光动力疗法治疗尿道尖锐湿疣的临床研究

A clinical study of photodynamic therapy with topical application of 5-aminolevulinic acid in ure-thral warts

目的探讨5-氨基酮戊酸光动力疗法(ALA-PDT)治疗尿道尖锐湿疣的最适ALA浓度和最佳敷药时间。方法将60例尿道尖锐湿疣患者分为0.5%、1%、3%、5%和10%ALA五组,分别在敷药1、3、5、7h时取材,进行原位定量原卟啉Ⅸ检测、常规组织病理检查和杂交捕获试验检测高危型、低危型HPV DNA。结果经不同浓度和时间的ALA湿敷后,皮损局部的表皮内均有不同程度的原卟啉Ⅸ砖红色荧光,荧光基本上分布于表皮全层,而真皮几乎见不到原卟啉Ⅸ荧光。原位定量原卟啉Ⅸ荧光强度在敷药3h时已经明显升高,在5h时到达最高峰,7h时再次下降为3h时的水平。随着ALA浓度的增高,其组织中原卟啉Ⅸ的荧光强度逐渐增高。经统计学分析,5%和10%ALA组原卟啉Ⅸ荧光强度显著高于其他组(P<0.05)。HPV DNA杂交捕获试验结果显示,尿道尖锐湿疣患者的临床标本中低危型HPV DNA 100% (60/60)阳性,18.3%(11/60)病例同时检测出高危型HPV DNA。结论ALA-PDT治疗尿道尖锐湿疣的最佳ALA浓度为5%或10%,最佳敷药时间为3-5h。

Objective To find out the optimal 5-aminolevulinic acid （ALA） concentration and duration of topical use in ALA-photodynamic therapy （ ALA-PDT ） for urethral warts. Methods Sixty patients with urethral warts were recruited into the study. ALA solution was applied to warty lesions in concentrations of 0.5%, 1%, 3%, 5% and 10%, for 1, 3, 5 and 7 h before biopsy. The fluorescence pattern of ALA induced protoporphyrin Ⅸ （ PPⅨ ） was quantified by fluorescence microscopy and digital image analysis in eryosections. The presence of low- or high-risk types of HPV was tested by FDA approved Hybrid Capture 2 HPV DNA assay. Results ALA-induced PPⅨ fluorescence was found in the epidermis in almost all of patients after application of 5-ALA, but hardly found in dermis. The intensity of PPⅨ fluorescence became strong at 3 h after application, reached peak at 5 h, and gradually declined afterwards. The equal intensity was identified between 3 h and 7 h after application. The intensity of PPⅨ fluorescence increased gradually in epidermis along with the increasing of ALA concentrations, which was stronger with 5% and 10% compared to as compared that with 0.5%, 1% and 3% ALA solution （ P〈 0.05 ）. Low-risk types were identified in all patients while high-risk types in 18.3% （ 11/60 ） simultaneously. Conclusions The results strongly suggest that ALA-PDT with 5% and 10% ALA applied for 3 - 5 hours is optimal for the treatment of urethral warts.