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

Kiyoshi Mihara ,Sachiko Matsuda,Osamu Itano,Yuko Kitagawa,Hiroshi Yagi,Moriaki Kusakabe,Yuki Nakamura,Minoru Kitago,Yuta Abe,Koichi Aiura,Masaki Sekino,Akihiro Kuwahata,Junko Kuramoto,Kaori Kameyama,Daiichiro Fuchimoto,Shunichi Suzuki,Masahiro Shinoda,Shinichi Chikaki,Akira Ōnishi

doi:10.1371/journal.pone.0248531

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.

Highlights

Application of the sentinel lymph node (SLN) theory is beneficial because it can result in less invasive surgery for many cancers, such as skin [1], breast [2], gastrointestinal [3] and gynaecological cancers [4], even during laparoscopic operations [5]
We found that detecting the SLNs of gallbladder cancer using a dual tracer laparoscopic technique with Indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) was feasible in a swine model
A magnetic tracer method has been used in patients with breast cancer and melanoma [14,29] and is reportedly not inferior to an RI technique regarding the rate of SLN detection

Summary

Introduction

Application of the sentinel lymph node (SLN) theory is beneficial because it can result in less invasive surgery for many cancers, such as skin [1], breast [2], gastrointestinal [3] and gynaecological cancers [4], even during laparoscopic operations [5]. The radioisotope (RI) tracer is injected 2 to 24 hours prior to surgery for accurate SLN detection [7], which limits the application of the SLN theory to organs that are accessible from the surface of the body or by endoscopy. The reported incidence of lymph node metastasis is 10.9% or less in patients with early gallbladder cancer [8], and the optimal surgical strategy for early gallbladder cancer remains debatable [9]. These patients may benefit from SLN mapping to enable planning of the appropriate extent of lymphadenectomy. Limitations on preoperative access have prevented the use of traditional RI tracer methods

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Discussion

Conclusion