Impact of the Pringle manoeuvre on the mitochondrial redox state of hepatocytes in colorectal cancer patients with liver metastases

Abstract

Introduction: Novel surgical strategies for metastatic colorectal cancer (CRC) treatment offer survival benefits even in the case of multiple bilobar liver injury. However, an inability to overcome the biological consequences of an ischaemia-reperfusion phenomenon among cancer patients remains an oncological issue throughout the last 3 decades. The aim of this study was to assess the values of molecular markers of the mitochondrial redox state of hepatocytes in CRC patients during liver surgery and Pringle manoeuvre (PM) application. Material and methods: We conducted a prospective study of 114 CRC patients who underwent liver resection for CRC metastases between March 2017 and December 2020. Results: PM application was associated with higher superoxide radicals (SR) level generation compared to liver surgery without blood inflow control - 0.32 ± 0.12 and 0.42 ± 0.21 nmol/gm raw tissue × min, respectively. Levels of NO-Fe-S cluster protein complexes in liver stump parenchyma in the end of transection with and without PM was 0.35 ± 0.09 RU and 0.16 ± 0.04 RU, respectively. The most significant impact of long-term ischaemia was found to be the rate of SR generation in liver stump: 152.4 ± 24.4 (95% CI: 104.1-200.7), R2 = 0.46, p = 0.001. Conclusions: PM exacerbates the disruption of the mitochondrial respiratory chain and potentiates SR generation. The redox status molecular markers of the hepatocytes in CRC patients with liver metastases can be used to assess the functional status of organ and tissues and improve the existing surgical strategies.