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使用三种光敏剂——ALA诱导的PPIX、血卟啉衍生物和MTHPC对胃肠道肿瘤进行光动力治疗。一项初步研究。

Photodynamic therapy for gastrointestinal tumors using three photosensitizers--ALA induced PPIX, Photofrin and MTHPC. A pilot study.

作者信息

Mĺkvy P, Messmann H, Regula J, Conio M, Pauer M, Millson C E, MacRobert A J, Bown S G

机构信息

Department of Gastroenterology, St. Elisabeth Oncological Institute, Bratislava, Slovakia.

出版信息

Neoplasma. 1998;45(3):157-61.

PMID:9717528
Abstract

Photodynamic therapy (PDT) produces localized necrosis with light after prior administration of a photosensitizing drug. As PDT lesions in the gastrointestinal tract heal well, the technique is suitable for repeated endoscopic use. In this study we used PDT to treat benign and malignant gastrointestinal tumors in esophagus, duodenum and rectum in 22 patients, who refused or were not suitable for surgery. Patients were sensitized with 0.15 mg/kg of body weight with mesotetrahydroxyphenylchlorin i.v. m-THPc (2 patients), with 2.0 mg/kg Photofrin i.v. (4 patients) or 60 mg/kg 5-aminolevulinic acid orally ALA (which is converted in vivo to active derivate protoporphyrin IX-PRIX) in fractionated doses (16 patients). Laser treatment was performed 2 days after Photofrin, 2 and 4 days after mTHPc and 4 hours after ALA, using a metal vapour laser (628 nm, 50-150 J/cm2 for ALA and Photofrin, 650 nm and 10-15 J/cm2 for mTHPc). Using ALA, the necrosis was only superficial (up to 1.8 mm depth). Four patients treated with Photofrin showed deeper necrosis, in one case of 8 mm colon cancer complete response, in three cases 1-1.5 cm adenomatous polyps involving the ampulla Vateri 50% longer term reduction in size-seen endoscopically. Two patients with rectal villous adenomas treated with mTHPc showed 60-80% reduction in size (observed endoscopically) within few days after PDT, with better effects for treatment carried out 4 rather than 2 days after the sensitization. In all patients the healing was without any complications. Photofrin and mTHPc work better, but cause cutaneous photosensitivity lasting 12 and 5 weeks, respectively. Better results with ALA are possible when using higher drug doses or modified light dosimetry. PDT is a promising treatment for small localized tumors in patients unsuitable for surgery, but further work is required to optimize the treatment conditions.

摘要

光动力疗法(PDT)是在预先给予光敏药物后,利用光产生局部坏死。由于胃肠道中的PDT损伤愈合良好,该技术适用于反复的内镜使用。在本研究中,我们使用PDT治疗了22例拒绝手术或不适合手术的食管、十二指肠和直肠的良性及恶性胃肠道肿瘤患者。患者静脉注射0.15mg/kg体重的中四羟基苯基氯卟啉(m-THPc)(2例患者)、2.0mg/kg的光卟啉(Photofrin)静脉注射(4例患者)或口服60mg/kg的5-氨基酮戊酸(ALA,其在体内转化为活性衍生物原卟啉IX-PPIX)分次给药(16例患者)进行致敏。使用金属蒸汽激光进行激光治疗,光卟啉治疗后2天、mTHPc治疗后2天和4天以及ALA治疗后4小时进行治疗,对于ALA和光卟啉使用波长628nm、能量密度50 - 150J/cm²,对于mTHPc使用波长650nm、能量密度10 - 15J/cm²。使用ALA时,坏死仅为浅表性(深度达1.8mm)。4例用光卟啉治疗的患者显示出更深的坏死,1例8mm结肠癌患者完全缓解,3例累及壶腹的1 - 1.5cm腺瘤性息肉在内镜下可见长期缩小50%。2例用mTHPc治疗的直肠绒毛状腺瘤患者在PDT后几天内(内镜观察)大小缩小60 - 80%,致敏后4天进行治疗的效果优于2天进行治疗的效果。所有患者愈合过程均无任何并发症。光卟啉和mTHPc效果更好,但分别导致皮肤光敏性持续12周和5周。当使用更高药物剂量或改进光剂量测定法时,ALA可能会取得更好的效果。对于不适合手术的患者,PDT是治疗小的局限性肿瘤的一种有前景的治疗方法,但需要进一步开展工作来优化治疗条件。

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