Targeted detection of cancer cells during biopsy allows real-time diagnosis of pulmonary nodules.

Targeted detection of cancer cells during biopsy allows real-time diagnosis of pulmonary nodules.
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DOI:
10.1007/s00259-022-05868-9
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发表时间:
2022-10
影响因子:
9.1
通讯作者:
Singhal, Sunil
Singhal, Sunil
中科院分区:
医学1区
文献类型:
--
作者:
Kennedy, Gregory T.;Azari, Feredun S.;Bernstein, Elizabeth;Nadeem, Bilal;Chang, Ashley;Segil, Alix;Sullivan, Neil;Encarnado, Emmanuel;Desphande, Charuhas;Kucharczuk, John C.;Leonard, Kaela;Low, Philip S.;Chen, Silvia;Criton, Aline;Singhal, Sunil

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孤立性肺结节(SPNs)的活检诊断率很低,特别是在亚实性病变中。我们开发了一种方法(NIR- ncle),通过整合(i)使用癌症靶向示踪剂(pafolacianine)的近红外(NIR)成像,以及(ii)可安装在活检针内的灵活的近红外共聚焦激光内窥镜(CLE)系统,在活检期间实现细胞水平的癌症检测。我们的目的是评估NIR-nCLE在SPNs中的体外诊断准确性。20例spn患者术前输注帕帕拉嘧啶。切除后,检查标本以确定感兴趣的病变。在病变内和正常肺组织中进行NIR-nCLE成像,然后进行组织活检。所有影像学序列(n = 115)由5名盲法评分者对荧光癌细胞的存在进行评分,并与胸部病理学家的诊断进行比较。大多数病变(n = 15, 71%)为腺癌谱系恶性肿瘤,包括7个磨玻璃混浊(33%)。NIR-nCLE对肿瘤活检的平均荧光强度(MFI)为20.6任意单位(a.u),正常肺的平均MFI为6.4 a.u (p < 0.001)。受试者工作特征分析的MFI曲线下面积较高(AUC = 0.951)。盲法评分者对NIR-nCLE序列对荧光癌细胞的存在进行评分,灵敏度和特异性分别为98%和97%。总体诊断准确率为97%。5个评分者的观察者间一致性极好(κ = 0.95)。NIR-nCLE允许敏感和特异性地检测spn中的癌细胞。这项技术对诊断穿刺活检和术中决策具有深远的意义。在线版本包含补充材料,可在10.1007/s00259-022-05868-9获得。
The diagnostic yield of biopsies of solitary pulmonary nodules (SPNs) is low, particularly in sub-solid lesions. We developed a method (NIR-nCLE) to achieve cellular level cancer detection during biopsy by integrating (i) near-infrared (NIR) imaging using a cancer-targeted tracer (pafolacianine), and (ii) a flexible NIR confocal laser endomicroscopy (CLE) system that can fit within a biopsy needle. Our goal was to assess the diagnostic accuracy of NIR-nCLE ex vivo in SPNs. Twenty patients with SPNs were preoperatively infused with pafolacianine. Following resection, specimens were inspected to identify the lesion of interest. NIR-nCLE imaging followed by tissue biopsy was performed within the lesion and in normal lung tissue. All imaging sequences (n = 115) were scored by 5 blinded raters on the presence of fluorescent cancer cells and compared to diagnoses by a thoracic pathologist. Most lesions (n = 15, 71%) were adenocarcinoma-spectrum malignancies, including 7 ground glass opacities (33%). Mean fluorescence intensity (MFI) by NIR-nCLE for tumor biopsy was 20.6 arbitrary units (A.U.) and mean MFI for normal lung was 6.4 A.U. (p < 0.001). Receiver operating characteristic analysis yielded a high area under the curve for MFI (AUC = 0.951). Blinded raters scored the NIR-nCLE sequences on the presence of fluorescent cancer cells with sensitivity and specificity of 98% and 97%, respectively. Overall diagnostic accuracy was 97%. The inter-observer agreement of the five raters was excellent (κ = 0.95). NIR-nCLE allows sensitive and specific detection of cancer cells in SPNs. This technology has far-reaching implications for diagnostic needle biopsies and intraprocedural decision-making. The online version contains supplementary material available at 10.1007/s00259-022-05868-9.
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