Dataset Information

Sentinel Lymph Node Mapping of Liver.

ABSTRACT: 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.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.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.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.

SUBMITTER: Wada H

PROVIDER: S-EPMC4644113 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Sentinel Lymph Node Mapping of Liver.

Wada Hideyuki H Hyun Hoon H Vargas Christina C Genega Elizabeth M EM Gravier Julien J Gioux Sylvain S Frangioni John V JV Choi Hak Soo HS

Annals of surgical oncology 20150513

<h4>Background</h4>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 provi ...[more]

PMID: 25968620

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Project description:Purpose: Sentinel lymph node biopsy (SLNB) has emerged as the preferred standard procedure in patients with breast cancer, melanoma and other types of cancer. Herein, we developed a method to intra-operatively map SLNs and differentiate tumor metastases within SLNs at the same time, with the aim to provide more accurate and real-time intraoperative guidance. Experimental Design: Hyaluronic acid (HA), a ligand of lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, is employed as a SLN mapping agent after being conjugated with a near-infrared fluorophore (Cy5.5). Different sized HAs (5, 10 and 20K) were tested in normal mice and mice with localized inflammation to optimize LN retention time and signal to background ratio. Cetuximab, an antibody against epidermal growth factor receptor (EGFR), and trastuzumab, an antibody against human epidermal growth factor receptor 2 (HER2), were labeled with near-infrared fluorophore (IRDye800) for detecting metastatic tumors. LN metastasis model was developed by hock injection of firefly luciferase engineered human head neck squamous carcinoma cancer UM-SCC-22B cells or human ovarian cancer SKOV-3 cells. The metastases within LNs were confirmed by bioluminescence imaging (BLI). IRDye800-Antibodies were intravenously administered 24 h before local administration of Cy5.5-HA. Optical imaging was then performed to identify nodal metastases. Results: Binding of HA with LYVE-1 was confirmed by ELISA and fluorescence staining. HA with a size of 10K was chosen based on the favorable migration and retention profile. After sequential administration of IRDye800-antibodies intravenously and Cy5.5-HA locally to a mouse model with LN metastases and fluorescence optical imaging, partially metastasized LNs were successfully distinguished from un-metastasized LNs and fully tumor occupied LNs, based on the different signal patterns. Conclusions: Fluorophore conjugated HA is a potential lymphatic mapping agent for SLNB. Dual-tracer imaging with the combination of lymphatic mapping agents and tumor targeting agents can identify tumor metastases within SLNs, thus may provide accurate and real-time intra-operative guidance to spare the time spent waiting for a biopsy result.

Project description:Rationale: Sentinel lymph node biopsy (SLNB) is a well-established minimally invasive staging procedure that maps the spread of tumour metastases from their primary site to the regional lymphatics. Currently, the procedure requires the local peri-tumoural injection of radiolabelled and/or optical agents, and is therefore operator dependent, disruptive to surgical workflow and restricted largely to a small subset of malignancies that can be readily accessed externally for local tracer injection. The present study set out to determine whether intravenous (IV) infusion of a tumor-targeted tracer could identify sentinel and metastatic lymph nodes (LNs) in order to overcome these limitations. Methods: We examined 27 patients with oral squamous cell carcinoma (OSCC), 18 of whom were clinically node negative (cN0). Patients were infused intravenously with 50mg of Panitumumab-IRDye800CW prior to surgical resection of their primary tumour with neck dissection and/or SLNB. Lymphadenectomy specimens underwent fluorescence molecular imaging to evaluate tracer distribution to LNs. Results: A total of 960 LNs were analysed, of which 34 (3.5%) contained metastatic disease. Panitumumab-IRDye800CW preferentially localized to metastatic and sentinel LNs as evidenced by a higher fluorescent signal relative to other lymph nodes. The median MFI of metastatic LNs was significantly higher than the median MFI of benign LNs (0.06 versus 0.02, p < 0.05). Furthermore, selecting the highest five fluorescence intensity LNs from individual specimens resulted in 100% sensitivity, 85.8% specificity and 100% negative predictive value (NPV) for the detection of occult metastases and 100% accuracy for clinically staging the neck. In the cN+ cohort, assessment of the highest 5 fluorescence LNs per patient had 87.5% sensitivity, 93.2% specificity and 99.1% NPV for the detection of metastatic nodes. Conclusion: When intravenously infused, a tumour-targeted tracer localized to sentinel and metastatic lymph nodes. Further validation of an IV tumor-targeted tracer delivery approach for SLNB could dramatically change the practice of SLNB, allowing its application to other malignancies where the primary tumour is not accessible for local tracer injection.

Dataset Information

Sentinel Lymph Node Mapping of Liver.

Publications

Sentinel Lymph Node Mapping of Liver.

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