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The purpose of the present study was to assess a new quantitative urinary tumor marker for transitional cell carcinoma of the urinary bladder (TCC), measuring fragments of cytokeratin 8 and 18 in the urine (UBC). Urine samples of 355 individuals (77 healthy volunteers, 111 patients with benign urologic disorders, 167 patients with histologically proven bladder cancer) were examined for the presence of UBC antigen. Samples of all patients were obtained prior to therapy. Compared to healthy volunteers or patients with benign urologic disease, patients with TCC had significantly higher median urinary levels of UBC antigen (0 vs. 4.18 vs. 7.46 microg/g creatinine; p<0.001, and p<0.01, respectively). UBC antigen levels were positively correlated with tumor grade and stage. Patients with invasive TCC had significantly higher levels of UBC antigen than patients with superficial TCC (p<0.001). Elevated levels of UBC antigen were also found in patients with benign urologic disorders (median: 4.18 microg/g creatinine vs. 7.46 microg/g creatinine in cancer patients). Using a cutoff of 14.06 microg/g creatinine (corresponding to 95% specificity in the group of healthy individuals), sensitivity of UBC antigen ranged between 21.6% (pTa) and 75% (pT4). Overall specificity was 76.6%. Based on our data we conclude that the UBC antigen test in its current format is not clinically useful for detection of bladder cancer.

We report the case of a 61-year-old man, with a rare combination of two advanced urological tumors: a concomitant spread of an adenocarcinoma beyond the kidney and a urothelial carcinoma beyond the bladder. We simultaneously performed a primary curative prostatovesiculectomy and a nephroureterectomy on the right with ileal neobladder. To our knowledge, a case report of concomitant spread of an adenocarcinoma beyond the kidney (pT3 pN0 M0 G3) and a urothelial carcinoma beyond the bladder (pT3a pN0 M0 G3) with subsequent curative therapy has thus far not been published. A combination of the two diseases described here is obviously a remarkable rarity.

Objectives: To assess the diagnostic quality of human complement factor H-related protein (hcfHrp, BTA STAT(TM)) as a qualitative urinary marker for bladder cancer., Methods: Urine samples of 354 individuals (76 healthy volunteers, 111 patients with benign urologic disorders, 167 patients with histologically proven bladder cancer) were examined prior to therapy for the presence of hcfHrp., Results: Overall test sensitivity was 62.9%. Sensitivity of low-grade/low-stage tumors was <50% and was thus comparable to published sensitivities of urinary cytology. In high-stage, high-grade tumors sensitivity was 100 and 77.3%, respectively. Superficial tumors with high risk of progression (pT1G3) were detected significantly better (88.9% sensitivity) than low-risk superficial tumors (pTa G1-3/pT1G1-2; 48.2%; p < 0.001). The overall specificity (healthy individuals and patients with benign urologic disease) was 93.0%., Conclusion: Since test sensitivity is comparable to urinary cytology and specificity is excellent, hcfHrp should be further evaluated in prospective studies focussing on the follow-up of patients with bladder cancer., (Copyright 2000 S. Karger AG, Basel)

Objectives: The aim of this study was to evaluate whether pelvic lymph node metastases in patients with neoplasms of the bladder or prostate can be detected applying positron emission tomography with 2-[(18)F]-2-deoxy-D-glucose (FDG-PET)., Methods: Eight patients with bladder cancer and 17 patients with prostate cancer were examined with FDG-PET before pelvic lymph node dissection. Results of PET were then compared to histology of pelvic lymph nodes obtained at surgery., Results: Lymph node metastases were detected by histopathological examination in 3 patients with bladder cancer and in 6 patients with prostate cancer. At the sites with histologically proven metastases, increased FDG uptake suspicious of metastatic disease was found in 2/3 and 4/6 patients, respectively. The smallest detected metastasis was a micrometastasis with a diameter of 0.9 cm. In 3 additional patients who all had histopathologically proven micrometastases (

Objective: The purpose of this study was to assess a new quantitative urinary tumor marker for transitional cell carcinoma of the urinary bladder (TCC), human complement factor H-related protein (hCFHrp, BTA TRAK)., Methods: Urine samples of 298 individuals (76 healthy volunteers, 118 patients with benign urologic disorders, 104 patients with histologically proven bladder cancer) were examined for the presence of hCFHrp. Samples of all patients were obtained prior to therapy., Results: In comparison to healthy volunteers, patients with TCC had significantly higher urinary levels of hCFHrp (117.60 vs. 2.05 U/ml; p < 0.001). HCFHrp levels were positively correlated with tumor grade and stage. Patients with invasive TCC had significantly higher levels of hCFHrp than patients with superficial TCC (p = 0.001). Marker levels in superficial bladder cancer at high risk of tumor progression (pT1G3) were significantly higher as compared to low and intermediate grade superficial cancers. Elevated levels of hCFHrp were also found in patients with benign urologic disorders (median: 72.65 vs. 117.60 U/ml in cancer patients). Using a cutoff of 17.1 U/ml, hCFHrp had a sensitivity of 72.1% and, due to a high rate of false-positive determinations in patients with benign urologic disorders, a total specificity of 50.5%., Conclusions: HCFHrp (BTA TRAK) is a sensitive test for detection of bladder cancer and for identification of patients at high risk. Due to a high rate of false-positive results in patients with benign urologic diseases, the test should not be used in an unselected population.

New, noninvasive methods for the early detection of urothelial carcinomas of the urinary bladder are needed for the diagnosis, follow-up, and screening of patients with bladder cancer. Detection of the enzyme telomerase in urine could offer these new diagnostic possibilities. The standard technique for detecting telomerase activity is the telomeric repeat amplification protocol (TRAP assay). Because of the instability of the ribonucleoprotein telomerase in an aggressive medium, such as urine, investigations conducted to date have yielded nonuniform or even contradictory findings. This study compares the detection of human telomerase RNA (hTR) by reverse transcriptase-PCR (RT-PCR) with detection of telomerase activity by the TRAP assay in the diagnosis of urothelial carcinoma of the urinary bladder. Sedimented cells obtained from urine of 30 patients with urothelial carcinoma, 15 patients with benign urological disorders, 3 patients as part of follow-up for malignant disease, and 20 healthy subjects were examined for the presence of hTR and for telomerase activity (TRAP). In patients with bladder cancer, telomerase activity was detected by the TRAP assay in only 2 of 30 specimens (7%). However, increased levels of hTR were detected by RT-PCR in 25 of the same 30 cases (83%). For patients with benign urological disorders, such as urolithiasis or urinary tract infections, hTR was detected in samples obtained from 4 of 15 patients (27%). Low hTR expression levels were found in 15% of the healthy controls. The detection of hTR by RT-PCR represents a promising new method for detecting malignant cells in urine.

Early diagnosis is still the most important prerequisite for successful cancer treatment and this holds true for bladder cancer. Urine cytology is commonly used as a non-invasive screening procedure for the detection of bladder carcinoma, but this method is labour-intensive and often generates false-negative results. The ribonucleoprotein telomerase appears to be promising new cancer marker, since its activity has been reported to correlate with indefinite growth. The aim of this study was to investigate whether telomerase activity can be detected in bladder cancer and in corresponding bladder washings. For this purpose, a sensitive non-radioactive TRAP (telomeric repeat amplification protocol) detection system was developed. With this technique, telomerase activity was found in 95 per cent of the carcinomas (n = 20), in 70 per cent of the corresponding bladder washings, but in none of the urine samples obtained from patients with bladder carcinoma. No telomerase activity was detectable in normal urothelium or in samples from dysplastic urothelium. The data obtained from bladder washings show that superficial carcinoma cells released into the bladder still harbour telomerase activity. The absence of telomerase activity in voided urine is thus most likely due to degradation or inactivation under these conditions. The high rate of telomerase activity in bladder carcinoma indicates that the activation of telomerase in a common step in the tumourigenesis of bladder cancer.

CD44 is the principal cell surface receptor for hyaluronate. Variant forms of the receptor, produced by alternative splicing, have been found to be associated with tumor progression in a variety of cancers. Based on investigations at the RNA level, it has recently been proposed that expression of CD44 variant V2 was present in urothelial cancer but not in normal urothelium. Since a distinctive marker for urothelial cancer would be extremely useful, frozen sections of normal urothelium and urothelial cancer were examined for expression of standard CD44 and CD44V2. Frozen sections of specimens of 35 patients with transitional cell carcinoma of the bladder, 16 specimens of normal bladder and 5 ureters were examined. Immunohistochemical staining was performed using a polyclonal antibody to CD44V2 (PAB CD44V2), a monoclonal antibody to CD44V2 (MAB CD44V2) and a monoclonal antibody to CD44S (MAB CD44S). CD44V2 and CD44S were also measured in lysates of urine sediments from 21 patients by enzyme-linked immunoabsorbent assay (ELISA). All investigated transitional cell carcinomas expressed CD44V2. There was no differentiation between invasive and noninvasive carcinoma. CD44V2 was also expressed in normal urothelium. Standard CD44 was expressed by the transitional cell carcinoma, normal urothelium, musculature and interstitial tissue. The amount of CD44V2 and CD44S in lysates of urine sediments is not correlated to diagnosis. In contrast to investigations at the RNA level, CD44V2 on the protein level seems not to be a distinctive marker for urothelial cancer. Therefore, CD44V2 will not be a useful diagnostic marker for detection of transitional cell carcinoma.

Objectives: To date, chemotherapy for advanced urothelial carcinoma has been associated with only moderate therapeutic success and minimal extension of survival. This, coupled with the occurrence of serious side effects and the resulting reduced quality of life, underscores the need for new chemotherapeutic agents. A first study investigating combination therapy with etoposide and ifosfamide reported not only comparable therapeutic effectiveness but, due primarily to the elimination of the cisplatin component, a reduction in nephrotoxic side effects. In the present study, therefore, patients with advanced urothelial carcinoma and minor compromised renal function received combination chemotherapy with etoposide and ifosfamide., Methods: Fourteen patients with advanced urothelial carcinoma underwent chemotherapy with a combination of etoposide and ifosfamide. On days 1-5, patients received 1,500 mg/m2 ifosfamide and 120 mg/m2 etoposide. The next corresponding cycle was started on day 22., Results: A number of serious side effects were observed. These consisted predominantly of high-grade myelosuppression requiring therapy, as well as disturbances in the central nervous system and impairment of renal function. Due to severe side effects, chemotherapy had to be prematurely terminated in 8 of 14 patients (57%). The efficacy of therapy, however, was observed in patients completing the treatment regimen., Conclusions: The new combined chemotherapy with etoposide and ifosfamide shows efficacy in the treatment of advanced urothelial carcinoma. This, however, is overshadowed by the high rate of serious side effects leading to premature interruption of therapy.

Objectives: Topically applied photosensitizers are particularly suited for use in the photodynamic therapy of urinary bladder tumors. The objective of the present study was to investigate the photodynamic effects of sulfonated aluminum chlorophthalocyanine on human bladder carcinoma cells., Methods: The photodynamic efficiency and the morphologic changes induced by sulfonated aluminum chlorophthalocyanine on human bladder carcinoma cells and normal bladder wall cells were investigated in vitro using light microscopy and in order to determine the subcellular target organelles using electron microscopy., Results: Examination of tumor cells with light microscopy after previous photodynamic therapy initially showed distension of the cells and, depending on the duration, a significant blistering of the cell membrane, leading, in some cases, to rupture of the cells. Electron microscopy revealed destruction of the mitochondria. No changes in other cell organelles or structures were observed., Conclusions: Sulfonated aluminum chlorophthalocyanine exhibits good photodynamic activity in bladder tumor cells with relative tumor selectivity. The primary cellular target of photodynamic therapy seems to be the mitochondria.