Detection of early cancerous changes and cancer in bladder tissue by autofluorescence and reflectance

Most new bladder cancers are transitional cell carcinoma (TCC). Dysplasia, which can progress to TCC, and a flat low-grade TCC known as carcinoma-in-situ (CIS) can progress into invasive TCC. Visual identification through a cystoscope is unreliable and taking random biopsies for a more reliable diagnosis is expensive. Differences in the observed fluorescence or reflectance spectra collected using an optical fiber probe could lead to guidance for taking fewer, better chosen biopsies or a diagnosis from the observed spectra alone. Two studies explored this: an in vivo study investigated papillary TCC and an in vitro study investigated dysplasia, CIS, invasive TCC, and papillary tumors. The spectra were analyzed with a multivariate technique of principal component analysis with logistic regression (PCA/LR). In all cases, biopsies were taken and evaluated by a pathologist.;For the in vivo study, at 400 nm excitation, which performed better than 370 nm, 23 non-diseased and 22 diseased sites from 10 patients analyzed with cross-validation to blind the PCA/LR algorithm achieved an 82% sensitivity and 96% specificity. Results without validation are often reported in various articles and 100% sensitivity and 100% specificity was achieved without validation. This was detecting papillary TCC.;For the in vitro study, 400 nm excited fluorescence performed best, although reflectance was not much worse suggesting absorptive effects are important. At 400 nm excitation with dysplasia and CIS classified as diseased, 84 non-diseased and 20 dysplasia and 25 sites of CIS from a composite of 30 patients achieved only 60% sensitivity and 66% specificity even without using a validation set. In contrast, papillary TCC and invasive cancer were detected well at both excitations and with white light reflectance.;Quantitative fluorescence microscopy of frozen unstained bladder sections identified the fluorophores as cross-linked collagen and occasional inflammatory cells, with the same fluorophores at 380 or 400 nm excitation. Bladder epithelium did not display fluorescence regardless of being benign, dysplastic, or CIS, which explains the difficult of differentiating dysplasia and CIS from benign mucosal tissue.