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

前言：我们最近的实验研究表明，在体内和体外，吖啶橙光动力或放射动力学疗法(AO-PDT或AO-RDT)对小鼠骨肉瘤细胞具有很强的杀伤作用。此外，在手术中，由于AO是亲瘤的，并具有通过激发发出荧光的能力，因此具有肿瘤可视化效果。在本研究中，我们尝试应用AO-PDT加或不加AO-RDT的病灶内切除(刮除)手术治疗肌肉骨骼肉瘤，以获得良好的肢体功能。材料与方法：自1999年7月至2005年2月，对47例肌肉骨骼肉瘤患者采用加/不加AO-RDT的AO-PDT刮除。对37例治疗后随访6个月以上的患者的临床结果进行分析。病理类型：滑膜肉瘤6例，横纹肌肉瘤6例，尤文肉瘤/PNETs 5例，骨肉瘤5例，MFH 3例，MPNST 2例，软骨肉瘤2例等。这些…患者的平均年龄男19例，女13例，年龄29岁(1~82岁)。术后随访6个月~68个月。首先对肿瘤进行肉眼刮除，然后在荧光手术显微镜下局部注射1g/mlAO溶液5min，然后用蓝光激发，在肿瘤可视化下进行显微刮除。最后，在手术显微镜下对肿瘤刮治区进行10分钟的AO-PDT治疗。手术创面闭合后不冲洗，立即用5GyX射线照射至切除区，行AO-RTD。结果：21例初治的患者中，仅1例局部复发。局部复发率为4.8%，是较好的局部控制。然而，在初次手术后未行AO-PDT的12个病灶中，有3个(25%)复发，即使在AO-PDT后也是如此。5例局部侵袭性肿瘤，如骨巨细胞瘤和硬纤维瘤，经AO-PDT治疗后无局部复发。所有被研究的患者都保持了良好的肢体或器官功能。所有患者均未发生全身或局部并发症。结论：根据上述结果，我们得出结论：在肌肉骨骼肉瘤中，AO-PDT联合AO-RDT将成为一种新的保肢方式，以抑制局部肿瘤的复发，保护良好的肢体或器官功能。较少

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