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EBioMedicine Jul 2023Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently...
BACKGROUND
Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently validated, and some results are contradictory. We provided a comprehensive evaluation of various types of cfRNA biomarkers and a full mining of the biomarker potential of new features of cfRNA.
METHODS
We first systematically reviewed reported cfRNA biomarkers and calculated dysregulated post-transcriptional events and cfRNA fragments. In 3 independent multicentre cohorts, we further selected 6 cfRNAs using RT-qPCR, built a panel called HCCMDP with AFP using machine learning, and internally and externally validated HCCMDP's performance.
FINDINGS
We identified 23 cfRNA biomarker candidates from a systematic review and analysis of 5 cfRNA-seq datasets. Notably, we defined the cfRNA domain to describe cfRNA fragments systematically. In the verification cohort (n = 183), cfRNA fragments were more likely to be verified, while circRNA and chimeric RNA candidates were neither abundant nor stable as qPCR-based biomarkers. In the algorithm development cohort (n = 287), we build and test the panel HCCMDP with 6 cfRNA markers and AFP. In the independent validation cohort (n = 171), HCCMDP can distinguish HCC patients from control groups (all: AUC = 0.925; CHB: AUC = 0.909; LC: AUC = 0.916), and performs well in distinguishing early-stage HCC patients (all: AUC = 0.936; CHB: AUC = 0.917; LC: AUC = 0.928).
INTERPRETATION
This study comprehensively evaluated full-spectrum cfRNA biomarker types for HCC detection, highlighted the cfRNA fragment as a promising biomarker type in HCC detection, and provided a panel HCCMDP.
FUNDING
National Natural Science Foundation of China, and The National Key Basic Research Program (973 program).
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Cell-Free Nucleic Acids; Biomarkers, Tumor; ROC Curve; MicroRNAs
PubMed: 37315449
DOI: 10.1016/j.ebiom.2023.104645 -
Acta Obstetricia Et Gynecologica... Apr 2024Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor and typically develops in the context of chronic liver disease, such as liver cirrhosis... (Review)
Review
INTRODUCTION
Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor and typically develops in the context of chronic liver disease, such as liver cirrhosis or chronic hepatitis B virus infection. Ultrasound evaluation, CT scan, and MRI are used to detect HCC. α-fetoprotein (AFP) is a common marker used to detect HCC in the non-pregnant population, which notoriously increases in pregnant women in relation to gestational age. Treatment is driven by the extent of the disease and the severity of underlying liver disease. Pregnancy may represent an obstacle to diagnosis and appropriate treatment of HCC. The aim of this descriptive systematic review was to describe the clinical features and maternal and neonatal outcomes of HCC in pregnancy.
MATERIAL AND METHODS
We performed a systematic review of the literature about HCC diagnosed in pregnancy and the postpartum period, with signs or symptoms arising in pregnancy. We included case reports and case series describing the clinical features of women diagnosed with HCC, fibrolamellar variant of HCC, and mixed HCC and cholangiocarcinoma during pregnancy or the postpartum period (with onset of symptoms during pregnancy), from inception to March 2023. The study protocol was registered with the PROSPERO database (Registration number: ID CRD42021275584).
RESULTS
We identified 180 records. The articles included in this systematic review were 47 case reports and 5 case series, for a total of 63 pregnancies. The two most frequent predisposing conditions were hepatitis B virus infection (30/63; 47%) and liver cirrhosis (14/63; 22%). Ultrasound evaluation was the most used technique to detect HCC. AFP was higher than normal in 28/46 patients tested (61%). Surgical treatment was the most used therapy, both during pregnancy and after delivery. Twenty-six patients (26/63; 42%) died within 6 months of diagnosis. Survival >24 months was 9% (4/46) in symptomatic and 29% (5/17) in asymptomatic women. No patient with cirrhotic liver survived more than 12 months. Thirty-eight newborns were alive at 28 days of age (38/63; 61%).
CONCLUSIONS
Hepatocellular carcinoma in pregnancy is associated with a high risk of maternal and neonatal mortality. Diagnosis in asymptomatic high-risk women or following abnormal maternal serum AFP screening is associated with better maternal outcomes.
Topics: Infant, Newborn; Humans; Female; Pregnancy; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Hepatitis B, Chronic; Liver Cirrhosis
PubMed: 37533304
DOI: 10.1111/aogs.14640 -
Frontiers in Immunology 2023To identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis.... (Meta-Analysis)
Meta-Analysis
Development and validation of prognostic risk prediction models for hepatocellular carcinoma patients treated with immune checkpoint inhibitors based on a systematic review and meta-analysis of 47 cohorts.
OBJECTIVE
To identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis. And to construct prediction models to aid in the prediction and improvement of prognosis.
METHODS
We searched PubMed, Embase, Web of Science and Cochrane Library for relevant studies from inception to March 29, 2023. After completing literature screening and data extraction, we performed meta-analysis, sensitivity analysis, and subgroup analysis to identify risk factors associated with OS and PFS. Using the pooled hazard ratio value for each risk factor, we constructed prediction models, which were then validated using datasets from 19 centers in Japan and two centers in China, comprising a total of 204 patients.
RESULTS
A total of 47 studies, involving a total of 7649 ICI-treated HCC patients, were included in the meta-analysis. After analyzing 18 risk factors, we identified AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number, vascular invasion and combination therapy as predictors for OS prediction model, while AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number and vascular invasion were selected as predictors for PFS model. To validate the models, we scored two independent cohorts of patients using both prediction models. Our models demonstrated good performance in these cohorts. In addition, in the pooled cohort of 204 patients, Our models also showed good performance with area under the curve (AUC) values of 0.712, 0.753, and 0.822 for the OS prediction model at 1-year, 2-year, and 3-year follow-up points, respectively, and AUC values of 0.575, 0.749 and 0.691 for the PFS prediction model Additionally, the calibration curve, decision curve analysis, and Kaplan-Meier curves in the pooled cohort all supported the validity of both models.
CONCLUSION
Based on the meta-analysis, we successfully constructed the OS and PFS prediction models for ICI-treated HCC patients. We also validated the models externally and observed good discrimination and calibration. The model's selected indicators are easily obtainable, making them suitable for further application in clinical practice.
Topics: Humans; Carcinoma, Hepatocellular; Prognosis; Immune Checkpoint Inhibitors; Liver Neoplasms; alpha-Fetoproteins
PubMed: 37520554
DOI: 10.3389/fimmu.2023.1215745 -
Updates in Surgery Dec 2023Anal fistula (AF) is a common disease with high prevalence and surgical operations are effective treatments in clinical work. There exist many well-known surgical... (Meta-Analysis)
Meta-Analysis Review
Anal fistula (AF) is a common disease with high prevalence and surgical operations are effective treatments in clinical work. There exist many well-known surgical techniques treating complex anal fistula (CAF), however, none is ideal. To compare the superiority of Anal fistula plug (AFP) and Endoanal advancement flap repair (EAFR) for complex anal fistula. We searched worldwide databases including Pubmed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and SinoMed from their inception to March 2023. Studies comparing the outcomes of AFP and EAFR were included according to the PICO principles. The indicators of the healing rate, recurrence rate, wound infection rate, and complication rate, et al. were extracted and compared between different surgical methods. 5 RCTS and 7 non-RCTs were included in the meta-analysis with a total of 847 patients (341 patients conducted with AFP and 506 patients with EAFR). By combining the total effect of the 12 articles, we found that there was a statistical difference reporting the healing rate of AFP 48.3% and EAFR 64.4% treating the CAF (OR 0.68, 95% CI 0.30,1.55, P = 0.03), and EAFR has a better healing rate. However, there was no significant difference in terms of the recurrence rate (OR 1.68, 95% CI 0.80,3.54, P = 0.17), the wound infection rate (OR 1.82, 95% CI 0.95,3.52, P = 0.07), and the complication rate (OR 1.06, 95% CI 0.70,1.61, P = 0.77) either in the 12 articles or in the subgroup. The meta-analysis indicated that the EAFR was superior to AFP in terms of the healing rate treating the CAF, however, there were no significant differences between the two groups when it came to the recurrence rate, the wound infection rate, and the complication rate. EAFR might be one initial treatment for the complex cryptoglandular anal fistulas compared with AFP.
Topics: Humans; alpha-Fetoproteins; Rectal Fistula; Treatment Outcome; Surgical Flaps; Fecal Incontinence; Wound Infection; Anal Canal
PubMed: 37882975
DOI: 10.1007/s13304-023-01674-6 -
Frontiers in Artificial Intelligence 2023Hepatocellular carcinoma is a malignant neoplasm of the liver and a leading cause of cancer-related deaths worldwide. The multimodal data combines several modalities,...
BACKGROUND
Hepatocellular carcinoma is a malignant neoplasm of the liver and a leading cause of cancer-related deaths worldwide. The multimodal data combines several modalities, such as medical images, clinical parameters, and electronic health record (EHR) reports, from diverse sources to accomplish the diagnosis of liver cancer. The introduction of deep learning models with multimodal data can enhance the diagnosis and improve physicians' decision-making for cancer patients.
OBJECTIVE
This scoping review explores the use of multimodal deep learning techniques (i.e., combining medical images and EHR data) in diagnosing and prognosis of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA).
METHODOLOGY
A comprehensive literature search was conducted in six databases along with forward and backward references list checking of the included studies. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) extension for scoping review guidelines were followed for the study selection process. The data was extracted and synthesized from the included studies through thematic analysis.
RESULTS
Ten studies were included in this review. These studies utilized multimodal deep learning to predict and diagnose hepatocellular carcinoma (HCC), but no studies examined cholangiocarcinoma (CCA). Four imaging modalities (CT, MRI, WSI, and DSA) and 51 unique EHR records (clinical parameters and biomarkers) were used in these studies. The most frequently used medical imaging modalities were CT scans followed by MRI, whereas the most common EHR parameters used were age, gender, alpha-fetoprotein AFP, albumin, coagulation factors, and bilirubin. Ten unique deep-learning techniques were applied to both EHR modalities and imaging modalities for two main purposes, prediction and diagnosis.
CONCLUSION
The use of multimodal data and deep learning techniques can help in the diagnosis and prediction of HCC. However, there is a limited number of works and available datasets for liver cancer, thus limiting the overall advancements of AI for liver cancer applications. Hence, more research should be undertaken to explore further the potential of multimodal deep learning in liver cancer applications.
PubMed: 37965284
DOI: 10.3389/frai.2023.1247195 -
World Journal of Surgical Oncology Feb 2024Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for 90% of cases worldwide and a significant contributor to cancer-related deaths.... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of laparoscopic liver resection versus radiofrequency ablation in patients with early and small hepatocellular carcinoma: an updated meta-analysis and meta-regression of observational studies.
BACKGROUND
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for 90% of cases worldwide and a significant contributor to cancer-related deaths. This study comprehensively compares the safety and efficacy of laparoscopic liver resection (LLR) versus laparoscopic or percutaneous radiofrequency ablation (LRFA or PRFA) in patients with early and small HCC.
METHODS
We systematically searched Cochrane Library, PubMed, Scopus, and Web of Science databases to include studies comparing LLR versus LRFA or PRFA in patients with early HCC meets the Milan criteria (defined as solitary nodule < 5 cm or three nodules ≤ 3 cm with no extrahepatic spread or vascular invasion). Pooled results were examined for overall survival, disease-free survival, recurrence-free survival, local, intrahepatic and extrahepatic recurrence rates, and complications. We conducted subgroup analyses based on the type of RFA. Meta-regression analyzed the association between overall survival, local recurrence, and various factors. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. We analyzed the data using the R (v.4.3.0) programming language and the "meta" package of RStudio software.
RESULTS
We included 19 observational studies, compromising 3756 patients. LLR showed higher 5-year overall survival compared to RFA (RR = 1.17, 95% CI [1.06, 1.3], P > 0.01). Our subgroup analysis showed that LLR had higher 5-year survival than PRFA (RR = 1.15, 95% CI [1.02, 1.31], P = 0.03); however, there was no significant difference between LLR and LRFA (RR = 1.26, 95% CI [0.98, 1.63], P = 0.07). LLR was associated with higher disease-free survival) RR = 1.19, 95% CI [1.05, 1.35], P < 0.01; RR = 1.61, 95% CI [1.31, 1.98], P < 0.01(and recurrence-free survival) RR = 1.21, 95% CI [1.09, 1.35], P < 0.01; RR = 1.45, 95% CI [1.15, 1.84], P < 0.01(at 1 and 3 years. LLR was associated with lower local (RR = 0.28, 95% CI [0.16, 0.47], P < 0.01) and intrahepatic recurrence (RR = 0.7, 95% CI [0.5, 0.97], P = 0.03) than RFA. However, complications were significantly higher with LLR (RR = 2.01, 95% CI [1.51, 2.68], P < 0.01). Our meta-regression analysis showed that younger patients had higher risk for local recurrence (P = 0.008), while age wasn't significantly linked to overall survival (P = 0.25). Other covariates like total bilirubin, alpha-fetoprotein levels, and tumor size also showed no significant associations with either overall survival or local recurrence.
CONCLUSION
LLR offers improved long-term outcomes and lower recurrence rates than PRFA. However, no significant distinctions were observed between LRFA and LLR in overall survival, recurrence-free survival, and local recurrence. More robust well-designed RCTs are essential to validate our findings.
Topics: Humans; Carcinoma, Hepatocellular; Hepatectomy; Laparoscopy; Liver Neoplasms; Neoplasm Recurrence, Local; Radiofrequency Ablation; Retrospective Studies; Treatment Outcome
PubMed: 38326841
DOI: 10.1186/s12957-023-03292-3 -
Frontiers in Immunology 2024It is unclear whether the systemic inflammation response index (SIRI) can predict the prognosis of patients with hepatocellular carcinoma (HCC). Consequently, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is unclear whether the systemic inflammation response index (SIRI) can predict the prognosis of patients with hepatocellular carcinoma (HCC). Consequently, the present study focused on systematically identifying the relationship between SIRI and the prognosis of patients with HCC through a meta-analysis.
METHODS
Systematic and comprehensive studies were retrieved from PubMed, Web of Science, Embase, and the Cochrane Library from their inception to August 10, 2023. The role of SIRI in predicting overall survival (OS) and progression-free survival (PFS) in HCC was determined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Odds ratios (ORs) and 95% CIs were pooled to analyze the correlations between SIRI and the clinicopathological features of HCC.
RESULTS
Ten articles involving 2,439 patients were included. An elevated SIRI was significantly associated with dismal OS (HR=1.75, 95% CI=1.52-2.01, p<0.001) and inferior PFS (HR=1.66, 95% CI=1.34-2.05, p<0.001) in patients with HCC. Additionally, according to the combined results, the increased SIRI was significantly related to multiple tumor numbers (OR=1.42, 95% CI=1.09-1.85, p=0.009) and maximum tumor diameter >5 cm (OR=3.06, 95% CI=1.76-5.30, p<0.001). However, the SIRI did not show any significant relationship with sex, alpha-fetoprotein content, Child-Pugh class, or hepatitis B virus infection.
CONCLUSION
According to our results, elevated SIRI significantly predicted OS and PFS in patients with HCC. Moreover, the SIRI was significantly associated with tumor aggressiveness.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/inplasy-2023-9-0003/, identifier INPLASY202390003.
Topics: Humans; Carcinoma, Hepatocellular; Prognosis; Liver Neoplasms; Progression-Free Survival; Inflammation
PubMed: 38469315
DOI: 10.3389/fimmu.2024.1291840 -
International Journal of Molecular... Jan 2024Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like... (Meta-Analysis)
Meta-Analysis Review
Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like imaging and alpha-fetoprotein (AFP). Although non-coding RNAs (ncRNAs) show promise as potential biomarkers in HCC, their true utility remains uncertain. We conducted a comprehensive review of 76 articles, analyzing 88 circulating lncRNAs in 6426 HCC patients. However, the lack of a standardized workflow protocol has hampered holistic comparisons across the literature. Consequently, we herein confined our meta-analysis to only a subset of these lncRNAs. The combined analysis of serum (HULC) gene expression with (HOTAIR) and (UCA1) demonstrated markedly enhanced sensitivity and specificity in diagnostic capability compared to traditional biomarkers or other ncRNAs. These findings could have substantial implications for the early diagnosis and tailored treatment of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; RNA, Long Noncoding; Genes, Homeobox; RNA, Antisense; Carcinoma, Transitional Cell; Gene Expression Regulation, Neoplastic; Urinary Bladder Neoplasms; RNA, Untranslated; Biomarkers; Gene Expression Profiling; Biomarkers, Tumor
PubMed: 38279264
DOI: 10.3390/ijms25021258 -
Journal of Clinical Medicine Research Jul 2023Protein induced by vitamin K absence or antagonist-II (PIVKA-II) and α-fetoprotein (AFP) are promising tumor markers for the diagnosis of hepatocellular carcinoma...
BACKGROUND
Protein induced by vitamin K absence or antagonist-II (PIVKA-II) and α-fetoprotein (AFP) are promising tumor markers for the diagnosis of hepatocellular carcinoma (HCC). Yet, their diagnostic performance differs throughout HCC investigations. The aim of this meta-analysis was to assess the effectiveness of PIVKA-II and AFP in the diagnosis of HCC.
METHODS
A systematic literature search was performed to identify relevant studies from eight databases, which were published up to February 2023, in order to compare the diagnostic performance of PIVKA-II and AFP for HCC. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic (SROC) curve was performed to assess the diagnostic accuracy of each biomarker.
RESULTS
Fifty-three studies were identified. The pooled sensitivity (95% confidence interval (CI)) of PIVKA-II and AFP was 0.71 (0.70 - 0.72) and 0.64 (0.63 - 0.65), respectively in diagnosis of HCC, and the corresponding pooled specificity (95% CI) was 0.90 (0.89 - 0.90) and 0.87 (0.87 - 0.88), respectively. The area under the ROC curve (AUC) of PIVKA-II and AFP was 0.89 (0.88 - 0.90) and 0.78 (0.77 - 0.79), respectively. Subgroup analysis demonstrated that PIVKA-II presented higher AUC values compared to AFP in terms of ethnic group (African, European, Asian, and American patients), etiology (mixed-type HCC, hepatitis C virus (HCV)-related, and hepatitis B virus (HBV)-related) and sample size of cases (≤ 100 and > 100).
CONCLUSION
This study reveals that PIVKA-II is a promising biomarker for identifying and tracking HCC, exhibiting greater accuracy than AFP. Our findings indicate that PIVKA-II outperforms AFP in detecting HCC across diverse racial groups and sample sizes, as well as in cases of HBV-related, HCV-related, or mixed-etiology HCC.
PubMed: 37575350
DOI: 10.14740/jocmr4951 -
BMC Cancer Dec 2023The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their contentious predictive value for patient outcomes.
METHODS
We conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library up to December 2022. Eligible studies that reported survival outcomes and examined the presence of CTC-WBC clusters in solid tumor patients were included. Hazard ratios (HR) were pooled to assess the association between CTC-WBC clusters and overall survival (OS), as well as progression-free survival (PFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/recurrence-free survival (RFS). Subgroup analyses were performed based on sampling time, treatment method, detection method, detection system, and cancer type.
RESULTS
A total of 1471 patients from 10 studies were included in this meta-analysis. The presence of CTC-WBCs was assessed as a prognostic factor for overall survival and PFS/DFS/MFS/RFS. The pooled analysis demonstrated that the presence of CTC-WBC clusters was significantly associated with worse OS (HR = 2.44, 95% CI: 1.74-3.40, P < 0.001) and PFS/DFS/MFS/RFS (HR = 1.83, 95% CI: 1.49-2.24, P < 0.001). Subgroup analyses based on sampling time, treatment method, detection method, detection system, cancer type, and study type consistently supported these findings. Further analyses indicated that CTC-WBC clusters were associated with larger tumor size (OR = 2.65, 95% CI: 1.58-4.44, P < 0.001) and higher alpha-fetoprotein levels (OR = 2.52, 95% CI: 1.50-4.22, P < 0.001) in hepatocellular carcinoma. However, no significant association was found between CTC-WBC clusters and TNM stage, depth of tumor invasion, or lymph node metastasis in the overall analysis.
CONCLUSIONS
CTC-WBC clusters are negative predictors for OS and PFS/DFS/MFS/RFS in patients with solid tumors. Monitoring CTC-WBC levels may provide valuable information for predicting disease progression and guiding treatment decisions.
Topics: Humans; Prognosis; Neoplastic Cells, Circulating; Disease-Free Survival; Progression-Free Survival; Liver Neoplasms
PubMed: 38087278
DOI: 10.1186/s12885-023-11711-7