Skip to main content

Identification of Hepatocellular Carcinoma

  • Chapter
Fluorescence Imaging for Surgeons

Abstract

Indocyanine green (ICG), an agent used to measure liver function, becomes fluorescent under near-infrared (NIR) light after binding to serum proteins. ICG fluorography enables the clear visualization of hepatocellular carcinoma (HCC) via deposition of preoperatively administered ICG. For successful detection, an interval of 2–7 days between ICG administration and surgery seems to be appropriate. HCC fluorescent imaging appearance is classified into three types: uniform (total) intra-lesion emission pattern, uneven (partial) intra-lesion emission pattern, and rim-like emission pattern. There is significant correlation between HCC differentiation and imaging appearance. ICG fluorography is useful in the detection of HCC, even in cases of extrahepatic metastasis. Further prospective studies are needed to determine whether incidental small emission spots identified during intraoperative NIR observation require resection.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  PubMed  Google Scholar 

  2. Heiken JP, Weyman PJ, Lee JK, Balfe DM, Picus D, Brunt EM, et al. Detection of focal hepatic masses: prospective evaluation with CT, delayed CT, CT during arterial portography, and MR imaging. Radiology. 1989;171(1):47–51.

    Article  CAS  PubMed  Google Scholar 

  3. Quaia E, Calliada F, Bertolotto M, Rossi S, Garioni L, Rosa L, et al. Characterization of focal liver lesions with contrast-specific US modes and a sulfur hexafluoride-filled microbubble contrast agent: diagnostic performance and confidence. Radiology. 2004;232(2):420–30.

    Article  PubMed  Google Scholar 

  4. Hammerstingl R, Huppertz A, Breuer J, Balzer T, Blakeborough A, Carter R, et al. Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions. Eur Radiol. 2008;18(3):457–67.

    Article  PubMed  Google Scholar 

  5. Mitsunori Y, Tanaka S, Nakamura N, Ban D, Irie T, Noguchi N, et al. Contrast-enhanced intraoperative ultrasound for hepatocellular carcinoma: high sensitivity of diagnosis and therapeutic impact. J Hepatobiliary Pancreat Sci. 2013;20(2):234–42.

    Article  PubMed  Google Scholar 

  6. Polom K, Murawa D, Rho YS, Nowaczyk P, Hunerbein M, Murawa P. Current trends and emerging future of indocyanine green usage in surgery and oncology: a literature review. Cancer. 2011;117(21):4812–22.

    Article  PubMed  Google Scholar 

  7. Hochheimer BF. Angiography of the retina with indocyanine green. Arch Ophthalmol. 1971;86(5):564–5.

    Article  CAS  PubMed  Google Scholar 

  8. Ganz W, Donoso R, Marcus HS, Forrester JS, Swan HJ. A new technique for measurement of cardiac output by thermodilution in man. Am J Cardiol. 1971;27(4):392–6.

    Article  CAS  PubMed  Google Scholar 

  9. Caesar J, Shaldon S, Chiandussi L, Guevara L, Sherlock S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci. 1961;21:43–57.

    CAS  PubMed  Google Scholar 

  10. Benson RC, Kues HA. Fluorescence properties of indocyanine green as related to angiography. Phys Med Biol. 1978;23(1):159–63.

    Article  CAS  PubMed  Google Scholar 

  11. Unno N, Inuzuka K, Suzuki M, Yamamoto N, Sagara D, Nishiyama M, et al. Preliminary experience with a novel fluorescence lymphography using indocyanine green in patients with secondary lymphedema. J Vasc Surg. 2007;45(5):1016–21.

    Article  PubMed  Google Scholar 

  12. Taggart DP, Choudhary B, Anastasiadis K, Abu-Omar Y, Balacumaraswami L, Pigott DW. Preliminary experience with a novel intraoperative fluorescence imaging technique to evaluate the patency of bypass grafts in total arterial revascularization. Ann Thorac Surg. 2003;75(3):870–3.

    Article  PubMed  Google Scholar 

  13. Raabe A, Beck J, Gerlach R, Zimmermann M, Seifert V. Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow. Neurosurgery. 2003;52(1):132–9. discussion 9.

    PubMed  Google Scholar 

  14. Kitai T, Inomoto T, Miwa M, Shikayama T. Fluorescence navigation with indocyanine green for detecting sentinel lymph nodes in breast cancer. Breast Cancer. 2005;12(3):211–5.

    Article  PubMed  Google Scholar 

  15. Kusano M, Tajima Y, Yamazaki K, Kato M, Watanabe M, Miwa M. Sentinel node mapping guided by indocyanine green fluorescence imaging: a new method for sentinel node navigation surgery in gastrointestinal cancer. Dig Surg. 2008;25(2):103–8.

    Article  PubMed  Google Scholar 

  16. Mitsuhashi N, Kimura F, Shimizu H, Imamaki M, Yoshidome H, Ohtsuka M, et al. Usefulness of intraoperative fluorescence imaging to evaluate local anatomy in hepatobiliary surgery. J Hepatobiliary Pancreat Surg. 2008;15(5):508–14.

    Article  PubMed  Google Scholar 

  17. Ishizawa T, Bandai Y, Kokudo N. Fluorescent cholangiography using indocyanine green for laparoscopic cholecystectomy: an initial experience. Arch Surg. 2009;144(4):381–2.

    Article  PubMed  Google Scholar 

  18. Sakaguchi T, Suzuki A, Unno N, Morita Y, Oishi K, Fukumoto K, et al. Bile leak test by indocyanine green fluorescence images after hepatectomy. Am J Surg. 2010;200(1):e19–23.

    Article  PubMed  Google Scholar 

  19. Gotoh K, Yamada T, Ishikawa O, Takahashi H, Eguchi H, Yano M, et al. A novel image-guided surgery of hepatocellular carcinoma by indocyanine green fluorescence imaging navigation. J Surg Oncol. 2009;100(1):75–9. doi:10.1002/jso.21272.

    Article  PubMed  Google Scholar 

  20. Ishizawa T, Fukushima N, Shibahara J, Masuda K, Tamura S, Aoki T, et al. Real-time identification of liver cancers by using indocyanine green fluorescent imaging. Cancer. 2009;115(11):2491–504. doi:10.1002/cncr.24291.

    Article  PubMed  Google Scholar 

  21. Morita Y, Sakaguchi T, Unno N, Shibasaki Y, Suzuki A, Fukumoto K, et al. Detection of hepatocellular carcinomas with near-infrared fluorescence imaging using indocyanine green: its usefulness and limitation. Int J Clin Oncol. 2013;18(2):232–41.

    Article  CAS  PubMed  Google Scholar 

  22. de Graaf W, Hausler S, Heger M, van Ginhoven TM, van Cappellen G, Bennink RJ, et al. Transporters involved in the hepatic uptake of (99 m)Tc-mebrofenin and indocyanine green. J Hepatol. 2011;54(4):738–45.

    Article  PubMed  Google Scholar 

  23. Zollner G, Wagner M, Fickert P, Silbert D, Fuchsbichler A, Zatloukal K, et al. Hepatobiliary transporter expression in human hepatocellular carcinoma. Liver Int. 2005;25(2):367–79.

    Article  CAS  PubMed  Google Scholar 

  24. Kitao A, Matsui O, Yoneda N, Kozaka K, Shinmura R, Koda W, et al. The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging. Eur Radiol. 2011;21(10):2056–66.

    Article  PubMed  Google Scholar 

  25. Huang L, Vore M. Multidrug resistance p-glycoprotein 2 is essential for the biliary excretion of indocyanine green. Drug Metab Dispos. 2001;29(5):634–7.

    CAS  PubMed  Google Scholar 

  26. Kusuhara H, Sugiyama Y. Pharmacokinetic modeling of the hepatobiliary transport mediated by cooperation of uptake and efflux transporters. Drug Metab Rev. 2010;42(3):539–50.

    Article  CAS  PubMed  Google Scholar 

  27. Ishizawa T, Masuda K, Urano Y, Kawaguchi Y, Satou S, Kaneko J, et al. Mechanistic background and clinical applications of indocyanine green fluorescence imaging of hepatocellular carcinoma. Ann Surg Oncol. 2014;21(2):440–8. doi:10.1245/s10434-013-3360-4.

    Article  PubMed  Google Scholar 

  28. Harada N, Ishizawa T, Muraoka A, Ijichi M, Kusaka K, Shibasaki M, et al. Fluorescence navigation hepatectomy by visualization of localized cholestasis from bile duct tumor infiltration. J Am Coll Surg. 2010;210(6):e2–6.

    Article  PubMed  Google Scholar 

  29. Satou S, Ishizawa T, Masuda K, Kaneko J, Aoki T, Sakamoto Y, et al. Indocyanine green fluorescent imaging for detecting extrahepatic metastasis of hepatocellular carcinoma. J Gastroenterol. 2013;48(10):1136–43.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yoshifumi Morita M.D., Ph.D. .

Editor information

Editors and Affiliations

Electronic Supplementary Material

Video 15.1

Intraoperative and postoperative ICG fluorography. Preoperative contrast-enhanced computed tomography (CT) showed large tumor with capsule, 12 cm in diameter. The tumor was mainly located in the anterior section. A cyst, 1 cm in diameter, was detected in the caudal surface of the lateral section. Intraoperative indocyanine green (ICG) fluorography showed heterogeneous emission in the liver surface of the anterior section. We could not see any other emission spot in the internal section, lateral section, or posterior section. ICG fluorography of the resected specimen showed uneven (partial) intra-lesion emission pattern (M2TS 148,896 kb)

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Morita, Y., Sakaguchi, T., Kikuchi, H., Unno, N., Konno, H. (2015). Identification of Hepatocellular Carcinoma. In: Dip, F., Ishizawa, T., Kokudo, N., Rosenthal, R. (eds) Fluorescence Imaging for Surgeons. Springer, Cham. https://doi.org/10.1007/978-3-319-15678-1_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-15678-1_15

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-15677-4

  • Online ISBN: 978-3-319-15678-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics