超声造影对肝细胞癌微血管形态术前分型的可行性

摘要

Objective To explore the feasibility of contrast-enhanced ultrasonograhy (CEUS) in preoperative classification of hepatocellular carcinoma (HCC) microvascular morphology.Methods Totally 94 HCC patients who underwent CEUS were analyzed retrospectively. And the offline Time-intensity curve (TIC) were drawn using SonoTumor. The tumor size, alpha fetoprotein (AFP), cirrhosis, Child-Pugh classifi cation, tumor differentiation and TNM stage were statistically analyzed. The intratumoralmicrovessels of HCC in 94 cases were evaluated by CD34 immunohistochemical staining. The relationship between intratumoral microvessel morphology and CEUS parameters were analyzed.Results CD34 immunohistochemical staining showed three distinct microvessel types in 94 cases of HCC: 28 cases of capillary-like type, 14 cases of sinusoid-like type and 52 cases of mixed type. There were no significant differences of clinical data among three microvascular morphology types. The parameters of peak strength (PE), rise time (RT), wash-in rate (WiR), wash-in perfusion index (WiPI), wash-in area under the curve (WiAUC) and mean transit time (MTT) in 28 cases of capillary-like type were (4350.7±2566.0) a.u, (10.7±3.2) s, (717.0±489.9) a.u, (12820.3±8331.6 )a.u, (128 240.8±74 487.1) a.u, (71.9±33.1)s. Those parameters in 14 cases of sinusoid-like type were (2471.6±1107.1) a.u, (16.2±4.2)s, (321.9±171) a.u, (5 561.4±2 938.0) a.u, (86 780.1±47 563.7) a.u, (117.8±69.6)s. And in 52 cases of mixed type they were (3563.2±2343.1) a.u, (14.1±4.8)s, (519.4±403.2) a.u, (9 015.3±6 884.7)a.u, (128 240.8±74 487.1) a.u, (71.9±33.1) s respectively. The CEUS parameters of WiR, WiPI in capillary-like type HCC patients were higher than sinusoid-like type and mixed type HCC patients, while RT was lower than sinusoid-like type and mixed type HCC patients, and the differences were signifi cant (WiR: t=3.87, 3.3, bothP=0.05; WiPI: t=2.96, 2.06, bothP=0.05; RT: t=3.19, 2.34, bothP=0.05). The parameter of PE in capillary-like type HCC patients were signifi cantly higher than that in sinusoid-like type HCC patients (t=2.51,P=0.05). And the parameter of PE in capillary-like type HCC patients was higher than mixed HCC patients, but there was no signifi cant difference. The parameters of PE, WiR and WiPI in mixed type HCC patients were higher than that in sinusoid-like type HCC patients, while RT in mixed type HCC patients were lower than that in sinusoid-like type HCC patients, but there were no signifi cant differences. No signifi cant differences of WiAUC and MTT were observed in HCC patients with different microvascular morphology.Conclusions There were signifi cant differences of CEUS parameters in different microvascular morphology types. And CEUS, as a non-invasive method, can be used for preliminary preoperative prediction of microvascular morphology in HCC patients.%目的：分析超声造影（CEUS）定量参数与肝细胞癌（HCC）微血管形态的关系，探讨应用CEUS术前对HCC微血管形态进行分型的可行性。方法回顾性分析2010年4月至2011年12月于中山大学肿瘤防治中心接受CEUS检查并行手术切除及病理证实的94例HCC患者，并脱机采用SonoTumor软件行时间-强度曲线分析，软件自动获得峰值强度（PE）、上升时间（RT）、灌注速率（WiR）、灌注指数（WiPI）、曲线下面积（WiAUC）和平均渡越时间（MTT）。术后病理标本行CD34免疫组化染色，对其进行微血管形态分型。采用Fisher确切概率法和χ2检验比较不同微血管形态分型HCC患者临床参数差异；采用单因素方差分析比较不同微血管形态分型HCC的PE、RT、WiR、WiPI、WiAUC、MTT差异，进一步组间两两比较采用LSD-t检验。结果 CD34免疫组化染色结果显示，94例HCC可分为毛细血管型28例、血窦型14例、混合型52例。不同微血管形态分型HCC患者的临床参数差异均无统计学意义。毛细血管型HCC的PE、RT、WiR、WiPI、WiAUC和MTT分别为（4350.7±2566.0）a.u、（10.7±3.2）s、（717.0±489.9）a.u、（12820.3±8331.6）a.u、（128240.8±74487.1） a.u、（71.9±33.1）s，血窦型HCC分别为（2471.6±1107.1）a.u、（16.2±4.2）s、（321.9±171.8）a.u、（5561.4±2938.0）a.u、（86780.1±47563.7） a.u、（117.8±69.6）s，混合型HCC分别为（3563.2±2343.1）a.u、（14.1±4.8）s、（519.4±403.2）a.u、（9015.3±6884.7）a.u、（110208.4±77511.3）a.u、（107.5±88.2）s。其中PE、WiR及WiPI呈毛细血管型-混合型-血窦型逐渐降低的趋势，RT呈毛细血管型-混合型-血窦型逐渐增加的趋势。毛细血管型HCC与血窦型、混合型HCC的WiR、WiPI、RT差异均有统计学意义（WiR：t值分别为3.87、3.3；WiPI：t值分别为2.96、2.06；RT：t值分别为3.19、2.34；均P＜0.05）；毛细血管型HCC与血窦型HCC的PE差异有统计学意义（t=2.51，P＜0.05）；毛细血管型HCC与混合型HCC的PE差异无统计学意义；混合型HCC与血窦型HCC的PE、WiR、WiPI、RT差异均无统计学意义。不同微血管形态分型HCC的WiAUC及MTT差异均无统计学意义。结论不同微血管形态分型HCC的CEUS定量参数差异显著，可利用非入侵性的CEUS技术对HCC的微血管形态进行初步判断。