BACKGROUND:The sensitivity of cytology for the detection of urothelial carcinoma (UC) is limited. Newer methods such as fluorescence in situ hybridization (FISH), immunocytology (uCytþ), and protein markers have been developed to improve urine-based detection of UC. As only little is known regarding the combined application of these markers, we investigated whether combinations of 4 of the most broadly available tests (cytology, FISH, uCytþ, and nuclear matrix

BackgroundThe role of urine markers in the surveillance of patients with non-muscle invasive bladder cancer (NMIBC) is discussed extensively. In case of negative cystoscopy the additional prognostic value of these markers has not been clearly defined yet. The present study is the first systematic approach to directly compare the ability of a urine marker panel to predict the risk of recurrence and progression in bladder cancer (BC) patients with no evidence of relapse during surveillance for NMIBC.MethodsOne hundred fourteen patients who underwent urine marker testing during surveillance for NMIBC and who had no evidence of BC recurrence were included. For all patients cytology, Fluorescence-in-situ-hybridization (FISH), immunocytology (uCyt+) and Nuclear matrix protein 22 enzyme-linked immunosorbent assay (NMP22) were performed. All patients completed at least 24 months of endoscopic and clinical follow-up of after inclusion.ResultsWithin 24 months of follow-up, 38 (33.0%) patients experienced disease recurrence and 11 (9.8%) progression. Recurrence rates in patients with positive vs. negative cytology, FISH, uCyt+ and NMP22 were 52.6% vs. 21.9% (HR = 3.9; 95% CI 1.75-9.2; p < 0.001), 47.6% vs. 25.0% (HR 2.7; 1.2-6.2; p = 0.01), 43.8% vs. 22.4% (HR 3.3; 1.5-7.6; p = 0.003) and 43.8% vs. 16.7% (HR 4.2; 1.7-10.8; p = 0.001). In patients with negative cytology, a positive NMP22 test was associated with a shorter time to recurrence (p = 0.01), whereas FISH or uCyt+ were not predictive of recurrence in these patients. In the group of patients with negative cytology and negative NMP22, only 13.5% and 5.4% developed recurrence and progression after 24 months.ConclusionsPatients with positive urine markers at time of negative cystoscopy are at increased risk of recurrence and progression. In patients with negative cytology, only NMP22 is predictive for recurrence. Patients with negative marker combinations including NMP22 harbour a low risk of recurrence. Therefore, the endoscopic follow-up regimen may be attenuated in this group of patients.

Objectives Computed tomography (CT) imaging of the clavicula displays the reference standard for forensic bone age diagnostics in adolescents and young adults. Consequently, highest efforts on radiation reduction are warranted. Therefore, the aim of this study was to investigate the feasibility of low-dose (LD) CT imaging of the clavicula for age estimation in living adolescents. Methods A total of 207 non-contrast chest CT of 144 patients born between 1988 and 2012, performed in 2018 due to various clinical indications, were included in this retrospective study. The mean patient age was 16.9 ± 6.6 years. Patients were divided into a LD (n = 146) and standard-dose (SD; n = 61) group. Image quality, confidence levels, and ossification stages (using the 5-stage classification including the subgroups 2a–3c) were assessed by two radiologists independently. Radiation dose was determined via dosimetry software. Results Dose simulation with z-axis reduction to depict the clavicula only resulted in a median exposure of 0.1 mSv (IQR: 0.0) in LD compared with 0.9 mSv (IQR: 0.6) in SD (p < 0.001). The median image quality was rated by both readers significantly worse in LD compared with SD on a Likert scale ranging from 1 to 4 with a median of 3 (IQR: 1) versus 4 (IQR: 0; p < 0.001 for both readers). There was an almost perfect agreement for the ossification stages between both readers with a Cohen’s kappa of 0.83 (p < 0.001). Median confidence levels of both readers were not significantly different between LD and SD in the decisive subgroups 2a–3c. Conclusions Low-dose CT imaging of the clavicula for age estimation in living adolescents is possible without loss of readers’ confidence. Key Points • Radiological bone age diagnostics in young delinquents with unknown exact chronological age is important as the judicial systems differentiate between youths and adults. • Low-dose computed tomography scanning of the medial clavicular joint for forensic age estimation is feasible in living adolescents without loss of readers’ confidence. • Sufficient image quality of the medial clavicular joint for forensic bone age diagnostics in living adolescents is achievable using a median dose of 0.1 mSv.

Objectives To assess the performance of urine markers determined in urine samples from the bladder compared to samples collected from the upper urinary tract (UUT) for diagnosis of UUT urothelial carcinoma (UC). Patients and Methods The study comprised 758 urine samples either collected from the bladder (n = 373) or UUT (n = 385). All patients underwent urethrocystoscopy and UUT imaging or ureterorenoscopy. Cytology, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and nuclear matrix protein 22 (NMP22) were performed. Results UUT UC was diagnosed in 59 patients (19.1%) (UUT urine) and 27 patients (7.2%) (bladder-derived urine). For UUT-derived samples, sensitivities for cytology, FISH, NMP22, and uCyt+ were 74.6, 79.0, 100.0, and 100.0, while specificities were 66.6, 50.7, 5.9, and 66.7%, respectively. In bladder-derived samples, sensitivities were 59.3, 52.9, 62.5, and 50.0% whereas specificities were 82.9, 85.0, 31.3, and 69.8%. In UUT-derived samples, concomitant bladder cancer led to increased false-positive rates of cytology and FISH. Conclusions Urine markers determined in urine collected from the UUT exhibit better sensitivity but lower specificity compared to markers determined in bladder-derived urine. Concomitant or recent diagnosis of UC of the bladder can further influence markers determined in UUT urine.

Background. The optimal use of urine markers in the surveillance of non-muscle-invasive bladder cancer (NMIBC) remains unclear. Aim of the present study was to investigate the combined and stepwise use of the four most broadly available urine markers to detect tumor recurrence in patients undergoing surveillance of NMIBC. Patients and Methods. 483 patients with history of NMIBC were included. Cytology, UroVysion, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and NMP22 ELISA were performed before surveillance cystoscopy. Characteristics of single tests and combinations were assessed by contingency analysis. Results. 128 (26.5%) patients had evidence of tumor recurrence. Sensitivities and negative predictive values (NPVs) of the single tests ranged between 66.4–74.3 and 82.3–88.2%. Two-marker combinations showed sensitivities and NPVs of 80.5–89.8 and 89.5–91.2%. A stepwise application of the two-test combinations with highest accuracy (cytology and FISH; cytology and uCyt+; uCyt+ and FISH) showed NPVs for high-risk recurrences (G3/Cis/pT1) of 98.8, 98.8, and 99.1%, respectively. Conclusions. Combinations of cytology, FISH, immunocytology, and NMP22 show remarkable detection rates for recurrent NMIBC. Stepwise two-test combinations of cytology, FISH, and immunocytology have a low probability of missing a high-risk tumor. The high sensitivities may justify the use of these combinations in prospective studies assessing the use of urine markers to individualize intervals between cystoscopies during follow-up.