Intraoperative Molecular Imaging for ex vivo Assessment of Peripheral Margins in Oral Squamous Cell Carcinoma
Intraoperative Molecular Imaging for ex vivo Assessment of Peripheral Margins in Oral Squamous Cell Carcinoma
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DOI：
10.3389/fonc.2019.01476
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发表时间：
2020-01-10
影响因子：
4.7
通讯作者：
Martin, Brock A.
中科院分区：
文献类型：
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作者：
Fakurnejad, Shayan;Krishnan, Giri;Martin, Brock A.
目的：完整的手术切除是治疗口腔癌的标准，但切缘阳性率仍为15-30%。从切除的标本和伤口床上采集组织进行冰冻切片分析(FSA)仍然是术中切缘评估的主要方法，但会受到抽样误差的影响，可能需要处理多个样本。我们试图了解一种使用肿瘤靶向荧光标记抗体的体外成像策略是否可以准确地识别切除的肿瘤标本粘膜表面最近的外围边缘，从而可以用这个“前哨边缘”来指导病理采样。材料和方法：接受手术切除的29例口腔鳞状细胞癌患者接受肿瘤靶向荧光标记抗体(Panitumumab IRDye800CW)的全身注射。手术切除后，使用闭合场荧光成像设备对肿瘤标本进行成像。对5例患者进行回顾性分析，获得相关的病理资料。对于这5名患者中的每一位，确定了两个边缘荧光强度最高的区域和一个荧光强度最低的区域，并将结果与组织学相关联，以确定沿粘膜边缘(即前哨边缘)的荧光强度最高区域是否真的是最接近的边缘。结果：术后即刻对标本粘膜表面图像采集30例，所有标本中，标本边缘荧光强度最高的区域边缘距离均明显小于其他取样区。最接近“哨兵”边缘的平均边缘距离为3.2毫米，而其他地区的边缘距离为8毫米(p<；0.0001)。结论：这项概念验证研究表明，当与常规FSA相结合时，体外荧光标本成像可以用来确定标本上最接近的手术切缘。这种方法可以减少术中评估的抽样误差，这最终应该会提高外科医生识别哨兵边缘的能力。这种快速的前哨边缘识别改善了外科医生对手术伤口床上最有可能呈阳性的区域的定向，并可能加快病理工作流程。
Objective: Complete surgical resection is the standard of care for treatment of oral cancer although the positive margin rate remains 15-30%. Tissue sampling from the resected specimen and from the wound bed for frozen section analysis (FSA) remains the mainstay for intraoperative margin assessment but is subject to sampling error and can require the processing of multiple samples. We sought to understand if an ex vivo imaging strategy using a tumor-targeted fluorescently labeled antibody could accurately identify the closest peripheral margin on the mucosal surface of resected tumor specimen, so that this "sentinel margin" could be used to guide pathological sampling. Materials and Methods: Twenty-nine patients with oral squamous cell carcinoma scheduled for surgical resection were consented for the study and received systemic administration of a tumor-targeted fluorescently labeled antibody (Panitumumab IRDye800CW). After surgical resection, the tumor specimen was imaged using a closed-field fluorescent imaging device. Relevant pathological data was available for five patients on retrospective review. For each of these five patients, two regions of highest fluorescence intensity at the peripheral margin and one region of lowest fluorescence intensity were identified, and results were correlated with histology to determine if the region of highest fluorescence intensity along the mucosal margin (i.e., the sentinel margin) was truly the closest margin. Results: Imaging acquisition of the mucosal surface of the specimen immediately after surgery took 30 s. In all of the specimens, the region of highest fluorescence at the specimen edge had a significantly smaller margin distance than other sampled regions. The average margin distance at the closest, "sentinel," margin was 3.2 mm compared to a margin distance of 8.0 mm at other regions (p < 0.0001). Conclusions: This proof-of-concept study suggests that, when combined with routine FSA, ex vivo fluorescent specimen imaging can be used to identify the closest surgical margin on the specimen. This approach may reduce sampling error of intraoperative evaluation, which should ultimately improve the ability of the surgeon to identify the sentinel margin. This rapid sentinel margin identification improves the surgeon's orientation to areas most likely to be positive in the surgical wound bed and may expedite pathology workflow.