Combined transarterial chemoembolization and tislelizumab for patients with unresectable hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) often presents as unresectable, necessitating effective treatment modalities. Combining transarterial chemoembolization (TACE) with immunotherapy and targeted therapy has shown promise, yet real-world evidence is needed. AIM: To investigate effectiveness and safety of TACE with tislelizumab ± targeted therapy for unresectable HCC in real-world setting. METHODS: This retrospective study included patients with unresectable HCC receiving combined treatment of TACE and tislelizumab. The clinical outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). All patients were evaluated according to the mRECIST criteria. The adverse event (AE) was also assessed. RESULTS: In this study of 56 patients with median follow-up of 10.9 months, 7 had previous immunotherapy. Tislelizumab was administered before TACE in 21 (37.50%) and after in 35 (62.50%) patients, with 91.07% receiving concurrent targeted therapy. Median PFS was 14.0 (95%CI: 7.0-18.00) months, and OS was 28 (95%CI: 2.94-53.05) months. Patients with prior immunotherapy had shorter PFS (6 vs. 18 months, P = 0.006). Overall ORR and DCR were 82.14% and 87.50%. Grade ≥ 3 treatment-related AEs included increased alanine aminotransferase (8.93%), aspartate aminotransferase (10.71%), and total bilirubin (3.57%). CONCLUSION: The combination of TACE and tislelizumab, with or without targeted therapy, demonstrated promising efficacy and safety in unresectable HCC, especially in immunotherapy-naive patients, warranting further prospective validation studies.

Role of transarterial chemoembolization for hepatocellular carcinoma with extrahepatic metastases in the era of advancing systemic therapy.

BACKGROUNDS/AIMS: Systemic therapy is the current standard treatment for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, some patients with HCC and EHM undergo transarterial chemoembolization (TACE) to manage intrahepatic tumors. Herein, we aimed to explore the appropriateness of TACE in patients with HCC and EHM in an era of advanced systemic therapy. METHODS: This study analyzed 248 consecutive patients with HCC and EHM (median age, 58.5 years; male, 83.5%; Child-Pugh A, 88.7%) who received TACE or systemic therapy (83 sorafenib, 49 lenvatinib, 28 immunotherapy-based) between January 2018 and January 2021. RESULTS: Among the patients, 196 deaths were recorded during a median follow-up of 8.9 months. Patients who received systemic therapy had a higher albumin-bilirubin grade, elevated tumor markers, an increased number of intrahepatic tumors, larger-sized tumors, and more frequent portal vein invasion than those who underwent TACE. TACE was associated with longer median overall survival (OS) than sorafenib (15.1 vs. 4.7 months; 95% confidence interval [CI], 11.1-22.2 vs. 3.7-7.3; hazard ratio [HR], 1.97; P<0.001). After adjustment for potential confounders, TACE was associated with statistically similar survival outcomes to those of lenvatinib (median OS, 8.0 months; 95% CI, 6.5-11.0; HR, 1.21; P=0.411) and immunotherapies (median OS, 14.3 months; 95% CI, 9.5-27.0; HR, 1.01; P=0.973), demonstrating survival benefits equivalent to these treatments. CONCLUSIONS: In patients with HCC and EHM, TACE can provide a survival benefit comparable to that of newer systemic therapies. Accordingly, TACE remains a valuable option in this era of new systemic therapies.

Efficacy and Safety of TACE Combined with a Tyrosine Kinase Inhibitor for the Treatment of TACE-Refractory Hepatocellular Carcinoma: A Retrospective Comparative Study.

PURPOSE: Combining angiogenesis inhibitors may enhance therapeutic efficacy synergistically after TACE refractoriness. The purpose of this study was to compare the outcomes of transarterial chemoembolization (TACE) plus a tyrosine kinase inhibitor (TACE-TKI) with TKI only for patients with TACE-refractory hepatocellular carcinoma (HCC). METHODS: From January 2019 to March 2022, 101 HCC patients confirmed with TACE-refractory were retrospectively reviewed in the study. Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were evaluated between groups. RESULTS: Fifty-two patients undergoing TACE-TKI, while 32 patients receiving TKI alone were included. The objective response rate (ORR) was higher in the TACE-TKI group compared with the TKI group (55.8% vs. 25.0%, P = 0.006). The median PFS in the TACE-TKI group was significantly longer than that in the TKI group (7.6 months vs. 4.9 months, P = 0.018). The median OS was non reach to statistical longer than that in the TKI alone group (19.5 months vs. 17.7 months, P = 0.055). Subgroup analysis showed that TACE-TKI treatment resulted in a significantly longer median PFS and OS for Barcelona Clinic Liver Cancer (BCLC) stage B patients (PFS 11.8 months vs. 5.1 months, P = 0.017; OS 30.3 months vs. 19.4 months, P = 0.022). CONCLUSION: For patients with TACE-refractory HCC, TACE-TKI appeared to be superior to TKI monotherapy with regard to tumor control and PFS. Furthermore, for the BCLC stage B subgroup, TACE-TKI therapy was superior to TKI monotherapy in both OS and PFS.

Chemoembolization versus radiofrequency ablation for single small (≤ 3 cm) hepatocellular carcinoma: a propensity score matching analysis.

OBJECTIVES: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A). MATERIALS AND METHODS: The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS). RESULTS: The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group. CONCLUSION: RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function. CLINICAL RELEVANCE STATEMENT: This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas. KEY POINTS: • The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear. • Overall survival rate was significantly higher in the RFA group. • The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.

Impact of Hyperglycemia on Complication and Mortality after Transarterial Chemoembolization for Hepatocellular Carcinoma.

BACKGRUOUND: Current guidelines regarding periprocedural glycemic control to prevent complications after nonsurgical invasive procedures are insufficient. Transarterial chemoembolization (TACE) is a widely used treatment for unresectable hepatocellular carcinoma. We aimed to investigate the association between diabetes mellitus (DM) per se and the degree of hyperglycemia with postprocedural complications after TACE. METHODS: A total of 22,159 TACE procedures performed at Seoul National University Hospital from 2005 to 2018 were retrospectively analyzed. The associations between DM, preprocedural glycosylated hemoglobin (HbA1c), and periprocedural average glucose with postprocedural adverse outcomes were evaluated. The primary outcome was occurrence of postprocedural bacteremia. Secondary outcomes were acute kidney injury (AKI), delayed discharge and death within 14 days. Periprocedural glucose was averaged over 3 days: the day of, before, and after the TACE procedures. Propensity score matching was applied for procedures between patients with or without DM. RESULTS: Periprocedural average glucose was significantly associated with bacteremia (adjusted odds ratio per 50 mg/dL of glucose, 1.233; 95% confidence interval, 1.071 to 1.420; P=0.004), AKI, delayed discharge, and death within 14 days. DM per se was only associated with bacteremia and AKI. Preprocedural HbA1c was associated with delayed discharge. Average glucose levels above 202 and 181 mg/dL were associated with a significantly higher risk of bacteremia and AKI, respectively, than glucose levels of 126 mg/dL or lower. CONCLUSION: Periprocedural average glucose, but not HbA1c, was associated with adverse outcomes after TACE, which is a nonsurgical invasive procedure. This suggests the importance of periprocedural glycemic control to reduce postprocedural complications.

Intermediate-stage (BCLC stage B) infiltrative hepatocellular carcinoma: safety and efficacy of chemoembolization.

OBJECTIVES: To evaluate the safety and efficacy of chemoembolization in patients with intermediate-stage infiltrative Hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study evaluated outcomes in treatment-naïve patients who received chemoembolization as first-line treatment for intermediate-stage infiltrative HCC between 2002 and 2022. Of the 2029 treatment-naïve patients who received chemoembolization as first-line treatment for intermediate-stage HCC, 244 (12%) were identified as having the infiltrative type. After excluding two patients lost to follow-up, 242 patients were evaluated. RESULTS: Median post-chemoembolization overall survival (OS) was 16 months. Multivariable Cox analysis identified four factors predictive of OS: Child-Pugh class B (hazard ratio [HR], 1.84; p = 0.001), maximal tumor size ≥ 10 cm (HR, 1.67; p < 0.001), tumor number ≥ 4 (HR, 1.42; p = 0.037), and bilobar tumor involvement (HR, 1.64; p = 0.003). These four factors were used to create pretreatment prediction models, with risk scores of 0-1, 2-4, and 5-7 defined as low, intermediate, and high risk, respectively. Median OS times in these three groups were 34, 18, and 8 months, respectively (p < 0.001). The objective tumor response rate following chemoembolization was 53%. The major complication rate was 9% overall and was significantly higher in the high-risk group (22%) than in the low (2%) and intermediate (3%) risk groups (p < 0.001). CONCLUSION: Chemoembolization is safe and effective in selected patients with intermediate-stage infiltrative HCC. Chemoembolization is not recommended in high-risk patients with intermediate-stage infiltrative HCC because of poor OS and high rates of major complications. CLINICAL RELEVANCE STATEMENT: A pretreatment prediction model was developed using four risk factors associated with overall survival following chemoembolization for intermediate-stage infiltrative hepatocellular carcinoma. This model may provide valuable information for clinical decision-making. KEY POINTS: • Four risk factors (Child-Pugh score B, maximal tumor size ≥ 10 cm, tumor number ≥ 4, and bilobar tumor involvement) were used to create pretreatment prediction models, with risk scores of 0-1, 2-4, and 5-7 defined as low, intermediate, and high risk, respectively. • Median overall survival (OS) times and major complication rate in these three groups were 34, 18, and 8 months, and 2%, 3%, and 22%, respectively (p < 0.001). Chemoembolization is not recommended in high-risk patients with intermediate-stage infiltrative Hepatocellular carcinoma (HCC) because of poor OS and high rates of major complications.

Real-world efficacy and safety of TACE plus camrelizumab and apatinib in patients with HCC (CHANCE2211): a propensity score matching study.

OBJECTIVES: This study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus camrelizumab, a monoclonal antibody targeting programmed death-1, and apatinib for patients with intermediate and advanced hepatocellular carcinoma (HCC) in a real-world setting. METHODS: A total of 586 HCC patients treated with either TACE plus camrelizumab and apatinib (combination group, n = 107) or TACE monotherapy (monotherapy group, n = 479) were included retrospectively. Propensity score matching analysis was used to match patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety in the combination group were described in comparison to monotherapy. RESULTS: After propensity score matching (1:2), 84 patients in the combination group were matched to 147 patients in the monotherapy group. The median age was 57 years and 71/84 (84.5%) patients were male in the combination group, while the median age was 57 years with 127/147 (86.4%) male in the monotherapy group. The median OS, PFS, and ORR in the combination group were significantly higher than those in the monotherapy group (median OS, 24.1 vs. 15.7 months, p = 0.008; median PFS, 13.5 vs. 7.7 months, p = 0.003; ORR, 59.5% [50/84] vs. 37.4% [55/147], p = 0.002). On multivariable Cox regression, combination therapy was associated with significantly better OS (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.26-0.64; p < 0.001) and PFS (adjusted HR, 0.52; 95% CI, 0.37-0.74; p < 0.001). Grade 3 or 4 adverse events occurred in 14/84 (16.7%) and 12/147 (8.2%) in the combination and monotherapy groups, respectively. CONCLUSIONS: TACE plus camrelizumab and apatinib showed significantly better OS, PFS, and ORR versus TACE monotherapy for predominantly advanced HCC. CLINICAL RELEVANCE STATEMENT: Compared with TACE monotherapy, TACE plus immunotherapy and molecular targeted therapy showed better clinical efficacy for predominantly advanced HCC patients, with a higher incidence of adverse events. KEY POINTS: • This propensity score-matched study demonstrates that TACE plus immunotherapy and molecular targeted therapy have a longer OS, PFS, and ORR compared with TACE monotherapy in HCC. • Grade 3 or 4 adverse events occurred in 14/84 (16.7%) patients treated with TACE plus immunotherapy and molecular targeted therapy compared with 12/147 (8.2%) patients in the monotherapy group, while no grade 5 adverse events were observed in all cohorts.

Use of doxorubicin-eluting bead transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein invasion: a prospective study.

Background/Aim: To evaluate the applicability of transarterial chemoembolization (TACE) treatment with doxorubicin drug-eluting beads (DEBs) in advanced hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). Methods: This prospective study was approved by the institutional review board and informed consent was obtained from all participants. A total of 30 HCC patients with PVI received DEB-TACE between 2015 and 2018. The following parameters were evaluated: complications during DEB-TACE, abdominal pain, fever, and laboratory outcomes, including liver function change. Overall survival (OS), time to progression (TTP), and adverse events were also analyzed and assessed. Results: DEBs measuring 100-300 µm in diameter were loaded with doxorubicin (150 mg per procedure). There were no complications during DEB-TACE and no significant differences in the levels of prothrombin time, serum albumin, or total bilirubin at follow-up compared to baseline. The median TTP was 102 days (95% confidence interval [CI], 42-207 days) and the median OS was 216 days (95% CI, 160-336 days). Three patients (10%) had severe adverse reactions, including transient acute cholangitis (n=1), cerebellar infarction (n=1), and pulmonary embolism (n=1), but no treatment-related death occurred. Conclusions: DEB-TACE may be a therapeutic option for advanced HCC patients with PVI.

A novel method for predicting hepatocellular carcinoma response to chemoembolization using an intraprocedural CT hepatic arteriography-based enhancement mapping: a proof-of-concept analysis.

BACKGROUND: To evaluate the feasibility of a novel approach for predicting hepatocellular carcinoma (HCC) response to drug-eluting beads transarterial chemoembolization (DEB-TACE) using computed tomography hepatic arteriography enhancement mapping (CTHA-EM) method. METHODS: This three-institution retrospective study included 29 patients with 46 HCCs treated with DEB-TACE between 2017 and 2020. Pre- and posttreatment CTHA-EM images were generated using a prototype deformable registration and subtraction software. Relative tumor enhancement (TPost/pre-RE) defined as the ratio of tumor enhancement to normal liver tissue was calculated to categorize tumor response as residual (TPost-RE > 1) versus non-residual (TPost-RE ≤ 1) enhancement, which was blinded compared to the response assessment on first follow-up imaging using modified RECIST criteria. Additionally, for tumors with residual enhancement, CTHA-EM was evaluated to identify its potential feeding arteries. RESULTS: CTHA-EM showed residual enhancement in 18/46 (39.1%) and non-residual enhancement in 28/46 (60.9%) HCCs, with significant differences on TPost-RE (3.05 ± 2.4 versus 0.48 ± 0.23, respectively; p < 0.001). The first follow-up imaging showed non-complete response (partial response or stable disease) in 19/46 (41.3%) and complete response in 27/46 (58.7%) HCCs. CTHA-EM had a response prediction sensitivity of 94.7% (95% CI, 74.0-99.9) and specificity of 100% (95% CI, 87.2-100). Feeding arteries to the residual enhancement areas were demonstrated in all 18 HCCs (20 arteries where DEB-TACE was delivered, 2 newly developed collaterals following DEB-TACE). CONCLUSION: CTHA-EM method was highly accurate in predicting initial HCC response to DEB-TACE and identifying feeding arteries to the areas of residual arterial enhancement.

Balloon-occluded transarterial chemoembolization versus conventional transarterial chemoembolization for the treatment of single hepatocellular carcinoma: a propensity score matching analysis.

OBJECTIVES: To compare the safety and efficacy of balloon-occluded transarterial chemoembolization (B-TACE) and conventional TACE (C-TACE) in treating single hepatocellular carcinoma (HCC). METHODS: This single-center retrospective study included 523 patients who underwent C-TACE and 44 who underwent B-TACE as first-line treatment for single HCCs between November 2017 and December 2019. After propensity score matching (PSM), initial tumor response rates, local tumor progression (LTP), and major complication rates were evaluated in the 32 pairs of PSM matched population. RESULTS: In the 32 pairs of PSM cohort, B-TACE showed distinct superiority over C-TACE in treating single HCCs, with significantly higher initial complete response (CR) rates (93.8% vs. 62.5%, p = 0.005). During a median follow-up of 37 months (range, 12.7-46.5 months), 13 patients (40.6%) who underwent B-TACE and 16 (50%) who underwent C-TACE showed LTP of treated lesions. Size-based sub-group analysis showed that the median times to LTP in patients with medium- to large-sized tumors (> 3 cm) were significantly longer in the B-TACE (27 months; 95% confidence interval [CI], 19.7-34.3 months) than in the C-TACE (13 months; 95% CI, 3.9-22.1 months) group (p = 0.019). The major complication rate was similar between the two groups. CONCLUSIONS: B-TACE had a higher initial CR rate than C-TACE in treating single HCCs. Moreover, size-based subgroup analysis showed that time to LTP was significantly longer in patients with medium- to large-sized HCCs (> 3 cm) who underwent B-TACE rather than C-TACE. KEY POINTS: • B-TACE was superior to C-TACE in treating single HCC, with a significantly higher initial complete response rate after one session of treatment. • In size-based subgroup analysis, time to LTP was significantly longer in patients with medium- to large-sized HCCs (>3 cm) who underwent B-TACE rather than C-TACE. • B-TACE should be considered an alternative treatment option for medium- to large-sized single HCCs (>3 cm) in patients with a nonresectable condition and those who prefer nonsurgical treatment.

Transarterial chemoembolization failure in patients with hepatocellular carcinoma: Incidence, manifestation and risk factors.

BACKGROUND: To identify the incidence, manifestation and risk factors of transarterial chemoembolization (TACE) failure defined as untreatable progression (UP) in patients with hepatocellular carcinoma (HCC) on short-term observation. METHODS: Patients from two hospitals with HCC treated with TACE were considered. According to the definition of UP, TACE failure was considered to be present in at least one of the following situations: situation I, failure to achieve objective response in the targeted tumor after at least two initial TACE treatments; situation II, failure to achieve objective response in local tumor progression or new intrahepatic tumor after another TACE session; situation III, presence of major progression; and situation IV, presence of impaired liver function or performance status that contraindicates TACE treatment. Patients were assessed for TACE failure on follow-up visits after two or three TACE sessions. Risk factors for TACE failure were evaluated with logistic regression analysis. RESULTS: A total of 206 patients were included. TACE failure occurred in 42 (42/206, 20.4%) patients, of whom 21, 1, 4, 0 and 16 patients manifested as situation I, II, III, IV alone, and combination of situation I with the others, respectively. Multivariate analysis showed that tumor without complete capsule (P < .001) and non-smooth margin (P = .004) were independent predictors of the presence of TACE failure. CONCLUSIONS: TACE failure was uncommon in patients with HCC, which manifested predominantly as failure of treatment response of the initial intrahepatic tumor. Non-smooth tumor margin and tumors without complete capsule were associated with the presence of TACE failure.

Radiological characteristics of hepatocellular carcinoma that achieved complete response after chemoembolization with drug-eluting beads for liver transplantation planning

ABSTRACT Objective To describe the radiological characteristics of hepatocellular carcinoma (HCC) lesions that achieved a complete response following drug-eluting bead transarterial chemoembolization (DEB-TACE) preceding liver transplantation. Methods This single-center case-control study enrolled patients with hepatocellular carcinoma who underwent neoadjuvant DEB-TACE therapy, were followed up with contrast-enhanced magnetic resonance imaging or computed tomography, and were successively evaluated according to the modified Response Evaluation Criteria in Solid Tumors. The HCCs were divided into two groups based on their diameter (Group A: ≤3cm; Group B: 3cm). Viability was assessed using the Kaplan-Meier method according to tumor size categories. The relationship between tumor variables was analyzed using bivariate Cox regression. Results Three-hundred and twenty-eight patients with 667 hepatocellular carcinomas who underwent their first DEB-TACE session were enrolled. A total of 105 hepatocellular carcinomas in 59 patients exhibited complete response after the initial DEB-TACE session and were divided into Group A (92 HCCs) and Group B (13 HCCs). The diameter in Group A decreased significantly compared to the pre-procedure size until the second assessment (p<0.001), with no subsequent reduction in diameter, despite maintaining a complete response. In Group B, the reduction in diameter remained significant compared with the initial value until the sixth imaging evaluation (p=0.014). The average reduction was 45.1% for Group B and a maximum of 14.9% in Group A. Conclusion HCCs >3cm exhibited a greater reduction in size and a longer time to recurrence. HCCs ≤3cm had a shorter relapse time. The recurrence rates were similar. These findings may aid in planning for liver transplantation.

Transradial versus transfemoral access without closure device for transarterial chemoembolization in patients with hepatocellular carcinoma: a randomized trial.

OBJECTIVES: To compare patient satisfaction, procedural variables, and safety with transradial access (TRA) and transfemoral access (TFA) in patients undergoing transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From February 2019 to August 2021, 130 patients undergoing TACE for HCC were randomly allocated to the TRA (n = 65) or TFA (n = 65) group. Vascular closure devices were not used after TFA-TACE. All patients completed the post-catheterization questionnaire and 8-item Short-Form Health Survey 1 day after TACE. RESULTS: Technical success rate, crossover rate, contrast agent dose, fluoroscopy time, procedure time, air kerma, dose-area product, length of hospital stay, and total cost were similar between the two groups (all p > 0.05). The incidence and severity of adverse events were also similar between the two groups (all p > 0.05). However, overall discomfort, difficulty going to the bathroom, difficulty feeding or self-caring, difficulty walking, general health, physical function, role physical function, social function, mental health, and role emotional function were better in the TRA group than in the TFA group (all p < 0.001). Consequently, more patients preferred the current access for their next procedure in the TRA group than in the TFA group (90.8% vs. 24.6%; p < 0.001). CONCLUSION: In patients undergoing TACE for HCC, using TRA instead of TFA can improve patient satisfaction without compromising procedural variables and safety. KEY POINTS: • Transradial access (TRA) enabled early ambulation after transarterial chemoembolization (TACE), resulting in significant increase in activities of daily living and health-related quality of life (HRQoL) compared to transfemoral access (TFA) when vascular closure devices were not used. • Procedural variables (contrast agent dose, fluoroscopy time, procedure time, air kerma, dose-area product, length of hospital stay, and total cost) were not significantly different between patients who received TRA-TACE and TFA-TACE. • The incidence and severity of adverse events were similar between patients who received TRA-TACE and TFA-TACE.

Effect of decoction of Fuzheng Jiedu Xiaoji formula plus chemoembolization on primary liver cancer in patients.

OBJECTIVE: To investigate the effect of the decoction of Fuzheng Jiedu Xiaoji formula (, FJXF) plus chemoembolization (TACE) on primary liver cancer (PLC) in patients, and study the underlying mechanism. METHODS: Patients with PLC who met the inclusion criteria were randomized into case group and control group. The case group was treated with FJXF combined with TACE. The control group was treated with TACE alone. The short-term clinical effect was evaluated; liver biochemistry, liver function index and multidrug resistance-associated indicators were detected. RESULTS: FJXF combined with TACE in the case group significantly increased the disease control rate than TACE alone in the control group (83.3% 61.1%). There was a reduction in the serum alpha-fetoprotein at 8 weeks after treatment in each group, while no difference between the two groups. The same trend can be observed for transaminase and direct bilirubin in both groups. In the case group, it showed a significant increase for albumin at 8 weeks after treatment, while no change in the control group. Multidrug resistance-associated indicators for multidrug resistance protein 1 and p-glycoprotein were upregulated in the case group but remained stable in the control group. CONCLUSIONS: FJXF combined TACE had a better short-term effect than TACE alone in patients with PLC. The potential mechanism was probably associated with alleviated multidrug resistance induced by FJXF. Additionally, FJXF didn't increase the risk of liver damage in the combined therapy.

Hepatocellular carcinoma with Budd-Chiari syndrome due to membranous obstruction of the inferior vena cava with long-term follow-up: a case report.

Membranous obstruction of the inferior vena cava (MOVC) is a rare subset of Budd-Chiari syndrome (BCS) with a subacute onset that is often complicated by cirrhosis and hepatocellular carcinoma (HCC). Here we report a case of recurrent HCC in a patient with cirrhosis and BCS that was treated with several episodes of transarterial chemoembolization followed by surgical tumorectomy, whereas the MOVC was successfully treated with balloon angioplasty followed by endovascular stenting. The patient was followed up for 9.9 years without anticoagulation and experienced no stent thrombosis. After the tumorectomy, the patient was HCC-free for 4.4 years of follow-up.

Comparison of metabolic and immunologic responses to transarterial chemoembolization with different chemoembolic regimens in a rabbit VX2 liver tumor model.

OBJECTIVES: The goal of this study was to investigate the effects of TACE using Lipiodol, Oncozene™ drug-eluting embolics (DEEs), or LUMI™-DEEs alone, or combined with bicarbonate on the metabolic and immunological tumor microenvironment in a rabbit VX2 tumor model. METHODS: VX2 liver tumor-bearing rabbits were assigned to five groups. MRI and extracellular pH (pHe) mapping using Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) were performed before and after intra-arterial therapy with conventional TACE (cTACE), DEE-TACE with Idarubicin-eluting Oncozene™-DEEs, or Doxorubicin-eluting LUMI™-DEEs, each with or without prior bicarbonate infusion, and in untreated rabbits or treated with intra-arterial bicarbonate only. Imaging results were validated with immunohistochemistry (IHC) staining of cell viability (PCNA, TUNEL) and immune response (HLA-DR, CD3). Statistical analysis was performed using Mann-Whitney U test. RESULTS: pHe mapping revealed that combining cTACE with prior bicarbonate infusion significantly increased tumor pHe compared to control (p = 0.0175) and cTACE alone (p = 0.0025). IHC staining revealed peritumoral accumulation of HLA-DR+ antigen-presenting cells and CD3 + T-lymphocytes in controls. cTACE-treated tumors showed reduced immune infiltration, which was restored through combination with bicarbonate. DEE-TACE with Oncozene™-DEEs induced moderate intratumoral and marked peritumoral infiltration, which was slightly reduced with bicarbonate. Addition of bicarbonate prior to LUMI™-beads enhanced peritumoral immune cell infiltration compared to LUMI™-beads alone and resulted in the strongest intratumoral immune cell infiltration across all treated groups. CONCLUSIONS: The choice of chemoembolic regimen for TACE strongly affects post-treatment TME pHe and the ability of immune cells to accumulate and infiltrate the tumor tissue. KEY POINTS: • Combining conventional transarterial chemotherapy with prior bicarbonate infusion increases the pHe towards a more physiological value (p = 0.0025). • Peritumoral infiltration and intratumoral accumulation patterns of antigen-presenting cells and T-lymphocytes after transarterial chemotherapy were dependent on the choice of the chemoembolic regimen. • Combination of intra-arterial treatment with Doxorubicin-eluting LUMI™-beads and bicarbonate infusion resulted in the strongest intratumoral presence of immune cells (positivity index of 0.47 for HLADR+-cells and 0.62 for CD3+-cells).

Intraarterial contrast-enhanced ultrasound to predict the short-term tumour response of hepatocellular carcinoma to Transarterial chemoembolization with Lipiodol.

BACKGROUND: Transarterial chemoembolization (TACE) is an effective locoregional therapy in hepatocellular carcinoma (HCC). However, it is difficult to predict the tumour response (TR) of TACE intraprocedurally. The aim of this study was to predict the TR after TACE (1-3 months) in HCC patients using intraprocedural intraarterial contrast enhanced ultrasound (IA-CEUS). METHODS: In this case-control study, consecutive patients who received TACE in our hospital from September 2018 to May 2019 were enrolled. IA-CEUS was performed before and after TACE. Postoperative contrast-enhanced liver MRI was performed 1-3 months after TACE as the gold standard. According to the modified Response Evaluation Criteria in Solid Tumours (mRECIST), ultrasonic manifestations were compared between the complete remission (CR) group and non-CR group by univariate and multivariate analyses. A logistic predictive model was established and validated, and its diagnostic efficiency was evaluated. RESULTS: Forty-four patients with sixty-one lesions were enrolled in the study. Multivariate analysis identified, the risk factors as a large lesion diameter (OR: 1.84; 95% confidence interval [CI]: 1.009, 3.080; P = 0.020), a larger dimension of non-enhancing area in superior mesenteric artery (SMA)-CEUS than the size in B-mode ultrasound preoperatively (OR: 3.379; 95% CI: 1.346,8.484; P = 0.010), presence of corona enhancement in hepatic artery (HA)-CEUS postoperatively (OR: 6.642; 95% CI: 1.214, 36.331; P = 0.029), and decreased corona enhancement thickness (per centimetre) postoperatively (OR: 0.025; 95% CI: 0.006,0.718; P = 0.025). The area under the receiver operating characteristic curve (AUROC) of the predictive model was 0.904 (95% CI: 0.804, 0.966; P < 0.001). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 81.08, 91.67, 85.25, 93.75, and 75.86%, respectively. Leave-one-out cross-validation (LOOCV) showed that the accuracy was 77.05%. CONCLUSIONS: Intraprocedural IA-CEUS can be used to predict the TR in HCC patients after TACE.

The role of muscle depletion and visceral adiposity in HCC patients aged 65 and over undergoing TACE.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) has been increasing among the elderly populations. Trans-arterial chemoembolization (TACE), a widely used first-line non-curative therapy for HCCs is an issue in geriatrics. We investigated the prognosis of elderly HCC patients treated with TACE and determined the factors that affect the overall survival. METHODS: We included 266 patients who were older than 65 years and had received TACE as initial treatment for HCC. We analyzed the skeletal muscle index (SMI) and visceral-to-subcutaneous fat ratio (VSR) around the third lumbar vertebrae using computed tomography scans. Muscle depletion with visceral adiposity (MDVA) was defined by falling below the median SMI and above the median VSR value sex-specifically. We evaluated the overall survival in association with MDVA and other clinical factors. RESULTS: The mean age was 69.9 ± 4.5 years, and 70.3% of the patients were men. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, 29, 136, and 101 patients were classified as BCLC 0, A, and B stages, respectively, and 79 (29.7%) had MDVA. During the median follow-up of 4.1 years, patients with MDVA had a shorter life expectancy than those without MDVA (P = 0.007) even though MDVA group had a higher objective response rate after the first TACE (82.3% vs. 75.9%, P = 0.035). Multivariate analysis revealed that MDVA (Hazard ratio [HR] 1.515) age (HR 1.057), liver function (HR 1.078), tumor size (HR 1.083), serum albumin level (HR 0.523), platelet count (HR 0.996), tumor stage (stage A, HR 1.711; stage B, HR 2.003), and treatment response after the first TACE treatment (HR 0.680) were associated with overall survival. CONCLUSIONS: MDVA is a critical prognostic factor for predicting survival in the elderly patients with HCC who have undergone TACE.

Optimal Timing of Radiotherapy after Incomplete Transarterial Chemoembolization for Barcelona Clinic Liver Cancer Stage B Hepatocellular Carcinoma.

PURPOSE: The optimal timing for radiotherapy (RT) after incomplete transarterial chemoembolization (TACE) remains unclear. This study investigated the optimal timing to initiate RT after incomplete TACE in patients with Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma. MATERIALS AND METHODS: This study included 116 lesions in 104 patients who were treated with RT after TACE between 2001 and 2016. The time interval between the last TACE session and RT initiation was retrospectively analyzed. The optimal cut-off time interval that maximized the difference in local failure-free rates (LFFRs) was determined using maximally selected rank statistics. RESULTS: The median time interval was 26 days (range: 2-165 days). At a median follow-up of 18 months (range: 3-160 months), the median overall survival was 18 months. The optimal cut-off time interval appeared to be 5 weeks; using this cut-off, 65 and 39 patients were classified into early and late RT groups, respectively. Early RT group had a significantly poorer Child-Pugh class and higher alpha-fetoprotein levels compared to late RT group. Other characteristics, including tumor size (7 cm vs. 6 cm; p=0.144), were not significantly different between the groups. The 1-year LFFR was significantly higher in the early RT group than in the late RT group (94.6% vs. 70.8%; p=0.005). On multivariate analysis, early RT was identified as an independent predictor of favorable local failure-free survival (hazard ratio: 3.30, 95% confidence interval: 1.50-7.29; p=0.003). CONCLUSION: The optimal timing for administering RT after incomplete TACE is within 5 weeks. Early administration of RT is associated with better local control.

New frontiers in endovascular therapies for locally advanced hepatocellular carcinoma.

Hepatocellular carcinoma is the most common primary malignant liver tumour and is a leading cause of death worldwide. Despite the advent of screening programmes, most cases of hepatocellular carcinoma are diagnosed late (in an advanced stage) which precludes curative treatments such as surgery and ablation. Therefore, intra-arterial locoregional treatments now play a central role in the management of advanced hepatocellular carcinoma, such treatments ranging from trans-arterial chemo-embolisation to the more recently developed trans-arterial radio-embolisation technique. In this essay, we discuss the state of the art of intra-arterial treatment for locally advanced hepatocellular carcinoma and the future directions for such treatment.

O carcinoma hepatocelular é o tumor hepático maligno primário mais frequentemente observado, sendo uma das principais causas de mortalidade mundial. Apesar do advento dos programas de triagem, na maioria dos casos o diagnóstico tardio está associado a um estágio avançado da doença que impede o tratamento curativo, como cirurgia ou ablação. Assim, os tratamentos locorregionais intra-arteriais têm agora um papel central no gerenciamento avançado do carcinoma hepatocelular, passando por quimioembolização transarterial e radioembolização. Neste ensaio, discutimos o estado da arte do tratamento intra-arterial atualmente disponível para o carcinoma hepatocelular localmente avançado e suas direções futuras.