Trend analysis and regional tumor incidence in Germany for testicular cancer between 2003 and 2014.

BACKGROUND: Testicular germ cell tumor (TGCT) is one the most common solid tumors in men between the age of 15 and 35 with an overall incidence rate of 1-1.5 %. Epidemiologic studies have demonstrated different incidence patterns in western civilized countries with overall rising incidence trends. OBJECTIVE: To analyze differences in regional tumor incidence rates for TGCT and perform a trend analysis for TGCT between 2003 and 2014 in Germany. MATERIAL AND METHODS: TGCT cases in Germany which were diagnosed between 2003 and 2014 were provided by the Robert-Koch-Institute, Berlin. For statistical analysis, cluster and spatial scan tests according to Kulldorff were used for cases with seminoma and non-seminoma. Results are presented in administrative districts and graphically illustrated. We performed a trend-analysis in order to evaluate age-adjusted incidence trends in Germany. Tests were two-sided with a level of significance of α=0.05. RESULTS: In total we included 35,066 patients. Overall, 22,634 cases had newly diagnosed seminoma and 12,432 were diagnosed as non-seminoma. Maximum incidence of seminoma and non-seminoma was observed for age-group 38-40 years and 26-28 years, respectively. No second peak for the incidences of seminoma and non-seminoma with respect to age were observed. Cluster analysis revealed areas with high and low incidence rates as well as slightly different spatial distribution in Germany between seminoma and nonseminoma. Furthermore, there was no significant increase in age-adjusted incidence rates over the reviewed time period in both cohorts. DISCUSSION: In this study differences in reginal tumor incidence rates for seminoma and non-seminoma are reported with both tumor entities revealing distinct clusters. Furthermore, tumor incidence trends for seminoma and nonseminoma between 2003 and 2014 were stable which might indicate the beginning of a plateau phase for TGCT incidence rates in Germany. CONCLUSION: In this analysis we were able to identify regions with significantly higher tumor incidence rates for both seminoma and non-seminoma which were specific for these two subtypes. Furthermore, trend analysis revealed a steady incidence rate for testicular cancer in Germany.

From novice to expert: analyzing the learning curve for MRI-transrectal ultrasonography fusion-guided transrectal prostate biopsy.

PURPOSE: To investigate the learning curve of a novice in MRI/TRUS software fusion biopsy and to compare his results with the expert standard at our institution. METHODS: Overall 126 MRI/TRUS fusion-guided transrectal biopsies were performed using an electromagnetic tracking ultrasonography platform. The learning progress of the novice was evaluated comparing his initial 42 procedures (group A) with his following 42 (group B). The institution's expert standard (group C), which was compared to the novice's groups, was defined by the expert's experience of 42 MRI/TRUS fusion biopsies. Primary learning curve parameters were targeted biopsy detection quotient and biopsy time. RESULTS: Overall detection of prostate cancer was 64% (27/42), 62% (26/42) and 62% (26/42) in groups A, B and C, respectively. The median target biopsy detection quotient significantly increased (p = 0.04) in group B (0.75, interquartile range (IQR) 0.25-1.0) compared to group A. (0.33, IQR 0.2-0.5). Group C revealed a median detection quotient of 0.5 (IQR 0.25-0.76) that did not differ significantly from the novice's groups (p = 0.2). Median biopsy time was significantly higher in group A (45 min, IQR 33-50 min) compared to groups B (25 min, IQR 23-29 min) and C (24 min, IQR 16-46 min) (p < 0.01). CONCLUSIONS: The present study revealed the individual learning curve of a novice in MRI/TRUS fusion biopsy and demonstrated significant learning progress regarding targeted biopsy detection quotient and biopsy time.

Prognostic value of the new Grade Groups in Prostate Cancer: a multi-institutional European validation study.

BACKGROUND: We aimed to assess the prognostic relevance of the new Grade Groups in Prostate Cancer (PCa) within a large cohort of European men treated with radical prostatectomy (RP). METHODS: Data from 27 122 patients treated with RP at seven European centers were analyzed. We investigated the prognostic performance of the new Grade Groups (based on Gleason score 3+3, 3+4, 4+3, 8 and 9-10) on biopsy and RP specimen, adjusted for established clinical and pathological characteristics. Multivariable Cox proportional hazards regression models assessed the association of new Grade Groups with biochemical recurrence (BCR). Prognostic accuracies of the models were assessed using Harrell's C-index. RESULTS: Median follow-up was 29 months (interquartile range, 13-54). The 4-year estimated BCR-free survival (bRFS) for biopsy Grade Groups 1-5 were 91.3, 81.6, 69.8, 60.3 and 44.4%, respectively. The 4-year estimated bRFS for RP Grade Groups 1-5 were 96.1%, 86.7%, 67.0%, 63.1% and 41.0%, respectively. Compared with Grade Group 1, all other Grade Groups based both on biopsy and RP specimen were independently associated with a lower bRFS (all P<0.01). Adjusted pairwise comparisons revealed statistically differences between all Grade Groups, except for group 3 and 4 on RP specimen (P=0.10). The discriminations of the multivariable base prognostic models based on the current three-tier and the new five-tier systems were not clinically different (0.3 and 0.9% increase in discrimination for clinical and pathological model). CONCLUSIONS: We validated the independent prognostic value of the new Grade Groups on biopsy and RP specimen from European PCa men. However, it does not improve the accuracies of prognostic models by a clinically significant margin. Nevertheless, this new classification may help physicians and patients estimate disease aggressiveness with a user-friendly, clinically relevant and reproducible method.

The hydrodynamic basis of the vacuum cleaner effect in continuous-flow PCNL instruments: an empiric approach and mathematical model.

PURPOSE: Passive removal of stone fragments in the irrigation stream is one of the characteristics in continuous-flow PCNL instruments. So far the physical principle of this so-called vacuum cleaner effect has not been fully understood yet. The aim of the study was to empirically prove the existence of the vacuum cleaner effect and to develop a physical hypothesis and generate a mathematical model for this phenomenon. METHODS: In an empiric approach, common low-pressure PCNL instruments and conventional PCNL sheaths were tested using an in vitro model. Flow characteristics were visualized by coloring of irrigation fluid. Influence of irrigation pressure, sheath diameter, sheath design, nephroscope design and position of the nephroscope was assessed. Experiments were digitally recorded for further slow-motion analysis to deduce a physical model. RESULTS: In each tested nephroscope design, we could observe the vacuum cleaner effect. Increase in irrigation pressure and reduction in cross section of sheath sustained the effect. Slow-motion analysis of colored flow revealed a synergism of two effects causing suction and transportation of the stone. For the first time, our model showed a flow reversal in the sheath as an integral part of the origin of the stone transportation during vacuum cleaner effect. The application of Bernoulli's equation provided the explanation of these effects and confirmed our experimental results. CONCLUSIONS: We widen the understanding of PCNL with a conclusive physical model, which explains fluid mechanics of the vacuum cleaner effect.

[Therapy of overactive bladder (OAB)]. / Therapie der überaktiven Blase (OAB).

Overactive bladder (OAB) is a symptom complex which is present in approximately 17% of the European population. It is observed in the presence or absence of incontinence (wet or dry) and is associated with a high degree of psychological stress as well as high costs for the healthcare system. Myogenic, urothelial and neurogenic factors lead to frequently unknown changes of muscular, neural and connective tissue. For the definition, etiology and diagnostics of the disease the previous continuing medical education (CME) article "Diagnosis of overactive bladder (OAB)" should be consulted. In recent years some improvements have been made in OAB-related research, in terms of pathophysiological models and new pharmacological approaches with the development of new therapeutic agents. Besides classical substances, recently approved agents are increasingly being used for the therapy of OAB. Furthermore, non-pharmaceutical approaches and surgical techniques still play an important role in the therapy of OAB.

[Diagnosis of overactive bladder (OAB)]. / Diagnostik der überaktiven Blase (OAB).

Overactive bladder (OAB) is a symptom complex which is present in approximately 17% of the European population. It is observed in the presence or absence of incontinence (wet or dry) and is associated with a high degree of psychological stress as well as high costs for the healthcare system. Myogenic, urothelial and neurogenic factors lead to frequently unknown changes of muscular, neural and connective tissue. The diagnosis of OAB is empirical and can be used as a basis for initial treatment, while lower urinary tract symptoms have to be evaluated up front. As there are no established biomarkers for OAB, a definitive diagnosis is problematic. It is important to carry out routine diagnostics including a detailed medical history and if needed urodynamic evaluation of the patient. Therapy of OAB will be the topic of a further continuing medical education (CME) article entitled "Therapy of overactive bladder (OAB)".

Lyn tyrosine kinase regulates androgen receptor expression and activity in castrate-resistant prostate cancer.

Castrate-resistant prostate cancer (CRPC) progression is a complex process by which prostate cells acquire the ability to survive and proliferate in the absence or under very low levels of androgens. Most CRPC tumors continue to express the androgen receptor (AR) as well as androgen-responsive genes owing to reactivation of AR. Protein tyrosine kinases have been implicated in supporting AR activation under castrate conditions. Here we report that Lyn tyrosine kinase expression is upregulated in CRPC human specimens compared with hormone naive or normal tissue. Lyn overexpression enhanced AR transcriptional activity both in vitro and in vivo and accelerated CRPC. Reciprocally, specific targeting of Lyn resulted in a decrease of AR transcriptional activity in vitro and in vivo and prolonged time to castration. Mechanistically, we found that targeting Lyn kinase induces AR dissociation from the molecular chaperone Hsp90, leading to its ubiquitination and proteasomal degradation. This work indicates a novel mechanism of regulation of AR stability and transcriptional activity by Lyn and justifies further investigation of the Lyn tyrosine kinase as a therapeutic target for the treatment of CRPC.Oncogenesis (2014) 3, e115; doi:10.1038/oncsis.2014.30; published online 18 August 2014.

[Cystectomy in the elderly patient]. / Zystektomie im Alter.

Bladder cancer is a carcinoma of the elderly population. The highest incidence of bladder cancer is between the ages of 70 and 80 years old. Radical cystectomy remains the gold standard for muscle invasive bladder cancer treatment. In this article different aspects of radical cystectomy in elderly patients are reviewed. The Pubmed-MEDLINE database was searched using the following keywords: radical, cystectomy, elderly and age.

[Palliative systemic therapy of castration-resistant prostate cancer: current developments]. / Palliative Systemtherapie des kastrationsresistenten Prostatakarzinoms : Aktuelle Entwicklungen.

Androgen withdrawal or surgical castration remains the standard therapy for advanced prostate cancer disease. Even for castration-resistant prostate cancer the therapeutic option of docetaxel-based chemotherapy is well studied and defined. Facing disease progression after docetaxel-based therapy there are multiple options to continue therapy but the evidence level is rather poor. In the last few years targeted therapy and immunomodulation have been the focus of clinical trials. The presented manuscript intends to provide an overview of classical cytostatic agents, endothelin inhibitors, immunotherapy, modified hormone therapy, multikinase inhibitors and radionuclide approaches which are currently under investigation for implementation in the clinical setting.

[Testosterone replacement therapy and prostate cancer. The current position 67 years after the Huggins myth]. / Testosteronsubstitution und Prostatakarzinom. Eine Standortbestimmung 67 Jahre nach dem Huggins-Mythos.

Hypogonadism is highly prevalent in the elderly and in men with prostate cancer. Symptoms of hypogonadism, such as depression, lack of libido, and decreased bone mineral density, can significantly impair quality of life. In addition, testosterone plays an important role in erectile preservation and in growth and function of the cavernosal and penile nerves. There are compelling data showing that testosterone replacement therapy (TRT) does not increase the risk of prostate cancer. The literature (four published studies) concerning men treated with TRT after definitive therapy for prostate cancer reports only one biochemical recurrence. Based on these data, physicians cannot really justify withholding TRT from symptomatic patients after they have been successful treated for prostate cancer. This review gives the practising urologist an overview of the latest literature and useful advice on this controversial topic.

[GreenLight laser therapy for benign prostatic hyperplasia: dilemma of reimbursement in the DRG system]. / Greenlightlaserbehandlung der BPS: Dilemma der Vergütung im DRG-System.

KTP or GreenLight laser vaporization of the prostate has increasingly become an established approach in the last 5 years. Since the additional costs for this treatment were initially not included in the DRG system, there was an extra possibility in 2000-2007 for billing these services as so-called new methods of examination and treatment. Since 2008 there is a new DRG (M11Z) for this procedure, but it does not cover the costs incurred. The reasons for this are to be found in the inhomogeneous assignment of costs by the clinics conducting the calculations. An improved cost reflection can only be expected by concerted action on the part of those hospitals designated as calculators that administer GreenLight laser therapy.

Joint toxicity of cadmium and phenanthrene in the freshwater amphipod Hyalella azteca.

The joint toxicity of combined metals and polynuclear aromatic hydrocarbons is poorly understood and may deviate from the summed concentration responses of the individual pollutants. The freshwater amphipod Hyalella azteca was exposed to sediment-amended Cd and phenanthrene (Phen) individually and in combination using United States Environmental Protection Agency 10-day sediment toxicity bioassays with lethality and growth end points. The lethal joint toxicity of Cd and Phen was investigated separately in 24-, 48-, and 72-hour aqueous exposures. In sediment exposures, a sublethal concentration of Phen (144 mg kg(-1)) in combination with Cd increased mortality across a range of Cd concentrations and decreased the 10-day LC50 for Cd from 523 mg kg(-1) (461 to 588, 95% confidence interval [CI]) to 263 mg kg(-1) (214 to 312, 95% CI). In contrast, sublethal concentrations of Phen had no effect on the lethal toxicity of Cd in aqueous exposures. Combined sediment-amended Cd and Phen acted independently on growth rate. Rate decreases were driven primarily by Cd. Our findings indicated that association with sediment influences the joint toxicity of Cd and Phen. Thus, mixtures of Cd and Phen may cause synergistic or independent toxicity in H. azteca depending on the end point investigated and the experimental protocol employed. As an implication of these results, the interpretation of standardized toxicity bioassays, including whole-effluent toxicity tests and single-compound toxicity tests, must be made with caution. These assessment protocols may underestimate potentially hazardous mixture effects in sediment environments. Therefore, risk assessment protocols for environments containing metal-PAH mixtures must include robust methods that can detect possible interactive effects among contaminants to optimize environmental protection.

Early transition metal complexes containing 1,2,4-triazolato and tetrazolato ligands: synthesis, structure, and molecular orbital studies.

Several early transition metal complexes bearing 1,2,4-triazolato and tetrazolato ligands have been prepared by reaction of the pyrazolato complexes Ti(tBu(2)pz)(4-x)Cl(x) (tBu(2)pz = 3,5-di-tert-butylpyrazolato; x = 1, 2) and M(tBu(2)pz)(5-x)Cl(x) (M = Nb, Ta: x = 2, 3) with the sodium or potassium salts derived from 1,2,4-triazoles and tetrazoles. The X-ray structure analysis of Ti(tBu(2)pz)(2)(Me(2)C(2)N(3))(2) shows eta(2)-coordination of the 1,2,4-triazolato ligands, while in Ti(tBu(2)pz)(3)(C(2)H(2)N(3)) and Nb(tBu(2)pz)(3)(Me(2)C(2)N(3))(2) the analogous groups are joined in a eta(1)-fashion in the solid-state structure. Solution NMR studies at different temperatures suggest transition states involving eta(2)-1,2,4-triazolato ligands for the complexes containing eta(1)-1,2,4-triazolato ligands in the solid state. X-ray crystal structures of analogous tetrazolato complexes Ti(tBu(2)pz)(3)(PhCN(4)) and Nb(tBu(2)pz)(3)(PhCN(4))(2) show eta(1)-coordination of the 2-nitrogen atoms of the tetrazolato ligands. Molecular orbital calculations have been carried out on several model titanium complexes and provide detailed insight into the bonding between early transition metal centers and 1,2,4-triazolato and tetrazolato ligands. The eta(2)-coordination mode of 1,2,4-triazolato and tetrazolato ligands is predicted to be more stable than the eta(1)-coordination mode by 13.8-5.2 kcal/mol.