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 evaluate the clinical efficacy,safety,and potency ratio of microwave ablation(MW A)combined with percutaneous osteoplasty(POP)for the treatment of flat bone metastases.Methods A total of 57 patients with flat bone metastases complicated by intractable pain,who underwent MWA combined with POP(combination therapy)or only POP(pure POP therapy)at the Zhongshan Municipal People's Hospital of China between January 2016 and January 2023,were enrolled in this study.The combination therapy group had 36 patients and the pure POP therapy group had 21 patients.Visual analog scale(VAS),Oswestry Disability Index(ODI),quality of life assessment scale(QOL)were used to evaluate the preoperative and the postoperative different period efficacy,and the results were compared between the two groups.The procedure-related complications in both groups were recorded.Results The technical success rate in the 57 patients was 100％,and no serious postoperative complications occurred.The mean follow-up time was(4.7±1.3)months(range of 3.4-7.2 months).The preoperative and the postoperative one-day,one-week,one-month and 3-month VAS scores in the combination therapy group were(7.39±1.09)points,(6.53±1.17)points,(1.94±0.70)points,(1.11±0.66)points and(1.39±0.59)points respectively,which in the pure POP therapy group were(7.52±1.01)points,(6.81±0.66)points,(3.38±0.65)points,(2.33±0.56)points and(2.52±0.50)points respectively.One week after operation,the VAS scores in the combination therapy group and the pure POP therapy group were decreased by(5.44±1.32)points and(4.14±0.96)points respectively.The differences in the postoperative one-week(t=-7.62,P＜0.01),one-month(t=-7.28,P＜0.01)and 3-month(t=-7.58,P＜0.01)VAS scores between the two groups were statistically significant.The preoperative and the postoperative one-day,one-week,one-month and 3-month ODI scores in the combination therapy group were(44.33±2.91)points,(44.08±2.82)points,(15.92±3.04)points,(14.00±2.39)points and(16.08±3.61)points respectively,which in the pure POP therapy group were(45.67±3.03)points,(45.14±2.80)points,(22.38±3.09)points,(19.76±2.99)points and(22.10±3.10)points respectively.One week after operation,the ODI score in the combination therapy group was decreased by(28.42±4.23)points,which in the pure POP therapy group was decreased by(23.29±4.28)points.The differences in the postoperative one-week(t=-7.50,P＜0.01),one-month(t=-7.37,P＜0.01)and 3-month(t=-6.51,P＜0.01)ODI scores between the two groups were statistically significant.The preoperative and the postoperative one-day,one-week,one-month and 3-month QOL scores in the combination therapy group were(24.69±3.92)points,(26.06±3.05)points,(38.67±3.00)points,(40.25±3.42)points and(39.58±3.99)points respectively,which in the pure POP therapy group were(24.43±3.53)points,(26.76±3.05)points,(32.81±2.17)points,(33.95±2.68)points and(31.19±4.27)points respectively.One week after operation,the QOL score in the combination therapy group was increased by(13.97±4.88)points,which in the pure POP therapy group was increased by(8.38±4.50)points.The differences in the postoperative one-week(t=8.34,P＜0.01),one-month(t=7.56,P＜0.01)and 3-month(t=7.18,P＜0.01)QOL scores between the two groups were statistically significant.The mean operation cost in the combination therapy group was 10 480.43 Chinese yuan,which was higher than that in the pure POP therapy group.Conclusion For the treatment of flat bone metastases,both pure POP therapy and MWA combined with POP therapy are clinically safe and effective,which can significantly relieve pain and improve quality of life.Compared with pure POP therapy,the MWA combined with POP therapy is more effective but its medical cost is more expensive.

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:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

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 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.

Objective: To synthesize a folic acid (FA)-modified pH-sensitive nanomicelle containing sorafenib (SF) and superparamagnetic iron oxide (SPIO), and to access its visibility in MRI and anti-cancer efficacy on hepatocellular carcinoma (HCC) in vitro. Methods: The copolymer FA-PEG-Pasp (DBA/DIP) of FA, poly(ethylene glycol), N,N-dibutylethylenediamine and N,N-diisopropylethylenediamine grafted poly (L-aspartic acid) were prepared. SF and SPIO were encapsulated inside the copolymer to synthesize the targeting micelle FA-PEG-PAsp (DBA/DIP)-SPIO/SF (FPASS). The folate-free micelle[PEG-PAsp (DBA/DIP)-SPIO/SF (PASS)] was used as nontargeting micelle. The physicochemical properties and drug release behavior of the micelles were analyzed. MRI of HepG2 cells incubated with FPASS and PASS with different Fe concentrations and Prussian blue staining of cells treated with the micelles (Fe concentration of 20 μg/ml) was performed to assess the drug delivery capability and imaging function of the micelles. For the FA competitive inhibition assay in these experiments, HepG2 cells were pre-treated with an excess amount of free FA prior to the incubation with FPASS. Cell viability, cell apoptosis, cell cycle and tube formation assays were conducted for evaluating the anti-HCC effects of the micelles. Comparison between groups was analyzed by one-way ANOVA, and multiple comparisons correction was performed by LSD test. Results: The diameters of FPASS and PASS were (102.3±5.2) nm and (107.1±5.7) nm, respectively; the δ potentials of them were (29.7±1.6) mV and (31.5±1.4) mV, respectively. The T₂ relaxivity of both the micelles was (5.2±0.4) ml·μg^-1·s^-1, which was much higher than that of water soluble Fe₃O₄ nanoparticles [(2.3±0.1) ml·μg^-1·s^-1; F=76.45, P<0.01]. SF released from the micelles was much faster at pH5.0 than at pH7.4, which indicated that the micelles had a pH-triggered drug release behavior. MRI of HepG2 cell samples revealed the signal intensity on T₂WI images and the T₂ value on T₂-map images decreased with the increasing Fe concentrations in the micelles. At the same Fe concentration (5, 10, 20 and 40 μg/ml), the cells of FPASS group exhibited a more significant decrease in T₂ signal intensity and T₂ value compared with those of PASS group or FA competitive inhibition group (F=8.69, 14.03, 27.27, 32.25 and 19.80, 45.76, 113.20, 66.80; P<0.01). Prussian blue staining verified the existing of SPIO in the cytoplasm of cells. Compared with PASS, FPASS presented significantly higher anticancer effects on inducing apoptosis, causing G0/G1 phase arrest on HepG2 cells and inhibiting tube formation on human umbilical vein endothelial cells (t=7.905, 4.399 and 3.454, respectively; P<0.01). Conclusions The pH-sensitive nanomicelle FPASS was successfully constructed. This micelle possessed a hypersensitive MRI-visible function and a targeting SF delivery capability which may contribute to a significant anti-HCC effect.

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 investigate the clinical effect of percutaneous transluminal angiography in diabetic infrapopliteal arterial disease patients and the influence of post-procedural intraluminal small dose urokinase infusion on infrapopliteal arterial blood flow.Methods From January 2011 to September 2013,37 limbs (16 left and 21 right) in 28 diabetic patients inflicted with infrapopliteal critical limb ischemia underwent endovascular recannalization at our institution and were retrospectively analyzed.Stenotic or occlusive lesions were demonstrated in 74 infrapopliteal vessels,including 30 anterior tibial arteries (ATA),22 posterior tibial arteries (PTA),and 22 peroneal arteries (PA).In 30 limbs,tandem lesions in iliac-femoral arteries were also diagnosed.Antegrade ipsilateral femoral access,retrograde contralateral femoral or brachial arterial access had all been adopted as well as both angioplasty and stenting.Case specific decisions were made based on pre-procedural computed tomographic angiogram (CTA).Ankle-brachial index (ABI) was recorded before and after each procedure.Urokinase was continuously infused through arterial sheath catheter into vessels of target limb from a microinfusion pump at 200 000 to 300 000 units per 24 hour for 48 hours after procedure.Angiogram was performed before and after thrombolysis therapy aiming to ascertain the number of frames of images obtained during the period of time it took blood flow to carry contrast medium from the level of tibial plateau to ankle,which was recorded as index frame count (IFC).Patients were followed up for at least 3 months.ABI and ultrasound or CTA were performed on each follow-up visit to validate patency.Quantitative data such as ABI value and IFC were analyzed using paired samples t-test.Results Thirty two limbs were radiographically recanalized by angioplasty or stenting.Technical success rate was 86.4％ (32/37).Average ABI of all limbs increased significantly from 0.70±0.31 to 0.90± 0.21 (t=10.734,P＜0.05).Of the 32 limbs recanalized,IFC decreased significantly from 6.3 ± 1.6 before thrombolysis to 4.7± 1.4 after thrombolysis (t=12.136,P＜0.05).Six rest pain patients reported significantly alleviated symptoms.Fourteen limbs presented with feet ulcers or gangrene.Of these patients after endovascular treatment,1 underwent ankle level amputation,3 underwent toe amputation and 3 patients who did not seek further treatment reported spontaneous autoamputation and wound healing.The remaining 9 patients reported wound healing within 1 to 3 months.Secondary angioplasty was needed for symptom recurrence in 3 limbs of 3 patients 3 to 24 months after first procedure.Conclusions Endovascular treatment of diabetic infrapopliteal arterial diseases exhibited significant short term effect and was safe to perform.Small dose urokinase infusion after recanalization procedure was safe and effective in helping to improve infragenicular blood flow.