Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC); however, TACE refractoriness remains a major clinical challenge. Increasing evidence suggests that post-embolization hypoxia-driven metabolic reprogramming, particularly dysregulated copper homeostasis, contributes to therapeutic resistance. This study aimed to elucidate the role of copper metabolism in TACE-refractory HCC and to develop a mechanism-driven nanoembolic strategy targeting the copper chaperone ATOX1 to induce cuproptosis and reverse TACE refractoriness. Clinical serum samples from HCC patients with TACE refractoriness or favorable response were analyzed for copper levels and copper transport-related proteins. A thermosensitive nanogel (Cu²⁺/DC_AC50@PNA) co-loaded with copper ions and the ATOX1 inhibitor DC_AC50 was synthesized and characterized. Its embolic performance, antitumor efficacy, and biosafety were evaluated in rabbit renal artery and VX2 orthotopic liver tumor models. In vitro assays using Huh-7 and LM3 cells under normoxic and hypoxic conditions assessed cell viability, migration, invasion, and cuproptosis-related signaling. Patients with TACE refractoriness exhibited significantly elevated serum copper levels and increased ATOX1 and ATP7B expression, indicating systemic copper dyshomeostasis. Cu²⁺/DC_AC50@PNA demonstrated favorable physicochemical properties, sustained embolic capability, and excellent biocompatibility. In vivo, this nanoembolization system markedly suppressed tumor growth, increased tumor necrosis, reduced metastasis, and prolonged survival compared with conventional cTACE. Mechanistically, Cu²⁺/DC_AC50@PNA disrupted intracellular copper transport, activated cuproptosis, inhibited HIF-1α/VEGF-mediated angiogenesis, and remodeled the tumor immune microenvironment by enhancing CD8⁺ T-cell infiltration. In vitro findings corroborated potent antitumor and anti-metastatic effects, particularly under hypoxic conditions. Copper metabolism dysregulation is a defining feature of TACE-refractory HCC. Targeting ATOX1-mediated copper homeostasis using Cu²⁺/DC_AC50@PNA represents a novel and effective strategy to induce cuproptosis, overcome TACE refractoriness, and improve therapeutic outcomes in HCC.

Hepatic arterial infusion chemotherapy (HAIC) is a potentially attractive locoregional therapy for patients with unresectable colorectal liver metastases (

BackgroundThe efficacy of RFA in the treatment of HCC with severe fibrosis is still unclear. The objective of this study is to compare the efficacy of RFA with liver resection in the treatment of HCC within Milan criteria.MethodsThe data used in the study were from the SEER database. Patients with HCC within Milan criteria were included in the study. A total of 1432 patients were included in the study; among them, 1038 patients received RFA, and 394 patients received liver resection. Propensity score matching (PSM) was used to reduce selection bias.ResultsBefore PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the resection group were longer than the mOS and mCSS in the RFA group. However, the8re were no statistically significant differences in mOS or mCSS between the two groups (both P>0.05). After PSM, similar results were presented, and the mOS and mCSS in the resection group were similar to those in the RFA group (both P>0.05). The multivariable Cox regression analysis showed that RFA did not increase the all-cause mortality risk and cancer-specific mortality risk compared with resection before PSM. In the competing risk analysis, after excluding the potential factors that might influence the outcomes, RFA still did not increase the mortality risk compared with resection before PSM and after PSM. In the subgroup analysis. The efficacy of RFA is comparable to that of resection in patients with tumor sizes no more than 3 cm before PSM and after PSM.ConclusionThe efficacy of RFA is similar to that of resection in the treatment of early HCC patients with severe fibrosis, especially in patients with tumor sizes no more than 3 cm.

BackgroundThere are no exact treatments been recommended for gastrointestinal tumor liver metastasis patients. This study intends to assess the safety and efficacy of transarterial chemoembolization (TACE) plus apatinib as a combination treatment for gastrointestinal tumor liver metastasis patients.MethodsFrom January 2015 to December 2019, 53 patients with gastrointestinal tumor liver metastases were included in the analysis.ResultsThe median progression-free survival (mPFS) and median overall survival (mOS) numbers were 7 months and 17 months, respectively. The mPFS of metastatic sites was 12 months. The disease control rate (DCR) and objective response rate (ORR) values were 86.8% (46/53) and 49.1% (26/53), respectively. The multivariate regression analysis showed that Child-Pugh and Eastern Cooperative Oncology Group (ECOG) were independent predictors for OS. The independent predictors for overall PFS include carbohydrate antigen 724 (CA 724), CA 199, TACE session, Child-Pugh, and ECOG; while for liver tumor PFS, the independent predictors are TACE session and ECOG scores. There were no changes of leukocyte, lymphocyte, carcinoemnryonicantigen (CEA), CA 724, CA 199, CA 125 of patients before receiving the treatments and one month after receiving the treatment (all P>0.05). Common adverse events at any grade were poor appetite (64.2%), hypertension (56.6%), and hand-foot syndrome (50.9%). Some patients had III or IV-grade adverse events after receiving the TACE-apatinib combination treatment. However, these adverse events alleviated after reducing apatinib administration or receiving symptomatic treatments.ConclusionsThe TACE-apatinib combination might be an effective treatment option against gastrointestinal tumors liver metastases with promising safety.

As recommended by Baveno VII consensus, the utilization of pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) has been considered as standard therapeutic approach for the management of acute variceal bleeding (AVB) associated with cirrhosis., but the 72-h window for pTIPS is too narrow. This study aimed to compare the clinical outcomes between patients who received <72 h pTIPS and 72 h-5d pTIPS. In this study, a total of 63 cirrhotic patients with AVB who underwent pTIPS between October 2016 and December 2021 were included in this retrospective study. They were divided into <72 h group (n = 32) and 72 h-5d group (n = 31), based on the timing of the intervention. The Kaplan-Meier curves demonstrated that there were no significant differences in the cumulative incidence of death (22.3% ± 7.4% vs. 19.9% ± 7.3%, log-rank P = 0.849), variceal rebleeding (9.7% ± 5.3% vs. 17.8% ± 7.3%, log-rank P = 0.406), OHE (28.5% ± 8.0% vs. 23.9% ± 8.0%, log-rank P = 0.641) and shunt dysfunction (8.6% ± 6.0% vs. 17.4% ± 8.1%, log-rank P = 0.328) between <72 h and 72 h-5d groups. In the total cohort, sarcopenia was identified as an independent risk factor for mortality (HR = 11.268, 95% CI = 1.435-88.462, P = 0.021) and OHE(HR = 12.504, 95% CI = 1.598-97.814, P = 0.016). In conclusion, the clinical outcomes of cirrhotic patients with AVB who underwent pTIPS within the 72-h to 5-day window were found to be comparable to those treated within the 72-h window.