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International Journal of Surgery... Feb 2024It is unclear which patients benefit from resection in intermediate-stage-hepatocellular carcinoma (HCC). The authors aimed to identify high-risk patients for early...
BACKGROUNDS
It is unclear which patients benefit from resection in intermediate-stage-hepatocellular carcinoma (HCC). The authors aimed to identify high-risk patients for early recurrence among patients with resectable intermediate-stage HCC.
METHODS
This multicenter retrospective study included patients who underwent resection or trans-arterial chemoembolization (TACE) for intermediate-stage HCC (2008-2019). Multivariable Cox proportional analysis was performed to identify high-risk patients when treated with resection. A prediction score for 2-year recurrence-free survival (RFS) was developed using the training cohort and validated. The 2-year RFS in each risk group was compared with that in TACE group, after propensity score matching (PSM).
RESULTS
A total of 1686 patients were included (480 and 1206 patients in the resection and TACE groups). During a median follow-up of 31.4 months, the 2-year RFS was significantly higher in the resection (47.7%) than in the TACE group (19.8%) [adjusted hazard ratio (aHR)=1.471, 95% CI: 1.199-1.803, P <0.001). On multivariate analysis, alpha-fetoprotein ≥5.0 ng/ml (aHR=0.202), ALBI grade ≥2 (aHR=0.709), tumor number ≥3 (aHR=0.404), and maximal tumor size ≥5 cm (aHR=0.323) were significantly associated with the lower risk of 2-year RFS in the resection group. The newly developed Surgery Risk score in BCLC-B (SR-B score) with four significant risk factors showed an area under the curve of 0.801 for the 2-year RFS and was validated. Based on the SR-B score, low-risk patients had a significantly higher 2-year RFS (training: aHR=5.834; validation: aHR=5.675) than high-risk patients (all P <0.001) did. In a PSM cohort, a low-risk resection group had a significantly higher (aHR=3.891); a high-risk resection group had a comparable 2-year RFS to those treated with TACE (aHR=0.816).
CONCLUSIONS
Resection may be beneficial for resectable intermediate-stage HCC based on the SR-B score.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; Neoplasm Staging; Prognosis; Chemoembolization, Therapeutic; Hepatectomy; Propensity Score
PubMed: 38016294
DOI: 10.1097/JS9.0000000000000941 -
Molecules (Basel, Switzerland) Oct 2023The labeling-free and immobilization-free homogeneous aptamer sensor offers advantages including simple operation, low cost, and high sensitivity, demonstrating great...
Label-Free Homogeneous Electrochemical Aptasensor Based on Size Exclusion/Charge-Selective Permeability of Nanochannel Arrays and 2D Nanorecognitive Probe for Sensitive Detection of Alpha-Fetoprotein.
The labeling-free and immobilization-free homogeneous aptamer sensor offers advantages including simple operation, low cost, and high sensitivity, demonstrating great potential in rapid detection of tumor biomarkers in biological samples. In this work, a labeling-free and immobilization-free homogeneous aptamer sensor was conveniently fabricated by combining size exclusion and charge-selective penetration of a nanochannel-modified electrode and two-dimensional (2D) nanorecognition probe which can realize selective and highly sensitive detection of alpha-fetoprotein (AFP) in serum. Vertically ordered mesoporous silica film (VMSF) with ultra-small, uniform, and vertically aligned nanochannels was easily grown on the simple, low-cost, and disposable indium tin oxide (ITO) electrode. Through π-π interaction and electrostatic force, the AFP aptamer (Apt) and electrochemical probe, tris(bipyridine)ruthenium(II) (Ru(bpy)), were coloaded onto graphene oxide (GO) through simple incubation, forming a 2D nanoscale recognition probe (Ru(bpy)/Apt@GO). Owing to the size exclusion effect of VMSF towards the 2D nanoscale probe, the electrochemical signal of Ru(bpy)/Apt@GO could not be detected. In the presence of AFP, the specific binding of AFP to the aptamer causes the dissociation of the aptamer and Ru(bpy) from GO, resulting in their presence in the solution. The efficient electrostatic enrichment towards Ru(bpy) by negatively charged VMSF allows for high electrochemical signals of free Ru(bpy) in the solution. Linear determination of AFP ranged from 1 pg/mL to 1000 ng/mL and could be obtained with a low limit of detection (LOD, 0.8 pg/mL). The high specificity of the adapter endowed the constructed sensor with high selectivity. The fabricated probe can be applied in direct determination of AFP in serum.
Topics: alpha-Fetoproteins; Biomarkers, Tumor; Aptamers, Nucleotide; Graphite; Electrochemical Techniques; Biosensing Techniques
PubMed: 37836778
DOI: 10.3390/molecules28196935 -
World Journal of Clinical Cases Dec 2023Liver cancer is the fifth most common tumor and the second highest death-related cancer in the world. Hepatocarcinoma (HCC) represents 90% of liver cancers. According to...
Liver cancer is the fifth most common tumor and the second highest death-related cancer in the world. Hepatocarcinoma (HCC) represents 90% of liver cancers. According to the Barcelona Clinic Liver Cancer group, different treatment options could be offered to patients in consideration of tumor burden, liver function, patient performance status and biochemical marker serum concentration such as alpha-fetoprotein. Trans-arterial chemoembolization (TACE) is the treatment of choice in patients with diagnosis of unresectable HCC not eligible for liver transplantation, and preserved arterial supply. TACE is known to be safe and its complications are generally mild such as post-TACE syndrome, a self-resolving adverse event that occurs in about 90% of patients after the procedure. However, albeit rarely, more severe adverse events such as biloma, sepsis, hepatic failure, chemoagents induced toxicities, and post-TACE liver necrosis can occur. A prompt diagnosis of these clinical conditions is fundamental to prevent further complications. As a result, biliary stenosis could be a rare post-TACE necrosis complication and can be difficult to manage. Complications from untreated biliary strictures include recurring infections, jaundice, chronic cholestasis, and secondary biliary cirrhosis.
PubMed: 38188216
DOI: 10.12998/wjcc.v11.i36.8434 -
Scientific Reports Dec 2023Fetuin-A acts as both an inhibitor of calcification and insulin signaling. Previous studies reported conflicting results on the association between fetuin-A and...
Fetuin-A acts as both an inhibitor of calcification and insulin signaling. Previous studies reported conflicting results on the association between fetuin-A and cardiometabolic diseases. We aim to provide further insights into the association between genetically predicted levels of fetuin-A and cardiometabolic diseases using a Mendelian randomization strategy. Genetic variants associated with fetuin-A and their effect sizes were obtained from previous genetic studies. A series of two-sample Mendelian randomization analyses in 412,444 unrelated individuals from the UK Biobank did not show evidence for an association of genetically predicted fetuin-A with any stroke, ischemic stroke, or myocardial infarction. We do find that increased levels of genetically predicted fetuin-A are associated with increased risk of type 2 diabetes (OR = 1.21, 95%CI 1.13-1.30, P = < 0.01). Furthermore, genetically predicted fetuin-A increases the risk of coronary artery disease in individuals with type 2 diabetes, but we did not find evidence for an association between genetically predicted fetuin-A and coronary artery disease in those without type 2 diabetes (P for interaction = 0.03). One SD increase in genetically predicted fetuin-A decreases risk of myocardial infarction in women, but we do not find evidence for an association between genetically predicted fetuin-A and myocardial infarction in men (P for interaction = < 0.01). Genetically predicted fetuin-A is associated with type 2 diabetes. Furthermore, type 2 diabetes status modifies the association of genetically predicted fetuin-A with coronary artery disease, indicating that fetuin-A increases risk in individuals with type 2 diabetes. Finally, higher genetically predicted fetuin-A reduces the risk of myocardial infarction in women, but we do not find evidence for an association between genetically predicted fetuin-A and myocardial infarction in men.
Topics: Female; Humans; Male; alpha-2-HS-Glycoprotein; alpha-Fetoproteins; Coronary Artery Disease; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Mendelian Randomization Analysis; Myocardial Infarction; Polymorphism, Single Nucleotide; Stroke
PubMed: 38052855
DOI: 10.1038/s41598-023-48600-9 -
BMC Cancer Sep 2023Studies have demonstrated that Sorting nexin 7 (SNX7) functions as an anti-apoptotic protein in liver tissue and plays a crucial role in the survival of hepatocytes...
Comprehensive analysis and validation of SNX7 as a novel biomarker for the diagnosis, prognosis, and prediction of chemotherapy and immunotherapy response in hepatocellular carcinoma.
BACKGROUND
Studies have demonstrated that Sorting nexin 7 (SNX7) functions as an anti-apoptotic protein in liver tissue and plays a crucial role in the survival of hepatocytes during early embryonic development. However, its diagnostic and prognostic value as well as the predictive value of chemotherapy and immunotherapy have not been reported in hepatocellular carcinoma (HCC).
METHODS
SNX7 mRNA expression and its diagnostic efficacy were examined in GEO datasets, and the findings were further confirmed in TCGA, ICGC cohorts, and cell lines. The protein level of SNX7 was determined using CPTAC and HPA databases, and the results were validated through immunohistochemistry (IHC). Survival analyses were performed in TCGA and ICGC cohorts, and the results were subsequently validated via Kaplan-Meier Plotter. The response to chemotherapy and immunotherapy was predicted via GDSC dataset and TIDE algorithm, respectively. R packages were employed to explore the relationship between SNX7 expression and immune infiltration, m6A modification, as well as the functional enrichment of differentially expressed genes (DEGs).
RESULTS
The expression of SNX7 at both mRNA and protein levels was significantly upregulated in HCC tissues. SNX7 exhibited superior diagnostic efficacy compared to AFP alone for HCC detection, and combining it with AFP improved the diagnostic accuracy for HCC. High SNX7 was associated with unfavorable outcomes, including poor overall survival, disease-specific survival, progression-free survival, and advanced pathological stage, in patients with HCC, and SNX7 was identified as an independent risk factor for HCC. Moreover, elevated SNX7 expression was positively correlated with increased sensitivity to various chemotherapy drugs, including sorafenib, while it was associated with resistance to immunotherapy in HCC patients. Correlation analysis revealed a relationship between SNX7 and multiple m6A-related genes and various immune cells. Finally, enrichment analysis demonstrated strong associations of SNX7 with critical biological processes, such as cell cycle regulation, cellular senescence, cell adhesion, DNA replication, and mismatch repair pathway in HCC.
CONCLUSIONS
Our study highlights the association of SNX7 with the immune microenvironment and its potential influence on HCC progression. SNX7 emerges as a promising novel biomarker for the diagnosis, prognosis, and prediction of response to chemotherapy and immunotherapy in patients with HCC.
Topics: Female; Pregnancy; Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Prognosis; Biomarkers; Immunotherapy; Tumor Microenvironment
PubMed: 37743471
DOI: 10.1186/s12885-023-11405-0 -
Scientific Reports Nov 2023It is difficult to determine whether an individual therapy contributes to the elongation of survival because of the difficulty of organizing clinical research in...
It is difficult to determine whether an individual therapy contributes to the elongation of survival because of the difficulty of organizing clinical research in patients who receive multiple treatments in HCC. We aimed to establish a new model of survival prediction in patients with intermediate stage HCC to establish standards in the recent and coming multi-MTA era. This analysis was prepared using a data set of 753 patients diagnosed HCC prior to 2017. Multiple regression analysis showed age, naïve or recurrence, the size of the largest tumor nodule, the number of nodules, total bilirubin, albumin and α-fetoprotein as independent predictors of survival. A Weibull model had the best fit and, based on these predictors, we established a new predicted survival model. The survival duration can be predicted the proposed model; EXP (4.02580 + (- 0.0086253) × age + (- 0.34667) × (naïve/recurrence) + (- 0.034962) × (number of nodules) + (- 0.079447) × (the size of the largest nodule) + (- 0.21696) × (total bilirubin) + 0.27912 × (albumin) + (- 0.00014741) × (α-fetoprotein)) × (- natural logarithm(0.5))^0.67250. This model is useful for the planning and evaluating the efficacy of recent sequential therapies in multi-MTA era.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Treatment Outcome; Neoplasm Staging; Bilirubin; Albumins; Retrospective Studies
PubMed: 38007597
DOI: 10.1038/s41598-023-48068-7 -
World Journal of Gastrointestinal... Apr 2024Alpha-fetoprotein (AFP), a commonly used biomarker for hepatocellular carcinoma (HCC), is normal in up to one-third of patients.
BACKGROUND
Alpha-fetoprotein (AFP), a commonly used biomarker for hepatocellular carcinoma (HCC), is normal in up to one-third of patients.
AIM
To evaluate the diagnostic performance of des-gamma-carboxy-prothrombin (DCP) alone and in combination with AFP.
METHODS
In this study, 202 patients with radiologically proven HCC were enrolled, and their DCP and AFP levels were evaluated for their diagnostic performance.
RESULTS
The mean age of the enrolled patients was 58.5 years; 72.0% were male. DCP was elevated in 86.6% ( = 175) of all patients, 100.0% ( = 74) of patients with portal vein thrombus, and 87.4% ( = 111) of patients with multicentric HCC. AFP was elevated in 64.3% ( = 130) of all the patients, 74% ( = 55) of the patients with portal vein thrombus, and 71.6% ( = 91) of the patients with multicentric HCC ( = 0.030, 0.001, and 0.015, respectively). In tumors less than 2 cm in size ( = 46), DCP was increased in 32 (69.5%) patients, and AFP was increased in 25 (54.3%) patients ( = 0.801). There was good pairing between DCP and AFP for HCCs of 2 cm size or larger ( < 0.001); however, the pairing among tumors < 2 cm size was not significant ( = 0.210). In 69 of the patients (34.1%), only one of the tumor markers was positive; DCP was elevated alone in 57/202 (28.2%) of all patients, and AFP alone was elevated in 12/202 (5.9%) of the patients. The areas under receiver operating characteristic curves (AUROC) for tumors > 2 cm was 0.74 for DCP and 0.59 for AFP; combining both markers resulted in an AUROC of 0.73. For tumors < 2 cm, the AUROC was 0.25 for DCP and 0.40 for AFP.
CONCLUSION
DCP, as an individual marker, had a better diagnostic performance in many cases of HCC. Hence, DCP may replace AFP as the primary HCC biomarker.
PubMed: 38682024
DOI: 10.4291/wjgp.v15.i1.90893 -
Scientific Reports Dec 2023An optimized hepatocellular carcinoma (HCC)-targeted methylation next generation sequencing assay was developed to discover HCC-associated methylation markers directly...
An optimized hepatocellular carcinoma (HCC)-targeted methylation next generation sequencing assay was developed to discover HCC-associated methylation markers directly from urine for HCC screening. Urine cell-free DNA (ucfDNA) isolated from a discovery cohort of 31 non-HCC and 30 HCC was used for biomarker discovery, identifying 29 genes with differentially methylated regions (DMRs). Methylation-specific qPCR (MSqPCR) assays were developed to verify the selected DMRs corresponding to 8 genes (GRASP, CCND2, HOXA9, BMP4, VIM, EMX1, SFRP1, and ECE). Using archived ucfDNA, methylation of GRASP, HOXA9, BMP4, and ECE1, were found to be significantly different (p < 0.05) between HCC and non-HCC patients. The four markers together with previously reported GSTP1 and RASSF1A markers were assessed as a 6-marker panel in an independent training cohort of 87 non-HCC and 78 HCC using logistic regression modeling. AUROC of 0.908 (95% CI, 0.8656-0.9252) was identified for the 6-marker panel with AFP, which was significantly higher than AFP-alone (AUROC 0.841 (95% CI, 0.778-0.904), p = 0.0026). Applying backward selection method, a 4-marker panel was found to exhibit similar performance to the 6-marker panel with AFP having 80% sensitivity compared to 29.5% by AFP-alone at a specificity of 85%. This study supports the potential use of methylated transrenal ucfDNA for HCC screening.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; DNA Methylation; alpha-Fetoproteins; Cell-Free Nucleic Acids; Biomarkers, Tumor
PubMed: 38062093
DOI: 10.1038/s41598-023-48500-y -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Feb 2024To assess the value of serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) and glypican-3 (GPC-3) in the diagnosis of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the value of serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) and glypican-3 (GPC-3) in the diagnosis of hepatocellular carcinoma (HCC).
METHODS
Studies of AFP, PIVKA-Ⅱ, GPC-3 or in combination for the diagnosis of HCC since 2002 were searched in PubMed, Web of Science and Embase databases. The literature was screened according to the inclusion and exclusion criteria, the quality of the included articles was evaluated by QUADAS checklist, and relevant data were extracted by Meta DiSc, Review Manager 5.4 and Stata 15.1. The diagnostic values of AFP, PIVKA-Ⅱ and GPC-3 alone or in combination for HCC were assessed with receiver operating characteristic (ROC) curve.
RESULTS
A total of 32 articles were included in the study. Meta-analysis showed that when a single marker was used to diagnose HCC, the area under the ROC curve (AUC) of PIVKA-Ⅱ was the highest (0.88, 95%: 0.85-0.91), followed by GPC-3 and AFP. The AUC of combination of serum markers was higher than that of a single marker, and the AUC of PIVKA-Ⅱ combined with GPC-3 was the highest (0.90, 95%: 0.87-0.92). When a single marker was used for diagnosis, the sensitivity of PIVKA-Ⅱ and GPC-3 were relatively high (0.75 and 0.76), while the specificity of PIVKA-Ⅱ (0.88) and AFP (0.87) were higher than that of GPC-3 (0.81). The sensitivity of the combination of serum markers was higher than that of a single marker, while the specificity was not significantly improved. When a single marker is used to diagnose HCC, the diagnostic odds ratio (DOR) of PIVKA-Ⅱ was the highest (22, 95%: 13-36), followed by GPC-3 and AFP. The DOR of the combination of two markers in the diagnosis of HCC was higher than that of a single marker, and the DOR of AFP combined with GPC-3 was the highest (25, 95%: 9-67). The DOR of the combination of the three markers was significantly reduced to 10 (95%: 7-45).
CONCLUSIONS
When a single marker is used, PIVKA-Ⅱ has a higher diagnostic value for HCC. The combination of two markers can significantly improve the diagnostic sensitivity, and AFP combined with PIVKA-Ⅱ is recommended for the diagnosis of HCC. The combination of all three markers failed to further improve the diagnostic value.
Topics: Humans; alpha-Fetoproteins; Biomarkers; Carcinoma, Hepatocellular; Glypicans; Liver Neoplasms; Protein Precursors; Prothrombin
PubMed: 38310085
DOI: 10.3724/zdxbyxb-2023-0483 -
Communicable Diseases Intelligence... Aug 2023For 30 years the Australian Paediatric Surveillance Unit (APSU) has conducted national surveillance of rare communicable diseases and rare complications of communicable...
For 30 years the Australian Paediatric Surveillance Unit (APSU) has conducted national surveillance of rare communicable diseases and rare complications of communicable diseases. In this report, we describe the results of thirteen such studies surveyed by the APSU in 2022, including reported case numbers and incidence estimates, demographics, clinical features, management and short-term outcomes. Conditions described are: acute flaccid paralysis (AFP); congenital cytomegalovirus (cCMV); neonatal and infant herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV) and paediatric HIV infection; severe complications of influenza; juvenile-onset recurrent respiratory papillomatosis (JoRRP); congenital rubella infection/syndrome; congenital varicella syndrome (CVS) and neonatal varicella infection (NVI); and the new conditions dengue; Q fever; and severe acute hepatitis. In 2022, cases of severe complications of influenza were reported to the APSU for the first time since 2019. This likely reflects the easing of government-mandated restrictions imposed in 2020-2021 to curb the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the re-emergence of a range of infectious diseases. As previously, AFP surveillance by the APSU contributed to Australia achieving a minimum target incidence of one AFP case per 105 children aged less than 15 years. Cases of JoRRP and NVI were reported in 2022. This indicates potential gaps in human papillomavirus (HPV) and varicella vaccination coverage respectively, especially in high-risk groups such as young migrant and refugee women of childbearing age from countries without universal vaccination programs. Paediatric HIV case numbers resulting from mother-to-child-transmission (MTCT) of HIV remain low in Australia due to use of effective intervention strategies. However, there has been an increase in the number of imported cases of HIV in children (mainly perinatally-acquired) from countries with a high HIV prevalence. Without effective vaccines, there has been no decline in the incidence of congenital CMV and neonatal HSV, indicating the importance of early identification and management to reduce morbidity and mortality. The first cases of dengue, Q fever and severe acute hepatitis were received by APSU in 2022, including two cases of acute hepatitis in which aetiology has not been confirmed to date. The APSU has an important ongoing role in monitoring rare childhood infections.
Topics: Infant; Infant, Newborn; Pregnancy; Humans; Female; Child; HIV Infections; Chickenpox; Influenza, Human; Q Fever; alpha-Fetoproteins; Australia; Infectious Disease Transmission, Vertical; Communicable Diseases; Cytomegalovirus Infections; Rubella Syndrome, Congenital; Hepatitis; Dengue
PubMed: 37817313
DOI: 10.33321/cdi.2023.47.46