Evans blue as a selective dye marker for white-light diagnosis of non-muscle-invasive bladder cancer: an in vitro study (original) (raw)
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Lund Reports in Atomic Physics, 1997
In this study three optical methods, autofluorescence, ALA-induced PpiX fluorescence and diffuse reflectance have been evaluated regarding their ability to detect malignant and dysplastic changes of human bladder tissue, in vivo. For the autofluorescence method, a single-fiber system based on a N2-laser was used. The 337 nm laser light excited the bladder tissue and the fluorescence was detected with an optical multichannel analyzer (OMA). The differences in the spectra from normal and malignant sites were investigated and the results showed a good demarcation between these tissue types. The sensitivity, specificity and positive and negative predictive values (non-malignant versus malignant) were found to be 73, 90, 73 and 90%, respectively. The second method utilized 5-aminolevulinic acid (ALA), which has a tendency to predominantly accumulate in malignant tissue. Through the heme cycle the ALA is converted to protoporphyrin IX (PpiX) which fluoresces red when excited with blue light. A filtered xenon-lamp was used to excite the PpiX and the red fluorescence was detected with a CCD camera mounted on a cystoscope. The images were stored on S-VHS tapes and the results were compared with the visual diagnosis made by the surgeon during the procedure as well as with the pathology report, if a biopsy of the site was taken. The easiness with which the PpiX is excited and the fluorescence detected, and the high tumor selectivity of ALA, make ALA-induced PpiX fluorescence a very helpful tool in finding tumors. The diffuse reflectance method utilized a white light source (xenon-lamp) and an OMA system to record the diffuse reflectance. By comparing the spectral differences between the malignant and non-malignant sites, a quantitative measure of the concentration of hemoglobin was obtained. In practice, this method showed only what was visible to the eye, that the tumor sites appeared red. Though, it provides a quantitative measure and avoids a subjective bias from the surgeon.
Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma* 1
Urology, 1998
Objectives. To assess the diagnostic potential of diffuse reflectance spectroscopy for the detection of bladder carcinoma during cystoscopy. Our hypothesis is that neovasculature in neoplastic (dysplastic and malignant) regions will lead to a blood absorption "signature" that is different from that of normal tissue. Methods. Diffuse reflectance measurements have been performed in 14 patients undergoing mucosal biopsies or transurethral resection of a bladder tumor. A quartz optical fiber was advanced through the working channel of a cystoscope and placed in gentle contact with the bladder surface. A standard cystoscopy xenon light source was used for illumination and the reflectance spectra were recorded using an optical multichannel analyzer (OMA) system. From the spectra, the relative concentrations of hemoglobin (Hb), oxyhemoglobin (HbO2), oxygen saturation (HbO2%), and the total amount of blood (arbitrary units) were calculated to assess their usefulness in differentiating between neoplastic and benign bladder areas. Results. The spectra of 26 bladder areas (9 malignant areas including 4 carcinomata in situ, 2 dysplastic lesions, and 15 benign areas) have been analyzed. Only the total amount of blood was a useful parameter for the differentiation between neoplastic and benign bladder areas. The sensitivity, specificity, and positive and negative predictive values of this method for neoplastic tissue were found to be 91%, 60%, 63%, and 90%, respectively. Conclusions. The measurement of diffuse reflectance is a fast, simple, and noninvasive method which allows in vivo determination of bladder blood perfusion. The total blood concentration was increased in neoplastic bladder tissue, making it a tool for tissue diagnosis. The relatively low specificity is a result of inflammatory areas also exhibiting an increased total blood concentration. This pilot study encourages further studies to assess the usefulness of reflectance measurements for enhanced detection of bladder cancer. UROLOGY 51: [342][343][344][345] 1998. © 1998, Elsevier Science inc. All rights reserved.
Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma
Urology, 1998
Objectives. To assess the diagnostic potential of diffuse reflectance spectroscopy for the detection of bladder carcinoma during cystoscopy. Our hypothesis is that neovasculature in neoplastic (dysplastic and malignant) regions will lead to a blood absorption "signature" that is different from that of normal tissue. Methods. Diffuse reflectance measurements have been performed in 14 patients undergoing mucosal biopsies or transurethral resection of a bladder tumor. A quartz optical fiber was advanced through the working channel of a cystoscope and placed in gentle contact with the bladder surface. A standard cystoscopy xenon light source was used for illumination and the reflectance spectra were recorded using an optical multichannel analyzer (OMA) system. From the spectra, the relative concentrations of hemoglobin (Hb), oxyhemoglobin (HbO2), oxygen saturation (HbO2%), and the total amount of blood (arbitrary units) were calculated to assess their usefulness in differentiating between neoplastic and benign bladder areas. Results. The spectra of 26 bladder areas (9 malignant areas including 4 carcinomata in situ, 2 dysplastic lesions, and 15 benign areas) have been analyzed. Only the total amount of blood was a useful parameter for the differentiation between neoplastic and benign bladder areas. The sensitivity, specificity, and positive and negative predictive values of this method for neoplastic tissue were found to be 91%, 60%, 63%, and 90%, respectively. Conclusions. The measurement of diffuse reflectance is a fast, simple, and noninvasive method which allows in vivo determination of bladder blood perfusion. The total blood concentration was increased in neoplastic bladder tissue, making it a tool for tissue diagnosis. The relatively low specificity is a result of inflammatory areas also exhibiting an increased total blood concentration. This pilot study encourages further studies to assess the usefulness of reflectance measurements for enhanced detection of bladder cancer. UROLOGY 51: [342][343][344][345] 1998. © 1998, Elsevier Science inc. All rights reserved.
Traditionally, ultraviolet light (100-400 nm) is considered an exogenous carcinogen while visible light (400-780 nm) is deemed harmless. In this work, a LED irradiation system for in vitro photocytotoxicity testng is described. The LED irradiation system was developed for testing photopharmaceutical drugs, but was used here to determine the basal level response of human cancer cell lines to visible light of different wavelengths, without any photo(chemo)therapeutic. The effects of blue (455 nm, 10.5 mW·cm−2), green (520 nm, 20.9 mW·cm−2), and red light (630 nm, 34.4 mW·cm−2) irradiation was measured for A375 (human malignant melanoma), A431 (human epidermoid carcinoma), A549 (human lung carcinoma), MCF7 (human mammary gland adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), and U-87 MG (human glioblastoma- grade IV) cell lines. In response to a blue light dose of 19 J·cm−2, three cell lines exhibited a minimal (20%, MDA- MB-231) to moderate (30%, A549 and 60%, A375) reduction in cell viability, compared to dark controls. The other cell lines were not affected. Effective blue light doses that produce a therapeutic response in 50% of the cell population (ED50) compared to dark conditions, were found to be 10.9 and 30.5 J·cm−2 for A375 and A549 cells, respectively. No adverse effects were observed in any of the six cell lines irradiated with a 19 J·cm−2 dose of 520 nm (green) or 630 nm (red) light. The results demonstrate that blue light irradiation can have an effect on the viability of certain human cancer cell types and controls should be used in photopharmaceutical testing, which uses high-energy (blue or violet) visible light activation.
Making cancer visible – Dyes in surgical oncology
Surgical Oncology, 2016
Dyes share an intricate relationship with oncology. Dyes can cause cancer as chemical carcinogens, but can also be harnessed against cancer when used as diagnostic and therapeutic agents. Histopathology, imaging, and newer molecular diagnostics all rely on dyes, and their use in sentinel lymph node biopsies and intra-operative imaging has helped drive a paradigm shift in cancer surgery towards minimallyinvasive and organ sparing approaches with enhanced resection accuracy. As therapeutic agents, the cytotoxicity of specific dyes can be employed in direct chemo-ablation or in photodynamic therapy. The same agent can have dual functionalities in cancer detection and treatment, in a novel field known as theranostics. This is facilitated by newer generation dyes conjugated with tumour-targeting probes such as antibodies, and these bio-conjugate agents can also incorporate nanotechnology or radio-isotopes. Further advances will be closely aligned with our increasing understanding of molecular oncology, and will form a new generation of cancer detection and treatment agents that promote precision medicine for cancer. Dyes and their roles have evolved and been reinvented, but they remain relevant as ever. This review explores the fascinating history of dyes, and their place in the state-of-the-art of oncology.
Fluorescent diagnosis of urinary bladder cancer—a comparison of two diagnostic modalities
Photodiagnosis and Photodynamic Therapy, 2004
White light cystoscopy (WLC) is considered to be a standard examination for localisation and surveillance of transitional cell cancer of urinary bladder. However, in patients who have undergone transurethral resection of bladder tumour (TUR-BT) sensitivity of this method is too low for early detection of cancer recurrence. In order to improve this unsatisfactory situation new diagnostic procedures are still under investigation. Fluorescent diagnosis is a modern diagnostic option based on the detection of distinctive fluorescence of normal and pathological tissue. Currently two techniques are in clinical use: autofluorescent diagnosis, also termed laser-induced fluorescence (LIF) and photodynamic diagnosis (PDD). In this study we have analysed sensitivity and specificity of the fluorescent diagnosis to validate the best mode of bladder cancer diagnosis. A total of 281 patients, after electroresection of bladder tumour due to transitional cell carcinoma, without any signs of tumour recurrence in white-light cystoscopy, were divided in two groups: 52 patients underwent PDD and in 229 patients autofluorescent diagnosis was performed. Bladder washings and excisions from suspicious red fluorescent spots were taken for histopathological and cytological analyses. Sensitivity and specificity of PDD equalled to 90.91 and 66.60%, respectively. In case of autofluorescence diagnosis these values amounted to: 97.83 and 70.07%, respectively. The overall sensitivity and specificity of fluorescent examination equalled to 96.49 and 69.46%, respectively. Conclusion: Autofluorescence diagnosis (LIF) of pathological lesions within urinary bladder has been proven to be more sensitive than PDD as evaluated by a nonparametrical test for structure indicators comparison (LIF versus PDD, P = 0.0056).
Journal of Biomedical Optics, 2008
Our aim is to apply image analysis on photosensitizer fluorescence and compare the relationship between histopathology and endoscopic fluorescence imaging. The correlation between hypericin fluorescence and histopathology of diseased tissue was explored in a clinical study involving 58 fluorescence cystoscopic images from 23 patients. Based on quantification of fluorescence colorimetric parameters extracted from the image analysis, diagnostic functions were developed to pathologically classify the bladder cancer. Our preliminary results show that the differences in fluorescence intensity ratios among the three different grades of bladder cancer are statistically significant. The results also show a decrease in macroscopic fluorescence intensity that correlated with higher cancer grades. By combining both the red-to-green and red-to-blue fluorescence intensity ratios into a 2-D scatter plot and defining diagnostic linear discrimination functions on the data points, this technique is able to yield an average sensitivity and specificity of around 68.6% and 86.1%, respectively, for pathological cancer grading of the three different grades of bladder cancer in our study. We conclude that our proposed approach in applying colorimetric intensity ratio analysis on hypericin fluorescence shows potential to optically grade bladder cancer in situ.
Cancer letters, 2007
The use of fluorescence diagnosis as a modern cancer diagnostic modality is rapidly gaining importance in the field of urology. It is based on the detection of distinctive light emission of tissues sensitized by fluorescent dyes, commonly referred to as photosensitizers, after irradiation with a specific light source. Therefore, the search for specific fluorescent dyes with high sensitivity and specificity for bladder cancer is constantly being sought after. The aim of this study is to investigate the use of a new formulation consisting a mixture of chlorin e6 and polyvinylpyrrolidone (Ce6-PVP) for the detection of human bladder cancer cells (MGH) implanted on the chick chorioallantoic membrane (CAM) model. Uptake kinetics studies were quantitatively determined for both systemic and topical administrations of Ce6-PVP to the normal CAM as well as the MGH human bladder tumor implanted on CAM using fluorescence imaging technique. Rapid elimination of Ce6-PVP was displayed following top...
Molecular and Clinical Oncology, 2012
The present study presents a novel near-infrared optical probe for the sentinel lymph node (SLN) detection in breast cancer patients, based on the recording of scattered photons. The aim of this study was to improve the detection of patent blue V (PBV), a dye routinely injected during clinical practice. A combined injection of the dye and radioactive colloid was used in the 24 patients enrolled in the study. The clinical results of the ex vivo detection of 70 dye-marked SLNs are reported, subsequent to the injection of various quantities of PBV (0.25-2 ml). The accuracy and success rate of an isotopic probe for the detection of radioactive colloid tracer, the eye visibility threshold of the surgeon and the use of a new optical probe were examined. The radio-labeled and dye-marked sentinel lymph nodes were all detected by the radio-isotopic probe, as opposed to the 75% detected by the eye visibility threshold of the surgeon. The optical probe detected all of the nodes, regardless of the volume of the dye injected. The relative PBV concentration computed by the probe facing SLNs with infravisible/visually undetectable dye-mark was relatively constant at 5.5±1.4 µmol/l. The optical detection of the sentinel lymph nodes using PBV and the probe presented in this study have the potential to reduce the false negative detection rate. This instrument is likely to provide surgeons with a simple diagnostic tool, without significantly changing their surgical procedures.