Comparison of sentinel lymph node biopsy guided by indocyanine green, blue dye, and their combination in breast cancer patients: a prospective cohort study

Jiajia Guo, Houpu Yang, Shu Wang, Yingming Cao, Miao Liu, Fei Xie, Peng Liu, Bo Zhou, Fuzhong Tong, Lin Cheng, Hongjun Liu, Siyuan Wang, Jiajia Guo, Houpu Yang, Shu Wang, Yingming Cao, Miao Liu, Fei Xie, Peng Liu, Bo Zhou, Fuzhong Tong, Lin Cheng, Hongjun Liu, Siyuan Wang

Abstract

Background: Recent studies show that near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve the performance of sentinel lymph node (SLN) mapping. The current cohort study was designed to assess the value of the combination of ICG and methylene blue (MB) dye in patients undergoing SLN biopsy.

Methods: A prospective self-controlled trial was designed to detect the difference in the detection efficacies of ICG, MB, and combined ICG and MB (ICG + MB) navigation methods. Between 2010 and 2013, 198 consecutive early breast cancer patients eligible for sentinel lymph node biopsy were enrolled and 200 biopsy procedures were performed by injection of both ICG and MB. SLNs were searched and removed under the guidance of fluorescence and/or blue dye. The mapping characteristics, the detection rate of SLNs and positive SLNs, and the number of SLNs of ICG, MB, and ICG + MB were compared. Injection safety of ICG and MB was evaluated.

Results: Fluorescence imaging of lymphatic flow, which is helpful to locate the incision site, could be seen in 184 of 200 procedures. The nodal detection rate of ICG, MB, and ICG + MB samples was 97, 89, and 99.5% (χ 2 = 26.2, p < 0.001), respectively, with the combination method yielding a superior identification result. The addition of ICG to the MB method resulted in the identification of more lymph nodes (median 3 versus 2) and more positive axillas (22.7% involved axillas were discovered by fluorescence only) than either method alone. No acute or chronic allergic reaction was observed in this study. However, 23 patients (23/82) who received breast-conserving therapy reported temporary skin staining, and 5 patients had permanent tattooing. Palpable subcutaneous nodules at the injection sites were reported in nine patients. There were no reports of skin necrosis.

Conclusions: The lymphatic navigation by ICG fluorescence detects SLNs at a high detection rate and improves the mapping performance when added to the MB method. The novel ICG + MB dual tracing modality, without involvement of radioactive isotopes, exhibits great potential as an alternative to traditional standard mapping methods.

Trial registration: ACTRN12612000109808 . Retrospectively registered on 23 January 2012.

Keywords: Breast neoplasm; Indocyanine green; Lymphography; Sentinel lymph node biopsy.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Ethical Committee of Peking University People’s Hospital, Beijing. Written informed consent from all patients was obtained before the operation. No individual data were contained in this work.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
SLN resection mapping by ICG fluorescence. a Two streams of dermal lymphatic vessels. b One stream of dermal lymphatic vessels (IS—injection site; white arrow—fluorescent lymph vessels). c SLN highlighted by ICG fluorescence (white arrow). d Fluorescence disappeared after all the SLNs were removed

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