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.

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.

Ablation alone is noninferior to radiotherapy plus ablation in the patients with early-stage hepatocellular carcinoma: a population-based study.

Recently, the efficacy of two low-invasive treatments, ablation, and radiotherapy, has been fully compared for the patients with the early-stage hepatocellular carcinoma (HCC). However, the comparison between radiotherapy plus ablation and ablation alone has been less frequently reported. Data from the Surveillance, Epidemiology, and End Results (SEER) database were searched for early-stage HCC patients treated with ablation plus radiotherapy or ablation alone. The outcome measures were overall survival (OS) and cancer-specific survival (CSS). The propensity score matching (PSM) was used to reduce selection bias. We included 240 and 6619 patients in the radiotherapy plus ablation group and ablation group before the PSM. After PSM, 240 pairs of patients were included. The median OS (mOS) and median CSS (mCSS) of patients receiving ablation alone were longer than that of receiving radiotherapy plus ablation (mOS: 47 vs. 34 months, P = 0.019; mCSS: 77 vs. 40 months, P = 0.018, after PSM) before and after PSM. The multivariate analysis indicated that radiotherapy plus ablation independent risk factor for OS and CSS before PSM, but the significance disappeared after PSM. The detailed subgroup analyses indicated ablation alone brought more benefit in very early-stage HCC and older patients. In addition, we found different types of radiotherapy might lead to different outcomes when combined with ablation. In conclusion, ablation alone is noninferior to radiotherapy plus ablation in patients with early-stage HCC. The additional radiation prior to ablation may bring survival benefits in the patients with higher tumor stage. However, due to the risk of selection bias in that study, the results should be interpreted cautiously.

Association of the pretreatment lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced hepatocellular carcinoma.

OBJECTIVE: To evaluate whether the pretreatment Lung Immune Prognostic Index (LIPI) is associated with outcomes in advanced hepatocellular carcinoma (HCC) patients under ICI. METHODS: A two-center retrospective study of patients with HCC treated with immune checkpoint inhibitors (ICIs) between January 2018 and January 2021 was performed. Based on pretreatment derived neutrophils/ (leukocytes minus neutrophils) ratio (dNLR) greater than 3 and a lactate dehydrogenase (LDH) level greater than the normal value, patients were stratified into three groups (good LIPI:0 risk factor, intermediate LIPI: 1 risk factor, and poor LIPI: 2 risk factors). The primary endpoints were overall survival (OS) and progression-free survival (PFS). The second endpoints were disease control rate (DCR) and objective response rate (ORR). RESULTS: In the pooled cohort (n = 224), 80 (35.7%) had a good LIPI (zero factor), 91 (40.6%) had intermediate LIPI (one factor), and 53 (23.7%) had poor LIPI (two factors). The median follow-up was 25.1 months. Median OS was 16.8 months, 12.5 months, and 9.5 months for the good, intermediate, and poor LIPI groups, respectively (P < 0.0001). Median PFS was 11.8 months, 7.8 months, and 4.0 months for the good, intermediate, and poor LIPI groups, respectively (P < 0.0001). Multivariate analysis indicated that the intermediate LIPI and poor LIPI both were independently associated with OS, PFS, and ORR, DCR (P < 0.05), as risk factors. CONCLUSION: Pretreatment LIPI was correlated with worse outcomes for ICIs suggesting that LIPI could be promising biomarker for advanced HCC patients under ICIs.

Recent advances in oncolytic virus therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly refractory cancer and the fourth leading cause of cancer-related mortality worldwide. Despite the development of a detailed treatment strategy for HCC, the survival rate remains unsatisfactory. Oncolytic virus has been extensively researched as a new cancer therapeutic agent in the treatment of HCC. Researchers have designed a variety of recombinant viruses based on natural oncolytic diseases, which can increase the targeting of oncolytic viruses to HCC and their survival in tumors, as well as kill tumor cells and inhibit the growth of HCC through a variety of mechanisms. The overall efficacy of oncolytic virus therapy is known to be influenced by anti-tumor immunity, toxic killing effect and inhibition of tumor angiogenesis, etc. Therefore, a comprehensive review of the multiple oncolytic mechanisms of oncolytic viruses in HCC has been conducted. So far, a large number of relevant clinical trials are under way or have been completed, and some encouraging results have been obtained. Studies have shown that oncolytic virus combined with other HCC therapies may be a feasible method, including local therapy, chemotherapy, molecular targeted therapy and immunotherapy. In addition, different delivery routes for oncolytic viruses have been studied so far. These studies make oncolytic virus a new and attractive drug for the treatment of HCC.

Morphine prophylaxis alleviates pain in transjugular intrahepatic portosystemic shunt procedure: A randomized clinical trial.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is an accepted minimal invasive procedure for the management of complications of portal hypertension. OBJECTIVE: This study aims to investigate the value of the preemptive administration of morphine, when compared with on-demand morphine, during TIPS. METHODS: The present study was a randomized control trial. A total of 49 patients were selected to receive 10 mg of morphine either before the TIPS procedure (group B, n= 26), or on demand when needed during the TIPS procedure (group A, n= 23). The patient's pain was scored using the visual analog scale (VAS) during the procedure. VAS, pain performance, HR, systolic pressure, diastolic pressure and SPO2 were recorded at four-time points: before the operation (T0), during the trans-hepatic puncture of the portal vein (T1), during the intrahepatic channel expansion (T2), and when the operation was finished (T3). The duration of the operation was also recorded. RESULTS: In group A, the proportion of severe pain at T1 was 4.3% (one case), two cases were combined with vagus reflex, and the proportion of severe pain at T2 was 65.2% (15 cases). No severe pain occurred in group B. The VAS score significantly decreased at T1, T2 and T3 in group B, when compared to group A (P< 0.05). HR, systolic pressure and diastolic pressure significantly decreased at T2 and T3 in group B, when compared to group A (P< 0.05). There was no significant difference between the two groups in terms of SPO2 (P> 0.05). CONCLUSION: Preemptive analgesia can effectively relieve severe pain during TIPS, improve patient comfort and compliance, ensure a routine procedure, and offer excellent safety, and is simple and effective.

The Feasibility of TACE Combined with TKIs Plus PD-1 Antibody for Advanced HCC.

Objective: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs: sorafenib, lenvatinib, and apatinib) plus camrelizumab (TACE-TKIs-C) vs TACE combined with TKIs (TACE-TKIs) for advanced hepatocellular carcinoma (HCC). Methods: In this two-center retrospective study, patients with advanced HCC treated with TACE-TKIs-C or TACE-TKIs were enrolled between January 1, 2018, to October 1, 2020. A total of 260 eligible patients received TACE-TKIs-C (N=70) or TACE-TKIs (N=190). The differences in overall survival (OS), progression-free survival (PFS) and tumor response were compared between two groups. Propensity score matching (PSM) analysis was applied to reduce patient selection bias. The risk factors affecting OS or PFS were analyzed. Results: Fifty-three pairs of patients were matched after PSM analysis. Before PSM analysis, the median OS and PFS of TACE-TKIs-C were significantly longer than those of the TACE-TKIs (OS: not reached vs 12.0 months, P<0.0001; PFS: 10.0 months vs 6.0 months, P<0.0001). After PSM analysis, the median OS and PFS of TACE-TKIs-C were significantly longer than those of the TACE-TKIs (OS: Not reached vs 13.0 months, P<0.0001; PFS: 9.0 months vs 6.0 months, P<0.0001); the uni- and multivariate analysis revealed that TACE-TKIs-C treatment was a protective factor of OS and PFS. Grade 3 or 4 hypertension occurred in 14.3% of patients in the TACE-TKIs-C group and other high-grade toxic effects were infrequent. Conclusion: In patients with advanced HCC, TACE-TKIs-C may improve overall and progression-free survival outcomes over TACE-TKIs with manageable safety profile.

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.

Association between sarcopenia and clinical outcomes in patients with hepatocellular carcinoma: an updated meta-analysis.

Although numerous studies have reported the association between sarcopenia and the prognosis of hepatocellular carcinoma (HCC) patients, there is lack of a newer and more comprehensive meta-analysis. Herein, a comprehensive literature search was performed on PubMed, Web of Science, the Cochrane Library, and Embase databases to identify relevant studies published up to February 2022. The outcomes were overall survival (OS), recurrence, progression-free survival, tumor response, severe postoperative complications, and toxicity of drugs. A total of 57 studies involving 9790 HCC patients were included in the meta-analysis. The pooled prevalence of sarcopenia in HCC patients was 41.7% (95% CI 36.2-47.2%). Results demonstrated that sarcopenia was significantly associated with impaired OS (HR: 1.93, 95% CI 1.73-2.17, P < 0.001), higher risk of tumor recurrence (HR: 1.75, 95% CI 1.56-1.96, P < 0.001), lower objective response rate (OR: 0.37 95% CI 0.17-0.81, P = 0.012), and more drug-related adverse events (OR: 2.23, 95% CI 1.17-4.28, P = 0.015) in HCC patients. The subgroup analyses revealed that the OS of patients at the early stage of tumor was more severely affected by sarcopenia than for patients at other stages. Moreover, the presence of cirrhosis and Child Pugh class B increased the hazard of mortality from sarcopenia. This study has shown that sarcopenia is highly associated with poor prognosis in HCC patients. In addition, cirrhosis and poor liver functional reserve increase the danger of sarcopenia. OS was more impaired in HCC patients with sarcopenia at early stage of tumor than at other tumor stages.

Pyogenic liver abscess in non-liver cancer patients and liver cancer patients treated with TACE: Etiological characteristics, treatment, and outcome analysis.

Clinical, laboratory, and microbiological features, clinical outcomes, and pyogenic liver abscess (PLA) prognosis evaluation in non-liver cancer (Non-LC) and liver cancer patients treated with transarterial chemoembolization (TACE, LC-TACE). Clinical data of 48 consecutive PLA patients from January 2016 to December 2020 were retrospectively analyzed. Mortality between two PLA patient groups were compared, and mortality risk factors were evaluated. A total of 48 PLA patients (31 males and 17 females) from January 2016 to December 2020 met the study's inclusion criteria. There were 32 and 16 patients in the Non-LC and LC-TACE groups, respectively. Positive pus culture rate in the Non-LC group was 87.5% and positive pus culture rate in LC-TACE group was 81.3%. In the Non-LC group, 28 patients improved after treatment, 1 patient did not improve, and 3 patients died during hospitalization, with a 9.4% mortality rate. In the LC-TACE group, nine patients improved after treatment, three patients did not improve, and four patients died during hospitalization, with a 25% mortality rate. The Non-LC group cure time was 37.4 ± 23.1 days, while the LC-TACE group was 91.5 ± 49.7 days. PLA of the Non-LC group and the LC-TACE group were different in terms of pathogenic bacteria and cure time, and so on. A more comprehensive treatment should be considered for PLA after TACE.

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.

Addition of Camrelizumab to Transarterial Chemoembolization in Hepatocellular Carcinoma With Untreatable Progression.

Purpose: The present retrospective study aimed to evaluate the efficacy and safety of camrelizumab addition to transarterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC) with TACE-related untreatable progression (UP). Methods: Patients with HCC who received addition of camrelizumab due to UP after initial TACE treatment were enrolled at our institution between May 2019 and January 2021. Patients were assessed for tumor response, progression-free survival (PFS), and adverse events (AEs). Risk factors for PFS were evaluated with logistic regression analysis. Results: A total of 41 patients were included. The objective response rates (ORR) and disease control rates (DCR) were 24.4% and 61.0% at 2 to 3 months, and 12.2% and 58.5% at 6 months, respectively. The median PFS of the patients were 6 months (95% confidence interval [CI]: 3.8 months, 8.2 months). Of the 41 patients, 23 received camrelizumab combined with TACE (hereafter, camrelizumab-TACE) on whom 52 combined TACE procedures were performed, with a median of 2 procedures (range: 1-6) per patient. The remaining 18 patients received camrelizumab alone due to TACE contraindications. Multivariable analysis indicated that camrelizumab-TACE was an independent prognostic factor for PFS. Subgroup analysis showed a median PFS of 8 months in the camrelizumab-TACE group and 3 months in the camrelizumab monotherapy group (P < .001). No treatment-related mortalities occurred. Seventeen patients (41.5%) developed at least 1 type of AE after treatment with camrelizumab, with reactive cutaneous capillary endothelial proliferation (RCCEP) (n = 14, 34.1%) being the most common AE. Conclusion: Addition of camrelizumab to TACE offered an effective and safe treatment for HCC with UP.

Safety and efficacy of lenvatinib combined with camrelizumab plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: A two-center retrospective study.

Objectives: To compare the safety and efficacy of lenvatinib (LEN) combined with camrelizumab plus transcatheter arterial chemoembolization (TACE-LEN-C) and TACE combined with LEN (TACE-LEN) in patients with unresectable hepatocellular carcinoma (uHCC). Methods: Eighty-three patients with uHCC treated with TACE-LEN-C or TACE-LEN from September 2018 to May 2021 were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), local tumor response, and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. Results: There were 31 patients in the TACE-LEN-C group and 52 patients in the TACE-LEN group. The median follow-up period was 14.2 months (range 7.2-25.2 months) in the whole study. The combination of triple therapy was found to significantly prolong the PFS (12.5 months vs. 6.6 months, P<0.001) and OS (18.9 months vs. 13.9 months, P<0.001. In terms of tumor response, the combination demonstrated a higher objective response rate (71% vs. 42.3% by the modified Response Evaluation Criteria in Solid Tumors, P=0.023) without a statistically significant difference in the disease control rate (93.5% in TACE-LEN-C, 80.8% in TACE-LEN, P=0.195). In the multivariate analysis, two independent factors affecting PFS were identified: number of tumors and treatment. Three independent factors affected OS: number of tumors, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment. All the AEs were tolerable. Conclusion: TACE-LEN-C is a safe and effective treatment for patients with uHCC, and could be a potential treatment option.

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.

Effect of Transarterial Chemoembolization Plus Percutaneous Ethanol Injection or Radiofrequency Ablation for Liver Tumors.

Background: The efficacy of the transarterial chemoembolization (TACE) process combined with percutaneous ethanol injection (PEI, TACE-P) or the radiofrequency ablation (RFA, TACE-R) process was found to be good when used for the treatment of patients suffering from early or intermediate hepatocellular carcinoma (eiHCC). The study was conducted to compare the efficacy and safety of the TACE-P with TACE-A processes followed during the treatment of patients with eiHCC. Methods: A total of 241 patients suffering from eiHCC, subjected to TACE-P (147 patients) or TACE-R (94 patients) processes from January 1, 2014, to December 31, 2018, were retrospectively reviewed and included. The propensity score matching (PSM) method was used to reduce selection bias. Results: The median overall survival (mOS) and progression-free survival (mPFS) of the TACE-P group were similar to those recorded for the TACE-R group (P>0.05) before using the PSM technique. Similar results were obtained post the use of the PSM technique. In the subgroup analysis after PSM, patients with single tumor (dimension: ≤5 cm), who were subjected to TACE-P-based treatment methods, exhibited worse tumor response than patients subjected to TACE-R-based methods (HR: 1.804, 95% CI: 1.083-3.005, P=0.023). Seven adverse events were reported. A statistically significant difference for all grades of adverse events (and grade III or IV adverse events) between the two groups (all P>0.05) was not reported. Conclusion: The benefits and advantages of using the TACE-P based method was similar was those obtained using the TACE-R in patients with eiHCC, especially for patients with a single large tumor or multiple tumors.

Arterial enhancement fraction in evaluating the therapeutic effect and survival for hepatocellular carcinoma patients treated with DEB-TACE.

BACKGROUND: Arterial enhancement fraction (AEF), derived from triphasic CT scans, is considered to indirectly reflect the ratio of hepatic arterial perfusion to total perfusion. The purpose of this study was to retrospectively investigate the relationship between AEF and treatment response and survival in hepatocellular carcinoma (HCC) patients treated with drug-eluting bead (DEB) TACE. METHODS: AEF of primary lesion (AEFpre) and residual tumor (AEFpost) in 158 HCC patients were obtained from triphasic liver CT examinations pre- and post-treatment. Wilcoxon-signed rank test was used to compare the AEFpre and AEFpost for different response groups. Survival curves for overall survival (OS) in patients with different AEF were created by using Kaplan-Meier method. Cox regression analyses were used to determine the association between AEF and OS. RESULTS: There was no correlation between AEFpre and treatment response. After DEB-TACE, AEFpost was significantly lower than AEFpre either in the partial response group (38.9% vs. 52.7%, p <  0.001) or in the stable disease group (49.3% vs. 52.1%, p = 0.029). In the progression disease group, AEFpost was numerically higher than AEFpre (55.5% vs. 53.0%, p = 0.604). Cox regression analyses showed that risk of death increased in patients with AEFpre > 57.95% (HR = 1.66, p = 0.019) or AEFpost > 54.85% (HR = 2.47, p <  0.001), and the risk reduced in patients with any reduction in tumor AEF (decrease ratio ≥ 0) and with increased AEF but not exceeding the ratio of 0.102 (increase ratio <  0.102) (HR = 0.32, p <  0.001). CONCLUSIONS: The change in AEF of viable tumor is correlated with response of HCC to DEB-TACE. In addition, the AEF could be a helpful predictor in future studies on the embolization treatment for HCC.

The Efficacy and Safety of Transarterial Chemoembolization Plus Iodine 125 Seed Implantation in the Treatment of Hepatocellular Carcinoma With Oligometastases: A Case Series Reports.

Background: Patients with different primary tumor oligometastases can obtain survival benefits from external radiotherapy. The study was conducted to explore the efficacy and safety of transarterial chemoembolization (TACE) plus iodine 125 seed (TACE-I) implantation for hepatocellular carcinoma (HCC) oligometastases. Methods: 187 patients who received TACE-I in our institution were retrospectively reviewed from January 2014 to December 2018. Thirty-two patients were included in the analysis. The primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). The secondary endpoints of the study were tumor response and PFS of the metastatic sites. Results: The median OS (mOS) of patients was 18 months, and the median PFS (mPFS) was 7 months. The objective response rate (ORR) and disease control rate (DCR) of patients three months after receiving TACE-I were 34.4% and 71.9%, respectively. The ORR and DCR of patients for metastatic sites were 50% and 81.3%, respectively. The mPFS of patients for metastatic sites was 14 months. The univariable and multivariable regression analyses indicated that the ECOG score was an independent predictor for mOS and mPFS. The number of iodine seeds and ECOG scores were independent predictors for mPFS for metastatic sites. After patients received TACE-I, the most common adverse events were abdominal pain, fever, and appetite. The adverse events of patients were relieved after receiving symptomatic treatments. Conclusion: Iodine 125 seed implantation may be an effective and safe treatment for patients with hepatocellular carcinoma with oligometastasis, thereby providing a new selective option for these patients.

Cascade Reaction of "Mn2+ -Catechol" Triggered by H2 O2 to Integrate Firm Tumor Vessel Embolization and Hypoxic Response Relief.

Transcatheter arterial embolization (TAE) therapy requires firm and long-term vessel embolization without recanalization. However, firm embolization usually leads to unanticipated hypoxic response which promotes tumor recurrence and metastasis. Herein, an injectable thermosensitive hydrogel containing catechol groups and Mn2+ (PNDM) has been developed to enhance embolization and inhibit hypoxic response utilizing augmented H2 O2 after TAE. This novel embolic agent converts H2 O2 into hydroxyl radicals via Mn2+ -dependent Fenton-like reaction, which are subsequently scavenged through a "catechol-quinone" transition to suppress hypoxic responses. Quinone structure can not only make hydrogel internal structure more compact, but also enhance hydrogel adhesion to vessel wall. In vivo experiments confirm that the rabbit renal artery can be firmly embolized for 84 days. Studies in liver VX2 tumor-bearing rabbits demonstrate that the PNDM-based TAE can promote tumor necrosis, inhibit angiogenesis and tumor metastasis, and greatly prolong rabbit survival. This strategy opens new sights in the TAE therapy for liver cancer.