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外用δ-氨基乙酰丙酸光动力疗法治疗浅表性非黑素瘤皮肤癌的长期随访及组织学变化

Long-term follow-up and histological changes of superficial nonmelanoma skin cancers treated with topical delta-aminolevulinic acid photodynamic therapy.

作者信息

Fink-Puches R, Soyer H P, Hofer A, Kerl H, Wolf P

机构信息

Department of Dermatology, University of Graz, Austria.

出版信息

Arch Dermatol. 1998 Jul;134(7):821-6. doi: 10.1001/archderm.134.7.821.

Abstract

OBJECTIVE

To investigate the immediate and long-term effects of photodynamic therapy with delta-aminolevulinic acid (ALA-PDT) on superficial basal cell carcinomas (BCC) and superficial squamous cell carcinomas (SCC).

DESIGN

Retrospective study with 60 months of maximal follow-up.

SETTING

University-based hospital in Graz, Austria.

PATIENTS

Forty-seven subjects with a total of 95 superficial BCC and 35 superficial SCC.

INTERVENTIONS

A compound of 20% delta-aminolevulinic acid was topically applied under an occlusive and light-shielding dressing before exposure to either UV-A or different wave bands of polychromatic visible light (full-spectrum visible light, >515, >570, or >610 nm).

MAIN OUTCOME MEASURES

Primary tumor responses and recurrence rates in the long-term follow-up, as well as histological changes associated with ALA-PDT, were studied.

RESULTS

The complete primary response rate for all wave bands of light was 86% (82/95) for superficial BCC and 54% (19/35) for superficial SCC. There was no statistically significant difference among the response rates to the different wave bands of light. After a median follow-up of 19 months (range, 3-60 months) for BCC and 8 months (range, 3-47 months) for SCC, the overall recurrence rate was 44% (36/81) and 69% (11/16), respectively. At 36 months after therapy, the projected disease-free rate was 50% (95% confidence interval, 43%-57%) for BCC vs 8% (95% confidence interval, 7%-9%) for SCC (P<.001, log-rank test). Histopathologic studies revealed a significant increase of fibrosis in the dermis after ALA-PDT and appearance of a sharp border between fibrotic and nonfibrotic tissue. In 15 of 16 BCC examined, the border between fibrotic and nonfibrotic tissue was deeper in the dermis than the maximum tumor thickness before therapy (P<.001, Wilcoxon signed rank test). Similar histopathologic observations were made in SCC.

CONCLUSIONS

Our study revealed poor long-term cure rates for superficial BCC and SCC treated with topical ALA-PDT and visible light. The histopathologic observations showing remarkable fibrosis in the dermis indicated that the effect of ALA-PDT reached deeper than the initial depth of invasiveness of the neoplastic tissue, suggesting in turn that the poor long-term results of ALA-PDT cannot be explained by insufficient penetration of the therapy effect.

摘要

目的

探讨用δ-氨基乙酰丙酸光动力疗法(ALA-PDT)治疗浅表性基底细胞癌(BCC)和浅表性鳞状细胞癌(SCC)的即刻和长期效果。

设计

进行为期60个月的最大随访的回顾性研究。

地点

奥地利格拉茨的一家大学附属医院。

患者

47名受试者,共患有95例浅表性BCC和35例浅表性SCC。

干预措施

在暴露于UV-A或多色可见光的不同波段(全光谱可见光、>515nm、>570nm或>610nm)之前,将20%的δ-氨基乙酰丙酸化合物在封闭且遮光的敷料下局部应用。

主要观察指标

研究长期随访中的原发肿瘤反应和复发率,以及与ALA-PDT相关的组织学变化。

结果

所有波段光对浅表性BCC的完全原发反应率为86%(82/95),对浅表性SCC为54%(19/35)。不同波段光的反应率之间无统计学显著差异。BCC的中位随访时间为19个月(范围3 - 60个月),SCC为8个月(范围3 - 47个月),总体复发率分别为44%(36/81)和69%(11/16)。治疗后36个月,BCC的预计无病生存率为50%(95%置信区间,43% - 57%),而SCC为8%(95%置信区间,7% - 9%)(P <.001,对数秩检验)。组织病理学研究显示,ALA-PDT后真皮中的纤维化显著增加,纤维化组织与非纤维化组织之间出现清晰边界。在检查的16例BCC中有15例,纤维化组织与非纤维化组织之间的边界在真皮中比治疗前肿瘤的最大厚度更深(P <.001,Wilcoxon符号秩检验)。在SCC中也有类似的组织病理学观察结果。

结论

我们的研究表明,用局部ALA-PDT和可见光治疗浅表性BCC和SCC的长期治愈率较低。组织病理学观察显示真皮中显著纤维化,这表明ALA-PDT的作用深度超过肿瘤组织最初的侵袭深度,进而表明ALA-PDT长期效果不佳不能用治疗效果穿透不足来解释。

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