Identification of drug responsible glycogene signature in liver carcinoma from meta-analysis using RNA-seq data.

Glycans have attracted much attention in cancer therapeutic strategies, and cell surface proteins and lipids with glycans are known to be altered during the carcinogenic process. However, our understanding of how the glycogenes profile responds to drug stimulation remains incomplete. In this study, we search public databases for Sequence Read Archive data on drug-treated liver cancer cells, with the aim to comprehensively analyze the drug responses of glycogenes via bioinformatic meta-analysis. The study comprised 86 datasets, encompassing eight distinct liver cancer cell lines and 13 different drugs. Differentially expressed genes were quantified, and 399 glycogenes were identified. The glycogenes signature was then analyzed using bioinformatics methodologies. In the Protein-protein interaction network analysis, we identified drug-responsive glycogenes such as Beta-1,4-Galactosyltransferase 1, GDP-Mannose 4,6-Dehydratase, UDP-Glucose Ceramide Glucosyltransferase, and Solute Carrier Family 2 Member 4 as key glycan biomarkers. In the enrichment analysis using the pathway list of glycogenes, the results also demonstrated that drug stimulation resulted in alterations to glycopathway-related genes involved in several processes, namely O-Mannosylation, POMGNT2 Type, Capping, Heparan Sulfate Sulfation, and Glucuronidation pathways. These genes and pathways commonly exhibit variable expression across multiple liver cancer cells in response to the same drug, making them potential targets for new cancer therapies. In addition to their primary roles, drugs may also participate in the regulation of glycans. The insights from this study could pave the way for the development of liver cancer therapies that target the regulation of gene profiles involved in the biosynthesis of glycans.

THAP3 recruits SMYD3 to OXPHOS genes and epigenetically promotes mitochondrial respiration in hepatocellular carcinoma.

Mitochondria harbor the oxidative phosphorylation (OXPHOS) system to sustain cellular respiration. However, the transcriptional regulation of OXPHOS remains largely unexplored. Through the cancer genome atlas (TCGA) transcriptome analysis, transcription factor THAP domain-containing 3 (THAP3) was found to be strongly associated with OXPHOS gene expression. Mechanistically, THAP3 recruited the histone methyltransferase SET and MYND domain-containing protein 3 (SMYD3) to upregulate H3K4me3 and promote OXPHOS gene expression. The levels of THAP3 and SMYD3 were altered by metabolic cues. They collaboratively supported liver cancer cell proliferation and colony formation. In clinical human liver cancer, both of them were overexpressed. THAP3 positively correlated with OXPHOS gene expression. Together, THAP3 cooperates with SMYD3 to epigenetically upregulate cellular respiration and liver cancer cell proliferation.

Fabrication of pure Bi2WO6 and Bi2WO6/MWCNTs nanocomposite as potential antibacterial and anticancer agents.

An essential research area for scientists is the development of high-performing, inexpensive, non-toxic antibacterial materials that prevent the transfer of bacteria. In this study, pure Bi2WO6 and Bi2WO6/MWCNTs nanocomposite were prepared by hydrothermal method. A series of characterization results by using XRD FTIR, Raman, FESEM, TEM, and EDS analyses, reveal the formation of orthorhombic nanoflakes Bi2WO6 by the addition of NaOH and pH adjustment to 7. Compared to pure Bi2WO6, the Bi2WO6/MWCNTs nanocomposite exhibited that CNTs are efficiently embedded into the structure of Bi2WO6 which results in charge transfer between metal ion electrons and the conduction or valence band of Bi2WO6 and MWCNTs and result in shifting to longer wavelength as shown in UV-visible and PL. The results confirmed that MWCNTs are stuck to the surface of the microflowers, and some of them embedded inside the Bi2WO6 nanoflakes without affecting the structure of Bi2WO6 nanoflakes as demonstrated by TEM. In addition, Pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite were tested against P. mirabilis and S. mutans., confirming the effect of addition MWCNTs materials had better antibacterial activity in opposition to both bacterial strains than pure Bi2WO6. Besides, pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite tested for cytotoxicity against lung MTT test on Hep-G2 liver cancer cells, and flow-cytometry. Results indicated that pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite have significant anti-cancer efficacy against Hep-G2 cells in vitro. In addition, the findings demonstrated that Bi2WO6 and Bi2WO6/MWCNTs triggered cell death via increasing ROS. Based on these findings, it appears that pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite have the potential to be developed as nanotherapeutics for the treatment of bacterial infections, and liver cancer.

Ginsenoside compound K induces ferroptosis via the FOXO pathway in liver cancer cells.

Liver cancer is a common malignant tumor worldwide, traditional Chinese medicine is one of the treatment measures for liver cancer because of its good anti-tumor effects and fewer toxic side effects. Ginsenoside CK (CK) is an active component of ginseng. This study explored the mechanism by which CK induced ferroptosis in liver cancer cells. We found that CK inhibited the proliferation of HepG2 and SK-Hep-1 cells, induced ferroptosis of cells. Ferrostatin-1, an ferroptosis inhibitor, was used to verify the role of CK in inducing ferroptosis of liver cancer cells. Network pharmacological analysis identified the FOXO pathway as a potential mechanism of CK, and western blot showed that CK inhibited p-FOXO1. In cells treated with the FOXO1 inhibitor AS1842856, further verify the involvement of the FOXO pathway in regulating CK-induced ferroptosis in HepG2 and SK-Hep-1 cells. A HepG2 cell-transplanted tumor model was established in nude mice, and CK inhibited the growth of transplanted tumors in nude mice, p-FOXO1 was decreased in tumor tissues, and SLC7A11 and GPX4 expressions were also down-regulated after CK treatment. These findings suggested that CK induces ferroptosis in liver cancer cells by inhibiting FOXO1 phosphorylation and activating the FOXO signaling pathway, thus playing an antitumor role.

Stigmatization of drinking patients with liver cancer: The role of socioeconomic status.

Patients with liver cancer may face stigmatization due to cancer, alcohol consumption, or both. This study addresses gaps in the existing literature regarding stigmatization of alcohol-related liver cancer patients, particularly its connection with socioeconomic status (SES). The study explores whether the SES of a fictional character with alcohol addiction and liver cancer influences stigma levels reported by participants. Additionally, it investigates how participants' personal characteristics, such as alcohol consumption and healthcare professional status, impact stigmatization. This study aims to provide new insights regarding the role of stigmatization in liver cancer treatment and management, emphasizing in socioeconomic determinants. The method is based on three scenarios describing a woman character with alcohol abuse and liver cancer. The scenarios depicted a woman character with either low, medium or high SES. Each participant (N = 991) was randomly assigned to one of the three scenarios. After reading it, each participant answered questionnaires assessing negative attitudes towards the character. Four scales were used: "Negative attributions about people with health problems", "Causality of cancer", "Controllability of drinking" and "Reluctance to helping behavior". Data were analyzed using ANOVA and t-tests. The scenario describing a character with a low SES significantly received more "Negative attributions about people with health problems" than the character with medium or high SES. Participants having higher alcohol consumption themselves showed lower stigma scores for three out of four scales than participants with lower consumption. In addition, participants identified as health professionals had lower stigma scores regarding the scales "Negative attributions about people with health problems" and "Controllability of drinking", and higher scores for the subscale "Reluctance to helping behavior", compared with non-professionals. A character with low SES received more negative attributions than the one with higher SES. Participants' own alcohol consumption and professional status (being health professional or not), influenced their stigmatizing attitudes.

Correlation Between Illness Uncertainty in Caregivers of Patients with Liver Cancer, Their Coping Styles, and Quality of Life.

Objective: This study explores the correlation between coping style, quality of life, and illness uncertainty in the family caregivers of patients with liver cancer. Methods: Employing convenience sampling, 210 family caregivers of patients with liver cancer who met the admission criteria were selected from a grade A infectious disease hospital in Beijing between January and December 2022. A cross-sectional survey was conducted using the Simplified Coping Style Questionnaire, Caregiver Quality of Life, and the Mishel Uncertainty in Illness Scale for Family Members. This study analysed the correlations between coping styles, quality of life, and illness uncertainty in these caregivers. Results: The study found that family caregivers of patients with liver cancer had average scores for illness uncertainty (83.44 ± 11.86), coping style (33.19 ± 9.79; both positive [23.02 ± 6.81] and negative [10.17 ± 5.05]), and quality of life (169.53 ± 32.46). A negative association was observed between illness uncertainty in these caregivers and positive coping style (r = -0.207, p = 0.003), physical status (r = -0.182, p = 0.008), psychological status (r = -0.200, p = 0.004), and social adaptation (r = -0.229, p = 0.001). Conclusion: The study concludes that illness uncertainty in family caregivers of patients with liver cancer is at a moderate level. Furthermore, there is a notable correlation between illness uncertainty, coping style, and quality of life in these caregivers.

Differences in influencing mechanism of clinicians' adoption behavior for liver cancer screening technology between the leading and subordinate hospitals within medical consortiums.

BACKGROUND: Medical consortiums have been extensively established to facilitate the integration of health resources and bridge the technical gap among member institutions. However, some commonly appropriate technologies remain stagnant in subordinate hospitals, although they have been routinely applied in leading hospitals. Besides, the mechanism underlying differences in clinicians' adoption behavior at different levels of institutions was unknown. Therefore, this study aimed to investigate the differences in influencing mechanisms of clinicians' hepatic contrast-enhanced ultrasound technology (CEUS) utilization behavior between leading and subordinate hospitals within medical consortiums, thus providing clues for expanding effective and appropriate technologies within integrated care systems. METHODS: A self-designed scale was developed based on the theory of planned behavior (TPB). A multistage sampling method was applied to investigate clinicians who were aware of CEUS and worked in liver disease-related departments within the sampled medical institutions. The final sample size was 289. AMOS 24.0 software was used to construct multi-group structural equation modeling (SEM) to validate the hypotheses and determine the mechanism of hepatic CEUS utilization. RESULTS: It revealed that behavioral intention significantly influenced adoption behavior, regardless of whether it was in leading hospitals or subordinate hospitals (ß = 0.283, p < 0.001). Furthermore, behavioral attitude (ß = 0.361, p < 0.001) and perceived behavioral control (ß = 0.582, p < 0.001) exerted significant effects on adoption behavior through behavioral intention. However, in leading hospitals, subjective norm had a significant positive effect on behavioral intention (ß = 0.183, p < 0.01), while it had a significant negative impact on behavioral intention in the subordinate hospitals (ß = -0.348, p < 0.01). CONCLUSION: To effectively translate the adoption intention into actual behavior, it is recommended to elucidate the demand and facilitators involved in the process of health technology adoption across leading and subordinate hospitals. Additionally, bolstering technical support and knowledge dissemination within subordinate hospitals while harnessing the influential role of key individuals can further enhance this transformative process.

The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignant cancer worldwide, characterized by high morbidity and mortality rates. Alpha-fetoprotein (AFP) is a glycoprotein synthesized by the liver and yolk sac during fetal development. However, the serum levels of AFP exhibit a significant correlation with the onset and progression of HCC in adults. Extensive research has demonstrated that the tumor microenvironment (TME) plays a crucial role in the malignant transformation of HCC, and AFP is a key factor in the TME, promoting HCC development. The objective of this review was to analyze the existing knowledge regarding the role of AFP in the TME. Specifically, this review focused on the effect of AFP on various cells in the TME, tumor immune evasion, and clinical application of AFP in the diagnosis and treatment of HCC. These findings offer valuable insights into the clinical treatment of HCC.

Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection: A systematic review.

BACKGROUND: Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma (HCC) in people with cirrhosis. Of the 6 HCV genotypes (G1-G6), genotype-3 accounts for 17.9% of infections. HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis. AIM: To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings. Consequently, we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023. METHODS: This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations. We searched Web of Science, Medline, EMBASE, and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings, 1946-2023. RESULTS: Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates. Three thousand eight hundred and eighty-four records were screened with 3514 excluded. Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis. Of the seven studies, three studies were retrospective case-control trials, two retrospective cohort studies, one a prospective cohort study and one a cross-sectional study design. All were based in hospital settings with four in Pakistan, two in South Korea and one in the United States. The total number of participants were 9621 of which 167 developed HCC (1.7%). All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age (five-studies), with two studies each showing male sex, high alpha feto-protein, directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC. CONCLUSION: Although, studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease, HCC, and liver-related death, there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3. Only cirrhosis and age have demonstrated an association; however, the number of studies is very small, and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.

Multi-Omics Integration for Liver Cancer Using Regression Analysis.

Genetic biomarkers have played a pivotal role in the classification, prognostication, and guidance of clinical cancer therapies. Large-scale and multi-dimensional analyses of entire cancer genomes, as exemplified by projects like The Cancer Genome Atlas (TCGA), have yielded an extensive repository of data that holds the potential to unveil the underlying biology of these malignancies. Mutations stand out as the principal catalysts of cellular transformation. Nonetheless, other global genomic processes, such as alterations in gene expression and chromosomal re-arrangements, also play crucial roles in conferring cellular immortality. The incorporation of multi-omics data specific to cancer has demonstrated the capacity to enhance our comprehension of the molecular mechanisms underpinning carcinogenesis. This report elucidates how the integration of comprehensive data on methylation, gene expression, and copy number variations can effectively facilitate the unsupervised clustering of cancer samples. We have identified regressors that can effectively classify tumor and normal samples with an optimal integration of RNA sequencing, DNA methylation, and copy number variation while also achieving significant p-values. Further, these regressors were trained using linear and logistic regression with k-means clustering. For comparison, we employed autoencoder- and stacking-based omics integration and computed silhouette scores to evaluate the clusters. The proof of concept is illustrated using liver cancer data. Our analysis serves to underscore the feasibility of unsupervised cancer classification by considering genetic markers beyond mutations, thereby emphasizing the clinical relevance of additional global cellular parameters that contribute to the transformative process in cells. This work is clinically relevant because changes in gene expression and genomic re-arrangements have been shown to be signatures of cellular transformation across cancers, as well as in liver cancers.

Mortality Burden of Liver Cancer in China: An Observational Study From 2008 to 2020.

Background and Aims: China accounts for nearly half of liver cancer deaths globally. A better understanding of the current liver cancer mortality will be helpful to establishing priorities for intervention and to decreasing the disease burden of liver cancer. The study aimed to explore and predict the mortality burden of liver cancer in China. Methods: Data were extracted from the Disease Surveillance Point system of the Chinese Center for Disease Control and Prevention from 2008 to 2020. Crude and age-standardized liver cancer mortality rates were reported by sex, urban or rural residence, and region. Trends in liver cancer mortality rates from 2008 to 2020 were estimated as average annual percentage change (AAPC). The changing trend of live cancer mortality in the future is also predicted. Results: In 2020, the crude mortality of liver cancer was 25.57/100,000, and males and people lived in rural areas had higher age-standardized liver cancer mortality rates than females and people lived in people in urban areas. Crude mortality and age-standardized mortality rates in southwest provinces (Guangxi, Sichuan, Tibet) and in a northeast province (Heilongjiang) were higher than that in other provinces, and age-specific mortality rates increased with age. From 2008 to 2020, liver cancer mortality rates decreased, but people under 50 years of age had a higher AAPC than those over 50 years of age, possibly because of the adoption of hepatitis B virus vaccination in newborns and children. Furthermore, the mortality of liver cancer in 2021-2030 is predicted to have a downward trend. Conclusions: Liver cancer mortality rates declined in China from 2008 to 2020. Future interventions to control liver cancer mortality need to focus on people of male sex, older age, and living in rural areas or less developed provinces.

Treatment Options for Hepatocellular Carcinoma Using Immunotherapy: Present and Future.

Hepatocellular carcinoma (HCC) is a common cancer, and the body's immune responses greatly affect its progression and the prognosis of patients. Immunological suppression and the maintenance of self-tolerance in the tumor microenvironment are essential responses, and these form part of the theoretical foundations of immunotherapy. In this review, we first discuss the tumor microenvironment of HCC, describe immunosuppression in HCC, and review the major biomarkers used to track HCC progression and response to treatment. We then examine antibody-based therapies, with a focus on immune checkpoint inhibitors (ICIs), monoclonal antibodies that target key proteins in the immune response (programmed cell death protein 1, anti-cytotoxic T-lymphocyte associated protein 4, and programmed death-ligand 1) which have transformed the treatment of HCC and other cancers. ICIs may be used alone or in conjunction with various targeted therapies for patients with advanced HCC who are receiving first-line treatments or subsequent treatments. We also discuss the use of different cellular immunotherapies, including T cell receptor (TCR) T cell therapy and chimeric antigen receptor (CAR) T cell therapy. We then review the use of HCC vaccines, adjuvant immunotherapy, and oncolytic virotherapy, and describe the goals of future research in the development of treatments for HCC.

Liver cancer wars: plant-derived polyphenols strike back.

Liver cancer currently represents the leading cause of cancer-related death worldwide. The majority of liver cancer arises in the context of chronic inflammation and cirrhosis. Surgery, radiation therapy, and chemotherapy have been the guideline-recommended treatment options for decades. Despite enormous advances in the field of liver cancer therapy, an effective cure is yet to be found. Plant-derived polyphenols constitute a large family of phytochemicals, with pleiotropic effects and little toxicity. They can drive cellular events and modify multiple signaling pathways which involves initiation, progression and metastasis of liver cancer and play an important role in contributing to anti-liver cancer drug development. The potential of plant-derived polyphenols for treating liver cancer has gained attention from research clinicians and pharmaceutical scientists worldwide in the last decades. This review overviews hepatic carcinogenesis and briefly discusses anti-liver cancer mechanisms associated with plant-derived polyphenols, specifically involving cell proliferation, apoptosis, autophagy, angiogenesis, oxidative stress, inflammation, and metastasis. We focus on plant-derived polyphenols with experiment-based chemopreventive and chemotherapeutic properties against liver cancer and generalize their basic molecular mechanisms of action. We also discuss potential opportunities and challenges in translating plant-derived polyphenols from preclinical success into clinical applications.

NETosis in tumour microenvironment of liver: From primary to metastatic hepatic carcinoma.

BACKGROUND: Hepatocellular carcinoma is a common and highly lethal tumour. The tumour microenvironment (TME) plays an important role in the progression and metastasis of hepatocellular carcinoma (HCC). A cell death mechanism, termed NETosis, has been found to play an important role in the TME of HCC. SUMMARY: This review article focuses on the role of NETosis in the TME of HCC, a novel form of cell death in which neutrophils capture and kill microorganisms by releasing a type of DNA meshwork fibres called "NETs". This process is associated with neutrophil activation, local inflammation and cytokines. The study suggests that NETs play a multifaceted role in the development and metastasis of HCC. The article also discusses the role of NETs in tumour proliferation and metastasis, epithelial-mesenchymal transition (EMT), and surgical stress. In addition, the article discusses the interaction of NETosis with other immune cells in the TME and related therapeutic strategies. A deeper understanding of NETosis can help us better understand the complexity of the immune system and provide a new therapeutic basis for the treatment and prevention of HCC. KEY INFORMATION: In conclusion, NETosis is important in the TME of liver. NETs have been shown to contribute to the progression and metastasis of liver cancer. The interaction between NETosis and immune cells in the TME, as well as related therapies, are important areas of research.

Low-abundance proteins-based label-free SERS approach for high precision detection of liver cancer with different stages.

BACKGROUND: Surface-enhanced Raman scattering (SERS) technology have unique advantages of rapid, simple, and highly sensitive in the detection of serum, it can be used for the detection of liver cancer. However, some protein biomarkers in body fluids are often present at ultra-low concentrations and severely interfered with by the high-abundance proteins (HAPs), which will affect the detection of specificity and accuracy in cancer screening based on the SERS immunoassay. Clearly, there is a need for an unlabeled SERS method based on low abundance proteins, which is rapid, noninvasive, and capable of high precision detection and screening of liver cancer. RESULTS: Serum samples were collected from 60 patients with liver cancer (27 patients with stage T1 and T2 liver cancer, 33 patients with stage T3 and T4 liver cancer) and 40 healthy volunteers. Herein, immunoglobulin and albumin were separated by immune sorption and Cohn ethanol fractionation. Then, the low abundance protein (LAPs) was enriched, and high-quality SERS spectral signals were detected and obtained. Finally, combined with the principal component analysis-linear discriminant analysis (PCA-LDA) algorithm, the SERS spectrum of early liver cancer (T1-T2) and advanced liver cancer (T3-T4) could be well distinguished from normal people, and the accuracy rate was 98.5% and 100%, respectively. Moreover, SERS technology based on serum LAPs extraction combined with the partial least square-support vector machine (PLS-SVM) successfully realized the classification and prediction of normal volunteers and liver cancer patients with different tumor (T) stages, and the diagnostic accuracy of PLS-SVM reached 87.5% in the unknown testing set. SIGNIFICANCE: The experimental results show that the serum LAPs SERS detection combined with multivariate statistical algorithms can be used for effectively distinguishing liver cancer patients from healthy volunteers, and even achieved the screening of early liver cancer with high accuracy (T1 and T2 stage). These results showed that serum LAPs SERS detection combined with a multivariate statistical diagnostic algorithm has certain application potential in early cancer screening.

Based on the prognosis model of immunogenes, the prognosis model was constructed to predict the invasion of immune genes and immune cells related to primary liver cancer and its experimental validation.

Background: Primary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients. Purpose: Revealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients. Methods: PLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments. Results: Through database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs (P < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses. Conclusion: Our study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.

Progression of portal hypertension after atezolizumab plus bevacizumab for hepatocellular carcinoma-report a case and literature review.

BACKGROUND: Atezolizumab/bevacizumab combination therapy became the first-line therapy for advanced hepatocellular carcinoma (HCC). Gastroesophageal varices should be monitored and managed before treatment. The progression of portal hypertension during bevacizumab-containing therapy is unclear. METHOD: A case of new development of esophageal varices, ascites, and hepatic hydrothorax during atezolizumab/bevacizumab therapy at National Taiwan University Hospital was reported, and relevant literature was reviewed. RESULTS: We presented an 83-year-old male with resolved hepatitis B without cirrhosis. He had BCLC stage C HCC and received tri-weekly atezolizumab/bevacizumab therapy for 34 cycles with sustained partial response. Progressive ascites, esophageal varices, and hepatic hydrothorax developed, though his portal vein was patent and the tumor was under control. Five similar cases of HCC (BCLC B/C: n = 3/2) had been reported previously. Among them, three had cirrhosis with pre-existing small esophageal varices before treatment. After the administration of 1-15 cycles of atezolizumab/bevacizumab therapy, one patient had a progression of varices, and the other four developed variceal bleeding. The association between atezolizumab/bevacizumab and portal hypertension was possible, which might relate to the VEGF pathway and immune-related adverse events with progressive hepatic fibrosis. CONCLUSION: Atezolizumab/bevacizumab treatment might exacerbate portal hypertension. Careful monitoring and management should be considered during treatment.

An ecological analysis of associations between ambient air pollution and cancer incidence rates in Taiwan.

Air pollution is deemed a human carcinogen and can be linked to certain types of cancer other than lung cancer. The present study aimed to investigate the pollutant-cancer associations in a population-level cohort. We obtained the annual age-standardized incidence rates of 28 different cancer types between 2015 to 2019 from the Taiwan Cancer Registry. Outdoor concentrations of particulate matter with a diameter of 10 µm or less (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ground-level ozone (O3), and carbon monoxide (CO) between 2001 to 2010 were retrieved from the Taiwan Air Quality Monitoring Network. Weighted quantile sum (WQS) regression models were used to determine the combined effects of five air pollutants on the relationship to cancer incidence rates after controlling for sex ratio, age, average disposable income per household, overweight/obesity prevalence, current smoking rate, and drinking rate. Trend analyses showed that NO2 and CO concentrations tended to decrease, while SO2 concentrations increased in some counties. WQS regression analyses revealed significantly positive correlations between air pollutants and liver cancer, lung and tracheal cancer, colorectal cancer, thyroid cancer, kidney cancer, and small intestine cancer. Altogether, the results from this ecological study unravel that exposure to ambient air pollution is associated with the incidence of several non-lung cancer types.

Outcomes of Liver Resection and Transarterial Chemoembolization in Patients with Multinodular BCLC-A Hepatocellular Carcinoma.

Background: This study aimed to compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) in patients with multinodular hepatocellular carcinoma (HCC) within the Milan criteria who were not eligible for liver transplantation. Methods: We retrospectively analyzed 483 patients with multinodular HCC within the Milan criteria, who underwent either LR or TACE as an initial therapy between 2013 and 2022. The overall survival (OS) in the entire population and recurrence-free survival (RFS) in patients who underwent LR and TACE and achieved a complete response were analyzed. Propensity score (PS) matching analysis was also used for a fair comparison of outcomes between the two groups. Results: Among the 483 patients, 107 (22.2%) and 376 (77.8%) underwent LR and TACE, respectively. The median size of the largest tumor was 2.0 cm, and 72.3% of the patients had two HCC lesions. The median OS and RFS were significantly longer in the LR group than in the TACE group (p <0.01 for both). In the multivariate analysis, TACE (adjusted hazard ratio [aHR], 1.81 and aHR, 2.41) and large tumor size (aHR, 1.43 and aHR, 1.44) were significantly associated with worse OS and RFS, respectively. The PS-matched analysis also demonstrated that the LR group had significantly longer OS and RFS than the TACE group (PS <0.05). Conclusion: In this study, LR showed better OS and RFS than TACE in patients with multinodular Barcelona Clinic Liver Cancer stage A HCC. Therefore, LR can be considered an effective treatment option for these patients.