceptable agreement.

Survival and Long-term Effects of Kidney-sparing Surgery Versus Radical Nephroureterectomy on Kidney Function in Patients with Upper Urinary Tract Urothelial Carcinoma.

Background: Current European Association of Urology (EAU) guidelines discriminate between high- and low-risk upper urinary tract urothelial carcinoma (UTUC) to determine treatment by means of radical nephroureterectomy (RNU) or kidney-sparing surgery (KSS). Objective: To compare long-term oncological outcomes and renal function for patients with UTUC treated by RNU versus KSS. Design setting and participants: A retrospective cohort study, including 186 renal units with nonmetastatic UTUC treated in a tertiary referral centre between 2010 and 2021, was conducted. Intervention: RNU, ureterorenoscopy, percutaneous tumour resection, and segmental ureteral resection. Outcome measurements and statistical analysis: Recurrence-free survival, metastasis-free survival (MFS), overall survival (OS), cancer-specific survival (CSS), and renal function were analysed by means of the log-rank test and the independent-sample t test. Results and limitations: OS was 71.1% for the RNU group and 81.9% for the KSS group. In a cohort matched for propensity weight based on EAU risk stratification progression-free survival (PFS; RNU 96.0%; KSS 86.0%), MFS (RNU 72.0%; KSS 84.0%), CSS (RNU 84.0%; KSS 86.0%), and OS (RNU 76.0%; KSS 76.0%) were all similar between both groups. No significant differences in renal function were seen at 2 and 5 yr after the intervention. Although this series represents the largest cohort of (high-risk) UTUC patients treated by means of KSS to date, it is not suitable for performing a multivariate analysis. Conclusions: PFS, MFS, CSS, and OS were all comparable when analysing the RNU and KSS groups. Similar results for groups with evenly distributed risk factors and a large percentage of high-risk disease suggest that current risk stratification might not be accurate in discriminating low-risk from high-risk disease. Patient summary: In this report, we looked at outcomes for upper urinary tract urothelial carcinoma in a specialised hospital. We conclude that kidney-sparing surgery and radical nephroureterectomy have comparable outcomes and that risk factors for worse outcome might not be identified correctly.

How to evaluate a flexible ureterorenoscope? Systematic mapping of existing evaluation methods.

OBJECTIVES: The objective of this study was to identify, map and review scope-related and user-related parameters used to evaluate the quality of flexible ureterorenoscopes. Thereby identifying key items and variability in grading systems. METHODS: A literature search of four databases (MEDLINE [Ovid], EMBASE [Ovid], Web of Science, Google scholar and the Cochrane Library) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines encompassing articles published up to August 2020. A total of 2386 articles were screened. RESULTS: A total of 48 articles were included in this systematic scoping review. All studies had a prospective design. Five key items in the assessment of flexible ureterorenoscopy were distinguished: 'Manoeuvrability' (87.5%), 'Optics' (64.6%), 'Irrigation' (56.3%), 'Handling' (39.6%) and 'Durability' (35.4%). After regrouping, every key item could be divided into specific subcategories. However, the quality assessment showed a wide variation in denomination, method of measurement, circumstances of measurement, tools used during measurements, number of measurements performed, number of observers, and units of outcomes. CONCLUSION: The research field regarding quality assessment of ureterorenoscopes is heterogeneous. In this systematic scoping review we identified five key parameters: Manoeuvrability, Optics, Irrigation, Handling and Durability, used to grade flexible ureterorenoscopes. However, within these categories we found a wide variety in terms of method of measurements. A standardised, uniform grading tool is required to assess and compare the quality of flexible ureterorenoscopes in the future.

Contemporary patterns of presentation, diagnostics and management of upper tract urothelial cancer in 101 centres: the Clinical Research Office of the Endourological Society Global upper tract urothelial carcinoma registry.

PURPOSE OF REVIEW: To assess patterns of presentation, diagnostics and treatment in patients with upper tract urothelial carcinoma (UTUC), a multicentre registry was launched. Clinical data of UTUC patients were prospectively collected over a 5-year period. RECENT FINDINGS: Data from 2380 patients were included from 2014 to 2019 (101 centres in 29 countries). Patients were predominantly male (70.5%) and 53.3% were past or present smokers. The majority of patients (58.1%) were evaluated because of symptoms, mainly macroscopic hematuria. Computed tomography (CT) was the most common performed imaging modality (90.5%). A ureteroscopy (URS) was part of the diagnostic process in 1184 (49.7%) patients and 488 (20.5%) patients were treated endoscopically. In total, 1430 patients (60.1%) were treated by a radical nephroureterectomy, 59% without a prior diagnostic URS. Eighty-two patients (3.4%) underwent a segmental resection, 19 patients (0.8%) were treated by a percutaneous tumour resection. SUMMARY: Our data is in line with the known epidemiologic characteristics of UTUC. CT imaging is the preferred imaging modality as also recommended by guidelines. Diagnostic URS gained a stronger position, however, in almost half of patients a definitive treatment decision was made without complete endoscopic information. Only one-third of patients with UTUC are currently treated with kidney sparing surgery.

Fluoroscopy-use during ureterorenoscopy: are urologists concerned about radiation exposure? A nationwide survey in Belgium and The Netherlands.

INTRODUCTION: To evaluate the use and awareness of radiation during URS among Belgian and Dutch urologists. MATERIAL AND METHODS: An online questionnaire was send to all members of the Belgian and Dutch Association of Urology. RESULTS: 170 urologists finished the complete questionnaire. 10% of the respondents are not familiar with the ALARA-principle. 29% starts with a KUB and 48% makes an XRPG at the beginning of the procedure. 85% uses fluoroscopy to place a wire or ureteral access sheet, 18% during stone treatment, 59% to screen for missed stones or calyces, 90% to place a JJ-stent or ureter-catheter and 23% to check for extravasation. 82% do not document radiation data. 51% does not wear a dosimeter during fluoroscopy. Almost all wear a lead apron during fluoroscopy, 47% uses additional thyroid shields and only 4% uses lead glasses. 88% intentionally reduces fluoroscopy time, 75% reduces the exposed area with a diaphragm, 72% brings the radiation source close to the patient and 44% uses pulsed fluoroscopy. CONCLUSION: There is a wide variety in the use and awareness of radiation during URS. To further reduce radiation and its negative effect for patients and medical staff, awareness about radiation safety should increase among urologists.

Consultation on kidney stones, Copenhagen 2019: aspects of intracorporeal lithotripsy in flexible ureterorenoscopy.

PURPOSE: To summarize current knowledge on intracorporeal laser lithotripsy in flexible ureterorenoscopy (fURS), regarding basics of laser lithotripsy, technical aspects, stone clearance, lithotripsy strategies, laser technologies, endoscopes, and safety. METHODS: A scoping review approach was applied to search literature in PubMed, EMBASE, and Web of Science. Consensus was reached through discussions at the Consultation on Kidney Stones held in September 2019 in Copenhagen, Denmark. RESULTS AND CONCLUSIONS: Lasers are widely used for lithotripsy during fURS. The Holmium laser is still the predominant technology, and specific settings for dusting and fragmenting have evolved, which has expanded the role of fURS in stone management. Pulse modulation can increase stone ablation efficacy, possibly by minimizing stone retropulsion. Thulium fibre laser was recently introduced, and this technology may improve laser lithotripsy efficiency. Small fibres give better irrigation, accessibility, and efficiency. To achieve optimal results, laser settings should be adjusted for the individual stone. There is no consensus whether the fragmentation and basketing strategy is preferable to the dusting strategy for increasing stone-free rate. On the contrary, different stone scenarios call for different lithotripsy approaches. Furthermore, for large stone burdens, all laser settings and lithotripsy strategies must be applied to achieve optimal results. Technology for removing dust from the kidney should be in focus in future research and development. Safety concerns about fURS laser lithotripsy include high intrarenal pressures and temperatures, and measures to reduce both those aspects must be taken to avoid complications. Technology to control these parameters should be targeted in further studies.

Evaluation of Patterns of Presentation, Practice, and Outcomes of Upper Tract Urothelial Cancer: Protocol for an Observational, International, Multicenter, Cohort Study by the Clinical Research Office of the Endourology Society.

BACKGROUND: Available guidelines on the management of upper tract urothelial carcinoma (UTUC) are restricted due to the lack of strong evidence-based recommendations. Adequate, well-powered randomized trials are missing due to the rarity of the disease. To overcome this problem, we need alternative study designs to provide generalizable data. OBJECTIVE: The primary aim of this registry is to provide a real-world overview on patterns of presentation and management of UTUC. Secondary objectives include comparison of outcomes of different treatments and tumor stages and evaluation of compliance with the current European Association of Urology recommendations for UTUC. METHODS: For this observational, international, multicenter, cohort study, clinical data of consecutive patients suspected of having UTUC, irrespective of type of management, will be prospectively collected up to 5 years after inclusion. Data on the patterns of presentation, diagnostics, and treatment as well as short-, mid-, and long-term oncological and functional outcomes will be analyzed. Possible associations between variables, basal characteristics, and outcomes will be tested by multivariable analyses. The methodology will address potential sources of bias and confounders. RESULTS: The registry was initiated in November 2014 after obtaining institutional review board approval. Data collection started in December 2014. At the time of submission of this manuscript, 2451 patients from 125 centers from 37 countries were included. Inclusion of patients will be closed 5 years after initiation of the registry. Quality checks will be performed centrally with continuous communication and feedback with the centers to ensure accuracy. The first results are expected in the first trimester of 2020. CONCLUSIONS: This large observational prospective cohort will generate landmark "real-world" data and hypotheses for further studies. We expect these data to optimize the management of UTUC, provide insights on harms and benefits of treatment, and serve as quality control. TRIAL REGISTRATION: ClinicalTrials.gov NCT02281188; https://clinicaltrials.gov/ct2/show/NCT02281188. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15363.

Validation of Confocal Laser Endomicroscopy Features of Bladder Cancer: The Next Step Towards Real-time Histologic Grading.

BACKGROUND: Cystoscopy enables the visualisation of suspicious bladder lesions but lacks the ability to provide real-time histopathologic information. Confocal laser endomicroscopy (CLE) is a probe-based optical technique that can provide real-time microscopic images. This high-resolution optical imaging technique may enable real-time tumour grading during cystoscopy. OBJECTIVE: To validate and adapt CLE criteria for bladder cancer diagnosis and grading. DESIGN, SETTING, AND PARTICIPANTS: Prospectively, 73 patients scheduled for transurethral resection of bladder tumour(s) were included. CLE imaging was performed intraoperatively prior to en bloc resection. Histopathology was the reference standard for comparison. INTERVENTION: Cystoscopic CLE imaging. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Three independent observers evaluated the CLE images to classify tumours as low- or high-grade urothelial carcinoma (UC), or benign lesions. Interobserver agreement was calculated with Fleiss kappa analysis and diagnostic accuracy with 2×2 tables. RESULTS AND LIMITATIONS: Histopathology of 66 lesions (53 patients) revealed 25 low-grade UCs, 27 high-grade UCs, and 14 benign lesions. For low-grade UC, most common features were papillary configuration (100%), distinct cell borders (81%), presence of fibrovascular stalks (79%), cohesiveness of cells (77%), organised cell pattern (76%), and monomorphic cells (67%). A concordance between CLE-based classification and histopathology was found in 19 cases (76%). For high-grade UC, pleomorphic cells (77%), indistinct cell borders (77%), papillary configuration (67%), and disorganised cell pattern (60%) were the most common features. A concordance with histopathology was found in 19 cases (70%). In benign lesions, the most prevalent features were disorganised cell pattern (57%) and pleomorphic cells (52%), and a concordance with histopathology was found in four cases (29%). CONCLUSIONS: The CLE criteria enable identification of UC. CLE features correlate to histopathologic features that may enable real-time tumour grading. However, flat lesions remain difficult to classify. PATIENT SUMMARY: Confocal laser endomicroscopy may enable real-time cancer differentiation during cystoscopy, which is important for prognosis and disease management.

Upper Tract Urothelial Carcinoma Grade Prediction Based on the Ureteroscopic Appearance: Caution Should be Taken.

OBJECTIVES: To investigate the diagnostic accuracy, inter-rater and intrarater agreement of grade predictions based on the visual appearance of papillary upper tract urothelial carcinoma (UTUC) during digital ureteroscopy. METHODS: Nine urologists predicted the histopathologic grade of 64 papillary UTUC (low-grade vs high-grade) by assessing the visual appearance of the tumors in videos from digital ureteroscopy. The diagnostic accuracy was estimated by comparing the grade predictions with the histopathology from colocalized biopsies. Inter-rater agreement was assessed by pairwise inter-rater percentage agreement and Fleiss Kappa analysis. The videos were rated in a random order again 30 days after the first assessment to evaluate the intrarater percentage agreement. RESULTS: Low-grade tumors were predicted correctly in 37%-85% of the cases with a median concordance of 59% for questionnaire 1 and 66% for questionnaire 2. High-grade tumors were predicted correctly in 26%-91% of the cases with a median concordance of 52% and 61% for each questionnaire. The median pairwise inter-rater percentage agreement was 66% for both questionnaires with a Fleiss Kappa of 0.29 and 0.38, respectively. The median intrarater percentage agreement was 81%. CONCLUSION: The histopathologic grade of UTUC is essential to the risk-stratification for treatment selection. Predictions of the histopathologic grade based on the visual appearance of papillary UTUC with digital ureteroscopy are often incorrect in comparison with biopsy results and yield low inter-rater agreement. Urologists must be aware of these limitations in the assessment of the tumor grade during digital ureteroscopy to warrant good clinical practice.

Consultation on UTUC, Stockholm 2018: aspects of treatment.

PURPOSE: To provide an overview of treatment modalities for management of upper tract urothelial carcinoma (UTUC). METHODS: In accordance with the standards for a scoping review, data presentation and discussion at the Consultation on UTUC in Stockholm, 6-7 September 2018, consensus was reached on the latest and most important treatment recommendations for UTUC. Using Pubmed, Web of Science, and Embase, publications were selected based on quality, clinical relevance, and level of evidence. RESULTS: Kidney-sparing surgery should be attempted for low-grade UTUC. Radical nephroureterectomy with bladder cuff excision is first option for high-grade disease. Post-operative bladder instillation of chemotherapy should be offered after RNU to reduce intravesical recurrence rate. Identification of tumor grade and stage is crucial when selecting treatment. Ureteroscopic management of low-grade and non-invasive UTUC achieves disease-free survival similar to that offered by radical nephroureterectomy but seems to be a risk factor for intravesical recurrence. Lymphadenectomy appears important for high-risk disease, although the therapeutic benefit needs further validation. There is little evidence supporting use of Bacillus Calmette-Guérin (BCG) and mitomycin C as monotherapy and adjuvant treatment in UTUC. A randomized clinical trial has indicated that platin-based chemotherapy for invasive UTUC improves disease-free survival, suggesting that adjuvant chemotherapy should be considered standard care for ≥ T2 N0-3M0 disease. CONCLUSIONS: Risk stratification assessment is feasible and mandatory in UTUC. Identification of tumor grade and stage is essential for optimal treatment selection. Kidney-sparing surgery should be offered in low-risk disease, whereas radical nephroureterectomy and adjuvant chemotherapy should be considered in high-risk disease.

Consultation on UTUC, Stockholm 2018 aspects of diagnosis of upper tract urothelial carcinoma.

PURPOSE: To summarize knowledge on upper urinary tract carcinoma (UTUC) regarding diagnostic procedures, risk factors and prognostic markers. METHODS: A scoping review approach was applied to search literature in Pubmed, Web of Science, and Embase. Consensus was reached through discussions at Consultation on UTUC in Stockholm, September 2018. RESULTS: Tumor stage and grade are the most important prognostic factors. CT urography (CTU) including corticomedullary phase is the preferred imaging modality. A clear tumor on CTU in combination with high-grade UTUC in urine cytology identifies high-risk UTUC, and in some cases indirect staging can be obtained. Bladder urine cytology has limited sensitivity, and in most cases ureterorenoscopy (URS) with in situ samples for cytology and histopathology are mandatory for exact diagnosis. Image-enhancing techniques, Image S1 and narrow-band imaging, may improve tumor detection at URS. Direct confocal laser endomicroscopy may help to define grade during URS. There is strong correlation between stage and grade, accordingly correct grading is crucial. The correlation is more pronounced using the 1999 WHO than the 2004 classification: however, the 1999 system risks greater interobserver variability. Using both systems is advisable. A number of tissue-based molecular markers have been studied. None has proven ready for use in clinical practice. CONCLUSIONS: Correct grading and staging of UTUC are mandatory for adequate treatment decisions. Optimal diagnostic workup should include CTU with corticomedullary phase, URS with in situ cytology and biopsies. Both WHO classification systems (1999 and 2004) should be used to decrease risk of undergrading or overtreatment.