Früherkennung von Prostatakarzinomen

The euphoria over PSA as an optimal marker for prostate cancer is gone. Measuring PSA levels has several deficiencies in detecting prostate cancer. First results of the randomized studies ERSPC and PLCO were not able to conclusively prove the value of PSA-based screening. Many attempts have been made to optimize early detection of prostate cancer like using modern imaging techniques or new biomarkers. This review deals with PSA isoforms und emerging biomarkers for the diagnosis of prostate cancer. Despite the inadequacies of PSA it is still the most important marker for the early detection of prostate cancer. Modern biomarkers with the ability to reliably predict aggressive prostate cancer are still missing.     

Targeted-Therapie des metastasierten Urothelkarzinoms

The current therapy concept for metastatic bladder cancer is chemotherapy with gemcitabine and cisplatin as the first line protocol. Within the last 20 years no real progress could be achieved; the median survival is 14 months, though many different protocols have been tested. Expression analyses of growth factor receptors in human tumor tissue showed that expression of certain receptors is correlated with a severe clinical course.For many of these growth factor receptors pharmacological inhibitors are available in order to perform targeted therapy. The following review gives a survey of current studies on targeted therapy of metastatic bladder carcinoma.     

Effect of a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on carotid intima-media thickness, endothelial function, and renal function in patients with mild to moderate chronic kidney disease: results from the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study

BACKGROUND: Patients with chronic kidney disease have an increased risk of cardiovascular disease. Oxidative stress has been proposed to play a role in the development of cardiovascular disease among these patients. METHODS: We conducted a randomized, double-blind trial in 93 patients (Cockcroft-Gault equation: creatinine clearance, 38+/-15 [mean+/-SD] mL/min per 1.73 m2 [0.63+/-0.25 mL/s per m2]) to investigate the effect of a treatment strategy designed primarily to achieve stepwise oxidative stress reduction on common carotid intima-media thickness (CC-IMT), brachial artery flow-mediated dilatation (BA-FMD), albuminuria, and renal function. The treatment group received a regimen of pravastatin to which vitamin E supplementation was added after 6 months and homocysteine-lowering therapy after another 6 months. Blood pressure in both groups was managed according to a standard protocol. The placebo group received matching placebos. Measurement of CC-IMT and BA-FMD was performed at randomization after 6, 12, and 18 months. Patients were followed up for 2 years. Generalized estimating equations were used for analysis. RESULTS: Compared with placebo, active treatment was associated with a decrease in CC-IMT (after 18 months: from 0.68 to 0.63 mm in the treatment group and from 0.65 to 0.71 mm in the placebo group; P<.001), an increase in BA-FMD (after 18 months: from 4.66% to 7.56% in the treatment group and from 6.21% to 4.73% in the placebo group; P<.001), and an attenuated increase in urinary albumin excretion over time (P=.04 for between-group difference after 24 months), but no effect was observed on renal function. CONCLUSION: In patients with mild to moderate chronic kidney disease, 18 months of a treatment strategy along with well-controlled blood pressure reduced CC-IMT and urinary albumin excretion and increased BA-FMD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00384618.     

Vergleich der perioperativen Methylenblau-gefärbten Schnellzytologie mit der nach Papanicolaou gefärbten Permanentzytologie in der Detektion von Patienten mit High-grade-Urothelkarzinomen der Harnblase

INTRODUCTION: The aim of the study was to investigate whether intraoperative methylene blue-stained and permanent Papanicolaou-stained urine cytologies show comparable accuracy in detection of high-grade urothelial carcinoma. PATIENTS AND METHODS: The study included 130 patients; 50 patients were without malignancy (25 follow-up, 25 with hematuria). In 80 patients transurethral resection due to urothelial carcinoma was performed. Per patient two cytology specimens were prepared: one immediate methylene blue-stained specimen, which was evaluated by the surgeon, and one Papanicolaou-stained permanent cytology slide, which was blinded and evaluated by one urologist. RESULTS: Cytology results of all patients without malignancy were unsuspicious irrespective of the staining method. Of 80 patients with urothelial carcinoma, 50 showed a low-grade tumor. Sensitivity of tumor detection was 20 and 30% for methylene blue/Papanicolaou-stained slides, respectively. Among 30 patients with high-grade carcinoma, 10 were detected by methylene blue cytology and 30 by Papanicolaou-stained slides, corresponding to a sensitivity of 40 and 100%, respectively. CONCLUSIONS: The results of standard Papanicolaou-stained urine cytology in the detection of clinically relevant high-grade urothelial carcinoma are excellent. The quality of cytological tumor detection by methylene blue-stained cytology made by different evaluators is insufficient in our opinion.     

Urinzytologische Charakterisierung von Patienten mit Urothelkarzinomen und Verbesserung und kombinierte Zytologie und Zytometrie zur Vermeidung von Fehlinterpretationen durch die Urinzytologie

Ohne Zusammenfassung     

Einsatz der Siliziumchiptechnologie zur Detektion von Tumormarkern auf Proteinbasis beim Harnblasenkarzinom

The protein structure of human tumor tissue has a significant influence on the molecular attributes. It was demonstrated that the individual prognosis of tumor patients is among other things dependent on molecular tumor tissue characteristics.A promising marker is E-cadherin, an adhesion glycoprotein which plays a central role in the mediation of cell-cell contacts. Aberrant E-cadherin expressions were described in several tumors such as in bladder cancer. This was also found to be correlated with tumor invasion and survival. There are hardly any fast, quantitative and easily automated protein assays in everyday practice which can analyze several markers at the same time. With silicon chip technology we have a new detection and measurement method which makes it possible to give a quantitative analysis of numerous different proteins in tissue, urine, or serum in a few minutes.     

Stimulatory effects of the multi-kinase inhibitor sorafenib on human bladder cancer cells

BACKGROUND AND PURPOSE

Sorafenib is an inhibitor of several intracellular signalling kinases with anti-proliferative, anti-angiogenic and pro-apoptotic effects in tumour cells. Sorafenib is used in the therapy of advanced renal cell carcinoma, and several phase II clinical trials are being carried out in patients with urothelial carcinomas.

EXPERIMENTAL APPROACH

Using a panel of human bladder cancer cell lines (RT4, T24, J82), we characterized systematically the effects of sorafenib on intracellular signalling, migration, proliferation and apoptosis.

KEY RESULTS

We demonstrated that at low concentrations (<1 µM), sorafenib is capable of significantly stimulating migration and proliferation of the bladder cancer cells. We hypothesize that these stimulatory effects on tumour cell functions might be explained by an activation of the Ras/ERK-1/2 signal transduction pathway. In addition, the comparison of different bladder cancer cell lines not only revealed a different biology (e.g. cell migration), but also a differential susceptibility to the anti-apoptotic effects of sorafenib. Finally, we confirmed in different bladder cancer cell lines the known inhibitory actions of sorafenib in pharmacological concentrations (≥3 µM) on ERK-1/2 phosphorylation, migration and proliferation, as well as the pro-apoptotic effects of the compound.

CONCLUSIONS AND IMPLICATIONS

Taken together, these findings suggest that although sorafenib has the potential to be used in the treatment of urothelial carcinoma, this compound might also activate bladder cancer cells at low concentrations. This should be relevant for dosing regiments to optimize the treatment with this promising anti-tumour drug.     

The f/t-PSA ratio in diagnosis of in-patients and out-patients: a unitary cutoff value is not useful!

Purpose

In the prostate specific antigen (PSA) range of 4–10 ng/ml after a negative digital rectal examination, the PSA value indicates a lack of specificity with a carcinoma detection rate of roughly 20%. To improve the biopsy/carcinoma ratio, the interdisciplinary consensus recommends free PSA (fPSA) measurement. This does not take into account the pre-analysis when the cutoff value is established for biopsy indication.

Methods

In the present study, an in-patient cohort whose blood samples were immediately analysed was compared with an out-patient cohort whose sample processing was delayed by between 24 and 48 h.

Results

The in-patient cohort comprises 382 patients with 99 prostate carcinomas, the out-patient cohort 987 patients with 235 carcinomas. In the in-patient cohort a sensitivity of 90% with a cutoff value of 25% for the f/t-PSA ratios is achieved with the theoretical possibility of reducing the number of punch biopsies by 34.6%. A sensitivity of 90% in the out-patient cohort necessitates a cutoff value of 18% for the f/t-PSA ratios. The specificity is 35.3% with a possible biopsy reduction of 29.1%.

Conclusions

The cutoff values from cohorts with an immediate fPSA measurement cannot be adopted for a typical out-patient cohort whose analyses are delayed. On the contrary, an individual adjustment is necessary which corresponds to the pre-analysis.