Genomic analyses of cell-free DNA (cfDNA) in plasma are enabling noninvasive blood-based biomarker approaches to cancer detection and disease monitoring. Current approaches for identification of circulating tumour DNA typically use targeted tumour-specific mutations or methylation analyses. An emerging approach is based on the recognition of altered genome-wide cfDNA fragmentation in patients with cancer. Recent studies have revealed a multitude of characteristics that can affect the compendium of cfDNA fragments across the genome, collectively called the 'cfDNA fragmentome'. These changes result from genomic, epigenomic, transcriptomic and chromatin states of an individual and affect the size, position, coverage, mutation, structural and methylation characteristics of cfDNA. Identifying and monitoring these changes has the potential to improve early detection of cancer, especially using highly sensitive multi-feature machine learning approaches that would be amenable to broad use in populations at increased risk. This Review highlights the rapidly evolving field of genome-wide analyses of cfDNA characteristics, their comparison to existing cfDNA methods, and recent related innovations at the intersection of large-scale sequencing and artificial intelligence. As the breadth of clinical applications of cfDNA fragmentome methods have enormous public health implications for cancer screening and personalized approaches for clinical management of patients with cancer, we outline the challenges and opportunities ahead.

PET and MRI both play valuable roles in the management of hepatobiliary and pancreatic (HBP) malignancies. Simultaneous PET/MRI combines the excellent soft-tissue resolution and anatomic details from MRI with functional information from PET in a single comprehensive examination. MRI is the main imaging modality in evaluating HCC, playing important roles in screening, characterization, local extent, and evaluating tumor response, whereas 18F-fluorodeoxyglucose (FDG) PET can help evaluate for lymph node involvement and metastatic disease. In cholangiocarcinoma and pancreatic malignancies, both PET and MRI have excellent utility in initial staging as well as assessing treatment response. In all HBP malignancies, FDG-PET/MRI is a unique problem-solving tool in complex cases and diagnostic challenges, especially after locoregional therapy and when differentiating residual or recurrent viable disease from inflammatory and other benign processes. In this manuscript, we review the role of PET/MRI in the diagnosis, staging, assessing treatment response, and characterizing post-treatment processes. With the introduction of multiple new tracers, the value of PET/MRI has not yet been fully realized, and more studies are needed to demonstrate the utility and efficacy of PET/MRI in improving patient care in hepatobiliary and pancreatic oncology.

Hepatocellular carcinoma (HCC) contributes significantly to global cancer-related mortality, often because patients present at advanced stages of the disease. HCC commonly metastasizes to the lung, abdominal lymph nodes, and bone. However, even among bony metastases, calvarial lesions are exceptionally rare, especially in the initial presentation.

We describe a unique case of a 65-year-old African American woman who presented with a rapidly growing skull lesion as her first clinical sign of metastatic HCC. Imaging revealed an extensive soft-tissue mass involving the left calvaria and partially obstructing the superior sagittal sinus. We suspected that the lesion was a meningioma and offered surgery. Histological examination and further systemic workup later confirmed HCC. She was started on adjuvant therapy but unfortunately deteriorated from complications secondary to disease progression. We also reviewed the literature on cases of isolated calvarial metastases as the initial presentation of HCC. A total of 36 case reports were reviewed which included 38 patients. There were 32 males (84.2%), and the mean age was 58.97 ± 9.09 years old. The most common location of presentation was the parietal or occipital region (13, 34.2%), and 18 patients (47.4%) underwent neurosurgical treatment of the lesion. Among the 26 cases that had a follow-up, 84.6% (n = 22) did not survive treatment, and the mean survival time was 6.15 ± 5.94 months.

Isolated calvarial lesions are rarely the initial presenting sign of metastatic HCC. Often, these lesions may be misdiagnosed as benign tumors, such as meningiomas or hemangiopericytomas, given their appearance on imaging. However, early identification of HCC skull lesions is crucial to initiating treatment, including resection, radiation, and immunotherapy, which may help improve symptoms and extend survival. Our case report adds to the limited literature on this exceedingly rare entity.

Lung cancer, the leading cause of cancer deaths globally, has better survival rates with early detection. Annual low-dose CT (LDCT) screenings are recommended for high-risk individuals due to age and smoking. These individuals are also at risk for other cancers. Our study explores gastrointestinal (GI) cancer mortality in lung cancer screening participants and the potential of LDCT screenings to detect pancreatic cancer. We utilized data from a prospective multi-institutional cohort study, the International Early Lung Cancer Action Project (I-ELCAP). We analyzed GI cancer deaths among participants in New York State (1992-2010), exploring demographics and GI cancer distribution. Radiologists retrospectively reviewed pancreatic cancer cases within 24 months post-LDCT, comparing findings with original reports. Among 10,150 participants, 189 died from GI cancers; mean age 75, mostly male smokers. Pancreatic cancer (41.8%) led, followed by esophageal (17.5%) and colon cancer (16.9%). Median time between baseline LDCT and death was 116 months (9.7 years). 82/189 (43.4%) participants died within 5 years of their last LDCT screening, with pancreatic cancer again prominent (45.1%). In 79 pancreatic cancer deaths, 17.7% occurred within 24 months post-LDCT. A re-review identified previously undetected pancreatic findings, with 4 out of 14 participants (28.6%) showing abnormalities. This underscores the potential of lung cancer screening programs to provide insights beyond lung health. This study of over 10,000 participants in a lung cancer screening program reveals that they are at risk for GI cancer deaths, particularly pancreatic cancer. Re-reviews of LDCT scans revealed previously undocumented pancreatic findings in a third of participants who died from pancreatic cancer, underscoring the need to identify, document, and follow up on these findings.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, with prognosis and treatment outcomes that are significantly influenced by the stage at diagnosis. Early detection through regular surveillance is crucial for improving patient outcomes, especially in high-risk groups such as those with cirrhosis or chronic hepatitis B. Geographic variations in HCC risk factors, including viral hepatitis and non-alcoholic fatty liver disease (NAFLD), have led to the development of different international surveillance guidelines. This review aims to compare and evaluate the surveillance strategies proposed by the Asian Pacific Association for the Study of the Liver (APASL), the American Association for the Study of Liver Diseases (AASLD), and the European Association for the Study of the Liver and European Organization for Research and Treatment of Cancer (EASL-EORTC).

The review examined and compared major international guidelines on HCC surveillance, focusing on patient selection, imaging modalities, and the integration of biomarkers. We also explored recent advancements in screening techniques, including artificial intelligence and emerging biomarkers, to identify future directions for improving surveillance strategies.

Our analysis identified key differences in the guidelines, particularly in imaging modality preferences and the use of biomarkers for early detection. While all guidelines place emphasis on high-risk populations, the inclusion criteria and surveillance intervals vary. Additionally, novel technologies such as artificial intelligence show potential to enhance the accuracy and efficiency of HCC detection.

This review highlights the need to harmonize the international guidelines, particularly in regard to patients with non-cirrhotic NAFLD who remain under-represented in current surveillance protocols. Future research should focus on integrating emerging technologies and biomarkers to improve early detection and overall patient outcomes.

Primary liver cancer is among the most common cancers globally. It is the sixth-most common malignancy encountered and the third-most common cause of cancer-related death. Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, accounting for about 90% of primary liver cancers. The majority of HCCs occur in patients with underlying cirrhosis, which results from chronic liver diseases such as fatty liver, hepatitis B and hepatitis C infections, and chronic alcohol use, which are the leading causes. The obesity pandemic has led to an increased prevalence of nonalcoholic fatty liver disease (NAFLD), which leads to nonalcoholic steatohepatitis and could progress to cirrhosis. As HCC is among the most common cancers and occurs in the setting of chronic liver disease in most patients, screening the population at risk could help in early diagnosis and management, leading to improved survival. Screening for HCC is performed using biochemical marker testing such as α-fetoprotein (AFP) and cross-sectional imaging. It is critical to emphasize that HCC could potentially occur in patients without cirrhosis (non-cirrhotic HCC), which can account for almost 20% of all HCCs. The lack of cirrhosis can cause a delay in surveillance, which could potentially lead to diagnosis at a later stage, worsening the prognosis for such patients. In this article, we discuss the diagnosis of cirrhosis in at-risk populations with details on the different modalities available for screening HCC in patients with cirrhosis, emphasizing the role of abdominal ultrasounds, the primary imaging modality in HCC screening.

Liver cancer (LC) screening, such as AFP test and abdominal ultrasound, is an effective way to prevent LC, one of the most common cancers worldwide. Despite the proven screening benefits, screening participation among high-risk populations for LC remains low. This suggests that targeted, systematic, and effective interventions should be provided to improve knowledge and awareness related to LC screening, enhance screening intentions, and thereby promote screening behaviors. Telephone is people's main medium of daily communication and mHealth-based programs offer a potential and effective solution for promoting health behaviors. The purpose of this study is to develop and implement a mHealth (WeChat app) based intervention guided by Fogg's Behavior Model (FBM) to augment the knowledge of LC prevention among people at risk of LC and enhance their motivation for screening, and to validate its effectiveness in improving LC screening.

We propose a two-arm, single-blind randomized controlled trial with 82 at-risk individuals of LC, delivering a 6-month mHealth-based intervention program with optional health counseling. Recruitment will be through tertiary hospitals and community organizations in 4 districts in Heng Yang. In total, 82 individuals at high risk for HCC will be randomized 1:1 to intervention or control (usual care) groups. The intervention group will receive intervention, whose contents are based on the FBM model, via multiple forms of media including PowerPoint presentation, multimedia video, health information booklet and screening message, which is delivered in the WeChat Applet. Control dyads will be provided with usual health education. Outcomes will be assessed at baseline and post-intervention.

The findings of this study will provide evidence of the benefits of utilizing mHealth-based approaches in intervention development to enhance the effectiveness of screening adherence for high-risk people of LC. Further, the findings would provide reference to the potential incorporation of the targeted intervention in local community organizations.

Chinese Clinical Trial Registry (ChiCTR2400080530) Date registered: 31/1/2024.

Understanding the patient journey of hepatocellular carcinoma (HCC) may inform future clinical decision-making and enhance the patient experience. The objectives of this study were to explore the patient experience of HCC in relation to treatment options, treatment decision-making and treatment goals throughout the disease journey. This study also aimed to determine the symptoms and impacts of HCC across early, intermediate and advanced HCC.

Semi-structured 60-min interviews were conducted with n = 50 patients with HCC and n = 12 healthcare professionals (HCPs) with experience of treating patients with HCC. Interview data were analyzed using directed content analysis techniques with a hybrid inductive and deductive approach. An assessment of conceptual saturation was conducted for patients' symptom experience.

Patients described treatment decisions as mostly HCP-led. In this study, surgery/resection was the most frequently offered treatment option across the HCC journey, and most patients were satisfied with the treatment options presented to them. Overall, patients described extending their overall survival (OS) and preserving quality of life (QoL) as their most important treatment goals, with patients diagnosed with advanced/unresectable HCC prioritizing QoL. HCPs also prioritized OS and progression-free survival (PFS) though reported that QoL became more important as HCC progressed. Patients experienced various symptoms across the HCC journey including fatigue, nausea, appetite loss, diarrhea and pain.

Overall, HCPs and patients collaborate throughout the treatment journey regarding treatment decisions and shared treatment goals. OS is critically important to patients and HCPs, though treatment goals may change depending on various clinical factors.

Multiple studies have reported models for predicting early recurrence of hepatocellular carcinoma (HCC) after liver resection (LR). However, these models are too complex to use in daily practice. We aimed to develop a simple model.

We enrolled 1133 patients with newly diagnosed HCC undergoing LR. The Kaplan - Meier method and log-rank test were used for survival analysis and Cox proportional hazards analysis to identify prognostic factors associated with early recurrence (i.e., recurrence within two years after LR).

Early recurrence was identified in 403 (35.1%) patients. In multivariate analysis, alpha-fetoprotein (AFP) 20-399 vs. < 20 ng/ml (HR = 1.282 [95% confidence interval = 1.002-1.639]; p = 0.048); AFP ≥ 400 vs. < 20 ng/ml (HR = 1.755 [1.382-2.229]; p < 0.001); 7th edition American Joint Committee on Cancer (AJCC) stage 2 vs. 1 (HR = 1.958 [1.505-2.547]; p < 0.001); AJCC stage 3 vs. 1 (HR = 4.099 [3.043-5.520]; p < 0.001); and pathology-defined cirrhosis (HR = 1.46 [1.200-1.775]; p < 0.001) were associated with early recurrence. We constructed a predictive model with these variables, which provided three risk strata for recurrence-free survival (RFS): low risk, intermediate risk, and high risk, with two-year RFS of 79%, 57%, and 35%, respectively (p < 0.001).

We developed a simple model to predict early recurrence risk for patients undergoing LR for HCC.

Abdominal imaging is frequently performed with breath holds or respiratory triggering to reduce the effects of respiratory motion. Diffusion weighted sequences provide a useful clinical contrast but have prolonged scan times due to low signal-to-noise ratio (SNR), and cannot be completed in a single breath hold. Echo-planar imaging (EPI) is the most commonly used trajectory for diffusion weighted imaging but it is susceptible to off-resonance artifacts. A respiratory resolved, three-dimensional (3D) diffusion prepared sequence that obtains distortionless diffusion weighted images during free-breathing is presented. Techniques to address the myriad of challenges including: 3D shot-to-shot phase correction, respiratory binning, diffusion encoding during free-breathing, and robustness to off-resonance are described.

A twice-refocused, M1-nulled diffusion preparation was combined with an RF-spoiled gradient echo readout and respiratory resolved reconstruction to obtain free-breathing diffusion weighted images in the abdomen. Cartesian sampling permits a sampling density that enables 3D shot-to-shot phase navigation and reduction of transient fat artifacts. Theoretical properties of a region-based shot rejection are described. The region-based shot rejection method was evaluated with free-breathing (normal and exaggerated breathing), and respiratory triggering. The proposed sequence was compared in vivo with multishot DW-EPI.

The proposed sequence exhibits no evident distortion in vivo when compared to multishot DW-EPI, robustness to B0 and B1 field inhomogeneities, and robustness to motion from different respiratory patterns.

Acquisition of distortionless, diffusion weighted images is feasible during free-breathing with a b-value of 500 s/mm2, scan time of 6 min, and a clinically viable reconstruction time.

Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy of a biomarker model in the detection of posttreatment viable tumors.

For model derivation, recipients with HCC undergoing liver transplant from 2018 to 2022 who had biomarkers collected within 3 months before transplant were included. We developed a generalized linear model for detecting posttreatment viable tumors with the 3 biomarkers as covariates, which we termed the "LAD Score." An independent cohort of 117 patients with HCC was used for external validation.

Among 205 recipients of transplant, 70.2% had evidence of viable tumor on explant. The median LAD score was higher among patients with viable versus nonviable tumors (1.06 vs. 0.465, p < 0.001). The LAD score had a sensitivity of 55.6% and a specificity of 85.1% at the cutoff of 0.927, which was more accurate than imaging for detecting posttreatment viable tumors (AUROC 0.736 vs. 0.643, respectively; p = 0.045). The superior performance of the LAD score over imaging is primarily driven by its greater accuracy in detecting tumors <2 cm in diameter (AUROC of the LAD score 0.721 vs. imaging 0.595, p = 0.02). In the validation data set, the LAD score had an AUROC of 0.832 (95% CI: 0.753, 0.911) with a sensitivity of 72.5% and a specificity of 89.4% at the cutoff of 0.927.

Our findings suggest the utility of LAD score in treatment response assessment after locoregional therapy for HCC, particularly in detecting small tumors. A larger prospective study is in progress to validate its accuracy and evaluate its performance in recurrence monitoring.

Introduction: Hepatocellular carcinoma (HCC), the most common type of liver cancer, is a major global health problem, ranking as the third leading cause of cancer-related death worldwide. Early identification and diagnosis of HCC requires the discovery of reliable biomarkers. Therefore, the study aimed to assess the diagnostic accuracy of miRNAs for HCC. The protocol was registered on PROSPERO website with the registration number CRD42023417494. Method: A literature search was conducted in PubMed, Scopus, Embase, Wiley Online Library, and Science Direct databases to identify pertinent articles published between 2018 and 30 July 2023. Stata 17.0 software was employed to determine the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the curve (AUC) for evaluating the accuracy of miRNAs in diagnosing HCC. The assessment of heterogeneity among studies involved the use of the Cochran-Q test and I2 statistic tests. Due to the observed significant heterogeneity, the random-effect model was chosen. Subgroup analysis and meta-regression analysis were also undertaken to explore potential sources contributing to heterogeneity. Deeks' funnel plot was used to assess publication bias. In addition, Fagan's nomogram and likelihood ratio scattergram were utilized to assess the clinical validity of miRNAs for HCC. Result: Twenty-four articles were included, involving 1,668 individuals diagnosed with HCC and 1,236 healthy individuals. The findings revealed pooled sensitivity of 0.84 (95% CI: 0.80-0.88), specificity of 0.81 (95% CI: 0.77-0.84), PLR of 4.36 (95% CI: 3.59-5.30), NLR of 0.19 (95% CI: 0.15-0.25), DOR of 22.47 (95% CI: 14.47-32.64), and an AUC of 0.89 (95% CI: 0.86-0.91) for the diagnosis of HCC using miRNAs. Furthermore, results from the subgroup analysis demonstrated that superior diagnostic performance was observed when utilizing plasma miRNAs, a large sample size (≥100), and miRNA panels. Conclusion: Hence, circulating miRNAs demonstrate substantial diagnostic utility for HCC and can serve as effective non-invasive biomarkers for the condition. Additionally, miRNA panels, miRNAs derived from plasma, and miRNAs evaluated in larger sample sizes (≥100) demonstrate enhanced diagnostic efficacy for HCC diagnosis. Nevertheless, a large pool of prospective studies and multi-center research will be required to confirm our findings in the near future.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer mortality. HCC has high morbidity, high mortality, and low survival rates. Screening is one of the most significant methods of lowering incidence and death while also increasing survival.

The aim of this study was to identify the facilitators and barriers to participation in HCC screening among high-risk populations.

A comprehensive and systematic search was undertaken in PubMed, Web of Science, MEDLINE, EMBACE, EBSCOhost and the Cochrane Library. A combination of synonyms of the keywords including HCC, screening, factors and adherence were used for searching. Studies addressing the facilitators and barriers to HCC screening compliance in at-risk individuals were included. Data were synthesized using Review Manager version 5.4. A random/fixed effects model meta-analysis was performed to estimate the pooled data and expressed with odds ratio (OR) and 95% confidence interval (CI).

A total of seven articles met the inclusion criteria. Qualitative (n = 1) and quantitative (n = 6) studies using various types of surgery were conducted. The most commonly mentioned barriers were insufficient knowledge and awareness of HCC screening, unawareness of the necessity for early detection of HCC and lack of physician recommendation. A meta-analysis of seven studies showed that individuals with a family history of HCC increased screening uptake by nearly three times (OR: 2.69, 95% CI: 1.93, 3.75). Other most frequently reported facilitators include age, education level, and perceived risk et al.

Many barriers to HCC screening were found. Meanwhile, this review points out that improving the awareness of high-risk populations toward HCC screening is expected to enhance compliance, thereby promoting early diagnosis of liver cancer, reducing mortality, and alleviating the burden of HCC.

The objective of our study was to study and compare the sonographic findings of hepatocellular carcinoma (HCC) and benign liver lesions, and apply these to an HCC surveillance program in patient with chronic hepatitis B virus (HBV).

Sonographic findings of HCC and benign liver lesions were retrospectively reviewed following diagnosis based on either computer tomography or magnetic resonance imaging from July 2010 to December 2020. Multiple sonographic features were analyzed, including internal echogenicity, rim characteristics, and posterior acoustic enhancement. Associations between sonographic characteristics and HCC were assessed using uni- and multi-variate logistic regression analyses.

Of the focal liver lesions in 337 chronic HBV patients, there were 25 HCC and 410 benign lesions, with median sizes of 1.6 and 1.0 cm, respectively. Three ultrasound patterns, homogeneous hypoechogenicity, heterogeneous echogenicity, and hypoechoic rims were more frequently found in HCC than in benign lesions. Moreover, the hypoechoic rim feature was the only sonographic pattern independently associated with HCC (Odds ratio, 68.05; 95% confidence interval, 7.37-628.10; p-values < 0.001). In a subgroup analysis of the lesions sized 2 cm or smaller, no sonographic findings were associated with HCC.

A hypoechoic rim was a sonographic feature independently associated with HCC. These findings may aid in improving HCC detection and guiding management during HCC screening and surveillance with ultrasound.

Hepatocellular carcinoma is one of the most common malignancies worldwide. However, brain metastases from this cancer are incredibly rare. While the hepatocellular carcinoma mortality rate in the United States has been increasing, hepatocellular carcinoma is rare among patients without underlying liver disease. Here we present a patient with a history of left optic nerve meningioma treated with stereotactic radiosurgery who presented with acute vision loss. Magnetic resonance imaging revealed an enhancing mass lesion in the region of the sella turcica. Neurosurgical histopathology revealed a metastatic lesion consistent with hepatocellular carcinoma. Systemic workup failed to identify a primary liver lesion.

Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains uncertain. We evaluated the impact of DAA on hepatocellular carcinoma (HCC) occurrence and recurrence, all-cause mortality, liver decompensation and liver transplantation as compared to non-DAA treated hepatitis C and the association to baseline liver status. A systematic search for articles from March 1993 to March 2022 was conducted using three electronic databases. Randomized, case-control and cohort studies with comparison to non-DAA treatment and reporting at least one outcome were included. Meta-analysis and sub-group meta-analysis based on baseline liver status were performed. Of 1497 articles retrieved, 19 studies were included, comprising of 266,310 patients (56.07% male). DAA reduced HCC occurrence significantly in non-cirrhosis (RR 0.80, 95% CI 0.69-0.92) and cirrhosis (RR 0.39, 95% CI 0.24-0.64) but not in decompensated cirrhosis. DAA treatment lowered HCC recurrence (RR 0.71, 95% CI 0.55-0.92) especially in patients with baseline HCC and waiting for liver transplant. DAA also reduced all-cause mortality (RR 0.43, 95% CI 0.23-0.78) and liver decompensation (RR 0.52, 95% CI 0.33-0.83) significantly. However, DAA did not prevent liver transplantation. The study highlighted the importance of early DAA initiation in hepatitis C treatment for benefits beyond sustained virological response. DAA therapy prevented HCC particularly in non-cirrhosis and compensated cirrhosis groups indicating benefits in preventing further worsening of liver status. Starting DAA early also reduced HCC recurrence, liver decompensation, and all-cause mortality.

  Incidence of hepatocellular cancer (HCC) in the Bronx is 61% higher than the rest of New York State. Underserved populations are not well represented in clinical trials of immune checkpoint inhibitors (ICI).

Demographics were tabulated for 194 patients treated with ICI at the Montefiore-Einstein Comprehensive Cancer Center (MECCC) between 2017 and 2022. Categorical variables were analyzed by Chi-squared test, and survival was analyzed using Kaplan-Meier (KM) curves.

MECCC patients were 40.7% Hispanic and 20.6% Black, compared with 3% and 2%, respectively, in the landmark IMbrave 150 study. Median overall survival (mOS) on ICI was 9.0 months, 25.0 months for the 100 (51.5%) favorable-prognosis Child Pugh A (CPA) patients included in HCC clinical trials. Disease control rate (DCR) was 58.5% among 123 evaluable patients per mRECIST 1.1. Baseline liver function, as defined by CP and the Model for End-Stage Liver Disease-Sodium (MELD-Na), correlated with survival (p < 0.001). Hepatitis C Virus (HCV) and alcoholism were over-represented relative to National Cancer Institute (NCI) data (56.2% vs 4.7% and 38.7% vs 8.2%, respectively). HCV treatment correlated with prolonged survival in infected patients (p = 0.0017). AFP decline correlated with response (p = 0.001). Hispanic patients lived longer when clinical variables were controlled for (mOS 52 vs 23 months; p = 0.011).

In an underserved HCC population, ICI yielded a DCR of 58.5% and low rates of severe toxicity. This work highlights ICI efficacy in minority groups, a need for earlier HCC diagnosis and for studies of genetic and environmental factors in Hispanics with HCC.

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 highly upregulated in liver cancer (HULC) gene expression with homeobox transcript antisense intergenic RNA (HOTAIR) and urothelial carcinoma-associated 1 (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.

Hepatocellular carcinoma (HCC) is a challenging malignancy with limited treatment options beyond surgery and chemotherapy. Recent advancements in targeted therapies and immunotherapy, including PD-1 and PD-L1 monoclonal antibodies, have shown promise, but their efficacy has not met expectations. Biomarker testing and personalized medicine based on genetic mutations and other biomarkers represent the future direction for HCC treatment. To address these challenges and opportunities, this comprehensive review discusses the progress made in targeted therapies and immunotherapies for HCC, focusing on dissecting the rationales, opportunities, and challenges for combining these modalities. The liver's unique physiology and the presence of fibrosis in many HCC patients pose additional challenges to drug delivery and efficacy. Ongoing efforts in biomarker development and combination therapy design, especially in the context of immunotherapies, hold promise for improving outcomes in advanced HCC. Through exploring the advancements in biomarkers and targeted therapies, this review provides insights into the challenges and opportunities in the field and proposes strategies for rational combination therapy design.

Changes in strategies in the coronavirus disease 2019 (COVID-19) crisis and the imposing of restrictions have isolated many vulnerable patients including those with hepatocellular carcinoma (HCC) from routine medical care. This study investigated how the COVID-19 pandemic is affecting the diagnosis and treatment of HCC.

An extensive search was conducted in the PubMed, Scopus, and Web of Science databases by using the appropriate keywords: COVID-19, hepatocellular carcinoma, hepatocellular cancer, and MeSH. Studies in English related to the purpose of the study were included in the analysis, and review studies, case reports, letters to editors, comments, and reports were excluded. The quality of the studies was assessed by the "Adapted Newcastle-Ottawa Quality Assessment Scales" checklist. The Endnote X7 software has been used for managing items.

The final qualitative analysis consisted of 27 articles. During the COVID-19 crisis, HCC diagnosis decreased from 20% to 34.13% compared to pre-crisis. The impact of the COVID-19 pandemic on HCC treatment encompasses a wide range of aspects. Generally, delays in treatment for patients with HCC ranged from more than one month for 21.5% of patients in France, to two months for 26% of patients in Italy, up to 30% in Austria, and 66.7% in Asia-Pacific countries.

According to the findings, developing and implementing appropriate diagnostic and therapeutic strategies and developing low-cost and high-precision screening programs among high-risk populations seem to be effective in reducing the impact of the COVID-19 pandemic on HCC management.

Hepatocellular carcinoma (HCC) ranks fourth in cancer-related deaths worldwide. Semiannual surveillance of the disease for patients with cirrhosis or hepatitis B virus allows for early detection with more favorable outcomes. The current underuse of surveillance programs demonstrates the need for intervention at both the patient and provider level. Mail outreach along with navigation provision has proven to increase surveillance follow-up in patients, while provider-targeted electronic medical record reminders and compliance reports have increased provider awareness of HCC surveillance. Imaging is the primary mode of diagnosis in HCC with The Liver Imaging Reporting and Data System (LI-RADS) being a widely accepted comprehensive system that standardizes the reporting and data collection for HCC. The management of HCC is complex and requires multidisciplinary team evaluation of each patient based on their preference, the state of the disease, and the available medical and surgical interventions. Staging systems are useful in determining the appropriate intervention for HCC. Early-stage HCC is best managed by curative treatment modalities, such as liver resection, transplant, or ablation. For intermediate stages of the disease, transarterial local regional therapies can be applied. Advanced stages of the disease are treated with systemic therapies, for which there have been recent advances with new drug combinations. Previously sorafenib was the mainstay systemic treatment, but the recent introduction of atezolizumab plus bevacizumab proves to have a greater impact on overall survival. Although there is a current lack of improved outcomes in Phase III trials, neoadjuvant therapies are a potential avenue for HCC management in the future.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the number of cases is constantly increasing. Early and accurate HCC diagnosis is crucial to improving the effectiveness of treatment. The aim of the study is to develop a supervised learning framework based on hierarchical community detection and artificial intelligence in order to classify patients and controls using publicly available microarray data. With our methodology, we identified 20 gene communities that discriminated between healthy and cancerous samples, with an accuracy exceeding 90%. We validated the performance of these communities on an independent dataset, and with two of them, we reached an accuracy exceeding 80%. Then, we focused on two communities, selected because they were enriched with relevant biological functions, and on these we applied an explainable artificial intelligence (XAI) approach to analyze the contribution of each gene to the classification task. In conclusion, the proposed framework provides an effective methodological and quantitative tool helping to find gene communities, which may uncover pivotal mechanisms responsible for HCC and thus discover new biomarkers.

Hepatocellular cancer (HCC) and biliary tract cancers (BTCs) have poor survival rates and a low likelihood of a cure, especially in advanced-stage disease. Early diagnosis is crucial and can significantly improve survival rates through curative treatment approaches. Current guidelines recommend abdominal ultrasonography (USG) and alpha-fetoprotein (AFP) monitoring for HCC screening in high-risk groups, and abdominal USG, magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) monitoring for biliary tract cancer. However, despite this screening strategy, many high-risk individuals still develop advanced-stage HCC and BTC. Blood-based biomarkers are being developed for use in HCC or BTC high-risk groups. Studies on AFP, AFP-L3, des-gamma-carboxy prothrombin, glypican-3 (GPC3), osteopontin (OPN), midkine (MK), neopterin, squamous cell carcinoma antigen (SCCA), Mac-2-binding protein (M2BP), cyclic guanosine monophosphate (cGMP), and interleukin-6 biomarkers for HCC screening have shown promising results when evaluated individually or in combination. In the case of BTCs, the potential applications of circulating tumor DNA, circulating microRNA, and circulating tumor cells in diagnosis are also promising. These biomarkers have shown potential in detecting BTCs in early stages, which can significantly improve patient outcomes. Additionally, these biomarkers hold promise for monitoring disease progression and evaluating response to therapy in BTC patients. However, further research is necessary to fully understand the clinical utility of these biomarkers in the diagnosis and management of HCC and BTCs.

Many patients with hepatocellular carcinoma (HCC) never receive cancer-directed therapy. In order to tailor interventions to increase access to appropriate therapy, we sought to understand the barriers and facilitators to HCC care.

Patients with recently diagnosed HCC were identified through the University of North Carolina (UNC) HCC clinic or local hospital cancer registrars (rapid case ascertainment, RCA). Two qualitative researchers conducted in-depth, semi-structured interviews. Interviews were audiotaped, transcribed, and coded.

Nineteen interviews were conducted (10 UNC, 9 RCA). Key facilitators of care were: physician knowledge; effective communication regarding test results, plan of care, and prognosis; social support; and financial support. Barriers included: lack of transportation; cost of care; provider lack of knowledge about HCC; delays in scheduling; or poor communication with the medical team. Participants suggested better coordination of appointments and having a primary contact within the healthcare team.

We primarily captured the perspectives of those HCC patients who, despite the challenges they describe, were ultimately able to receive HCC care.

This study identifies key facilitators and barriers to accessing care for HCC in North Carolina. Use of the RCA system to identify patients from a variety of settings, treated and untreated, enabled us to capture a broad range of perspectives. Reducing barriers through improving communication and care coordination, assisting with out-of-pocket costs, and engaging caregivers and other medical providers may improve access. This study should serve as the basis for tailored interventions aimed at improving access to appropriate, life-prolonging care for patients with HCC.

Obesity is a global epidemic and overwhelming evidence indicates that it is a risk factor for numerous cancers, including hepatocellular carcinoma (HCC), the third leading cause of cancer-related deaths worldwide. Obesity-associated hepatic tumorigenesis develops from nonalcoholic fatty liver disease (NAFLD), progressing to nonalcoholic steatohepatitis (NASH), cirrhosis and ultimately to HCC. The rising incidence of obesity is resulting in an increased prevalence of NAFLD and NASH, and subsequently HCC. Obesity represents an increasingly important underlying etiology of HCC, in particular as the other leading causes of HCC such as hepatitis infection, are declining due to effective treatments and vaccines. In this review, we provide a comprehensive overview of the molecular mechanisms and cellular signaling pathways involved in the pathogenesis of obesity-associated HCC. We summarize the preclinical experimental animal models available to study the features of NAFLD/NASH/HCC, and the non-invasive methods to diagnose NAFLD, NASH and early-stage HCC. Finally, since HCC is an aggressive tumor with a 5-year survival of less than 20%, we will also discuss novel therapeutic targets for obesity-associated HCC and ongoing clinical trials.

Liver cancer is a leading cause of cancer-related death worldwide, and its early detection and treatment are crucial for improving morbidity and mortality. Biomarkers have the potential to facilitate the early diagnosis and management of liver cancer, but identifying and implementing effective biomarkers remains a major challenge. In recent years, artificial intelligence has emerged as a promising tool in the cancer sphere, and recent literature suggests that it is very promising in facilitating biomarker use in liver cancer. This review provides an overview of the status of AI-based biomarker research in liver cancer, with a focus on the detection and implementation of biomarkers for risk prediction, diagnosis, staging, prognostication, prediction of treatment response, and recurrence of liver cancers.