Serum Alpha-fetoprotein Levels Research Articles

Use of Maternal Race and Weight Provides Equitable Performance in Serum Screening for Open Neural Tube Defects.

Maternal serum alpha-fetoprotein (AFP) levels are used in screening for open neural tube defects (ONTD). Historical reports show that AFP levels and maternal weights are higher in self-reported Black than White individuals, but recent reports question the need to account for these variables in screening. Our study compares screening performance with and without accounting for race. Retrospective analysis was performed on deidentified prenatal screening records including maternal weight and self-reported race of White or Black. Gestational age-specific medians and weight-adjusted multiples of the median levels were calculated separately for each group and using a race-agnostic analysis. Outcome measures included the proportion of screen-positive results. Records for analysis (n = 13 316) had an ultrasound confirmed gestational age between 15 and 21 completed weeks, singleton pregnancy, and self-reported race. Race was Black for 26.3%. AFP levels for pregnancies in Black individuals were higher than in White individuals: 6% to 11% depending on gestational age. Race-specific gestational age and maternal weight analyses resulted in similar screen-positive rates for self-reported White and Black individuals at 0.74% vs 1.00%, respectively (P = 0.14). However, use of race-agnostic analyses resulted in a screen-positive rate that was 2.4 times higher in Black than White individuals (P < 0.001). These data show that the historical method of accounting for maternal race and weight in prenatal screening for ONTD provides equitable performance. Using a race-agnostic methodology results in an increased screen-positive rate and a disproportionate rate of required follow-up care for individuals who self-identify as Black.

Diagnostic Value of Plasma Methylated Septin 9 in Detection of Hepatocellular Carcinoma in Egyptian Patient with Post Hepatitis C Liver Cirrhosis in Comparison to Serum Level of Alphafeto Protein

Abstract Background Egypt has the highest hepatitis C virus (HCV) prevalence worldwide. Cirrhosis secondary to HCV is associated with the highest annual risk for developing hepatocellular carcinoma. The burden of HCC has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. HCC contributes to 14.8% of all cancer mortality in Egypt. Most HCCs (80%) arise in a cirrhotic liver, a situation where there has been longstanding hepatocyte damage and chronic inflammation leading to fibrosis. Aim of the Work This study aims to evaluate the diagnostic value of plasma mSEPT9 assay in detection of HCC in Egyptian patients with post hepatitis C liver cirrhosis in comparison to serum level of α-fetoprotein (AFP). Patients and Methods This is a prospective case-control study conducted at the Gastroenterology department in Ain Shams University Hospital. The study population consisted of 80 subjects, divided into three groups: 40 patients with hepatocellular carcinoma, 20 patients with liver cirrhosis, and 20 healthy subjects as controls with matched age and gender. Results The study found that hepatocellular carcinoma (HCC) was more frequent in male patients and that the age of HCC patients was statistically significantly higher than patients with cirrhosis and healthy controls. Patients with HCC and cirrhosis had a higher Child Pugh score than healthy controls. Portal hypertension and portal vein thrombosis were more frequent in HCC and cirrhosis patients than in the control group. Liver enzymes were higher in patients with HCC and cirrhosis compared to healthy controls, while hemoglobin and platelet levels were lower in patients with HCC. Hepatitis C antibody and PCR were positive in HCC and cirrhosis patient groups. AFP and Methylated Septin 9 levels were higher in patients with HCC and cirrhosis than in healthy controls, and AFP had better diagnostic accuracy than Methylated Septin 9. Both AFP and Methylated Septin 9 levels were positively correlated with age, Child Score, liver enzymes, and coagulation profile and negatively correlated with platelet count and hemoglobin level. AFP level was positively correlated with the number of focal lesions and liver size. Conclusion This study demonstrated that plasma Methylated Septin 9 can be a promising noninvasive and circulating epigenetic biomarker for HCC diagnosis at the individual level. However, our results showed that AFP was superior than Methylated Septin 9 in the detection of HCC, Methylated Septin 9 has higher Sensitivity. It was suggested that the combination of plasma mSEPT9 and AFP could enhance the sensitivity of Methylated Septin 9 or AFP alone in the diagnosis of HCC. Further comparative studies with larger sample size and longer follow-up are needed to confirm our results and to identify risk factors of adverse events.

Assessment of Galectin 3 as a New Biomarker of Liver Fibrosis in Chronic HCV Egyptian Patients and its Correlation to Transient Elastography, FIB-4 Index, and APRI Score

Abstract Background Invasive liver biopsy is the current method for the assessment of liver fibrosis. In search of noninvasive alternatives, galectin-3-binding protein (G3BP) was introduced as a candidate-marker of hepatitis C-related fibrosis based on serum proteomics. Aim of the Work to evaluate serum Galectin-3 as a marker of liver fibrosis and correlate it to the stage of fibrosis assessed by FibroScan, FIB-4 index and APRI score Patients and Methods This was prospective study, was carried out on 30 patients with liver fibrosis/cirrhosis due to chronic HCV inthe Hepatic Virology Unit and the gastroenterology department of Ain Shams university hospitals and 30 health controls with normal, non fibrotic and non cirrhotic, liver, from January 2022 to June 2022 Results There were high significant difference between both groups as regard Serum level of Galectin-3 and APRI score. Conclusion Serum level of galectin-3 was highly expressed in chronic HCV Egyptain patients and positively correlated to FIB-4 index, APRI score and fibroscan.so the serum level of galectin-3 beside other modalities, lab investigations and clinical examination may guide us about the progression to fibrosis and cirrhosis in those patients. In these patients, if galectin-3 levels were found to be high, serum alpha-feto protein level and ultrasonographic examination could be repeated at more frequent intervals. This may also guide us in terms of the treatment plan. Measurement of galectin-3 in sera of large number of patients and follow up may pave the way to pick up early fibrosis and showed its prognostic effect.

GCT-21. MULTINATIONAL ANALYSIS OF PEDIATRIC RELAPSED/REFRACTORY CENTRAL NERVOUS SYSTEM NON-GERMINOMATOUS GERM CELL TUMORS

Abstract BACKGROUND Patients with relapsed/refractory central nervous system (CNS) non-germinomatous germ cell tumors (NGGCTs) have poor prognosis. We explored prognostic factors to guide the management of these patients. METHODS We performed a multinational retrospective study of relapsed/refractory CNS NGGCTs. Data were summarized using standard descriptive statistics. Overall survival (OS) was evaluated using Kaplan-Meier and Fisher’s exact test to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS We identified 31 patients from eight centers. The median age at initial diagnosis was 11 years (interquartile range (IQR): 9-15.3). Twenty patients (64.5%) suffered a relapse, and 11 patients (35.5%) had refractory disease. The median follow-up time since relapse/progression was 17.5 months (range:1-295). The median time to relapse/progression was 12.1 months (IQR: 5.5-27.5). Ten patients (32.3%) received high-dose chemotherapy (HDCx) with stem cell rescue. Sixteen patients (51.6%) received re-irradiation at relapse/progression. Nine patients (29%) achieved complete remission (CR). Ten patients (32.3%) were alive at the time of the last follow-up. Among the ten survivors, the median serum and cerebrospinal fluid (CSF) alpha-fetoprotein levels were 2.3 ng/dl (range: 0-17) and 2.1 ng/dl (range: 0-55), respectively, the median serum and CSF beta-human chorionic gonadotropin were 23 IU/L (0-168) and 139 IU/L(0-601), none underwent gross total resection, eight received HDCx, and seven received radiotherapy (craniospinal irradiation (n=6), abdominal radiotherapy (n=1)). HDCx (OR=19.8, 95%CI: 2.7-145.7; p=0.01) and achieving CR at the end of relapse treatment (OR=160, 95%CI: 8.9-2880.5; p=&amp;lt;0.001) were associated with a survival benefit. Re-irradiation (OR=3.3 95%CI: 0.53-20.9; p=0.24) was not associated with a survival benefit. CONCLUSIONS A subset of patients with relapsed NGGCTs are salvageable at relapse. HDCx and achieving CR at the end of relapse therapy were associated with a survival benefit. More studies are required to identify these patients who would benefit from salvage therapy.

Liver Resection Criteria for Patients with Hepatocellular Carcinoma and Multiple Tumors Based on Total Tumor Volume.

In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. Patients with TTV ≤ 275 cm3 and AFP ≤ 20ng/mL can have good outcomes even exceed the Milan criteria.

Efficacy and safety in advanced hepatocellular carcinoma between patients with negative and positive APF treated with targeted and immunotherapy.

e16162 Background: Serum alpha-fetoprotein (AFP) is widely accepted as a crucial tool for clinical diagnosis and screening of HCC. However, there are cases where patients test negative for AFP but are confirmed to have Hepatocellular Carcinoma through imaging or pathological examinations. Despite these findings, there is limited research focusing on the medicine selection for AFP-negative patients. Methods: This retrospective cohort study, involving 223 untreated advanced HCC patients, and the first-line regimen consisted of targeted therapy and TKI+ICIs therapy. Patients are categorized into negative and positive AFP groups based on initial serum levels. Main efficacy endpoint was progression free survival (PFS), evaluated in accordance with RECIST v1.1. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: According to the level of serum AFP, they were divided into negative group(100) and positive group(123). The two groups showed no statistically significant differences in age, gender, Child-Pugh score and other baseline clinical characteristics( P&gt; 0.05). At data cut-off at February 2023, median OS was not matured and mPFS in negative group was higher than positive group(8.2 vs 5.3months, P&lt; 0.0001). In the ICIs+TKI therapy cohort, mPFS in the negative AFP group(52) was significantly higher than in the positive AFP group(70) (10 vs. 5.8 months, P = 0.0021). Considering all patients in the negative AFP group as a subgroup, an analysis of survival benefits between those receiving targeted therapy and those receiving TKI+ICIs therapy revealed no significant difference in PFS( P&gt; 0.05). Moreover, AEs were compared between the negative and positive group, with no significant differences observed in Any Grade or Grade 3/4( P&gt; 0.05). Conclusions: Patients with negative AFP exhibited superior survival benefits compared to those with positive AFP in first-line therapy. Regarding PFS, the TKI+ICIS therapy did not demonstrate a better benefit over targeted therapy in the negative AFP subgroup.

Efficacy and safety in advanced hepatocellular carcinoma between patients with negative and positive APF treated with targeted and immunotherapy.

e16162 Background: Serum alpha-fetoprotein (AFP) is widely accepted as a crucial tool for clinical diagnosis and screening of HCC. However, there are cases where patients test negative for AFP but are confirmed to have Hepatocellular Carcinoma through imaging or pathological examinations. Despite these findings, there is limited research focusing on the medicine selection for AFP-negative patients. Methods: This retrospective cohort study, involving 223 untreated advanced HCC patients, and the first-line regimen consisted of targeted therapy and TKI+ICIs therapy. Patients are categorized into negative and positive AFP groups based on initial serum levels. Main efficacy endpoint was progression free survival (PFS), evaluated in accordance with RECIST v1.1. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: According to the level of serum AFP, they were divided into negative group(100) and positive group(123). The two groups showed no statistically significant differences in age, gender, Child-Pugh score and other baseline clinical characteristics( P&gt; 0.05). At data cut-off at February 2023, median OS was not matured and mPFS in negative group was higher than positive group(8.2 vs 5.3months, P&lt; 0.0001). In the ICIs+TKI therapy cohort, mPFS in the negative AFP group(52) was significantly higher than in the positive AFP group(70) (10 vs. 5.8 months, P = 0.0021). Considering all patients in the negative AFP group as a subgroup, an analysis of survival benefits between those receiving targeted therapy and those receiving TKI+ICIs therapy revealed no significant difference in PFS( P&gt; 0.05). Moreover, AEs were compared between the negative and positive group, with no significant differences observed in Any Grade or Grade 3/4( P&gt; 0.05). Conclusions: Patients with negative AFP exhibited superior survival benefits compared to those with positive AFP in first-line therapy. Regarding PFS, the TKI+ICIS therapy did not demonstrate a better benefit over targeted therapy in the negative AFP subgroup.

A rare case report: multiple intrahepatic masses in a pediatric patient with citrin deficiency

Deficiency of citrin, the liver-type aspartate-glutamate carrier, arises from biallelic mutations of the gene SLC25A13. Although citrin deficiency (CD) is associated with higher risk of hepatocellular carcinoma (HCC) in adult patients, this association remains inconclusive in pediatric cases. The patient in this paper had been diagnosed to have CD by SLC25A13 analysis at the age 10 months, and then in response to dietary therapy, her prolonged jaundice and marked hepatosplenomegaly resolved gradually. However, she was referred to the hospital once again due to recurrent abdominal distention for 2 weeks at her age 4 years and 9 months, when prominently enlarged liver and spleen were palpated, along with a strikingly elevated serum alpha-fetoprotein (AFP) level of 27605 ng/mL as well as a large mass in the right liver lobe and a suspected tumor thrombus within the portal vein on enhanced computed tomography. After 4 rounds of adjuvant chemotherapy, right hepatic lobectomy and portal venous embolectomy were performed at her age 5 years and 3 months, and metastatic hepatoblastoma was confirmed by histopathological analysis. Afterwards, the patient underwent 5 additional cycles of chemotherapy and her condition remained stable for 7 months after surgery. Unfortunately, hepatoblastoma recurred in the left lobe at the age 5 years and 10 months, which progressed rapidly into liver failure, and led to death at the age 6 years and 1 month. As far as we know, this is the the first case of hepatoblastoma in a patient with CD, raising the possibility of an association between these two conditions.

Correlation between maternal serum biomarkers and the risk of fetal chromosome copy number variants: a single-center retrospective study.

To explore the association between the concentration of maternal serum biomarkers and the risk of fetal carrying chromosome copy number variants (CNVs). Pregnant women identified as high risk in the second-trimester serological triple screening and underwent traditional amniotic fluid karyotype analysis, along with comparative genomic hybridization array (aCGH)/copy number variation sequencing (CNV-seq), were included in the study. We divided the concentration of serum biomarkers, free beta-human chorionic gonadotropin (fβ-hCG), alpha fetoprotein (AFP) and unconjugated estriol (uE3), into three levels: abnormally low, normal and abnormally high. The prevalence of abnormally low, normal and abnormally high serum fβ-hCG, AFP and uE3 levels in pregnant women with aberrant aCGH/CNV-seq results and normal controls was calculated. Among the 2877 cases with high risk in the second-trimester serological triple screening, there were 98 chromosome abnormalities revealed by karyotype analysis, while 209 abnormalities were detected by aCGH/CNVseq (P＜0.001) . The carrying rate of aberrant CNVs increased significantly when the maternal serum uE3 level was less than 0.4 multiple of median (MoM) of corresponding gestational weeks compared to normal controls, while the carrying rate of aberrant CNVs decreased significantly when the maternal serum fβ-hCG level was greater than 2.5 MoM compared to normal controls. No significant difference was found in the AFP group. Low serum uE3 level (<0.4 MoM) was associated with an increased risk of aberrant CNVs.

Natural History of Indeterminate Liver Nodules in Patients With Advanced Liver Disease: A Multicenter Retrospective Cohort Study.

Indeterminate liver nodules (ILNs) are frequently encountered on diagnostic imaging after positive hepatocellular carcinoma (HCC) surveillance results, but their natural history remains unclear. We conducted a multicenter retrospective cohort study among patients with ≥1 newly detected LI-RADS 3 (LR-3) lesion ≥1 cm or LI-RADS 4 (LR-4) lesion of any size (per LI-RADS v2018) between January 2018 and December 2019. Patients were followed with repeat imaging at each site per institutional standard of care. Multivariable Fine-Gray models were used to evaluate associations between potential risk factors and patient-level time-to-HCC diagnosis, with death and liver transplantation as competing risks. Of 307 patients with ILNs, 208 had LR-3 lesions, 83 had LR-4 lesions, and 16 had both LR-3 and LR-4 lesions. HCC incidence rates for patients with LR-3 and LR-4 lesions were 110 (95% CI 70-150) and 420 (95% CI 310-560) per 1,000 person-year, respectively. In multivariable analysis, incident HCC among patients with LR-3 lesions was associated with older age, thrombocytopenia (platelet count ≤150 ×10 9 /L), and elevated serum alpha-fetoprotein levels. Among those with LR-4 lesions, incident HCC was associated with a maximum lesion diameter >1 cm. Although most patients had follow-up computed tomography or magnetic resonance imaging, 13.7% had no follow-up imaging and another 14.3% had follow-up ultrasound only. ILNs have a high but variable risk of HCC, with 4-fold higher risk in patients with LR-4 lesions than those with LR-3 lesions, highlighting a need for accurate risk stratification tools and close follow-up in this population.

Assessing clinical pathological characteristics and gene expression patterns associated with hepatoid adenocarcinoma of the stomach.

The objective of this study is to assess the clinical pathological attributes of Hepatoid Adenocarcinoma of the Stomach (HAS) and to delineate the differential diagnostic considerations about it. The investigation involved analyzing 31 HAS cases using histomorphological assessment, immunohistochemical profiling, and relevant gene detection methodologies. Among the 31 HAS cases, 9 (29.0%) were of trabecular hepatoid adenocarcinoma of the stomach, 7 (22.6%) were of glandular hepatoid adenocarcinoma of the stomach, 4 (12.9%) were of nesting hepatoid adenocarcinoma of the stomach, 3 (9.7%) were of clear cell hepatoid adenocarcinoma of the stomach, and 8 (25.8%) were of diverse hepatoid adenocarcinoma of the stomach. Of these 31 cases, 24 were male, accounting for 77.4% of the cases. Serum alpha-fetoprotein (AFP) levels were notably elevated, with radioimmunoassay results reaching 1240ng/ml; 28 out of 31 cases had AFP levels below 25µg/l, accounting for 90.3%. Related genes: HER2 protein indicated positive expression on the cell membrane in 35.5% (11/31) of the cases; HER2 gene amplification detected by the FISH technique was 12.9% (4/31). Tumoral stromal lymphocytes exhibited a PD-1 positive expression rate of 58.1% (18/31). In gastric cancer tissues, the PD-L1 positive rate was 45.1% (14/31). HAS represents a distinctive subtype of gastric cancer with a propensity for mimicking other forms of tumors, underscoring the significance of discerning its unique histopathological attributes for accurate differential diagnosis and tailored therapeutic interventions.

Lysyl oxidase-like 2 as a predictor of hepatocellular carcinoma in patients with hepatitis C virus after sustained virological response

Lysyl oxidase-like 2 (LOXL2) mediates the crosslinking of extracellular collagen, reflecting qualitative changes in liver fibrosis. This study aimed to validate the utility of serum LOXL2 levels as a predictive biomarker for the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection who achieved a sustained virological response (SVR). This retrospective study included 137 patients with chronic HCV infection without history of HCC development and who achieved SVR via direct-acting antiviral therapy. Median LOXL2 levels decreased significantly after SVR achievement (pre-Tx, 2.33 ng/mL; post-Tx, 1.31 ng/mL, p < 0.001). Post-Tx LOXL2 levels, fibrosis-4 index, platelet counts, Wisteria floribunda agglutinin-positive human Mac-2 binding protein levels, and alpha-fetoprotein (AFP) levels were identified as independent predictive factors for post-SVR HCC development in the univariate analysis. The incidence of post-SVR HCC development was significantly higher in patients with post-Tx LOXL2 levels ≥ 2.08 ng/mL and AFP levels ≥ 5.0 ng/mL than in patients with elevated levels of either marker or with lower marker levels. Serum LOXL2 levels can serve as a predictive biomarker for HCC development after achieving SVR. The combination of serum LOXL2 and AFP levels provides robust risk stratification for HCC development after SVR, suggesting an enhanced surveillance strategy.

Management of Neonatal Hepatic Hemangiomas: A Single-Center Experience Focused on Challenging Cases.

Background: Management of hepatic hemangioma (HH) in infancy ranges from close monitoring to surgical resection. We analyzed the clinical characteristics and outcomes of HH according to its treatment options, with particular focus on challenging cases. Methods: Data of patients diagnosed with HHs in their first year of life and followed up for at least 1 year were retrospectively reviewed and divided into treatment and observation groups. Serial imaging results, serum alpha-fetoprotein (AFP) levels, medications, and clinical outcomes were compared. The detailed clinical progress in the treatment group was reviewed separately. Results: A total of 87 patients (75 in the observation group and 12 in the treatment group) were included. The median HH size at the initial diagnosis and the maximum size were significantly larger in the treatment group than the observation group (2.2 [0.5-10.3] cm vs. 1.0 [0.4-4.0] cm and 2.1 [0.7-13.2] vs. 1.1 [0.4-4.0], respectively; all p < 0.05]. The median initial and last serum AFP levels were significantly higher in the treatment group than in the observation group (76,818.7 vs. 627.2 and 98.4 vs. 8.7, respectively; all p < 0.05). Serum AFP levels in both groups rapidly declined during the first 3 months of life and were almost undetectable after 6 months. Among the challenging cases, a large (14 × 10 × 6.5 cm sized) focal HH was successfully treated using stepwise medical-to-surgical treatment. Conclusions: Patients with large HH and mild symptoms can be treated using stepwise pharmacotherapy. More aggressive surgical treatment of tumors unresponsive to initial pharmacotherapy may help shorten the treatment period and improve outcomes.

Long-term results of liver thermal ablation in patients with hepatocellular carcinoma and colorectal cancer liver metastasis regarding spatial features and tumor-specific variables

Colorectal cancer liver metastasis (CRLM) and hepatocellular carcinoma (HCC) are widely treated using microwave and radiofrequency ablation. Local tumor progression (LTP) may develop depending on the shortest vascular distance and large lesion diameter. This study aims to explore the effect of these spatial features and to investigate the correlation between tumor-specific variables and LTP. This is a retrospective study covering the period between January 2007 and January 2019. One hundred twenty-five patients (CRLM: HCC: 64:61) with 262 lesions (CRLM: HCC: 142:120) were enrolled. The correlation between LTP and the variables was analyzed using the chi-square test, Fischer's exact test, or the Fisher-Freeman-Halton test where applicable. The local progression-free survival (Loc-PFS) was analyzed using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were performed to identify prognostic factors. Significant correlations were observed for LTP in both CRLM and HCC at a lesion diameter of 30-50 mm (P = 0.019 and P < 0.001, respectively) and SVD of ≤3 mm (P < 0.001 for both). No correlation was found between the ablation type and LTP (CRLM: P = 0.141; HCC: P = 0.771). There was no relationship between residue and the ablation type, but a strong correlation with tumor size was observed (P = 0.127 and P < 0.001, respectively). In CRLM, LTP was associated with mutant K-ras and concomitant lung metastasis (P < 0.001 and P = 0.003, respectively). In HCC, a similar correlation was found for Child-Pugh B, serum alpha-fetoprotein (AFP) level of >10 ng/mL, predisposing factors, and moderate histopathological differentiation (P < 0.001, P = 0.008, P = 0.027, and P < 0.001, respectively). In CRLM, SVD of ≤3 mm proved to be the variable with the greatest negative effect on Loc-PFS (P = 0.007), followed by concomitant lung metastasis (P = 0.027). In HCC, a serum AFP level of >10 ng/mL proved to be the variable with the greatest negative effect on Loc-PFS (P = 0.045). In addition to the lesions' spatial features, tumor-specific variables may also have an impact on LTP.

Radiomic Analysis of Contrast-Enhanced CT Predicts Glypican 3-Positive Hepatocellular Carcinoma.

The Glypican 3 (GPC3)-positive expression in Hepatocellular Carcinoma (HCC) is associated with a worse prognosis. Moreover, GPC3 has emerged as an immunotherapeutic target in advanced unresectable HCC systemic therapy. It is significant to diagnose GPC3-positive HCCs before therapy. Regarding imaging diagnosis of HCC, dynamic contrast-enhanced CT is more common than MRI in many regions. The aim of this study was to construct and validate a radiomics model based on contrast-enhanced CT to predict the GPC3 expression in hepatocellular carcinoma. This retrospective study included 141 (training cohort: n = 100; validation cohort: n = 41) pathologically confirmed HCC patients. Radiomics features were extracted from the Artery Phase (AP) images of contrast-enhanced CT. Logistic regression with the Least Absolute Shrinkage and Selection Operator (LASSO) regularization was used to select features to construct radiomics score (Rad-score). A final combined model, including the Rad-score of the selected features and clinical risk factors, was established. Receiver Operating Characteristic (ROC) curve analysis, Delong test, and Decision Curve Analysis (DCA) were used to assess the predictive performance of the clinical and radiomics models. 5 features were selected to construct the AP radiomics model of contrast-enhanced CT. The radiomics model of AP from contrast-enhanced CT was superior to the clinical model of AFP in training cohorts (P < 0.001), but not superior to the clinical model in validation cohorts (P = 0.151). The combined model (AUC = 0.867 vs. 0.895), including AP Rad-score and serum Alpha-Fetoprotein (AFP) levels, improved the predictive performance more than the AFP model (AUC = 0.651 vs. 0.718) in the training and validation cohorts. The combined model, with a higher decision curve indicating more net benefit, exhibited a better predictive performance than the AP radiomics model. DCA revealed that at a range threshold probability approximately above 60%, the combined model added more net benefit compared to the AP radiomics model of contrastenhanced CT. A combined model including AP Rad-score and serum AFP levels based on contrast-enhanced CT could preoperatively predict GPC3-positive expression in HCC.

EVALUATION OF SOME LIVER ENZYMES AND ALPHA-FETOPROTEIN IN WORKERS OCCUPATIONALLY EXPOSED TO E-WASTE IN NNEWI, ANAMBRA STATE NIGERIA

BACKGROUND: The advent of electricity has spurred significant technological advancements, leading to the production of numerous electrical and electronic devices. This progress, however, has resulted in a surge of largely irreparable electronic waste (e-waste) being constantly shipped to Nnewi, a metropolitan city with large-scale commercial and industrialactivities. E-waste contains thousands of chemicals, many of which are toxic to humans upon exposure.AIM OF THE STUDY: To evaluate the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and serum levels of alpha-fetoprotein (AFP) in workers occupationally exposed to e-waste.METHODOLOGY: The study comprised 40 e-waste workers (exposed group) and 40 healthy individuals (control group). Approximately 5 ml of venous blood was collected from each participant. The liver enzymes – ALT, AST, and ALP were evaluated colorimetrically, while AFP was assayed by Enzyme-linked Immunosorbent Assay (ELISA) method. Data obtained was statistically analyzed using SPSS windows version 25 with significance set as p&lt;0.05 at 95% confidence interval; Independent T-test, descriptive statistics and Pearson correlation were employed where relevant. Results were presented as means ± standard deviation in contingency tables.RESULT: There was no significant difference (p&gt;0.05) in the activities of ALT, AST, ALP and serum level of AFP between the exposed subjects and the control. However, significantly negative correlation was found between age and ALT (r = -0.294; p= 0.024), while DOE also had negative correlation with ALP (r= -0.294; P= 0.024) - all among e-waste exposed group.CONCLUSION: This study has shown that exposure to e-waste may not have a harmful effect on the liver function, since there was no significant difference in the liver function enzymes, and serum levels of AFP. However, age and longer duration of exposure to e-waste could be detrimental to health.

Pre-operative enhanced magnetic resonance imaging combined with clinical features predict early recurrence of hepatocellular carcinoma after radical resection.

Indentifying predictive factors for postoperative recurrence of hepatocellular carcinoma (HCC) has great significance for patient prognosis. To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) combined with clinical features in predicting early recurrence of HCC after resection. A total of 161 patients with pathologically confirmed HCC were enrolled. The patients were divided into early recurrence and non-early recurrence group based on the follow-up results. The clinical, laboratory, pathological results and Gd-EOB-DTPA enhanced MRI imaging features were analyzed. Of 161 patients, 73 had early recurrence and 88 were had non-early recurrence. Univariate analysis showed that patient age, gender, serum alpha-fetoprotein level, the Barcelona Clinic Liver Cancer stage, China liver cancer (CNLC) stage, microvascular invasion (MVI), pathological satellite focus, tumor size, tumor number, tumor boundary, tumor capsule, intratumoral necrosis, portal vein tumor thrombus, large vessel invasion, nonperipheral washout, peritumoral enhancement, hepatobiliary phase (HBP)/tumor signal intensity (SI)/peritumoral SI, HBP peritumoral low signal and peritumoral delay enhancement were significantly associated with early recurrence of HCC after operation. Multivariate logistic regression analysis showed that patient age, MVI, CNLC stage, tumor boundary and large vessel invasion were independent predictive factors. External data validation indicated that the area under the curve of the combined predictors was 0.861, suggesting that multivariate logistic regression was a reasonable predictive model for early recurrence of HCC. Gd-EOB-DTPA enhanced MRI combined with clinical features would help predicting the early recurrence of HCC after operation.

The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignant cancer worldwide, characterized by high morbidity and mortality rates. Alpha-fetoprotein (AFP) is a glycoprotein synthesized by the liver and yolk sac during fetal development. However, the serum levels of AFP exhibit a significant correlation with the onset and progression of HCC in adults. Extensive research has demonstrated that the tumor microenvironment (TME) plays a crucial role in the malignant transformation of HCC, and AFP is a key factor in the TME, promoting HCC development. The objective of this review was to analyze the existing knowledge regarding the role of AFP in the TME. Specifically, this review focused on the effect of AFP on various cells in the TME, tumor immune evasion, and clinical application of AFP in the diagnosis and treatment of HCC. These findings offer valuable insights into the clinical treatment of HCC.

Colorectal adenocarcinoma with enteroblastic differentiation: a clinicopathological analysis of eight cases

Objective: To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED). Methods: Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed. Results: Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 μg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases. Conclusions: CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Salvage Therapy of Relapsed/Refractory Germ Cell Tumors: A Single-Center Experience

Introduction: The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy. Methods: We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1–3 plus etoposide 750 mg/m2 on days 1–3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment-related complications and survival outcomes were recorded. Results: The median age of the patients was 31 (range 18–62). The median follow-up was 31.1 months (95% CI, 28.9–33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1–43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival (OS) rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline. Conclusion: One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%.