Objective: To investigate the clinical value of serum glypican-3 (GPC3) detection in predicting recurrence of primary hepatocellular carcinoma (HCC). Methods: Through univariate and multivariate logistic regression analysis, the patients pathologically diagnosed with HCC in our hospital from March 2019 to January 2021 were enrolled as the experimental group (n=113), and patients with follow-up time longer than 6 months were included in the prognosis group(n=64). At the same time,20 healthy individuals and 20 individuals with benign liver disease from the physical examination center were enrolled by simple random sampling as control group (n=40). The serum GPC3 and alpha-fetoprotein (AFP) levels were respectively detected by ELISA and chemiluminescence. Then, the study explored the influential factors of the recurrence in HCC patients and constructed the HCC-GPC3 recurrence predicting model by logistic regression. Results: In the research, the sensitivity of GPC3 for the diagnosis of HCC was 61.95% (70/113) and AFP was 52.21% (59/113), meanwhile, the specificity of GPC3 could reach 87.50% (35/40) and AFP was 90.00% (36/40),respectively; The serum GPC3 levels of HCC patients with progressive stage, tumor size≥3 cm, vascular cancer thrombosis and portal venous thromboembolism were significantly higher than that of HCC patients with early stage, tumor size<3 cm, vascular cancer thrombosis and portal venous thromboembolism (Z=2.677, 2.848, 2.995, 2.252, P<0.05), independent of different ages, presence or absence of ascites, peritoneal metastasis, cirrhosis, intrahepatic metastasis (Z=-1.535, 1.011, 0.963, 0.394, 1.510, P>0.05), respectively. Univariate analysis showed that there were no statistically significant differences between the recurrence group and the non-recurrence group in terms of different age, tumor size, presence or absence of vascular cancer thrombosis, ascites, peritoneal metastasis, cirrhosis and AFP levels (χ²=2.012, 0.119, 2.363, 1.041, 0.318, 0.360, Z=0.748, P>0.05); The ratio of those with the progressive stage, portal venous thromboembolism and intrahepatic metastasis and GPC3 levels were all higher in the recurrence group than in the non-recurrence group (χ²=4.338, 11.90, 4.338, Z=2.805, P<0.05).Including the above risk factors in the logistic regression model, the logistic regression analysis showed that the stage, the presence of portal venous thromboembolism,intrahepatic metastasis and GPC3 levels were correlated with the prognosis recurrence of HCC patients (Wald χ² =4.421, 5.681, 4.995, 4.319, P<0.05), and the HCC-GPC3 recurrence model was obtained as: OcScore=-2.858+1.563×[stage]+1.664×[intrahepatic metastasis]+2.942×[ portal venous thromboembolism]+0.776×[GPC3]. According to the receiver operating characteristic curve(ROC), the area under the curve(AUC)of the HCC-GPC3 prognostic model was 0.862, which was better than that of GPC3 alone (AUC=0.704). The cut-off value of model SCORE was 0.699 (the cut-off value of GPC3 was 0.257 mg/L), furthermore, the total sensitivity and specificity of model were 83.3% and 82.4%, which were better than those of GPC3(60.0% and 79.4%).Kaplan-Meier showed that the median PFS was significantly shorter in HCC patients with high GPC3 levels (≥0.257 mg/L) and high values of the model SCORE (≥0.700) (χ²=12.73, 28.16, P<0.05). Conclusion: Besides diagnosing of HCC, GPC3 can may be an independent risk indicator for the recurrence of HCC and can more efficiently predicting the recurrence of HCC patients when combined with the stage, the presence or absence of intrahepatic metastasis and portal venous thromboembolism.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/diagnosis* ; alpha-Fetoproteins/analysis* ; Biomarkers, Tumor ; Glypicans ; Ascites ; Venous Thromboembolism ; Peritoneal Neoplasms ; Liver Cirrhosis

Objective: To investigate hepatic perivascular epithelioid cell tumor (PEComa) diagnosis and treatment plan. Methods: 24 cases diagnosed with PEComa clinical manifestations, serum alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), imaging findings, surgical methods, postoperative hospital stay, pathological results and prognosis were analyzed retrospectively from September 2015 to September 2020. Results: Majority of patients were females (79.2%), aged 41.5±11.4 years. Tumors were predominantly located in the right liver (50.0%). 76.7% of the cases were mostly clinically asymptomatic. AFP, CEA and CA199 indices were all negative. CT mostly showed low density tumor in the plain scan phase, enhanced in the enhancement phase, and enhanced and weakened in portal venous and equilibrium phase (66.7%). MRI manifestations of most tumors were hypointense on T₁WI and hyperintense on T₂WI (72.7%). B-ultrasound mostly showed hyperechoic mass in the tumor area with punctate vascular shadow (52.9%). Postoperative hospital stay was 9.0±2.4 days for laparoscopic surgery patients (n=13), 13.4±6.3 days for traditional laparotomy (hereinafter referred to as laparotomy, n=10), and 3 days for 1 patient with microwave ablation. All postoperative pathological results were positive for HMB45 and Melan-A. Follow-up results: 21 cases survived normally, with no tumor recurrence in the recent physical examination; two cases had tumor recurrence and they died two and three years after surgery, and one case was lost to follow-up. Conclusion: Hepatic PEComa more commonly occurs in middle-aged women, with no specific features for tumor markers and clinical manifestations. Some imaging findings are specific, so its features can be combined as a basis for diagnosis. Postoperative pathological examination results can confirm the diagnosis. Therefore, surgery remains the initial treatment plan. Microwave ablation and laparoscopic surgery are recommended as the preferred option because of shorter hospital stays and less trauma than open surgery.
Adult ; Biomarkers, Tumor/analysis* ; Carbohydrates ; Carcinoembryonic Antigen ; Female ; Humans ; Liver/pathology* ; MART-1 Antigen ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Perivascular Epithelioid Cell Neoplasms/surgery* ; Retrospective Studies ; alpha-Fetoproteins

PURPOSE: To identify the prognostic factors that could influence survival and to compare prognoses of the patients with the number of the risk factors that might assist in the adequate management of hepatocellular carcinoma (HCC) patients with bone metastases that showed a heterogeneous range of survival. MATERIALS AND METHODS: A total of 41 patients, treated with radiotherapy (RT) for bone metastases from HCC from 2014 to 2017, were enrolled retrospectively. Survival was determined by the Kaplan–Meier method from the start of the RT for metastatic bone lesions. Pre-RT clinical features were evaluated and their influences on survival were analyzed. The significant factors were considered to compare survivals according to the number of prognostic factors. RESULTS: Median follow-up was 6.0 months (range, 0.5 to 47.0 months). The median overall survival was 6.5 months, and the 1-year and 2-year survival rates were 35.5% and 13.5%, respectively. Multivariate analysis revealed that the Child-Pugh class A group, alpha-fetoprotein increased more than 30 ng/mL, and HCC size of more than 5 cm were associated with worse overall survival. The median survivals in HCC with none, 1, 2, and 3 of the aforementioned risk factors were 19.5, 9.0, 2.5, and 1.0 months, respectively (p < 0.05). CONCLUSION: Our results show that the overall survivals were significantly different according to the number of the risk factors among HCC patients with bone metastases who showed various lengths of survival.
alpha-Fetoproteins ; Carcinoma, Hepatocellular ; Follow-Up Studies ; Humans ; Methods ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Radiotherapy ; Retrospective Studies ; Risk Factors ; Survival Rate ; Triage

BACKGROUND/AIMS: The treatments and outcomes of hepatocellular carcinoma (HCC) with bile duct invasion are not well known. We aimed to confirm the safety of transarterial chemolipiodolization (TACL) and identify prognostic factors for patients with bile duct invasion treated with TACL. METHODS: Fifty patients with central bile duct invasion treated with TACL between 2005 and 2017 were enrolled. Patients were divided into three groups: hyperbilirubinemia (total bilirubin ≥2.5 mg/dL) with pre-TACL biliary drainage, hyperbilirubinemia without biliary drainage, and without hyperbilirubinemia. Tumor response to TACL, survival outcomes, length of hospitalization, adverse events using Common Terminology Criteria for Adverse Events (CTCAE), and factors affecting overall survival were compared. RESULTS: TACL-induced changes of mean CTCAE grades for albumin, alanine aminotransferase, creatinine, prothrombin time, and platelet were not significantly different among patients with or without initial hyperbilirubinemia. Serum bilirubin level was not significantly changed after TACL in all the three groups. Overall survival was not significantly different among the three groups (P=0.097). On multivariate analysis, alpha-fetoprotein < 400 ng/dL (hazard ratio [HR]=0.477, P=0.048) and highest total bilirubin level of < 2.5 mg/dL within one month after TACL (HR=0.335, P=0.004) were significantly associated with longer survival. CONCLUSIONS: TACL was a safe treatment for HCC patients with central bile duct invasion, irrespective of the presence of initial hyperbilirubinemia.
Alanine Transaminase ; alpha-Fetoproteins ; Bile Ducts ; Bile ; Bilirubin ; Blood Platelets ; Carcinoma, Hepatocellular ; Chemoembolization, Therapeutic ; Creatinine ; Drainage ; Hospitalization ; Humans ; Hyperbilirubinemia ; Multivariate Analysis ; Prothrombin Time

BACKGROUND/AIMS: α-Fetoprotein (AFP) is normally <10 ng/mL in adults without malignancy or liver regeneration. However, hereditary or nonhereditary persistence of AFP in healthy adults may be encountered in clinical practice. This study describes four cases of persistent AFP elevation in healthy adults and investigates mutations in key transcription regulatory regions of the AFP gene as potential drivers of AFP overexpression. METHODS: Four healthy adults with persistently elevated AFP levels (12.1 to 186.1 ng/mL) for >1 year, and 20 controls with low AFP levels (<0.61 to 2.9 ng/mL) were included in the study. AFP levels were collected from the families of two of the patients. We sequenced five regions that are critical for AFP expression: a promoter, two enhancers, and two silencers. RESULTS: One of the two cases in which family information was represented is the first case of hereditary persistence of AFP in South Korea. Mutations related to AFP overexpression were not found in the transcription regulatory regions among the four patients. CONCLUSIONS: Persistent AFP elevation is a heterogeneous condition with or without a hereditary pattern and may be caused by factors outside of transcription regulatory region changes. Further research on the mechanism of AFP elevation is needed.
Adult* ; alpha-Fetoproteins ; Biomarkers ; DNA Mutational Analysis ; Humans ; Korea ; Liver Regeneration ; Regulatory Sequences, Nucleic Acid

PURPOSE: Patient, surgical, and tumor factors affect the outcome after surgical resection for hepatocellular carcinoma (HCC). The surgical factors are only modifiable by the surgeon. We reviewed our experience with curative resection for HCC in terms of surgical factors. METHODS: After analyses of the prospectively collected clinical data of 256 consecutive patients undergoing surgical resection for HCC, prognostic factors for disease-free survival (DFS) and overall survival (OS) were identified; all patients were stratified by tumor diameters > or <5 cm and their outcomes were compared. RESULTS: Multivariate analyses showed that microvascular invasion, estimated blood loss, blood transfusion, and the number of tumors were independent adverse prognostic factors for DFS, whereas microvascular invasion, serum alpha fetoprotein, and tumor diameter were independent adverse prognostic factors for OS. Blood transfusion had borderline significance (P = 0.076). After stratification by tumor diameter, blood transfusion was only associated with poor DFS and OS in patients with tumor diameters > 5 cm. CONCLUSION: Tumor recurrence after liver resection for HCC depends on tumor status, bleeding, and transfusions, which subsequently lead to poor patient survival. Surgeons can help improve the prognosis of patients by minimizing blood loss and transfusion, particularly in patients with larger tumors.
alpha-Fetoproteins ; Blood Transfusion ; Carcinoma, Hepatocellular* ; Disease-Free Survival ; Hemorrhage ; Hepatectomy ; Humans ; Liver ; Liver Cirrhosis ; Multivariate Analysis ; Prognosis ; Prospective Studies ; Recurrence ; Surgeons

To establish a fetal biparietal diameter (BPD)-gestational age formula based on the data of pregnant women from Xiaoshan District of Hangzhou, and to evaluate its application in prenatal screening.Data of 3500 pregnant women with gestational age between 15 weeks and 19 weeks+6 receiving prenatal screening in Xiaoshan Hospital during May 2014 and May 2015 were collected. BPDs were used to establish a localized BPD-gestational age formula. The localized formula was used to evaluate the prenatal screening risks in 1759 pregnant women with irregular menstrual cycles or uncertain last menstrual period (LMP) in Xiaoshan District, and the results were compared with those calculated using formula in LifeCycle 4.0.With localized formula, the total positive rate of Down syndrome, trisomy 18 syndrome and deformity of neural tube was decreased from 6.96% to 5.85% (<0.05), in which the positive rate of Down syndrome decreased (<0.05), that of deformity of neural tube increased (<0.05), and that of trisomy 18 syndrome remained the same (>0.05). The median MoMs of free-hCG β and &alpha;-fetoprotein calculated using localized formula were significantly different from those calculated using the formula in LifeCycle 4.0 (all<0.05), and the former ones were more closer to 1. For women of fetus diagnosed with the above diseases, the positive rate calculated using localized formula was almost the same as that calculated using the formula in LifeCycle 4.0.BPD-gestational age formula should be localized based on the statistical analysis of the local population, which will help to reduce the false positive rate, and make the results more accurate and reliable in prenatal screening.
Adult ; Body Weights and Measures ; standards ; Cephalometry ; standards ; statistics & numerical data ; Chorionic Gonadotropin, beta Subunit, Human ; blood ; standards ; Chromosomes, Human, Pair 18 ; Down Syndrome ; diagnosis ; embryology ; Epidemiologic Measurements ; Female ; Fetal Development ; Gestational Age ; Head ; embryology ; Humans ; Mass Screening ; methods ; standards ; statistics & numerical data ; Menstrual Cycle ; Neural Tube Defects ; diagnosis ; embryology ; Pregnancy ; Prenatal Diagnosis ; methods ; standards ; statistics & numerical data ; Reference Values ; Trisomy ; diagnosis ; Trisomy 18 Syndrome ; alpha-Fetoproteins ; analysis ; standards

BACKGROUND/AIMS: The aim of this study was to evaluate the feasibility of alpha-fetoprotein (AFP) as a diagnostic tool for hepatocellular carcinoma (HCC) in Korean patients. METHODS: We retrospectively reviewed the medical records of HCC and cirrhosis patients at three hospitals. For each HCC patient, a cirrhosis patient matched for age, sex, etiology, and Child-Pugh classification was selected by simple random sampling. The performance of AFP in the diagnosis of HCC was determined using receiver operating characteristic curve analysis. RESULTS: A total of 732 patients with HCC or cirrhosis were selected for each case and the control groups. The mean age was 54 years, and 72.4% of patients were male. The mean serum AFP levels in the HCC group and cirrhosis group were 3,315.6 and 117.2 ng/mL, respectively (p < 0.001). The area under the receiver operating characteristic curve for all HCC patients was 0.757. The sensitivity, specificity, and positive predictive value of AFP was 50.55%, 87.70%, and 80.43%, respectively, at a cut-off of 20 ng/mL; 37.70%, 95.90%, and 90.20%, respectively, at a cut-off of 100 ng/mL, and 30.05%, 97.27%, and 91.67%, respectively, at a cut-off of 200 ng/mL. A cut-off of 100 ng/mL was more sensitive than one of 200 ng/mL with equivalent specificity and positive predictive value. CONCLUSIONS: The cut-off AFP value for early-stage HCC was 17.4 ng/mL. Our study cautiously suggests that AFP has a role in the diagnosis of HCC, and that the appropriate value of AFP for the diagnosis of HCC may be 100 ng/mL rather than 200 ng/mL.
Aged ; Area Under Curve ; Carcinoma, Hepatocellular/*blood/*diagnosis/pathology ; Feasibility Studies ; Female ; Humans ; Liver Neoplasms/*blood/*diagnosis/pathology ; Male ; Middle Aged ; Neoplasm Staging ; Predictive Value of Tests ; ROC Curve ; Republic of Korea ; Retrospective Studies ; alpha-Fetoproteins/*analysis

The bone is a common site for metastasis in hepatocellular carcinoma (HCC). However, bone marrow metastasis from HCC is rarely reported, and its frequency is unclear. Here we report a rare case of bone marrow metastasis that presented as bicytopenia originating from HCC without bone metastasis. A 58-year-old man was admitted for investigation of a liver mass with extensive lymph node enlargement that was detected when examining his general weakness and weight loss. Laboratory findings revealed anemia, thrombocytopenia, mild elevated liver enzymes, normal prothrombin time percentage and high levels of tumor markers (α-fetoprotein and des-γ-carboxyprothrombin). Abdominal computed tomography showed multiple enhanced masses in the liver and multiple enlarged lymph nodes in the abdomen. A bone marrow biopsy revealed only a few normal hematopoietic cells and abundant tumor cells. Despite its rarity, bone marrow metastasis should always be suspected in HCC patients even if accompanied by cirrhosis.
Biomarkers/analysis ; Bone Marrow/*pathology ; Carcinoma, Hepatocellular/*diagnosis ; Humans ; Liver Neoplasms/*diagnosis ; Male ; Middle Aged ; Neoplasm Metastasis ; Positron Emission Tomography Computed Tomography ; Protein Precursors/analysis ; Prothrombin/analysis ; Thrombocytopenia/diagnosis ; Tomography, X-Ray Computed ; alpha-Fetoproteins/analysis

BACKGROUND/AIMS: Several studies have suggested that surgical resection (SR) can provide a survival benefit over transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) at the intermediate stage according to the Barcelona Clinic Liver Cancer (BCLC) staging system. However, the criteria for SR remain to be determined. This study compared the long-term outcome of intermediate-stage HCC patients treated by either TACE or SR as a primary treatment modality, with the aim of identifying the patient subgroup that gained a survival benefit by either modality. METHODS: In total, 277 BCLC intermediate-stage HCC patients treated by either TACE (N=225) or SR (N=52) were analyzed. RESULTS: The overall median survival time was significantly better for SR than TACE (61 vs. 30 months, P=0.002). Decision-tree analysis divided patients into seven nodes based on tumor size and number, serum alpha-fetoprotein (AFP) level, and Child-Pugh score, and these were then simplified into four subgroups (B1-B4) based on similarities in the overall hazard rate. SR provided a significant survival benefit in subgroup B2, characterized by ‘oligo' (2-4) nodules of intermediate size (5-10 cm) when the AFP levels was <400 ng/ml, or ‘oligo' (2-4) nodules of small to intermediate size (<10 cm) plus a Child-Pugh score of 5 when the AFP level was ≥400 ng/mL (median survival 73 vs. 28 months for SR vs. TACE respectively; P=0.014). The survival rate did not differ significantly between SR and TACE in the other subgroups (B1 and B3). CONCLUSIONS: SR provided a survival benefit over TACE in intermediate-stage HCC, especially for patients meeting certain criteria. Re-establishing the criteria for optimal treatment modalities in this stage of HCC is needed to improve survival rates.
Adult ; Aged ; Carcinoma, Hepatocellular/mortality/pathology/*surgery ; Chemoembolization, Therapeutic ; Female ; Hepatectomy ; Humans ; Liver Neoplasms/mortality/pathology/*surgery ; Male ; Middle Aged ; Neoplasm Staging ; Proportional Hazards Models ; Survival Rate ; Treatment Outcome ; alpha-Fetoproteins/analysis