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Ziel dieser prospektiven Studie ist es, die Faktoren zu ermitteln, die bei Patienten nach Therapie eines Prostatakarzinom ohne Verdacht auf ein Tumorrezidiv die Langzeitlebensqualitat (HRQoL) beeinflussen. Es wurden epidemiologische, onkologischen Daten sowie Fragebogen zur Inkontinenz und Sexualitat mit Methoden der deskriptiven und explorativen Statistik ausgewertet. Von 488 Patienten lagen pratherapeutische und Daten nach 36 Monaten vor. Ausgeschlossen wurden 162 Patienten (33,2%), bei denen nach den Richtlinien der EAU oder wegen Unvollstandigkeit der Daten ein Rezidiv nicht ausgeschlossen werden konnte. In einer univariaten Analyse waren Belastungsinkontinenz, „lower urinary tract symptoms“ (LUTS), „overactive bladder“ (OAB), Drangsymptomatik, Vorlagengebrauch und sexuelle Aktivitat sowie Selbsteinschatzung der pratherapeutischen Lebensqualitat, ein hoherer Schulabschluss und der Versicherungsstatus auf einem Signifikanzniveau

The location of stem cells in the epithelium of the prostatic acinus remains uncertain, as does the cellular origin of prostatic neoplasia. Here, we apply lineage tracing to visualize the clonal progeny of stem cells in benign and malignant human prostates and understand the clonal architecture of this epithelium. Cells deficient for the mitochondrially-encoded enzyme cytochrome c oxidase (CCO) were identified in 27 frozen prostatectomy specimens using dual colour enzyme histochemistry and individual CCO-normal and -deficient cell areas were laser-capture microdissected. PCR-sequencing of the entire mitochondrial genome (mtDNA) of cells from CCO-deficient areas found to share mtDNA mutations not present in adjacent CCO-normal cells, thus proving a clonal origin. Immunohistochemistry was performed to visualize the three cell lineages normally present in the prostatic epithelium. Entire CCO-deficient acini, and part-deficient acini were found. Deficient patches spanned either basal or luminal cells, but sometimes also both epithelial cell types in normal, hyperplastic or atrophic epithelium, and prostatic intraepithelial neoplasia (PIN). Patches comprising both PIN and invasive cancer were observed. Each cell area within a CCO-deficient patch contained an identical mtDNA mutation, defining the patch as a clonal unit. CCO-deficient patches in benign epithelium contained basal, luminal and endocrine cells, demonstrating multilineage differentiation and therefore the presence of a stem cell. Our results demonstrate that the normal, atrophic, hypertrophic and atypical (PIN) epithelium of human prostate contains stem cell-derived clonal units that actively replenish the epithelium during ageing. These deficient areas usually included the basal compartment indicating the basal layer as the location of the stem cell. Importantly, single clonal units comprised both PIN and invasive cancer, supporting PIN as the pre-invasive lesion for prostate cancer.

Little is known about the clonal architecture of human urothelium. It is likely that urothelial stem cells reside within the basal epithelial layer, yet lineage tracing from a single stem cell as a means to show the presence of a urothelial stem cell has never been performed. Here, we identify clonally related cell areas within human bladder mucosa in order to visualize epithelial fields maintained by a single founder/stem cell. Sixteen frozen cystectomy specimens were serially sectioned. Patches of cells deficient for the mitochondrially encoded enzyme cytochrome c oxidase (CCO) were identified using dual-colour enzyme histochemistry. To show that these patches represent clonal proliferations, small CCO-proficient and -deficient areas were individually laser-capture microdissected and the entire mitochondrial genome (mtDNA) in each area was PCR amplified and sequenced to identify mtDNA mutations. Immunohistochemistry was performed for the different cell layers of the urothelium and adjacent mesenchyme. CCO-deficient patches could be observed in normal urothelium of all cystectomy specimens. The two-dimensional length of these negative patches varied from 2-3 cells (about 30 µm) to 4.7 mm. Each cell area within a CCO-deficient patch contained an identical somatic mtDNA mutation, indicating that the patch was a clonal unit. Patches contained all the mature cell differentiation stages present in the urothelium, suggesting the presence of a stem cell. Our results demonstrate that the normal mucosa of human bladder contains stem cell-derived clonal units that actively replenish the urothelium during ageing. The size of the clonal unit attributable to each stem cell was broadly distributed, suggesting replacement of one stem cell clone by another.

Introduction: Only few studies comparing treatment outcome for patients with localized prostate cancer control their results for the possible confounding of demographic and clinical parameters. This fact prompted us to compare epidemiological data of patients before receiving brachytherapy (BT) to patients envisaged for radical prostatectomy (RP). Methodology: We looked at demographic and clinical data as well as standardized questionnaires for 856 patients. In a logistic regression analysis parameters proven to be significantly different in a university analysis were further analyzed. Results: Data of 676 patients (79%) could be evaluated. Patients before radical prostatectomy (RPP) scored best in physical functioning, role functioning and sexual activity. Patients planned for low-dose rate brachytherapy (LDR) indicated the biggest problems in partnership and sexuality. The health insurance status was not equally distributed. However, in a logistic regression analysis of patients envisaged for surgical treatment only age and physical functioning could be identified as independent factors that differ significantly between treatment groups (p

Contexto: la aparición de nuevos datos relacionados con el diagnóstico y tratamiento de cáncer vesical músculo-invasivo y metastásico (CaV-MiM) ha obligado a una actualización de las Guías sobre el CaV-MiM de la Asociación Europea de Urología (EAU). Objetivo: revisión de las nuevas guías de la EAU para el CAV-MiM. Evidencia adquirida: un grupo de urólogos, oncólogos y radiólogos designados por el Comité de Guías Clínicas de la EAU ha realizado un exhaustivo trabajo de revisión de la literatura procedente de Medline, el registro central Cochrane de revisiones sistemáticas y las citas bibliográficas de publicaciones y artículos de revisión. Se han tenido en cuenta las recomendaciones basadas en la literatura previa disponible sobre este aspecto. Además, han sido añadidos niveles de evidencia y grados de recomendación, según las modificaciones del Oxford Centre for Evidence-based Medicine. Evidencia sintetizada: el diagnóstico de cáncer vesical músculo-invasivo (CaVMI) se realiza mediante la resección transuretral y el consiguiente estudio histopatológico. Una vez confirmada la existencia de CaVMI es preciso realizar el estadiaje mediante tomografía computarizada toraco-abdómino-pélvica, si se dispone de ella. Actualmente, la quimioterapia adyuvante solamente se recomienda en el contexto de ensayos clínicos. La cistectomía radical es el tratamiento de elección en ambos sexos, y la linfadenectomía debe constituir una parte integral de la misma. Tanto a hombres como a mujeres se les debe ofrecer la sustitución vesical ortotópica siempre que no existan contraindicaciones, tales como la existencia de tumor en el margen uretral. En la actualidad, los tratamientos multimodales para la conservación vesical en casos de enfermedad localizada constituyen un alternativa terapéutica solamente en pacientes seleccionados, adecuadamente informados, y en aquellos en los que se desestima la cistectomía por motivos clínicos o personales. Los protocolos de seguimiento deben diseñarse sobre la base de: a) historia natural de la recurrencia; b) probabilidades de recurrencia; c) deterioro funcional en localizaciones específicas; y d) consideraciones sobre el tratamiento de la recurrencia. En la enfermedad metastásica el tratamiento de primera línea para los pacientes con un estado general adecuado para tolerar el cisplatino es la quimioterapia combinada basada en este fármaco. Actualmente no existe una quimioterapia estandarizada de segunda línea. Conclusiones: estas guías de la EAU constituyen un resumen de la exhaustiva visión de conjunto de las guías recientemente actualizadas del CaV-MiM, publicadas en las guías clínicas de la EAU, también disponibles en la National Guideline Clearinghouse. Context: New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. Objective: To review the new EAU guidelines for MiM-BC. Evidence acquisition: A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. Evidence synthesis: The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on: a) natural timing of recurrence; b) probability of disease recurrence; c) functional deterioration at particular sites; and d) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy. Presently, there is no standard second-line chemotherapy. Conclusions: These EAUguidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.

Contexto: la aparición de nuevos datos relacionados con el diagnóstico y tratamiento de cáncer vesical músculo-invasivo y metastásico (CaV-MiM) ha obligado a una actualización de las Guías sobre el CaV-MiM de la Asociación Europea de Urología (EAU). Objetivo: revisión de las nuevas guías de la EAU para el CAV-MiM. Evidencia adquirida: un grupo de urólogos, oncólogos y radiólogos designados por el Comité de Guías Clínicas de la EAU ha realizado un exhaustivo trabajo de revisión de la literatura procedente de Medline, el registro central Cochrane de revisiones sistemáticas y las citas bibliográficas de publicaciones y artículos de revisión. Se han tenido en cuenta las recomendaciones basadas en la literatura previa disponible sobre este aspecto. Además, han sido añadidos niveles de evidencia y grados de recomendación, según las modificaciones del Oxford Centre for Evidence-based Medicine. Evidencia sintetizada: el diagnóstico de cáncer vesical músculo-invasivo (CaVMI) se realiza mediante la resección transuretral y el consiguiente estudio histopatológico. Una vez confirmada la existencia de CaVMI es preciso realizar el estadiaje mediante tomografía computarizada toraco-abdómino-pélvica, si se dispone de ella. Actualmente, la quimioterapia adyuvante solamente se recomienda en el contexto de ensayos clínicos. La cistectomía radical es el tratamiento de elección en ambos sexos, y la linfadenectomía debe constituir una parte integral de la misma. Tanto a hombres como a mujeres se les debe ofrecer la sustitución vesical ortotópica siempre que no existan contraindicaciones, tales como la existencia de tumor en el margen uretral. En la actualidad, los tratamientos multimodales para la conservación vesical en casos de enfermedad localizada constituyen un alternativa terapéutica solamente en pacientes seleccionados, adecuadamente informados, y en aquellos en los que se desestima la cistectomía por motivos clínicos o personales. Los protocolos de seguimiento deben diseñarse sobre la base de: a) historia natural de la recurrencia; b) probabilidades de recurrencia; c) deterioro funcional en localizaciones específicas; y d) consideraciones sobre el tratamiento de la recurrencia. En la enfermedad metastásica el tratamiento de primera línea para los pacientes con un estado general adecuado para tolerar el cisplatino es la quimioterapia combinada basada en este fármaco. Actualmente no existe una quimioterapia estandarizada de segunda línea. Conclusiones: estas guías de la EAU constituyen un resumen de la exhaustiva visión de conjunto de las guías recientemente actualizadas del CaV-MiM, publicadas en las guías clínicas de la EAU, también disponibles en la National Guideline Clearinghouse.

Hintergrund Der Morbus Bowen und die Erythroplasie Queyrat sind eine intraepidermale Neoplasie, die derzeit als plattenepitheliales Carcinoma in situ klassifiziert werden und eine prainvasive Form des Plattenepithelkarzinoms des Penis darstellen. Nur in seltenen Fallen entwickelt sich aus einem Morbus Bowen ein invasives Karzinom – dieser Prozess kann bis zu 20 Jahren dauern.

OBJECTIVE To compare the efficacy of two types of botulinum toxin type A (BTX-A; DysportTM, Ipsen Ltd, Slough, UK) or BotoxTM (Allergan Inc., Irvine, CA, USA) and examine the possible dose-effect relation for Dysport in those patients, as multifocal detrusor injections with BTX-A are effective for severe neurogenic detrusor overactivity in adults. PATIENTS AND METHODS This was an open-label, observational case-control study comparing Dysport and Botox, and the dose-effect relation for Dysport. The patients included were treated with either Dysport (cases; 500, 750, or 1000 IU), or with Botox (controls: 300 IU, and exceptionally 200 or 400 IU). The continence volume (primary), mean and maximum catheterized volume, and antimuscarinic use were assessed, and cystometric variables measured were overactivity volume (primary), detrusor compliance, and cystometric capacity. All variables were assessed at baseline, 3 and 9 months after treatment, and results analysed using analysis of variance (paired) t-tests, chi-square tests and regression analysis. RESULTS There were 28 cases and 28 matched controls; their demographic characteristics, bladder management, and baseline values were comparable between the groups. At 3 months there was a significant improvement in cystometric variables and continence volume in both groups, but in mean catheterized volume and reduced use of antimuscarinics in cases only. At 9 months there was no significant improvement over baseline except for the continence volume in the cases. There were no significant differences in results between the groups except for the continence volume at 3 months (459 mL after Dysport and 396 mL after Botox; P = 0.015). There was no dose-related response for Dysport at 3.8 months of follow-up. The interval between injections (9.5, 14.5 and 16.1 months for Dysport 500, 750, and 1000 IU; 10.1 months for Botox) was not significant. There were nine non-responders in the Dysport group and seven in the Botox group; the patient characteristics and baseline data were comparable to those of the responders. There was transient hypoasthenia in one of the responders (750 IU Dysport). CONCLUSIONS A single treatment session with either Dysport or Botox in a setting combined with antimuscarinics might improve the patient’s condition for up to a year. There was no clear dose-related effect for Dysport in adults.

The aim of the study was to compare intra-operative and postplanning at different intervals with special focus on sources placed close to the rectal wall.In 61 consecutive patients, CT scans were performed on day 1 and day 30 after an I-125 implant with stranded seeds. The number of sourcesor =7 mm to the rectal wall was determined, and displacements were analyzed. The angulation of strands relative to rectal wall was compared between intra-operative transrectal ultrasound (TRUS) and both postplanning CT scans.Sources close to the rectum on day 1 (n=204) have been the most apical in a strand in 98.5% (n=201). By comparing day 1 and day 30 data, significant inferior source displacements (mean 3.6 mm; p=0.02) relative to pelvic bones and a decreasing distance to the rectal wall (mean 1.2 mm; p0.01)--consequentially increasing rectal dose--were determined only for sources initiallyor =3 mm to the rectum. In contrast to an almost parallel arrangement of the needle track and the rectal wall in TRUS, strands and rectal wall converged towards the apex in the postplanning CT scans (mean30 degrees).Posterior preplanning margins around the prostate should be particularly limited at the level of the prostate apex.

Contains fulltext : 81147.pdf (Publisher’s version ) (Closed access) CONTEXT: New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review the new EAU guidelines for MiM-BC. EVIDENCE ACQUISITION: A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. EVIDENCE SYNTHESIS: The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on (1) natural timing of recurrence, (2) probability of disease recurrence, (3) functional deterioration at particular sites, and (4) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy. Presently, there is no standard second-line chemotherapy. CONCLUSIONS: These EAU guidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.

Background: The Expanded Prostate Cancer Index Composite questionnaire is widely used as a comprehensive assessment of health-related quality of life issues in prostate cancer manag

Die Indikation zur inguinalen Lymphadenektomie orientiert sich am klinischen Befund der Leistenregion und dem Risikoprofil des Primartumors. Die pelvine Lymphadenektomie soll bei mehr als 2 Lymphknotenmetastasen oder extranodalem Befall durchgefuhrt werden. Obwohl es derzeit kein Standardprotokoll fur die Chemotherapie gibt, ist sie praoperativ bei grosen und/oder fixierten inguinalen Lymphknoten sowie bei in der Bildgebung sichtbaren iliakalen Lymphknoten angezeigt und der adjuvanten Chemotherapie vorzuziehen.

Objectives Imaging techniques with high resolution are evolving rapidly for medical applications and may substitute invasive diagnostic techniques. The use of ultrahigh resolution optical coherence tomography (UHR-OCT) to image healthy and morphologically altered bladder tissue with virtual histology is evaluated ex vivo to define parameters necessary for future, diagnostically relevant in vivo systems. Here, special focus is on the visualization of the basement membrane zone. Methods Optical coherence tomography examinations were performed by using a modified commercial OCT system comprising a Ti:sapphire femtosecond laser to support an enhanced resolution of 3 μm axial × 10 μm lateral. Tomograms of 142 fresh human bladder tissue samples from cystectomies, radical prostatectomies, and transurethral tumor resections were recorded and referenced to histologic sections using standard hematoxylin and eosin staining. Results OCT of normal bladder mucosa allows for a clear differentiation of urothelium and lamina propria. The basement membrane zone is identified as a narrow, low-scattering band between these layers. This allows for reliable exclusion of invasion. Healthy urothelial tissue, carcinoma in situ, and transitional cell carcinoma can be differentiated using this imaging technique. Sensitivity of UHR-OCT for malignant bladder tissue could be determined to be 83.8%, and specificity to be 78.1%. Conclusions UHR-OCT is considered promising in the attempt to strive for fluorescence cystoscopy-guided virtual histology as a means of supporting therapeutic decisions for bladder neoplasia.

PURPOSE For patients with prostate cancer (CaP) the proof of osteoblastic bone metastases is decisive regarding the prognosis as well as the therapeutical concept. To evaluate the efficiency of skeletal alkaline phosphatase (SAP) as staging marker for bone metastases in prostate cancer, SAP was measured in CaP-patients with and without bone metastases compared with prostate-specific antigen (PSA) as the marker of choice till now. METHOD 73 patients with histological proven, but still untreated CaP were entered into the study. After staging the patients were divided into 3 groups: group I: patients with CaP and bone metastases (n = 21), group II: patients with locally advanced CaP without bone metastases (n = 26), group III: patients with clinically localized CaP without bone metastases (n = 26). Serum concentration for SAP and PSA were determined using radioimmunassay. As reference range we defined serum concentrations for SAP 100 ng/ml). This resulted in a sensitivity and specificity of 71% and 100% for SAP and 71% and 81% for PSA. The positive predictive value for osteoblastic bone metastases was 100% for SAP and 60% for PSA. CONCLUSION SAP is a useful staging marker in prostate cancer and can contribute for an early detection of osteoblastic bone metastases.

Obstructive uropathy such as ureteropelvic junction obstruction in the newborn is a major diagnostic and therapeutic dilemma. We investigated whether urinary sodium dodecyl sulfate electrophoresis with polyacrylamide gel electrophoresis with silver staining could be used to discriminate between children requiring and those not requiring pyeloplasty.In a pilot study we analyzed the urine of 18 children (mean age 2.7 years) with grade III or IV hydronephrosis according to the Society for Fetal Urology classification. A total of 44 healthy children were studied as controls. Children with hydronephrosis were followed using ultrasound, (99m)technetium mercaptoacetyltriglycine diuretic renography and voiding cystourethrography. Urine was obtained by spontaneous voiding and studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis with silver staining using Melzer's modification. After the study period test results were compared to outcomes, ie whether patients required surgery, and to normalization of previously abnormal protein excretion patterns.All but 1 of the healthy controls had a normal electrophoresis assessment. Of 9 patients followed for hydronephrosis 7 had an abnormal electrophoresis result preoperatively. One child had to be operated on twice because of relapse of ureteropelvic junction obstruction. Six children returned to a normal electrophoresis result postoperatively, including the child who was operated on twice. All children with an initially normal electrophoresis assessment displayed persistent normal values, except 1. Children shifting from a normal to an abnormal electrophoresis result underwent surgery after exclusion of urinary tract infection.Sodium dodecyl sulfate polyacrylamide gel electrophoresis with silver staining seems to be a good predictive test for clinically relevant ureteropelvic junction obstruction. Further studies are being performed to see whether the test can stand against the gold standard, (99m)technetium mercaptoacetyltriglycine diuretic renography.

With an incidence of 0.1-0.9/100,000 men per year penile cancer is a rare cancer of the urogenital tract in Western Europe. At the time of initial diagnosis up to 45% of the patients already demonstrate metastatic disease and need some type of systemic treatment. It is the aim of this paper to review the current concepts of adjuvant and neoadjuvant chemotherapy for locally advanced penile cancer. A curative effect of combined surgical and cytotoxic management can only be achieved in patients with locoregional spread to the lymph nodes, but not with systemic spread. Although there are prospective randomized trials available indicating the optimal cytotoxic regime, cisplatin-based protocols or combination therapies with bleomycin, vincristine, and methotrexate appear to be the most effective options. Finally, there are no data available with regard to the effect of adjuvant chemotherapy on progression-free survival. In patients with locoregional bulky disease or with fixed inguinal lymph nodes, neoadjuvant chemotherapy will result in a partial response in 20-60% of patients and enables complete resection of the mass. For the future, the use of taxane-based chemotherapy as described for squamous cell cancer of other origin might improve outcome.

The aim of the study was to analyze source displacements and dose-volume changes in the first month after a permanent implant.In 51 consecutive patients, CT scans were performed at the postoperative day (day 1) and one month (day 30) after an (125)I implant with stranded seeds. Seed positions were determined relative to pelvic bones for five seeds at the base and five seeds at the apex for each patient (n=510) and compared. To verify these results, treatment margins (TM=distance of prescription isodose to prostate) and displacements of the prostate surface (anterior/posterior/right/left/superior/inferior) relative to pelvic bones were measured.Seed positions have moved significantly between day 1 and 30 in the posterior (mean 1.0mm; p0.001) and inferior (mean 3.8mm; p0.001) directions. TM increased particularly at the posterior (mean 2.2mm; p0.001) and apical (median 3.0mm; p0.001) prostate contour with decreasing oedema. With a stable apex position and a mean inward posterior surface displacement of 1.1mm (p0.001) relative to pelvic bones, seed displacements could be well correlated with prescription isodose displacements (Pearson correlation coefficientsor=0.81; p0.001).Both changes of prostate volume and seed displacements need to be considered to explain dosimetric changes after permanent prostate brachytherapy.

Der perineale Zugang wurde bei 10 Patienten mit Fisteln zwischen Harnblase oder Urethra zum Rektum und zur Haut zum Fistelverschluss angewendet. Bei radiogenen Fisteln (n=2) und Rezidiven (n=4) erfolgte die Anlage eines Anus praeter und die Interposition des M. gracilis. Bei 3 Patienten wurde zusatzlich die Prostatektomie durchgefuhrt. Alle Harntraktsfisteln wurden erfolgreich bei geringer Morbiditat korrigiert.

Objectives This review focuses on advances in regenerative therapies using stem cells in urology. Methods A detailed literature search was performed using the PubMed database of the National Center of Biotechnology Information. Publications of experimental investigations and clinical trials using stem cells in reconstructive urology have been summarized and critically reviewed. Results Tissue engineering and autologous cell therapy techniques have been developed to generate prostheses for different urological tissues and organ systems. During the last decade, increasing numbers of studies have described stem cells in the context of therapeutic tools. The ability of adult and embryonic stem cells as well as progenitors to improve bladder wall architecture, improve renal tubule formation, or promote restoration of spermatogenesis or recovery of continence has been investigated in several animal models. Although results have been encouraging, only a myoblast-based therapy of incontinence has reached clinical trials. Conclusions Several populations of adult stem cells and progenitor cells have been studied as useful cellular sources in the treatment and reconstruction of urological organs. However, considerable basic research still needs to be performed to ensure the controlled differentiation and long-term fate of stem cells following transplantion.

Penile cancer, with an incidence of 0.1-0.9/100,000 males/year, is one of the least common malignant tumors. Most patients are over 50 years old and the tumor is slow growing. Therapeutic success is highly dependent on lymph node status. Cancer related death is usually due to local complications such as arrosion bleeding caused by the tumor or infected inguinal metastases. The therapy for advanced penile cancer and its complications represents a challenge. Taking into consideration quality of life, the therapeutic strategy should be based on the patient's age, his sexual function, motivation and psychological condition, as well as previous illnesses and tumor biology. Palliative therapy requires good interdisciplinary work between oncologists, radiologists, plastic surgeons, physiotherapists and psychologists.

Histological tumor subtyping, staging, and grading are of utmost importance to stratify patients with bladder cancer for treatment and should be as precise as possible. In the presented study, we investigated the prognostic impact of standard clinicopathological parameters in cystectomy patients and compared embedding of the entire bladder with standard partial embedding via a virtual superimposed approach. The study included 121 cystectomy specimens, which were completely embedded. Clinical and histopathological data of patients were obtained (median follow-up 21.5 months; range 1–67 months). For 88 patients two-dimensional tumor maps (macrophotographs and histology-based maps) were prepared, and embedding of the entire bladder was compared with a virtual standard partial embedding, created by a virtual overlay and data extraction of the tumor maps. Kaplan-Meier plots, Cox regression estimators, Chi-square, and McNemar tests were used. In a multivariate Cox regression model for overall survival, only venous invasion (p = 0.008, HR = 3.35, 95 % CI 1.375–8.161) and organ-confined (pTis–pT2) versus non-organ-confined diseases (pT3–pT4; p = 0.021, HR 2.669, 95 % CI 1.157–6.159) were found significant. Advanced versus standard embedding revealed significant improvement in the detection of carcinoma in situ (50 versus 61, p = 0.003) and lymphatic invasion (18 versus 24, p = 0.041), but no significant advantage in the detection of tumor stage, tumor multifocality, or venous invasion (all p > 0.05). TNM classification, including lymphatic and venous invasion, is of utmost importance to stratify patients with advanced invasive bladder cancer. Histopathological details are detected more reliably by whole organ embedding, but this approach showed no significant benefit in terms of outcome-related parameters (max. tumor stage, venous invasion) in our cohort.

To determine dosimetric risk factors for increased toxicity after permanent interstitial brachytherapy for prostate cancer.Quality of life questionnaires (Expanded Prostate Cancer Index Composite) of 60 and 56 patients were analyzed after a median posttreatment time of 6 weeks (A-acute) and 16 months (L-late). The corresponding CT scans were performed 30 days after the implant. The prostate, rectal wall, and base of seminal vesicles were contoured. Prostate volume, number of seeds and needles as well as dosimetric parameters were correlated with the morbidity scores.For a prostate volume of 38 +/- 12 cm(3) (mean +/- standard deviation), 54 +/- 7 (125)I sources (Rapid Strands), activity of 22.6 +/- 3.0 MBq [0.61 +/- 0.08 mCi]) were implanted using 20 +/- 6 needles. Improved late urinary function scores resulted from a higher number of sources per cm(3) (or = 1.35). A prostate D(90)170 Gy (A)/185 Gy (L) and base of seminal vesicle D(10)190 Gy (A and L) were associated with higher urinary function scores. Late rectal function scores were significantly higher for patients with a prostate V(200)50% and V(150)75%. Patients with a prostate volume40 cm(3) reached better sexual function scores (A and L). A higher number of needles per cm(3) (or = 0.5) resulted in improved late urinary, bowel and sexual function scores.Quality of life after a permanent implant can be improved by using an adequate amount of sources and needles. With an increasing number of seeds per cm(3), dose homogeneity is improving. A prostate D(90)170 Gy and a base of seminal vesicle D(10)190 Gy (as an indicator of the dose to the bladder neck and urethral sphincter) can be recommended to maintain a satisfactory urinary function.

Reconstruction of bladder and ureter tissue is indicated in cases of injury, stenosis, infection or tumor. Substitution by ileum, colon or pure synthetic polymers generates a variety of complications. Biohybrid tissue mimicking structural and functional attributes of the multilayered wall architecture of the urinary conduit may be the solution to current problems. This study reports on porcine urinary tract cells isolated and placed on UroMaix matrices with different degrees of cross-linking produced from highly purified type I collagen from medically approved porcine tissue. A patented procedure revealed membrane structures composed of a dense fibrous side and an open fibrous side. These scaffolds with the porcine urinary tract cells were incubated in a batch culture system for up to 14 days. Cell growth and topographical orientation were examined. Urothelial cells showed maximum attachment and a significant increase of living cells on the dense fiber layer of UroMaix-1. No attachment of urothelial cells occurred on the other prototypes. Smooth muscle cells showed similar behavior within the open fiber layer of all UroMaix matrices. Both urothelial and smooth muscle cells retained their phenotypes as demonstrated by the immunostaining of epithelial cytokeratin 18 and the smooth muscle myosin heavy chain respectively. Thus we could show that UroMaix scaffolds support the attachment and proliferation of urinary tract cells. The elastomeric properties of the collagenous matrices promise attractive applications in the tissue engineering of the urinary tract with its high mechanical demands.

Objectives To characterize the influence of neoadjuvant hormonal therapy (NHT) on health-related quality of life after permanent iodine-125 brachytherapy (BT) for prostate cancer. Methods A cross-sectional survey using the Expanded Prostate Cancer Index Composite health-related quality-of-life instrument was administered to 134 consecutive patients a median of 29 months after BT. A separate group of 111 patients with comparable demographic characteristics without any prior treatment for prostate cancer rendered the baseline information (control group). The scores and symptom rates were compared. The effect of NHT was tested for independence in a multivariate analysis. Results In contrast to patients who received NHT, prostatic edema was hardly detectable 30 days after implantation in patients who received BT alone (comparing median preimplant and postimplant volumes), resulting in a greater dose to the prostate and anterior rectal wall. However, compared with the control group and the patients who received BT alone, the addition of NHT to BT led to lower health-related quality-of-life scores in all domains. Score differences of more than 10 points with a statistical significance were found for the urinary bother, sexual function/bother, and hormonal function/bother domains. Apart from the sexual function scores (patient age shown to be the crucial factor), the influence of NHT remained independent on multivariate analysis. Conclusions The results stress the need for well-considered administration of NHT before BT and the need for reporting the use of NHT in studies dealing with BT-related toxicity.

Das Peniskarzinom gehort in Europa zu den seltensten bosartigen Tumoren mit einer Inzidenz von 0,1–0,9/100.000 Manner/Jahr. Der Erfolg der lokalen Therapie wird durch den Lymphknotenstatus beeinflusst. Bei Erstdiagnose weisen 17–45% der Patienten Lymphknotenmetastasen auf. Die beidseitige inguinale und pelvine Lymphadenektomie wird bei diesen Patienten als kurative Masnahme eingesetzt. Die induktive Chemotherapie fuhrt bei grosen Lymphknotenmetastasen in 21–60% der Patienten zur Remission und damit zur Verbesserung der Resektabilitat. Der Einfluss auf das Uberleben ist jedoch nicht belegt. Ebenso ist die Effektivitat der adjuvanten Therapie nach kompletter Resektion von Lymphknotenmetastasen nicht gesichert. Besteht eine Fernmetastasierung, kann nur bei wenigen Patienten durch eine Polychemotherapie eine komplette Tumorremission erzielt werden. Die Polychemotherapieprotokolle enthalten Cisplatin, Bleomycin, Methotrexat und 5-Fluorouracil. Die Remissionsraten werden mit 15–32% angegeben. Wegen der geringen Wirksamkeit der derzeitigen Chemotherapieprotokolle muss nach neuen Therapieansatzen gesucht werden, die im Ansatz der Behandlung von Plattenepithelkarzinomen anderer Organe folgen sollten.

OBJECTIVE To develop a tissue-engineered bladder wall replacement with autologous cells and a biodegradable scaffold, as whenever there is a lack of native urological tissue the bladder is reconstructed with different bowel segments, which has inevitable complications. MATERIAL AND METHODS Skin biopsies were taken from six minipigs, and primary fibroblast and keratinocyte cell cultures established. A partial resection of the urinary bladder was reconstructed by a cell-seeded scaffold covered with completely differentiated epithelium and supported by a mucosa-free pedicled ileum graft. Each pig was assessed urodynamically and by cystography before operation and every month until explantation; the pigs were killed at 1, 2 and 3 months after augmentation. Control groups (of six pigs each) with bladder augmentation with complete or denuded ileum were used. The bladders were assessed histologically and by distensibility measurements RESULTS The differentiated keratinocyte epithelium was still present on the reconstructed bladder wall after 3 months. The overall shrinkage rate was 6.5%. The engineered bladder wall had lower distensibility than the native one. The inflammatory reaction present initially had disappeared after 3 months. CONCLUSIONS The implanted, tissue-engineered substitution of the bladder wall is not only a bridging graft, but also a complete reconstruction. With this model, extended bladder wall substitution seems feasible and should be investigated in further studies.

Objective: To evaluate the potency in patients after radical perineal prostatectomy with wide excision of both neurovascular bundles. Material and Methods: In this prospective study, a quality-of-life questionnaire was completed by 128 patients at the preoperative stage, and 6 and 12 months postoperatively. Ten questions concerning the patient’s sexuality were included on the pre- and both postoperative questionnaires. In addition, 6 patients who recorded some erectile function were sent a separate questionnaire containing eight more detailed questions. Results: Preoperatively, 74/128 (57.8%) patients reported erections sufficient for sexual intercourse, and of these 74, 6 (8.1%) described having spontaneous erections 1 year postoperatively. These spontaneous erections occurred 1–5 times per week. The reply to the separate mailing made clear that the reported erections were insufficient for intercourse. Conclusions: Patients undergoing standardized radical prostatectomy with wide excision of the neurovascular bundle have a very small chance of spontaneous erections sufficient for intercourse postoperatively.

The aim of the present study was to test the value of urinary cytology in the diagnosis of bladder cancer.One thousand three hundred and eighty voided urine and bladder wash specimens of 495 patients were evaluated by urinary cytology. All patients then underwent transurethral resection of suspicious bladder areas if cystoscopy and/or preceding biopsy were positive. Statistical differences were analysed using the two-sided Fisher's exact test and Cochran's test (p0.05).In 495 patients including 142 patients with bladder cancer urinary cytology revealed a sensitivity of 38.0% and a specificity of 98.3% with a positive and negative predictive value of 90.6 and 78.6, respectively. Sensitivity increased significantly with malignancy grade (p0.05). In high grade tumours sensitivity improved from initial 52.2% up to 78.3% after the third sample. In sensitivity and specificity of voided urine and barbotage washing samples no significant difference was detected.Urinary cytology has its place as an additive diagnostic tool to cystoscopy. None of the currently available urinary markers can replace cystoscopy but are helpful for specific diagnostic problems.

Objectives To assess, in a prospective study, the incidence of fecal incontinence after radical perineal prostatectomy. Methods Bowel symptoms were evaluated with questionnaires mailed to 132 patients preoperatively and 6 months postoperatively, and annually thereafter. All patients had undergone extrafascial perineal prostatectomy for Stage cT1-cT3N0M0 prostate cancer. The data of 116 patients (88%), who answered at least the preoperative and 12-month questionnaires, were analyzed. Reduced sensibility, reduced discrimination, urgency, or stool smearing were symptoms indicative of fecal incontinence. Patients with one symptom of fecal incontinence were evaluated further with a structured telephone interview. Results Daily stool smearing was reported preoperatively by 4% of the patients. Two symptoms related to fecal incontinence were present preoperatively in 6% of the patients. At 12 months postoperatively, 15 patients (13%) reported at least two symptoms of fecal incontinence. The structured telephone interview revealed that 6 of these 15 patients had symptoms of fecal incontinence that were related to the perineal prostatectomy; 9 patients had newly developed symptoms not related to surgery or symptoms due to tumor recurrence or radiotherapy. Patients with the presence of at least one symptom of fecal incontinence before surgery had an almost fourfold increased risk of developing at least two symptoms of fecal incontinence postoperatively compared with patients without any symptom of fecal incontinence. Conclusions Significant fecal incontinence after radical extrafascial perineal prostatectomy is a rare event. The results of questionnaires should be supplemented by additional interviews to obviate wrong interpretations.

Aim: We determine the efficacy of unilateral nerve-sparing radical perineal prostatectomy in preserving the sexual function. Patients and Methods: Ninety-two patients with histologically confirmed unilateral prostate cancer were scheduled for contralateral nerve preservation. The perioperative morbidity was assessed using the patients’ chart reviews. Postoperative health-related quality of life, urinary continence, and potency were evaluated prospectively with questionnaires provided before surgery and then after 6, 12, and 24 months. Results: Unilateral nerve preservation was performed in 88 of the 92 patients. Due to extensive scarring or prostatic size, the procedure was terminated as regular radical prostatectomy in 4 other patients. The perioperative complication rate was low and of minor significance, except in 1 patient who experienced a significant myoglobulinuria due to a prolonged procedure. Blood transfusions were necessary in 5 (5.4%) patients. Ureteral reimplantation was performed in 1 patient because of ureteral stricture. Positive surgical margins were present in 12 (18%) of 67 pT2 patients and in 8 (35%) of 23 pT3 patients. A proportion of 48% (15/31) of the patients followed for more than 24 months and who had a good erectile function prior to surgery reported unassisted sexual intercourse. However, only 4 of these patients were completely satisfied with all aspects of sexual performance, as asked in a short version of the International Index of Erectile Function questionnaire. Conclusions: Unilateral nerve-sparing radical perineal prostatectomy is technically feasible and yields excellent results in terms of potency preservation for prostates

To assess the quality of life in patients with prostate cancer after permanent brachytherapy (BT) or radical perineal prostatectomy (RP).The American Brachytherapy Society recommends the permanent implantation of radioactive seeds as a monotherapy for patients with T1-T2aN0M0 prostate cancer and a prostate-specific antigen (PSA) level ofor = 10 ng/mL, a Gleason score of7 and a prostate volume of60 mL. Using these criteria, 132 patients with low-risk prostate cancer were selected; 52 had BT with 125I-seed implantation, 38 had RP with unilateral nerve-sparing (RP + NS) and 42 extended RP (RP group). Only patients with unilateral tumour on biopsy were considered. Before therapy and 6, 12 and 24 months afterward, patients completed questionnaires to assess perceived health and function. PSA relapse was diagnosed with a PSA of0.1 ng/mL for patients in the RP groups, and three consecutive PSA increases for those after BT.Extraprostatic tumours were found in 18% of specimens taken during RP, and bilateral tumours in 63% of patients. After a mean follow-up of 27 months, there was PSA relapse in two of the 80 patients in the RP and RP + NS groups, and six of the 52 patients in the BT group; a significant difference, with a hazard ratio of 5.2. The acute morbidity was low in all groups. At 1 year, more than two incontinence pads were used by 5% of patients after RP and by 4% after BT. Similarly, at 1 year 15% of patients after RP and 13% after BT were bothered by urinary incontinence. Newly-developed fecal soiling was reported by 4%, 5% and 11% of the RP, RP + NS and BT groups respectively; none of the patients after RP and 4% after BT were bothered by this symptom. The duration and stiffness of erection was assessed after 1 year and reported to be equal or slightly decreased by a third after RP + NS and 38% after BT. Taking a 5-10 point difference as clinically relevant, role, emotional and social functioning were improved considerably after RP + NS than after BT, but sexual activity was impaired significantly after RP + NS than after BT.Both therapies showed typical acute and late morbidity; the most bothersome late symptoms were urinary incontinence for patients after RP and fecal soiling after BT. Sexual function was impaired significantly in patients who were potent before RP + NS, whereas after BT men reported only a minor change in sexual performance at 1 year. Tumour control after a median follow-up of 27 months was better after RP but biochemical recurrence may still occur afteror = 5 years; therefore the present results are not mature enough and there were too few patients to provide a more definitive statement. As approximately 18% of patients considered to be appropriate candidates for BT had tumours extending beyond the prostate capsule or invading the seminal vesicles, nomograms are needed for more accurate information before therapy.

T1 transitional cell cancer of the urinary bladder is associated with a significant risk of tumor progression when transurethral resection (TUR) is the only treatment. Additional intravesical immunotherapy can reduce this risk; however, long-term results of more than 15 years of follow-up indicate that almost half of the patients may lose their bladder or even die due to recurrent tumor. The alternative to TUR is cystectomy at either the initial presentation or time of first recurrence. However, although the results of this treatment strategy are encouraging, an unknown percentage of patients will lose their bladder and go on to experience all possible complications of urinary diversion unnecessarily. The central issue of conservative treatment but also the indication for cystectomy is the quality of TUR. From the present literature, it is evident that a 'textbook TUR' cannot be performed on every patient, i.e. macroscopical clearance of the bladder from tumor, separate thorough resection of the tumor base and separate biopsies of the borders of the resection area. Moreover, even in cases of a so-called 'correct TUR', a significant percentage of residual tumor is left behind and will be the source of local recurrence or progression. In addition, TUR specimens may be difficult to diagnose accurately, especially in respect to grade and stage. Recent publications demonstrate that the routinely performed second TUR detects residual tumors of similar or higher stage in a significant percentage of patients. The clinical implications of these findings can be considerable as the absence or presence of tumor may determine whether patients undergo conservative or aggressive treatment. Moreover, results of retrospective studies support this suggestion. Currently, there is no standard appropriate treatment of T1 tumors. However, we strongly recommend that future studies on the conservative treatment of T1 tumors include a second TUR within 2 to 4 weeks after the first one.

Von insgesamt 405 Patienten einer internationalen prospektiv randomisierten Phase-III-Studie zur systemischen Chemotherapie des fortgeschrittenen Urothelkarzinoms [maximal 6 Zyklen Gemcitabin/Cisplatin (GC) vs. Methotrexat/Vinblastin/Adriamycin/Cisplatin (MVAC)] wurden 70 Patienten aus bundesdeutschen uroonkologischen Zentren rekrutiert. Zu diesen Patienten, die innerhalb der "Arbeitsgemeinschaft Urologische Onkologie" empfohlenen Studie AB 12/96 rekrutiert wurden, wird uber das 5-Jahres-Langzeituberleben sowie uber therapierelevante Daten berichtet. Die Tumorremissionsraten (GC=54%, MVAC=53%) sowie die 5-Jahres-Gesamtuberlebensrate (GC=10%, MVAC=18%), die tumorspezifische Uberlebensrate (GC=14%, MVAC=22%) und die progressionsfreie Uberlebensrate (GC=13%, MVAC=7%) waren in den beiden Behandlungsarmen nicht signifikant unterschiedlich.

Objectives On behalf of the European Association of Urology (EAU) guidelines for diagnosis, therapy and follow-up of bladder cancer patients were established. Criteria for recommendations were evidence based, and included aspects of cost-effectiveness and clinical feasibility. Method A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts. Results TNM 1997 classification and WHO grading 1998 are recommended. Recommendations are developed for diagnosis for bladder cancer in general, treatment of superficial and infiltrative bladder cancer, and follow-up after different types of treatment modalities, such as intravesical instillations, radical cystectomy, urinary diversions, radiotherapy and chemotherapy.

Objective To compare the ability of magnetic resonance urography (MRU), enhanced using gadolinium and frusemide diuresis, and conventional intravenous urography (IVU) to diagnose the cause of ureteric obstruction. Patients and methods The study included 82 patients in whom IVU showed or suggested obstruction and who also underwent MRU. The images from both methods were interpreted by various investigators independently; two evaluated the IVU and two others the MRU, the latter being unaware of the diagnosis after IVU. If the diagnosis remained unclear, further investigations (e.g. computed tomography, retrograde pyelography or ureteroscopy) were conducted. Results The diagnoses were ureteric calculi in 72 patients, ureteric tumours in eight and extra-ureteric tumours in two. In those with urolithiasis, the diagnosis was correct with IVU in 49 patients and with MRU in 64. The diagnosis in this group was incorrect with MRU in only two patients. The main reason for the failure of IVU was absent contrast medium excretion. Three of eight patients with ureteric tumours were correctly diagnosed by IVU but in three patients the diagnosis was incorrect. MRU correctly diagnosed seven of the eight patients in this group, with no false diagnosis. Conclusion IVU is currently likely to remain the standard procedure for imaging the upper urinary tract, but this study shows the potential of MRU when enhanced with gadolinium and frusemide. MRU may be helpful if there is a dilated system with no excretory function, in pregnant women, in children and in those with contrast medium allergy.

The aim of this study was to investigate the utility of different gadolinium-enhanced T1-weighted gradient-echo techniques in excretory MR urography. In 74 urologic patients, excretory MR urography was performed using various T1-weighted gradient-echo (GRE) sequences after injection of gadolinium-DTPA and low-dose furosemide. The examinations included conventional GRE sequences and echo-planar imaging (GRE EPI), both obtained with 3D data sets and 2D projection images. Breath-hold acquisition was used primarily. In 20 of 74 examinations, we compared breath-hold imaging with respiratory gating. Breath-hold imaging was significantly superior to respiratory gating for the visualization of pelvicaliceal systems, but not for the ureters. Complete MR urograms were obtained within 14–20 s using 3D GRE EPI sequences and in 20–30 s with conventional 3D GRE sequences. Ghost artefacts caused by ureteral peristalsis often occurred with conventional 3D GRE imaging and were almost completely suppressed in EPI sequences (p < 0.0001). Susceptibility effects were more pronounced on GRE EPI MR urograms and calculi measured 0.8–21.7 % greater in diameter compared with conventional GRE sequences. Increased spatial resolution degraded the image quality only in GRE-EPI urograms. In projection MR urography, the entire pelvicaliceal system was imaged by acquisition of a fast single-slice sequence and the conventional 2D GRE technique provided superior morphological accuracy than 2D GRE EPI projection images (p < 0.0003). Fast 3D GRE EPI sequences improve the clinical practicability of excretory MR urography especially in old or critically ill patients unable to suspend breathing for more than 20 s. Conventional GRE sequences are superior to EPI in high-resolution detail MR urograms and in projection imaging.

Die reverse Transkriptase-Polymerase-Kettenreaktion fur das prostataspezifische Antigen und die Immunozytochemie fur Zytokeratin 18 (CK-18) kann zur Detektion eines mikrodisseminierten Prostatakarzinoms eingesetzt werden. In der Untersuchung von Knochenmarkaspiraten und peripher venosem Blut bei 50 Patienten mit einem klinisch lokal begrenzten Prostatakarzinom wurde die Rate positiver Resultate mit beiden Methoden bestimmt und zu pT-Stadium, Serum-PSA und vorheriger antiandrogener Behandlung in Beziehung gesetzt. Es lag kein Zusammenhang zwischen dem Nachweis von PSA-mRNA-Expression bzw. CK-18-positiven Zellen und diesen Parametern vor. Die Polymerasekettenreaktion und die Immunozytochemie sollten derzeit nur in prospektiven Untersuchungen eingesetzt werden, die eine standardisierte Methode verwendet und einen Serum-PSA Langzeitverlauf garantiert.

Mit der Zielsetzung eine biodegradierbare Harnleiterschiene zu entwickeln, wurden verschiedene Polylaktide untersucht und mit einer organadaptierten Oberflache versehen. Zur Formgebung kam das neuartige CESP-Verfahren zum Einsatz (controlled expansion of saturated polymers), bei dem das Polymerpulver in einer Kavitat nicht, wie in der Kunststoffverarbeitung sonst ublich durch Warme, sondern durch Aufschaumen unter hohem Gasdruck geformt wird. Im Rahmen der Materialauswahl wurden die synthetischen, hydrolytisch biodegradierbaren Homo- und Kopolymere Poly (D,L-Lactid: PDLLA), Poly (D,L-Lactid-co-Trimethylencarbonat: PDLLA-co-TMC), Poly (D,L-Lactid-co-Glycolid: PDLLA-co-Gly), allesamt Derivate der Milch- bzw. Glykolsaure und Oberflachenmodifizierungen mit Hydroxyethylmethacrylat (HEMA) und Oligoethylenoxidmonomethacrylat (OEOMA) hinsichtlich ihrer Zytotoxizitat und Zelladhasion analysiert. Methacrylate zeichnen sich insbesondere durch minimierte Protein- und Zelladhasion aus und erzeugen ebenfalls bei der Degradation nicht toxische Produkte. Es zeigte sich eine Biokompatibilitat der Materialien und eine deutliche Reduktion der Zelladhasion nach HEMA-Beschichtung. Ein 3 cm langer und 7 Ch messender Prototyp der Schiene wurde aus PDLLA-co-TMC mit Hilfe des CESP-Verfahrens hergestellt und durch die Pfropfkopolymerisation mit einer HEMA-Oberflache versehen. Im Tierexperiment wurde dieser Stent unilateral nach Ureterotomie in den distalen Harnleiter von Schafen implantiert. Die wochentlich durchgefuhrten Blut- und Urinkontrollen, sowie Ultraschalluntersuchungen waren uber den gesamten Versuchszeitraum ebenso wie die abschliesende Sektion unauffallig. Histologisch fand sich ein regelrechtes Urothel ohne jegliche Veranderung durch den Kontakt mit dem Stent und eine gute Regeneration aller Wandschichten im Bereich der Anastomose.

125 konsekutive Patienten mit Adenokarzinom der Prostata wurden einer erweiterten radikalen perinealen Prostatektomie entsprechend der Technik von Weldon unterzogen. Diese Technik wurde durch die primare komplette Mobilisation der Prostatahinterflache und der Samenblasen, der Inzision der Faszia endopelvina, der queren Inzision der Denonvillier-Faszia am Apex und der partiellen Durchtrennung des dorsalen Venenkomplexes nach vorangegangener Durchstechungsligatur modifiziert. Die perioperative Morbiditat war gering. Eine operative Wundrevision war bei 4 (3,2%) der Patienten wegen subkutaner arterieller Blutung aus dem Drainagekanal (n=1), Wundinfekt (n=2) und rektokutaner Fistel (n=1) erforderlich. Der Dauerkatheter wurde bei 104 (83%) Patienten am 4.–8. Tag entfernt. Positive Schnittrander fanden sich nur bei 22 (17,6%) Patienten. Es handelte sich dabei um 17 pT3- und 5 pT4-Tumoren mit Gleason-Score ≥7 (n=17), ausgedehntem, multifokalem Kapseldurchbruch (n=18), Infiltration der Samenblasen (n=11) und Lymphknotenmetastasen (n=4). Die unifokal positiven Schnittrander fanden sich am Apex (n=3), dorsolateral (n=6) und am Blasenhals (n=4); 9-mal lag ein multifokal positiver Schnittrand vor. Die Wahrscheinlichkeit des positiven Schnittrandes ist abhangig vom Serum-PSA, Gleason-Score und Tumorvolumen. Wird auf eine Potenzerhaltung verzichtet, so wird zur Vermeidung von positiven Schnittrandern die erweiterte radikale perineale Prostatektomie mit den angegebenen Modifikationen empfohlen.

The purpose of this study was to test the hypothesis that renal cell carcinoma (RCC) exhibits an increased intratumoral interstitial fluid pressure (IT-IFP). Therefore, resected tumors from human primary (n = 23) or metastatic RCC (n = 3) were xenografted in SCID mice. The IFP of single tumor nodules (n = 65) and normal mouse tissue (n = 195) was measured by means of the "wick-in-needle" technique. Data demonstrate that the mean IT-IFP at neoplasia was 35 times greater than in normal tissue, and decreased precipitously at the tumor boundary. IT-IFP values tended to increase with the grade of malignancy of the tumor cells and tumor size. The mean IT-IFP of xenografts derived from primary RCC was twice as high as that from metastatic RCC tissue. These findings indicate a biophysical barrier to drug delivery in RCC; this may, in concert with cellular-based drug resistance mechanisms, be an additional explanation for resistance of the tumor to certain blood-borne anticancer therapies.

Clonal chromosome aberrations identified after short-term culture are presented for three cases of chromophobe renal cell carcinomas (RCC). All tumors revealed abnormal karyotypes with a varying proportion of polyploid tumor cells. Common numerical abnormalities were combined losses of chromosomes 1, 2, 6, 10, 13, and 17. Clonal karyotypic evolution was demonstrated in one case in which several related clones could be identified. An additional balanced translocation t(3;14)(p24;q22) observed in this case proved to be of constitutional nature by cytogenetic analysis of normal kidney cells and peripheral blood lymphocytes. These cytogenetic findings provide further evidence that chromophobe renal cell carcinomas are characterized by a highly specific combination of chromosomal losses most commonly including chromosomes 1, 2, 6, 10, 13, and 17.

Pelvic lymphadenectomy in patients with organ confined prostate cancer (PCa) is of no therapeutic value and is questionable in many patients because of the low incidence of metastases. 49 patients with ≤ cT2 b, G1 + 2, PSA ≤ 10 ng/ml underwent laparocopic pelvine lymphadenectomy and radical perineal prostatectomy. Only 1 patient (2 %) had microscopic metastases which were missed on frozen section. Because of these own results and those reported in the literature we then performed in patients with this constellation the radical perineal prostatectomy without lymphadenectomy (n = 32). The differences present in both groups concerning complication rate and morbidity are due to laparoscopic lymphadenectomy and the learning curve in perineal prostatectomy.

Objective: To examine whether prostate-specific antigen (PSA) is present in amniotic fluid, whether the amniotic fluid PSA concentration changes with gestational age, and whether there is an association between amniotic fluid PSA and fetal sex. Methods: The PSA concentration was measured in the amniotic fluid of 48 pregnant women. Thirty-four samples were obtained during routine amniotic fluid analyses performed during gestational weeks 16–18, whereas 14 samples were obtained during cesarean section performed after gestational week 36. Results: PSA was detected in all amniotic fluid samples. The median amniotic fluid PSA was 0.193 ng/ml during gestational weeks 16–18 and 0.39 ng/ml after gestational week 36 (p = 0.1). Furthermore, no significant association was seen between amniotic fluid PSA and fetal sex. The median amniotic fluid PSA level was 0.233 ng/ml for the 21 boys and 0.222 ng/ml for the 27 girls investigated (p = 0.72). Conclusions: These results confirm recent literature reports that PSA may serve as a growth regulator during normal fetal development. However, further studies are necessary to elucidate the exact role of PSA during fetal development.

To evaluate the clinical utility and morphologic accuracy of gadolinium-enhanced excretory magnetic resonance (MR) urography after low-dose diuretic injection and to correlate the results with those of conventional urography.In 71 patients with urologic symptoms, excretory MR urography was performed after intravenous injection of 5-10 mg furosemide and, 30-60 seconds later, 0.1 mmol of gadopentetate dimeglumine per kilogram of body weight. The MR urograms were interpreted by three radiologists, who were blinded to the clinical outcome, and subsequently compared with conventional urograms.Injection of furosemide before contrast material led to rapid, uniform gadolinium distribution inside a sufficiently distended collecting system such that there was no excessive concentration of gadolinium in the urine. In patients with normal or moderately reduced excretory function, this effect allowed complete visualization of the urinary tract within 5-20 minutes of contrast material injection while minimizing gadolinium-related endoluminal T2* effects. The clinical course helped verify almost all MR urographic results. The MR urographic technique was significantly superior to conventional urography in the assessment of the ureters and bladder (P.0001). Delineation of small caliceal abnormalities is still problematic. The best depiction of the pelvicaliceal system was obtained with fat-suppressed MR imaging, although it was still slightly inferior to conventional urography (P.05).Gadolinium-enhanced excretory MR urography performed after low-dose diuretic injection is a promising and accurate alternative to conventional excretory urography for imaging the morphology of the urinary tract.

Residual tumor, tumor progression or relapse after chemotherapy of patients with advanced or metastasized transitional cell carcinoma of the bladder (TCCB) are suggested to reflect intrinsic drug resistance of cancer cells, or the development of chemotherapy-resistant tumor cell populations. The present study aimed to establish drug-resistant subculture cell lines from human TCCB, selected for anticancer drugs, administered in the cisplatin, methotrexate and vinblastine (CMV) polychemotherapy protocol. Tumor cells from chemonaive cell lines of human TCCB (HT1376, TCCSUP) have been exposed to progressively increasing concentrations of cis-diamminedichloroplatinum (II) (CDDP), methotrexate (MTX), vinblastine (VBL) or etoposide (VP16). The resulting drug-resistant subculture cell lines (HT1376-CDDP, HT1376-MTX, HT1376-VBL, HT1376-VP, TCCSUP-CDDP, TCCSUP-MTX, TCCSUP-VBL, TCCSUP-VP) were analyzed with regard to the achieved resistance factor (RF) for the inductive anticancer agent, the acquisition of cross-resistance, DNA content, cell cycle distribution and cellular morphology. Parental HT1376 cells were intrinsically less sensitive to all anticancer drugs (1.7-50x), compared with TCCSUP cells. Relative resistance against the inductive anticancer agents was similar for the final drug-resistant subculture cell lines of both parental cell lines concerning CDDP and VP-16 (RF: 4-5x), but were reciprocal for MTX and VBL, respectively. MTX led to much stronger resistance (RF > 200) than the other drugs (RF < 10). Pleiotropic cross-resistances were observed in six out of eight (75%) drug-resistant subculture cell lines. Highest RF (50-500x) and frequency of cross-resistance (five of six cell lines) occured for MTX, and the least from exposure to CDDP (one of six cell lines). Overall, the results corroborated the central role of CDDP against urothelial carcinoma whereas repetitive applications of MTX appeared to be a doubtful strategy. Moreover, the experiments provide the largest panel so far of drug-resistant cell lines of human TCCB. They represent an appropriate tool for basic research on drug-resistance mechanisms, for the development and screening of future anticancer drugs or to elaborate strategies to overcome drug resistance for those patients who ultimately fail to respond to standard chemotherapy.

To improve sensitivity and specificity of urinary cytology for bladder cancer cell detection we used deoxyribonucleic acid (DNA) image cytometry and the monoclonal anti-Lewis X antibody P12.Spontaneously voided urine and additional barbotage bladder washings of 25 patients with transitional cell carcinomas and 25 patients with benign diseases of the bladder were analyzed by conventional cytology, immunocytology and DNA image cytometry. The DNA content was determined in specimens stained with Feulgen according to the European Society for Analytical Cellular Pathology consensus report on standardization of DNA image cytometry. For the immunocytological examination we used the avidin-biotin-complex immunoperoxidase method with the monoclonal antibody P12 directed against the Lewis X determinant.The cytological examination revealed a sensitivity of 72% and a specificity of 100%. By using DNA image cytometry with Kolmogoroff-Smirnow test sensitivity increased up to 84% with a specificity of 100%. The immunocytological examination with Lewis X showed a sensitivity of 84% and a specificity of 80%.Combining cytology and DNA cytometry the overall sensitivity increased to 92% and with the additional application of immunocytology for Lewis X antigen sensitivity it increased to 96% but was accompanied by a decrease in specificity to 80%. DNA image cytometry and Lewis X antigen detection are not suitable for screening but suspicious urothelial cells in urinary cytology specimens can be evaluated specifically by DNA measurements. In the future it needs to be clarified whether DNA image cytometry in combination with Lewis X antigen detection can help to signal relapse and progression of transitional cell carcinoma of the bladder.

Purpose: To study the efficacy of prostate-specific antigen (PSA) and skeletal alkaline phosphatase (SAP) as staging markers in discriminating patients with cancer of the prostate (CaP) with (M+) and without bone metastases (M0). Material and Methods: 73 patients with untreated CaP entered the study. After staging the patients were divided into 3 groups: group I, patients with CaP and bone metastases (n = 21); group II, patients with locally advanced CaP without bone metastases (n = 26), and group III, patients with clinically localized CaP without bone metastases (n = 26). Results: None of the M0 patients but 71% of the M+ patients exhibited an increased SAP. A corresponding cutoff point of 100 ng/ml for PSA showed that 19% of M0 patients and 71% of the M+ patients exhibited a value of >100 ng/ml. This resulted in a sensitivity and specificity of 71 and 100% of SAP and 71 and 81% for PSA, respectively. Conclusion: SAP could become a useful marker in the evaluation of patients with newly diagnosed CaP as it provides additional information concerning the skeletal status of these patients.