Correction to: The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.

The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

PURPOSE: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. METHODS: A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. RESULTS: With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. CONCLUSIONS: Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.

Gender reassignment surgery--a 13 year review of surgical outcomes.

PURPOSE: The aim of this study is to thoroughly report on surgical outcomes from 332 patients who underwent male to female gender reassignment surgery (GRS). MATERIAL AND METHODS: Records from 332 patients who underwent GRS from 1995 to 2008 were reviewed. All patients were submitted to penile inversion vaginoplasty with glans-derived sensate clitoroplasty. Mean age was 36.7 years (range 19-68 years). Surgical complications were stratified in 5 main groups: genital region, urinary tract, gastrointestinal events, wound healing disorders and unspecific events. RESULTS: Progressive obstructive voiding disorder due to meatal stenosis was the main complication observed in 40% of the patients, feasibly corrected during the second setting. Stricture recurrence was found in 15%. Stricture of vaginal introitus was observed in 15% of the cases followed by 12% and 8% of vaginal stenosis and lost of vaginal depth, respectively. Rectal injury was seen in 3% and minor wound healing disorders in 33% of the subjects. CONCLUSION: Regarding male to female GRS, a review of the current literature demonstrated scarce description of complications and their treatment options. These findings motivated a review of our surgical outcomes. Results showed a great number of adverse events, although functionality preserved. Comparision of our outcomes with recent publications additionally showed that treatment options provide satisfying results. Moreover, outcomes reaffirm penile inversion vaginoplasty in combination with glans-derived sensate clitoroplasty as a safe technique. Nevertheless, discussing and improving surgical techniques in order to reduce complications and their influence on patient's quality of life is still strongly necessary and theme of our future reports.

Lack of association of the genotype in the GNAS Fok I polymorphism and prostate cancer.

BACKGROUND: G proteins are ubiquitously expressed signal transduction proteins playing a key role in multiple signal transduction pathways. The Gαs subunit has been considered as an apoptosis factor. In this study the role of GNAS T393C genotypes of the GNAS gene encoding Gαs was analyzed for its influence on the development and progression of prostate cancer. METHODS: Genotyping of the GNAS T393C polymorphism in 196 prostate cancer patients and 200 healthy controls was performed by DNA extraction followed by PCR and restriction analysis. RESULTS: We observed no evidence of effects related to GNAS T393C genotype as demonstrated by a comparison of the genotype distribution in prostate cancer patients and healthy controls, the genotype distribution dependent on grade of the primary diagnosis or data on clinical follow-up. CONCLUSIONS: In conclusion, this study did not demonstrate an association between the GNAS T393C genotype and prostate cancer though such a relationship has been described for other cancer entities.

The Zeiss-loop stone extraction: minimal invasive and effective or obsolete?

PURPOSE: Through the introduction of ureterorenoscopy (URS) and extracorporal shock wave lithotripsy (ESWL) into stone treatment, the Zeiss-loop procedure has lost more and more its importance. Current guidelines recommend on the level of an expert-opinion, that stone extraction without endoscopic-visual control should not be performed anymore. Nevertheless, stone extraction using the Zeiss-loop is still being performed in our clinic and therefore we wanted to determine its position in stone treatment in the age of URS and ESWL. METHODS: The data of 253 patients with ureter stones, who were treated with the Zeiss-loop were evaluated. The loop is always pulled through completely under radiological control. RESULTS: In 221 cases, the concrement was located in the distal ureter. All concrements have been maximally 10 mm in size. Independently of size and position, in 219 patients the loop extraction resulted in a complete stone removal. Complication rates are low. No complete tear-off of the ureter occurred. The overall success rates of loop extraction were superior to those of ESWL in ureter stones but worse than URS. Referring to distal stones, success rates are similar, but stones treated by URS have been bigger. CONCLUSIONS: Therefore, in our opinion, immediate stone extraction under fluoroscopic control with the Zeiss-loop, is still a possible treatment alternative for small distal stones (<10 mm). Being aware of these first "new" data of an old procedure, the Zeiss-loop will still play a role in endoscopic stone treatment in our department and should not be completely abandoned due to its bad reputation.

Genetic association study of the GNB3 C825T, the ACE I/D and the eNOS G894T polymorphisms and the risk to develop erectile dysfunction in a German ED population.

Erectile dysfunction (ED) is often associated with cardiovascular disorders such as hypertension, coronary heart disease, hypercholesterolaemia and diabetes mellitus. The genotypes in the GNB3 C825T, the ACE I/D and the eNOS G894T polymorphisms have been identified as genetic risk factors for cardiovascular disorders. The association between the genotypes in these polymorphisms and the risk to develop ED was analysed. In 455 German ED patients and 111 age-matched healthy controls genotyping in the candidate polymorphisms was performed after DNA extraction from whole blood. Association studies between the genotype distribution in the control group in comparison with the ED-group and age of onset of the disease as well as erectile response to intracorporal prostaglandin injection in dependence of candidate polymorphism genotype were performed using the SPSS-Software(R). Genotype distribution of the GNB3 C825T, the ACE I/D and the eNOS G894T polymorphisms was similar in the ED population and the healthy control group. The age of onset of the disease as well as the erectile response to intracorporal prostaglandin injection was independent of the genotypes in the three candidate polymorphisms. In contrast to the previous studies in this analysis, the risk to develop ED is not influenced by the genotypes in the GNB3 C825T, the ACE I/D and the eNOS G894T polymorphisms.

[Treatment mapping of lower urinary tract symptoms due to benign prostatic hyperplasia-an analysis of the Governing Body of German Prostate Centers]. / Versorgungsabbild des benignen Prostatasyndroms ­ eine Analyse des Dachverbandes der Prostatazentren Deutschlands (DVPZ) e. V.

BACKGROUND: Due to the high incidence and demographic development, there is an urgent need for healthcare research data on lower urinary tract symptoms due to benign prostatic hyperplasia (LTUS/BPH). Since 2005 the Governing Body of German Prostate Centers (DVPZ) has been collecting data from 22 prostate centers in order to determine the quality and type of cross-sectoral care in particular for LUTS/BPH patients. OBJECTIVES: Presentation of the DVPZ database in general, as well as an investigation of treatment patterns for medical and instrumental therapies. MATERIALS AND METHODS: The analysis is based on UroCloud data sets from 30 November 2017. In the UroCloud data on diagnostics, therapy and course of disease are recorded in a web-based manner. RESULTS: A total of 29,555 therapies were documented for 18,299 patients (1.6/patient), divided into 48.5% instrumental, 29.2% medical treatment, and 18.0% "wait and see" (in 4.3% no assignment was possible). Patients treated with an instrumental therapy were oldest (median: 72 years, interquartile range: 66-77), had the largest prostate volumes (50 ml, 35-75 ml), and were mostly bothered by symptoms (International Prostate Symptom Score = 19/4). The majority of patients under medical treatment received alphablockers (56%); phytotherapeutics were used least frequently (3%). Instrumental therapies are dominated by transurethral resection (TUR) of the prostate (60.0%), open prostatectomy (9.4%) and laser therapy (5.0%), with laser therapy having the shortest hospital stay (5 days) and the lowest transfusion and re-intervention rates (1.0% and 4.6%, respectively). CONCLUSIONS: The DVPZ certificate covers the complete spectrum of cross-sectoral care for LUTS/BPH patients and documents the use of the various therapies as well as their application and effectiveness in the daily routine setting.

Epac inhibits migration and proliferation of human prostate carcinoma cells.

BACKGROUND: It was recently found that cAMP mediates protein kinase A-independent effects through Epac proteins. The aim of this study was to investigate the role of Epac in migration and proliferation of prostate carcinoma cells. METHODS: The effect of Epac activation was determined by [(3)H]thymidine incorporation and scratch assays in PC-3 and DU 145 cells. Furthermore, cytoskeletal integrity was analysed by phalloidin staining. The participation of intracellular Epac effectors such as mitogen-activated protein (MAP) kinases, Rap1- and Rho-GTPases was determined by immunoblotting and pull-down assay. RESULTS: The specific Epac activator 8-pCPT-2'-O-Me-cAMP (8-pCPT) interfered with cytoskeletal integrity, reduced DNA synthesis, and migration. Although 8-pCPT activated Rap1, it inhibited MAP kinase signalling and RhoA activation. These findings were translated into functional effects such as inhibition of mitogenesis, cytoskeletal integrity, and migration. CONCLUSION: In human prostate carcinoma cells, Epac inhibits proliferative and migratory responses likely because of inhibition of MAP kinase and RhoA signalling pathways. Therefore, Epac might represent an attractive therapeutic target in the treatment of prostate cancer.

The f/t-PSA ratio in diagnosis of in-patients and out-patients: a unitary cutoff value is not useful!

PURPOSE: In the prostate specific antigen (PSA) range of 4-10 ng/ml after a negative digital rectal examination, the PSA value indicates a lack of specificity with a carcinoma detection rate of roughly 20%. To improve the biopsy/carcinoma ratio, the interdisciplinary consensus recommends free PSA (fPSA) measurement. This does not take into account the pre-analysis when the cutoff value is established for biopsy indication. METHODS: In the present study, an in-patient cohort whose blood samples were immediately analysed was compared with an out-patient cohort whose sample processing was delayed by between 24 and 48 h. RESULTS: The in-patient cohort comprises 382 patients with 99 prostate carcinomas, the out-patient cohort 987 patients with 235 carcinomas. In the in-patient cohort a sensitivity of 90% with a cutoff value of 25% for the f/t-PSA ratios is achieved with the theoretical possibility of reducing the number of punch biopsies by 34.6%. A sensitivity of 90% in the out-patient cohort necessitates a cutoff value of 18% for the f/t-PSA ratios. The specificity is 35.3% with a possible biopsy reduction of 29.1%. CONCLUSIONS: The cutoff values from cohorts with an immediate fPSA measurement cannot be adopted for a typical out-patient cohort whose analyses are delayed. On the contrary, an individual adjustment is necessary which corresponds to the pre-analysis.

[Single base polymorphisms and erectile dysfunction]. / Einzelbasenpaarpolymorphismen und erektile Dysfunktion.

The risk for erectile dysfunction is closely linked to cardiovascular morbidities such as coronary heart disease, arterial hypertension, hypercholesterolemia, and diabetes. Molecular analysis revealed an association between the genotypes in single base polymorphisms and the risk for these cardiovascular morbidities. In this review the current knowledge of association studies of single nucleotide polymorphisms and erectile dysfunction and the response to the PDE-5 inhibitor sildenafil is described.

[Value of targeted therapy for prostate cancer]. / Der Stellenwert der Targeted-Therapie beim Prostatakarzinom.

Prostate cancer is the most frequent malignancy of the male population. Every year in Germany approximately 12,000 patients die of their hormone-refractory prostate cancer even though early detection is able to find more curable prostate cancers. In a hormone-refractory stage we only have limited options for treatment. Although docetaxel is currently the standard of care in most hormone-refractory prostate cancers, it is not the magic therapy that will dramatically change the patient's poor survival. This drug provides an overall survival advantage of 2 months. During recent years, significant progress has been made in the field of molecular therapy in urologic oncology. Targeted therapy leads to an inhibition of angiogenesis and proliferation in malignant tumors. Even if there is a great theoretical potential, mono- and combination therapies with target substances are not relevant in the clinical routine.

[Targeted therapy for metastatic bladder cancer]. / Targeted-Therapie des metastasierten Urothelkarzinoms.

The current therapy concept for metastatic bladder cancer is chemotherapy with gemcitabine and cisplatin as the first line protocol. Within the last 20 years no real progress could be achieved; the median survival is 14 months, though many different protocols have been tested. Expression analyses of growth factor receptors in human tumor tissue showed that expression of certain receptors is correlated with a severe clinical course.For many of these growth factor receptors pharmacological inhibitors are available in order to perform targeted therapy. The following review gives a survey of current studies on targeted therapy of metastatic bladder carcinoma.

[From marker expression to individual therapy of patients with bladder cancer]. / Von der Markerexpression zur individuellen Prognoseabschätzung urothelialer Neoplasien.

Urothelial carcinoma of the bladder is a tumor entity with a heterogenous clinical course. At one end of the spectrum, patients are treated for low-grade carcinomas, which are likely to reccur but show low rates of tumor progression. At the other end, patients suffer from noninvasive or early invasive high-grade carcinomas. In these cases, risk-adapted treatment decisions are more complicated. The following article gives an overview of research activities on bladder cancer with the aim to individualize treatment of patients with bladder cancer.

Insertion/deletion polymorphism in the promoter of NFKB1 as a potential molecular marker for the risk of recurrence in superficial bladder cancer.

OBJECTIVE: Bladder cancer is a leading cause of morbidity and mortality. Despite intensive research efforts, histopathological diagnosis of grade and stage, the most important markers for predicting the outcome of the disease, is still necessary. Therefore, a new candidate gene was investigated with regard to its potential utility as a prognostic marker for the course of disease in bladder cancer. A functional insertion/deletion polymorphism has recently been identified in the promoter region of NFKB1 which regulates transcription of the transcription factor NF-kappaB. Several genes involved in oncogenic processes are controlled by NF-kappaB and might be influenced by alterations in its expression. MATERIAL AND METHODS: Genotype distributions in patients with bladder cancer (n = 242), in a subgroup consisting only of patients with superficial bladder cancer (n = 101, stage pTa and pT1) and in a group of healthy control subjects (n = 307) were determined using pyrosequencing. The results were compared and the relationship between genotype and survival, and genotype and first recurrence were determined. NFKB1 expression was assessed using native tumor tissue and quantitative real-time PCR. RESULTS: No statistically significant differences in genotype frequency between healthy controls and patients were detected. Survival was not dependent on the genotype of the polymorphism. Nevertheless, time to first recurrence differed significantly between genotypes (p = 0.037) and this difference could be ascribed to the patients with superficial tumors (p = 0.013). Moreover, multivariate analysis showed that this promoter variant was an independent risk factor. The risk of recurrence in patients with superficial tumors and the homozygous deletion was higher (HR 2.86, p = 0.005) than in those with the homozygous insertion. NFKB1 mRNA expression was highest in tumors from patients carrying the homozygous insertion genotype (p = 0.038). CONCLUSION: These results suggest that the NFKB1 promoter polymorphism is a useful marker for the identification of patients with superficial bladder cancer where the risk of recurrence is high.

[Inductive systemic therapy of urological tumors with curative intent]. / Induktive Systemtherapie mit kurativer Zielsetzung urologischer Tumoren.

Up to now systemic therapy with curative intent is possible in only a few tumors. Concerning advanced malignant tumors in urology only testicular cancer can be cured. In metastatic urothelial cancer of the bladder this might be possible in single cases. In advanced renal cell carcinoma a recent group of new substances, so-called target-specific substances, have gained attention. In several phase III studies with sunitinib, sorafenib, and temsirolimus at least progression-free survival could be clearly prolonged. The amazing results in testicular cancer were possible by consistent performance of clinical trials. The success in treatment also is an example for interdisciplinarity. Especially in advanced stages treatment consists of two components, chemotherapy, correctly performed concerning dose and interval, followed by complete residual tumor resection.

[Palliative therapy concepts for patients with urothelial cancer of the urinary bladder]. / Palliative Therapiekonzepte bei Patienten mit Urothelkarzinom der Harnblase.

Urothelial carcinoma usually occurs in older patients. At initial diagnosis, about 30% of all patients show muscle invasive tumor growth or metastases. Due to their advanced clinical stage, palliative therapy concepts become more and more interesting. Gross and intractable hematuria can be treated with special bladder irrigation or selective arterial embolization. Hydronephrosis can be treated in the long-term with self-expanding memotherm stents. Palliative pelvic radiation is still controversial.

[Testicular perfusion injury. Cytokines and cell adhesion molecules in humans]. / Testikuläre Ischämie. Verlauf von Zytokinen und Zelladhäsionsmolekülen beim Menschen.

BACKGROUND: Ischemia and reperfusion (I/R) lead to cellular damage. A disturbance of testicular perfusion occurs during the therapy of cryptorchidism and in cases of testicular torsion. This results in the activation of mediator cells with an increasing synthesis of mediators of infection like TNF-alpha and the expression of cell adhesion molecules like ICAM (intercellular adhesion molecule) and VCAM (vascular cell adhesion molecule) at the cellular surface. METHODS: The expression of the cytokines IL-10 and TNF-alpha and the adhesion molecules ICAM and VCAM after defined testicular I/R injury in nine male transsexuals was evaluated with rt-PCR. Furthermore we examined lactate and the diameter of the testicular tubulus under ischemic conditions. RESULTS: During ischemia ICAM, IL-10, and VCAM do not show significant changes on the side of testicular ischemia and the contralateral side; the same was seen for the tubulus diameter. TNF-alpha and the testicular lactate values showed a significant change of the expression pattern. DISCUSSION: The statistical changes of TNF-alpha and testicular lactate are the expression of leukocyte migration, infectious reaction, and immune response. To what extent the TNF-alpha expression represents a severe immunological reaction remains undefined. This human study shows primary results for the immunological understanding of and cellular response to testicular ischemia.

[Does cigarette smoking influence the survival of patients with prostate cancer?]. / Beeinflusst Rauchen das Uberleben von Prostatakarzinompatienten?

In the last few years, prostate cancer has become one of the most common causes of mortality worldwide. It is therefore important to detect possible risk factors for this malignant disease. Besides risk factors which increase incidence, attention should be paid to factors which have a possible influence on the course of the disease. In our analysis, we demonstrate a worse course for the disease in patients with prostate cancer who smoked cigarettes at the time of first diagnosis. In spite of comparable staging, grading and PSA values at the time of primary diagnosis, individuals who smoked had a threefold higher risk of dying from prostate cancer. This effect is probably caused by metabolic changes which are activated by cigarette smoking and promote tumor growth and the development of metastases.

[The management of cutaneous metastases]. / Management kutaner Metastasen.

Cutaneous metastases are rare and usually signify a poor prognosis. The manifestation of cutaneous metastases is variable; crucial to their diagnosis is their inclusion in the differential diagnosis. The therapy occurs mostly with palliative intention. The quality of life of the patient should take first priority. A combination chemotherapy is usually carried out because of systemic progress. For local tumor control and wound care, metastasis surgery and radiotherapy are used.

[Prevention of osteoporosis--important for the urologist?]. / Prävention der Osteoporose--wichtig für den Urologen?

Osteoporosis is a systemic disease of the bones with increasing incidence in the elderly. Over the age of 50 years bone mineral density continuously decreases resulting in osteoporotic fracture. Osteoporosis is positively correlated with late-onset hypogonadism and increases under androgen deprivation therapy. The evaluation of osteoporosis should be done in cooperation with an endocrinologist. Measurement of bone mineral density is recommended before starting androgen deprivation therapy. Patients with fracture and/or decreased bone mineral density 2.5 or more standard deviations below normal peak bone mass of young men should be treated. The appropriate treatment is calcium and vitamin D substitution combined with oral or i.v. administration of bisphosphonates.