Reply to: “Portal uptake function in veno-occlusive regions evaluated by real-time fluorescent imaging using indocyanine green”
Authors: Yoshikuni Kawaguchi, Takeaki Ishizawa, Norihiro Kokudo
Journal: Journal of Hepatology (2013)

Portal uptake function in veno-occlusive regions evaluated by real-time fluorescent imaging using indocyanine greenJournal of HepatologyVol. 58Issue 2PreviewAlthough recent advances in preoperative imaging have enabled accurate estimation of the regional liver volume with venous occlusion, the extent of functional decrease in such regions remains unclear. In this study, the portal uptake function in postoperative veno-occlusive regions and non-veno-occlusive regions was evaluated by intraoperative fluorescent imaging after intravenous injection of indocyanine green (ICG). Full-Text PDF Portal uptake function in veno-occlusive regions evaluated by real-time fluorescent imaging using indocyanine greenJournal of HepatologyVol. 59Issue 3PreviewWe have read with great interest the article by Kawaguchi et al. [1]. The authors measured, in the operating room, the hepatic concentrations of indocyanine green (ICG) to evaluate the function of congestive hepatic segments. Three groups of patients were studied: partial hepatectomy, remnant liver of living donors, and hepatic grafts of recipients. Although preoperative three-dimensional computer tomography estimates the postoperative segment volumes, the function of congestive segments is not evaluated by the imaging technique. Full-Text PDF Open Access We have read with interest the comments made by Kobbe et al. to our recently published article, which demonstrated that portal uptake of indocyanine green (ICG) in veno-occlusive regions caused by dissection of the major hepatic veins decreased to approximately 40% of that in non-veno-occlusive regions (ranging from 10% to 80%) by using intraoperative fluorescence imaging [[1]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: 247-253Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar]. In veno-occlusive hepatic regions, the portal veins can act as drainage of arterial blood flow, according to the severity of venous occlusion. Thus, we hypothesized that, in hepatic regions with severe venous occlusion, ICG flowed into the sinusoids from the hepatic arteries and portal veins following intravenous administration, but regurgitated and drained into the portal system before reaching the hepatocytes, leading to the decreased concentration of ICG in the hepatic parenchyma. This should be confirmed in further studies by using in vivo fluorescence microscopy [[2]Goetz M. Deris I. Vieth M. Murr E. Hoffman A. Delaney P. et al.Near-infrared confocal imaging during mini-laparoscopy: a novel rigid endomicroscope with increased imaging plane depth.J Hepatol. 2010; 53: 84-90Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar], which may enable visualization of intrahepatic microvascular blood flow in the veno-occlusive regions. Although the decreased portal uptake of ICG in the early phase of the hepatic venous occlusion would be caused by the intrahepatic hemodynamic changes, postoperative functional and regenerative disorders in veno-occlusive hepatic regions may be associated with the altered expression of hepatic transporters, as pointed out by Kobbe et al. We have evaluated expression levels of hepatic uptake transporters for ICG (organic anion-transporting polypeptide 8 [OATP8, SLCO1B3] and Na+/taurocholate co-transporting polypeptide [NTCP, SLC10A1]) [[3]de Graaf W. Hausler S. Heger M. van Ginhoven T.M. van Cappellen G. Bennink R.J. et al.Transporters involved in the hepatic uptake of (99m)Tc-mebrofenin and indocyanine green.J Hepatol. 2011; 54: 738-745Abstract Full Text Full Text PDF PubMed Scopus (206) Google Scholar] by using immunohistochemical staining and gene expression analysis, in order to elucidate mechanistic background of ICG accumulation in hepatocellular carcinoma following preoperative intravenous administration, which enables real-time identification of cancerous tissues during hepatectomy [[4]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: 2491-2504Crossref PubMed Scopus (626) Google Scholar]. It would be valuable to assess the expression levels of hepatic transporters in veno-occlusive and non-veno-occlusive regions, if postoperative tissue samples are available to adopt similar approach. Gadoxetic acid-enhanced magnetic resonance imaging is a good alternative to evaluate postoperative portal uptake and excretion function in veno-occlusive and non-veno-occlusive hepatic regions, although it should be noted that gadoxetic acid can be excreted not only into bile through multidrug resistance-associated protein 2 (MRP2), but also into blood sinusoids through MRP3 [[5]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: 817-826Crossref PubMed Scopus (284) Google Scholar], while ICG is exclusively excreted into the bile canaliculus through MRP2. This work was supported by grants from the Takeda Science Foundation, the Kanae Foundation for the Promotion of Medical Science, and the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 23689060). The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.