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Annals of Laboratory Medicine Jun 2024In recent decades, the analytical quality of clinical laboratory results has substantially increased because of collaborative efforts. To effectively utilize laboratory...
BACKGROUND
In recent decades, the analytical quality of clinical laboratory results has substantially increased because of collaborative efforts. To effectively utilize laboratory results in applications, such as machine learning through big data, understanding the level of harmonization for each test would be beneficial. We aimed to develop a quantitative harmonization index that reflects the harmonization status of real-world laboratory tests.
METHODS
We collected 2021-2022 external quality assessment (EQA) results for eight tests (HbA1c, creatinine, total cholesterol, HDL-cholesterol, triglyceride, alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], and prostate-specific antigen [PSA]). This EQA was conducted by the Korean Association of External Quality Assessment Service, using commutable materials. The total analytical error of each test was determined according to the bias% and CV% within peer groups. The values were divided by the total allowable error from biological variation (minimum, desirable, and optimal) to establish a real-world harmonization index (RWHI) at each level (minimum, desirable, and optimal). Good harmonization was arbitrarily defined as an RWHI value ≤ 1 for the three levels.
RESULTS
Total cholesterol, triglyceride, and CEA had an optimal RWHI of ≤ 1, indicating an optimal harmonization level. Tests with a desirable harmonization level included HDL-cholesterol, AFP, and PSA. Creatinine had a minimum harmonization level, and HbA1c did not reach the minimum harmonization level.
CONCLUSIONS
We developed a quantitative RWHI using regional EQA data. This index may help reflect the actual harmonization level of laboratory tests in the field.
PubMed: 38919008
DOI: 10.3343/alm.2024.0082 -
Asian Pacific Journal of Cancer... Jun 2024The aim of this study was to evaluate the expression profiles of PIWI-like protein- 2 (PIWIL2), and HepPar1 and their immunohistochemical (IHC) characteristics in...
OBJECTIVE
The aim of this study was to evaluate the expression profiles of PIWI-like protein- 2 (PIWIL2), and HepPar1 and their immunohistochemical (IHC) characteristics in Hepatocellular Carcinoma (HCC), and determine their correlation with clinicopathological parameters of this type of cancer to determine their diagnostic value in combination.
METHODS
Seventy-five patients with HCC were assessed for the expression of PIWIL2 in serum and tissue using real-time polymerase chain reaction (RT-PCR) and IHC was performed for PIWIL2 and HepPar1 was performed on all patients.
RESULTS
A statistically significantly higher level of PIWIL2 was found in HCC compared to controls (p≤0.001). Both HepPar1 and PIWIL2 were detected in 84% of HCC cases, the diagnostic and prognostic factors for PIWIL2 were found to be significant in liver tumour tissue samples and non-tumorous sections p<0.001, and the same was observed for serum samples and results of healthy serum controls (p<0.001) when compared to AFP.
CONCLUSION
Our results affirm the hypothesis that reactivation of PIWI expression in various caner types is crucial for cancer development, and that a possible panel maybe used for these markers HCC diagnosis.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Argonaute Proteins; Biomarkers, Tumor; Male; Female; Middle Aged; Prognosis; Case-Control Studies; Follow-Up Studies; Adult; alpha-Fetoproteins; Aged
PubMed: 38918675
DOI: 10.31557/APJCP.2024.25.6.2123 -
Testicular Mixed Germ Cell Tumor (TMGCT) Management: Addressing Infection and Tumor Marker Dynamics.Cureus May 2024We report the case of a 23-year-old male presenting with right testicular swelling, post-coital pain, and fever. Initial MRI and local examination suggested testicular...
We report the case of a 23-year-old male presenting with right testicular swelling, post-coital pain, and fever. Initial MRI and local examination suggested testicular carcinoma. Elevated serum alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) levels were observed. Biopsy confirmed a mixed germ cell tumor (MGCT). Concurrently, the patient was diagnosed with an infection and treated with antibiotics. Remarkably, following antibiotic therapy, fever resolved, and tumor marker levels significantly decreased. Subsequent orchidectomy confirmed the diagnosis of MGCT. This case underscores the importance of recognizing and treating concurrent infections, which may influence both clinical presentation and tumor marker levels in testicular germ cell tumors.
PubMed: 38915994
DOI: 10.7759/cureus.61062 -
Clinical Nuclear Medicine Jun 2024A 43-year-old man with chronic hepatitis B and elevated alpha-fetoprotein levels showed no malignant evidence on 18F-FDG PET/CT. However, subsequent assessment using...
A 43-year-old man with chronic hepatitis B and elevated alpha-fetoprotein levels showed no malignant evidence on 18F-FDG PET/CT. However, subsequent assessment using 68Ga-FAPI-04 PET/MR identified a lesion with increased FAPI uptake in the liver, coupled with detailed enhancement patterns on MRI, leading to a diagnosis of hepatocellular carcinoma, later confirmed by pathology. This case highlights the pivotal role of integrated 68Ga-FAPI-04 PET and enhanced MRI in refining hepatocellular carcinoma diagnostics, advancing a more nuanced imaging approach over conventional modalities for comprehensive evaluation of hepatic lesions.
PubMed: 38914096
DOI: 10.1097/RLU.0000000000005342 -
European Radiology Jun 2024To investigate the prognostic value of preoperative body composition and serum tumor markers (STM) in patients undergoing surgical treatment for colorectal cancer (CRC)...
OBJECTIVE
To investigate the prognostic value of preoperative body composition and serum tumor markers (STM) in patients undergoing surgical treatment for colorectal cancer (CRC) and to establish the prognostic score for patients with CRC.
METHODS
This study enrolled 365 patients (training set 245, validation set 120) with CRC who underwent surgical resection. The predictive value of various body composition features and STM for determining CRC prognosis were compared. A novel index score based on the independent risk factors from Cox regression for CRC patients was established and evaluated for its usefulness.
RESULTS
Multivariate Cox regression showed that low skeletal muscle radiodensity (SMD) (p = 0.020), low subcutaneous fat area (SFA) (p = 0.029), high carcinoembryonic antigen (CEA) (p = 0.008), and high alpha-fetoprotein (AFP) (p = 0.039) were all independent prognostic factors for poor overall survival (OS). The multifactorial analysis indicated that high intermuscular fat area (IMFA) (p = 0.033) and high CEA (p = 0.009) were independent prognostic factors for poor disease-free survival (DFS). Based on these findings, two scoring systems for OS and DFS were established in the training datasets. CRC patients who scored higher on the new scoring systems had lower OS and DFS (both p < 0.001) as shown in the Kaplan-Meier survival curves in the training and validation datasets.
CONCLUSION
In predicting the prognosis of CRC patients, SFA and SMD are superior to other body composition measurements. A scoring system based on body composition and STM can have prognostic value and clinical applicability.
CLINICAL RELEVANCE STATEMENT
This scoring system, combining body composition and serum tumor markers, may help predict postoperative survival of CRC patients and help clinicians make well-informed decisions regarding the treatment of patients.
KEY POINTS
Colorectal cancer prognosis can be related to body composition. High intermuscular fat area and CEA were independent prognostic factors for poor disease-free survival. This scoring system, based on body composition and tumor markers, can prognosticate for colorectal cancer patients.
PubMed: 38913246
DOI: 10.1007/s00330-024-10849-7 -
The Indian Journal of Radiology &... Jul 2024Accurate differentiation within the LI-RADS category M (LR-M) between hepatocellular carcinoma (HCC) and non-HCC malignancies (mainly intrahepatic cholangiocarcinoma...
Radiomics-Based Machine Learning Classification Strategy for Characterization of Hepatocellular Carcinoma on Contrast-Enhanced Ultrasound in High-Risk Patients with LI-RADS Category M Nodules.
Accurate differentiation within the LI-RADS category M (LR-M) between hepatocellular carcinoma (HCC) and non-HCC malignancies (mainly intrahepatic cholangiocarcinoma [CCA] and combined hepatocellular and cholangiocarcinoma [cHCC-CCA]) is an area of active investigation. We aimed to use radiomics-based machine learning classification strategy for differentiating HCC from CCA and cHCC-CCA on contrast-enhanced ultrasound (CEUS) images in high-risk patients with LR-M nodules. A total of 159 high-risk patients with LR-M nodules (69 HCC and 90 CCA/cHCC-CCA) who underwent CEUS within 1 month before pathologic confirmation from January 2006 to December 2019 were retrospectively included (111 patients for training set and 48 for test set). The training set was used to build models, while the test set was used to compare models. For each observation, six CEUS images captured at predetermined time points (T1, peak enhancement after contrast injection; T2, 30 seconds; T3, 45 seconds; T4, 60 seconds; T5, 1-2 minutes; and T6, 2-3 minutes) were collected for tumor segmentation and selection of radiomics features, which included seven types of features: first-order statistics, shape (2D), gray-level co-occurrence matrix, gray-level size zone matrix, gray-level run length matrix, neighboring gray tone difference matrix, and gray-level dependence matrix. Clinical data and key radiomics features were employed to develop the clinical model, radiomics signature (RS), and combined RS-clinical (RS-C) model. The RS and RS-C model were built using the machine learning framework. The diagnostic performance of these three models was calculated and compared. Alpha-fetoprotein (AFP), CA19-9, enhancement pattern, and time of washout were included as independent factors for clinical model (all < 0.05). Both the RS and RS-C model performed better than the clinical model in the test set (area under the curve [AUC] of 0.698 [0.571-0.812] for clinical model, 0.903 [0.830-0.970] for RS, and 0.912 [0.838-0.977] for the RS-C model; both < 0.05). Radiomics-based machine learning classifiers may be competent for differentiating HCC from CCA and cHCC-CCA in high-risk patients with LR-M nodules.
PubMed: 38912232
DOI: 10.1055/s-0043-1777993 -
The Oncologist Jun 2024The value of serum biomarkers, particularly alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), gains increasing attention in...
Prognostic significance of postoperative serological incomplete conversion of AFP and PIVKA-II after hepatic resection for hepatocellular carcinoma: a multicenter analysis of 1755 patients.
BACKGROUND
The value of serum biomarkers, particularly alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), gains increasing attention in prognostic evaluation and recurrence monitoring for patients with hepatocellular carcinoma (HCC). This study investigated the implications of serological incomplete conversion (SIC) of these 2 biomarkers as prognostic indicators for long-term outcomes after HCC resection.
METHODS
A multicenter observational study was conducted on a cohort of HCC patients presenting with AFP (>20 ng/mL) or PIVKA-II (>40 mAU/mL) positivity who underwent curative-intent resection. Based on their postoperative AFP and PIVKA-II levels at first postoperative follow-up (4~8 weeks after surgery), these patients were stratified into the serological incomplete conversion (SIC) and serological complete conversion (SCC) groups. The study endpoints were recurrence and overall survival (OS).
RESULTS
Among 1755 patients, 379 and 1376 were categorized as having SIC and SCC, respectively. The SIC group exhibited 1- and 5-year OS rates of 67.5% and 26.3%, with the corresponding recurrence rates of 53.2% and 79.0%, respectively; while the SCC group displayed 1- and 5-year OS rates of 95.8% and 62.5%, with the corresponding recurrence rates of 16.8% and 48.8%, respectively (both P < .001). Multivariate Cox regression analysis demonstrated that postoperative SIC was an independent risk factor for both increased recurrence (HR: 2.40, 95% CI, 2.04-2.81, P < .001) and decreased OS (HR: 2.69, 95% CI, 2.24-3.24, P < .001).
CONCLUSION
The results emphasize that postoperative incomplete conversion of either AFP or PIVKA-II is a significant prognostic marker, indicating a higher risk for adverse oncologic outcomes following HCC resection. This revelation has crucial implications for refining postoperative adjuvant therapy and surveillance strategies for HCC patients.
PubMed: 38907676
DOI: 10.1093/oncolo/oyae139 -
International Journal of Surgery... Jun 2024Alpha-fetoprotein (AFP) has been established as a biomarker for hepatocellular carcinoma (HCC); however, whether its dynamic changes could predict the response to...
BACKGROUND
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.
METHODS
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 (400 ng/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).
RESULTS
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.
CONCLUSION
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.
PubMed: 38905506
DOI: 10.1097/JS9.0000000000001860 -
Mikrochimica Acta Jun 2024The conventional electrochemical detection strategy for alpha-fetoprotein (AFP) is limited by the antigen-antibody (Ag-Ab) reactions and suffers from low sensitivity and...
Tetrahedral DNA-linked aptamer-antibody-based sandwich-type electrochemical sensor with Ag@Au core-shell nanoparticles as a signal amplifier for highly sensitive detection of α-fetoprotein.
The conventional electrochemical detection strategy for alpha-fetoprotein (AFP) is limited by the antigen-antibody (Ag-Ab) reactions and suffers from low sensitivity and poor reproducibility due to the inconsistency of Ab-modified electrodes. Herein, we designed and explored a sandwich-type electrochemical sensor for highly sensitive detection of AFP based on aptamer (Apt)-AFP-Ab interaction mode with silver@gold (Ag@Au) core-shell nanoparticles (NPs) as a signal amplifier. AuNPs were electrodeposited onto MXene (TiCT)-modified glassy carbon electrode (GCE) to get AuNPs/MXene/GCE and further used as the signal amplification substrate. The tetrahedral DNA-linked AFP aptamers were immobilized onto AuNPs/MXene/GCE surface via Au-S bonds and used as the sensing and recognition platform for AFP capturing. Ag@AuNPs with core-shell structures were synthesized, characterized, and bound with Ab as detection elements by catalyzing HO reduction. In the presence of AFP, a stable Apt-AFP-Ab sandwich structure was formed owing to the high affinities of aptamer and Ab toward the target AFP. The catalytic current produced by HO reduction increased linearly with the logarithm of AFP concentration from 5 × 10 ng/mL to 1 × 10 ng/mL, accompanied by a low detection limit (1.6 × 10 ng/mL). Moreover, the novel sandwich-type electrochemical sensor shows high sensitivity, outstanding selectivity, and promising performance in the analysis of actual samples, displaying a broad application prospect in bioanalysis.
Topics: alpha-Fetoproteins; Aptamers, Nucleotide; Gold; Metal Nanoparticles; Electrochemical Techniques; Silver; Limit of Detection; Humans; Biosensing Techniques; Hydrogen Peroxide; Electrodes; DNA
PubMed: 38904836
DOI: 10.1007/s00604-024-06485-z -
Frontiers in Oncology 2024The utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors...
Prognostic implications of preoperative, postoperative, and dynamic changes of alpha-fetoprotein and des-gamma (γ)-carboxy prothrombin expression pattern for hepatocellular carcinoma after hepatic resection: a multicenter observational study.
BACKGROUND
The utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated.
METHODS
From a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns.
RESULTS
Preoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers.
CONCLUSIONS
AFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies.
PubMed: 38903723
DOI: 10.3389/fonc.2024.1425292