Skip to main content
Top
Published in: Annals of Surgical Oncology 3/2015

01-12-2015 | Hepatobiliary Tumors

Sentinel Lymph Node Mapping of Liver

Authors: Hideyuki Wada, MD, Hoon Hyun, PhD, Christina Vargas, MD, Elizabeth M. Genega, MD, Julien Gravier, PhD, Sylvain Gioux, PhD, John V. Frangioni, MD, PhD, Hak Soo Choi, PhD

Published in: Annals of Surgical Oncology | Special Issue 3/2015

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127:392–9.PubMedCrossRef Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127:392–9.PubMedCrossRef
2.
go back to reference Cox CE, Pendas S, Cox JM, et al. Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg. 1998;227:645–51; discussion 651–643.PubMedPubMedCentralCrossRef Cox CE, Pendas S, Cox JM, et al. Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg. 1998;227:645–51; discussion 651–643.PubMedPubMedCentralCrossRef
3.
go back to reference Ikai I, Arii S, Okazaki M, et al. Report of the 17th Nationwide Follow-up Survey of Primary Liver Cancer in Japan. Hepatol Res. 2007;37:676–91.PubMedCrossRef Ikai I, Arii S, Okazaki M, et al. Report of the 17th Nationwide Follow-up Survey of Primary Liver Cancer in Japan. Hepatol Res. 2007;37:676–91.PubMedCrossRef
4.
go back to reference de Jong MC, Nathan H, Sotiropoulos GC, et al. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol. 2011;29:3140–5.PubMedCrossRef de Jong MC, Nathan H, Sotiropoulos GC, et al. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol. 2011;29:3140–5.PubMedCrossRef
5.
go back to reference Igami T, Nishio H, Ebata T, et al. Surgical treatment of hilar cholangiocarcinoma in the “new era”: the Nagoya University experience. J Hepatobil Pancreatic Sci. 2010;17:449–54.CrossRef Igami T, Nishio H, Ebata T, et al. Surgical treatment of hilar cholangiocarcinoma in the “new era”: the Nagoya University experience. J Hepatobil Pancreatic Sci. 2010;17:449–54.CrossRef
6.
go back to reference Nagino M, Ebata T, Yokoyama Y, et al. Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections. Ann Surg. 2013;258:129–40.PubMedCrossRef Nagino M, Ebata T, Yokoyama Y, et al. Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections. Ann Surg. 2013;258:129–40.PubMedCrossRef
7.
go back to reference Mavros MN, Mayo SC, Hyder O, Pawlik TM. A systematic review: treatment and prognosis of patients with fibrolamellar hepatocellular carcinoma. J Am Coll Surg 2012;215:820–30.PubMedCrossRef Mavros MN, Mayo SC, Hyder O, Pawlik TM. A systematic review: treatment and prognosis of patients with fibrolamellar hepatocellular carcinoma. J Am Coll Surg 2012;215:820–30.PubMedCrossRef
8.
go back to reference Fonseca GM, Varella AD, Coelho FF, Abe ES, Dumarco RB, Herman P. Downstaging and resection after neoadjuvant therapy for fibrolamellar hepatocellular carcinoma. World J Gastrointest Surg. 2014;6:107–11.PubMedPubMedCentral Fonseca GM, Varella AD, Coelho FF, Abe ES, Dumarco RB, Herman P. Downstaging and resection after neoadjuvant therapy for fibrolamellar hepatocellular carcinoma. World J Gastrointest Surg. 2014;6:107–11.PubMedPubMedCentral
9.
go back to reference Ito K, Ito H, Allen PJ, et al. Adequate lymph node assessment for extrahepatic bile duct adenocarcinoma. Ann Surg. 2010;251:675–81.PubMedCrossRef Ito K, Ito H, Allen PJ, et al. Adequate lymph node assessment for extrahepatic bile duct adenocarcinoma. Ann Surg. 2010;251:675–81.PubMedCrossRef
10.
go back to reference Birnbaum DJ, Vigano L, Russolillo N, Langella S, Ferrero A, Capussotti L. Lymph node metastases in patients undergoing surgery for a gallbladder cancer: extension of the lymph node dissection and prognostic value of the lymph node ratio. Ann Surg Oncol. 2014;22(3):811–8.PubMedCrossRef Birnbaum DJ, Vigano L, Russolillo N, Langella S, Ferrero A, Capussotti L. Lymph node metastases in patients undergoing surgery for a gallbladder cancer: extension of the lymph node dissection and prognostic value of the lymph node ratio. Ann Surg Oncol. 2014;22(3):811–8.PubMedCrossRef
11.
go back to reference Ashitate Y, Hyun H, Kim S, et al. Simultaneous mapping of pan and sentinel lymph nodes for real-time image-guided surgery. Theranostics. 2014;4:693–700.PubMedPubMedCentralCrossRef Ashitate Y, Hyun H, Kim S, et al. Simultaneous mapping of pan and sentinel lymph nodes for real-time image-guided surgery. Theranostics. 2014;4:693–700.PubMedPubMedCentralCrossRef
12.
go back to reference Choi HS, Nasr K, Alyabyev S, et al. Synthesis and in vivo fate of zwitterionic near-infrared fluorophores. Angewandte Chem Int Ed Eng. 2011;50:6258–63.CrossRef Choi HS, Nasr K, Alyabyev S, et al. Synthesis and in vivo fate of zwitterionic near-infrared fluorophores. Angewandte Chem Int Ed Eng. 2011;50:6258–63.CrossRef
13.
14.
go back to reference Ashitate Y, Tanaka E, Stockdale A, Choi HS, Frangioni JV. Near-infrared fluorescence imaging of thoracic duct anatomy and function in open surgery and video-assisted thoracic surgery. J Thorac Cardiovasc Surg. 2011;142:31–8; e31–2.CrossRef Ashitate Y, Tanaka E, Stockdale A, Choi HS, Frangioni JV. Near-infrared fluorescence imaging of thoracic duct anatomy and function in open surgery and video-assisted thoracic surgery. J Thorac Cardiovasc Surg. 2011;142:31–8; e31–2.CrossRef
15.
go back to reference Gioux S, Choi HS, Frangioni JV. Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation. Mol Imaging. 2010;9:237–55. Gioux S, Choi HS, Frangioni JV. Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation. Mol Imaging. 2010;9:237–55.
16.
go back to reference Troyan SL, Kianzad V, Gibbs-Strauss SL, et al. The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping. Ann Surg Oncol. 2009;16:2943–52.PubMedPubMedCentralCrossRef Troyan SL, Kianzad V, Gibbs-Strauss SL, et al. The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping. Ann Surg Oncol. 2009;16:2943–52.PubMedPubMedCentralCrossRef
17.
go back to reference Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2009. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2009.
18.
go back to reference Sobin LH, Gospodarowicz M, Wittekind C. TNM classification of malignant tumours. 7th ed. Oxford: Wiley-Blackwell; 2009. Sobin LH, Gospodarowicz M, Wittekind C. TNM classification of malignant tumours. 7th ed. Oxford: Wiley-Blackwell; 2009.
19.
go back to reference Nakayama A, Bianco AC, Zhang CY, Lowell BB, Frangioni JV. Quantitation of brown adipose tissue perfusion in transgenic mice using near-infrared fluorescence imaging. Mol Imaging. 2003;2:37–49.CrossRef Nakayama A, Bianco AC, Zhang CY, Lowell BB, Frangioni JV. Quantitation of brown adipose tissue perfusion in transgenic mice using near-infrared fluorescence imaging. Mol Imaging. 2003;2:37–49.CrossRef
20.
go back to reference Gibbs-Strauss SL, Nasr KA, Fish KM, et al. Nerve-highlighting fluorescent contrast agents for image-guided surgery. Mol Imaging. 2011;10:91–101. Gibbs-Strauss SL, Nasr KA, Fish KM, et al. Nerve-highlighting fluorescent contrast agents for image-guided surgery. Mol Imaging. 2011;10:91–101.
21.
go back to reference Winer JH, Choi HS, Gibbs-Strauss SL, Ashitate Y, Colson YL, Frangioni JV. Intraoperative localization of insulinoma and normal pancreas using invisible near-infrared fluorescent light. Ann Surg Oncol. 2010;17:1094–100.PubMedPubMedCentralCrossRef Winer JH, Choi HS, Gibbs-Strauss SL, Ashitate Y, Colson YL, Frangioni JV. Intraoperative localization of insulinoma and normal pancreas using invisible near-infrared fluorescent light. Ann Surg Oncol. 2010;17:1094–100.PubMedPubMedCentralCrossRef
22.
go back to reference Parungo CP, Ohnishi S, Kim SW, et al. Intraoperative identification of esophageal sentinel lymph nodes with near-infrared fluorescence imaging. J Thorac Cardiovasc Surg. 2005;129:844–50.PubMedPubMedCentralCrossRef Parungo CP, Ohnishi S, Kim SW, et al. Intraoperative identification of esophageal sentinel lymph nodes with near-infrared fluorescence imaging. J Thorac Cardiovasc Surg. 2005;129:844–50.PubMedPubMedCentralCrossRef
23.
go back to reference Schaafsma BE, van der Vorst JR, Gaarenstroom KN, et al. Randomized comparison of near-infrared fluorescence lymphatic tracers for sentinel lymph node mapping of cervical cancer. Gynecol Oncol. 2012;127:126–30.PubMedPubMedCentralCrossRef Schaafsma BE, van der Vorst JR, Gaarenstroom KN, et al. Randomized comparison of near-infrared fluorescence lymphatic tracers for sentinel lymph node mapping of cervical cancer. Gynecol Oncol. 2012;127:126–30.PubMedPubMedCentralCrossRef
24.
go back to reference Vera DR, Wallace AM, Hoh CK, Mattrey RF. A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran. J Nucl Med. 2001;42:951–9. Vera DR, Wallace AM, Hoh CK, Mattrey RF. A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran. J Nucl Med. 2001;42:951–9.
25.
go back to reference Baker JL, Pu M, Tokin CA, et al. Comparison of [Tc]Tilmanocept and filtered [Tc]sulfur colloid for identification of SLNs in breast cancer patients. Ann Surg Oncol. 2014; 22(1):40–5.PubMedPubMedCentralCrossRef Baker JL, Pu M, Tokin CA, et al. Comparison of [Tc]Tilmanocept and filtered [Tc]sulfur colloid for identification of SLNs in breast cancer patients. Ann Surg Oncol. 2014; 22(1):40–5.PubMedPubMedCentralCrossRef
Metadata
Title
Sentinel Lymph Node Mapping of Liver
Authors
Hideyuki Wada, MD
Hoon Hyun, PhD
Christina Vargas, MD
Elizabeth M. Genega, MD
Julien Gravier, PhD
Sylvain Gioux, PhD
John V. Frangioni, MD, PhD
Hak Soo Choi, PhD
Publication date
01-12-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4601-5

Other articles of this Special Issue 3/2015

Annals of Surgical Oncology 3/2015 Go to the issue