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Sentinel Lymph Node Mapping of Liver

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Although the sentinel lymph node (SLN) hypothesis has been applied to many tissues and organs, liver has remained unstudied. Currently, it is unclear whether hepatic SLNs even exist. If so, they could alter the management of intrahepatic cholangiocarcinoma and other hepatic malignancies by minimizing the extent of surgery while still providing precise nodal staging. This study investigated whether invisible yet tissue-penetrating near-infrared (NIR) fluorescent light can provide simultaneous identification of both the SLN and all other regional lymph nodes (RLNs) in the liver.

Methods

In 25 Yorkshire pigs, this study determined whether SLNs exist in liver and compared the effectiveness of two clinically available NIR fluorophores [methylene blue and indocyanine green (ICG)], and two novel NIR fluorophores previously described by our group (ESNF14 and ZW800-3C) for SLN and RLN mapping.

Results

In this study, ESNF14 showed the highest signal-to-background ratio and the longest retention time in SLNs without leakage to second-tier lymph nodes. The findings showed that ICG had apparent leakage to second-tier nodes, and ZW800-3C had poor migration after intraparenchymal injection. However, when injected intravenously, ZW800-3C was able to highlight all RLNs in liver during a 4- to 6-h period. Simultaneous dual-channel imaging of SLN (ESNF14) and RLN (ZW800-3C) permitted unambiguous identification and image-guided resection of SLNs and RLNs in liver.

Conclusion

The NIR imaging technology enables real-time intraoperative identification of SLNs and RLNs in the liver of swine. If these results are confirmed in patients, new strategies for the surgical management of intrahepatic malignancies should be possible.

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Acknowledgment

We thank Rita G. Laurence for assistance with animal surgery, David J. Burrington Jr for editing, Eugenia Trabucchi for administrative assistance, and Frank Kettenring and Florin Neacsu for assistance with development and maintenance of the FLARE imaging system and software. This study was supported by the following grants from the National Institutes of Health: NCI BRP Grant #R01-CA-115296 (J.V.F.), NIBIB Grant #R01-EB-010022 (J.V.F. and H.S.C.), and NIBIB Grant #R01-EB-011523 (H.S.C. and J.V.F.). The content of this report is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosures

John V. Frangioni, MD, PhD, currently is CEO of Curadel, Curadel ResVet Imaging, and Curadel Surgical Innovations, which have licensed FLARE imaging systems and contrast agents from the Beth Israel Deaconess Medical Center.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

    Hideyuki Wada MD, Hoon Hyun PhD, Christina Vargas MD, Julien Gravier PhD, Sylvain Gioux PhD, John V. Frangioni MD, PhD & Hak Soo Choi PhD

  2. Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Hideyuki Wada MD

  3. Division of Plastic and Reconstructive Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Christina Vargas MD

  4. Department of Pathology and Laboratory Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA

    Elizabeth M. Genega MD

  5. INSERM, CRI, U823, Institut Albert Bonniot, Grenoble, France

    Julien Gravier PhD

  6. Curadel, LLC, Worcester, MA, USA

    John V. Frangioni MD, PhD

  7. Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

    John V. Frangioni MD, PhD

Authors
  1. Hideyuki Wada MD
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  2. Hoon Hyun PhD
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  4. Elizabeth M. Genega MD
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  6. Sylvain Gioux PhD
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  7. John V. Frangioni MD, PhD
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  8. Hak Soo Choi PhD
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Corresponding author

Correspondence to Hak Soo Choi PhD.

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Wada, H., Hyun, H., Vargas, C. et al. Sentinel Lymph Node Mapping of Liver. Ann Surg Oncol 22 (Suppl 3), 1147–1155 (2015). https://doi.org/10.1245/s10434-015-4601-5

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  • DOI: https://doi.org/10.1245/s10434-015-4601-5

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