Fichtl Jakub, Treska Vladislav, Lysak Daniel, Mirka Hynek, Duras Petr, Karlikova Marie, Skalicky Tomas, Vodička Josef, Topolcan Ondrej
Department of Surgery, School of Medicine, University Hospital Pilsen, Pilsen, Czech Republic
Department of Surgery, School of Medicine, University Hospital Pilsen, Pilsen, Czech Republic.
Anticancer Res. 2016 Apr;36(4):1901-7.
Liver metastases occur in 60-80% of patients with colorectal carcinoma. The only potentially curative method is surgical resection, with an operability of 20-25%. The main reason for such low resectability is insufficient future liver remnant volume (FLRV). Portal vein embolization (PVE) alone is associated with failure in up to 40% of patients. A new method that could lead to acceleration of FRLV growth appears to be combination of PVE and application of hematopoietic stem cells (HSCs). The aim of our study was to evaluate the importance of growth factors and interleukins for FLRV growth after PVE and HSC application and also their possible effect on growth of colorectal liver metastases.
From June 2010 to July 2014, PVE was combined with application of adult HSCs in 16 primarily inoperable patients with colorectal liver metastases. We determined the serum levels of growth factors [hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binging protein 3 (IGF-BP3), epidermal growth factor (EGF), transforming growth factor (TGFα), tumor necrosis factor (TNF)] and interleukins (IL2, -6, -8 and -10) at given time intervals by immunoanalytic methods. The growth of FLRV was evaluated by multidetector computed tomography at intervals of 1 week until sufficient growth of FLRV.
We were able to perform radical surgery in 13 primarily inoperable patients (81.4%). The average FLRV growth was 23.1% (range=21.9-38.6%); from an initial FLRV of 30.5% (range=20.6-39%) to 40.1% (range=29-48%) before resection. The combination of levels of EGF, HGF, VEGF, IGF, TGFα and IL2,-6,-8 appears to be crucial for predicting operability. IL8 was statistically significant for the growth of colorectal liver metastases, and TGFα, IL2, and IL8 are important for a longer disease-free interval.
60% - 80%的结直肠癌患者会发生肝转移。唯一可能治愈的方法是手术切除，可切除率为20% - 25%。可切除性如此低的主要原因是未来肝剩余体积（FLRV）不足。单纯门静脉栓塞术（PVE）在高达40%的患者中会失败。一种可能加速FLRV生长的新方法似乎是PVE与造血干细胞（HSCs）应用相结合。我们研究的目的是评估生长因子和白细胞介素对PVE和HSC应用后FLRV生长的重要性，以及它们对结直肠癌肝转移生长的可能影响。
2010年6月至2014年7月，对16例最初无法手术的结直肠癌肝转移患者将PVE与成人HSCs应用相结合。我们通过免疫分析方法在特定时间间隔测定血清生长因子[肝细胞生长因子（HGF）、血管内皮生长因子（VEGF）、胰岛素样生长因子1（IGF - 1）、胰岛素样生长因子结合蛋白3（IGF - BP3）、表皮生长因子（EGF）、转化生长因子（TGFα）、肿瘤坏死因子（TNF）]和白细胞介素（IL2、 - 6、 - 8和 - 10）的水平。通过多排螺旋计算机断层扫描每隔1周评估FLRV的生长情况，直至FLRV充分生长。
我们能够对13例最初无法手术的患者（81.4%）进行根治性手术。FLRV的平均生长率为23.1%（范围 = 21.9% - 38.6%）；从切除前初始FLRV的30.5%（范围 = 20.6% - 39%）增长至40.1%（范围 = 29% - 48%）。EGF、HGF、VEGF、IGF、TGFα和IL2、 - 6、 - 8水平的组合似乎对预测可切除性至关重要。IL8对结直肠癌肝转移的生长具有统计学意义，而TGFα、IL2和IL8对更长的无病生存期很重要。
