Liver Cancer最新文献

Introduction: Previous research has demonstrated that an isocaloric diet rich in trans-fatty acid (TFA), saturated fatty acid (SFA), and cholesterol (Chol) promoted steatosis-derived hepatic tumorigenesis in hepatitis C virus core gene transgenic (HCVcpTg) mice in different manners. Growth factor signaling and ensuing angiogenesis/lymphangiogenesis are key factors in hepatic tumorigenesis that have become recent therapeutic targets for hepatocellular carcinoma. However, the influence of dietary fat composition on these factors remains unclear. This study investigated whether the type of dietary fat would have a specific impact on hepatic angiogenesis/lymphangiogenesis in HCVcpTg mice.

Methods: Male HCVcpTg mice were treated with a control diet, an isocaloric diet containing 1.5% cholesterol (Chol diet), or a diet replacing soybean oil with hydrogenated coconut oil (SFA diet) for a period of 15 months or with shortening (TFA diet) for 5 months. The degree of angiogenesis/lymphangiogenesis and the expression of growth factors, including fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF), were evaluated in non-tumorous liver tissues using quantitative mRNA measurement, immunoblot analysis, and immunohistochemistry.

Results: Long-term feeding of SFA and TFA diets to HCVcpTg mice increased the expressions of vascular endothelial cell indicators, such as CD31 and TEK receptor tyrosine kinase, in addition to lymphatic vessel endothelial hyaluronan receptor 1, indicating that angiogenesis/lymphangiogenesis were upregulated only by these fatty acid-enriched diets. This promoting effect correlated with elevated VEGF-C and FGF receptor 2 and 3 levels in the liver. c-Jun N-terminal kinase (JNK) and hypoxia-inducible factor (HIF) 1α, both key regulators of VEGF-C expression, were enhanced in the SFA- and TFA-rich diet groups as well. The Chol diet significantly increased the expressions of such growth factors as FGF2 and PDGF subunit B, without any detectable impact on angiogenesis/lymphangiogenesis.

Conclusion: This study revealed that diets rich in SFA and TFA, but not Chol, might stimulate hepatic angiogenesis/lymphangiogenesis mainly through the JNK-HIF1α-VEGF-C axis. Our observations indicate the importance of dietary fat species for preventing hepatic tumorigenesis.

Introduction: The present study aimed to evaluate the influence of biological characteristics of hepatocellular carcinoma (HCC) on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasound (CEUS) in patients with high risk and compare the outcomes among different categories after radical resection.

Methods: Between June 2017 and December 2020, standardized CEUS data of liver nodules were prospectively collected from multiple centers across China. We conducted a retrospective analysis of the prospectively collected data on HCCs measuring no more than 5 cm, as diagnosed by pathology. LI-RADS categories were assigned after thorough evaluation of CEUS features. Then, CEUS LI-RADS categories and major features were compared in different differentiation, Ki-67, and microvascular invasion (MVI) statuses. Differences in recurrence-free survival (RFS) among different LI-RADS categories were further analyzed.

Results: A total of 293 HCC nodules in 293 patients were included. This study revealed significant differences in the CEUS LI-RADS category of HCCs among differentiation (p < 0.001) and levels of Ki-67 (p = 0.01) and that poor differentiation (32.7% in LR-M, 12% in LR-5, and 6.2% in LR-4) (p < 0.001) and high level of Ki-67 (median value 30%) were more frequently classified into the LR-M category, whereas well differentiation (37.5% in LR-4, 15.1% in LR-5, and 11.5% in LR-M) and low levels of Ki-67 (median value 11%) were more frequently classified into the LR-4 category. No significant differences were found between MVI and CEUS LI-RADS categories (p > 0.05). With a median follow-up of 23 months, HCCs assigned to different CEUS LI-RADS classes showed no significant differences in RFS after resection.

Conclusions: Biological characteristics of HCC, including differentiation and level of Ki-67 expression, could influence major features of CEUS and impact the CEUS LI-RADS category. HCCs in different CEUS LI-RADS categories showed no significant differences in RFS after resection.

Introduction: We aimed to investigate the significance of lymph node metastasis from hepatocellular carcinoma and the efficacy of local treatment.

Methods: We included patients diagnosed hepatocellular carcinoma with lymph node metastasis. The pattern of lymph node metastasis was evaluated based on imaging examinations and stratified by three locations: regional (group A), beyond regional intra-abdomen (group B), and extra-abdomen (group C) lymph node metastasis.

Results: Among 14,474 patients, 852 (5.8%) were identified as having lymph node metastasis. Regarding the location of presentation, group A showed the highest incidence, followed by groups B and C. The 1-year overall survival of patients was 31.7%. The survival significantly differed according to the location of lymph node metastasis. The 1-year overall survival rates were 39.8%, 25.5%, and 22.2% in groups A, B, and C, respectively. All patients underwent systemic treatment, with others receiving additional local treatment. Local treatment yielded superior overall survival compared with no local treatment. After propensity score matching, local treatment was associated with improved survival. Additionally, patients were stratified based on disease status at the time of diagnosis of lymph node metastasis: lymph node alone and combined extra-nodal metastasis. The survival benefits of local treatment were observed in both groups.

Conclusions: Our findings demonstrated the clinical significance of lymph node metastasis from hepatocellular carcinoma, which was well discriminated according to location, favoring regional metastasis. In patients with hepatocellular carcinoma presenting lymph node metastasis, active application of local treatment for lymph node metastasis can improve oncologic outcomes.

Introduction: We conducted a systematic literature review to assess the utility of liver function assessments for predicting disease prognosis and response to systemic anticancer therapy in patients with advanced hepatocellular carcinoma (aHCC).

Methods: This was a PRISMA-standard review and was registered with PROSPERO (CRD42021244588). MEDLINE and Embase were systematically searched (March 24, 2021) to identify publications reporting the efficacy and/or safety of systemic anticancer therapy (vs. any/no comparator) in liver-function-defined subgroups in phase 2 or 3 aHCC trials. Screening was completed by a single reviewer, with uncertainties resolved by a second reviewer and/or the authors. English-language full-text articles and congress abstracts were eligible for inclusion. Included publications were described and assessed for risk of bias using the GRADE methodology.

Results: Twenty (of 2,579) screened publications were eligible; seven categorized liver function using the albumin-bilirubin system, nine using the Child-Pugh system, four using both. GRADE assessment classified ten, nine, and one publication(s) as reporting moderate-quality, low-quality, and very-low-quality evidence, respectively. Analyses of cross-trial trends of within-exposure arm analyses (active and control) reported a positive relationship between baseline liver function and overall survival and progression-free survival, supporting liver function as a prognostic marker in aHCC. There were also signals for a modest relationship between more preserved baseline liver function and extent of systemic treatment benefit, and with more preserved liver function and lower incidence of safety events.

Conclusion: This review supports liver function as a prognostic variable in aHCC and highlights the value of a priori stratification of patients by baseline liver function in aHCC trials. The predictive value of liver function warrants further study. Findings were limited by the quality of available data.

Introduction: Proton beam therapy (PBT) is known to be an effective locoregional treatment for hepatocellular carcinoma (HCC). However, few comparative studies in treatment-naïve cases have been reported. The aim of this study was to compare the survival outcomes of PBT with those of radiofrequency ablation (RFA) in patients with treatment-naïve solitary HCC.

Methods: Ninety-five consecutive patients with treatment-naïve HCC, a single nodule measuring ≤5 cm in diameter, and a Child-Pugh score of ≤8 who were treated with PBT at the University of Tsukuba Hospital between 2001 and 2013 were enrolled in the study. In addition, 836 patients with treatment-naïve HCC treated by RFA at the University of Tokyo Hospital during the same period were analyzed as controls. Recurrence-free survival (RFS) and overall survival (OS) were compared in 83 patient pairs after propensity score matching.

Results: The 1-year, 3-year, and 5-year RFS rates were 86.6%, 49.5%, and 35.5%, respectively, in the PBT group and 59.5%, 34.0%, and 20.9% in the RFA group (p = 0.058); the respective OS rates were 97.6%, 77.8%, and 57.1% in the PBT group and 95.1%, 81.7%, and 67.7% in the RFA group (p = 0.16). Regarding adverse effects, no grade 3 or higher adverse events were noted in the PBT; however, two grade 3 adverse events occurred within 30 days of RFA in the RFA group: one hemoperitoneum and one hemothorax.

Discussion: After propensity score matching, PBT showed no significant difference in RFS and OS compared to RFA. PBT can be an alternative for patients with solitary treatment-naïve HCC.