[Influence of the working model on the education of young urologists : Education through the ages]. / Auswirkung eines Arbeitszeitmodells auf den Facharzt für Urologie : Eine Ausbildung im Wandel der Zeit.

BACKGROUND: There is a trend of increasing discontent of urologic residents with educational programs. One point being mentioned is lack of time during residency for education and self-training. We analyzed the available time for education in our department depending on the used working model through the last 25 years. MATERIALS AND METHODS: We calculated the absolute availability of residents during their residency for working models in 1996, 2000, 2007 and 2017. As a basis we used the working model of 1996 as no compensatory time-off for being on call was used. All days on which a delayed start is planned and no schedule in daily routine is possible had been excluded from education time. The numbers implemented in the regulation on further education in the corresponding years had been used to calculate the expenditure of time on the basis of median length of the different intervention. In addition, the patient numbers on the ward and our outpatient clinic had been documented over time. RESULTS: With increasing patient numbers in the in- and outpatient clinic there is a continuous decreasing time available for education. The absolute available time in our department is calculated to be 3.1 years compared to 5 years in 1996. With the first day of training a resident has to complete 66.9 min of self-contained diagnostics or interventions per day in addition to clinical routine and administration to meet the requested numbers of the regulation on further education. CONCLUSIONS: The limited time being available for the educational program is improved by the current regulation of education. To teach the complex segments of urology there is an urgent need for a well-structured curriculum, which should be used nationwide.

Disruption of the FA/BRCA pathway in bladder cancer.

Bladder carcinomas frequently show extensive deletions of chromosomes 9p and/or 9q, potentially including the loci of the Fanconi anemia (FA) genes FANCC and FANCG. FA is a rare recessive disease due to defects in anyone of 13 FANC genes manifesting with genetic instability and increased risk of neoplasia. FA cells are hypersensitive towards DNA crosslinking agents such as mitomycin C and cisplatin that are commonly employed in the chemotherapy of bladder cancers. These observations suggest the possibility of disruption of the FA/BRCA DNA repair pathway in bladder tumors. However, mutations in FANCC or FANCG could not be detected in any of 23 bladder carcinoma cell lines and ten surgical tumor specimens by LOH analysis or by FANCD2 immunoblotting assessing proficiency of the pathway. Only a single cell line, BFTC909, proved defective for FANCD2 monoubiquitination and was highly sensitive towards mitomycin C. This increased sensitivity was restored specifically by transfer of the FANCF gene. Sequencing of FANCF in BFTC909 failed to identify mutations, but methylation of cytosine residues in the FANCF promoter region was demonstrated by methylation-specific PCR, HpaII restriction and bisulfite DNA sequencing. Methylation-specific PCR uncovered only a single instance of FANCF promoter hypermethylation in surgical specimens of further 41 bladder carcinomas. These low proportions suggest that in contrast to other types of tumors silencing of FANCF is a rare event in bladder cancer and that an intact FA/BRCA pathway might be advantageous for tumor progression.

[Future of chemotherapy]. / Zukunft der Chemotherapie.

The future development of chemotherapy is derived based upon recent advances. With regard to adjuvant therapy a trend towards standardized prediction of recurrence risk using all available prognostic markers (e.g., nomograms) is observed. Furthermore, in some tumors major progress has been made regarding the development of "molecular classifiers" defining tumor biology (predicting clinical outcome) by analysis of molecular changes. In adjuvant therapy considerable advances may be achieved by use of new chemotherapeutic agents as well as sequential, dose-dense and dose-intensified regimens. However, in metastatic disease no breakthrough can be expected at least with regard to survival suggesting that quality of life needs to be addressed with more emphasis. Using targeted drugs alone or in combination with chemotherapy advances concerning adjuvant therapy as well as metastatic disease are observed. Further targeted drugs have entered clinical development. However, clarification of the relation between detection of the target(s) and drug activity will fundamentally change current treatment concepts.

[Microarrays]. / MicroarraysTechnik und Potenzial beim Prostatakarzinom.

Microarrays allow a simultaneous gene expression analysis of thousands of genes, providing an expression profile of the specimen investigated. Thus, this procedure is well suited to characterize the complex genetic alterations of malignant tumors. Using unsupervised hierarchical cluster analysis, characteristic expression profiles for individuals, organs and tissues, as well as for different cell types, can be identified. Molecular signatures have been observed in tumors compared to normal tissue, for different tumor stages, risk groups or response therapy. In prostate cancer, many tumor-specific gene expression alterations have been identified. Among these, the cell surface protease hepsin and alpha-methyl-acryl-CoA-racemase might gain importance as diagnostic tools. Moreover, gene expression profiles were identified which are associated with advanced tumor stage, poor differentiation or progress after radical prostatectomy. Increased expression of enzymes of steroid biosynthesis and the androgen receptor appears to be part of the molecular signature of hormone refractory prostate cancer.