Molecular mechanisms of liver damage during neoadjuvant treatment for hepatic metastases of colorectal cancer

Colorectal Cancer

Ann Ital Chir. 2020;91:291-297.


BACKGROUND: The main drawbacks of neoadjuvant chemotherapy of colorectal liver cancer metastases are related to the toxic liver damage. To determine the degree of biochemical and morphologic liver damage after therapeutic protocol treatment with "bevacizumab plus FOLFOX IV", as well as the correlation between the sex, age, the existence of metabolic syndrome, the length of neoadjuvant therapy treatment and the degree of liver damage.

METHODS: The study includes the total of 60 colorectal cancer metastases operated patients, divided into two groups of 30 patients: the group of patients who were treated with "bevacizumab plus FOLFOX IV" protocol as a neoadjuvant therapy - prior to liver metastases surgery and the control group, patients with the liver resection done without previous neoadjuvant chemotherapy. The following parameters were examined: biochemical liver function parameters, the presence of metabolic syndrome, pathohistological assessment of the degree of steatosis and SOS syndrome.

RESULTS: The increase in AF was observed in the experimental group (Z = 2.566, p = 0.010), Dbilirubin (Z = 1.970, p = 0.037), LDH (Z = 2.951, p = 0.003) and decrease in albumin values (t = 5.100, p <0.001). The pathohistological examination in only 3.3% showed moderate liver steatosis, while SOS syndrome was recorded in as many as two-thirds (66.66%) of patients in the study group. In 14 patients (46.7%) a mild degree was registered, and in 6 (20.0%) moderate levels of this type of liver damage. Pole (p = 0.13), age (p = 0.09) and length of administration of chemotherapy (p = 0.35), as well as the presence of metabolic syndrome (χ2 = 0.390, p = 0.830), did not have any statistically significant effect on the liver damage degree.

CONCLUSION: In our study, after the administration of the "bevacizumab plus FOLFOX IV" protocol, a statistically significant increase in AF, Dbilirubin and LDH, as well as a decrease in albumin values, were found. Dominant liver damage was by type of SOS syndrome (66.7%), while steatosis of the liver was recorded in only 3.3% of patients. Gender, age, the presence of metabolic syndrome and the number of chemotherapy cycles did not have any statistic significance on the biochemical parameters and

morphological degree of liver damage.

KEY WORDS: Colorectal cancer metastases, Liver surgery, Oncology, Neoadjuvant chemotherapy, Liver damage.