术前钆塞酸二钠增强磁共振成像检查预测肝细胞癌微血管侵犯和瘤内三级淋巴结构的临床价值

Clinical value of preoperative Gd-EOB-DTPA-enhanced magnetic resonance imaging in predic-ting microvascular invasion and intratumoral tertiary lymphoid structures in hepatocellular carcinoma

  • 摘要:
    目的 探讨术前钆塞酸二钠(Gd‑EOB‑DTPA)增强磁共振成像(MRI)检查预测肝细胞癌微血管侵犯(MVI)和瘤内三级淋巴结构(TLSs)的临床价值。
    方法 采用回顾性队列研究方法。收集2021年6月至2023年6月陆军军医大学第一附属医院收治的304例及重庆医科大学附属第二医院收治的10例肝细胞癌患者的临床病理资料;男272例,女42例;年龄为(56±11)岁。314例患者通过随机数字表法按7∶3比例分为训练集220例和验证集94例。314例患者中,合并MVI、TLSs肝细胞癌(MT⁃HCC)患者106例,非MT‑HCC患者208例。患者术前均行Gd‑EOB‑DTPA增强MRI检查并完成根治性切除术。观察指标:(1)MT‑HCC和非MT‑HCC患者临床病理特征。(2)MT‑HCC和非MT‑HCC患者影像学特征。(3)诊断MT‑HCC相关的影像学特征。(4)MT‑HCC的列线图预测模型构建及评估。正态分布的计量资料组间比较采用t检验;偏态分布的计量资料组间比较采用非参数秩和检验。单因素分析根据数据类型采用对应的统计学方法。多因素分析采用logistic回归模型。根据多因素分析结果构建列线图预测模型,绘制受试者工作特征曲线(ROC),以曲线下面积评估列线图预测模型的效能。采用校准曲线和决策曲线分析评估列线图预测模型的校准度和临床有效性。
    结果 (1)MT‑HCC和非MT⁃HCC患者临床病理特征。训练集患者中,MT‑HCC和非MT‑HCC患者年龄、白细胞计数、甲胎蛋白水平比较,差异均有统计学意义(t=2.488,Z=-2.515,χ2=4.014,P<0.05)。(2)MT‑HCC和非MT‑HCC患者影像学特征。训练集患者中,MT‑HCC和非MT‑HCC患者肿瘤形态、瘤内出血、动脉期瘤周异常强化、包膜、瘤内坏死或缺血>20%、瘤内坏死或缺血>50%、肝胆期瘤周低信号、静脉内癌栓、动脉期环状高强化、马赛克结构比较,差异均有统计学意义(χ2=8.811、5.586、13.962、31.616、10.154、4.835、5.111、14.425、7.112、5.526,P<0.05)。(3)诊断MT‑HCC相关的影像学特征。多因素分析结果显示:缺乏瘤内出血、包膜不完整、马赛克结构均是诊断MT‑HCC的独立危险因素(风险比=3.846、7.827、2.345,P<0.05)。(4)MT‑HCC的列线图预测模型构建及评估。根据多因素分析结果纳入缺乏瘤内出血、包膜不完整、马赛克结构构建MT‑HCC的列线图预测模型。ROC曲线显示:列线图预测模型训练集的曲线下面积为0.778(95%可信区间为0.714~0.843)、灵敏度为0.857、特异度为0.573;验证集上述指标分别为0.825(95%可信区间为0.745~0.926)、0.655、0.877。列线图预测模型训练集和验证集的校准曲线与标准曲线均贴合较好,校准度较高。决策曲线显示:训练集阈值为0.130~0.690、验证集阈值为0.060~0.750,临床应用时可获得净收益。
    结论 缺乏瘤内出血、包膜不完整、马赛克结构是诊断MT‑HCC的独立危险因素。基于影像学特征构建的列线图模型可预测MT‑HCC。

     

    Abstract:
    Objective To investigate the clinical value of preoperative gadolinium ethoxy-benzyldiethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in predicting microvascular invasion (MVI) and intratumoral tertiary lymphoid structures (TLSs) in hepatocellular carcinoma (HCC).
    Methods The retrospective cohort study was conducted. The clinicopathological data of 304 HCC patients who were admitted to The First Affiliated Hospital of Army Medical University and 10 HCC patients who were admitted to The Second Affiliated Hospital of Chongqing Medical University from June 2021 to June 2023 were collected. There were 272 males and 42 females, aged (56±11)years. Using a random number table method, patients were divided into a training set including 220 cases and a validation set including 94 cases in a 7:3 ratio. Among the 314 patients, 106 cases had MVI and TLSs-positive HCC (MT-HCC), and 208 cases had non-MT-HCC. All patients underwent preoperative Gd-EOB-DTPA-enhanced MRI and radical resection. Observation indicators: (1) clinicopathological characteristics of MT-HCC and non-MT-HCC patients; (2) imaging characteristics of MT-HCC and non-MT-HCC patients; (3) imaging features associated with MT-HCC diagnosis; (4) nomogram predictive model construction and evaluation for MT-HCC. Comparison of measurement data with normal distribution between groups was analyzed using the t test. Comparison of measurement data with skewed distribution between groups was analyzed using the nonpara-meter rank sum test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the logistic regression model. A nomo-gram predictive model was constructed based on results of multivariate analysis, and receiver operating characteristic (ROC) curves were plotted to evaluate the model's performance with the area under curve (AUC). Calibration curve and decision curve analyses were used to assess the calibration and clinical validity of nomogram predictive model.
    Results (1) Clinicopathological characteristics of MT-HCC and non-MT-HCC patients. In the training set, there were significant differences between MT-HCC and non-MT-HCC patients in terms of age, white blood cell count, and alpha fetoprotein level (t=2.488, Z=-2.515, χ2=4.014, P<0.05). (2) Imaging characteristics of MT-HCC and non-MT-HCC patients. In the training set, there were significant differences in tumor morphology, intratumoral hemorrhage, peritumoral abnormal enhancement in arterial phase, capsule presence, intratumoral necrosis or ischemia >20%, intratumoral necrosis or ischemia >50%, peritumoral hypointensity in the hepatobiliary phase, intravascular tumor thrombus, arterial phase rim-like hyperenhancement, and mosaic architecture between MT-HCC and non-MT-HCC patients (χ2=8.811, 5.586, 13.962, 31.616, 10.154, 4.835, 5.111, 14.425, 7.112, 5.526, P<0.05). (3) Imaging features associated with MT-HCC diagnosis. Results of multivariate analysis identified the absence of intratumoral hemorrhage, incom-plete capsule, and mosaic architecture as independent risk factors for diagnosing MT-HCC (hazard ratio=3.846, 7.827, 2.345, P<0.05). (4) Nomogram predictive model construction and evaluation for MT-HCC. A nomogram predictive model for MT-HCC was constructed based on the independent risk factors (absence of intratumoral hemorrhage, incomplete capsule, and mosaic architecture) iden-tified in the multivariate analysis. The ROC curve analysis showed that AUC of nomogram predictive model was 0.778 (95% confidence interval as 0.714-0.843), with sensitivity and specificity of 0.857 and 0.573 in the training set. In the validation set, the area under the curve, sensitivity, and specifi-city were 0.825 (95% confidence interval as 0.745-0.926), 0.655, and 0.877, respectively. The calibra-tion curves for both the training set and the validation set closely aligned with the standard curve, indicating high calibration accuracy. The decision curve analysis demonstrated net clinical benefits at thresholds of 0.130-0.690 in the training set and 0.060-0.750 in the validation set.
    Conclusions The absence of intratumoral hemorrhage, incomplete capsule, and mosaic architecture are independent risk factors for diagnosing MT-HCC. A nomogram model based on imaging features can predict MT-HCC in HCC patients.

     

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