Department of Surgery, University of California San Diego, San Diego, CA 92093-0987, USA.
J Am Coll Surg. 2012 Jul;215(1):126-35; discussion 135-6. doi: 10.1016/j.jamcollsurg.2012.02.021. Epub 2012 May 24.
Negative surgical margins are vital to achieve cure and prolong survival in patients with pancreatic cancer. We inquired if fluorescence-guided surgery (FGS) could improve surgical outcomes and reduce recurrence rates in orthotopic mouse models of human pancreatic cancer.
A randomized active-control preclinical trial comparing bright light surgery (BLS) to FGS was used. Orthotopic mouse models of human pancreatic cancer were established using the BxPC-3 pancreatic cancer cell line expressing red fluorescent protein (RFP). Two weeks after orthotopic implantation, tumors were resected with BLS or FGS. Pre- and postoperative images were obtained with the OV-100 Small Animal Imaging System to assess completeness of surgical resection in real time. Postoperatively, noninvasive whole body imaging was done to assess recurrence and follow tumor progression. Six weeks postoperatively, mice were sacrificed to evaluate primary pancreatic and metastatic tumor burden at autopsy.
A more complete resection of pancreatic cancer was achieved using FGS compared with BLS: 98.9% vs 77.1%, p = 0.005. The majority of mice undergoing BLS (63.2%) had evidence of gross disease with no complete resections; 20% of mice undergoing FGS had complete resection and an additional 75% had only minimal residual disease (p = 0.0001). The mean postoperative tumor burden was significantly less with FGS compared with BLS: 0.08 ± 0.06 mm(2) vs 2.64 ± 0.63 mm(2), p = 0.001. The primary tumor burden at termination was significantly less with FGS compared with BLS: 19.3 ± 5.3 mm(2) vs 6.2 ± 3.6 mm(2), p = 0.048. FGS resulted in significantly longer disease-free survival than BLS (p = 0.02, hazard ratio = 0.39, 95% CI 0.17, 0.88).
Surgical outcomes were improved in pancreatic cancer using fluorescence-guidance. This novel approach has significant potential to improve surgical treatment of cancer.
在胰腺癌患者中,获得阴性切缘对于治愈和延长生存至关重要。我们研究了荧光引导手术(FGS)是否可以改善手术结果并降低人胰腺癌细胞原位模型中的复发率。
我们使用随机、主动对照的临床前试验比较了亮场手术(BLS)和 FGS。使用表达红色荧光蛋白(RFP)的 BxPC-3 胰腺癌细胞系建立人胰腺癌细胞原位模型。原位种植两周后,用 BLS 或 FGS 切除肿瘤。使用 OV-100 小动物成像系统在术前和术后获得图像,实时评估手术切除的完整性。术后,进行非侵入性全身成像以评估复发并跟踪肿瘤进展。术后 6 周,处死小鼠,在尸检时评估原发性胰腺和转移性肿瘤负担。
与 BLS 相比,FGS 实现了更完全的胰腺癌切除:98.9% vs 77.1%,p=0.005。接受 BLS 的大多数小鼠(63.2%)有肉眼可见疾病,无完全切除;接受 FGS 的 20%小鼠有完全切除,另外 75%的小鼠仅有最小残留疾病(p=0.0001)。与 BLS 相比,FGS 的术后肿瘤负担明显更小:0.08±0.06 mm² vs 2.64±0.63 mm²,p=0.001。与 BLS 相比,FGS 的原发肿瘤负担明显更小:19.3±5.3 mm² vs 6.2±3.6 mm²,p=0.048。FGS 比 BLS 显著延长了无病生存期(p=0.02,风险比=0.39,95%CI 0.17,0.88)。
在胰腺癌中,荧光引导手术改善了手术结果。这种新方法有很大潜力改善癌症的手术治疗。