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Cancers Apr 2023Hepatobiliary cancers are notoriously difficult to detect, frequently leading to diagnosis in later stages of disease when curative treatment is not an option. The... (Review)
Review
BACKGROUND
Hepatobiliary cancers are notoriously difficult to detect, frequently leading to diagnosis in later stages of disease when curative treatment is not an option. The currently used biomarkers such as AFP (alpha-fetoprotein) and CA19.9 lack sensitivity and specificity. Hence, there is an unmet need for an alternative biomarker.
AIM
To evaluate the diagnostic accuracy of volatile organic compounds (VOCs) for the detection of hepatobiliary and pancreatic cancers.
METHODS
A systematic review of VOCs' use in the detection of hepatobiliary and pancreatic cancers was performed. A meta-analysis was performed using the software R. Heterogeneity was explored through meta-regression analysis.
RESULTS
A total of 18 studies looking at 2296 patients were evaluated. Pooled sensitivity and specificity of VOCs for the detection of hepatobiliary and pancreatic cancer were 0.79 (95% CI, 0.72-0.85) and 0.81 (97.5% CI, 0.76-0.85), respectively. The area under the curve was 0.86. Meta-regression analysis showed that the sample media used contributed to heterogeneity. Bile-based VOCs showed the highest precision values, although urine and breath are preferred for their feasibility.
CONCLUSIONS
Volatile organic compounds have the potential to be used as an adjunct tool to aid in the early diagnosis of hepatobiliary cancers.
PubMed: 37190235
DOI: 10.3390/cancers15082308 -
International Journal of Molecular... Mar 2023This systematic review aimed to assess the prognostic significance of programmed cell death-ligand 1 (PDL-1) and programmed cell death protein 1 (PD-1) in hepatocellular... (Meta-Analysis)
Meta-Analysis Review
Navigating through the PD-1/PDL-1 Landscape: A Systematic Review and Meta-Analysis of Clinical Outcomes in Hepatocellular Carcinoma and Their Influence on Immunotherapy and Tumor Microenvironment.
This systematic review aimed to assess the prognostic significance of programmed cell death-ligand 1 (PDL-1) and programmed cell death protein 1 (PD-1) in hepatocellular carcinoma (HCC). Medline, EMBASE, and Cochrane Library database searches were conducted, revealing nine relevant cohort studies (seven PDL-1 and three PD-1). Our meta-analysis showed that PD-1/PDL-1 was a marker of poor survival, regardless of the assessment method (PD-1 overall survival (OS): hazard ratio (HR) 2.40; 95% confidence interval (CI), 1.30-4.42; disease-free survival (DFS): HR 2.12; 95% CI, 1.45-3.10; PDL-1: OS: HR 3.61; 95% CI, 2.75-4.75; and DFS: HR 2.74; 95% CI, 2.09-3.59). Additionally, high level of PD-1/PDL-1 expression was associated with aging, multiple tumors, high alpha-fetoprotein levels, and advanced Barcelona Clinic Liver Cancer stage. This high level significantly predicted a poor prognosis for HCC, suggesting that anti-PD-1 therapy is plausible for patients with HCC. Furthermore, HIF-1 induces PD-1 expression, and PD1SOCS3 is associated with a better prognosis. Taken together, combination therapy may be the key to effective immunotherapy. Thus, exploring other markers, such as HIF-1 and SOCS3, along with PD-1/PDL-1 immunotherapy, may lead to improved outcomes.
Topics: Humans; B7-H1 Antigen; Biomarkers, Tumor; Carcinoma, Hepatocellular; Immunotherapy; Ligands; Liver Neoplasms; Tumor Microenvironment; Programmed Cell Death 1 Receptor
PubMed: 37047482
DOI: 10.3390/ijms24076495 -
BMC Gastroenterology Mar 2023The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and cirrhosis. Besides, some papers showed that GP73 levels are correlated with liver fibrosis. This study conducts a meta-analysis to evaluate the value of GP73 in diagnosing HCC and differential diagnosing HCC from liver cirrhosis.
METHODS
36 studies with a sample size of 8314 cases concerning the accuracy of GP73 in the diagnosis of HCC were selected through a systematic review. Seven of these studies included a total of 438 HCC samples and 426 cirrhosis samples and calculated the sensitivity and specificity of GP73 for differential diagnosing HCC from cirrhosis. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. Statistical analyses were performed using StataSE16 software.
RESULTS
The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve were 0.79(95%CI 0.74-0.83),0.85(95%CI 0.80-0.89),5.4(95%CI 3.8-7.5), 0.25(95%CI 0.20-0.31), 22(95%CI 13-35), and 0.88 for GP73 diagnosing HCC;0.74(95%CI 0.64-0.81),0.70(95%CI 0.49-0.85),2.40(95%CI 1.3-4.7),0.38(95%CI 0.23-0.61),6(95%CI 2-19), and 0.78 for GP73 differential diagnosing HCC from liver cirrhosis.
CONCLUSION
The results suggest that GP73 has a high diagnostic value for HCC and a moderate value for differential diagnosis of HCC from liver cirrhosis.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Membrane Proteins; Liver Cirrhosis; Fibrosis; Biomarkers, Tumor
PubMed: 36964524
DOI: 10.1186/s12876-023-02685-8 -
Diagnostics (Basel, Switzerland) Feb 2023the early diagnosis of hepatocellular carcinoma (HCC) benefits from the use of alpha-fetoprotein (AFP) together with imaging diagnosis using abdominal ultrasonography,...
BACKGROUND AND OBJECTIVES
the early diagnosis of hepatocellular carcinoma (HCC) benefits from the use of alpha-fetoprotein (AFP) together with imaging diagnosis using abdominal ultrasonography, CT, and MRI, leading to improved early detection of HCC. A lot of progress has been made in the field, but some cases are missed or late diagnosed in advanced stages of the disease. Therefore, new tools (serum markers, imagistic technics) are continually being reconsidered. Serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA II) diagnostic accuracy for HCC (global and early disease) has been investigated (in a separate or cumulative way). The purpose of the present study was to determine the performance of PIVKA II compared to AFP.
MATERIALS AND METHODS
systematic research was conducted in PubMed, Web of Science, Embase, Medline and the Cochrane Central Register of Controlled Trials, taking into consideration articles published between 2018 and 2022.
RESULTS
a total number of 37 studies (5037 patients with HCC vs. 8199 patients-control group) have been included in the meta-analysis. PIVKA II presented a better diagnostic accuracy in HCC diagnostic vs. alpha-fetoprotein (global PIVKA II AUROC 0.851 vs. AFP AUROC 0.808, respectively, 0.790 vs. 0.740 in early HCC cases). The conclusion from a clinical point of view, concomitant use of PIVKA II and AFP can bring useful information, added to that brought by ultrasound examination.
PubMed: 36899960
DOI: 10.3390/diagnostics13050816 -
Liver Cancer Feb 2023Sorafenib was historically the standard of care for advanced hepatocellular carcinoma (aHCC) until it was superseded by the combination of atezolizumab and bevacizumab....
INTRODUCTION
Sorafenib was historically the standard of care for advanced hepatocellular carcinoma (aHCC) until it was superseded by the combination of atezolizumab and bevacizumab. Thereafter, several novel first-line combination therapies have demonstrated favorable outcomes. The efficacies of these treatments in relation to current and previous standards of care are unknown, necessitating an overarching evaluation.
METHODS
A systematic literature search was conducted on PubMed, EMBASE, Scopus, and the Cochrane Controlled Register of Trials for phase III randomized controlled trials investigating first-line systemic therapies for aHCC. Kaplan-Meier curves for overall survival (OS) and progression-free survival (PFS) were graphically reconstructed to retrieve individual patient-level data. Derived hazard ratios (HRs) for each study were pooled in a random-effects network meta-analysis (NMA). NMAs were also conducted using study-level HRs for various subgroups, according to viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion, and extrahepatic spread. Treatment strategies were ranked using scores.
RESULTS
Among 4,321 articles identified, 12 trials and 9,589 patients were included for analysis. Only two therapies showed OS benefit over sorafenib: combined anti-programmed-death and anti-VEGF pathway inhibitor monoclonal antibodies (Anti-PD-(L)1/VEGF Ab), including atezolizumab-bevacizumab and sintilimab-bevacizumab biosimilar (HR = 0.63, 95% CI = 0.53-0.76) and tremelimumab-durvalumab (HR = 0.78, 95% CI = 0.66-0.92). Anti-PD-(L)1/VEGF Ab showed OS benefit over all other therapies except tremelimumab-durvalumab. Low heterogeneity ( = 0%) and inconsistency (Cochran's = 0.52, = 0.773) was observed. scores for OS ranked Anti-PD-(L)1/VEGF Ab as the best treatment in all subgroups, except hepatitis B where atezolizumab-cabozantinib ranked highest for both OS and PFS, as well as nonviral HCC and AFP ≥400 μg/L where tremelimumab-durvalumab ranked highest for OS.
CONCLUSION
This NMA supports Anti-PD-(L)1/VEGF Ab as the first-line therapy for aHCC and demonstrates a comparable benefit for tremelimumab-durvalumab which also extends to certain subgroups. Results of the subgroup analysis may guide treatment according to baseline characteristics, while pending further studies.
PubMed: 36872922
DOI: 10.1159/000526639 -
Journal of Clinical Medicine Jan 2023Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its... (Review)
Review
Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its diagnostic ability has been validated in different populations with a wide variation. Therefore, we conducted a meta-analysis to investigate its overall diagnostic performance in differentiating HCC in chronic liver diseases. Methods Eligible studies were searched in the , , , , , and databases by 29 May 2022. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals (CI) were estimated. Results Fifteen original studies (comprising 19,021 patients) were included. For detecting any-stage HCC, GALAD score yielded an excellent ability, with pooled sensitivity, specificity, and AUC of 0.82 (95%CI: 0.78-0.85), 0.89 (95%CI: 0.85-0.91), and 0.92 (95%CI: 0.89-0.94), respectively. Notably, further analyses demonstrated a good diagnostic accuracy of GALAD score for identifying Barcelona Clinic Liver Cancer staging (BCLC) 0/A HCC, with a moderate sensitivity (0.73 (95%CI: 0.66-0.79)) and a high specificity (0.87 (95%CI: 0.81-0.91)); by contrast, only 38% of early-stage patients can be identified by alpha-fetoprotein, with an AUC value of 0.70 (95%CI: 0.66-0.74). Following subgroup analyses based on different HCC etiologies, higher sensitivities and AUC values were observed in subgroups with hepatitis C or non-viral liver diseases. For detecting BCLC 0/A HCC in the cirrhotic population, GALAD score had a pooled sensitivity, specificity, and AUC of 0.78 (95%CI: 0.66-0.87), 0.80 (95%CI: 0.72-0.87), and 0.86 (95%CI: 0.83-0.89). Conclusions We highlighted the superior diagnostic accuracy of GALAD score for detecting any-stage HCC with a high sensitivity and specificity, especially for early-stage HCC, with a relatively stable diagnostic performance. The addition of GALAD score into ultrasound surveillance may identify more HCC patients. Our findings imply the robust power of the GALAD score as a HCC screening or diagnostic tool, and it should be further validated by more studies with high quality.
PubMed: 36769597
DOI: 10.3390/jcm12030949 -
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 -
Pituitary Feb 2023In the past few decades, acromegaly and colonic polyps have been associated with an increased risk of colorectal cancer. Previous studies highlighted the importance of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
In the past few decades, acromegaly and colonic polyps have been associated with an increased risk of colorectal cancer. Previous studies highlighted the importance of serum biomarkers of colonic polyps in patients with acromegaly.
METHODS
We reviewed studies on serum biomarkers of colonic polyps in patients with acromegaly, published on PubMed, Embase, Cochrane Library, Medline, and Chinese databases from January 1, 1966, to May 8, 2022. Meta-analysis and systematic review were conducted using Stata MP 14.0.
RESULTS
Eight articles were included in this study. The mean (standard deviation) concentrations of serum biomarkers for acromegaly with and without colorectal polyps were extracted from these studies. Meta-analysis results showed that, compared to patients without colonic polyps, the levels of insulin-like growth factor-1 × upper limit of normal range (IGF-1 × ULN) and fasting insulin were significantly increased; while the levels of growth hormone (GH) were significantly decreased in patients with acromegaly and colonic polyps (IGF-1 × ULN: SMD 0.23; 95% CI 0.03-0.42, p < 0.05) (fasting insulin: SMD 0.95; 9 5% CI 0.11-1.8, p < 0.05) (GH: SMD - 0.25; 95% CI - 0.41 to - 0.08, p < 0.05). IGF-1 and FPG levels did not differ significantly (IGF-1: SMD -0.03; 95% CI - 0.22 to 0.17, p > 0.05) (FPG: SMD 0.14; 95% CI - 0.23 to 0.52, p > 0.05). The systematic review results suggest no significant differences in hemoglobin A1C, TSH, free thyroxine, FT4, T3, PRL, total cholesterol, HDL, LDL, fibrinogen, clathrate antigen, serum antigen 19-9, and α-fetoprotein levels, but serum Klotho levels.
CONCLUSION
We present the first meta-analysis and systematic review of serum biomarkers in patients with acromegaly or colonic polyps. The prevalence of colonic lesion polyps, is associated with higher IGF-1 × ULN levels, higher insulin levels in acromegaly. Further research is required to confirm GH and serum soluble Klotho levels as biomarkers of colonic polyps. When IGF-1 × ULN, fasting insulin levels change in patients with acromegaly, the occurrence of colonic polyps should be monitored. Early detection may reduce the possibility of developing malignant colon neoplasms.
Topics: Humans; Acromegaly; Colonic Polyps; Insulin-Like Growth Factor I; Growth Hormone; Human Growth Hormone; Insulin; Biomarkers
PubMed: 36542278
DOI: 10.1007/s11102-022-01287-z -
Expert Review of Gastroenterology &... Jan 2023The prognostic value of alpha-fetoprotein (AFP) response for efficacy of targeted therapy or immune checkpoint inhibitors (ICIs) has not been established. The purpose of... (Meta-Analysis)
Meta-Analysis
Early alpha-fetoprotein response predicts prognosis of immune checkpoint inhibitor and targeted therapy for hepatocellular carcinoma: a systematic review with meta-analysis.
BACKGROUND
The prognostic value of alpha-fetoprotein (AFP) response for efficacy of targeted therapy or immune checkpoint inhibitors (ICIs) has not been established. The purpose of this meta-analysis is to elucidate the relationship between AFP response and survival outcomes in hepatocellular carcinoma (HCC) patients who received targeted therapy or ICIs.
METHODS
The hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the relationship between AFP response and overall survival (OS)/progression-free survival (PFS).
RESULTS
Twenty-six articles containing 3056 HCC patients were finally included in the study. The pooled results showed that after targeted therapy or ICIs, patients with decrease in AFP had better prognosis (OS:HR = 0.48, 95%CI:0.40-0.56; PFS:HR = 0.39, 95%CI:0.33-0.46), while patients with increase in AFP had worse prognosis (OS:HR = 2.30, 95%CI:1.82-2.89; PFS:HR = 2.34, 95%CI = 1.69-3.24). Subgroup analysis revealed that compared to AFP decrease >50%, AFP decrease >20% can better predict the prognosis of patients who received targeted therapy (OS:HR = 0.51, 95%CI:0.41-0.62; PFS:HR = 0.39, 95%CI:0.30-0.51) or ICIs treatment (OS:HR = 0.34, 95%CI:0.16-0.71; PFS:HR = 0.22, 95%CI:0.10-0.47), and 8 weeks after targeted therapy may be the appropriate time point for AFP assessment.
CONCLUSION
AFP decrease >20% within 8 weeks may be the appropriate definition for early AFP response which probably works best in predicting the efficacy of therapy.
REGISTRATION
The review was not registered.
Topics: Humans; alpha-Fetoproteins; Carcinoma, Hepatocellular; Immune Checkpoint Inhibitors; Liver Neoplasms; Prognosis
PubMed: 36476076
DOI: 10.1080/17474124.2022.2156859 -
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