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INDOCYANINE GREEN AND NEAR-INFRARED FLUORESCENCE IMAGING IN GASTRIC CANCER PRECISION SURGICAL APPROACH

Uso da fluorescência a laser com infravermelho e indocianina verde no tratamento cirúrgico do câncer gástrico

Gastric cancer (GC) is the 4th most lethal cancer11. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021;71:209-49. doi.org/10.3322/caac.21660.
https://doi.org/10.3322/caac.21660...
. Radical gastrectomy is the main treatment for GC and D2 lymphadenectomy is recommended for advanced lesions, while limited lymph node dissection is adequate in early lesions, decreasing morbidity22. Kinami S, Nakamura N, Tomita Y, Miyata T, Fujita H, Ueda N, et al. Precision surgical approach with lymph-node dissection in early gastric cancer. World J Gastroenterol. 2019;25:1640-52. doi.org/10.3748/wjg.v25.i14.1640
https://doi.org/10.3748/wjg.v25.i14.1640...
. By tailoring the procedure according to the disease’s extent, the best oncological results may be achieved while minimizing the patient’s risk.

Currently, augmented reality is available and can be used for real-time assessment of the operative field and anatomy. One of the main modalities is the Indocyanine green (ICG) and Near-infrared (NIR) fluorescence imaging33. Schaafsma BE, Mieog JSD, Hutteman M, van der Vorst JR, Kuppen PJK, Löwik CWGM, et al. The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery. J Surg Oncol. 2011;104:323-32. doi.org/10.1002/jso.21943.
https://doi.org/10.1002/jso.21943...
.

NIR light characteristics include low absorption, low scattering, and low autofluorescence, providing deeper tissue penetration than visible light. With fluorescent contrast agents, specific structures as lymphatic vessels, lymph nodes and blood vessels can be clearly visualized33. Schaafsma BE, Mieog JSD, Hutteman M, van der Vorst JR, Kuppen PJK, Löwik CWGM, et al. The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery. J Surg Oncol. 2011;104:323-32. doi.org/10.1002/jso.21943.
https://doi.org/10.1002/jso.21943...
.

ICG is a sterile water-soluble tricarbocyanine dye, approved by the United States, Food and Drug Administration (FDA), with very rare reports of hypersensitivity reactions, besides being a nonionizing and nontoxic modality. It rapidly binds to plasma proteins, staying confined to the vascular compartment and, when excited by NIR light (700-900 nm), emits fluorescence at a wavelength of approximately 820 nm33. Schaafsma BE, Mieog JSD, Hutteman M, van der Vorst JR, Kuppen PJK, Löwik CWGM, et al. The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery. J Surg Oncol. 2011;104:323-32. doi.org/10.1002/jso.21943.
https://doi.org/10.1002/jso.21943...
,44. Ushimaru Y, Omori T, Fujiwara Y, Yanagimoto Y, Sugimura K, Yamamoto K, et al. The Feasibility and Safety of Preoperative Fluorescence Marking with Indocyanine Green (ICG) in Laparoscopic Gastrectomy for Gastric Cancer. J Gastrointest Surg. 2019;23:468-76. doi.org/10.1007/s11605-018-3900-0.
https://doi.org/10.1007/s11605-018-3900-...
.

In GC, ICG and NIR fluorescence imaging may be used for sentinel lymph node biopsy and analysis, lymphadenectomy guidance and quality control, and localization of the tumor44. Ushimaru Y, Omori T, Fujiwara Y, Yanagimoto Y, Sugimura K, Yamamoto K, et al. The Feasibility and Safety of Preoperative Fluorescence Marking with Indocyanine Green (ICG) in Laparoscopic Gastrectomy for Gastric Cancer. J Gastrointest Surg. 2019;23:468-76. doi.org/10.1007/s11605-018-3900-0.
https://doi.org/10.1007/s11605-018-3900-...

5. Chen Q-Y, Xie J-W, Zhong Q, Wang J-B, Lin J-X, Lu J, et al. Safety and efficacy of indocyanine green tracer-guided lymph node dissection during laparoscopic radical gastrectomy in patients with gastric cancer: a randomized clinical trial. JAMA Surg. 2020;155:300-11. doi:10.1001/jamasurg.2019.6033.
https://doi.org/10.1001/jamasurg.2019.60...
-66. Sakamoto E, Dias AR, Ramos MFKP, Zeide Charruf A, Ribeiro-Junior U, Zilberstein B, et al. Laparoscopic Completion Total Gastrectomy for Remnant Gastric Cancer. J Laparoendosc Adv Surg Tech A. 2020;31. doi.org/10.1089/lap.2020.0569.
https://doi.org/10.1089/lap.2020.0569...
. At present, a prospective, single-arm study is ongoing at our institution to evaluate the usefulness of ICG fluorescence imaging in GC (ClinicalTrials ID: NCT03021200). In this E-VIDEO* * E-VIDEO: https://youtu.be/Dvue8UuhIks , we demonstrate ICG and NIR fluorescence applications in GC surgery.

First, a laparoscopic sentinel lymph node biopsy is performed. Intraoperative endoscopic injection of 0.2 mL of ICG is injected into the submucosal layer at four points around the lesion. The Sentinel Lymph node is identified (Figure 1) and removed for detailed analysis. Next, a robotic D2 gastrectomy in an obese patient is shown. ICG was endoscopically injected the day before and it allows for intraoperative identification of the lesion location and margin check (Figure 2), lymphadenectomy guidance and verification of its adequacy. In this particular case, a lymph node from station six was identified and rescued thanks to the NIR fluorescence (Figure 3). After the end of the surgery, the fluorescence system is activated, for final control of residual lymph nodes.

FIGURE 1
Sentinel Lymph node identification.

FIGURE 2
Localization of the tumor and determination of the surgical margins.

FIGURE 3
Station 6 lymph node.

REFERENCES

  • 1
    Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021;71:209-49. doi.org/10.3322/caac.21660.
    » https://doi.org/10.3322/caac.21660
  • 2
    Kinami S, Nakamura N, Tomita Y, Miyata T, Fujita H, Ueda N, et al. Precision surgical approach with lymph-node dissection in early gastric cancer. World J Gastroenterol. 2019;25:1640-52. doi.org/10.3748/wjg.v25.i14.1640
    » https://doi.org/10.3748/wjg.v25.i14.1640
  • 3
    Schaafsma BE, Mieog JSD, Hutteman M, van der Vorst JR, Kuppen PJK, Löwik CWGM, et al. The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery. J Surg Oncol. 2011;104:323-32. doi.org/10.1002/jso.21943.
    » https://doi.org/10.1002/jso.21943
  • 4
    Ushimaru Y, Omori T, Fujiwara Y, Yanagimoto Y, Sugimura K, Yamamoto K, et al. The Feasibility and Safety of Preoperative Fluorescence Marking with Indocyanine Green (ICG) in Laparoscopic Gastrectomy for Gastric Cancer. J Gastrointest Surg. 2019;23:468-76. doi.org/10.1007/s11605-018-3900-0.
    » https://doi.org/10.1007/s11605-018-3900-0
  • 5
    Chen Q-Y, Xie J-W, Zhong Q, Wang J-B, Lin J-X, Lu J, et al. Safety and efficacy of indocyanine green tracer-guided lymph node dissection during laparoscopic radical gastrectomy in patients with gastric cancer: a randomized clinical trial. JAMA Surg. 2020;155:300-11. doi:10.1001/jamasurg.2019.6033.
    » https://doi.org/10.1001/jamasurg.2019.6033
  • 6
    Sakamoto E, Dias AR, Ramos MFKP, Zeide Charruf A, Ribeiro-Junior U, Zilberstein B, et al. Laparoscopic Completion Total Gastrectomy for Remnant Gastric Cancer. J Laparoendosc Adv Surg Tech A. 2020;31. doi.org/10.1089/lap.2020.0569.
    » https://doi.org/10.1089/lap.2020.0569
  • Disclosure of funding: the study is financed by PRONON (National Oncology Care Support Program by Brazilian Ministry of Health) and is registered online (Plataforma Brasil - CAAE: 56687616.5.0000.0065 - Clinical trial - NCT03021200).

Publication Dates

  • Publication in this collection
    10 Dec 2021
  • Date of issue
    Oct-Dec 2021

History

  • Received
    27 Apr 2021
  • Accepted
    07 June 2021
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