Metabolic changes from liver regeneration after metastatic colorectal cancer surgery

Abstract

Background. The pathological effect of the surgical ischemia-reperfusion technique is a cause for the development of liver damage and occurrence of acute liver failure during the postoperative period in cancer patients after major resection as well as after transplantation. Despite the urgency of the problem, most of the pathological processes that accompany the above-mentioned conditions are still only incompletely studied.

Objective. To investigate the mechanisms of the damaging effects of stress reaction after liver resection, to evaluate the functional state of residual liver tissue and to find ways to influence the regeneration and apoptosis of the resected liver, which in the future would make the liver surgery safer.

Methods. The results of treatment of 15 patients with colorectal cancer (mCRC) and liver metastases, who had undergone surgery in the period from December 2015 to November 2016 at the National Cancer Institute. Determination of the state of the detoxifying function of hepatocytes and the coupling of biological oxidation and phosphorylation in the mitochondria of hepatocytes were performed by electron paramagnetic resonance at the temperature of liquid nitrogen.

Results. It has been found that the levels of the oxidized and low-spin forms of cytochrome P-450 in the catalytic cycle of the detoxification system were 0.33 ± 0.08 relative units and 1.11 ± 0.13 relative units, respectively (the normal levels are 0.59 ± 0.03 relative units and 2.56 ± 0.02 relative units). Also, an increase registered in the levels of formation of complexes of NO-FeS-proteins up to the values of 0.33 ± 0.08 relative units (the normal level is 0.14 ± 0.07). We believe that such changes are the cause of disturbances in the energy function of mitochondria and the formation of cell hypoxia, which correlates with an increase of lactate levels in tissue of the future liver remnant. The liver remnant levels are > 2.00 mM/g·tissue, while the normal is 1.80 ± 0.26 mm/g·tissue. This confirms the functioning of hepatocytes under hypoxic conditions.

Conclusions. In the residual liver tissue, we have found a decrease in detoxification system deficiency and the energy supply of hepatocytes. In hepatocytes of the future liver remnant, reprogramming of the metabolism of mitochondria from oxidative phosphorylation in glycolysis is registered, resulting in the formation of cell hypoxia and an increase in levels of lactate and superoxide radicals. To assess the degree of ALF in the postoperative period, we suggest use of the levels of lactate, the activity of cytochrome P-450, the levels of formation of complexes of NO and FeS-proteins in mitochondria ETC and the generation rate of SR as the markers.