肝细胞癌血管包绕肿瘤细胞簇阳性的危险因素分析及其风险评分模型的应用价值

Risk factor analysis of hepatocellular carcinoma with vessels encapsulating tumor clusters and the application value of its risk scoring model

  • 摘要:
    目的 探讨影响肝细胞癌血管包绕肿瘤细胞簇(VETC)阳性的危险因素及VETC风险评分模型的应用价值。
    方法 采用回顾性横断面研究方法。收集2017年1月至2020年4月国内2家医学中心收治的149例(江南大学附属中心医院97例和河北医科大学附属邢台市人民医院52例)肝细胞癌患者的临床病理资料;男116例,女33例;年龄为(58±12)岁;VETC阳性74例,VETC阴性75例。观察指标:(1)VETC阳性与阴性患者的临床特征。(2)VETC阳性与阴性患者的影像学检查特征。(3)影响肝细胞癌患者VETC阳性的多因素分析。(4)VETC风险评分模型构建和效能评估。(5)模型预测和组织病理学检查确定的VETC阳性和阴性患者术后早期肿瘤复发情况。正态分布的计量资料以x±s表示,组间比较采用t检验;计数资料以绝对数表示,组间比较采用χ²检验或连续校正χ²检验。将临床特征和影像学特征有统计学意义的变量纳入多因素分析,多因素分析采用Logistic回归模型向后逐步回归法。根据Logistic回归模型结果构建VETC风险评分模型。绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC)、灵敏度、特异度和准确度及其95%可信区间(CI)。约登指数最大值为预测VETC阳性最佳截断值。VETC风险评分模型的预测值与真实值一致性采用Hosmer‑Lemeshow拟合优度检验。采用Kaplan‑Meier法计算生存率和绘制生存曲线,Log‑rank检验进行生存分析。
    结果 (1)VETC阳性与阴性患者的临床特征。术前白蛋白<36 g/L的VETC阳性患者为57例,VETC阴性患者为68例,两者比较,差异有统计学意义(χ²=5.13,P<0.05)。(2)VETC阳性与阴性患者的影像学检查特征。VETC阳性患者影像学检查特征中非周边廓清,马赛克结构,病灶内出血,晕环状强化,不光滑的肿瘤边缘,动脉期瘤周强化,瘤内动脉,肝胆期瘤周低信号,强化类型(均匀低强化、均匀高强化、不均匀强化伴裂隙、不均匀强化伴不规则环状结构),肿瘤坏死或缺血及肿瘤长径>5 cm分别为73,35,33,15,39,28,42,27,(4、5、27、38),45,46例,VETC阴性患者上述指标分别为64,16,13,3,19,15,9,13,(9、35、5、26),10,10例,两者上述指标比较,差异均有统计学意义(χ²=8.92,11.15,12.97,9.28,11.74,5.77,33.14,6.96,41.79,36.05,37.86,P<0.05)。(3)影响患者VETC阳性的多因素分析。多因素分析结果示:强化类型为不均匀强化伴裂隙、强化类型为不均匀强化伴不规则环状结构、肿瘤坏死或缺血、肿瘤长径>5 cm是影响患者VETC阳性的独立危险因素(风险比=4.18、7.62、4.23、4.08,95%CI为1.60~11.60、2.00~31.70、1.71~10.90、1.60~10.80,P<0.05)。(4)VETC风险评分模型构建和效能评估。构建VETC风险评分模型:VETC风险评分=(不均匀强化伴裂隙,有:1.0,无:0)+(不均匀强化伴不规则环状结构,有:1.5,无:0)+(肿瘤坏死或缺血,有:1.0,无:0)+(肿瘤长径>5 cm,有:1.0,无:0)。VETC风险评分模型AUC为0.86(95%CI为0.80~0.92),灵敏度、特异度和准确度分别为79.7%(95%CI为69.2%~87.3%)、80.0%(95%CI为69.6%~87.5%)和79.9%(95%CI为72.7%~85.5%)。Hosmer‑Lemeshow拟合优度检验结果显示:模型预测的VETC结果与术后组织病理学诊断结果一致性良好(P>0.05)。(5)模型预测和组织病理学检查确定的VETC阳性和阴性患者术后早期肿瘤复发情况。149例患者均获得随访,随访时间为29(26~35)个月,肿瘤复发时间为29(24~33)个月,2年肿瘤累积复发率为43.0%。模型预测的VETC阳性和阴性患者术后2年肿瘤累积复发率分别为47.8%和37.9%,两者比较,差异有统计学意义(χ²=3.90,P<0.05)。术后组织病理学检查确定的VETC阳性和阴性患者2 年肿瘤累积复发率分别为47.4%和38.1%,两者比较,差异有统计学意义(χ²=4.20,P<0.05)。
    结论 影像学特征的强化类型中不均匀强化伴裂隙或不规则环状结构、肿瘤坏死或缺血、肿瘤长径>5 cm是影响肝细胞癌患者VETC阳性的独立危险因素;以此构建的VETC风险评分模型具有良好的术前诊断效能。

     

    Abstract:
    Objective To investigate the risk factor of hepatocellular carcinoma (HCC) with vessels encapsulating tumor clusters (VETC) and the application value of its risk scoring model.
    Methods The retrospective cross‑sectional study was conducted. The clinicopathological data of 149 patients with HCC who were admitted to two medical centers, including 97 cases in the Jiangnan University Medical Center and 52 cases in the Affiliated Xingtai People′s Hospital of Hebei Medical University, from January 2017 to April 2020 were collected. There were 116 males and 33 females, aged (58±12)years. There were 74 cases with VETC and 75 cases without VETC. Observation indica-tors: (1) clinical characteristics of patients with and without VETC; (2) imaging features of patients with and without VETC; (3) multivariable analysis of HCC patients with VETC; (4) construction of VETC related risk scoring model and its performance evaluation; (5) postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the t test. Count data were described as absolutes, and comparison between groups was conducted using the chi‑square test and continuous correction chi-square test. Variables of clinical and imaging characteristics with statistically signifi-cant were included in the multivariate analysis. Multivariate analysis was conducted using the Logistic regression model of backward stepwise selection. VETC related risk scoring model was constructed based on the results of Logistic regression model. The receiver operating characteristic (ROC) curve was drawn, and the area under curve (AUC), the sensitivity, specificity, accuracy and their 95% confidence interval (CI) were calculated. The maximizing Youden index was the optimal cutoff value for VETC prediction. The Hosmer Lemeshow goodness of fit test was used to assess the consistency between VETC risk scoring model predicted VTEC status and the true VETC status. The Kaplan‑Meier method was used to calculate survival rates and draw survival curves. The Log‑rank test was used for survival analysis.
    Results (1) Clinical characteristics of patients with and without VETC. Cases with postoperative albumin <36 g/L were 57 in patients with VETC, versus 68 in patients without VETC, respectively, showing a significant difference between them (χ²=5.13, P<0.05). (2) Imaging features of patients with and without VETC. Cases with lesion imaging presence as nonperipheral washout, cases with lesion imaging presence as mosaic architecture, cases with lesion imaging presence as intratumoral hemorrhage, cases with lesion imaging presence as corona enhancement, cases with lesion imaging presence as non‑smooth tumor margin, cases with lesion imaging presence as peritumoral enhancement in arterial phase, cases with lesion imaging presence as intratumoral arteries, cases with lesion imaging presence as peritumoral hypointensity in hepatobiliary phase, cases with lesion imaging enhancement type as uniform low enhancement, uniform high enhance-ment, heterogeneous enhancement with septations and heterogeneous enhancement with irregular ring-like structures, cases with intratumoral necrosis or ischemic, cases with tumor diameter >5 cm were 73, 35, 33, 15, 39, 28, 42, 27, 4, 5, 27, 38, 45, 46 in patients with VETC, versus 64, 16, 13, 3, 19, 15, 9, 13, 9, 35, 5, 26, 10, 10 in patients without VETC, respectively, showing significant differences in the above indicators between them (χ²=8.92, 11.15, 12.97, 9.28, 11.74, 5.77, 33.14, 6.96, 41.79, 36.05, 37.86, P<0.05). (3) Multivariable analysis of patients with VETC. Results of multivariable analysis showed that lesion imaging enhancement as heterogeneous enhancement with septations, lesion imaging enhancement as heterogeneous enhancement with irregular ring‑like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm were independent risk factors influen-cing patients with VETC (odds ratio=4.18, 7.62, 4.23, 4.08, 95%CI as 1.60‒11.60, 2.00‒31.70, 1.71‒10.90, 1.60‒10.80), P<0.05). (4) Construction of VETC related risk scoring model and its performance evaluation. The VETC related risk scoring model was constructed as (heterogeneous enhancement with septations, presence: 1.0, absence: 0)+(heterogeneous enhancement with irregular ring‑like structures, presence: 1.5, absence: 0)+(intratumoral necrosis or ischemia, presence: 1.0, absence: 0)+(main tumor diameter >5 cm, presence: 1.0, absence: 0). The AUC, sensitivity, specificity, and accuracy of VETC related risk scoring model were 0.86 (95%CI as 0.80‒0.92), 79.7% (95%CI as 69.2%‒87.3%), 80.0% (95%CI as 69.6%‒87.5%) and 79.9% (95%CI as 72.7%‒85.5%), respectively. Results of Hosmer⁃Lemeshow goodness of fit test showed a good consistency between VETC risk scoring model predicted VETC status and true VETC status (P>0.05). (5) Postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. All 149 patients were followed up for 29(range, 26‒35)months. The time to tumor recurrence and 2‑year cumulative tumor recurrence rate of 149 patients were 29(range, 24‒33)months and 43.0%, respectively. The 2‑year tumor cumulative recurrence rate of patients with and without VETC predicted by risk scoring model was 47.8% and 37.9%, respectively, showing a significant difference between (χ²=3.90, P<0.05). The 2‑year cumulative tumor recurrence rate of patients with and without VETC confirmed by postoperative histopathological examination was 47.4% and 38.1%, respectively, showing a significant difference between (χ²=4.20, P<0.05).
    Conclusions Lesion imaging enhancement as heterogeneous enhancement with septations or irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm are independent risk factors influen-cing HCC patients with VETC. The proposed risk scoring model based on those three risk factors achieves an optimal preoperative diagnostic performance.

     

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