Serum Α-fetoprotein Research Articles

Hepatocellular Carcinoma from a Hepatologist's Perspective.

Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, represents a growing health challenge worldwide. The incidence of HCC is rising, which, in turn, has led to a corresponding increase in the associated number of deaths. HCC will become the third leading cause of cancer-related deaths in the United States by 2030. HCC usually develops in the setting of chronic liver disease. Individuals at increased risk of HCC are recommended to undergo surveillance with ultrasound every 6 months along with serum α-fetoprotein testing. Computed tomography (CT) and magnetic resonance imaging (MRI) are considered alternatives based on specific patient factors. Lesions suspicious for HCC are recommended to undergo a diagnostic testing, which includes contrast-enhanced multiphase CT or MRI and liver biopsy when findings are indeterminate. The Barcelona Clinic Liver Cancer prognosis and treatment strategy is the most used assessment for patients with HCC ( Fig. 2 ). Curative therapies include resection, liver transplantation, and ablation. Locoregional therapies, such as transarterial chemoembolization and radioembolization, can be used for patients with intermediate-stage HCC. For patients with advanced-stage HCC, systemic therapy is often used. This review aims to provide an overview of HCC from a hepatologist's perspective, including epidemiology, screening, surveillance, diagnosis, and management.

Development and Assessment of Nomogram Based on AFP Response for Patients with Unresectable Hepatocellular Carcinoma Treated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have been increasingly used to treat hepatocellular carcinoma (HCC). Prognostic biomarkers are an unmet need. We aimed to develop a prognostic nomogram for patients with unresectable HCC receiving ICIs therapy. A total of 120 patients with unresectable HCC receiving ICIs treatment were enrolled in this study. Patients were randomly divided into a training set (n = 84) and a validation set (n = 36) in a 7:3 ratio. Clinical characteristics were retrospectively analyzed. Serum α-fetoprotein protein (AFP) response was defined as a decline of ≥20% in AFP levels within the initial eight weeks of treatment. Univariable and multivariable Cox analyses were used to select relevant variables and construct the nomogram. The areas under the receiver operating characteristic curves (AUCs) were used to determine the performance of the model. Kaplan-Meier analysis with the log-rank test was used to compare different risk groups. The median progression-free survival (PFS) was 7.7 months. In the multivariate Cox analysis, the presence of extrahepatic metastasis (hazard ratio [HR] = 2.08, 95% confidence interval [CI]: 1.02-4.27, p < 0.05), white blood cell count (HR = 3.48, 95% CI: 1.02-11.88, p < 0.05) and AFP response (HR = 0.41, 95% CI: 0.18-0.95, p < 0.05) independently predicted PFS. A nomogram for PFS was established with AUCs of 0.79 and 0.70 in the training and validation sets, respectively. The median PFS of the high- and low-risk subgroups was 3.5 and 11.7 months, respectively (p < 0.05). The nomogram could predict PFS in patients with unresectable HCC receiving ICIs treatment and further help decision making in daily clinical practice.

Added value of CE-CT radiomics to predict high Ki-67 expression in hepatocellular carcinoma

BackgroundThis study aimed to develop a computed tomography (CT) model to predict Ki-67 expression in hepatocellular carcinoma (HCC) and to examine the added value of radiomics to clinico-radiological features.MethodsA total of 208 patients (training set, n = 120; internal test set, n = 51; external validation set, n = 37) with pathologically confirmed HCC who underwent contrast-enhanced CT (CE-CT) within 1 month before surgery were retrospectively included from January 2014 to September 2021. Radiomics features were extracted and selected from three phases of CE-CT images, least absolute shrinkage and selection operator regression (LASSO) was used to select features, and the rad-score was calculated. CE-CT imaging and clinical features were selected using univariate and multivariate analyses, respectively. Three prediction models, including clinic-radiologic (CR) model, rad-score (R) model, and clinic-radiologic-radiomic (CRR) model, were developed and validated using logistic regression analysis. The performance of different models for predicting Ki-67 expression was evaluated using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis (DCA).ResultsHCCs with high Ki-67 expression were more likely to have high serum α-fetoprotein levels (P = 0.041, odds ratio [OR] 2.54, 95% confidence interval [CI]: 1.04–6.21), non-rim arterial phase hyperenhancement (P = 0.001, OR 15.13, 95% CI 2.87–79.76), portal vein tumor thrombus (P = 0.035, OR 3.19, 95% CI: 1.08–9.37), and two-trait predictor of venous invasion (P = 0.026, OR 14.04, 95% CI: 1.39–144.32). The CR model achieved relatively good and stable performance compared with the R model (AUC, 0.805 [95% CI: 0.683–0.926] vs. 0.678 [95% CI: 0.536–0.839], P = 0.211; and 0.805 [95% CI: 0.657–0.953] vs. 0.667 [95% CI: 0.495–0.839], P = 0.135) in the internal and external validation sets. After combining the CR model with the R model, the AUC of the CRR model increased to 0.903 (95% CI: 0.849–0.956) in the training set, which was significantly higher than that of the CR model (P = 0.0148). However, no significant differences were found between the CRR and CR models in the internal and external validation sets (P = 0.264 and P = 0.084, respectively).ConclusionsPreoperative models based on clinical and CE-CT imaging features can be used to predict HCC with high Ki-67 expression accurately. However, radiomics cannot provide added value.

Preoperative serum CA125 level is a good prognostic predictor in patients with intrahepatic cholangiocarcinoma after hepatectomy: A single-center retrospective study.

Serum carbohydrate antigen 125 (CA125) is associated with the prognosis of various malignancies, including ovarian and pancreatic cancer. The relationship between preoperative serum CA125 level and the survival of patients with intrahepatic cholangiocarcinoma (ICC) has not been fully studied. The aim of this study was to explore the prognostic value of CA125 in ICC after hepatectomy. We retrospectively reviewed the clinicopathological data of 178 ICC patients who underwent hepatic resection. Receiver operating characteristic analyses were performed to estimate the relationships of serum CA125, α-fetoprotein, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 with the prognosis of ICC. The predictive value of CA125 for the prognosis of ICC patients was demonstrated by univariate analyses and Cox proportional hazards models. CA125 was correlated with tumor size, differentiation, capsulation, tumor node-metastasis stage, recurrence, and CEA. Univariate analysis indicated that CA125, sex, tumor number, tumor size, differentiation, surgical resection margin, tumor node metastasis stage, and CEA were risk factors for both the overall survival and the disease-free survival of ICC patients. Cox proportional hazards models showed that preoperative elevated CA125, a tumor size > 5 cm, and an R1 surgical resection margin were independent prognostic predictors of overall survival and disease-free survival. CA125 also had strong predictive value for the prognosis of different ICC subgroups, including patients without lymph node metastasis and with elevated carbohydrate antigen 19-9 levels. Preoperative elevated serum CA125 level is a noninvasive, simple, and reliable indicator of the prognosis of ICC patients after hepatectomy.

Treatment Outcomes for Hepatoblastoma: 15-Years-Experience of a Single Institution – Sheikh Khalifa Medical City, Abu Dhabi, UAE

Background: Hepatoblastoma is the most common malignant liver tumor in children. Treatment protocols varies. In our center, we have adopted the Children’s Oncology Group (COG) AHEP0731 protocol, in addition to some experimental regimens for relapsed solid tumors. Methods: We aimed to investigate the outcome of the current hepatoblastoma treatment protocol at our center. 15 patients were included between January 2008 and June 2023. A retrospective review was carried to review the clinical presentation, serum α-fetoprotein (AFP) level at diagnosis, histological subtype, treatment, and outcomes. Results: 12 patients (80%) were symptomatic at time of diagnosis, with abdominal mass being the most common presenting complaint. Nine patients (60%) presented in stage 3 PRETEXT staging system. Epithelial histopathological subtype was predominant subtype. Thirteen patients have received preoperative chemotherapy, followed by surgical resection; only one patient underwent upfront surgical resection followed by chemotherapy. Preoperative chemotherapy consists of 2 to 4 cycles of Cisplatin, Fluorouracil, Vincristine and Doxorubicin (C5VD), followed by surgical resection. Four of them underwent neoadjuvent experimental chemotherapy utilizing agents such as Pazopanib, Pembrolizumab and Sorafenib. During followup, six patients died of progressive disease. The median survival time was 42 months (95% confidence interval: 18–42%). Five-year overall survival was 44.09% (95% confidence interval: 18–42%). Conclusions: The combination of surgery and chemotherapy for hepatoblastoma is an effective approach. Utilization of new-targeted therapies and relapsed solid tumors regimens may prolong life in patients who did not respond to standard therapy. Further studies are required to validate its usage on patients with advanced hepatoblastoma.

FIB‑4 index and serum α‑fetoprotein are useful predictors of hepatocellular carcinoma occurrence in hepatitis B patients with nucleos(t)ide analogs therapy.

Current antiviral therapies cannot achieve eradication of hepatitis B virus (HBV) and can reduce but not eliminate the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV infection. The present study aimed to identify the risk factors for HCC development by analyzing nucleoside analogue (NA)-treated patients as a retrospective cohort using fibrosis-4 index (FIB-4 index) as a non-invasive fibrosis marker. A total of 260 patients with HBV receiving NAs without a history of HCC between January 2001 and January 2021 were included in the present study. The incidence of HCC in patients with HBV during NA therapy and the factors contributing to HCC occurrence were identified using clinical characteristics and blood test results. Among the 260 patients, 40 patients (15.4%) developed HCC. Univariate and multivariate analysis showed that age [hazard ratio (HR), 1.03; P=0.045], male sex (HR, 3.14; P<0.01) and FIB-4 index at 6 months after NA treatment <1.95 (HR, 4.35; P<0.01) correlated with the incidence of HCC. The cumulative incidence of HCC in patients with FIB-4 index at 6 months after NA treatment >1.95 was significantly higher compared with that in patients with FIB-4 index ≤1.95 (P<0.01). Multivariate analysis in patients in which serum α-fetoprotein (AFP) level at 6 months after NA treatment was measured showed that FIB-4 index >1.95 (HR, 8.27; P=0.014) and serum AFP level >4 ng/ml (HR, 4.26; P=0.033) contributed to HCC occurrence. FIB-4 index at 6 months after NA treatment and serum AFP levels at 6 months after NA treatment were predictors for the development of HCC in patients with HBV during NA treatment. Further study of hepatocarcinogenesis during NA with a longer follow-up period and larger numbers of participants is required.

A novel approach for the treatment of advanced hepatocellular carcinoma (HCC).

35 Background: No established treatments for patients with advanced HCC and moderate hepatic dysfunction (Child-Pugh B; CPB) are available. Namodenoson is an A3 adenosine-receptor agonist currently under clinical development as a treatment for advanced HCC with CPB. Methods: Wereport the results of a prospective placebo-controlled randomized (2:1) phase 2 trial investigating namodenoson (25 mg BID) as a second-line therapy in HCC with CPB and focus on a case of a long-term complete response (CR). Results: The study included 78 patients (50 namodenoson-treated, 28 placebo-treated). Namodenoson was well-tolerated and no treatment-related deaths were reported. Median overall survival (OS, the primary endpoint) was not statistically significantly different between the namodenoson and placebo arms (4.1 and 4.3 months, respectively, hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.49‒1.38; p=.46). The difference in 12-month OS was statistically significant (44% vs 18%, respectively, p=.028). Pre-planned analysis of patients with CPB7 (34 namodenoson-treated, 22 placebo-treated) showed nonsignificant improvements in OS and progression-free survival (PFS). OS: 6.9 vs 4.3 months; HR, 0.81; 95% CI: 0.45‒1.43; p=.46. PFS: 3.5 vs 1.9 months; HR, 0.89; 95% CI: 0.51‒1.55; p=.67. Of the patients with ≥1 assessment post-baseline, partial response (PR) was reported in 3 of 34 (8.8%) namodenoson-treated patients and none of the 21 placebo-treated patients. One of 3 the patients who achieved a PR (a 61-year old woman with CPB7, Barcelona Clinic Liver Cancer stage C, and Eastern Cooperative Oncology Group performance status 2) continued treatment with namodenoson under an open-label extension program (treatment is ongoing for &gt;6 years). The patient achieved a CR (determined via CT scans) 4 years after treatment initiation. Furthermore, the patient's baseline ALT and AST levels which were elevated at baseline (68 U/L and 44 U/L, respectively) normalized after 4 weeks, and her serum α-fetoprotein level, which was 47 ng/ml at baseline, declined to normal levels after 20 weeks of treatment and reached 1.3 ng/mL at time of CR. The patient experienced no treatment-related adverse events. At present (6 years from treatment initiation), the response is ongoing as shown by liver function evaluation and imaging studies. Conclusions: Treatment with namodenoson can result in a complete and long-term response. The findings support the clinical development of namodenoson as a treatment for HCC with CPB7. Clinical trial information: NCT02128958 .

Increased expression of autophagy-related gene 5 indicates poor prognosis in patients with Hepatocellular carcinoma.

As an critical component of the autophagic machinery, autophagy-related gene 5 (ATG5) is essential for autophagosome formation. Autophagy participates in various malignant tumor transformation and progression, but the role of ATG5 involved in hepatocellular carcinoma (HCC) remains to be illustrated. The expression of ATG5 was evaluated in 89 pairs of liver tumor and adjacent normal tissues. The correlation between ATG5 expression and clinicopathological characteristics or prognosis were evaluated. Moreover, clinical special analysis was conducted in the young patients group and the old patients group respectively, and nomograms estimating overall survival and disease-free survival were investigated. Our study demonstrated that the ATG5 level was increased in tumor specimens than adjacent normal tissues. Upregulated ATG5 level had positive association with serum α-fetoprotein (AFP). Moreover, cases with higher ATG5 level had poorer disease-free survival (DFS) and overall survival (OS) than those with lower ATG5 level. Multivariate analysis showed that overexpression of ATG5 predicts poor OS and DFS. Further analysis indicated that cases with higher ATG5 level had poorer OS and DFS in the young patients and solitary tumor number subgroup. The nomogram models suggested that it had a coherence between nomogram prediction and actual situation. Together these findings revealed that ATG5 promotes progression of HCC, making it a potentially biomarker in diagnosis and therapeutic target of hepatocellular carcinoma. This article is protected by copyright. All rights reserved.

An observational study of donafenib as adjuvant therapy to prevent hepatocellular carcinoma recurrence after curative surgery.

e16227 Background: The five-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection is as high as 70% and remains a major clinical challenge. Many investigators have suggested adjuvant therapy to prevent HCC recurrence, and several promising outcomes have been reported. Donafenib has been approved as a standard treatment for patients with unresectable HCC in China. Here, we describe our preliminary results regarding the efficacy and safety of donafenib as an adjuvant therapy for patients with HCC after hepatectomy. Methods: This was an observational study of patients with HCC following hepatectomy treated with donafenib in routine practice at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. The enrolled patients were 75 years or younger, had been diagnosed with HCC, showed no evidence of recurrence at radiological follow-up within one month after hepatectomy, and had at least one high recurrence risk factor, such as tumor diameter ≥5 cm, tumor number ≥2, microvascular invasion, or serum a-fetoprotein level before surgery ≥400 ng/mL. All of the patients had adequate hematologic, hepatic, and renal functions. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints included 6- and 12-month RFS rates, overall survival, and adverse events. Results: Seventeen patients were enrolled in this study. The median age was 56 years (range, 40–72), 88.2% were males, 82.4% with HBV, 17.6% had preoperative serum a-fetoprotein levels ≥400 ng/mL, 35.3% had tumor diameters ≥5 cm, 29.4% had tumor numbers ≥2, and 29.4% had microvascular invasion. The median follow-up time for the entire patient cohort was 16 months (95% confidence interval [CI], 11.9–20.1), and 5 of 17 patients relapsed, with a recurrence rate of 29.4%. The median RFS was not reached; the 6- and 12-month RFS rates were 88.2% and 70.1%, respectively. Treatment-related adverse events (TRAEs) occurred in 82.4% of the patients, most of which were grades 1–2. Grade 3 TRAEs, including hand-foot skin reaction and rash, were observed in three (16.4%) patients. No grade 4 or 5 TRAEs occurred. Conclusions: The findings of the present study suggest that donafenib as adjuvant therapy may be a potentially effective way to prevent HCC recurrence after curative surgery. Our findings should be validated in a larger, prospectively evaluated sample. Clinical trial information: ChiCTR2200064030 .

Immuno-Mass Spectrometry Workflow for Quantification of Serum α-Fetoprotein Using Antibody-Immobilized Magnetic Beads and Modified Eluents.

Immuno-mass spectrometry (MS) is a powerful method for the quantitative analysis of low-abundance proteins in biological specimens. In these procedures, collecting specifically and efficiently the target protein antigens from the antigen-antibody complex generated on the surface of nanocarrier beads is crucial and can be performed by hydrolyzing the proteins directly on the beads or after elution. Herein, we optimized the conditions of the immunoaffinity purification via elution using serum α-fetoprotein (AFP) as a model and its specific antibody immobilized covalently on magnetic beads. Antibody-coated beads were incubated with human serum spiked with standard AFP for antigen-antibody reaction. AFP was then eluted from the beads using various eluents, including organic solvents, to optimize the elution conditions. After proteolytically hydrolyzing the eluted protein, stable isotope-labeled standard peptides were added to the hydrolysate to quantify the eluted AFP via liquid chromatography-tandem MS. Using an optimized workflow for quantitative analysis afforded a correlation between the amount of spiked AFP and heavy to light ratios calculated based on peptide ion peak areas, from which an endogenous AFP concentration of 2.3±0.6 ng/mL was determined in normal serum; this is consistent with previous reports using radioimmunoassay methods. The present immuno-MS workflow could apply to the detection and quantitation of other low-abundance biofluid biomarkers.

Combined maternal risk factors and the Quadruple test to predict late-onset preeclampsia in pregnant Thai women

BackgroundThis study aimed to evaluate the predictive power of a model combining maternal risk factors and the Quadruple screen test for late-onset preeclampsia (PE).MethodsAll pregnant women that received the Quadruple test for Down syndrome at 15+ 0-20+ 6 weeks’ gestation were recruited. Maternal serum α-fetoprotein, β-human chorionic gonadotropin, unconjugated estriol, and inhibin A were measured as multiples of the median. A logistic regression model was used to identify predictors associated with late-onset PE with severe features. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the model’s predictive ability.ResultsFifty-five of the 2,000 pregnant women had PE, and 31 of 55 women had late-onset PE. Multivariate analysis identified maternal age ≥ 35 years, inhibin A, history of previous PE, history of infertile, cardiac disease, chronic hypertension, and thyroid disease as significant risk factors. The area under the curve of the receiver operating characteristic curve was 0.78. The likelihood ratio to predict late-onset PE was 49.4 (total score > 60).ConclusionsOur model combining serum inhibin A with maternal risk factors was useful in predicting late-onset PE. Close monitoring of these patients is recommended.

Comparison of Four Albumin-Based Liver Reserve Models (ALBI/EZ-ALBI/PALBI/PAL) against MELD for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

(1) Background: The severity of liver functional reserve plays an important role in the management of hepatocellular carcinoma (HCC). Noninvasive models such as the model for end-stage liver disease (MELD), albumin-bilirubin (ALBI) grade and easy (EZ)-ALBI grade, platelet-albumin-bilirubin (PALBI) and platelet-albumin (PAL) are used to evaluate liver dysfunction. We aimed to compare the prognostic performance of these four albumin-based models against MELD in HCC patients undergoing transarterial chemoembolization (TACE). (2) Methods: A total of 1038 treatment naïve HCC patients who received TACE as the primary treatment were enrolled. A multivariate Cox model was used to determine independent survival predictors. (3) Results: Multivariate analysis revealed that higher serum creatinine and α-fetoprotein level, vascular invasion, large tumor size, ALBI grades 2-3, EZ-ALBI grades 2-3, PALBI grades 2-3, PAL grades 2-3, but not the MELD score, were independent predictors associated with decreased survival in different Cox models. Among these models, the PALBI grade had the highest homogeneity and lowest corrected Akaike information criteria value, followed by EZ-ALBI, PAL, ALBI and, lastly, MELD. (4) Conclusions: All four albumin-based liver reserve models are better prognostic tools than MELD score in HCC patients undergoing TACE. Of these, the PALBI score is the best model to evaluate the liver reserve and should be considered a surrogate marker in these patients.

WRH-2412 alleviates the progression of hepatocellular carcinoma through regulation of TGF-β/β-catenin/α-SMA pathway

Hepatocellular carcinoma is considered one of the most lethal cancers, which is characterised by increasing prevalence associated with high level of invasion and metastasis. The novel synthetic pyrazolo[3,4-b]pyridine compound, WRH-2412, was reported to exhibit in vitro antitumor activity. This study was conducted to evaluate the antitumor activity of WRH-2412 in HCC induced in rats through affecting the TGF-β/β-catenin/α-SMA pathway. Antitumor activity of WRH-2412 was evaluated by calculating the rat’s survival rate and by assessment of serum α-fetoprotein. Protein expression of TGF-β, β-catenin, E-cadherin, fascin and gene expression of SMAD4 and α-SMA were determined in hepatic tissue of rats. WRH-2412 produced antitumor activity by significantly increasing the rats’ survival rate and decreasing serum α-fetoprotein. WRH-2412 significantly reduced an HCC-induced increase in hepatic TGF-β, β-catenin, SMAD4, fascin and α-SMA expression. In addition, WRH-2412 significantly increased hepatic E-cadherin expression.

Diffusion-Weighted Imaging as a Quantitative Imaging Biomarker for Predicting Proliferation Rate in Hepatocellular Carcinoma: Developing a Radiomics Nomogram.

This study aimed to explore the predictive performance of diffusion-weighted imaging with apparent diffusion coefficient map in predicting the proliferation rate of hepatocellular carcinoma and to develop a radiomics-based nomogram. This was a single-center retrospective study. A total of 110 patients were enrolled. The sample included 38 patients with low Ki67 expression (Ki67 ≤10%) and 72 with high Ki67 expression (Ki67 >10%) as demonstrated by surgical pathology. Patients were randomly divided into either a training (n = 77) or validation (n = 33) cohort. Diffusion-weighted imaging with apparent diffusion coefficient maps was used to extract radiomic features and the signal intensity values of tumor (SI tumor ), normal liver (SI liver ), and background noise (SI background ) from all samples. Subsequently, the clinical model, radiomic model, and fusion model (with clinical data and radiomic signature) were developed and validated. The area under the curve (AUC) of the clinical model for predicting the Ki67 expression including serum α-fetoprotein level ( P = 0.010), age ( P = 0.015), and signal noise ratio ( P = 0.026) was 0.799 and 0.715 in training and validation cohorts, respectively. The AUC of the radiomic model constructed by 9 selected radiomic features was 0.833 and 0.772 in training and validation cohorts, respectively. The AUC of the fusion model containing serum α-fetoprotein level ( P = 0.011), age ( P = 0.019), and rad score ( P < 0.001) was 0.901 and 0.781 in training and validation cohorts, respectively. Diffusion-weighted imaging as a quantitative imaging biomarker can predict Ki67 expression level in hepatocellular carcinoma across various models.

Combined serum CXCL8, CXCL9and CXCL13 tests for the prediction of microvascular invasion in hepatocellular carcinoma.

Aim: This work is to explore the predictive and diagnostic value of chemokine C-X-C motif ligand 8 (CXCL8), CXCL9and CXCL13 combined detections for microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. Materials & methods: A total of82 HCC patients with MVI were recruited as the MVI group and 154 patients with nonMVI were recruited as the non MVI group. Results: In HCC patients with MVI, CXCL8, CXCL9, CXCL13 levels were significantly elevated. Child-Pugh scores and serum α-fetoprotein level had positive correlation with CXCL8, CXCL9and CXCL13 levels. The serum levels of CXCL8, 9and 13 were effective in predicting MVI in HCC patients. Conclusion: CXCL8, CXCL9 and CXCL13 levels in HCC patients are valuable parameters in the prediction of MVI.

Glycoproteomic Analysis of Urinary Extracellular Vesicles for Biomarkers of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for the most common form of primary liver cancer cases and constitutes a major health problem worldwide. The diagnosis of HCC is still challenging due to the low sensitivity and specificity of the serum α-fetoprotein (AFP) diagnostic method. Extracellular vesicles (EVs) are heterogeneous populations of phospholipid bilayer-enclosed vesicles that can be found in many biological fluids, and have great potential as circulating biomarkers for biomarker discovery and disease diagnosis. Protein glycosylation plays crucial roles in many biological processes and aberrant glycosylation is a hallmark of cancer. Herein, we performed a comprehensive glycoproteomic profiling of urinary EVs at the intact N-glycopeptide level to screen potential biomarkers for the diagnosis of HCC. With the control of the spectrum-level false discovery rate ≤1%, 756 intact N-glycopeptides with 154 N-glycosites, 158 peptide backbones, and 107 N-glycoproteins were identified. Out of 756 intact N-glycopeptides, 344 differentially expressed intact N-glycopeptides (DEGPs) were identified, corresponding to 308 upregulated and 36 downregulated N-glycopeptides, respectively. Compared to normal control (NC), the glycoproteins LG3BP, PIGR and KNG1 are upregulated in HCC-derived EVs, while ASPP2 is downregulated. The findings demonstrated that specific site-specific glycoforms in these glycoproteins from urinary EVs could be potential and efficient non-invasive candidate biomarkers for HCC diagnosis.

Clinical characteristics and risk factors analysis for the recurrence of pelvic endodermal sinus tumors

This study investigated the clinicopathological characteristics and factors influencing the recurrence of pelvic endodermal sinus tumor (PEST). 54 cases were retrospectively analyzed from at the Zhejiang Cancer Hospital. Progression-free survival (PFS) and related factors on disease recurrence were evaluated. Six patients had extragonadal endodermal sinus tumor, and four had histological features of endodermal sinus tumor (EST) combined with embryonal carcinoma (EC). 39 patients underwent fertility-preserving surgery, 18 patients had a childbearing history, and eight patients had residual tumor after initial treatment as surgery or chemotherapy. 26 patients had a tumor diameter of more than 15 cm, and 30 patients had a serum αfetoprotein (AFP) level greater than 10,000 ng/mL before initial management. The median follow-up was 47.5 months (range, 14–212 months). During follow-up, 15 patients experience recurrence, with a recurrence rate of 27.8% and a 5-year PFS rate of 61.1%. In univariate analysis, the FIGO (International Federation of Gynecology and Obstetrics) stage (stage III–IV vs. I–II; hazard ratio (HR) = 9.73, p &lt; 0.001), residual tumor (yes vs. no for the first surgery; HR = 4.86, p = 0.001), histological features (EST combined with EC vs. EST; HR = 4.08, p = 0.017), and use of platinum-based chemotherapy (courses ≥3 vs. courses &lt;3; HR = 0.19, p = 0.004) were independent factors influencing recurrence. In multivariate analysis, only stage was an independent risk factor for PFS (stage III–IV vs. I–II; HR = 6.92, p = 0.02). Stage is a prognostic factor for recurrence of PEST. The aim of the initial surgery is to maximally debulk all grossly visible tumor and the post-operative treatment should include a sufficient dose and full course of platinum-based chemotherapy, which may reduce the recurrence rate. Maybe some gene expression that could be associate with PEST.

Increased Severity due to Aflatoxin in Viral Cause of Hepatocellular Carcinoma: A Case Control Study

The objective of our study was to assess the presence of aflatoxin in Hepatocellular Carcinoma patients and their severity. This case control study was conducted in the Asian Institute of Medical Sciences (AIMS) Hyderabad and Nuclear Institute of Medicine and Radiotherapy (NIMRA) Jamshoro for the period of 02 years from March 2018 to February 2020. The calculated sample size was 218 subjects, 109 patients were diagnosed with cases of HCC (76 male and 33 female), and 109 were included as control. Control was selected from the relatives of the patients who were Viral Hepatitis-Negative. Non-probability convenience sampling was used. Majority of the cases and controls were for 40 to 49 years of age. Serum α-fetoprotein (AFP) was significantly high in 80 (73.4%) cases who were culture positive with (p=0.013). There is no association between the AG ratio and mycological culture media-positive cases. A strong correlation is observed between Viral Hepatitis infection and the development of hepatocellular carcinoma (HCC) in Pakistan. The toxin produced by fungi has worse outcomes in patients with liver compromise especially hepatocellular carcinoma. The poor prognosis was observed in HCC and Liver Cirrhosis patients, especially in low-income countries where health services are poor. Therefore, preventive strategies need to be applied to control these toxins. Proper handling and cooking of common food and good hygiene, especially for high-risk patients, can help prevent and controlling the spread of these toxins. Keywords: hepatocellular carcinoma, aflatoxins, hepatitis B, hepatitis C, Pakistan. https://doi.org/10.55463/issn.1674-2974.50.2.4

Yttrium-90 Radioembolization as the Major Treatment of Hepatocellular Carcinoma.

The purpose of this study was to assess the safety and efficacy of Yttrium-90 radioembolization using in unresectable hepatocellular carcinoma. From 2017 to 2021, 32 patients with unresectable hepatocellular carcinoma, with mean tumor diameter about 7cm (21 males, 11 females; median age, 57.5 years of age), treated with Yttrium-90 radioembolization using resin microspheres were reviewed at pre-Yttrium-90 and post-Yttrium-90 follow-up. Tumor response was assessed according to the modified Response Evaluation Criteria in Solid Tumors. Outcomes including overall survival and progression-free survival were reported. Median follow-up was 18 months. At follow-up examinations at 3-, 6-, and 12-months follow-up, the overall survival rates were 94%, 87% and 59%, and the progression-free survival rates were 78%, 64% and 60%, respectively. Complete response, partial response, stable disease, and progressive disease were noted in 7 (21.9%), 14 (43.7%), 4 (12.5%), and 7 (21.9%) patients, respectively. The disease control rate was 78.1%, the objective response rate was 65.6%, and the successful downstage rate was 34.4% (11 of 32). Nine of thirty-two patients underwent resection or transplantation after Yttrium-90 radioembolization with 2-year overall survival being 100%. No serious adverse events occurred after Yttrium-90 treatment. Worse overall survival was related to the larger tumor, higher stage, Eastern Cooperative Oncology Group performance status, and Child-Pugh score. And worse progression-free survival was related to the higher tumor burden, and pre-Yttrium-90 serum α-fetoprotein level >100. Yttrium-90 Radioembolization can control hepatocellular carcinoma well even in advanced diseases. Patients successfully downstaging/bridging to resection or transplantation have excellent overall survival.

Evaluating the Anticancer Activity of Blocking TNF Type 1 Receptors in Thioacetamide-Induced Hepatocellular Carcinoma in a Rat Model.

Background Hepatocellular carcinoma (HCC) can explicate about 90% of the total primary liver cancer cases, with approximately 800,000 new cases identified each year worldwide. In addition, any changes in the expression of the tumor necrosis factor α (TNF-α) type 1 receptor (TNFR1) might impact many biological processes, which may lead to cancer. Aims We conducted the following study to investigate the ability of CAY10500, a TNF-α inhibitor that prevents binding to the TNF receptor 1, to produce anticancer effects against hepatocellular carcinoma experimentally induced in rats and to discover its effect on nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Materials and methods HCC was induced in rats via 200 mg/kg thioacetamide followed by treating some rats with IV 1 mg/kg CAY10500. Assessment of the liver impairment was by measuring the serum α-fetoprotein (AFP) and investigation of liver sections stained with hematoxylin/eosin. The hepatic expression of both the messenger RNA (mRNA) and protein levels ofTNF-α, TNFR1, Nrf2, and HO-1 was assessed. Results We found that CAY10500 increased the survival percent of rats associated with a reduction in serum AFP and the number of hepatic nodules. Besides, CAY10500 reduced the expression of TNFR1 without affecting the expression of TNF-α. Finally, CAY10500 increased the expression of both Nrf2 and HO-1. Conclusions Inhibition of TNFR1 expression in HCC by using CAY10500 produced therapeutic effects as indicated by increasing the survival rate, reducing the serum AFP level, decreasing liver nodules, and improving hepatocytes' structure. In addition, TNFR1 significantly enhanced the expression of Nrf2 and HO-1.