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中华医学超声杂志(电子版) ›› 2025, Vol. 22 ›› Issue (05) : 451 -461. doi: 10.3877/cma.j.issn.1672-6448.2025.05.011

腹部超声影像学

基于超声造影定量指标预测肝细胞癌微血管侵犯及评估其复发的研究
顾怡君1, 李奕冉1, 钱艺1, 蒋栋1,()   
  1. 1. 200438 上海,海军军医大学第三附属医院东方肝胆外科医院超声诊疗科
  • 收稿日期:2025-01-14 出版日期:2025-05-01
  • 通信作者: 蒋栋
  • 基金资助:
    东方肝胆外科医院医工交叉研究项目(2022YGJ001)东方肝胆外科医院国家自然科学基金青年培养项目(2021GZR003)

Prediction of microvascular invasion and postoperative recurrence in hepatocellular carcinoma based on quantitative indices derived from contrast-enhanced ultrasonography

Yijun Gu1, Yiran Li1, Yi Qian1, Dong Jiang1,()   

  1. 1. Department of Ultrasound Diagnosis and Treatment, Shanghai Eastern Hepatobiliary Surgery Hospital,Shanghai 200438, China
  • Received:2025-01-14 Published:2025-05-01
  • Corresponding author: Dong Jiang
引用本文:

顾怡君, 李奕冉, 钱艺, 蒋栋. 基于超声造影定量指标预测肝细胞癌微血管侵犯及评估其复发的研究[J/OL]. 中华医学超声杂志(电子版), 2025, 22(05): 451-461.

Yijun Gu, Yiran Li, Yi Qian, Dong Jiang. Prediction of microvascular invasion and postoperative recurrence in hepatocellular carcinoma based on quantitative indices derived from contrast-enhanced ultrasonography[J/OL]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2025, 22(05): 451-461.

目的

探讨超声造影定量指标在预测肝细胞癌(HCC)患者微血管侵犯(MVI)及术后复发中的应用价值,为临床决策提供依据。

方法

选择海军军医大学第三附属医院东方肝胆外科医院在2022 年8 月至2023 年8 月间收治的180 例HCC 患者,术前行超声造影检查,并完成肝切除术及术后病理诊断。采集患者基础信息及临床数据(包括肿瘤情况、实验室检查等),按术后病理MVI 情况分为MVI 阴性组(M0 级)与MVI 阳性组(M1 及M2 级)。术后患者规范随访至2024 年8 月1 日,记录复发情况。采用Vuebox 软件量化分析超声造影定量指标,如占位和肝组织流入相斜率(WoR),采用Logistic 回归模型分析与MVI 及术后复发相关的影响因素,并绘制其受试者操作特征(ROC)曲线评估预测效能。

结果

与MVI 阴性组(92 例)相比,MVI 阳性组(88 例)患者肿瘤数量多发比例高(38.60% vs 20.70%),总胆红素水平高[(16.70±6.97)μmol/L vs (13.82±6.63)μmol/L],凝血酶原时间长[(12.45±1.24)s vs (11.76±1.32)s],国际标准化比值高[(1.04±0.11) vs (0.98±0.12)], 占位WoR 低[528.10(65.05,591.82)a.u vs 996.09(131.63,1208.03)a.u],肝组织WoR 高[247.97(64.5,375.52)a.u vs 157.19(26.55,211.11)a.u],差异均具有统计学意义(χ2=7.002,P=0.008;t=-2.842,P=0.008;t=-3.452,P=0.001;t=-3.354,P=0.002;Z=-2.424,P=0.031;Z=-2.379,P=0.027)。多元Logistic 回归分析显示,肿瘤数量(B=0.877,OR=2.405,P=0.019)、 凝血酶原时间(B=0.362,OR=1.437,P=0.012)、 占位WoR(B=0.000,OR=1.000,P=0.022)为独立预测HCC 患者MVI 的因素,三者联合预测MVI 的ROC 曲线下面积为0.754。术后复发预测方面,占位WoR(B=0.000,OR=1.000,P=0.025)和肝组织WoR(B=0.001,OR=1.001,P=0.042)与术后1 年内复发密切相关,两参数预测术后复发的ROC 曲线下面积分别为0.673(95%CI:0.568 ~0.778)和0.625(95%CI:0.526 ~0.724)。

结论

超声造影定量指标尤其是占位WoR 和肝组织WoR,在术前预测HCC 患者MVI 及术后复发方面具有显著临床价值,可为制定个体化手术方案和预测患者预后提供重要参考。

Objective

To evaluate the value of contrast-enhanced ultrasound (CEUS)quantitative parameters in predicting microvascular invasion (MVI) and postoperative recurrence in hepatocellular carcinoma (HCC) patients, in order to provide a basis for clinical decision-making.

Methods

A total of 180 HCC patients admitted to Shanghai Eastern Hepatobiliary Surgery Hospital between August 2022 and August 2023 were included.Patient baseline characteristics and clinical data were collected.Based on postoperative pathology, the patients were divided into either an MVInegative group (M0) or an MVI-positive group (M1 and M2).The postoperative patients were followed until August 1, 2024, and recurrence was recorded.CEUS data including the washout ratio (WoR) of both the lesion and surrounding liver parenchyma were quantitatively analyzed.Logistic regression analysis was performed to identify independent predictors of MVI and 1-year postoperative recurrence.Receiver operating characteristic (ROC) curves were generated to evaluate predictive performance.

Results

Compared to the MVI-negative group (n=92), the MVI-positive group (n=88) exhibited significantly different tumor number (38.60% vs 20.70%; χ2=7.002, P=0.008), total bilirubin [(16.70±6.97) μmol/L vs (13.82±6.63)μmol/L; t=-2.842, P=0.008], prothrombin time [(12.45±1.24) s vs (11.76±1.32) s; t=-3.452, P=0.001],international normalized ratio [(1.04±0.11) vs (0.98±0.12); t=-3.354, P=0.002], lesion WoR [528.10(65.05, 591.82) a.u vs 996.09 (131.63, 1208.03) a.u; Z=-2.424, P=0.031], and liver parenchyma WoR[247.97 (64.5, 375.52) a.u vs 157.19 (26.55, 211.11) a.u; Z=-2.379, P=0.027].Multivariate logistic regression analysis identified tumor number (B=0.877, odds ratio (OR)=2.405, P=0.019), prothrombin time (B=0.362,OR=1.437, P=0.012), and lesion WoR (B=0.000, OR=1.000, P=0.022) as independent predictors of MVI,and their combination had an area under the ROC curve (AUC) of 0.754.Lesion WoR (B=0.000, OR=1.000,P=0.025) and liver parenchyma WoR (B=0.001, OR=1.001, P=0.042) were significantly associated with 1-year recurrence, yielding AUC values of 0.673 (95%CI: 0.568-0.778) and 0.625 (95%CI: 0.526-0.724),respectively.

Conclusion

CEUS quantitative parameters, particularly lesion WoR and liver parenchyma WoR, demonstrate significant clinical value in the preoperative prediction of MVI and postoperative recurrence in HCC patients.These findings provide critical insights for individualized surgical planning and prognostic assessment, highlighting their potential for broad clinical application.

图1 肝细胞癌患者超声造影检查及定量参数分析。超声检查示肝右叶一类圆形稍低回声区,大小约4.5 cm×3.8 cm(图a),注射造影剂后,在动脉期(图b)病灶呈现快速、不均匀、高增强,表现为肿瘤的高血供;在门静脉期(图c)和延迟期(图d),病灶则表现为低增强,提示病灶血流灌注不均。定量分析(图e):选择包含病灶及周围肝组织的参照区(蓝色区域),并绘制病灶的感兴趣区域(ROI,绿色)以及相同深度的周围肝组织ROI(黄色),生成时间-强度曲线(TIC,图f)。TIC 分析发现病灶(绿色曲线)在动脉期早期呈现快速增强后迅速消退,而周围肝组织(黄色曲线)则呈现较为平缓的增强曲线,提示病灶与正常肝组织之间存在明显的血流动力学差异
表1 MVI 阴性组与MVI 阳性组肝细胞癌患者临床资料对比
特征 MVI阴性组(n=92) MVI阳性组(n=88) 统计值 P值
基本信息
性别[例(%)] χ2=1.262 0.261
79(85.90) 70(79.50)
13(14.10) 18(20.50)
年龄(岁,x̄ ± s) 53.83±9.90 55.26±11.21 t=-0.911 0.153
BMI(kg/m²,x̄ ± s) 23.53±2.70 23.3±3.49 t=0.497 0.618
高血压[例(%)] χ2=0.531 0.982
78(84.80) 71(80.70)
14(15.20) 42(19.30)
糖尿病[例(%)] χ2=1.731 0.188
85(92.40) 76(86.40)
7(7.60) 12(13.60)
吸烟史[例(%)] χ2=0.006 0.940
58(63.00) 55(62.51)
34(37.00) 33(37.50)
饮酒史[例(%)] χ2=0.279 0.597
77(83.70) 71(80.70)
15(16.30) 17(19.30)
直径(cm) 5.99±4.46 5.88±4.04 t=0.183 0.254
乙肝史[例(%)] χ2=1.339 0.247
46(56.10) 36(43.90)
46(50.00) 52(58.60)
丙肝史[例(%)] χ2=1.519 0.218
71(56.35) 55(43.65)
21(38.89) 33(61.11)
肝硬化[例(%)] χ2=2.605 0.107
58(63.00) 45(51.10)
34(37.00) 43(48.90)
肿瘤数目[例(%)] χ2=7.002 0.008
单个 73(79.30) 54(61.40)
多个 19(20.70) 34(38.60)
实验室检查
总胆红素(μmol/L,x̄ ± s) 13.82±6.63 16.70±6.97 t=-2.842 0.008
直接胆红素(μmol/L,x̄ ± s) 6.36±3.58 6.74±4.18 t=-0.633 0.526
间接胆红素(μmol/L,x̄ ± s) 9.10±4.38 9.45±5.05 t=-0.479 0.631
白蛋白(g/L,x̄ ± s) 41.63±6.64 40.18±4.83 t=1.606 0.120
前白蛋白(g/L,x̄ ± s) 168.16±60.12 161.75±69.94 t=0.602 0.545
丙氨酸[μmol/L,M(Q₁,Q₃)] 35.00(18.00,41.75) 45.06(21.00,47.00) Z=-1.720 0.105
门冬氨酸[μmol/L,M(Q₁,Q₃)] 41.78(23.00,52.00) 59.34(26.00,64.00) Z=-2.073 0.060
谷氨酰[μmol/L,M(Q₁,Q₃)] 130.98(37.00,158.50) 140.22(53.00,169.00) Z=-0.381 0.702
尿素(μmol/L,x̄ ± s) 4.81±1.42 4.75±1.44 t=0.265 0.790
肌酐(μmol/L,x̄ ± s) 69.72±19.44 70.13±16.41 t=-0.152 0.879
尿酸[μmol/L,M(Q₁ ,Q)] 293.23(232.75,357.00) 301.20(234.50,36.00) Z=-0.512 0.607
凝血酶原时间(s) 11.76±1.32 12.45±1.24 t=-3.452 0.001
特征 MVI阴性组(n=92) MVI阳性组(n=88) 统计值 P值
国际标准化比值(x̄ ± s) 0.98±0.12 1.04±0.11 t=-3.354 0.002
甲胎蛋白[ng/ml,M(Q₁,Q₃)] 448.05(4.90,1210.00) 501.36(4.2,1210.00) Z=-0.623 0.531
癌胚抗原[ng/ml,M(Q₁,Q₃)] 4.67(1.40,3.63) 2.84(1.30,3.88) Z=1.128 0.410
异常凝血酶原[mAUg/ml,M(Q₁,Q₃)] 25739.48(32.00,6554.00) 11745.37(26.00,3916.00) Z=1.004 0.380
白细胞(×10⁹/L,x̄ ± s) 5.74±2.06 6.33±2.77 t=-1.546 0.130
血红蛋白(g/L,x̄ ± s) 136.73±18.93 131.48±18.11 t=1.817 0.074
血小板(×10⁹/L,x̄ ± s) 173.44±72.32 183.2±79.09 t=-0.828 0.408
中性粒细胞(×10⁹/L,x̄ ± s) 3.86±1.76 4.24±2.38 t=-1.211 0.232
淋巴细胞[×10⁹/L,M(Q₁,Q₃)] 1.72(1.03,1.67) 1.40(1.03,1.71) Z=-0.786 0.501
超声造影定量指标[M(Q₁,Q₃)]
占位PE(a.u) 10829.93(2742.93,15060.23) 10935.35(2946.45,13211.70) Z=-0.052 0.958
占位MeanLin(a.u) 4277.52(1288.50,5093.47) 4082.49(1321.66,5464.57) Z=0.319 0.749
占位WiAUC(a.u) 79231.59(20894.73,105250.5) 75894.57(18364.50,93539.88) Z=0.274 0.783
占位RT(s) 12.77(7.24,15.92) 13.16(7.52,16.91) Z=-0.320 0.748
占位MTT(s) 138.14(39.78,175.51) 137.16(42.24,154.46) Z=0.043 0.966
占位TTP(s) 16.75(11.55,20.24) 17.59(10.76,23.08) Z=-0.649 0.516
占位WiR(a.u) 1805.88(376.69,2605.32) 2119.21(326.61,1946.20) Z=-0.691 0.491
占位WiPI(a.u) 7059.97(1738.35,10097.61) 7085.46(1967.32,8360.77) Z=-0.020 0.984
占位WoAUC(a.u) 184795.40(47501.09,227755.15) 164008.5(40307.43,228182.89) Z=0.644 0.526
占位WiWoAUC(a.u) 257046.99(70666.41,303769.59) 216766.84(77191.04,264680.46) Z=1.046 0.299
占位FT(s) 30.46(13.88,43.10) 29.3(14.09,44.07) Z=0.327 0.742
占位WoR(a.u) 996.09(131.63,1208.03) 528.10(65.05,591.82) Z=-2.424 0.031
占位QOF(%) 66.73(51.22,83.53) 56.11(41.81,72.38) Z=3.547 0.001
占位Area(cm²) 1.79(0.45,1.51) 3.09(0.62,1.67) Z=-1.749 0.104
肝组织MeanLin(a.u) 3579.51(1526.70,4698.39) 4072.64(1359.78,5215.37) Z=-0.864 0.390
肝组织PE(a.u) 6627.29(2606.59,8848.99) 7574.41(2869.76,10115.55) Z=-0.870 0.386
肝组织WiAUC(a.u) 99327.21(40965.60,144788.25) 103283.69(35975.08,135759.75) Z=-0.295 0.767
肝组织RT(s) 26.00(18.30,30.55) 23.35(17.76,29.09) Z=1.596 0.118
肝组织MTT(s) 183.82(55.85,290.67) 174.74(47.83,262.24) Z=0.370 0.710
肝组织TTP(s) 33.49(24.62,38.27) 31.66(24.04,37.25) Z=0.993 0.323
肝组织WiR(a.u) 513.44(143.46,622.81) 633.32(182.37,705.15) Z=-1.025 0.316
肝组织WiPI(a.u) 4334.19(1670.28,5993.01) 4925.64(1859.23,6552.49) Z=-0.841 0.402
肝组织WoAUC(a.u) 249813.16(102952.53,396677.02) 264657.32(73001.75,377809.59) Z=-0.392 0.694
肝组织WiWoAUC(a.u) 352237.04(148904.49,509769.22) 375104.48(97494.96,504870.72) Z=-0.436 0.661
肝组织FT(s) 57.60(38.48,69.57) 53.93(33.51,75.28) Z=0.833 0.405
肝组织WoR(a.u) 157.19(26.55,211.11) 247.97(64.5,375.52) Z=-2.379 0.027
肝组织QOF(%) 58.35(41.63,78.60) 55.68(39.27,69.98) Z=0.862 0.388
肝组织Area(cm²) 1.04(0.62,1.25) 1.01(0.58,1.27) Z=0.263 0.791
表2 与肝细胞癌患者微血管侵犯相关的单因素Logistic 回归分析
因素 B值 标准误差 瓦尔德 OR值(95%置信区间) P值
基本信息
性别 0.446 0.399 1.250 1.563(0.714~3.418) 0.264
年龄 0.013 0.014 0.832 1.013(0.985~1.042) 0.362
BMI -0.024 0.048 0.249 0.976(0.888~1.073) 0.618
高血压 0.288 0.396 0.528 1.334(0.613~2.901) 0.467
糖尿病 0.651 0.501 1.687 1.917(0.718~5.120) 0.194
吸烟史 0.023 0.308 0.006 1.024(0.559~1.873) 0.940
饮酒史 0.206 0.391 0.279 1.229(0.572~2.643) 0.597
直径 -0.006 0.035 0.034 0.994(0.927~1.064) 0.854
乙肝史 0.348 0.301 1.335 1.417(0.785~2.558) 0.248
丙肝史 1.009 0.850 1.409 2.744(0.518~14.531) 0.235
肝硬化 0.489 0.304 2.591 1.630(0.899~2.955) 0.107
肿瘤数目 0.883 0.338 6.830 2.419(1.247~4.692) 0.009
实验室检查
总胆红素 0.068 0.025 7.145 1.071(1.018~1.125) 0.008
直接胆红素 0.025 0.040 0.402 1.026(0.948~1.109) 0.526
间接胆红素 0.016 0.033 0.230 1.016(0.952~1.084) 0.631
白蛋白 -0.046 0.029 2.423 0.955(0.902~1.012) 0.120
前白蛋白 -0.002 0.003 0.366 0.998(0.994~1.003) 0.545
丙氨酸 0.008 0.005 2.628 1.008(0.998~1.018) 0.105
门冬氨酸 0.008 0.004 3.539 1.008(1.000~1.016) 0.060
谷氨酰 0.000 0.001 0.146 1.000(0.998~1.002) 0.702
尿素 -0.029 0.109 0.071 0.971(0.785~1.203) 0.790
肌酐 0.001 0.008 0.023 1.001(0.985~1.018) 0.879
尿酸 0.001 0.002 0.264 1.001(0.998~1.004) 0.607
凝血酶原时间 0.445 0.140 10.134 1.561(1.187~2.053) 0.001
国际标准化比值 4.925 1.585 9.651 137.685(6.158~3078.26) 0.002
甲胎蛋白 0.000 0.000 0.392 1.000(1.000~1.001) 0.531
癌胚抗原 -0.033 0.040 0.678 0.968(0.896~1.046) 0.410
异常凝血酶原 0.000 0.000 0.770 1.000(1.000~1.000) 0.380
白细胞 0.103 0.068 2.287 1.108(0.970~1.266) 0.130
血红蛋白 -0.016 0.009 3.182 0.984(0.968~1.002) 0.074
血小板 0.002 0.002 0.685 1.002(0.998~1.006) 0.408
中性粒细胞 0.089 0.074 1.431 1.093(0.945~1.265) 0.232
淋巴细胞 -0.059 0.087 0.453 0.943(0.794~1.119) 0.501
超声造影定量指标
占位MeanLin 0.000 0.000 0.103 1.000(1.000~1.000) 0.749
占位PE 0.000 0.000 0.003 1.000(1.000~1.000) 0.958
占位WiAUC 0.000 0.000 0.076 1.000(1.000~1.000) 0.783
占位RT 0.006 0.019 0.103 1.006(0.970~1.043) 0.748
占位MTT 0.000 0.001 0.002 1.000(0.998~1.002) 0.966
占位TTP 0.011 0.017 0.422 1.011(0.978~1.046) 0.516
占位WiR 0.000 0.000 0.474 1.000(1.000~1.000) 0.491
占位WiPI 0.000 0.000 0.000 1.000(1.000~1.000) 0.984
占位WoAUC 0.000 0.000 0.402 1.000(1.000~1.000) 0.526
占位WiWoAUC 0.000 0.000 1.078 1.000(1.000~1.000) 0.299
占位FT -0.002 0.007 0.108 0.998(0.983~1.012) 0.742
占位WoR 0.000 0.000 4.658 1.000(1.000~1.000) 0.031
因素 B 值 标准误差 瓦尔德 OR 值(95%置信区间) P 值
占位 Area 0.060 0.037 2.640 1.06 (20.988 ~ 1.142) 0.104
肝组织 MeanLin 0.000 0.000 0.738 1.000 (1.000 ~ 1.000) 0.390
肝组织 PE 0.000 0.000 0.753 1.000 (1.000 ~ 1.000) 0.386
肝组织 WiAUC 0.000 0.000 0.088 1.000 (1.000 ~ 1.000) 0.767
肝组织 RT -0.022 0.014 2.447 0.978 (0.951 ~ 1.006) 0.118
肝组织 MTT 0.000 0.001 0.138 1.000 (0.998 ~ 1.001) 0.710
肝组织 TTP -0.012 0.012 0.978 0.988 (0.964 ~ 1.012) 0.323
肝组织 WiR 0.000 0.000 1.005 1.000 (1.000 ~ 1.000) 0.316
肝组织 WiPI 0.000 0.000 0.703 1.000 (1.000 ~ 1.000) 0.402
肝组织 WoAUC 0.000 0.000 0.155 1.000 (1.000 ~ 1.000) 0.694
肝组织 WiWoAUC 0.000 0.000 0.192 1.000 (1.000 ~ 1.000) 0.661
肝组织 FT -0.005 0.006 0.695 0.995 (0.983 ~ 1.007) 0.405
肝组织 WoR 0.002 0.001 4.899 1.002 (1.000 ~ 1.003) 0.027
肝组织 Area -0.059 0.224 0.070 0.942 (0.607 ~ 1.463) 0.791
表3 与肝细胞癌患者微血管侵犯相关的多因素Logistic 回归分析
图2 预测肝细胞癌微血管侵犯的多因素受试者操作特征曲线图 注:WoR 为流出相斜率
表4 肝超声造影定量指标与肝细胞癌复发相关的单因素Logistic 回归分析
超声造影定量指标 B 值 标准误差 瓦尔德 OR 值(95%置信区间) P 值
占位 MeanLin 0.000 0.000 1.956 1.000 (1.000~1.000) 0.162
占位 PE 0.000 0.000 7.307 1.000 (1.000~1.000) 0.007
占位 WiAUC 0.000 0.000 2.299 1.000 (1.000~1.000) 0.129
占位 RT -0.003 0.025 0.013 0.997 (0.950~1.046) 0.909
占位 MTT 0.000 0.001 0.051 1.000 (0.997~1.002) 0.821
占位 TTP -0.002 0.023 0.010 0.998 (0.937~1.031) 0.919
占位 WiR 0.000 0.000 3.809 1.000 (1.000~1.000) 0.051
占位 WiPI 0.000 0.000 3.456 1.000 (1.000~1.000) 0.063
占位 WoAUC 0.000 0.000 0.665 1.000 (1.000~1.000) 0.415
占位 WiWoAUC 0.000 0.000 0.520 1.000 (1.000~1.000) 0.471
占位 FT -0.012 0.011 1.252 0.988 (0.966~1.009) 0.263
占位 WoR 0.000 0.000 5.007 1.000 (1.000~1.000) 0.025
占位 Area -0.025 0.047 0.270 0.976 (0.889~1.070) 0.603
肝组织 MeanLin 0.000 0.000 1.540 1.000 (1.000~1.000) 0.215
肝组织 PE 0.000 0.000 2.701 1.000 (1.000~1.000) 0.100
肝组织 WiAUC 0.000 0.000 2.536 1.000 (1.000~1.000) 0.111
肝组织 RT -0.006 0.018 0.117 0.994 (0.959~1.030) 0.732
肝组织 MTT 0.000 0.001 0.041 1.000 (0.998~1.003) 0.839
肝组织 TTP 0.001 0.016 0.006 1.001 (0.971~1.033) 0.936
肝组织 WiR 0.000 0.000 2.049 1.000 (1.000~1.001) 0.152
肝组织 WiPI 0.000 0.000 2.492 1.000 (1.000~1.000) 0.114
肝组织 WoAUC 0.000 0.000 1.777 1.000 (1.000~1.000) 0.183
肝组织 WiWoAUC 0.000 0.000 1.953 1.000 (1.000~1.000) 0.162
肝组织 FT -0.007 0.008 0.714 0.993 (0.977~1.009) 0.398
肝组织 WoR 0.001 0.001 4.132 1.001 (1.000~1.003) 0.042
肝组织 Area 0.014 0.290 0.002 1.014 (0.574~1.791) 0.962
图3 占位流出相斜率(WoR)和肝组织WoR 预测肝细胞癌患者术后复发的受试者操作特征曲线图
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