Alpha-fetoprotein Values Research Articles

The Dynamic Changes of AFP From Baseline to Recurrence as an Excellent Prognostic Factor of Hepatocellular Carcinoma After Locoregional Therapy: A 5-Year Prospective Cohort Study.

BackgroundAlthough many studies have confirmed the prognostic value of preoperative alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC), the association between AFP at baseline (b-AFP), subsequent AFP at relapse (r-AFP), and AFP alteration and overall survival in HCC patients receiving locoregional therapy has rarely been systematically elucidated.Patients and MethodsA total of 583 subjects with newly diagnosis of virus-related HCC who were admitted to Beijing You ‘an Hospital, Capital Medical University from January 1, 2012 to December 31, 2016 were prospectively enrolled. The influence of b-AFP, subsequent r-AFP, and AFP alteration on relapse and post-recurrence survival were analyzed.ResultsBy the end of follow-up, a total of 431 (73.9%) patients relapsed and 200 (34.3%) died. Patients with positive b-AFP had a 24% increased risk of recurrence compared with those who were negative. Patients with positive r-AFP had a 68% increased risk of death after relapse compared with those who were negative. The cumulative recurrence-death survival (RDS) rates for 1, 3, 5 years in patients with negative r-AFP were 85.6% (184/215), 70.2%(151/215), and 67.4%(145/215), while the corresponding rates were 75.1% (154/205), 51.2% (105/205), and 48.8% (100/205) in those with positive AFP (P<0.001). 35 (21.6%) of the 162 patients with negative b-AFP turned positive at the time of recurrence, and of this subset, only 12 (34.3%) survived. Of the 255 patients with positive b-AFP, 86 (33.7%) turned negative at the time of relapse, and of this subset, only 30 (34.9%) died. The 1-, 3-, and 5-year cumulative RDS rates were also compared among groups stratified by AFP at baseline and relapse. The present study found that patients with positive AFP at baseline and relapse, as well as those who were negative turned positive, had the shortest RDS and OS.ConclusionsNot only AFP at baseline but also subsequent AFP at relapse can be used to predict a post-recurrence survival, which can help evaluate mortality risk stratification of patients after relapse.

Alpha-Fetoprotein in Predicting Survival of Patients with Ruptured Hepatocellular Carcinoma after Resection

Background/Aim: Alpha-fetoprotein (AFP) had been used as a prognostic factor in hepatocellular carcinoma but it was unknown what level of AFP could predict the survival of patients with ruptured hepatocellular carcinoma (rHCC) after resection. This retrospective study was to identify the best cutoff value of AFP for this prediction. Methods: Data of patients having hepatectomy for rHCC from 1989 to 2015 were reviewed. The receiver operating characteristic curve and Youden’s index were used to identify the cutoff value of AFP affecting survival. The patients were then divided into two groups by the cutoff for comparison. Results: Totally 114 patients were included. An AFP level of 256 ng/ml was found to affect survival (area under curve 63.1%, 95% confidence interval 0.514–0.748, p = 0.027; sensitivity 0.6, specificity 0.706). The 114 patients were divided into Group A (AFP < 256 ng/ml, n = 56) and Group B (AFP ≥ 256 ng/ml, n = 58). The median AFP level was 13.0 ng/ml (range, 2–253 ng/ml) in Group A and 11206.5 ng/ml (range, 259–481,000 ng/ml) in Group B (p < 0.001). Group A had a larger proportion of patients receiving transarterial embolization at the time of rupture, and the time to hepatectomy was longer in this group. Patients in Group B had more blood loss, more complications, larger tumors, and more cases of macrovascular/microvascular invasion. Overall survival (p = 0.013) and disease-free survival (p = 0.024) were significantly better in Group A. On multivariate analysis, AFP ≥ 256 ng/ml was an independent risk factor for overall survival. Conclusion: AFP ≥ 256 ng/ml had an adverse impact on the survival of patients with rHCC after resection.

Pre-Transplant Alpha-Fetoprotein > 25.5 and Its Dynamic on Waitlist Are Predictors of HCC Recurrence after Liver Transplantation for Patients Meeting Milan Criteria.

Simple SummaryIn the setting of liver transplantation, prediction of hepatocellular carcinoma (HCC) recurrence persists as a fundamental issue, and few tools are available during the waitlist. Biological features such as alpha-fetoprotein values are strong predictors, but it is necessary to understand how we can use them. In this study, an AFP cut-off value was individuated and also its dynamic increase on the waitlist was defined as a predictor.Background and Aim: Hepatocellular carcinoma (HCC) recurrence rates after liver transplantation (LT) range between 8 and 20%. Alpha-fetoprotein (AFP) levels at transplant can predict HCC recurrence, however a defined cut-off value is needed to better stratify patients. The aim of this study was to evaluate the rate of HCC recurrence at our centre and to identify predictors, focusing on AFP. Methods: We retrospectively analysed 236 consecutive patients that were waitlisted for HCC who all met the Milan criteria from January 2001 to December 2017 at our liver transplant centre. A total of twenty-nine patients dropped out while they were waitlisted, and 207 patients were included in the final analysis. All survival analyses included the competing-risk model. Results: The mean age was 56.8 ± 6.8 years. A total of 14% were female (n = 29/207). The median MELD (model for end-stage liver disease) at LT was 12 (9–16). The median time on the waitlist was 92 (41–170) days. The HCC recurrence rate was 16.4% (n = 34/208). The mean time to recurrence was 3.3 ± 2.8 years. The median AFP levels at transplant were higher in patients with HCC recurrence (p < 0.001). At multivariate analysis, the AFP value at transplant that was greater than 25.5 ng/mL (AUC 0.69) was a strong predictor of HCC recurrence after LT [sHR 3.3 (1.6–6.81); p = 0.001]. The HCC cumulative incidence function (CIF) of recurrence at 10 years from LT was significantly higher in patients with AFP > 25.5 ng/mL [34.3% vs. 11.5% (p = 0.001)]. Moreover, an increase in AFP > 20.8%, was significantly associated with HCC recurrence (p = 0.034). Conclusions: In conclusion, in our retrospective study, the AFP level at transplant > 25.5 ng/mL and its increase greater than 20.8% on the waitlist were strong predictors of HCC recurrence after LT in a cohort of patients that were waitlisted within the Milan criteria. However further studies are needed to validate these data.

Dual Cancer in a Patient with Type 1 Gaucher Disease: Case Report and Literature Review

Gaucher Disease (GD) is a rare inherited lysosomal storage disease caused by biallelic mutations in the gene encoding the lysosomal enzyme acid β-glucocerebrosidase, with progressive accumulation of the sphingolipid glucosylceramide in the lysosomes of macrophages, mainly in the liver, spleen, bone, and bone marrow. It is characterized by anemia, thrombocytopenia, hepatosplenomegaly, sometimes severe bone involvement and, in certain forms, neurological involvement. We present the case of a 77-year-old male, diagnosed in 2006, at 63, with GD type1. At the onset, the patient presented fatigue, asthenia, upper abdominal discomfort, skin pallor and minor bone pain. During follow-up, CT was performed and displayed an enlarged spleen (25 cm) and a well-defined mass in the kidney cortex, but it could not establish whether it was malignant or not. Considering the patient refused surgery at that moment, a new CT exam was performed six months later, and the kidney tumor significantly increased in size. Nephrectomy and necessity splenectomy were performed, and recovery was uneventful. The histopathological examination revealed clear cell renal cell carcinoma, grade 2 Fuhrman. Enzyme substitution therapy with Imiglucerasum was initiated in 2012 with favorable evolution. Seven years later, during a routine ultrasound follow-up, a 4/3.8 cm hyperechoic mass was found in the eighth liver segment. The biological tests revealed a high value of alpha-fetoprotein (AFP-185.2 ng/mL). Considering the patient’s history, possible diagnoses of the newly found focal liver lesion were: gaucheroma, metastasis secondary to kidney cancer, or a primitive liver tumor. Core biopsy was performed, and it was suggestive of a poorly differentiated hepatocellular carcinoma G3. A non-anatomical resection of liver segments VII and VIII with partial resection of inferior vena cava was performed, followed by full post-operative recovery. A histopathological examination confirmed the initial diagnosis. Currently, one month postoperatively, the patient in good clinical condition, continues the enzyme replacement treatment and is undergoing oncological follow-up. We presented a complex case of GD, diagnosed at an advanced age, who responded well to substitution therapy in regard to hematologic and bone symptoms, but who unfortunately developed two types of cancer managed aggressively despite the advanced age.

Liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis.

Traditionally, liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis is not recommended. However, with recent developments in locoregional therapies for hepatocellular carcinoma, more aggressive treatments have been attempted for advanced hepatocellular carcinoma. Recently, various studies on locoregional therapies for downstaging followed by living donor liver transplantation reported inspiring overall survival and recurrence-free survival of patients. These downstaging procedures included three-dimensional conformal radiation therapy, trans-arterial chemoembolization, stereotactic body radiation therapy, trans-arterial radioembolization, hepatic arterial infusion chemotherapy and combinations of these therapies. Selection of the optimal downstaging protocol should depend on tumor location, biology and background liver status. The risk factors affecting outcome include pre-downstaging alpha-fetoprotein values, delta alpha-fetoprotein values, disappearance of portal vein tumor thrombosis on imaging and meeting the Milan criteria or not after downstaging. For hepatocellular carcinoma with portal vein tumor thrombosis, downstaging procedure with liver transplantation in mind would be helpful. If the reaction of the downstaged tumor is good, liver transplantation may be performed.

New Thresholds for AFP and Des-γ-Carboxy Prothrombin in Chronic Liver Disease Depending on the Use of Nucleoside Analogs and an Integrated Nomogram.

BackgroundThe thresholds of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (PIVKA-II) when detecting hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with antiviral nucleoside analog (NA) remain controversial. A relevant integrated nomogram needs to be developed.MethodsWe enrolled a consecutive series of 5666 cases diagnosed with CHB either with or without antiviral agents and randomly allocated them to the training set (n=3966, 70.00%) and the validation set (n=1700, 30.00%).ResultsIn the training set, the levels of AFP and PIVKA-II of NA-treated patients were significantly lower than those of untreated patients. The most appropriate cut-off values of AFP and PIVKA-II were 151.40 ng/mL (a sensitivity of 39.77% and a specificity of 92.17%) and 35.50 mAU/mL (a sensitivity of 84.85% and a specificity of 69.43%) for NA-treated patients. As for BCLC-0/A HCC, the most appropriate cut-off values of AFP and PIVKA-II were 151.40 ng/mL and 32.50 mAU/mL for NA-treated patients, respectively. A logistic regression model composed of AFP, PIVKA-II and other clinical parameters to predict the risk of HBV-related HCC for NA-treated patients was established and verified to have an AUROC of 0.868 (95% CI, 0.827–0.909) for all-stage HCC and an AUROC of 0.856 (95% CI, 0.809–0.903) for BCLC-0/A HCC.ConclusionThe new detection thresholds of AFP and PIVKA-II might lead to the ability to perform early detection for hepatoma in NA-treated patients and the innovative risk prediction model is a valuable tool for identifying high-risk CHB patients.

Value of precontrast and portal venous phases for evaluating atypical hepatocellular carcinoma mimicking arterioportal shunt

PurposeTo evaluate the value of precontrast phase (PP) and portal venous phase (PVP) for differentiation of small hypervascular hepatocellular carcinomas (HCCs) without delayed washout from arterioportal (AP) shunts in high-risk patients of HCC. MethodsA total of 122 lesions (73 AP shunts and 49 HCCs) detected on quadriphasic CT in 101 patients with chronic liver disease were analyzed. All lesions (≤2 cm) showed arterial enhancement and isodensity on delayed phase (DP) with exclusion of typical features of AP shunts. Lesion morphologic features (size, location, shape, margin) on biphasic CT (arterial phase and DP), Alpha-fetoprotein (AFP) values and coexistent HCC were evaluated. The qualitative and quantitative analyses of lesion attenuation on quadriphasic CT were performed. Diagnostic performances for prediction of AP shunts over HCC were compared among the biphasic CT, triphasic CT (adding PP or PVP) and quadriphasic CT. ResultsIn multivariate analysis, the presence of concomitant HCC (p = 0.0005, odds ratio [OR] = 0.11), visual hypodensity on PP (p = 0.0004, OR = 17.72) and visual hyperdensity on PVP (p = 0.0003, OR = 0.051) were independent predictors for HCCs rather than AP shunts. Additional review of PP and PVP revealed significantly improved diagnostic performance yielding the highest diagnostic performance. ConclusionsHypodensity on PP and hyperdensity on PVP are significant predictive features in differentiating atypical small hypervascular HCC from AP shunts in patients with high-risk of HCC. Careful evaluation of the PP and PVP may reduce underdiagnosis and lead to earlier diagnosis of atypical small HCCs.

PRM-MS Quantitative Analysis of Isomeric N-Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular Carcinoma.

Currently, surveillance strategies have inadequate performance for cirrhosis and early detection of hepatocellular carcinoma (HCC). The glycosylation of serum haptoglobin has shown to have significant differences between cirrhosis and HCC, thus can be used for diagnosis. We performed a comprehensive liquid chromatography—parallel reaction monitoring—mass spectrometry (LC-PRM-MS) approach, where a targeted parallel reaction monitoring (PRM) strategy was coupled to a powerful LC system, to study the site-specific isomerism of haptoglobin (Hp) extracted from cirrhosis and HCC patients. We found that our strategy was able to identify a large number of isomeric N-glycopeptides, mainly located in the Hp glycosylation site Asn207. Four N-glycopeptides were found to have significant changes in abundance between cirrhosis and HCC samples (p < 0.05). Strategic combinations of the significant N-glycopeptides, either with alpha-fetoprotein (AFP) or themselves, better estimate the areas under the curve (AUC) of their respective receiver operating characteristic (ROC) curves with respect to AFP. The combination of AFP with the isomeric sialylated fucosylated N-glycopeptides Asn207 + 5-6-1-2 and Asn207 + 5-6-1-3, resulted with an AUC value of 0.98, while the AUC value for AFP alone was 0.85. When comparing cirrhosis vs. early HCC, the isomeric N-glycopeptide Asn207 + 5-6-0-1 better estimated AUC with respect to AFP (AUCAFP = 0.81, and AUCAsn207 + 5-6-0-1 = 0.88, respectively).

Hepatoid Adenocarcinoma of the Lung: A Systematic Review of the Literature From 1981 to 2020

ObjectivesWe report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study its main treatment methods, prognosis, and the relationship between prognosis and the serum alpha-fetoprotein (AFP) level before treatment.MethodsWe report a 66-year-old male case who was diagnosed with locally advanced HAL with PIK3CA mutation and carried out a systematic literature search for HAL cases documented between 1981 and 2020. General patient information including case characteristics was extracted and summarized. The median OS (mOS) of HAL patients was determined using the KM survival curve. The Cox proportional hazards regression model was used to evaluate the effect of tumor size, location, and serum AFP value before treatment and radical surgery (RS) on the prognosis of patients.ResultsA total of 46 studies including 51 HAL patients was included in our review. Our study revealed that 52.9% of tumors were located in the upper lobe of the right lung. The proportion of serum AFP-positive patients before treatment, early-stage patients (TNM stage I and II), and patients who had received surgery were 69.2%, 34.1%, and 40%, respectively. The mOS of HAL patients was 16.0 months. The 2-year and 5-year survival rates of the patients were 35.3% and 8.0%, respectively. In the subgroup analysis, the 2-year survival rate for patients who received RS was 62.5%, while for patients who were unable to undergo RS, it was only 12.5% (p = 0.009). The Cox proportional hazards regression model indicated that RS can significantly improve the prognosis of HAL patients (p = 0.011), although the location and size of tumor as well as the serum AFP value before treatment had no significant effect on their prognosis (p = 0.82, p = 0.96, p = 0.25).ConclusionsHAL patients have a poor prognosis, and the survival benefits for patients receiving chemoradiotherapy or chemotherapy alone appear to be limited. We demonstrate statistically for the first time that pretreatment serum AFP values are not related to the prognosis of HAL patients and RS can significantly improve patient prognosis.

Percentage of Teratoma in Orchiectomy and Risk of Retroperitoneal Teratoma at the Time of Postchemotherapy Retroperitoneal Lymph Node Dissection in Germ Cell Tumors.

Presence of teratoma in the orchiectomy and residual retroperitoneal mass size are known predictors of finding teratoma during postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). We sought to determine if the percentage of teratoma in the orchiectomy specimen could better stratify the risk of teratoma in the retroperitoneum. The Indiana University Testis Cancer Database was reviewed to identify patients who underwent PC-RPLND for nonseminomatous germ cell tumors from 2010 to 2018. A logistic regression model was fit to predict the presence of retroperitoneal teratoma using teratoma and yolk sac tumor in the orchiectomy, residual mass size and log transformed values of prechemotherapy alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin. The study cohort was split into 60% training and 40% validation sets using 200 bootstraps. A predictive nomogram was developed for predicting teratoma in the retroperitoneum. A total of 422 men were included. Presence of teratoma in the orchiectomy (OR 1.02, p <0.001), residual mass size (OR 1.16, p <0.001) and log transformed prechemotherapy AFP (OR 1.12, p=0.002) were predictive factors for having teratoma in the retroperitoneum. The C-statistic using this model demonstrated a predictive ability of 0.77. Training set C-statistic was 0.78 compared to 0.75 for the validation set. A nomogram was developed to aid in clinical utility. The model better predicts patients at higher risk for teratoma in the retroperitoneum following chemotherapy, which can aid in a more informed referral for surgical resection.

VALUE OF SERUM MIDKINE LEVEL IN PATIENTS WITH LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA

Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Risk factors for HCC include chronic hepatitis B and hepatitis C, alcohol addiction, metabolic liver disease and exposure to dietary toxins such as aflatoxins and aristolochic acid. Objective: To determine the value of serum Medkine level as a potential biomarker for patients with hepatocellular carcinoma. Patients and methods: This study was conducted at the Gastroenterology and Hepatology Unit, Department of Internal Medicine Al-Azhar and Misr University for Science and Technology. 90 Egyptian patients were recruited and were divided into 3 Group I included 30 patients with liver cirrhosis, HCC was excluded in these patients at time of recruitment in the study, exclusion of HCC was based on the absence of any hepatic focal lesion in abdominal ultrasonography scanning. Group II included 40 patients with HCC. Diagnosis of HCC was based on the appearance of typical vascular pattern of enhancement in triphasic spiral CT scan of the abdomen. Control Group included 20 age and sex-matched apparently healthy subjects. Results: Different liver function tests showed no statistically difference between two groups except for ALK. Ph and gamma glutamyltransferase (GGT) which were significant higher in group II than group I. There was a highly statistically significance difference regarding alpha-fetoprotein (AFP) which was higher in group II than group I and control group. Serum AFP levels were found to be significantly correlated with larger tumor size in this study. In addition, patients with advanced-stage hepatocellular carcinomas had significantly higher median AFP serum levels (BCLC B/C) than that of early-stage tumors (BCLC 0/A) (237ng/mL versus 23ng/mL). However, no significant correlation was found between serum midkine (MDK) levels with tumor size, number or serum levels of AFP, and no significant association was found between serum MDK levels and BCLC stages. The best cutoff values for MDK and AFP to discriminate HCC cases from those with liver cirrhosis were 0.39 and 10ng/mL, respectively, with sensitivities (90% versus 77.5%), specificities (60% versus 80%). The overall diagnostic performance of MDK for HCC diagnosis was much better than that of AFP. On comparing the sensitivities and specificities of MDK at the cutoff 0.39ng/mL to those of AFP at different cutoff values (10 and 400), the overall diagnostic performance of MDK for HCC diagnosis was much better than that of AFP. Conclusion: Alpha-fetoprotein and midkine may have a complementary role in hepatocellular carcinoma surveillance and screening. Midkine increased the diagnostic yield in alpha-fetoprotein -negative hepatocellular carcinoma and the presence of either elevated alpha-fetoprotein or midkine increased the sensitivity of hepatocellular carcinoma detection. Midkine was also superior to alpha-fetoprotein in the diagnosis of NASH-related hepatocellular carcinoma and this finding postulated an exciting novel role for midkine in NASH-related carcinogenesis.

Serum level of cytokeratin 19 as a diagnostic and prognostic marker in patients with HCV-related hepatocellular carcinoma

BackgroundThe heterogeneous nature of human hepatocellular carcinoma (HCC) impedes both treatment strategies and prognostic predictions. Several markers have been proposed for the diagnosis of HCC. Cytoskeleton-associated proteins have been known as cellular integrators in neoplasm formation. Hepatic progenitor cells are thought to express alpha-fetoprotein (AFP) and hematopoietic as well as biliary markers such as cytokeratin 19 (CK 19) and cytokeratin 7. The aim of this study was to verify the role of serum CK 19 alone or in combination with AFP as a diagnostic marker of HCC and to assess the changes in its levels after ablation of HCV-related HCC to evaluate its role as a predictor marker for recurrence of HCC after ablation. The study was conducted on 102 HCV-related cirrhotic patients categorized into three different groups according to the clinical, laboratory, and radiological evaluation: group I—62 patients with early or intermediate HCC who underwent locoregional intervention, group II—20 patients with advanced HCC not fit for any intervention apart from best supportive treatment, and group III—20 cirrhotic patients with no evidence of HCC as proved by two imaging techniques.ResultsThe mean serum levels of CK 19 were 6.5 ± 5.7, 10.5 ± 12.5, and 6.8 ± 2.8 ng/ml in groups I, II, and III, respectively, with no significant difference between groups. Sensitivity, specificity, positive, and negative predictive values of combined AFP and human CK 19 at cutoff levels of 25.5 ng/ml and 6.25 ng/ml were 93.9%, 45%, 87.5%, and 64.3%, respectively. In group I patients, CK 19 levels were comparable in patients with ablated focal lesion and those who did not at baseline; then, it was significantly higher in ablated patients than in patients with residual tumor 1 and 6 months after the intervention.ConclusionsCombination of both AFP and CK 19 levels could increase the diagnostic accuracy of suspected HCCs. CK 19 levels are good predictors of ablation/recurrence in patients who underwent interventional procedures minimizing the need for follow-up imaging modalities.

Detection of Hepatocellular Carcinoma in a High-Risk Population by a Mass Spectrometry-Based Test.

Simple SummaryLiver cancer is one of the most common causes of cancer worldwide, but unfortunately, current technology has a limited ability to detect it early in high-risk patients. This study investigates a machine learning algorithm based on protein levels in the blood that can be used to help with diagnosis. The test shows promising results, especially in patients with smaller tumors and compared to current blood detection tests. This research suggests an important role in the future for machine learning algorithm-based blood detection tests.Hepatocellular carcinoma (HCC) is one of the fastest growing causes of cancer-related death. Guidelines recommend obtaining a screening ultrasound with or without alpha-fetoprotein (AFP) every 6 months in at-risk adults. AFP as a screening biomarker is plagued by low sensitivity/specificity, prompting interest in discovering alternatives. Mass spectrometry-based techniques are promising in their ability to identify potential biomarkers. This study aimed to use machine learning utilizing spectral data and AFP to create a model for early detection. Serum samples were collected from three separate cohorts, and data were compiled to make Development, Internal Validation, and Independent Validation sets. AFP levels were measured, and Deep MALDI® analysis was used to generate mass spectra. Spectral data were input into the VeriStrat® classification algorithm. Machine learning techniques then classified each sample as “Cancer” or “No Cancer”. Sensitivity and specificity of the test were >80% to detect HCC. High specificity of the test was independent of cause and severity of underlying disease. When compared to AFP, there was improved cancer detection for all tumor sizes, especially small lesions. Overall, a machine learning algorithm incorporating mass spectral data and AFP values from serum samples offers a novel approach to diagnose HCC. Given the small sample size of the Independent Validation set, a further independent, prospective study is warranted.

Serum vascular endothelial growth factor as a tumor marker for hepatocellular carcinoma in hepatitis C virus-related cirrhotic patients.

BACKGROUNDHepatocellular carcinoma (HCC) accounts for 8.2% of all cancer-related deaths worldwide. Being a vascular tumor, vascular endothelial growth factor (VEGF) plays a vital role in HCC pathogenesis, growth, and spread.AIMTo determine the accuracy of serum VEGF and VEGF/platelet (PLT) as tumor markers in the early detection of HCC cases in patients with hepatitis C virus (HCV)-related liver cirrhosis.METHODSWe conducted a case-control study with HCV patients from the outpatient and inpatient hepatology clinics. Patients were classified into three groups: (1) HCC group; (2) Cirrhosis group; and (3) HCV without cirrhosis (control group). Patients were clinically evaluated, and blood samples were drawn for the analysis; serum VEGF levels were measured by a specific VEGF human recombinant enzyme-linked immunosorbent assay kit. Data from the three study groups were compared by the one-way analysis of variance or Kruskal-Wallis test. Receivers operating characteristic curves were constructed to determine the optimal cut-off values of alpha fetoprotein (AFP), VEGF, and VEGF/PLT that provided the best diagnostic accuracy. The sensitivity and specificity at the optimal cut-off value of each biomarker were then calculated. RESULTSThis study included one hundred patients (HCC, cirrhosis, and control groups: n = 40, 30, 30, respectively). HCC patients had significantly higher serum VEGF and VEGF/PLT levels than the non-HCC groups (P = 0.001). Serum VEGF and VEGF/PLT showed significant positive correlations with and HCC tumor size, stage, vascular invasion, and Child-Pugh classification. Moreover, a VEGF cut-off the value of 250 pg/mL provided 80% sensitivity and 81.7% specificity for discriminating HCC patient from non-HCC patients. Similarly, the ratio of VEGF/PLT provided sensitivity and specificity of 77.5% and 80%, respectively which is higher than the accuracy provided by AFP. The combination of AFP, VEGF, and VEGF/PLT increases the accuracy of diagnosing HCC to > 95%.CONCLUSIONIn HCV patients, serum VEGF and VEGF/PLT separately or in combination with AFP are reliable biomarkers for early and accurate HCC diagnosis.

Clinical Utility of Protein Induced by Vitamin K Absence-II in Patients with Hepatocellular Carcinoma.

Objective:Despite moderate sensitivity, alpha fetoprotein (AFP) is widely used in screening and prognostication for hepatocellular carcinoma (HCC). The objective of the current study was to assess clinical utility of Prothrombin induced by Vitamin K absence-II (PIVKAII) in addition to AFP in patients with HCC. Methods:We retrospectively reviewed 244 patients with documented AFP, PIVKA II and dynamic imaging of the liver. Using ROC curves, cutoff values for AFP and PIVKAII for HCC detection, tumor grade and microvascular invasion (MVI) were assessed. In patients who underwent liver transplantation (LT) for HCC, survival was determined using Kaplan Meier curves. Results:The median PIVKAII in healthy living donors was 28.6mAU/ml (15.9-55). In cirrhotics, the sensitivity of an AFP cutoff of 7.6 ng/ml or PIVKAII cutoff of 250 mAU/ml for HCC detection was 91.7% (176/192) and specificity was 62.9%(68/108) (P<0.0001). In patients with HCC, PIVKAII values were significantly elevated with tumor size > 5 cm (P < 0.0001), tumor nodules > 3(P=0.01), and macrovascular invasion(P<0.0001). The high risk group (patients with AFP ≥ 40 ng/ml + PIVKAII ≥ 350 mAU/ml), had a sensitivity of (23/33) 69.6% and specificity of (22/22)100% for MVI (P <0.001). The estimated 3 year RFS after LT in the low risk group (AFP <40 ng/ml or PIVKAII< 350 mAU/ml) was 100% versus 63%(P=0.001). The estimated 3 year RFS based with and without MVI was 80% and 100% (P=0.03). Conclusion:PIVKAII in combination with AFP, appears to have a promising role in surveillance and prognostication for HCC. It also allows improved patient selection for liver transplantation.

Preterm Delivery: Predictive Value of Salivary Estriol, and Alpha Feto Protien

Background: Preterm labor is defined by the presence of painful uterine contractions that lead to progressivechanges in the cervix that allow descent and delivery of the newborn before the 37th week of gestation.Objective: To assess the predictive value of salivary estriol and Alpha feto protein in preterm delivery.Patients and Method: A prospective study were carried out in our hospital during the period from 1/1/2020to the 30/8/2020 among the patients who attended for consultation, 120 patients with gestational age between16 and 18 weeks were selected and divided into two groups. Results: The serum level of Alpha-feto proteinwas (338. 15 ± 182.55 in case group vs. 239. 68 ± 112. 51 in control group) with significant association(p=0.01). In spite of the decrease of the estriol level in preterm group we found no significant differenceswere found between both groups regarding the estriol level (P&gt;0.05)Conclusion: The increase in free estriol in saliva in this study was not significantly associated with pretermdelivery in asymptomatic patients at risk, and there is a significantly increase in AFP concentration inpreterm pregnant patients.

Hepatocellular carcinoma progression in hepatitis B virus-related cirrhosis patients receiving nucleoside (acid) analogs therapy: A retrospective cross-sectional study.

BACKGROUNDAntiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma (HCC). Furthermore, there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog (NA) therapy.AIMThe study aim was to clarify risk factors and the diagnostic value of alpha-fetoprotein (AFP) for HCC progression in NA-treated hepatitis B virus (HBV)-related cirrhosis patients.METHODSIn this retrospective cross-sectional study, we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People’s Hospital. The patients were divided into two groups, 145 who did not progress to HCC (No-HCC group), and 121 who progressed to HCC during NA treatment (HCC group). The logistic regression analysis was used to analyze the risk factors of HCC progression. The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic (ROC) curve analysis.RESULTSUnivariate analysis showed that age ≥ 60 years (P = 0.001), hepatitis B and alcoholic etiology (P = 0.007), smoking history (P < 0.001), family history of HBV-related HCC (P = 0.002), lamivudine resistance (P = 0.011), HBV DNA negative (P = 0.023), aspartate aminotransferase > 80 U/L (P = 0.002), gamma-glutamyl transpeptidase > 120 U/L (P = 0.001), alkaline phosphatase > 250 U/L (P = 0.001), fasting blood glucose (FBG) ≥ 6.16 (mmol/L) (P = 0.001) and Child-Pugh class C (P = 0.005) were correlated with HCC progression. In multivariate analysis, age ≥ 60 years [hazard ratio (HR) = 3.089, 95% confidence interval (CI): 1.437-6.631, P = 0.004], smoking history (HR = 4.001, 95%CI: 1.836-8.716, P < 0.01), family history of HBV-related HCC (HR = 6.763, 95%CI: 1.253-36.499, P < 0.05), lamivudine resistance (HR = 2.949, 95%CI: 1.207-7.208, P = 0.018), HBV DNA negative (HR = 0.026, 95%CI: 0.007-0.139, P < 0.01), FBG ≥ 6.16 mmol/L (HR = 7.219, 95%CI: 3.716-14.024, P < 0.01) were independent risk factors of HCC progression. ROC of AFP for diagnosis of HCC was 0.746 (95%CI: 0.674-0.818). A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609, and specificity of 0.818 for diagnosing HCC.CONCLUSIONAge ≥ 60 years, smoking history, family history of HCC, lamivudine resistance, HBV DNA negative, FBG ≥ 6.16 mmol/L were risk factors of HCC progression. Serum AFP had limited diagnostic value for HCC.

Outcomes of pregnancies diagnosed with circumvallate placenta, and use of uterine artery pulsatility index and maternal serum alpha-fetoprotein for prediction of adverse outcomes

ObjectivesTo evaluate the outcomes, and predictive value of uterine artery pulsatility index (UtA-PI) and second-trimester maternal serum alpha-fetoprotein (MSAFP) for adverse obstetric outcomes in cases with morphologically confirmed circumvallate placenta by comparison with normal pregnancies. Study designThis prospective study was conducted in a tertiary referral hospital between January 2017 and December 2019. During the study period, 77 patients with a circumvallate placenta and 77 patients without any placental or feto-maternal diseases or abnormalities were evaluated. The final diagnosis was made based on macroscopic examination of the placenta soon after birth. Demographic characteristics, MSAFP, obstetric complications, haemoglobin after delivery, gestational week of birth, fetal sex, 1- and 5-min Apgar scores, postnatal complications and type of delivery were retrieved from hospital records. Bilateral mean transabdominal UtA-PI and MSAFP were evaluated for the prediction of adverse outcomes. SPSS Version 21.0 for Windows was used for statistical analysis, and receiver operating characteristic (ROC) curves were used for the prediction model of adverse outcomes. ResultsSmoking rate, MSAFP, preterm birth and intrauterine growth restriction (IUGR) were higher in the patients with a circumvallate placenta (p = 0.005, 0.00, 0.025 and 0.027, respectively). The cut-off value of MSAFP was 1.41 (0.60–3.32) and the cut-off value of UtA-PI was 1.2 using the ROC curves, and had sensitivity of 73.7 % and specificity of 71.9 %, and sensitivity of 73.7 % and specificity of 76.3 %, respectively (p < 0.05). ConclusionsCircumvallate placenta was associated with a higher rate of IUGR, preterm birth and bleeding at the time of delivery. In patients with a circumvallate placenta, UtA-PI and MSAFP may be valuable as predictors of IUGR.

Alpha-fetoprotein for Gastric Cancer Staging: An Essential or Redundant Tumor Marker?

This study was designed to clarify the value of routine alpha-fetoprotein (AFP) testing for patients with gastric cancer (GC). A total of 905 patients with newly diagnosed GC and available pretreatment carcinoembryonic antigen (CEA), cancer-related antigen 19-9 (CA19-9), and AFP data from 2010 to 2016 were collected for comparison of tumor stage and survival. In total, 139 patients (15.4%), 155 patients (17.1%), and 27 patients (3.0%) had elevated CEA, CA19-9, and AFP levels, respectively. The c-index values of elevated AFP levels in predicting stage IV disease and the 1-year mortality rate were 0.564 (95%CI=0.520-0.608) and 0.594 (95%CI=0.553-0.635), respectively, which were significantly lower than those of CEA (0.673 and 0.665) and CA19-9 (0.619 and 0.618). Elevated AFP is rare in patients with newly diagnosed GC. Routine AFP sampling would not provide a higher survival prediction in GC patients than CEA or CA19-9.

Hepatic Resection Versus Stereotactic Body Radiation Therapy Plus Transhepatic Arterial Chemoembolization for Large Hepatocellular Carcinoma: A Propensity Score Analysis

Background and AimsThere are no comparative studies on the efficacy of hepatic resection (HR) and CyberKnife stereotactic body radiation therapy (CK-SBRT) plus transhepatic arterial chemotherapy embolization (TACE) in the treatment of large hepatocellular carcinoma (HCC). Therefore, this study aimed to compare the efficacy of HR and CK-SBRT+TACE in large HCC.MethodsA total of one hundred and sixteen patients were selected from November 2011 to December 2016. Among them, 50 were allocated to the CK-SBRT+TACE group and 66 were allocated to the HR group. The Kaplan-Meier method was applied to calculate overall survival (OS) and progression-free survival (PFS) rates. Propensity score matching was performed to control for baseline differences between the groups.ResultsThirty-six paired patients were selected from the CK-SBRT+TACE and HR groups. After propensity score matching, the 1-, 2- and 3-year OS rates were 83.3%, 77.8% and 66.7% in the HR group and 80.6%, 72.2% and 52.8% in the CK-SBRT+TACE group, respectively. The 1-, 2- and 3-year PFS rates were 71.6%, 57.3% and 42.3% in the HR group and 66.1%, 45.8% and 39.3% in the CK-SBRT+TACE group, respectively (OS: p=0.143; PFS: p=0.445). Both a high platelet count and low alpha-fetoprotein value were revealed as influencing factors in improving OS and PFS.ConclusionsCK-SBRT+TACE brought local effects that were similar to those of HR in HCC patients with a large and single lesion. Moreover, the liver injury occurrence rate was acceptable in both groups.