Preoperative use of Biological Therapy Does not Influence Liver Regeneration after Large Resection-Porcine Experimental Model with Monoclonal Antibody against Epidermal Growth Factor

Background: The aim of this work was to study the influence of isolated biological therapy administered immediately before extended liver resection on liver function and regenerative capacity of future liver remnant (FLR) in a large-animal experiment. Materials and Methods: Nineteen piglets were included in this study (10 in the control group and 9 in the experimental group). A port-a-cath was introduced into the superior caval vein. On days 11 and 4 before liver resection, cetuximab was administered via this port at 400 mg/m2 of piglet body surface. Physiological solution was applied to the control group. Resection of the left lateral, left medial and right medial hepatic lobes was followingly performed (reduction of 50-60% of liver parenchyma). Blood samples were collected at different times before the operation and after liver resection. Serum levels of bilirubin, urea, creatinine, alkaline phosphatase, gamma glutamyltransferase, cholinesterase, aspartate aminotransferase, alanine aminotransferase, albumin, C-reactive protein and transforming growth factor-β1 were assessed. The ultrasonographic examinations at different time points were performed pre-operatively and after liver resection in order to assess the liver volume. The biopsies from the liver parenchyma were examined for proliferative activity, binocluated hepatocytes, size of hepatocytes, and the length of the lobuli. The comparison of distribution of the studied parameters between the groups was carried out using the Wilcoxon test. The Spearman rank correlation co-efficient was used because of the non-Gaussian distribution of the parameter values. The whole development of the studied parameters over time was compared between the groups using ANOVA. Results: There were no important complications of administration of biologic therapy during the operation or throughout the peri-operative period. There was no statistically significant difference in the regeneration of FLR nor were any differences in biochemical, immunoanalytical and histological parameters detected. Conclusion: The achieved results of comparable liver regeneration in both the experimental and control groups confirms the use of biological treatment with cetuximab in the pre-operative period for minimizing the recovery period. Possibilities for liver surgery have been extended in recent years by new surgical techniques, and more highly developed procedures and skills. At present, surgery is the only curative option for the treatment of liver metastases from primary colorectal carcinoma. Today we are able to perform large radical resections of malignant liver lesions. Nevertheless, many patients with primary or secondary liver malignancies that undergo oncologic treatment before liver surgery are not directed to the radical surgical therapy that could extend their chance of complete remission for the malignancy. We fear the increased risk of acute liver failure after extended liver resection, where the liver parenchyma could be affected by previous chemotherapy and the liver functions could be reduced (1-3). Many patients are indicated for neoadjuvant oncologic treatment with the aim of down-staging and downsizing the liver malignancy (4-7). The use of standard combination of chemotherapy [oxaliplatin/5-fluorouracil (5-FU) or irinotecan/5-FU) has increased the resection rate up to 20-40% in selected patients (8). The addition of anti-EGFR monoclonal antibody, and 683 Correspondence to: Lubos Holubec, M.D., Ph.D., Department of Oncology and Radiotherapy, Charles University, Medical School and Teaching Hospital Pilsen, Alej svobody 80, 304 60 Pilsen, Czech Republic, Tel.: +420 377105533, Fax: +420 377105454, email: holubec@fnplzen.cz