基于术前血清学指标AFP和GGT的标准在预测肝细胞癌患者肝移植术后长期生存中的作用研究

目的  分析术前血清学指标对肝细胞癌（HCC）患者肝移植术后长期生存和肿瘤复发的预测作用,探索其对扩大米兰标准的意义。方法  回顾性分析669例HCC肝移植受者的临床资料,采用受试者工作特征（ROC）曲线计算最佳截取值,采用单因素和多因素回归分析影响HCC患者肝移植术后总生存率和无复发生存率的危险因素,分析术前血清肝酶与肿瘤病理学特征的相关性,比较甲胎蛋白（AFP）联合γ-谷氨酰转移酶（GGT）以及不同肝移植标准对HCC患者肝移植术后生存和复发的预测价值。结果  超米兰标准、肿瘤直径之和（TTD） > 8 cm、AFP > 200 ng/mL和GGT > 84 U/L是影响HCC患者肝移植术后总生存率和无复发生存率的独立危险因素（均为P < 0.05）。相关性分析结果显示,术前血清GGT水平与TTD,肿瘤数量,静脉侵犯,微卫星病变,包膜侵犯,肿瘤、淋巴结、转移（TNM）分期,Child-Pugh评分,超米兰标准均存在相关性（均为P < 0.05）。将米兰标准、TTD与血清肝酶指标（AFP和GGT）结合,提出Milan-AFP-GGT-TTD（M-AGT）标准。符合M-AGT标准者（其中111例超米兰标准）术后5年总生存率和无复发生存率均高于符合杭州标准者（均为P < 0.05）,与符合加州大学旧金山分校（UCSF）标准者的术后5年总生存率和无复发生存率比较差异均无统计学意义（均为P > 0.05）。结论  术前血清学指标AFP和GGT可有效预测HCC患者肝移植术后长期生存和肿瘤复发,建立基于血清学指标的M-AGT标准有助于补充米兰标准,且简单易行。     

BZW2和IVD在肝癌组织中的表达及其对肝癌肝移植受者预后的影响

目的  探讨碱性亮氨酸拉链和W2结构域2（BZW2）及异戊酰辅酶A脱氢酶（IVD）在肝细胞癌（肝癌）中的表达及其对肝移植受者预后的影响。方法  回顾性分析87例肝癌肝移植受者的病理标本及临床资料,分析肝癌肝移植受者术后肿瘤复发转移情况。采用免疫组织化学染色检测BZW2和IVD的表达情况,分析BZW2和IVD与肝癌临床病理参数的关系及其对肝移植术后肿瘤复发和受者预后的影响。结果  87例受者中,共有31例肿瘤复发,复发率为36%,复发时间为术后2~49个月,复发时间中位数为7个月。免疫组织化学染色结果显示,肝癌组织的BZW2阳性表达率高于正常肝组织（76%比30%）,IVD阳性表达率低于正常肝组织（51%比69%）,差异均有统计学意义（均为P < 0.01）。BZW2表达与肿瘤直径、有否肿瘤包膜有关（均为P < 0.05）,IVD表达与肿瘤直径,甲胎蛋白（AFP）水平,肿瘤、淋巴结、转移（TNM）分期,有否血管侵犯有关（均为P < 0.05）。BZW2高表达组受者肿瘤累积复发率高于BZW2低表达组,累积生存率低于BZW2低表达组;IVD低表达组患者肿瘤累积复发率高于IVD高表达组,累积生存率低于IVD高表达组（均为P < 0.05）。结论  在肝癌组织中,BZW2蛋白表达水平上调,IVD蛋白表达水平下调。且BZW2高表达和IVD低表达的肝移植受者的累积复发率较高,累积生存率较低。     

超声造影肝脏影像报告与数据系统在甲胎蛋白阴性肝细胞癌高危患者中的应用

目的 研究超声造影肝脏影像报告与数据系统2017版（CEUS LI-RADS v2017）在甲胎蛋白（AFP）阴性的肝细胞癌（HCC）高危患者肝局灶性病变中的应用价值。方法 回顾性分析2018年1月至2021年10月在我院行CEUS检查的AFP阴性HCC高危患者108例（134个结节）,采用CEUS LI-RADS v2017对结节进行分类,以组织病理学结果或增强影像学检查和随访结果为金标准,计算CEUS LI-RADS对AFP阴性患者HCC和肝内其他恶性肿瘤（OM）的诊断敏感性、特异性、阳性预测值、阴性预测值、准确率、受试者工作特征曲线下面积（AUC）。结果 AFP阴性HCC较OM小（P＜0.001）。CEUS LR-5类、LR-4类、LR-3类对AFP阴性HCC的阳性预测值分别为88.37%、47.06%、12.9%。LR-5类诊断AFP阴性HCC的敏感性、特异性、准确率和AUC分别为73.07%、 93.90%、85.82%和0.87。LR-M类诊断OM的敏感性、特异性、阳性预测值、阴性预测值、准确率和AUC分别为90.91%、97.32%、86.96%、98.20%、96.27%和0.94。结论AFP阴性HCC较OM小,CEUS LI-RADS v2017对AFP阴性HCC诊断特异性较高而敏感性较低,对OM有较好的诊断价值。     

血清巨噬细胞抑制因子1联合甲胎蛋白异质体3含量检测在原发性肝癌诊断中的价值

目的 探讨酶联免疫吸附（ELISA）法检测血清巨噬细胞抑制因子Ⅰ（MIC-1）联合甲胎蛋白异质体3（AFP-L3）对原发性肝癌的诊断价值.方法 选择116例临床确诊的原发性肝癌患者,应用ELISA法检测患者血清MIC-1和AFP-L3含量,分析二者联合检测在原发性肝癌诊断中的价值.结果 原发性肝癌组AFP-L3浓度为（127.12±51.43）ng/ml,明显高于正常对照组的（27.11±7.26） ng/ml（P＜ 0.001）,以AFP-L3＞ 38.0 ng/ml为临界值时,灵敏度为85.34％（99/116）,特异度为88.33％（53/60）,诊断准确度为86.36％（152/176）;原发性肝癌组MIC-1浓度为（3140.43±1138.23）pg/ml,明显高于正常对照组的（701.88±302.34） pg/ml（P＜0.001）,灵敏度为91.38％（106/116）,特异度为85.00％（51/60）,诊断准确度为89.20％（157/176）.二者联合检测灵敏度为83.62％（97/116）,特异度为91.67％（55/60）,诊断准确度为86.36％（152/176）.结论 MIC-1联合AFP-L3检测可提高原发性肝癌诊断的特异度,具有一定的临床价值.     

血清GP73联合AFP在肝细胞癌诊断中的价值

目的 探讨血清高尔基体蛋白73（GP73）与甲胎蛋白（AFP）联合检测在肝细胞癌（HCC）诊断中的价值。方法 收集2011年2月至2012年1月30例HCC患者（HCC组）、30例肝硬化患者（肝硬化组）和20例健康人（健康对照组）的血清,分别用酶联免疫吸附法（ELISA）和电化学发光免疫法（ECLIA）检测各组血清中GP73和AFP水平。结果 HCC组、肝硬化组和健康对照组血清GP73水平分别为（251.9±130.2）ng／ml、（74.7±40.6）ng／ml和（12.2±4.0）ng／ml,AFP水平分别为（141.6±158.3）ng／ml、（36.0±35.0）ng／ml和（2.2±1.5）ng／ml。GP73 检测HCC的敏感度为76.7％,特异度82.0％,约登指数58.7％,准确度80.0％。AFP检测HCC的敏感度为63.3％,特异度80.0％,约登指数43.3％,准确度68.8％。两者联合检测的敏感度为86.7％,特异度78.0％,约登指数64.7％,准确度81.3％。结论 HCC患者血清中GP73和AFP水平较高,两者联合检测可以显著提高HCC的诊断能力。     

Enhanced Liver Metastatic Potential of Alpha-fetoprotein-producing Human Gastric Carcinoma after Carbon Tetrachloride-induced Liver Damage in Nude Mice

The liver metastatic potential of alpha-fetoprotein (AFP)-producing human gastric carcinoma (NSC-3) was examined in male, BALB/c, nude mice. Metastatic nodules in the liver were produced by intrasplenic (IS) injection of tumor cell suspension prepared by trypsinization from subcutaneous NSC-3 tumor. The serum AFP level increased exponentially after IS injection along with the growth of metastatic nodules in the liver, and a positive correlation was observed between the estimated weight of metastatic nodules and serum AFP level. To investigate the effect of liver damage by carbon tetrachloride (CCI₄) on the metastatic potential of NSC-3 cells injected intrasplenlcally, the mice were divided into 4 groups: Group 1 received IS injection of 1×10⁶ of NSC-3 cells without CCI₄, treatment; Groups 2, 3 and 4 received IS injection 7 days, 2 days and 1 day after CCI₄ treatment, respectively. All mice were killed 64 days after IS injection. The incidence of liver metastasis was 80% in Group 1, but 100% in Groups 2, 3 and 4. The mean numbers of metastatic nodules per liver were 4.2 in Group 1, 16.8 in Group 2, 18.0 in Group 3 and 44.5 in Group 4. Significant differences in the mean numbers of metastatic nodules were observed between Group 4 and the other groups. It was clearly demonstrated that the metastatic potential of AFP-producing human gastric carcinoma cells (NSC-3) is enhanced in the situation prevailing after liver parenchymal cells are damaged by CCI₄.     

Ask the expert

The editors invite questions for this section     

Immature ovarian teratoma with peritoneal gliomatosis and elevated serum alpha-fetoprotein associated with a second mature teratoma

A 7-year-old girl had a huge immature grade 2 teratoma of the left ovary with peritoneal gliomatosis and elevated serum alpha-fetoprotein (AFP). The serum AFP level reached 3543 ng/ml and returned to normal after left salpingo-oophorectomy and chemotherapy. Twenty-two months later, a second mature teratoma was removed from the left subdiaphragmatic region. The AFP level had been within the normal range and the patient had been symptom-free for 3 years following the previous operation. AFP was positive in the tubular epithelium of the immature tissues on immunohistochemical study. Offprint requests to: A. Hokama     

Protein induced by vitamin K absence or antagonist-Ⅱ versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis

Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.     

Blood Serum Alpha Fetoprotein Enhancer Binding Protein,a Tumor Suppressor,Decreases in Chronic HBV Hepatitis Patients as Hepatocellular Cancer Appears

Chronic hepatitis increases the risk of hepatocellular carcinoma (HCC). To test whether circulating proteins reflect hepatic carcinogenesis, sera from patients and controls were albumin depleted, enriched for glycoproteins, digested with trypsin, and subjected to reverse phase chromatography and tandem mass spectrometry. Alpha-fetoprotein enhancer binding protein (AFPebp), a tumor suppressor, was repeatedly identified in sera from chronic HBV hepatitis patients. We independently identified and quantified AFPebp with a deuterated, phenylisocyanate-labeled synthetic peptide standard. Elevated AFPebp levels in sera from chronic HBV hepatitis patients decreased as cancer developed. These data suggest that rising AFPebp levels in chronic HBV hepatitis may be protective, while falling levels may contribute to HCC development.