From the Department of Radiology, Division of Vascular & Interventional Radiology (J.R., D.M., R.T.G., G.J., W.C., P.V.S., W.P.R., D.R.S., C.Y.K.), and Department of Medicine (A.B.N., M.D.S., J.C.B., H.I.H.), Duke University Medical Center, Box 3808 Duke University Medical Center, 2301 Erwin Road, Durham, NC 27710.
Radiology. 2017 Oct;285(1):311-318. doi: 10.1148/radiol.2017162555. Epub 2017 Aug 8.
Purpose To identify changes in a broad panel of circulating angiogenesis factors after bland transcatheter arterial embolization (TAE), a purely ischemic treatment for hepatocellular carcinoma (HCC). Materials and Methods This prospective HIPAA-compliant study was approved by the institutional review board. Informed written consent was obtained from all participants prior to entry into the study. Twenty-five patients (21 men; mean age, 61 years; range, 30-81 years) with Liver Imaging Reporting and Data System category 5 or biopsy-proven HCC and who were undergoing TAE were enrolled from October 15, 2014, through December 2, 2015. Nineteen plasma angiogenesis factors (angiopoietin 2; hepatocyte growth factor; platelet-derived growth factor AA and BB; placental growth factor; vascular endothelial growth factor A and D; vascular endothelial growth factor receptor 1, 2, and 3; osteopontin; transforming growth factor β1 and β2; thrombospondin 2; intercellular adhesion molecule 1; interleukin 6 [IL-6]; stromal cell-derived factor 1; tissue inhibitor of metalloproteinases 1; and vascular cell adhesion molecule 1 [VCAM-1]) were measured by using enzyme-linked immunosorbent assays at 1 day, 2 weeks, and 5 weeks after TAE and were compared with baseline levels by using paired Wilcoxon tests. Tumor response was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Angiogenesis factor levels were compared between responders and nonresponders by mRECIST criteria by using unpaired Wilcoxon tests. Results All procedures were technically successful with no complications. Fourteen angiogenesis factors showed statistically significant changes following TAE, but most changes were transient. IL-6 was upregulated only 1 day after the procedure, but showed the largest increases of any factor. Osteopontin and VCAM-1 demonstrated sustained upregulation at all time points following TAE. At 3-month follow-up imaging, 11 patients had responses to TAE (complete response, n = 6; partial response, n = 5) and 11 patients were nonresponders (stable disease, n = 9; progressive disease, n = 2). In nonresponders, the percent change in IL-6 on the day after TAE (P = .033) and the mean percent change in osteopontin after TAE (P = .024) were significantly greater compared with those of responders. Conclusion Multiple angiogenesis factors demonstrated significant upregulation after TAE. VCAM-1 and osteopontin demonstrated sustained upregulation, whereas the rest were transient. IL-6 and osteopontin correlated significantly with radiologic response after TAE. RSNA, 2017.
在单纯的缺血性治疗肝癌（HCC）后，鉴定广泛的循环血管生成因子的变化。
这项符合 HIPAA 规定的前瞻性研究得到了机构审查委员会的批准。在进入研究之前，所有参与者均获得了知情书面同意。
从 2014 年 10 月 15 日至 2015 年 12 月 2 日，纳入 25 名接受 Bland 经导管动脉栓塞术（TAE）的肝脏成像报告和数据系统（LI-RADS）类别 5 或经活检证实为 HCC 且正在接受 TAE 的患者（21 名男性；平均年龄 61 岁；范围 30-81 岁）。
通过酶联免疫吸附试验在 TAE 后 1 天、2 周和 5 周测量了 19 种血浆血管生成因子（血管生成素 2；肝细胞生长因子；血小板衍生生长因子 AA 和 BB；胎盘生长因子；血管内皮生长因子 A 和 D；血管内皮生长因子受体 1、2 和 3；骨桥蛋白；转化生长因子β1 和β2；血栓调节蛋白 2；细胞间黏附分子 1；白细胞介素 6 [IL-6]；基质细胞衍生因子 1；组织金属蛋白酶抑制剂 1；和血管细胞黏附分子 1 [VCAM-1]），并通过配对 Wilcoxon 检验与基线水平进行比较。根据改良的实体瘤反应评价标准（mRECIST）评估肿瘤反应。通过非配对 Wilcoxon 检验，根据 mRECIST 标准比较反应者和非反应者的血管生成因子水平。
所有手术均技术成功，无并发症。
TAE 后有 14 种血管生成因子发生统计学上的显著变化，但大多数变化是短暂的。IL-6 仅在手术后 1 天被上调，但显示出任何因子中最大的增加。骨桥蛋白和 VCAM-1 在 TAE 后所有时间点均表现出持续上调。在 3 个月的随访影像学检查中，11 名患者对 TAE 有反应（完全缓解 6 例；部分缓解 5 例），11 名患者无反应（稳定疾病 9 例；疾病进展 2 例）。在无反应者中，TAE 后第 1 天的 IL-6 百分比变化（P=.033）和 TAE 后骨桥蛋白的平均百分比变化（P=.024）明显大于反应者。
TAE 后多种血管生成因子显著上调。VCAM-1 和骨桥蛋白表现出持续上调，而其余的则是短暂的。IL-6 和骨桥蛋白与 TAE 后的放射学反应显著相关。
放射学学会，2017 年。
