Fakurnejad Shayan, Krishnan Giri, van Keulen Stan, Nishio Naoki, Birkeland Andrew C, Baik Fred M, Kaplan Michael J, Colevas A Dimitrios, van den Berg Nynke S, Rosenthal Eben L, Martin Brock A
Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United States.
The Department of Otorhinolaryngology, Head and Neck Surgery, The University of Adelaide, Woodville South, SA, Australia.
Front Oncol. 2020 Jan 10;9:1476. doi: 10.3389/fonc.2019.01476. eCollection 2019.
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 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. 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. 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 ( < 0.0001). This proof-of-concept study suggests that, when combined with routine FSA, 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.
完整的手术切除是口腔癌治疗的标准治疗方法，尽管切缘阳性率仍为15%-30%。对切除标本和创面床进行组织取样以进行冰冻切片分析（FSA）仍然是术中切缘评估的主要方法，但存在取样误差，并且可能需要处理多个样本。我们试图了解使用肿瘤靶向荧光标记抗体的成像策略是否能够准确识别切除肿瘤标本黏膜表面最接近的外周切缘，以便这个“前哨切缘”能够用于指导病理取样。29例计划进行手术切除的口腔鳞状细胞癌患者同意参与本研究，并接受了肿瘤靶向荧光标记抗体（帕尼单抗IRDye800CW）的全身给药。手术切除后，使用封闭场荧光成像设备对肿瘤标本进行成像。回顾性分析时可获得5例患者的相关病理数据。对于这5例患者中的每一例，在周边切缘确定两个荧光强度最高的区域和一个荧光强度最低的区域，并将结果与组织学进行关联，以确定黏膜切缘处荧光强度最高的区域（即前哨切缘）是否真的是最接近的切缘。手术后立即对标本黏膜表面进行成像采集耗时30秒。在所有标本中，标本边缘荧光强度最高的区域与其他取样区域相比，切缘距离明显更小。最接近的“前哨”切缘的平均切缘距离为3.2毫米，而其他区域的切缘距离为8.0毫米（<0.0001）。这项概念验证研究表明，与常规FSA相结合时，荧光标本成像可用于识别标本上最接近的手术切缘。这种方法可能会减少术中评估的取样误差，最终应能提高外科医生识别前哨切缘的能力。这种快速的前哨切缘识别改善了外科医生对手术创面床中最可能呈阳性区域的定位，并可能加快病理工作流程。
