Background and objectives: Transarterial chemoembolization (TACE) and 125I seed implantation are methods used to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), PVTT often associated with arterioportal shunts(APS), there are few reports on the combined use of TACE and 125I seed implantation for such patients. This study aimed to evaluate the efficacy and safety of TACE combined with PVTT 125I seed implantation in the treatment of HCC patients with APS.
Methods: Forty-two patients diagnosed with HCC combined with PVTT and APS between January 2020 and December 2021 were included. Appropriate materials were selected to transarterial embolization of the APS, and 125I seeds were implanted into the PVTT. The occlusion effect was observed and recorded after 3 months, the efficacy of intrahepatic lesions and PVTT was evaluated, and the patient survival, prognostic factors affecting APS recanalization were analyzed.
Results: All 42 patients completed the follow-up three months after treatment. The immediate APS improvement rate was 100%, and the APS improvement rate at the three-month follow-up was 64.29%. The disease control rates of PVTT and intrahepatic lesions were 81.00% and 78.60%, respectively. The patients' 6-month and 12-month survival rates were 78.6% and 46.8%. The median OS for all patients was 11.90 months, and the median OS was 13.30 months in the APS effective treatment group and 8.30 months in the ineffective group. The PVTT type is the only independent factor affecting APS recanalization. (P=0.02).
Conclusion: For HCC patients with PVTT and APS, TACE combine with 125I seed implantation in PVTT is a potentially effective and safe method that contributes to prolonging patient survival.
Purpose: To predict the efficacy of patients treated with hepatectomy and transarterial chemoembolization (TACE) based on machine learning models using clinical and radiomics features.
Patients and methods: Patients with HCC whose first treatment was hepatectomy or TACE from June 2016 to July 2021 were collected in the retrospective cohort study. To ensure a causal effect of treatment effect and treatment modality, perfectly matched patients were obtained according to the principle of propensity score matching and used as an independent test cohort. Inverse probability of treatment weighting was used to control bias for unmatched patients, and the weighted results were used as the training cohort. Clinical characteristics were selected by univariate and multivariate analysis of cox proportional hazards regression, and radiomics features were selected using correlation analysis and random survival forest. The machine learning models (Deathhepatectomy and DeathTACE) were constructed to predict the probability of patient death after treatment (hepatectomy and TACE) by combining clinical and radiomics features, and an optimal treatment regimen was recommended. In addition, a prognostic model was constructed to predict the survival time of all patients.
Results: A total of 418 patients with HCC who received either hepatectomy (n=267, mean age, 58 years ± 11 [standard deviation]; 228 men) or TACE (n=151, mean age, 59 years ± 13 [standard deviation]; 127 men) were recruited. After constructing the machine learning models Deathhepatectomy and DeathTACE, patients were divided into the hepatectomy-preferred and TACE-preferred groups. In the hepatectomy-preferred group, hepatectomy had a significantly prolonged survival time than TACE (training cohort: P < 0.001; testing cohort: P < 0.001), and vise versa for the TACE-preferred group. In addition, the prognostic model yielded high predictive capability for overall survival.
Conclusion: The machine learning models could predict the outcomes difference between hepatectomy and TACE, and prognostic models could predict the overall survival for HCC patients.
Purpose: To study the MRI features (based on LI-RADS) and clinical characteristics of P53-mutated hepatocellular carcinoma (HCC) patients.
Patients and methods: This study enrolled 344 patients with histopathologically confirmed HCC (P53-mutated group [n = 196], non-P53-mutated group [n = 148]). We retrospectively evaluated the preoperative MRI features, clinical and pathologic features of the lesions and assigned each lesion according to the LI-RADS. MRI findings, clinical features, and pathologic findings were compared using the Student's t test, χ2 test, and multivariable regression analysis.
Results: Most HCC patients were categorized as LR-5. On multivariate analysis, the Edmondson-Steiner grade (odds ratio, 2.280; 95% CI: 1.268, 4.101; p = 0.006) and rim enhancement (odds ratio, 2.517; 95% CI: 1.095, 5.784; p = 0.030) were found to be independent variables associated with P53-mutated HCC. In the group of HCC lesions with the largest tumor diameter (LTD) greater than or equal to 10mm and less than or equal to 20mm, enhancing capsule was an independent predictor of P53-mutated HCC (odds ratio, 6.200; 95% CI: 1.116, 34.449; p = 0.037). Among the HCC lesions (20 mm ˂ LTD ≤ 50 mm), corona enhancement (odds ratio, 2.102; 95% CI: 1.022, 4.322; p = 0.043) and nodule-in-nodule architecture (odds ratio, 2.157; 95% CI: 1.033, 4.504; p = 0.041) were found to be independent risk factors for P53 mutation. Among the HCC lesions (50 mm ˂ LTD ≤ 100 mm), diameter (odds ratio, 1.035; 95% CI: 1.001, 1.069; p = 0.044) and AFP ≥ 400 (ng/mL) (odds ratio, 3.336; 95% CI: 1.052, 10.577; p = 0.041) were found to be independent variables associated with P53-mutated HCC.
Conclusion: Poor differentiation and rim enhancement are potential predictive biomarkers for P53-mutated HCC, while HCCs of different diameters have different risk factors for predicting P53 mutations.
Purpose: Alanine glyoxylate aminotransferase (AGXT) family members are crucial in cancer processes, but their role in hepatocellular carcinoma (HCC) metabolism is unclear. This study investigates AGXT2's function in HCC.
Patients and methods: AGTX2 expression was studied using bioinformatics, real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), Western blot, and Enzyme-linked immunosorbent assay (ELISA). A lentivirus-induced AGTX2 overexpression cell model was analyzed with RNA sequencing (RNA-seq) and liquid chromatography-mass spectrometry (LC-MS). Cholesterol levels were confirmed by Oil Red O staining. AGTX2 effects were evaluated through cell cycle analysis, wound healing, and transwell migration assays.Tumorigenic effects were observed in NOD-SCID IL2Rγnull (NTG) mice in subcutaneous experiments. Protein interaction was examined through co-immunoprecipitation methods.
Results: We observed a significant reduction in AGXT2 mRNA and protein levels in both HCC tumor tissues and serum samples from patients with liver cancer, which was associated with a worse prognosis. The activation of AGXT2 has been shown to effectively decrease cholesterol levels in liver cancer cells, serving as an antagonist in the cholesterol metabolism pathway. An increase in low density lipoprotein receptor (LDLR) mRNA was noted in cells overexpressing AGXT2, accompanied by a decrease in LDLR protein and an elevation in proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA and protein levels. Molecular docking and co-immunoprecipitation experiments further elucidated the interaction between AGXT2 and LDLR proteins. AGXT2 was observed to suppress the migratory and invasive capabilities of HCC cells, inducing cell cycle arrest in the G2/M phase. AGXT2 activation inhibited subcutaneous liver cancer tumor growth in NTG mice.
Conclusion: AGXT2 was found to lower cholesterol levels in liver cancer cells, possibly through interactions with the LDLR protein and modulation of PCSK9-mediated LDLR degradation. This mechanism may impede cholesterol transport to liver cancer cells, thereby suppressing their growth and metastasis.
Purpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib and tislelizumab (TACE-Len-T) versus TACE plus lenvatinib (TACE-Len) as the first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).
Patients and methods: This retrospective study included 136 uHCC patients treated with TACE-Len-T or TACE-Len from January 1, 2021, to June 30, 2023. Clinical outcomes including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs) were compared between the two groups. The risk factors affecting OS and PFS were also analyzed.
Results: The median OS and PFS of the TACE-Len-T group were significantly longer than those of the TACE-Len group (Median OS: not reached vs 13.8 months, P<0.001; Median PFS: 13.0 months vs 2.7 months, P<0.001). The best overall objective response rate (ORR) was also better with TACE-Len-T treatment (ORR: 72.1% vs 29.4%, P<0.001), and the disease control rate (DCR) significantly increased in the TACE-Len-T group (88.2% vs 48.5%, P<0.001). Multivariate analyses revealed that TACE-Len treatment, tumor number >3, and cTACE were independent risk factors for OS, whereas TACE-Len treatment was the only independent risk factor for PFS. The frequency and severity of AEs in the TACE-Len-T group were comparable to those in the TACE-Len group (any grade: 92.6% vs 91.2%, P=0.753; grade 3 or 4: 33.8% vs 32.3%, P=0.855).
Conclusion: TACE-Len-T treatment significantly improved OS, PFS, ORR, and DCR over TACE-Len treatment, with a manageable safety profile in uHCC.
Background: The prognosis of initially unresectable hepatocellular carcinoma (iuHCC) has been improved by TACE with TKIs and PD-1 inhibitors (TTP). However, the role of timing of tumor progression and and early salvage surgery during TTP therapy remains unclear.
Patients and methods: The data of 151 patients who received TTP for iuHCC consecutively between November 2019 and December 2022 were retrospectively analyzed. The X-Tile software was used to determine the optimal threshold of progression timing to differentiate the post-progression survival (PPS) for patients with tumor progression, ultimately yielding 9 months as the optimal cut-off time. Early tumor progression was defined as patients with tumor recurrence (surgical patients) or progressive disease by mRECIST (nonsurgical patients) within 9 months of initial treatment. Accordingly, early salvage surgery was defined as salvage surgery performed within 9 months of the initial treatment.
Results: Out of all the patients, 55 (36.4%) patients showed early tumor progression, 33 (34.4%) showed late tumor progression, and 63 (41.7%) showed non-progression. Patients who experienced early tumor progression had a median PPS of 5.2 months, while those with late tumor progression had a median PPS of 16.8 months (P < 0.001). Multivariable analysis revealed a robust independent correlation between early tumor progression and PPS (HR = 3.279, 95% CI: 1.591-6.756; P = 0.001). Patients who received early salvage surgery showed a considerably lower early tumor progression rate when compared with patients who did not receive early surgery (12.5% vs 42.9%, P = 0.002). The multivariable analysis revealed that early salvage surgery was an independent factor influencing early tumor progression (OR = 0.246; 95% CI: 0.078-0.773; P = 0.016).
Conclusion: Early tumor progression is associated with worse PPS in patients with iuHCC receiving TTP therapy. Early salvage surgery can further improve patient outcomes by lowering the incidence of early progression.
Background and aims: Six-monthly ultrasound surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis. Surveillance enhances early detection and improves survival. Yet, despite clear benefits, uptake remains low. We aim to identify and explore ways to overcome patient-related barriers to HCC surveillance with the aim of producing invitations for surveillance.
Methods: Using the COM-B model of behaviour and a co-design process, we collaborated with patients, liver health charities and advocacy groups, to identify patient-related barriers to attending HCC surveillance. We performed qualitative thematic analysis of co-production workshops on HCC surveillance to develop information leaflets and surveillance invitations.
Results: Twenty-eight participants attended five workshops. Fear of a serious diagnosis and stigma from healthcare professionals were highlighted as main patient-related barriers to attending surveillance appointments. Co-design was used to develop informative, user-friendly, non-judgemental invitations and information regarding HCC surveillance relevant to populations with cirrhosis.
Conclusion: We identified potential patient barriers to surveillance uptake and developed patient facing material that directly addressed these barriers to be trialled in the clinic. Targeting patient-specific barriers may increase uptake of surveillance and therefore enhance early diagnosis.
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