目的 探討酶聯免疫吸附試驗(ELISA)檢測血清甲胎蛋白異質體(AFP-L3)含量對原發性肝癌(PLC)的診斷價值。 方法 選擇2011年3月-11月門診或住院的137例患者臨床檢測甲胎蛋白(AFP)為陽性的肝病患者血清,應用上海逸峰生物科技有限公司提供的ELISA法AFP-L3檢測試劑盒檢測AFP-L3濃度,137例中男98例,女39例,年齡28~77歲。其中PLC 92例,良性肝病45例,后者包括肝硬化37例、慢性肝炎8例。分析PLC組與良性肝病組AFP-L3濃度差異,運用受試者工作特征曲線(ROC)分析AFP-L3含量在PLC鑒別診斷中的價值。 結果 PLC組AFP-L3濃度[(109.04 ± 62.51)ng/mL]明顯高于良性肝病組[(25.96 ± 49.43)ng/mL,兩組差異有統計學意義(t=8.28 ,P<0.001)。ROC分析結果顯示,曲線下面積為0.819,以AFP-L3濃度37.89 ng/mL為臨界值,分析92例PLC患者與45例良性肝病患者AFP-L3濃度異常的靈敏度為83.69%,特異度為88.88%,陽性預測值為93.90%(77/82),陰性預測值為72.72%(40/55),診斷準確度為85.40%。 結論 應用簡便快速的ELISA法檢測AFP-L3濃度在PLC與良性肝病鑒別診斷中具有較高的臨床價值,便于臨床推廣。
【Abstract】Objective To investigate whether liver resection for hepatocellular carcinoma (HCC) causes dissemination of liver tumor cells into blood circulation. Methods Fourteen patients with HCC, but without evidences of metastasis, were enrolled for the study. Blood samples of peripheral blood before skin incision and after abdominal wall suture, and of hepatic venous blood and portal venous blood after liver parenchyma dissection, were obtained. AFPmRNA was detected by reverse transcription polymerase chain reaction assays, the change of the level of its expression during operation was assessed by semi-quantitative analysis. Results The rate of its expression before and after operation in peripheral blood, and during operation in portal venous blood and in hepatic venous was 42.9%, 35.7%, 42.9% and 57.1% respectively. There were no differences between them. However, the level of its expression in hepatic venous blood was significantly higher than others (P<0.05). Conclusion Liver resection for HCC induces releases of cells from the liver, probably including tumor cells, into blood circulation.
ObjectiveTo evaluate the relationship between the expression of alpha fetoprotein (AFP) and chemoresistance in hepatocellular carcinoma.MethodsHepatocellular carcinoma was screened from liver tumor tissue samples, which was obtained by puncture before transcatheter arterial chemoembolization (TACE). Immuno-histochemical staining was used to detect the expression of AFP in HCC tissues and the effect of AFP expression in HCC on the effect of chemotherapy was analyzed.ResultsA total of 62 patients met the inclusion criteria, of which 36 were in the chemotherapy resistant group and 26 in the chemotherapy sensitive group. There were 42 patients with positive expression of AFP in tumor tissues (including 29 patients with chemoresistance) and 20 patients with negative expression of AFP in tumor tissues (including 7 patients with chemoresistance). There were no significant difference between the two groups in sex, age, tumor differentiation, Child-Pugh classification of liver function, tumor size, tumor site and hepatitis (P>0.05). In elevated serum AFP level, tumor single, and with portal vein tumor thrombus (PVTT), the proportion of patients in the chemosensitivity group were significantly lower than that in the chemosensitivity group (P<0.05). The results of logistic multivariate regression analysis showed that positive expression of AFP [OR=0.280, 95%CI (0.092, 0.950), P=0.045] and PVTT [OR=0.026, 95%CI (0.004, 0.322), P=0.005] were independent risk factors for chemotherapeutic resistance in hepatocellular carcinoma.ConclusionAFP positive expression in liver tumor tissues and PVTT are useful indicators of resistance to chemotherapy.
Objective The usefulness of measurement of nuclear DNA content elevation for diagnosis of early hepatocellular carcinoma was evaluated by a study of 186 patients with liver cirrhosis. Methods Nuclear DNA content was measured using an automatic image analysis system.Results ①Hepatocellular carcinoma was found in 37 patients during 10 years follow-up, the cumulative incidence of hepatocellular carcinoma was 19.89%. ②The incidence of hepatocellular carcinoma increased with the increase of the patterns of α-fetoprotein (AFP), 5c exceeding rate (5cER), FORM PE, but positive predictive value of 5cER was the highest of three parameters, the difference among all groups was significant by the χ2 test (P<0.05). ③When 5cER joined AFP for monitoring development of hepatocellular carcinoma, the incidence of hepatocellular carcinoma was 72.00%, which was significantly higher than that of 5cER or AFP alone, the difference between groups was highly significant (P<0.01). Conclusion Patients who had 5cER levels of 3%-5% or more, who had transient increases in 5cER or who had both, should be treated as being in a super-highrisk group for hepatocellular carcinoma. Frequent and careful examination by ultrasonography of such patients is recommended. It is important that measurement of 5cER join with AFP in cirrhotic patients monitored for early development of hepatocellular carcinoma.
ObjectivesTo evaluate the accuracy of liver cancer screening techniques to inform screening intervention and early diagnosis.MethodsWe searched PubMed, The Cochrane Library, EMbase, Web of Science, CNKI, WanFang Data, CBM, VIP databases to collect relevant diagnostic accuracy studies of screening technologies for liver cancer from January 1980 to December 2017. Two reviewers independently screened the literature, extracted the data and assessed the risk of bias of included studies. Then meta-analysis was performed by using Meta-Disc 1.4 software.ResultsA total of 54 publications with 47 728 individuals were included. In terms of pooled sensitivity from the meta-analysis, it was estimated as 0.71 (95%CI 0.70 to 0.72), 0.57 (95%CI 0.56 to 0.59) and 0.43 (95%CI 0.41 to 0.45); the pooled specificity was estimated as 0.92 (95%CI 0.92 to 0.93), 0.95 (95%CI 0.94 to 0.96) and 0.95 (95%CI 0.94 to 0.96); the pooled positive likelihood ratio was 5.65 (95%CI 4.37 to 7.30), 13.24(95%CI 4.25 to 41.22) and 11.39 (95%CI 4.01 to 32.35); the pooled negative likelihood ratio was 0.35 (95%CI 0.31 to 0.39), 0.38 (95%CI 0.29 to 0.52) and 0.49 (95%CI 0.39 to 0.62); the diagnosis odds ratio was 17.23 (95%CI 12.26 to 24.20), 33.79 (95%CI 12.65 to 90.24) and 24.41(95%CI 9.23 to 64.53) for AFP alone with cut-off of 20, 200 and 400 ng/mL, respectively. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnosis odds ratio were 0.65 (95%CI 0.62 to 0.69), 0.97 (95%CI 0.97 to 0.97), 16.48 (95%CI 9.55 to 28.42), 0.27 (95%CI 0.18 to 0.42) and 64.54 (95%CI 30.16 to 138.11) for ultrasound examination alone. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnosis odds ratio were 0.96 (95%CI 0.94 to 0.98), 0.96 (95%CI 0.96 to 0.96), 10.76 (95%CI 2.62 to 44.27), 0.07 (95%CI 0.02 to 0.22) and 160.59 (95%CI 31.61 to 816.03) for the combined strategy.ConclusionFor liver cancer screening technologies, the overall accuracy of serum AFP test alone is the optimum at cut-off of 20 ng/mL, and the sensitivity increased substantially when combined with ultrasound examination.
ObjectiveTo study the clinical value of changes of serumα-fetoprotein(AFP) and soluble cell adhesion molecule-1(sICAM-1) levels before and after surgical treatment of primary hepatocellular carcinoma(PHC) as predictors of patient survival. MethodsThe clinical data and followed-up results of 86 patients with hepatocellular carcinoma received hepatectomy or radiofrequency ablation(RFA) in Xijing Hospital and the 451st Hospital of PLA were retrospectivly analyzed. The changes of peripheral blood AFP and sICAM-1 levels in patients before and in 1 month after treatment were observed and all patients were divided into different groups according to the changes in both two markers. Then survival rates of each group were analyzed. ResultsThe patients with AFP < 20μg/L or sICAM-1 < 1 000 U/L before treatment had lower tumor recurrence rate and higher survival rate than patients with elevated serum levels of the both markers(AFP:P=0.018, P < 0.001;sICAM-1:P=0.027, P < 0.001). The larger tumor, late TNM stage, and higher rate of recurrence were associated with elevated serum levels of the both markers(AFP:P=0.016, P=0.026 and P=0.025;sICAM-1:P < 0.001, P=0.024 and P=0.032). The better survival situation was closely related with these cases treated with hepatectomy and their levels of both markers were lower than the above cutoff values both before and after treatment, or leves of both markers above the cut-off values returned to within the normal range after treatment (AFP:P=0.006, P=0.001;sICAM-1:P=0.001, P=0.002). The patients who had simultaneous increase of AFP and sICAM-1 after operation showed the worst tumor-free and overall survivals(P=0.007, P < 0.001). ConclusionTo test the changes of serum AFP and sICAM-1 levels in early stage after treatment for patients who received radical resection of hepatocellular carcinoma has good clinical value for monitoring of tumor recurrence and predict prognosis.
Objective To study the effect of alpha fetoprotein-tumor burden score (ATS) on the long-term prognosis of hepatocellular carcinoma (HCC) after resection. MethodsThe data of 2 907 patients with HCC who underwent first hepatectomy from West China Hospital of Sichuan University, West China Ziyang Hospital/Ziyang Central Hospital, The First People’s Hospital of Neijiang, West China Yibin Hospital/the Second People’s Hospital of Yibin, and the Affiliated Hospital of Chengdu University between 2015 and 2022, were retrospectively analyzed. The X-tile software was used to calculate the optimal truncation of the ATS score. Cox proportional hazard regression model was used to explore risk factors affecting postoperative recurrence-free survival (RFS) and overall survival (OS) in HCC patients, respectively. ResultsAll patients were followed-up with a median of 37 months (1–90 months), 1 364 cases (46.9%, the recurrence time was 1–89 months after surgery) of them experienced recurrence and 847 cases (29.1%) died (the death time was 1–88 months after surgery). The 1-, 2- and 3-year OS rates were 89.3%, 81.4% and 75.9%, respectively. The 1-, 2- and 3-year RFS rates were 76.0%, 64.3% and 57.2%, respectively. The 5-year RFS rate of HCC patients with low-, medium-, and high-ATS scores were 56.4%, 45.0% and 27.2%, respectively, and patients with low ATS score had better RFS (χ2=264.747, P<0.001). The 5-year OS rates of HCC patients with low-, medium-, and high-ATS scores were 78.0%, 59.8% and 38.8%, respectively, and patients with low-ATS score had better OS (χ2=372.685, P<0.001). Multivariate Cox proportional hazard regression model suggested that, in condition of adjusting other factors, medium-ATS score [RR=1.375, 95%CI (1.209, 1.564), P<0.001] and high-ATS score [RR=2.048, 95%CI (1.764, 2.377), P<0.001] were risk factors for postoperative RFS; the medium-ATS score [RR=1.779, 95%CI (1.499, 2.112), P<0.001] and high ATS score [RR=2.676, 95%CI (2.211, 3.239), P<0.001] were also risk factors affecting postoperative OS. ConclusionATS score can predict the prognosis of HCC patients after resection, patients with high ATS score had a higher incidence of postoperative recurrence and mortality.
目的 通過檢測肝病患者血清甲胎蛋白異質體(AFP-L3)濃度和AFP-L3/血清甲胎蛋白(AFP)比值,分析探討并聯運用兩指標在肝細胞癌(HCC)診斷中的價值。 方法 選取2011年3月-11月137例的住院患者血清標本,AFP檢測均為陽性。依據病理學診斷,將137例患者分為兩組,HCC組92例,良性肝病組45例,后者包括肝硬化結節37例、慢性活動性肝炎8例。采用酶聯免疫吸附試驗(ELISA)檢測所有患者血清AFP-L3濃度;同時運用微量吸附柱法分離血清中的AFP-L3,采用電化學發光法檢測分離后的AFP-L3和血清中總AFP濃度,計算AFP-L3/AFP比值。計算采用AFP-L3濃度與AFP-L3/AFP比值以及AFP-L3濃度與AFP-L3/AFP比值兩指標并聯診斷HCC的靈敏度、特異度、Youden指數等統計學指標,探討其在原發性肝癌診斷中的價值。 結果 ① HCC組 AFP-L3濃度(109.04 ± 62.51)ng/mL,明顯高于良性肝病組(25.96 ± 49.43)ng/mL,差異有統計學意義(t=8.28,P<0.001)。HCC組血清AFP-L3/AFP比值(17.35 ± 14.48%)高于良性肝病組(5.617 ± 6.38%), 差異有統計學意義(t=6.545,P<0.0001)。② 以血清AFP-L3濃度>38.0 ng/mL作為臨界值診斷原發性肝癌的靈敏度為83.69%,特異度為88.88%,以AFP-L3/AFP比值>10%作為臨界值診斷原發性肝癌的靈敏度為83.69%,特異度為95.55%。③ 并聯應用血清AFP-L3濃度>38.0 ng/mL、AFP-L3/AFP>比值7.5%診斷HCC的靈敏度為97.83%,特異度為84.44%。 結論 并聯應運AFP-L3濃度與AFP-L3/AFP比值診斷HCC較應用單一指標診斷特異度稍有下降,但明顯提高了診斷的靈敏度,更有利于HCC的早期診斷。
【Abstract】Objective To explore the changes of expression of AFP mRNA in human hepatocellular carcinoma (HCC) tissues after oral Xeloda therapy.Methods Total RNA was extracted from HCC tissue samples collect after operation and nested reverse transcription polymerase chain reaction (RT-nested PCR) assay was performed to determine the expression of AFP mRNA in this study.Results The final product of AFP mRNA amplified by RT-PCR was 174 bp and by RT-nested PCR was 101 bp. The AFP mRNA is positive in 12 of 21 patients (positive rate 57.14%) amplified by RT-nested PCR assay in Xeloda treatment group which is much lower than control group: 18 of 20 patients (positive rate 90.00%),P<0.05.The serum AFP value of Xeloda treatment group 〔(23.2±12.8) μg/L〕 is much lower than that of control group 〔(39.6±24.3) μg/L〕 four weeks after operation (P<0.05). However, There was no difference between two groups in serum AFP value before operation.Conclusion Xeloda can effectively suppress the expression of AFP mRNA in human HCC tissues and lower it’s product serum AFP value.The clinical application of Xeloda in HCC patients deserve further study.