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Time to maximum indocyanine green fluorescence of gastric sentinel lymph nodes and feasibility of combined indocyanine green/sodium fluorescein gastric lymphography

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Abstract

Purpose

Indocyanine green (ICG) and sodium fluorescein (SF) are fluorescent dyes used for sentinel lymph node mapping. In oncological gastric surgery, ICG lymphography has increased the number of resected lymph nodes. However, the optimal time to administer ICG is unclear, and both preoperative and intraoperative injections have been practised. As dye spillage will diminish lymphogram visibility, a second dye with different excitation and emission spectra may present a clinical alternative. We measured the time until maximum ICG fluorescence of gastric sentinel lymph nodes and investigated the feasibility of combined lymphography with two fluorescent dyes: ICG and SF.

Methods

Ten Danish Landrace/Yorkshire pigs were used in this study. After completion of the laparoscopic setup, ICG and then SF were endoscopically injected into the gastric submucosa. Lymphograms for both dyes were recorded, and the time until maximum ICG sentinel lymph node fluorescence was determined.

Results

The mean time until maximum ICG fluorescence of gastric sentinel lymph nodes was 50 s (± 12.5), and the fluorescent signal then remained stable until the end of the recorded period (45 min). A lymphogram showing both ICG and SF was acquired for eight of the ten pigs.

Conclusions

Because of the short time until maximum ICG fluorescence of sentinel lymph nodes, intraoperative injections could be a sufficient alternative to preoperative injections for oncological gastric surgery. Combined ICG and SF lymphography was feasible and resulted in clear lymphograms with no interference between the two dyes. The ability to use multiple dyes during a surgical procedure offers the exciting prospect of simultaneously assessing perfusion and performing fluorescence lymphography.

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Notes

  1. The light source (CLV-180 EVIS EXERA II; Olympus, Tokyo, Japan) emits narrowband wavelengths that excite SF. However, our laparoscope was an older model, which the light source did not “accept.” We thus modified (manually overrode) the light source to “accept” our laparoscope.

References

  1. Dan AG, Saha S, Monson KM, Wiese D, Schochet E, Barber KR, Ganatra B, Desai D, Kaushal S (2004) 1% lymphazurin vs 10% fluorescein for sentinel node mapping in colorectal tumors. Arch Surg 139(11):1180–1184. https://doi.org/10.1001/archsurg.139.11.1180

    Article  CAS  PubMed  Google Scholar 

  2. Ren L, Liu Z, Liang M, Wang L, Song X, Wang S (2016) 10% fluorescein sodium vs 1% isosulfan blue in breast sentinel lymph node biopsy. World J Surg Oncol 14(1):280. https://doi.org/10.1186/s12957-016-1031-1

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wada T, Kawada K, Takahashi R, Yoshitomi M, Hida K, Hasegawa S, Sakai Y (2017) ICG fluorescence imaging for quantitative evaluation of colonic perfusion in laparoscopic colorectal surgery. Surg Endosc 31(10):4184–4193. https://doi.org/10.1007/s00464-017-5475-3

    Article  PubMed  Google Scholar 

  4. Zeng H-C, Hu J-L, Bai J-W, Zhang G-J (2019) Detection of sentinel lymph nodes with near-infrared imaging in malignancies. Mol Imaging Biol 21(2):219–227. https://doi.org/10.1007/s11307-018-1237-4

    Article  CAS  PubMed  Google Scholar 

  5. Tajima Y, Murakami M, Yamazaki K, Masuda Y, Kato M, Sato A, Goto S, Otsuka K, Kato T, Kusano M, Tajima Y, Surg A (2010) Sentinel node mapping guided by indocyanine green fluorescence imaging during laparoscopic surgery in gastric cancer. Oncol 17:1787–1793. https://doi.org/10.1245/s10434-010-0944-0

    Article  Google Scholar 

  6. Lan Y-T, Huang K-H, Chen P-H, Liu C-A, Lo S-S, Wu C-W, Shyr Y-M, Fang W-L (2017) A pilot study of lymph node mapping with indocyanine green in robotic gastrectomy for gastric cancer. SAGE Open Med 5:1–8. https://doi.org/10.1177/2050312117727444

    Article  Google Scholar 

  7. Kwon IG, Son T, Kim H Il, Hyung WJ (2019) Fluorescent lymphography-guided lymphadenectomy during robotic radical gastrectomy for gastric cancer. JAMA Surg 154(2):141–9. https://doi.org/10.1001/jamasurg.2018.4267

    Article  Google Scholar 

  8. Kim TH, Kong SH, Park JH, Son YG, Huh YJ, Suh YS, Lee HJ, Yang HK (2018) Assessment of the completeness of lymph node dissection using near-infrared imaging with indocyanine green in laparoscopic gastrectomy for gastric cancer. J Gastric Cancer 18(2):161–171. https://doi.org/10.5230/jgc.2018.18.e19

    Article  PubMed  PubMed Central  Google Scholar 

  9. Chen Q-Y, Xie J-W, Zhong Q, Wang J-B, Lin J-X, Lu J, Cao L-L, Lin M, Tu R-H, Huang Z-N, Lin J-L, Zheng H-L, Li P, Zheng C-H, Huang C-M (2020) Safety and efficacy of indocyanine green tracer-guided lymph node dissection during laparoscopic radical gastrectomy in patients with gastric cancer. JAMA Surg 1–12. https://doi.org/10.1001/jamasurg.2019.6033

  10. Kinami S, Oonishi T, Fujita J, Tomita Y, Funaki H, Fujita H, Nakano Y, Ueda N, Kosaka T (2016) Optimal settings and accuracy of indocyanine green fluorescence imaging for sentinel node biopsy in early gastric cancer. Oncol Lett 11(6):4055–4062. https://doi.org/10.3892/ol.2016.4492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kim MJ, Shin R, Oh H-K, Park JW, Jeong S-Y, Park J-G (2011) The impact of heavy smoking on anastomotic leakage and stricture after low anterior resection in rectal cancer patients. World J Surg 35(12):2806–2810. https://doi.org/10.1007/s00268-011-1286-1

    Article  PubMed  Google Scholar 

  12. Cianchi F, Indennitate G, Paoli B, Ortolani M, Lami G, Manetti N, Tarantino O, Messeri S, Foppa C, Badii B, Novelli L, Skalamera I, Nelli T, Coratti F, Perigli G, Staderini F (2020) The clinical value of fluorescent lymphography with indocyanine green during robotic surgery for gastric cancer: a matched cohort study. J Gastrointest Surg 24(10):2197–2203. https://doi.org/10.1007/s11605-019-04382-y

    Article  PubMed  Google Scholar 

  13. Schlottmann F, Barbetta A, Mungo B, Lidor AO, Molena D (2017) Identification of the lymphatic drainage pattern of esophageal cancer with near-infrared fluorescent imaging. J Laparoendosc Adv Surg Tech 27(3):268–271. https://doi.org/10.1089/lap.2016.0523

    Article  Google Scholar 

  14. Kong SH, Marchegiani F, Soares R, Liu YY, Suh YS, Lee HJ, Dallemagne B, Yang HK, Marescaux J, Diana M (2019) Fluorescence lymphangiography-guided full-thickness oncologic gastric resection. Surg Endosc 33(2):620–32. https://doi.org/10.1007/s00464-018-6402-y

    Article  PubMed  Google Scholar 

  15. Shida A, Mitsumori N, Fujioka S, Takano Y, Fujisaki M, Hashizume R, Takahashi N, Ishibashi Y, Yanaga K (2018) Sentinel node navigation surgery for early gastric cancer: analysis of factors which affect direction of lymphatic drainage. World J Surg 42(3):766–772. https://doi.org/10.1007/s00268-017-4226-x

    Article  PubMed  Google Scholar 

  16. Bischoff PM, Niederberger HJ, Török B, Speiser P (1995) Simultaneous indocyanine green and fluorescein angiography. Retina 15(2):91–99

    Article  CAS  Google Scholar 

  17. Krogh A (1929) The progress of physiology. Am J Physiol Content 90(2):243–251. https://doi.org/10.1152/ajplegacy.1929.90.2.243

    Article  Google Scholar 

  18. Soltesz EG, Kim S, Kim S-W, Laurence RG, De Grand AM, Parungo CP, Cohn LH, Bawendi MG, Frangioni JV (2006) Sentinel lymph node mapping of the gastrointestinal tract by using invisible light. Ann Surg Oncol 13(3):386–396. https://doi.org/10.1245/ASO.2006.04.025

    Article  PubMed  Google Scholar 

  19. Nohara K, Goto O, Takeuchi H, Sasaki M, Maehata T, Yahagi N, Kitagawa Y (2019) Gastric lymphatic flows may change before and after endoscopic submucosal dissection: in vivo porcine survival models Gastric Cancer 1–8. https://doi.org/10.1007/s10120-018-00920-w

  20. Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M et al (2020) The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. J Physiol 598(18):3793–801. https://doi.org/10.1113/JP280389

    Article  CAS  PubMed  Google Scholar 

  21. Russell WMS, Burch R (1959) The principles of humane experimental technique. Russell WMS, Burch R, editors. London: Methuen

  22. Osterkamp J, Strandby R, Nerup N, Svendsen M, Svendsen L, Achiam M (2020) Quantitative fluorescence angiography detects dynamic changes in gastric perfusion. Surg Endosc. https://doi.org/10.1007/s00464-020-08183-2

    Article  PubMed  Google Scholar 

  23. Harris CR, Millman KJ, van der Walt SJ, Gommers R, Virtanen P, Cournapeau D et al (2020) Array programming with NumPy [Internet]. Vol. 585, Nature. Nature Research p 357–62. https://doi.org/10.1038/s41586-020-2649-2

  24. Lütken CD, Achiam MP, Osterkamp J, Svendsen MB, Nerup N (2020) Quantification of fluorescence angiography: toward a reliable intraoperative assessment of tissue perfusion—a narrative review. Langenbeck’s Arch Surg

  25. Sano T, Kodera Y (2011) Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer 14(2):101–12. https://doi.org/10.1007/s10120-011-0041-5

    Article  Google Scholar 

  26. Eagon JC, Miedema BW, Kelly KA (1992) Postgastrectomy syndromes [Internet]. Vol. 72, Surgical Clinics of North America. Surg Clin North Am p 445–65. https://doi.org/10.1016/S0039-6109(16)45689-6

  27. Takahashi N, Nimura H, Fujita T, Mitsumori N, Shiraishi N, Kitano S, Satodate H, Yanaga K (2017) Laparoscopic sentinel node navigation surgery for early gastric cancer: a prospective multicenter trial. Langenbeck’s Arch Surg 402(1):27–32. https://doi.org/10.1007/s00423-016-1540-y

    Article  Google Scholar 

  28. Miwa K, Kinami S, Taniguchi K, Fushida S, Fujimura T, Nonomura A (2003) Mapping sentinel nodes in patients with early-stage gastric carcinoma. Br J Surg 90(2):178–182. https://doi.org/10.1002/bjs.4031

    Article  CAS  PubMed  Google Scholar 

  29. Kinami S, Fujimura T, Ojima E, Fushida S, Ojima T, Funaki H, Fujita H, Takamura H, Ninomiya I, Nishimura G, Kayahara M, Ohta T, Yoh Z (2008) PTD classification: proposal for a new classification of gastric cancer location based on physiological lymphatic flow. Int J Clin Oncol 13(4):320–329. https://doi.org/10.1007/s10147-007-0755-x

    Article  PubMed  Google Scholar 

  30. Kitagawa Y, Takeuchi H, Takagi Y, Natsugoe S, Terashima M, Murakami N et al (2013) Sentinel node mapping for gastric cancer: a prospective multicenter trial in Japan. J Clin Oncol 31(29):3704–3710. https://doi.org/10.1200/JCO.2013.50.3789

    Article  PubMed  Google Scholar 

  31. Tani T, Sonoda H, Tani M (2016) Sentinel lymph node navigation surgery for gastric cancer: does it really benefit the patient? [Internet]. Vol. 22, World Journal of Gastroenterology. Baishideng Publishing Group Co., Limited p 2894–9. https://doi.org/10.3748/wjg.v22.i10.2894

  32. Lirosi MC, Biondi A, Ricci R (2017) Surgical anatomy of gastric lymphatic drainage [Internet]. Vol. 2017, Translational Gastroenterology and Hepatology. AME Publishing Company. https://doi.org/10.21037/tgh.2016.12.06

  33. Herrera-Almario G, Patane M, Sarkaria I, Strong VE (2016) Initial report of near-infrared fluorescence imaging as an intraoperative adjunct for lymph node harvesting during robot-assisted laparoscopic gastrectomy. J Surg Oncol 113(7):768–770. https://doi.org/10.1002/jso.24226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kawai Y, Ajima K, Nagai T, Kaidoh M, Ohhashi T (2011) Real-time imaging of the lymphatic channels and sentinel lymph nodes of the stomach using contrast-enhanced ultrasonography with Sonazoid in a porcine model. Jpn Cancer Assoc 102(11). https://doi.org/10.1111/j.1349-7006.2011.02048.x

  35. Heuveling DA, Visser GWM, de Groot M, de Boer JF, Baclayon M, Roos WH, Wuite GJL, Leemans CR, de Bree R, van Dongen GAMS (2012) Nanocolloidal albumin-IRDye 800CW: a near-infrared fluorescent tracer with optimal retention in the sentinel lymph node. Eur J Nucl Med Mol Imaging 39(7):1161–1168. https://doi.org/10.1007/s00259-012-2080-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Acerbi F, Restelli F, Broggi M, Schiariti M, Ferroli P (2016) Feasibility of simultaneous sodium fluorescein and indocyanine green injection in neurosurgical procedures. Clin Neurol Neurosurg 146:123–129. https://doi.org/10.1016/j.clineuro.2016.05.003

    Article  CAS  PubMed  Google Scholar 

  37. Freeman WR, Bartsch DU, Mueller AJ, Banker AS, Weinreb RN (1998) Simultaneous indocyanine green and fluorescein angiography using a confocal scanning laser ophthalmoscope. Arch Ophthalmol 116(4):455–463. https://doi.org/10.1001/archopht.116.4.455

    Article  CAS  PubMed  Google Scholar 

  38. Ladak F, Dang JT, Switzer N, Mocanu V, Tian C, Birch D, Turner SR, Karmali S (2019) Indocyanine green for the prevention of anastomotic leaks following esophagectomy: a meta-analysis. Surg Endosc 33(2):384–394. https://doi.org/10.1007/s00464-018-6503-7

    Article  PubMed  Google Scholar 

  39. Luo RJ, Zhu ZY, He ZF, Xu Y, Wang YZ, Chen P (2021) Efficacy of indocyanine green fluorescence angiography in preventing anastomotic leakage after McKeown minimally invasive esophagectomy. Front Oncol 10:3076. https://doi.org/10.3389/fonc.2020.619822

    Article  Google Scholar 

  40. Blair NP, Evans MA, Lesar4 TS, Zeimer RC (1986) Fluorescein and fluorescein glucuronide pharmacokinefics after intravenous injection. Invest Ophthalmol Vis Sci 27

  41. Juhl K, Christensen A, Persson M, Ploug M, Kjaer A (2016) Peptide-based optical uPAR imaging for surgery: in vivo testing of ICG-Glu-Glu-AE105. PLoS One 11(2). https://doi.org/10.1371/journal.pone.0147428

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Acknowledgements

We thank Mikkel Marquard Jessen, Anders Bech Jørgensen, Olivia Mortensen, August Olsen, Karina Adler Riemenschneider, Andreas Arendtsen Rostved, and Søren Roepstorff (Department of Surgical Gastroenterology, Rigshospitalet, University Hospital of Copenhagen, Denmark) for their assistance with the surgical procedures. We would also like to thank the Department of Pathology (Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark) for their assistance with the tissue analyses.

Funding

The corresponding author received funding from the Department of Surgical Gastroenterology, Rigshospitalet research fund.

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Authors and Affiliations

Authors

Contributions

Study conception and design: JO, RS, NN, MBS, LBS, MA. Acquisition of data: JO, RS, NN, MBS. Analysis and interpretation of data: JO, RS, NN, MBS, LBS, MA. Drafting of the manuscript: JO. Critical revision and final approval of the manuscript: JO, RS, NN, MBS, LBS, MA.

Corresponding author

Correspondence to Jens Osterkamp.

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Ethical approval

The study received approval from the Danish Animal Experiments Inspectorate (2019–15-0201–01664) and followed the Danish and European Union legislation on animal experimentation. It was supervised by research veterinarians at the Department of Experimental Medicine (The Panum Institute, University of Copenhagen, Copenhagen, Denmark).

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The authors declare no competing interests.

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Osterkamp, J., Strandby, R.B., Nerup, N. et al. Time to maximum indocyanine green fluorescence of gastric sentinel lymph nodes and feasibility of combined indocyanine green/sodium fluorescein gastric lymphography. Langenbecks Arch Surg 406, 2717–2724 (2021). https://doi.org/10.1007/s00423-021-02265-y

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