Construction of an Injectable Composite Double-Network Hydrogel as a Liquid Embolic Agent.

Conventional embolists disreputably tend to recanalization arising from the low filling ratio due to their rigidity or instability. As a result, intelligent hydrogels with a tunable modulus may meaningfully improve the therapeutic efficacy. Herein, an injectable composite double-network (CDN) hydrogel with high shear responsibility was prepared as a liquid embolic agent by cross-linking poly(vinyl alcohol) (PVA) and carboxymethyl chitosan (CMC) via dynamic covalent bonding of borate ester and benzoic-imine. A two-dimensional nanosheet, i.e., layered double hydroxide (LDH), was incorporated into the network through physical interactions which led to serious reduction of yield stress for the injection of the hydrogel and the capacity for loading therapeutic agents like indocyanine green (ICG) and doxorubicin (DOX) for the functions of photothermal therapy (PTT) and chemotherapy. The CDN hydrogel could thus be transported through a thin catheter and further in situ strengthened under physiological conditions, like in blood, by secondarily cross-linking with phosphate ions for longer degradation duration and better mechanical property. These characteristics met the requirements of arterial interventional embolization, which was demonstrated by renal embolism operation on rabbits, and meanwhile favored the inhibition of subcutaneous tumor growth on an animal model. Therefore, this work makes a breakthrough in the case of largely reducing the embolism risks, thus affording a novel generation for interventional embolization.

Efficacy and Safety of HepaSphere Drug-Eluting Bead Transarterial Chemoembolization Combined with Hepatic Arterial Infusion Chemotherapy as the Second-Line Treatment in Advanced Hepatocellular Carcinoma.

Purpose: Recently, hepatic arterial infusion chemotherapy (HAIC) has also gained popularity for hepatocellular carcinoma (HCC). Several studies have compared HAIC and Transarterial chemoembolization (TACE). However, comparisons between TACE plus HAIC and HAIC are rarely reported. Here, we evaluated the performance of HepaSphere DEB-TACE combined with HAIC (Hepa-HAIC) compared to HAIC in patients with advanced HCC. Patients and Methods: In this retrospective study, we enrolled 167 patients diagnosed with advanced HCC and treated at Peking University Cancer Hospital from May 2018 to May 2022. The cohort comprised 74 patients who received HepaSphere DEB-TACE combined with HAIC-FOLFOX (Hepa-HAIC) and 93 patients who received HAIC-FOLFOX. Over 60% of patients received prior treatments. To avoid selection bias, propensity score matching was applied to the efficacy and safety analyses. The primary endpoints are progression-free survival (PFS) and overall survival (OS); the secondary endpoints include objective response rate (ORR), disease control rate (DCR), and safety. Results: Propensity-matching yielded 48 pairs, and group baselines were almost equal after matching. Median PFS and median OS were both higher in the matched Hepa-HAIC cohort (median PFS: 8.9 vs 5.8 months, p = 0.035; median OS: 22.4 vs 9.5 months, p = 0.027), which was consistent with pre-matching analysis. The ORR in the Hepa-HAIC and HAIC cohorts was 75.0% and 37.5%, respectively; the DCR was 93.8% after Hepa-HAIC and 81.3% after HAIC. There was no treatment-related death. Grade 3-4 ALT elevation was more frequent in the Hepa-HAIC group (33.3% vs 8.3%, p = 0.003), while vomiting was more frequent in the HAIC group (29.2% vs 12.5%, p = 0.084). Conclusion: The Hepa-HAIC group is superior to the HAIC group in metrics of PFS, OS, ORR, and DCR, which indicates the combination of HepaSphere DEB-TACE and HAIC may lead to improved outcomes with a comparable safety profile in advanced HCC.

High-dose oxaliplatin induces severe hypersensitivity reactions and high recurrence rates during rechallenge in patients treated with hepatic arterial infusion chemotherapy.

AIM: To analyze the risk factors for oxaliplatin (OXA)-induced severe hypersensitivity reactions and identify the recurrence rate of the reactions after an OXA rechallenge in patients treated with hepatic arterial infusion chemotherapy (HAIC). METHODS: Among the 2251 patients treated with HAIC (OXA), 84 patients with gastrointestinal cancer who displayed hypersensitivity reactions between May 2013 and May 2022 were included in this study. Among the 84 patients, 23 (27.4%) developed severe anaphylactic reactions (grade III/IV), and 61 (72.6%) developed grade I/II reactions. We explored the risk factors for severe OXA-induced hypersensitivity reactions. Twenty-seven patients with grade I/II reactions underwent retreatment (HAIC with OXA), and the recurrence rate of the hypersensitivity reactions was determined. A multivariate logistic regression model was used to analyze the risk factors for OXA-induced hypersensitivity reaction. RESULTS: In the study, multivariate analysis indicated that the dose of OXA (odds ratio [OR] 3.077, 95 % confidence interval [CI] 1.106-8.558, p = 0.031) was an independent risk factor for OXA-induced severe hypersensitivity reactions. Twenty-seven patients with non-severe hypersensitivity reactions underwent retreatment HAIC with OXA and 14 (51.9 %) experienced HSR recurrence, including 2 (7.4 %) who experienced hypersensitivity shock. CONCLUSIONS: The administration of OXA doses is a risk factor for OXA-induced severe hypersensitivity reactions in patients treated with HAIC (OXA). Rechallenging HAIC with OXA appears to be associated with a higher recurrence rate of the HSR.

A Novel Nomogram for Predicting the Overall Survival in Patients with Unresectable HCC after TACE plus Hepatic Arterial Infusion Chemotherapy.

BACKGROUND AND AIM: Transarterial chemoembolization combined with hepatic arterial infusion chemotherapy (TACE-HAIC) has shown encouraging efficacy in the treatment of unresectable hepatocellular carcinoma (HCC). We aimed to develop a novel nomogram to predict overall survival (OS) of patients with unresectable HCC treated with TACE-HAIC. METHODS: A total of 591 patients with unresectable HCC treated with TACE-HAIC between May 2009 and September 2020 were enrolled. These patients were randomly divided into training and validation cohorts. The independent prognostic factors were identified with Cox proportional hazards model. The model's discriminative ability and accuracy were validated using concordance index (C-index), calibration plots, the area under the time-dependent receiver operating characteristic curve (AUC) and decision curve analyses (DCAs). RESULTS: The median OS was 15.6 months. A nomogram was established based on these factors, including tumor size, vein invasion, extrahepatic metastasis, tumor number, alpha fetoprotein (AFP), and albumin-bilirubin (ALBI), to predict OS for patients with unresectable HCC treated with TACE-HAIC. The C-index of the nomogram were 0.717 in the training cohort and 0.724 in validation cohort. The calibration plots demonstrated good agreement between the predicted outcomes and the actual observations. The AUC values were better than those of three conventional staging systems. The results of DCA indicated that the nomogram may have clinical usefulness. The patients in the low-risk group had a longer OS than those in intermediate-risk and high-risk groups (P<0.001). CONCLUSION: A prognostic nomogram was developed and validated to assist clinicians in accurately predicting the OS of patients with unresectable HCC after TACE-HAIC.

Real-world study of hepatic artery infusion chemotherapy combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors for advanced hepatocellular carcinoma.

Aim: We investigated the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors (TKIs) for advanced hepatocellular carcinoma (HCC). Method: This retrospective study included HCC patients treated with HAIC, TKIs and anti-PD-1 antibodies between May 2019 and November 2020 in our hospital. Primary end points were progression-free survival and safety. Results: Twenty-seven advanced HCC patients were analyzed. The median follow-up was 12.9 months (range: 4.0-24.0 months) and the median progression-free survival was 10.6 months. The objective response rate and disease control rate were 63.0 and 92.6%, respectively. No treatment-related deaths occurred. Conclusion: In patients with advanced HCC, treatment with HAIC, anti-PD-1 antibodies and oral TKIs was effective and safe.

Lay abstract Some tyrosine kinase inhibitors (TKIs) that inhibit tumor vessel growth, such as sorafenib and lenvatinib, have been recommended as first-line treatment for advanced hepatocellular carcinoma (HCC). In hepatic artery infusion chemotherapy, chemotherapeutic drugs can be delivered via a microcatheter to the tumor-supplying artery to increase the local drug concentration, leading to higher local disease control rates and less toxicity than systemic chemotherapy. The combination of anti-PD-1 immunotherapy plus TKIs was shown in a previous study to be a safe and effective treatment for advanced HCC. This study explored the safety and effectiveness of hepatic artery infusion chemotherapy, TKIs and an anti-PD-1 antibody for the treatment of advanced HCC and found that combination therapy is effective, with good tolerability.

Reduction of microwave ablation needle related metallic artifacts using virtual monoenergetic images from dual-layer detector spectral CT in a rabbit model with VX2 tumor.

The purpose of the study was to investigate the application of virtual monoenergetic images (VMIs) in reducing metal artifacts in rabbit VX2 liver cancer models treated with microwave ablation (MWA) therapy. A total of 31 VX2 liver cancer models that accepted CT-guided percutaneous microwave ablation were analyzed. Conventional images (CIs) with the most severe metallic artifacts and their corresponding energy levels from 40 to 200 keV with 10 keV increment of VMIs were reconstructed for further analysis. Objective image analysis was assessed by recording the attenuation (HU) and standard deviation of the most severe hyper/hypodense artifacts as well as artifact-impaired liver parenchyma tissue. Two radiologists visually evaluated the extent of artifact reduction, assessed data obtained by a diagnostic evaluation of liver tissues, and appraised the appearance of new artifacts according to the grade score. Statistical analysis was performed to compare the difference between CIs and each energy level of VMIs. For subjective assessment, reductions in hyperdense and hypodense artifacts were observed at 170-200 keV and 160-200 keV, respectively. The outcomes of the diagnostic evaluation of adjacent liver tissue were statistically higher at 140-200 keV for VMIs than for CIs. In terms of objective evaluation results, VMIs at 90-200 keV reduced the corrected attenuation of hyperdense and of artifact-impaired liver parenchyma compared with CIs (P < 0.001). When VMIs at 80-200 keV decreased the hypodense artifacts (P < 0.001). Therefore, we concluded that VMIs at 170-200 keV can obviously decrease the microwave ablation needle-related metal artifacts objectively and subjectively in rabbit VX2 liver cancer models.

Endovascular management of arterio-ureteral fistula in a patient with a challenging hematuria.

Arterio-ureteral fistula (AUF) is a rare, but life-threatening disease that causes massive hematuria. We present a case of a 43-year-old female with AUF successfully treated with coil embolization and deployment of endovascular stents, along with a literature review. AUF symptoms most commonly occur with intermittent hematuria. AUF can occur in association with ureteral stenting, radiation, and prior pelvic or vascular surgery. Arteriography or ureteral pyelography are recommended as the most effective diagnostic strategies. Recent treatment efforts have focused on the use of endovascular stenting techniques as an alternative to open surgery.

Safety and feasibility within 24 h of discharge in patents with inoperable malignant lung nodules after percutaneous microwave ablation.

CONTEXT: Minimally invasive interventional therapy is now the more effective treatment strategy for organ-confined malignancy in patients who are poor candidates for surgery. Microwave ablation (MWA) in lung malignancy has been receiving much attention as an effective minimally invasive approach. AIMS: The aim of this study is to evaluate the safety and feasibility within 24 h of discharge of patients treated with percutaneous MWA for inoperable malignant lung nodules, and elucidate the factors predisposing to hospital readmission. SUBJECTS AND METHODS: From September 2014 to April 2016, a total of eighty patients with inoperable malignant lung nodules who underwent 24 h of discharge following percutaneous MWA were consecutively enrolled in this retrospective study. Primary endpoints included the rate of short-term admission and procedure-related complications within 30 days of hospital discharge. The secondary outcomes included the rate of technical success and hospital readmission. STATISTICAL ANALYSIS USED: Student's t- test and Fisher exact test were used to analysis parametric and categorical variables accordingly. RESULTS: The technical success was achieved in 94% of ablation sessions. Within 24 h of discharge was feasible in 73 cases (91.3%), and 7 (8.7%) required short-term admission. The complication rate was 27.5% (22/80), included the major 40.9% (9/22) and minor 59.1% (13/22) complications. Postoperative adverse event was 17.5% (14/80), these was managed conservatively. The lesion location and puncture technique were associated with an increased need for readmission. CONCLUSIONS: Routine 24 h discharge following percutaneous MWA for malignant lung nodules is safe and feasible, with relatively low complications and few requirements for short-term readmission.