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Erschienen in: Annals of Surgical Oncology 2/2014

01.02.2014 | Hepatobiliary Tumors

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

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

Erschienen in: Annals of Surgical Oncology | Ausgabe 2/2014

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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.

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.
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Metadaten
Titel
Mechanistic Background and Clinical Applications of Indocyanine Green Fluorescence Imaging of Hepatocellular Carcinoma
verfasst von
Takeaki Ishizawa, MD,PhD
Koichi Masuda, MD
Yasuteru Urano, PhD
Yoshikuni Kawaguchi, MD
Shouichi Satou, MD,PhD
Junichi Kaneko, MD,PhD
Kiyoshi Hasegawa, MD,PhD
Junji Shibahara, MD,PhD
Masashi Fukayama, MD,PhD
Shingo Tsuji, PhD
Yutaka Midorikawa, MD,PhD
Hiroyuki Aburatani, MD,PhD
Norihiro Kokudo, MD,PhD
Publikationsdatum
01.02.2014
Verlag
Springer US
Erschienen in
Annals of Surgical Oncology / Ausgabe 2/2014
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-3360-4

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