钆塞酸二钠增强磁共振成像联合磁共振扩散加权成像对肝细胞癌微血管侵犯和预后的预测价值

目的探讨钆塞酸二钠(Gd-EOB-DTPA)增强磁共振成像(MRI)征象和扩散加权成像(DWI)对肝细胞癌(HCC)患者病理学微血管侵犯(pMVI)的联合预测价值及其预测结果与患者预后的关系。方法收集2012年1月至2018年6月中国医学科学院肿瘤医院收治的181例初诊HCC患者,评估病灶的影像学特征并测量表观扩散系数(ADC)。分析影像学特征和ADC值在不同pMVI组中的差异,应用多因素logistic回归和受试者工作特征(ROC)曲线分析有意义的参数对pMVI预测的价值。分析MRI预测的结果(mrMVI)与患者无复发生存时间(RFS)的关系。结果 pMVI阳性组51例,pMVI阴性组130例。pMVI阳性组的ADC值为(1.10±0.17)×10^-3 mm²/s,明显低于pMVI阴性组[(1.27±0.22)×10^-3 mm²/s,P<0.001]。不完整的增强假包膜、肿瘤边缘不光滑、动脉期瘤周强化、马赛克征和肝胆期瘤周低信号的发生率在pMVI阳性组明显高于pMVI阴性组(均P<0.05)。多因素logistic回归分析显示,肿瘤边缘、动脉期瘤周强化、肝胆期瘤周低信号和ADC值与pMVI独立相关(均P<0.05)。ROC分析显示,联合上述参数预测pMVI的曲线下面积、敏感度和特异度分别为0.830、76.5%和81.5%。mrMVI阳性组患者的中位RFS为23.6个月,明显低于mrMVI阴性组(38.2个月,P=0.004)。结论肿瘤边缘、动脉期瘤周强化、肝胆期瘤周低信号和ADC值是HCC发生pMVI的独立预测因素,且mrMVI与患者的RFS有关。     

肝细胞癌术前循环肿瘤细胞与微血管侵犯关系的临床研究

目的:探讨肝细胞癌患者术前外周血循环肿瘤细胞（CTC）与微血管侵犯（MVI）的相关性。方法:回顾性分析2018年1月至2020年3月在中山大学附属中山医院行肝细胞癌切除术的227例患者资料,术前通过Cyttel法检测患者的CTC。分析术前外周血CTC与患者临床特征的关系;采用多因素logistic回归模型分析MVI的独...     

最小表观扩散系数联合最小表观扩散系数比值预测肝细胞癌微血管侵犯及风险等级价值

目的 探讨最小表观扩散系数(ADCmin)联合ADCmin比值(rADCmin)对肝细胞癌微血管侵犯(MVI)及风险等级的鉴别诊断价值。方法 回顾性分析2019-08-01-2022-05-31滨州医学院附属医院手术病理确诊且术前有上腹部MRI平扫+增强检查的136例肝细胞癌患者临床和病理资料。根据肝细胞癌患者有无MVI分为MVI阳性组和MVI阴性组,根据MVI数量及分布区域,将MVI风险等级分为低危组和高危组。测量肿瘤实质ADCmin值,采用非肿瘤区域肝实质对ADCmin值进行标准化,计算rADCmin值。采用Mann-Whitney U检验、t检验和χ²检验分析比较各组临床特征及ADCmin、rADCmin的差异,并进行受试者工作特征(ROC)曲线分析,评估ADCmin、rADCmin及其联合参数ADCmin+rADCmin对肝细胞癌MVI及危险等级的诊断效能。结果 MVI阴性组90例,MVI阳性组46例。2组甲胎蛋白(AFP)水平(以400μg/L为分界)差异有统计学意义,χ²=14.427,P<0.001。MVI阳性组的ADCm...     

肝细胞癌合并微血管侵犯的术前预测模型及临床应用

目的 构建肝细胞癌(HCC)合并微血管侵犯(MVI)术前预测模型,分析手术切除(SR)和射频消融术(RFA)的选择在合并MVI的HCC患者中应用价值。方法 回顾性分析天津医科大学肿瘤医院2015-01-01-2019-12-31肝外科数据库中1 200例行SR的HCC患者(SR组)和169例行RFA的HCC患者(RFA组)术前临床资料,男1 146例,女223例。将行SR的HCC患者以7∶3比例随机分为训练组(n=840)和验证组(n=360),分别用于开发预测模型和评估预测模型的准确性。利用多因素logistic回归分析MVI独立危险因素并建立MVI术前预测列线图。在验证组中使用一致性指数(C指数)和校准曲线评估列线图预测性能。使用倾向评分匹配(PSM)评估SR和RFA治疗的HCC患者合并MVI预测风险的早期无复发生存期(RFS)和总生存期。结果 多因素logistic回归分析显示术前甲胎蛋白(20～400 ng/mL vs<20 ng/mL:OR=3.000,95%CI为2.005～4.517,P<0.001;>400 ng/mL vs<20 ng/mL:O...     

术前预测肝细胞癌微血管侵犯的研究进展

肝细胞癌（hepatocellular carcinoma,HCC）防治是世界范围内的重要公共卫生问题,目前,手术是HCC治疗的主要方式,而复发转移是提高HCC患者生存率的主要障碍。微血管侵犯(microvascular invasion, MVI)是肝血管内微转移的癌细胞栓子,与HCC术后复发转移及不良预后密切相关。目前MVI仅能通过术后病理检查确认,而术前预测MVI有助于HCC患者的精准治疗、提高患者生存率及筛选最佳肝移植受者。本文强调了术前预测MVI对HCC患者精准治疗的重要性,总结了影像学特征、常规血清蛋白标志物、新型分子标志物在预测MVI中的最新进展,以及多指标联合模型对MVI的预测能力,并评估了液体活检在MVI预测方面的巨大潜力。      

术前MR影像特征对肝细胞癌手术切除术后早期复发的预测价值

目的:探究肝细胞癌(hepatocellular carcinoma,HCC)术前临床资料及MR影像特征对HCC手术切除术后早期复发(2年内复发)的预测价值。方法:回顾性分析2015年1月至2018年1月间在天津医科大学肿瘤医院行手术切除术的244例HCC患者资料。对可能影响HCC手术切除术后早期复发的术前临床资料及MR影像特征行单因素、多因素分析。所有患者出院后均规律随访,终点事件为术后2年内肝内复发。结果:单因素分析筛选出肿瘤最大径、肿瘤包膜、瘤周肝实质强化、环形强化、TTPVI、瘤内坏死、卫星灶、动态增强模式、DWI/T2WI不匹配等MR影像特征及甲胎蛋白(alpha-fetoprotein,AFP)、TNM分期、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、谷氨酸氨基转移酶(glutamatergic aminotransferase,AST)、直接胆红素(direct bilirubin,DBIL)、γ-谷氨酰转肽酶(γ-glutamyl transferase,γ-GT)等临床资料为肝癌患者切除术后早期复发的影响因素。将上述变量纳入多因素Co...     

肝细胞癌磁共振扩散加权成像与肿瘤细胞密度及微血管密度的相关性研究

[目的]评价肝细胞癌磁共振扩散加权成像(DWI)及表观扩散系数(ADC)值与肿瘤细胞密度、微血管密度的相关性.[方法]60例肝细胞癌患者行DWI扫描,测量并计算病灶的ADC值,其中12例外科手术切除病灶行肿瘤细胞密度及微血管密度检测,并进行统计学相关性分析.[结果]肝细胞癌病灶平均ADC值为(1.15±0.23)×10-3mm2/s,正常肝组织平均ADC值为(1.71±0.30)×10-3mm2/s,两者差异有统计学意义(P＜0.001).平均肿瘤细胞密度为0.80±0.14,微血管密度为78.67±32.17,肝细胞癌ADC与肿瘤细胞密度呈负相关(r=-0.873,P＜0.001),与微血管密度呈正相关(r=0.731,P＜0.05).[结论]磁共振DWI及ADC值能够反映肿瘤组织微观结构状态,对评价肿瘤的治疗及预后具有较高临床实用价值.     

原发性肝细胞肝癌微血管侵犯的术前预测及其模型的建立

目的 全面探讨原发性肝细胞肝癌(HCC)微血管侵犯(MVI)的相关危险因素并构建预测模型.方法 分析2012年10月至2020年8月间南通大学附属医院肝胆外科二病区行肝癌切除术的病例,在术后病理诊断为HCC的病例中运用简单随机抽样方法抽选162例HCC患者的临床资料,其中术后病理提示60例患者伴有MVI、102例患者不...     

Preoperative predictors of microvascular invasion in multinodular hepatocellular carcinoma

Background

The preoperative predictors of microvascular invasion (MVI) in multinodular hepatocellular carcinoma (HCC) are currently unclear.

Methods

We retrospectively analyzed 266 patients who underwent potentially curative resection of multinodular HCC. MVI was diagnosed on pathological examination in 64 patients. Preoperative risk factors for MVI were identified and survival curves were analyzed.

Results

Patients with MVI had significantly lower overall and recurrence-free survival rates than those without MVI (overall survival, 1 year: 86% vs. 71%, 3 years: 58% vs. 16%; recurrence-free survival, 1 year: 69% vs. 12%; 3 years: 48% vs. 12%; both P < 0.001). Multivariate analysis showed that serum alpha-fetoprotein (AFP) level >400 μg/L (odds ratio [OR] = 3.732, P = 0.016), serum gamma-glutamyltransferase (GGT) level >130 U/L (OR = 19.779, P < 0.001), total tumor diameter >8 cm (OR = 5.545, P = 0.010), and tumor number >3 (OR = 11.566, P = 0.007) were independent predictors of MVI. A scoring system was constructed, and the MVI rate was significantly higher in patients with a score of ≥3 than those with a score of <3 (64.1% vs. 10.9%, P < 0.001). Overall and recurrence-free survival rates were significantly lower in patients with a score of ≥3 (both P < 0.001).

Conclusions

Serum AFP level >400 μg/L, serum GGT level >130 U/L, total tumor diameter >8 cm, and tumor number >3 were preoperative predictors of MVI in patients with multinodular HCC. In patients with a high risk of MVI and well-preserved liver function, anatomic resection may be worth considering.     

A novel multimodal deep learning model for preoperative prediction of microvascular invasion and outcome in hepatocellular carcinoma

BackgroundAccurate preoperative identification of the microvascular invasion (MVI) can relieve the pressure from personalized treatment adaptation and improve the poor prognosis for hepatocellular carcinoma (HCC). This study aimed to develop and validate a novel multimodal deep learning (DL) model for predicting MVI based on multi-parameter magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CT).MethodsA total of 397 HCC patients underwent both CT and MRI examinations before surgery. We established the radiological models (R^CT, R^MRI) by support vector machine (SVM), DL models (DL^CT_ALL, DL^MRI_ALL, DL^CT + MRI) by ResNet18. The comprehensive model (C^ALL) involving multi-modality DL features and clinical and radiological features was constructed using SVM. Model performance was quantified by the area under the receiver operating characteristic curve (AUC) and compared by net reclassification index (NRI) and integrated discrimination improvement (IDI).ResultsThe DL^CT + MRI model exhibited superior predicted efficiency over single-modality models, especially over the DL^CT_ALL model (AUC: 0.819 vs. 0.742, NRI > 0, IDI > 0). The DL^MRI_ALL model improved the performance over the R^MRI model (AUC: 0.794 vs. 0.766, NRI > 0, IDI < 0), but no such difference was found between the DL^CT_ALL model and R^CT model (AUC: 0.742 vs. 0.710, NRI < 0, IDI < 0). Furthermore, both the DL^CT + MRI and C^ALL models revealed the prognostic power in recurrence-free survival stratification (P < 0.001).ConclusionThe proposed DL^CT + MRI model showed robust capability in predicting MVI and outcomes for HCC. Besides, the identification ability of the multi-modality DL model was better than any single modality, especially for CT.     

微血管侵犯对肝癌肝移植患者预后的影响

目的探讨微血管侵犯(MVI)对肝细胞癌肝移植患者总生存时间(OS)和无复发生存时间(RFS)的影响。方法收集2004年5月至2017年10月接受肝移植术的肝癌患者的临床病理资料。采用Kaplan-Meier法和Cox比例风险模型分析MVI对OS和RFS的影响。结果共纳入141例肝癌肝移植患者,其中54例(38.3%)MVI阳性,87例(61.7%)MVI阴性。与MVI阴性患者比较,MVI阳性患者具有更高的甲胎蛋白(AFP)和血小板水平,更高的中性粒细胞-淋巴细胞计数比值,更大的肿瘤直径,更高比例的卫星灶、低分化肿瘤和超米兰标准病例(P<0.05)。随访截止于2020年1月15日,55例(39.0%)肿瘤复发,56例(39.7%)死亡。MVI阳性患者1、3、5、10年无复发生存率分别为48.1%、36.5%、36.5%和19.0%,低于MVI阴性患者的85.1%、76.8%、71.9%和60.0%(P<0.001)。MVI阳性患者1、3、5、10年生存率分别为77.8%、42.3%、42.3%和23.3%,低于MVI阴性患者的94.3%、83.6%、77.2%和68.4%(P<0.001)。Cox多因素分析显示,MVI、AFP水平、肿瘤直径和肿瘤数目是影响肝癌肝移植患者RFS和OS的独立因素。结论MVI对肝癌肝移植患者的预后具有显著影响,MVI侵犯的患者预后不良。     

A novel prognostic nomogram based on microvascular invasion and hematological biomarkers to predict survival outcome for hepatocellular carcinoma patients

PurposeThis study aimed to develop and validate a nomogram for overall survival (OS) prediction in which combine clinical characteristics and hematological biomarkers in patients with hepatocellular carcinoma (HCC).MethodsWe performed a retrospective analysis of 807 HCC patients. All the clinical data of these patients were collected through electronic medical record (EMR). The independent predictive variables were identified by cox regression analysis. We tested the accuracy of the nomograms by discrimination and calibration, and then plotted decision curves to assess the benefits of nomogram-assisted decisions in a clinical context, and compared with the TNM staging systems and microvascular invasion (MVI) on HCC prognosis.ResultsThe primary cohort consisted of 545 patients with clinicopathologically diagnosed with HCC from 2008 to 2013, while 262 patients from 2014 to 2016 in external validation cohort. Variables included in the nomograms were TNM Stage, microvascular invasion (MVI), alpha fetoprotein (AFP), platelet to lymphocyte ratio (PLR) and prothrombin time (PT). The C-index of nomogram was 0.768, which was superior than the C-index of TNM Stage (0.660, P < 0.001) and MVI(0.664, P < 0.001) alone in the primary cohort. In the validation cohort, the models had a C-index of 0.845, and were also statistically higher when compared to C-index values for TNM Stage (0.687, P < 0.001) and MVI(0.684, P < 0.001). Calibration curves showed adequate calibration of predicted and reported OS prediction throughout the range of HCC outcomes. Decision curve analysis demonstrated that the nomogram was clinically useful than the TNM Stage and MVI alone. Moreover, patients were divided into three distinct risk groups for OS by the nomogram: low risk group, middle risk group and a high risk group, respectively.ConclusionThe nomogram presents more accurate and useful prognostic power, which could be used to predict OS for patients with HCC.     

A novel classification in predicting prognosis and guiding postoperative management after R0 liver resection for patients with hepatocellular carcinoma and microvascular invasion

BackgroundMicrovascular invasion (MVI) is a significant risk factor affecting survival outcomes of patients after R0 liver resection (LR) for hepatocellular carcinoma (HCC). The current classification of MVI is not refined enough to prognosticate long-term survival of these patients, and a new MVI classification is needed.MethodsPatients with HCC who underwent R0 LR at the Eastern Hepatobiliary Surgery Hospital from January 2013 to December 2013 and with resected specimens showing MVI were included in this study with an aim to establish a novel MVI classification. The classification which was developed using multivariate cox regression analysis was externally validated.ResultsThere were 180 patients in the derivation cohort and 131 patients in the external validation cohort. The following factors were used for scoring: α-fetoprotein level (AFP), liver cirrhosis, tumor number, tumor diameter, MVI number, and distance between MVI and HCC. Three classes of patients could be distinguished by using the total score: class A, ≤3 points; class B, 3.5–5 points and class C, >5 points with distinct long-term survival outcomes (median recurrence free survival (mRFS), 22.6, 10.2, and 1.9 months, P < 0.001). The predictive accuracy of this classification was more accurate than the other commonly used classifications for HCC patients with MVI. In addition, the mRFS of class C patients was significantly prolonged (1.9 months vs. 6.2 months, P < 0.001) after adjuvant transcatheter arterial chemoembolization (TACE).ConclusionsA novel MVI classification was established in predicting prognosis of HCC patients with MVI after R0 LR. Adjuvant TACE was useful for class C patients.     

Anatomic resection improved the long-term outcome of hepatocellular carcinoma patients with microvascular invasion: A prospective cohort study

BACKGROUNDThe long-term effect of anatomic resection (AR) is better than that of non-anatomic resection (NAR). At present, there is no study on microvascular invasion (MVI) and liver resection types.AIMTo explore whether AR improves long-term survival in patients with hepatocellular carcinoma (HCC) by removing the peritumoral MVI.METHODSA total of 217 patients diagnosed with HCC were enrolled in the study. The surgical margin was routinely measured. According to the stratification of different tumor diameters, patients were divided into the following groups: ≤ 2 cm group, 2-5 cm group, and > 5 cm group.RESULTSIn the 2-5 cm diameter group, the overall survival (OS) of MVI positive patients was significantly better than that of MVI negative patients (P = 0.031). For the MVI positive patients, there was a statistically significant difference between AR and NAR (P = 0.027). AR leads to a wider surgical margin than NAR (2.0 ± 2.3 cm vs 0.7 ± 0.5 cm, P < 0.001). In the groups with tumor diameters < 2 cm, both AR and NAR can obtain a wide surgical margin, and the surgical margins of AR are wider than that of NAR (3.5 ± 5.8 cm vs 1.6 ± 0.5 cm, P = 0.048). In the groups with tumor diameters > 5 cm, both AR and NAR fail to obtain wide surgical margin (0.6 ± 1.0 cm vs 0.7 ± 0.4 cm, P = 0.491). CONCLUSIONFor patients with a tumor diameter of 2-5 cm, AR can achieve the removal of peritumoral MVI by obtaining a wide incision margin, reduce postoperative recurrence, and improve prognosis.     

超声造影联合免疫组织化学诊断小肝细胞癌微血管侵犯：两个医院的回顾性研究

目的 探讨超声造影（contrast enhanced ultrasound,CEUS）联合免疫组织化学（immunohistochemistry,IHC）在术前诊断小肝细胞癌（hepatocellular carcinoma,HCC）微血管侵犯（microvascular invasion,MVI）中的价值。方法 回顾性收集日本横滨市立大学附属市民综合医疗中心和西安交通大学第一附属医院142例HCC患者的资料,包括177个新发的、最大直径不超过3 cm的HCC病灶。根据手术切除标本的病理学诊断分为MVI（+）组（n=37）和MVI（-）组（n=140）。在术前CEUS动脉期（arterial phase,AP）和血管后期（post-vascular phase,PVP）图像上分别观察病灶周边有无高灌注、低灌注;采用IHC检测热休克蛋白70(heat shock protein,HSP70)、磷脂酰肌醇蛋白聚糖3(glypican 3,GPC3)在术前穿刺活检标本中的表达。结果 CEUS指标（AP、PVP）和IHC指标（GPC3、HSP70）单独诊断MVI时,PVP的诊断效率最高,准确...     

Association of type 2 diabetes mellitus with incidences of microvascular invasion and survival outcomes in hepatitis B virus-related hepatocellular carcinoma after liver resection: A multicenter study

BackgroundMicrovascular invasion (MVI) adversely affects long-term survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to examine the association between preoperative type 2 diabetes mellitus (T2DM) with incidences of MVI and prognosis in HBV-related HCC after liver resection (LR).Material and methodsData of HBV-related HCC patients who underwent LR as an initial therapy from four hospitals in China were retrospectively collected. Clinicopathological factors associated with the incidence of MVI were identified using univariate and multivariate logistic regression analysis. The recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test.ResultsOf 1473 patients who were included, 219 (14.9%) patients had T2DM. Preoperative T2DM, HBV DNA load, antiviral treatment, AFP level, varices, and tumor encapsulation were identified to be independent predictors of the incidence of MVI. Patients with HBV-related HCC and T2DM had a higher incidence of MVI (65.8%) than those without T2DM (55.4%) (P = 0.004). The RFS and OS were significantly worse in patients with T2DM than those without T2DM (median RFS: 11.1 vs 16.7 months; OS: 26.4 vs 42.6 months, both P < 0.001). Equivalent results were obtained in HCC patients with MVI who had or did not have T2DM (median RFS: 10.0 vs 15.9 months; OS: 24.5 vs 37.9 months, both P < 0.001).ConclusionsPreoperative T2DM was an independent risk factor of incidence of MVI. Patients with HBV-related HCC and T2DM had worse prognosis than those without T2DM after LR.     

Adjuvant transarterial chemoembolization improves survival outcomes in hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis

BackgroundThe benefits of adjuvant transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remain controversial. We compared the efficacy and safety of adjuvant TACE and hepatic resection (HR) alone for HCC patients with MVI.MethodsThe PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare adjuvant TACE and HR alone for the treatment of HCC with MVI from inception to January 1, 2019. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors.Results12 trials involving 2190 patients were evaluated. A meta-analysis of 11 studies suggested that the 1-, 3-, and 5-year overall survival (OS) rates (OR = 0.33, P < 0.001; OR = 0.49, P < 0.001; and OR = 0.59, P < 0.01; respectively), favored adjuvant TACE over HR alone. 11 studies were included in the meta-analysis of DFS, and adjuvant TACE showed better 1-, 3-, and 5-DFS (OR = 0.45, P < 0.001; OR = 0.50, P < 0.001; and OR = 0.58, P < 0.001; respectively) compared to HR alone. Subgroup analysis demonstrated that adjuvant TACE could benefit HCC patients with MVI with tumor diameter >5 cm or multinodular tumors.ConclusionAdjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI. However, these results need to be validated through further high-quality clinical studies.Lay summaryThe benefits of adjuvant TACE in HCC patients with microvascular invasion remain controversial. Twelve studies involving 2190 patients were include in our meta-analysis. Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI.