Purpose

Local recurrence occurs in ~ 19% of sinonasal inverted papilloma (SNIP) surgeries and is strongly associated with incomplete resection. During surgery, it is technically challenging to visualize and resect all SNIP tissue in this anatomically complex area. Proteins that are overexpressed in SNIP, such as vascular endothelial growth factor (VEGF), may serve as a target for fluorescence molecular imaging to guide surgical removal of SNIP. A proof-of-concept study was performed to investigate if the VEGF-targeted near-infrared fluorescent tracer bevacizumab-800CW specifically localizes in SNIP and whether it could be used as a clinical tool to guide SNIP surgery.

Methods

In five patients diagnosed with SNIP, 10 mg of bevacizumab-800CW was intravenously administered 3 days prior to surgery. Fluorescence molecular imaging was performed in vivo during surgery and ex vivo during the processing of the surgical specimen. Fluorescence signals were correlated with final histopathology and VEGF-A immunohistochemistry. We introduced a fluorescence grid analysis to assess the fluorescence signal in individual tissue fragments, due to the nature of the surgical procedure (i.e., piecemeal resection) allowing the detection of small SNIP residues and location of the tracer ex vivo.

Results

In all patients, fluorescence signal was detected in vivo during endoscopic SNIP surgery. Using ex vivo fluorescence grid analysis, we were able to correlate bevacizumab-800CW fluorescence of individual tissue fragments with final histopathology. Fluorescence grid analysis showed substantial variability in mean fluorescence intensity (FI_mean), with SNIP tissue showing a median FI_mean of 77.54 (IQR 50.47–112.30) compared to 35.99 (IQR 21.48–57.81) in uninvolved tissue (p < 0.0001), although the diagnostic ability was limited with an area under the curve of 0.78.

Conclusions

A fluorescence grid analysis could serve as a valid method to evaluate fluorescence molecular imaging in piecemeal surgeries. As such, although substantial differences were observed in fluorescence intensities, VEGF-A may not be the ideal target for SNIP surgery.

Trial registration

NCT03925285.

中文翻译：

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用于评估鼻窦内翻性乳头状瘤分段手术的荧光网格分析：概念验证研究

目的

局部复发发生在约 19% 的鼻窦内翻性乳头状瘤 (SNIP) 手术中，并且与不完全切除密切相关。在手术过程中，可视化和切除这个解剖学复杂区域中的所有 SNIP 组织在技术上具有挑战性。在 SNIP 中过表达的蛋白质，如血管内皮生长因子 (VEGF)，可作为荧光分子成像的靶标，以指导手术切除 SNIP。进行了一项概念验证研究，以调查靶向 VEGF 的近红外荧光示踪剂 bevacizumab-800CW 是否特异性定位于 SNIP，以及它是否可以用作指导 SNIP 手术的临床工具。

方法

在 5 名诊断为 SNIP 的患者中，10 mg 贝伐单抗-800CW 在手术前 3 天静脉内给药。荧光分子成像在手术期间在体内进行，在手术标本处理期间在体外进行。荧光信号与最终的组织病理学和 VEGF-A 免疫组织化学相关。我们引入了荧光网格分析来评估单个组织碎片中的荧光信号，这是由于外科手术的性质（即分段切除）允许检测小的 SNIP 残留物和离体示踪剂的位置。

结果

在所有患者中，在内窥镜 SNIP 手术期间体内检测到荧光信号。使用离体荧光网格分析，我们能够将单个组织片段的 bevacizumab-800CW 荧光与最终组织病理学相关联。荧光网格分析显示平均荧光强度（FI_平均值）存在很大差异，SNIP 组织的FI_平均值为 77.54（IQR 50.47-112.30），而未受累组织为 35.99（IQR 21.48-57.81）（p  < 0.0001），尽管诊断能力有限，曲线下面积为 0.78。

结论

荧光网格分析可以作为评估分段手术中荧光分子成像的有效方法。因此，尽管观察到荧光强度存在显着差异，但 VEGF-A 可能不是 SNIP 手术的理想目标。

试用注册

NCT03925285。