肝细胞肝癌微血管侵犯术前影像学预测研究进展

微血管侵犯（Microvascular invasion, MVI）是肝细胞肝癌（Hepatocellular carcinoma, HCC）的一种侵袭性行为，与HCC患者预后及治疗后复发直接相关。术前无创性精准预测MVI，对于选取合理的治疗方案，提高患者预后具有重要意义。目前临床尚无公认的MVI术前诊断指标，随着医学影像学技术的迅猛发展，MVI术前影像学预测成为当下研究热点，本文就肝癌MVI术前影像学预测研究进展进行综述。     

影像学术前预测肝细胞肝癌微血管侵犯研究进展

微血管侵犯（MVI）是肝细胞肝癌（HCC）的侵袭性行为之一，与患者预后及治疗后复发相关。术前无创性精准预测MVI对合理选择治疗方案及改善预后具有重要意义。对于术前诊断MVI目前尚无公认标准，术前影像学预测MVI是当前研究热点。本文就影像学术前预测MVI研究进展进行综述。     

术前MRI预测肝细胞癌微血管侵犯研究进展

肝细胞癌是全球常见的恶性肿瘤,最主要的治疗方法是手术切除肿瘤,但经常复发,很大一部分原因与微血管侵犯相关.因此,寻找一种无创的术前预测微血管侵犯的方法对于指导手术治疗、改善患者预后、提高患者生存率等具有重要意义.磁共振成像(magnetic resonance imaging,MRI)技术的多序列、多模态成像以及基于M...     

术前MRI预测肝细胞癌微血管侵犯的研究进展

微血管侵犯(microvascular invasion,MVI)是影响肝细胞癌术后复发及转移的重要因素之一,与患者预后及治疗密切相关.然而MVI只能通过病理学确诊,通过MRI检查精确预测MVI对选择治疗措施及改善患者预后具有重要意义及发展前景.目前已经提出了较多基于MRI检查的成像特征用于MVI的预测,包括肿瘤大小、...     

Gd-EOB-DTPA MRI动态增强预测孤立性肝细胞癌微血管侵犯的单因素及多因素回归分析

目的分析Gd-EOB-DTPA MRI动态增强扫描(DCE)影像特征与单发原发性肝细胞癌(HCC)微血管侵犯(MVI)的相关性,总结提示HCC MVI的MRI影像特征,探讨利用这些影像特征术前预测HCC MVI的可能性。方法分析66例单发HCC的术前MRI资料,利用单因素及多因素Logistic回归分析分析MRI各项影像特征与MVI的相关性,并采用ROC曲线分析肿瘤直径对MVI的诊断价值。结果单因素分析结果表明肿瘤直径(P=0.011)、肿瘤边缘(P=0.019)、瘤周强化(P=0.001)、肝胆特异性期瘤周低信号(P=0.002)是MVI的危险因素,肿瘤信号不均匀(P=0.157)、肿瘤包膜(P=0.207)、ADC值(P=0.481)、T_1减低值比率(P=0.689)与MVI无相关性。多因素Logistic回归模型分析显示肿瘤直径(P=0.007;OR=1.024)与瘤周强化(P=0.005;OR=6.670)是MVI的独立危险因素。肿瘤直径的ROC分析显示肿瘤直径56 mm诊断MVI,AUC=0.741,敏感度为0.588,特异度为0.833。有瘤周强化组MVI的发生率是52.4%。结论利用Gd-EOB-DTPA MRI动态增强扫描可术前预测HCC的MVI,肿瘤越大、有瘤周强化的HCC更容易出现MVI。     

Diagnostic value of serum squamous cell carcinoma antigen for hepatocellular carcinoma: a systematic review and meta-analysis

The aim of this study was to ascertain the diagnostic value of serum squamous cell carcinoma antigen (SCCA) and SCCA-IgM for hepatocellular carcinoma (HCC). After a comprehensive search of PubMed and Web of Science databases, we identified eligible studies on the diagnostic value serum SCCAs for HCC. The quality of the eligible studies was assessed using the revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tool. The overall diagnostic value of SCCAs for HCC was pooled using a bivariate model. Twelve studies were included in this systematic review and meta-analysis. The pooled sensitivities for SCCA and SCCA-IgM were 0.61 (95% confidence interval [CI], 0.37–0.81) and 0.70 (95% CI, 0.55–0.82), respectively. The corresponding specificities were 0.80 (95% CI, 0.52–0.94) and 0.62 (95% CI, 0.51–0.72), respectively. The areas under summary receiver operating characteristic (sROC) curves for SCCA and SCCA-IgM were 0.76 (95% CI, 0.72–0.80) and 0.70 (95% CI, 0.66–0.74), respectively. Major design deficiencies of the included studies were two-gate design and partial verification bias. Therefore, we concluded that both serum SCCA and SCCA-IgM have a fair diagnostic value for HCC.     

Diagnostic accuracy of serum glypican-3 for hepatocellular carcinoma: A systematic review and meta-analysis

Objective

Many individual studies have evaluated the diagnostic efficiency of serum glypican-3 (GPC-3) for diagnosing hepatocellular carcinoma (HCC), but the results have been inconsistent. The aim of present study was to meta-analyze the overall diagnostic accuracy of serum GPC-3 for diagnosing HCC.

Design and methods

English language studies which evaluated the diagnostic performance of GPC-3 and published before March 22, 2013 were retrieved. The quality of the studies was assessed by revised QUADAS tools. The performance characteristics were pooled and determined by random-effects models.

Results

Twelve studies with a total of 898 HCC patients and 835 non-HCC patients were included. For the studies in which the majority of reference participants had HBV or HCV infections, the overall diagnostic sensitivity and specificity were 0.53 (95% CI: 0.49–0.57) and 0.77 (95% CI: 0.74–0.81), respectively. The area under summary receiver operating characteristic (sROC) curves (AUC) was 0.82. The major design deficiencies of included studies were differential verification bias, and a lack of clear exclusion and inclusion criteria.

Conclusions

GPC-3 has moderate diagnostic accuracy for HCC. Due to the design limitations, results in published studies should be carefully interpreted. In addition, more well-designed studies with large sample sizes should be performed to rigorously evaluate the diagnostic value of the GPC-3.     

Adoptive immunotherapy for postoperative hepatocellular carcinoma: a systematic review

The high risk of recurrence in post-operative hepatocellular carcinoma (HCC) highlights the need for an effective adjuvant treatment. A systematic review of randomised controlled trials (RCTs) was performed to evaluate the clinical efficacy of adjuvant adoptive immunotherapy (AIT) for post-operative HCC patients. Electronic (MEDLINE, EMBASE and Cochrane Library databases) and manual searches were conducted throughout May 2011 to identify RCTs evaluating postoperative AIT for patients with HCC. Methodological quality was assessed in accordance with the QUOROM statement. Four RCTs totalling 423 patients met the eligibility criteria. All RCTs reported significantly improved disease-free survival rate or reduced recurrence rate after treating with adjuvant AIT (p < 0.05). The overall survival rates of AIT group are slightly higher than those of the control group in one study. Moreover, AIT was a safe treatment, with fever as the main adverse effects. This study adds to the evidence that postoperative HCC patients treated with adjuvant AIT show an improvement in disease-free survival rate or recurrence rate.     

基于影像学和血清学特征构建的列线图模型可较好预测原发性肝细胞癌的微血管浸润

目的 探讨术前基于影像学和血清学特征构建的列线图模型对肝癌微血管浸润(MVI)的预测价值。 方法 回顾性分析2015年1月~2020年12月于中山市人民医院接受切除或肝移植的548例肝细胞癌(HCC)患者的临床资料,最终纳入315例肝癌MVI患者,年龄53.2±11.5岁,肿瘤最大直径3.7~7.0 cm。收集患者临床及影像学资料并进行分析,采取单因素与多因素Logistic分析,筛查出能预测MVI的独立风险因素,构建预测HCC中MVI的列线图模型,利用ROC曲线、校准曲线和决策曲线对模型进行评估。 结果 MVI (+)患者的中位生存时间为13月(95%CI：8.1~17.9),1、3、5年无病生存率分别为50.6%、38.5%和30.9%(P < 0.05);MVI (-)患者的中位生存时间为47月(95%CI：32.7~61.3),1、3、5年无病生存率分别为77.9%、62.3%和38.8%(P < 0.05)。多因素Logistic回归分析显示,更大的肿瘤体积、突破肝外生长、缺乏或不完整假包膜、存在动脉期瘤周强化以及术前过高的球蛋白值是MVI (+)的独立危险因素(P < 0.05)。最终模型效能曲线下面积为0.895,95%CI为0.859-0.930,准确性为85.1%,敏感度为85.9%,特异性为84.1%。校准曲线显示预测概率与病理结果MVI (+)/MVI (-)概率有良好的一致性。决策曲线显示模型具有良好的临床应用价值。 结论 构建的列线图及预测模型能较好地术前预测MVI (+)的概率,可以根据MVI发生的风险调整HCC的治疗计划,以优化生存结果。     

Radiofrequency ablation with or without transarterial chemoembolization for hepatocellular carcinoma: A systematic review and meta-analysis

AIM: To determine whether combined transarterial chemoembolization(TACE) and radiofrequency ablation(RFA) improve overall and recurrence-free survival(RFS) compared with RFA alone. METHODS: We reviewed randomized clinical trials(RCTs) comparing overall survival rate as well as recurrence-free rate for hepatocellular carcinoma(HCC) between TACERFA therapy and RFA alone published before April 2015 by conducting a systematic review and meta-analysis. Eligible studies were identified by searching Pub Med and EMBASE up to April 2015. Additional studies were retrieved via China Medical Collections, Google Scholar or a hand review of the reference lists of the retrieved articles. The summarized relative risks(RRs) with their 95%CIs were estimated using random-effects model. I2 statistic was calculated to measure the heterogeneity of RRs across studies and Cochran's Q test was used to test the statistical significance accordingly. Publication bias was assessed primarily based on visual assessment using a funnel plot, and secondly by using Egger's regression asymmetry test or Begg's rank correlation test as appropriate. Meta-regression was implemented to examine potential effect modifiers. RESULTS: Nine single-center RCTs conducted in China and Japan were included, with a total of 618 patients with HCC; 321 of whom(51.9%) received TACE/RFA therapy and 297 received RFA alone. The pooled RRs with corresponding CIs comparing combined TACE/RFA to RFA alone were 1.12(1.004-1.26) and 1.20(1.02-1.41) for 1-year and 3-year survival rates, respectively. Similar positive associations were found for 1-year(1.19; 1.05-1.35) and 3-year(1.44; 1.00-2.07) RFS. Thebeneficial effect was more evident in patients with medium-sized(3-5 cm) tumors and among the Chinese population. CONCLUSION: Combined TACE/RFA has a beneficial effect on survival and recurrence rates compared with RFA alone, especially for medium-sized HCC and among Chinese patients.     

TED: Two-stage expert-guided interpretable diagnosis framework for microvascular invasion in hepatocellular carcinoma

Microvascular invasion (MVI) has been clinically recognized as a prognostic factor for hepatocellular carcinoma (HCC) after surgical treatment. Detection of MVI before surgical operation greatly benefit patients’ prognosis and survival. Most of the existing methods for automatic diagnosis of MVI directly use deep neural networks to make predictions, which do not take into account clinical knowledge and lack of interpretability. To simulate the radiologists’ decision process, this paper proposes a Two-stage Expert-guided Diagnosis (TED) framework for MVI in HCC. Specifically, the first stage aims to predict key imaging attributes for MVI diagnosis, and the second stage leverages these predictions as a form of attention as well as soft supervision through a variant of triplet loss, to guide the fitting of the MVI diagnosis network. The attention and soft supervision are expected to jointly guide the network to learn more semantically correlated representations and thereafter increase the interpretability of the diagnosis network. Extensive experimental analysis on a private dataset of 466 cases has shown that the proposed method achieves 84.58% on AUC and 84.07% on recall, significantly exceeding the baseline methods.     

基于非增强MRI的影像组学术前预测肝细胞癌微血管浸润的研究

目的建立基于非增强MRI的影像组学模型对肝细胞癌(hepatocellular carcinoma,HCC)的微血管侵犯(microvascularinvasion,MVI)进行术前预测。材料与方法回顾性分析经手术病理证实是否有MVI的HCC病人129例。所有患者术前2周内行3.0 T MRI。在T2WI-FS及ADC图中逐层勾画病灶区域提取影像组学特征。使用三步降维方法Variance Threshold、SelectKBest、LASSO算法依次进行降维来进行特征选择。分别使用六种分类器包括逻辑回归(logistic regression,LR)、支持向量机(supportvectormachine,SVM)、K近邻(K-NearestNeighbor,KNN)、决策树(decision tree,DT)、随机森林(random forest,RF)、极限梯度增强树(extreme gradient boosting,XGBoost)对提取的特征进行机器学习。通过绘制ROC曲线下面积(areaundercurve,AUC)、敏感度(sensitivity)、特异度(specificity)三个指标来评价各分类器所构建模型的效能。结果从T2WI-Fat suppressed (FS)及ADC图中分别提取出1409个影像组学特征。经过降维,最终从T2WI-FS图中筛选出12个以及从ADC图中选出8个最优特征来分别构建两个组学模型。两种分类器SVM、LR基于T2WI-FS特征所构建的模型性能最佳,对应的受试者工作特征AUC值分别为0.869、0.801,准确度为0.78、0.81。结论使用T2WI-FS的12个组学特征,可以获得较高的AUC值和准确度。因此,认为基于T2WI-FS的三维成像组学特征可以作为潜在的生物标志物来对肝细胞癌的微血管浸润进行术前非侵入性预测。     

预测肝癌微血管侵犯及早期复发的临床研究

目的探讨预测肝癌患者微血管侵犯的因素,并探讨影响肝癌患者术后早期复发的因素。方法回顾性分析147例肝癌根治性切除患者的临床病理特征。其中,有微血管侵犯的患者93例(甲组),无微血管侵犯的患者54例(乙组)。单因素及多因素分析预测微血管侵犯及早期复发的因素,随访患者术后无瘤生存期,分析预测术后早期复发的因素,ROC曲线评价预测微血管侵犯和预测术后早期复发的因素。结果 Logistic回归分析提示肿瘤直径是预测肝癌微血管侵犯的独立因素;ROC曲线下面积为0.823,肿瘤直径越大越容易出现微血管侵犯(P<0.001)。Cox回归分析提示肿瘤大体分型、微血管侵犯是预测肝癌患者术后早期复发(<2年)的独立因素,ROC曲线下面积分别为0.695,0.727。肿瘤大体分型级别越高或存在微血管侵犯的患者,手术后易早期复发(P<0.001)。结论术前明确肿瘤分型,预测肝癌微血管侵犯可以推测患者预后,并对术后治疗有一定的指导作用。     

多模态MRI术前诊断肝细胞癌微血管浸润应用进展

肝细胞癌（HCC）微血管浸润（MVI）是影响肿瘤术后复发及患者预后的重要因素。术前明确诊断MVI对改善HCC预后意义重大。目前诊断MVI主要依据HCC术后组织病理学检查,难以满足术前诊断的需要。随着影像学技术的发展,临床已将DWI、扩散峰度成像、体素内不相干运动、增强MRI及MRI影像组学分析等多模态MRI技术应用于术前诊断MVI。本文对上述多模态MRI应用于HCC术前诊断MVI的进展进行综述。     

拉伸指数弥散加权成像模型直方图分析预测单发肝细胞癌微血管侵犯

目的 评估拉伸指数模型弥散加权成像（DWI）直方图分析术前预测单发肝细胞癌（HCC）微血管侵犯（MVI）的价值。方法 回顾性分析43例经病理确诊单发HCC患者的腹部MRI,根据病理结果分为MVI（+）组（n=22）和MVI（-）组（n=21）。采用拉伸指数模型分析DWI,获得表观弥散系数（ADC）、分布弥散系数（DDC）和水分子各向异质性（α）直方图参数,比较组间临床资料及直方图参数差异;应用受试者工作特征（ROC）曲线分析差异有统计学意义的参数预测MVI的效能,并以多因素Logistic回归分析MVI的独立预测因素。结果 组间肿瘤直径、ADC第5百分位数（5th）、DDC第5、25、50百分位数（5th、25th、50th）及平均值差异均有统计学意义（P均<0.05）,其余直方图参数差异均无统计学意义（P均>0.05）。DDC 5th预测MVI的曲线下面积（AUC）最大,为0.86,高于DDC（25th、50th）及平均值、ADC 5th、肿瘤直径（Z=1.96~2.91,P均<0.05）,其余参数两两比较差异均无统计学意义（Z=0.12~1.91,P均>0.05）。DDC 5th是MVI的独立预测因素（P=0.005）。结论 拉伸指数DWI模型直方图分析有助于术前预测单发HCC的MVI,以DDC 5th诊断效能最佳。     

基于钆塞酸二钠增强MRI的机器学习模型可预测肝细胞癌的微血管侵犯

目的  探讨基于钆塞酸二钠增强MRI的机器学习模型预测肝细胞癌微血管侵犯(MVI)的价值。方法  回顾性分析2017年1月~2020年12月接受钆塞酸二钠增强MR扫描的59例经病理证实为肝细胞癌患者的MRI图像资料及临床资料,依据术后病理结果分为MVI阴性组(n=34)及阳性组(n=25)。分别在肝胆特异期及表观弥散系数图像上测量得到信噪比及对比噪声比。采用主成分分析法对特征进行降维并构建支持向量机模型,采用ROC曲线及混淆矩阵评价模型的诊断效能。结果  构建的支持向量机预测模型诊断MVI的曲线下面积为0.92(95% CI: 0.83, 0.95),准确率为0.80,敏感度为0.64,特异性为0.91。结论  基于钆塞酸二钠增强MRI构建的机器学习模型在肝细胞癌术前诊断MVI具有较好的应用价值。