Granulocyte colony-stimulating factor impairs CD8(+) T cell functionality by interfering with central activation elements.

Besides mobilizing stem cells into the periphery, granulocyte colony-stimulating factor (G-CSF) has been shown to influence various types of innate and adaptive immune cells. For example, it impairs the effector function of cytotoxic T lymphocytes (CTLs). It is assumed that this effect is mediated indirectly by monocytes, regulatory T cells and immunomodulatory cytokines influenced by G-CSF. In this study, isolated G-CSF-treated CD8(+) T cells were stimulated antigen-dependently with peptide-major histocompatibility complex (pMHC)-coupled artificial antigen-presenting cells (aAPCs) or stimulated antigen-independently with anti-CD3/CD28 stimulator beads. By measuring the changes in interferon (IFN)-γ and granzyme B expression at the mRNA and protein level, we showed for the first time that G-CSF has a direct effect on CD8(+) CTLs, which was confirmed based on the reduced production of IFN-γ and granzyme B by the cytotoxic T cell line TALL-104 after G-CSF treatment. By investigating further elements affected by G-CSF in CTLs from stem cell donors and untreated controls, we found a decreased phosphorylation of extracellular-regulated kinase (ERK)1/2, lymphocyte-specific protein tyrosine kinase (Lck) and CD3ζ after G-CSF treatment. Additionally, miRNA-155 and activation marker expression levels were reduced. In summary, our results show that G-CSF directly influences the effector function of cytotoxic CD8(+) T cells and affects various elements of T cell activation.

Impact of cardiovascular risk factors and related comorbid conditions and medical therapy reported at baseline on the treatment response to tadalafil 5 mg once-daily in men with lower urinary tract symptoms associated with benign prostatic hyperplasia: an integrated analysis of four randomised, double-blind, placebo-controlled, clinical trials.

PURPOSE: The influence of cardiovascular risk factors/comorbidities on response to oral once-daily tadalafil 5 mg was explored in men with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). METHODS: This post hoc analysis pooled data from four double-blind studies in which 1498 men with > 6-mo history of LUTS/BPH were randomised and received either once-daily placebo (n = 746) or tadalafil 5 mg (n = 752) for 12 weeks. Descriptive statistics were reported for changes in total International Prostate Symptom Score (IPSS), IPSS voiding and storage subscores, and IPSS quality-of-life (QoL) index. Treatment group differences by baseline clinical and cardiovascular factors and medical therapies were examined using analysis of covariance. RESULTS: Tadalafil was effective in men with LUTS/BPH and cardiovascular risk factors/comorbidities except for patients receiving > 1 antihypertensive medication. Placebo-adjusted least squares (LS) mean improvements in total IPSS were -1.2 (95% CI: -2.5 to -0.0) in men taking > 1 antihypertensive medication vs. -3.3 (95% CI: -4.4 to -2.1) in men taking one medication (interaction p = 0.020). In addition, placebo-adjusted LS mean improvements in total IPSS were -0.2 (95% CI, -2.1 to 1.7) in men who reported use of diuretics vs. -2.8 (95% CI, -3.7 to -1.9) in men who reported taking other antihypertensive medications vs. -2.3 (95% CI, -3.2 to -1.5) in men who reported not using any antihypertensive drug (p-value for interaction = 0.053). CONCLUSIONS: Once-daily tadalafil 5 mg improved LUTS/BPH, regardless of severity, in men with coexisting cardiovascular risk factors/comorbidities, except for patients with history of > 1 drug for arterial hypertension. Use of diuretics may contribute to patients' perception of a negated efficacy of tadalafil on LUTS/BPH. Comorbidities should be considered when choosing the optimal medicine to treat men with LUTS/BPH.

Improving the health care of geriatric patients: management of urinary incontinence: a position paper.

A multidisciplinary German expert group met in 2012 to discuss the current status and prospects of health care of geriatric patients with urinary incontinence in Germany. The purpose of this position paper is to raise awareness among health care providers for the challenges associated with adequate management of urinary incontinence in frail elderly. The experts agree that a multidisciplinary collaboration is essential for the successful treatment of urinary incontinence symptoms which are often associated with loss of autonomy and social isolation. For most geriatric patients, usually the general practitioner is the first contact when seeking help. Hence, the general practitioner plays a crucial role in the coordination of diagnosis and treatment. The involved health care providers should have adequate education and training in their respective disciplines and should be networked allowing quick turnaround times. Non-pharmacological treatments (e.g. behavioural interventions) should have been tried before any pharmacotherapy is initiated. If pharmacological treatment of urinary incontinence involves the use of anticholinergic agents, cognitive performance should be monitored regularly. If indicated, anticholinergic agents with a documented efficacy and safety profile, explicitly assessed in the elderly population, should be preferred.

Detrusor underactivity: a plea for new approaches to a common bladder dysfunction.

AIMS: Detrusor underactivity (DU) is defined by the International Continence Society as a contraction of reduced strength and/or duration resulting in prolonged or incomplete emptying of the bladder but has yet received only little attention. The purpose of this report is to summarize the ICI-RS meeting in Bristol in 2010 exploring current knowledge on DU and outline directions for future research. METHODS: A think tank discussion was held and the summary of discussions was presented to all ICI-RS participants. This report is based on the final discussions. RESULTS: The understanding of the pathophysiology, epidemiology, assessment, and treatment of DU remains rudimentary. DU is defined by pressure-flow analysis but no consensus exists regarding which of the available formulae should be used for quantification of detrusor work. DU is likely to be multifactorial. Aging causes a decay in detrusor activity but other concomitant causes, either myogenic or neurogenic, may aggravate the problem resulting in decrease of detrusor contractility. No effective pharmacotherapy for the condition exists. Only a few surgical therapeutic strategies have been explored, such as neuromodulation and skeletal muscle myoplasties. Consequently, the management of affected individuals remains unsatisfactory. CONCLUSIONS: Future directions recommended by the ICI-RS panel include assessment of pathogenesis by developing novel animal models in addition to new non-invasive tests allowing longitudinal trials. Furthermore, optimizing the existing evaluation algorithms to support standard testing for DU and further epidemiological studies to quantify the size of the problem are required for the development of future treatment modalities.

Novel cellular microarray assay for profiling T-cell peptide antigen specificities.

We present a novel cellular microarray assay using soluble peptide-loaded HLA A2-Ig dimer complexes that optimizes the avidity of peptide-HLA binding by preserving the molecular flexibility of the dimer complex while attaining much higher concentrations of the complex relative to cognate T-cell receptors. A seminal advance in assay development is made by separating the molecular T-cell receptor recognition event from the binding interactions that lead to antigen-specific cell capture on the microarray. This advance enables the quantitative determination of antigen-specific frequencies in heterogeneous T-cell populations without enumerating the number of cells captured on the microarray. The specificity of cell capture, sensitivity to low antigen-specific frequencies, and quantitation of antigenic T-cell specificities are established using CD8 T-cell populations with prepared antigen-specific CTL frequencies and heterogeneous T cells isolated from peripheral blood. The results demonstrate several advantages for high-throughput broad-based, quantitative assessments of low-frequency antigen specificities. The assay enables the use of cellular microarrays to determine the stability and flux of antigen-specific T-cell responses within and across populations.

Thulium laser enucleation of the prostate (ThuLEP): transurethral anatomical prostatectomy with laser support. Introduction of a novel technique for the treatment of benign prostatic obstruction.

BACKGROUND: Transurethral removal of prostatic tissue is the treatment choice for benign prostatic enlargement and benign prostatic obstruction. Urodynamic results are directly linked to the amount of removed tissue which, however, is directly associated with intra- and postoperative morbidity. Transurethral laser operations of the prostate offer the advantage of decreased bleeding complications and the possibility to treat patients with bleeding disorders or anticoagulative treatment. The aim of the article is to present a novel technique of complete transurethral removal of the transition zone (enucleation) with the support of the Thulium laser to combine complete anatomical enucleation and maximum urodynamic efficacy with minimal side-effects. MATERIALS AND METHODS: We present five distinct surgical steps for transurethral complete removal of the transition zone of the prostate (Thulium laser enucleation of the prostate, ThuLEP). Surgical steps are presented in chronological order with the help of intraoperative pictures. Laser energy of 70-90 W is only used for the incision at the verumontanum and bladder neck for removal of the middle lobe, whereas laser energy of 30 W was only used for coagulation of small vessel crossing the surgical capsule towards the transition zone and bladder neck for dissection of the lateral lobes. The lobes themselves are liberated by blunt dissection. CONCLUSIONS: ThuLEP offers complete removal of the transition zone no matter what prostatic size. The techniques combine maximum efficacy with minimal side-effects. Clinical results comparing ThuLEP with open prostatectomy or transurethral resection are awaited.

[Sophisticated surgical management of distinctive patients with benign prostatic hyperplasia (BPH)]. / Differenziertes operatives Management unterschiedlicher Patienten mit benignem Prostatasyndrom (BPS).

Herein we describe four clinical scenarios. For the standard patient (prostate volume 30-80 ml, life expectancy >10 years) transurethral resection of the prostate (TURP) remains the standard of care, while endoscopic enucleation is a valuable alternative. Patients with a relevant middle lobe profit most from TURP, endourological enucleation procedures, or laser vaporization. In the case of the absence or a moderate-sized middle lobe and the absence of severe bladder outlet obstruction (BOO), minimally invasive procedures such as Rezum®, UroLift® or prostate artery embolization (PAE) can be offered. Patients have to be informed that long-term data on this specific indication are lacking. Particularly younger men requiring BPH surgery are interested in preserving ejaculatory function. In the presence of severe BOO, ejaculatory-protective TURP or endoscopic enucleation by preserving the pericollicular region or aquablation are the methods of choice providing an antegrade ejaculation in 60-90% of cases. Rezum®, AquaBeam®, and UroLift® enable preservation of ejaculation in almost 100%; data on PAE with this respect are more controversial. For patients with a small prostate and significant post void residual, a thorough preoperative work-up, including urodynamics and bladder/detrusor wall thickness measurement, is of great importance. Desobstructive surgery provides satisfactory short- and midterm outcome, yet the long-term outcome is disappointing and remains to be determined in greater detail. The broad spectrum of therapeutic options enables today an individualized minimally invasive or surgical management of BPH considering patient wishes, anatomical factors or urodynamic factors. The time of a "one therapy fits all" strategy is definitely history.

[Use of synthetic slings and mesh implants in the treatment of female stress urinary incontinence and prolapse : Statement of the Working Group on Urological Functional Diagnostics and Female Urology of the Academy of the German Society of Urology]. / Einsatz von synthetischen Band- und Netzimplantaten bei der Behandlung von Belastungsinkontinenz und Descensus genitalis der Frau : Stellungnahme des Arbeitskreises Urologische Funktionsdiagnostik und Urologie der Frau der Akademie der Deutschen Gesellschaft für Urologie.

Due to a safety alert issued by the US Food and Drug Administration (FDA) in 2011 for transvaginal mesh implants to treat female prolapse as a result of numerous reports of complications such as infection, chronic pain, dyspareunia, vaginal erosion, shrinkage and erosion into other organs nearly all industrial products have been withdrawn from the market in the meantime. The United Kingdom, Australia, and New Zealand extended warnings and prohibitions even on the implantation of midurethral slings (TVT, TOT). In view of these current international controversies regarding the use of implanted materials for the treatment of stress incontinence and prolapse and the lack of clear guidelines for the use of biomaterials, the opinion of the Working Group on Urological Functional Diagnostics and Female Urology should provide clarity. The Opinion is based on the SCENIHR Report of the "European Commission's Scientific Committee on Emerging and Newly Identified Health Risks", the "Consensus Statement of the European Urology Association and the European Urogynaecological Association on the Use of Implanted Materials for Treating Pelvic Organ Prolapse and Stress Urinary Incontinence" and in compliance with relevant EAU and national guidelines and the opinion of the Association for Urogynaecology and Plastic Pelvic Floor Reconstruction (AGUB eV). In addition, recommendations are given for the future handling of implants of slings and meshes for the treatment of stress incontinence and prolapse from a urologic viewpoint.

Laser treatments of the prostate vs TURP/ open prostatectomy: systematic review of urodynamic data.

UNLABELLED: Bladder outlet obstruction (BOO) is believed to be the major component of benign prostatic hyperplasia (BPH) that harms the urinary tract. Therefore, BOO relief is the primary treatment objective in patients with obstructive BPH. This systematic review aims to analyze urodynamic data of laser treatment modalities of the prostate in direct comparison with standard treatment (TURP or open prostatectomy). We systematically searched the literature for randomized-controlled trials (RCTs) of prostate laser treatments in which urodynamic results were compared to TURP or open prostatectomy. The literature search included articles that were published between January 1995 and January 2009. Thirty five RCTs were identified encompassing in total 3669 patients. Of all available laser treatments, only one RCT used pressure-flow data to compare the laser treatment of the prostate (holmium laser enucleation, HoLEP) with standard treatment. Improvement of maximum urinary flow rate (Q(max)) of free uroflowmetry was similar for contact laser ablation (CLAP) with Nd:YAG, interstitial laser coagulation with Nd:YAG, potassium potassium-titanyl-phosphate (KTP)/Nd: YAG hybrid treatment, and HoLEP. Qmax improvement was also similar for holmium laser ablation (HoLAP) with 60-80 Watts, holmium laser resection, and thulium laser resection but limited to only one study each. The laser hybrid therapy with CLAP/visual laser ablation of the prostate (VLAP)/Nd:YAG was inferior to TURP. VLAP and KTP showed inhomogeneous RESULTS: Most contemporary laser treatments modalities provide similar Qmax improvement compared to standard treatment. However, precise differences can only be determined by comparative computer urodynamic investigations. Therefore, new laser techniques (such as thulium laser vapoenucleation of the prostate) should be investigated by urodynamic studies in the future.

[Diagnostic procedures and diagnostic strategy for lower urinary tract symptoms/benign prostatic hyperplasia : An overview]. / Diagnostik und diagnostische Strategie beim benignen Prostatasyndrom : Ein Überblick.

BACKGROUND: Lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) is the most common condition affecting the lower urinary tract of men. Evidence-based assessment is the basis for an ideal treatment approach. OBJECTIVES: To provide an overview of the current status of diagnostic measures for LUTS/BPH. MATERIALS AND METHODS: Descriptive review of the literature on the diagnosis of LUTS/BPH. RESULTS: A medical history inquiring about LUTS/BPH symptoms and burden as well as a standardized and validated symptom questionnaire such as the International Prostate Symptom Score (IPSS) are the basis of the assessment. A physical examination including a rectal exam and the ultrasonography of the lower and upper urinary tract are also part of the basic diagnostic workup. Prostate size is ideally measured by transrectal ultrasound. Serum prostate-specific antigen measurement may help to estimate the prostate size and the risk fo progression. It can also be helpful in the detection of prostate cancer. Urine dipstick or sediment is used to exclude urinary tract infection, hematuria, or glucosuria. Voiding dysfunction can be detected by uroflowmetry. In addition to the aforementioned examinations, further tests such as frequency-voiding charts, multichannel urodynamic evaluation, measurement of detrusor wall thickness and X­ray imaging of the upper urinary tract as well as a cystoscopy may be offered if needed. CONCLUSIONS: Diagnostics of LUTS/BPH consist of basic exams as well as optional exams and can be used to assess the progression risk, to identify complications and to offer the ideal treatment.

[Fake News BPH - what is really true!] / Hartnäckige Mythen zum Thema BPS ­ und was davon wirklich stimmt!

BACKGROUND: Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) is the fourth most common and the fifth most costly disease in men aged 50 years or older. Despite the high prevalence of LUTS/BPH in clinical practice and evidence-based guideline recommendations, there are still plenty of misconceptions on the terminology and pathophysiology of the disease, leading to false assumptions and malpractice. OBJECTIVES: Listing of commonly used false assumptions and clarification of the correct terminology and pathophysiology. MATERIALS AND METHODS: Critical reflection of 12 selected fake news based on PubMed search. RESULTS: Average prostate weight in healthy men is 20 g but varies between 8-40 g. The BPH-disease does not progress in stages; therefore, the BPH-classifications according Alken or Vahlensieck should not be used anymore. There is only a weak and inconsistent relationship between bladder outlet obstruction (BOO) and prostate size, diverticula/pseudo-diverticula, postvoid residual, urinary retention or renal insufficiency, which is too unreliable for BOO-diagnosis in the individual patient. Urethro-cystoscopy with grading of the degrees of occlusion of the prostatic urethra and bladder trabeculation is insufficient for BOO-diagnosis. There is no clinically relevant reduction of BOO with licensed BPH-drugs and no convincing data that prostate resection (TURP) has to be complete until the surgical capsule in order to obtain optimal results. CONCLUSIONS: The reasons for the persistent use of wrong terminology and pathophysiology are diverse. One reason is lack of implementation of evidence-based guidelines into clinical practice due to lack of knowledge, individual beliefs, costs, availability and reimbursement policies. Another reason is the increasing focus on oncology, coupled with underrepresented education and training on BPH.

[Expression of corticotropin releasing factor receptor 2 (CRFR2) in the human prostate. A new potential target for medical therapy of benign prostatic hyperplasia]. / Expression des "Corticotropin releasing faktor rezeptors 2" (CRFR2) in der humanen Prostata. Ein möglicher Ansatzpunkt bei der Therapie der benignen Prostatahyperplasie.

BACKGROUND: Expression of urocortin (Ucn), a 40-amino-acid neuropeptide, was demonstrated in the prostatic tissue of patients with benign prostatic hyperplasia (BPH). Ucn showed a significant role in the regulation of local inflammation, proliferation, and relaxation of smooth muscle tone in different organs through activation of corticotropin releasing factor receptor 2 (CRFR2). However, CRFR2 expression in human benign prostatic tissue remains unknown. Our study therefore aimed to investigate CRFR2 expression in prostatic tissue. METHODS: CRFR2 expression was evaluated in tissue samples of human prostate (n=8) by means of reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: mRNA of CRFR2 was abundantly present in RT-PCR of prostate lysates. Immunohistochemistry revealed CRFR2 expression in the cytoplasm of basal and luminal epithelial cells as well as in cystic glands. Smooth muscle components of the stroma and vascular endothelial cells also showed extensive staining for CRFR2. CONCLUSIONS: Our study showed for the first time that human prostatic tissue expresses CRFR2. Pharmacological CRFR2 modulation might be a potential medical treatment for clinical BPH.

[Anticholinergics for overactive bladder: does subtype selectivity play a role?]. / Anticholinergika bei überaktiver Blase: Spielt Subtypselektivität eine Rolle?

Anticholinergics act in the treatment of overactive bladder by blocking muscarinic receptors of which five subtypes exist. Their desired effects occur via M(3) receptors, but a role for M(2) receptors is being discussed. Adverse effects such as dry mouth and constipation occur also via M(3) receptors, but M(2) and M(1) receptors can mediate side effects in the heart or on cognitive function, respectively. Therefore, an M(3)-selective drug such as darifenacin could theoretically be less effective but also have fewer cardiac or central nervous side effects. However, the limited available clinical data do not support a smaller efficacy or better general tolerability. The lack of adverse effects on cognitive function is well documented for darifenacin, but it cannot yet be determined definitively whether this discriminates it from other modern anticholinergics.

[Gynaecomastia and male infertility as symptoms of a nonpalpable Leydig cell tumour]. / Gynaecomastie en infertiliteit bij een man met een niet-palpabele leydigceltumor.

A 35-year-old man and his partner were referred for intracytoplasmic sperm injection treatment (ICSI) because of secondary infertility due to severe oligoasthenoteratospermia. Three years earlier he had presented elsewhere with left unilateral gynaecomastia. A hypertrophic mammary gland had been excised one year later. Histopathological investigation showed benign hypertrophy. One year later he developed gynaecomastia on the other side. Physical examination and incomplete hormonal screening showed no abnormalities. The couple were referred to our tertiary clinic for ICSI treatment. The patient still had unilateral gynaecomastia. Hormonal screening showed not only severe oligoasthenoteratospermia, but also an elevated serum oestrogen level. Scrotal ultrasound revealed a 17 mm mass in his right testicle. Subsequently unilateral orchidectomy was performed. Histology showed a benign Leydig cell tumour for which no further therapy was required. Four months after surgery the gynaecomastia diminished, oestrogen levels became normal and improvement in semen parameters followed. Patients with severe male infertility or gynaecomastia are at a higher risk of developing a testicular neoplasm. Besides history taking, physical examination of breasts and testicles, hormonal screening and scrotal sonography should be performed as some testicular neoplasms are not apparent on palpation.

[Pharmacological treatment of benign prostatic hyperplasia]. / Medikamentöse Therapie des benignen Prostatasyndroms.

The pharmacological treatment of benign prostatic hyperplasia (BPH) is indicated when men suffer from lower urinary tract symptoms (LUTS) but there are no absolute indications for prostate surgery or severe bladder outlet obstruction. Phytotherapy can be used in men with mild to moderate LUTS and alpha-blockers can quickly and effectively decrease the LUTS and symptomatic disease progression. Phosphodiesterase type 5 inhibitors (PDE5-I) are an alternative to alpha-blockers when men experience bothersome side effects from alpha-blockers or erectile dysfunction. If patients predominantly have bladder storage symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of alpha-blocker plus muscarinic receptor antagonist is more efficacious in reducing LUTS than the single drugs alone. The 5 alpha-reductase inhibitors (5ARI) can significantly decrease LUTS and disease progression (e.g. acute urinary retention and need for prostate surgery) in men with larger prostates (> 30-40 ml). The combination of 5ARI plus alpha-blocker can reduce LUTS and disease progression more effectively than drug monotherapy. Combination therapy with PDE5-I (tadalafil) plus 5ARI (finasteride) reduces LUTS more substantially than 5ARI alone and, additionally, PDE5-Is reduce the sexual side effects during 5ARI treatment.

[S2e guideline of the German urologists: Conservative and pharmacologic treatment of benign prostatic hyperplasia]. / S2e-Leitlinie der Deutschen Urologen : Konservative und medikamentöse Therapie des benignen Prostatasyndroms.

This report summarizes the relevant aspects of the S2e guideline of the German Urologists for the conservative and pharmacological treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. Recommendations are given regarding watchful waiting, behavioral therapy, phytotherapy and pharmacological mono- and combination therapy. The influence of the different therapeutic options on bladder outlet obstruction (BOO) is described in detail.

[S2e guideline of the German urologists: Instrumental treatment of benign prostatic hyperplasia]. / S2e-Leitlinie der Deutschen Urologen : Instrumentelle Therapie des benignen Prostatasyndroms.

This report summarizes the relevant aspects of the S2e guideline of the German Urologists for the instrumental treatment of the lower urinary tract symptoms due to benign prostatic hyperplasia. Recommendations are given regarding open and transurethral procedures (TUR-P, bipolar TUR-P, TUI-P, HE-TUMT, TUNA, and the different Laser techniques). Recommendations are also given concerning intraprostatic stents and injection therapies. The influence of the different therapeutic options on bladder outlet obstruction (BOO) is described in detail.

Generation and purification of CD8+ melan-A-specific cytotoxic T lymphocytes for adoptive transfer in tumor immunotherapy.

Tumor antigens that might serve as potential targets for adoptive T-cell therapy have been defined in different tumor entities, especially in malignant melanoma. To generate conditions to induce primary T-cell responses against different HLA-A*0201-restricted melanoma peptides and to allow further expansion of peptide-specific T cells for adoptive transfer, CD8+-purified T cells from healthy donors were stimulated with Melan-A-pulsed autologous dendritic cells. Dendritic cells were generated in vitro from monocytes with granulocyte macrophage colony-stimulating factor, interleukin-4, and transforming growth factor-beta1. After 3-4 weekly stimulation cycles with Melan-A-pulsed DCs, we were able to induce a strong peptide-specific CTL response in vitro. MHC-peptide tetramer staining revealed a frequency of up to 3.5% CD8+/Melan-A+ T cells. Additional antigen-independent expansion with anti-CD3/anti-CD28 monoclonal antibodies together with interleukin-2 gave rise to 600-fold expansion of CD8+ CTLs that maintained Melan-A specificity and were able to efficiently lyse Melan-A-expressing melanoma cells. To enrich antigen-specific T cells in vitro, we used a recently established technology for analysis and sorting of live cells according to secreted cytokines. In the present study, we demonstrated that Melan-A-specific T cells can be purified by magnetic separation according to secreted IFN-gamma. These cells revealed a very potent monospecific CTL response, even at low E:T ratios, against Melan-A-pulsed and Melan-A-expressing target cells. Altogether, our study demonstrated that we have developed an efficient method for generating large numbers of peptide-specific T cells in vitro that may be used for adoptive T-cell transfer in tumor immunotherapy.

[Urinary incontinence in men]. / Harninkontinenz des Mannes.

Stress urinary incontinence in men is predominantly iatrogenic whereby radical prostatectomy is the most common cause with persistent stress urinary incontinence rates varying between 10 % and 25 %. The first line therapy for postoperative male stress urinary incontinence is physiotherapy, especially pelvic floor muscle rehabilitation. If conservative treatment fails to show sufficient improvement, surgical therapy is recommended. Several treatment options are currently available for the surgical treatment of male stress urinary incontinence including artificial sphincters, adjustable and functional sling systems, bulking agents and implantable balloon systems.

p53 overexpression as a prognostic factor for advanced stage bladder cancer.

Overexpression of the TP53 gene protein detected by immunohistochemistry appears to identify those patients with superficial bladder cancer at risk of the development of muscle invasive or metastatic disease. However, the role of p53 overexpression in patients with advanced or metastatic bladder cancer is not yet well established. In the present study, 44 specimens from 44 patients with advanced stage bladder tumours (T2-T4) undergoing radical cystectomy were investigated for different biological and clinical characteristics as possible prognostic factors: sex, age, depth of tumour infiltration, T-stage, histological grade, lymph node status, application of adjuvant systemic chemotherapy (MVAC), proliferative activity (staining for proliferating cell nuclear antigen (PCNA) by monoclonal antibody (PC10) as well as overexpression of the p53 oncoprotein (monoclonal antibody pAb 1801)). After a median follow-up of 22 months, 16 of the 23 patients (70%) with more than 40% of tumour cells stained positively for p53 (Group B) died from tumour progression compared with 7 of the 21 patients (33%) with less than 40% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.008), staining for PCNA (> or = 80% of cells positive) (P = 0.01) and tumour stage (P = 0.01) were significant prognostic factors for survival, among which p53 overexpression (P = 0.023) as well as T-stage (P = 0.012) remained independent significant predictors during multivariate analysis. Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with advanced bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for prognostically defined subgroups of patients.