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Determination of the surgical margin in laparoscopic liver resections using infrared indocyanine green fluorescence

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Abstract

Purpose

Laparoscopic liver resection is increasingly used to treat patients with hepatic tumor. However, during laparoscopic resection, information obtained by palpation using laparoscopic forceps or from intraoperative ultrasonography is extremely limited, which may pose a risk for positive surgical margins. This study aimed to investigate the feasibility and clinical application of near-infrared (NIR) fluorescence imaging to guide laparoscopic liver resection of a liver tumor and secure the surgical margins.

Methods

A preliminary study in 25 patients was conducted. NIR imaging was used intraoperatively during laparoscopic liver resection. The liver tumors were preoperatively labeled by intravenously injecting the patients with indocyanine green dye (0.5 mg/kg), an NIR fluorescence agent. During the surgical procedure, the PINPOINT Endoscopic Fluorescence Imaging System was used to assess the surgical margin by using real-time endoscopic high-definition visible and NIR fluorescence imaging.

Results

All tumors were identified and resected laparoscopically by using the PINPOINT system, and all resections successfully secured the surgical margin. The pathological findings of all tumors indicated negative margins, defined as R0.

Conclusions

This technique showed the potential to improve the intraoperative identification and demarcation of tumors. Its use could potentially reduce the number of positive resection margins.

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References

  1. Reich H, McGlynn F, DeCaprio J, Budin R (1991) Laparoscopic excision of benign liver lesions. Obstet Gynecol 78:956–958

    PubMed  CAS  Google Scholar 

  2. Hibi T, Cherqui D, Geller DA et al (2016) Expanding indications and regional diversity in laparoscopic liver resection unveiled by the International Survey on Technical Aspects of Laparoscopic Liver Resection (INSTALL) study. Surg Endosc 30:2975–2983

    Article  PubMed  Google Scholar 

  3. Tanaka T, Choi HS, Fujii H et al (2006) Image-guided oncologic surgery using invisible light: completed pre-clinical development for sentinel lymph node mapping. Ann Surg Oncol 13:1671–1681

    Article  PubMed  PubMed Central  Google Scholar 

  4. Weissleder R, Tung CH, Mahmood U, Bogdanov A (1999) In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 17:375–378

    Article  PubMed  CAS  Google Scholar 

  5. Choi HS, Gibbs SL, Lee JH, Kim SH, Ashitate Y, Liu F, Hyun H, Park GL, Xie Y, Bae S, Henary M, Frangioni JV (2013) Targeted zwitterionic near-infrared fluorophores for improved optical imaging. Nat Biotechnol 31:148–153

    Article  PubMed  CAS  Google Scholar 

  6. Olson ES, Jiang T, Aguilera TA, Nguyen QT, Ellies LG, Scadeng M, Tsien RY (2010) Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases. Proc Natl Acad Sci U S A 107:4311–4316

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ohnishi S, Lomnes SJ, Laurence RG, Gogbashian A, Mariani G, Frangioni JV (2005) Organic alternatives to quantum dots for intraoperative near-infrared fluorescent sentinel lymph node mapping. Mol Imaging 4:172–181

    Article  PubMed  Google Scholar 

  8. Emerson DK, Limmer KK, Hall DJ, Han SH, Eckelman WC, Kane CJ, Wallace AM, Vera DR (2012) A receptor-targeted fluorescent radiopharmaceutical for multireporter sentinel lymph node imaging. Radiology 265:186–193

    Article  PubMed  PubMed Central  Google Scholar 

  9. Brouwer OR, Klop WM, Buckle T et al (2012) Feasibility of sentinel node biopsy in head and neck melanoma using a hybrid radioactive and fluorescent tracer. Ann Surg Oncol 19:1988–1994

    Article  PubMed  Google Scholar 

  10. Hyde D, de Kleine R, MacLaurin SA et al (2009) Hybrid FMT-CT imaging of amyloid-beta plaques in a murine Alzheimer’s disease model. Neuroimage 44:1304–1311

    Article  PubMed  Google Scholar 

  11. Pham W, Zhao BQ, Lo EH, Medarova Z, Rosen B, Moore A (2005) Crossing the blood-brain barrier: a potential application of myristoylated polyarginine for in vivo neuroimaging. Neuroimage 28:287–292

    Article  PubMed  Google Scholar 

  12. Deguchi JO, Aikawa M, Tung CH et al (2006) Inflammation in atherosclerosis: visualizing matrix metalloproteinase action in macrophages in vivo. Circulation 114:55–62

    Article  PubMed  Google Scholar 

  13. Sosnovik DE, Nahrendorf M, Deliolanis N, Novikov M, Aikawa E, Josephson L, Rosenzweig A, Weissleder R, Ntziachristos V (2007) Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo. Circulation 115:1384–1391

    Article  PubMed  Google Scholar 

  14. Figueiredo JL, Siegel C, Nahrendorf M, Weissleder R (2010) Intraoperative near-infrared fluorescent cholangiography (NIRFC) in mouse models of bile duct injury. World J Surg 34:336–343

    Article  PubMed  PubMed Central  Google Scholar 

  15. Aoki T, Yasuda D, Shimizu Y, Odaira M, Niiya T, Kusano T, Mitamura K, Hayashi K, Murai N, Koizumi T, Kato H, Enami Y, Miwa M, Kusano M (2008) Image-guided liver mapping using fluorescence navigation system with indocyanine green for anatomical hepatic resection. World J Surg 32:1763–1767

    Article  PubMed  Google Scholar 

  16. Ishizawa T, Fukushima N, Shibahara J, Masuda K, Tamura S, Aoki T, Hasegawa K, Beck Y, Fukayama M, Kokudo N (2009) Real-time identification of liver cancers by using indocyanine green fluorescent imaging. Cancer 115:2491–2504

    Article  PubMed  Google Scholar 

  17. Uchiyama K, Ueno M, Ozawa S, Kiriyama S, Shigekawa Y, Yamaue H (2010) Combined use of contrast-enhanced intraoperative ultrasonography and a fluorescence navigation system for identifying hepatic metastases. World J Surg 34:2953–2959

    Article  PubMed  Google Scholar 

  18. Peloso A, Franchi E, Canepa MC, Barbieri L, Briani L, Ferrario J, Bianco C, Quaretti P, Brugnatelli S, Dionigi P, Maestri M (2013) Combined use of intraoperative ultrasound and indocyanine green fluorescence imaging to detect liver metastases from colorectal cancer. HPB (Oxford) 15:928–934

    Article  Google Scholar 

  19. Ishizuka M, Kubota K, Kita J, Shimoda M, Kato M, Sawada T (2012) Intraoperative observation using a fluorescence imaging instrument during hepatic resection for liver metastasis from colorectal cancer. Hepatogastroenterology 59:90–92

    Article  PubMed  CAS  Google Scholar 

  20. Troyan SL, Kianzad V, Gibbs-Strauss SL, Gioux S, Matsui A, Oketokoun R, Ngo L, Khamene A, Azar F, Frangioni JV (2009) The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping. Ann Surg Oncol 16:2943–2952

    Article  PubMed  PubMed Central  Google Scholar 

  21. Mieog JS, Troyan SL, Hutteman M et al (2011) Toward optimization of imaging system and lymphatic tracer for near-infrared fluorescent sentinel lymph node mapping in breast cancer. Ann Surg Oncol 18:2483–2491

    Article  PubMed  PubMed Central  Google Scholar 

  22. Crane LM, Themelis G, Pleijhuis RG et al (2011) Intraoperative multispectral fluorescence imaging for the detection of the sentinel lymph node in cervical cancer: a novel concept. Mol Imaging Biol 13:1043–1049

    Article  PubMed  Google Scholar 

  23. Yamauchi K, Nagafuji H, Nakamura T, Sato T, Kohno N (2011) Feasibility of ICG fluorescence-guided sentinel node biopsy in animal models using the HyperEye Medical System. Ann Surg Oncol 18:2042–2047

    Article  PubMed  Google Scholar 

  24. Cahill RA, Anderson M, Wang LM, Lindsey I, Cunningham C, Mortensen NJ (2012) Near-infrared (NIR) laparoscopy for intraoperative lymphatic road-mapping and sentinel node identification during definitive surgical resection of early-stage colorectal neoplasia. Surg Endosc 26:197–204

    Article  PubMed  Google Scholar 

  25. van der Poel HG, Buckle T, Brouwer OR, Valdés Olmos RA, van Leeuwen FWB (2011) Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodal tracer. Eur Urol 60:826–833

    Article  PubMed  Google Scholar 

  26. Moroga T, Yamashita S, Tokuishi K, Miyawaki M, Anami K, Yamamoto S, Kawahara K (2012) Thoracoscopic segmentectomy with intraoperative evaluation of sentinel nodes for stage I non-small cell lung cancer. Ann Thorac Cardiovasc Surg 18:89–94

    Article  PubMed  Google Scholar 

  27. Jafari MD, Wexner SD, Martz JE, McLemore EC, Margolin DA, Sherwinter DA, Lee SW, Senagore AJ, Phelan MJ, Stamos MJ (2015) Perfusion assessment in laparoscopic left-sided/anterior resection (PILLAR II): a multi-institutional study. J Am Coll Surg 220:82–92

    Article  PubMed  Google Scholar 

  28. Hamady ZZ, Lodge JP, Welsh FK et al (2014) One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach. Ann Surg 259:543–548

    Article  PubMed  Google Scholar 

  29. Kokudo N, Miki Y, Sugai S et al (2002) Genetic and histological assessment of surgical margins in resected liver metastases from colorectal carcinoma: minimum surgical margins for successful resection. Arch Surg 137:833–840

    Article  PubMed  Google Scholar 

  30. Muratore A, Ribero D, Zimmitti G, Mellano A, Langella S, Capussotti L (2010) Resection margin and recurrence-free survival after liver resection of colorectal metastases. Ann Surg Oncol 17:1324–1329

    Article  PubMed  Google Scholar 

  31. Nuzzo G, Giuliante F, Ardito F, Vellone M, Giovannini I, Federico B, Vecchio FM (2008) Influence of surgical margin on type of recurrence after liver resection for colorectal metastases: a single-center experience. Surgery 143:384–393

    Article  PubMed  Google Scholar 

  32. Figueras J, Burdio F, Ramos E, Torras J, Llado L, Lopez-Ben S, Codina-Barreras A, Mojal S (2007) Effect of subcentimeter nonpositive resection margin on hepatic recurrence in patients undergoing hepatectomy for colorectal liver metastases. Evidences from 663 liver resections. Ann Oncol 18:1190–1195

    Article  PubMed  CAS  Google Scholar 

  33. Gotoh K, Yamada T, Ishikawa O, Takahashi H, Eguchi H, Yano M, Ohigashi H, Tomita Y, Miyamoto Y, Imaoka S (2009) A novel image-guided surgery of hepatocellular carcinoma by indocyanine green fluorescence imaging navigation. J Surg Oncol 100:75–79

    Article  PubMed  Google Scholar 

  34. Ishizawa T, Tamura S, Masuda K et al (2009) Intraoperative fluorescent cholangiography using indocyanine green: a biliary road map for safe surgery. J Am Coll Surg 208:e1–e4

    Article  PubMed  Google Scholar 

  35. Kawaguchi Y, Ishizawa T, Masuda K et al (2011) Hepatobiliary surgery guided by a novel fluorescent imaging technique for visualizing hepatic arteries, bile ducts, and liver cancers on color images. J Am Coll Surg 212:e33–e39

    Article  PubMed  Google Scholar 

  36. Kawaguchi Y, Ishizawa T, Harada Y et al (2013) IntraoperativeIdentification of bile duct perforation following ERCP using indocyanine green-fluorescence imaging. Dig Dis Sci 59:1063–1065

    Article  PubMed  Google Scholar 

  37. Kubota K, Kita J, Shimoda M, Rokkaku K, Kato M, Iso Y, Sawada T (2006) Intraoperative assessment of reconstructed vessels in living-donor liver transplantation, using a novel fluorescence imaging technique. J Hepato-Biliary-Pancreat Surg 13:100–104

    Article  Google Scholar 

  38. Kawaguchi Y, Ishizawa T, Miyata Y, Yamashita S, Masuda K, Satou S, Tamura S, Kaneko J, Sakamoto Y, Aoki T, Hasegawa K, Sugawara Y, Kokudo N (2013) Portal uptake function in veno-occlusive regions evaluated by real-time fluorescent imaging using indocyanine green. J Hepatol 58:247–253

    Article  PubMed  Google Scholar 

  39. Kawaguchi Y, Sugawara Y, Ishizawa T, Satou S, Kaneko J, Tamura S, Aoki T, Sakamoto Y, Hasegawa K, Kokudo N (2013) Identification of veno-occlusive regions in a right liver graft after reconstruction of vein segments 5 and 8: application of indocyanine green fluorescence imaging. Liver Transpl 19:778–779

    Article  PubMed  Google Scholar 

  40. Shimada S, Ohtsubo S, Ogasawara K, Kusano M (2015) Macro- and microscopic findings of ICG fluorescence in liver tumors. World J Surg Oncol 13:198. https://doi.org/10.1186/s12957-015-0615-5

    Article  PubMed  PubMed Central  Google Scholar 

  41. Vahrmeijer AL, Hutteman M, van der Vorst JR, van de Velde CJH, Frangioni JV (2013) Image-guided cancer surgery using near-infrared fluorescence. Nat Rev Clin Oncol 10:507–518

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Kudo H, Ishizawa T, Tani K, Harada N, Ichida A, Shimizu A, Kaneko J, Aoki T, Sakamoto Y, Sugawara Y, Hasegawa K, Kokudo N (2014) Visualization of subcapsular hepatic malignancy by indocyanine-green fluorescence imaging during laparoscopic hepatectomy. Surg Endosc 28:2504–2508

    Article  PubMed  Google Scholar 

  43. Takahashi H, Zaidi N, Berber E (2016) An initial report on the intraoperative use of indocyanine green fluorescence imaging in the surgical management of liver tumors. J Surg Oncol 114:625–629

    Article  PubMed  Google Scholar 

  44. Ciria R, Cherqui D, Geller DA, Briceno J, Wakabayashi G (2016) Comparative short-term benefits of laparoscopic liver resection: 9000 cases and climbing. Ann Surg 263:761–777

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank Dr. Kosuke Yamada, Dr. Koji Nogaki, and Dr. Yoshihiko Tashiro (Showa University) for their assistance with acquisition of data; Dr. Yusuke Wada, Dr. Tomoki Hakozaki, Dr. Kodai Tomioka, and Dr. Hideki Shibata (Showa University); and Dr. Kris Siriratsivawong (Showa University) for the revision of the manuscript.

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Authors and Affiliations

Authors

Contributions

T. A. and M. M. were responsible for the study conception and design; T. K., K. M., A. F., and T. K. for the acquisition of data; Y. E., S. G., M. W., and K. O. for the analysis and interpretation of data; T. A. for the drafting of the manuscript; and M. M. for the critical revision of the manuscript.

Corresponding author

Correspondence to Takeshi Aoki.

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The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Aoki, T., Murakami, M., Koizumi, T. et al. Determination of the surgical margin in laparoscopic liver resections using infrared indocyanine green fluorescence. Langenbecks Arch Surg 403, 671–680 (2018). https://doi.org/10.1007/s00423-018-1685-y

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  • DOI: https://doi.org/10.1007/s00423-018-1685-y

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