[Innovative ultrasound-based diagnosis of renal tumors]. / Innovative Ultraschalldiagnostik bei Nierentumoren.

BACKGROUND: In Germany, renal tumours are detected earlier also due to advancing technology within ultrasound devices and its more widespread application. Ultrasound diagnosis is usually the first imaging procedure available to urologists. For all renal lesions larger than 1 cm in diameter, fat content can be revealed by quantitative measurements within CT/MRI diagnostic modalities to confirm the suspected diagnosis of angiomyolipoma, or in patients with potentially malignant renal lesions referral (with all the their imaging data) to the multidisciplinary tumour team. As a further step, biopsy may be indicated, especially in the case of inflammatory lesions or suspected lymphoma; otherwise patients with a solid tumour are treated within a tumour stage-appropriate urological therapy regime. RESULTS: Contrast-enhanced ultrasonography (CEUS) is currently unable to distinguish between benign and malignant renal tumours. Nevertheless, this noninvasive method is useful in everyday clinical practice: in excluding renal pseudolesions, in inflammatory lesions, for follow-up of traumatic pseudolesions, and for the differential diagnosis of atypical renal cyst diagnosis versus renal cancer. Contrast-enhanced sonography also reveals the microperfusion of kidney tumors, providing clues for distinguishing between clear cell and papillary types of renal cell carcinoma. The method is also utilised in CEUS-controlled biopsy procedures of renal lesions. CONCLUSIONS: Contrast-enhanced sonography augments CT/MRI imaging with real-time information on the perfusion of the kidney tumour and can be a therapy-relevant aid for the multidisciplinary cancer conference with the ultrasound examinations being presented as video clips for comment thereon.

[Muscle-invasive urothelial carcinoma of the bladder. Detection and topography of micrometastases in lymph nodes]. / Muskelinvasives Urothelkarzinom der Harnblase. Detektion und Topographie von Mikrometastasen in Lymphknoten.

Detection of metastases in lymph nodes is an important prognostic factor for progression-free survival in bladder cancer patients. Patients undergoing radical cystectomy with pelvic lymphadenectomy are randomized in the LEA study (AUO AB 25/02) into two groups receiving standard (obturator and external nodes) or extended lymphadenectomy (complete pelvic nodes up to the inferior mesenteric artery).The aim of this study is the detection of lymph node metastases that are not identified with classic pathological methods using RT-PCR as a highly sensitive and specific method. For detection of occult disseminated tumor cells we analyze the expression of the tumor markers cytokeratin 20 (CK-20), uroplakin II (UP II), mucin 2 (MUC2), and mucin 7 (MUC7).We examined 315 lymph nodes from 19 cystectomy patients for the expression of CK-20. In 93 lymph nodes CK-20 expression was detected whereas only 18 lymph nodes were histopathologically positive. More than one third of CK-20-positive lymph node metastases were located outside the standard lymphadenectomy field. We did not detect any skip lesions. Follow-up data will validate if there is a correlation between detection of occult disseminated tumor cells and progression-free survival.

[Intravesical radioimmunotherapy of carcinoma in situ of the urinary bladder after BCG failure]. / Intravesikale Radioimmuntherapie des Carcinoma in situ der Harnblase nach BCG-Versagen.

BACKGROUND: In failure to respond to bacillus Calmette-Guérin (BCG) in patients with carcinoma in situ (CIS) of the urinary bladder, radical cystectomy remains the mainstay after BCG failure. OBJECTIVES: The aim of this pilot study was to evaluate tolerability and safety of the α­emitter radioimmunoconjugate instillation in patients after BCG failure. MATERIALS AND METHODS: Nine patients were included. After emptying the bladder via a transurethral catheter, Bi-213-anti-EGFR-mAb was instilled. Treatment was terminated by emptying of the radioimmunoconjugate from the bladder 120 min after instillation. Efficacy was evaluated via endoscopy and histology 6 weeks after instillation. RESULTS: All patients showed excellent toleration of the treatment without any side effects. Treatment resulted in complete eradication of tumor cells in 3 patients and persistent tumor detection in the other 6 patients. CONCLUSIONS: Intravesical instillation of Bi-213-anti-EGFR-mAb is a promising therapeutic option for treatment of in situ bladder cancer after BCG failure for patients who wish to preserve the bladder.

[Systemic therapy of metastatic renal cell carcinoma]. / Systemische Therapie des metastasierten Nierenzellkarzinoms.

Cytokine-based immunotherapy was the only viable option in metastatic, nonresectable renal cell carcinoma (RCC) for many years. Systemic immunotherapy has become increasingly established as a standard therapy during the last 15 years. In this context, interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) turned out to be the most effective single agents in RCC. Subsequently, the approved subcutaneous application of these compounds was the preferred administration route in Germany. Response rates with cytokine combination therapy were almost similar to those of more aggressive concepts using additional chemotherapeutic agents.Currently, new compounds targeting specific signaling pathways are readily available and have passed clinical testing. Such small molecules like tyrosine kinase inhibitors, monoclonal antibodies, or the mTOR inhibitor CCI-779 may dramatically change the established concepts of systemic RCC treatment. This paper gives an overview of established, current, and evolving concepts of systemic therapy in RCC.

[Translational research in renal cell cancer. Illustrated by the example of the vascular endothelial growth factor pathway]. / Translation molekularer Zusammenhänge in die klinische Anwendung. Dargestellt am Beispiel des Vascular-Endothelial-Growth-Factor- (VEGF-)Pathway.

For patients with metastatic renal cell cancer (RCC), therapeutic options after cytokine failure are rather limited. There is a considerable need to identify new substances for systemic therapy. Due to upregulation after the loss of a functional von Hippel Lindau gene product, the vascular endothelial growth factor (VEGF) pathway is a promising target for a molecular based therapy. Over the last few years, therapeutic agents have been developed which inhibit this pathway at various levels. Here, we provide an overview of the molecular background and currently used drugs which have entered clinical trials in the setting of metastatic RCC disease. Until now, the results from early clinical trials are very promising, however, the best schedule, dosage, potential combination regimens, as well as long time efficacy, are still to be determined.

[c-MET Oncogene in Renal Cell Carcinomas]. / c-Met Onkogen bei Nierenzellkarzinomen.

c-Met plays a significant role in multiple cellular processes. Being encoded by a proto-oncogene, tyrosine kinase supports aggressive tumour behaviour such as tumour invasiveness and formation of metastases. For some subtypes of renal cell carcinoma studies have shown a association between c-Met expression and clinical outcome or prognosis. Therefore, c-Met represents a prognostic marker in renal cell carcinoma.Furthermore, c-MET will play a decisive role as a possible target for targeted therapies in the era of personalised medicine. Especially for RCC, the dual inhibition of VEGF and c-MET tyrosine kinase in cases of metastatic, treatment-resistant tumours is gaining clinical relevance. The role of c-Met has not been fully elucidated for all subtypes of renal cell carcinomas. The relevance of c-Met for the remaining subtypes of renal tumours has yet to be clarified.

[Hands-on teaching for students in urology: the use of peer teaching and simulators]. / Praktische Studentenausbildung in der Urologie: Einsatz von studentischen Tutoren und Simulatoren.

BACKGROUND: Hands-on training in urology for medical students is characterized by several challenges. We tried to improve our practical training day using peer teaching/peer-assisted learning and simulators. MATERIAL AND METHODS: An average of 116 students participated in our practical training day every semester between 2007/2008 and summer semester 2011. We evaluated students' satisfaction, human resources, and student to teacher ratio before and after the restructuring. RESULTS: After the restructuring in 2008/2009, all categories showed improvement (1=best; 6=worst). The general rating rose from 2.2 (2008) to 1.45 (2011); practical training improved from 2.85 (2008) to 1.55 (2011). DISCUSSION: Peer teaching and simulators are reasonable tools in medical education in urology. They increase individual coaching of students and lead to improved satisfaction and subjective learning success. Interprofessional education with the selective use of nursing staff as teachers was widely accepted. With these tools essential hands-on skills in urology can be acquired by all medical students.

[The significance of extended pelvic lymphadenectomy in bladder cancer]. / Stellenwert der extendierten pelvinen Lymphadenektomie beim Harnblasenkarzinom.

Despite radical surgery, invasive urothelial carcinoma has a high risk of systemic progression. This might be due to the presence of occult but already disseminated tumor cells in lymph nodes, blood, or bone marrow. In all retrospective series presented here, extended pelvic lymphadenectomy seems to provide a clear benefit for survival in pN0 and pN+ patients. Lymph node density and absolute number of positive lymph nodes appear to affect patient outcome and survival. However, only the randomized, prospective German LEA study will hopefully provide conclusive new data.

[Psychosomatic aspects of chronic recurrent cystitis]. / Psychosomatische Aspekte der chronisch rezidivierenden Zystitis.

INTRODUCTION: In spite of intensive research, chronic recurrent cystitis is etiologically a still insufficiently understood clinical picture. CASE REPORT: A 52-year-old patient presented with recurrent cystitis that had been treated exclusively somatically for years for which at least a psychosomatic co-pathogenesis of magnitude of the discomfort was diagnostically representable as well as being of therapeutic utility. CONCLUSION: In recollection of a bio-psychosocial understanding of human diseases, psychosomatic considerations should be undertaken at last but not least in patients with persistent cystitis.

Analysis of chromosome replication by a BrdU antibody technique.

Chromosome replication was studied without synchronization in human lymphocyte and amniotic cell cultures visualizing very short 5-bromodeoxyuridine (BrdU) pulses by an immunologic technique (BAT). The findings agree in general with those facts known from earlier BrdU staining techniques. The very high sensitivity of BAT was shown to allow the detection of replication in a band where 1 in 200 nucleotides is replaced by BrdU. The main observations are: though the replication patterns after BAT appear strange the bands correspond to those described by the Paris Conference (1971). At the beginning of the S-phase a stepwise onset of replication in only a subset of R-bands is confirmed. There is a considerable difference in the sensitivity between early and late S (SE and SL) for the detection of BrdU pulses. This difference probably reflects a different spatial arrangement of chromatin in R-bands as compared with G-bands below the level of cytogenetic analysis. The use of short pulses did not reveal any additional subdivision of SE or SL. The correspondence between chromosomal bands and replicon clusters is discussed briefly with respect to the different time they need for replication.

Detection of bromodeoxyuridine-incorporation in mammalian chromosomes by a bromodeoxyuridine-antibody. I. Demonstration of replication patterns.

We have shown that a commercially available antibody allows the demonstration of bromodeoxyuridine (BrdU) incorporation into mammalian chromosomes by the typical immunologic staining techniques. The replication patterns obtained are comparable to those after BrdU-incorporation and FPG-staining, though with reversed staining specificity. The quality of the patterns equals that of commonly used differential staining but the sensitivity of BrdU-detection is superior. Thus the new technique may be very promising for all cytogenetic studies concerning any kind of chromosome replication.

Demonstration of replication patterns on histone-depleted chromosomes.

A modified immunologic technique is described for the purpose of demonstrating replication patterns on mammalian chromosomes after partial histone depletion. Replication patterns were induced by BrdU substitution and visualized by BrdU antibodies, coupled with peroxidase (diaminobenzidine/H2O2) or immunogold-detection. The replication patterns obtained by this technique did not reveal any additional details of replication compared to those shown by conventional cytogenetic staining. However, the possibility of demonstrating replication patterns on these partially histone-depleted chromosomes may prove useful for chromosomal in situ hybridization studies since the chromosomes produced are considerably larger than those seen in conventional preparations.

[Brain protection in the surgical reconstruction of the supra-aortic arteries]. / Zur Hirnprotektion während der operativen Rekonstruktion supraaortaler Arterien.

The importance of brain protection in surgical handling of supra-aortic arteries may be derived from the specific nature of cerebral blood flow and from the pathophysiology of damaged cerebral vessels. There is a wide range of special protective methods which have proved to be effective, including strict observance of established rules on surgical indication and tactics, maintenance of circulatory homoeostasis, heparinisation, and use of an intra-luminal shunt. Results obtained from operations on 486 patients for occlusion of supra-aortic arteries are discussed, with particular emphasis being laid on the need for intra-operative EEG monitoring. Reference is also made to measures of brain protection in the postoperative phase.