Mechanistic Background and Clinical Applications of Indocyanine Green Fluorescence Imaging of Hepatocellular Carcinoma

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• 作者：Takeaki Ishizawa MD ; PhD (1)
  Koichi Masuda MD (1)
  Yasuteru Urano PhD (2)
  Yoshikuni Kawaguchi MD (1)
  Shouichi Satou MD ; PhD (1)
  Junichi Kaneko MD ; PhD (1)
  Kiyoshi Hasegawa MD ; PhD (1)
  Junji Shibahara MD ; PhD (3)
  Masashi Fukayama MD ; PhD (3)
  Shingo Tsuji PhD (4)
  Yutaka Midorikawa MD ; PhD (4)
  Hiroyuki Aburatani MD ; PhD (4)
  Norihiro Kokudo MD ; PhD (1)
  
• 刊名：Annals of Surgical Oncology
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：21
• 期：2
• 页码：440-448
• 全文大小：672 KB
• 作者单位：Takeaki Ishizawa MD,PhD (1)
  Koichi Masuda MD (1)
  Yasuteru Urano PhD (2)
  Yoshikuni Kawaguchi MD (1)
  Shouichi Satou MD,PhD (1)
  Junichi Kaneko MD,PhD (1)
  Kiyoshi Hasegawa MD,PhD (1)
  Junji Shibahara MD,PhD (3)
  Masashi Fukayama MD,PhD (3)
  Shingo Tsuji PhD (4)
  Yutaka Midorikawa MD,PhD (4)
  Hiroyuki Aburatani MD,PhD (4)
  Norihiro Kokudo MD,PhD (1)
  
  1. Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, University of Tokyo, Tokyo, Japan
  2. Laboratory of Chemical Biology and Molecular Imaging, University of Tokyo, Tokyo, Japan
  3. Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  4. Genome Science Division, Research Center for Advanced Science & Technology, The University of Tokyo, Tokyo, Japan
  
• ISSN：1534-4681

文摘

Background Although clinical applications of intraoperative fluorescence imaging of liver cancer using indocyanine green (ICG) have begun, the mechanistic background of ICG accumulation in the cancerous tissues remains unclear. Methods In 170 patients with hepatocellular carcinoma cells (HCC), the liver surfaces and resected specimens were intraoperatively examined by using a near-infrared fluorescence imaging system after preoperative administration of ICG (0.5?mg/kg i.v.). Microscopic examinations, gene expression profile analysis, and immunohistochemical staining were performed for HCCs, which showed ICG fluorescence in the cancerous tissues (cancerous-type fluorescence), and HCCs showed fluorescence only in the surrounding non-cancerous liver parenchyma (rim-type fluorescence). Results ICG fluorescence imaging enabled identification of 273 of 276 (99?%) HCCs in the resected specimens. HCCs showed that cancerous-type fluorescence was associated with higher cancer cell differentiation as compared with rim-type HCCs (P?<?0.001). Fluorescence microscopy identified the presence of ICG in the canalicular side of the cancer cell cytoplasm, and pseudoglands of the HCCs showed a cancerous-type fluorescence pattern. The ratio of the gene and protein expression levels in the cancerous to non-cancerous tissues for Na+/taurocholate cotransporting polypeptide (NTCP) and organic anion-transporting polypeptide 8 (OATP8), which are associated with portal uptake of ICG by hepatocytes that tended to be higher in the HCCs that showed cancerous-type fluorescence than in those that showed rim-type fluorescence. Conclusions Preserved portal uptake of ICG in differentiated HCC cells by NTCP and OATP8 with concomitant biliary excretion disorders causes accumulation of ICG in the cancerous tissues after preoperative intravenous administration. This enables highly sensitive identification of HCC by intraoperative ICG fluorescence imaging.