ProPSA and the Prostate Health Index as predictive markers for aggressiveness in low-risk prostate cancer-results from an international multicenter study.

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 × âˆšPSA) 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.

Acquired undescended testes and fertility potential: is orchiopexy at diagnosis better than awaiting spontaneous descent?

The aim of this study was to evaluate testicular function in men with previous acquired undescended testis (UDT) in whom orchiopexy was performed at diagnosis compared with a similar group of men in whom spontaneous descent was awaited until puberty. Secondly, we examined the influence of age at orchiopexy on fertility parameters in adult life. A total of 169 men of the 'orchiopexy at diagnosis' group and 207 men of the 'wait and see' protocol group were invited for participation. All participants underwent an andrological evaluation, including medical history, physical examination, scrotal ultrasound, determination of reproductive hormones, and semen analysis. Results were compared for men in whom orchiopexy was performed at diagnoses with men in whom spontaneous descent was awaited until puberty followed by orchiopexy in case of non-descent. In the 'orchiopexy at diagnosis' group, 63 men of whom 14 with bilateral UDT, and in the 'wait and see' protocol group, 65 men of whom 15 with bilateral UDT were included. For unilateral UDT Inhibin B was found to be significantly lower and median progressive motility was higher in men with orchiopexy at diagnosis. For bilateral UDT, semen concentration and progressive motility showed a trend toward a favorable outcome for orchiopexy at diagnosis. Age at orchiopexy being under or above 10 years of age had no significant influence on the fertility potential. The outcome of physical examination, scrotal ultrasound, endocrine function, and semen analysis indicates a compromised fertility potential in men with previous acquired UDT. None of the protocols proved to be superior. For bilateral UDT, a trend toward favorable outcome of orchiopexy at diagnosis was seen. Furthermore, age at orchiopexy did not have an influence on fertility parameters. Therefore, in our opinion a 'conservative policy' is warranted for unilateral UDT, especially because over 50% of acquired UDT descend spontaneously.

Uptake of (18)F-fluoro-2-deoxyglucose in the Healthy Testes of Young Men as Assessed by Positron Emission Tomography/Computed Tomography; Including the Inter- and Intra-observer Variation.

Knowledge of the physiological testicular accumulation of (18)F-fluoro-2-deoxyglucose (FDG) is essential in order to discriminate between normal and pathological findings. In this study, the (18)F-FDG-uptake in healthy testes of young men was assessed using positron emission tomography/computed tomography (PET/CT)-scans. A total of 40 testes of 20 men with a mean age of 26.5 ± 3.9 years were evaluated. (18)F-FDG-uptake was expressed as the standardized uptake value (SUV). Testicular volume was measured on CT and PET. All scans were assessed by three researchers, one of whom assessed every scan twice. Laterality indices and inter- and intra-observer variation were evaluated. Correlation between the SUVmax and SUVpeak, between SUVmean and SUVpeak and between age and SUVpeak were assessed. Testes showed an average SUVmax of 3.42 ± 0.61, SUVpeak of 3.06 ± 0.54 and SUVmean of 2.44 ± 0.44. The average testicular volume on CT was 23.0 ± 6.4 ml, whereas on PET it was 18.0 ± 5.1 ml. Laterality indices were calculated of 0.077 ± 0.065 (SUVmax), 0.074 ± 0.066 (SUVpeak), 0.072 ± 0.063 (SUVmean), 0.245 ± 0.259 (CT), and 0.200 ± 0.188 (PET), respectively. Inter- and intra-observer reliability were found to be perfect for the SUVs (intraclass correlation coefficient [ICC] 0.992-1.0), but poor for testicular volumes (ICC 0.854-0.902). Testicular (18)F-FDG uptake in young men can be measured accurately on PET/CT and shows high symmetry. Consequently, (18)F-FDG PET/CT has the potential to become a useful instrument in the evaluation of the functioning of the individual testis.

Testicular microlithiasis in acquired undescended testis after orchidopexy at diagnosis.

The aim of this study was to observe the prevalence of testicular microlithiasis (TM) in surgically corrected acquired undescended testis (UDT). The prevalence of TM was assessed by ultrasound. Boys and young men who had undergone orchidopexy (ORP) for acquired UDT in mid or late childhood were observed to study the long-term testicular volume. During this examination, the presence or absence of TM was also assessed. TM was defined as echogenic foci without shadowing within the testis parenchyma. We included 106 patients who had undergone ORP at the Medical Center Alkmaar (1986-1999) and 155 patients who had undergone ORP at the Juliana Children's Hospital (1996-2009). The majority of patients were white, Caucasian (82%). The median age at follow-up, 25.8 years (range 14.0-31.6 years) was higher in Medical Center Alkmaar than in Juliana Children's Hospital 13.4 years (range 5.1-26.6 years). From 2009 to 2011, these 261 patients (median age 18.9 years) underwent an ultrasound examination. Median follow-up after ORP was 11.3 years (range 1.4-23.5 years); age at ORP ranged from 2.1 to 16.2 years, with a median of 8.5 years. TM was found in 17 (6.5%) patients (median age at follow-up 20.4 years; range 11-28). No significant association was found with the incidence of TM and the operated testis, the age at ORP or the racial variance (p > 0.05). ORP at diagnosis for acquired UDT is associated with a 6.5% prevalence of TM in boys and young adults.

Increased rate of positive biopsies using a combination of MR-Tomography, spectroscopy and diffusion-weighted magnetic resonance imaging prior to prostate biopsies in patients with persistent elevated prostate-specific antigen values: A retrospective analysis.

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.

[Health economics evaluation of magnetic resonance imaging for the staging of prostate cancer for Austria and Germany]. / Gesundheitsökonomische Evaluation der Magnetresonanzbildgebung im Staging von Prostatakarzinomen für Österreich und Deutschland.

PURPOSE: The aim of this study was the health economics analysis of MR imaging in the preoperative staging of patients with prostate carcinoma (PCa). MATERIALS AND METHODS: The health economics analysis consisted of the following steps: modeling, determination of probabilities and parameters based on a detailed literature search, evaluation using the averages of the parameters, and sensitivity analyses of the results over the ranges of values. We performed a cost-utility analysis from health insurance's perspective for Austria and Germany. The population under investigation included patients with confirmed PCa. The alternative was a decision for therapy with or without staging using MR imaging. A localized PCa was treated by prostatectomy and locally advanced PCa by radiation/hormone therapy. The result parameters were quality adjusted life years (QALYs) and costs per patient. RESULTS: The evaluation showed that MR imaging is useful regarding costs and utilities prior to radical prostatectomy which is expensive and may be associated with serious clinical consequences. The costs per patient were lower by € 2635 and the utilities were higher by 0.099 QALYs. The strategy without MR imaging for staging was dominated by the strategy using MR imaging for staging in the evaluation using the base values and in almost all sensitivity analyses. CONCLUSION: For the parameters used and almost all scenarios of the sensitivity analysis, our decision-analytic model revealed a higher cost-utility ratio for the strategy using MR imaging for the staging of PCa.

[Health-economic evaluation of magnetic resonance imaging before biopsy for diagnosis of prostate cancer]. / Gesundheitsökonomische Evaluation einer Magnetresonanzbildgebung vor Biopsie zur Diagnose von Prostatakarzinomen.

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.

Developmental changes and individual differences in risk and perspective taking in adolescence.

Despite the assumed prevalence of risk-taking behavior in adolescence, the laboratory evidence of risk taking remains scarce, and the individual variation poorly understood. Drawing from neuroscience studies, we tested whether risk and reward orientation are influenced by the perspective that adolescents take when making risky decisions. Perspective taking was manipulated by cuing participants prior to each choice whether the decision was made for "self," or from the perspective of an "other" (the experimenter in Experiment 1; a hypothetical peer in Experiment 2). In Experiment 1, we show a developmental decrease in risk-taking behavior across different stages of adolescence. In addition, all age groups made fewer risky choices for the experimenter, but the difference between self and other was larger in early adolescence. In Experiment 2, we show that high sensation-seeking (SS) adolescents make more risky choices than low SS adolescents, but both groups make a similar differentiation for other individuals (low risk-taking or high risk-taking peers). Together, the results show that younger adolescents and high SS adolescents make more risky choices for themselves, but can appreciate that others may make fewer risky choices. The developmental change toward more rational decisions versus emotional, impulsive decisions may reflect, in part, more efficient integration of others' perspectives into one's decision making. These developmental results are discussed regarding brain systems important for risk taking and perspective taking.

The ageing male reproductive tract.

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.

Human chorionic gonadotropin (hCG) in the male reproductive tract.

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 hCGalpha, hCGbeta and its metabolite hCGbeta core fragment (cf) in human testis, prostate and seminal plasma. Both organs synthesize hCGalpha and hCGbeta, which are subsequently detectable at high concentrations in seminal plasma of healthy probands (n=17): hCGalpha 2630+/-520 ng/mL (mean+/-S.E.M.), hCGbeta 2+/-0.28 ng/mL, hCGbetacf and hCG 0.19+/-0.039 ng/mL. These parameters significantly exceed physiological values, e.g. ten thousand-fold in the case of hCGalpha, in serum of young men (n=20): hCGalpha 0.142+/-0.054 ng/mL (mean+/-S.E.M.), hCGbeta 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 GPHalpha (M(r,app) 23k) 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 hCGalpha:hCGbeta:hCG in seminal plasma. hCGalpha is not derived from heterodimeric GPH suggesting hCG-independent functions of hCGalpha and hCGbeta in male and female fertility.

GAGEC1, a cancer/testis associated antigen family member, is a target of TGF-beta1 in age-related prostatic disease.

Transforming growth factor beta (TGF-beta) is a multi-functional cytokine that plays a fundamental role during embryonic development and tissue homeostasis in metazoans. Changes in TGF-beta 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-beta1 in primary prostatic stromal and epithelial cells. Our data suggest that disease-associated increases in TGF-beta1 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.

[Urinary tract injuries in polytraumatized patients]. / Verletzungen der ableitenden Harnwege bei polytraumatisierten Patienten.

BACKGROUND: Within the S3 Guideline Project of the European Association of Urology (EAU) an expert committee was set up to develop guidelines for the appropriate management of genitourinary trauma. These European guidelines were accepted in principle as national guidelines by the German Urological Society. Therefore, they also became the basis of the contribution of the German Urological Society to the S3 Guideline Project "Polytrauma" of the German Society for Trauma Surgery. METHOD: For the guideline "management of genitourinary trauma" all the requirements for classification as S3 guidelines were full-filled. The guideline itself was developed in accordance with the principles of "evidence-based medicine". A systematic analysis of literature published between 1966 and 2004 was carried out. The articles retrieved were assessed in respect of study design and clinical relevance and classified following the scheme of the Centre for Evidence-Based Medicine in Oxford. CONCLUSION: In suspected renal injuries the hemodynamic situation of the patient is the benchmark for the diagnostic and therapeutic algorithm. The diagnostic gold standard for the assessment of haemodynamically stable patients is CT scanning. Uncontrolled haemodynamic instability is an indication for immediate explorative laparotomy. Partial ureteral tears are managed by stenting; complete tears by immediate surgical repair. Pelvic fractures are often associated with bladder ruptures. Extraperitoneal bladder ruptures, identified by retrograde cystography, are in most cases safely managed by simple catheter drainage. Intraperitoneal ruptures require surgical intervention. Blood at the meatus may suggest a urethral lesion-blind urethral catheterization should not be attempted. Suprapubic cystostomy and delayed urethroplasty are recommended.

Relationship between testosterone serum levels and lifestyle in aging men.

OBJECTIVE: The aim of this study was to evaluate the association between serum levels of testosterone and free testosterone to lifestyle in aging males. METHODS: Men between 45 and 85 years were assessed regarding body mass index (BMI), nicotine and alcohol consumption, stress level, physical and social activity, and sleeping quality by a self-administered questionnaire. In parallel, serum levels of testosterone (T), free testosterone (fT), LH, FSH, DHEA-S, E2 and SHBG were obtained. RESULTS: In total, 375 men with a mean age of 59.9 years (9.2 +/- SD) entered this study; 25.4% and 27.4% had hypogonadal testosterone or free testosterone serum levels, respectively. Nicotine consumption (smokers had higher levels of T and fT; p < 0.01), BMI (negative correlation to T; p < 0.01) and age (negative correlation to fT; p < 0.001) correlated with serum levels of testosterone or free testosterone. Physical and social activity, nicotine and alcohol consumption, stress level and sleep quality did not show a significant association with serum androgen levels. CONCLUSION: This prospective study of 375 men aged 45 to 85 years confirms the correlation between age, BMI and smoking with serum levels of testosterone and free testosterone, whereas the investigated variety of lifestyle factors did not show a significant association to serum androgen levels.

The buccinator muscle: an original morphogenetical study.

The buccinator muscle, a cutaneous muscle derived from the second arc, is innervated by the facial nerve. It is made of 3 bundles extended into the cheek, from the pterygo-mandibular ligament to the modiolus. It is used for diverse buccal functions. This study attempts to give a better insight of the embryogenesis and the development of the muscle. After taking samples by microdissection under binocular microscope, of this region of embryos and foeti, we performed histological sections. They were then coloured by Masson's trichome for their observation under photon microscopy. From seventieth week we observed the presence of a peri-mucous mesenchyma between the cartilaginous condensation of the "pre premier arc" and Meckel's cartilage. The buccinator presents an insertion on the modiolus, sliding under the latter it runs forwards, it is at the origin of the formation of the orbicularis internus of the lips (musculus orbicularis oris). This muscle displaces its posterior insertion downwards, with the development of the face in the child and the adolescent, notably with the modification in vertical dimension due to the arrival of the deciduous teeth before the permanent dentition. Furthermore it appears that buccinator does not play a role as a sphincter in the secretion of the parotid glands.

TGF-beta cytokines increase senescence-associated beta-galactosidase activity in human prostate basal cells by supporting differentiation processes, but not cellular senescence.

The family of transforming growth factors betas (TGF-betas) comprises molecules involved in growth inhibition, stress-induced premature senescence, epithelial mesenchymal transition and differentiation processes. The aim of this study was to clarify the effect of long term exposure of human prostate basal cells to TGF-betas, which are found in high concentrations in prostatic fluid and areas of benign prostatic hyperplasia (BPH). Basal cell cultures established from prostate explants (n=3) were either grown into cellular senescence, or stimulated with TGF-beta1, beta2 and beta3. Similar to cellular senescence, TGF-beta stimulation resulted in an increase of SA-beta galactosidase (SA-beta-gal) activity, flattened and enlarged cell morphology, and down-regulation of the inhibitor of differentiation Id-1. TGF-beta-treated prostate epithelial cells neither showed terminal growth arrest nor induction of important senescence-relevant genes, such as p16(INK4A), IFI-6-16, IGFBP-3 or Dkk-3. Cells stained positive for cytokeratins 8/18, but did not express other lumenal markers, such as prostate-specific antigen and androgen-receptors. TGF-betas increased also the expression of the mesenchymal marker vimentin, indicating that basal epithelial cells underwent differentiation with lumenal and mesenchymal features. In contrast, in vitro-differentiated neuroendocrine-like cells from prostate organoide cultures, expressing chromogranin A and cytokeratin 18, strongly stained positive for SA-beta-gal. Thus, SA-beta-gal activity is not only a marker for senescence, but also for differentiation of human prostate epithelial cells. With regard to the in vivo situation, in addition to cellular senescence, TGF-beta could contribute to the increased number of SA-beta-gal positive epithelial cells in BPH.

Association of DHEA-S and estradiol serum levels to symptoms of aging men.

OBJECTIVES: A number of interactions between age-related changes in serum levels of dehydroepiandrostendione sulfate (DHEA-S) and estradiol and symptoms of aging men have been proposed, yet data regarding this issue are scant. We therefore set up a prospective study to analyze these associations. METHODS: In a prospective, cross-sectional study, men aged 45-85 years were recruited. All men completed a questionnaire containing 38 items covering a number of aspects of the aging male. Questionnaires were compiled by using items from previously published and validated questionnaires. Several socioeconomic parameters were also determined. In parallel, serum levels of testosterone, free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), DHEA-S, estradiol, sex hormone binding globulin and prostate-specific antigen (PSA) were quantified by commercially available immunoassays. RESULTS: A total of 375 men with a mean age of 59.9 +/- 9.2 years (mean +/- standard deviation) were analyzed. Average DHEA-S and estradiol levels of 135.8 +/- 90.9 micrograms/dl and 29.7 +/- 14.6 pg/ml, respectively, were recorded. DHEA-S serum levels were negatively correlated to patient age, sexual function score, total score and PSA. Estradiol serum levels were positively correlated to testosterone and free testosterone. None of the other scores or questions revealed a correlation with DHEA-S or estradiol serum levels. CONCLUSION: This prospective study elucidates only small interactions between partial androgen deficiency of the aging male (PADAM)-related symptoms and serum levels of DHEA-S and estradiol. Nevertheless, the data suggest an impact of DHEA-S on sexual function.

Seminal plasma factors induce in vitro PRL secretion in smooth muscle cells of the human prostate.

Next to the sex steroid hormone T, PRL has been shown to influence prostatic function and development. Transgenic mice overexpressing the rat PRL gene develop dramatic enlargements of the prostate gland. Proliferation and secretory activities of epithelial cells are stimulated by PRL in rodents and men. Low concentrations of human PRL (hPRL) and hPRL receptors have been observed in human prostatic epithelial cells (ECs). The aim of this study was to compare regulation of the in vitro hPRL secretion in prostatic ECs and stromal smooth muscle cells (SMCs) after stimulation with seminal plasma (SMP), containing a variety of prostatic factors. SMCs released up to 1 ng hPRL/ml (i.e., approximately 500-fold more than unstimulated SMCs and ECs). Quantification of PRL mRNA by highly sensitive quantitative RT-PCR revealed that hPRL gene expression increased 5-fold within 24 h of SMP incubation. Sex steroids (dihydrotestosterone, progesterone, 17beta-estradiol), prostaglandins (PGE-1, PGE-2), and cAMP-stimulating substances (forskolin) were not responsible for induction of hPRL. Compared with endometrial SMCs, regulation of prostatic hPRL secretion was independent of progesterone and cAMP. HPLC analysis of human SMP revealed that the common action of at least two different proteins and a low molecular cofactor is required. We concluded that prostatic ECs secrete proteins acting synergistically with low-molecular-weight cofactors to induce differentiation and hPRL release in SMCs. Age-related increases in SMC-derived hPRL might contribute to the development of benign hyperplasia of the prostate.

Efficacy and safety of thoracoscopic sympathicotomy for hyperhidrosis of the upper limb. Results of 734 sympathicotomies.

BACKGROUND: Thoracoscopic sympathicotomy (TS) evolved as treatment of choice in severe hyperhidrosis. The aim of this study was to assess the role of video-assistance in TS (VATS) versus conventional TS (CTS) for primary hyperhidrosis of the upper limb with regard to safety, side-effects and long-term outcome. METHODS: 734 TS were performed from below T1 to T4 in 406 patients. In the CTS and in the VATS group 558 and 176 procedures were performed, respectively. Follow-up was completed in 82% of all patients after a median observation period of 16 years. RESULTS: Dry limbs were immediately achieved in 92% (CTS) and 97% (VATS, p = 0.98). Only one patient (CTS) underwent conversion due to bleeding. In the CTS group Horner's syndrome occurred in 2.2% and rhinitis in 9.9% of procedures. No patient of the VATS group experienced Horner's syndrome (p = 0.025), 3 patients developed rhinitis (p = 0.11). At follow-up compensatory sweating was observed in 67.6% vs. 55.6% (p = 0.051) and gustatory sweating in 50.4% and 33.3% (p = 0.01). There were 5 failures or recurrences (1.9%) in the CTS group and 2 (2.8; p > 0.05) in the VATS group at reevaluation. Overall 6.5% (CTS) and 5.6% (VATS) of patients regret the operation (p = 0.7). CONCLUSIONS: We observed a significant decrease of the incidence of complete or incomplete Horner's syndrome and gustatory sweating when the procedure was guided by video-imaging while success rate was similar when compared with CTS.

Pilot study on liposomal recombinant human superoxide dismutase for the treatment of Peyronie's disease.

OBJECTIVE: To assess the efficacy and safety of liposomally encapsulated recombinant human superoxide dismutase (lrhSOD) for the treatment of Peyronie's disease. METHODS: In an uncontrolled phase-2 study, 20 patients with Peyronie's disease were treated with a gel containing lrhSOD (1.5 mg/g). Patients with penile deviation of >45 degrees or plaque calcifications of >5 mm were regarded as candidates for surgical correction and excluded from this study. RESULTS: Elimination of pain was observed in 7/13 patients (in 2 patients after only 3 days of therapy), and an almost complete resolution of pain was reported by the remaining 6/13 patients. Plaque size was reduced in 8/14 patients. Minimal improvement of penile deviation was observed in 3/12 patients. Post-therapeutic improvement of sexual function, mainly due to cessation of pain, was reported by 12/15 patients. No systemic or local side effects were observed. CONCLUSION: In the present study, 100% pain relief as well as a plaque size reduction in 56% of Peyronie's disease patients were observed after a maximum of 6 weeks of lrhSOD therapy. The convenience and safety of lrhSOD gel therapy were superior compared to other current regimens. The present results suggest that lrhSOD gel is a promising treatment for patients with early stage Peyronie's disease. Early institution of lrhSOD therapy may prevent disease progression to penile deviation. The present preliminary results are the basis of a placebo-controlled randomized study.

Long-term followup after laparoscopic nephropexy for symptomatic nephroptosis.

PURPOSE: Symptomatic nephroptosis is a rare disease requiring surgical therapy only in select cases. Laparoscopic nephropexy has been reported as minimally invasive treatment for symptomatic patients. We evaluated our long-term outcome after laparoscopic fixation of the kidney with an alloplastic mesh graft. MATERIALS AND METHODS: Since 1992, 30 patients have undergone laparoscopic transperitoneal nephropexy for symptomatic nephroptosis. All patients were preoperatively investigated by excretory urography (IVP) and split renal scan in the supine and upright positions. For fixing the kidney to the abdominal wall a polyglactin and polypropylene mesh graft was used in 6 and 24 cases, respectively. A total of 17 patients with a minimum followup of 5 years participated in an assessment of long-term outcome. Clinical examination, IVP and split renal function testing were performed with patients lying and standing. Patients were further questioned about postoperative satisfaction and whether they would undergo the procedure again. RESULTS: Of 17 patients 10 completed all investigations, 3 were contacted by telephone and 4 were lost to followup. Median followup was 5.9 years. Improvement in symptoms was reported in all cases with complete relief in 11 and intermittent flank pain requiring no medication in 2. There were no postoperative urinary tract infections or hematuria observed with improved hypertension requiring no postoperative medication in 1 case. Postoperatively IVP showed no recurrence in 8 of 10 patients but there was 5 cm. or greater recurrent ptosis in 2. Recurrence developed after using the polyglactin and polypropylene mesh grafts. Comparing preoperative and postoperative (123)iodine renal scans revealed significant improvement in renal function in 9 cases (p <0.05). There was no postoperative difference in split renal function and only 1 patient did not improve. No complications were noted except 1 symptomatic recurrence 3 months after the initial operation that required open surgical fixation. A total of 11 patients were completely satisfied with the long-term outcome and 2 were moderately satisfied. Of the patients 12 would undergo the procedure again, including 2 with persistent slight flank pain. One patient was inconsistent in regard to whether she would undergo the procedure again. CONCLUSIONS: Symptomatic nephroptosis is a bothersome disease requiring therapy only after thorough evaluation, including IVP and split renal scan with patients supine and upright. The good clinical outcome and highly satisfactory cosmetic result support laparoscopic nephropexy as the treatment of choice. Short-term and long-term results prove the efficacy of renal fixation with alloplastic mesh graft as minimally invasive therapy with a high success rate.