Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.

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Study Type – Prognosis (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? There is increasing evidence for a prognostic significance of pretherapeutically elevated serum C‐reactive protein levels in various cancers. However, little is known about its significance in patients with invasive bladder cancer. This study shows that serum CRP is an independent predictor for cancer‐specific survival in bladder cancer, and its incorporation into a new outcome model (TNR‐C Score) encompassing major pathological determinants for survival, increases significantly its predictive accuracy. OBJECTIVE • To assess the predictive value of preoperative C‐reactive protein (CRP) in patients undergoing radical cystectomy (RC) for carcinoma invading the bladder in light of recent data showing it to be an independent indicator of adverse oncological outcome in other malignancies. PATIENTS AND METHODS • A contemporary, consecutive series of 246 patients undergoing RC and bilateral pelvic lymphadenectomy for bladder cancer between 1999 and 2009. • Elevated CRP was defined as >0.5 mg/dL and was consistent during the study period. The median (range) follow‐up was 30 (6–116) months. • Kaplan–Meier analysis was used to estimate cancer‐specific survival (CSS) using a log‐rank test and Cox regression analysis for multivariate analysis of risk factors. • Based on regression estimates of significant parameters in multivariate analysis, a new CRP‐based scoring model was developed to predict cancer‐specific outcomes. The predictive accuracy of the model was evaluated using the concordance index. RESULTS • The 3‐year CSS was 74.0% in patients with normal and 44.0% with elevated CRP (P < 0.001). • In multivariate analysis, CRP (P < 0.001; used as a continuous variable), tumour stage (P= 0.001), lymph‐node density ≥0.09 (P= 0.02) and resection margin status (P < 0.001) were independent predictors of CSS. • The 3‐year CSS in patients with a score in the ranges 0–2, 3–6 and 7–10 was 80.5%, 44.9% and 7.1%, respectively (P < 0.001). Consideration of CRP in the final model increased its predictive accuracy by 4.9% with a concordance index of 0.788 (P= 0.01). CONCLUSIONS • This is the largest, contemporary series to date indicating that preoperative serum CRP is an independent risk factor for CSS. • CRP may be a useful parameter to include in predictive bladder cancer nomograms.

Es wird mit Hilfe yon Gedankenexperimenten gezeigt, dal3 es entgegen verbreiteter Auffassung sehr wohl Mel~vorg~nge gibt, die keineflei Rfickwirkung auf das Mef3-objekt austiben. Diese ,,negativen" Messungen bestehen in experimenteller Featstellung des Ausbleibens von mit bestimmter Wahrscheinlichkeit zu erwartenden Ereignissen, Feststellungen, die --Kennzeichen ,,echter" lVfessungen --neue Prognosen fiber das Mel3objekt vermitteln, somit ,,Reduktion de:~ Wellenfunktion" ganz ebenso verursachen wie die normalen, ,,positiven", das Mel3Objekt st6renden Beobachtungen. Daraus folgt zwingend, dab die vielfach iibliehe ansehauliche ]3egrtindung der Unbestimmtheits-t~elation rnit angeblich prinzipiell unvermeidlicher Rfickwirkung jedes Mef3vorgangs auf das Mel3objekt unzul~ssig ist, dab sie vielmehr ihre wirklich tragende Begriindullg in der Einwirkung hat, die alle Materie der n~heren und ferneren Umgebung eines Teilchens ununterbrochen auf dieses austibt, unabhXngig davon, ob sie einer Mef3apparatul ~ angeh6rt oder nicht.

Study Type – Prognosis (cohort series) Level of Evidence 2a What's known on the subject? and What does the study add? Preoperative thrombocytosis has been identified as a predictor of poor outcome in various cancer types. However, the prognostic role of platelet count in patients with invasive bladder cancer undergoing radical cystectomy is unknown. The present study demonstrates that preoperative thrombocytosis is an independent risk factor for decreased cancer‐specific survival after radical treatment of invasive bladder cancer. We developed a new prognostic scoring model for cancer‐specific outcomes after radical cystectomy including platelet count and established pathological risk factors. Consideration of platelet count in the final model increased its predictive accuracy significantly. Thrombocytosis may be a useful parameter to include within established international bladder cancer nomograms. OBJECTIVE To investigate the oncological significance of preoperative thrombocytosis in patients with invasive bladder cancer undergoing radical cystectomy, as it has been reported as a marker for aggressive tumour biology in a variety of solid tumours. PATIENTS AND METHODS The series comprised 258 patients undergoing radical cystectomy between 1999 and 2010 in whom different clinical and histopathological parameters were assessed. Elevated platelet count was defined as >450 × 109/L. Based on regression estimates of significant parameters in multivariable analysis a new weighted scoring model was developed to predict cancer‐specific outcomes. RESULTS The median follow‐up was 30 months (6–116). Of the 258 patients, 26 (10.1%) had elevated and 232 (89.9%) had normal platelet count. The 3‐year cancer‐specific survival in patients with normal and elevated platelet count was 61.5% and 32.7%, respectively (P < 0.001). In multivariable analysis, cancer‐specific survival was significantly lower in patients with locally advanced disease (≥pT3a) (relative risk 2.91, 1.54–5.65; P= 0.001), positive soft tissue surgical margins (4.03, 1.99–7.92; P= 0.001) and thrombocytosis (2.68, 1.26–5.14; P= 0.011). The 3‐year cancer‐specific survival in patients with a score 0 (low risk), 1–2 (intermediate risk) and 3–5 (high risk) was 81.0%, 54.8% and 8.2%, respectively (P < 0.001). Consideration of preoperative platelet count in the final model increased its predictive accuracy by 1.8% with a concordance index of 0.745 (P= 0.040). CONCLUSIONS The presence of thrombocytosis at radical cystectomy portends unfavourable prognosis. We constructed a simple weighted prognostic model for cancer‐specific outcomes after radical cystectomy based on pretreatment platelet count and established pathological risk factors. These data warrant external validation and may allow for tailored monitoring and selection of appropriate patients for neoadjuvant and adjuvant trials.

This study examined the diagnostic and prognostic value of vascular endothelial growth factor (VEGF) levels in the cerebrospinal fluid (CSF) of 39 patients with leptomeningeal metastasis (LM). Vascular endothelial growth factor levels at diagnosis were significantly higher in patients with LM (median 359 pg ml À1 ) than in patients with other neurological diseases (median o25 pg ml À1 ). The specificity of VEGF levels above 250 pg ml À1 for LM was high (98.3%), while the sensitivity was low (51.4%; 73% for VEGF values above 100 pg ml À1 ). In 49% of the LM patients, particularly with lymphoma or medulloblastoma, VEGF levels were below 250 pg ml À1 and thus in the range of VEGF levels in other neurological diseases. Vascular endothelial growth factor levels correlated significantly with CSF lactate and albumin. Vascular endothelial growth factor levels mirrored the clinical course with a marked reduction in response to therapy and an increase at relapse in some patients who had serial CSF samples available. Multivariate Cox regression analysis showed VEGF below 100 pg ml À1 (relative risk (RR) ¼ 4.24, P ¼ 0.0002) and age below 60 years (RR ¼ 2.5, P ¼ 0.004) to be associated with longer survival in LM. In conclusion, CSF VEGF levels in LM vary considerably. High VEGF levels have a very high specifity for LM and may help to establish the diagnosis. The role of VEGF as a predictor of outcome should be substantiated in prospective studies.

Muscle invasion, carcinoma in situ and prostatic stromal or urethral involvement at time of RC have no significant effect on UR. Orthotopic neobladder is associated with a significant lower risk of UR after RC.