Nakai Yasushi, Ozawa Toshiyuki, Mizuno Fumiko, Onishi Sayuri, Owari Takuya, Hori Syunta, Morizawa Yosuke, Tatsumi Yosihiro, Miyake Makito, Tanaka Nobumichi, Tsuruta Daisuke, Fujimoto Kiyohide
Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.
Department of Dermatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
J Cancer Res Clin Oncol. 2017 Nov;143(11):2309-2316. doi: 10.1007/s00432-017-2476-5. Epub 2017 Jul 19.
To evaluate the feasibility of hexaminolevulinate (HAL) for the photodynamic detection of cancer cells in voided urine.
This study included 50 patients with bladder cancer that was confirmed histologically after transurethral resection (bladder cancer group) and 50 outpatients without a history of urothelial carcinoma or cancer-related findings (no malignancy group). One third of the voided urine samples were incubated with aminolevulinic acid (ALA-treated samples), one third were incubated with HAL (HAL-treated samples), and the remaining samples were incubated without treatment (untreated samples). For detecting cellular protoporphyrin IX levels, the intensity of the samples at the excitation wavelength of 405 nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated or HAL-treated samples and the untreated samples at 635 nm was calculated.
HAL-induced fluorescence cytology (HFC) showed that the difference was significantly higher in patients with high-grade tumors than in those with low-grade tumors (p = 0.0003) and the difference was significantly higher in patients with low-grade tumors than in those without a history of urothelial carcinoma or cancer-related findings (p = 0.021). The areas under the receiver operating characteristic curves of ALA-induced fluorescence cytology (AFC) and HFC were 0.77 and 0.81, respectively. The AUC of HFC was significantly higher than that of AFC (p < 0.0001). The overall sensitivity values for conventional cytology, AFC, and HFC were 49, 74, and 74%, respectively. The overall specificity values for AFC and HFC were 70 and 94%, respectively.
Spectrophotometric photodynamic detection involving extracorporeal treatment with HAL for bladder cancer cells in voided urine showed high accuracy. This bladder cancer detection method is easy and cost-effective, and has the potential for clinical use.
评估六氨基乙酰丙酸(HAL)用于光动力检测晨尿中癌细胞的可行性。
本研究纳入50例经尿道切除术后经组织学确诊的膀胱癌患者(膀胱癌组)和50例无尿路上皮癌病史或癌症相关发现的门诊患者(无恶性肿瘤组)。将三分之一的晨尿样本与氨基乙酰丙酸一起孵育(ALA处理样本),三分之一与HAL一起孵育(HAL处理样本),其余样本不进行处理直接孵育(未处理样本)。为检测细胞原卟啉IX水平,使用分光光度计测量样本在405nm激发波长下的强度。计算ALA处理或HAL处理样本与未处理样本在635nm处强度的差异。
HAL诱导荧光细胞学(HFC)显示,高级别肿瘤患者的差异显著高于低级别肿瘤患者(p = 0.0003),低级别肿瘤患者的差异显著高于无尿路上皮癌病史或癌症相关发现的患者(p = 0.021)。ALA诱导荧光细胞学(AFC)和HFC的受试者工作特征曲线下面积分别为0.77和0.81。HFC的AUC显著高于AFC(p < 0.0001)。传统细胞学、AFC和HFC的总体敏感性值分别为49%、74%和74%。AFC和HFC的总体特异性值分别为70%和94%。
采用分光光度法光动力检测,对晨尿中的膀胱癌细胞进行HAL体外处理,显示出较高的准确性。这种膀胱癌检测方法简便且经济高效,具有临床应用潜力。