Introduction:To evaluate and compare the benefits of multiparametric magnetic resonance imaging (mpMRI) in combination with fusion prostate biopsy (fPBx) and find out what happened with patients underwent single MRI without fPBx.Materials and methods: 125 patients underwent prostate mpMRI.Sixty-five of these patients additionally underwent ultrasound-guided fPBx.Prostate lesions were scored using the Prostate Imaging Reporting and Data System version 2, and the results were verified with prostate biopsies.Results: Sixty-five patients (52%) underwent fPBx after mpMRI, and 60 patients (48%) underwent mpMRI alone as ordered by their physician.Of the 65 men who underwent fPBx, PCa was verified in 33 men (50.77%) who exhibited suspicious lesions on mpMRI, whereas 20 men (30.77%) yielded negative results, although suspicious lesions were observed by mpMRI.Among the 65 men, 7 (10.76%)and 5 (7.7%) men had atypical small acinar proliferation and chronic prostatitis, respectively.The mean PCa detection rate for standard biopsy was 21.9% (SD, 26.4), whereas that of the mpMRI combined with fPBx was 49.5% (SD, 41.9) (p-value <0.0001).Of the 53 patients who underwent biopsy, 13 patients underwent the algorithm mpMRI/fPBx for first-line diagnosis, with nearly 70% patients (n=9) experiencing positive results. Conclusion:fPBx detected considerably more cases of PCa than standard biopsies, demonstrating the clear advantages of the former method.Because of the wellknown low specificity of mpMRI, this method alone is insufficient for the diagnosis of PCa if no further diagnostic interventions are planned.

Background: One of the major challenges in prostate cancer (PCa) treatment is distinguishing insignificant PCa from those forms that need active treatment. We evaluated the impact of PSA isoforms on risk stratification in patients with low-risk PCa as well as in active surveillance (AS) candidates who underwent radical prostatectomy. Methods: A total of 112 patients with biopsy confirmed Gleason score (GS) 6 PCa of four different international institutions were prospectively enrolled in the study. Blood withdrawal was performed the day before radical prostatectomy. In addition, patients were classified according to the EAU and NCCN criteria for AS candidates. PSA, free PSA (fPSA) and proPSA were measured using dual monoclonal antibody sandwich immunoassays. In addition, the Prostate Health Index (PHI=proPSA/fPSA × √PSA) was calculated. Final histology of the radical prostatectomy specimens was correlated to PSA, its isoforms and PHI. Results: Serum proPSA levels were significantly elevated in those patients with an upgrade in final histology (GS⩾7). In addition, higher proPSA levels were predictive for extraprostatic extension (⩾pT3a) as well as for positive surgical margins. Interestingly, PHI had an even higher predictive power when compared with proPSA alone concerning GS upgrading, extraprostatic extension and surgical margins in both the total and the AS patient group. Conclusion: We showed in a multicenter study that proPSA is a valuable biomarker to detect patients with aggressive PCa in a cohort of GS 6 patients, who would benefit from active tumor therapy. Combining proPSA with the standard markers PSA and fPSA using PHI further increases the predictive accuracy significantly. Moreover, our data support the use of PHI for monitoring PCa patients under AS.

Purpose: Persistently elevated prostate-specific antigen (PSA) values following negative biopsies result in a diagnostic dilemma. In order to improve detection rates in patients with former negative biopsies and persistently elevated PSA values, magnetic resonance tomography (MRT), magnetic resonance spectroscopy (MRS), and diffusion-weighted magnetic resonance imaging (DW-MRI) were performed prior to prostate rebiopsies. Materials and Methods: Over a 14-month period, 67 patients (mean age of 66 years) with a history of 1-5 negative biopsies underwent endorectal magnetic resonance imaging (MRI) using T2-weighted MRT MRS and DW-MRI before an additional prostate biopsy was performed. Subsequently, 5 contrast-enhanced transrectal ultrasound-guided biopsies were performed according to a 10-core systematic scheme. Out of the 67 men, 25 patients had positive biopsies and opted for radical prostatectomy. Histological evaluation of cancer localization, PSA, diameters of primary tumors, numbers and diameters of satellite tumors, prostate volume, and staging pathology was performed. These findings were compared with MRI and MRS results. Results: Serum PSA levels ranged from 3.1 to 19.5 g/ml (median level of 7.96 ng/ml). After the 25 patients underwent radical prostatectomy, analysis of 20 whole-mount sections of 25 radical retropubic prostatectomy (RPE) specimens presented results agreeing with the tumor location from MRI and MRS data. Conclusions: The aim of image-guided diagnostics should be to provide more critical information prior to biopsy. Furthermore, the acquisition of such data is important for better risk stratification in therapeutic decisions.

Zusammenfassung Ziel: Ziel dieser Studie war eine gesundheitsökonomische Analyse der Anwendung der MR-Bildgebung (MRT) im präoperativen Staging des Prostatakarzinoms (PCa). Material und Methoden: Die gesundheitsökonomische Analyse umfasste folgende Schritte: Erstellung des entscheidungsanalytischen Modells, Bestimmung von Wahrscheinlichkeiten und Parametern basierend auf einer detaillierten Literaturrecherche, Evaluierung des Modells mit den Mittelwerten der Parameter und Sensitivitätsanalysen der Ergebnisse über die entsprechenden Wertebereiche. Es wurde eine Kosten-Nutzwert-Analyse aus Sicht der Krankenkassen für Österreich und Deutschland durchgeführt. Die Zielpopulation waren Patienten mit gesichertem PCa, die Handlungsalternativen waren die Therapiewahl ohne bzw. mit Staging mittels MRT. Therapieoptionen waren eine Prostatektomie bei lokal begrenztem PCa und eine Strahlen-/Hormontherapie bei lokalfortgeschrittenem PCa. Die Ergebnisparameter waren Quality Adjusted Life Years (QALYs) und Kosten pro Patient. Ergebnisse: Die Evaluierung zeigte, dass die Durchführung einer MRT vor einer relativ teuren und folgenschweren Therapiemaßnahme wie der radikalen Prostatektomie aus Sicht des Kostenträgers sowohl hinsichtlich der Kosten wie auch der Nutzwerte sinnvoll ist. Die Kosten pro Patient waren um € 2635 niedriger, die Nutzwerte um 0,099 QALYs höher. Die Strategie ohne MRT war nicht nur bei der Evaluation mit den Basiswerten, sondern auch bei fast allen Sensitivitätsanalysen hinsichtlich der Kosten wie auch der Nutzwerte der Strategie eines vorherigen Stagings mit MRT unterlegen. Schlussfolgerung: Unser entscheidungsanalytisches Modell hat für die gewählten Rahmenbedingungen und fast alle Szenarien innerhalb der Sensitivitätsanalyse ein besseres Kosten-Nutzwert-Verhältnis für die Strategie mit MRT zum Staging des PCas aufgezeigt.

Gleason score of prostate needle biopsy specimens and Gleason score in radical prostatectomy specimens only match in 31% to 63% of the cases depending on different reports. CD147 expression has been shown to be a significant prognostic factor in human prostate cancer. The aim of this study was to evaluate the use of immunohistochemical detection of CD147 expression in prostate needle biopsy specimens to obtain additional presurgical information.

Ziel: Material und Methoden: Ergebnisse: Schlussfolgerung: Purpose: Materials and Methods: Results: Conclusion:

PURPOSE:The aim of this study was the health-economic analysis of MR imaging in the diagnostics of suspicious prostate carcinoma (PCa) before execution of a first biopsy. MATERIALS AND METHODS:The health-economic analysis included four steps: modeling, determination of probabilities, evaluation, and sensitivity analyses. We performed an effectiveness analysis from the patient perspective as well as a cost-effectiveness and a cost-utility analysis from the health insurance perspective for Austria and Germany. The effectiveness and cost-effectiveness analysis used a hypothetical cohort of 100,000 patients. The result parameters were number of biopsies, number of detected PCa, and monetary costs. For the cost-efficiency analysis, the result parameters, quality-adjusted life years (QALYs) and costs, were calculated for an individual patient. RESULTS:The efficiency analysis showed that MRI before a first biopsy can prevent ca. 64,000 unnecessary biopsies/ 100,000 patients. The diagnostic efficiency was higher by a factor of 1.7. Due to MRI, eight PCas were additionally detected. From a health insurance perspective, MRI was not cost-effective. Extra costs of ca. 42 m. € per 100,000 patients and of 650 € per prevented biopsy were calculated. The costs per detected PCa were increased by 1395 €. The attainable QALYs were a little higher for the MRI alternative, which was therefore not dominated. CONCLUSION:Our results do not permit a clear recommendation for or against the application of MRI in the diagnostics of PCa. From the patient perspective, it is to be endorsed due to the higher medical efficiency. However, it is connected with higher health insurance costs.

Antibiotic-resistant strains are an increasing problem in medicine. The aim of this study was to assess the prevalence and increasing resistance of Escherichia coli bacteria as well as the extended spectrum beta-lactamase (ESBL) E.coli in urinary tract infections in a local community hospital.

Proper prostate function and maintenance of cellular homeostasis is achieved through extensive crosstalk between the fibromuscular stroma and overlying secretory epithelium. These interactions are mediated via locally-derived and systemic paracrine- and autocrine-acting growth factors and sex steroid hormones. Alterations in transforming growth factor beta (TGF-beta) and sex steroid hormone signalling are implicated in the stromal tissue remodelling that is characteristic of benign prostatic hyperplasia (BPH) and prostate cancer (PCa), two of the most common proliferative disorders affecting elderly men. We previously demonstrated that GAGEC1, a member of cancer-testis associated antigens, is up-regulated in response to TGF-beta in in vitro models of age-associated prostatic stromal remodelling. GAGEC1 expression is restricted to male and female reproductive tissues and is up-regulated in symptomatic BPH and PCa. Consistent with its restricted expression profile to classical steroidogenic tissues, GAGEC1 is induced by sex steroid hormones, particularly oestradiol and dihydrotestosterone. Transiently expressed recombinant GAGEC1 undergoes constant shuttling between cytoplasmic and nuclear cell compartments, a process that may be regulated via post-translational phosphorylation. Our data suggest that age/disease-associated changes in TGF-β1 and sex steroid hormones may account for the reported increase in GAGEC1 expression in BPH and PCa. Functional analyses indicate that the biological activity of GAGEC1 is regulated via phosphorylation-dependent nucleocytoplasmic trafficking raising the possibility that GAGEC1 is involved in signal transduction mechanisms. Given that its expression is restricted in males to the prostate and testis, GAGEC1 represents a promising target for therapeutic intervention of BPH and PCa.

Normal hypothalamic-pituitary testicular and prostatic functions are essential for maintenance of male fertility, whereby glycoprotein hormones (GPH) as well as androgens are major endocrine and local regulators. We have investigated whether the GPH human chorionic gonadotropin (hCG) and the free alpha and beta subunits thereof are produced in the target organs themselves and potentially act as auto/paracrine modulators of fertility. Immunofluorometric assays (IFMAs) based on our panel of highly selective monoclonal antibodies, immunohistochemistry (IHC), confocal laser scanning microscopy (CLSM) and 1- and 2D gel electrophoreses with subsequent western blotting have been utilized for the detection of hCGα, hCGβ and its metabolite hCGβ core fragment (cf) in human testis, prostate and seminal plasma. Both organs synthesize hCGα and hCGβ, which are subsequently detectable at high concentrations in seminal plasma of healthy probands (n = 17): hCGα 2630 ± 520 ng/mL (mean ± S.E.M.), hCGβ 2 ± 0.28 ng/mL, hCGβcf and hCG 0.19 ± 0.039 ng/mL. These parameters significantly exceed physiological values, e.g. ten thousand-fold in the case of hCGα, in serum of young men (n = 20): hCGα 0.142 ± 0.054 ng/mL (mean ± S.E.M.), hCGβ 0.05 ng/mL and hCG 0.004 ± 0.003 ng/mL. Levels of these markers were not correlated with sperm counts. Of all body fluids including those of pregnant women seminal plasma is the richest physiological source for genuine free i.e. non-dissociated GPHα (Mr,app 23 k) which may even appear as di- or tetramers. Its concentration is similar to that observed in maternal serum (weeks 10–12 of gestation) and in extra-embryonic coelomic fluid. In contrast to those fluids where ratios of free subunits to hCG are in the range of 1:100 highly inverse ratios in the range of 10.000:1.000:1 were observed for hCGα:hCGβ:hCG in seminal plasma. hCGα is not derived from heterodimeric GPH suggesting hCG-independent functions of hCGα and hCGβ in male and female fertility.

Transforming growth factor beta (TGF-β) is a multi-functional cytokine that plays a fundamental role during embryonic development and tissue homeostasis in metazoans. Changes in TGF-β signalling are implicated in prostate cancer (PCa) and benign prostatic hyperplasia (BPH), two of the most common diseases affecting ageing males. GAGEC1 belongs to the GAGE-related family of cancer/testis associated antigens and in males is expressed only in prostate and testis. Previous reports demonstrate that GAGEC1 is up-regulated in symptomatic BPH and PCa. We demonstrate GAGEC1 up-regulation by TGF-β1 in primary prostatic stromal and epithelial cells. Our data suggest that disease-associated increases in TGF-β1 may account for the increase in GAGEC1 expression in BPH and PCa. Given its restricted spatial expression in males, GAGEC1 represents a promising target for therapeutic intervention of BPH and PCa.

Ageing of the male reproductive system is characterized by changes in the endocrine system, hypogonadism, erectile dysfunction and proliferative disorders of the prostate gland. Stochastic damage accumulating within ageing leads to progressive dysregulation at each level of the hypothalamic–pituitary–gonadal (HPG) axis and in local auto/paracrine interactions, thereby inducing morphological changes in reproductive target organs, such as the prostate, testis and penis. Despite age‐related changes in the HPG axis, endocrine functions are generally sufficient to maintain fertility in elderly men. Ageing of the male reproductive system can give rise to clinically relevant manifestations, such as benign prostatic hyperplasia (BPH), prostate cancer (PCa) and erectile dysfunction (ED). In this review, we discuss morphological/histological changes occurring in these organs and current views and concepts of the underlying pathology. Moreover, we emphasize the molecular/cellular pathways leading to reduced testicular/penile function and proliferative disorders of the prostate gland. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

14604 Background: PDE 5 is highly expressed in cavernosal and prostatic tissue. The mechanism of PDE-5 inhibitors on cavernosal tissue is well established but the effects of PDE-5 inhibitors on prostatic cells are unknown. The aim of this study was to analyze in vitro effects of PDE-5 inhibitors on prostate primary cells, fibroblasts (PrSC), basal epithelial cells (PrEC) and prostate cancer cell lines. Methods: Cultivated PrEC and PrSC, immortalized BPH cells (BPH 1), androgen dependent (LNCaP) and androgen independent (PC3) prostate carcinoma cell lines were exposed to increasing concentrations of commercially available PDE 5 inhibitors Sildenafil (Sil), Tadalafil (Tad), Vardenafil (Var). After incubation for 3 days cell viability was determined by a WST-1 assay (Roche-Biochemicals). Cells were evaluated morphologically by invert-light microscopy. PDE-5 protein concentrations were determined by western blot analyses and tissue distribution of PDE-5 by immunohistochemistry (IHC) with a polyclonal antiserum. Results: None of the PDE-5 inhibitors induced cell proliferation. Significant decreases in proliferation and viability were observed at high concentrations (1 mg/ml) of all substances in PrSC and PrEC. In PrSC, proliferation rate decreased to 37.7% in Sil, to 16.9% in Tad and to 63.7% for Var as compared to controls. In PrEC, proliferation decreased to 72.7%, 21.6% and 84.4% for Sil, Tad and Var, respectively. At 0.1 mg/ml only Tad reduced proliferation significantly to 57.4%. Moreover, Tad induced neuroendocrine-like morphology in some PrEC. High protein concentrations of PDE 5 were observed in PrEC, low concentrations in PrSC but none in cancer cells. Conclusions: Sil, Tad and Var inhibit proliferation of prostate primary cells in vitro. Tad showed highest inhibition. Tumor cells were insensitive to PDE-5 inhibitors, due to the lack of PDE-5 protein. It seems unlikely that any of these substances increases proliferation of prostate carcinoma. Tad induced neuroendocrine-like morphology in some basal PrEC indicating effects on cellular differentiation. No significant financial relationships to disclose.

Proliferative disorders of the prostate, such as prostate cancer (PCa) and benign prostatic hyperplasia (BPH), represent two of the most common diseases affecting the ageing male. Alterations in stromal cell composition, function and the presence of reactive myofibroblasts are thought to play a key role in BPH and PCa. These myofibroblasts are generated by the pro-inflammatory cytokine transforming growth factor beta 1 (TGF-β1), and support proliferation, angiogenesis and invasion. We previously showed that GAGEC1 (JM27) is up-regulated in trans-differentiated prostatic stromal myofibroblasts induced by TGF-β1. The stromal-specific gene GAGEC1 is also up-regulated in tissues from patients with BPH and prostate cancer. There have been very few biochemical studies of GAGEC1 and the function of the encoded gene product remains unknown. GAGEC1 is related to the GAGE family of cancer/testis assocaited antigens. In normal tissues, GAGEC1 expression is restricted to male and female reproductive tissues, placenta and the prostate. Transiently expressed recombinant GAGEC1 is distributed throughout the mammalian cell with predominant nuclear staining observed in all tumour and prostatic primary cell lines tested. Consistently the highly conserved N-terminus of in silico-identified GAGEC1 orthologues contains a putative nuclear localisation signal. We demonstrate that whilst ectopic expression of GAGEC1 has no effect on cellular proliferation, apoptosis-related mechanisms may be affected. The observation that GAGEC1 is up-regulated in BPH and PCa together with its restricted expression pattern in normal tissues, suggests that GAGEC1 may be a promising target in the diagnosis and/or treatment of proliferative diseases of the prostate.