Xuhua Duan

Objective: We hypothesized that preoperative administration of liposome arsenic trioxide (LATO) would downregulate hypoxia-inducible factor-1α (HIF-1α) in residual tumors following incomplete radiofrequency ablation (iRFA), thereby modulating the tumor microenvironment, suppressing residual tumor proliferation and angiogenesis, and consequently enhancing the antitumor efficacy of programmed death-ligand 1 (PD-L1) blockade. Methods: Using a murine Hepa1–6 hepatocellular carcinoma model subjected to incomplete radiofrequency iRFA, cohorts were stratified based on preoperative LATO administration and postoperative anti-PD-L1 antibody combination therapy, and the indexes such as proliferation and immune infiltration of residual tumor were tested respectively. Results: After iRFA, residual tumors exhibited significant up-regulation of PCNA, CD31, and HIF-1α compared with the control group (all p < 0.0001). Intravenous infusion of LATO before RFA could significantly decrease the expression of PCNA, CD31 and HIF-1α in the residual tumor, promote the infiltration of immune cells (CD4 ⁺ , CD8 ⁺ ) and prolong the survival time of mice. After RFA, combined use of anti-PD-L1 antibody can further reduce the expression of cell proliferation and tumor proliferation. Conclusion: Pre-treatment with LATO prior to RFA appears to modulate the tumor microenvironment, which may contribute to improved ablation efficacy and help restrain the progression of residual tumors. Furthermore, it could potentially enhance the antitumor effect of combining RFA with anti-PD-L1 antibody therapy by sensitizing the tumor immune response.

Purpose: We aimed to investigate the safety and therapeutic effectiveness of the combination of transcatheter arterial chemoembolization (TACE) with DynaCT-guided microwave ablation (MWA) for the treatment of liver tumors ≤5 cm located in high-risk areas. Methods: The clinical materials of 55 newly diagnosed liver cancer patients with ≤5 cm unifocal lesion admitted to our department from September 2019 to January 2021 were collected. The liver function change, adverse reactions, tumor control rates, cumulative survival rates, overall survival (OS), and progression-free survival (PFS) of the group were compared. Results: All participants successfully underwent combination treatment with TACE and MWA. According to the Common Terminology Criteria for Adverse Events (CTCAE5.0), adverse events (AEs) and the majority of the complications were classified as grade 1 or 2, involving mild symptoms that required either no intervention or only local, noninvasive management. The mean OS in the high-risk location group was 41.0 months (95%CI = 39.6–42.5), and the mean PFS was 31.2 months (95%CI = 30.7–31.7). The Kaplan–Meier survival curves for OS and PFS are shown in Figures 1A, B, respectively. The objective response rate (ORR) 1 month after the first combination treatment in the high-risk location group was 96.4%, and the disease control rate (DCR) was 98.2%. The cumulative survival rates at 6, 12, 24, and 36 months in the high-risk location group were 98.1%, 94.5%, 85.4%, and 74.5%, respectively. Conclusions: TACE combined with sequential DynaCT-guided MWA may be a safe and promising treatment option for liver cancers ≤5 cm in high-risk locations.

To compare safety and efficacy of transarterial chemoembolization (TACE) combined with microwave ablation (MWA) (TACE+MWA) versus only MWA treating hepatocellular carcinoma (HCC) 3–5 cm. A retrospective analysis was conducted on data collected from 202 HCC patients who attended four hospitals between January 2014 and December 2017. Diagnosis of all lesions was based on histopathology and radiology. In total, 202 patients with HCC 3–5 cm were included in this retrospective cohort study. These patients were classified into TACE+MWA and MWA groups based on the treatment. Patients were followed up with contrast enhanced CT or MRI. Images were evaluated and compared for treatment response and Adverse Events (AEs). Observe the occurrence of overall survival (OS), progression free survival (PFS) and AEs after the patient’s treatment. Survival analysis was performed using Kaplan-Meier method. Multivariate Cox proportional hazards regression analysis was performed to explore the relevant factors influencing the prognosis of patients. A total of 202 patients (median age, 58 years; 178 male) were included, with 102 in the TACE+MWA group and 100 in the MWA group. Baseline characteristics were well balanced between the two groups. Complete response (CR) was achieved by 78.4% of patients who received combined therapy compared with 76% with only MWA. The median PFS was 49.2 months (95% CI: 45.4–53.0) in the TACE+MWA group and 46.3 months (95% CI: 42.1–50.5) in the MWA group, with no significant difference (P=0.530). The median OS was significantly longer in the TACE+MWA group compared with the MWA group (81.7 months [95% CI: 78.2–85.3] vs. 72.3 months [95% CI: 68.9–75.7], P=0.013). The objective response rates (ORR) were comparable between the two groups (100.0% vs. 100.0%, P=1.000). The incidence of AEs was similar between the two groups, with no significant differences in major or minor complications. No treatment-related deaths were observed. TACE combined with MWA was associated with improved OS compared with MWA alone in patients with 3–5 cm HCC, while maintaining a comparable safety profile. These findings suggest that combination therapy may be a promising treatment strategy, although further prospective studies are needed to confirm these results.

Objective : C-arm computed tomography (CT) has always played an important role in neurointerventional surgery, in this study, we aimed to investigate the value of high-resolution C-arm CT in evaluating stent expansion and apposition in carotid arteries of Guangxi Bama piglets.Methods : Twenty-four stents were implanted in the carotid arteries of 24 Guangxi Bama piglets. High-resolution C-arm CT was performed to evaluate stent expansion and the quality of processed images, followed by three-dimensional digital subtraction angiography (3D-DSA). The DSA and high-resolution C-arm CT images were transmitted to a postprocessing workstation for image reconstruction (dual-volume reconstruction method). High-resolution C-arm CT reconstructed images after diluted contrast agent injection (diluted contrast method) were also acquired. In addition to assessing radiation exposure, the accuracy of stent apposition assessment by the two methods was compared, using intravascular ultrasound as the reference standard. Adverse events during and within 24 hours after the procedure were recorded.Results : One stent was incompletely expanded, while the remaining 23 stents were fully expanded without disruption. The image quality of high-resolution CT was grade I in most cases (n=22/24). Both methods clearly demonstrated stent apposition with a consistency of 100%. However, the dual-volume reconstruction method was associated with significantly higher radiation exposure (p<0.001). Mild-tomoderate vasospasm occurred in four piglets when the diluted contrast method was used. Overall, no serious complications occurred in this study.Conclusion : High-resolution C-arm CT enables clear microstructure visualization and can be used in combination with different postprocessing techniques to accurately assess the apposition of intracranial stents.

Thermal ablation offers minimally invasive treatment options for hepatocellular carcinoma (HCC) therapy. However, local recurrence due to sublethal temperatures enhances tumor cell survival. This study aims to investigate the tumor-promoting effects of hyperthermia on HCC cells, the role of tanshinone IIA (Tan IIA) in mitigating these effects, and the underlying mechanisms involved. We observed that temperature at 44 °C increased the aggressiveness of HCC cells, and Tan IIA inhibited cell viability and cell invasion, and induced cell cycle arrest and apoptosis of heat-pretreated HCC cells. ALDH7A1 was identified as a target of Tan IIA, and its altered expression resulted in dysregulation of cell viability, invasion, apoptosis, ATP production, glycolysis, osmolyte levels, and reactive oxygen species (ROS). Under hyperosmotic conditions, ALDH7A1 knockdown sensitized heated Huh-7 cells, while its overexpression promoted cell survival and invasion, with corresponding changes in energy metabolism and enzymatic products. Tan IIA and the specific ALDH7A1 inhibitor, 4-diethylaminobenzaldehyde, demonstrated similar effects on gene expression patterns, glycolysis, osmotic regulation, and ROS levels in heated Huh-7 cells. Moreover, Tan IIA is able to direct interact with ALDH7A1 protein. In vitro, Tan IIA combined with hyperosmotic stress significantly inhibited cell invasion and induced apoptosis in heat-induced Huh-7 cells and ALDH7A1 overexpression partially reversed the effects of Tan IIA. In vivo, Tan IIA combined with hyperosmotic stress or glycolysis inhibitor yielded better therapeutic efficacy for HCC. In conclusion, Tan IIA sensitizes HCC cells to sublethal heat by targeting ALDH7A1, leading to disrupted glycolytic and osmolytic balance, subsequently hindering tumor cell survival and increasing apoptosis. These findings highlight a potentially novel strategy for preventing or treating recurrent HCC post-thermal ablation using Tan IIA with hyperosmotic reagents.

To confirm transcatheter arterial chemoembolization (TACE) combined with apatinib for advanced perihilar cholangiocarcinoma (PCC) is effective and safe. A comprehensive treatment plan involving TACE combined with targeted therapy was implemented for the patients with pathologically diagnosed advanced PCC, where TACE was performed every 4–6 weeks to deliver albumin paclitaxel and gemcitabine for a maximum of six times. Oral apatinib was administered in between TACE cycles. The main endpoint of this study was the objective response rate (ORR), and the secondary endpoints were progression free survival (PFS), overall survival (OS), and adverse events. Kaplan-Meier method was used to assess survival risk factors. From November 2019 to October 2020, a total of 41 patients were enrolled with perihilar cholangiocarcinoma who were pathologically diagnosed. All underwent TACE treatment and received at least two treatment cycles. As of October 2022, the median follow-up period of this study was 28.3 months, the ORR of this study reached 56.1% (95% CI 39.7–71.5%); DCR reached 90.2% (95% CI 76.9–97.3%), and the median PFS was 9.7 months (95% CI 7.6–11.8 months), the median OS was 16.5 months (95% CI 13.6–19.3 months). The treatment-related adverse events (AEs) in this study were mild, mainly Grade 1 or 2. Among the most common AEs were bone marrow suppression and hand-foot syndrome, while no patient had Grade 4 AE. Comprehensive treatment combining TACE with apatinib for advanced PCC had favorable therapeutic effects, and no major safety issue was observed in the patients enrolled.

Purpose Recurrent esophageal variceal bleeding and/or refractory ascites in patients with cavernous transformation of the portal vein (CTPV) is associated with a high fatality rate. Transjugular intrahepatic portosystemic shunt (TIPS) provides a treatment option for preventing esophageal variceal rebleeding and/or refractory ascites. This retrospective study evaluated the safety and efficacy of TIPS for the patients involved. Methods The records of 41 consecutive patients with CTPV who underwent TIPS at our institution from January 2015 to May 2019 were reviewed. Among the 41 patients, 36 patients had variceal rebleeding only, and 5 patients exhibited both variceal rebleeding and refractory ascites. Ten of these patients underwent TIPS via a transjugular pathway alone; a combined transjugular/transhepatic pathway and a combined transjugular/transsplenic pathway were adopted for 21 and 3 patients, respectively; and the remaining 7 patients failed TIPS. Results TIPS succeeded in 34 of 41 (82.9%) patients. Four of 34 patients with CTPV were successfully cured with a thick collateral caval stent shunt operation. After TIPS, the mean portosystemic pressure gradient declined from 24.60 ± 6.15 mmHg to 15.89 ± 4.08 mmHg (P < 0.01). The occurrence rate of variceal rebleeding in the TIPS success group was lower than that in the TIPS failure group (11.8% vs 42.9%, P < 0.05). The occurrence rate of recurrent ascites in the TIPS failure group was greater than that in the TIPS success group (75% vs 15.8%, P < 0.05). TIPS patency was 76.5% (26 of 34 patients). During the follow-up time (median 12.64 months), the rate of hepatic encephalopathy was 5.9%, and the survival rate was 85.3%. Conclusions TIPS is an effective and safe alternative therapy for preventing esophageal variceal rebleeding and/or refractory ascites in patients who exhibit CTPV, and these findings may be beneficial to clinical research.

Immunotherapy shows great therapeutic potential for long-term protection against tumor relapse and metastasis. Innate immune sensors, such as cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), dissolve DNA and induce type I interferon. Through activation of the cGAS/STING pathway, chemotherapy drugs and reversine (REV) may provide synergetic anti-tumor effects. Here, we prepared drug-loaded cell membrane hybrid lipid nanovesicles (LEVs) (designated LEV@DOX@REV) by fusion of cell membranes, phospholipids, doxorubicin (DOX), and REV, to realize accurate delivery to tumors and chemo-immunotherapy. The cell membranes of LEVs confer “homing” abilities. DOX can induce immunogenic cell death as a result of its specific immunomodulatory effects, which promotes the maturation of immune cells and improves the microenvironment of the immune system. REV is proven to efficiently activate cGAS/STING signaling, thereby enhancing the immune system. The antitumor efficacy of LEV@DOX@REV was evaluated in a 4T1 subcutaneous tumor xenograft model, a distant metastatic tumor model, and a liver metastatic tumor model. LEV@DOX@REV facilitated the infiltration of cytotoxic T lymphocytes within tumors, increased the secretion of proinflammatory cytokines, and modified the tumor microenvironment. In conclusion, LEV@DOX@REV displayed favorable antitumor effects and extended the survival of tumor-bearing mice. We therefore successfully developed nanoparticles capable of enhancing immune activation that have potential therapeutic applications for cancer immunotherapy.