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Introduction Aside from the neurotransmitters of the sympathetic adrenergic system, vasoconstrictor peptides may also play a role in mediating the constant tone of the erectile tissue during penile flaccidity and in returning the erect penis to the flaccid state. Neuropeptide Y (NPY) is present in high concentrations in the male genital tract. The peptide has been shown to induce contraction of isolated human penile tissue (corpus cavernosum, penile arteries) and potentiate its response to noradrenaline. Objective The purpose of our study was to measure in the cavernous and systemic blood of healthy male volunteers the course of NPY through different stages of sexual arousal. Methods Whole blood was drawn from the corpus cavernosum and the cubital vein of 15 healthy male volunteers during penile flaccidity (Fl), tumescence (Tu), rigidity (Ri) and detumescence (Det). Penile tumescence and erection were induced by applying audiovisual and tactile stimulation. Plasma levels of NPY (given in pmol/L) were determined by means of an enzyme-linked immunoassay (ELISA, IBL GmbH, Hamburg, Germany). Results NPY significantly decreased in the cavernous blood with the beginning of sexual arousal, when the flaccid penis became tumescent and finally rigid (Fl: 88.8 ± 35.8, Tu: 62.4 ± 22.7, Ri: 62.3 ± 19.7). In the phase of detumescence, only a slight increase was noted (64.8 ± 23). In the systemic circulation, no pronounced alterations in the concentration of NPY were registered through the different penile stages (Fl: 64.4 ± 27, Tu: 65.8 ± 19, Ri: 59.6-25, Det: 67.6 ± 29.3). Conclusions Our findings are in favor of the hypothesis that NPY could contribute to the maintenance of the resting state of cavernous smooth muscle. It remains to be elucidated whether the peptide may play a role in the pathophysiology of erectile dysfunction. Disclosure No

Background Long-term remission can be achieved by surgery in patients with metastatic renal cell carcinoma (mRCC), without chronic toxicity due to systemic treatment. Data on metastasectomy are mostly based on observations of metachronous metastasis. However, it is unclear whether patients with synchronous oligometastasis may also benefit from surgery alone as an alternative to highly effective systemic treatment combined with resection of the primary tumor. Materials and methods The authors performed an unstructured literature search in PubMed including systematic reviews and meta-analyses. Results are discussed in regard of the current data and clinical practice. Results and discussion Although there is no uniform definition for oligometastasis in mRCC, cytoreductive nephrectomy in selected patients seems to be mandatory before metastasectomy is performed in primary oligometastatic RCC. In particular, in those patients with oligometastasis of the lung, bone, central nervous system, liver, adrenal gland, and thyroid, metastasectomy appears to be an important therapeutic option. Ultimately, among the therapeutic options, surgery is also an important therapeutic approach in primary oligometastatic mRCC. A balanced consideration between surgery, other local therapies, and modern systemic treatment demands interdisciplinary decision-making that takes into account the patients' preference.

Long-term remission can be achieved by surgery in patients with metastatic renal cell carcinoma (mRCC), without chronic toxicity due to systemic treatment. Data on metastasectomy are mostly based on observations of metachronous metastasis. However, it is unclear whether patients with synchronous oligometastasis may also benefit from surgery alone as an alternative to highly effective systemic treatment combined with resection of the primary tumor.The authors performed an unstructured literature search in PubMed including systematic reviews and meta-analyses. Results are discussed in regard of the current data and clinical practice.Although there is no uniform definition for oligometastasis in mRCC, cytoreductive nephrectomy in selected patients seems to be mandatory before metastasectomy is performed in primary oligometastatic RCC. In particular, in those patients with oligometastasis of the lung, bone, central nervous system, liver, adrenal gland, and thyroid, metastasectomy appears to be an important therapeutic option. Ultimately, among the therapeutic options, surgery is also an important therapeutic approach in primary oligometastatic mRCC. A balanced consideration between surgery, other local therapies, and modern systemic treatment demands interdisciplinary decision-making that takes into account the patients' preference.HINTERGRUND: Es existieren vielfache Hinweise auf den kurativen Effekt der Resektion sich metachron entwickelnder Metastasen beim Nierenzellkarzinom (NZK) als Alternative zur Systemtherapie. Hier stellt sich die Frage, ob auch Patienten mit primär oligometastasiertem NZK von einem rein chirurgischen Behandlungskonzept als Alternative zu einer mit einer Resektion des Primärtumortumors kombinierten hocheffektiven systemischen Behandlung profitieren können.Es erfolgte eine unstrukturierte Literaturrecherche in PubMed und die Bewertung der Publikationen, inklusive systemischer Reviews und Metaanalysen durch die Autoren. Die Arbeiten wurden in den klinischen Kontext gesetzt. ERGEBNISSE UND DISKUSSION: Beim NZK existiert keine einheitliche Definition einer Oligometastasierung. Daten zur Metastasektomie, die häufig gute Langzeitergebnisse beschreiben, beziehen sich oftmals auf die metachrone Metastasierung. So oder so gilt es in der primären Oligometastasierung, die vorherige zytoreduktive Nephrektomie kritisch zu evaluieren. Bei Metastasierung in Lunge, Knochen, zentralem Nervensystem (ZNS), Leber, Nebenniere und Schilddrüse scheint eine primär chirurgische Strategie in der primär oligometastasierten Situation eine wichtige Therapiesäule darstellen zu können. Die systemischen Kombinationstherapien haben bei der primären Behandlung einer Oligometastasierung im Vergleich zum primär chirurgischen Vorgehen bei einem ideal definierten Patienten noch keine „prime time“, dies könnte sich je nach Verfügbarkeit randomisierter Studien möglicherweise ändern. Gegenwärtig kann die therapeutische Entscheidung nur aus einem v. a. auch die Patientenpräferenz berücksichtigenden multidisziplinären Konsens resultieren.

In the present paper the aluminum alloys EN AW-6082 (peak-aged and overaged) and EN AW-5083 (solution annealed) were investigated regarding the long fatigue crack growth behavior in the range of very low amplitudes and therefore very high number of load cycles. The cracks were initiated at micro notches, prepared by means of focused ion beam technology and examined in situ by a long distance microscope. In first experiments the threshold for each material condition was defined. Subsequently the tests were carried out at constant ΔK values. Further analysis such as electron backscatter diffraction (EBSD) and confocal microscopy were executed to analyze the fatigue crack growth behavior. A microstructural barrier function of the primary precipitates could be detected for each material condition. Grain boundaries seem to influence the crack growth only in case of the work hardening alloy (EN AW-5083), which is the material with smaller average grain size compared to EN AW-6082.

Self-concept consists of self-perceptions and is influenced by the life course of the person.This study investigated associations between self-concept and erectile dysfunction (ED) in 45-year-old German men.Forty-five-year-old, heterosexual men who had participated in the PROBASE-study were included. Erectile Function was evaluated using the International Index of Erectile Function (IIEF-6). The presence of ED was defined by IIEF-6 score ≤ 25. Self-concept was assessed using the facets "body image" (three items from the Dresden Body Image Inventory, DKB-35), "perception of masculinity" (three items from the Male Role Norms Scale, MRNS), "perceived social pressure with regard to sexual performance" (four newly constructed items), and "sexual self-esteem" (three newly constructed items). Scores for these facets of self-concept can range from 1 to 5. Higher scores indicate a more positive body image, higher sexual self-esteem, a more modern understanding of masculinity, and greater perceived social pressure. Differences in self-concept between men with ED and without ED were analyzed using the Mann-Whitney-U-test. Furthermore, Cohen's d effect sizes (ES d) were calculated.The responses of 3143 men were analyzed. Men with ED (16.2 %) have significantly lower scores regarding body image (mean 3.6 ± 0.6 vs 3.8 ± 0.5; p 0.001; ES d = -0.5), perception of masculinity (mean 3.4 ± 0.7 vs 3.7 ± 0.6; p 0.001; ES d = -0.4), and sexual self-esteem (mean 3.6 ± 0.6 vs 3.9 ± 0.5; p 0.001, ES d = -0.4) than men without ED. Furthermore, they had significantly higher scores for perceived social pressure (mean 2.1 ± 0.7 vs 1.5 ± 0.5; p 0.001; ES d = 1.2).Self-concept and ED are associated in 45-year-old men. Men with ED have a more negative body image, a more traditional understanding of masculinity, more negative sexual self-esteem, and greater perceived social pressure with regard to sexual performance than men without ED.

Follow-up of patients after curative treatment of urological cancer is an important component of the treatment of patients. The aim of the follow-up is to monitor the success of treatment and to identify local or distant recurrences early to be able to initiate further treatment. Investigations used for the monitoring should follow the principle "as much as necessary, as little as possible". The interval and method of follow-up investigations should be based on the risk of recurrence for the individual patient. In recent years follow-up schemes have been improved and, for example in testicular cancer, have been adjusted to the individual risk group. In contrast, for other tumors, such as metastatic bladder carcinoma, recommendations for follow-up do not seem to be individualized. This article therefore gives an overview on current recommendations and evidence for the follow-up of the most important genitourinary tumor types.

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception

Although histamine has been suggested to be involved in the control of male sexual function, including the induction of penile erection, its role in the human corpus cavernosum penis is still poorly understood. The aim of our study was to evaluate the course of histamine plasma levels through different stages of sexual arousal in the systemic and cavernous blood of healthy male subjects. Thirty four (34) healthy men were exposed to erotic stimuli to elicit penile erection. Blood was aspirated from the corpus cavernosum and a cubital vein during the penile conditions flaccidity, tumescence, rigidity and detumescence. Blood was also collected in the post-ejaculatory period. Plasma levels of histamine (ng ml(-1)) were determined by means of a radioimmunoassay. Histamine slightly decreased in the cavernous blood when the penis became tumescent. During rigidity, histamine decreased further but remained unaltered in the phase of detumescence and after ejaculation. In the systemic circulation, no alterations were observed with the initiation or termination of penile erection, whereas a significant drop was registered following ejaculation. Results are not in favour of the hypothesis of an excitatory role of histamine in the control of penile erection. Nevertheless, the amine might mediate biological events during the post-ejaculatory period.

Lysosomal proteases may be involved in facilitating cancer invasion and metastatic spread by degradation of basement membranes and intercellular matrix. Overexpression of cathepsin D, a lysosomal aspartyl protease, has been reported in different tumours and seems to constitute a prognostic factor for survival in patients with breast cancer. The current study investigates immunohistochemical staining using anti-cathepsin D monoclonal antobodies (M1G8) in prostate cancer specimens and tissue from patients with benign prostatic hyperplasia (BPH). Among 41 tumours expression of cathepsin D was observed in 14 of 26 (54%) low stage and grade tumours (T-1-2/G(1-2)) and in 12 of 15 (86%) high stage and grade tumours (T-3, G(3)). Cathepsin D positivity was found within the cytoplasm and at the surface of tumour cells localized in glandular structures and in single cells invading the prostatic stroma, while no staining was observed in normal prostatic tissue and in mesenchymal cells. Two of ten specimens from patients with benign prostatic hyperplasia showed a weakly positive staining reaction within glandular structures. The clinical course of localized prostate cancer appears to be highly variable and the different treatment strategies (radical prostatectomy, radiation therapy or surveillance) have come under debate. For the determination of the biological aggressiveness of prostate cancer in the individual patient easily available biological prognostic factors are needed. This report demonstrates overexpression of cathepsin D in prostate cancer specimens with increasing frequency in patients with tumours of high grade and stage. The usefulness of cathepsin D immunohistochemistry as a prognostic factor should be prospectively evaluated.

Leydig cell tumours constitute 1-2% of all testicular cancers and only 10% of patients with Leydig cell tumours will develop metastatic disease. They are considered refractory to chemo- and radiotherapy. The management of metastatic disease and the effects of systemic therapy have only been described in case reports. We report on four patients with metastic Leydig cell tumours, one of which was accompanied with excess sex hormone production. One patient was rendered tumour free by the surgical resection of retroperitoneal lymph nodes. and remains without recurrence for 10+ months. The other three patients received systemic treatment due to inoperable metastatic disease. One patient with progressive abdominal and supraclavicular lymph node metastases achieved a minor remission after 4 cycles of cisplatin-based chemotherapy, lasting for ten months. A second response to carboplatin-based chemotherapy was achieved in this patient at progression. The other two patients died 9 and 21 months after diagnosis of metastatic disease and never responded to chemotherapy. A review of the different treatment options for metastatic Leydig cell tumours is given. Surgery, which might include the resection of retroperitoneal lymph nodes or solitary pulmonary metastases, seems to be the only curative modality. Radiotherapy has apparently no effect and responses to systemic chemo- or hormonal therapy are infrequent and usually of short duration.

In a prospective study, results of the extracorporeal shock wave lithotripsy (ESWL™) of salivary stones were evaluated. The study was performed with the currently available technical aid of electromagnetic systems to produce indication criteria for this particular procedure. With accurate sonographical localization a therapeutical outcome with complete emission of the concrement or an adequate disintegration of these stones was achieved in 100% of the parotid gland stones and in 29% of the sub-mandibular gland stones. Considering the risks of parotid surgery we see an absolute indication for lithotripsy in stones localized distally from the masseter banding of the parotid duct. Due to the low rate of success and the comparatively low risk connected with surgical therapy, the indication regarding concrement formations must be more critically viewed in the outlet path system of the submandibular gland. At present the lack of clinical symptoms observed following lithotripsy does not give any bearing on long-...

Patients with metastatic renal cell carcinoma have a life-limiting prognosis. Therefore, the aim of therapy is normally palliative care. Nevertheless, substantial achievements have been made in the past years. Cytokines as long-term standard therapy have been replaced by new targeted therapies. Sunitinib, the combination of bevacizumab+interferon-alfa, pazopanib and temsirolimus are now approved for first-line therapy. Sunitinib and pazopanib can also be administered as second-line options - for pazopanib the use is restricted to the event of cytokine failure. Everolimus (after TKI therapy) und sorafenib (after cytokines) are other compounds now available for second-line therapy. In addition, axitinib was approved for second-line therapy after failure of sunitinib or cytokines. For questions regarding the optimal sequence, first study results are now available from the phase III trial.The purpose of an interdisciplinary expert meeting held in 2014 was to debate about which criteria should influence the therapy decision. The members discussed several aspects of treating patients with the disease. Results from the 2012 conference provided the basis for the 2014 meeting 1. As in previous years, the experts intended to provide common recommendations for clinical practice. The results of the 2012 conference are presented as short theses and a current therapy algorithm.

Minimally invasive percutaneous nephrolithopaxy (MIP) was developed to combine the excellent stone-free rates of the conventional percutaneous nephrolithopaxy (PCNL) technique with the low morbidity of the miniaturized PCNL (Mini-Perc) and, at the same time, achieve a high level of patient comfort. The procedure is characterized not only by the diameter of the miniaturized 18-Fr Amplatz sheath that was adopted from the Mini-Perc but also by the following features: ultrasound-guided puncture of the kidney; single-step dilatation of the access tract; ballistic lithotripsy; a low-pressure irrigation system together with stone retraction by irrigation with a specially designed nephroscope sheath, for the so-called vacuum cleaner effect; and a sealed and tubeless access tract with primary closure of the channel independent of hemorrhage and without a second-look procedure.The results of the first 57 patients demonstrate primary stone-free rates of 92.9% with operating times averaging 62 (25-123) min. Severe complications, such as sepsis or bleeding requiring blood transfusion, did not occur. The high and predictable stone-free rate and a low morbidity comparable to that of ureteroscopy and extracorporeal shock-wave lithotripsy make MIP an attractive option for patients and urologists. The "vacuum cleaner effect" with quick removal of stone fragments reduces operating time and prevents new stone formation by avoiding residual fragments. The direct and primary closure of the access tract increases patient comfort and is justified by the reintervention rate of less than 8% in the presented cohort.The lack of a need for second-look nephroscopies, the vacuum cleaner effect, improved patient comfort without nephrostomy tubes, as well as surgery times comparable to that of traditional PCNL demonstrate a consequent evolution of the Mini-Perc. MIP therefore represents a promising and future-oriented module in modern stone therapy.

After sufficient oncological treatment of prostate cancer the life quality becomes most important. A multi disciplinary research network aims to optimize the diagnostics and the resulting treatment of prostate cancer.Main characteristics of the interdisciplinary cooperation are the interlocked individual projects. A major research field is investigation of the whole mounted prostate sections to study the peripheral nerves and the comparison of histological tumor locations with the MRI. Using serial sections of prostate specimens, three-dimensional computer-animated models are created illustrating the tumors histological and immunohistochemical distributions. For nodal staging, a new methodology is investigated to demonstrate single tumor cells in lymphatic tissue lysates. A retrospective evaluation of life quality including the functional outcome is performed by using questionnaire surveys.Anatomical studies gave new insights into the exact localizations of peripheral nerves which may lead to an improvement of the surgical approach in nerve-sparing radical prostatectomy. For the preoperative planning the MRI imaging might need a different interpretation in relation to the topographic location. Studies using molecular markers and their relation and distribution patterns gave new insights regarding interpretation of histological biopsy results concerning the tumor extension. Numerical quantification of tumor cells in each lymph node demonstrated micro metastases in histological negative nodes contributing to the nodal staging. A close connection of the nerve-sparing technique was demonstrated with quality of life aspects and functional results.An interdisciplinary approach is mandatory for translational prostate cancer research. As a result, individualized diagnostic and therapeutic approaches improve oncological results and at the same time provide the best quality of life in these patients.

Due to the chemoresistance of renal cell cancer, cytokine-based therapeutic approaches were considered the standard treatment for patients with metastatic disease. At present, data that are available from a few phase II/III studies, dealing both with the first- and second-line treatment of patients suffering from systemic progression of RCC, indicate the significantly higher clinical efficacy of multikinase inhibitors when compared with cytokine-based therapeutic regimens. In this context, sorafenib (Nexavar, BAY 43-9006) and sunitinib (Sutent, SU 011248) are the most frequently applied and most intensively investigated substances. In Germany, with regard to a phase III study reported at the ASCO congress in 2006, sunitinib received approval for the first-line therapy of metastatic RCC. The application of multikinase inhibitors follows the principle of targeting such mediators that are considered to be substantially involved in the pathogenesis and particularly progression of renal cell cancer within relatively well-defined molecular pathways. The aim of the present paper is to address and to critically discuss the clinical data that are currently available regarding the therapeutic efficacy of kinase inhibitors during the treatment of metastatic RCC.

Systemic treatment of advanced-stage adrenal malignancies is most often only palliative. Mitotane alone or in combination with other chemotherapeutic agents such as cisplatin, etoposide, and vincristine are established therapeutic concepts for the treatment of metastatic adrenal cancer. Suramin and gossypol are rarely employed. New therapeutic options are tumor vaccination and treatment with antiangiogenic drugs. Metaiodobenzylguanidine as a radiotherapeutic drug or chemotherapeutic combination therapies that include cyclophosphamide, vincristine, and dacarbazine are applied for systemic treatment of malignant pheochromocytomas.. However, the clinical efficacy of the latter regimen needs further evaluation.

The expression of the negative cell cycle regulator p27For analysis of p27In univariate survival analysis, decreased expression of p27Our analysis demonstrated that p27

The expression of the negative cell cycle regulator p27(Kip1) is frequently found to be deregulated in various human cancer types. Whether expression of p27(Kip1) can be used as prognostically relevant biological variables for renal cell cancer patients still remains to be clarified. Therefore, in the present investigation the expression within different tissue areas obtained from renal cell carcinomas was determined.For analysis of p27(Kip1) in 420 tumor nephrectomy specimens obtained from 420 consecutively included patients, tissue microarrays were used comprising of 1,260 tissue samples each obtained from the tumor itself, the invasive front as well as non-malignant surrounding parenchyma. A sufficient follow-up after surgical therapy was available in 251 cases.In univariate survival analysis, decreased expression of p27(Kip1) within tissue cores obtained from the invasion front was significantly correlated with the patients' disease-specific long-term survival (p = 0.02, log-rank test). In contrast, expression of p27(Kip1) protein within the primary tumors was not identified to reveal any prognostically important information. In Cox regression analysis, histological stage and grade (p0.01), the presence of regional lymph node (p0.01) or distant metastases at the time of surgery (p0.01) as well as decreased expression of p27(Kip1) (p = 0.04) within the invasion front tissue samples independently predicted the disease-specific long-term survival following surgery.Our analysis demonstrated that p27(Kip1) is heterogeneously expressed in renal cell carcinomas. Moreover, the result of the present study supports the prognostic value of p27(Kip1) protein expression for patients diagnosed with renal cell carcinoma.

First results of a study about the efficacy of magnetic resonance-(MR-)guided radiofrequency ablation of renal cell carcinomas (RCC) are presented.Eight patients (63 to 82 years old) with RCC up to 3.9 cm in diameter were treated by percutaneous RF ablation under MR-guidance in an open MR scanner at 0.2T field strength. For positioning of the RF-electrode, fluoroscopic rapid gradient echo sequences (acquisition time about 2 sec) were used. The ablation was monitored by intermittent imaging with T1- and T2-weighted spin echo sequences.In each patient, the applicator was successfully positioned within the tumor using MR-guidance. Seven of eight patients were completely treated within one single session; one patient had to be retreated for tumor relapse at 13 months. The mean number of electrode repositionings under MR guidance for complete ablation was 2.0; ablation time ranged between 12 and 28 minutes. Maximum diameter (volume) of induced coagulation necrosis within one session was 3.9 cm (30.2 cm (3)) by using cluster electrodes. With single electrodes, maximum short axis diameter of coagulation without repositioning was 2.4 cm (11.6 cm (3)). All patients are now disease-free after a mean follow up of 13 months (5 to 21 months). No major complications occurred during or after the ablation procedure.MR-guided RF ablation in an open interventional 0.2T MR-unit is a safe and effective modality for the treatment of RCC. Fast MR-imaging is a convenient method for exact positioning of MR-compatible RF-electrodes. Near on-line MR-monitoring of ablation procedure with T2-weighted imaging allows for immediate assessment of the coagulation extent.

In the case of an insufficient response to primary treatment or a tumor relapse, regardless of an initially complete remission, conventional as well as high dose chemotherapy regimens are available as salvage therapy for metastatic germ cell tumors. A multimodal approach should include the radiation of simultaneously occurring brain metastases as well as the surgical resection of residual tumour masses still detectable after completion of chemotherapy. Nowadays, an attempt is made to adjust the salvage modality selected to the individual situation according to a risk stratification of patients. However, a recurrence-free survival of 50% is worse when compared with that observed after primary chemotherapy. Salvage therapy should be reserved for specialized centres due to the increased complexity of a salvage approach and a significantly increased therapy-induced morbidity.

Traditionally, oncological factors have been the only ones used in the evaluation of treatment outcome for urological tumor patients. With increased diagnoses of early, curable tumors in younger individuals, health-related quality of life and functional aspects are gaining importance. Sexual and urinary function are significant aspects of quality of life, which are especially vulnerable in urological patients. New insights into the anatomy and physiology of the pelvic organs have resulted in an improvement in surgical therapy. In this article, we present the results of current experimental and clinical studies, which underline the importance of nerve sparing techniques for maintaining a satisfying urinary and sexual function in this patient population.

As a result of the observation that the potential biological aggressiveness of even early stage renal cell cancer (RCC) strongly correlates with tumor size, the 5th edition of the TNM system (1997), which classifies all renal tumors up to a maximum diameter of 7 cm as T1, was modified in the current classification to distinguish T1a and T1b tumors based on a cut-off of 4 cm. Only a few larger investigations supporting this cut-off are available in the literature and these are based on univariate statistical analysis. To determine whether this cut-off best reflects the correlation between aggressive potential and tumor size and thus differentiates patients at low or high risk of progression, this investigation was performed using both univariate and multivariate statistical analysis.Between 1981 and 2000, a total of 652 patients underwent tumor nephrectomy for renal cell carcinoma. Of these, the 243 patients with local RCC not extending beyond the renal capsule were subjected to univariate (log rank test) and multivariate (Cox regression model) statistical analysis.It became evident that, while during univariate analysis the prognostic calue of a cut-off size of 4 cm was confirmed, multivariate analysis identified the highest relative risk of cause-specific death (2.93) in those patients with tumors larger than 5 cm maximum diameter.The 5 cm cut-off thus appears to best determine the clinical prognosis for patients undergoing tumor nephrectomy for early stage renal call cancer. Taking this into consideration, the present study clearly demonstrates the reed for a multivariate statistical approach when the current modification of the TNM classification system is critically reevaluated.

Since in the absence of clinically overt metastatic disease tumorous lesions within the adrenal gland are found in only 2-10% of cases, the majority of renal cell cancer patients are overtreated by adrenalectomy as an integral part of nephrectomy. The medical records of 847 patients undergoing adrenalectomy in combination with nephrectomy irrespective of the local extent of the primary tumor or the clinical stage at first diagnosis were reviewed to determine the reliability of currently available imaging modalities regarding the prediction of adrenal gland metastases. Several patient and tumor characteristics correlated with the presence of intra-adrenal metastases, and their prognostic value was determined by a multivariate logistic regression model. Metastatic spread into the adrenal gland was observed in 27 of 847 (3%) patients. In only three of eight patients in whom the adrenal was identified as the only metastatic site, preoperative abdominal CT scans were interpreted as false negative. During multivariate statistical analysis, only the presence of distant metastases, vascular invasion within the primary tumor, and multifocal growth of renal cell cancer within the tumor-bearing kidney were identified to independently predict the likelihood for the presence of intra-adrenal metastases. None of the patient or tumor characteristics evaluated reliably predicted the likelihood for the presence of adrenal metastases in patients without evidence of disseminated metastatic spread. As we believe and as the current investigation demonstrates, routine adrenalectomy should not be recommended in cases of preoperatively normal radiological examinations.

P53 regulated maspin protein expression determines recurrence-free survival of patients with localised prostate cancer

To further clarify the need for routine adrenalectomy during the surgical treatment of renal cell cancer, as in the absence of clinically overt metastatic disease, tumorous lesions within the adrenal gland are found in only 2-10% of patients, with most being over-treated by adrenalectomy.The medical records of 819 patients undergoing adrenalectomy combined with nephrectomy, irrespective of the local extension of the primary tumour or the clinical stage at first diagnosis, were reviewed to determine the reliability of currently available imaging methods in predicting adrenal gland metastases. Several patient and tumour characteristics were correlated with the presence of intra-adrenal metastases, and their possible independent prognostic value was determined by a multivariate logistic regression model.There was metastatic spread into the adrenal gland in 27 of 819 (3.3%) patients. In only three of eight patients in whom the adrenal was identified as the only metastatic site were preoperative abdominal computed tomography scans interpreted as false-negative. On multivariate statistical analysis only the presence of distant metastases, vascular invasion within the primary tumour and multifocal growth of renal cell cancer within the tumour-bearing kidney were identified as independent predictors of the presence of intra-adrenal metastases.None of the patient or tumour characteristics evaluated reliably predicted the likelihood of adrenal metastases in patients with no evidence of disseminated metastatic spread. However, previously published data indicate that the frequency of metachronous metastases within the contralateral kidney (1.8-3.8%) is significantly higher than the risk of a preoperatively undetected isolated intra-adrenal metastatic lesion when currently available imaging modalities are applied. Therefore, routine adrenalectomy should not be recommended if the preoperative radiological examinations are normal.

Das Harnblasenkarzinom ist ein haufig diagnostizierter maligner Tumor mit einer weltweit ansteigenden Neuerkrankungsrate. Wahrend die globale Inzidenz mit 261.000 angenommen wird, versterben jahrlich etwa 115.000 Menschen an dieser Erkrankung [43].

Die Diagnose „Interstitielle Zystitis“ wurde in den letzten Jahren zunehmend fur einen Symptomenkomplex mit irritativer Miktionssymptomatik und chronischem Schmerz in der Blasenregion verwendet. Da aber besonders die initialen Symptome haufig eher unspezifisch sind, wird auch heute die Erkrankung wiederholt verkannt und als chronisch — bakterielle Zystitis, „Urethrales Syndrom“, Trigonitis, pseudomembranose Trigonitis, Prostatitis, Prostatodynie oder subvesikale Blasenobstruktion fehlinterpretiert. Die Tatsache, dass neueste Untersuchungen zur Inzidenz und Praevalenz der Interstitiellen Zystitis belegen, dass die statistischen Zahlen nach oben korrigiert werden mussen, hat zu einer stetigen Zunahme der Berichte uber wissenschaftliche Untersuchungen zur Klarung der Atiologie und Pathogenese sowie der Therapieoptionen der Erkrankung gefuhrt. Da sich das vorliegende Buch insbesondere als Therapieleitfaden fur den praktisch tatigen Urologen versteht, sollen auch in diesem Kapitel schwerpunktmasig die aktuell existierenden Behandlungsmoglichkeiten dieses komplexen Krankheitsbildes dargestellt werden. Dabei mus ausdrucklich darauf hingewiesen werden, dass es sich bei der Mehrzahl der bisher berichteten medikamentosen Behandlungsformen um experimentelle Therapieansatze handelt, die noch nicht in validierten klinischen Studien gepruft wurden.

The p21WAF/Cip and the p27Kip1 genes have been identified as inductors of cell cycle arrest at the G1-checkpoint. Alterations of both genes have been suggested to be involved in the development of a variety of human malignancies due to a loss of critical antiproliferative mechanisms. To evaluate the prognostic importance of these alterations for patients with clinically localized prostate cancer, in 86 specimens (T1-T4) from 86 patients undergoing radical prostatectomy at the Department of Urology at Hannover University Medical School, were investigated. The immunohistochemical expression of the p27Kip1 and p21WAF/Cip protein was correlated to recurrence-free and long-term survival, age, depth of tumour infiltration, histological grade and lymph node status in these patients. After a median follow-up of 71 months (1-198 months), 14 of 20 (70%) patients (Group 1) with loss of p27Kip1 protein expression or a relative amount of10% of positively stained tumour cells developed recurrent disease in contrast to 18 of 66 (27%) patients (Group 2) with retained p27Kip1 protein expression (or = 10% of positively stained tumour cells). The median recurrence-free survival times were 39 (4-134) months and 67 (4-198) months for patients in Groups 1 and 2 (p0.01), respectively. In multivariate analysis, loss of p27Kip1 protein expression was identified as the only independent prognostic parameter for recurrence-free survival. Univariate analysis (log-rank test) identified histological grading (p0.01) and reactivity for p27Kip1 (p = 0.046) (or = 10% positivity) as prognostic factors for disease-specific long-term survival. However, during multivariate analysis none of the biological variables investigated retained independent prognostic importance regarding overall survival. Neither a low or a high expression of p21Waf/Cip could be correlated with the clinical prognosis of the patients following radical prostatectomy. This study confirms the independent prognostic value of decreased p27Kip1 protein expression in patients with localized prostate cancer, while a prognostic importance of p21Waf/Cip in addition to established patients' and tumour characteristics like tumour stage and histological grading appears rather unlikely.

An "Interdisciplinary Consensus Statement on the Diagnosis and Therapy of Testicular Tumors" was prepared in 1996 by the "Interdisciplinary Testicular Tumor Working Group" (IAH) with input from representatives from diagnostic and therapeutic disciplines of various working groups of the German Cancer Society (Strahlenther Onkol 1997;173:397-406). In 1998 the IAH met again together with the "Testicular Tumor Working Party" of the Urooncology Working Group (AUO) and formed the "German Testicular Cancer Study Group" (GTCSG). Defined and accepted interdisciplinary standards from the initial meeting were revised based on current scientific developments and clinical results. This cooperating effort increased the quality of the initial recommendations and helped to put the recommendations for diagnosing and treating testicular tumor on a broader scientific basis.According to the principles of "evidence-based medicine" (EBM), the Consensus from 1996 was modified, based on the current level of evidence from the published literature. The methodological process and evaluation criteria used were that of the "Cochrane Collaboration".An "Interdisciplinary Update Consensus Statement" summarizes and defines the diagnostic and therapeutic standards according to the current scientific practices in testicular cancer. For 21 separate areas scientifically based decision criteria are suggested. For treatment areas where more than one option exist without a consensus being reached for a preferred strategy, such as in seminoma in clinical Stage I or in non-seminoma Stages CS I or CS IIA/B, all acceptable alternative strategies with their respective advantages and disadvantages are presented. This "Interdisciplinary Update Consensus" was presented at the 24th National Congress of the German Cancer Society on March 21st and subsequently evaluated and approved by the various German scientific medical societies.

Since it is difficult to predict the probability of persistent teratoma or of a viable tumor in patients with normalized tumor markers and a normal CT scan following chemotherapy for advanced stage testis cancer, recommendations regarding adjunctive surgery have ranged from observation to surgical exploration for all patients. Suggested variables for patients in whom surgery can be omitted safely, include normal post-chemotherapy CT scans, residual abdominal masses of less than 1.5 cm, a 90% or greater decrease in the volume of the retroperitoneal mass with chemotherapy and no teratomatous elements in the orchiectomy specimen. In contrast, during several investigations, the application of the above mentioned criteria resulted in a false-negative prediction of approximately 20%. However, recognizing the morbidity of the operative procedure itself in addition to the fact that only 2-4% of patients will develop recurrent tumor confined to the retroperitoneal space that can then be managed surgically or by administration of further chemotherapy, secondary surgery should be avoided if a sufficient follow-up after chemotherapy is guaranteed. The extent of adjunctive surgery in patients revealing a residual tumor mass after first-line chemotherapy remains a subject of ongoing discussions. It has been indicated that extensive retroperitoneal surgery after chemotherapy is associated with significant clinical morbidity. A limitation of post-chemotherapy surgery to a resection of the residual mass with or without an additional modified template dissection appears to result in an acceptable frequency of retroperitoneal recurrences and a decreased complication rate.

Risk factor analysis to identify low-risk patients for occult metastatic disease (vascular invasion, percentage embryonal carcinoma, MIB-I proliferation rate) yields reliable results if performed by experts. A correct prediction is possible at the 90% level. Similar accuracy, however, may be achieved if the computed tomography (CT) staging is optimized and the evaluation performed by an experienced investigator. The combination of both methods (biological risk factor analysis and CT staging) may virtually exclude the risk of relapse in a limited number of patients. However, so far, no risk factor that is able to reliably predict occult metastatic disease or relapse in clinical state I patients has been identified in prospective trials. The preliminary results of the current German Multicenter Trial suggest an inferior value of prediction for low-risk patients if risk factor analysis and/or CT staging is performed in non-specialized centers.

The observation of extremely variable clinical courses for patients with renal cell carcinomas of an identical pathological stage as well as a comparable histological differentiation resp. growth pattern strongly indicates the existence of tumors harboring different biological aggressiveness. Currently available histopathological classification systems do not predict the biological behaviour of renal cell cancer as sufficiently as the establishment of a therapeutical strategy adjusted to the individual patient would require. The need for a more refined characterization of the biological potential of the individual tumor results from the introduction of modified operative strategies as organ-preserving surgery, for example, as well as from the recently suggested application of an adjuvant systemic therapy adapted to the individual risk for tumor recurrence resp. the development of progressive disease. Therefore, the clinically orientated basic scientist and the basic scientifically orientated clinician intensively try to determine prognostically important biological variables which would allow to better predict the biological aggressiveness of a single tumor in addition to "classical" prognostic parameters (T-stage, histological grading, growth patterns). In this context, several biological parameters including the identification of alterations on the DNA-, RNA- and protein level have been discussed as possible biological prognostic markers for renal cell cancer. The present review tries to reflect currently available biological characteristics of RCC which might gain clinical importance with regard to an individualized therapy in the near future.

In approximately 4-10 % of patients presenting with renal cell cancer the transluminal propagation of a tumor thrombus into the vena cava inferior or the right atrium comes to diagnosis. Recent investigations have indicated that the presence of neoplastic extension into the venous system does not reveal independent prognostic value regarding the clinical course of the disease. Although the complete surgical removal of vena cava thrombosis in patients without simultaneously occurring regional lymph node or distant metastases has become a well established treatment modality, several questions concerning this surgical strategy still remain the subject of ongoing discussions. In the present investigation that included 92 patients with renal cell cancer and intracaval neoplastic extension it was clearly demonstrated that the use of cardiopulmonary bypass, deep hypothermia and circulatory arrest preferably during the removal of intracaval thrombosis extending into the right atrium does not result in a substantially increased treatment-related intra- or postoperative mortality. However, in contrast to a previously reported observation this treatment option did not reveal any substantial impact on the long-term survival of the patients following surgical therapy. Accordingly, the cranial extension of intracaval thrombosis was not identified as a biological variable of any prognostic importance for renal cell cancer patients.