Alpha-fetoprotein Values Research Articles

B-333 Optimizing AFP Cutoffs for Hepatocellular Carcinoma Screening: Insights from the National Cancer Screening Program in Korea

Abstract Background The incidence rate and mortality rate of liver cancer were 11.6 (ranked 8th among cancers) and 10.7 (4th) per 100,000 individuals respectively globally in 2020, whereas in Korea, they were higher at 29.5 (7th) and 20.6 (2nd) per 100,000 individuals. The National Cancer Screening Program (NCSP) in Korea conducts biannual concurrent liver ultrasound and serum alpha-fetoprotein (AFP) measurement for hepatocellular carcinoma (HCC) surveillance in high-risk groups, including those with chronic hepatitis B and C, and liver cirrhosis. The effectiveness of surveillance is impacted by varying AFP cutoffs; however, within the NCSP, different cutoffs are being used, and it is not clear which cutoffs are being employed. Harmonization of AFP test results by major reagent manufacturers have been achieved, enabling the adoption of a uniform threshold. This study aims to assess the variation of AFP cutoffs among institutions within the NCSP and suggest a unified and optimal AFP threshold. Methods This study examined HCC screening results from the NCSP between 2018 and 2020, investigating unit and cutoff usage for AFP test across institutions each year (number of institutions were 4452 for 2018, 4754 for 2019, and 4847 for 2020). To determine the optimal AFP cutoff for HCC screening, datasets comprised unique patient results from 2018 to 2020 (number of patients = 819,644). Receiver operating characteristic (ROC) curve analyses were conducted for determine best AFP cutoffs. Cancer diagnosis was defined by billing records indicating HCC within one year post-screening. Results More than 96% of institutions used ng/mL as a unit of AFP test. Among institutions using ng/mL, the most frequently used AFP cutoff was 7 ng/mL, with frequency percentages of 75.7%, 72.2%, and 62.2% in 2018, 2019, 2020, respectively. The percentiles (1st, 10th, 90th, 99th) of AFP cutoff usage for the years 2018, 2019, and 2020 were (7, 7, 8.8, 15), (7, 7, 8.9, 15), and (7, 7, 9, 15) respectively. The AUC of ROC was 0.824 and some cut-off points with their sensitivity and specificity values were as follows: 5 ng/mL (0.648, 0.874); 10 (0.457, 0.976); 20 (0.327, 0.993); 40 (0.246, 0.997); 100 (0.169, 0.998); 200 (0.123, 0.999); 400 (0.084, 1). Conclusions Different cutoffs observed across institutions in NCSP. Our study cautiously suggests that the optimal AFP value for screening HCC in NCSP may range from 10 to 20 ng/mL, considering sensitivity and specificity when AFP is combined with ultrasound in regions with a high prevalence of HCC. For a more suitable AFP cutoff recommendation, additional analyses based on ultrasound findings and underlying diseases should be considered.

Development of an indirect ELISA to detect antigens using DNA origami nanoantenna labeled specific monoclonal antibodies

This research examines the development of an indirect ELISA to detect antigens using DNA origami nanoantenna-labeled specific monoclonal antibodies. Hepatocellular carcinoma (HCC) is one of the five most common cancers and the second leading cause of cancer-related death worldwide. More than 60% of cases are detected in the late stage, with the absence of specific symptoms in the early stage of the disease. Adding measurements of AFP (Alpha-Fetoprotein), TXN (Thioredoxin), and DCP (Des-γ-Carboxy Prothrombin) has the potential to improve the accuracy of diagnosing hepatocellular carcinoma. DNA origami technology is revolutionizing the forefront of cancer diagnostics, particularly for HCC. In this study, an indirect enzyme-linked immunosorbent assay (ELISA) method targeting the assessment of the effectiveness of specific monoclonal antibody-conjugated DNA origami particles was developed. The results of DNA origami folding into complex nanostructures and labeled biomarkers like AFP, DCP, and TXN have explored the high specificity and sensitivity for targeting HCC. We found the cut-off values for AFP, DCP, and TXN to be 0.132, 0.156, and 0.150, respectively. The coefficients of variation for samples remained consistently under 10%, indicating the method's high degree of stability and reproducibility. This innovation, combined with biomarkers, promised in early HCC detection, holds the potential to significantly enhance patient outcomes in the fight against liver cancer. The platform also has enormous potential for advancing personalized medicine.

Preoperative prediction of hepatocellular carcinoma microvascular invasion based on magnetic resonance imaging feature extraction artificial neural network.

Hepatocellular carcinoma (HCC) recurrence is highly correlated with increased mortality. Microvascular invasion (MVI) is indicative of aggressive tumor biology in HCC. To construct an artificial neural network (ANN) capable of accurately predicting MVI presence in HCC using magnetic resonance imaging. This study included 255 patients with HCC with tumors < 3 cm. Radiologists annotated the tumors on the T1-weighted plain MR images. Subsequently, a three-layer ANN was constructed using image features as inputs to predict MVI status in patients with HCC. Postoperative pathological examination is considered the gold standard for determining MVI. Receiver operating characteristic analysis was used to evaluate the effectiveness of the algorithm. Using the bagging strategy to vote for 50 classifier classification results, a prediction model yielded an area under the curve (AUC) of 0.79. Moreover, correlation analysis revealed that alpha-fetoprotein values and tumor volume were not significantly correlated with the occurrence of MVI, whereas tumor sphericity was significantly correlated with MVI (P < 0.01). Analysis of variable correlations regarding MVI in tumors with diameters < 3 cm should prioritize tumor sphericity. The ANN model demonstrated strong predictive MVI for patients with HCC (AUC = 0.79).

Association of serum alpha-fetoprotein (AFP) with indirect prognosis in gastric cancer

Aims: Alpha-fetoprotein (AFP) is a glycoprotein secreted from the yolk sac and hepatocytes during fetal life. Elevated levels in adults are considered markers for yolk sac tumors, hepatocellular carcinoma and gastric cancer. There is still no consensus on the definition of AFP-secreting gastric cancers, but AFP-secreting gastric cancers have been reported to have a worse prognosis. In this study, AFP levels in gastric cancers with high AFP were compared with pathology results and evaluated in terms of indirect prognosis. Methods: Patients with gastric cancer operated in the General Surgery Clinic of Ankara Bilkent City Hospital between 2019 and 2023 were retrospectively screened. Among the screened patients, those whose information could not be reached and those with incomplete information were excluded and 126 patients were included in the study. Serum AFP levels of these patients were compared with pathology results, stages and tumor sizes. Results: The mean age of the patients in our study was 66±11 years, 42 (33.6%) were female and 84 (66.7%) were male. Of the 126 patients analyzed in the study, 107 (84.9%) were AFP-negative and 19 (15.1%) were AFP-positive. There was no significant difference in AFP levels between all patients in terms of liver metastasis, peritoneal metastasis, disease stage, perineural invasion and tumor location. However, serum AFP levels were significantly higher in patients with lymphovascular invasion and lung metastases (p=0.042; p=0.024). In the analysis for serum AFP level in the presence of lymphovascular invasion, ROC value was 2.35 ng/ml, sensitivity 58.2%, specificity 55.9%, area under the curve (AUC) 0.618, 95% confidence interval (95% CI) 0.512-0.723 and p=0.028. Conclusion: Lymphovascular invasion is a poor prognostic factor in gastric cancer. In this study, a significant correlation was found between serum AFP value and lymphovascular invasion. In gastric cancers without AFP secretion, a serum AFP value above 2.35 ng/ml may be indirectly associated with poor prognosis because it predicts lymphovascular invasion.

Half-life of serum alpha-fetoprotein in prepubertal testicular yolk sac tumors: an index significantly associated with prognosis.

To evaluate the association between serum alpha-fetoprotein (AFP) half-life (HL) and prognosis in prepubertal children with elevated AFP values 3 to 4 weeks after surgery for testicular yolk sac tumors (YST). Prepubertal patients with testicular YST treated with radical orchiectomy between January 2016 and December 2022 were retrospectively reviewed. Negative outcomes were defined as relapse, metastasis or death. Univariate and multivariate logistic regression analyses were conducted to select risk factors for negative outcomes. A total of 42 patients were eventually enrolled into the study. Patients were divided into non-negative and negative outcomes groups, consisting of 35 and 7 patients, respectively. Thirty-five patients were stage I, two cases were stage II, and five cases were stage IV, according to the Children's Oncology Group staging system. The overall survival (OS) rate was 100%. Average AFP values significantly decreased after resection (P < 0.001). A significant positive correlation was shown between pre- and postoperative AFP values (r = 0.60, P < 0.001). Long AFP HL was considered as an independent risk factor for negative outcomes in YST patients underwent radical orchiectomy (P = 0.04). The cut-off value for AFP HL was 5.78 days, regardless of age division. Testicular YST is a relatively rare disease in children with an OS of 100%, and salvage chemotherapy is effective even in grade IV patients. The postoperative AFP HL was significantly associated with prognosis in prepubertal patients with testicular YST. The cut-off value for AFP HL is 5.78 days regardless of the effect of physiological AFP elevation.

Prognostic Value of Alpha-Fetoprotein in Unresectable Hepatocellular Carcinoma Treated with Hepatic Artery Infusion Chemotherapy Combined with Lenvatinib and Camrelizumab.

This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab. A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a >20% decrease in AFP within 4 weeks, and AFP response as a >75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated. The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p<0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p<0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333-6.585, p=0.008, and HR 6.182, 95% CI 1.780-21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107-4.318, p=0.024, and HR 3.078, 95% CI 1.407-6.730, p=0.005), serving as significant prognostic values. Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.

Dynamic changes of serum α-fetoprotein predict the prognosis of bevacizumab plus immunotherapy in hepatocellular carcinoma.

Alpha-fetoprotein (AFP) has been established as a biomarker for hepatocellular carcinoma (HCC); however, whether its dynamic changes could predict the response to systemic therapy remains elusive. This study explored the AFP trajectory and the association with survival in patients received bevacizumab plus immunotherapy. We retrospectively enrolled 536 HCC patients received bevacizumab plus immunotherapy between February 2021 and February 2023. Patients were divided into two groups according to AFP values before treatment (400ng/ml). Dynamic changes of AFP were fitted using a latent class model to generate the AFP trajectories. Multivariable Cox models were utilized to compute hazard ratios (HRs) for survival. Inverse-probability-of-treatment weighted analyses were conducted to mitigate the influence of unmeasured confounding variables. The primary endpoint is progression free survival (PFS). The second endpoint is overall survival (OS). Three distinct trajectories were identified for AFP-low and AFP-high patients, respectively. In AFP-low group, compared with the high-rising class (25%; n=69), HRs of PFS were 0.39 and 0.2 for the low-stable class (59.1%; n=163) and sharp-falling class (15.9%; n=44), after adjusting by tumor diameter, tumor number, and extra-hepatic metastasis. In AFP-high group, compared with the high-stable class (18.5%; n=48), HRs of PFS were 0.3 and 0.04 for the middle-stable class (56.5%; n=147) and sharp-falling class (25%; n=65), after adjusting by tumor diameter, tumor number, and extra-hepatic metastasis. Furthermore, the AFP trajectories exhibited the utmost relative importance among all covariates regarding PFS and OS in the multivariable regression models. The AFP trajectories in HCC patients receiving bevacizumab and immunotherapy, constituted an independent biomarker indicative of clinical outcomes. Findings from this study hold potential clinical utility in dynamically forecasting the prognosis of systemic therapy in HCC patients and facilitating clinical decision-making. Rapid reduction of AFP post-treatment can lead to favorable patient prognoses.

Evaluation of surgical strategies and long-term outcomes in pediatric hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the second most common pediatric malignant liver tumor after hepatoblastoma, represents 1% of all pediatric tumors. A retrospective study was conducted on children with HCC treated at our center from March 2002 to October 2022, excluding those with inadequate follow-up or records. Demographic data, initial complaints, alpha-fetoprotein (AFP) values, underlying disease, size and histopathological features of the masses, chemotherapy, and long-term outcomes were analyzed. Fifteen patients (8 boys, 7 girls) with a mean age of 11.4 ± 4.1years (0.8-16.4years) were analyzed. The majority presented with abdominal pain, with a median AFP of 3.9ng/mL. Hepatitis B cirrhosis in one patient (6.6%) and metabolic disease (tyrosinemia type 1) in two patients (13.3%) were the underlying diseases. Histopathological diagnoses were fibrolamellar HCC (n:8; 53.3%), HCC (n:6; 40%). Four of the 15 patients underwent liver transplantation, and 9 underwent surgical resection. Due to late diagnosis, two patients were considered inoperable (13.3%). The survival rate for the four patients who underwent liver transplantation was found to be 75%. Surgical treatment of various variants of HCC can be safely performed in experienced centers with a multidisciplinary approach, and outcomes are better than in adults.

Role of biomarkers in the diagnosis and management of HCC.

For many cancers, biomarkers have served as an important tool across the cancer care continuum from risk stratification and early detection to diagnosis and treatment. Alpha fetoprotein (AFP) remains one of the few validated biomarkers for patients with hepatocellular carcinoma (HCC). Although AFP has shown potential for each of these steps, its performance when used alone has often been suboptimal. There continues to be discordant recommendations about AFP's value when combined with ultrasound for surveillance as well as its role in diagnostic algorithms. Conversely, high AFP levels are associated with aggressive tumor biology and survival, so it remains a key factor for selection of liver transplant candidates. There have been immense efforts to identify and validate additional biomarkers for each of these steps in the HCC care continuum. Indeed, biomarker panels have shown promising data for HCC risk stratification and surveillance among patients with cirrhosis, as well as prognostication and detection of minimal residual disease in patients undergoing HCC treatment. Several large prospective studies to evaluate the role of these emerging biomarkers in clinical practice are currently ongoing.

FOXM1 and CHD4 expression is associated with chemoresistance in hepatoblastoma

Hepatoblastoma (HB) is the most common malignant liver tumor in childhood. Although pre-operative cisplatin (CDDP)-based chemotherapy is often used in cases of HB, about 20％ of HB patients exhibit resistance to CDDP. Forkhead box protein M1 (FOXM1) and chromo-domain-helicase-DNA-binding protein 4 (CHD4) have been associated with CDDP resistance in various tumors. We here analyzed the immunohistochemical expression of FOXM1 and CHD4 in HB specimens of 33 patients (mean age: 20 months) post-chemotherapy. The differentiation of specimens was assessed using the digital pathology software QuPath®, and then the relation between the FOXM1 or CHD4 expression and the differentiation and various other clinicopathological parameters was investigated. The histological type was epithelial in 19 cases (57.6%) and mixed epithelial and mesenchymal in 14 cases (42.4%). Nine cases had only a fetal component, 1 case had only an embryonal component, 22 cases had both fetal and embryonal components, and 1 case had no viable tumor. Both the FOXM1 and CHD4 immunoexpressions were found significantly more frequently in the embryonal than fetal components (p<0.0001 and p<0.0001, respectively). Regarding chemotherapy efficacy, the alpha-fetoprotein (AFP) level after chemotherapy was correlated with both the imaging shrinkage rate (R=-0.52) and histological residual rate (the percentage of the viable tumors of HB after chemotherapy)(R=0.62). High FOXM1 score was correlated with a high-postoperative AFP value (p<0.01) and a low AFP attenuation rate (p<0.05), but the FOXM1 score was not correlated with the imaging shrinkage rate (p=0.4418) or histological residual rate (p=0.4418). High CHD4 score showed a nonsignificant trend toward correlation with high postoperative AFP value (p=0.0849) and was not significantly correlated with the other parameters. Collectively, our results showed that FOXM1 expression may be useful in evaluating the response to CDDP-based chemotherapeutic regimens. Accurate measurement of FOXM1 expression by our scoring system using QuPath® is important in cases with mixed HB components of various differentiation levels.

Prognostic Role of Basal Serum Alpha-Fetoprotein in Patients with Hepatocellular Carcinoma Suitable for Curative Treatment.

Background and Objectives: Serum alpha-fetoprotein (AFP) is a recognized affordable oncological marker in patients with hepatocellular carcinoma (HCC). However, AFP's prognostic role has been assessed mainly after specific treatments, and no unanimously recognized cut-offs have been identified. The aim of this study is to investigate the prognostic role of different basal AFP cut-offs on survival and HCC course. Materials and Methods: In this single-center, retrospective study, all patients newly diagnosed with HCC between January 2009 and December 2021 were prospectively enrolled. Only patients suitable for curative HCC treatments were included in the analyses. Patients were stratified according to AFP cut-offs of 20, 200, 400, and 1000 ng/mL, which were correlated with survival outcomes and clinical parameters. Results: A total of 266 patients were analyzed, with a median follow-up time of 41.5 months. Median overall survival (OS) of all cohort was 43 months. At the multivariate Cox-regression analysis, AFP value ≥ 1000 ng/mL correlated with impaired OS (1-year OS: 67% vs. 88%, 5-year OS: 1% vs. 43%; p = 0.005); other risk factors were tumor dimension ≥ 5 cm (HR 1.73; p = 0.002), Child-Pugh class B-C (HR 1.72; p = 0.002), BCLC stage A (vs. 0) (HR 2.4; p = 0.011), and malignant portal vein thrombosis (HR 2.57; p = 0.007). AFP ≥ 1000 ng/mL was also associated with a reduced recurrence-free survival (HR 2.0; p = 0.038), while starting from AFP ≥ 20 ng/mL, a correlation with development of HCC metastases over time (HR 3.5; p = 0.002) was seen. AFP values ≥ 20 ng/mL significantly correlated with tumor size and higher histological grading; starting from AFP values ≥ 400 ng/mL, a significant correlation with Child-Pugh class B-C and female gender was also observed. Conclusions: Basal AFP correlates with relevant outcomes in patients with HCC. It could help identify patients at a higher risk of worse prognosis who might benefit from personalized surveillance and treatment programs. Prospective studies are needed to confirm these results.

PIVKA-II combined with alpha-fetoprotein for the diagnostic value of hepatic tumors in children: a multicenter, prospective observational study

BackgroundTo investigate whether protein induced by vitamin K antagonist-II (PIVKA-II) combined with alpha-fetoprotein (AFP) can improve the diagnostic and differential diagnostic accuracy of childhood hepatic tumors.MethodsA multi-center prospective observational study was performed at nine regional institutions around China. Children with hepatic mass (Group T) were divided into hepatoblastoma group (Group THB) and hemangioendothelioma group (Group THE), children with extrahepatic abdominal mass (Group C). Peripheral blood was collected from each patient prior to surgery or chemotherapy. The area under the curve (AUROC) was used to evaluate the diagnostic efficiency of PIVKA-II and the combined tumor markers with AFP.ResultsThe mean levels of PIVKA-II and AFP were both significantly higher in Group T than Group C (p = 0.001, p < 0.001), in Group THB than Group THE (p = 0.018, p = 0.013) and in advanced HB than non-advanced HB (p = 0.001, p = 0.021). For the diagnosis of childhood hepatic tumors, AUROC of PIVKA-II (cut-off value 32.6 mAU/mL) and AFP (cut-off value 120 ng/mL) was 0.867 and 0.857. The differential diagnostic value of PIVKA-II and AFP in hepatoblastoma from hemangioendothelioma was further assessed, AUROC of PIVKA-II (cut-off value 47.1mAU/mL) and AFP (cut-off value 560 ng/mL) was 0.876 and 0.743. The combined markers showed higher AUROC (0.891, 0.895 respectively) than PIVKA-II or AFP alone.ConclusionsThe serum level of PIVKA-II was significantly higher in children with hepatic tumors, especially those with malignant tumors. The combination of PIVKA-II with AFP further increased the diagnostic performance.Trial registrationClinical Trials, NCT03645655. Registered 20 August 2018, https://www.clinicaltrials.gov/ct2/show/NCT03645655.

Validation of Japanese indication criteria for deceased donor liver transplantation for hepatocellular carcinoma: Analysis of US national registry data.

The Japanese indication criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC) have been updated based on living donor LT data to include either the Milan criteria (MC) or the 5-5-500 rule, which requires a nodule size of ≤5cm, ≤5 nodules, and an alpha-fetoprotein (AFP) level ≤500ng/mL. We aimed to validate the 5-5-500 rule and the MC for deceased donor LT (DDLT). Using national registry data from the United States from 2010 to 2014, we separated DDLT patients into four groups based on the MC and the 5-5-500 rule. The AFP values were stratified into categories: ≤100, 101-300, 301-500, and >500ng/mL. The 5-year survival rate was significantly lower for patients in the groups within MC/beyond 5-5-500 (56.3%) or beyond MC/5-5-500 (60.7%) than for patients in the groups within MC/5-5-500 (76.2%) and beyond MC/within 5-5-500 (72.3%) (p<0.01). Hepatocellular carcinoma recurrence at 5years was highest for the within MC/beyond 5-5-500 (25.4%) group, followed by the beyond MC/within 5-5-500 (13.1%), beyond MC/5-5-500 (9.6%), and within MC/5-5-500 (7.4%) groups. The stratified 5-year survival rates after DDLT were 76.5%, 72.4%, 58.4%, and 55.6% in the AFP ≤100, 101-300, 301-500, and >500 categories, respectively (p<0.01). The 5-5-500 rule guides the appropriate selection of patients with HCC for DDLT. Patients with AFP levels from 300 to 500ng/mL had inferior outcomes even when they met the 5-5-500 rule, so further investigation is needed to guide their treatment.

Combination of serum alpha-fetoprotein, PIVKA-Ⅱ and glypican-3 in diagnosis of hepatocellular carcinoma: a meta-analysis.

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). 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. 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%CI: 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%CI: 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%CI: 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%CI: 9-67). The DOR of the combination of the three markers was significantly reduced to 10 (95%CI: 7-45). 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.

The Prognostic Value of Alpha-Fetoprotein Ratio in Patients With Resectable Alpha-Fetoprotein-Negative Hepatocellular Carcinoma.

This study aimed to investigate the prognostic value of alpha-fetoprotein (AFP) ratio in patients with AFP-negative hepatocellular carcinoma (HCC). We retrospectively analyzed 600 AFP-negative HCC patients who underwent hepatectomy. The AFP ratio was calculated as the ratio of AFP level 1week before surgery to the level 20-40days after hepatectomy. Immunohistochemistry assay was used to assess protein expression in HCC tissue. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). The study found that a cutoff value of 1.6ng/ml for AFP ratio, determined using X-tile software, was optimal for predicting prognosis. Patients with a high AFP ratio had a worse prognosis compare to those with a low AFP ratio (DFS, P = .026; OS, P = .034). Patients with a high AFP ratio had a worse prognosis compared to those with a low AFP ratio. Multivariate analysis revealed that AFP ratio >1.6, negative HepPar-1 expression, and vascular invasion were independent predictors of both DFS and OS. Vascular invasion had a higher area under the curve (AUC) than AFP ratio and HepPar-1 expression in predicting recurrence and death. The combination of AFP ratio, HepPar-1 expression, and vascular invasion provided better predictive accuracy for DFS and OS. The AFP ratio is a potential prognostic marker for AFP-negative HCC patients after hepatectomy. Combining the analysis of AFP ratio with HepPar-1 expression and vascular invasion can enhance the accuracy of predicting prognosis in these patients.

Spontaneous regression of hepatocellular carcinoma after severe acute respiratory syndrome coronavirus 2 vaccination:a case report

An 86-year-old male patient with sustained virological response of chronic hepatitis type C was diagnosed with hepatocellular carcinoma (HCC) in hepatic segment 3. He was treated with transcatheter arterial chemoembolization (TACE) and radiation therapy because the tumor was located at the edge of the liver and umbilical portion of the portal vein. The value of alpha-fetoprotein (AFP) which is a serological tumor marker decreased, and the tumor size did not increase;however, another tumor was recognized at S3 of the liver 15 months post-TACE. The patient underwent a second TACE, and computed tomography revealed HCC recurrence at S3, S8/4, and S1 of the liver 6 months later. The patient refused to undergo another treatment, but the AFP and Des-γ-carboxy prothrombin values and the tumor size decreased 3 months postrecurrence. Two months after multiple recurrences of HCC, he received the third dose of messenger RNA-based vaccine for severe acute respiratory syndrome coronavirus 2. Tumor regression may occur after an immune-inflammatory response induced by messenger RNA-based vaccine.

Valor clínico da alfafetoproteína na detecção de carcinoma mamário em cadelas

ABSTRACT This study aimed to assess the behavior of Alpha-Fetoprotein (AFP) in healthy female dogs, those with non-metastatic mammary carcinomas, and those with metastatic mammary carcinomas. Additionally, it aimed to evaluate serum levels concerning the clinical-pathological variables of diseased dogs. To achieve this, sera from 35 female dogs were utilized, divided into three groups: G1 (n=10), control group (dogs free of neoplasms); G2 (n=20), dogs with mammary carcinoma without lymph node metastasis; and G3 (n=5), dogs with mammary carcinoma with lymph node metastasis. AFP was measured through ELISA, and the results were assessed using the Tukey test with a significance level of 5% in terms of the marker's presence in the patient's serum, its relationship with the neoplasm's biological behavior, and the clinical-pathological alterations encountered. Additionally, sensitivity and specificity values were obtained to establish the clinical value of AFP as a serological marker. The results revealed that AFP values (p&lt;0.001) were significantly higher in dogs with mammary carcinoma compared to healthy dogs. Furthermore, there was a significant increase in AFP in non-spayed animals (p=0.0307). The marker demonstrated a sensitivity of 92% and specificity of 90% in distinguishing diseased animals from healthy ones. No relationship was found between the variables of tumor size, lymph node metastasis, histological grade, necrosis, ulceration, and inflammation with AFP (p&lt;0.05). The findings indicated that AFP is elevated in female dogs with mammary tumors and could be a promising marker for monitoring dogs with mammary neoplasms. Future studies that include patient follow-up will be necessary.

Diagnostic value of Midkine and AFP in the detection of hepatocellular carcinoma: A systematic review and meta-analysis.

Hepatocellular carcinoma (HCC) posed significant health problems and deaths. There are various challenges in the management of HCC, including the late detection or diagnosis. The ongoing diagnostic method in HCC also hinders the detection on the early stages of the disease, thus biomarkers need to be explored further for HCC detection. Serum alpha fetoprotein (AFP) and Midkine (MDK) are two proteins which might be the biomarker of choice in the detection of HCC. This meta-analysis aims to analyze the accuracy of Midkine and AFP in the detection of HCC. The systematic review and meta-analysis was conducted by adhering to the Preferred Reporting System for Systematic Review and Meta-Analysis (PRISMA) guidelines. We conduct literature screening and selection followed by quality assessment from various databases such as PubMed, MEDLINE, SpringerLink, ProQuest, EBSCOhost, Cochrane, and EMBASE. The included studies were then extracted and analyzed cumulatively using MedCalc and MetaDTA with forest plot and ROC curve as outcome. 12 studies were included in this study. The AFP biomarker yields sensitivity value of 62.5% (97.5% CI 0.442 - 0.778) and specificity value of 95% (97.5% CI 0.842 - 0.986), while the Midkine biomarker denotes sensitivity value of 91.6% (97.5% CI 0.83 - 0.961) and specificity value of 82.2% (97.5% CI 0.83 - 0.96). Both AFP and MDK are proven to be a good diagnostic tool or biomarker in the detection of HCC. The use of both in combination should provide high quality diagnostic marker for HCC suspected patients. Further studies on this should be conducted.

Predictive value of coagulation function, alpha-fetoprotein and placental growth factor in patients with perilous placenta previa

Predictive value of coagulation function, alpha-fetoprotein and placental growth factor in patients with perilous placenta previa

Correlation between Neutrophil-to-Lymphocyte Ratio and Diabetic Neuropathy in Chinese Adults with Type 2 Diabetes Mellitus Using Machine Learning Methods.

One of the most frequent consequences of diabetes mellitus has been identified as diabetic peripheral neuropathy (DPN), and numerous inflammatory disorders, including diabetes, have been documented to be reflected by the neutrophil-to-lymphocyte ratio (NLR). This study aimed to explore the correlation between peripheral blood NLR and DPN, and to evaluate whether NLR could be utilized as a novel marker for early diagnosis of DPN among those with type 2 Diabetes Mellitus (T2DM). We reviewed the medical records of 1154 diabetic patients treated at Tongji Hospital Affiliated to Tongji University from January 2022 to March 2023. These patients did not have evidence of acute infections, chronic inflammatory status within the past three months. The information included the clinical, laboratory, and demographic characteristics of the patient. Finally, a total of 442 T2DM individuals with reliable, complete, and accessible medical records were recruited, including 216 T2DM patients without complications (DM group) and 226 T2DM patients with complications of DPN (DPN group). One-way ANOVA and multivariate logistic regression were applied to analyze data from the two groups, including peripheral blood NLR values and other biomedical indices. The cohort was divided in a 7 : 3 ratio into training and internal validation datasets following feature selection and data balancing. Based on machine learning, training was conducted using extreme gradient boosting (XGBoost) and support vector machine (SVM) methods. K-fold cross-validation was applied for model assessment, and accuracy, precision, recall, F1-score, and the area under the receiver operating characteristic curve (AUC) were used to validate the models' discrimination and clinical applicability. Using Shapley Additive Explanations (SHAP), the top-performing model was interpreted. The values of 24-hour urine volume (24H UV), lower limb arterial plaque thickness (LLAB thickness), carotid plaque thickness (CP thickness), D-dimer and onset time were significantly higher in the DPN group compared to the DM group, whereas the values of urine creatinine (UCr), total cholesterol (TC), low-density lipoprotein (LDL), alpha-fetoprotein (AFP), fasting c-peptide (FCP), and nerve conduction velocity and wave magnitude of motor and sensory nerve shown in electromyogram (EMG) were considerably lower than those in the DM group (P < 0.05, respectively). NLR values were significantly higher in the DPN group compared to the DM group (2.60 ± 4.82 versus 1.85 ± 0.98, P < 0.05). Multivariate logistic regression analysis revealed that NLR (P = 0.008, C = 0.003) was a risk factor for DPN. The multivariate logistic regression model scores were 0.6241 for accuracy, 0.6111 for precision, 0.6667 for recall, 0.6377 for F1, and 0.6379 for AUC. Machine learning methods, XGBoost and SVM, built prediction models, showing that NLR can predict the onset of DPN. XGBoost achieved an accuracy of 0.6541, a precision of 0.6316, a recall of 0.7273, a F1 value of 0.6761, and an AUC value of 0.690. SVM scored an accuracy of 0.5789, a precision of 0.5610, a recall of 0.6970, an F1 value of 0.6216, and an AUC value of 0.6170. Our findings demonstrated that NLR is highly correlated with DPN and is an independent risk factor for DPN. NLR might be a novel indicator for the early diagnosis of DPN. XGBoost and SVM models have great predictive performance and could be reliable tools for the early prediction of DPN in T2DM patients. This trial is registered with ChiCTR2400087019.