Clinical Trials Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2016; 22(13): 3644-3651
Published online Apr 7, 2016. doi: 10.3748/wjg.v22.i13.3644
Near-infrared fluorescence sentinel lymph node detection in gastric cancer: A pilot study
Quirijn R J G Tummers, Leonora S F Boogerd, Wobbe O de Steur, Floris P R Verbeek, Martin C Boonstra, Henricus J M Handgraaf, John V Frangioni, Cornelis J H van de Velde, Henk H Hartgrink, Alexander L Vahrmeijer
Wobbe O de Steur, Martin C Boonstra, Henk H Hartgrink, Alexander L Vahrmeijer, Quirijn RJG Tummers, Leonora SF Boogerd, Floris PR Verbeek, Henricus JM Handgraaf, Cornelis JH van de Velde, Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
John V Frangioni, Division of Hematology/Oncology, Department of Medicine and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States
John V Frangioni, Curadel LLC, 377 Plantation Street, Worcester, MA 01605, United States
Author contributions: Tummers QRJG and Boogerd LSF contributed equally to the study and share first authorship; Tummers QRJG, Boogerd LSF designed research and performed analysis; Tummers QRJG, Boogerd LSF, de Steur WO, Verbeek FPR, Boonstra MC, Handgraaf HJM and Hartgrink HH acquired the data; Tummers QRJG, Boogerd LSF, de Steur WO, Hartgrink HH, Vahrmeijer AL assisted in interpretation of the data; all authors contributed to writing of the paper; Frangioni JV, van de Velde CJH made critical revisions to the manuscript; all authors approved the final version of the article.
Institutional review board statement: This study was approved and reviewed by the Local Medical Ethics Committee of the Leiden University Medical Center (LUMC).
Clinical trial registration statement: The trial was approved by the Medical Ethics Committee of the Leiden University Medical Center and was performed in accordance with the ethical standards of the Helsinki Declaration of 1975. This trial is registered with the Netherlands Trial Register as NTR4280.
Informed consent statement: All involved persons provided informed consent prior to study inclusion.
Conflict-of-interest statement: Tummers QRJG, Boogerd LSF, de Steur WO, Verbeek FPR, Boonstra MC, Handgraaf HJM, van de Velde CJH, Hartgrink HH and Vahrmeijer AL have no conflicts of interest or financial ties to disclose; Frangioni JV FLARE™ technology is owned by Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School; Dr. Frangioni has started three for-profit companies, Curadel, Curadel ResVet Imaging, and Curadel Surgical Innovations, which has optioned FLARE™ technology for potential licensing from Beth Israel Deaconess Medical Center.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Alexander L Vahrmeijer, MD, PhD, Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. a.l.vahrmeijer@lumc.nl
Telephone: +31-71-5262309 Fax: +31-71-5266750
Received: November 10, 2015
Peer-review started: November 10, 2015
First decision: December 11, 2015
Revised: December 31, 2015
Accepted: January 30, 2016
Article in press: January 30, 2016
Published online: April 7, 2016
Processing time: 138 Days and 21.9 Hours
Abstract

AIM: To investigate feasibility and accuracy of near-infrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node (SLN) detection in gastric cancer.

METHODS: A prospective, single-institution, phase I feasibility trial was conducted. Patients suffering from gastric cancer and planned for gastrectomy were included. During surgery, a subserosal injection of 1.6 mL ICG:Nanocoll was administered around the tumor. NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE™ NIR fluorescence imaging system. Lymphatic pathways and SLNs were visualized. Of every detected SLN, the corresponding lymph node station, signal-to-background ratio and histopathological diagnosis was determined. Patients underwent standard-of-care gastrectomy. Detected SLNs outside the standard dissection planes were also resected and evaluated.

RESULTS: Twenty-six patients were enrolled. Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection. In 21 of the remaining 22 patients, at least 1 SLN was detected by NIR Fluorescence imaging (mean 3.1 SLNs; range 1-6). In 8 of the 21 patients, tumor-positive LNs were found. Overall accuracy of the technique was 90% (70%-99%; 95%CI), which decreased by higher pT-stage (100%, 100%, 100%, 90%, 0% for respectively Tx, T1, T2, T3, T4 tumors). All NIR-negative SLNs were completely effaced by tumor. Mean fluorescence signal-to-background ratio of SLNs was 4.4 (range 1.4-19.8). In 8 of the 21 patients, SLNs outside the standard resection plane were identified, that contained malignant cells in 2 patients.

CONCLUSION: This study shows successful use of ICG:Nanocoll as lymphatic tracer for SLN detection in gastric cancer. Moreover, tumor-containing LNs outside the standard dissection planes were identified.

Keywords: Gastric cancer; Sentinel lymph node; Near-infrared fluorescence imaging; Image-guided surgery; Indocyanine green

Core tip: Sentinel lymph node (SLN) detection using indoyanine green adsorbed to nanocolloid (ICG:Nanocoll) was investigated in 26 patients with gastric cancer. Adsorption of ICG to nanocolloid results in better retention in SLNs and staining of less 2nd tier nodes. After subserosal injection, fluorescent SLN detection using the Mini-FLARE™ system was performed. A mean number of 3.1 SLNs per patient were found and overall accuracy was 90%. In 8 patients, SLNs outside the standard resection planes were identified, that contained malignant cells in 2 patients. To conclude, NIR fluorescence imaging using ICG:Nanocoll as lymphatic tracer identified SLNs in- and outside standard dissection planes.