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Aim: We previously reported that abdominal aortic calcification is associated with poor overall and recurrence‐free survival after hepatectomy for hepatocellular carcinoma (HCC). However, the effect of abdominal aortic calcification on cancer‐specific prognosis in very old patients with several comorbidities remains unknown. This multicenter study aimed to evaluate the impact of abdominal aortic calcification on the cumulative recurrence rate and recurrence‐free survival in patients with HCC aged >80 years. Methods: We retrospectively analyzed the data of 128 patients (aged ≥80 years) who underwent liver resection for hepatocellular carcinoma at seven hospitals belonging to Hiroshima Surgical Study Group of Clinical Oncology between January 2014 and December 2018. Patients were divided into two groups: high and low abdominal aortic calcification groups. The primary endpoints were cumulative recurrence rate and recurrence‐free survival. Results: Kaplan–Meier survival curve analysis demonstrated that the cumulative recurrence rate in the high abdominal aortic calcification group was significantly higher than that in the low abdominal aortic calcification group, and the high abdominal aortic calcification group had a significantly lower recurrence‐free survival rate. In the multivariate analysis, high abdominal aortic calcification (p = 0.03), high des‐gamma‐carboxyprothrombin score (p = 0.04), and multiple tumors (p < 0.01) were independent predictive factors for recurrent HCC, and high abdominal aortic calcification (p = 0.01) and high des‐gamma‐carboxyprothrombin (p = 0.01) were independent predictive factors for poor cancer‐specific survival. Conclusions: Our results indicate that the abdominal aortic calcification score is associated with cumulative recurrence rate and recurrence‐free survival in very old patients with HCC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the leading causes of death in which the molecular tumorigenesis and cellular heterogeneity are poorly understood. The genetic principle that specific driver mutations in oncogenes, DNA repair genes, and tumor-suppressor genes can independently drive cancer development has been widely explored. Additionally, a repertory of harmful epigenetic modifications in DNA and chromatin—impacting the expression of genes involved in cellular proliferation, differentiation, genome stability, cell-cycle control, and DNA repair—are now acknowledged across various biological contexts that contribute to cancer etiology. Notably, the dynamic hypermethylation and hypomethylation in enhancer and promoter regions that promote activation or silencing of the master regulatory genes of the epigenetic programs is often altered in tumor cells due to mutation. Genome instability is one of the cancer hallmarks that contribute to transdifferentiation and intratumoral heterogeneity. Thus, it is broadly accepted that tumor tissue is dominated by genetically and epigenetically distinct sub-clones which display a set of genetic and epigenetic mutations. Here we summarize some functions of key genetic and epigenetic players and biochemical pathways leading to liver cell transformation. We discuss the role of the potential epigenetic marks in target genes thought to be involved in sequential events following liver lipid metabolism dysregulation, inflammation, fibrosis, cirrhosis, and finally hepatocellular carcinoma. We also briefly describe new findings showing how epigenetic drugs together with chemotherapy and immunotherapy can improve overall responses in patients with hepatic tumors. [ABSTRACT FROM AUTHOR]

Abstract Aim We previously reported that abdominal aortic calcification is associated with poor overall and recurrence‐free survival after hepatectomy for hepatocellular carcinoma (HCC). However, the effect of abdominal aortic calcification on cancer‐specific prognosis in very old patients with several comorbidities remains unknown. This multicenter study aimed to evaluate the impact of abdominal aortic calcification on the cumulative recurrence rate and recurrence‐free survival in patients with HCC aged >80 years. Methods We retrospectively analyzed the data of 128 patients (aged ≥80 years) who underwent liver resection for hepatocellular carcinoma at seven hospitals belonging to Hiroshima Surgical Study Group of Clinical Oncology between January 2014 and December 2018. Patients were divided into two groups: high and low abdominal aortic calcification groups. The primary endpoints were cumulative recurrence rate and recurrence‐free survival. Results Kaplan–Meier survival curve analysis demonstrated that the cumulative recurrence rate in the high abdominal aortic calcification group was significantly higher than that in the low abdominal aortic calcification group, and the high abdominal aortic calcification group had a significantly lower recurrence‐free survival rate. In the multivariate analysis, high abdominal aortic calcification (p = 0.03), high des‐gamma‐carboxyprothrombin score (p = 0.04), and multiple tumors (p

Hepatocellular carcinoma (HCC) is one of the leading causes of death in which the molecular tumorigenesis and cellular heterogeneity are poorly understood. The genetic principle that specific driver mutations in oncogenes, DNA repair genes, and tumor-suppressor genes can independently drive cancer development has been widely explored. Additionally, a repertory of harmful epigenetic modifications in DNA and chromatin—impacting the expression of genes involved in cellular proliferation, differentiation, genome stability, cell-cycle control, and DNA repair—are now acknowledged across various biological contexts that contribute to cancer etiology. Notably, the dynamic hypermethylation and hypomethylation in enhancer and promoter regions that promote activation or silencing of the master regulatory genes of the epigenetic programs is often altered in tumor cells due to mutation. Genome instability is one of the cancer hallmarks that contribute to transdifferentiation and intratumoral heterogeneity. Thus, it is broadly accepted that tumor tissue is dominated by genetically and epigenetically distinct sub-clones which display a set of genetic and epigenetic mutations. Here we summarize some functions of key genetic and epigenetic players and biochemical pathways leading to liver cell transformation. We discuss the role of the potential epigenetic marks in target genes thought to be involved in sequential events following liver lipid metabolism dysregulation, inflammation, fibrosis, cirrhosis, and finally hepatocellular carcinoma. We also briefly describe new findings showing how epigenetic drugs together with chemotherapy and immunotherapy can improve overall responses in patients with hepatic tumors.

Background: This work analyzed the efficacy of Cone-Beam Computed Tomography (CBCT) enhanced scan in evaluating the therapeutic effect and prognosis of interventional therapy in patients with liver cancer (LC). Materials and Methods: Eighty-two individuals diagnosed with primary LC were enrolled here and grouped according to the intraoperative treatment. Patients in group A were only treated with digital subtraction angiography (DSA) during the operation, while those in group B received DSA and CBCT during the operation. The operation time, radiation dose, detection rate of tumor lesions, and lipiodol deposition were compared between two groups. Results: In group A, 54 lesions were identified before operation, 48 lesions during intraoperative angiography, and 6 lesions remained undetected. In group B, 57 LC lesions were identified before operation, and 57 lesions during intraoperative CBCT enhanced scan, and 2 small LC lesions not presented previously were detected. The number of lesions with complete lipiodol precipitation in group B (42) was clearly higher as against group A (32) (P < 0.05). The operation time of group B was clearly longer as against group A (P < 0.05), but there existed no substantial difference in radiation dose patients in different groups (P > 0.05). Conclusion: The results indicated that CBCT enhanced scan was superior to conventional DSA in detecting tumor lesions, nutrient arteries, and lipiodol deposition in patients undergoing LC chemoembolization. Importantly, this enhanced method did not increase radiation dose but prolonged the operation time. [ABSTRACT FROM AUTHOR]

Background: Several studies have demonstrated a relationship between genetic polymorphisms of interleukin‐1 beta (IL‐1β) and cancer development; however, their influence on cancer prognosis is unknown. In the present study, we aimed to evaluate the impact of IL‐1β single nucleotide polymorphisms on the hematogenous dissemination and prognosis of hepatocellular carcinoma. Methods: We conducted a retrospective cohort study including patients with hepatocellular carcinoma who underwent primary liver resection at our hospital between April 2015 and December 2018. The primary endpoints were overall and recurrence‐free survival. Secondary endpoints were microscopic portal vein invasion and number of circulating tumor cells. Results: A total of 148 patients were included, 32 with rs16944 A/A genotype. A/A genotype was associated with microscopic portal vein invasion and number of circulating tumor cells (p =.03 and.04). In multivariate analysis, A/A genotype, alpha‐fetoprotein level, and number of circulating tumor cells were associated with microscopic portal vein invasion (p =.01,.01, and <.01). A/A genotype, Child‐Pugh B, and intraoperative blood loss were independent predictive factors for overall survival (p =.02, <.01, and <.01). Conclusions: Our results indicate that the IL‐1β rs16944 A/A genotype is involved in number of circulating tumor cells, microscopic portal vein invasion, and prognosis in HCC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is a refractory tumor with poor prognosis and high mortality. Many oncolytic viruses are currently being investigated for the treatment of hepatocellular carcinoma. Based on previous studies, we constructed a recombinant GM-CSF-carrying Sindbis virus, named SINV-GM-CSF, which contains a mutation (G to S) at amino acid 285 in the nsp1 protein of the viral vector. The potential of this mutated vector for liver cancer therapy was verified at the cellular level and in vivo, respectively, and the changes in the tumor microenvironment after treatment were also described. The results showed that the Sindbis virus could effectively infect hepatocellular carcinoma cell lines and induce cell death. Furthermore, the addition of GM-CSF enhanced the tumor-killing effect of the Sindbis virus and increased the number of immune cells in the intra-tumor microenvironment during the treatment. In particular, SINV-GM-CSF was able to efficiently kill tumors in a mouse tumor model of hepatocellular carcinoma by regulating the elevation of M1-type macrophages (which have a tumor-resistant ability) and the decrease in M2-type macrophages (which have a tumor-promoting capacity). Overall, SINV-GM-CSF is an attractive vector platform with clinical potential for use as a safe and effective oncolytic virus. [ABSTRACT FROM AUTHOR]

Diffusion‐derived vessel density (DVDD) is a physiological surrogate of the area of microvessels per unit tissue area. DDVD is calculated according to DDVD(b0b2) = Sb0/ROIarea0 – Sb2/ROIarea2, where Sb0 and Sb2 refer to the liver signal when b is 0 or 2 s/mm2. Pathohistological studies and contrast‐enhanced CT/MRI data showed higher blood volume in hepatocellular carcinoma (HCC) relative to native liver tissue. With intravoxel incoherent motion (IVIM) imaging, most authors paradoxically reported a decreased perfusion fraction of HCC relative to the adjacent liver. This study applied DDVD to assess the perfusion of HCC. MRI was performed with a 3.0‐T magnet. Diffusion‐weighted images with b‐values of 0 and 2 s/mm2 were acquired in 72 HCC patients. Thirty‐two patients had microvascular invasion (MVI(+)) and 40 patients did not have microvascular invasion (MVI(−)). Fifty‐eight patients had Edmondson–Steiner grade I or II HCC, and 14 patients had Edmondson–Steiner grade III or IV HCC. DDVD measurement was conducted on the axial slice that showed the largest HCC size. DDVD(b0b2) T/L = HCC DDVD(b0b2)/liver DDVD(b0b2). DDVD(b0b2) T/L median (95% confidence interval) of all HCCs was 2.942 (2.419–3.522), of MVI(−) HCCs was 2.699 (2.030–3.522), of MVI(+) HCCs was 2.988 (2.423–3.990), of Edmondson–Steiner grade I/II HCCs was 2.873 (2.277–3.465), and of Edmondson–Steiner grade III/IV HCCs was 3.403 (2.008–4.485). DDVD(b0b2) T/L approximately agrees with contrast agent dynamically enhanced CT/MRI literature data, whereas it differs from earlier IVIM study results, where HCC perfusion fraction was paradoxically lower relative to native liver tissue. A weak trend was noted with MIV(+) HCCs had a higher DDVD(b0b2) T/L than that of MVI(−) HCCs, and a weak trend was noted with the poorly differentiated group of HCCs (Edmondson–Steiner grade III and IV) had a higher DDVD(b0b2) T/L than that of the better differentiated group of HCCs (Edmondson–Steiner grade I and II). [ABSTRACT FROM AUTHOR]

Summary: Background: Loss of heterozygosity (LOH) diminishes genetic diversity within cancer genomes. A tumour arising in an individual heterozygous for a functional and a loss-of-function (LoF) allele of a gene occasionally retain only the LoF allele. This can result in deficiency of specific protein activities in cancer cells, creating unique differences between tumour cells and normal cells of the individual. Such differences may constitute vulnerabilities that can be exploited through allele-specific therapies. Methods: To discover frequently lost genes with prevalent LoF alleles, we mined the 1000 Genomes dataset for SNVs causing protein truncation through base substitution, indels or splice site disruptions, resulting in 60 LoF variants in 60 genes. From these, the variant rs3892097 in the liver enzyme CYP2D6 was selected because it is located within a genomic region that frequently undergoes LOH in several tumor types including hepatocellular cancers. To evaluate the relationship between CYP2D6 activity and the toxicities of anticancer agents, we screened 525 compounds currently in clinical use or undergoing clinical trials using cell model systems with or without CYP2D6 activity. Findings: We identified 12 compounds, AZD-3463, CYC-116, etoposide, everolimus, GDC-0349, lenvatinib, MK-8776, PHA-680632, talazoparib, tyrphostin 9, VX-702, and WZ-3146, using an engineered HEK293T cell model. Of these, talazoparib and MK-8776 demonstrated consistently heightened cytotoxic effects against cells with compromised CYP2D6 activity in engineered hepatocellular cancer cell models. Moreover, talazoparib displayed CYP2D6 genotype dependent effects on primary hepatocellular carcinoma organoids. Interpretation: Exploiting the loss of drug-metabolizing enzyme gene activity in tumor cells following loss of heterozygosity could present a promising therapeutic strategy for targeted cancer treatment. Funding: This work was funded by Barncancerfonden (T.S, PR2022-0099 and PR2020-0171, X.Z, TJ2021-0111), Cancerfonden (T.S, 211719Pj and D.G, 222449Pj), Vetenskapsrådet (T.S, 2020-02371 and D.G, 2020-04707), and the Erling Persson Foundation (T.S, 2020-0037 and T.S, 2023-0113).

Abstract Background Increasing evidence suggests that hepatocellular carcinoma (HCC) stem cells (LCSCs) play an essential part in HCC recurrence, metastasis, and chemotherapy and radiotherapy resistance. Multiple studies have demonstrated that stemness-related genes facilitate the progression of tumors. However, the mechanism by which stemness-related genes contribute to HCC is not well understood. Here, we aim to construct a stemness-related score (SRscores) model for deeper analysis of stemness-related genes, assisting with the prognosis and individualized treatment of HCC patients.Further, we found that the gene LPCAT1 was highly expressed in tumor tissues by immunohistochemistry, and sphere-forming assay revealed that knockdown of LPCAT1 inhibited the sphere-forming ability of hepatocellular carcinoma cells. Methods We used the TCGA-LIHC dataset to screen stemness-related genes of HCC from the MSigDB database. Prognosis, tumor microenvironment, immunological checkpoints, tumor immune dysfunction, rejection, treatment sensitivity, and putative biological pathways were examined. Random forest created the SRscores model. The anti-PD-1/anti-CTLA4 immunotherapy, tumor mutational burden, medication sensitivity, and cancer stem cell index were compared between the high- and low-risk score groups. We also examined risk scores for different cell types using single-cell RNA sequencing data and correlated transcription factor activity in cancer stem cells with SRscores genes. Finally, we tested core marker expression and biological functions. Results Patients can be divided into two subtypes (Cluster1 and Cluster2) based on the TCGA-LIHC dataset's identification of 11 stemness-related genes. Additionally, a SRscores was developed based on subtypes. Cluster2 and the group with the lowest SRscores had superior survival and immunotherapy response than Cluster1 and the group with the highest SRscores. The group with a high SRscores was significantly more enriched in classical tumor pathways than the group with a low SRscores. Multiple transcription factors and SRscores genes are correlated. The core gene LPCAT1 is highly expressed in rat liver cancer tissues and promotes tumor cell sphere formation. Conclusion A SRscores model can be utilized to predict the prognosis of HCC patients as well as their response to immunotherapy.

Background: Increasing evidence suggests that hepatocellular carcinoma (HCC) stem cells (LCSCs) play an essential part in HCC recurrence, metastasis, and chemotherapy and radiotherapy resistance. Multiple studies have demonstrated that stemness-related genes facilitate the progression of tumors. However, the mechanism by which stemness-related genes contribute to HCC is not well understood. Here, we aim to construct a stemness-related score (SRscores) model for deeper analysis of stemness-related genes, assisting with the prognosis and individualized treatment of HCC patients.Further, we found that the gene LPCAT1 was highly expressed in tumor tissues by immunohistochemistry, and sphere-forming assay revealed that knockdown of LPCAT1 inhibited the sphere-forming ability of hepatocellular carcinoma cells. Methods: We used the TCGA-LIHC dataset to screen stemness-related genes of HCC from the MSigDB database. Prognosis, tumor microenvironment, immunological checkpoints, tumor immune dysfunction, rejection, treatment sensitivity, and putative biological pathways were examined. Random forest created the SRscores model. The anti-PD-1/anti-CTLA4 immunotherapy, tumor mutational burden, medication sensitivity, and cancer stem cell index were compared between the high- and low-risk score groups. We also examined risk scores for different cell types using single-cell RNA sequencing data and correlated transcription factor activity in cancer stem cells with SRscores genes. Finally, we tested core marker expression and biological functions. Results: Patients can be divided into two subtypes (Cluster1 and Cluster2) based on the TCGA-LIHC dataset's identification of 11 stemness-related genes. Additionally, a SRscores was developed based on subtypes. Cluster2 and the group with the lowest SRscores had superior survival and immunotherapy response than Cluster1 and the group with the highest SRscores. The group with a high SRscores was significantly more enriched in classical tumor pathways than the group with a low SRscores. Multiple transcription factors and SRscores genes are correlated. The core gene LPCAT1 is highly expressed in rat liver cancer tissues and promotes tumor cell sphere formation. Conclusion: A SRscores model can be utilized to predict the prognosis of HCC patients as well as their response to immunotherapy. [ABSTRACT FROM AUTHOR]

Abstract Background Kinetic estimation provides fitted parameters related to blood flow perfusion and fluorine-18-fluorodeoxyglucose (18F-FDG) transport and intracellular metabolism to characterize hepatocellular carcinoma (HCC) but usually requires 60 min or more for dynamic PET, which is time-consuming and impractical in a busy clinical setting and has poor patient tolerance. Methods This study preliminarily evaluated the equivalence of liver kinetic estimation between short-term (5-min dynamic data supplemented with 1-min static data at 60 min postinjection) and fully 60-min dynamic protocols and whether short-term 18F-FDG PET-derived kinetic parameters using a three-compartment model can be used to discriminate HCC from the background liver tissue. Then, we proposed a combined model, a combination of the maximum-slope method and a three-compartment model, to improve kinetic estimation. Results There is a strong correlation between the kinetic parameters K 1 ~ k 3, HPI and $${{\varvec{V}}}_{{\varvec{b}}}$$ V b in the short-term and fully dynamic protocols. With the three-compartment model, HCCs were found to have higher k 2, HPI and k 3 values than background liver tissues, while K 1, k 4 and $${{\varvec{V}}}_{{\varvec{b}}}$$ V b values were not significantly different between HCCs and background liver tissues. With the combined model, HCCs were found to have higher HPI, K 1 and k 2, k 3 and $${{\varvec{V}}}_{{\varvec{b}}}$$ V b values than background liver tissues; however, the k 4 value was not significantly different between HCCs and the background liver tissues. Conclusions Short-term PET is closely equivalent to fully dynamic PET for liver kinetic estimation. Short-term PET-derived kinetic parameters can be used to distinguish HCC from background liver tissue, and the combined model improves the kinetic estimation. Clinical relevance statement Short-term PET could be used for hepatic kinetic parameter estimation. The combined model could improve the estimation of liver kinetic parameters. Graphical Abstract

Growing concern about photothermal tumor therapy (PTT) as a promising alternative to conventional liver cancer treatment, which is a treatment strategy that utilizes near‐infrared (NIR) light‐induced photothermal agents (PTAs) to yield photothermal effects to localize thermal damage for tumors. Herein, given the gap between experimental research and clinical application, this review seeks to timely summarize and highlight the recent progress of PTAs used for photothermal treatment of liver cancer in vivo and in vitro in the last five‐year. The implications of various PTAs on the multifunctional photothermal conversion capability, the structure‐performance correlations of PTT, together with the evaluation of their potential in application are systematically dissected to further dig out what the buried mechanism is. Besides, higher requirements are put forward for the discrepancies and crucial issues faced by different PTAs in PTT with related medical technical obstacles being conquered, which lays a solid theoretical foundation for the medical field of oncology treatment as a whole, especially liver cancer. Finally, it is expected that this review can present valuable guidance for the design of efficient, photostability, and biosafety‐aware PTAs for anticancer therapy while stepping into the fast traffic lane for the conversion from bench to bedside in the foreseeable future. [ABSTRACT FROM AUTHOR]

Tobacco contains many harmful chemicals, toxins, and carcinogens which cause serious health hazards. Mycotoxins and Aflatoxins are present in all tobacco including chewing and smokeless tobacco. We detected and isolated the aflatoxins-producing fungi Aspergillus sp. by microbial and molecular-based techniques. 50 samples were collected randomly and grown on SDA media by spread plate method. Isolates of A. flavus were analyzed for Aflatoxin production by Ammonia vapor test and the DNA of isolates was extracted and subjected for further molecular identification. Different fungal genera were observed including the most common Aspergillus while the other were Penicillium, Rhizopus, candida, and Trichophyton. Aspergillus flavus was isolated and characterized as a white soft velvety surface. The diameter of colonies was observed as 50 - 70 mm. Coconut-based medium detection by UV light of 365 nm showed the production of blue-green fluorescence on the reverse of colonies on coconut agar medium. DNA extracted from all the strains producing aflatoxins was quantified by VICAM. High levels of Aflatoxin ranging from 21 - 47 ug/kg were detected in 10 different samples while the remaining samples had a range of 10 - 20 ug/kg. the study showed both quantitative and qualitative techniques for the detection of aflatoxin-producing fungi in chewing tobacco. aflR and aflS were observed as potential candidates for the detection of aflatoxigenic fungi. [ABSTRACT FROM AUTHOR]

Background: The expression level of Ribonuclease H2, subunit A (RNASEH2A) in hepatocellular carcinoma (HCC) has been reported, but the function of RNASEH2A on HCC cells development and the related molecular mechanisms remain unclear. Herein, we intend to explore the upstream regulator of RNASEH2A and its role in the HCC progression. Methods: GEPIA website was employed to determine the level of RNASEH2A in HCC tissues and get a survival analysis. After reducing RNASEH2A expression by RNA interference, cell counting kit-8, colony formation, Western blot, Transwell and wound healing assays were performed to estimate the malignant properties of HCC cells. The transcriptional factor of RNASEH2A was predicted by UCSC and JASPAR database and confirmed by dual luciferase assay and Ch-IP assay. The expression level of EMT pathway related molecules was determined by western blotting. Results: An increased expression of RNASEH2A was presented in HCC and predicted worse prognosis of HCC patients. Functionally, the results demonstrated that depletion of RNASEH2A suppressed HCC cell proliferation, cell cycle, migration and invasion. Moreover, we illustrated that SP1 targeted to the promoter of RNASEH2A and modulated its expression in HCC cell lines. RNASEH2A knockdown counteracted the function of SP1 overexpression in modulating HCC cell growth, cell cycle, and mobility. Then, our data showed that the SP1/RNASEH2A axis affected the malignant behaviors of HCC cells by regulating EMT process. Conclusions: In summary, these results demonstrated that RNASEH2A promoted HCC cells development through regulating EMT process and was transcriptionally modulated by SP1.

Background: Kinetic estimation provides fitted parameters related to blood flow perfusion and fluorine-18-fluorodeoxyglucose (18F-FDG) transport and intracellular metabolism to characterize hepatocellular carcinoma (HCC) but usually requires 60 min or more for dynamic PET, which is time-consuming and impractical in a busy clinical setting and has poor patient tolerance. Methods: This study preliminarily evaluated the equivalence of liver kinetic estimation between short-term (5-min dynamic data supplemented with 1-min static data at 60 min postinjection) and fully 60-min dynamic protocols and whether short-term 18F-FDG PET-derived kinetic parameters using a three-compartment model can be used to discriminate HCC from the background liver tissue. Then, we proposed a combined model, a combination of the maximum-slope method and a three-compartment model, to improve kinetic estimation. Results: There is a strong correlation between the kinetic parameters K1 ~ k3, HPI and V b in the short-term and fully dynamic protocols. With the three-compartment model, HCCs were found to have higher k2, HPI and k3 values than background liver tissues, while K1, k4 and V b values were not significantly different between HCCs and background liver tissues. With the combined model, HCCs were found to have higher HPI, K1 and k2, k3 and V b values than background liver tissues; however, the k4 value was not significantly different between HCCs and the background liver tissues. Conclusions: Short-term PET is closely equivalent to fully dynamic PET for liver kinetic estimation. Short-term PET-derived kinetic parameters can be used to distinguish HCC from background liver tissue, and the combined model improves the kinetic estimation. Clinical relevance statement: Short-term PET could be used for hepatic kinetic parameter estimation. The combined model could improve the estimation of liver kinetic parameters. Key points: Short-term PET could be used for hepatic kinetic parameter estimation. Short-term PET was very similar to full dynamic PET in the estimation of liver kinetic parameters. The combined models could improve the estimation of liver kinetic parameters. [ABSTRACT FROM AUTHOR]

Objectives: To comprehensively evaluate the reporting quality, risk of bias, and radiomics methodology quality of radiomics models for predicting microvascular invasion in hepatocellular carcinoma. Methods: A systematic search of available literature was performed in PubMed, Embase, Web of Science, Scopus, and the Cochrane Library up to January 21, 2022. Studies that developed and/or validated machine learning models based on radiomics data to predict microvascular invasion in hepatocellular carcinoma were included. These studies were reviewed by two investigators and the consensus data were used for analyzing. The reporting quality, risk of bias, and radiomics methodological quality were evaluated by Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD), Prediction model Risk of Bias Assessment Tool, and Radiomics Quality Score (RQS), respectively. Results: A total of 30 studies met eligibility criteria with 24 model developing studies and 6 model developing and external validation studies. The median overall TRIPOD adherence was 75.4% (range 56.7–94.3%). All studies were at high risk of bias with at least 2 of 20 sources of bias. Furthermore, 28 studies showed unclear risks of bias in up to 5 signaling questions because of the lack of specified reports. The median RQS score was 37.5% (range 25–61.1%). Conclusion: Current radiomic models for MVI-status prediction have moderate to good reporting quality, moderate radiomics methodology quality, and high risk of bias in model development and validation. Key Points: • Current microvascular invasion prediction radiomics studies have moderate to good reporting quality, moderate radiomics methodology quality, and high risk of bias in model development and validation. • Data representativeness, feature robustness, events-per-variable ratio, evaluation metrics, and appropriate validation are five main aspects futures studies should focus more on to improve the quality of radiomics. • Both Radiomics Quality Score and Prediction model Risk of Bias Assessment Tool are needed to comprehensively evaluate a radiomics study. [ABSTRACT FROM AUTHOR]

Objective: Primary liver tumors are rare pediatric malignancies. Knowledge of the epidemiology of pediatric liver tumors is limited. This study aims to present the national incidence trends of pediatric liver tumors over 18 years, according to sociodemographic and histological subtype variation. Methods: The Surveillance, Epidemiology, and End Results registry was queried from 2000 to 2017 for 1,099 patients between ages 0 and 19 with liver tumors. Age-standardized incidence rates by age, sex, and race/ethnicity were examined among histological subtypes. Annual percentage change (APC) was calculated via joinpoint regression for various sociodemographic and histotype subgroups. Results: An increase of age-adjusted incidence rate of pediatric hepatic cancers was observed between 2000 and 2017 (APC, 1.7% [95% confidence interval or CI: 0.6%–2.8%], p-value = 0.006), which may likely attribute to the increasing incidence of hepatoblastoma and mesenchymal tumors (APC, 2.5% [95% CI: 1.1%–3.8%], p-value = 0.001). The incidence trend of hepatocellular carcinoma remained stable in the study period. The non-Hispanic Asian/Pacific Islander children and adolescents had a higher risk of hepatic tumors (incidence rate ratio or IRR, 1.42 [95% CI: 1.16–1.72], p-value = 0.0007) when compared with the non-Hispanic white subgroup, while a non-Hispanic black child was associated with a lower incidence rate (IRR, 0.64 [95% CI: 0.50–0.80], p-value < 0.0001). Significantly lower hepatic tumor incidence occurred in females than males, with an incidence rate ratio of 0.69 (95% CI: 0.61–0.78; p-value < 0.0001). Hepatic tumor incidence was also significantly lower in those aged 1–4 years (IRR, 0.47 [95% CI: 0.40–0.54]; p-value < 0.001) and 5–19 years (IRR, 0.09 [95% CI: 0.08–0.10]; p–value < 0.001) when compared with the youngest age group aged less than 1 year. These significant differences were also detected for the subgroup of hepatoblastoma and mesenchymal liver tumors but less among hepatocellular carcinomas (all p-values less than 0.0001). Conclusion: Continued increasing incidence of pediatric hepatoblastoma and mesenchymal liver tumors was discovered and warranted further investigation. Additional findings include a lower incidence of hepatic cancer among non-Hispanic black individuals and higher incidence of hepatic cancer in non-Hispanic Asian/Pacific Islander, male, and aged 1–4-year children and adolescents. [ABSTRACT FROM AUTHOR]

DNA glycosylases promote genomic stability by initiating base excision repair (BER) in both the nuclear and mitochondrial genomes. Several of these enzymes have overlapping substrate recognition, through which a degree of redundancy in lesion recognition is achieved. For example, OGG1 and NEIL1 both recognize and release the imidazole-ring-fragmented guanine, FapyGua as part of a common overall pathway to cleanse the genome of damaged bases. However, these glycosylases have many differences, including their differential breadth of substrate specificity, the contrasting chemistries through which base release occurs, the subsequent steps required to complete the BER pathway, and the identity of specific protein-binding partners. Beyond these differences, the complexities and differences of their in vivo biological roles have been primarily elucidated in studies of murine models harboring a knockout of Neil1 or Ogg1, with the diversity of phenotypic manifestations exceeding what might have been anticipated for a DNA glycosylase deficiency. Pathologies associated with deficiencies in nuclear DNA repair include differential cancer susceptibilities, where Ogg1-deficient mice are generally refractory to carcinogenesis, while deficiencies in Neil1-deficient mice confer cancer susceptibility. In contrast to NEIL1, OGG1 functions as a key transcription factor in regulating inflammation and other complex gene cascades. With regard to phenotypes attributed to mitochondrial repair, knockout of either of these genes results in age- and diet-induced metabolic syndrome. The adverse health consequences associated with metabolic syndrome can be largely overcome by expression of a mitochondrial-targeted human OGG1 in both wild-type and Ogg1-deficient mice. The goal of this review is to compare the roles that NEIL1 and OGG1 play in maintaining genomic integrity, with emphasis on insights gained from not only the diverse phenotypes that are manifested in knockout and transgenic mice, but also human disease susceptibility associated with polymorphic variants. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficiency of radiomics signatures in predicting the response of transarterial chemoembolization (TACE) therapy based on preoperative contrast-enhanced computed tomography (CECT).Materials: This study consisted of 111 patients with intermediate-stage hepatocellular carcinoma who underwent CECT at both the arterial phase (AP) and venous phase (VP) before and after TACE. According to mRECIST 1.1, patients were divided into an objective-response group (n = 38) and a non-response group (n = 73). Among them, 79 patients were assigned as the training dataset, and the remaining 32 cases were assigned as the test dataset.Methods: Radiomics features were extracted from CECT images. Two feature ranking methods and three classifiers were used to find the best single-phase radiomics signatures for both AP and VP on the training set. Meanwhile, multi-phase radiomics signatures were built upon integration of images from two CECT phases by decision-level fusion and feature-level fusion. Finally, multivariable logistic regression was used to develop a nomogram by combining radiomics signatures and clinic-radiologic characteristics. The prediction performance was evaluated by AUC on the test dataset.Results: The multi-phase radiomics signature (AUC = 0.883) performed better in predicting TACE therapy response compared to the best single-phase radiomics signature (AUC = 0.861). The nomogram (AUC = 0.913) showed better performance than any radiomics signatures.Conclusion: The radiomics signatures and nomogram were developed and validated for predicting responses to TACE therapy, and the radiomics model may play a positive role in identifying patients who may benefit from TACE therapy in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Accumulating evidence suggests that light at night (LAN) disrupts circadian rhythms and may increase risk of liver cancer. However, there is no population-based study that examined LAN and liver cancer risk. Therefore, we aimed to investigate the association between outdoor LAN and liver cancer risk in a prospective cohort.Methods: Residential outdoor LAN level was measured from satellite imagery in the NIH-AARP Diet and Health Study, a prospective cohort of 451,945 men and women, 50-71 years old. Relative risks (RR) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models that adjusted for known risk factors for liver cancer and neighborhood characteristics.Results: During an average 12.2 years of follow-up, 897 liver cancers, 603 of which were hepatocellular carcinomas (HCC), were diagnosed. Residential outdoor LAN was not associated with risk of liver cancer (RRQ5 vs Q1 = 0.96, 95% CI: 0.77-1.20, p trend = 0.771) or HCC (RRQ5 vs Q1 = 0.82, 95% CI: 0.62-1.07, p trend = 0.425).Conclusion: No association between outdoor LAN and risk of liver cancer or HCC may in part be due to limitations in LAN assessment. More studies on the relationship between light intensity, duration, timing, and wavelength and liver cancer are warranted. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic performance of LR‐5 for diagnosing poorly differentiated hepatocellular carcinoma (p‐HCC). To build a contrast‐enhanced ultrasound (CEUS) signature for improving the differential diagnostic performance between p‐HCC and intrahepatic cholangiocarcinoma (ICC). Methods: The B‐mode ultrasound (BUS) and CEUS features of 60 p‐HCCs and 56 ICCs were retrospectively analyzed. The CEUS LI‐RADS category was assigned according to CEUS LI‐RADS v2017. A diagnostic CEUS signature was built based on the independent significant features. An ultrasound (US) signature combining both BUS and CEUS features was also built. The diagnostic performances of the CEUS signature, US signature, and LR‐5 were evaluated by receiver operating characteristic (ROC) analysis. Results: One (1.7%) p‐HCC and 26 (46.4%) ICC patients presented cholangiectasis or cholangiolithiasis (P <.001). Fifty‐four (90.0%) p‐HCCs and 8 (14.3%) ICCs showed clear boundaries in the artery phase (P <.001). The washout times of p‐HCCs and ICCs were 81.0 ± 42.5 s and 34.7 ± 8.6 s, respectively (P <.001). The AUC, sensitivity, and specificity of the CEUS signature, US signature, and LR‐5 were 0.955, 91.67%, and 90.57% versus 0.976, 96.67%, and 92.45% versus 0.758, 51.67%, and 100%, respectively. The AUC and sensitivity of CEUS LI‐RADS were much lower than those of the CEUS and US signatures (P <.001). Conclusion: LR‐5 had high specificity but low sensitivity in diagnosing p‐HCC. When the washout time and tumor boundary were included in the CEUS signature, the sensitivity and AUC were remarkably increased in the differentiation between p‐HCC and ICC. [ABSTRACT FROM AUTHOR]

Background: Several studies have demonstrated a relationship between genetic polymorphisms of interleukin-1 beta (IL-1β) and cancer development; however, their influence on cancer prognosis is unknown. In the present study, we aimed to evaluate the impact of IL-1β single nucleotide polymorphisms on the hematogenous dissemination and prognosis of hepatocellular carcinoma., Methods: We conducted a retrospective cohort study including patients with hepatocellular carcinoma who underwent primary liver resection at our hospital between April 2015 and December 2018. The primary endpoints were overall and recurrence-free survival. Secondary endpoints were microscopic portal vein invasion and number of circulating tumor cells., Results: A total of 148 patients were included, 32 with rs16944 A/A genotype. A/A genotype was associated with microscopic portal vein invasion and number of circulating tumor cells (p = .03 and .04). In multivariate analysis, A/A genotype, alpha-fetoprotein level, and number of circulating tumor cells were associated with microscopic portal vein invasion (p = .01, .01, and <.01). A/A genotype, Child-Pugh B, and intraoperative blood loss were independent predictive factors for overall survival (p = .02, <.01, and <.01)., Conclusions: Our results indicate that the IL-1β rs16944 A/A genotype is involved in number of circulating tumor cells, microscopic portal vein invasion, and prognosis in HCC., (© 2024 The Author(s). Journal of Hepato‐Biliary‐Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Combination therapies targeting two immune checkpoint regulators (PD-1 and CTLA-4) or PD-1 concurrently with the angiogenic pathway prolong the overall survival time to nearly twice that of patients receiving monotherapy ([3]; also reviewed by He et al. below). Keywords: Hepatocellular carcinomas; biomarkers; immune-checkpoint inhibitors; PD-1; PD-L1; immunotherapies; bioinformatics EN Hepatocellular carcinomas biomarkers immune-checkpoint inhibitors PD-1 PD-L1 immunotherapies bioinformatics 1 2 2 03/14/22 20220310 NES 220310 Hepatocellular carcinomas (HCCs), made up of 75-85% of primary liver cancers, remain the leading cause of new cancer cases (>0.7 million) and cancer deaths (>0.6 million) globally according to the data collected up to 2020 before the coronavirus disease 2019 (COVID-19) pandemic ([1]). Hepatocellular carcinomas, biomarkers, immune-checkpoint inhibitors, PD-1, PD-L1, immunotherapies, bioinformatics. [Extracted from the article]