Serum Α-fetoprotein Research Articles

Can the Severity of Intrahepatic Cholestasis of Pregnancy be Predicted by Second Trimester Screening Test Parameters?

Abstract Objective The second trimester triple test although declared inadequate for the screening of aneuploidies by the International Society for Prenatal Diagnosis remains a widely employed test. We aim to investigate the associations between the biochemical parameters of the triple test and the severity of intrahepatic cholestasis of pregnancy (ICP). Material and Methods The triple test parameters of 102 healthy pregnant women and 100 pregnant women with ICP were evaluated retrospectively. Serum bile acid level of ≥ 40 μmol/L was categorized as severe ICP. Serum α-fetoprotein (AFP), β-human chorionic gonadotropin (β-hCG), and unconjugated estriol (uE3) multiple of the median (MoM) values and the perinatal outcomes were recorded. The Student’s t-test, Mann–Whitney U test, Kruskal–Wallis test, and receiver operating characteristic curve analysis were used to compare the data. Results The AFP, β-hCG, and uE3 MoM values were higher in the severe ICP group when compared to those with mild ICP and those without ICP (p < 0.01). The sensitivity and specificity values for ICP were 80.95% and 73.42%, respectively, with AFP values ≥ 1.26 MoM, 76.19% and 88.61%, respectively, with β-hCG values ≥ 1.78 MoM, and 61.90% and 94.94%, respectively, with uE3 values ≥ 1.58 MoM [95% confidence interval; area under the curve (AUC) ± standard error (SE) = 0.810 ± 0.049, AUC ± SE: 0.790 ± 0.065, and AUC ± SE: 0.797 ± 0.065, respectively]. Conclusion An increase in the AFP, β-hCG, and uE3 MoM values in the triple test can predict the risk of developing severe ICP.

Detection of Circulating Tumor Cells (CTCs) in Patients with Testicular Germ Cell Tumors.

While the majority of patients with advanced testicular germ cell tumors (GCT) achieve complete responses after chemotherapy and if indicated after postchemotherapy resection of residual lesions, about 20% of patients have incomplete responses or show relapses. Moreover, toxicity of chemotherapy is high, and severe adverse chronic effects have been described. Therefore, there is an urgent need for biomarkers that could help to improve tumor staging, and support decision-making, ideally including monitoring of therapy response and prediction of relapse. Besides the well-established serum markers lactate dehydrogenase, α-fetoprotein, and β-subunit of human chorionic gonadotropin, during recent years new noninvasive liquid biopsy markers have been investigated in GCT, including cell-free nucleic acids like microRNAs, and circulating tumor cells (CTCs).Prognostic relevance has been demonstrated for circulating tumor cells (CTCs) in patients with different cancers. However, little is known in GCT patients. Histologically, GCT are a very heterogeneous group of tumors comprising pure seminomas (consisting of cells that remember primordial germ cells) and nonseminomas, which are either undifferentiated (embryonal carcinoma) or differentiated, exhibiting different degrees of embryonic (teratoma) or extraembryonic (yolk sac tumor and choriocarcinoma) differentiation. This heterogeneity hampers capture and detection of CTCs deriving from those tumors using a single method or a single antibody. To date, label-independent capture methods that enrich tumor cells according to the density of GCT cells, which is similar to that of mononuclear cells, have been successfully applied. Since testicular GCT might also express epithelial proteins, methods based on enrichment of CTCs using epithelial markers are promising to detect CTCs in certain subgroups of patients with GCTs as well.Here, we describe and discuss a combination of methods to capture and detect GCT cells with epithelial and germ cell characteristics in blood.

Transarterial- chemoembolization remains an effective therapy for intermediate-stage hepatocellular carcinoma with preserved liver function.

To evaluate outcomes as well as prognostic factors of transarterial chemoembolization (TACE) in intermediate-stage hepatocellular carcinoma (HCC) with preserved liver function to determine positioning of TACE. Of 158 treatment-naïve patients with intermediate-stage HCC who received initial TACE from February 2007 to January 2016, 113 patients met the following inclusion criteria: no combined therapy within 4weeks after initial TACE, and Child-Pugh score under 7. Response rate and overall survival were evaluated. The prognostic factors were investigated in univariate and multivariate analyses using Cox proportional hazards models. The deterioration of liver function after repeated TACE was also evaluated. The response rate was 92.7% (complete response, 63.3%; partial response, 29.4%). The median survival time was 45.2months. Survival rates at 1, 2, and 3years were 90.4%, 77.0%, and 60.8% respectively. Age ≥ 75years (P = 0.022), serum α-fetoprotein level ≥ 200ng/mL (P = .010), tumor number ≥ 11 (P = 0.008), and heterogeneous enhancement on dynamic computed tomography (P = 0.024) were poor prognostic factors. The deterioration rate of Child-Pugh score and albumin-bilirubin grade was 18.5% and 12.3%, respectively, after the first TACE, 15.6% and 5.1%, respectively, after the second TACE, and 14.5% and 11.1%, respectively, after the third TACE. Superselective TACE can achieve high tumor response rates with prolonged overall survival for patients with intermediate-stage HCC with preserved liver function. Age, serum α-fetoprotein level, tumor number ≥ 11, and heterogeneous enhancement on dynamic computed tomography indicated significantly poor prognosis.

Impact of tenofovir antiviral treatment on survival of chronic hepatitis B related hepatocellular carcinoma after hepatectomy in Chinese individuals from Qingdao municipality

The impact of different antiviral regimen on prognosis of chronic hepatitis B (CHB) related hepatocellular carcinoma (HCC) remains to be explored.A total of 479 CHB-related HCC patients after curative liver resection were enrolled receiving tenofovir (TDF, TDF group) or lamivudine, telbivudine, and entecavir (non-TDF group). Both the overall survival and diseases-free survival were analyzed and compared.A total of 242 patients received TDF treatment and 237 patients received other antiviral regimen. Child-Pugh score, serum α-fetoprotein (AFP) level, total bilirubin level, status of hepatitis B e antigen (HBeAg), and cirrhosis were compared between groups. Kaplan-Meier analysis revealed that patients with TDF treatment had significantly longer overall survival than those of patients with other regimen (P = .015). Similarly, compared with patients with non-TDF treatment, disease-free survival time was longer (P = .042) in those with TDF treatment. Multivariate analysis showed that TDF treatment (P = .04), AFP level (P = .03) were significant independent factors associated with overall survival of CHB-related HCC patients. While TDF treatment (P = .04) and serum AFP level (P = .03) were independent factors associated with disease-free survival.Anti-virus treatment with TDF benefits for both overall survival and disease-free survival of CHB-related patients than other Nucleos(t)ide analogues.

Imaging in gynecological disease (17): ultrasound features of malignant ovarian yolk sac tumors (endodermal sinus tumors).

To describe the clinical and sonographic characteristics of malignant ovarian yolk sac tumors (YSTs). In this retrospective multicenter study, we included 21 patients with a histological diagnosis of ovarian YST and available transvaginal ultrasound images and/or videoclips and/or a detailed ultrasound report. Ten patients identified from the International Ovarian Tumor Analysis (IOTA) studies had undergone a standardized preoperative ultrasound examination, by an experienced ultrasound examiner, between 1999 and 2016. A further 11 patients were identified through medical files, for whom ultrasound images were retrieved from local image workstations and picture archiving and communication systems. All tumors were described using IOTA terminology. The collected ultrasound images and videoclips were used by two observers for additional characterization of the tumors. All cases were pure YSTs, except for one that was a mixed tumor (80% YST and 20% embryonal carcinoma). Median age at diagnosis was 25 (interquartile range (IQR), 19.5-30.5) years. Seventy-six percent (16/21) of women had an International Federation of Gynecology and Obstetrics (FIGO) Stage I-II tumor at diagnosis. Fifty-eight percent (11/19) of women felt pain during the ultrasound examination and one presented with ovarian torsion. Median serum α-fetoprotein (S-AFP) level was 4755 (IQR, 1071-25 303) µg/L and median serum CA 125 level was 126 (IQR, 35-227) kU/L. On ultrasound assessment, 95% (20/21) of tumors were unilateral. The median maximum tumor diameter was 157 (IQR, 107-181) mm and the largest solid component was 110 (IQR, 66-159) mm. Tumors were classified as either multilocular-solid (10/21; 48%) or solid (11/21; 52%). Papillary projections were found in 10% (2/21) of cases. Most (20/21; 95%) tumors were well vascularized (color score, 3-4) and none had acoustic shadowing. Malignancy was suspected in all cases, except in the patient with ovarian torsion, who presented a tumor with a color score of 1, which was classified as probably benign. Image and videoclip quality was considered as adequate in 18/21 cases. On review of the images and videoclips, we found that all tumors contained both solid components and cystic spaces, and that 89% (16/18) had irregular, still fine-textured and slightly hyperechoic solid tissue, giving them a characteristic appearance. Malignant ovarian YSTs are often detected at an early stage, in young women usually in the second or third decade of life, presenting with pain and markedly elevated S-AFP. On ultrasound, malignant ovarian YSTs are mostly unilateral, large and multilocular-solid or solid, with fine-textured slightly hyperechoic solid tissue and rich vascularization. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology..

Risk of Liver Cirrhosis and Hepatocellular Carcinoma after Fontan Operation: A Need for Surveillance.

Liver cirrhosis and hepatocellular carcinoma (HCC) are serious late complications that can occur after the Fontan procedure. This study aimed to investigate the cumulative incidence of cirrhosis and HCC and to identify specific features distinguishing HCC from benign arterial-phase hyperenhancing (APHE) nodules that developed after the Fontan operation. We retrospectively enrolled 313 post-Fontan patients who had been followed for more than 5 years and had undergone ultrasound or computed tomography (CT) of the liver between January 2000 and August 2018. Cirrhosis was diagnosed radiologically. The estimated cumulative incidence rates of cirrhosis at 5, 10, 20, and 30 years after the Fontan operation were 1.3%, 9.2%, 56.6%, and 97.9%, respectively. Multiphasic CT revealed that 18 patients had APHE nodules that were ≥1 cm in size and showed washout in the portal venous phase (PVP)/delayed phase, which met current noninvasive HCC diagnosis criteria. Among them, only seven patients (38.9%, 7/18) were diagnosed with HCC. After cirrhosis developed, the annual incidence of HCC was 1.04%. The appearance of washout in the PVP (p = 0.006), long time elapsed since the initial Fontan operation (p = 0.04), large nodule size (p = 0.03), and elevated serum α-fetoprotein (AFP) level (p < 0.001) were significantly associated with HCC. In conclusion, cirrhosis is a frequent late complication after Fontan operation, especially after 10 years, and HCC is not a rare complication after cirrhosis development. Diagnosis of HCC should not be based solely on the current imaging criteria, and washout on PVP and clinical features might be helpful to differentiate HCC nodules from benign APHE nodules.

Usefulness of Tumor Tissue Biopsy for Predicting the Biological Behavior of Hepatocellular Carcinoma.

Assessment of the biological behavior of tumors is important for choosing an appropriate cancer therapy. In hepatocellular carcinoma (HCC), the biological behaviour can be assessed by tumor morphology and molecular biology. This study investigated the usefulness of tumor tissue biopsy for predicting the biological behavior of HCC. We studied 43 patients who underwent hepatectomy and preoperative liver tumor biopsy for HCC. We performed clinicopathological and immunohistochemical (IHC) analyses. The expression of the following molecules was examined: regulator of G-protein signaling 5 (RGS5), glypican-3 (GPC3), keratin 19 (K19), epithelial cell adhesion molecule (EpCAM), protein induced by vitamin K absence or antagonist-II (PIVKA-II), β-Catenin, and p53. There was an overall 83.7% agreement regarding tumor differentiation between the preoperative biopsy specimens and the resected specimens. The accuracy of IHC analysis was more than 70% for all molecules between the preoperative biopsy specimens and the resected specimens. The RGS5-positive biopsy cases had higher serum α-fetoprotein levels (p=0.04), a higher rate of moderately or poorly differentiated tumors (p=0.02) and portal vein invasion (p=0.0003) than the RGS5-negative biopsy cases. The GPC3-positive biopsy cases were younger (p=0.04), had higher serum PIVKA-II levels (p=0.01), and a higher rate of portal vein invasion (p=0.03) than the GPC3-negative biopsy cases. The PIVKA-II-positive biopsy cases had significantly higher serum PIVKA-II levels than the PIVKA-II-negative biopsy cases (p=0.02). The other molecular markers showed no significantly different clinical findings between the positive and negative cases. In HCC, there was a high agreement rate of both the histopathological and IHC findings between preoperative biopsy specimens and resected specimens. In the biopsy specimens of HCC, RGS5 and GPC3 expression were useful molecular makers for predicting portal vein invasion. Liver tumor biopsy is useful for predicting the biological behavior of HCC through histopathological and immunohistochemical findings.

Assessment of Hepatocellular Carcinoma Response to 90Y Radioembolization Using Dynamic Contrast Material-enhanced MRI and Intravoxel Incoherent Motion Diffusion-weighted Imaging.

To quantify diffusion and perfusion changes in hepatocellular carcinoma (HCC) induced by yttrium 90 (90Y) radioembolization and to assess the value of dynamic contrast material-enhanced (DCE) MRI and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) for predicting HCC response. Institutional review board approval was obtained for this prospective study (clinical trial registry NCT01871545). Twenty-four participants with HCC (mean age, 69 years ± 9 [standard deviation], 18 men) underwent multiparametric MRI, including IVIM DWI and gadoxetic acid DCE MRI before (n = 24) and 6 weeks (n = 21) after radioembolization. IVIM DWI and DCE MRI histogram parameters were quantified in HCCs and liver parenchyma. HCC response was assessed by using modified Response Evaluation Criteria in Solid Tumors at 6 weeks and 6-12 months after radioembolization. Logistic regression analysis was used to evaluate the diagnostic performance of baseline MRI and clinical parameters for prediction of response. Twenty-five HCCs were analyzed (mean size, 3.6 cm ± 1.9). Radioembolization resulted in significantly decreased perfusion (DCE MRI arterial flow, P = .002; IVIM pseudodiffusion coefficient [D*], P = .014). Multivariate logistic regression selected combined serum α-fetoprotein and portal flow (F p ) skewness (area under the curve [AUC] = 0.924) and combined D* standard deviation and F p kurtosis (AUC = 0.916) for prediction of objective and complete response at 6 weeks, respectively. Standard deviation of DCE MRI parameter arterial fraction was selected as the optimal predictor for complete response at 6-12 months (AUC = 0.857). Diffusion and perfusion MRI can be used to evaluate the response of HCC to radioembolization. Pretreatment DCE MRI histogram parameters may be useful for radioembolization treatment stratification. Supplemental material is available for this article. © RSNA, 2020.

Long-Term Follow-Up of the First in Human Intravascular Delivery of AAV for Gene Transfer: AAV2-hFIX16 for Severe Hemophilia B

Adeno-associated virus (AAV) vectors are a leading platform for gene-based therapies for both monogenic and complex acquired disorders. The success of AAV gene transfer highlights the need to answer outstanding clinical questions of safety, durability, and the nature of the human immune response to AAV vectors. Here, we present longitudinal follow-up data of subjects who participated in the first trial of a systemically delivered AAV vector. Adult males (n= 7) with severe hemophilia B received an AAV2 vector at doses ranging from 8× 1010 to 2× 1012 vg/kg to target hepatocyte-specific expression of coagulation factor IX; a subset (n= 4) was followed for 12-15 years post-vector administration. No major safety concerns were observed. There was no evidence of sustained hepatic toxicity or development of hepatocellular carcinoma as assessed by liver transaminase values, serum α-fetoprotein, and liver ultrasound. Subjects demonstrated persistent, increased AAV neutralizing antibodies (NAbs) to the infused AAV serotype 2 (AAV2) as well as all other AAV serotypes tested (AAV5 and AAV8) for the duration of follow-up. These data represent the longest available longitudinal follow-up data of subjects who received intravascular AAV and support the preliminary safety of intravascular AAV administration at the doses tested in adults. Data demonstrate, for the first time, the persistence of high-titer, multi-serotype cross-reactive AAV NAbs for up to 15 years post- AAV vector administration. Our observations are broadly applicable to the development of AAV-mediated gene therapy.

Radiologic-Pathologic Correlation of Hepatobiliary Phase Hypointense Nodules without Arterial Phase Hyperenhancement at Gadoxetic Acid-enhanced MRI: A Multicenter Study.

Background Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) at gadoxetic acid-enhanced MRI may indicate hepatocellular carcinoma (HCC) or nonmalignant cirrhosis-associated nodules. Purpose To assess the distribution of pathologic diagnoses of HBP hypointense nodules without APHE at gadoxetic acid-enhanced MRI and to evaluate clinical and imaging features in differentiating their histologic grades. Materials and Methods This retrospective multicenter study included pathologic analysis-confirmed HBP hypointense nodules without APHE (≤30 mm) in patients with chronic liver disease or cirrhosis screened between January 2008 and June 2016. Central pathologic review by 10 pathologists determined final histologic grades as progressed HCC, early HCC, high-grade dysplastic nodule (DN), and low-grade DN or regenerative nodule. Gadoxetic acid-enhanced MRI features were analyzed by three radiologists. Multivariable logistic regression analyses with elastic net regularization were performed to identify clinical and imaging features for differentiating histologic grades. Results There were 298 patients (mean age, 59 years ± 10; 226 men) with 334 nodules evaluated, and progressed HCCs were diagnosed in 44.0% (147 of 334), early HCCs in 20.4% (68 of 334), high-grade DNs in 27.5% (92 of 334), and low-grade DNs or regenerative nodules in 8.1% (27 of 334). Serum α-fetoprotein level 100 ng/mL or greater (odds ratio, 2.7; P = .01) and MRI features including well-defined margin (odds ratio, 5.5; P = .003), hypointensity at precontrast T1-weighted imaging (odds ratio, 3.2; P < .001), intermediate hyperintensity at T2-weighted imaging (odds ratio, 3.4; P < .001), and restricted diffusion (odds ratio, 1.9; P = .04) were independent predictors for progressed HCC at multivariable analysis. Conclusion In patients at high risk for hepatocellular carcinoma (HCC), hepatobiliary phase hypointense nodules without arterial phase hyperenhancement at gadoxetic acid-enhanced MRI corresponded mainly to progressed HCCs, early HCCs, and high-grade dysplastic nodules. High α-fetoprotein level and some imaging features at MRI helped to differentiate progressed HCC from lower grade nodules. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Motosugi in this issue.

Predictive value of changes in plasma vascular endothelial growth factor at eight weeks after lenvatinib administration in patients with unresectable hepatocellular carcinoma.

4594 Background: Lenvatinib (LEN) has been used in patients with unresectable hepatocellular carcinoma (u-HCC) and there is no established predictive biomarker. Previously it was reported that a plasma vascular endothelial growth factor (VEGF) concentration decrease at 8 weeks after starting sorafenib might predict favorable overall survival (OS) in patients with u-HCC (Tsuchiya, et al. Cancer, 2013). We aimed to investigate the value of changes in plasma VEGF at 8 weeks after LEN administration in patients with u-HCC. Methods: Forty-six patients with u-HCC who received LEN between April 2018 and August 2019 at our institution were enrolled. Plasma concentrations of VEGF and serum α-fetoprotein (AFP) levels were measured at baseline, 4 and 8 weeks after administration of LEN. A VEGF decrease was defined as &gt; 5% decrease during 8 weeks after the beginning of LEN therapy. AFP response was defined as &gt; 20% decrease during 8 weeks according to the previous reports. Results: Median overall survival (OS) was not reached and progression-free survival (PFS) was 5.9 months. Median observation period and treatment duration were 10.1 and 6.3 months. The objective response rate and disease control rate by mRECIST criteria were 43.5% and 82.6%. Median PFS in patients who had a VEGF decrease at week 8 (n = 29) was significantly longer than those who did not have a VEGF decrease (n = 17; 7.1 months vs 5.0 months; p = 0.014). AFP response was not associated with PFS. There were no significant differences in baseline VEGF, AFP, ALBI score, and extrahepatic metastasis between the patients with and without a VEGF decrease. A VEGF decrease was significantly associated with radiological objective response (p = 0.001) and 18 of 20 patients who achieved CR (n = 3) or PR (n = 17) had a VEGF response in LEN therapy. Conclusions: A decrease of plasma VEGF level at 8 weeks in patients with u-HCC on LEN was significantly associated with PFS. Changes in plasma VEGF could become a new biomarker for molecular targeted therapies including VEGF inhibitors in patients with unresectable HCC.

New Arterial Phase Enhancing Nodules on MRI of Cirrhotic Liver: Risk of Progression to Hepatocellular Carcinoma and Implications for LI-RADS Classification

OBJECTIVE. The purposes of this study were to evaluate the outcome of new arterial phase enhancing nodules at MRI of cirrhotic livers, including clinical and imaging factors that affect progression to hepatocellular carcinoma (HCC), and to assess the diagnostic performance of Liver Imaging Reporting and Data System version 2018 (LI-RADSv2018) versus version 2017 (LI-RADSv2017) in categorizing these nodules. MATERIALS AND METHODS. A database search identified 129 new arterial phase enhancing, round, solid, space-occupying nodules in 79 patients with cirrhosis who underwent surveillance MRI. Three readers assessed the nodules for LI-RADS findings and made assessments based on the 2017 and 2018 criteria. Clinical information and laboratory values were collected. Outcome data were assessed on the basis of follow-up imaging and pathology results. Interreader agreement was assessed. Logistic regression and ROC curve analyses were used to assess the utility of the features for prediction of progression to HCC. RESULTS. Of the 129 nodules, 71 (55%) progressed to HCC. LI-RADSv2017 score, LIRADSv2018 score, and mild-to-moderate T2 hyperintensity were significant independent predictors of progression to HCC in univariate analyses. Serum α-fetoprotein level, hepatitis B or C virus infection as the cause of liver disease, and presence of other HCCs were significant predictors of progression to HCC in multivariate analyses. The rates of progression of LI-RADS category 3 and 4 observations were 38.1% and 57.6%, respectively, for LI-RADSv2017 and 44.4% and 69.9%, respectively, for LI-RADSv2018. CONCLUSION. New arterial phase enhancing nodules in patients with cirrhosis frequently progress to HCC. Factors such as serum α-fetoprotein level and presence of other HCCs are strong predictors of progression to HCC.

Evaluation for clinical and prognostic implications of glypican-3 and α-fetoprotein in hepatocellular carcinoma: a new subtype?

BackgroundIn this retrospective study, we investigated clinicopathological features and prognosis of hepatocellular carcinoma (HCC) patients applying an immunosubtyping method based on the serum α-fetoprotein (AFP) levels and glypican-3 (GPC3) immunohistochemical expression.MethodsTwo hundred and twenty-nine HCC patients, who had been subjected to hepatectomy and accepted serum AFP and GPC immunohistochemical expression tests, were divided into four groups: AFP+GPC3+, AFP+GPC3–, AFP–GPC3+, and AFP–GPC3– groups. During the study, HCC patients’ sex ratios, ages, incidence of cirrhosis, clinicopathological features—such as tumor lesion, tumor size, histological grade, vascular invasion, regional lymph node involvement, distant metastasis—and their follow-up time were observed and continuously recorded.ResultsRegarding their clinicopathological features, the four groups only differed in the histological grade with statistical significance. Furthermore, the four subtypes showed statistically significant differences in sex ratios and incidence of cirrhosis. Among the four subtypes, the prognosis was just statistically different between the AFP+GPC3+ and AFP–GPC3+ groups, and AFP–GPC3+ was associated with a better prognosis.ConclusionsA new HCC subtype could guide the personalized therapy of HCC patients to a certain extent. The four different subtypes resulting from the AFP- and GPC3-based subclassification of HCC, especially for AFP+GPC3+ and AFP−GPC3− groups, were meaningful prognostic markers for HCC.

Hepatocellular carcinoma and multiple myeloma with elevated globulin: a case report and literature review

A 60-year-old male patient presented with a serum α-fetoprotein (AFP) level of 2940.5 ng/mL accompanied by a significant increase in serum globulin. Hepatitis B virus (HBV) DNA was 2.85 × 103 (normal value <1.0 × 103). B-mode ultrasound and magnetic resonance imaging showed characteristic manifestations and he was clinically diagnosed with hepatocellular carcinoma in January 2015. He received radiofrequency ablation and tenofovir disoproxil anti-HBV therapy and his serum AFP and globulin levels were significantly reduced. In March 2018, he presented at our Hematology Department with fatigue and a pale complexion. At that time, his serum AFP level was normal, with hemoglobin 61 g/L and globulin 64.7 g/L. He was diagnosed with multiple myeloma (MM) by bone marrow examination, and immunofixation electrophoresis. The patient received PCD chemotherapy (bortezomib 2.0 g/dL on days 1, 4, 8, and 11 plus cyclophosphamide 0.3 g/dL on days 1–4 plus dexamethasone 20 mg/dL on days 1–2, 4–5, 8–9, and 11–12). The patient finally died of MM complicated by disseminated intravascular coagulation.

The diagnostic accuracy of maternal serum alpha-fetoprotein variants (AFP-L2 and AFP-L3) in predicting fetal open neural tube defects and abdominal wall defects

IntroductionTo evaluate a risk model of the maternal serum α-fetoprotein variants L2 and L3 (AFP-L2 and AFP-L3) for predicting fetal open neural tube defects (ONTD) and abdominal wall defects (AWD). MethodsSubjects were divided into the ONTD group (21), the AWD group (16) and the control group (38). Comparative analysis was performed using a risk model, receiver operating characteristic (ROC) curves and area under the curve (AUC) were used for screening performance of AFP-L2 and AFP-L3. ResultsAFP-L2 and AFP-L3 concentrations in the ONTD group and the AWD group were both significantly higher than those in the control group (P < 0.001). The AUC for screening ONTD or AWD using AFP-L2 was 0.830 [95% confidence interval (CI):0.734–0.926, P < 0.001], while using AFP-L3 was 0.886 (95% CI: 0.809–0.963, P < 0.001). ROC curves indicated that the optimal threshold values for ONTD or AWD by AFP-L2 and AFP-L3 were 1.467 multiple of the median (MoM) and 1.944 MoM. The corresponding sensitivity, specificity and Youden index for AFP-L2 and AFP-L3 were 0.703, 0.947, 0.650 and 0.730, 0.974, 0.703, respectively. ConclusionAFP-L2 and AFP-L3 are favorable biomarkers for screening ONTD and AWD fetuses, and the risk model using AFP-L2 and AFP-L3 is of superior sensitivity and specificity.

Multiphase Liver MRI for Identifying the Macrotrabecular-Massive Subtype of Hepatocellular Carcinoma.

Background The recently described "macrotrabecular-massive" (MTM) histologic subtype of hepatocellular carcinoma (HCC) (MTM-HCC) represents an aggressive form of HCC and is associated with poor survival. Purpose To investigate whether preoperative MRI can help identify MTM-HCCs in patients with HCC. Materials and Methods This retrospective study included patients with HCC treated with surgical resection between January 2008 and February 2018 and who underwent preoperative multiphase contrast material-enhanced MRI. Least absolute shrinkage and selection operator (LASSO)-penalized and multivariable logistic regression analyses were performed to identify clinical, biologic, and imaging features associated with the MTM-HCC subtype. Early recurrence (within 2 years) and overall recurrence were evaluated by using Kaplan-Meier analysis. Multivariable Cox regression analysis was performed to determine predictors of early and overall recurrence. Results One hundred fifty-two patients (median age, 64 years; interquartile range, 56-72 years; 126 men) with 152 HCCs were evaluated. Twenty-six of the 152 HCCs (17%) were MTM-HCCs. LASSO-penalized logistic regression analysis identified substantial necrosis, high serum α-fetoprotein (AFP) level (>100 ng/mL), and Barcelona Clinic Liver Cancer (BCLC) stage B or C as independent features associated with MTM-HCCs. At multivariable analysis, substantial necrosis (odds ratio = 32; 95% confidence interval [CI] = 8.9, 114; P < .001), high serum AFP level (odds ratio = 4.4; 95% CI = 1.3, 16; P = .02), and BCLC stage B or C (odds ratio = 4.2; 95% CI = 1.2, 15; P = .03) were independent predictors of MTM-HCC subtype. Substantial necrosis helped identify 65% (17 of 26; 95% CI: 44%, 83%) of MTM-HCCs (sensitivity) with a specificity of 93% (117 of 126; 95% CI: 87%, 97%). In adjusted models, only the presence of satellite nodules was independently associated with both early (hazard ratio = 3.7; 95% CI: 1.5, 9.4; P = .006) and overall (hazard ratio = 3.0; 95% CI: 1.3, 7.2; P = .01) tumor recurrence. Conclusion At multiphase contrast-enhanced MRI, substantial necrosis helped identify macrotrabecular-massive hepatocellular carcinoma subtype with high specificity. © RSNA, 2020.

Integrative analysis of DNA methylation and gene expression reveals distinct hepatocellular carcinoma subtypes with therapeutic implications.

We aimed to develop an HCC classification model based on the integrated gene expression and methylation data of methylation-driven genes. Genome, methylome, transcriptome, proteomics and clinical data of 369 HCC patients from The Cancer Genome Atlas Network were retrieved and analyzed. Consensus clustering of the integrated gene expression and methylation data from methylation-driven genes identified 4 HCC subclasses with significant prognosis difference. HS1 was well differentiated with a favorable prognosis. HS2 had high serum α-fetoprotein level that was correlated with its poor outcome. High percentage of CTNNB1 mutations corresponded with its activation in WNT signaling pathway. HS3 was well differentiated with low serum α-fetoprotein level and enriched in metabolism signatures, but was barely involved in immune signatures. HS3 also had high percentage of CTNNB1 mutations and therefore enriched in WNT activation signature. HS4 was poorly differentiated with the worst prognosis and enriched in immune-related signatures, but was barely involved in metabolism signatures. Subsequently, a prediction model was developed. The prediction model had high sensitivity and specificity in distributing potential HCC samples into groups identical with the training cohort. In conclusion, this work sheds light on HCC patient prognostication and prediction of response to targeted therapy.

Percutaneous Radiofrequency Ablation With a Multiple-Electrode Switching System for Medium-Sized Hepatocellular Carcinomas

Objective This study aimed to retrospectively evaluate the safety and short-term therapeutic efficacy of radiofrequency ablation (RFA) with a multiple-electrode switching system (MESS) to treat medium-sized (3.1–5.0 cm) hepatocellular carcinomas (HCCs). Summary of Background Data Conventional monopolar RFA is limited in achieving local control for tumors larger than 3 cm. Therefore, MESS-RFA was developed, and it can create a sufficiently large ablation volume, including the target tumor and a 5- to 10-mm safety margin in medium-sized tumors. Methods We performed a total of 168 RFAs with a MESS for 166 patients. The patients were treated under ultrasonographic guidance by a percutaneous switching system RFA with a multichannel RF generator and 2 or 3 internally cooled electrodes. Technical effectiveness, local progression, and remote recurrence of HCC were determined. Results For the 166 isolated HCC tumors, the complete ablation rate of MESS-RFA was 98.79% (164 of 166). Mean ablation time per procedure was 12.33 ± 3.01 minutes; mean ablation diameter was 5.79 ± 0.61 cm. The complication rate was 2.41%. During follow-up (averaging 16.54 months), local tumor progression occurred in 15 of 166 patients (9.03%) with technical effectiveness, whereas new HCCs were detected in 40 of 166 patients (24.09%). Multivariate analyses revealed that local tumor progression was only associated with serum α-fetoprotein levels above 100 ng/mL as a risk factor. Conclusion MESS-RFA for achieving sufficient ablation volume is safe and efficient. This method also showed relatively successful therapeutic effectiveness on short-term follow-up in the treatment of medium-sized HCCs.

Soluble Axl Is a Novel Diagnostic Biomarker of Hepatocellular Carcinoma in Chinese Patients with Chronic Hepatitis B Virus Infection.

PurposeThe purpose of this study was to evaluate the diagnostic value of soluble Axl (sAxl) in hepatocellular carcinoma (HCC) in comparison with serum α-fetoprotein (AFP).Materials and MethodsEighty HCC patients, 80 liver cirrhosis patients (LC), 80 patients with hepatitis B virus (HBV) infection, and 80 healthy controls (HC) were enrolled. sAxl levels were measured by an enzyme-linked immunosorbent assay, serum AFP levelswere measured by an electrochemiluminescence immunoassay. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic performances.ResultsThe results show that levels of sAxl were high expression in patients with HCC (p < 0.05), varied with disease state as follows: HCC > LC > HC > HBV. Logistic regression and ROC curve analysis identified the optimal cut-off for sAxl in differentiating all HCC and non-HCC patients was 1,202 pg/mL (area under the receiver operating characteristic [AUC], 0.888; 95% confidence interval [CI], 0.852 to 0.924) with sensitivity 95.0%, specificity 73.3%. Furthermore, differential diagnosis of early HCC with non-HCC patients for sAxl showed the optimal cut-off was 1,202 pg/mL (AUC, 0.881; 95% CI, 0.831 to 0.931; sensitivity, 94.1%; specificity, 73.3%). Among AFP-negative HCC patients with non-HCC patients, the cut-off was 1,301 pg/mL (AUC, 0.898; 95% CI, 0.854 to 0.942) with a sensitivity of 84.6%, a specificity of 76.3%. The optimal cut-off for sAxl in differentiating all HCC and chronic liver disease patients was 1,243 pg/mL (AUC, 0.840; 95% CI, 0.791 to 0.888) with sensitivity 93.8%, specificity 61.9%. The combination of AFP and sAxl increased diagnostic value for HCC.ConclusionsAxl outperforms AFP in detecting HCC, especially in early HCC and in AFP-negative HCC. Combination sAxl with AFP improved the specificity for early HCC diagnosis. In summary, sAxl is a candidate serum marker for diagnosing HCC.

The Association of Serum Estradiol Level with the Susceptibility and Clinicopathological Features of Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease

Abstract Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The most common underlying causes of Hepatocellular car-cinoma (HCC) are chronic liver diseases and cirrhosis. Aim of Study: Our study aimed to investigate the serum estradiol levels in patients with nonalcoholics steatohepatitis (NASH) related HCC and to explore their correlations with clinicopathological features of HCC. Patients and Methods: A Controlled Cross-Sectional Study included 200 patients with NAFLD (181 patients with NAFLD and 23 patients with NAFLD related HCC) and 50 controls. Serum estradiol was measured by enzyme-linked immuno-sorbent assay (ELISA). Results: The serum level of estradiol was significantly lowered in patients with NAFLD (32.24±7.3pg/ml) compared to controls (42.9±3.9pg/ml). Moreover, our findings revealed lower concentrations of serum estradiol in the HCC group (28.6±5.3pg/ml) compared to the NAFLD group (33.45 ±4.3pg/ml, p<0.00 1). We found significant negative correla-tions between serum estradiol levels and clinicopathological features of HCC (portal vein thrombosis, lymph node metas-tasis, number of tumor lesions, advanced clinical stage, tumor size, tumor site, distant metastasis) in patients with NAFLD complicated with HCC. linear regression test and we observed that serum triglycerides and a-fetoprotein were significantly associated with serum estradiol among the HCC group. Conclusion: Serum estradiol level was significantly low-ered in the HCC subgroup compared to the NAFLD group and negatively correlated with clinicopathological features of HCC. Serum estradiol can be used as a promising predictor of HCC in female patients with NAFLD.