A Urine Based Genomic Assay to Triage Patients with Hematuria for Cystoscopy.

PURPOSE: Current clinical guidelines recommend cystoscopy in patients who present with hematuria to rule out a bladder tumor. We evaluated whether our previously developed urine assay was able to triage patients with hematuria for cystoscopy in a large prospective cohort. MATERIALS AND METHODS: A urine sample was collected before cystoscopy and mutation/methylation status of 6 genes was determined on cellular DNA. The existing diagnostic model was validated on this cohort. Logistic regression was applied to investigate other potential variables. The primary end point was the model performance as indicated by the AUC. Secondary end points were sensitivity, specificity and negative predictive value. Clinical usefulness was determined by the net benefit approach. RESULTS: In 838 patients biomarker status could be determined for all genes. Urothelial cancer was observed in 112 patients (98 of 457 in the gross and 14 of 381 in the microscopic hematuria group). Validation of the existing model resulted in an AUC of 0.93. Logistic regression analysis identified type of hematuria as a significant additional variable. Adding type of hematuria resulted in an AUC of 0.95 (96% sensitivity, 73% specificity, 99% negative predictive value). The assay identified all upper tract tumors not visible by cystoscopy (in 6). Net benefit analysis showed that the urine assay should be preferred over current clinical practice. Implementing the urine assay as a triage tool could lead to a 53% reduction in cystoscopies. CONCLUSIONS: The urine assay detected urothelial cancer with a very high accuracy and can be used to triage patients presenting with hematuria for cystoscopy.

A Molecular Urine Assay to Detect Recurrences During Surveillance of High-Risk Non-Muscle Invasive Bladder Cancer.

BACKGROUND: High-risk non-muscle invasive bladder cancer (HR-NMIBC) patients require long-term surveillance with cystoscopies, cytology and upper tract imaging. Previously, we developed a genomic urine assay for surveillance of HR-NMIBC patients with high sensitivity and anticipatory value. OBJECTIVE: We aimed to validate the performance of the assay in an unselected prospectively collected cohort of HR-NMIBC patients under surveillance. METHODS: We included patients from five centers and collected urine sample pairs (evening and morning urines) prior to cystoscopy. Mutation status (FGFR3/TERT) and methylation status (OTX1) was analyzed on DNA from voided urine specimens. A test was considered positive if≥1 alteration was detected in at least one urine sample. The primary endpoint was tumor recurrence. Sensitivity and specificity were determined. A generalized mixed effects model was used to adjust for within-patient correlation. Cox proportional hazard analyses with time-dependent covariates assessed the anticipatory effect of the urine assay. RESULTS: In total, 204 patients and 736 sample pairs were collected. Sixty-three recurrences were diagnosed for which we had concomitant assay results. On cross-sectional analyses, the assay detected 75% (95% CI 62.1% -84.7%) of recurrences, with a specificity of 70% (95% CI 66.4% -73.5%). Furthermore, mixed effects model analyses revealed OTX1 (p = 0.005) and TERT (p = 0.004) as significant predictors for disease recurrence. Median follow-up was 25.3 months (IQR 18.6-30.7). Twenty-nine tumors were diagnosed without concomitant urine samples, which included recurrences detected after urine collection ended. Longitudinal analyses showed that a positive urine assay predicted a recurrence over time (HR 3.5, p < 0.001). Furthermore, a recurrence during the study period was also a predictor for developing future recurrences (HR 2.1, p < 0.001). CONCLUSIONS: This study validates the performance of a previously developed urine assay in an unselected cohort of HR-NMIBC patients under surveillance. With a robust sensitivity/specificity and a strong anticipatory effect, this assay proves a useful adjunct ready for evaluation in a future randomized controlled trial.

Bilateral Adrenal and testicular Tumours; When a Simple Diagnosis Becomes Complicated.

A 78-year-old man with a BMI 28.7, a moon face and a medical history of diabetes mellitus, hypothyroidism, undefined adrenal insufficiency and history of cardiac ablation, had been in urological follow up for both prostate and bladder cancer. PSA remained low after radiation and adjuvant ADT. Cystoscopy revealed no recurrence after transurethral resection of bladder tumour and instillation of BCG. A routine CT scan as indicated by EAU guideline, showed bilateral enlargement of the adrenal glands as the only abnormality de novo. Patient had no other symptoms than already long-existing fatigue. Considering patient's medical history, subsequently a FDG PET scan was performed which showed intense FDG uptake not only bilaterally in the adrenal glands, but also in both testes. An ultrasound of the testes demonstrated hypodense lesions with increased flow. US imaging raised the suspicion of testicular adrenal rest tumours. Differential diagnoses were primary testis tumour, metastatic disease, BCG-itis, lymphoma or rare endocrine disorders. The combination of bilateral adrenal gland hyperplasia and testicular masses reminded us of seeking the rare diagnosis of ectopic adrenal remnant in both testis and a Cushing-like feature. Endocrinological evaluation could not establish an all-encompassing diagnosis to explain all of the clinical findings. Bilateral orchidectomy was performed. Histological examination showed localization of diffuse large B cell lymphoma (DLBCL) in both testes. Patient was referred to the haematologist and started with chemotherapy, R-CHOP. The diagnostic process in this case was challenging and misleading.

Isolated cerebellar metastasis from urothelial carcinoma: A case report of a rare phenomenon.

Introduction: Although urothelial carcinoma (UC) generally is non-invasive, contrastingly in 25% of patients UC metastasizes. Isolated central nervous system (CNS) metastasis from UC without other distant metastases are considered rare. In this report we describe a patient with an isolated and solitary cerebellar metastasis from UC. Research question: In this case report we explore the value of histological analysis of CNS metastases, imaging, treatment options and survival. Material and methods: A rare case is presented of a patient diagnosed with an isolated CNS metastasis originating from UC. Through a systematic review of literature route of dissemination, current imaging and treatment options, and survival are discussed. Results: A 77-year-old male was diagnosed with a pT2N0M0 high-grade UC and treated with transurethral resection and chemoradiation therapy. Several months later, the patient presented with neurological symptoms, and radiological imaging revealed a solitary cerebellar mass. A body CT scan showed no other metastasis. After surgical resection, histology confirmed urothelial origin of the mass, matching his primary UC and the patient received post-operative stereotactic radiotherapy at the surgical site. Recurrence of the cerebellar mass occurred after 6 months for which the patient received re-resection. The patient died 5.5 months after re-resection. Discussion and conclusion: Isolated brain metastases without other distant metastases from UC are rare, so histologic confirmation of the brain metastasis is essential, particularly when the time interval between diagnosis of the UC and brain metastasis increases. Early brain CT is not recommended. PET CT may have additional value in detection of other distant metastases from UC. Despite advancements in treatments, prognosis for CNS metastasis from UC remains poor.

Patients and physician satisfaction of Degarelix in androgen deprivation therapy for advanced hormone-dependent prostate cancer in the Netherlands.

BACKGROUND: To explore the effectiveness and safety of the gonadotropin-releasing hormone antagonist, Degarelix, for the treatment of advanced hormone-dependent prostate cancer (PCa) in a real-world setting. METHODS: In this noninterventional study, patients with advanced hormone-dependent PCa were included. Primary endpoints were progression-free survival (PFS) failure defined as either prostate-specific antigen failure, additional therapy related to PCa, or death. Secondary endpoints included patient and physician satisfaction scores, urinary symptoms, and adverse events (AEs). RESULTS: Of 274 patients with PCa, 271 received at least 1 dose of Degarelix. At a median follow-up of 12.2 (interquartile range 6.2-22.0) months, 148 patients (60.2%) had PFS failure. Thirty-five patients (13%) withdrew from the study due to AEs, 23 patients (8.4%) died, and 36 patients (13%) completed 3 years' follow-up. Urinary symptoms significantly decreased over time. In the safety population, 87.8% of patients reported AEs, with injection-site reactions commonly reported. The majority of physicians and patients considered the therapy satisfactory and well tolerated. CONCLUSIONS: In this observational study, Degarelix treatment was well accepted by men with advanced hormone-dependent PCa. Compared with phase III studies, a higher proportion of patients had PFS failure, possibly due to the inclusion of men with more advanced disease in the current study, and more men reported AEs.

Simultaneous transurethral resection of the prostate and cystolithotripsy: A urological dilemma examined.

INTRODUCTION: Controversy exists over whether transurethral resection of the prostate (TURP) in men with bladder stones prevents recurrence of stone formation and facilitates stone discharge. We sought to evaluate whether TURP in patients who underwent cystolithotripsy led to a lower recurrence of bladder stones for which a re-cystolithotripsy was necessary. METHODS: Patients (n=127) who underwent transurethral cystolithotripsy with (n=38) or without simultaneous TURP (n=89) between January 2009 and December 2013 were retrospectively included in five centers in the Netherlands. Median followup was 48 months. The primary endpoint was to compare the relative risk between both groups for re-cystolithotripsy due to recurrent bladder stones. Secondary outcomes were the relative risk of urinary retention, the need for a (re-)TURP and the average time until recurrence. RESULTS: Patients who underwent a cystolithotripsy with a simultaneous TURP had a lower need for re-cystolithotripsy, resulting in a risk reduction of 72%. (relative risk [RR] 0.28 [0.07-1.13], p=0.06, number needed to treat [NNT]=7). The length of in hospital stay (3.4 vs. 1.6 days, p=0.04) and operative time (58 vs. 33 minutes, p<0.01) was longer when a TURP was performed. There was no significant difference in complication rate, occurrence of urinary retention, re-TURP, and re-admission. Eighty-one percent of patients who did not undergo a TURP remained free of bladder stone recurrence. Due to the retrospective nature of the study, essential data concerning prostate volume and micturition analysis was lacking. CONCLUSIONS: A simultaneous TURP in patients who underwent a cystolithotripsy showed a trend towards a protective effect on the need for re-cystolithotripsy.

The influence of pelvicalyceal system anatomy on minimally invasive treatments of patients with renal calculi.

INTRODUCTION AND OBJECTIVES: Nephrolithiasis has a multifactorial etiology, wherein, besides metabolic factors, the anatomy of the pelvicalyceal system might play a role. Using 3D-reconstructions of CT-urography (CT-U), we studied the morphometric properties of pelvicalyceal anatomy affecting kidney stone formation and compared those with existing literature on their effect on minimally invasive treatment techniques for renal calculi. METHODS: CT-U's were made between 01-01-2017 and 30-09-2018. Patients were chronologically included in two groups: a nephrolithiasis group when ≥ 1 calculus was present on the CT-U and a control group of patients with both the absence of calculi on the CT-U and no medical history of urolithiasis. Patients with a medical history of diseases leading to higher risks on urolithiasis were excluded. In the nephrolithiasis group affected kidneys were measured. In the control group, left and right kidneys were alternately measured. RESULTS: Twenty kidneys were measured in both groups. Mean calyceopelvic tract width was significantly larger in the lower segments of affected kidneys (3.9 vs. 2.7 mm). No significant differences between the groups were found in number of calyces, infundibular length, infundibular width, calyceopelvic angle, upper-lower angle and diameters of the pelvis. Transversal calyceal orientation in hours was significantly smaller in the upper and lower segments of the nephrolithiasis group (7.69 vs. 8.52 and 8.08 vs. 9.09 h), corresponding with more dorsally located calyces in stone-forming kidneys. CONCLUSION: Pelvicalyceal anatomy differs between stone-forming and non-stone-forming kidneys. Understanding the pelvicalyceal system and etiology of stone formation can improve development of endourological techniques.

Antegrade pyelography, a survey among urologists.

PURPOSE: Antegrade pyelography (APG) is a useful modality for imaging the upper urinary tract. Little scientific evidence exists concerning optimal pressure while performing an APG. Methods of implementation seem to vary between hospitals as no specific guideline exists. Our aim was to describe current practice patterns in pre-procedural prophylaxis, describe methods of contrast administration, and estimate rate of complications during APG as reported by urologist, in order to stimulate discussion on defining guidelines. METHODS: A digital questionnaire with 16 questions concerning APG was set out among EAU members via an ESUI twitter link. Fifty urologists from different centers responded. Outcomes were use of antibiotics, used pressure in upper urinary tract, and estimated urosepsis prevalence. Percentages and confidence intervals (95% CI) were calculated. RESULTS: Forty-two percent (95% CI 30-56) of respondents stated that antibiotic prophylaxis was always administered. Fifty-two percent (95% CI 38-65) of urologists sometimes performed a pre-procedural culture. Seventy percent (95% CI 56-81) indicated that administration of contrast during APG was performed using a syringe. A local guideline was only used in 8% of cases (95% CI 2.8-17.9) The self-estimated average percentage of urosepsis as a result of performing an APG was mentioned to be 4% (range 0-20%). CONCLUSION: Despite a considerable risk of urosepsis, no guideline or consensus exists on how to perform APG. This is urgently needed in order to prevent complications. Low response rate is a major limitation of these findings.

FGFR3 Mutation Status and FGFR3 Expression in a Large Bladder Cancer Cohort Treated by Radical Cystectomy: Implications for Anti-FGFR3 Treatment?†.

Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer (BC). FGFR3 mutations are common in noninvasive BC and associated with favorable BC prognosis. Overexpression was reported in up to 40% of FGFR3 wild-type muscle-invasive BC. We analyzed FGFR3 mutations, FGFR3, and p53 protein expression and assessed their prognostic value in a cohort of 1000 chemotherapy-naive radical cystectomy specimens. FGFR3 mutations were found in 11%, FGFR3 overexpression was found in 28%, and p53 overexpression was found in 69% of tumors. Among FGFR3 mutant tumors, 73% had FGFR3 overexpression versus 22% among FGFR3 wild-type tumors. FGFR3 mutations were significantly associated with lower pT stage, tumor grade, absence of carcinoma in situ, pN0, low-level p53, and longer disease-specific survival (DSS). FGFR3 overexpression was associated only with lower pT stage and tumor grade. Moreover, FGFR3 overexpression was not associated with DSS in patients with FGFR3 wild-type tumors. In conclusion, FGFR3 mutations identified patients with favorable BC at cystectomy. Our results suggest that FGFR3 mutations have a driver role and are functionally distinct from FGFR3 overexpression. Hence, patients with FGFR3 mutations would be more likely to benefit from anti-FGFR3 therapy. Ideally, further research is needed to test this hypothesis. PATIENT SUMMARY: Oncogenic fibroblast growth factor receptor 3 (FGFR3) mutations are very common in bladder cancer. In this report, we found that these FGFR3 mutations were associated with favorable features and prognosis of bladder cancer compared with patients with FGFR3 overexpressed tumors only. As a consequence, patients with FGFR3 mutant tumors would be more likely to benefit from anti-FGFR3 therapy than patients with FGFR3 protein overexpression only.

The anatomy of the renal pyelocaliceal system studied by CTU.

INTRODUCTION AND OBJECTIVES: Knowledge of the pyelocaliceal system anatomy is essential for the safe and successful performance of endourologic procedures. The purpose of this study was to provide a better understanding of the full three-dimensional pyelocaliceal system anatomy. METHODS: Morphometric parameters of the three-dimensional reconstructions of computed tomography intravenous urography scans (n = 25 scans) were analyzed. Both kidneys were divided into three equal-sized segments (US: upper segment, MS: mid segment, LS: lower segment). Infundibular length (IL), infundibular width (IW), the number of calyces, and the transverse orientation in hours of a clock of each calyx as well as the dimension of the pyelum were determined. RESULTS: The mean upper IL (n = 92) was longer than the middle (n = 154) and lower IL (n = 112) (30.6 ± 7.9 mm vs. 16.4 ± 7.7 mm vs. 16.0 ± 6.0 mm, respectively; P = < 0.0001). IW was significantly smaller in the MS [3.7 ± 1.9 mm], followed by the US [4.6 ± 1.9 mm], and the LS [4.9 ± 2.2] in the increasing order. No correlation was found between IL and IW (Pearson correlation coefficient = 0.1). The US calyces were predominantly orientated lateral (8-10 o'clock: 44.5%) and medial (2-4 o'clock: 30.5%), in the MS lateral (8-10 o'clock: 87.6%) and anterolateral in the LS (9-12 o'clock: 67.9%). 74% of the kidneys consisted of 6-8 calyces (mean 7.2 ± 1.4, range 4-10), with the majority of the calyces in the MS (3.1 ± 0.8) followed by the LS (2.24 ± 0.8), and US (1.8 ± 0.7). There were no statistical differences between the right and left kidneys in terms of IL (P = 0.112) and number of calyces (P = 0.685). CONCLUSION: Anatomic differences between the three segments of the pyelocaliceal system in terms of IL, IW, calyces number, and orientation are seen and should be considered when performing an endourologic procedure.

The Influence of Pain on the Outcome of Extracorporeal Shockwave Lithotripsy.

INTRODUCTION: The aim of this study was to determine the predictive value of pain scores on the efficacy of extracor-poreal shockwave lithotripsy (ESWL) and to identify other predictive risk factors for treatment success. MATERIALS AND METHODS: A total of 476 patients who underwent ESWL (piezoelectric lithotripsy) for urolithiasis between September 2011 and December 2015 were identified. The primary end-point of this study was success rate, which was evaluated 4 months after ESWL. The secondary outcome was the occurrence of complications as a result of ESWL. RESULTS: The average pain perception was reported at 5 on a scale from 0 to 10. The overall success rate of ESWL was found to be 43.9% and the success rate after the first ESWL was 35.1%. Univari-ate analysis showed no significant correlation between pain score and success of ESWL (p = 0.135). The level of intensity was correlated with pain scores (Pearson correlation -0.423, p < 0.001). Univariate analysis identified five predictive factors: sex, stone location, stone size, hydronephrosis and the use of tamsulosin. Multivariate logistic regression analysis showed that sex, stone location and size independently in-fluenced the success of ESWL (p = 0.045, p = 0.001 and p < 0.001). CONCLUSION: No correlation was found between the pain scores and efficacy of ESWL. Despite this absence, pain scores during ESWL sessions remain high and additional analgesia would improve patient satisfaction.

Lessons from Literature: Nephrostomy Versus Double J Ureteral Catheterization in Patients with Obstructive Urolithiasis-Which Method Is Superior?

Purpose: To review the literature on optimal methods of drainage for obstructive urolithiasis in adult patients, comparing percutaneous nephrostomy (PCN) with retrograde ureteral catheterization (Double J [JJ]) regarding success of procedure, efficacy, complications, quality of life (QoL), and costs. Methods: Web of Science and the Medline, Embase, Emcare, and Cochrane controlled trial databases were searched for all relevant publications until November 2018. A review protocol was created, using the PRISMA statement. Two reviewers independently screened the titles and abstracts in Endnote X8, using criteria as stated in the research protocol. A total of 1108 abstracts were screened of which 9 were included in the qualitative synthesis. Level of evidence of the studied articles varies between 1b and 2c. Results: Both JJ and PCN have high success rates (80%-100% and 99%-100%, respectively). No major complications were reported in both groups. Procedural and fluoroscopy times are significantly shorter for JJ than for PCN (31-33 minutes vs 35-49 minutes and 5 minutes vs 7 minutes, respectively). Time to clinical improvement did not differ. In the JJ group, analgesics were used more frequently than in the PCN group. Data regarding procedural costs were contradictory, but overall the PCN group was associated with higher costs. In pregnant women, PCN placement appears to be significantly more effective than placement of JJ. A significant decrease between pre- and postintervention QoL was found with patients receiving a JJ. Back pain was reported more frequently in the PCN group, urinary symptoms were more common in the patients with a JJ. Conclusions: Both PCN and JJ have comparable success rates for patients with obstructive urolithiasis and procedure-related complications are rare. Overall, higher rates of sepsis, longer hospital stay, and higher costs were found in the PCN group, but that could be explained by patient selection. Patients with JJ experienced a lower QoL and experience more lower urinary tract symptoms.

Antegrade Ureteral Stenting is a Good Alternative for the Retrograde Approach.

BACKGROUND/AIMS: Double J (JJ) stents for treating obstructive ureteral pathology are generally inserted through a retrograde route with cystoscopic guidance. Antegrade percutaneous insertion using fluoroscopy can be performed alternatively but is less known. Indications, success rate and complications of antegrade ureteral stenting were evaluated. METHODS: Data of consecutive patients in which antegrade ureteral stenting was performed were retrospectively analysed using the radiology information system and patient records. Patient characteristics, details of the antegrade JJ stent insertion procedure and registered complications were collected. Furthermore, it was investigated if prior to the antegrade procedure a retrograde attempt for JJ stent insertion was performed. RESULTS: Total 130 attempts for antegrade JJ stent insertion were performed in 100 patients. A percutaneous nephrostomy catheter had already been placed in the majority of kidneys (n = 109) for initial treatment of hydronephrosis. Most prevelant indication for a JJ stent was obstructive ureteral pathology due to malignancy (n = 63). A JJ stent was successfully inserted in 125 of 130 procedures. In 21 cases, previous retrograde ureteral stenting had failed but, subsequent antegrade ureteral stenting was successful. There were 8 procedure related complications; 6 infections, 1 false tract and 1 malposition. CONCLUSION: Antegrade percutaneous insertion of a JJ stent is a good alternative for retrograde insertion.

Pyoderma Gangrenosum in the Urologist Clinic.

Pyoderma gangrenosum is a rare non-infectious skin disorder. It is often associated with systemic diseases, like the inflammatory bowel disease, rheumatological disease and (hematological) malignancy. The diagnosis is affirmed through a process of elimination and is principally based on clinical presentation and course. We present a 59-year-old male with T-cell large granular lymphocyte leukemia and pyoderma gangrenosum of penis and scrotum. Finally the patient was successfully treated with systemic prednisolone.

Treatment and outcome of fibroepithelial ureteral polyps: A systematic literature review.

INTRODUCTION: Fibroepithelial polyps of the ureter are rare. Cases and small series are reported in the literature. The treatment of choice, outcome and appropriate follow-up regimen remain unclear. METHODS: We conducted a systematic literature review of papers reporting fibroepithelial polyps of the ureter in adult patients. Articles published before 1980 were excluded. RESULTS: The search yielded 144 papers, of which 68 met the inclusion criteria. A reference scan from the included 68 yielded an additional 7 new articles. In total, our study included 75 articles (68 + 7). A total of 134 patients were described. Most patients had a single lesion (range: 1-10). The median length of the polyp was 4.0 cm (range: 0.4-17.0). The percentage of polyps resected endoscopically increased from 0% before 1985 to 67% after 2005. Two perioperative complications were reported in 72 procedures (2.8%): a deep venous thrombosis and a case of mesenteric lymphadenopathy. Both of these occurred after open surgery. Follow-up data were available for 57 patients. The median follow-up was 12 months (range: 1-180). Four patients (7.0%) developed recurrent complaints: 2 had urinary stones, 1 had a ureteral stricture and 1 had recurrence of the polyp. Three of these events followed endoscopic resection, and occurred within a year after the procedure. CONCLUSION: Endoscopic resection of fibroepithelial polyps seems to be safe and effective. It is minimally invasive and should be considered the gold standard where endoscopic expertise is available. We advise follow-up imaging by computed tomographic intravenous urography after 3 months and ultrasound after 1 year to detect late complications.

Considerations in minimally invasive surgery for renal and ureteric calculi: a bicenter quality control study.

BACKGROUND: The use of minimally invasive surgery is increasing. Evaluating the quality of care brings new sights in the optimization of operating techniques. METHODS: We included all procedures performed in two hospitals during 2010 and 2011. A total of 264 patients were included in the ureterorenoscopy (URS) group and 77 patients in the percutaneous nephrolitholapaxy (PCNL) group. Data were gathered by retrospectively reviewing medical records. RESULTS: Mean stone diameter in the URS group was 9 mm. Patients suffered from a single stone in 79% of the cases. Calculi in the distal ureter, defined as the part of the ureter below the lower border of the sacroiliac joint, were most likely to be removed. A stone-free status was reached in 69% of the cases using URS. Mean stone diameter in the PCNL group was 23 mm. PCNL was successful in 70% of the cases in Haga Hospital versus 53% in Medisch Centrum Haaglanden. Incidence of complications was comparable between the hospitals (p = 0.5). Outcome and quality of both PCNL and URS was not influenced by sex, age or body mass index. CONCLUSION: The clinical results were comparable with results in the literature. Further improvement can be made by optimization of technical aspects and centralization of treatment by urologists experienced in minimally invasive techniques.