• ferroptosis
• iodine-131
• liver cancer
• nanoparticles
• transarterial radioembolization

• Iodine Radioisotopes/chemistry
• Iodine Radioisotopes/therapeutic use
• Iodine Radioisotopes/pharmacology
• Animals
• Ferroptosis/drug effects
• Ferroptosis/radiation effects
• Embolization, Therapeutic/methods
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Liver Neoplasms/radiotherapy
• Humans
• Mice
• Ethiodized Oil/chemistry
• Ethiodized Oil/pharmacology
• Iron/chemistry
• Male
• Cell Line, Tumor
• Apoptosis/drug effects
• Nanoparticles/chemistry
• Rats

• Cancer starvation therapy
• Combination of therapies
• Multifunctional nanomaterials

• Humans
• Neoplasms/therapy
• Neoplasms/pathology
• Neoplasms/drug therapy
• Nanostructures/therapeutic use
• Nanostructures/chemistry
• Nanostructures/administration & dosage
• Animals

• FT240100280 Australian Research Council
• Griffith University

• Cell death
• Chemotherapy
• Radiation therapy
• Sphingolipids
• Ultrasound-stimulated microbubbles

• Microbubbles/therapeutic use
• Humans
• Neoplasms/therapy
• Neoplasms/diagnostic imaging
• Neoplasms/radiotherapy
• Animals
• Ultrasonic Therapy/methods
• Ultrasonography
• Magnetic Resonance Imaging
• Combined Modality Therapy

• anti-tumour mechanism
• hepatocellular carcinoma
• immune function
• nanotechnology
• tumor

• Drug delivery
• Hepatocellular carcinoma
• Peptide
• Transcatheter arterial chemoembolization

• Chemoembolization, Therapeutic/methods
• Carcinoma, Hepatocellular/therapy
• Doxorubicin/administration & dosage
• Liver Neoplasms/therapy
• Animals
• Rats
• Antibiotics, Antineoplastic/administration & dosage
• Oxidation-Reduction
• Peptides
• Ethiodized Oil/administration & dosage
• Rats, Sprague-Dawley
• Disease Models, Animal
• Male
• Humans

• 82172038 National Natural Science Foundation of China

• biomaterials
• chemoembolization
• embolic agent
• radioembolization

• Humans
• Microspheres
• Prospective Studies
• Embolization, Therapeutic/methods
• Liver Neoplasms/therapy
• Biocompatible Materials

• Antitumor effect
• Celecoxib
• Cisplatin
• Drug-eluting microspheres
• Transarterial chemoembolization

• Drug-eluting beads
• Epirubicin
• Pharmacokinetics
• Transarterial chemoembolization

• 20ZR1452700 Natural Science Foundation of Shanghai
• 2017YFC0109205 the National Key Research and Development Program of China

• HCC
• Lenvatinib
• TACE
• Transcatheter arterial chemoembolization
• Unresectable hepatocellular carcinoma

• CalliSpheres® DEB-TACE
• Conventional TACE
• Refractory colorectal cancer liver metastases
• Survival profile
• Treatment response

• Humans
• Liver Neoplasms/pathology
• Carcinoma, Hepatocellular/pathology
• Retrospective Studies
• Microspheres
• Treatment Outcome
• Chemoembolization, Therapeutic

• deposition
• embolization
• lipiodol
• liver tumor
• washout

• Hepatocellular carcinoma
• medical oncology
• recent therapeutics
• surgery
• treatment

• DEBIRI-TACE
• FDG PET/CT
• case report
• colorectal liver metastases
• irinotecan
• prognosis

• Ga based liquid metal
• Hepatocellular carcinoma (HCC)
• Micro/nano materials
• Multifunctional flexible embolic agents
• Particulate embolic agents
• Transarterial chemoembolization (TACE)

• Humans
• Magnetic Resonance Imaging
• Robotics
• Magnetics
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/therapy

• Korea Health Industry Development Institute

• Embolization
• Hepatocellular carcinoma
• Liver failure
• Transarterial chemoembolization
• Tumor size

• barcelona clinic liver cancer stage
• child-pugh (c-p) classification
• deb-tace
• hepatocellular carcinoma (hcc)
• neoadjuvant chemoembolization
• radio-frequency ablation
• tace complication
• transarterial chemoembolization (tace)
• transcatheter arterial embolization
• unresectable hcc

• arteriovenous malformations
• embolic agents
• embolization
• hepatocellular carcinoma
• polymers
• uterine fibroids

More than half of new cases of hepatocellular carcinoma (HCC) and associated deaths occurring annually worldwide are recorded in China. Chinese patients with HCC exhibit special characteristics in terms of etiology, leading to differences in prognosis versus Western patients. In recent years, several angiogenesis inhibitors were approved, and immune checkpoint blockers (ICBs) were recommended as second-line therapy for advanced HCC. In addition, the recent success of a combination of atezolizumab with bevacizumab signals resulted in an essential change in the first-line treatment of HCC. We investigated the characteristics of patients with HCC in China and summarized the rapidly emerging relevant clinical data, which relate to the prospects and challenges associated with the use of ICBs in this setting. We further evaluated the efficacy of ICBs in Chinese patients with HCC based on data obtained from global trials, and discussed possible factors influencing the effectiveness of ICBs in patients with HCC in China. Immunotherapy offers new options for the treatment of advanced HCC, though responses varied between patients. Currently, there is a need to discover specific biomarkers for the accurate identification of patients who would more likely benefit from immunotherapy. Furthermore, investigation of patient characteristics in different countries is necessary to provide a clinical practice basis and reference value for the diagnosis and treatment of HCC.

• hepatocellular carcinoma
• imaging
• microspheres
• nanoparticles
• therapy
• transarterial chemoembolization

• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/pathology
• Chemoembolization, Therapeutic/adverse effects
• Humans
• Liver Neoplasms/drug therapy
• Microspheres
• Nanoparticles/therapeutic use
• Treatment Outcome

• P30 DK048522 NIDDK NIH HHS

The in-situ post-embolization fluorescence-guided hepatectomy for hepatocellular carcinoma (HCC) requires precise embolic formulation that meets both preoperative and intraoperative needs of hepatobiliary surgeons. In this Editorial, we highlight the development of Superstable Homogeneous Iodinated Formulation Technology (SHIFT) for locoregional HCC treatment. It is believed that such an intelligent solution could resolve unmet formulation needs and make a major stride to bridge the preoperative gap of precision hepatectomy.

• Embolization
• Fluorescence
• HCC
• Hepatectomy
• ICG
• SHIFT

Transarterial chemoembolization (TACE) is a minimally invasive procedure involving intra-arterial catheter-based chemotherapy to selectively administer high doses of cytotoxic drugs to the tumor bed along with ischemic necrosis induced by arterial embolization. Chemoembolization forms the essential core of management in patients with hepatocellular carcinoma (HCC) who are not suitable for curative therapies such as transplantation, resection, or percutaneous ablation. TACE of hepatic cancer(s) has proven to be helpful in achieving local tumor control, and has supported the ability to prevent tumor progression, prolong patient life, and manage patient symptoms. Recent data have demonstrated that, in patients with single-nodule HCC ≤3 ​cm without vascular invasion, the 5-year overall survival with TACE was found to be comparable with hepatic resection and radiofrequency ablation. Used for several years, Lipiodol continues to play a vital role as a tumor-seeking and radiopaque drug delivery vector in interventional oncology. Efforts have been made to enhance the administration of chemotherapeutic agents to tumors. Compared with conventional TACE, drug-eluting bead TACE is a fairly new drug delivery embolization technique that permits fixed dosing and has the ability to provide sustained release of anticancer agents over a period of time. The present review discusses the basic procedure of TACE and its properties, and the effectiveness of conventional and drug-eluting bead chemoembolization systems currently available or presently undergoing clinical evaluation.

• Drug-eluting bead
• Hepatocellular carcinoma
• Transarterial chemoembolization

• LAG-3
• PD-L1
• hepatocellular carcinoma
• transarterial chemoembolization
• tumor response

Background: There is a sparsity of data on the use of ethiodized poppy seed oil (EPO) contrast agent (Lipiodol) in patients. We investigated the safety of EPO in children, adolescents, and some adults for diagnostic and therapeutic interventions. Methods: All patients who underwent procedures with EPO between 1995 and 2014 were retrospectively included. Demographic characteristics, diagnosis, dose, route of administration, preparation of EPO in combination with other agents, and complications were recorded. Results: In 1422 procedures, EPO was used for diagnostic or treatment purposes performed in 683 patients. The mean patient age was 13.4 years (range: 2 months–50 years); 58% of patients were female. Venous malformations (n = 402, 58.9%) and arteriovenous malformations (n = 60, 8.8%) were the most common diagnosis. Combined vascular anomalies included capillary–lymphatic–venous malformations, fibroadipose vascular anomalies (n = 54, 7.9%), central conducting lymphatic anomalies (n = 31, 4.5%), lymphatic malformations (n = 24, 3.5%), aneurysmal bone cysts (n = 22, 3.2%), and vascularized tumors (n = 11, 1.6%). In 1384 procedures (96%), EPO was used in various combinations with sclerosing and embolization agents, including sodium tetradecyl sulfate, ethanol, and glue. The mean volume of EPO used in interventions was 3.85 mL (range: 0.1–25 mL) per procedure with a mean patient weight of 45.9 kg (range: 3.7–122.6 kg) and a weight-adjusted dose of 0.12 mL/kg (range: 0.001–1.73 mL/kg). In 56 procedures (4%), EPO was used as a single agent for diagnostic lymphangiography. The mean volume was 4.8 mL (range: 0.3–13 mL) per procedure with a mean patient weight of 27.4 kg (range: 2.4–79.3 kg) and a weight-adjusted dose of 0.2 mL/kg (range: 0.04–0.54 mL/kg). Procedural-related complications occurred in 25 (1.8%) procedures. The 20 minor and 5 major complications were related to the primary treatment agents. None of them were directly related to EPO. No allergic reactions were noted. Conclusion: The use of an ethiodized poppy seed oil contrast agent in children, adolescents, and adults for diagnostic or therapeutic purposes is safe.

• EPO
• embolization
• ethiodized poppy seed oil
• safety
• sclerotherapy
• vascular malformation

Transarterial chemoembolization (TACE) is, currently, the recommended treatment for hepatocellular carcinoma (HCC). However, long-term chemoembolization triggers the inflammatory response and may lead to postembolization syndrome (PES). Although several types of degradable microspheres have been developed to reduce drug toxicity and PES incidence, the clinical outcomes remain unsatisfactory. Previously, we have developed a new type of spherical, calibrated, biodegradable, radiopaque microspheres (SCBRM) and demonstrated their safety and efficacy in a pig model. Thus, the goal of this feasibility study was to determine the clinical safety and efficacy of the new SCBRM in intermediate-stage HCC patients. In this study, 12 intermediate-stage HCC patients underwent TACE using SCBRM with a calibrated size of 100–250 μm. The disease control rates at 1 month and 3 months after TACE-SCBRM treatment were 100% and 75.0%, respectively. The objective response rates at 1 month and 3 months after treatment were 66.7% and 58.3%, respectively. Very few adverse events were observed with one patient developing nausea. One day after the treatment, alanine aminotransferase, alanine aminotransferase, and total bilirubin levels were slightly elevated in the patients, but all returned to baseline on day 7. The median and mean overall survival times were 33 months (interquartile range, 12.8–42.0) and 29.2 ± 14.3 months, respectively. The 1-year and 2-year survival rates were 91.7% and 58.3%, respectively. In conclusion, TACE with the new SCBRM microspheres is clinically safe and effective, and it represents a promising approach in the management of intermediate-stage HCC.

To develop and validate a pre-transcatheter arterial chemoembolization (TACE) MRI-based radiomics model for predicting tumor response in intermediate-advanced hepatocellular carcinoma (HCC) patients.

Ninety-nine intermediate-advanced HCC patients (69 for training, 30 for validation) treated with TACE were enrolled. MRI examinations were performed before TACE, and the efficacy was evaluated according to the mRECIST criterion 3 months after TACE. A total of 396 radiomics features were extracted from T2-weighted pre-TACE images, and least absolute shrinkage and selection operator (LASSO) regression was applied to feature selection and model construction. The performance of the model was evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curves.

The AFP value, Child-Pugh score, and BCLC stage showed a significant difference between the TACE response (TR) and non-TACE response (nTR) patients. Six radiomics features were selected by LASSO and the radiomics score (Rad-score) was calculated as the sum of each feature multiplied by the non-zero coefficient from LASSO. The AUCs of the ROC curve based on Rad-score were 0.812 and 0.866 in the training and validation cohorts, respectively. To improve the diagnostic efficiency, the Rad-score was further integrated with the above clinical indicators to form a novel predictive nomogram. Results suggested that the AUC increased to 0.861 and 0.884 in the training and validation cohorts, respectively. Decision curve analysis showed that the radiomics nomogram was clinically useful.

The radiomics and clinical indicator-based predictive nomogram can well predict TR in intermediate-advanced HCC and can further be applied for auxiliary diagnosis of clinical prognosis.

• The therapeutic outcome of TACE varies greatly even for patients with the same clinicopathologic features.

• Radiomics showed excellent performance in predicting the TACE response.

• Decision curves demonstrated that the novel predictive model based on the radiomics signature and clinical indicators has great clinical utility.

The online version contains supplementary material available at 10.1007/s00330-021-07910-0.

• Hepatocellular carcinoma
• Nomogram
• Prognosis
• Therapeutic chemoembolization

• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/therapy
• Chemoembolization, Therapeutic
• Humans
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/therapy
• Magnetic Resonance Imaging
• Nomograms
• Retrospective Studies

• the National Key Research and Development projects intergovernmental cooperation in science and technology of China
• National Natural Science Foundation of China
• Zhejiang Medical and Health Science Project
• Natural Science Foundation of Zhejiang Province
• The Key Research and Development Program of Lishui City

The study aimed to explore the efficacy and safety of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) plus intercostals arterial infusion chemotherapy in non-small cell lung cancer (NSCLC) patients with refractory malignant pleural effusion (MPE).

17 NSCLC patients with refractory MPE treated by DEB-BACE plus the intercostals arterial infusion chemotherapy (DEB-BACE group) were recruited. Their treatment response [complete remission (CR), partial remission (PR), overall efficacy, failure] for MPE was assessed at 1 month after therapy; adverse effects were recorded; MPE progression-free survival and overall survival (OS) were calculated. Moreover, 19 NSCLC patients with refractory MPE treated by conventional chemotherapy were reviewed as control (chemotherapy group), then their medical records were collected.

With respect to MPE response, DEB-BACE group exhibited increased CR (82.4% vs. 10.5%, P<0.001) and overall efficacy (100.0% vs. 52.6%, P=0.001), similar PR (17.6% vs. 42.1%, P=0.112) while less failure (0.0% vs. 47.4%, P=0.001) compared to chemotherapy group. Furthermore, OS was prolonged in DEB-BACE group (median: 13.4; 95% CI: 11.0–15.8 months) than chemotherapy group (median: 7.0; 95% CI: 4.4–9.6 months) (P=0.002). Further analyses displayed that in DEB-BACE group, CR was associated with improved ECOG score and longer MPE progression-free survival, and adverse events mainly included fever, chest distress/pain, gastrointestinal side effects, myelosuppression, rash and hemoptysis, which were all mild and tolerable.

DEB-BACE plus intercostals arterial infusion chemotherapy could serve as a salvage treatment option for NSCLC patients with refractory MPE.

• Non-small cell lung cancer (NSCLC)
• drug-eluting beads bronchial arterial chemoembolization (DEB-BACE)
• efficacy
• intercostals arterial infusion chemotherapy
• refractory malignant pleural effusion (MPE)
• safety

Colorectal cancer liver metastasis occurs in more than 50% of patients with colorectal cancer and is thought to be the most common cause of death from this cancer. The mainstay of treatment for inoperable liver metastasis has been combination systemic chemotherapy with or without the addition of biological targeted therapy with a goal for disease downstaging, for potential curative resection, or more frequently, for disease control. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies including hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are alternative treatment strategies that have shown promising results, most commonly in the salvage setting in patients with chemo-refractory disease. In recent years, their role in the first-line setting in conjunction with concurrent systemic chemotherapy has also been explored. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future.

The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, major advances in modern chemotherapy and personalized biological agents have improved overall survival in patients with unresectable liver metastasis. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies such as hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are treatment strategies which are increasingly being considered to improve local tumor response and to reduce systemic side effects. Currently, these therapies are mostly used in the salvage setting in patients with chemo-refractory disease. However, their use in the first-line setting in conjunction with systemic chemotherapy as well as to a lesser degree, in a neoadjuvant setting, for downstaging to resection have also been investigated. Furthermore, some clinicians have considered these therapies as a temporizing tool for local disease control in patients undergoing a chemotherapy ‘holiday’ or acting as a bridge in patients between different lines of systemic treatment. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future.

• colorectal liver metastasis
• hepatic arterial infusion therapy
• liver-directed intra-arterial therapy
• radioembolization
• trans-arterial chemoembolization

• Hepatocellular carcinoma
• Hypoxia-inducible factor-1α (HIF-1α)
• Prognosis
• Transcatheter arterial chemoembolization
• VEGF

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/blood
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/therapy
• Chemoembolization, Therapeutic/mortality
• Female
• Follow-Up Studies
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit/blood
• Liver Neoplasms/blood
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Prognosis
• Retrospective Studies
• Survival Rate

• 81172193 National Natural Science Foundation of China

• clinical trials
• gut microbiota
• liver cancer
• sex
• treatments

• K01 OD019924 NIH HHS

• EORTC
• HRQLQ-C30/-HCC18
• Hepatocellular carcinoma
• Palliative therapy
• Quality of life
• Transarterial chemoembolization

• Drug-eluting beads transarterial chemoembolization
• Hepatocellular carcinoma
• Radiofrequency ablation
• Recurrent
• Ultrasound
• Untreated

Sequential transarterial chemoembolization (TACE) and portal vein embolization (PVE) are associated with long time interval that can allow tumor growth and nullify treatments' benefits.

To evaluate the effect of simultaneous TACE and PVE for patients with large hepatocellular carcinoma (HCC) prior to elective major hepatectomy.

Fifty-one patients with large HCC who underwent PVE combined with or without TACE prior to hepatectomy were included in this study, with 13 patients in the simultaneous TACE + PVE group, 17 patients in the sequential TACE + PVE group, and 21 patients in the PVE-only group. The outcomes of the procedures were compared and analyzed.

All patients underwent embolization. The mean interval from embolization to surgery, the kinetic growth rate of the future liver remnant (FLR), the degree of tumor size reduction, and complete tumor necrosis were significantly better in the simultaneous TACE + PVE group than in the other groups. Although the patients in the simultaneous TACE + PVE group had a higher transaminase levels after PVE and TACE, they recovered to comparable levels with the other two groups before surgery. The intraoperative course and the complication and mortality rates were similar among the three groups. The overall survival and disease-free survival were higher in the simultaneous TACE + PVE group than in the other two groups.

Simultaneous TACE and PVE is a safe and effective approach to increase FLR volume for patients with large HCC before major hepatectomy.

• Transcatheter arterial chemoembolization
• Portal vein embolization
• Major hepatectomy
• Hepatocellular carcinoma
• Future liver remnant

• Carcinoma, Hepatocellular/therapy
• Chemoembolization, Therapeutic/adverse effects
• Embolization, Therapeutic/adverse effects
• Hepatectomy/adverse effects
• Humans
• Liver Neoplasms/surgery
• Portal Vein/diagnostic imaging
• Treatment Outcome

Transcatheter arterial embolization (TAE) plays an important role in clinical liver tumor therapy. However, hypoxia after TAE limit the medium-long term efficacy of TAE. Thus, in our study, we explored the treatment effect and mechanism of combining transcatheter arterial embolization with adopted iodized oil containing Apatinib on suppressing tumor growth and metastasis. We simulated the changing of tumor microenvironment before and after TAE both in vitro and in vivo models. The anti-angiogenic effect of Apatinib was explored by bioassays in human umbilical vein endothelial cells (HUVECs), including cell migration, invasion and apoptosis, tube formation, and wound healing. Further experiments showed that Apatinib inhibited tumor microangiogenesis to achieve the aims of inhibiting tumor growth and recurrence by means of down-regulating the phosphorylation of the RAF-mek-erk, PI3K-akt and P38MAPK pathways. The antitumor growth and anti-angiogenic effect of Apatinib was further validated by the animal experiment. Taken together, we concluded that Apatinib inhibits the angiogenesis and growth of liver cancer by down-regulating the PI3K-akt, RAF-mek-erk and P38MAPK pathways, and has a stronger inhibitory effect in hypoxic environments. Combining TAE with adopted iodized oil containing Apatinib has a stronger inhibitory effect in VX2 liver tumor growth and metastasis, which suggesting such combinations may provide a new target and strategy for interventional therapy of liver cancer.

The aim of this study was to investigate the safety and efficacy of transarterial chemoembolization and sorafenib (TACE-S) combined with microwave ablation (TACE-S-MWA) for the treatment of patients with advanced primary hepatocellular carcinoma (HCC).

Between January 2015 and December 2018, 152 consecutive advanced HCC patients, who underwent TACE-S-MWA (MWA group, n=77) or TACE-S (Non-MWA group, n=75), were investigated. Overall survival (OS), time to progression (TTP) and safety were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model.

Baseline patient characteristics were balanced between the two groups. MWA group was associated with a higher OS (median, 19.0 vs 13.0 months; P<0.001) and a longer TTP (median, 6.0 vs 3.0 months; P<0.001) compared with non-MWA group. Multivariate analyses showed that portal vein tumor thrombosis (PVTT) (P=0.002), duration of sorafenib (P<0.001), and MWA treatment (P=0.011) were independently associated with OS. MWA treatment strategy (P<0.001) was a significant predictor of TTP. There were no treatment-related mortalities in either group. The rates of minor complications (42.9% vs 38.7%, P=0.599) and major complications (1.29% vs 1.33%, P=0.985) in the MWA group were similar to those in the non-MWA group.

TACE-S-MWA was safe and effective for advanced primary HCC. TACE-S-MWA resulted in better OS and TTP than did TACE-S for treatment of patients with advanced primary HCC.

• hepatocellular carcinoma
• microwave ablation
• sorafenib
• survival
• transarterial chemoembolization

• CRC-LM
• DEBIRI
• colorectal cancer
• liver metastases
• liver resection

Locoregional therapies for hepatocellular carcinoma (HCC) include endovascular treatments such as chemoembolization (TACE) and bland embolization (TAE). TACE is the most adopted technique, despite a lack of definitive evidence of superiority over TAE, which is less costly and better tolerated due to the absence of chemotherapy. However, few studies have reported data on TAE monotherapy for unresectable HCC. We report our results in a cohort of 230 patients with unresectable HCC treated with TAE (TAE with 40-100micron microparticles, TAE with microparticles plus n-butyl-2-cyanoacrylate, TAE with Lipiodol) over the course of seven years. Thirty-seven patients (14%) were down-staged during observation and also received a percutaneous ablation. We observed 1-, 2-, 3-, 4- and 5-year rates of 84,8%, 58,7%, 38,3%, 28,3%, and 18,7%. Patients who also received percutaneous treatment performed best. Our results broaden the body of evidence for the use of TAE in advanced HCC.

• Aged
• Aged, 80 and over
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/therapeutic use
• Carcinoma, Hepatocellular/therapy
• Chemoembolization, Therapeutic/methods
• Ethiodized Oil/administration & dosage
• Ethiodized Oil/therapeutic use
• Female
• Humans
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Survival Analysis

Transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA) are the main methods for the treatment of liver cancer worldwide. TACE can block the blood vessels of liver cancer and clearly show the area where the tumor is located. The solid tumor can be completely ablated by MWA. However, postoperative recurrence is still a difficult problem to solve.

To assess the efficacy of TACE combined with MWA in the treatment of liver cancer at early Barcelona clinic liver cancer (BCLC) stage and identify the factors affecting recurrence.

A retrospective analysis was performed on 42 patients with post-hepatitis B virus (HBV) liver cancer at early BCLC stage who underwent TACE combined with MWA at our hospital from February 2016 to November 2017. After surgery, the efficacy was evaluated and complications were recorded. The patients were followed at 1 mo, 2 mo, 3, mo 6 mo, 12 mo, and 18 mo after WMA for CT, alpha fetoprotein (AFP), liver function, or hepatic angiography, and the time to recurrence was recorded.

By the last follow-up, the total effective rate was 61.5% and the lesion control rate was 84.2%. The median progression-free-survival (PFS) was 7.3 mo (range, 2.3-34). Univariate analysis showed that female patients had a PFS of 14 mo and male patients had a PFS of 11 mo. Patients ≥ 60 years of age had a PFS of 3.8 mo, and patients < 60 years of age had a PFS of 8.9 mo. The PFS of patients with tumor < 3 cm, 3 to 5 cm, and 5-10 cm was 14, 10.5, and 11.2 mo, respectively. The PFS of patients with single tumor and multiple tumors was 13.6 and 4 mo, respectively. The PFS of patients with Child A and Child B disease was 20.8 mo vs 11.2 mo. The PFS of BCLC stage 0 patients and BCLC stage A patients was 15.5 mo vs 11.2 mo. HBV-DNA positive patients had a PFS of 11.2 mo, and HBV-DNA negative patients had a PFS of 13.3 mo. The median PFS of HBeAg-positive cases was 11.2 mo, and that of HBeAg-negative cases was 13.3 mo. Univariate analysis showed that gender, age, Child grade, number of tumors, and BCLC stage were significantly correlated with PFS, but tumor size, preoperative HBV-DNA, and HBeAg status did not. In multivariate analysis, Child grade, BCLC stage, and gender were identified to be independent risk factors for PFS in early BCLC stage liver cancer patients undergoing sequential treatment of TACE and MWA (P < 0.05).

TACE combined with MWA is safe and effective in the treatment of early BCLC stage liver cancer. Child grade, BCLC stage, and gender may affect postoperative recurrence.

• Transcatheter arterial chemoembolization
• Microwave ablation
• Early liver cancer
• Recurrence

Cardiac-cerebral thrombosis and malignant tumor endanger the safety of human life seriously. Traditional chemotherapy drugs have side effects which restrict their applications. Drug-loaded microbubbles can be destroyed by ultrasound irradiation at the focus position and be used for thrombolysis and tumor therapy. Compared with traditional drug treatment, the drug-loaded microbubbles can be excited by ultrasound and release drugs to lesion sites, increasing the local drug concentration and the exposure dose to nonfocal regions, thus reducing the cytotoxicity and side effects of drugs. This article reviews the applications of drug-loaded microbubbles combined with ultrasound for thrombolysis and tumor therapy. We focus on highlighting the advantages of using this new technique for disease treatment and concluding with recommendations for future efforts on the applications of this technology.

• catheter-based delivery
• embolic agents
• interventional radiology
• minimally invasive surgery
• vascular embolization

• Animals
• Biocompatible Materials/chemistry
• Embolization, Therapeutic/instrumentation
• Embolization, Therapeutic/methods
• Endovascular Procedures
• Humans
• Metals/chemistry
• Microspheres
• Polymers/chemistry

• P30 CA008748 NCI NIH HHS
• R01 HL137193 NHLBI NIH HHS
• R01 HL140951 NHLBI NIH HHS
• R21EB021148 NIH HHS

There are currently two methods widely used in clinical practice to perform transarterial chemoembolization (TACE). One is based on mixing an aqueous drug with an iodized oil (Lipiodol) and creating an emulsion that is delivered intraarterially, followed by embolization with a particulate agent. The other is based on a one-step TACE using Drug-eluting Beads (DEBs) loaded with drug. It is not recommended to mix Lipiodol with DEBs due to incompatibility. For the first time, novel DEB: Lipiodol: doxorubicin (Dox) emulsions are identified using lyophilized polyvinyl alcohol (PVA) hydrogels (non-iodinated or iodinated) DEBs.

Methods: 15 DEB emulsions (50mg Dox) were assessed for stability and deliverability in vitro and in vivo in a swine model. Dox release from selected formulations was measured in vitro using a vascular flow model and in vivo in a VX2 rabbit tumor model.

Results: Both DEB formats were shown to be able to form emulsions, however only Iodinated DEBs consistently met defined handling criteria. Those based on the non-iodinated DEB achieved >99%+ Dox loading in <5 minutes but were generally less stable. Those prepared using iodinated DEBs, which are more hydrophobic, were able to form stable Pickering-like emulsions (separation time ≥ 20 minutes) and demonstrated handling, administration and imaging observations more akin to Lipiodol™ TACE emulsions in both embolization models. Controlled Dox release and hence beneficial in vivo pharmacokinetics associated with DEB-TACE were maintained.

Conclusions: This study demonstrates that it is possible to formulate novel DEB emulsions suitable for TACE that combine positive elements of both Lipiodol™ based and DEB-TACE procedures.

• Drug-loaded emulsions
• Transarterial chemoembolization
• in vitro-in vivo correlation.

Transarterial chemoembolization (TACE) delivers cytotoxic drugs intra-arterially and induces ischemic necrosis by arterial embolization. Embolization is achieved using a variety of agents that differ widely in particle size and range, deformation, and in vivo arterial distribution. The clinical significance of these differences has not been thoroughly characterized. The present study is to compare the efficacy of Embosphere and Embozene microspheres in TACE therapy for hepatocellular carcinoma.

This retrospective study includes 108 hepatocellular carcinoma (HCC) patients who received TACE/doxorubicin with Embozene (70 patients) or Embosphere (38 patients) at a single medical center. Patient outcomes, including liver function, tumor size, tumor response, and complications after treatment, were analyzed. The change in total target lesion size and tumor response was evaluated according to embolization agent and clinical characteristics.

The postoperative glutamate oxaloacetate transaminase (mean, 194.5 vs. 147.5; p=0.032) and bilirubin (mean, 1.11 mg/dL vs. 0.73 mg/dL; p=0.016) were higher among patients treated with Embozene, the decrease in the number (55.86±25.55% vs. 41.81±38.51%, p=0.027) and size (56.37±25.91 mm vs. 43.44±37.89 mm, p=0.001) of liver tumors relative to baseline was greater in these patients than in those treated with Embosphere. These greater antitumor effects were achieved using lower doses of doxorubicin than for treatment with Embozene. Minor complications were more common among patients treated with Embosphere than with Embozene.

These results suggest that Embozene is more efficacious than Embosphere for HCC treatment using TACE/doxorubicin.

• Bland microsphere
• Uniformity
• Well calibration

Despite improvements in the development of drugs for the treatment of cancer, drug resistance remains a major obstacle. In colon cancer, following an initially promising response, patients develop drug resistance, which impacts the efficacy and halts the response of cancerous cells towards drugs. In the present study, a phosphatase and tensin homolog (PTEN) knockdown model of LS180 cells, doxorubicin-resistant models of LS180 cells as well as doxorubicin-resistant LS180 (PTEN) knockdown model were established. The present study demonstrated that doxorubicin resistance led to the activation of interleukin (IL)6 signalling pathway which was enhanced by knockdown of PTEN. There was also an increase in the levels of IL8 and IL2 which were further enchanced by knockdown of PTEN. Doxorubicin resistance also led to an increase in the population of cancer stem cells in LS180 and shPTEN-treated LS180 cells. Notably, doxorubicin resistance also induced epithelial to mesenchymal transition and increased the formation of mammospheres. Furthermore, the present study also reported that IL6 receptor antibody not only decreased IL6 levels but also led to a significant decreased number of cancer stem cell like population and mammosphere formation. In conclusion, in the present study it was demonstrated that doxorubicin resistance led to activation of IL6 signalling pathway which was further elevated by the knockdown of PTEN in the colon cancer cell line LS180. Thus, inhibiting the IL6 loop may provide an alternative pathway to tackle doxorubicin resistance.

• cancer stem cells
• colon cancer
• doxorubicin
• epithelial-mesenchymal transition
• resistance

Transarterial embolization (TAE) is a palliative option commonly used for the treatment of advanced, unresectable hepatocellular carcinoma (HCC). However, patient prognosis in regards to overall survival has not improved with this method, mainly due to hypoxia-inducible factor-1α (HIF-1α)-induced angiogenesis and invasiveness. Thus, it is hypothesized that HIF-1α may be an ideal knockout target for the treatment of HCC in combination with TAE. Thus, in the present study, HIF-1α knockout was conducted in human liver cancer SMMC-7721 cells and a xenograft HCC model was established using a lentivirus-mediated CRISPR/Cas system (LV-Cas) with small guide RNA-721 (LV-H721). Furthermore, hepatic artery ligation (HAL) was used to mimic human transarterial chemoembolization in mice. The results revealed that HIF-1α was highly expressed in both HCC patient tissues and SMMC-7721-induced tumor tissues. The HIF-1α knockout in SMMC-7721 cells significantly suppressed cell invasiveness and migration, and induced cell apoptosis under CoCl₂-mimicking hypoxic conditions. Compared with the control groups, HAL + LV-H721 inhibited SMMC-7721 tumor growth in orthotopic HCC and markedly prolonged the survival of HCC-bearing mice, which was accompanied by a lower CD31 expression (tumor angiogenesis) and increased apoptosis in the tumor cells. These findings demonstrated a valuable antitumor synergism in combining CRISPR/Cas9-mediated HIF-1α knockout with TAE in mice and highlighted the possibility that HIF-1α may be an effective therapeutic knockout target in combination with TAE for HCC treatment.