High IDO-1 expression in tumor endothelial cells is associated with response to immunotherapy in metastatic renal cell carcinoma.

Nivolumab belongs to the standard therapy in the second-line setting of metastatic renal cell carcinoma (mRCC). Although deep and long-lasting responses are seen in some patients, the majority of patients will further progress. PD-L1 is still under critical evaluation as a predictive biomarker. Thus, more accurate biomarkers are clearly warranted. Here, we investigated for the first time the predictive role of IDO-1, a negative immune-regulatory molecule, on clear cell RCC tissues of 15 patients undergoing nivolumab therapy. IDO-1 and other immune inhibitory molecules (PD-L1, PD-L2, FOXP3) as well as immune cell subsets (CD3, CD4 and CD8) were measured on formalin-fixed, paraffin-embedded sections of RCC specimens by immunohistochemistry. IDO-1 was predominantly expressed in tumor endothelial cells, and was totally absent from tumor cells itself. IDO-1 overexpression (>10%) could be detected more frequently in responders (100%, n = 6/6) compared to non-responders (33.3%, n = 3/9; P = .028), resulting in a better progression-free survival during immunotherapy (IDO-1 ≤ 10% vs >10%, median: 3.5 vs not estimated (NE) months, P = .01 by log-rank test). In addition, IDO-1 was positively correlated with CD8+ T cell expression (rs = .691, P = .006). PD-L1 expression on tumor cells was negative in 13 (86.7%) of 15 patients, irrespective of therapeutic response (responders vs non-responders: 83.3% vs 88.9%). No differences were noticed in the PD-L1 expression on tumor-infiltrating immune cells (PD-L1 < 1% in 66.7% of both responders and non-responders). In contrast to PD-L1, these results suggest that IDO-1 may be a more promising predictive biomarker for response to immune-based cancer therapy in mRCC.

Increased accuracy of a novel mRNA-based urine test for bladder cancer surveillance.

OBJECTIVES: To 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 METHODS: A 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. RESULTS: The overall sensitivity (0.84) and NPV (0.93) of the Xpert BC Monitor were significantly superior to those of bladder washing cytology (0.33 and 0.76; P < 0.001). Subgroup analyses confirmed the high sensitivity of the Xpert BC Monitor even in low-grade (0.77) and pTa (0.82) disease compared with barbotage cytology (low-grade: 0.13; pTa: 0.21). The overall specificity of the Xpert BC Monitor and barbotage cytology was similar (0.91 vs 0.94; P = 0.41). Combining the Xpert BC Monitor with barbotage cytology (AUC = 0.85) did not enhance diagnostic performance compared with the performance of the Xpert BC Monitor alone (AUC = 0.87). CONCLUSION: In 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.

Unrecognized paraganglioma of the urinary bladder as a cause for basilar-type migraine.

Extra-adrenal paraganglioma with isolated localization in the urinary bladder is a rare neuroendocrine tumor. Although the typical symptoms like headache, nausea, weight loss, flushing, heart palpitation or paroxysmal hypertension during micturition are well established, we present an unusual case of bladder paraganglioma, 'misdiagnosed' with basilar-type migraine due to headache for the past 8 years. As urologists linked the presence of a tumor (by CT) and symptoms connected with micturition, no cystoscopy and no transurethral resection of the bladder was performed prior to detailed diagnostic workup. After diagnosis of an extra-adrenal paraganglioma, the patient was scheduled for open partial cystectomy. In consideration of the fact that bladder paraganglioma is an infrequent genitourinary cancer, this case report clearly points out the importance of an exact anamnesis and clinical examination to minimize the probability of misdiagnosis with possible fatal consequences in any case with clinical suspicion of bladder paraganglioma.

Prevalence of the human papillomavirus (HPV) expression of the inner prepuce in asymptomatic boys and men.

OBJECTIVE: To investigate the prevalence of high-risk (HR) and low-risk (LR) human papillomavirus (HPV) in prepuces of boys and men without any HPV related lesions. PATIENTS AND METHODS: Between 2009 and 2011, a total collective of 250 boys and men were investigated in this prospective study. The samples were subdivided into 3 groups regarding their age, consisting of 125 (50%) children (0-10 years), 38 (15.2%) adolescents (11-20 years) and 87 (34.8%) adults (>20 years). In situ hybridization (ISH) was performed to detect HR and LR virus types within the epithelium, followed by microscopic interpretation and determination between episomal and integrative signal pattern. RESULTS: Our results revealed high levels of HPV concentration (HR and LR) in all age groups: HR versus LR positivity was seen in 45.5 versus 35% (children), 60.6 versus 63.6% (adolescents) and 58.3 versus 48.6% (adults). The topmost rate of HR (59.8%)- and LR (50.6%)-positive probes was found in the group with high estimated sexual activity (>14 years). CONCLUSION: Concerning the high prevalence of male HPV infection even in children, indicating non-sexual transmission pathways, inclusion of boys in the vaccination program seems to be required reducing their burden of HPV related disease.