Advertisement

Identification of Hepatocellular Carcinoma Recurrence after Resection

  • Yoshikuni Kawaguchi
  • Kosuke Kobayashi
  • Kiyoshi HasegawaEmail author
Chapter
  • 18 Downloads

Abstract

Fluorescence imaging technique using indocyanine green (ICG) as a fluorophore has been increasingly used for many surgical procedures since the 2000s. Because ICG is taken into hepatocyte and exclusively excreted into the bile, the technique is used for hepatobiliary surgery. ICG-fluorescence imaging visualizes the flow of hepatic artery and portal vein, primary and metastatic liver tumors, the bile duct, and portal venous territory. The technique is also used for evaluating hepatic perfusion in regions with outflow obstruction. Liver resection is the optimal treatment option for hepatocellular carcinoma (HCC), and fluorescence imaging guides surgeons for identifying HCC during surgery in real time. Although cumulative recurrence rates after HCC resection remain high, repeat hepatectomy was reported to lead better cumulative long-term survival from initial resection. The problem of repeat hepatectomy lies in technical complexity because of adhesions and changes in liver anatomy after previous operation. These changes may hinder surgeons from identifying HCCs in the operating room. Fluorescence imaging is helpful for visualizing HCC recurrence on the thick connective tissue after previous resection because of adhesions after initial liver resection. In conclusion, ICG-fluorescence imaging can be used for visualizing HCC recurrence in patients undergoing repeat hepatectomy as in patients undergoing initial liver resection. The technique may be useful for complementing visual inspection, palpation, and intraoperative ultrasonography.

Keywords

Fluorescence imaging Indocyanine green Hepatocellular carcinoma Repeat hepatectomy Recurrence 

Supplementary material

Video 15.1

Fluorescence imaging of hepatocellular carcinoma. After mobilization of the liver, a near-infrared camera is placed above left lateral sector of the liver. Two HCCs (arrow and arrowhead) were identified as fluorescence on the surface of the cirrhotic liver (MP4 16200 kb)

Video 15.2

Fluorescence imaging of recurrence of hepatocellular carcinoma. After dissecting adhesions and mobilizing the liver, a near-infrared camera is placed above segment 6. HCC is visualized as fluorescence on the thick connective tissue of the liver surface. Another HCC in segment 4 is also identified as fluorescence on the liver surface (MP4 37523 kb)

References

  1. 1.
    Rubens FD, Ruel M, Fremes SE. A new and simplified method for coronary and graft imaging during CABG. Heart Surg Forum. 2002;5:141–4.PubMedPubMedCentralGoogle Scholar
  2. 2.
    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;75:870–3.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Ogata F, Narushima M, Mihara M, Azuma R, Morimoto Y, Koshima I. Intraoperative lymphography using indocyanine green dye for near-infrared fluorescence labeling in lymphedema. Ann Plast Surg. 2007;59:180–4.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Kitai T, Inomoto T, Miwa M, Shikayama T. Fluorescence navigation with indocyanine green for detecting sentinel lymph nodes in breast cancer. Breast Cancer. 2005;12:211–5.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    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;25:103–8.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Miyashiro I, Miyoshi N, Hiratsuka M, Kishi K, Yamada T, Ohue M, et al. Detection of sentinel node in gastric cancer surgery by indocyanine green fluorescence imaging: comparison with infrared imaging. Ann Surg Oncol. 2008;15:1640–3.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Kubota K, Kita J, Shimoda M, Rokkaku K, Kato M, Iso Y, et al. Intraoperative assessment of reconstructed vessels in living-donor liver transplantation, using a novel fluorescence imaging technique. J Hepato-Biliary-Pancreat Surg. 2006;13:100–4.CrossRefGoogle Scholar
  8. 8.
    Kawaguchi Y, Ishizawa T, Masuda K, Sato S, Kaneko J, Aoki T, et al. 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. 2011;212:e33–9.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    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;100:75–9.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    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;115:2491–504.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    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 Hepato-Biliary-Pancreat Surg. 2008;15:508–14.CrossRefGoogle Scholar
  12. 12.
    Ishizawa T, Bandai Y, Ijichi M, Kaneko J, Hasegawa K, Kokudo N. Fluorescent cholangiography illuminating the biliary tree during laparoscopic cholecystectomy. Br J Surg. 2010;97:1369–77.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Aoki T, Murakami M, Yasuda D, Shimizu Y, Kusano T, Matsuda K, et al. Intraoperative fluorescent imaging using indocyanine green for liver mapping and cholangiography. J Hepatobiliary Pancreat Sci. 2010;17:590–4.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Miyata A, Ishizawa T, Tani K, Shimizu A, Kaneko J, Aoki T, et al. Reappraisal of a dye-staining technique for anatomic hepatectomy by the concomitant use of indocyanine green fluorescence imaging. J Am Coll Surg. 2015;221:e27–36.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Kobayashi Y, Kawaguchi Y, Kobayashi K, Mori K, Arita J, Sakamoto Y, et al. Portal vein territory identification using indocyanine green fluorescence imaging: technical details and short-term outcomes. J Surg Oncol. 2017;116:921.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Kawaguchi Y, Ishizawa T, Miyata Y, Yamashita S, Masuda K, Satou S, et al. Portal uptake function in veno-occlusive regions evaluated by real-time fluorescent imaging using indocyanine green. J Hepatol. 2013;58:247–53.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Kawaguchi Y, Sugawara Y, Ishizawa T, Satou S, Kaneko J, Tamura S, et al. 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. 2013;19:778–9.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Kawaguchi Y, Nomura Y, Nagai M, Koike D, Sakuraoka Y, Ishida T, et al. Liver transection using indocyanine green fluorescence imaging and hepatic vein clamping. Br J Surg. 2017;104:898–906.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Kudo H, Ishizawa T, Tani K, Harada N, Ichida A, Shimizu A, et al. Visualization of subcapsular hepatic malignancy by indocyanine-green fluorescence imaging during laparoscopic hepatectomy. Surg Endosc. 2014;28:2504–8.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Kawaguchi Y, Nagai M, Nomura Y, Kokudo N, Tanaka N. Usefulness of indocyanine green-fluorescence imaging during laparoscopic hepatectomy to visualize subcapsular hard-to-identify hepatic malignancy. J Surg Oncol. 2015;112:514.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Kawaguchi Y, Velayutham V, Fuks D, Christidis C, Kokudo N, Gayet B. Usefulness of indocyanine green-fluorescence imaging for visualization of the bile duct during laparoscopic liver resection. J Am Coll Surg. 2015;221:e113–7.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Terasawa M, Ishizawa T, Mise Y, Inoue Y, Ito H, Takahashi Y, et al. Applications of fusion-fluorescence imaging using indocyanine green in laparoscopic hepatectomy. Surg Endosc. 2017;31:5111.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Aoki T, Murakami M, Koizumi T, Matsuda K, Fujimori A, Kusano T, et al. Determination of the surgical margin in laparoscopic liver resections using infrared indocyanine green fluorescence. Langenbeck’s Arch Surg. 2018;403:671.CrossRefGoogle Scholar
  24. 24.
    Kitao A, Zen Y, Matsui O, Gabata T, Kobayashi S, Koda W, et al. Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR imaging--correlation with molecular transporters and histopathologic features. Radiology. 2010;256:817–26.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    de Graaf W, Hausler S, Heger M, van Ginhoven TM, van Cappellen G, Bennink RJ, et al. Transporters involved in the hepatic uptake of (99m)Tc-mebrofenin and indocyanine green. J Hepatol. 2011;54:738–45.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    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;21:440–8.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Shibasaki Y, Sakaguchi T, Hiraide T, Morita Y, Suzuki A, Baba S, et al. Expression of indocyanine green-related transporters in hepatocellular carcinoma. J Surg Res. 2015;193:567–76.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Uchiyama K, Ueno M, Ozawa S, Kiriyama S, Shigekawa Y, Yamaue H. Combined use of contrast-enhanced intraoperative ultrasonography and a fluorescence navigation system for identifying hepatic metastases. World J Surg. 2010;34:2953–9.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Tanaka T, Takatsuki M, Hidaka M, Hara T, Muraoka I, Soyama A, et al. Is a fluorescence navigation system with indocyanine green effective enough to detect liver malignancies? J Hepatobiliary Pancreat Sci. 2014;21(3):199–204.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    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;18:232–41.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Zhang YM, Shi R, Hou JC, Liu ZR, Cui ZL, Li Y, et al. Liver tumor boundaries identified intraoperatively using real-time indocyanine green fluorescence imaging. J Cancer Res Clin Oncol. 2017;143:51–8.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Boogerd LS, Handgraaf HJ, Lam HD, Huurman VA, Farina-Sarasqueta A, Frangioni JV, et al. Laparoscopic detection and resection of occult liver tumors of multiple cancer types using real-time near-infrared fluorescence guidance. Surg Endosc. 2017;31:952–61.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Belghiti J, Panis Y, Farges O, Benhamou JP, Fekete F. Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis. Ann Surg. 1991;214:114–7.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Grazi GL, Ercolani G, Pierangeli F, Del Gaudio M, Cescon M, Cavallari A, et al. Improved results of liver resection for hepatocellular carcinoma on cirrhosis give the procedure added value. Ann Surg. 2001;234:71–8.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg. 2002;235:373–82.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Imamura H, Matsuyama Y, Miyagawa Y, Ishida K, Shimada R, Miyagawa S, et al. Prognostic significance of anatomical resection and des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma. Br J Surg. 1999;86:1032–8.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Nakajima Y, Ko S, Kanamura T, Nagao M, Kanehiro H, Hisanaga M, et al. Repeat liver resection for hepatocellular carcinoma. J Am Coll Surg. 2001;192:339–44.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Adam R, Bhangui P, Vibert E, Azoulay D, Pelletier G, Duclos-Vallee JC, et al. Resection or transplantation for early hepatocellular carcinoma in a cirrhotic liver: does size define the best oncological strategy? Ann Surg. 2012;256:883–91.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Zheng Z, Liang W, Milgrom DP, Schroder PM, Kong NS, Yang C, et al. Liver transplantation versus liver resection in the treatment of hepatocellular carcinoma: a meta-analysis of observational studies. Transplantation. 2014;97:227–34.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Mise Y, Hasegawa K, Shindoh J, Ishizawa T, Aoki T, Sakamoto Y, et al. The feasibility of third or more repeat hepatectomy for recurrent hepatocellular carcinoma. Ann Surg. 2015;262:347–57.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Kawaguchi Y, Aoki T, Ishizawa T, Arita J, Satou S, Kaneko J, et al. Education and imaging: hepatobiliary and pancreatic: identification of recurrent hepatocellular carcinoma by intraoperative fluorescent imaging. J Gastroenterol Hepatol. 2013;28:587.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Abo T, Nanashima A, Tobinaga S, Hidaka S, Taura N, Takagi K, et al. Usefulness of intraoperative diagnosis of hepatic tumors located at the liver surface and hepatic segmental visualization using indocyanine green-photodynamic eye imaging. Eur J Surg Oncol. 2015;41:257–64.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Yoshikuni Kawaguchi
    • 1
  • Kosuke Kobayashi
    • 1
  • Kiyoshi Hasegawa
    • 1
    Email author
  1. 1.Hepato-Biliary-Pancreatic Surgery Division, Department of SurgeryGraduate School of Medicine, The University of TokyoTokyoJapan

Personalised recommendations