Intraoperative laparoscopic detection of sentinel lymph nodes with indocyanine green and superparamagnetic iron oxide in a swine gallbladder cancer model

PLoS One. 2021 Mar 11;16(3):e0248531. doi: 10.1371/journal.pone.0248531. eCollection 2021.

Abstract

Mapping of sentinel lymph nodes (SLNs) can enable less invasive surgery. However, mapping is challenging for cancers of difficult-to-access visceral organs, such as the gallbladder, because the standard method using radioisotopes (RIs) requires preoperative tracer injection. Indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) have also been used as alternative tracers. In this study, we modified a previously reported magnetic probe for laparoscopic use and evaluated the feasibility of detecting SLNs of the gallbladder using a laparoscopic dual tracer method by injecting ICG and SPIO into five swine and one cancer-bearing swine. The laparoscopic probe identified SPIO nanoparticles in the nodes of 4/5 swine in situ, the magnetic field counts were 2.5-15.9 μT, and fluorescence was detected in SLNs in all five swine. ICG showed a visual lymph flow map, and SPIO more accurately identified each SLN with a measurable magnetic field quite similar to the RI. We then developed an advanced gallbladder cancer model with lymph node metastasis using recombination activating gene 2-knockout swine. We identified an SLN in the laparoscopic investigation, and the magnetic field count was 3.5 μT. The SLN was histologically determined to be one of the two metastatic lymph nodes. In conclusion, detecting the SLNs of gallbladder cancer in situ using a dual tracer laparoscopic technique with ICG and SPIO was feasible in a swine model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Gallbladder Neoplasms* / diagnosis
  • Gallbladder Neoplasms* / pathology
  • Gallbladder Neoplasms* / surgery
  • Humans
  • Indocyanine Green* / pharmacokinetics
  • Indocyanine Green* / pharmacology
  • Laparoscopy*
  • Lymphatic Metastasis
  • Magnetic Iron Oxide Nanoparticles*
  • Neoplasms, Experimental* / diagnosis
  • Neoplasms, Experimental* / pathology
  • Neoplasms, Experimental* / surgery
  • Sentinel Lymph Node / pathology
  • Sentinel Lymph Node / surgery
  • Sentinel Lymph Node Biopsy*
  • Swine

Substances

  • Indocyanine Green

Grants and funding

This study was supported by the Project for Medical Device Development from the Japan Agency for Medical Research and Development (AMED) (Grant Number JP18he0902010h0004 to YK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.