5-氨基乙酰丙酸诱导荧光膀胱镜在膀胱肿瘤诊断中的应用（附31例报告）

目的：研究5-氨基乙酰丙酸（5-ALA）诱导荧光光动力学对膀胱肿瘤的早期诊断价值。方法：对血尿患者行5-ALA诱导荧光膀胱镜检查及活组织检查,以5-ALA膀胱灌注,2h后采用D-light光源系统进行膀胱镜检,对荧光阳性区域及白光下肉眼可见异常但荧光阴性区域进行活检,活检后行经尿道膀胱肿瘤电切术。结果：31例患者中有4例荧光阴性且普通光肉眼观阴性者未活检。余27例患者共取活检96处,其中荧光阳性区域取活检89处（包括普通光肉眼观阴性区域35处）,切缘取活检7处。病理检查结果显示：尿路上皮癌65处,阳性率为73．03％（65／89）,非肿瘤性病变24例,假阳性率为27％（24／89）,切缘活检7处为阴性。荧光下阳性而白光下阴性的肿瘤位点11处,切缘活检7处均为阴性。结论：5-ALA诱导荧光光动力学诊断对膀胱肿瘤有较高价值,能发现早期肿瘤,同时进行电切将更彻底。     

5-氨基乙酰丙酸荧光膀胱镜在膀胱肿瘤诊治中的应用评价(附56例报告)

目的 与普通膀胱镜相比较，评价5-氨基已酰丙酸荧光膀胱镜检查在膀胱肿瘤诊断和治疗中的价值。方法 术前1.5h，1．4％的碳酸氢钠溶液50mL溶解1．5g的5一氨基乙酰丙酸（5-ALA），膀胱灌注。术中对普通光下及蓝光下的可疑部位取活检，并对活检部位电切和电灼，活检组织送病理检查。结果 56例患者共取活检155处，平均2．8次／人。荧光膀胱镜的敏感性98．4％（63／64位点），特异性73．5%（61／83位点），两者有显著统计学差异（P〈0．01）。蓝光下发现普通光下未发现的肿瘤位点14处。未发现5-ALA的局部和全身毒副作用。结论 5-ALA荧光膀胱镜是一种高敏感的用于膀胱肿瘤诊断和治疗的有效方法，能够提高对膀胱原位癌的诊断敏感性及降低术中因未发现和切除不完全所带来的膀胱肿瘤复发危险性。     

5-ALA诱导荧光膀胱镜下膀胱肿瘤电切除术(附31例报告)

目的:探讨5-ALA诱导荧光膀胱镜下膀胱肿瘤电切治疗的彻底性.方法:对31例血尿患者在5-ALA诱导荧光染色膀胱镜下行活组织检查及电切术.结果:31例呈荧光阳性,其中26例经术后病理证实为尿路上皮癌,5例为良性病变.其中11例移行细胞癌患者在癌旁或远处发现普通膀胱镜下无法识别的微小荧光阳性区域,经活检均证实有肿瘤存在.对该区域均在荧光指示下进行电切或电灼术.结论:5-ALA诱导荧光膀胱镜检对膀胱肿瘤诊断高度敏感,能发现微小及癌旁肿瘤,在荧光指示下能彻底切除肿瘤,减少复发.     

窄光成像膀胱镜在膀胱肿瘤诊断中的应用

目的 探讨窄光成像诱导光动力学检查对膀胱肿瘤早期诊断的应用价值. 方法 应用高清窄光成像膀胱镜系统对28例血尿患者进行膀胱镜检,术中分别对普通光下及窄光下的可疑部位膀胱黏膜组织活检,普通光组取样35处,窄光组取样79处(含普通光35处,普通光镜下疑似者窄光均显示镜下疑似,不重复取样)送病理检查.比较窄光取样组和普通光取样组肿瘤检出敏感性.结果 窄光取样组活检病理报告尿路上皮癌32处(21例),其中原位癌11处,腺性膀胱炎5处(2例),良性病变(炎性病变)3处(2例),正常黏膜4处(3例).普通光取样组尿路上皮癌17处(15例),腺性膀胱炎2处(1例),无原位癌.活检病理阳性32处,窄光组病理阳性32处,肿瘤检出率100%(32/32);普通光组病理阳性17处.肿瘤检出率53%(17/32);膀胱肿瘤及原位癌检出率2组比较差异有统计学意义(P<0.01).共取样79处,其中窄光组阳性32处,敏感性41%(32/79);普通光组阳性17处,敏感性22%(17/79),2组肿瘤取样敏感性比较差异有统计学意义(P<0.01). 结论 窄光成像膀胱镜能提高对膀胱肿瘤特别是原位癌的诊断敏感性,降低术中残存率,减少膀胱肿瘤复发危险性.     

应用5-氨基乙酰丙酸的荧光膀胱镜在膀胱肿瘤诊断中的作用

5 氨基乙酰丙酸是一种应用于口腔及肠道肿瘤诊断及治疗的荧光物质。 5 氨基乙酰丙酸经膀胱灌注后 ,特异性地标记膀胱肿瘤组织 ,具有较高敏感性。本文介绍了 5 氨基乙酰丙酸的作用机理及 5 氨基乙酰丙酸荧光膀胱镜的应用现状和最新进展     

应用5—氨基乙酰丙酸的荧光膀胱镜在膀胱肿瘤诊断中的作用

5－氨基乙酰丙酸是一种应用于口腔及肠道肿瘤诊断及治疗的荧光物质。5－氨基乙酰丙酸经膀胱灌注后，特异性地标记膀胱肿瘤组织，具有较高敏感性，本文介绍了5－氨基乙酰丙酸的作用机理及5－氨基乙酰丙酸荧光膀胱镜的应用现状和最新进展。     

5-氨基乙酰丙酸体外诱导膀胱癌细胞株BIU-87内生性原卟啉IX的动力学研究

目的研究5-氨基乙酰丙酸(5-ALA)体外诱导膀胱癌细胞内生性荧光物质原卟啉(PpIX)荧光随时间的动力学变化及5-ALA的浓度、pH值对产生PpIX的影响。方法0.5×106个/孔BI U-87单细胞悬液接种于6孔板培养24h,加入新鲜培养液和浓度为1mmol/L的5-ALA,于不同时间终止培养,取出用流式细胞仪测各孔细胞内PpIX含量。另以不同pH值终浓度为1mmol/L的5-ALA培养液以及不同浓度的5-ALA培养液分别孵育BI U-87细胞2h,同法用流式细胞仪测各孔PpIX含量。结果5-ALA培养液孵育肿瘤细胞2h后终止5-ALA继续作用,肿瘤细胞内PpIX含量在第3小时达到最高峰,之后逐渐回落。5-ALA仅作用20min在培养2h后观察PpIX含量最低,与40min以后组差异有统计学意义,5-ALA作用40min后PpIX逐渐上升,但各观察组间差异无统计学意义。最佳pH值为6.7,而最适宜浓度为1~2mmol/L。结论5-ALA可体外诱导膀胱癌细胞产生PpIX,其含量是一个动态过程,且受5-ALA作用时间、pH值及浓度的影响,实验数据可为临床应用5-ALA诱导荧光的光动力学诊断膀胱肿瘤提供参考。     

5-氨基乙酰丙酸介导的光动力学治疗人脑胶质瘤

颅内胶质瘤是临床上常见病、多发病。目前多采用手术、放疗、化疗等综合治疗，但治疗效果仍不甚满意。目前在临床上广泛使用的血卟啉制剂所介导的肿瘤光动力治疗(photodynamic therapy，PDT)虽然在肿瘤的临床诊断和治疗中都取得了肯定的疗效，但仍有很多不足之处。5-氨基乙酰丙酸(5-aminolevulinicacid，5-ALA)是目前光动力疗法领域中最活跃的光敏剂前体物，     

5-氨基乙酰丙酸光动力学疗法对两种人卵巢癌细胞的体外杀伤作用

目的：探讨5-氨基乙酰丙酸（5-ALA）光动力学疗法（photodynamic therapy,PDT）对体外培养人卵巢癌SKOV3和AO细胞的杀伤作用。方法：于体外培养的SKOV3和AO细胞分别加入不同浓度的5-ALA（0．1、0．5、1．0、2．5、12．5mmol／L）孵育4h,以波长为630nm的半导体激光进行照射,照射能量密度分别为0．1、0．5、2．5、12．5J／cm^2。用四唑盐（MTT）比色法测定细胞存活率,并与单纯药物对照组（不同浓度5ALA孵育、无光照）、单纯光照组（无5-ALA孵育、不同能量密度光照）与阴性对照组（无药物孵育、无光照）进行比较。计算5ALA—PDT对SKOV3和AO细胞的半数杀伤浓度（IC50）。结果：5-ALA—PDT处理后两种卵巢癌细胞存活率均明显下降（P〈0．05）,提示5ALA—PDT对体外培养的人卵巢癌SKOV3和AO细胞均有杀伤作用,其杀伤作用随5-ALA的浓度和激光能量密度增加而增加,当5-ALA浓度超过2．5mmol／L或照射能量密度超过2．5J／cm^2时细胞存活率变化不明显。单纯药物对照组、单纯光照组的细胞存活率与阴性对照组相比差异无显著性（P〉0．05）。5-ALA-PDT对两种卵巢癌细胞杀伤效应强弱不同,对SKOV3及AO细胞的半抑制浓度（IC50）分别为0．34mmol／L和2．50mmol／L,两者差异有显著性（P〈0．05）。结论：5-ALA-PDT可有效杀伤体外培养的人卵巢癌细胞SKOV3和AO细胞,且对两种细胞的杀伤作用有差异,对SKOV3细胞株的杀伤效应要强于AO细胞株。     

使用5-氨基乙酸丙酸(5-ALA)诱导荧光诊断(FD)降低表浅膀胱癌复发危险--5年研究结果

单中心随机前瞻性研究应用 5 ALA诱导FD经尿道切除 (TUR)表浅膀胱癌的疗效是否优于传统白光 (WL )TUR ,评估肿瘤复发率和无瘤存活率。方法 :1997～ 2 0 0 0年内腔镜诊断膀胱癌 3 0 1例 ,随机分两组 ,WL TUR组 150例 ,FD TUR组 151例 ,分别行TUR ,手术无肉眼肿瘤残留。组织学检查为 pTa、pT1,G1～G3 和Cis者 ,6周后在WL下对原肿瘤基部和切缘行TUR评估肿瘤残留率 ,肿瘤侵袭肌层及检查阴性者不计入评估。术后处理按美国泌尿外科协会有关规定进行 ,再切除术后 3个月首次随访。结果 :WL组可评估的 10 3例中肿瘤残留率为 2 5.2 % …     

Transurethral resection for bladder cancer using 5-aminolevulinic acid induced fluorescence endoscopy versus white light endoscopy

PURPOSE: Endoscopy done under fluorescence induced by 5-aminolevulinic acid has proved to be a procedure with high sensitivity for detecting transitional cell carcinoma of the bladder. In this multicenter, parallel group, phase III study we compared 5-aminolevulinic acid fluorescence endoscopy guided transurethral bladder resection with transurethral bladder resection done using only white light endoscopy. The proportion of tumor-free resected cases in the 2 groups was evaluated. MATERIALS AND METHODS: After patient stratification according to participating centers and European Organization for the Research and Treatment of Cancer risk score 65 and 64 were randomized to the 5-aminolevulinic acid fluorescence and white light endoscopy groups, respectively. Residual tumor was evaluated in the 2 groups by repeat transurethral resection 10 to 14 days later. Analysis was performed according to the intent to treat principle with all patients randomized, followed by per protocol analysis. RESULTS: Intent to treat analysis revealed that in the white light endoscopy group 40.6% of cases were resected tumor-free at primary resection, whereas with 5-aminolevulinic acid fluorescence endoscopy guided transurethral resection 61.5% were resected tumor-free (p <0014). On protocol analysis 46.9% patients in the white light and 67.3% in the 5-aminolevulinic acid fluorescence endoscopy groups were resected tumor-free (p <0.031). No difference was noted in the 2 groups in regard to side effects or laboratory findings. CONCLUSIONS: The risk of residual tumor after transurethral resection of transitional cell carcinoma is significantly decreased by 5-aminolevulinic acid fluorescence endoscopy.     

Fluorescence diagnosis of endometriosis using 5-aminolevulinic acid

Background: The diagnosis of nonpigmented endometrial lesions by simple laparoscopic visualization is difficult and often inaccurate. We therefore sought to establish a new and more accurate method to visualize these nonpigmented peritoneal changes caused by endometriosis. Methods: A total of 37 patients received 30 mg 5-aminolevulinic acid/kg body weight 10 to 14 hs prior to surgery. Laparoscopy was then performed using a D-light system (Storz, Tuttlingen, Germany). The findings were evaluated first in the white-light mode; the D-light system was then activated, and all areas of fluorescence were documented. Multiple specimens were obtained by biopsy. Results: The sensitivity of the fluorescence diagnosis in detecting endometriosis in nonpigmented areas and normal-looking peritoneum is 100%, with a specificity of 75%. Diagnosis by simple visualization under white illumination has a sensitivity of only 69% and a specificity of 70%. Occult areas of endometriosis were discovered using fluorescence diagnosis. Conclusions: Our findings suggest that fluorescence diagnosis using 5-aminolevulinic acid is feasible and can improve the diagnosis of endometriosis in nonpigmented and occult endometrial lesions. Fluorescence diagnosis is a promising new tool in the diagnosis of endometriosis. Received: 12 November 1998/Accepted: 13 May 1999     

5-氨基乙酰丙酸介导的光动力学对裸鼠人胃癌移植瘤的治疗作用

目的观察5-氨基乙酰丙酸（5-ALA）介导的光动力学治疗对裸鼠人胃癌移植瘤的治疗作用。探索5-ALA介导的光动力学（PDT）治疗胃癌的可能机制。方法以MGC-803人胃癌细胞制备裸鼠人胃癌移植瘤模型：整体荧光成像系统下观察动物瘤体发出的荧光信号：测量荷瘤对照组、单纯激光组、单纯5-ALA组和5-ALA介导的PDT治疗组治疗后第1、3、7、14、21天的裸鼠肿瘤大小并计算肿瘤体积：末次测量后切除肿瘤行病理检查和透射电镜观察，TUNEL法检测组织细胞凋亡。结果常规方法培养MGC一803人胃癌细胞并接种裸鼠．可以成功制备出裸鼠人胃癌移植瘤的模型：荷瘤裸鼠肿瘤组织在特定波长的荧光激发下可发出特有的红色荧光。荷瘤对照组、单纯激光组、单纯5-ALA组和5-ALA介导的PDT治疗组治疗后第1、3、7、14、21天4组间的肿瘤体积差异有统计学意义（肚1003．086，P=0．000），PDT治疗组明显小于其他3组；病理检查提示．PDT治疗后肿瘤细胞大片凝固性坏死；透射电镜观察提示，PDT治疗组肿瘤组织存在大量死亡细胞及部分凋亡细胞：TUNEL法检测发现，PDT治疗组的肿瘤组织凋亡指数显著高于其他3组（χ^2=18．237．P=0．000）。结论5-ALA介导的PDT对于裸鼠人胃癌移植瘤具有明显的治疗效果．而单纯给予5-ALA或激光辐射对肿瘤无明显抑制作用；肿瘤细胞的坏死及凋亡是5-ALA介导的PDT产生细胞毒作用的重要机制。     

Photodynamic Diagnosis Using 5-Aminolevulinic Acid for the Detection of Positive Surgical Margins during Radical Prostatectomy in Patients with Carcinoma of the Prostate: A Multicentre, Prospective, Phase 2 Trial of a Diagnostic Procedure

Background

Surgical margin status after radical prostatectomy (RP) is a significant risk factor for tumour recurrence. It is an intriguing concept to find a fluorescence marker for photodynamic diagnosis (PDD) to make tumour margins visible during surgery.

Objective

To investigate the feasibility of identification of positive surgical margins (PSM) during open retropubic or endoscopic extraperitoneal RP by 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) to enhance surgical radicality.

Design, setting, and participants

Thirty-nine patients (Gleason score 6–10, prostate-specific antigen [PSA] 2.3–120 ng/ml) received 20 mg/kg of body weight of 5-ALA orally and underwent RP (24 endoscopic extraperitoneal, 15 open retropubic).

Measurements

A PDD-suitable laparoscopy optic (Karl-Storz GmbH, Tuttlingen, Germany) with a yellow long-pass filter was coupled to a fibre-optic light cord with an excitation light source (380–420 nm, D-Light, Karl-Storz GmbH, Tuttlingen, Germany) for fluorescence excitation of PpIX and to a PDD-suitable camera for video and photo documentation by the AIDA DVD system (Karl-Storz GmbH, Tuttlingen, Germany).

Results and limitations

There were more false-negative cases in the open group (four vs two) than in the endoscopic group but more false-positive cases in the endoscopic group (two vs none) than in the open group. The overall sensitivity and specificity were 56% and 91.6%, respectively. The sensitivity of the endoscopic cases was much higher (75% vs 38%) than for the open cases, while the specificity was higher for the open group (88.2% vs 100%).

Conclusions

PDD with 5-ALA–induced PpIX during RP might be a feasible and effective method for reducing the rate of PSM. The technique seems to be more practicable during endoscopic RP rather than open RP. Further clinical studies with higher patient volumes and further development of the technique seem justified.

Trial registration

EudraCT: 2005-004406-93.     

Quantification of 5-aminolevulinic acid induced fluorescence improves the specificity of bladder cancer detection

PURPOSE: 5-Aminolevulinic acid induced fluorescence endoscopy has outstanding sensitivity for detecting early stage bladder cancer. Nevertheless, a third of the lesions that show specific fluorescence are histologically benign. We decreased the false-positive rate of 5-aminolevulinic acid induced fluorescence endoscopy by incorporating protoporphyrin IX fluorescence quantification into the standard cystoscopy procedure. MATERIALS AND METHODS: In 25 cases (53 biopsies) of a history of or suspicion for bladder cancer 5-aminolevulinic acid induced fluorescence endoscopy and fluorescence image quantification were performed. For fluorescence image quantification images obtained with a target integrating color charge-coupled device camera were digitized and stored in a personal computer. Red-to-blue ratios were calculated from fluorescence positive lesions and results were correlated with hematoxylin and eosin histology. RESULTS: Malignant fluorescence positive lesions showed significantly stronger fluorescence intensity than fluorescing lesions with benign histology. A threshold was established that decreased the false-positive rate by 30% without affecting sensitivity. CONCLUSIONS: Fluorescence image quantification is a new endoscopic method for objectively selecting multicolor fluorescence bladder lesion images for biopsy. It has the potential of eliminating human error by different surgeons with variable experience in fluorescence endoscopy.