吲哚菁绿示踪前哨淋巴结在早期宫颈癌中的应用

doi:10.12280/gjfckx.20250018

摘要/Abstract

摘要：

宫颈癌是威胁女性健康的恶性肿瘤之一，其传统手术清扫范围通常为系统性淋巴结清扫，但该方法可能导致术后并发症增多，影响患者生活质量。前哨淋巴结活检（sentinel lymph node biopsy，SLNB）技术旨在评估患者的淋巴结转移状态，为部分前哨淋巴结（sentinel lymph node，SLN）阴性患者减少了不必要的淋巴结清扫，从而降低手术创伤。吲哚菁绿（indocyanine green，ICG）作为一种荧光示踪剂，在早期宫颈癌的SLNB中显示出高敏感度和特异度，检出率优于生物染料、纳米碳悬液和放射性核素，是目前最常用的示踪剂之一。因其组织穿透力有限，进一步研究应关注ICG联合载体技术的临床转化，以克服现有技术的局限性。综述ICG示踪SLN在早期宫颈癌中的应用，为推进SLNB技术的临床应用提供参考。

关键词: 前哨淋巴结, 前哨淋巴结活组织检查, 吲哚花青绿, 宫颈肿瘤, 示踪剂

Abstract:

Cervical cancer is one of the malignant tumors that threaten women′s health. The traditional surgical approach typically involves systemic lymph node dissection, which may lead to increased postoperative complications and affect the quality of life of patients. Sentinel lymph node biopsy (SLNB) technology aims to assess the lymph node metastasis status of patients and reduce unnecessary lymph node dissection for some patients with negative sentinel lymph node (SLN), thereby reducing surgical trauma. Indocyanine green (ICG), as a fluorescent tracer, has shown high sensitivity and specificity in SLNB for early cervical cancer, with a detection rate superior to that of biological dyes, carbon nanoparticles, and radioactive isotopes. It is currently one of the most commonly used tracers. Due to its limited tissue penetration, further research should focus on the clinical transformation of ICG combined with carrier technology to overcome the limitations of existing techniques. This article aims to provide a comprehensive review of the application of ICG-traced SLN in early cervical cancer, providing a reference to promote the clinical application of SLNB technology.

Key words: Sentinel lymph node, Sentinel lymph node biopsy, Indocyanine green, Uterine cervical neoplasms, Tracer

柴玲娜, 李艳丽, 石洁, 高晗, 欧阳夕颜, 程诗语. 吲哚菁绿示踪前哨淋巴结在早期宫颈癌中的应用[J]. 国际妇产科学杂志, 2025, 52(2): 175-179.

CHAI Ling-na, LI Yan-li, SHI Jie, GAO Han, OUYANG Xi-yan, CHENG Shi-yu. Clinical Application of Indocyanine Green Tracing of Sentinel Lymph Nodes in Early Cervical Cancer[J]. Journal of International Obstetrics and Gynecology, 2025, 52(2): 175-179.

图/表 1

参考文献 40

[1]	郑荣寿, 张思维, 孙可欣, 等. 2016年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2023, 45(3):212-220. doi: 10.3760/cma.j.cn112152-20220922-00647.
[2]	Ferrandina G, Pedone Anchora L, Gallotta V, et al. Can We Define the Risk of Lymph Node Metastasis in Early-Stage Cervical Cancer Patients? A Large-Scale, Retrospective Study[J]. Ann Surg Oncol, 2017, 24(8):2311-2318. doi: 10.1245/s10434-017-5917-0. pmid: 28608117
[3]	Morales-Conde S, Licardie E, Alarcón I, et al. Indocyanine green (ICG) fluorescence guide for the use and indications in general surgery: recommendations based on the descriptive review of the literature and the analysis of experience[J]. Cir Esp(Engl Ed), 2022, 100(9):534-554. doi: 10.1016/j.cireng.2022.06.023.
[4]	Pantelis AG, Machairiotis N, Stavros S, et al. Current applications of indocyanine green (ICG) in abdominal, gynecologic and urologic surgery: a meta-review and quality analysis with use of the AMSTAR 2 instrument[J]. Surg Endosc, 2024, 38(2):511-528. doi: 10.1007/s00464-023-10546-4.
[5]	况燕, 王毅雯. 宫颈癌前哨淋巴结活检术的临床价值和挑战[J]. 中国医师杂志, 2021, 23(2):178-182,188. doi: 10.3760/cma.j.cn431274-20201230-01762.
[6]	Koh WJ, Abu-Rustum NR, Bean S, et al. Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology[J]. J Natl Compr Canc Netw, 2019, 17(1):64-84. doi: 10.6004/jnccn.2019.0001.
[7]	Reinhart MB, Huntington CR, Blair LJ, et al. Indocyanine Green: Historical Context, Current Applications, and Future Considerations[J]. Surg Innov, 2016, 23(2):166-175. doi: 10.1177/1553350615604053. pmid: 26359355
[8]	Alander JT, Kaartinen I, Laakso A, et al. A review of indocyanine green fluorescent imaging in surgery[J]. Int J Biomed Imaging, 2012, 2012:940585.doi: 10.1155/2012/940585.
[9]	Li X, Ni R, Ji Z. ICG signal denoising based on ICEEMDAN and PSO-VMD methods[J]. Phys Eng Sci Med, 2024, 47(4):1547-1556. doi: 10.1007/s13246-024-01467-0.
[10]	Ott P. Hepatic elimination of indocyanine green with special reference to distribution kinetics and the influence of plasma protein binding[J]. Pharmacol Toxicol, 1998, 83(Suppl 2):1-48. doi: 10.1111/j.1600-0773.1998.tb01945.x.
[11]	Dai ZY, Shen C, Mi XQ, et al. The primary application of indocyanine green fluorescence imaging in surgical oncology[J]. Front Surg, 2023, 10:1077492. doi: 10.3389/fsurg.2023.1077492.
[12]	Lu CH, Hsiao JK. Indocyanine green: An old drug with novel applications[J]. Tzu Chi Med J, 2021, 33(4):317-322. doi: 10.4103/tcmj.tcmj_216_20.
[13]	Choi HJ, Kim TJ, Lee YY, et al. Time-lapse imaging of sentinel lymph node using indocyanine green with near-infrared fluorescence imaging in early endometrial cancer[J]. J Gynecol Oncol, 2016, 27(3):e27. doi: 10.3802/jgo.2016.27.e27.
[14]	Abu-Rustum NR, Yashar CM, Arend R, et al. NCCN Guidelines^® Insights: Cervical Cancer, Version 1.2024[J]. J Natl Compr Canc Netw, 2023, 21(12):1224-1233. doi: 10.6004/jnccn.2023.0062.
[15]	Zhang X, Bao B, Wang S, et al. Sentinel lymph node biopsy in early stage cervical cancer: A meta-analysis[J]. Cancer Med, 2021, 10(8):2590-2600. doi: 10.1002/cam4.3645.
[16]	Wang T, Xu Y, Shao W, et al. Sentinel Lymph Node Mapping: Current Applications and Future Perspectives in Gynecology Malignant Tumors[J]. Front Med(Lausanne), 2022, 9:922585. doi: 10.3389/fmed.2022.922585.
[17]	Kim JH, Kim DY, Suh DS, et al. The efficacy of sentinel lymph node mapping with indocyanine green in cervical cancer[J]. World J Surg Oncol, 2018, 16(1):52. doi: 10.1186/s12957-018-1341-6.
[18]	Muallem MZ, Sayasneh A, Armbrust R, et al. Sentinel Lymph Node Staging with Indocyanine Green for Patients with Cervical Cancer: The Safety and Feasibility of Open Approach Using SPY-PHI Technique[J]. J Clin Med, 2021, 10(21):4849. doi: 10.3390/jcm10214849.
[19]	Swerdlow M, Vangsness KL, Kress GT, et al. Determining Accurate Dye Combinations for Sentinel Lymph Node Detection: A Systematic Review[J]. Plast Reconstr Surg Glob Open, 2024, 12(2):e5598. doi: 10.1097/GOX.0000000000005598. pmid: 38333031
[20]	陈永霞, 于风胜, 孙欣, 等. 纳米炭和吲哚菁绿在早期子宫颈癌治疗中的示踪效果比较[J]. 临床医学进展, 2024, 14(3):1514-1522. doi: 10.12677/acm.2024.143873.
[21]	齐美敬, 王静, 张治宁. 纳米碳标识前哨淋巴结在早期宫颈癌淋巴结转移评估中的临床价值[J]. 宁夏医科大学学报, 2022, 44(11):1121-1124. doi: 10.16050/j.cnki.issn1674-6309.2022.11.008.
[22]	Baeten I, Hoogendam JP, Braat A, et al. Fluorescent Indocyanine Green versus Technetium-99m and Blue Dye for Bilateral SENTinel Lymph Node Detection in Stage Ⅰ-ⅡA Cervical Cancer (FluoreSENT): protocol for a non-inferiority study[J]. BMJ Open, 2022, 12(9):e061829. doi: 10.1136/bmjopen-2022-061829.
[23]	Zhao X, Li S, Song Y, et al. Construction of a near infrared fluorescence system for imaging of biological tissues[J]. Sci Rep, 2024, 14(1):1626. doi: 10.1038/s41598-024-51583-w.
[24]	蒋思悦, 王文华, 曾超, 等. 吲哚菁绿荧光成像技术在宫颈癌根治术中的应用进展[J]. 国际生殖健康/计划生育杂志, 2022, 41(6):524-528. doi: 10.12280/gjszjk.20220354.
[25]	Wess B, Kohler C, Plaikner A, et al. Comparative study using indocyanine green and patent blue dye for sentinel lymph node biopsy in patients with early-stage cervical cancer[J]. Int J Gynecol Cancer, 2024, 34(5):675-680. doi: 10.1136/ijgc-2023-005206.
[26]	Pölcher M, Matz S, Braun M, et al. Sentinel lymph node mapping with indocyanine green compared to blue dye tracer in gynecologic malignancies-A single center experience of 218 patients[J]. J Surg Oncol, 2021, 123(4):1092-1098. doi: 10.1002/jso.26338. pmid: 33333589
[27]	王熠昕, 曹蒙, 王焱. 国产纳米炭混悬液在恶性肿瘤前哨淋巴结活检中的应用进展[J]. 国际肿瘤学杂志, 2023, 50(1):22-27. doi: 10.3760/cma.j.cn371439-20220816-00004.
[28]	Amengual Vila J, Torrent Colomer A, Sampol Bas C, et al. Detecting Atypical Sentinel Lymph Nodes in Early-Stage Cervical Cancer Using a Standardized Technique with a Hybrid Tracer[J]. Cancers(Basel), 2024, 16(15):2626. doi: 10.3390/cancers16152626.
[29]	Pitsinis V, Kanitkar R, Vinci A, et al. Results of a Prospective Randomized Multicenter Study Comparing Indocyanine Green (ICG) Fluorescence Combined with a Standard Tracer Versus ICG Alone for Sentinel Lymph Node Biopsy in Early Breast Cancer: The INFLUENCE Trial[J]. Ann Surg Oncol, 2024, 31(13):8848-8855. doi: 10.1245/s10434-024-16176-x.
[30]	Zheng J, Xie W, Huang Y, et al. The technique of 3D reconstruction combining with biochemistry to build an equivalent formula of indocyanine green (ICG) clearance test to assess the liver reserve function[J]. BMC Surg, 2020, 20(1):283. doi: 10.1186/s12893-020-00952-z. pmid: 33183305
[31]	中华医学会核医学分会, 中华医学会数字医学分会, 中国医师协会肝癌专业委员会, 等. 吲哚菁绿近红外二区荧光成像在肝癌切除术中应用的专家共识[J]. 中华核医学与分子影像杂志, 2023, 43(7):418-425. doi: 10.3760/cma.j.cn321828-20220210-00041.
[32]	Salehi O, Kazakova V, Vega EA, et al. Indocyanine green staining for intraoperative perfusion assessment[J]. Minerva Surg, 2021, 76(3):220-228. doi: 10.23736/S2724-5691.21.08673-1. pmid: 34080819
[33]	王亚婷, 李斌. 子宫颈癌前哨淋巴结活检技术的研究进展[J]. 中华肿瘤杂志, 2022, 44(5):377-381. doi: 10.3760/cma.j.cn112152-20200324-00254.
[34]	Balaya V, Mathevet P, Magaud L, et al. Predictive factors of unexpected lymphatic drainage pathways in early-stage cervical cancer[J]. Gynecol Oncol, 2019, 154(1):102-109. doi: 10.1016/j.ygyno.2019.04.008. pmid: 31003746
[35]	赵锦丽, 刘光新, 于鹤. 不同部位注射吲哚菁绿示踪下肢淋巴回流通路及子宫旁淋巴回流通路观察[J]. 新乡医学院学报, 2024, 41(3):262-265. doi: 10.7683/xxyxyxb.2024.03.012.
[36]	中国研究型医院学会妇产科学专业委员会. 子宫颈癌前哨淋巴结活检临床应用中国专家共识[J]. 中华肿瘤杂志, 2021, 43(10):981-998. doi: 10.3760/cma.j.cn112152-20210720-005268.
[37]	Nowak K, Karampinis I, Gerken A. Application of Fluorescent Dyes in Visceral Surgery: State of the Art and Future Perspectives[J]. Visc Med, 2020, 36(2):80-87. doi: 10.1159/000506910. pmid: 32355664
[38]	Niu G, Ren Y, Zhai Y. Association Study between the Sentinel Lymph Node Biopsy and the Clinicopathological Features of Patients with Cervical Cancer[J]. Dis Markers, 2022, 2022:9697629.doi: 10.1155/2022/9697629.
[39]	Frumovitz M, Plante M, Lee PS, et al. Near-infrared fluorescence for detection of sentinel lymph nodes in women with cervical and uterine cancers (FILM): a randomised, phase 3, multicentre, non-inferiority trial[J]. Lancet Oncol, 2018, 19(10):1394-1403. doi: 10.1016/S1470-2045(18)30448-0. pmid: 30143441
[40]	Li N, Wang M, Zhou J, et al. Progress of NIR-Ⅱ fluorescence imaging technology applied to disease diagnosis and treatment[J]. Eur J Med Chem, 2024, 267:116173. doi: 10.1016/j.ejmech.2024.116173.

示踪剂	优点	缺点
蓝色染料	成本低；安全性高；不需要高昂的显影设备	容易弥散至周围组织导致手术视野不清晰；显影不持久
纳米碳悬液	具有淋巴管趋向性；不需要显影设备；显影持久；安全性高	无穿透性，对于深部SLN观察不利；目前国内外相关研究较少
放射性核素	高敏感度；较高准确性；不易引流至下一站淋巴结	具有放射性；不易获取；成本高昂；需要特殊设备保存；操作不易
ICG	成本低；检出率高；实时观察淋巴动态循环；安全性高；使用方式简单；敏感度和特异度高	需要高昂显像设备；有一定的假阴性率；淋巴显影具有局限性；存在血管、淋巴管外渗可能，往往渗透至下一站淋巴结

示踪剂	优点	缺点
蓝色染料	成本低；安全性高；不需要高昂的显影设备	容易弥散至周围组织导致手术视野不清晰；显影不持久
纳米碳悬液	具有淋巴管趋向性；不需要显影设备；显影持久；安全性高	无穿透性，对于深部SLN观察不利；目前国内外相关研究较少
放射性核素	高敏感度；较高准确性；不易引流至下一站淋巴结	具有放射性；不易获取；成本高昂；需要特殊设备保存；操作不易
ICG	成本低；检出率高；实时观察淋巴动态循环；安全性高；使用方式简单；敏感度和特异度高	需要高昂显像设备；有一定的假阴性率；淋巴显影具有局限性；存在血管、淋巴管外渗可能，往往渗透至下一站淋巴结