Department of General, Visceral, Vascular and Paediatric Surgery, University of Saarland, Homburg/Saar, Germany.
Br J Surg. 2010 Jun;97(6):917-26. doi: 10.1002/bjs.7003.
Portal branch ligation (PBL) is being used increasingly before hepatectomy for colorectal metastases. This study evaluated the effect of PBL on angiogenesis, growth factor expression and tumour growth in a mouse model of hepatic colorectal metastases.
CT26.WT cells were implanted into the left liver lobe of BALB/c mice. Animals underwent PBL of the left liver lobe or sham treatment. Angiogenesis, microcirculation, growth factor expression, cell proliferation and tumour growth were studied over 14 and 21 days by intravital multifluorescence microscopy, laser Doppler flowmetry, immunohistochemistry and western blotting.
Left hilar blood flow and tumour microcirculation were significantly diminished during the first 7 days after PBL. This resulted in tumour volume being 20 per cent less than in sham controls by day 14. Subsequently, PBL-treated animals demonstrated recovery of left hilar blood flow and increased expression of hepatocyte growth factor and transforming growth factor alpha, associated with increased cell proliferation and acceleration of growth by day 21.
PBL initially reduced vascular perfusion and tumour growth, but this was followed by increased growth factor expression and cell proliferation. This resulted in delayed acceleration of tumour growth, which might explain the stimulated tumour growth observed occasionally after PBL.
门静脉分支结扎术(PBL)在结直肠癌肝转移的肝切除术前越来越多地被应用。本研究通过建立小鼠肝转移模型,评估了 PBL 对血管生成、生长因子表达和肿瘤生长的影响。
将 CT26.WT 细胞植入 BALB/c 小鼠的左肝叶。动物接受左肝叶 PBL 或假手术处理。通过活体多荧光显微镜、激光多普勒血流仪、免疫组织化学和 Western blot 分析,在 14 天和 21 天内研究血管生成、微循环、生长因子表达、细胞增殖和肿瘤生长情况。
PBL 后第 1 天,左肝门血流量和肿瘤微循环明显减少,导致 PBL 组第 14 天肿瘤体积比假手术组小 20%。随后,PBL 组动物表现出左肝门血流恢复,以及肝细胞生长因子和转化生长因子-α表达增加,与第 21 天的细胞增殖增加和生长加速相关。
PBL 最初减少了血管灌注和肿瘤生长,但随后生长因子表达和细胞增殖增加,导致肿瘤生长的延迟加速,这可能解释了 PBL 后偶尔观察到的肿瘤生长刺激现象。