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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Targeted molecular therapies (cetuximab and bevacizumab) do not induce additional hepatotoxicity: preliminary results
Aims:
To analyse the effects of the preoperative targeted molecular therapy (cetuximab (cetu) or bevacizumab (beva)) on non-tumorous liver parenchyma, and the clinical and biological outcome after liver resection for colorectal liver metastases (CLM).
Methods:
Between January 2005 and December 2007, 36 patients receiving preoperatively cetu (n = 15) or beva (n = 21) were, respectively, matched to a control group of patients who did not receive targeted molecular therapy. They were matched on the basis of age, gender, body mass index, extent of hepatectomy, and type and number of neoadjuvant chemotherapy. Liver function tests, postoperative outcome and histopathology of the resected liver were compared.
Results:
There was no mortality. Postoperative morbidity and perioperative bleeding rates were similar in both groups. In the beva group, liver function tests showed higher serum bilirubin level on postoperative day (POD) 1 (p = 0.001) and POD 3 (p = 0.01), higher serum aspartate aminotransferase on POD 1 (p = 0.004), and lower prothrombin time on POD 5 (p = 0.02). In both groups, cetu and beva, the postoperative peaks of gamma-glutamyl transpeptidase and alkaline phosphatase were statistically higher than in the control groups. Interestingly, the prevalence of sinusoidal injury and fibrosis was lower in patients receiving cetu (p = 0.04), while the prevalence of steatohepatitis was lower in patients receiving beva (p = 0.04).
Conclusion:
The addition of beva or cetu to the neoadjuvant chemotherapy regimens does not appear to increase the morbidity rates after hepatectomy for CLM. The pathological examination did not show additional injury to the non-tumorous liver parenchyma.
Insights
Preoperative targeted therapies like cetuximab and bevacizumab did not increase complications after liver resection for colorectal metastases. Pathological analysis revealed no additional injury to non-tumorous liver tissue.
Area of Science:
- Hepatobiliary Surgery
- Surgical Oncology
- Molecular Targeted Therapy
Background:
- Colorectal liver metastases (CLM) often require surgical resection.
- Preoperative therapies are used to manage CLM, but their impact on non-tumorous liver parenchyma needs evaluation.
- Targeted molecular therapies, such as cetuximab and bevacizumab, are options for neoadjuvant treatment.
Purpose of the Study:
- To analyze the effects of preoperative targeted molecular therapy (cetuximab or bevacizumab) on non-tumorous liver parenchyma.
- To assess the clinical and biological outcomes following liver resection for CLM in patients who received targeted therapy.
- To compare outcomes between patients receiving targeted therapy and a matched control group.
Main Methods:
- A retrospective matched-cohort study involving 36 patients who received preoperative cetuximab (n=15) or bevacizumab (n=21).
- Patients were matched to a control group based on age, gender, BMI, extent of hepatectomy, and neoadjuvant chemotherapy.
- Evaluated liver function tests, postoperative outcomes, and histopathology of resected liver tissue.
Main Results:
- No mortality was observed. Postoperative morbidity and bleeding rates were similar between groups.
- Bevacizumab group showed transient increases in serum bilirubin and aspartate aminotransferase, and a decrease in prothrombin time.
- Both cetuximab and bevacizumab groups exhibited higher postoperative peaks in gamma-glutamyl transpeptidase and alkaline phosphatase compared to controls.
- Interestingly, cetuximab was associated with lower rates of sinusoidal injury and fibrosis, while bevacizumab showed lower rates of steatohepatitis.
Conclusions:
- Addition of bevacizumab or cetuximab to neoadjuvant chemotherapy does not increase morbidity after hepatectomy for CLM.
- Pathological examination of non-tumorous liver parenchyma did not reveal significant additional injury in patients receiving targeted therapies.
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