Kriegmair M, Stepp H, Steinbach P, Lumper W, Ehsan A, Stepp H G, Rick K, Knüchel R, Baumgartner R, Hofstetter A
Urologische Klinik, Ludwig-Maximillians-Universität München, Germany.
Urol Int. 1995;55(4):190-6. doi: 10.1159/000282784.
Methods have been sought for the in vivo marking of tiny papillary tumors of the bladder and flat urothelial lesions such as dysplasia or carcinoma in situ, which can easily be missed during conventional endoscopy under white light. A new procedure is reported for the fluorescence detection of urothelial dysplasia and early bladder cancer. The method is based on intravesical application of 5-aminolevulinic acid (ALA). ALA if applied exogenously induces accumulation of protoporphyrin IX (PPIX) in the urothelium of the bladder. PPIX is an intensively red fluorescing agent. The mean ratio of fluorescence intensity between urothelial cancer and normal epithelium was found to be 17:1. Fluorescence excitation was achieved by violet light from a krypton ion laser (lambda = 406.7 nm) or from a xenon arc lamp with a bandpass filter system (lambda = 375-440 nm). Both light sources proved to be of equal suitability for fluorescence excitation. Fluorescence microscopy revealed that the PPIX fluorescence is strictly limited to the urothelium. It could not be detected from the submucosa or muscle of the bladder. Bladder wall biopsies were taken from 90 patients with suspicion of bladder cancer under fluorescence view. The fluorescence detection proved to be of high sensitivity (98%). No serious side effects which would preclude further clinical testing, especially no cutaneous photoreaction, were observed. Tumor-associated fluorescence induced by topical ALA application offers new perspectives in the diagnosis and treatment of bladder cancer. In case of suspicious or positive urine cytologic findings, ALA fluorescence cystoscopy may be useful for detecting the precise site of the malignancy. The procedure might be helpful in complete resection or coagulation of urothelial neoplasms. Due to this, diminishing recurrence rates are expected. However, this hypothesis has to be studied in prospective clinical trials.
人们一直在寻找对膀胱微小乳头状肿瘤以及扁平尿路上皮病变（如发育异常或原位癌）进行体内标记的方法，这些病变在白光下的传统内镜检查中很容易被遗漏。本文报道了一种用于尿路上皮发育异常和早期膀胱癌荧光检测的新方法。该方法基于膀胱内应用5-氨基酮戊酸（ALA）。外源性应用ALA可诱导原卟啉IX（PPIX）在膀胱尿路上皮中蓄积。PPIX是一种强烈发红光的物质。发现尿路上皮癌与正常上皮之间的荧光强度平均比值为17:1。通过氪离子激光（波长=406.7nm）发出的紫光或带有带通滤光系统（波长=375-440nm）的氙弧灯实现荧光激发。两种光源在荧光激发方面被证明具有同等适用性。荧光显微镜检查显示，PPIX荧光严格局限于尿路上皮。在膀胱黏膜下层或肌肉中未检测到。在荧光观察下，从90例疑似膀胱癌患者中获取膀胱壁活检组织。荧光检测被证明具有高灵敏度（98%）。未观察到会妨碍进一步临床试验的严重副作用，尤其是未观察到皮肤光反应。局部应用ALA诱导的肿瘤相关荧光为膀胱癌的诊断和治疗提供了新的视角。在尿液细胞学检查结果可疑或阳性的情况下，ALA荧光膀胱镜检查可能有助于检测恶性肿瘤的确切部位。该方法可能有助于尿路上皮肿瘤的完全切除或凝固。因此，预计复发率会降低。然而这一假设必须在前瞻性临床试验中进行研究。
