Increased urinary bladder volume improves the detectability of urinary stones at the ureterovesical junction in non-enhanced computed tomography (NECT).

OBJECTIVES: To evaluate the influence of the urinary bladder volume on the detectability of urolithiasis at the ureterovesical junction (UVJ) using a low-dose CT (LD-CT) with iterative reconstruction (IR) and a standard-dose CT (SD-CT) without IR in a large cohort. METHODS: Four hundred patients (278 males (69.5%), mean 44.6 ± 14.7 years) with urolithiasis at the UVJ were investigated either by an LD-CT with IR (n = 289, 72%) or an SD-CT without IR (n = 111, 28%) protocol. The detectability of distal urolithiasis was assessed by a dichotomous assessment (definite or questionable) by two radiologists in consensus and by a quantitative analysis of the signal density distribution across a line drawn parallel to the distal ureter. Based on the resulting graph, minimum/maximum density values and mean/maximum upslopes and downslopes were derived and calculated automatically. In all patients, the total bladder volume was calculated by a slice-by-slice approach on axial CT images. RESULTS: Patients with definite stones showed significantly higher urinary bladder volumes compared to patients with questionable stones in both LD-CT and SD-CT (p < 0.01). These results were independent of stones' length and patients' BMI values. Using cutoffs of 92 ml for LD-CT and 69 ml for SD-CT, high positive predictive values/accuracy rates of 96%/85% (LD-CT) and 98%/86% (SD-CT) were observed to identify definite urinary stones. CONCLUSIONS: Urinary bladder volume has a significant impact on the detectability of distal urolithiasis. Moderate bladder filling by pre-CT hydration with subsequent CT scan at the time of high urge to void increases the detectability of urinary stones at the UVJ in clinical routine. KEY POINTS: • Urinary bladder volume significantly affects the detectability of distal urolithiasis • Higher bladder volumes are associated with improved detectability of distal urinary stones • Oral pre-CT hydration for urolithiasis is easily applicable and cost-effective.

A nonrandomized, prospective, clinical study on the impact of circulating tumor cells on outcomes of urothelial carcinoma of the bladder patients treated with radical cystectomy with or without adjuvant chemotherapy.

To investigate outcomes of urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC) according to the presence of circulating tumor cells (CTC) and the administration of adjuvant chemotherapy (AC). We prospectively enrolled 226 UCB patients treated with RC without neoadjuvant chemotherapy at our institution between 2007 and 2013. Blood samples were obtained from all patients preoperatively and analyzed for CTC using the CellSearch® system. Platinum-based AC was administered in 50 patients (27.0%). Cox regression models evaluated the association of CTC with disease recurrence, cancer-specific and overall mortality according to AC administration. 185 patients were available for analyses. CTC were present in 41 patients (22.2%). Patients with presence of CTC received AC more frequently, compared to patients without CTC (p = 0.027). At a median follow-up of 31 months, the presence of CTC was associated with disease recurrence, cancer-specific and overall mortality (p-values < 0.001) in patients without AC administration. In patients who received AC, there was no difference in either endpoint between patients with or without presence of CTC. In multivariable analysis of patients without AC administration, the presence of CTC was an independent predictor for disease recurrence (HR: 4.9; p < 0.001), cancer-specific (HR: 4.2; p = 0.003) and overall mortality (HR: 4.2; p = 0.001). The CTC status may be implemented in decision-making regarding AC administration in UCB patients following RC. CTC measurement should be implemented in future UCB studies on systemic chemotherapy to validate our findings.

Detection and oncological effect of circulating tumour cells in patients with variant urothelial carcinoma histology treated with radical cystectomy.

OBJECTIVES: To investigate for the presence of circulating tumour cells (CTC) in patients with variant urothelial carcinoma of the bladder (UCB) histology treated with radical cystectomy (RC), and to determine their impact on oncological outcomes. PATIENTS AND METHODS: We prospectively collected data of 188 patients with UCB treated with RC without neoadjuvant chemotherapy. Pathological specimens were meticulously reviewed for pure and variant UCB histology. Preoperatively collected blood samples (7.5 mL) were analysed for CTC using the CellSearch® system (Janssen, Raritan, NJ, USA). RESULTS: Variant UCB histology was found in 47 patients (25.0%), most frequently of squamous cell differentiation (16.5%). CTC were present in 30 patients (21.3%) and 12 patients (25.5%) with pure and variant UCB histology, respectively. At a median follow-up of 25 months, the presence of CTC and non-squamous cell differentiation were associated with reduced recurrence-free survival (RFS) and cancer-specific survival (pairwise P ≤ 0.016). Patients without CTC had better RFS, independent of UCB histology, than patients with CTC with any UCB histology (pairwise P < 0.05). In multivariable analyses, the presence of CTC, but not variant UCB histology, was an independent predictor for disease recurrence [hazard ratio (HR) 3.45; P < 0.001] and cancer-specific mortality (HR 2.62; P = 0.002). CONCLUSION: CTC are detectable in about a quarter of patients with pure or variant UCB histology before RC, and represent an independent predictor for outcomes, when adjusting for histological subtype. In addition, our prospective data confirm the unfavourable influence of non-squamous cell-differentiated UCB on outcomes.

Anterior Urethral Strictures in Children: Disease Etiology and Comparative Effectiveness of Endoscopic Treatment vs. Open Surgical Reconstruction.

Pediatric anterior urethral strictures are rare and recommendations regarding treatment strategies derive from small monocentric case series. In 2014, a collaborative effort of the Société Internationale d'Urologie and the International Consultation on Urological Diseases drafted the first systematic and evidence-based guideline for diagnosis and treatment of urethral strictures in children. Against this backdrop, we performed an updated literature review to provide a comprehensive summary of the available evidence and contemporary outcomes with a focus on comparative effectiveness of endoscopic treatment (dilation or urethrotomy) vs. open surgical reconstruction. Overall, 22 articles reporting on children with anterior urethral strictures were included into the review. Most strictures were iatrogenic (48%) and traumatic (34%), whereas congenital (13%), inflammatory (4%), or postinfectious strictures (1%) were rather rare. The cumulative success rate of endoscopic treatment and urethroplasty was 46% (range: 21-75; N = 334) and 84% (range: 25-100; N = 347), respectively. After stratifying patients according to urethroplasty technique, success rates were 82% (range: 25-100; N = 206) for excision and primary anastomosis, 94% (range: 75-100; N = 40) for graft augmentation, 97% (range: 87-100; N = 30) for flap urethroplasty, and 70% (one study; N = 20) for pull-through urethroplasty. In conclusion, endoscopic approaches are rather ineffective in the long-term and open surgical reconstruction via urethroplasty should be preferred to avoid multiple, repetitive interventions. Future research may involve multi-institutional, collaborative, and prospective studies, incorporating well-defined outcome criteria and assessing objective surgical endpoints as well as patient-reported functional outcomes.

The contemporary role and impact of urine-based biomarkers in bladder cancer.

Despite advances in the surgical and medical treatment of bladder cancer, there have only been minor improvements in mortality and morbidity rates over the past decades. Urine-based markers help to improve diagnosing bladder cancer with the aim of complementing or probably in future replacing cystoscopy. Biomarkers may allow individualized risk stratification and support decision-making regarding therapy and follow-up. This review summarizes the existing urine-based biomarkers in bladder cancer. We conducted a comprehensive review of the literature. We conducted a PubMed/Medline based research on English language articles and selected original articles and review articles that provided both description and assessment of urinary markers at time of screening, initial diagnosis, monitoring and prognostic evaluation of urothelial bladder cancer. Our research covered studies published between 2000 and 2017. The aim of this study was to give clinicians keys to understand the existing or promising urinary markers that may become alternatives to cytology/cystoscopy pair in the near future. Many urinary markers are now available, often with superior sensitivity to cytology. Their uses have been evaluated in numerous clinical situations in addition to the time of initial diagnosis and surveillance such as cases of isolated macroscopic hematuria or atypical cytology discordant with the rest of the explorations. However, their superiority over the cytology/cystoscopy association is not demonstrated. These new markers are lacking for the most part of standardization and simplicity making their use in common practice difficult. the types and forms of these new markers are very heterogeneous among themselves and between the studies that evaluate them. Well-designed protocols and prospective, controlled trials are needed to provide the basis to determine whether integration of urine- and blood-based biomarkers into clinical decision-making will be of value for bladder cancer detection and screening in the future.

Copy number variations of circulating, cell-free DNA in urothelial carcinoma of the bladder patients treated with radical cystectomy: a prospective study.

The aim of the present study was to establish a rapid profiling method using multiplex ligation-dependent probe amplification (MLPA) and characterize copy number variations (CNV) in circulating, cell-free DNA (cfDNA) in 85 urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). MLPA was tested for the use of cfDNA extracted from serum and plasma by various commercial extraction kits. Eighteen probes served as reference to control denaturation, ligation and amplification efficiency. MLPA was exclusively suitable for cfDNA extracted from serum. Serum from 72 patients (84.7%) could be analyzed. Thirty-five patients (48.6%) had presence of CNV in cfDNA. The median CNV count in patients with presence of CNV was 2. Predominantly, CNV were located in the genes CDH1, ZFHX3, RIPK2 and PTEN in 15 patients (20.8%), 12 patients (16.7%), 9 patients (12.5%) and 7 patients (9.7%), respectively. CNV in TSG1, RAD21, KIAA0196, ANXA7 and TMPRSS2 were associated with presence of variant UCB histology (p = 0.029, 0.029, 0.029, 0.029, 0.043, respectively). Furthermore, CNV in miR-15a, CDH1 and ZFHX3 were associated with presence of incidental prostate cancer (p = 0.023, 0.003, 0.025, respectively). Patients with CNV in KLF5, ZFHX3 and CDH1 had reduced cancer-specific survival, compared to patients without CNV in these genes (pairwise p = 0.028, 0.026, 0.044, respectively). MLPA represents an efficient method for the detection of CNV among numerous genes on various chromosomal regions. CNV in specific genes seem to be associated with aggressive UCB biologic features and presence of incidental prostate cancer, and may have a negative impact on cancer-specific survival.

Lymph node dissection during radical cystectomy for bladder cancer treatment: considerations on relevance and extent.

Despite advances in the surgical and medical treatment for urothelial carcinoma of the bladder (UCB), there have only been limited improvements in disease-specific mortality rates over the past decades. Lymph node dissection (LND) during radical cystectomy is an integral part of the treatment for muscle-invasive and high-risk UCB. LND may detect and remove lymph node (LN) metastasis and thus guide patient counseling and decision making regarding additional treatment decisions. In addition, LND may improve survival in patients both with and without LN metastasis. In this non-systematic review article, we discuss benefits and risks of LND, the role of limited versus extended LND and the dilemma of preoperative LN staging.

High tissue density of FOXP3+ T cells is associated with clinical outcome in prostate cancer.

Cell-mediated immunity may impact prostate cancer progression and has great therapeutic potential. Here, we investigated the clinical significance of the numeric density of regulatory T cells (Tregs) in prostate cancer as the presence of such cells in the tumour microenvironment has been linked to clinical outcome in other tumour entities. We detected Tregs by FOXP3 immunohistochemistry in 88.8% of 2002 prostate cancer specimens in tissue microarray format, the largest cohort so far in which Tregs have been quantified. The density of Tregs in tumour tissue was compared with pathological parameters and clinical outcome. The number of Tregs identified per 0.6mm tissue spot ranged from 1 to 10 in normal and 1 to 103 FOXP3+ cells in tumour samples. Prostate-specific antigen (PSA) recurrence-free survival was significantly reduced in patients with higher numbers of Tregs (p=0.0151). Further, a higher number of intratumoural FOXP3+ Tregs was associated with a more advanced tumour stage (p=0.0355) and higher Ki67 labelling index (p<0.0001). The tissue density of Tregs was unrelated to other clinical parameters such as spread to lymph nodes, preoperative PSA level and Gleason score. Our study suggests that the intratumoural presence of regulatory T cells may have substantial functional impact and may confer an adverse clinical course in prostate cancer.