And Α-fetoprotein Levels Research Articles

Disparities of tumour markers in intraperitoneal drainage fluid between laparoscopic and open radical gastrectomy for gastric cancer.

Despite the remarkable progress in minimally invasive surgery, the potential association between laparoscopic gastrectomy and the risk of peritoneal metastasis remains uncertain. To investigate variations in tumour markers in intraperitoneal drainage fluid between laparoscopic radical gastrectomy and open radical gastrectomy for gastric cancer. A total of 106 patients diagnosed with gastric cancer between July 2018 and November 2020 were included in this study, 45 of whom underwent laparoscopic radical gastrectomy (laparoscopic group) and 61 underwent open radical gastrectomy (open group). Variations in the levels of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 199 (CA199), and α-fetoprotein (AFP) in the intraperitoneal drainage fluid were compared and analysed on postoperative days (PODs) 1, 2, 3, and 5 between the two groups. Additionally, the postoperative 3-year survival rates between the two groups were compared and analysed. No significant differences in CEA, CA199, and AFP levels in the intraperitoneal drainage fluid were observed between the two groups on postoperative days (PODs) 1, 2, 3, and 5 (p > 0.05). However, the level of CA125 in the intraperitoneal drainage fluid of the laparoscopic group was notably higher than that of the open group on POD 2 (p < 0.05); however, there were no significant differences between the two groups on PODs 1, 3, and 5 (p > 0.05). There was no significant difference in the 3-year postoperative survival rates between the two groups. There were no significant differences in CEA, CA125, CA199, and AFP levels in the intraperitoneal drainage fluid between laparoscopic radical gastrectomy and open radical gastrectomy for gastric cancer, confirming from another perspective that laparoscopic radical gastrectomy does not increase the risk of intraperitoneal metastasis.

A Pineal Germinoma with Rapid Enlargement following Tumor Resection

The natural course of pineal germ cell tumors (GCTs), particularly their post-operative progression, is not well understood. We report a rare case of pineal region GCT showing rapid enlargement within 2 weeks following surgical resection. A young adult male presented with progressive headache and diplopia for several weeks. Although elevation of β-human chorionic gonadotropin (β-HCG) and α-fetoprotein (AFP) levels suggested that a large pineal mass lesion observed on magnetic resonance imaging (MRI) might be a β-HCG/AFP-producing tumor, whether the mass was truly a GCT remained unclear. We performed an endoscopy-assisted suboccipital infratentorial approach with removal of the tumor that was diagnosed as germinoma via histopathological investigation. During the week preceding chemotherapy, the patient’s consciousness rapidly worsened. MRI showed that the residual pineal germinoma had enlarged and even compressed the tectum and thalamus. Emergency chemotherapy and radiotherapy were prescribed, and the patient received invasive ventilation for respiratory failure. Unexpectedly, the patient recovered within a short period. Importantly, total regression of the pineal germinoma, accompanied by β-HCG and AFP levels returning to normal range, was observed 4 months after chemotherapy. These phenomena suggest that the rapid enlargement of the pineal germinoma, which might be induced by aggressive surgical cytoreduction, responds well to chemoradiotherapy.

Combining γ-GT, PIVKA-II, and AFP to predict long-term prognosis in patients with hepatocellular carcinoma after hepatectomy.

Hepatocellular carcinoma (HCC) is one of the top five contributors to the cancer burden in China, with a poor prognosis and heavy disability-adjusted life year burden. The criteria used for HCC prognosis are complicated and therefore restricted in routine clinical practice. Multiple factors influence HCC malignancy and progression. In this study, we retrospectively evaluated 173 patients with HCC who underwent curative resection for 9 years to evaluate the correlation of a combination of γ-glutamyl transferase (γ-GT), protein induced by vitamin K absence or antagonist-II (PIVKA-II), and α-fetoprotein (AFP) with the long-term survival of patients with HCC. Multivariate analysis revealed that the γ-GT level was an independent prognostic factor for recurrence. The prediction rate of early recurrence with γ-GT, PIVKA-II, and AFP levels individually was 63.5%, 79.4%, and 39.7%, respectively, whereas the prediction rate of early recurrence was 95.2% with the combination of γ-GT, PIVKA-II, and AFP levels as a composite indicator. Our long-term retrospective study revealed that γ-GT, PIVKA-II, and AFP can aid in predicting long-term prognosis of HCC recurrence. The combination of γ-GT, PIVKA-II, and AFP can further aid in identifying patients with early recurrence. Together, γ-GT, PIVKA-II, and AFP may a be used to develop a new prediction method to improve the prognosis of patients with HCC, and our results indicate the requirement of more active HCC treatment strategies.

Prediction Model and Nomogram of Early Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation Based on Logistic Regression Analysis.

The purpose of this study was to screen for high-risk factors leading to the early recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) and to construct a prediction model and nomogram. This retrospective study included 108 patients with primary HCC who underwent RFA treatment at the Harbin Medical University Cancer Hospital between January 2018 and June 2019. Four risk factors were screened for using univariate and multivariate logistic regression analyses: number of tumors (hazard ratio [HR]=14.684, 95% confidence interval [CI]: 1.099-196.215, p=0.042), neutrophil-to-lymphocyte ratio (NLR) (HR=2.178, 95% CI: 1.003-4.730, p=0.049), contrast-enhanced ultrasound (CEUS) performance (HR=6.482, 95% CI: 1.161-36.184, p=0.033) and α-fetoprotein (AFP) level (HR=1.001, 95% CI: 1.000-1.003, p=0.040). We established a prediction model: Logit(p)=-3.096+2.827×(number of tumors >1=1)+1.851×(CEUS revealing rapid enhancement of blood flow signal in the arterial phase and clearance in the portal phase=1)+1.941×(NLR >1.55=1)+0.257×(AFP >32.545=1). Through clinical decision curve analysis, the model's threshold was 0.043-0.873, indicating a high clinical value. Patients with a high AFP level, typical CEUS enhancement pattern, multiple tumors and elevated NLR are more likely to relapse early.

Risk of hepatocellular carcinoma after sustained virologic response in hepatitis C virus patients without advanced liver fibrosis.

Hepatocellular carcinoma (HCC) after sustained virologic response (SVR) has been observed even in hepatitis C virus (HCV) patients without advanced liver fibrosis. Identifying predictors for HCC incidence in patients without advanced liver fibrosis will enable efficient post-SVR HCC surveillance. This study aimed to develop a scoring system to predict the incidence of HCC after SVR in HCV patients without advanced liver fibrosis. A total of 1682 HCV patients without advanced liver fibrosis (defined as Fibrosis-4 index <3.25) with no history of HCC who initiated direct-acting antiviral treatment between September 2014 and October 2020 at 26 institutions, and achieved SVR24, were included. We divided 1682 patients into training (1122) and validation (560) cohorts. In the multivariate analysis, baseline age ≥65years (p=0.030), alanine aminotransferase (ALT) levels at SVR24≥30 U/l (p=0.001), and α-fetoprotein (AFP) levels at SVR24≥5.0ng/ml (p=0.001) were independent predictors for HCC incidence in the training cohort. We developed a scoring system to predict HCC incidence after SVR24 using these three factors (1 point was added for each factor). The cumulative HCC incidence rates at 5years were 7.1% in patients who scored 2 or 3, and no patients developed HCC in those who scored 0 in the validation cohort. Our scoring system using the three factors of baseline age, ALT levels at SVR, and AFP levels at SVR is useful for post-SVR HCC surveillance of patients without advanced liver fibrosis.

Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach.

e16094 Background: Hepatoid adenocarcinoma (HAC) is a rare pathological subtype of extrahepatic tumor, featured by hepatoid differentiation and α-fetoprotein (AFP)-production. Hepatoid adenocarcinoma of the stomach (HAS), accounting for 0.17 to 15% of gastric cancers, is the most common subtype of HAC, and has attracted increasing attention duo to its high degree of malignancy. Compared with classic gastric cancer (GC), HAS showed a higher rate of vascular invasion, lymph node metastasis, and liver metastasis, with only 9% survival at 5 years. In this study, we aim to investigate the molecular features of HAS and identify the potential therapeutic targets for HAS. Methods: We conducted whole-exome sequencing (WES) of 40 paired tumor and normal samples, including 25 HAS, 6 HAC of other organ and 9 AFP-producing gastric cancer (AFPGC). All patients underwent radical surgery at Shanghai Zhongshan Hospital between July 2013 and September 2017. qRT-PCR, Western blot and immunohistochemistry were detected to explore MUC19 expression in HAS. CCK8 assay, Transwell assay, immunofluorescence assay and subcutaneous xenograft tumor model were used to detect functional effects and the mechanism of MUC19. Results: In HAS patients, the top 5 frequently mutated genes were TP53 (44%), TTN (44%), MUC19 (40%), CCNE1 (28%) and CDC27 (28%). Further compared with TCGA datasets, MUC19, CCNE1, CDC27 mutations were almost undetectable in STAD, CRC and HCC. In terms of CNV analysis, VSTM2B, PLEKHF1, POP4, URI1 and TERT were the most frequently amplificated genes in HAS tumor tissues. Interestingly, amplification of 4 genes (VSTM2B, CCNE1, LEKHF1, POP4), which located in chr19q12, was significantly associated with poor prognosis. The tumor mutational burden (TMB) levels and AFP expression of HAS and AFPGC patients were no significantly different, while patients with higher TMB had a remarkably longer overall survival ( p= 0.0065). Moreover, we found MUC19 expression was positively correlated with AFP levels in HAS and MUC19 promoted the transcription of AFP in GC cells. Mechanistically, MUC19 contributed to the aggressive malignancy phenotypes of GC cells through activating the Wnt/β-catenin signaling pathway. Conclusions: MUC19 may be a potential target for HAS diagnosis and treatment. Amplification of genes located in chr19q12 occurred frequently in HAS and were associate with poor prognosis. TMB was sensitive for the overall survival of HAS patients.

Downregulation of LHPP Expression Associated with AFP Acts as a Good Prognostic Factor in Human Hepatocellular Carcinoma.

Background Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) serves as a tumor suppressor in hepatocellular carcinoma (HCC), but the correlation between the expression of LHPP and the clinical parameters of oncogenic progression is still not well defined. This study is to reveal the correlation between the expression of LHPP in HCC and their clinical parameters. Methods Immunohistochemical analysis was used to assess the correlation between the expression of LHPP and the clinical parameters of HCC. Expressions of LHPP in HCC tissues and cultured HCC cells were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). LHPP, gamma-glutamyl transferase (GGT), and α-fetoprotein (AFP) expression levels in blood or HCC tissues were detected by enzyme-linked immunosorbent assay (ELISA). The Spearman rank correlation coefficient was used to evaluate the correlation of the expression of LHPP and the clinical index of HCC. Correlation of survival and expression of LHPP were analyzed using the Kaplan-Meier method and the log-rank test. Results Expressions of LHPP in HCC tissues were significantly downregulated than their paired adjacent normal tissues. A significant positive correlation was found between the cytoplasm and nuclear expression of LHPP in both HCC and their paired adjacent normal tissues. The expression of LHPP negatively correlated with the levels of GGT in the cytoplasm of adjacent tissues and with the AFP level in the nucleus of HCC cells. Relative levels of LHPP in HCC tissues were markedly lower than those of the paired adjacent normal tissues. Relative levels of LHPP in LO-2 cells were higher than those of HepG2, BEL-7404, and SMMC-7721 cell lines. The overall survival and DSF survival of patients with the high expression of LHPP were much higher than those with the low expression of LHPP in paired adjacent normal tissue. Conclusions LHPP is associated with the AFP level and acts as a good prognostic factor in HCC.

Predictive effects of preoperative serum CA125 and AFP levels on post-hepatectomy survival in patients with hepatitis B-related hepatocellular carcinoma.

The association between the serum levels of cancer antigen 125 (CA125; also termed MUC16) and the prognosis of patients with hepatocellular carcinoma (HCC) has not been widely reported to date. The aim of the present study was to determine the association between preoperative serum CA125 levels and prognosis of patients with hepatitis B virus (HBV)-related HCC after hepatectomy. The study included 306 patients with HBV-related HCC who underwent liver resection and were classified into four subgroups based on their baseline CA125 and α-fetoprotein (AFP) levels. The perioperative clinical data were compared and analyzed. Kaplan-Meier and Cox regression analyses were performed to determine the associations between patient clinicopathological characteristics and survival. The results revealed that the median follow-up time was 35 months. Patients with low preoperative serum CA125 levels presented with improved 3-year disease-free survival (DFS) (79.3 vs. 75.7%; P=0.278) and overall survival (OS) (84.4 vs. 77.1%; P=0.001) rates compared with those among patients with high preoperative serum CA125 levels. High preoperative serum CA125 levels were a risk factor associated with short DFS and OS rates in all patients. In patients with baseline AFP levels >100 ng/ml, low preoperative serum CA125 levels were significantly associated with prolonged DFS and OS rates (log-rank test P=0.002 and P=0.005, respectively). In patients with AFP levels ≤100 ng/ml, no significant differences were observed in DFS or OS rates between the high and low preoperative serum CA125 groups. Patients with high preoperative serum CA125 and AFP levels exhibited the worst prognosis (low DFS and OS rates). In conclusion, high baseline CA125 levels may be associated with a poor prognosis in patients with HBV-related HCC.

Simple scoring system for prediction of hepatocellular carcinoma occurrence after hepatitis C virus eradication by direct-acting antiviral treatment: All Kagawa Liver Disease Group Study.

Direct acting antivirals (DAA) have recently been developed to treat patients with hepatitis C virus (HCV) infection, and interferon-free DAA treatment has improved the cure rate of patients. However, the occurrence rate of hepatocellular carcinoma (HCC) following HCV eradication remains unknown. Therefore, the present study aimed to identify predictors of HCC occurrence following DAA treatment. Among 1,454 patients infected with HCV, 1,088 patients who achieved sustained virologic response and who had no history of HCC treatment were recruited between September 2014 and November 2018. The incidence of HCC in patients infected with HCV following DAA treatment, and the predictors contributing to HCC occurrence were identified using clinicopathological characteristics and blood test results. During the present study, 26 patients developed HCC. The incidence of HCC was 0.61, 1.88, 2.82 and 3.71% at 6, 12, 18 and 24 months after treatment with DAA, respectively. The results of multivariate analysis identified age [hazard ratio (HR), 1.0729; P=0.0044] and α-fetoprotein (AFP) level after DAA treatment (HR, 1.0486; P=0.0486) as independent factors that may contribute to HCC occurrence following DAA treatment. By using these two factors, a novel scoring system (0–2 points) was established to predict HCC occurrence following HCV eradication by DAA treatment. The incidence of HCC at 2 years was 0.3% in the 0 points group, 6.27% in the 1 point group and 18.37% in the 2 points group. In conclusion, AFP level after DAA treatment and age at DAA administration were identified as independent predictors of HCC occurrence in patients that were treated with DAA. The scoring system that was established in the present study is simple and easy, and using pre-treatment factors may be a convenient tool to predict the risk of HCC occurrence in HCV-free patients following DAA treatment.

Glutamine synthetase promotes tumor invasion in hepatocellular carcinoma through mediating epithelial-mesenchymal transition.

Glutamine synthetase (GS) levels increase gradually with the development of hepatocellular carcinogenesis. In this study, we aimed to investigate the clinical significance of GS and the underlying mechanism of GS promoting hepatocellular carcinoma (HCC) invasion. Serum concentration of GS and α-fetoprotein (AFP) in HCC patients, liver cirrhosis patients, and healthy individuals were detected. The GS-mRNA level and its prognostic value were explored in an independent HCC cohort from The Cancer Genome Atlas database. GS expression in HCC tissue and matched para-tumor tissue was determined. The effect of GS on HCC invasion was assessed invitro and invivo. The serum GS and AFP level in HCC patients was higher than that in healthy controls and liver cirrhosis patients. The area under the receiver operating characteristic curve for HCC diagnosis was 0.848 and 0.861 for GS and AFP, respectively. The area under the receiver operating characteristic curve of GS for diagnosis of AFP-negative HCC was 0.913. Combining GS with AFP achieved a diagnostic sensitivity and specificity of 82.5% and 93%, respectively. The GS level was higher in tumor tissues than that in para-tumor tissues. High GS expression was associated with poor prognosis of moderately differentiated HCC patients. Invitro, GS exerted an influence on HCC cell migration by mediating epithelial-mesenchymal transition. The lung and liver metastatic model of HCC further confirmed that GS expression affected the invasion of HCC cells invivo. GS is a useful biomarker for HCC diagnosis, especially for AFP-negative patients. In addition, GS affects HCC metastasis through mediating epithelial-mesenchymal transition.

Changing Patterns of Hepatocellular Carcinoma after Treatment with Direct Antiviral Agents

Introduction: The impact of direct antiviral agents (DAAs) on the development of hepatocellular carcinoma (HCC) is controversial. One important aspect of this controversy is the changing pattern of HCC. Objective: In this study, we attempted to assess the changes in the pattern of HCC after treatment with DAAs. Methods: A total of 51 HCC patients after DAA treatment and 54 HCC patients without DAA treatment were included. The diagnosis of HCC was based on typical dynamic CT and/or MRI criteria in both groups. Liver status was assessed by means of the fibrosis 4 index (Fib-4), Child-Pugh classification, and model for end-stage liver disease (MELD). HCC infiltrative pattern, portal vein thrombosis (PVT), local and distant metastases, and α-fetoprotein (AFP) level were compared in the 2 groups. The staging of HCC and treatment decisions were made in both groups following the Milan criteria, Barcelona Clinic Liver Cancer staging, tumor-node-metastasis staging, and Cancer of the Liver Italian Program categorization. Results: The mean age of the HCC patients after DAA treatment (59.1± 7.4 years) was older than that of the HCC patients without DAA treatment. There was no significant difference between groups regarding sex distribution. The mean Fib-4 score (4.84 ± 3.53) was significantly lower in HCC patients after DAA treatment than in those without DAA treatment. The frequency of the infiltrative HCC pattern, PVT, and regional lymph node metastasis was significantly higher in HCC patients after DAA treatment than in those without DAA treatment (p ≤ 0.05); mean AFP level (5,085.2 ± 11,883.2 ng/mL) was also significantly higher. HCC patients after DAA treatment had significantly advanced stages and limited treatment options (p ≤ 0.05). Conclusion: The changing HCC pattern after DAA treatment may suggest the need for new HCC staging and treatment protocols.

FDG PET/CT Evaluation of Pediatric Patients With Yolk Sac Tumor

OBJECTIVE. The objective of our study was to evaluate the clinical utility of FDG PET/CT in staging and restaging pediatric patients with yolk sac tumor (YST). MATERIALS AND METHODS. We retrospectively reviewed the data from 31 pediatric patients with pathologically confirmed YST who underwent 34 PET/CT studies for the purpose of staging or restaging. The PET/CT studies were read by two nuclear medicine doctors in consensus. Histopathology combined with clinical and imaging follow-up was taken as the reference standard. The results of PET/CT were also compared with conventional imaging and α-fetoprotein (AFP) levels when available. RESULTS. Of the total 34 studies, six were performed for initial staging and the other 28 for posttherapy evaluation. FDG PET/CT was true-positive in all six staging studies, detected only a few more metastatic foci than conventional imaging, and changed the therapeutic regimen in none of the six patients. Nevertheless, PET/CT showed high accuracy in the restaging group, with a sensitivity of 100% and specificity of 85.7%. The treatment regimen was changed in 46.4% of the patients in the restaging group according to the PET/CT study. In addition, PET/CT had higher accuracy than AFP levels in YST restaging. Overall, the per-study performance of PET/CT was a sensitivity of 100%, specificity of 85.7%, positive predictive value of 90.9%, and negative predictive value of 100%. CONCLUSION. FDG PET/CT was only slightly superior to conventional imaging in staging YST in pediatric patients. However, PET/CT of posttherapy patients with YST showed high diagnostic accuracy and had a great impact on therapeutic management.

Significance of PIVKA-II levels for predicting microvascular invasion and tumor cell proliferation in Chinese patients with hepatitis B virus-associated hepatocellular carcinoma.

The present study aimed to determine the levels of prothrombin induced by vitamin K absence-II (PIVKA-II) according to the Barcelona Clinic Liver Cancer (BCLC) staging system, to develop an appropriate strategy for managing hepatocellular carcinoma (HCC), particularly early HCC, and to investigate the value of PIVKA-II for predicting prognosis-associated pathological parameters. Clinical information of 117 patients with hepatitis B-associated HCC was retrospectively collected. Preoperative serum PIVKA-II and α-fetoprotein (AFP) levels were measured using a chemiluminescence method. The efficiency of PIVKA-II levels for predicting pathological parameters was evaluated using step-wise logistic regression. The receiver operator characteristic curve was used to evaluate the predictive performance of PIVKA-II levels. It was demonstrated that except for the difference between stages B and C HCC (P=0.923), serum PIVKA-II levels significantly increased according to BCLC stage (P<0.050), however AFP levels did not. In early HCC (stage 0+A), the correlation between PIVKA-II and AFP levels (dual-positive, 64.70% in stage 0; 46.97% in stage A) was relatively weak (r=0.410). PIVKA-II >40 mAU/ml was an independent predictor of microvascular invasion [hazard ratio (HR), 3.77; 95% confidence interval (CI), 1.31–10.88; P=0.014; and high Ki67 expression in situ (HR, 2.99; 95% CI, 1.19–7.52; P=0.020). Combined analysis of PIVKA and AFP levels may contribute to an effective strategy for the management of patients with early HCC, as high PIVKA-II levels indicated a more aggressive tumor phenotype. Further investigation of PIVKA-II levels may provide novel insights into the mechanism underlying the metastasis of HCC cells and facilitate the development of novel therapeutic strategies for HCC.

Data mining of routine laboratory tests can predict liver disease progression in Egyptian diabetic patients with hepatitis C virus (G4) infection: a cohort study of 71 806 patients.

Hepatitis C virus (HCV) and diabetes mellitus (DM) are prevalent diseases worldwide, associated with significant morbidity, mortality, and mutual association. The aims of this study were as follows: (i) find the prevalence of DM among 71 806 Egyptian patients with chronic HCV infection and its effect on liver disease progression and (ii) using data mining of routine tests to predict hepatic fibrosis in diabetic patients with HCV infection. A retrospective multicentered study included laboratory and histopathological data of 71 806 patients with HCV infection collected by Egyptian National Committee for control of viral hepatitis. Using data mining analysis, we constructed decision tree algorithm to assess predictors of fibrosis progression in diabetic patients with HCV. Overall, 12 018 (16.8%) patients were diagnosed as having diabetes [6428: fasting blood glucose ≥126 mg/dl (9%) and 5590: fasting blood glucose ≥110-126 mg/dl (7.8%)]. DM was significantly associated with advanced age, high BMI and α-fetoprotein (AFP), and low platelets and serum albumin (P≤0.001). Advanced liver fibrosis (F3-F4) was significantly correlated with DM (P≤0.001) irrespective of age. Of 16 attributes, decision tree model for fibrosis showed AFP was most decisive with cutoff of 5.25 ng/ml as starting point of fibrosis. AFP level greater than cutoff in patients was the first important splitting attribute; age and platelet count were second important splitting attributes. (i) Chronic HCV is significantly associated with DM (16.8%). (ii) Advanced age, high BMI and AFP, low platelets count and albumin show significant association with DM in HCV. (iii) AFP cutoff of 5.25 is a starting point of fibrosis development and integrated into mathematical model to predict development of liver fibrosis in diabetics with HCV (G4) infection.

CD133 expression and α-fetoprotein levels define novel prognostic subtypes of HBV-associated hepatocellular carcinoma: A long-term follow-up analysis.

Hepatocellular carcinoma (HCC) is a highly heterogeneous type of tumor, which may be caused by the stem/progenitor cell features of particular HCC cells. Recent studies have subclassified HCC into different prognostic subtypes according to just one stemness-associated marker. However, one stemness-associated marker is not sufficient to clearly define cancer stem cells, or to decipher the heterogeneous nature of HCC. For a more precise subtype classification for prognostic application, a combination of multiple stemness-associated markers is required. Cluster of differentiation 133 (CD133) and α-fetoprotein (AFP) are common stemness-associated markers for HCC that have not yet been employed for HCC subtype classification. In the present study, CD133 expression was assessed by immunohistochemistry in 127 hepatitis B virus-associated HCC tumor specimens. Based on CD133 immunostaining and serum AFP levels, the HCC cases were subclassified into four subtypes, which demonstrated different clinicopathological features and varying prognoses. Among the four subtypes, the number of tumor lesions, histological grade and vascular invasion were significantly different (P=0.002, P=0.018 and P=0.022, respectively). CD133+AFP+ HCC was associated with a relatively poor prognosis, CD133−AFP− HCC was associated with a relatively good prognosis, while CD133+AFP− HCC and CD133−AFP+ HCC were associated with an intermediate prognosis. These prognostic values were confirmed by borderline or statistical significance (between all groups, overall survival, P=0.061; recurrence-free survival, P=0.015). These results define a novel and simple system, based on CD133 and AFP, for classifying HCC into four distinct prognostic subtypes. This classification system may aid the assessment of patients with HCC for personalized therapy.

Characteristics of Hepatocellular Carcinoma Aggressiveness Factors in Turkish Patients

A large cohort of hepatocellular carcinoma (HCC) patients from several collaborating Turkish institutions were examined for the tumor parameters of maximum diameter (MTD), portal vein thrombosis (PVT), and α-fetoprotein (AFP) levels. A relationship was found between MTD and blood platelet levels. Patients with large ≥5 cm tumors who had normal platelet levels had significantly larger tumors, higher percent of PVT, and significantly lower blood total bilirubin and liver cirrhosis than similar ≥5 cm tumor patients having thrombocytopenia. A comparison of patients with and without PVT showed significantly larger tumors, greater multifocality, blood AFP, and C-reactive protein levels, and, interestingly, lower HDL levels in the patients with PVT. Fifty-eight percent of the total cohort had AFP levels ≤100 IU/mL (and 42.1% had values ≤20 IU/mL). These patients had significantly smaller tumors, less tumor multifocality and percent PVT, lower total bilirubin, and less cirrhosis. There was considerable geographic heterogeneity within Turkey in the patterns of HCC presentation, with areas of higher and lower hepatitis B virus, hepatitis D virus, cirrhosis, and tumor aggressiveness parameters. Turkish patients thus have distinct patterns of presentation, but the biological relationships between MTD and both platelets and bilirubin levels are similar to the relationships that have been reported in other ethnic patient groups.

Maternal Serum PLGF, PAPPA, β-hCG and AFP Levels in Early Second Trimester as Predictors of Preeclampsia.

Identifying women at risk of preeclampsia (PE) by maternal serum screening is conducive to prompt gestational management and thereby improve both maternal and perinatal outcomes. The purpose of the present study was to evaluate the association between the concentrations of maternal serum placental growth factor (PLGF), pregnancy associated plasma protein-A (PAPPA), free β-human chorionic gonadotropin (β-hCG), and αFetoprotein (AFP) and the development of preeclampsia early in the second trimester. Forty pregnant women subsequently developed mild PE, 21 pregnant women subsequently developed severe PE, and 61 cases of normotensive controls were included. Maternal serum concentrations of PLGF, PAPPA, β-hCG, and AFP were measured at 15 - 20 weeks of gestation. Serum PLGF level was lower in women who subsequently developed PE than in normotensive controls. However, the significant difference was only found between the severe PE and control groups (p = 0.015). Serum PAPPA, β-hCG, and AFP levels were not significantly different between the PE and control groups. Serum PLGF level was lower in women who subsequently developed severe PE early in the second trimester, suggesting its role in prediction of PE.

Subclassification of patients with intermediate-stage (Barcelona Clinic Liver Cancer stage-B) hepatocellular carcinoma using the up-to-seven criteria and serum tumor markers.

Intermediate-stage [Barcelona Clinic Liver Cancer stage-B (BCLC-B)] hepatocellular carcinoma (HCC) comprises of a heterogeneous population of patients with a wide range of tumor burdens. We therefore formulated a subclassification of BCLC-B HCC using the up-to-seven criteria and tumor markers according to the results of a retrospective analysis of these patients. This study included 125 patients newly diagnosed with BCLC-B HCC who underwent transarterial chemoembolization. Among them, 39 and 86 were within or beyond the up-to-seven criteria, respectively. Multivariate Cox proportional hazards analysis was performed to investigate factors that contributed to better prognosis associated with the criteria. Cumulative overall survival (OS) and disease-free survival rates were significantly higher for patients within the up-to-seven criteria compared with those beyond (p=0.034 and p=0.001, respectively). Multivariate analysis revealed that low concentrations of des-γ-carboxy prothrombin (DCP) (<150 mAU/ml) and α-fetoprotein (AFP) (<100ng/ml) were independent contributors to better OS of patients within or beyond the up-to-seven criteria, respectively. Accordingly, the patients were classified as follows: group A (patients within the up-to-seven criteria with DCP <150mAU/ml), group C (patients beyond the up-to-seven criteria with AFP≥100ng/ml), and group B (other patients). OS differed significantly among groups (p<0.001), and the median survival times of group A, B, and C were 4.2, 2.7, and 1.5years, respectively. The subclassification system incorporating the up-to-seven criteria combined with DCP and AFP levels may serve as better predictors of prognosis that may guide efforts to improve treatment strategies.

Validation of Clinical Scoring Systems ART and ABCR after Transarterial Chemoembolization of Hepatocellular Carcinoma

PurposeTo perform an external validation of the Assessment for Retreatment with Transarterial Chemoembolization (ART) and α-fetoprotein (AFP), Barcelona Clinic Liver Cancer (BCLC), Child–Pugh, and response (ABCR) scores and to compare them in terms of prognostic power. Materials and MethodsFrom 2000 to 2015, 871 patients with hepatocellular carcinoma underwent transarterial chemoembolization at a tertiary referral hospital, and 176 met all inclusion and exclusion criteria for both scores and were analyzed. Nineteen percent (n = 34) had BCLC stage A disease and 81% had stage B disease. Thirty-nine patients (22%) presented with elevated AFP levels. Overall survival was calculated. Scores were validated and compared with a Harrell C-index, integrated Brier score (IBS), and prediction error curves. ResultsBefore the second chemoembolization procedure, 22 patients (12%) showed an increase of 1 point in Child–Pugh score and 51 patients (22%) had an increase of ≥ 2 points. Thirty-one patients (23%) showed a > 25% increase in aspartate aminotransferase level, and 114 (65%) showed a response to treatment. Consequently, 127 patients (72%) had a low ART score and 49 (28%) had a high ART score. One hundred fifty-eight patients (90%) had a low ABCR score, whereas 18 (10%) had a high ABCR score. Low and high ART score groups had median survival durations of 20.8 and 15.3 mo, respectively. Harrell C-indexes were 0.572 and 0.608, and IBSs were 0.135 and 0.128, for ART and ABCR, respectively. For both scores, an increase in Child–Pugh score ≥ 2 points and a radiologic response were significantly associated with survival. ConclusionsBoth scores were of limited predictive value, and neither was sufficient to support clear-cut clinical decisions. Further effort is necessary to determine criteria for making valid clinical predictions.

Prediction of development of hepatocellular carcinoma using a new scoring system involving virtual touch quantification in patients with chronic liver diseases.

This study aimed to establish a new scoring system that combined several risk factors, including virtual touch quantification (VTQ) values and fasting plasma glucose (FPG) levels, for predicting the development of hepatocellular carcinoma (HCC) in patients with chronic liver disease. A total of 1808 chronic liver disease patients who underwent VTQ measurement were analyzed. Risk factors for developing HCC were selected by multivariate Cox proportional hazards models. VTQ (>1.33m/s), FPG (≥110mg/dl), sex (male), age (≥55years), and α-fetoprotein (AFP) level (≥5ng/ml) were independently selected as risk factors for HCC development by multivariate analysis. Using these parameters, we established a new scoring system (0 to 5 points), based on VTQ, FPG, sex, age, and AFP level, named VFMAP. As compared with the low VFMAP score group (0 or 1 point), the hazard ratio for the incidence of HCC was 17.37 [95% confidence interval (CI), 2.35-128.40] in the intermediate-score group (2 or 3 points) and 66.82 (95% CI, 9.01-495.80) in the high-score group (4 or 5 points). The area under the receiver operating characteristic curve of the VFMAP score for predicting HCC development within 5years was 0.82 (95% CI, 0.76-0.87), indicating a moderate diagnostic value. A VFMAP cutoff value of 3 excluded HCC within 5years with a high negative predictive value (98.2%). The VFMAP score accurately predicted HCC in patients with chronic liver disease.