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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-11-20

AUTHORS

Takeaki Ishizawa, Koichi Masuda, Yasuteru Urano, Yoshikuni Kawaguchi, Shouichi Satou, Junichi Kaneko, Kiyoshi Hasegawa, Junji Shibahara, Masashi Fukayama, Shingo Tsuji, Yutaka Midorikawa, Hiroyuki Aburatani, Norihiro Kokudo

ABSTRACT

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. MethodsIn 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).ResultsICG 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.ConclusionsPreserved 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. More... »

PAGES

440-448

Identifiers

URI

http://scigraph.springernature.com/pub.10.1245/s10434-013-3360-4

DOI

http://dx.doi.org/10.1245/s10434-013-3360-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1036991606

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24254203


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27 schema:description 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. MethodsIn 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).ResultsICG 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.ConclusionsPreserved 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.
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33 schema:keywords Cancerous
34 HCC cells
35 ICG
36 ICG accumulation
37 ICG fluorescence
38 NTCP
39 accumulation
40 accumulation of ICG
41 administration
42 analysis
43 applications
44 background
45 canalicular side
46 cancer
47 cancer cell cytoplasm
48 cancer cell differentiation
49 cancerous tissues
50 carcinoma
51 carcinoma cells
52 cell cytoplasm
53 cell differentiation
54 cells
55 clinical application
56 cotransporting
57 cytoplasm
58 differentiated HCC cells
59 differentiation
60 disorders
61 examination
62 expression levels
63 expression profile analysis
64 fluorescence
65 fluorescence imaging
66 fluorescence imaging system
67 fluorescence microscopy
68 fluorescence pattern
69 gene expression profile analysis
70 genes
71 hepatocellular carcinoma
72 hepatocellular carcinoma cells
73 hepatocytes
74 identification
75 imaging
76 imaging system
77 immunohistochemical staining
78 indocyanine green fluorescence imaging
79 intraoperative ICG fluorescence
80 intraoperative fluorescence imaging
81 intravenous administration
82 levels
83 liver cancer
84 liver parenchyma
85 liver surface
86 mechanistic background
87 microscopic examination
88 microscopy
89 non-cancerous liver parenchyma
90 non-cancerous tissues
91 parenchyma
92 patients
93 patterns
94 polypeptides 8
95 portal uptake
96 preoperative administration
97 preoperative intravenous administration
98 presence
99 presence of ICG
100 profile analysis
101 protein expression levels
102 pseudoglands
103 ratio
104 resected specimens
105 sensitive identification
106 side
107 specimens
108 staining
109 surface
110 system
111 tissue
112 uptake
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