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European Journal of Surgical Oncology :... Jun 2024To predict the early recurrence of HCC patients who received radical resection using preoperative variables based on Gd-EOB-DTPA enhanced MRI, followed by the comparison...
BACKGROUND
To predict the early recurrence of HCC patients who received radical resection using preoperative variables based on Gd-EOB-DTPA enhanced MRI, followed by the comparison with the postoperative model and clinical staging systems.
METHODS
One hundred and twenty-nine HCC patients who received radical resection were categorized into the early recurrence group (n = 48) and the early recurrence-free group (n = 81). Through COX regression analysis, statistically significant variables of laboratory, pathologic, and Gd-EOB-DTPA enhanced MRI results were identified. The preoperative and postoperative models were established to predict early recurrence, and the prognostic performances and differences were compared between the two models and clinical staging systems.
RESULTS
Six variables were incorporated into the preoperative model, including alpha-fetoprotein (AFP) level, aspartate aminotransferase/platelet ratio index (APRI), rim arterial phase hyperenhancement (rim APHE), peritumoral hypointensity on hepatobiliary phase (HBP), CER (tumor-to-liver SI ratio on hepatobiliary phase imaging), and ADC value. Moreover, the postoperative model was developed by adding microvascular invasion (MVI) and histological grade. The C-index of the preoperative model and postoperative model were 0.889 and 0.901 (p = 0.211) respectively. Using receiver operating characteristic curve analysis (ROC) and decision curve analysis (DCA), it was determined that the innovative models we developed had superior predictive capabilities for early recurrence in comparison to current clinical staging systems. HCC patients who received radical resection were stratified into low-, medium-, and high-risk groups on the basis of the preoperative and postoperative models.
CONCLUSION
The preoperative and postoperative MRI-based models built in this study were more competent compared with clinical staging systems to predict the early recurrence in hepatocellular carcinoma.
PubMed: 38870875
DOI: 10.1016/j.ejso.2024.108476 -
The British Journal of Radiology Jun 2024Microvascular invasion (MVI) is a recognized biomarker associated with poorer prognosis in patients with hepatocellular carcinoma (HCC). Dual-energy computed tomography...
OBJECTIVES
Microvascular invasion (MVI) is a recognized biomarker associated with poorer prognosis in patients with hepatocellular carcinoma (HCC). Dual-energy computed tomography (DECT) is a highly sensitive technique that can determine the iodine concentration (IC) in tumor and provide an indirect evaluation of internal microcirculatory perfusion. This study aimed to assess whether the combination of DECT with laboratory data can improve preoperative MVI prediction.
METHODS
This retrospective study enrolled 119 patients who underwent DECT liver angiography at two medical centers preoperatively. To compare DECT parameters and laboratory findings between MVI-negative and -positive groups, Mann-Whitney U test was used. Additionally, principal component analysis (PCA) was conducted to determine fundamental components. Mann-Whitney U test was applied to determine whether the PC scores varied across MVI groups. Finally, a general linear classifier was used to assess the classification ability of each principal component (PC) score.
RESULTS
Significant differences were noted (P < 0.05) in alpha fetoprotein (AFP) level, normalized arterial phase IC, and normalized portal phase IC between the MVI groups in the primary and validation datasets. The PC1-PC4 accounted for 67.9% of the variance in the primary dataset, with loadings of 24.1%, 16%, 15.4%, and 12.4%, respectively. In both primary and validation datasets, PC3 and PC4 were significantly different across MVI groups, with area under the curve values of 0.8410 and 0.8373, respectively.
CONCLUSIONS
The recombination of DECT iodine concentration and laboratory features based on varying factor loadings can well predict MVI preoperatively.
ADVANCES IN KNOWLEDGE
Utilizing principal component analysis, the amalgamation of Dual-energy computed tomography iodine concentration and laboratory features, considering diverse factor loadings, showed substantial promise in accurately classifying microvascular invasion. There have been limited endeavors to establish such a combination, offering a novel paradigm for comprehending data in related research endeavors.
PubMed: 38870535
DOI: 10.1093/bjr/tqae116 -
Mikrochimica Acta Jun 2024A novel construction strategy is introduced for an ultrasensitive dynamic light scattering (DLS) immunosensor targeting alpha fetoprotein (AFP). This approach relies...
A novel construction strategy is introduced for an ultrasensitive dynamic light scattering (DLS) immunosensor targeting alpha fetoprotein (AFP). This approach relies on a self-assembled heptamer fusion protein (A1-C4bpα), incorporating the dual functions of multivalent recognition and crosslinking aggregation amplification due to the presence of seven AFP-specific A1 nanobodies on the A1-C4bpα heptamer. Leveraging antibody-functionalized magnetic nanoparticles for target AFP capture and DLS signal output, the proposed heptamer-assisted DLS immunosensor offers high sensitivity, strong specificity, and ease of operation. Under the optimized conditions, the designed DLS immunosensor demonstrates excellent linear detection of AFP in the concentration range 0.06 ng mL to 512 ng mL, with a detection limit of 15 pg mL. The selectivity, accuracy, precision, practicability, and reliability of this newly developed method were further validated through an assay of AFP levels in spiked and actual human serum samples. This work introduces a novel approach for constructing ultrasensitive DLS immunosensors, easily extendable to the sensitive determination of other targets via simply replacing the nanobody sequence, holding great promise in various applications, particularly in disease diagnosis.
Topics: alpha-Fetoproteins; Humans; Limit of Detection; Immunoassay; Dynamic Light Scattering; Antibodies, Immobilized; Biosensing Techniques; Single-Domain Antibodies; Magnetite Nanoparticles
PubMed: 38869719
DOI: 10.1007/s00604-024-06437-7 -
Journal of Infection in Developing... May 2024Chronic HC leads to the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The treatment of chronic HC with DAAs reduces mortality from LC and...
INTRODUCTION
Chronic HC leads to the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The treatment of chronic HC with DAAs reduces mortality from LC and HCC. The study aimed to investigate the serological markers specific to HCC (PIVKA-II and AFP) in patients with chronic HC before and after DAA treatment.
METHODOLOGY
The study involved 35 HCV patients (mean age: 56.23 ± 1.45) divided into two groups. Group 1 included 15 HCV + HCC patients and Group 2 included 20 HCV non-HCC patients.
RESULTS
At the end of treatment all the patients were HCV RNA negative. Three months after the end of antiviral treatment, HCV RNA was undetectable in all patients, while a complete biochemical and virological response was observed in 66.7% of HCV + HCC patients and 85.0% of HCV non-HCC patients. PIVKA-II levels before the initiation of antiviral treatment were high in all patients. At the end of the treatment, in the HCV non-HCC group, normalization of PIVKA-II levels was observed only in 20.0% cases, and in 60.0% of cases 3 months after the treatment. Meanwhile, in patients with HCC and chronic HCV, PIVKA-II levels were within the normal range 3 months after treatment in only 13.3% of patients.
CONCLUSIONS
It is necessary to monitor HCV patients with cirrhosis (F4) and severe fibrosis (F3) without HCC, who have high PIVKA-II and AFP levels and/or ALT activity despite obtaining sustained virologic response 3 months after treatment with DAAs.
Topics: Humans; Hepatitis C, Chronic; Carcinoma, Hepatocellular; Antiviral Agents; Middle Aged; Male; Liver Neoplasms; Female; Biomarkers; alpha-Fetoproteins; Prothrombin; Liver Cirrhosis; Aged
PubMed: 38865409
DOI: 10.3855/jidc.18410 -
Journal of Hepatocellular Carcinoma 2024Portal vein tumor thrombosis (PVTT) is one of the hallmarks of advanced Hepatocellular carcinoma (HCC). Platelet (PLT) function parameters and CD8T cells (CD8Ts) play an...
PURPOSE
Portal vein tumor thrombosis (PVTT) is one of the hallmarks of advanced Hepatocellular carcinoma (HCC). Platelet (PLT) function parameters and CD8T cells (CD8Ts) play an important role in HCC progression and metastasis. This study is committed to establishing an efficient prognosis prediction model and exploring the combined effect of PLT and CD8Ts on PVTT prognosis.
PATIENTS AND METHODS
This retrospective study collected 932 HCC patients with PVTT from 2007 to 2017 and randomly divided them into a training cohort (n = 656) and a validation cohort (n = 276). We performed multivariable Cox and Elastic-net regression analysis, constructed a nomogram and used Kaplan-Meier survival curves to compare overall survival and progression-free survival rates in different substrata. Relationships between indicators involved were also analyzed.
RESULTS
We found tumor number, size, treatment, PLT, γ-glutamyl transferase, alpha-fetoprotein, mean platelet volume, and CD8Ts were related to the 5-year OS of patients with PVTT, and established a nomogram. The area under the receiver operating characteristic curve (AUCs) for predicting the 1-year OS rates were 0.767 and 0.794 in training and validation cohorts. The calibration curve and decision curve indicated its predictive consistency and strong clinical utility. We also found those with low PLT (<100*10^9/L) and high CD8Ts (>320 cells/μL) had a better prognosis.
CONCLUSION
We established a well-performing prognostic model for PVTT based on platelet functional parameters and CD8Ts, and found that PT-8 formed by PLT and CD8Ts was an excellent predictor of the prognosis of PVTT.
PubMed: 38863997
DOI: 10.2147/JHC.S452688 -
Annals of Surgery Jun 2024Describe the utility of circulating tumor DNA in the post-operative surveillance of hepatocellular carcinoma (HCC).
Tumor Mutational Burden from Circulating Tumor DNA Predicts Recurrence of Hepatocellular Carcinoma After Resection: An Emerging Biomarker for Surveillance: An Emerging Biomarker for Surveillance.
OBJECTIVE
Describe the utility of circulating tumor DNA in the post-operative surveillance of hepatocellular carcinoma (HCC).
SUMMARY BACKGROUND DATA
Current biomarkers for HCC like Alpha-fetoprotein (AFP) are lacking. ctDNA has shown promise in colorectal and lung cancers, but its utility in HCC remains relatively unknown.
METHODS
Patients with HCC undergoing curative-intent resection from 11/1/2020-7/1/2023 received ctDNA testing using the Guardant360 platform. TMB is calculated as the number of somatic mutations-per-megabase of genomic material identified.
RESULTS
Forty seven patients had post-operative ctDNA testing. Mean follow-up was 27 months and maximum was 43.2 months. Twelve patients (26%) experienced recurrence. Most (n=41/47, 87.2%) had identifiable ctDNA post-operatively; 55.3%(n=26) were TMB-not detected versus 45.7% (n=21) TMB-detectable. Post-operative identifiable ctDNA was not associated with RFS (P=0.518). Detectable TMB was associated with reduced RFS (6.9 vs. 14.7months, P=0.049). There was a higher rate of recurrence in patients with TMB (n=9/21, 42.9%, vs. n=3/26, 11.5%, P=0.02). Area-Under the Curve (AUC) for TMB-prediction of recurrence was 0.752 versus 0.550 for AFP. ROC-analysis established a TMB cut-off of 4.8mut/mB for predicting post-operative recurrence (P=0.002) and RFS (P=0.025). AFP was not correlated with RFS using the lab-normal cut-off (<11 ng/mL, P=0.682) or the cut-off established by ROC-analysis (>4.6 ng/mL, P=0.494). TMB-high was associated with poorer RFS on cox-regression analysis (HR=5.386, 95%CI1.109-26.160, P=0.037) while micro-vascular invasion (P=0.853) and AFP (P=0.439) were not.
CONCLUSIONS
Identifiable TMB on post-operative ctDNA predicts HCC recurrence, and outperformed AFP in this cohort. Perioperative ctDNA may be a useful surveillance tool following curative-intent hepatectomy. Larger-scale studies are needed to confirm this utility and investigate additional applications in HCC patients, including the potential for prophylactic treatment in patients with residual TMB after resection.
PubMed: 38860385
DOI: 10.1097/SLA.0000000000006386 -
American Journal of Cancer Research 2024Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare and aggressive subtype of gastric cancer associated with poor prognosis. This study aimed to investigate the...
Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare and aggressive subtype of gastric cancer associated with poor prognosis. This study aimed to investigate the recurrent metastatic patterns and prognostic factors in AFPGC patients undergoing radical surgical resection. Data from 241 AFPGC patients diagnosed between January 2017 and January 2020 who underwent surgical resection were analyzed across multiple centers. Recurrence patterns, metastatic sites, and survival outcomes were evaluated. Univariate and multivariate analyses were performed to identify risk factors for recurrent metastasis, overall survival (OS), and disease-free survival (DFS). There is an annual increase in the proportion of AFPGC cases, rising from 3.45% in 2017 to 7.88% in 2023. Higher serum AFP level was associated with increased likelihood of lymph node metastasis (P=0.006), deeper invasion depth (P=0.000) and greater tumor diameter (P=0.036). Independent predictors of recurrent metastasis included T4 infiltration, lymph node metastasis, tumor diameter >5 cm, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP levels. The 5-year OS and DFS rates were 36.5% and 34.2%, respectively, with poorer survival linked to higher preoperative AFP levels and postoperative increasing trend in AFP level. Independent risk factors for poor OS and DFS included T4 infiltration, lymph node metastasis, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP. Serum AFP level can serve as a potential predictive and prognostic biomarker. Identifying independent risk factors informs risk stratification and personalized treatment for AFPGC patients.
PubMed: 38859826
DOI: 10.62347/IIIO8739 -
ACS Applied Materials & Interfaces Jun 2024Polypyrrole (Ppy) is a biologically compatible polymer that is used as a matrix, in which drugs and enzymes can be incorporated by doping. Here, we suggest an inventive...
Polypyrrole (Ppy) is a biologically compatible polymer that is used as a matrix, in which drugs and enzymes can be incorporated by doping. Here, we suggest an inventive application of Ppy as a biorecognition film encapsulated with an antibody (Ab) as an alternative strategy for the on-site multistep functionalization of thiol-based self-assembled monolayers. The fabrication steps of the recognition films were followed by dropping pyrrole and Ab mixed solutions onto the electrode and obtaining a thin film by direct current electropolymerization. The efficiency of Ab immobilization was studied by using fluorescence microscopy and electrochemical (EC) methods. Finally, the Ab density was increased and immobilized in 1 min, and the sensing performance as an EC immunosensor was demonstrated using α-fetoprotein with a limit of detection of 3.13 pg/mL and sensing range from 1 pg/mL to 100 ng/mL. This study demonstrates the potential for electrochemical functionalization of biomolecules with high affinity and rapidity.
Topics: Pyrroles; Immunoassay; Polymers; Electrochemical Techniques; Antibodies, Immobilized; Biosensing Techniques; Polymerization; alpha-Fetoproteins; Electrodes; Limit of Detection; Humans
PubMed: 38857116
DOI: 10.1021/acsami.4c00730 -
Journal of Visualized Experiments : JoVE May 2024This study showcases a comprehensive treatment protocol for high-risk hepatocellular carcinoma (HCC) patients, focusing on the combined use of Y-90 transarterial...
This study showcases a comprehensive treatment protocol for high-risk hepatocellular carcinoma (HCC) patients, focusing on the combined use of Y-90 transarterial radioembolization (TARE) and Programmed Cell Death-1 (PD-1) inhibitors as neoadjuvant therapy. Highlighted through a case report, it offers a step-by-step reference for similar therapeutic interventions. A retrospective analysis was conducted on a patient who underwent hepatectomy following Y-90 TARE and PD-1 inhibitor treatment. Key demographic and clinical details were recorded at admission to guide therapy selection. Y-90 TARE suitability and dosage calculation were based on Technetium-99m (Tc-99m) macroaggregated albumin (MAA) perfusion mapping tests. Lesion coverage by Y-90 microspheres was confirmed through single photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging, and adverse reactions and follow-up outcomes were meticulously documented. The patient, with a 7.2 cm HCC in the right hepatic lobe (T1bN0M0, BCLC A, CNLC Ib) and an initial alpha-fetoprotein (AFP) level of 66,840 ng/mL, opted for Y-90 TARE due to high recurrence risk and initial surgery refusal. The therapy's parameters, including the lung shunting fraction (LSF) and non-tumor ratio (TNR), were within therapeutic limits. A total of 1.36 GBq Y-90 was administered. At 1 month post-therapy, the tumor shrank to 6 cm with partial necrosis, and AFP levels dropped to 21,155 ng/mL, remaining stable for 3 months. After 3 months, PD-1 inhibitor treatment led to further tumor reduction to 4 cm and AFP decrease to 1.84 ng/mL. The patient then underwent hepatectomy; histopathology confirmed complete tumor necrosis. At 12 months post-surgery, no tumor recurrence or metastasis was observed in follow-up sessions. This protocol demonstrates the effective combination of Y-90 TARE and PD-1 inhibitor as a bridging strategy to surgery for HCC patients at high recurrence risk, providing a practical guide for implementing this approach.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Neoadjuvant Therapy; Embolization, Therapeutic; Yttrium Radioisotopes; Male; Retrospective Studies; Immune Checkpoint Inhibitors; Middle Aged; Aged; Radiopharmaceuticals
PubMed: 38856215
DOI: 10.3791/66407 -
Neurology. Genetics Apr 2024This study investigates atypical late-onset ataxia-telangiectasia (AT) cases in a Korean family, diagnosed via Nanopore long-read sequencing, diverging from the typical...
OBJECTIVES
This study investigates atypical late-onset ataxia-telangiectasia (AT) cases in a Korean family, diagnosed via Nanopore long-read sequencing, diverging from the typical early childhood onset caused by biallelic pathogenic ATM variants.
METHODS
A 52-year-old Korean woman exhibiting dystonia and tremor, with a family history of similar symptoms in her older sister, underwent comprehensive tests including routine laboratory tests, neuropsychological assessments, and neuroimaging. Genetic analysis was conducted through targeted sequencing of 29 dystonia-associated genes and Nanopore long-read sequencing to assess the configuration of 2 gene variants.
RESULTS
Routine blood tests and brain imaging studies returned normal results, except for elevated α-fetoprotein levels. Neurologic examination revealed dystonia in the face, hand, and trunk, along with cervical dystonia in the proband. Her sister exhibited similar symptoms without evident telangiectasia. Genetic testing revealed 2 heterozygous pathogenic gene variants (p.Glu2014Ter and p.Glu2052Lys). Nanopore long-read sequencing confirmed these variants were in configuration, establishing a definite molecular diagnosis in the proband.
DISCUSSION
This report expands the known clinical spectrum of AT, highlighting a familial case of atypical AT. Moreover, it underscores the clinical utility of Nanopore long-read sequencing in phasing variant haplotypes, essential for diagnosing autosomal recessive disorders, especially beneficial for cases without parental samples.
PubMed: 38854973
DOI: 10.1212/NXG.0000000000200141