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PloS One 2022To evaluate the clinical value of Aldo-keto reductase family 1 member B10 (AKR1B10) in the diagnosis and prognosis of hepatocellular carcinoma (HCC). (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the clinical value of Aldo-keto reductase family 1 member B10 (AKR1B10) in the diagnosis and prognosis of hepatocellular carcinoma (HCC).
METHODS
A search of the PubMed, China Biology Medicine, Cochrane, and Embase databases was performed to conduct meta-analyses to evaluate the accuracy of AKR1B10 in diagnosing HCC and to assess the impact on prognosis of patients after curative resection of HCC.
RESULTS
A total of 12 different cohorts from 11 studies including 2747 HCC patients and 2053 controls showed that the pooled specificity and the pooled sensitivity of AKR1B10 for the diagnosis of HCC were 0.78 (95% CI: 0.69-0.85) and 0.85 (95% CI: 0.77-0.90), respectively. The pooled sensitivity and specificity of serum AKR1B10 for the diagnosis of HCC were 0.80 (95% CI: 0.70-0.86) and 0.87 (95% CI: 0.77-0.93), respectively. The pooled sensitivity and specificity of AKR1B10 in malignant tumor tissue for the diagnosis of HCC were 0.78 (95% CI: 0.61-0.89) and 0.82 (95% CI: 0.69-0.90), respectively. The pooled sensitivity and specificity of AKR1B10 to distinguish HCC from benign liver disease were 0.71 (95% CI: 0.62-0.78) and 0.84 (95% CI: 0.77-0.89), respectively. The sensitivity and specificity of AKR1B10 combined with alpha fetoprotein (AFP) in the diagnosis of HCC were 0.84 (95% CI: 0.79-0.88) and 0.88 (95% CI: 0.73-0.95), respectively. The pooled sensitivity and specificity of AKR1B10 in malignant tumor tissue for the diagnosis of early-stage HCC were 0.85 (95% CI: 0.62-0.95) and 0.88 (95% CI: 0.81-0.93), respectively. A meta-analysis of five studies including 798 patients demonstrated that high AKR1B10 expression in liver malignant tumor was associated with better overall survival in patients with HCC after hepatectomy (HR = 0.54, 95% CI: 0.41-0.72, p < 0.001).
CONCLUSIONS
AKR1B10 exhibits a great clinical value in the diagnosis of HCC, especially for early-stage HCC, with excellent diagnostic accuracy. Furthermore, AKR1B10 expression can predict the prognosis of HCC patients after hepatic resection.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Aldo-Keto Reductases; Aldehyde Reductase; Biomarkers, Tumor
PubMed: 36584078
DOI: 10.1371/journal.pone.0279591 -
The Science of the Total Environment Feb 2023Cardiovascular disease (CVD) and cancer are collectively responsible for tens of millions of global deaths each year. These rates are projected to intensify as the... (Review)
Review
Cardiovascular disease (CVD) and cancer are collectively responsible for tens of millions of global deaths each year. These rates are projected to intensify as the COVID-19 pandemic has caused delays in individualized diagnostics, or exacerbated prevalence due to Post Acute Coronavirus (COVID-19) Syndrome. Wastewater-based epidemiology (WBE) has successfully been employed as a useful tool for generating population-level health assessments, and was examined here in this systematic scoping literature review to (i) identify endogenous human biomarkers reported to indicate CVD or cancer in clinical practice, (ii) assess specificity to the indicated diseases, (iii) evaluate the utility for estimating population-level disease prevalence in community wastewater, and (iv) contextualize the obtained information for monitoring CVD and cancer presence via WBE. A total of 48 peer-reviewed papers were critically examined identifying five urinary protein biomarkers: cardiac troponin I (cTnI) (heart attack/heart failure), cystatin C (atherosclerosis), normetanephrine (tumor presence), α-fetoprotein (prostate and liver cancer), and microtubule assisted serine/threonine kinase 4 (MAST4) (breast cancer). Next, urinary excretion information was utilized to predict biomarker concentrations extant in community wastewater, resulting in average healthy concentrations ranging from 0.02 to 1159 ng/L, and disease-indicating thresholds from 0.16 to 3041 ng/L. Finally, estimating prevalence-adjusted wastewater measurements was explored in order to assess community-level CVD and cancer presence utilizing U.S. reported prevalence rates. Results obtained suggest that WBE can serve as a viable tool in support of current methods for CVD and cancer assessment to reduce morbidities and mortalities worldwide.
Topics: Humans; Wastewater-Based Epidemiological Monitoring; Cardiovascular Diseases; Pandemics; COVID-19; Neoplasms; Microtubule-Associated Proteins; Protein Serine-Threonine Kinases
PubMed: 36370774
DOI: 10.1016/j.scitotenv.2022.160103 -
Journal of Pediatric Surgery Sep 2020The incidence of children developing recurrent sacrococcygeal teratoma (SCT) is 2-35%. Serum alpha-fetoprotein (AFP) is often used as a tumor marker for (malignant)...
BACKGROUND
The incidence of children developing recurrent sacrococcygeal teratoma (SCT) is 2-35%. Serum alpha-fetoprotein (AFP) is often used as a tumor marker for (malignant) recurrences of SCT and could potentially be used during routine follow-up after SCT resection. However, the diagnostic accuracy of serum AFP levels during follow-up has not been well established. Therefore, we aimed to systematically review the diagnostic accuracy of serum AFP levels in recurrent SCT.
METHODS
We queried Search Premier, COCHRANE Library, EMCARE, EMBASE, PubMed, ScienceDirect and Web of Science databases to identify studies regarding patients with SCT with follow-up using serum AFP levels postoperative. We estimated sensitivity and specificity of serum AFP levels.
RESULTS
Fifteen studies (613 patients, 121 recurrences) were included and these mainly described serum AFP levels in patients with recurrent SCT (n = 111); 83 (75%) patients with recurrent SCT had elevated serum AFP levels. A subgroup analysis of articles that measured serum AFP levels in all patients (n = 6, 136 patients, 14 recurrences) showed a sensitivity and specificity of 79% and 95%, respectively. The sensitivity of AFP levels to detect malignant recurrence was 96%.
CONCLUSION
Diagnostic accuracy of serum AFP levels to detect recurrent SCT seems promising, though sensitivity could be overestimated since serum AFP levels are mainly described in patients with elevated AFP levels or at recurrent SCT. Furthermore, serum AFP levels could be helpful to detect malignant recurrences.
TYPE OF STUDY
Systematic review of level 2-4 studies.
LEVEL OF EVIDENCE
Level 2-4 (mostly level 2).
Topics: Biomarkers, Tumor; Child; Humans; Neoplasm Recurrence, Local; Pelvic Neoplasms; Sacrococcygeal Region; Sensitivity and Specificity; Spinal Neoplasms; Teratoma; alpha-Fetoproteins
PubMed: 32376010
DOI: 10.1016/j.jpedsurg.2020.03.014 -
Frontiers in Oncology 2021We report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study...
OBJECTIVES
We report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study its main treatment methods, prognosis, and the relationship between prognosis and the serum alpha-fetoprotein (AFP) level before treatment.
METHODS
We report a 66-year-old male case who was diagnosed with locally advanced HAL with PIK3CA mutation and carried out a systematic literature search for HAL cases documented between 1981 and 2020. General patient information including case characteristics was extracted and summarized. The median OS (mOS) of HAL patients was determined using the KM survival curve. The Cox proportional hazards regression model was used to evaluate the effect of tumor size, location, and serum AFP value before treatment and radical surgery (RS) on the prognosis of patients.
RESULTS
A total of 46 studies including 51 HAL patients was included in our review. Our study revealed that 52.9% of tumors were located in the upper lobe of the right lung. The proportion of serum AFP-positive patients before treatment, early-stage patients (TNM stage I and II), and patients who had received surgery were 69.2%, 34.1%, and 40%, respectively. The mOS of HAL patients was 16.0 months. The 2-year and 5-year survival rates of the patients were 35.3% and 8.0%, respectively. In the subgroup analysis, the 2-year survival rate for patients who received RS was 62.5%, while for patients who were unable to undergo RS, it was only 12.5% ( = 0.009). The Cox proportional hazards regression model indicated that RS can significantly improve the prognosis of HAL patients ( = 0.011), although the location and size of tumor as well as the serum AFP value before treatment had no significant effect on their prognosis ( = 0.82, = 0.96, = 0.25).
CONCLUSIONS
HAL patients have a poor prognosis, and the survival benefits for patients receiving chemoradiotherapy or chemotherapy alone appear to be limited. We demonstrate statistically for the first time that pretreatment serum AFP values are not related to the prognosis of HAL patients and RS can significantly improve patient prognosis.
PubMed: 34422656
DOI: 10.3389/fonc.2021.702216 -
Frontiers in Genetics 2021The lack of an accurate biomarker in hepatocellular carcinoma (HCC) has hindered early detection, diagnosis, and treatment. Circular RNAs (circRNAs), which can be used...
The lack of an accurate biomarker in hepatocellular carcinoma (HCC) has hindered early detection, diagnosis, and treatment. Circular RNAs (circRNAs), which can be used as novel biomarkers in liquid biopsies, have been brought to light as a result of the advances in research on molecular biomarkers and the progression of genomic medicine. We conducted a meta-analysis of the diagnostic accuracy of serum/plasma circRNAs or the combination of circRNAs and α-fetoprotein (AFP) in HCC. We identified eight studies that met the inclusion/exclusion criteria from PubMed, Web of Science, EMBASE, and Cochrane Library databases. The data were pooled, and the sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) with 95% confidence intervals (CIs) were calculated. The areas under the summary receiver operator characteristic (SROC) curves (AUCs) were also calculated. The sensitivity of circRNAs was 0.82 (95% CI: 0.78-0.85), and the specificity was 0.82 (95% CI: 0.78-0.86). The sensitivity of AFP was 0.65 (95% CI: 0.61-0.68), and the specificity was 0.90 (95% CI: 0.85-0.93). The AUC was 0.89 (95% CI: 0.86-0.91) for circRNAs and 0.77 (95% CI: 0.74-0.81) for AFP. The sensitivity of the combination of circRNAs and AFP was 0.88 (95% CI: 0.84-0.92), specificity was 0.86 (95% CI: 0.80-0.91), and AUC was 0.94 (95% CI: 0.91-0.96). Additionally, a subgroup analysis was conducted based on the control groups used; the diagnostic accuracy was particularly high in the comparison of HCC vs. healthy controls. In summary, serum/plasma circRNAs are accurate biomarkers suitable for clinical use for detecting HCC, and the combination of circRNAs and AFP improved the diagnostic accuracy.
PubMed: 34659344
DOI: 10.3389/fgene.2021.722208 -
Journal of Gastrointestinal Cancer Jun 2023Hepatocellular carcinoma has a dismal prognosis, except in patients diagnosed early who are candidates for potentially curative therapies. Most HCC cases develop in... (Review)
Review
PURPOSE
Hepatocellular carcinoma has a dismal prognosis, except in patients diagnosed early who are candidates for potentially curative therapies. Most HCC cases develop in patients with chronic liver disease. Therefore, expert society guidelines recommend surveillance every 6 months with ultrasound with or without serum alpha-fetoprotein for high-risk patients. However, fewer than 20% of patients in the USA undergo appropriate surveillance.
METHODS
A systematic scoping review was performed with the objective of identifying barriers to screening among high-risk patients in the USA including mapping key concepts in the relevant literature, identifying the main sources and types of evidence available, and identifying gaps in the literature. A total of 43 studies published from 2007 to 2021 were included. Data were extracted and a conceptual framework was created.
RESULTS
Assessment of quantitative studies revealed poor surveillance rates, often below 50%. Three categories of barriers to surveillance were identified: patient-level, provider-level, and system-level barriers. Prevalent patient-level barriers included financial constraints, lack of awareness of surveillance recommendations, and scheduling difficulties. Common provider-level barriers were lack of provider awareness of guidelines for surveillance, difficulty accessing specialty resources, and time constraints in the clinic. System-level barriers included fewer clinic visits and rural/safety-net settings. Proposed interventions include improved patient/provider education, patient navigators, increased community/academic collaboration, and EMR-based reminders.
CONCLUSION
Based on these findings, there is a crucial need to implement and evaluate proposed interventions to improve HCC surveillance.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Prognosis; Ultrasonography; Early Detection of Cancer; Liver Cirrhosis
PubMed: 35879510
DOI: 10.1007/s12029-022-00851-x -
Liver Transplantation : Official... Dec 2022Patients with indeterminate liver nodules, classified as LR-3 and LR-4 observations per the Liver Imaging Reporting and Data System, are at risk of developing...
Clinical outcomes of patients with Liver Imaging Reporting and Data System 3 or Liver Imaging Reporting and Data System 4 observations in patients with cirrhosis: A systematic review.
Patients with indeterminate liver nodules, classified as LR-3 and LR-4 observations per the Liver Imaging Reporting and Data System, are at risk of developing hepatocellular carcinoma (HCC), but risk estimates remain imprecise. We conducted a systematic review of Ovid MEDLINE, EMBASE, and Cochrane databases from inception to December 2021 to identify cohort studies examining HCC incidence among patients with LR-3 or LR-4 observations on computed tomography (CT) or magnetic resonance imaging (MRI). Predictors of HCC were abstracted from each study, when available. Of 13 total studies, nine conducted LR-3 observation-level analyses, with the proportions of incident HCC ranging from 1.2% to 12.5% at 12 months and 4.2% to 44.4% during longer study follow-up. Among three studies with patient-level analyses, 8%-22.2% of patients with LR-3 lesions developed LR-4 observations and 11.1%-24.5% developed HCC. Among nine studies conducting LR-4 observation-level analyses, incident HCC ranged from 30.8% to 44.0% at 12 months and 30.9% to 71.0% during study follow-up; conversely, 6%-42% of observations were downgraded to LR-3 or lower. Patient-level factors associated with HCC included older age, male sex, higher alpha-fetoprotein levels, viral etiology, and prior history of HCC; observation-level factors included maximum diameter, threshold growth, T2 hyperintensity, and visibility on ultrasound. Studies were limited by small sample sizes, inclusion of patients with prior HCC, short follow-up duration, and failure to account for clustering of observations in patients or competing risks of transplantation and death. LR-3 and LR-4 observations have elevated but variable risks of HCC. Higher quality studies are necessary to identify high-risk patients who warrant close CT or MRI-based follow-up.
Topics: Humans; Male; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; Liver Transplantation; Liver Cirrhosis; Magnetic Resonance Imaging; Contrast Media; Sensitivity and Specificity
PubMed: 35980600
DOI: 10.1002/lt.26562 -
Value in Health : the Journal of the... May 2021Many economic evaluations of hepatocellular carcinoma (HCC) screenings have been conducted; however, these vary substantially with regards to screening strategies,...
OBJECTIVES
Many economic evaluations of hepatocellular carcinoma (HCC) screenings have been conducted; however, these vary substantially with regards to screening strategies, patient group, and setting. This review aims to report the current knowledge of the cost-effectiveness of screening and describe the published data.
METHODS
We conducted a search of biomedical and health economic databases up to July 2020. We included full and partial health economic studies if they evaluated the costs or outcomes of HCC screening strategies.
RESULTS
The review included 43 studies. Due to significant heterogeneity in key aspects across the studies, a narrative synthesis was conducted. Most studies reported using ultrasound or alpha fetoprotein as screening strategies. Screening intervals were mostly annual or biannual. Incidence, diagnostic performance, and health state utility values were the most critical parameters affecting the cost-effectiveness of screening. The majority of studies reported HCC screening to be cost-effective, with the biannual ultrasound + alpha fetoprotein standing out as the most cost-effective strategy. However, few studies considered the utilization rate, and none considered the diagnostic performance of ultrasound in the context of central adiposity. Computed tomography and magnetic resonance imaging were also evaluated, but its cost-effectiveness was still controversial.
CONCLUSIONS
Although many studies suggested HCC screening was cost-effective, substantial limitations of the quality of these studies means the results should be interpreted with caution. Future modeling studies should consider the impact of central adiposity on the precision of ultrasound, real-world utilization rates and projections of increased HCC incidence.
Topics: Carcinoma, Hepatocellular; Cost-Benefit Analysis; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Mass Screening; Quality-Adjusted Life Years; Tomography, X-Ray Computed; Ultrasonography; alpha-Fetoproteins
PubMed: 33933243
DOI: 10.1016/j.jval.2020.11.014 -
Therapeutic Advances in Medical Oncology 2021Hepatocellular carcinoma (HCC) is a highly recurrent tumor after resection and has been closely related to hypoxia. Hypoxia-inducible factors 1α and 2α (HIF-1α and...
BACKGROUND
Hepatocellular carcinoma (HCC) is a highly recurrent tumor after resection and has been closely related to hypoxia. Hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) have been shown to contribute to tumor progression and therapy resistance in HCC. We evaluated the prognostic and clinicopathological significance of HIF-1α and HIF-2α in HCC patients.
METHODS
We systematically searched Embase, Cochrane, PubMed, Scopus and Web of Science (WOS) from inception to 1 June 2020 for studies evaluating HIF-1α and/or HIF-2α expression in HCC. Selected articles evaluate at least one factor by immunohistochemistry (IHC) in HCC patients who underwent surgical resection, and its relationship with prognosis and/or clinicopathological features. Study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CDR42020191977). We meta-analyzed the data extracted or estimated according to the Parmar method employing STATA software. We evaluated the overall effect size for the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI), as well as heterogeneity across studies with the statistic and chi-square-based Q test. Moreover, we conducted subgroup analysis when heterogeneity was substantial. Publication bias was assessed by funnel plot asymmetry and Egger's test.
RESULTS
HIF-1α overexpression was correlated with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and clinicopathological features including Barcelona Clinic Liver Cancer (BCLC), capsule infiltration, intrahepatic metastasis, lymph node metastasis, tumor-node-metastasis (TNM), tumor differentiation, tumor number, tumor size (3 cm), vascular invasion and vasculogenic mimicry. We also detected a possible correlation of HIF-1α with alpha-fetoprotein (AFP), cirrhosis, histological grade, tumor size (5 cm) and albumin after subgroup analysis. Initially, only DFS/RFS appeared to be associated with HIF-2α overexpression. Subgroup analysis denoted that HIF-2α overexpression was related to OS and capsule infiltration.
CONCLUSIONS
HIF-1α and HIF-2α overexpression is related to poor OS, DFS/RFS and some clinicopathological features of HCC patients, suggesting that both factors could be useful HCC biomarkers.
PubMed: 33613697
DOI: 10.1177/1758835920987071 -
Clinical Gastroenterology and... Dec 2020Liquid biopsies, or blood samples, can be analyzed to detect circulating tumor cells (CTCs), cell-free DNA (cfDNA), and extracellular vesicles, which might identify... (Review)
Review
BACKGROUND & AIMS
Liquid biopsies, or blood samples, can be analyzed to detect circulating tumor cells (CTCs), cell-free DNA (cfDNA), and extracellular vesicles, which might identify patients with hepatocellular carcinoma (HCC) or help determine their prognoses. We performed a systematic review of studies of analyses of liquid biopsies from patients with HCC and their comparisons with other biomarkers.
METHODS
We performed a systematic review of original studies published before December 1, 2019. We included studies that compared liquid biopsies alone and in combination with other biomarkers for the detection of HCC, performed multivariate analyses of the accuracy of liquid biopsy analysis in determining patient prognoses, or evaluated the utility of liquid biopsy analysis in monitoring treatment response.
RESULTS
Our final analysis included 112 studies: 67 on detection, 46 on determining prognosis, and 25 on treatment monitoring or selection. Ten studies evaluated assays that characterized cfDNA for detection of HCC in combination with measurement of α-fetoprotein (AFP)-these studies found that the combined measurement of cfDNA and AFP more accurately identified patients with HCC than measurement of AFP alone. Six studies evaluated assays for extracellular vesicles and 2 studies evaluated assays for CTC in detection of HCC, with and without other biomarkers-most of these studies found that detection of CTCs or extracellular vesicles with AFP more accurately identified patients with HCC than measurement of AFP alone. Detection of CTCs before surgery was associated with HCC recurrence after resection in 13 of 14 studies; cfDNA and extracellular vesicles have been studied less frequently as prognostic factors. Changes in CTC numbers before vs after treatment more accurately identify patients with HCC recurrence than pretreatment counts alone, and measurements of cfDNA can identify patients with disease recurrence or progression before changes can be detected by imaging. We found little evidence that analyses of liquid biopsies can aid in the selection of treatment for HCC. Quality assessment showed risk of bias in studies of HCC detection and determination of prognosis.
CONCLUSIONS
In a systematic review of 112 studies of the accuracy of liquid biopsy analysis, we found that assays for CTCs and cfDNA might aid in determining patient prognoses and monitoring HCC, and assays for cfDNA might aid in HCC detection, but there is a risk of bias in these studies. Studies must be standardized before we can assess the clinical utility of liquid biopsy analysis in the detection and management of patients with HCC.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liquid Biopsy; Liver Neoplasms; Neoplasm Recurrence, Local; Prognosis; alpha-Fetoproteins
PubMed: 32289533
DOI: 10.1016/j.cgh.2020.04.019