Molecular genetic methods in the diagnosis of invasive bladder cancer.

Development and progression of tumours is generally driven by an accumulation of genetic alterations. In this study we correlated chromosome 17 aneuploidy to invasiveness of bladder cancer by the method of fluorescence in situ hybridisation (FISH) in urinary cytospins. We investigated the value of FISH compared to DNA cytophotometry in the diagnosis of bladder cancer. 39 patients with or suspicious for bladder tumour were analyzed. 19 patients had a bladder tumor at the time of diagnosis, 14 superficial (Ta-T1) and 5 invasive (T2-3). The remaining 20 patients had no tumour at the time of diagnosis, however 9 of them had one in prehistory (Ta-T2). For FISH we used the DNA probe of HER-2/neu located on chromosome 17. DNA image cytometry was performed according to single cell interpretation of Böcking. Our results showed a correlation between HER-2/neu CEP 17 alterations and invasive bladder cancer to the extent of 10-70% aberrant cells for patients with current invasive bladder tumour as well as for patients who had been cured but with as invasive bladder cancer in prehistory. On the other hand, the percentage of aneuploid cells for negative biopsy and superficial tumour was 0-2%. The DNA cytophotometry brought an uniform aneuploidy only for present invasive tumours: negative biopsies, superficial cancer and invasive tumour just in prehistory, showed mixed diploid-aneuploid DNA patterns. Our results showed that for the detection of aberrant tumour cells the method of FISH is more sensitive than DNA cytometry. FISH could provide important information in the prognosis of bladder cancer.

Control of hepatic parameters in renal cell carcinoma (RCC) by interleukin-6 (IL-6)?

RCC can go hand-in-hand with an elevation of various hepatic proteins. An interrelationship between the IL-6 titer, C-reactive protein (CRP) and the blood sedimentation rate (BSR) has already been proven. The aim of the present study was to study 1) the possibility of differentiating between healthy and RCC patients via IL-6 in the serum and 2) the relationship of IL-6 to hepatic parameters {alkaline phosphatase (AP), gamma-glutamyltransferase (gGT), serum proteins (E'p)} and the usual clinical prognostic parameters (tumor grading, staging). Serum analysis of 38 healthy patients via ELISA (DPC-Biermann, Germany) showed normal values of 1.2 ng/ml for IL-6, with a standards deviation of +/- 1.7 and a peak concentration of 3 ng/ml (specificity: 95%). In 20 RCCs there were IL-6 titers of 10.7 ng/ml +/- 6.56 in the pre-operative serum. The sensitivity of IL-6 was about 90%. The difference was statistically significant (p < 0.0001, Wilcoxon test). For IL-6 there was a positive correlation with the BSR (1-hour value: r = 0.7; 2-hour value: r = 0.6), CRP (r = 0.85), E'p (r = 0.6), and gGT (r = 0.6). No correlation was found between AP, the Robson stage, grading, and IL-6. IL-6 is potentially suitable for differentiating between healthy and RCC patients but is not tumor specific. IL-6 has a strong correlation with all laboratory values which were analyzed except AP thus there is considerable evidence for a cytokine (IL-6) control of the hepatic changes. Since some of the above-named laboratory parameters have prognostic relevance, IL-6 can be regarded as a cumulative prognostic parameter.

[ImmunoCyt--a new urine test in diagnosis of bladder cancer]. / Urinzytologie beim Harnblasenkarzinom. Diagnostische Wertigkeit eines neuen immunologischen Fluoreszenztestes.

ImmunoCyt is a new immunocytologic fluorescence test promising a higher diagnostic sensitivity, esp. for TaG1 carcinomas. The aim of the study was to evaluate the sensitivity of the test in diagnosis of bladder cancer as compared to both urinary cytology and histopathology. A total of 121 spontaneous urine samples of 92 patients (age range 28 to 86, mean 62.5 years) was examined. 41 of the samples were of patients suspicious of transitional cell carcinoma, 46 of patients in whom symptoms were suggestive of tumor recurrence, and 34 of patients who were part of a follow-up protocol. Cystoscopy was performed in all patients. The ImmunoCyt-test was carried out according to the manufacturers protocol using 3 fluorescent monoclonal antibodies. A total of 113 specimens could be evaluated. In 87 cystoscopy and/or histology was negative (control group). There was histologic evidence of 7 pTaG1, 4 pTaG2, 8 pT1G2/G3, and 7 pT2G2/G3 bladder cancers. As for ImmunoCyt and cytology specificity was 83.9% and 91.9%, resp. The combined specificity was 81.6%. Sensitivity amounted to 38.5% and 34.6%, resp., the combined sensitivity to 53.8%. Sensitivity for TaG1 carcinomas was 14.3% each, for TaG2 carcinomas 25% and 50%, for T1G2/G3 carcinomas 37.5% each, and for T2G2/G3 carcinomas 71.4% and 42.9%, resp. In our study the ImmunoCyt test did not show the expected increase in the detection of TaG1 bladder cancers. Because of false-positive results the test should only be used in combination with urinary cytology which reveals a higher specificity. In conclusion the ImmunoCyt test can not replace cystoscopy (with biopsy) in diagnosis and monitoring of bladder cancer.

[Impact of tumor size on long-term survival of patients with organ-confined renal cell cancer]. / Welche Tumorgrösse korreliert am besten mit dem Progressionsrisiko lokal organbegrenzter Nierenzellkarzinome?

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of tumor size on the long-term survival of patients with early stage renal cell cancer.

As the biological behaviour of even early stage renal cell cancer (RCC) strongly correlates with tumor size, it has been argued that the inclusion of RCC up to a maximum diameter of 7 cm into a common subgroup classified as T1 according to the 5th edition of the TNM system would not adequately represent the different biological aggressiveness of these malignancies. Taking this into account, the TNM classification, which now categorizes T1 RCC as T1a and T1b according to a cutoff size of 4 cm, was recently modified. However, only a few larger investigations, mainly based on univariate statistical analyses, that support the suitability of this cutoff are at present available from the literature. Therefore, it was the aim of the present investigation to determine the tumor size that best separates patients with low responses from those with high risk for tumor progression by univariate (log rank test) and multivariate (Cox regression model) statistical analyses. Between 1981 and 2000, 652 patients (443 males and 209 females) underwent tumor nephrectomy in our clinic for the diagnosis of RCC. Of these, 243 patients revealed primary tumors with a local growth not extending beyond the renal capsula at the time of surgery. For the different cutoff levels (starting from 2 cm in increments of 1 cm up to 8 cm) that were selected to subdivide the patients into groups according to the maximum tumor diameter, the correlation between tumor size and overall survival was determined by univariate and multivariate statistical analyses. It became evident that although during univariate analysis the prognostic value of a cutoff size of 4 cm was confirmed, multivariate analysis identified the highest relative risk for cause-specific death (2.93) for patients having tumors larger than 5 cm in maximum diameter. Therefore, the 5 cm cutoff seems to best determine the clinical prognosis of patients undergoing tumor nephrectomy for early stage RCC. The present study demonstrates the need for multivariate statistical approaches when the latest modification of the TNM classification system is critically evaluated.

Measurement of BBN-induced alterations in rat urothelium by electron microscopic X-ray microanalysis.

The aim of this study was to analyse N-butyl-n-butanol-4-nitrosamine (BBN)-induced alterations of the urothelium in rats concerning its content of phosphorus, sulphur, chlorine, potassium and calcium using electron microscopic X-ray microanalysis (REM analysis). The following histopathological findings of the bladder mucosa were discovered after exposure to BBN: normal urothelium (n = 36); focal epithelial proliferations (n = 12) following 6-12 week's exposure; epithelial hyperplasia (n = 8) after urothelial carcinoma (n = 4) following 12 weeks' exposure. The observed phosphorus/sulphur and phosphorus/calcium ratios based on REM analysis did not show any statistical correlation with the morphological changes classified by light microscopy. Our data do not support the hypothesis raised by other investigators that an increase in phosphorus content or phosphorus/sulphur or phosphorus/calcium ratio could indicate early neoplastic transformations of urothelial cells as "tumor markers".

Schistosomiasis: a critical review.

Precise data on epidemiology, morbidity, post-treatment resolution, reinfection, and resurgence of schistosomiasis could be helpful in establishing purposeful treatment plans for the disease in endemic populations. Here we give a concise overview of recent publications on bilharziasis. A main emphasis is placed on studies on the prevalence of schistosomiasis, partly including long term surveillance of morbidity following treatment with praziquantel. As genito-urinary schistosomiasis may be a risk factor for the spread of HIV, the involvement of the reproductive tract has become another focus in research on the disease. A novel diagnostic tool, eosinophil cationic protein (ECP), is proposed to correlate with the degree of inflammation of the genito-urinary tract.