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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. The risk factors for HCC include chronic hepatitis B and C virus infections, excessive alcohol consumption, obesity, metabolic disease, and aflatoxin exposure. In addition to these viral and environmental risk factors, individual genetic predisposition is a major determinant of HCC risk. Familial clustering of HCC has been observed, and a hereditary factor likely contributes to the risk of HCC development. The familial aggregation may depend on a shared environment and genetic background as well as the interactions of environmental and genetic factors. Genome-wide association studies (GWASs) are one of the most practical tools for mapping the patterns of inheritance for the most common form of genomic variation, single nucleotide polymorphisms. This approach is practical for investigating genetic variants across the human genome, which is affected by thousands of common genetic variants that do not follow Mendelian inheritance. This review article summarizes the academic knowledge of GWAS-identified genetic loci and their association with HCC. We summarize the GWASs in accordance with various chronic hepatitis virus infection statuses. This genetic profiling could be used to identify candidate biomarkers to refine HCC screening and management by enabling individual risk-based personalization and stratification. A more comprehensive understanding of the genetic mechanisms underlying individual predisposition to HCC may lead to improvements in the prevention and early diagnosis of HCC and the development of effective treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose. To retrospectively evaluate the efficacy and safety of TACE combined with microwave ablation (MWA) and TACE combined with cryoablation (CRA) in the treatment of large hepatocellular carcinoma. Methods. A retrospective analysis was performed on 81 patients with large hepatocellular carcinoma (tumor diameter 5～8 cm cm) who received TACE combined with ablation in our hospital from February 2015 to February 2019. The study patients were divided into TACE combined with MWA group (T-MWA, n = 41) and TACE combined with CRA group (T-CRA, n = 40) according to the treatment plan. Overall survival (OS) and progress free survival (PFS) were compared between the two groups, and complications were observed. Survival curves for OS and PFS were constructed by the Kaplan–Meier method. Differences in overall survival were compared using the log-rank test. Results. There was no statistical difference in general conditions between the two groups of patients. The results showed that 30 (73.2%) patients in T-MWA group achieved objective response (OR) and 39 (95.1%) patients achieved disease control (DC), compared with 24 (60.0%) patients in T-CRA group who achieved objective response (OR) and 37 (92.5%) patients who achieved disease control (DC). The median OS was 19.2 months in the T-MWA group and 18.6 months in the T-CRA group (P = 0.64). The median PFS was 9.3 months in the T-MWA group and 12.3 months in the T-CRA group (P = 0.6). Univariate and multivariate analysis showed that portal vein tumor thrombus (PVTT), intrahepatic tumor diameter, and the number of tumor lesions were common prognostic factors for OS and PFS. In terms of surgery-related complications and adverse reactions, abdominal pain and gastrointestinal reactions were observed in 13 (31.7%) and 11(26.8%) cases in the T-MWA group, while we observed 4 (10.0%) and 2 (5.0%) cases in the T-CRA group, respectively. The difference between the two was statistically significant (P < 0.05). Conclusion. TACE combined with MWA and TACE combined with CRA were equally effective in the treatment of large hepatocellular carcinoma. TACE-CRA can effectively reduce the incidence of abdominal pain and gastrointestinal reactions in patients. However, compared with TACE-MWA, TACE-CRA is more likely to cause thrombocytopenia. [ABSTRACT FROM AUTHOR]

Background: Whether the weaning outcome of solid cancer patients receiving mechanical ventilation (MV) in the intensive care unit (ICU) is comparable to that in non-cancer patients is unknown. The aim of this study was to compare the weaning outcomes between non-cancer patients and patients with different types of cancer.Methods: We studied patients requiring MV during ICU stay for medical reasons between 2012 and 2014. Cancer patients were grouped into those with lung cancer (LC), head and neck cancer (HNC), hepatocellular carcinoma (HCC), and other cancers (OC). The primary endpoint was successful weaning at day 90 after the initiation of MV, and the main secondary endpoints were 28-day and 90-day mortality after ICU admission.Results: Five hundred and eighteen patients with solid cancers and 1362 non-cancer patients were recruited. The rate of successful weaning at day 90 was 57.9% in cancer patients, which was lower than 68.9% in non-cancer patients (p < 0.001). Compared to non-cancer patients, LC was associated with a lower probability of weaning at day 90 (hazard ratio 0.565, 95% CI 0.446 to 0.715), while HNC, HCC, and OC had similar probabilities. The 28-day and 90-day mortality rates were higher in cancer patients than in non-cancer patients (45.2% vs. 29.4%, and 65.6% vs. 37.7%, respectively, both p < 0.001).Conclusion: Among mechanically ventilated patients in the ICU, those with LC were associated with a lower probability of weaning at day 90 compared to non-cancer patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous microwave ablation (MWA) in the treatment of advanced hepatocellular carcinoma (HCC).Materials and Methods: Three thousand cases of advanced HCC patients were randomly divided into two groups: 1500 cases in the treatment group were treated with TACE combined with MWA and 1500 cases in the control group were treated with TACE.Results: The effective rate of the treatment group and control group was 71.4% and 42.8%, respectively, and the difference between the two groups was statistically significant (P < 0.05). During the follow-up period at 6, 12, 18, and 24 months postoperatively, the survival rates of the treatment group were 88.1%, 73.8%, 52.3%, and 33.3%, and the survival rates of the control group were 76.2%, 57.1%, 30.9%, and 9.5%, respectively. There was no significant difference in postoperative complications between the two groups.Conclusion: It is safe and effective to use TACE combined with MWA in the treatment of advanced HCC, and the effect of combined treatment is better than that of TACE alone. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To assess patient radiation dose reduction and the image quality of a new X-ray imaging technology during repetitive transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Methods: Fifty HCC patients (36 men; 57 ± 11 years) undergoing repetitive TACE were first randomly assigned to receive a TACE treatment on a reference X-ray system or a low-dose system with advanced real-time image processing. The alternate system was used for a repeated TACE (treatment interval, 0.5-6 months). Fluoroscopy time, number of digital subtraction angiography (DSA), air kerma (AK), and dose area product (DAP) were compared between the two systems and between the two repetitive TACE. Three interventional radiologists independently rated the image quality in blinded offline readings. Results: Fluoroscopy time (8.7 ± 5.9 minutes vs. 8.7 ± 7.9 minutes, P = .981), numbers of DSA runs (6 ± 4 vs. 6 ± 4, P = .735), and exposure images (173 ± 86 vs. 168 ± 91, P = .916) were equivalent between the two systems. No statistical difference in X-ray usage was found between repeated treatments. Compared to the reference system, the technology significantly reduced AK and DAP by 48.6% (0.17 ± 0.13 Gy vs. 0.41 ± 0.36 Gy, P < .0001) and 50.3% (77.3 ± 55.2 Gy cm(2) vs. 195.0 ± 155.5 Gy cm(2), P < .0001), respectively. Image quality was rated comparable between the new system and the reference, with average scores of 3.9 ± 0.3 versus 4.4 ± 0.3 in fluoroscopy and 4.5 ± 0.2 versus 4.3 ± 0.3 in DSA. Conclusions: Patient radiation exposure can be substantially reduced by a factor of approximately two with the novel X-ray imaging technology while maintaining image quality. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Altered actin isoform expression occurs in some pathological conditions including muscular malignancies. This study was to investigate whether a similar event occurs in hepatocellular carcinoma. Methods: Cellular RNA was extracted from cancerous and non-cancerous hepatoma tissues. Reverse transcription (RT)-PCR followed by cloning and sequencing was performed to obtain populations of actin sequences. Phylogenetic analysis was carried out to identify novel actin isoforms. Interaction between the novel actin isoform and other cellular proteins was examined by the yeast two-hybrid system. The relative amounts of the novel actin isoform in the cancerous and non-cancerous tissues were further assayed using real-time PCR with specific primers. Results: When compared between the cancerous and non-cancerous tissues, the proportion of non-β-actins in the cancerous parts increased significantly in three of four cases included. Among the non-β-actins, a novel group of isoforms was identified, temporarily named κ-actins. Two genetically closely related sequences, FKSG30 and an actin-like sequence in the Cat Eye syndrome region, were found to cluster with the κ-actins. Protein interaction assay indicated that the interaction between κ-actin and prefoldin 2 was greatly diminished. The relative amounts of κ-actin increased in 12 of 20 cancerous tissues assayed. Conclusions: A novel class of actin isoforms was expressed in some hepatocellular carcinoma tissues, replacing β-actins to become the major constituents of actin cytoskeleton. [Copyright &y& Elsevier]

AbstractBackground: The purpose of this study was to determine the potential role of three-dimensional (3-D) conformal radiotherapy (RT) in treatment of unresectable hepatocellular carcinoma (HCC). Methods: Thirteen patients were included in this study, which was conducted between 1993 and 1996. Nine patients (group A) were treated with 3-D conformal RT alone because of main portal vein thrombosis, inferior vena cava thrombosis, obstructive jaundice and failure of previous transcatheter arterial chemoembolization (TACE) to control the disease. The remaining four patients (group B) were treated with a combination of TACE and 3-D conformal RT. Results: The greatest dimension of the main tumour in the whole group of patients ranged from 6 to 25 cm (median 15 cm). The radiation dose ranged from 40 to 60 Gy. The tumour response was evaluated by computed tomography scans of the liver 6–8 weeks after completion of radiotherapy. Partial response was observed in 58% of the patients (seven of 12) and minimal response in another 25% of patients (three of 12). One patient could not be evaluated because of the development of hepatic failure 1 month after completion of RT. All patients in group B lived for more than 1 year (range 16–40 months). In group A, one patient who had a large tumour (11 × 10 × 21 cm) with portal vein thrombosis was converted to become resectable after 45 Gy of radiation. The resection specimen revealed no residual cancer cells. This patient is alive longer than 15 months after treatment without the evidence of disease. Conclusions: Our experience indicates that HCC is more radiosensitive than it was traditionally expected. Three-dimensional reconstruction of tumour and surrounding organs helps to avoid excessive exposure of the liver and adjacent organs to RT and makes it a safer treatment modality for unresectable HCC. Our preliminary data show promise and are worthy of further study to explore the potential role of radiotherapy in the treatment strategy for HCC at various stages of involvement. © 1999 Blackwell Science Asia Pty Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Hepatocellular carcinoma (HCC) often develops on a background of chronic inflammation and a complex immunosuppressive network with increased regulatory T cells, impaired CD8+ T cells and the secretion of immunosuppressive cytokines. Previous clinical studies have reported a superior disease-free survival (DFS) following a radiofrequency-based ablation or resection in HCC tumours compared to conventional liver resection techniques. The aim of this study was to investigate whether there is any correlation with the use of a radiofrequency-assisted liver resection and clinical outcome. Material and Methods: Patients' peripheral blood was collected prior and 7 days following surgery from patients undergoing a liver resection for HCC. There were 5 liver resections performed using CUSA and 6 liver resections with the RF-based device, HabibTM 4X. The primary endpoint of the study was to assess the immunological parameters of circulating immune cell populations as well as serum cytokines. The Student's t-test, chi-square or Fisher's Exact test were applied for statistical comparisons, as appropriate. Results: Patients undergoing an RF-assisted liver resection with HabibTM 4X had a significant decrease in the inhibitory Treg cells (p = 0.002) and a significant increase in CD8+ T lymphocytes (p = 0.050) and CD4+CD45RO+/CD4+ memory T cells (p = 0.002) compared to those patients undergoing a liver resection with CUSA. It was also noted that the RF-assisted liver resection group had a significant decrease in circulating TGF-ß (p = 0.000), IL10 (p = 0.000) and a significant increase in IFN-gamma (p = 0. 027) and IL-17 compared to the CUSA group. Conclusion: A liver resection with RF-based device HabibTM 4X was associated with positive immunomodulatory changes in circulating immune cells and circulating cytokines which could explain the significant improvement in DFS. [ABSTRACT FROM AUTHOR]

Abstract: A cDNA encoding hepatitis C virus NS5A protein was isolated from the serum of a patient with hepatocellular carcinoma. The NS5AHCC was localized in both the cytoplasmic and nuclear fractions of Huh-7 cells. Immunoprecipitation and electrophoresis experiments showed four major phosphorylated species of NS5AHCC, p58, p56, p53, and p50. Two mutants (NS5AHCC-NLSmt and NS5AHCC-TSmt) carrying mutations on the putative nuclear localization signal were engineered. NS5AHCC-NLSmt was localized exclusively in the cytoplasm, whereas some forms of NS5AHCC-TSmt can be transported into the nucleus. These NS5AHCC mutant proteins were capable of transactivating c-fos and SV40 promoters. However, the transactivation efficiency was not dependent on its capability of nuclear localization. Subsequently, interaction between NS5AHCC mutants and Grb2 was studied. While capable of transactivating oncogenic promoters, NS5AHCC-TSmt could not interact with Grb2. Our results suggested that other cytosolic pathways independent of Grb2-mediated mechanisms were involved in the transactivation activity of HCV NS5A. [Copyright &y& Elsevier]

Twelve patients with hepatocellular carcinoma and chronic hepatitis developed radiation-induced liver disease (RILD) after three-dimensional conformal radiotherapy. Six patients died of RILD and six recovered. Mean prescribed dose was 50.6±4.3 Gy, in a daily fraction of 1.8–2.0 Gy. Commonly used dosimetric parameters, such as fraction volume of normal liver with radiation dose >30 Gy, prediction score, and normal tissue complication probability, failed to differentiate the fatality and clinical types of this complication. Elevated transaminases are more frequently seen than ascites and elevated alkaline phosphamide are seen in patients with RILD. [Copyright &y& Elsevier]