Ultrasmall Metal TPZ Complexes with Deep Tumor Penetration for Enhancing Radiofrequency Ablation Therapy and Inducing Antitumor Immune Responses.

Radiofrequency ablation (RFA) is one of the most common minimally invasive techniques for the treatment of solid tumors, but residual malignant tissues or small satellite lesions after insufficient RFA (iRFA) are difficult to remove, often leading to metastasis and recurrence. Here, Fe-TPZ nanoparticles are designed by metal ion and (TPZ) ligand complexation for synergistic enhancement of RFA residual tumor therapy. Fe-TPZ nanoparticles are cleaved in the acidic microenvironment of the tumor to generate Fe2+ and TPZ. TPZ, an anoxia-dependent drug, is activated in residual tumors and generates free radicals to cause tumor cell death. Elevated Fe2+ undergoes a redox reaction with glutathione (GSH), inducing a strong Fenton effect and promoting the production of the highly toxic hydroxyl radical (•OH). In addition, the ROS/GSH imbalance induced by this treatment promotes immunogenic cell death (ICD), which triggers the release of damage-associated molecular patterns, macrophage polarization, and lymphocyte infiltration, thus triggering a systemic antitumor immune response and noteworthy prevention of tumor metastasis. Overall, this integrated treatment program driven by multiple microenvironment-dependent pathways overcomes the limitations of the RFA monotherapy approach and thus improves tumor prognosis. Furthermore, these findings aim to provide new research ideas for regulating the tumor immune microenvironment.

Efficacy and Safety of TACE Combined with Regorafenib versus TACE Combined with Camrelizumab in Hepatocellular Carcinoma With Untreatable Progression After TACE Combined with Sorafenib Therapy: A Case Control Study.

PURPOSE: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with regorafenib (hereafter, TACE-regorafenib) or camrelizumab (hereafter, TACE-camrelizumab) for treating hepatocellular carcinoma (HCC) with untreatable progression after TACE and sorafenib therapy. METHODS: The medical records of patients with HCC who received TACE-regorafenib or TACE-camrelizumab between September 2018 and December 2023 were retrospectively evaluated. Therapeutic response, overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups. RESULTS: A total of 76 patients were enrolled in this study, with 41 and 35 patients in the TACE-regorafenib and TACE-camrelizumab groups, respectively. The objective response rates in the TACE-regorafenib and TACE-camrelizumab groups were 9.8% and 8.6%, respectively, with no statistically significant difference between the two groups (P = 0.859). Similarly, there was no statistically significant difference in disease control rates between the two groups (61.0% vs 68.6%, P = 0.838). The median OS was 11 months in the TACE-regorafenib group and 10 months in the TACE-camrelizumab group, with no significant difference between the two groups (P = 0.348). The TACE-regorafenib group had a median PFS of 7 months, which was significantly longer than that of the TACE-camrelizumab group (4 months, P = 0.004). There was no significant difference in the incidence of AEs between the two groups (P = 0.544). CONCLUSIONS: TACE-regorafenib was safe, well-tolerated, and showed promising efficacy in patients with sorafenib-refractory advanced HCC, whereas TACE-camrelizumab demonstrated similar survival benefits.

Endovascular treatment of aorto-iliac occlusive disease with TASC II C and D lesions: 10 year's experience of clinical technique.

OBJECTIVES: The purpose of this study was to evaluate the therapeutic efficacy and safety of endovascular treatment aorto-iliac occlusive disease (AIOD) with TransAtlantic Inter-Society Consensus II (TASC II) C and D lesions. In addition, 10 years of experience with interventional procedures and treatment options in our center were also worthy of further discussion. METHODS: Between January 2011 and December 2020, a total of 26 consecutive AIOD patients with TASC-II C and D lesions treated endovascular approach were enrolled in this study. Patients' demographic and clinical data were collected, and the safety and efficacy of endovascular therapy were evaluated. In addition, operation procedures were also described. RESULTS: The mean age of patients was 62.2 ± 7 years (49-57 years), and the mean body mass index of patients was 24.2 ± 2.6 kg/m2. Fifteen patients (57.7%) were Rutherford 4, 5 each (19.2%) were Rutherford 3 and 5, and 1 (3.8%) was Rutherford 2. No other serious complications occurred except death in 3 patients. Most of the patients (73.1%) had a history of smoking, and hypertension and hyperlipidemia were common comorbidities. Endovascular therapy was successfully performed in 25 patients, and the technical success rate was 96.2%. The patient's ankle-brachial index improved significantly postoperatively compared with preoperatively (preoperative 0.33 ± 0.14 vs 1.0 ± 0.09, P < 0.001). The primary patency rates were 100%, 95.7%, and 91.3% at 1, 3, and 5 years, while the secondary patency rates were 100%. No treatment-related deaths or serious complications occurred. CONCLUSIONS: Endovascular treatment of AIOD patients with TASC-II C and D lesions might be safe and have a high rate of middle-term and long-term primary patency.

Renal and hepatic artery embolization with Pickering gel emulsion of lipiodol in rabbit.

OBJECTIVE: This research aimed to evaluate the feasibility of a novel liquid embolic agent Pickering gel emulsion of lipiodol (PGEL) for renal and hepatic artery embolization in the rabbit experimental model. METHODS: Embolization was performed in the right renal artery of 24 adult New Zealand White rabbits and 24 VX2 tumors in the left liver lobe. The rabbits were randomly allocated to four treatment groups (n = 6 per group): (A) normal saline (NS), (B) lipiodol, (C) 180-300 µm polyvinyl alcohol (PVA), and (D) PGEL. RESULTS: Renal artery embolization in normal rabbits and transarterial embolization (TAE) in VX2 tumor-bearing rabbits indicated that PGEL achieved a better embolization effect for a longer time than lipiodol and PVA. The tumor growth ratio of the PGEL group was significantly lower than that of the NS, lipiodol, and PVA groups at 3 (P < 0.001) and 7 (P < 0.001) days after embolization. In addition, hematoxylin and eosin and immunohistochemical staining revealed that the tumor necrosis ratio was higher in the PGEL group than in the NS, lipiodol, and PVA groups (P < 0.01), and the expression levels of HIF-1α, VEGF, and CD31 decreased after PGEL embolization compared with the lipiodol and PVA treatments. CONCLUSION: PGEL is an effective embolic material that provides immediate and total occlusion of the renal artery and may be a potential therapeutic embolic agent for TAE of HCC.

Transarterial chemoembolization combined with camrelizumab for recurrent hepatocellular carcinoma.

PURPOSE: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with camrelizumab (hereafter, TACE-camrelizumab) in the treatment of patients with recurrent hepatocellular carcinoma (R-HCC) after curative resection. PATIENTS AND METHODS: R-HCC patients who underwent TACE plus camrelizumab or TACE-alone from January 2016 to August 2021 were retrospectively evaluated. Patients were assessed for tumor response, progression-free survival, survival rates and adverse events. RESULTS: Seventy-one patients were included in this study, including 20 patients in the TACE- camrelizumab group and 51 patients in the TACE-alone group. The objective response rate was 56.9% in the TACE-alone group and 40% in the TACE-camrelizumab group at 3 months (P = 0.201). The disease control rates were 84.3% in TACE-alone group and 80% in TACE-camrelizumab group at 3 months (P = 0.663). The progression-free survival (PFS) of the TACE-alone group was slightly longer than those of the TACE- camrelizumab group (9 months vs. 6 months). However, there were no statistically significant differences in the median PFS (P = 0.586). Similarly, there were no significant differences in the half-year and one-year survival rates (P = 0.304, P = 0.430). Multivariate analysis revealed that Neutrophil-to-lymphocyte ratio (NLR) was associated with PFS significantly. 75% patients developed at least one type of AEs related to camrelizumab in TACE-camrelizumab group, and no patients developed severe AEs. CONCLUSION: Comparing with TACE-Alone, the efficacy of TACE-camrelizumab for patients with R-HCC was similar. Meanwhile, the results of this study also indicated that TACE is still a better choice for patients with R-HCC.

Multimodal Imaging Response after the Singular or Combination Treatments of Vascular Endothelial Growth Factor Inhibitor and Immune Checkpoint Inhibitor.

This study aims to dynamically assess tumor changes after variable treatments with vascular endothelial growth factor (VEGF) inhibitor and/or immune checkpoint inhibitor (ICI) using multimodal imaging of MRI and 18F-FDG PET/CT in a hepatocellular carcinoma (HCC) mice model. Based on different treatments, 24 mice were randomly divided into four groups: control (isotype-matched IgG antibody 10 mg/kg), VEGF inhibitor (sorafenib 50 mg/kg), ICI (anti-PD-L1 antibody 10 mg/kg), and combination groups (sorafenib 50 mg/kg + anti-PD-L1 antibody 10 mg/kg). Quantitative imaging assessments, including volume transfer constant (Ktrans), apparent diffusion coefficient (ADC), lactate/choline ratio, and the maximum standardized 18F-FDG uptake value ratio of tumor to muscle (SUVtumor/SUVmuscle ratio), were acquired at different time points (before treatment and 7, 14, and 21 days after treatment). Quantitative data were presented as the mean ± standard errors and two-way repeated-measure ANOVA tests were performed for intergroup and intertime point comparisons. After 21 days from the initiation of therapies, combination group showed the lowest tumor volume and weight, followed by ICI, VEGF inhibitor, and control group, with no significance between the VEGF inhibitor and control groups. In addition, Ktrans values significantly decreased, and the lactate/choline ratio and SUVtumor/SUVmuscle ratio were significantly elevated in the VEGF inhibitor group. ADC significantly increased in the ICI and combination groups, with no significant differences in ADC observed between the control and VEGF inhibitor groups, which showed a similar dynamic change to the tumor volume. Furthermore, Ktrans, lactate/choline ratio, and ADC were significantly correlated with CD31+ area, hypoxyprobe+ area, and apoptosis, respectively. Our results suggest that the singular treatment and combination of the VEGF inhibitor and ICI treatments for HCC present different multimodal imaging changes in accordance with the specific histopathological features. These findings might facilitate the formulation of better treatment response criteria; besides, we find ADC is probably an indicator easily to obtain for treatment response evaluation.

Efficacy of Drug-Eluting Beads Transarterial Chemoembolization Plus Camrelizumab Compared With Conventional Transarterial Chemoembolization Plus Camrelizumab for Unresectable Hepatocellular Carcinoma.

OBJECTIVES: The purpose of this study was to compare the efficacy and safety of drug-eluting beads transarterial chemoembolization plus camrelizumab (D-TACE-C) with conventional transarterial chemoembolization plus camrelizumab (C-TACE-C) in the treatment of patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This was a retrospective study that evaluated the consecutive medical records of patients with unresectable HCC who had undergone D-TACE-C or C-TACE-C from April 2020 to August 2021. Efficacy of treatment was evaluated using tumor response, progression-free survival (PFS) and survival rates. The adverse events were recorded. RESULTS: A total of 54 patients were included in this study, including 27 patients who had received D-TACE-C treatment, and 27 patients who had received C-TACE-C treatment. The median PFS and DCR in the D-TACE-C group were significantly longer than those for the C-TACE-C group (PFS: 10 vs. 3 months, P=.017; DCR: 70.4% vs. 40.7%, P = .028). Cox regression analysis showed that D-TACE-C was the only protective factor for PFS. The 6-month and 12-month survival rates in D-TACE-C group and C-TACE-C group were 85.2% versus 79.4% (P = .646) and 65.2% versus 65.1% (P = .903), respectively. Reactive cutaneous capillary endothelial proliferation was the most common adverse event associated with the treatment. There was no significant difference in the adverse events related to TACE and camrelizumab between the two groups. No treatment-related deaths occurred in this study. CONCLUSIONS: D-TACE-C is a safe and well-tolerated treatment, and may produce better PFS and tumor response in patients with unresectable HCC than C-TACE-C.

Value of 18F-FDG PET/MR Imaging in the Early Evaluation of Treatment Response following Radiofrequency Ablation of Liver Cancer in a Rabbit Model.

PURPOSE: To test the hypothesis that 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging can detect early residual tumor following radiofrequency (RF) ablation of liver cancer using a VX2 tumor model. MATERIALS AND METHODS: Twenty-four rabbits with VX2 liver tumors were randomly divided into 3 groups (n = 8/group): Group 1 without RF ablation treatment, Group 2 with complete ablation, and Group 3 with partial ablation. An 18F-FDG PET/MR imaging scan was obtained within 2 hours after RF ablation. The maximum standardized uptake values (SUV) of the nontreated liver tumor, benign periablational enhancement (BPE), residual tumor, ablated tumor, and adjacent liver parenchyma and mean SUV of the normal liver were measured. The ratios of maximum SUV for these targets to the mean SUV of the normal liver (TNR) were calculated and compared. RESULTS: The mean TNR of the nontreated liver tumors in Group 1 was significantly greater than that of the adjacent liver parenchyma (8.68 ± 0.71 vs 1.89 ± 0.26, P < .001). In Group 2, the mean TNR of BPE was significantly greater than that of the adjacent liver parenchyma (2.85 ± 0.20 vs 1.86 ± 0.25, P < .001). In Group 3, the mean TNR of the residual tumor was significantly greater than that of BPE (8.64 ± 0.59 vs 2.78 ± 0.23, P < .001), which was significantly greater than that of completely ablated tumor (2.78 ± 0.23 vs 0.50 ± 0.06, P < .001). CONCLUSIONS: 18F-FDG PET/MR imaging may serve as a promising imaging tool for the early detection of viable residual tumors due to incomplete tumor ablation.

Sequential transarterial chemoembolization and early radiofrequency ablation improves clinical outcomes for early-intermediate hepatocellular carcinoma in a 10-year single-center comparative study.

BACKGROUND: Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective treatment methods for unresectable hepatocellular carcinoma (HCC). However, there is still a lack of clinical research on whether early sequential RFA, compared with late combination therapy, can improve the long-term efficacy of initial TACE treatment. METHODS: This retrospective study investigated a cohort of patients who underwent combination therapy using TACE and RFA (TACE followed by RFA) from January 2010 to January 2020 at our medical centre. A total of 96 patients underwent TACE combined with early RFA (usually during the first hospitalization), which was called TACE + eRFA. Thirty-four patients received 1-2 palliative TACE treatments first and then underwent TACE treatment combined with late RFA (TACE + lRFA). All patients continued to receive palliative TACE treatments after intrahepatic lesion progression until reaching intolerance. The overall survival (OS) rate, time to tumour progression (TTP), tumour response rate and major complication rates were compared between the two groups. RESULTS: There were significant differences in the median OS (46 months vs 33 months; P = 0.013), median TTP (28 months vs 14 months; P < 0.00), objective response rate (ORR) (89.6% vs 61.8%, P = 0.000) and disease control rate (DCR) (94.8% vs 73.5% P = 0.002) between the two groups. Multivariable analysis revealed that the Barcelona Clinic Liver Cancer stage was an independent risk factor for OS. Meanwhile, multivariable analysis revealed that TACE + eRFA was associated with an enhanced TTP. CONCLUSION: Early sequential RFA treatment in patients with early-intermediate HCC can improve local tumour control and clinical outcomes while reducing the frequency of TACE treatment. In clinical practice, in HCC patients initially treated with TACE, it is recommended to combine RFA as soon as possible to obtain long-term survival.

Endovascular management of transplant renal artery stenosis: A single-center retrospective study.

OBJECTIVES: The aim is to evaluate the efficacy and complications of percutaneous transluminal angioplasty (PTA)/stenting in the treatment of transplant renal artery stenosis (TRAS). BACKGROUND: TRAS is a relatively rare condition, and currently, there is not enough study about interventional therapy for TRAS. METHODS: Between April 2011 and July 2018, 33 patients with TRAS underwent interventional therapy. Analysis of parameters was as follows: technical success, pretreatment and posttreatment serum creatinine, and blood pressure, and vessel patency via ultrasound at 1, 6, and 12 months posttreatment and once a year thereafter. RESULTS: One procedure failed. The success rate of PTA/stenting placement was 97.0%. Fourteen PTAs with 16 stents were primary interventions, with 2 stent procedures performed subsequently due to restenosis; the restenosis rate was 6.3%. During the follow-up period, two patients progressed to graft renal failure and three patients were lost to follow-up. The rest of the patients still had stable graft function and blood pressure. Compared with preoperative conditions, blood pressure and serum creatinine significantly decreased (p < .05). No treatment-related deaths or serious complications occurred. CONCLUSIONS: PTA/stenting is a safe and effective treatment for TRAS. For selected TRAS patients, PTA or PTA with stent may achieve good therapeutic outcomes. Selecting appropriate puncture pathways may help improve the success rate and affect the operation results, and open surgery may be avoided.

Platelet-to-lymphocyte ratio predicts therapy outcomes of transarterial chemoembolization plus apatinib in the treatment of advanced hepatocellular carcinoma.

To evaluate the predictive value of preoperative biochemical marker [platelet-to-lymphocyte ratio (PLR)] in patients with advanced hepatocellular cancer receiving transarterial chemoembolization (TACE) plus targeted molecular therapy (apatinib) treatment. Clinical records of 134 patients receiving the treatment of TACE + apatinib (TACE-A) and the treatment of TACE alone were compared in a single-center study. Time to progression (TTP) and overall survival (OS) were compared between TACE-A and TACE alone groups in patients with PLR > 150 and PLR ≤ 150, respectively. The area under the receiver operating characteristic (ROC) curve was used to determine the prediction power of PLR. The median TTP and OS in the TACE-A group were significantly longer than those in the TACE alone group (P < 0.001). The median TTP and OS in the TACE-A (PLR ≤ 150) group were longer than those in the TACE-A (PLR > 150) group (P < 0.05). There was no significant difference between TACE-A (PLR > 150) and TACE alone (P = 0.232) groups in OS, but the median TTP in the TACE-A (PLR > 150) group was longer than that in the TACE alone group (P = 0.001). ROC analysis showed that the area under the curve was 0.643 and 0.623 for 6- and 12-month survival, respectively. PLR might predict the results of patients with advanced hepatocellular carcinoma received TACE-A treatment.

Transarterial chemoembolization combined with iodine 125 seeds versus transarterial chemoembolization combined with radiofrequency ablation in the treatment of early- and intermediate-stage hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and iodine 125 seeds implantation are optional treatments for hepatocellular carcinoma (HCC). The aim of this study is to compare the efficacy of the combined treatment of TACE with iodine 125 seeds implantation (TACE-iodine 125) with TACE with RFA (TACE-RFA) in patients with early- and intermediate-stage HCC. METHODS: The study included 112 patients who were diagnosed with early- and intermediate-stage HCC from January 1, 2014, to May 31, 2018. Among them, 38 patients were treated with TACE-Iodine 125, and 74 with TACE-RFA. The efficacy of the two treatment groups was retrospectively analyzed. To reduced the selective bias, a propensity score matching (PSM) analysis and inverse probability of treatment weighting (IPTW) method were used to compare the outcomes between the two groups. RESULTS: In the absence of PSM and IPTW, the median overall survival (OS) and progression-free survival (PFS) of the TACE-RFA group were slightly longer than those of the TACE-Iodine 125 group (OS: 41 months vs. 36 months; PFS: 18 months vs. 15 months). However, there were no statistically significant differences in the median OS, PFS, and objective response rate (ORR) between the two groups (P > 0.05). After adjusting the age, gender, Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, and Alpha-fetoprotein (AFP), TACE-Iodine 125 treatment was not associated with a significant increasing the risks of death (HR: 0.763; 95%CI: 0.403,1.345, P = 0.320) and recurrence (HR: 1.020; 95%CI: 0.645,1.611, P = 0.934). After PSM, 35 matched pairs of patients were obtained, and there were no statistically significant differences in the median OS and PFS between the two groups. After IPTW, similar results presented. CONCLUSIONS: The combination of TACE with iodine 125 seeds implantation may represent an effective treatment for patients with early- and intermediate-stage HCC.

The efficacy of surgery in advanced hepatocellular carcinoma: a cohort study.

BACKGROUND: It is still controversial whether hepatocellular carcinoma (HCC) patients with lymph node invasion should receive surgery treatment. This study aimed to evaluate the efficacy of surgery (liver resection and local tumor destruction treatments) in HCC patients with regional lymph node metastasis. METHODS: The study utilized data from the Surveillance, Epidemiology, and End Results-18 (SEER-18) cancer registry. Patients for whom the treatment type was not clear or those with distant metastasis or without regional lymph nodule invasion were excluded. For survival analysis, patients with the survival months coded as 0 and 999 were excluded. All 1434 patients were included in the analysis. Among them, 168 patients were treated surgically and the other 1266 received non-surgery therapy. Propensity score matching (PSM) model was used to reduce selection bias. RESULTS: Before PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) of patients treated surgically were longer than that of receiving non-surgery treatment (mOS 20 months, 95% CI 15.3-24.7 vs. 7 months, 95% CI 6.4-7.6, P < 0.001; mCSS 21 months, 95% CI 115.5-26.5 vs. 6 months, 95% CI 5.3-6.7, P < 0.001). Subgroup analysis found no significant differences in mOS and mCSS between liver resection and non-liver resection surgery cohorts (P = 0.886 and P = 0.813, respectively). Similar results were obtained in the PSM analysis. The mOS and mCSS in the surgery group were longer than those in the non-surgery group (mOS 20 months vs. 7 months, P < 0.001; mCSS 20 months vs. 6 months, P < 0.001). The multivariate analysis documented that surgery was an independent predictor for OS and CSS before and after PSM. CONCLUSIONS: HCC patients with invasion of regional lymph nodules may get more survival benefit from surgery than other types of treatment.

Improved clinical outcome using transarterial chemoembolization combined with radiofrequency ablation for patients in Barcelona clinic liver cancer stage A or B hepatocellular carcinoma regardless of tumor size: results of a single-center retrospective case control study.

BACKGROUND: To determine the safety and efficacy of transarterial chemoembolization (TACE) combined with radiofrequency ablation (hereafter, TACE-RFA) in treating Barcelona Clinic Liver Cancer (BCLC) Stage A or B (hereafter, BCLC A/B) hepatocellular carcinoma (HCC) patients, and to explore the range of tumor sizes suitable for combination therapy. METHODS: This retrospective study assessed the consecutive medical records of HCC patients with BCLC A/B who received TACE-RFA or TACE from September 2009 to September 2018. Progression-free survival (PFS), overall survival (OS), therapeutic response, and complications were compared between the two groups. RESULTS: Among 2447 patients who received TACE-RFA or TACE, 399 eligible patients were enrolled in our study, including 128 patients in the TACE-RFA group and 271 patients in the TACE group. Compared with the TACE group, the PFS and OS rates of 1,3,5,8 years in the TACE-RFA group were significantly better, with higher objective tumor regression rate and better disease control rate. RFA treatment did not increase the risk of death in patients with HCC, and both liver subcapsular hematoma and bile duct injury were improved by symptomatic treatment. Serum α-fetoprotein level and treatment method were important independent prognostic factors for OS, whereas albumin, hepatitis B and treatment method were important independent prognostic factors for PFS. Subgroup analysis showed that patients in the TACE-RFA group always showed better OS and PFS. CONCLUSIONS: TACE-RFA had an advantage over TACE alone in prolonging PFS and improving OS in HCC patients with BCLC A/B, and can benefit patients regardless of tumor size.

Prospective Comparison of Conventional CTA With Angiography-CT for Identification of Culprit Systemic Arteries in Patients Undergoing Bronchial Artery Embolization for Hemoptysis.

In this prospective study of patients undergoing bronchial artery embolization for hemoptysis, preprocedural conventional CTA identified 86.3% of culprit systemic arteries confirmed by selective angiography, whereas intraprocedural angio-CT identified 97.1%. The findings indicate a role of angio-CT to help identify target vessels for embolization during such procedures.

Hepatic arterial infusion chemotherapy combined with toripalimab and surufatinib for the treatment of advanced intrahepatic cholangiocarcinoma.

PURPOSE: The aim of the present study is to report the clinical results of patients with advanced intrahepatic cholangiocarcinoma (ICC) who received combination therapy of hepatic arterial infusion chemotherapy (HAIC), toripalimab and surufatinib. METHODS: The study cohort consisted of 28 patients with advanced ICC who were treated with HAIC (mFOLFOX6 regimen, Q3W) in combination with intravenous toripalimab (240 mg, Q3W) and oral surufatinib (150 mg, once daily). The cohort had 14 male and 14 female patients. The baseline characteristics of the study cohort were obtained. The tumor response and drug-associated toxicity were assessed and reported. RESULTS: During the follow-up period (median follow-up time: 11.3 months; range: 4-19 months), four patients died of tumor progression. The objective response rate and disease control rate were 58% and 79%, respectively. The mPFS was 9.5 months, and the overall survival rate was 83.3%. The most frequent adverse events were nausea and vomiting (100%) and abdominal pain (85.7%). Serious complications related to death were not observed. CONCLUSION: The combination treatment schedule for advanced ICC demonstrated positive efficacy and safety profiles. CLINICAL SIGNIFICANCE: This study provides promising clinical guidance for the treatment of advanced cholangiocarcinoma and is expected to modify the treatment strategy for this disease.

The time window for pre-emptive transjugular intrahepatic portosystemic shunt could be extended to 5 days.

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.

Drug-eluting beads transarterial chemoembolization combined apatinib/camrelizumab for advanced hepatocellular carcinoma with hepatic arterioportal shunts.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of drug-eluting beads transarterial chemoembolization (D-TACE) combined with apatinib/camrelizumab in advanced hepatocellular carcinoma (HCC) patients with hepatic arterioportal shunts (APS). METHODS: From January 2021 to December 2022, consecutive medical records of advanced HCC patients with APS receiving D-TACE combined apatinib/camrelizumab were reviewed for eligibility. Overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) were assessed. RESULTS: A total of 23 patients were included in this study, and the median follow-up time was 11 months (range, 2-26 months). In this study, 8 patients (34.8%) achieved PR, 13 patients (56.5%) achieved SD, and 2 patients (8.7%) developed PD. The objective response rate and disease controlled rate were 34.8% and 91.3%, respectively. OS and PFS were 11 months and 7 months, respectively. Multivariate analysis indicated that tumor number was an independent prognostic factor affecting PFS. AEs occurred in 19 patients after oral apatinib and in 8 patients after camrelizumab treatment. No treatment-related death occurred. CONCLUSIONS: D-TACE combined with apatinib/camrelizumab had meaningful efficacy and controllable AEs in advanced HCC patients with APS, which may be a promising treatment option. ADVANCES IN KNOWLEDGE: •1.We investigate a new treatment strategy for advanced HCC patients with hepatic arterioportal shunts；2.D-TACE combined with apatinib/camrelizumab had meaningful efficacy and controllable AEs in advanced HCC patients with APS, which may be a promising treatment option.

Melatonin enhances the efficacy of anti-PD-L1 by improving hypoxia in residual tumors after insufficient radiofrequency ablation.

The hypoxic microenvironment and inflammatory state of residual tumors caused by insufficient radiofrequency ablation (iRFA) are major reasons for rapid tumor progression and pose challenges for immunotherapy. We retrospectively analyzed the clinical data of patients with hepatocellular carcinoma (HCC) treated with RFA and observed that iRFA was associated with poor survival outcomes and progression-free survival. Using an orthotopic HCC mouse model and a colorectal liver metastasis model, we observed that treatment with melatonin after iRFA reduced tumor growth and metastasis and achieved the best outcomes when combined with anti-programmed death-ligand 1 (anti-PD-L1) therapy. In mechanism, melatonin inhibited the expression of epithelial-mesenchymal transitions, hypoxia-inducible factor (HIF)-1α, and PD-L1 in tumor cells after iRFA. Flow cytometry revealed that melatonin reduced the proportion of myeloid-derived suppressor cells and increased the proportion of CD8+ T cells. Transcriptomic analysis revealed an upregulation of immune-activated function-related genes in residual tumors. These findings demonstrated that melatonin can reverse hypoxia and iRFA-induced inflammation, thereby overcoming the immunosuppressive tumor microenvironment (TME) and enhancing the efficacy of immunotherapy.