Abstract
Simple SummaryFewer than 30% of patients with liver metastases are eligible for major liver resection, because liver remaining after such a surgery would be insufficient to cover the patient’s needs; this is called a low percentage of future liver remnant (FLR). Folinic acid (FA) has been shown to play a crucial role in cellular synthesis, regeneration, and nucleotide and amino acid biosynthesis. The aim of this piece of research was to evaluate the effect of FA as a potential hypertrophic hepatic enhancer agent after selective portal vein ligation (PVL) to ensure adequate FLR. We have confirmed in our rodent model that FA accelerates liver regeneration after PVL and enhances recovery of liver function. These findings may allow more patients to be eligible for liver resection without jeopardizing postoperative liver function.Liver resection remains the gold standard for hepatic metastases. The future liver remnant (FLR) and its functional status are two key points to consider before performing major liver resections, since patients with less than 25% FLR or a Child–Pugh B or C grade are not eligible for this procedure. Folinic acid (FA) is an essential agent in cell replication processes. Herein, we analyze the effect of FA as an enhancer of liver regeneration after selective portal vein ligation (PVL). Sixty-four male WAG/RijHsd rats were randomly distributed into eight groups: a control group and seven subjected to 50% PVL, by ligation of left portal branch. The treated animals received FA (2.5 m/kg), while the rest were given saline. After 36 h, 3 days or 7 days, liver tissue and blood samples were obtained. FA slightly but significantly increased FLR percentage (FLR%) on the 7th day (91.88 ± 0.61%) compared to control or saline-treated groups (86.72 ± 2.5 vs. 87 ± 3.33%; p < 0.01). The hepatocyte nuclear area was also increased both at 36 h and 7days with FA (61.55 ± 16.09 µm2, and 49.91 ± 15.38 µm2; p < 0.001). Finally, FA also improved liver function. In conclusion, FA has boosted liver regeneration assessed by FLR%, nuclear area size and restoration of liver function after PVL.
Highlights
Despite advances in chemotherapeutic approaches and other techniques for the ablative treatment of liver tumors, liver resection remains the gold standard treatment for colorectal cancer liver metastases (CRCLM) or other liver malignancies [1,2,3,4]; CRCLM are the main indication for liver surgery in western countries [4,5]
Different studies indicate that up to 75% of the hepatic parenchyma could be safely removed without compromising liver function in patients with a good hepatic functional status, increasing the risk of liver failure when the liver remnant is less than 25%
In each and every animal subjected to portal vein ligation (PVL), selective ligation of the left portal vein induced some degree of lateral lobe (LLL) atrophy, with different levels of compensatory liver hypertrophy according to the experimental groups
Summary
Despite advances in chemotherapeutic approaches and other techniques for the ablative treatment of liver tumors, liver resection remains the gold standard treatment for colorectal cancer liver metastases (CRCLM) or other liver malignancies [1,2,3,4]; CRCLM are the main indication for liver surgery in western countries [4,5]. Most of them have a gastrointestinal origin, which can be explained since the tumor cells can migrate from the primary tumor through the blood vessels to the liver, establishing and developing new tumor implants in this organ [4]. This explains why a high percentage of patients with primary tumors of the gastrointestinal tract present CRCLM at the time of diagnosis (synchronous metastases) [2,3,4]. It is important to ensure a sufficient FLR or to increase it, as a previous stage to liver resection, in order to meet the patient’s metabolic requirements, and this is achieved with techniques that induce hepatic hypertrophy
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