PURPOSE Previous studies suggested that serum levels of microRNA (miR)-371a-3p (so-called M371 test) have a much higher sensitivity and specificity than the classic markers of testicular germ cell tumors (GCTs) and are applicable toward both seminoma and nonseminoma. We sought to confirm the usefulness of this test as a novel biomarker for GCT. PATIENTS AND METHODS In a prospective, multicentric study, serum samples of 616 patients with testicular GCTs and 258 male controls were examined for serum levels of miRNA-371a-3p (miR levels) by quantitative polymerase chain reaction. The GCT population encompassed 359 patients with seminoma and 257 with nonseminoma; 371 had clinical stage I disease, 201 had systemic disease, and 46 had relapses. Paired measurements before and after orchiectomy were performed in 424 patients; 118 with systemic disease had serial measurements during treatment. miR levels were compared with those of β-human chorionic gonadotropin, α-fetoprotein, and lactate dehydrogenase. RESULTS For the primary diagnosis of GCT, the M371 test showed a sensitivity of 90.1%, a specificity of 94.0%, an area under the curve of 0.966 upon receiver operating characteristic analysis, and a positive predictive value of 97.2%. α-Fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase had sensitivities of less than 50% in seminoma and slightly higher sensitivities in nonseminomas. miR levels were significantly associated with clinical stage, primary tumor size, and response to treatment. Relapses had elevated miR levels that subsequently dropped to normal upon remission. Teratoma did not express miR-371a-3p. CONCLUSION The M371 test outperforms the classic markers of GCT with both a sensitivity and a specificity greater than 90%. All histologic subgroups, except teratoma, express this marker. The test could be considered for clinical implementation after further validation.

Although Bacillus Calmette-Guérin (BCG) is the most successful immunotherapy for high-risk non-muscle-invasive bladder cancer, approximately 30% of patients are unresponsive to treatment. New biomarkers are important to identify patients who will benefit most from BCG during a worldwide BCG shortage. Local immune cell subsets were measured on formalin-fixed, paraffin-embedded tissue sections of bladder cancer by immunohistochemistry, using monoclonal antibodies to tumor-associated macrophages (TAMs; CD68, CD163), B-lymphocytes (CD20) and T-lymphocyte subsets (CD3, CD4, CD8, GATA3, T-bet, FOXP3 and CD25). Cell densities in the lamina propria without invasion, at the invasive front if present, in the papillary tumor stroma, and in the neoplastic urothelium were calculated. Twenty-nine (72.5%) of 40 patients were classified as BCG responders after a mean follow-up of 35.3 months. A statistically significant association was observed for BCG failure with low density of CD4+ and GATA3+ T-cells, and increased expression of FOXP3+ and CD25+ regulatory T-cells (Tregs) as well as CD68+ and CD163+ TAMs. Survival analysis demonstrated prolonged recurrence-free survival (RFS) in patients with an increased count of CD4+ and GATA3+ T-cells. TAMs, Tregs and T-bet+ T-cells were inversely correlated with RFS. Thus, the tumor microenvironment seems to influence the therapeutic response to BCG, permitting an individualized treatment.

RTE demonstrated all testicular tumors as lesions with increased tissue stiffness. Because of its higher specificity, RTE can provide additional information in cases with indeterminate US findings.

ObjectivesTo evaluate the diagnostic accuracy of the Xpert Bladder Cancer (BC) Monitor, compared with cystoscopy and cytology in the oncological follow-up of non-muscle-invasive bladder cancer (NMIBC). Material and MethodsA total of 140 patients with a history of NMIBC undergoing routine surveillance at our institution were enrolled prospectively in this study (ISRCTN study registry number 37210907). Urine cytology was evaluated according to the Paris classification system. In addition, urinary specimens were analysed using the Xpert BC Monitor, which measures five target mRNAs (ABL1, CRH, IGF2, UPK1B, ANXA10) using real-time PCR. Descriptive analysis, diagnostic accuracy including sensitivity, specificity, positive (PPV) and negative predictive value (NPV), receiver-operating characteristic curve, and area under the curve (AUC) were calculated. ResultsThe overall sensitivity (0. ConclusionIn this study, we report for the first time that the Xpert BC Monitor, a new mRNA-based urine test, outperforms cytology with regard to sensitivity and NPV, even in low-grade and pTa tumours, with no reduction of specificity.

Renal cell cancer (RCC) is a highly vascularized and immunogenic tumor type. The inhibition of vessel formation by anti-angiogenic therapies, as well as the stimulation of the immune system by immunotherapy has revolutionized the therapeutic landscape of RCC in recent years. Nevertheless, both therapies are associated with therapy resistance due to a highly dynamic, adaptive and heterogeneous tumor microenvironment (TME). The aim of this short review article is to provide an overview of the components of the RCC TME as well as to discuss their contribution to disease progression. In addition, we report on preclinical and clinical findings and how the different TME components can be modulated to impede treatment progression as well as to overcome therapy resistance to anti-angiogenic or immunomodulating therapy concepts. Furthermore, we discuss the predictive and prognostic role of the TME in RCC therapy. We also report on the concept of combinational targeting of anti-angiogenic therapies and immune checkpoint inhibitor therapy, also including the latest results of clinical studies discussed at recent oncological meetings. Finally, promising new therapeutic targets within the TME are mentioned.

Study Type – Therapy (outcomes research)
Level of Evidence 2c OBJECTIVE To evaluate the efficacy and safety of a transobturator retroluminal repositioning sling suspension in the treatment of male stress urinary incontinence (SUI) after prostate surgery. PATIENTS AND METHODS In 118 men with SUI after prostatic surgery, a transobturator retroluminal repositioning sling suspension was implanted. Patients were evaluated including: complete history and physical examination, 24‐h pad test, a questionnaire (International Consultation on Incontinence Questionnaire, Short‐Form), urodynamic evaluation and endoscopy. The surgical technique was described previously. The findings before and at 1 year after sling placement were compared. RESULTS At the 12‐month follow‐up, 73.7% of the men were cured, 16.9% were improved, and 9.3% were still incontinent. After sling placement the daily pad use decreased significantly (P < 0.001), while the ICIQ‐SF improved significantly (P < 0.01). The detrusor voiding pressure, postvoid residual urine volume and maximal flow rates remained unchanged, while the Valsalva leak‐point pressure improved significantly (P < 0.01). In 19.5% of the men, there was transient scrotal pain or perineal discomfort. In 5.1% of the men, postoperative urinary retention occurred but resolved spontaneously after a few weeks of catheter placement. In 1.7% of the men adductor pain was reported, which resolved spontaneously. There were no major complications. CONCLUSION The transobturator retroluminal repositioning sling suspension for the treatment of male SUI is effective and safe with a low complication rate after 1 year of follow‐up.

Purpose To evaluate the diagnostic accuracy of multiparametric ultrasonography (US) consisting of gray-scale US, color Doppler US, strain elastography, and contrast agent-enhanced US in the assessment of intratesticular lesions. Materials and Methods Institutional review board approval was obtained for this retrospective study. From January 2012 to December 2015, 55 focal testicular lesions that were indeterminate on gray-scale US scans were further characterized with color Doppler US, strain elastography, and contrast-enhanced US. Strain elastography was performed to assess tissue elasticity, and hard lesions were defined as malignant. Color Doppler US and contrast-enhanced US were performed to determine the absence or presence of vascularization. Avascular lesions were defined as benign. Histopathologic results or follow-up examinations served as reference standards. Correct classification rate, sensitivity, specificity, and likelihood ratio were calculated. Results Of 55 testicular lesions, 43 (78.2%) were benign and 12 (21.8%) were malignant. Single-modality sensitivities and specificities were 66.7% and 88.4% for color Doppler US, 100% and 76.7% for contrast-enhanced US, and 100% and 72.1% for strain elastography, respectively. Among 12 malignant lesions, color Doppler US failed to demonstrate vascularization in four (33.3%) lesions, which were positive for cancer at contrast-enhanced US. By combining strain elastography and contrast-enhanced US, a sensitivity of 100% and specificity of 93.0% were achieved in differentiating benign and malignant focal testicular lesions. Positive likelihood ratio was 5.7 for color Doppler US, 4.3 for contrast-enhanced US, 3.6 for strain elastography, 14.3 for strain elastography combined with color Doppler US, and 14.3 for strain elastography combined with contrast-enhanced US. Conclusion Multiparametric US allows for a reliable differentiation of benign and malignant intratesticular lesions and can potentially be useful in deciding whether orchiectomy can be replaced with follow-up or less invasive organ-sparing strategies. RSNA, 2017.

Study Type – Therapy (case series)
Level of Evidence 4 OBJECTIVE To report a new dorsal labia minora skin‐graft urethroplasty as a simple, safe and effective therapeutic alternative for female urethral strictures, as although distal urethral strictures can be treated by meatoplasty, proximal and mid‐urethral strictures need appropriate urethroplasty. PATIENTS AND METHODS Eight women with a confirmed proximal or mid‐urethral stricture had indications for urethroplasty with the use of a thin free labia minora skin graft using a dorsal (6 o’clock position) urethroplasty technique. Full informed consent was obtained. From the inner aspect of one labium minora a thin free skin flap was prepared. The strictured urethra and the anterior vaginal wall were transected and the graft sutured into the defect. All scar tissue was removed and the anterior vaginal wall closed in two layers over the area of the urethroplasty. Continence was evaluated by a stress test with a full bladder. RESULTS All patients were operated on with no complications during or after surgery. After 1 and 2 years of follow‐up seven and six of the eight patients had no recurrence of stricture disease. All patients remained continent. CONCLUSION The urethroplasty using an inlay of free thin genital skin graft was safe, uncomplicated and effective.