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在小动物模型中,开腹肝切除与腹腔镜肝切除术后残余肝细胞癌中血管内皮生长因子转录增加。

Increased vascular endothelial growth factor transcription in residual hepatocellular carcinoma after open versus laparoscopic hepatectomy in a small animal model.

机构信息

Department of Surgery, Oregon Health and Science University, Mail Code L223A, 3181 Sam Jackson Park Road, Portland, OR 97239, USA.

出版信息

Surg Endosc. 2010 May;24(5):1151-7. doi: 10.1007/s00464-009-0742-6. Epub 2009 Nov 14.

DOI:10.1007/s00464-009-0742-6
PMID:19915910
Abstract

BACKGROUND

Vascular endothelial growth factor (VEGF) is overexpressed in hepatocellular carcinoma (HCC), and findings have shown that its upregulation in these tumors has an impact on tumor growth. The authors hypothesized that compared with open liver resection, laparoscopic hepatectomy would result in a decreased local angiogenic response in residual tumor cells.

METHODS

Right- and left-lobe hepatomas were induced in Buffalo rats via laparoscopically guided subcapsular injection of Morris hepatoma cells. After 1 week, the animals were randomized to laparoscopic or open left lateral hepatectomy. In 14 days after resection, the rats were killed, the residual right lobe tumors were measured, and tissue was procured for RNA extraction. Transcript levels of VEGF messenger RNA (mRNA) were quantified with reverse transcriptase-polymerase chain reaction (RT-PCR), and VEGF serum levels were measured by enzyme-linked immunoassay (ELISA) both before resection and at the time of tissue harvest.

RESULTS

None of the animals had development satellite liver lesions or distant metastases in the abdomen or thorax. The median residual tumor volume was 320 mm(3) in the open group compared with 180 mm(3) in the laparoscopic group (p = 0.164). The animals that underwent open resection had a 1.3-fold increase in VEGF mRNA transcript levels compared with the laparoscopic resection group (p = 0.008). The serum VEGF levels were not significantly different between the laparoscopic and open groups at baseline (open tumor resection [OR], 23.7 +/- 12.0 pg/ml; laparoscopic tumor resection [LR], 30.7 +/- 15.5 pg/ml; p = 0.334) nor at the time of tissue harvest (OR, 19.9 +/- 19.6 pg/ml; LR, 26.9 +/- 34.5 pg/ml; p = 0.549).

CONCLUSIONS

Laparoscopic hepatic resection produces decreased VEGF mRNA expression in residual hepatoma cells compared with open resection. Decreased stimulation of angiogenesis promoters in the tumor microenvironment after minimally invasive liver resection may contribute to a lower residual disease burden and ultimately lead to a lower recurrence rate.

摘要

背景

血管内皮生长因子(VEGF)在肝细胞癌(HCC)中过度表达,研究结果表明,其在这些肿瘤中的上调会影响肿瘤生长。作者假设,与开腹肝切除术相比,腹腔镜肝切除术会导致残留在肿瘤细胞中的局部血管生成反应减少。

方法

通过腹腔镜引导的包膜下注射 Morris 肝癌细胞在水牛大鼠中诱导右叶和左叶肝癌。1 周后,将动物随机分为腹腔镜或开腹左外侧肝切除术。切除后 14 天,处死大鼠,测量残留的右叶肿瘤,并采集组织进行 RNA 提取。采用逆转录聚合酶链反应(RT-PCR)定量 VEGF 信使 RNA(mRNA)的转录水平,并通过酶联免疫吸附试验(ELISA)测量切除前和组织采集时的 VEGF 血清水平。

结果

所有动物均未在腹部或胸部发生卫星肝脏病变或远处转移。开腹组的中位残留肿瘤体积为 320mm3,腹腔镜组为 180mm3(p=0.164)。与腹腔镜切除术组相比,接受开腹切除术的动物 VEGF mRNA 转录水平增加了 1.3 倍(p=0.008)。腹腔镜组和开腹组的血清 VEGF 水平在基线时(开腹肿瘤切除术[OR],23.7+/-12.0pg/ml;腹腔镜肿瘤切除术[LR],30.7+/-15.5pg/ml;p=0.334)和组织采集时(OR,19.9+/-19.6pg/ml;LR,26.9+/-34.5pg/ml;p=0.549)均无显著差异。

结论

与开腹切除术相比,腹腔镜肝切除术可降低残留在肝癌细胞中的 VEGF mRNA 表达。微创肝切除术后肿瘤微环境中血管生成促进剂的刺激减少可能有助于降低残留疾病负担,并最终降低复发率。

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