Abstract
Selective portal vein ligation (PVL) allows the two-stage surgical resection of primarily unresectable liver tumours by generating the atrophy and hypertrophy of portally ligated (LL) and non-ligated lobes (NLL), respectively. To evaluate critically important underlying functional alterations, present study characterised in vitro and vivo liver function in male Wistar rats (n = 106; 210–250 g) before, and 24/48/72/168/336 h after PVL. Lobe weights and volumes by magnetic resonance imaging confirmed the atrophy-hypertrophy complex. Proper expression and localization of key liver transporters (Ntcp, Bsep) and tight junction protein ZO-1 in isolated hepatocytes demonstrated constantly present viable and well-polarised cells in both lobes. In vitro taurocholate and bilirubin transport, as well as in vivo immunohistochemical Ntcp and Mrp2 expressions were bilaterally temporarily diminished, whereas LL and NLL structural acinar changes were divergent. In vivo bile and bilirubin-glucuronide excretion mirrored macroscopic changes, whereas serum bilirubin levels remained unaffected. In vivo functional imaging (indocyanine-green clearance test; 99mTc-mebrofenin hepatobiliary scintigraphy; confocal laser endomicroscopy) indicated transitionally reduced global liver uptake and -excretion. While LL functional involution was permanent, NLL uptake and excretory functions recovered excessively. Following PVL, functioning cells remain even in LL. Despite extensive bilateral morpho-functional changes, NLL functional increment restores temporary declined transport functions, emphasising liver functional assessment.
Highlights
With a worldwide ranking of sixth in incidence and third in cancer-related deaths, liver malignancies represent a chief challenge for liver surgery[1]
In vivo liver lobe volumes following portal vein ligation (PVL) were assessed in the mebrofenin group by serial postoperative magnetic resonance imaging (MRI) scans
Portal vein ligation-induced liver regeneration remains an essential element of arsenal in liver surgery for the curative two-stage resection of primarily unresectable liver tumours
Summary
With a worldwide ranking of sixth in incidence and third in cancer-related deaths, liver malignancies represent a chief challenge for liver surgery[1]. Much different clinical management is required in patients with large liver tumours, requiring extensive resections, sparing only an undersized ‘future liver remnant’ (FLR), and thereby risking the development of liver failure. A ‘full-scale’ hepatic functional quantification remains a platonic idea, the analysis of organic anion (bilirubin, bile salts, etc.) transport may be fairly representative, judging from its central physiological and clinical relevance[11]. On one hand, this may be well performed in in vitro cell cultures, which provide basic information regarding the specific characteristics of the involved transport routes. We wished to clarify the role that cellular junction proteins and organic anion transporters play in the regenerative potential of ligated lobes undergoing involution
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