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OBJECTIVES: We investigated the diagnostic efficacy of the prostate health index (PHI) and PHI density (PHID) to avoid unnecessary prostate biopsies in 3 urological practices. METHODS: In 122 patients, total prostate-specific antigen (PSA), free PSA (f-PSA), the quotient from total PSA and f-PSA (f-PSA%), and [-2]pro-PSA were measured in the serum; PHI, PHID, and PSA density (PSAD) were calculated prior to prostate biopsy. Tissue sampling via transrectal biopsy was indicated in case of suspicious PSA (progression and/or elevation of PSA) and/or suspicious digital rectal examination. PSAD, PHI, and PHID were not used for biopsy indication. The diagnostic efficacy was determined with receiver-operating characteristic (ROC)and decision curve analyses. RESULTS: Based on prostate biopsies, 38% (n = 46) of the cases had no prostate carcinoma (PCa), 21% (n = 26) no clinically significant (insignificant) PCa, and 41% (n = 50) had clinically significant PCa. ROC analyses of the PSA parameters showed higher diagnostic efficacy for PHI and PHID (AUC 0.722 and 0.739) than for f-PSA%, PSA, and PSAD (AUC 0.612, 0.595, and 0.698, respectively) regarding carcinoma diagnosis. With a combined use of PHI and PHID (cutoff >40 and >0.9, respectively), only 1 clinically significant PCa would have been missed (sensitivity 98%); in 24 (20%) patients, biopsy could have been avoided. CONCLUSION: The integration of PHI and PHID could improve the diagnostic efficacy of risk calculators to avoid unnecessary prostate biopsies. However, as a prerequisite, validation of cutoff values in prospective studies is urgently required.

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PURPOSE: As shown in various studies 5-aminolevulinic acid (ALA) induces fluorescence of malignant and dysplastic bladder tissue and increases tumor detection rates by about 20%. However, data on the long-term benefits are sparse. Thus, the 5-year outcome data of a prospective randomized trial comparing patients who initially underwent bladder tumor resection (TUR) under standard white light or with ALA induced fluorescence were evaluated. MATERIALS AND METHODS: A total of 115 patients with suspected superficial bladder cancer were randomized to undergo standard or ALA assisted TUR. After the second look TUR at 6 weeks patients were followed for a median of 39 (standard) and 42 (ALA) months. RESULTS: Median time to first recurrence was 5 months in the standard and 12 months in the ALA group. Recurrence-free survival was 25% in the standard and 41% in the ALA group. The recurrence rate at 2, 12, 36 and 60 months after initial TUR was 41%, 61%, 73% and 75%, and 16%, 43%, 59% and 59% in the white light and ALA groups, respectively. The total number of recurrences was 82 in the standard and 61 in the ALA group. Tumor progression occurred in 9 patients in the standard and 4 in the ALA group. Cost analysis suggests a considerable economical advantage of ALA fluorescence assisted TUR compared to the standard procedure. CONCLUSIONS: The initial advantage of improved tumor detection and decreased recurrence rates by ALA fluorescence assisted TUR is maintained for years, and effectively reduces morbidity and costs in patients with superficial bladder tumors.

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OBJECTIVES: To assess the potential of confocal laser scanning microscopy for imaging of the urinary bladder after intravesical instillation of a fluorescent dye. METHODS: The study was performed on the bladder of male Copenhagen rats. For confocal fluorescence microscopy (CFM), a standard confocal laser scanning microscope (Zeiss LSM 410) was used. Before measuring, the fluorescent marker SYTO 17 was instilled intravesically. After 2 hours of incubation, the rat was killed, the bladder excised and opened, and CFM was performed starting from the surface going through the urothelium and superficial layers of the lamina propria. Except for the opening incision, the bladder was left intact and no biopsies were taken. After imaging, the bladder was sent for conventional histologic studies. RESULTS: CFM allows imaging of cellular details of the entire urothelium (superficial umbrella cells, intermediate, and basal urothelial cells) and superficial layers of the lamina propria. CFM images are close to those obtained by standard microscopy after conventional hematoxylin-eosin staining. Cell structure (eg, shape, size, chromatin texture, nucleoli, mitotic figures, nuclear/cytoplasmic ratio), as well as the structure of the connective tissue (eg, collagen fibers, blood vessels, erythrocytes), can be studied, allowing a standard histologic evaluation. Furthermore, in contrast to conventional histologic evaluation, CFM provides three-dimensional information and allows the study of intact tissue representing the true in vivo situation. CONCLUSIONS: CFM enables the study of the microscopic anatomy of bladder mucosa in its in vivo state. In combination with optical fiber bundles, endoscopic microscopy of the bladder may be possible in the future.

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OBJECTIVES: Cathepsin B, H, and L (CB, CH, CL) are lysosomal proteolytic enzymes that belong to the group of cysteine proteinases. The imbalance between proteinases and their inhibitors is believed to correlate with tumor progression and shortened patient survival. In transitional cell carcinoma (TCC) only limited data have been published. METHODS: Using spectrofluorometric assays, catalytic activities of CB, CH, and CL in urine were measured to evaluate the potential diagnostic and prognostic value for patients with TCC of the bladder. Second morning urine was collected and used for measurements. CB, CH, and CL activities were determined for groups of patients with superficial disease (Ta-1, n = 43) and muscle-invasive tumors (T2, n = 18; or greater than T2, n = 9), as well as for different tumor grades (G1, n = 12; G2, n = 26; and G3, n = 31). For comparison, 14 urine samples from patients with bladder inflammation and 43 samples from a control group were also included. RESULTS: Compared with the control group, patients with superficial Stage Ta-T1 disease and muscle-invasive Stage T2 or greater disease, as well as patients with G3 tumors, revealed significantly higher urinary CL activity. CB and CH did not show any tumor-related activity increase. CB was significantly lower in patients with nonrecurrent tumors. CONCLUSIONS: These results suggest that elevated levels of CL in urine might be indicative of a cellular proteolytic imbalance in TCC of the bladder and may have a prognostic and/or diagnostic value.

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