Department of Urology, Nara Medical University, Kashihara-shi, Nara, Japan.
Cancer Sci. 2014 May;105(5):616-22. doi: 10.1111/cas.12393. Epub 2014 Apr 6.
Bladder urothelial carcinoma is diagnosed and followed up after transurethral resection using a combination of cystoscopy, urine cytology and urine biomarkers at regular intervals. However, cystoscopy can overlook flat lesions like carcinoma in situ, and the sensitivity of urinary tests is poor in low-grade tumors. There is an emergent need for an objective and easy urinary diagnostic test for the management of bladder cancer. In this study, three different modalities for 5-aminolevulinic acid (ALA)-based photodynamic diagnostic tests were used. We developed a compact-size, desktop-type device quantifying red fluorescence in cell suspensions, named "Cellular Fluorescence Analysis Unit" (CFAU). Urine samples from 58 patients with bladder cancer were centrifuged, and urine sediments were then treated with ALA. ALA-treated sediments were subjected to three fluorescence detection assays, including the CFAU assay. The overall sensitivities of conventional cytology, BTA, NMP22, fluorescence cytology, fluorescent spectrophotometric assay and CFAU assay were 48%, 33%, 40%, 86%, 86% and 87%, respectively. Three different ALA-based assays showed high sensitivity and specificity. The ALA-based assay detected low-grade and low-stage bladder urothelial cells at shigher rate (68-80% sensitivity) than conventional urine cytology, BTA and NMP22 (8-20% sensitivity). Our findings demonstrate that the ALA-based fluorescence detection assay is promising tool for the management of bladder cancer. Development of a rapid and automated device for ALA-based photodynamic assay is necessary to avoid the variability induced by troublesome steps and low stability of specimens.
膀胱尿路上皮癌是通过经尿道切除术后，结合膀胱镜检查、尿液细胞学和尿液生物标志物定期进行诊断和随访的。然而，膀胱镜检查可能会忽略扁平病变，如原位癌，并且尿液检测的灵敏度在低级别肿瘤中较差。因此，迫切需要一种客观、简便的尿液诊断测试来管理膀胱癌。在这项研究中，使用了三种不同的 5-氨基酮戊酸（ALA）基光动力诊断测试方法。我们开发了一种名为“细胞荧光分析单元”（CFAU）的紧凑型台式设备，可定量细胞悬浮液中的红色荧光。从 58 例膀胱癌患者的尿液样本中离心，然后用 ALA 处理尿液沉淀物。将 ALA 处理过的沉淀物进行三种荧光检测分析，包括 CFAU 分析。常规细胞学、BTA、NMP22、荧光细胞学、荧光分光光度法和 CFAU 分析的总灵敏度分别为 48%、33%、40%、86%、86%和 87%。三种不同的 ALA 基检测方法均显示出较高的灵敏度和特异性。与传统尿液细胞学、BTA 和 NMP22 相比（灵敏度 8-20%），ALA 基检测方法能够以更高的敏感性（68-80%）检测到低级别和低分期的膀胱尿路上皮细胞。我们的研究结果表明，ALA 基荧光检测方法是管理膀胱癌的一种很有前途的工具。需要开发一种快速、自动化的 ALA 基光动力检测设备，以避免因繁琐步骤和标本稳定性差而引起的变异性。
