Development of photodynamic and radiodynamic therapy with acridine orange for new limb salvage surgery in musculoskeletal sarcomas

简介：最近我们的实验研究表明，光动力或放射动力疗法与吖啶橙子（AO-PDT或AO-RDT）在体外和体内对小鼠骨肉瘤细胞有很强的杀伤作用。此外，AO在手术期间具有肿瘤可视化效果，因为AO是亲肿瘤的并且具有通过激发发射荧光的能力。在这项研究中，我们已经尝试应用AO-PDT病灶内切除（刮除）的复位手术与/AO-RDT的肌肉骨骼sarcoma.Materials和方法：47例患者进行刮除术与AO-PDT与/AO-RDT在1999年7月至2005年2月期间，获得良好的肢体功能。对37例随访6个月以上的患者进行了临床疗效分析。组织学上，滑膜肉瘤6例，横纹肌肉瘤6例，尤文氏肉瘤5例，骨肉瘤5例，MFH 3例，MPNST 2例，软骨肉瘤等2例。 关于我们 男19例，女13例，年龄29岁（1 ~ 82岁）。随访6 ~ 68个月。对于这些患者，首先进行肿瘤的肉眼刮除，然后在局部施用1□g/ml AO溶液5分钟后，使用荧光手术显微镜用蓝光激发，在肿瘤可视化下进行显微刮除。最后，在手术显微镜下将AO-PDT应用于肿瘤刮除区域10分钟。结果：21例患者经AO-PDT联合或不联合AO-RDT治疗后，仅1例局部复发。局部复发率为4.8%，局部控制较好。然而，在未经AO-PDT的初次手术后复发的12个病变中，有3个（25%）即使在AO-PDT后也再次复发。5例骨巨细胞瘤、硬纤维瘤等局部侵袭性肿瘤患者经AO-PDT治疗后均未出现局部复发。所有患者均保持了良好的肢体或器官功能。任何患者都没有全身或局部并发症AO管理或AO-PDT和AO-RDT.Conclusion：基于这些结果，我们得出结论，AO-PDT与AO-RDT将成为一种新的保肢方式，以抑制局部肿瘤复发，并保持良好的肢体或器官功能的肌肉骨骼肉瘤。少

Introduction : Recent our experimental study revealed that photodynamic or radiodynamic therapy with acridine orange (AO-PDT or AO-RDT) had a strong cytocidal effect in vitro as well as in vivo on mouse osteosarcoma cells. Also AO had a tumor visualization effect during surgery, because AO is tumorphilic and has a capability to emit fluorescence by excitation. In this study, we have attempted to apply reduction surgery of intralesional excision (curettage) by AO-PDT with/without AO-RDT to musculoskeletal sarcoma patients, to obtain good limb function.Materials & Methods : 47 patients with musculosketetal sarcomas were treated by curettage using AO-PDT with/without AO-RDT during July 1999 to February 2005. Clinical out come was analysed in 37 patients who are followed longer than 6 months after the treatment. Histologically, 6 were synovial sarcomas, 6 rhabdomyosarcomas, 5 Ewing'sarcomas/PNETs, 5 osteosarcomas, 3 MFHs, 2 MPNST, 2 chondrosarcomas, etc. Average age of these patients with … More 19 males and 13 females was 29 years (1 to 82 years). Follow-up period was ranged from 6 month to 68 months. For these patients, macroscopic curettage of tumor was first performed, and then microscopic curettage under tumor visualization was done after local administration of 1□g/ml AO solution for 5 minutes followed by excitation with blue light using fluorescence surgical microscope. Finally, AO-PDT was applied to tumor curettage area for 10 minutes using surgical microscope. After closure of surgical wound without washing of AO, 5 Gy of X-ray was immediately irradiated to resected area for AO-RTD.Results : Out of 21 patients primarily treated wit AO-PDT with/without AO-RDT, only one patient had a local recurrence. Local recurrence rate was 4.8%, which is quite better local control. However, 3(25%) of 12 lesions which recurred after primary surgery without AO-PDT recurred again even after AO-PDT. 5 patients with locally aggressive tumors such as bone GCT and desmoid tumor did not show local recurrence after AO-PDT. All of patients studied maintained an excellent limb or organ function. Any patients did not have systemic or local complications by AO administration or AO-PDT and AO-RDT.Conclusion : Based on these results, we concluded that AO-PDT with AO-RDT will become a novel limb salvage modality to inhibit local tumor recurrence and to preserve an excellent limb or organ function in musculoskeletal sarcomas. Less