CD8+ tumor-infiltrating T cells (CD8-TILs) are found in many types of tumors including human renal cell carcinoma. However, tumor rejection rarely occurs, suggesting limited functional activity in the tumor microenvironment. In this study, we document that CD8-TILs are unresponsive to CD3 stimulation, showing neither lytic activity, nor lytic granule exocytosis, nor IFN-γ production. Mechanistically, no deficits in TCR proximal signaling molecules (lymphocyte-specific protein tyrosine kinase, phospholipase Cγ) were identified. In contrast, distal TCR signaling was suppressed, as T cells of TILs showed strongly reduced steady-state phosphorylation of the MAPK ERK and were unable to increase phosphorylation of ERK and JNK as well as AKT and AKT client proteins (IκB, GSK3) after stimulation. These deficits were tumor-specific as they were not observed in CD8+ T cells infiltrating non-tumor kidney areas (CD8+ non-tumor kidney-infiltrating lymphocytes; CD8-NILs). Diacylglycerol kinase-α (DGK-α) was more highly expressed in CD8-TILs compared with that in CD8-NILs, and its inhibition improved ERK phosphorylation and lytic granule exocytosis. Cultivation of TILs in low-dose IL-2 reduced DGK-α protein levels, increased steady-state phosphorylation of ERK, improved stimulation-induced phosphorylation of ERK and AKT, and allowed more CD8-TILs to degranulate and to produce IFN-γ. Additionally, the protein level of the AKT client molecule p27kip, an inhibitory cell cycle protein, was reduced, whereas cyclin E, which promotes G1–S phase transition, was increased. These results indicate that the tumor-inflicted deficits of TILs are reversible. DGK-α inhibition and provision of IL-2 signals could be strategies to recruit the natural CD8+ T cells to the anti-tumor response and may help prevent inactivation of adoptively transferred T cells thereby improving therapeutic efficacy.

• HistoScanning™ is a novel ultrasonography technique for visualization of prostate cancer. The technology it uses and its encouraging results in prostate cancer foci detection in 29 men with prostate cancer have been described previously.A recent study confirmed these results in 31 patients. The sensitivity and specificity of prostate cancer foci detection were 90% and 72%, respectively. These promising results raised the question of whether HistoScanning™ technology might also be helpful in therapy planning.• Preoperative knowledge of the distribution and size of tumours might be useful for treatment planning of a nerve-sparing radical prostatectomy. We tested the ability of HistoScanning™ to predict a negative surgical margin in 80 patients undergoing radical prostatectomy. Objective• To assess the accuracy of HistoScanning™ (HS) as a visualization tool for preoperative treatment planning for nerve-sparing (NS) radical prostatectomy (RP). Patients and Methods• A retrospective study was carried out on 80 patients with prostate cancer undergoing RP from October 2009 to December 2009. • All patients underwent a HS procedure 1 day before surgery.• Frozen sections (FSs) were performed on each latero-posterior side of the prostate to assess for the presence of cancer.• On the HS analysis, the region corresponding to that removed at FS was assessed for suspicious lesions. The size of suspicious lesions within this volume was compared with the FS histopathological analysis. Results• HS results corresponded to a 93% probability of having a negative surgical margin in the FSs. The presence of a HS volume Ն0.2 mL in a specific side was associated with a 3.7 times increased risk of a positive surgical margin at FS. Conclusions• HS has the potential to assist in the planning of NSRP.• Larger, multicentre studies need to be performed for validation of these encouraging results.

Objective: In spite of readily available evidence-based guidelines on urolithiasis treatment, practical applications of treatments vary from country to country, or even within countries. The choice of treatment depends not only on the evidence, but often on general non-medical decision factors such as infrastructure, expertise, trends, patient demands, industry drive and reimbursement levels. In turn, many of these factors are interdependent and a result of the individual National Health System. Method: In an attempt to get a crude picture of trends and practices in stone treatment across Europe, a group of well-renowned international experts in the field were asked to reply to a set of standard questions relating to stone treatments, health systems and adherence to guidelines (level of evidence D = expert opinion). Results: The above-mentioned interdependencies showed a varying picture in different countries. Overall, there is a trend away from lithotripsy and toward ureterorenoscopy. However, the choice of treatment is largely dependent on the affordability of infrastructure. Urologists may make choices based on the national reimbursement system, too. Conclusion: Without claiming to represent a scientifically sound study, this survey represents an interesting insight into a representative cross-section of European urological current practices and trends in urolithiasis treatment.

In conclusion, it has to be recognized that women bothered by these symptoms should be examined for POP and appropriately advised for possibility of cure by pelvic floor surgery after careful selection. VIDEO ABSTRACT.