Introduction. Surgical injury can stimulate tumor growth in metastatic colorectal cancer (mCRC), due to mitochondrial dysfunction.
The objective of the study was to analyze the clinical significance of the molecular marker of 8-hydroxydeoxyguanosine and the oncological influence of the liver parenchyma warm ischemia on the prognosis of mCRC.
Materials and methods. The study involved 89 CRC patients with metachronous metastatic liver disease treated in The National Cancer Institute of the Ministry of Health, Kyiv, Ukraine, from 2015 till 2018, and 19 conditionally healthy donors. 8-Hydroxy-deoxyguanosine (8-OHdG) level in the urine of patients with mCRC was determined. Urine sampling was done 24-hours before and on day 3 after surgery. Measurements of the marker of oxidative DNA damage were repeated three times. The state of the hepatocyte detoxification energy system, the levels of superoxide radicals (O2-) in the tumour tissue were determined by electron paramagnetic resonance (EPR) and Spin Trapping Technology.
Results. The urinary 8-OHdG level of donors was within 0.24±0.063 nM/kg ∙ day, whereas before the resection and on day 3 after the R0-resection of liver in mCRC patients it was 3.42±0.18 nM/kg∙day and 2.12±0.08 nM/kg∙day (p < 0.05), respectively. On day 1 after the liver resection with a total duration of warm ischemia period < 30 min and > 30 min have had marker at level 2.108 ± 0.13 nM/kg∙day and 2.9883 ± 0.159 nM/kg∙day (p < 0.0001), respectively. The volume of metastatic tissue (Vmts) significantly and directly increased the level of urine 8-OhdG. The duration of surgical intervention (resection t) and duration of warm liver ischemia (t ischemia) significantly increased urine level of 8-OhdG.
Conclusions. R0-resection of liver metastases in mCRC patients decreases urine 8-OHdG level after surgery. Warm liver ischemia during the Pringle maneuver (≥ 40 min), surgical intervention duration (≥ 300 min) and metastatic tissue volume (≥ 12 cm3) in liver parenchyma in mCRC patients significantly increase urine 8-OHdG levels. The level of 8-OHdG correlates with the extent of organ resection, duration of ischemia, volume of post-resection liver tissue, volume of metastases and rate of superoxide radicals’ generation.
Keywords: colorectal cancer, 8-hydroxy-deoxyguanosine, superoxide radicals, liver metastases, liver resection.
mCRC – metastatic colorectal cancer
DNA – Deoxyribonucleic acid
O2- – superoxide radicals
8-OHdG – 8-Hydroxydeoxyguanosine
EPR – electron paramagnetic resonance
Vmts – volume of metastatic tissue
resection t – time of resection
t ischemia – duration of warm liver ischemia
I/R – ischemia-reperfusion
PM – Pringle maneuver
CTX – chemotherapy
CT – computed tomography
CRC – colorectal cancer
ALF – acute liver failure
ISGLS – International Study Group of Liver Surgery
Bogomolets National Medical University, Kyiv, Ukraine
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