收稿日期: 2022-05-24
录用日期: 2022-08-28
网络出版日期: 2022-09-28
基金资助
国家自然科学基金(91859202);上海市高水平地方高校创新团队(SHSMU-ZDCX20210402)
Exploratory study on detection of cervical lymph node metastasis and extra-nodal extension of oral squamous cell carcinoma using fluorescent probe cMBP-ICG
Received date: 2022-05-24
Accepted date: 2022-08-28
Online published: 2022-09-28
Supported by
National Natural Science Foundation of China(91859202);Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20210402)
目的·探索利用表面涂抹式荧光探针细胞间充质-上皮转化因子(cellular-mesenchymal epithelial transition factor,c-Met)结合肽(c-Met-binding peptide,cMBP)-吲哚菁绿(indocyanine green,ICG)实现术中实时荧光成像诊断口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)颈部淋巴结转移及淋巴结包膜外侵犯(extra-nodal extension,ENE)的可行性。方法·选取5名上海交通大学医学院附属第九人民医院原发性OSCC患者作为研究对象,通过制备、配制荧光探针cMBP-ICG,采用表面涂抹法对入组的患者颈部淋巴结清扫切除的可疑淋巴结进行实时荧光成像。收集并整理患者临床资料、病理结果及淋巴结实时荧光成像的荧光强度(fluorescence intensity,FI)数据,并根据cMBP-ICG实时荧光成像的FI对淋巴结转移与ENE进行预测。结果·术中对可疑淋巴结进行cMBP-ICG实时荧光成像,获得不同FI的实时成像结果。对5例患者的49个可疑淋巴结的分析结果显示,cMBP-ICG预测淋巴结转移的敏感度为100%,特异度为84%,阳性预测值(positive predictive value,PPV)为67%,阴性预测值(negative predictive value,NPV)为100%。cMBP-ICG预测淋巴结ENE的敏感度为100%,特异度为93%,PPV为63%,NPV为100%。结论·表面涂抹式荧光探针cMBP-ICG术中实时荧光成像能较为有效地识别OSCC转移淋巴结及ENE,可作为术中诊断淋巴结转移及ENE的辅助方法。
关键词: 口腔鳞状细胞癌; 淋巴结包膜外侵犯; 实时荧光成像; 分子影像; 细胞间充质-上皮转化因子
杨琳 , 王晶波 , 黄小娟 , 任继亮 , 袁瑛 , 陶晓峰 . 荧光探针cMBP⁃ICG检测口腔鳞状细胞癌颈部淋巴结转移及包膜外侵犯的探索性研究[J]. 上海交通大学学报(医学版), 2022 , 42(9) : 1296 -1302 . DOI: 10.3969/j.issn.1674-8115.2022.09.016
Objective ·To explore the feasibility of intraoperative real-time fluorescence imaging in the diagnosis of oral cancer cervical lymph node metastasis and extra-nodal extension (ENE) in the patients with oral squamous cell carcinoma (OSCC) by using the surface-smeared fluorescent probe cellular-mesenchymal epithelial transition factor (c-Met)?binding peptide (cMBP)? indocyanine green (ICG). Methods ·The five patients with primary OSCC in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were selected as the research subjects. The fluorescent probe cMBP-ICG was prepared, and real-time fluorescence imaging was performed by surface smear method on the suspicious lymph nodes of the enrolled patients who underwent neck lymph node dissection. The clinical information, the pathological results and the fluorescence intensity (FI) values of lymph node real-time fluorescence imaging were collected and sorted, and lymph node metastasis and ENE were predicted according to the FIs of cMBP-ICG real-time fluorescence imaging. Results ·Intraoperative cMBP-ICG real-time fluorescence imaging of suspicious lymph nodes were performed, and imaging results of different FIs were obtained in real time. The results of 49 suspicious lymph nodes in the 5 patients showed that the sensitivity of cMBP-ICG in predicting lymph node metastasis was 100%, the specificity was 84%, the positive predictive value was 67%, and the negative predictive value was 100%. The sensitivity of cMBP-ICG in predicting lymph node ENE was 100%, the specificity was 93%, the positive predictive value was 63%, and the negative predictive value was 100%. Conclusion ·Intraoperative cMBP-ICG real-time fluorescence imaging can effectively identify lymph node metastatic and ENE in OSCC, which can provide an auxiliary method for intraoperative diagnosis of lymph node metastasis and ENE.
1 | DU M, NAIR R, JAMIESON L, et al. Incidence trends of lip, oral cavity, and pharyngeal cancers: global burden of disease 1990?2017[J]. J Dent Res, 2020, 99(2): 143-151. |
2 | VEGH A, BANYAI D, UJPAL M, et al. Prevalence of diabetes and impaired fasting glycemia in patients with oral cancer: a retrospective study in Hungary[J]. Anticancer Res, 2022, 42(1): 109-113. |
3 | CHAKRABORTY D, NATARAJAN C, MUKHERJEE A. Advances in oral cancer detection[J]. Adv Clin Chem, 2019, 91: 181-200. |
4 | ALMANGUSH A, M?KITIE A A, TRIANTAFYLLOU A, et al. Staging and grading of oral squamous cell carcinoma: an update[J]. Oral Oncol, 2020, 107: 104799. |
5 | BOSETTI C, CARIOLI G, SANTUCCI C, et al. Global trends in oral and pharyngeal cancer incidence and mortality[J]. Int J Cancer, 2020, 147(4): 1040-1049. |
6 | TSAI C K, LIN C Y, KANG C J, et al. Nuclear magnetic resonance metabolomics biomarkers for identifying high risk patients with extranodal extension in oral squamous cell carcinoma[J]. J Clin Med, 2020, 9(4): E951. |
7 | 何渝, 金观桥. 影像学对头颈部鳞癌淋巴结转移包膜外侵犯诊断价值的研究进展[J]. 广西医学, 2020, 42(21): 2866-2868, 2875. |
7 | HE Y, JIN G Q. Diagnostic value of imaging for extranodal extension of lymph node metastasis of head and neck squamous cell carcinoma: a literature review[J]. Guangxi Med J, 2020, 42(21): 2866-2868, 2875. |
8 | BLASCO M A, NOEL C W, TRUONG T, et al. Radiologic-pathologic correlation of major versus minor extranodal extension in oral cavity cancer[J]. Head Neck, 2022, 44(6): 1422-1429. |
9 | HO T Y, CHAO C H, CHIN S C, et al. Classifying neck lymph nodes of head and neck squamous cell carcinoma in MRI images with radiomic features[J]. J Digit Imaging, 2020, 33(3): 613-618. |
10 | LEE H R, ROH J, GU G Y, et al. Differential expression of podoplanin in metastatic lymph node is associated with extranodal extension in oropharyngeal cancer[J]. Sci Rep, 2022, 12(1): 3665. |
11 | LI G P, ZHANG P, WEI T, et al. Prognostic implications of extranodal extension in papillary thyroid carcinomas: a propensity score matching analysis and proposal for incorporation into current tumor, lymph node, metastasis staging[J]. Surgery, 2022, 171(2): 368-376. |
12 | EGLOFF-JURAS C, BEZDETNAYA L, DOLIVET G, et al. NIR fluorescence-guided tumor surgery: new strategies for the use of indocyanine green[J]. Int J Nanomedicine, 2019, 14: 7823-7838. |
13 | 季春宜, 尹强, 袁妙贤, 等. 吲哚菁绿荧光成像技术在腹腔镜下肠隔膜手术中的应用研究[J]. 临床小儿外科杂志, 2021, 20(10): 911-915. |
13 | JI C Y, YIN Q, YUAN M X, et al. Application of indocyanine green fluorescent imaging for laparoscopy of intestinal diaphragm [J]. J Clin Pediatr Surg, 2021, 20(10): 911-5. |
14 | ROTHENBERGER NJ, STABILE LP. Hepatocyte growth factor/c-Met signaling in head and neck cancer and implications for treatment[J]. Cancers, 2017, 9(4): 39. |
15 | WU J, YUAN Y, TAO X F. Targeted molecular imaging of head and neck squamous cell carcinoma: a window into precision medicine[J]. Chin Med J (Engl), 2020, 133(11): 1325-1336. |
16 | LIN B, WU J, WANG Y X, et al. Peptide functionalized upconversion/NIR Ⅱ luminescent nanoparticles for targeted imaging and therapy of oral squamous cell carcinoma[J]. Biomater Sci, 2021, 9(3): 1000-1007. |
17 | WU J, LIU J, LIN B, et al. Met-targeted dual-modal MRI/NIR Ⅱ imaging for specific recognition of head and neck squamous cell carcinoma[J]. ACS Biomater Sci Eng, 2021, 7(4): 1640-1650. |
18 | SCHOUW H M, HUISMAN L A, JANSSEN Y F, et al. Targeted optical fluorescence imaging: a meta-narrative review and future perspectives[J]. Eur J Nucl Med Mol Imaging, 2021, 48(13): 4272-4292. |
19 | COLEVAS A D, YOM S S, PFISTER D G, et al. NCCN guidelines insights: head and neck cancers, version 1.2018[J]. J Natl Compr Canc Netw, 2018, 16(5): 479-490. |
20 | BHALLI H, CHEN S Q, DAY A, et al. Factors associated with lymph node count in mucosal squamous cell carcinoma neck dissection[J]. Laryngoscope, 2021, 131(7): 1516-1521. |
21 | ABDEL-HALIM C N, ROSENBERG T, DYRVIG A K, et al. Diagnostic accuracy of imaging modalities in detection of histopathological extranodal extension: a systematic review and meta-analysis[J]. Oral Oncol, 2021, 114: 105169. |
22 | TIRELLI G, DE GROODT J, SIA E, et al. Accuracy of the Anatomage Table in detecting extranodal extension in head and neck cancer: a pilot study[J]. J Med Imaging (Bellingham), 2021, 8(1): 014502. |
23 | AIKEN A H, POLIASHENKO S, BEITLER J J, et al. Accuracy of preoperative imaging in detecting nodal extracapsular spread in oral cavity squamous cell carcinoma[J]. AJNR Am J Neuroradiol, 2015, 36(9): 1776-1781. |
24 | PHAM T D, WATANABE Y, HIGUCHI M, et al. Texture analysis and synthesis of malignant and benign mediastinal lymph nodes in patients with lung cancer on computed tomography[J]. Sci Rep, 2017, 7: 43209. |
25 | ZOUMALAN R A, KLEINBERGER A J, MORRIS L G, et al. Lymph node central necrosis on computed tomography as predictor of extracapsular spread in metastatic head and neck squamous cell carcinoma: pilot study[J]. J Laryngol Otol, 2010, 124(12): 1284-1288. |
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