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    Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma. Wang Ting,Liu Mei,Zheng Su-Jun,Bian Dan-Dan,Zhang Jin-Yan,Yao Jia,Zheng Qing-Fen,Shi A-Meng,Li Wen-Han,Li Lu,Chen Yu,Wang Jin-Hai,Duan Zhong-Ping,Dong Lei World journal of gastroenterology AIM:To determine the prevalence and diagnostic value of autoantibodies in α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC). METHODS:Fifty-six serum samples from AFP-negative HCC cases, 86 from AFP-positive HCC cases, 168 from chronic liver disease cases, and 59 from normal human controls were included in this study. Autoantibodies to nucleophosmin (NPM)1, 14-3-3zeta and mouse double minute 2 homolog (MDM2) proteins in AFP-negative HCC serum were evaluated by enzyme-linked immunosorbent assay. Partially positive sera were further evaluated by western blotting. Immunohistochemistry was used to detect the expression of three tumor-associated antigens (TAAs) in AFP-negative HCC and normal control tissues. RESULTS:The frequency of autoantibodies to the three TAAs in AFP-negative HCC sera was 21.4%, 19.6% and 19.6%, which was significantly higher than in the chronic liver disease cases and normal human controls ( < 0.01) as well as AFP-positive HCC cases. The sensitivity of the three autoantibodies for diagnosis of AFP-negative HCC ranged from 19.6% to 21.4%, and the specificity was approximately 95%. When the three autoantibodies were combined, the sensitivity reached 30.4% and the specificity reached 91.6%. CONCLUSION:Autoantibodies to NPM1, 14-3-3zeta and MDM2 may be useful biomarkers for immunodiagnosis of AFP-negative HCC. 10.3748/wjg.v23.i19.3496
    [Characteristics of contrast-enhanced ultrasound in alpha-fetoprotein-negative recurrent small hepatocellular carcinoma]. Fu X B,Yuan J J,Yang L,Wang Q,Zhao X J Zhonghua zhong liu za zhi [Chinese journal of oncology] To investigate the characteristics of contrast-enhanced ultrasound (CEUS) in alpha-fetoprotein (AFP)-negative recurrent small hepatocellular carcinoma (rsHCC). The imaging characteristics of CEUS were retrospectively analyzed in 132 lesions from 116 patients with rsHCC, including 59 lesions from 51 AFP-negative patients and 73 lesions from 65 AFP-positive patients. The hemodynamic parameters such as contrast-enhanced onset time, time-to-peak, isoenhancement start time, low-enhancement start time, and perfusion mode were compared between two groups. The time-to-peak, isoenhancement start time, low-enhancement start time of AFP-negative group were significantly increased than those in AFP-positive group (23.22±5.08)s vs. (20.30±3.41)s, (59.44±39.75)s vs. (40.75±16.16)s, (102.89±44.45)s vs. (87.08±25.27)s (all of <0.05). Meanwhile, the proportion of isoenhancement during the portal and late phases in AFP-negative group was significantly higher than those in AFP-positive group (59.3% vs. 37.0%, 16.9% vs. 4.1%; all of <0.05). However, there was no significant difference between the two groups in the enhancement start time (14.87±6.00)s vs. (14.35±5.30)s (>0.05) as well as isoenhancement proportion in the arterial phase (94.9% vs. 98.6%, >0.05). The enhancement pattern of CEUS in AFP-negative rsHCC patients was "fast-in and slow-out" with a diverse and atypical trend. Recognizing its regular features will facilitate the early detection of AFP-negative rsHCC. 10.3760/cma.j.cn112152-20190408-00222
    Preoperative Carbohydrate Antigen 19-9: Its Neglected Role in Alpha-Fetoprotein-Negative Hepatocellular Carcinoma Patients. Lu Liang-He,Zhang Yong-Fa,Wei Wei,Shi Ming,Guo Rong-Ping Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract PURPOSE:The study aimed to investigate the prognostic role of the preoperative carbohydrate antigen 19-9 (CA19-9) level in alpha-fetoprotein (AFP)-negative (AFP < 25 ng/ml) hepatocellular carcinoma (HCC) patients. METHODS:From December 2004 to December 2013, 750 patients diagnosed with AFP-negative HCC following curative resection were enrolled. Both univariate and multivariate analyses were performed to clarify the prognostic factors for overall survival (OS) and disease-free survival (DFS). RESULTS:The optimal cutoff point for preoperative CA19-9 was 32.6 U/ml, and the value of the area under the curve was 0.640. The 1-, 3-, and 5-year OS rates were 88.4, 72.2, and 57.0%, respectively, for the CA19-9 > 32.6 U/ml group and 97.0, 83.3, and 79.9%, respectively, for the CA19-9 ≤ 32.6 U/ml group (P < 0.001). The 1-, 3-, and 5-year DFS rates were 71.8, 47.7, and 34.8%, respectively, for the CA19-9 > 32.6 U/ml group and 80.8, 63.6, and 55.5%, respectively, for the CA19-9 ≤ 32.6 U/ml group (P < 0.001). The multivariate analysis showed that CA19-9 > 32.6 U/ml was one of the most significant unfavorable predictors of OS and DFS (P < 0.001 for both). CONCLUSIONS:Preoperative CA19-9 > 32.6 U/ml is a predictor of dismal prognosis and can be employed as a prognostic marker for patient selection in AFP-negative HCC management. 10.1007/s11605-017-3528-5