Objective:To investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for hepatocellular carcinoma (HCC) larger than 7 cm with portal vein tumor thrombosis (PVTT).Methods:The data from patients diagnosed with HCC (>7 cm) and PVTT who received either Len+DEB-TACE+HAIC ( n=99) or Len+DEB-TACE ( n=102) between July 2019 and June 2021 at six institutions in China were collected and retrospectively analyzed. Tumor responses were evaluated based on modified Response Evaluation Criteria in Solid Tumors. Objective response rate (ORR), disease control rate (DCR), time to progression (TTP), overall survival (OS), and treatment-related adverse event (TRAE) were compared between the two groups by propensity score matching. Subgroup analyses were performed for TTP and OS. Results:After propensity score matching, 83 pairs of patients were included in the study cohorts. The ORR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 66.3% and 38.6% ( χ2=12.78, P<0.001), respectively. The DCR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 91.6% and 79.5% ( χ2=4.87, P=0.027), respectively. The median TTP and median OS for the Len+DEB-TACE+HAIC group were significantly longer than those for the Len+DEB-TACE group (TTP, 10.1 months vs. 6.1 months, χ2=35.28, P<0.001; OS, 17.3 months vs. 12.9 months, χ2=16.84, P<0.001). The incidence of ≥grade 3 TRAEs was 38.6% in the Len+DEB-TACE+HAIC group and 33.7% in the Len+DEB-TACE group ( χ2=0.42, P=0.518). Conclusion:Compared with Len+DEB-TACE, Len+DEB-TACE+HAIC led to improved tumor response, TTP and OS with an acceptable safety profile in patients with large HCC and PVTT.

The incidence and mortality of hepatocellular carcinoma (HCC) in China are among the highest in the world, imposing a heavy social burden. Liver resection and liver transplantation are the primary radical treatments for HCC, although most patients are no longer able to meet the surgical requirements at initial diagnosis. Yttrium-90 microsphere selective internal radiation therapy (⁹⁰Y-SIRT) has the advantages of shrinking tumors, enlarging residual liver, regressing portal vein tumor thrombus and improving the quality of life, which can be used for conversion, downstaging and bridging therapy for HCC before surgical treatment, enabling patients regain the chance of radical treatment and reducing the postoperative recurrence rate. This review focuses on the clinical application and progress of ⁹⁰Y-SIRT in this field.

Objective:To investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for hepatocellular carcinoma (HCC) larger than 7 cm with portal vein tumor thrombosis (PVTT).Methods:The data from patients diagnosed with HCC (>7 cm) and PVTT who received either Len+DEB-TACE+HAIC ( n=99) or Len+DEB-TACE ( n=102) between July 2019 and June 2021 at six institutions in China were collected and retrospectively analyzed. Tumor responses were evaluated based on modified Response Evaluation Criteria in Solid Tumors. Objective response rate (ORR), disease control rate (DCR), time to progression (TTP), overall survival (OS), and treatment-related adverse event (TRAE) were compared between the two groups by propensity score matching. Subgroup analyses were performed for TTP and OS. Results:After propensity score matching, 83 pairs of patients were included in the study cohorts. The ORR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 66.3% and 38.6% ( χ2=12.78, P<0.001), respectively. The DCR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 91.6% and 79.5% ( χ2=4.87, P=0.027), respectively. The median TTP and median OS for the Len+DEB-TACE+HAIC group were significantly longer than those for the Len+DEB-TACE group (TTP, 10.1 months vs. 6.1 months, χ2=35.28, P<0.001; OS, 17.3 months vs. 12.9 months, χ2=16.84, P<0.001). The incidence of ≥grade 3 TRAEs was 38.6% in the Len+DEB-TACE+HAIC group and 33.7% in the Len+DEB-TACE group ( χ2=0.42, P=0.518). Conclusion:Compared with Len+DEB-TACE, Len+DEB-TACE+HAIC led to improved tumor response, TTP and OS with an acceptable safety profile in patients with large HCC and PVTT.

Objective:To investigate the clinical efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus PD-1 inhibitor (TACE+Len+PD-1) versus TACE combined with lenvatinib (TACE+Len) for patients with unresectable intermediate-advanced hepatocellular carcinoma (HCC).Methods:The data of 94 patients with intermediate-advanced HCC who received TACE+Len+PD-1 (One week after TACE, the patient were treated with lenvatinib and PD-1 inhibitor. lenvatinib, 8 or 12 mg/d, orally; PD-1 inhibitor, 200 mg/3 weeks, iv) or TACE+Len (One week after TACE, the patient were treated with lenvatinib.lenvatinib, 8 or 12 mg/d, orally) in the Second Affiliated Hospital of Guangzhou Medical University from June 2019 to February 2021 were collected and retrospectively analyzed. Among these patients, 44 were in the TACE+Len+PD-1 group and 50 were in the TACE+Len group. Tumor responses were evaluated according to modified response evaluation criteria in solid tumors. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were compared between the two groups. The potential prognostic factors for PFS and OS were determined.Results:The ORR of TACE+Len+PD-1 group and TACE+Len group was 72.8% (32/44) and 52.0% (26/50) (χ2=4.25, P=0.039), respectively. The DCR of TACE+Len+PD-1 group and TACE+Len group was 86.4% (38/44) and 62.0% (31/50) (χ2=7.12, P=0.008), respectively. The median PFS and median OS in TACE+Len+PD-1 group were significantly longer than those in TACE+Len group (PFS, 7.9 vs. 5.6 months, χ2=7.91, P=0.005; OS, 18.5 vs. 13.6 months, χ2=4.40, P=0.036). Multivariate Cox regression analyses showed that TACE+Len (HR=2.184,95%CI 1.366-3.493), incomplete tumor capsule (HR=2.002,95%CI 1.294-3.209) and extrahepatic metastasis (HR=1.765,95%CI 1.095-2.844) were the independent risk factors for PFS, while TACE+Len (HR=2.081,95%CI 1.097-3.948) and BCLC stage C (HR=7.325,95%CI 2.260-23.746) were the independent risk factors for OS. The incidence of ≥grade 3 AEs in TACE+Len+PD-1 group was similar to that in TACE+Len group (χ2=0.45, P=0.501). Conclusion:Compared with TACE+Len, TACE+Len+PD-1 resulted in a better tumor response and a longer PFS and OS in patients with intermediate-advanced HCC.

Objective:To study the use of radioactive I-125 seed implantation in the treatment of transarterial chemoembolization (TACE)-refractory hepatocellular carcinoma (HCC).Methods:A retrospective study was conducted on 70 patients with HCC who were initially treated with TACE between July 1, 2016 and August 31, 2019 at the Second Affiliated Hospital of Guangzhou Medical University. After these patients were found to be refractory to TACE, 29 patients were converted to radioactive I-125 seed implantation (the 125I seed group), and 41 patients were continued with TACE (the TACE group). The objective response rate, progression-free survival (PFS), overall survival (OS), total overall survival (TOS) of the two groups were compared. Results:There were 59 males and 11 females, aged (60.5±11.9 ) years in this study. At 1, 3, 6 months after treatment, the objective response rates of the 125I seed group were 20.7%, 40.7%, 34.6%, respectively, which were significantly higher than that of the TACE group of 2.6%, 3.3%, 5.0%, respectively. The PFS, OS, TOS in the 125I seed group were 7.6, 21.1, 32.1 months, respectively, which were significantly better when compared with the TACE group (3.5, 8.5, 14.8 months, respectively, all P<0.05). There was no significant difference in the embolization syndrome between the two groups [93.1%(27/29) vs 100.0%(41/41), P>0.05]. Child-Pugh B grading ( HR=0.311, 95% CI: 0.160-0.603, P=0.005) and TACE ( HR=0.308, 95% CI: 0.159-0.597, P=0.002) were independent risk prognostic factors for survival. Conclusion:This study showed better treatment efficacy and safety using radioactive I-125 seed implantation in TACE-refractory HCC and this treatment significantly improved survival of patients when compared with TACE alone.

Objective:To evaluate the efficacy and safety of anti-programmed cell death 1 (PD-1) receptor monoclonal antibody (MoAb) in patients with advanced hepatocellular carcinoma (HCC) after treatment of transcatheter arterial chemoembolization (TACE) combined with tyrosine kinase inhibitor (TKI).Methods:From February 2019 to February 2020, 56 HCC patients who relapsed after TACE-TKI treatment in Department of Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University were enrolled. All patients received anti-PD-1 MoAb (sintilimab injection) and followed up every 6 weeks. According to mRECIST, the curative effect was evaluated as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). Objective response rate (ORR) and disease control rate (DCR), progression-free survival (PFS) and treatment-related adverse events (TRAEs) were recorded. Univariate analysis by Chi-square test and binary logistic regression model was used to determine the influencing factors of DCR. The Kaplan-Meier method and Cox proportional hazard regression model were used to analyze the survival data.Results:A total of 48 patients were enrolled in this study including 42 males and 6 females, with a median age of 55 years (29-71 years). ECOG scores comprised of 0 in 24 cases, 1-2 in 24 cases. Thirty-six patients were in Child-Pugh grade A of liver function and 12 cases were grade B. The median follow-up time was 4.5 months. There were 2 patients achieved CR, 12 patients with PR and 16 with SD. ORR was 29.2%, DCR was 62.5%. The independent influencing factors of DCR was ECOG score and AFP level ( P=0.031, P=0.012). Median PFS was 4.1 months (95% CI 2.7-5.4 months), and ECOG score was the independent influencing factor of PFS ( P=0.042). Treatment-related adverse events were reported in 70.8% (34/48) patients. Incidence of grade Ⅲ-Ⅳ TRAEs was 22.9% (11/48). Conclusion:In patients with HCC who relapse from TACE and TKI treatment, anti-PD-1 monoclonal antibody is efficacious safe especially in those with ECOG 0 score.

Brachytherapy ; Carcinoma, Hepatocellular/drug therapy* ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Humans ; Iodine Radioisotopes ; Liver Neoplasms/drug therapy* ; Portal Vein ; Retrospective Studies ; Sorafenib/therapeutic use* ; Thrombosis ; Treatment Outcome

Objective To establish two types of portal hypertension (PHT) models in mice by using bile duct ligation (BDL) method and carbon tetrachloride (CCl4) induction technique respectively. Methods A total of 24 C57BL/6 mice were randomly and equally divided into the following four groups with 6 mice in each group: group BDL, control group of BDL, group CCl4, and control group of CCI4. After the establishment of PHT, the main portal vein was punctured in all experimental mice to measure the portal vein pressure, and blood sampling was collected to test serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Using hematoxylin eosin (HE) and sirius red staining the liver tissues were pathologically examined. Immunohistochemical study of alpha smooth muscle actin (SMA) was adopted to evaluate the liver function, hepatic fibrosis and hepatic stellate cell activation status. Results Both modeling methods could make the portal vein pressure increased in experimental mice. The increasing of portal vein pressure in group CCl4 was more obvious. Compared with their corresponding control groups, the degree of liver damage, hepatic fibrosis and hepatic stellate cell activation in group BDL and group CCl4 were more serious. Conclusion Both BDL method and CCl4 induction technique can successfully establish the mouse model of PHT. All the portal venous pressure, the serum biochemical indices and the changes of liver pathology of the mouse model are well in line with the characteristics of PHT in human. (J Intervent Radiol, 2018, 27:242-246)

Objective To evaluate the therapeutic effect of transarterial chemoembolization (TACE) combined with CT-guided 125I seed implantation in treating hepatocellular carcinoma (HCC) complicated by portal vein tumor thrombus(PVTT), and to discuss the technical points. Methods A total of 48 HCC patients with PVTT were enrolled in this study. TACE combined with CT-guided 125I seed implantation was carried out in all 48 patients. Based on the sites of PVTT, the lesions were classified into type A (PVTT within main portal vein), type B(PVTT within level-1 portal branch) and type C(PVTT within level-2 or more distal portal branch). According to whether the 125I seeds were directly implanted into the PVTT or not, the patients were divided into direct in-tumor thrombus implantation group (group A) and around tumor thrombus implantation group (group B; the 125I seeds were implanted in the liver parenchyma or in tumor tissue around the tumor thrombus within 1.7 cm region). The tumor thrombus control rate(TTCR), the disease control rate(DCR), the time to progress(TTP) and the overall survival rate of patients(OS) were determined, and the results were compared among different types and groups. Results TACE combined with CT-guided 125I seed implantation was successfully accomplished in all 48 patients. The median OS of type A, B and C was 8, 11.5 and 15 months respectively(P=0.003);the TTCR of type A, B and C was 61.5%, 70.8%and 72.7%respectively(P=0.548); the DCR of type A, B and C was 69.2%, 75%and 81.8% respectively (P=0.483); the median TTP of type A, B and C was 4.5, 8 and 11 months respectively(P=0.030);the median TTP of intra-hepatic tumor of type A, B and C was 5, 9 and 9.5 months respectively(P=0.012). The median OS in group A and group B was 10 and 11.5 months respectively (P=0.239); the TTCR in group A and group B was 69.2% and 68.2%respectively(P=0.591); the DCR of intra-hepatic tumor in group A and group B was 73.1% and 77.3%respectively(P=0.502); the median TTP of tumor thrombus in group A and group B was 7 and 10 months respectively(P=0.276); and the median TTP of intra-hepatic tumor in group A and group B was 8 and 9.5 months respectively(P=0.089). Conclusion For the treatment of hepatocellular carcinoma complicated by portal vein tumor thrombus, TACE combined with CT-guided 125I seed implantation can effectively control the progress of both the tumor thrombus and the intra- hepatic tumor and prolong patient’s survival time. Implantation of 125I seeds into the portal vein tumor thrombus and implantation of 125I seeds into the liver parenchyma around the tumor thrombus have the same therapeutic results. (J Intervent Radiol, 2015, 24:488-493)

Objective To investigate the clinical outcome and treatment of portal vein thrombosis (PVT) following partial splenic embolization (PSE).Methods From April 2006 to April 2010,105patients with hypersplenism caused by cirrhotic portal hypertension were treated with PSE.Contrastenhanced abdominal computed tomography or magnetic resonance imaging was performed routinely in 60patients before PSE and 1 -3 months after PSE.PVT was detected in 10 patients on images after the procedures.After PVT was diagnosed,4 patients received anticoagulant therapy immediately,and the other 6 patients did not receive therapy.Clinical data of these 10 PVT patients were analyzed retrospectively.Results 3 of 4 patients who received anticoagulant therapy had complete or partial resolution of the thrombus,and one developed mild ascites without thrombosis progression.Of the 6 patients who did not receive anticoagulant therapy,follow-up studies (6- 48 months,mean 16.9 months) demonstrated partial clot calcification in one,thrombosis progression in 5.Among those 5 patients with thrombosis progression,two experienced hematemesis due to variceal rupture and underwent transjugular intrahepatic portosystemic shunt,2 developed cavernous transformation,extensive collateral circulation,ascites and variceal progression,and one had variceal progression with melena during the follow-up period.Conclusions PVT is a severe complication of PSE.Early diagnosis and prompt anticoagulant therapy is effective in preventing PVT.