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.

OBJECTIVETo assess benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), both considered to be associated with urogenital ageing, in ageing men in a cross-sectional population study, comparing them with healthy controls by using symptom scores and contrastenhanced colour Doppler ultrasonography (CDUS). PATIENTS, SUBJECTS AND METHODSTransrectal CDUS and quantitative measurement of colour pixel intensity (CPI) are excellent minimally invasive techniques for assessing normal and pathological blood flow. CDUS was performed using the microbubble-based ultrasound enhancer for evaluating prostate, bladder neck and corpus cavernosum vascularity in young healthy men, men with BPH, and men with severe vascular damage (diabetes mellitus type 2). Resistive index measurements and computerassisted quantification of CPI were used to objectively evaluate perfusion. The International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF) were applied to quantify the symptoms. RESULTSIn patients with BPH, perfusion of the transition zone (TZ) of the prostate was significantly lower and the resistive index of the TZ significantly higher (both P < 0.001) than in healthy controls. The perfusion patterns of men with BPH and those who also had severe vascular damage (diabetes mellitus type 2) showed that vascularity in the latter group was lower in the prostatic TZ and the corpora cavernosa. In patients with BPH the IPSS, quality-of-life and IIEF scores were significantly worse than in the control group. Men with concomitant atherosclerosis had even worse symptom scores. CONCLUSIONThese results strongly support the hypothesis that age-related impairment of blood supply to the lower urinary tract is important in the development of BPH and ED. Vascular damage may cause chronic ischaemia and thus be a contributing factor in the pathogenesis of BPH and ED.

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Leydig cell tumours (LCTs) of the testis are rare tumours, accounting for 1–3% of all testicular neoplasms. Our data indicate that using scrotal ultrasound with high resolution imaging in routine checkups leads to an earlier detection of LCTs. Most patients underwent an organ‐sparing surgery and no androgen deprivation was observed. OBJECTIVE • To report an observed high frequency of Leydig cell tumours (LCTs) diagnosed at our centre. PATIENTS AND METHODS • Charts of all patients who underwent surgery for a testicular tumour between 1999 and 2008 at our department were searched and data from patients with LCT were collected. • Before surgery all patients underwent ultrasound and complete staging. In all but two patients with LCT an organ‐sparing surgery was performed. Surgery was performed under ultrasound or palpation guidance. • All patients underwent postoperative follow‐up. We retrospectively reviewed surgical technique, histology, epidemiology and outcome in all LCT patients. RESULTS • In the study period, 197 testicular tumours were surgically removed of which 29 were diagnosed as LCT (14.7% of 197; further study group) in 25 patients. Mean age of patients with LCT was 45 years (range 21–68 years). • Tumour size ranged from 1.2 to 80 mm (mean 10.23 mm). In two patients (8%) the lesion was palpable whereas incidental diagnosis was made in seven patients (28%). • In the remaining patients diagnosis was made by ultrasound performed for testicular pain (six patients, 24%) or during infertility or erectile dysfunction evaluation (10 patients, 40%). • Definitive histology reported no malignant histopathological features in all but one patient; this particular patient experienced tumour progression after 2 months and died from advanced disease 1 year later. All other patients are free of disease after a mean follow up of 56 months (range 7–93 months). • During this period one patient developed a second LCT on the contralateral side; another patient had a recurrence within the same testicle, but on the opposite pole. Both underwent a subsequent organ‐sparing tumour resection. CONCLUSION • The percentage of LCT (14.7% of all testicular tumours removed) was significantly higher than expected from the literature. One possible explanation for this phenomenon is the increasing use of better ultrasound technology and the subsequent increased detection of small nodules that have not been found in historical series. Use of ‘observation‐only’ for very small lesions detected at infertility clinics is under debate.

The potentially oncogenic mevalonate pathway provides building blocks for protein prenylation and induces cell proliferation and as such is an important therapeutic target. Among mevalonate metabolites, only isopentenyl pyrophosphate (IPP) has been considered to be an immunologically relevant antigen for primate-specific, innate-like Vg9Vd2 T cells with antitumor potential. We show here that Vg9Vd2 T cells pretreated with the stress-related, inflammasome-dependent cytokine interleukin 18 (IL-18) were potently activated not only by IPP but also by all downstream isoprenoid pyrophosphates that exhibit combined features of antigens and cell-extrinsic metabolic cues. Vg9Vd2 T cells induced this way effectively proliferated even under severe lymphopenic conditions and the antioxidant N-acetylcysteine significantly improved reconstitution of gd T cells predominantly with a central memory phenotype. The homeostatic cytokine IL-15 induced the differentiation of effector cells in an antigen-independent fashion, which rapidly produced abundant interferon g (IFNg) upon antigen re-encounter. IL-15 induced effector gd T cells displayed increased levels of the cytotoxic lymphocyte-associated proteins CD56, CD96, CD161 and perforin. In response to stimulation with isoprenoid pyrophosphates, these effector cells upregulated surface expression of CD107a and exhibited strong cytotoxicity against tumor cells in vitro. Our data clarify understanding of innate immunosurveillance mechanisms and will facilitate the controlled generation of robust Vg9Vd2 T cell subsets for effective cancer immunotherapy.

This large, prospective, noninterventional study assessed the efficacy and safety of sorafenib in patients with advanced renal cell carcinoma (RCC) in a clinical practice setting. Sorafenib was generally well tolerated, with no unexpected adverse events observed, and provided clinical benefit in this diverse patient population. Background: Patients with advanced renal cell carcinoma in routine clinical practice can differ considerably from those in phase III studies. Patients and Methods: PREDICT (Patient characteristics in REnal cell carcinoma and Daily practICe Treatment with sorafenib) was a prospective, noninterventional study of open-label sorafenib for the treatment of advanced RCC conducted in 18 countries. Patient characteristics, therapy duration, tumor status, and tolerability were assessed at baseline and during routine follow-up. Results: Overall, 2599 patients were evaluable for safety and 2311 for efficacy. The diverse population included patients with brain metastases (5%), non-clear-cell histologies (17%), high Memorial Sloan-Kettering Cancer Center risk score (11%), poor Eastern Cooperative Oncology Group performance status (PS ! 2, 29%), and patients with no previous nephrectomy (16%) or no previous systemic therapy (37%). The median duration of sorafenib therapy was 7.3 months and was similar in clinically relevant subgroups (eg, patients with PS 2, brain metastases, or concomitant hypertension or diabetes [range, 6.7-7.0 months]). The median duration of therapy was shorter for patients with PS 3 or non-clear-cell histologies (4.6 and 4.8 months, respectively). The most common drug-related adverse events were handefoot skin reaction (20%), diarrhea (17%), and rash (8%). Conclusion: Sorafenib was generally well tolerated and provided clinical benefit in a large, diverse population of patients with advanced RCC treated in routine clinical practice.

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Patients with metastatic renal cell carcinoma (RCC) undergoing cytokine or targeted therapies may show a remarkable decline in quality of life (QoL). We wanted to evaluate QoL in patients with metastatic RCC undergoing therapeutic vaccination with dendritic cells (DCs). In a cross-sectional analysis, QoL was therefore assessed in RCC patients participating in three consecutive clinical trials of DC vaccination. Before the first and after the third vaccination with DCs, patients completed a QoL questionnaire (EORTC QLQ-C30, version 3). Data were transformed into scale scores and analysed using SPSS 12.0 software. Mean values of the resulting scores obtained before and after DC vaccination were compared using students t test and Wilcoxon rank-sum test. P < 0.05 was considered statistically significant. The questionnaire was completed by 55 of 71 patients (compliance rate, 77.5%) who had a median age of 58.7 years (from 30 to 75 years). No significant reductions in functioning scales including physical, emotional and social criteria as well as symptom scores, which assess typical symptoms of tumour therapies, were observed indicating that QoL remained high during DC vaccination. Significant correlations were found between overall survival and functional as well as symptom scores. Our data indicate that DC vaccination, which is a personalised treatment modality, maintains QoL and thus represents an attractive nontoxic treatment option for patients with metastatic RCC. It will be important to identify the most effective conditions of DC vaccination including combinations with other therapeutics to maximise clinical efficacy while still preserving QoL.