Department of Surgery, Medical School and Teaching Hospital Pilsen, Charles University Prague, Alej svobody 80, 304 60 Pilsen, Czech Republic.
In Vivo. 2012 Jul-Aug;26(4):683-91.
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.
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.
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.
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.
本研究旨在通过大型动物实验，研究在扩大肝切除术前即刻进行单独的生物治疗对肝切除术后剩余肝脏（FLR）的肝功能和再生能力的影响。
本研究纳入 19 头小猪（对照组 10 头，实验组 9 头）。经颈内静脉内置入端口。在肝切除术前 11 天和 4 天，通过该端口以 400mg/m2 猪体表面积给予西妥昔单抗。对照组给予生理盐水。随后进行左外侧、左内侧和右内侧肝叶切除术（切除 50-60%的肝实质）。在手术前和肝切除后不同时间采集血样。评估术前和肝切除后不同时间的血清胆红素、尿素、肌酐、碱性磷酸酶、γ-谷氨酰转移酶、胆碱酯酶、天门冬氨酸氨基转移酶、丙氨酸氨基转移酶、白蛋白、C-反应蛋白和转化生长因子-β1 水平。在术前和肝切除后不同时间点进行超声检查，以评估肝脏体积。对肝实质活检进行增生活性、双核肝细胞、肝细胞大小和肝小叶长度检查。使用 Wilcoxon 检验比较两组间研究参数的分布。由于参数值的非正态分布，使用 Spearman 秩相关系数。使用 ANOVA 比较两组间研究参数随时间的整体发展。
在手术过程中或围手术期内，生物治疗的给药均无重要并发症。FLR 的再生没有统计学差异，生化、免疫分析和组织学参数也没有差异。
实验组和对照组肝再生结果相当，证实了术前使用西妥昔单抗进行生物治疗可缩短恢复期。
