Original Article

Split Viewer

J Innov Med Technol 2024; 2(1): 20-24

Published online May 30, 2024

https://doi.org/10.61940/jimt.240001

© Korean Innovative Medical Technology Society

Indocyanine-coated fluorescent clips for localization of gastrointestinal tumors

Kyonglin Park1 , Hongrae Kim2 , Hyoung-Jun Kim3 , Yongdoo Choi3 , Sung-Jae Park4 , Jae-Suk Park4 , Min-Kyu Choi4 , Dae Kyung Sohn1,2

1Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea, 2Biomedical Engineering Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea, 3Diagnostics and Therapeutics Technology Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea, 4KOSCO Intercare Co., Ltd., Siheung, Korea

Correspondence to : Dae Kyung Sohn
Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea
e-mail gsgsbal@ncc.re.kr
https://orcid.org/0000-0003-3296-6646

Received: April 18, 2024; Accepted: April 19, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: The innovative use of the fluorescent dye indocyanine green (ICG) represents a significant advancement in surgical oncology. This study aimed to assess the feasibility of ICG-coated clips for enhancing tumor localization during minimally invasive gastrointestinal surgery.
Materials and Methods: This study was conducted using female Yucatan miniature pigs, which approximate the human anatomy. Two pigs, each weighing 25–30 kg, underwent simulated gastrointestinal surgery. The ICG-coated clips used were VITTZ clips, which were not yet approved by the Korea Food and Drug Administration but utilized for research purposes. The visibility of the clips was evaluated using Stryker 1588 and 1688 Advanced Imaging Modalities platforms with SPY fluorescence technology. The procedure involved the endoscopic placement of clips in the stomach and colon, followed by laparoscopic visualization using ICG imaging systems.
Results: The ICG-coated clips demonstrated superior visibility in both the stomach and colon. In the stomach, the Endoscopic Near-Infrared Visualization (ENV) mode revealed four bright spots on the gastric wall, with two distinctly visible in the overlay mode. Three bright fluorescent lights were discernible in the sigmoid colon using both imaging modes. The fluorescence intensity was slightly clearer in the ENV mode than in the overlay mode.
Conclusion: ICG-coated clips can improve tumor localization, which is important during minimally invasive gastrointestinal surgery. This innovative approach may provide safer and more accurate alternatives.

Keywords Indocyanine green; Endoscopic clips; Tumor localization; Fluorescent clip

Indocyanine green (ICG), a water-soluble fluorescent dye, has been widely applied in medical contexts since its development in 1955 and subsequent Food and Drug Administration (FDA) approval in 19591-4. Known for its fluorescent properties within the near-infrared (NIR) spectrum (750–950 nm)3, ICG is primarily bound to plasma proteins and is metabolized and excreted by the liver, with its half-life varying based on liver functionality4-6. The introduction of ICG in medical procedures, especially in fluorescence-guided surgery, represents a significant advancement in medical imaging and intraoperative navigation7-9.

Revolutionizing various surgical fields, ICG fluorescence-guided surgery enhances the visualization of anatomical structures, thus facilitating precise surgical navigation3,9. The utility of ICG in abdominal surgery is extensive, aiding in tasks such as evaluating perfusion, delineating extrahepatic bile duct anatomy, navigating lymph nodes, and assisting with liver surgery7-10. This technique is particularly valuable in colorectal surgery for intraoperative guidance, where it is applied in a range of procedures from assessing perfusion to identifying hepatic and peritoneal metastases2-5. Although research is still ongoing, early results are promising, especially for reducing anastomotic leaks in colorectal surgery1,2.

In gastrointestinal (GI) cancer surgery, accurate tumor localization is crucial, particularly for early stage cancers for which minimally invasive techniques are the norm. Traditional localization methods, such as endoscopic tattooing and metallic clipping, present challenges, including control issues in dye spreading and clip visibility11-13. ICG fluorescence imaging, known for its minimal toxicity and cost-effectiveness, has significant advantages. Notably, it enhances the visualization of tumor location, particularly those of a small size that are challenging to detect with standard radiological tools13,14.

This study aimed to evaluate the feasibility and effectiveness of ICG-coated clips for GI tumor localization in minimally invasive procedures using animal models.

In this study, we used female Yucatan miniature pigs that were about 16 months old (obtained from Optipharm Co., Ltd.), with weights ranging from 25 to 30 kg (29.0 kg for the first pig, 29.8 kg for the second). Prior to surgery, the pigs were fasted for 48 hours and allowed only water. After this fasting period, they were moved to the laboratory where they received general anesthesia along with respiratory support through a ventilator. All animal experiments were carried out in approved facilities following standard animal experiment guidelines. The study protocol was approved by the Institutional Animal Care and Use Committee (BIOSTEP IACUC 24-HB-0179; March 5, 2024).

The ICG-coated clips used in this study were VITTZ clips from KOSCO Intercare Co., Ltd. The clips were not approved by the Korea Food and Drug Administration and were used exclusively for experimental research purposes. Surgical visualization of the ICG-coated clip was facilitated using Stryker 1588 and 1688 Advanced Imaging Modalities (AIM) Platforms with SPY fluorescence technology developed by Stryker Corporation.

For the stomach procedures, a gastroscope was used to mark an imagined tumor location in the stomach, around which four fluorescent clips were placed in a circle. After placing the clips, we removed any remaining air from the stomach using a gastroscope and withdrew the endoscope. We inserted laparoscopic ports (an 11 mm port for the camera and a 5 mm port for the instruments) and filled the abdominal cavity with carbon dioxide. We attempted to detect the clip locations using the ICG imaging system and checked these locations endoscopically for accurate detection.

During the colon procedures, we inserted a colonoscope through the anus to a site approximately 25–30 cm above the anal opening, which was assumed to be the tumor site, and applied three ICG-coated clips in different directions just below the tumor area. Subsequently, we removed the endoscope and confirmed the clip locations using ICG laparoscopy, following same steps as before. This process was repeated in the second pig.

The process of assessing clip location using the ICG laparoscopic system was conducted in two steps. Initially, in the first pig, the clip location was identified using the Endoscopic Near-Infrared Visualization (ENV) mode, which displays green NIR fluorescence on a grayscale image. In this mode, four bright illuminated spots were observed through the stomach wall at mid-body. Subsequently, in the overlay mode, which projects green NIR fluorescence onto a standard-color high-definition video image, bright illumination was detected in two of the four clips. However, the fluorescence intensity in overlay mode was notably weaker than that in ENV mode, as shown in Fig. 1. In the second pig, the fluorescent light from all four clips was easily discernible in both ENV and overlay modes.

Figure 1.Localization of a gastric lesion using indocyanine green (ICG)-coated clips in a porcine model. (A) Endoscopic placement of fluorescent clips around a simulated tumor site. (B) Endoscopic Near-Infrared Visualization (ENV) mode showing clip fluorescence through the gastric wall. (C) Overlay mode presenting clip fluorescence on color imaging.

While locating the clip in the large intestine, three exceptionally bright fluorescent lights were easily discernible in the sigmoid colon using both the ENV and overlay modes. As in the case of the stomach, the fluorescence brightness in the ENV mode was confirmed more clearly than in the overlay mode in the case of the colon (Fig. 2). These observations were also confirmed in the second pig.

Figure 2.Localization of a colonic lesion using indocyanine green (ICG)-coated clips in a porcine model. (A) Endoscopic application of three clips beneath a target tumor area. (B) Endoscopic Near-Infrared Visualization (ENV) mode highlighting intense fluorescence of clips in the sigmoid colon. (C) Overlay mode showing the clips’ fluorescence integrated with color imaging.

In this study, we confirmed that the use of ICG-coated clips for tumor localization during GI surgery is feasible and promising. These new approaches are noticeably different from existing methods traditionally used in the field. In this study, the feasibility of ICG-coated clips was investigated using the ICG laparoscopic system currently used in clinical practice, with a focus on its application in tumor localization during laparoscopic surgery. Our results were very clear, with ICG-coated clips providing improved visibility, which is critical for minimally invasive surgery in which traditional palpation methods are not possible. The implications of these findings are significant and are expected to revolutionize the way tumors are located during surgery, potentially improving surgical and minimally invasive surgical outcomes that consider patient function.

An important aspect of our study is that we depart from traditional methods such as endoscopic tattooing or endoscopic metal clipping, which are commonly used for localization14,15. Our method leverages the unique fluorescence properties of ICG to provide a noninvasive and highly accurate alternative for locating tumors, which is a safer and more accurate approach. This change is consistent with the growing trend in minimally invasive surgical procedures. Our study stands out methodologically because it integrates commercially available imaging platforms such as the Stryker 1588 and 1688 AIM platforms with SPY fluorescence technology. ICG-coated clips offer distinct advantages over various materials or fluorescent markers used in previous studies13,14. In addition, our method demonstrated compatibility with a wider range of surgical procedures including gastric or colon surgery. An analysis of our results compared to the existing literature indicates a significant improvement in the precise visualization of tumor localization. A level of precision in tumor site identification that was difficult to achieve in many previous studies can now be achieved owing to the improved visibility and ease of identification provided by ICG-coated clips.

However, our study has several limitations, such as the relatively small number of subjects, which may have affected the generalizability of the results. Another major limitation is that our results have not been validated using diverse imaging systems. Our results may differ for different systems, and these techniques may not be universally available. Additionally, the regulatory approval status of these ICG-coated clips is limited, as they have not yet been approved by regulatory agencies, such as the FDA. Moreover, as with any new technology, there is a potential for bias in its interpretation and application. Despite these limitations, the strengths of this study were noteworthy. Our innovative approach represents a groundbreaking leap forward in surgical technology, especially in minimally invasive surgeries. The excellent visibility of the clip greatly aids in accurate tumor localization. Moreover, our approach is consistent with the trend towards minimally invasive surgical techniques and is therefore highly relevant and timely in the context of modern surgical practice. The novelty of our study is the groundbreaking application of ICG-coated clips in GI surgery, which increases precision, and the introduction of a tumor localization method that is well suited to modern surgical practice.

Based on these findings, future studies on the application of ICG-coated clips in GI surgery should focus on several key areas. First, it would be beneficial to conduct comparative studies of ICG-coated clips and other fluorophores. This will help establish the specific advantages or potential limitations of ICG compared with alternative compounds, particularly its effects on tumor localization, biocompatibility, and long-term effects on the body. Further investigation into the use of various imaging systems with ICG-coated clips is important. These studies reveal how different imaging modalities affect the effectiveness of ICG-coated clips and may provide valuable insights for surgeons to select the most appropriate combination of dyes and imaging techniques for specific surgical applications. Moreover, translating these findings from animal models to human clinical trials is an important area of follow-up research. Future studies should focus on the challenges and nuances of applying these methods to human surgery, considering anatomical and physiological differences and the potential for diverse responses to ICG. It is also important to expand the scope of clinical trials to include broader and more diverse populations to ensure the generalizability of the results. A comprehensive cost-benefit analysis comparing ICG-coated clips with traditional tumor localization methods, along with clinical studies, could provide essential data for healthcare systems to evaluate the feasibility and economic viability of adopting this technology. Finally, continuing to explore the application of ICG in other types of surgery and various clinical conditions will likely greatly advance our understanding of the full potential of ICG in surgical oncology.

In conclusion, we anticipate that the use of ICG-coated clips in GI surgery could be an important advancement in surgical oncology. Although further research and clinical trials, particularly in human subjects, are essential for wider understanding and application, our findings demonstrate the potential for use in a new era of minimally invasive surgery.

No potential conflict of interest relevant to this article was reported.

This work was supported by a grant from the National Research Foundation of Korea (NRF-2022R1A2C2009757) funded by the Ministry of Education, and the Korea Medical Device Development Fund (KMDF), grant number RS-2020-KD000107.

  1. Diana M, Halvax P, Dallemagne B, et al. Real-time navigation by fluorescence-based enhanced reality for precise estimation of future anastomotic site in digestive surgery. Surg Endosc 2014;28:3108-1318. https://doi.org/10.1007/s00464-014-3592-9.
    Pubmed CrossRef
  2. Schols RM, Connell NJ, Stassen LP. Near-infrared fluorescence imaging for real-time intraoperative anatomical guidance in minimally invasive surgery: a systematic review of the literature. World J Surg 2015;39:1069-1079. https://doi.org/10.1007/s00268-014-2911-6.
    Pubmed CrossRef
  3. Garoufalia Z, Wexner SD. Indocyanine green fluorescence guided surgery in colorectal surgery. J Clin Med 2023;12:494. https://doi.org/10.3390/jcm12020494.
    Pubmed KoreaMed CrossRef
  4. Filippello A, Porcheron J, Klein JP, Cottier M, Barabino G. Affinity of indocyanine green in the detection of colorectal peritoneal carcinomatosis. Surg Innov 2017;24:103-108. https://doi.org/10.1177/1553350616681897.
    Pubmed CrossRef
  5. Park SY, Park JS, Kim HJ, Woo IT, Park IK, Choi GS. Indocyanine green fluorescence imaging-guided laparoscopic surgery could achieve radical d3 dissection in patients with advanced right-sided colon cancer. Dis Colon Rectum 2020;63:441-449. https://doi.org/10.1097/DCR.0000000000001597.
    Pubmed CrossRef
  6. Belloni E, Muttillo EM, Di Saverio S, Gasparrini M, Brescia A, Nigri G. The role of indocyanine green fluorescence in rectal cancer robotic surgery: a narrative review. Cancers (Basel) 2022;14:2411. https://doi.org/10.3390/cancers14102411.
    Pubmed KoreaMed CrossRef
  7. Watanabe J, Ohya H, Sakai J, et al. Long-term outcomes of indocyanine green fluorescence imaging-guided laparoscopic lateral pelvic lymph node dissection for clinical stage II/III middle-lower rectal cancer: a propensity score-matched cohort study. Tech Coloproctol 2023;27:759-767. https://doi.org/10.1007/s10151-023-02761-x.
    Pubmed CrossRef
  8. Peltrini R, Podda M, Castiglioni S, et al. Intraoperative use of indocyanine green fluorescence imaging in rectal cancer surgery: the state of the art. World J Gastroenterol 2021;27:6374-6386. https://doi.org/10.3748/wjg.v27.i38.6374.
    Pubmed KoreaMed CrossRef
  9. Nagaya T, Nakamura YA, Choyke PL, Kobayashi H. Fluorescence-guided surgery. Front Oncol 2017;7:314. https://doi.org/10.3389/fonc.2017.00314.
    Pubmed KoreaMed CrossRef
  10. Sikkenk DJ, Sterkenburg AJ, Burghgraef TA, et al. Robot-assisted fluorescent sentinel lymph node identification in early-stage colon cancer. Surg Endosc 2023;37:8394-8403. https://doi.org/10.1007/s00464-023-10394-2.
    Pubmed KoreaMed CrossRef
  11. Kawai K, Iida Y, Ishihara S, et al. Intraoperative colonoscopy in patients with colorectal cancer: review of recent developments. Dig Endosc 2016;28:633-640. https://doi.org/10.1111/den.12663.
    Pubmed CrossRef
  12. Choi Y, Kim KG, Kim JK, Nam KW, Kim HH, Sohn DK. A novel endoscopic fluorescent clip for the localization of gastrointestinal tumors. Surg Endosc 2011;25:2372-2377. https://doi.org/10.1007/s00464-010-1557-1.
    Pubmed CrossRef
  13. Hyun JH, Kim SK, Kim KG, et al. A novel endoscopic fluorescent band ligation method for tumor localization. Surg Endosc 2016;30:4659-4663. https://doi.org/10.1007/s00464-016-4785-1.
    Pubmed CrossRef
  14. Lee SJ, Sohn DK, Han KS, et al. Preoperative tattooing using indocyanine green in laparoscopic colorectal surgery. Ann Coloproctol 2018;34:206-211. https://doi.org/10.3393/ac.2017.09.25.
    Pubmed KoreaMed CrossRef
  15. Hyun JH, Han KS, Kim BC, et al. Preoperative endoscopic clipping for rectal tumor localization in laparoscopic anterior resection. Minim Invasive Ther Allied Technol 2019;28:326-331. https://doi.org/10.1080/13645706.2018.1547765.
    Pubmed CrossRef

Article

Original Article

J Innov Med Technol 2024; 2(1): 20-24

Published online May 30, 2024 https://doi.org/10.61940/jimt.240001

Copyright © Korean Innovative Medical Technology Society.

Indocyanine-coated fluorescent clips for localization of gastrointestinal tumors

Kyonglin Park1 , Hongrae Kim2 , Hyoung-Jun Kim3 , Yongdoo Choi3 , Sung-Jae Park4 , Jae-Suk Park4 , Min-Kyu Choi4 , Dae Kyung Sohn1,2

1Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea, 2Biomedical Engineering Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea, 3Diagnostics and Therapeutics Technology Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea, 4KOSCO Intercare Co., Ltd., Siheung, Korea

Correspondence to:Dae Kyung Sohn
Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea
e-mail gsgsbal@ncc.re.kr
https://orcid.org/0000-0003-3296-6646

Received: April 18, 2024; Accepted: April 19, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: The innovative use of the fluorescent dye indocyanine green (ICG) represents a significant advancement in surgical oncology. This study aimed to assess the feasibility of ICG-coated clips for enhancing tumor localization during minimally invasive gastrointestinal surgery.
Materials and Methods: This study was conducted using female Yucatan miniature pigs, which approximate the human anatomy. Two pigs, each weighing 25–30 kg, underwent simulated gastrointestinal surgery. The ICG-coated clips used were VITTZ clips, which were not yet approved by the Korea Food and Drug Administration but utilized for research purposes. The visibility of the clips was evaluated using Stryker 1588 and 1688 Advanced Imaging Modalities platforms with SPY fluorescence technology. The procedure involved the endoscopic placement of clips in the stomach and colon, followed by laparoscopic visualization using ICG imaging systems.
Results: The ICG-coated clips demonstrated superior visibility in both the stomach and colon. In the stomach, the Endoscopic Near-Infrared Visualization (ENV) mode revealed four bright spots on the gastric wall, with two distinctly visible in the overlay mode. Three bright fluorescent lights were discernible in the sigmoid colon using both imaging modes. The fluorescence intensity was slightly clearer in the ENV mode than in the overlay mode.
Conclusion: ICG-coated clips can improve tumor localization, which is important during minimally invasive gastrointestinal surgery. This innovative approach may provide safer and more accurate alternatives.

Keywords: Indocyanine green, Endoscopic clips, Tumor localization, Fluorescent clip

Introduction

Indocyanine green (ICG), a water-soluble fluorescent dye, has been widely applied in medical contexts since its development in 1955 and subsequent Food and Drug Administration (FDA) approval in 19591-4. Known for its fluorescent properties within the near-infrared (NIR) spectrum (750–950 nm)3, ICG is primarily bound to plasma proteins and is metabolized and excreted by the liver, with its half-life varying based on liver functionality4-6. The introduction of ICG in medical procedures, especially in fluorescence-guided surgery, represents a significant advancement in medical imaging and intraoperative navigation7-9.

Revolutionizing various surgical fields, ICG fluorescence-guided surgery enhances the visualization of anatomical structures, thus facilitating precise surgical navigation3,9. The utility of ICG in abdominal surgery is extensive, aiding in tasks such as evaluating perfusion, delineating extrahepatic bile duct anatomy, navigating lymph nodes, and assisting with liver surgery7-10. This technique is particularly valuable in colorectal surgery for intraoperative guidance, where it is applied in a range of procedures from assessing perfusion to identifying hepatic and peritoneal metastases2-5. Although research is still ongoing, early results are promising, especially for reducing anastomotic leaks in colorectal surgery1,2.

In gastrointestinal (GI) cancer surgery, accurate tumor localization is crucial, particularly for early stage cancers for which minimally invasive techniques are the norm. Traditional localization methods, such as endoscopic tattooing and metallic clipping, present challenges, including control issues in dye spreading and clip visibility11-13. ICG fluorescence imaging, known for its minimal toxicity and cost-effectiveness, has significant advantages. Notably, it enhances the visualization of tumor location, particularly those of a small size that are challenging to detect with standard radiological tools13,14.

This study aimed to evaluate the feasibility and effectiveness of ICG-coated clips for GI tumor localization in minimally invasive procedures using animal models.

Materials and Methods

In this study, we used female Yucatan miniature pigs that were about 16 months old (obtained from Optipharm Co., Ltd.), with weights ranging from 25 to 30 kg (29.0 kg for the first pig, 29.8 kg for the second). Prior to surgery, the pigs were fasted for 48 hours and allowed only water. After this fasting period, they were moved to the laboratory where they received general anesthesia along with respiratory support through a ventilator. All animal experiments were carried out in approved facilities following standard animal experiment guidelines. The study protocol was approved by the Institutional Animal Care and Use Committee (BIOSTEP IACUC 24-HB-0179; March 5, 2024).

The ICG-coated clips used in this study were VITTZ clips from KOSCO Intercare Co., Ltd. The clips were not approved by the Korea Food and Drug Administration and were used exclusively for experimental research purposes. Surgical visualization of the ICG-coated clip was facilitated using Stryker 1588 and 1688 Advanced Imaging Modalities (AIM) Platforms with SPY fluorescence technology developed by Stryker Corporation.

For the stomach procedures, a gastroscope was used to mark an imagined tumor location in the stomach, around which four fluorescent clips were placed in a circle. After placing the clips, we removed any remaining air from the stomach using a gastroscope and withdrew the endoscope. We inserted laparoscopic ports (an 11 mm port for the camera and a 5 mm port for the instruments) and filled the abdominal cavity with carbon dioxide. We attempted to detect the clip locations using the ICG imaging system and checked these locations endoscopically for accurate detection.

During the colon procedures, we inserted a colonoscope through the anus to a site approximately 25–30 cm above the anal opening, which was assumed to be the tumor site, and applied three ICG-coated clips in different directions just below the tumor area. Subsequently, we removed the endoscope and confirmed the clip locations using ICG laparoscopy, following same steps as before. This process was repeated in the second pig.

Results

The process of assessing clip location using the ICG laparoscopic system was conducted in two steps. Initially, in the first pig, the clip location was identified using the Endoscopic Near-Infrared Visualization (ENV) mode, which displays green NIR fluorescence on a grayscale image. In this mode, four bright illuminated spots were observed through the stomach wall at mid-body. Subsequently, in the overlay mode, which projects green NIR fluorescence onto a standard-color high-definition video image, bright illumination was detected in two of the four clips. However, the fluorescence intensity in overlay mode was notably weaker than that in ENV mode, as shown in Fig. 1. In the second pig, the fluorescent light from all four clips was easily discernible in both ENV and overlay modes.

Figure 1. Localization of a gastric lesion using indocyanine green (ICG)-coated clips in a porcine model. (A) Endoscopic placement of fluorescent clips around a simulated tumor site. (B) Endoscopic Near-Infrared Visualization (ENV) mode showing clip fluorescence through the gastric wall. (C) Overlay mode presenting clip fluorescence on color imaging.

While locating the clip in the large intestine, three exceptionally bright fluorescent lights were easily discernible in the sigmoid colon using both the ENV and overlay modes. As in the case of the stomach, the fluorescence brightness in the ENV mode was confirmed more clearly than in the overlay mode in the case of the colon (Fig. 2). These observations were also confirmed in the second pig.

Figure 2. Localization of a colonic lesion using indocyanine green (ICG)-coated clips in a porcine model. (A) Endoscopic application of three clips beneath a target tumor area. (B) Endoscopic Near-Infrared Visualization (ENV) mode highlighting intense fluorescence of clips in the sigmoid colon. (C) Overlay mode showing the clips’ fluorescence integrated with color imaging.

Discussion

In this study, we confirmed that the use of ICG-coated clips for tumor localization during GI surgery is feasible and promising. These new approaches are noticeably different from existing methods traditionally used in the field. In this study, the feasibility of ICG-coated clips was investigated using the ICG laparoscopic system currently used in clinical practice, with a focus on its application in tumor localization during laparoscopic surgery. Our results were very clear, with ICG-coated clips providing improved visibility, which is critical for minimally invasive surgery in which traditional palpation methods are not possible. The implications of these findings are significant and are expected to revolutionize the way tumors are located during surgery, potentially improving surgical and minimally invasive surgical outcomes that consider patient function.

An important aspect of our study is that we depart from traditional methods such as endoscopic tattooing or endoscopic metal clipping, which are commonly used for localization14,15. Our method leverages the unique fluorescence properties of ICG to provide a noninvasive and highly accurate alternative for locating tumors, which is a safer and more accurate approach. This change is consistent with the growing trend in minimally invasive surgical procedures. Our study stands out methodologically because it integrates commercially available imaging platforms such as the Stryker 1588 and 1688 AIM platforms with SPY fluorescence technology. ICG-coated clips offer distinct advantages over various materials or fluorescent markers used in previous studies13,14. In addition, our method demonstrated compatibility with a wider range of surgical procedures including gastric or colon surgery. An analysis of our results compared to the existing literature indicates a significant improvement in the precise visualization of tumor localization. A level of precision in tumor site identification that was difficult to achieve in many previous studies can now be achieved owing to the improved visibility and ease of identification provided by ICG-coated clips.

However, our study has several limitations, such as the relatively small number of subjects, which may have affected the generalizability of the results. Another major limitation is that our results have not been validated using diverse imaging systems. Our results may differ for different systems, and these techniques may not be universally available. Additionally, the regulatory approval status of these ICG-coated clips is limited, as they have not yet been approved by regulatory agencies, such as the FDA. Moreover, as with any new technology, there is a potential for bias in its interpretation and application. Despite these limitations, the strengths of this study were noteworthy. Our innovative approach represents a groundbreaking leap forward in surgical technology, especially in minimally invasive surgeries. The excellent visibility of the clip greatly aids in accurate tumor localization. Moreover, our approach is consistent with the trend towards minimally invasive surgical techniques and is therefore highly relevant and timely in the context of modern surgical practice. The novelty of our study is the groundbreaking application of ICG-coated clips in GI surgery, which increases precision, and the introduction of a tumor localization method that is well suited to modern surgical practice.

Based on these findings, future studies on the application of ICG-coated clips in GI surgery should focus on several key areas. First, it would be beneficial to conduct comparative studies of ICG-coated clips and other fluorophores. This will help establish the specific advantages or potential limitations of ICG compared with alternative compounds, particularly its effects on tumor localization, biocompatibility, and long-term effects on the body. Further investigation into the use of various imaging systems with ICG-coated clips is important. These studies reveal how different imaging modalities affect the effectiveness of ICG-coated clips and may provide valuable insights for surgeons to select the most appropriate combination of dyes and imaging techniques for specific surgical applications. Moreover, translating these findings from animal models to human clinical trials is an important area of follow-up research. Future studies should focus on the challenges and nuances of applying these methods to human surgery, considering anatomical and physiological differences and the potential for diverse responses to ICG. It is also important to expand the scope of clinical trials to include broader and more diverse populations to ensure the generalizability of the results. A comprehensive cost-benefit analysis comparing ICG-coated clips with traditional tumor localization methods, along with clinical studies, could provide essential data for healthcare systems to evaluate the feasibility and economic viability of adopting this technology. Finally, continuing to explore the application of ICG in other types of surgery and various clinical conditions will likely greatly advance our understanding of the full potential of ICG in surgical oncology.

Conclusion

In conclusion, we anticipate that the use of ICG-coated clips in GI surgery could be an important advancement in surgical oncology. Although further research and clinical trials, particularly in human subjects, are essential for wider understanding and application, our findings demonstrate the potential for use in a new era of minimally invasive surgery.

Acknowledgments

None.

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Funding

This work was supported by a grant from the National Research Foundation of Korea (NRF-2022R1A2C2009757) funded by the Ministry of Education, and the Korea Medical Device Development Fund (KMDF), grant number RS-2020-KD000107.

Fig 1.

Figure 1.Localization of a gastric lesion using indocyanine green (ICG)-coated clips in a porcine model. (A) Endoscopic placement of fluorescent clips around a simulated tumor site. (B) Endoscopic Near-Infrared Visualization (ENV) mode showing clip fluorescence through the gastric wall. (C) Overlay mode presenting clip fluorescence on color imaging.
Journal of Innovative Medical Technology 2024; 2: 20-24https://doi.org/10.61940/jimt.240001

Fig 2.

Figure 2.Localization of a colonic lesion using indocyanine green (ICG)-coated clips in a porcine model. (A) Endoscopic application of three clips beneath a target tumor area. (B) Endoscopic Near-Infrared Visualization (ENV) mode highlighting intense fluorescence of clips in the sigmoid colon. (C) Overlay mode showing the clips’ fluorescence integrated with color imaging.
Journal of Innovative Medical Technology 2024; 2: 20-24https://doi.org/10.61940/jimt.240001

References

  1. Diana M, Halvax P, Dallemagne B, et al. Real-time navigation by fluorescence-based enhanced reality for precise estimation of future anastomotic site in digestive surgery. Surg Endosc 2014;28:3108-1318. https://doi.org/10.1007/s00464-014-3592-9.
    Pubmed CrossRef
  2. Schols RM, Connell NJ, Stassen LP. Near-infrared fluorescence imaging for real-time intraoperative anatomical guidance in minimally invasive surgery: a systematic review of the literature. World J Surg 2015;39:1069-1079. https://doi.org/10.1007/s00268-014-2911-6.
    Pubmed CrossRef
  3. Garoufalia Z, Wexner SD. Indocyanine green fluorescence guided surgery in colorectal surgery. J Clin Med 2023;12:494. https://doi.org/10.3390/jcm12020494.
    Pubmed KoreaMed CrossRef
  4. Filippello A, Porcheron J, Klein JP, Cottier M, Barabino G. Affinity of indocyanine green in the detection of colorectal peritoneal carcinomatosis. Surg Innov 2017;24:103-108. https://doi.org/10.1177/1553350616681897.
    Pubmed CrossRef
  5. Park SY, Park JS, Kim HJ, Woo IT, Park IK, Choi GS. Indocyanine green fluorescence imaging-guided laparoscopic surgery could achieve radical d3 dissection in patients with advanced right-sided colon cancer. Dis Colon Rectum 2020;63:441-449. https://doi.org/10.1097/DCR.0000000000001597.
    Pubmed CrossRef
  6. Belloni E, Muttillo EM, Di Saverio S, Gasparrini M, Brescia A, Nigri G. The role of indocyanine green fluorescence in rectal cancer robotic surgery: a narrative review. Cancers (Basel) 2022;14:2411. https://doi.org/10.3390/cancers14102411.
    Pubmed KoreaMed CrossRef
  7. Watanabe J, Ohya H, Sakai J, et al. Long-term outcomes of indocyanine green fluorescence imaging-guided laparoscopic lateral pelvic lymph node dissection for clinical stage II/III middle-lower rectal cancer: a propensity score-matched cohort study. Tech Coloproctol 2023;27:759-767. https://doi.org/10.1007/s10151-023-02761-x.
    Pubmed CrossRef
  8. Peltrini R, Podda M, Castiglioni S, et al. Intraoperative use of indocyanine green fluorescence imaging in rectal cancer surgery: the state of the art. World J Gastroenterol 2021;27:6374-6386. https://doi.org/10.3748/wjg.v27.i38.6374.
    Pubmed KoreaMed CrossRef
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Journal of Innovative Medical Technology
Nov 30, 2024 Vol.2 No.2, pp. 29~79

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