Conventional Transarterial Chemoembolization Research Articles

Safety, efficacy, and survival of drug-eluting beads-transarterial chemoembolization vs. conventional-transarterial chemoembolization in advanced HCC patients with main portal vein tumor thrombus

ObjectivesTo compare the efficacy, overall survival (OS) and safety of drug-eluting beads-TACE (DEB-TACE) and C-TACE as initial treatment in advanced hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (mPVTT).MethodsThe medical records of consecutive advanced HCC patients with mPVTT who underwent initial DEB-TACE or C-TACE from September 2015 to October 2021 were retrospectively evaluated. Treatment crossover was allowed in this retrospective research. The adverse events, disease control rate (DCR), time to tumor progression (TTP) and OS of patients who underwent DEB-TACE were compared with those of patients who underwent C-TACE.ResultsEighty-three patients were included: 42 patients in DEB-TACE group and 41 patients in C-TACE group. DEB-TACE could be safely performed in HCC patients with mPVTT, and they gained a better DCR than those submitted to the C-TACE (76.2% vs. 53.7%, P = 0.031), which might have resulted in longer TTP (median TTP: 9.0 months vs. 3.0 months, P < 0.001). Furthermore, DEB-TACE showed significant OS benefits compared with C-TACE (median OS: 12.0 months vs. 5.0 months, P < 0.001). DEB-TACE, absence of arterioportal shunts (APS), leisons with capsular non-infiltration were found to be independent prognostic factors for better OS. Furthermore, subgroup analysis proved that patients with good DCR gained longer OS in DEB-TACE group.ConclusionsDEB-TACE could be safely performed and improve the DCR of HCC patients with mPVTT, which resulting in longer TTP and OS, compared with C-TACE.

Evaluation of the Safety and Efficacy of Conventional Transarterial Chemoembolization (cTACE) and Drug-Eluting Bead (DEB)-TACE in the Management of Unresectable Hepatocellular Carcinoma: A Systematic Review.

Transarterial chemoembolization (TACE) is considered the preferred loco-regional treatment option for hepatocellular carcinoma (HCC) not amenable to resection due to its distinctive blend of precise drug administration, localized tumor management, and reduced systemic adverse effects, setting it apart from the plethora of alternative treatments available. There is an ongoing debate regarding the optimal choice for managing HCC using TACE, particularly between its two major types: conventional TACE (cTACE) and drug-eluting bead TACE (DEB-TACE). The medical community remains divided on which approach offers superior safety and efficacy, with conflicting evidence and varied outcomes adding to the complexity of this nuanced decision. Given the lack of consensus surrounding the preferred TACE technique in treatment-naive patients for HCC, we conducted a rigorous systematic review to assess and contrast the relative safety and efficacy of cTACE versus DEB-TACE in patients diagnosed with HCC who did not receive any prior treatment for HCC. Our study aimed to provide much-needed clarity on this controversial topic, shedding light on thetwo approaches' comparative safety and efficacy to inform clinical decision-making. After a comprehensive search of databases and search enginesand through a methodical screening process, including standardized quality assessmentsand relevant filterapplication based on our eligibility criteria, we identified 10 articles pertinent to our research query comprising two randomized controlled trials, one meta-analysis, and seven observational studies. The collective sample size of the studies was 5,288 patients with HCC, of which 2,959 were in the cTACE armand 2,324 were in the DEB-TACE arm.

Transarterial chemoembolization for hepatocellular carcinoma: 2023 expert consensus-based practical recommendations of the Korean Liver Cancer Association.

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

Comparison of the Treatment Response of Drug-Eluting Bead Transarterial Chemoembolization and Conventional Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma.

Introduction Hepatocellular carcinoma (HCC) is a common primary hepatic cancer. Its early diagnosis can aid in its treatment by curative means such as surgery or ablation. Advanced-stage diagnosis limits these treatment options, and such cases can be treated with transarterial chemoembolization (TACE). Conventional transarterial chemoembolization (cTACE) and drug-eluting beadtransarterial chemoembolization (DEB-TACE) are usually used, and follow-up response is evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. This study was done to compare the treatment response of cTACE and DEB-TACE in patients with HCC. Materials and methods A retrospective review of electronic medical records of all patients diagnosed with HCC from January 2021 to August 2022 who underwent cTACE or DEB-TACE was undertaken at the Department of Interventional Radiology, Indus Hospital and Health Network. Both male and female patients aged 18 years or above with Child-Pugh class A and B were included. DEB-TACE or cTACE was performed by a fellowship-trained interventional radiologist, and the response was evaluated at six weeks follow-up using mRECIST criteria. Results A total of 129 patients were included in this study, with a mean age of 54.1 ± 10.8 years. The mean size of HCC was 3.1 ± 1.7 cm. Seventy-eight (60.5%) patients underwent cTACE, and 51 (39.5%) underwent DEB-TACE. Out of the 78patients who underwent cTACE, complete response (CR) was found in 28 (35.9%), partial response (PR)was found in 33 (42.3%), stable disease (SD) was found in 12 (15.4%), and progressive disease (PD) was found in five (6.4%) patients. Of the 51 patients who underwentDEB-TACE, CR was found in 13 (25.5%), PR was found in 20 (39.2%), SD was found in 11 (21.6%), and PD was found in seven (13.7%) patients. Conclusion The response rate of TACE in the form of complete or partial response was higher with a lower frequency of stable or progressive disease. cTACE has a high response rate as compared to DEB-TACE.

C-Arm Computed Tomographic Image Fusion for Repetitive Transarterial Chemoembolization of Hepatocellular Carcinoma.

The aim of this study was to evaluate the potential implications of fusion imaging with C-arm computed tomography (CACT) scans for repetitive conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma. Fifty-six cTACE sessions were performed using fusion CACT images from September 2020 to June 2021 in a tertiary referral center, and the data were retrospectively analyzed. Fusion of unenhanced and enhanced CACT images was considered when previously accumulated iodized oil hampered the identification of local tumor progression or intrahepatic distant metastasis (indication A), when a tumor was supplied by multiple arteries with different origins from the aorta and missing tumor enhancement was suspected (indication B), or when iodized oil distribution on immediate post-cTACE CACT images needed to be precisely compared with the pre-cTACE images (indication C). Fusion image quality, initial tumor response, time to local progression (TTLP) of index tumors, and time to progression (TTP) were evaluated. The fusion quality was satisfactory with a mean misregistration distance of 1.4 mm. For the 40 patients with indication A, the initial tumor responses at 3 months were nonviable, equivocal, and viable in 27 (67.5%), 4 (10.0%), and 9 (22.5%) index tumors, respectively. The median TTLP and TTP were 14.8 months and 4.5 months, respectively. For 10 patients with indication B, the median TTLP and TTP were 8.3 months and 2.6 months, respectively. Among the 6 patients with indication C, 2 patients were additionally treated at the same cTACE session after confirming incomplete iodized oil uptake on fusion imaging. Fusion CACT images are useful in patients with hepatocellular carcinoma undergoing repetitive cTACE.

Imaging biomarkers on Angio-CT for predicting the efficacy of transarterial chemoembolization in hepatocellular carcinoma.

This study aimed to evaluate whether the lipiodol deposition pattern on intraprocedural Angio-CT could predict tumor treatment response in hepatocellular carcinoma (HCC) patients treated with conventional transarterial chemoembolization (c-TACE). This retrospective study enrolled intermediated and advanced HCC nodules treated with c-TACE and Angio-CT from June 2021 to June 2022. The therapeutic efficacy was evaluated according to the mRECIST standards. First, Angio-CT was used to determine lipiodol deposition at the end of c-TACE, redefined as complete, partial-complete, and incomplete groups. Second, the mean CT value of lipiodol deposition and its association with therapeutic efficacy were calculated in the complete model. Finally, the relationship between imaging biomarkers and efficacy was evaluated. A total of 45 patients with 72 HCC nodules were enrolled with 28 nodules in the complete group, 31 nodules in the partial-complete group, and 13 nodules in the incomplete group. The complete response (CR) proportion was significantly higher in patients with good lipiodol deposition compared with patients with poor lipiodol deposition (P<0.0001). There was no significantly different CR rate between CT value ≥800 and <800 HU (P=0.119) in the complete group. Meanwhile, the non-CR rate in cases with hepatic vein development was significantly higher than that in cases with no hepatic vein development in the arterial phase (P<0.0001). Complete lipiodol deposition on Angio-CT during c-TACE was a predictive factor for therapeutic response to TACE. For HCC nodules with well-deposited lipiodol, hepatic vein development on Angio-CT in the arterial phase was strongly associated with poor efficacy of TACE.

Multidisciplinary Taiwan consensus for the use of conventional TACE in hepatocellular carcinoma treatment.

Developed in early 1980s, transarterial chemoembolization (TACE) with Lipiodol was adopted globally after large-scale randomized control trials and meta-analyses proving its effectiveness were completed. Also known as "conventional TACE" (cTACE), TACE is currently the first-line treatment for patients with unresectable intermediate stage hepatocellular carcinoma (HCC) and delivers both ischemic and cytotoxic effects to targeted tumors. Although new technology and clinical studies have contributed to a more comprehensive understanding of when and how to apply this widely-adopted therapeutic modality, some of these new findings and techniques have yet to be incorporated into a guideline appropriate for Taiwan. In addition, differences in the underlying liver pathologies and treatment practices for transcatheter embolization between Taiwan and other Asian or Western populations have not been adequately addressed, with significant variations in the cTACE protocols adopted in different parts of the world. These mainly revolve around the amount and type of chemotherapeutic agents used, the type of embolic materials, reliance on Lipiodol, and the degree of selectiveness in catheter positioning. Subsequently, interpreting and comparing results obtained from different centers in a systematic fashion remain difficult, even for experienced practitioners. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to devise modernized recommendations that reflect recent clinical experiences, as well as cTACE protocols which are tailored for use in Taiwan. The conclusions of this expert panel are described herein.

Robot-Assisted Transarterial Chemoembolization of Hepatocellular Carcinoma Using a Coaxial Microcatheter Driving Controller-Responder Robot System: Clinical Pilot Study

PurposeTo evaluate the feasibility and safety of robot-assisted transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) using a new coaxial microcatheter driving controller-responder robot (CRR) system. Materials and MethodsA single-center prospective pilot study approved by the institutional review board was conducted using this CRR developed after analyzing 20 cases of conventional TACE procedures from May to October 2021. The study included 10 patients with HCCs: 5 (median age, 72 years; range, 64–73 years) underwent robot-assisted TACE, and 5 (median age, 57 years; range, 44–76 years) underwent conventional TACE for comparison. The feasibility and safety of robot-assisted TACE were evaluated by assessing the technical success, procedure time, adverse event rate, radiation dose, and early tumor response. ResultsThe entire TACE procedure was divided into 30 steps, of which 8 could be robotized. In robot-assisted TACE, technical success was achieved in 4 (80%) of 5 patients. No procedure-related adverse event was observed. The median procedure time was 56 minutes. At the 1-month follow-up, 3 of the 4 patients showed a complete or partial response after robot-assisted TACE. The median radiation doses for the operator and patients were 0.4 and 2,167.5 μSv in robot-assisted TACE and 53.2 and 2,989.7 μSv in conventional TACE, respectively. ConclusionsRobot-assisted TACE using a new CRR system was feasible and safe for the treatment of HCC and could remarkably decrease radiation exposure for the operators.

Safety and Efficacy of Drug-Eluting Bead Transarterial Chemoembolization Combined with Lenvatinib and Anti-PD-1 Antibodies for Unresectable Hepatocellular Carcinoma: A Retrospective Analysis.

Drug-eluting bead transarterial chemoembolization (DEB-TACE) has good efficacy in the treatment of unresectable hepatocellular carcinoma (uHCC), with a relatively high objective response rate (ORR) compared to conventional transarterial chemoembolization (cTACE). This study aimed to evaluate the safety and medium-term clinical efficacy of DEB-TACE combined with lenvatinib (LEN) plus PD-1 inhibitors as a triple therapy for the treatment of uHCC. Data of patients with uHCC who received triple therapy of DEB-TACE combined with LEN plus PD-1 inhibitors from January 2019 to June 2021 were analyzed retrospectively. The study endpoints were ORR, progression-free survival (PFS), and treatment-related adverse events based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Thirty-five patients were included in this study, with a median follow-up period of 15 months. The median cycle of DEB-TACE was 1, while that of all forms of TACE procedures per patient was 2. The median administration time of LEN was 7 months, and the median number of PD-1 inhibitor treatment was 4 cycles. The ORR based on mRECIST was 82.9%, disease control rate was 91.4%, and the median time to response was 7 weeks. Among these, the ORR of Barcelona Clinic Liver Cancer (BCLC) stage A reached 100%, while that of BCLC stages B and C reached 84.6% and 78.9%, respectively. The median PFS was 9 months; the mOS was not reached. Fourteen patients (40%) successfully underwent downstaging conversion and surgical resection, 32 patients (91.4%) experienced treatment-related adverse events, and no grade 5-related adverse reactions occurred. DEB-TACE combined with LEN and PD-1 inhibitors has a high ORR and surgical conversion rate in the treatment of uHCC tumors, and the toxicity and side effects were tolerable.

Donafenib combined with anti-PD-1 antibody and transarterial chemoembolization (TACE) as first-line (1L) treatment for unresectable/advanced hepatocellular carcinoma (HCC).

e16107 Background: Targeted drugs, immune checkpoint inhibitors and TACE are important non-surgical approaches to treat HCC. A triple combination of the three is under investigation. This prospective study was conducted to assess the efficacy and safety of donafenib combined with anti-PD-1 antibody and TACE as first-line treatment for unresectable or advanced HCC. Methods: Patients (pts) who had histologically or clinically confirmed HCC and with no prior systemic therapy, at least one measurable lesion per mRECIST, Child-Pugh score ≤7, and ECOG PS score 0-1 were enrolled and received donafenib 100 mg twice daily, anti-PD-1 antibody Q3W and on-demand conventional TACE. CT/MRI scans were performed every six weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival and safety. Results: A total of 30 pts were enrolled between Dec 2021 and Nov 2022. All pts had HBV-related HCC and baseline ECOG PS score of 0. Baseline characteristics are shown in the Table. As of 6 Feb 2023, eleven pts had discontinued the triple therapy. The median follow up time was 3.6 months (range, 1.8-13.4). The median number of on-study TACE sessions was 2 (range, 1-4). Among 29 efficacy evaluable pts, five pts had disease progression and no death occurred. The median PFS was not reached (95%CI, 2.4 months -NE). The 6-month PFS rate was 69.4% (95%CI, 34.5%-84.0%). Five pts had a complete response and 13 had a partial response (responders). ORR and DCR were 62.1% (95%CI, 42.3%-79.3%) and 86.2% (95%CI, 68.3%-96.1%) per mRECIST. The median time to response was 1.3 months (95%CI, 1.1-1.6). The median duration of response was not reached (95%CI, 3.4 weeks-NE). Four pts (1 with BCLC B, 3 with BCLC C) underwent successful surgical resection after a median treatment duration of 2.9 months (range, 1.8-3.3) and no recurrence was noted with a median of 5.9 months (range, 2.8-10.2) follow-up after hepatectomy. In the safety population (n = 30), any grade and grade 3 treatment-related adverse events (TRAEs) occurred in 15 (50.0%) and 7 (23.3%) pts with no grade 4 TRAEs or toxic death. Rash was the most common grade 3 TRAE (incidence: 13.3%) and led to treatment discontinuation in one pt. Conclusions: The triple combination of donafenib plus anti-PD-1 antibody and TACE showed promising efficacy and was well tolerated in pts with unresectable or advanced HCC. Clinical trial information: NCT05262959 . [Table: see text]

Updated results from ALTER-H004 trial: Anlotinib combined with TACE as adjuvant therapy for patients with hepatocellular carcinoma at high risk of recurrence after surgery—A single arm, multi-center, phase II clinical trial.

e16222 Background: Hepatectomy is deemed as a curative treatment for patients (pts) with hepatocellular carcinoma (HCC). Unfortunately, high recurrent risk after curative resection compromised the long-term survival of HCC significantly. Transarterial chemoembolization (TACE) as adjuvant therapy was proved to improve therapeutic outcomes for pts with high recurrent risk after hepatectomy. However, the survival benefit of TACE remained unsatisfactory. ALTER-H004 trial was designed to identify the efficacy and safety of anlotinib as maintenance adjuvant treatment following TACE in pts with HCC. The preliminary results of ALTER-H004 had been reported at 2022 ASCO (e16120). Here we reported the results at the data cutoff of January 15, 2023. Methods: Pts with one of the following high risk factors after hepatectomy were eligible: ≥5cm and &lt;10cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus (Cheng's classification I/II). Eligible pts received conventional TACE treatment within 1-2 months after hepatectomy, and on the 4th day after TACE treatment, oral anlotinib (12mg, qd, 2 weeks on 1 week off) was given until disease recurrence or unacceptable toxicity. The predefined sample size was 30. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: At January 15, 2023, 29 pts were enrolled and 28 pts were available for prognostic assessment, among whom, 11 pts were still on treatment and 9 relapsed, 3 withdrew the consent, 5 discontinued own to intolerable adverse reactions. The longest duration of treatment is 27.83 months. The median DFS has not reached yet and the 1-year DFS rate was 76.46% (95% CI: 54.83~88.70) and 2-year DFS rate was 65.41% (95% CI: 41.70~81.39). Safety profile indicated that 18 pts (64.3%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs were detected in 5 pts (17.9%) including hypertension (7.1%), leukocytopenia (7.1%) and ascites (3.6%). No grade 4 or 5 TRAEs were observed. Conclusions: Anlotinib combined with TACE as adjuvant therapy in pts with HCC at high recurrent risk exhibited promising prognosis and tolerable safety profile preliminarily, and the conclusion needed to be confirmed in large-scale clinical trials subsequently. Clinical trial information: NCT04213118 .

Predictive factors of large liver cell carcinoma tumor response after first conventional transarterial chemoembolization in Indonesia according to the modified response evaluation in solid tumors criteria: a preliminary study

Background: Various factors affect the response of large hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE), and the high demand for TACE procedures highlights the need for information and methods on the criteria for patient selection. Methods: Thirty-six HCC patients who were treated with conventional TACE between January 2014 and January 2020 and had pre- and postoperative imaging data were included in the analysis. The patients were categorized as tumor responders (complete or partial response) or nonresponders (stable or progressive disease) according to the modified response evaluation criteria in solid tumors (mRECIST). Eight predictive factors (Tumor diameter, Tumor amount, tumor vascularity, portal vein invasion, tumor location, presence of tumor capsule, Child–Pugh class, and alpha-fetoprotein (AFP) level) of tumor response were evaluated using multivariate analysis with logistic regression. Results: Only 42% of patients fell into the category of responders after conventional TACE. None of the Child–Pugh class B patients showed a tumor response. A multivariate analysis of the Child–Pugh class A patient group showed that a lesion diameter of 5–10 cm (OR: 8.78, 95% CI: 1.73–44.55; P = 0.009) are an independent predictor of tumor response after the first TACE procedure. Conclusions: A tumor diameter of 5–10 cm could be use as a predictor of tumor response after the first conventional TACE in Child–Pugh A patients, further researches are needed to confirm this finding.

Vascular Normalization Caused by Short-Term Lenvatinib Could Enhance Transarterial Chemoembolization in Hepatocellular Carcinoma

We describe the clinical effects of short-term lenvatinib administration prior to conventional transarterial chemoembolization (cTACE) on tumor vasculature. Two patients with unresectable hepatocellular carcinoma underwent high-resolution digital subtraction angiography (DSA) and perfusion four-dimensional computed tomography during hepatic arteriography (4D-CTHA) before and after administration of lenvatinib treatment. The doses and periods of lenvatinib administration were, respectively, 12 mg/day for 7 days and 8 mg/day for 4 days. In both cases, high-resolution DSA revealed a decrease in dilatation and tortuosity of the tumor vessels. Furthermore, the tumor staining became more refined, and newly formed tiny tumor vessels were observed. Perfusion 4D-CTHA revealed a decrease in arterial blood flow to the tumor by 28.6% (from 487.9 to 139.5 mL/min/100 mg) and 42.5% (from 288.2 to 122.6 mL/min/100 mg) in the two cases, respectively. The cTACE procedure resulted in good lipiodol accumulation and complete response. Patients have remained recurrence-free for 12 and 11 months after the cTACE procedure, respectively. The administration of short-term lenvatinib in these two cases resulted in the normalization of tumor vessels, which likely led to improved lipiodol accumulation and a favorable antitumor effect.

Efficacy of glass membrane emulsification device in conventional transarterial chemoembolization for hepatocellular carcinoma: a preliminary study.

Transarterial chemoembolization (TACE) is the standard treatment for Barcelona Clinic Liver Cancer (BCLC)-B hepatocellular carcinoma (HCC). A novel glass membrane emulsification device (GMD) produces a high percentage of water/oil emulsions with homogeneous and stable droplets. There are few reports on the efficacy of GMD-conventional-TACE (GMD-c-TACE); therefore, we aimed to evaluate the effectiveness of GMD-c-TACE. Seventy-one patients with HCC with tumor diameter <5 cm who underwent c-TACE with and without GMD were included in this study to investigate local recurrence and hepatic functional reserve. The local recurrence rates of TACE without GMD were 3.0% at 6 months, 16.7% at 12 months, and 35.0% at 18 months, around where it plateaued. In contrast, the local recurrence rates in the GMD-c-TACE group were 0.0% at 12 months and 15.4% at 18 months, respectively. Thus, GMD-c-TAE had a significantly lower local recurrence. ALBI score of c-TACE with GMD significantly preserved hepatic reserve. Multivariate analysis showed that GMD-c-TACE could suppress local recurrence and maintain hepatic reserve. GMD-c-TACE allows dense lipiodol accumulation in the tumor and the attainment of good local control. Additionally, in vitro evaluation of the sustained release properties of GMD, the inhibition of the release of anticancer drugs may lead to maintain hepatic reserve. GMD-c-TACE is useful in preventing local recurrence and is expected to become the standard treatment form of c-TACE in the future.

Outcomes of conventional transarterial chemoembolization using guidance software for hepatocellular carcinoma in the caudate lobe of the liver

Outcomes of conventional transarterial chemoembolization using guidance software for hepatocellular carcinoma in the caudate lobe of the liver

Hepatogastric fistula formation after liver chemoembolization in a patient with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) accounts for 75% to 95% of all cases of primary liver cancer. The number of cases of newly diagnosed hepatocellular cancer (HCC) in the Russian Federation in 2019 accounted to 9324. Currently, the method of transarterial chemoembolization (TACE) is widely used for the treatment of patients with malignant liver tumors. Various methods of transarterial embolization of the liver are used, including selective or superselective catheterization and the use of various chemotherapeutic and embolizing agents. In recent years, calibrated synthetic microspheres loaded with a chemotherapeutic agent have been developed. They ensure uniform and prolonged release of the drug and the achievement of high concentrations of the chemotherapeutic agent in tumor cells. The method of transarterial embolization of the liver using grains containing the drug is known as DEB‑TACE (Drug‑eluting bead transarterial chemoembolization). The traditional TACE (conventional transarterial chemoembolization), technique is also widely used, in which a chemotherapeutic drug is administered together with lipiodol, and then with occlusive material. When comparing the techniques, no differences were found in their safety profiles. Despite the fact that transarterial embolization of the liver is considered a safe procedure, it is not without the risk of complications, the most common of which are acute cholecystitis and leukopenia. Also, a frequent undesirable phenomenon after transarterial chemoembolization of the liver is postembolization syndrome, which includes abdominal pain, hyperthermia up to 38 ° C and nausea. One of the rare complications occurring in less than 1% of cases is a complication of liver TACE – the development of a liver abscess against the background of tumor necrosis. It is believed that the formation of an abscess can lead to the formation of fistulas: hepaticobronchial, hepaticoduodenal, hepaticogastric, etc. Our article presents a rare clinical case of hepatogastric fistula formation after liver TACE.

Vessels That Encapsulate Tumor Clusters (VETC) Predict cTACE Response in Hepatocellular Carcinoma.

To investigate the correlation between hepatocellular carcinoma (HCC) pathological types and conventional transarterial chemoembolization (cTACE), and to evaluate the predictive value of the pathological types for efficacy of cTACE. We investigated 186 naive HCC patients from 2 hospitals, including 63 patients with recurrence after surgical resection, and 123 unresectable cases, who underwent at least one cTACE procedure as the first treatment. All patients were histologically diagnosed with HCC by surgical resection and/or liver biopsy. Lipiodol deposition rate, ORR (objective response rate), PFS (progression-free survival), OS (overallsurvival) were compared among different HCC pathological types. This study evaluated 186 naive HCC patients and 189 tumor nodules. Vessels that encapsulate tumor clusters (VETC), macrotrabecular-massive (MTM), CK19-positive types were identified in 38% (72/189), 40% (76/189), and 28% (53/189) of the whole cohort, respectively. VETC, MTM and CK19-negative HCCs derived significantly better lipiodol deposition rate and ORR. cTACE prolonged the PFS of VETC and CK19-negative HCCs compared with non-VETC and CK19-positive HCCs in the recurrence, liver biopsy and combining whole cohorts, whereas the OSs of different pathological types were not significantly different. Multivariate analysis showed that VETC (OR, 4.671, 95% CI [1.954, 11.166], P<0.001) and CK19-positive type (OR, 0.127, 95% CI [0.044, 0.362], P<0.001) were independent predictive factors for the first cTACE response. However, only VETC type was significantly associated with the second cTACE response in multivariate analysis (OR, 3.31, 95% CI [1.24, 8.83], P=0.017), suggesting that VETC might be a more useful predictor of cTACE response. Our study suggests that VETC is an effective predictor of cTACE response in patients with HCC.

The impact of drug-eluting bead (vs. conventional) transarterial chemoembolization on hepatic fibrosis in treating intermediate or advanced hepatocellular carcinoma

ABSTRACT Objective Limited studies have reported the impact of drug-eluting bead transarterial chemoembolization (DEB-TACE) on hepatic fibrosis in hepatocellular carcinoma (HCC). This study evaluated multiple hepatic fibrosis indicators, aiming to comprehensively compare the influence of DEB-TACE and conventional transarterial chemoembolization (cTACE) on hepatic fibrosis in treating HCC patients. Methods Intermediate/advanced HCC patients (N = 121) were divided into the DEB-TACE group (n = 62) and the cTACE group (n = 59) based on their chosen treatment. Serum hyaluronic acid (HA), pro-collagen type-III (PC-III), collagen type-IV (IV-C), and laminin (LN) were detected; aminotransferase to platelet ratio index (APRI) and fibrosis index based on the four factors (FIB-4) were calculated; liver stiffness measurement (LSM) was assessed by real-time shear wave elastography. Results HA, PC-III, IV-C, and LN at 1 month after the second TACE and at 12 months after the first TACE were all decreased in DEB-TACE group compared with cTACE group (all P < .050). Then, APRI, FIB-4, and LSM were further assessed, which also showed a decreasing trend at aforementioned timepoints in DEB-TACE group compared with cTACE group (all P < .050). Additionally, the multivariate logistic regression analysis revealed that DEB-TACE (vs. cTACE) was independently associated with reduced occurrence of severe hepatic fibrosis at 12 months (OR = 0.215, 95%CI: 0.058–0.802, P = .022). Concerning the liver function indexes, alanine aminotransferase, aspartate aminotransferase, and total bilirubin after treatment were not different between the two groups (all P > .050). Conclusion DEB-TACE displays attenuated hepatic fibrosis progression and noninferior tolerance compared to cTACE in treating intermediate- or advanced-stage HCC patients.

Efficacy of dexamethasone and N-acetylcysteine combination in preventing post-embolization syndrome after transarterial chemoembolization in hepatocellular carcinoma

Conventional transarterial chemoembolization (cTACE) is the current standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Post-embolization syndrome (PES) is complex clinical syndrome that presents as fever, abdominal pain, nausea, and vomiting. Either dexamethasone (DEXA) or N-acetylcysteine (NAC) is used to prevent PES; however, the synergistic effect of their combined therapy for preventing PES and liver decompensation has not been determined. To evaluate the efficacy of DEXA and NAC combination in preventing PES and liver decompensation after cTACE. Patients with Barcelona Clinic Liver Cancer stage A or B HCC who were scheduled for TACE were prospectively enrolled. All patients were randomly stratified to receive NAC and DEXA or placebo. The dual therapy (NAC + DEXA) group received intravenous administration of 10 mg DEXA every 12 h, NAC 24 h prior to cTACE (150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h), and a continuous infusion of 6.25 mg/h NAC plus 4 mg DEXA every 12 h for 48 h after cTACE. The placebo group received an infusion of 5% glucose solution until 48 h after procedure. PES was defined by South West Oncology Group toxicity code grading of more than 2 that was calculated using incidence of fever, nausea, vomiting, and pain. One-hundred patients were enrolled with 50 patients in each group. Incidence of PES was significantly lower in the NAC + DEXA group compared with in the placebo group (6% vs 80%; P < 0.001). Multivariate analysis showed that the dual treatment is a protective strategic therapy against PES development [odds ratio (OR) = 0.04; 95% confidence interval (CI): 0.01-0.20; P < 0.001). Seven (14%) patients in the placebo group, but none in the NAC + DEXA group, developed post-TACE liver decompensation. A dynamic change in Albumin-Bilirubin score of more than 0.5 point was found to be a risk factor for post-TACE liver decompensation (OR = 42.77; 95%CI: 1.01-1810; P = 0.049). Intravenous NAC + DEXA administration ameliorated the occurrence of PES event after cTACE in patients with intermediate-stage HCC.

Idarubicin-loaded biodegradable microspheres enhance sensitivity to anti-PD1 immunotherapy in transcatheter arterial chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary hepatocellular carcinoma (HCC). However, conventional TACE formulations such as epirubicin-lipiodol emulsion are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. To overcome these limitations, we used biodegradable Idarubicin loaded microspheres (BILMs), which were prepared from gelatin and carrageenan and could be loaded with Idarubicin (IDA-MS). The morphology and the ability to load and release IDA of BILMs were characterized in vitro. We evaluated tumor changes and side effects after TACE treatment with IDA-MS in VX2 rabbit and C57BL/6 mice HCC models. In addition, the effect of IDA-MS on the tumor immune microenvironment of HCC tumors was elucidated via mass spectrometry and immunohistochemistry. Result showed that IDA-MS was developed as a new TACE formulation to overcome the poor delivery of drugs due to rapid elimination of the anticancer drug into the systemic circulation. We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment. STATEMENT OF SIGNIFICANCE: Conventional transarterial chemoembolization (TACE) formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in hepatocellular carcinoma (HCC). To overcome these limitations, we used biodegradable microspheres called BILMs, which could be loaded with Idarubicin (IDA-MS). We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment.