Factors predicting overall response and overall survival in hepatocellular carcinoma patients undergoing balloon-occluded transcatheter arterial chemoembolization: A retrospective cohort study.

AIM: This study aimed to investigate the factors predicting overall response and overall survival in hepatocellular carcinoma patients undergoing balloon-occluded transcatheter arterial chemoembolization (B-TACE). METHODS: Sixty-six patients treated with B-TACE at a Japanese tertiary referral hospital between January 2011 and August 2015 were included in this retrospective cohort study. RESULTS: The overall response was classified as complete response, partial response, stable disease, and progressive disease in 35 (53.0%), 7 (10.6%), 13 (19.7%), and 11 (16.7%) patients, respectively. The response rate was 63.6%, and the disease control rate was 83.3%. The number of tumors (hazard ratio [HR], 4.44; 95% confidence interval [CI], 1.26-15.7; P = 0.021) and α-fetoprotein level (HR, 11.40; 95% CI, 2.75-46.9; P < 0.001) were significantly associated with the tumor response in a multivariate analysis. The 1-, 2-, and 3-year survival rates were 76.8% (95% CI, 64.5-85.3%), 57.3% (95% CI, 42.3-69.7%), and 46.7% (95% CI, 30.7-61.2%), respectively. The median survival time was 902 days. Albumin (≥3.4 g/dL) (HR, 0.28; 95% CI, 0.12-0.63; P = 0.002) and overall response (complete response and partial response) (HR, 0.33; 95% CI, 0.16-0.71; P = 0.004) were factors significantly associated with overall survival in a multivariate analysis. No mortalities were observed, but biloma requiring percutaneous transhepatic biliary drainage occurred in one patient (1.5%). CONCLUSION: Balloon-occluded transcatheter arterial chemoembolization may exert a good antitumor effect and result in good overall survival in select hepatocellular carcinoma patients.

Hemodynamic Changes on Cone-Beam Computed Tomography during Balloon-Occluded Transcatheter Arterial Chemoembolization Using Miriplatin for Hepatocellular Carcinoma: A Preliminary Study.

BACKGROUND/AIM: Balloon-occluded transcatheter arterial chemoembolization (B-TACE) using miriplatin (MPT) is anticipated as a new strategy for hepatocellular carcinoma (HCC). This study was aimed at evaluating the hemodynamic changes with/without balloon occlusion of the hepatic artery, correlation of cone-beam CT (CBCT) pixels, and CT value after B-TACE for HCC. METHODS: A total of 52 patients with HCC, who underwent B-TACE using MPT in addition to the balloon-occluded CBCT hepatic arteriography, were studied. RESULTS: After balloon occlusion, CBCT pixel values increased in 37 lesions, whereas it decreased in 15 lesions. Intratumoral CT values after B-TACE were lower with decreased CBCT pixel values than with increased CBCT pixel values. CONCLUSION: Hemodynamic changes on CBCT during balloon occlusion can be used to predict the efficacy of B-TACE using MPT.

Usefulness and limitations of balloon-occluded transcatheter arterial chemoembolization using miriplatin for patients with four or fewer hepatocellular carcinoma nodules.

AIM: The aim of this study is to clarify the usefulness and limitations of balloon-occluded transcatheter arterial chemoembolization (B-TACE) using miriplatin for patients with four or fewer hepatocellular carcinoma (HCC) nodules. METHODS: We studied 47 nodules in 30 consecutive patients who received miriplatin by B-TACE to treat HCC with four or fewer nodules per patient. The treatment effect was evaluated using the Response Evaluation Criteria in Cancer of the Liver. RESULTS: Nodules were divided according to the presence or absence of portal vein visualization during B-TACE. In the presence group, dynamic computed tomography at 3 months post-therapy showed Response Evaluation Criteria in Cancer of the Liver treatment effect (TE) 4 in 88% (14/16), TE3 in 0% (0/16), TE2 in 0% (0/16), TE1 in 12% (2/16), and objective response in 88% of nodules. In the absence group, the results were TE4 in 35% (11/31), TE3 in 13% (4/31), TE2 in 26% (8/31), TE1 in 26% (8/31), and objective response decreased to 48% of nodules. In addition to typical hypervascular nodules, we treated three nodules with irregular ring enhancement that predicted poorly differentiated HCC and four nodules that included a hypoenhancement area that predicted well to moderately differentiated HCC. All irregular ring enhancement nodules achieved TE4. Other nodules that were predicted to be well to moderately differentiated HCC did not have portal vein visualization during B-TACE and could not achieve TE4. CONCLUSION: Balloon-occluded transcatheter arterial chemoembolization is a useful technique for treatment of classical hypervascular HCC, and portal vein visualization during the B-TACE procedure may provide more favorable local control.

Temporal variations in stump pressure and assessment of images obtained from cone-beam computed tomography during balloon-occluded transarterial chemoembolization.

AIM: Balloon-occluded transcatheter arterial chemoembolization (B-TACE) was used to show the optimized duration of balloon occlusion to start injection of lipiodol in order to maximize lipiodol deposition in the nodule, and to reveal the endpoint of lipiodol injection. METHODS: Of 29 consecutive patients who underwent balloon-occluded TACE between November 2013 and February 2014, we were able to measure stump pressure for 219 nodules in 27 patients. Tumors were counted, measured and could be visually assessed in 20 of these patients at 26 sites. Tumors with multiple feeders were found in eight patients. Arterial blood pressure was measured before, immediately after and 5 min after balloon occlusion prior to intra-arterial injection, as well as before and after balloon deflation after intra-arterial injection. Images were assessed qualitatively by two radiologists as well as quantitatively by calculating the contrast-to-noise ratio. RESULTS: We found no significant difference in pressure between immediately after and 5 min after balloon occlusion. Mean stump pressure before balloon deflation after intra-arterial injection was 70.4 mmHg. We observed a significant increase in qualitative scores after balloon occlusion (P < 0.001), and the mean score in the third-order branch was significantly higher than that in the first-order branch (P = 0.048). CONCLUSION: Our results indicate that intra-arterial injection can be started at any time after balloon occlusion and that 70 mmHg may be considered as a possible indicator of the end-point for arterial injection.

Safety and efficacy of balloon-occluded transcatheter arterial chemoembolization using miriplatin for hepatocellular carcinoma.

AIM: Balloon-occluded transcatheter arterial chemoembolization (B-TACE) using a microballoon catheter was performed to administrate miriplatin, and the early therapeutic efficacy and safety of the procedure were evaluated. METHODS: Out of 158 patients who received miriplatin using B-TACE for hepatocellular carcinoma, 49 patients with a single lesion at either stage I or II (according to the Liver Cancer Study Group of Japan) were evaluated in comparison with 48 matched patients who received miriplatin using conventional TACE (C-TACE). RESULTS: The mean total dose and median dose of miriplatin in each group were 32.5 ± 31.7 mg and 20 mg (C-TACE) and 50.1 ± 31.3 mg and 40 mg (B-TACE), respectively (P < 0.01). The treatment effect (TE) on the target nodule classified as TE4, TE3, TE2 or TE1 was 39.6%, 33.3%, 25.0% and 2.1%, respectively, in the C-TACE group, and 55.1%, 38.8%, 4.1% and 2.0%, respectively, in the B-TACE group. Therefore, the TE was significantly higher in the B-TACE group (P < 0.05). Although abdominal blood tests revealed adverse, increased levels of serum alanine aminotransferase (ALT) in a significantly higher number of B-TACE-treated patients, serum ALT levels returned to baseline levels in all patients within 1 month. There were no significant differences in clinical symptoms between the two groups. CONCLUSION: Compared with C-TACE, B-TACE significantly improved cancer nodule control, and it was satisfactory in terms of safety. B-TACE is an effective procedure that enhances the effects of catheterization with miriplatin.

Prediction of common hepatic artery catheter insertion based on celiac trunk morphology

PURPOSE: This study aimed to predict the ability to insert a 4-5 French (Fr) catheter insertion with a guidewire into the common hepatic artery (CHA) based on celiac trunk morphology. METHODS: This retrospective study included 64 patients who underwent balloon-occluded transcatheter arterial chemoembolization (n = 56), transcatheter arterial chemotherapy (n = 2), or were fitted with an implantable port system (n = 6) between June 2019 and December 2019 in our institution. The morphology of the celiac trunk was classified into three types (upward, horizontal, and downward) based on celiac angiography. The aortic-celiac trunk angle was measured on sagittal images of preprocedural contrast-enhanced computed tomography (CT). We reviewed whether a 4-5-Fr shepherd's hook catheter could advance beyond the CHA using a 0.035-inch guidewire (Radifocus® Guidewire M; Terumo). Three patients were diagnosed with median arcuate ligament syndrome (MALS) based on the characteristic hook shape of the celiac artery on sagittal images of contrast-enhanced CT. The predictive ability of celiac angiography and preprocedural CT for CHA insertion success was evaluated. In unsuccessful cases, the balloon anchor technique (BAT) was attempted as follows: (1) a 2.7/2.8-Fr microballoon catheter (Attendant Delta; Terumo) was placed beyond the proper hepatic artery, and (2) the balloon was inflated as an anchor for parent catheter advancement. RESULTS: Upward, horizontal, and downward celiac trunk types were noted in 42, 9, and 13 patients, respectively. The median CT angle was 122.83° (first quartile-third quartile, 102.88°-136.55°). Insertion in the CHA using the guidewire was successful in 56 of 64 patients (87.50%), and the success rate in the downward type was significantly lower than that in the upward type [42/42 (100%) vs. 7/13 (53.85%), P < 0.001]. The CT angle was significantly larger downward in the unsuccessful group than in the successful group (121.03° vs. 140.70°, P = 0.043). Celiac angiography had a significantly higher area under the curve (AUC) than preprocedural CT (AUC = 0.91 vs. AUC = 0.72, P = 0.040). All three cases of MALS showed unsuccessful CHA insertion. In all eight patients with unsuccessful insertion, the catheter could be advanced using the BAT [8/8 (100%)]. CONCLUSION: Celiac angiography and preprocedural CT could predict CHA catheter insertion using a guidewire, and celiac angiography had high predictability. CT could detect MALS, a risk factor for unsuccessful CHA insertion.

Percutaneous Thermal Segmentectomy: Proof of Concept.

AIM: To report the multicenter retrospective experience on combination of balloon-occluded MWA(b-MWA) followed by balloon-occluded TACE(b-TACE) in patients with liver malignancies > 3 cm, focusing on appearance and volume of necrotic area, safety profile and oncological results. MATERIALS AND METHODS: Twenty-three patients with liver primary malignancies (hepatocellular carcinoma,HCC = 18; intrahepatic cholangiocarcinoma,iCC = 2) and metastasis (colorectal cancer metastasis = 1;sarcoma metastasis = 1;breast metastasis = 1) were treated. Maximum mean diameter of lesions was 4.4 cm (± 1 cm). Treatments were performed using a single-step approach:b-MWA was performed after balloon-microcatheter inflation, followed by b-TACE (with epirubicin or irinotecan). Necrotic area shape and discrepancy with the expected volume of necrosis suggested by vendor's ablation chart were assessed at post-procedural CT. Complications were categorized according to CIRSE classification. Oncological results at 1 and 3-6 months were evaluated using m-RECIST(HCC) and RECISTv1.1(metastasis/iCC). RESULTS: Mean volume of necrotic area was 75 cm3 (± 36). Discrepancy with vendor chart consisted in a medium percentage of volumetric incrementation of necrotic area of 103.2% (± 99.8). Non-spherical shape was observed in 22/23 patients (95.7%). No complications occurred; Post-embolization syndrome occurred in 12/23patients. Complete response and partial response were, respectively, 91, 3% (21/23) and 8.7% (2/23) at 1 month, 85.7% (18/21) and 9.5% (2/21) at 3-6 months. Progression of disease was 4.7% (1/21) at 3-6 months for extra-hepatic progression. Among partial responders, average percentage of tumor volume debulking was 78.8% (± 9.8%). CONCLUSION: b-MWA followed by b-TACE in a single-step procedure led to larger necrotic areas than the proposed by vendors ablation chart, non-spherical in shape and corresponded to the vascular segment occluded during ablation. This permitted to safely achieve promising oncological results in patients with > 3 cm tumors.

Balloon-Occluded Transarterial Chemoembolization: In Which Size Range Does It Perform Best? A Comparison of Its Efficacy versus Conventional Transarterial Chemoembolization, Using Propensity Score Matching.

INTRODUCTION: The aim of this multicenter comparison of balloon-occluded transarterial chemoembolization (B-TACE) versus conventional TACE (cTACE) in treating hepatocellular carcinoma (HCC) was to assess in which size range the 2 techniques offered higher complete response (CR) and objective response (OR) rates in a single session, and to evaluate the possibility of using B-TACE to reduce the need for re-treatment. METHODS: 325 patients were retrospectively evaluated: 91 patients in the B-TACE group (22 with cTACE [B-cTACE] and 69 with drug-eluting microsphere TACE [B-DEM-TACE]) and 234 in the cTACE group. The results were compared according to tumor size: (A) <30 mm, (B) 30-50 mm, and (C) >50 mm; OR and CR rates after the first session and the number of TACE re-interventions within a 6-month period were also evaluated using propensity score matching (PSM). RESULTS: The best target ORs were very high (93.2%) and similar between the 2 treatments both before (94.4% for cTACE and 90.1% for B-TACE) and after PSM (94.5% for cTACE and 90.1%; p = 0.405), with slightly better results for the cTACE cohort probably due to better cTACE effectiveness in smaller lesions. In lesions <30 mm, cTACE obtained a slightly higher CR rate than B-TACE (61.9 vs. 56.3%, p = 0.680), whereas in intermediate-sized HCCs (30-50 mm), B-TACE showed a significant superiority in achieving a CR (72.3 vs. 54.1%, respectively; p = 0.047). In larger lesions (>50 mm), cTACE and B-TACE performed equally, with a poor CR rate (22.6 vs. 23.1%, respectively; p = 1.000). These results were additionally confirmed using PSM. The patients treated with B-TACE had a significantly lower re-treatment rate than the cTACE cohort (12.1 vs. 26.9%, respectively; p = 0.005). B-cTACE and B-DEM-TACE demonstrated similar ORs, with a slightly better CR rate for B-cTACE (68.2 vs. 56.5%, respectively; p = 0.456). CONCLUSION: In HCCs of 30-50 mm, B-TACE should be preferred to cTACE, whereas in smaller nodules (<30 mm), cTACE can suffice in achieving a good CR rate. The statistically significant lower re-treatment rate of the B-TACE cohort after a single procedure reduced the risk of complications due to multiple TACE, which could worsen the patient prognosis.

Retrospective European Multicentric Evaluation of Selective Transarterial Chemoembolisation with and without Balloon-Occlusion in Patients with Hepatocellular Carcinoma: A Propensity Score Matched Analysis.

PURPOSE: The aim of this retrospective multicentric study was to compare the tumour response rates of Balloon-occluded Transarterial Chemoembolisation (B-TACE) to non-B-TACE using propensity score matching (PSM) in patients with hepatocellular carcinoma and to investigate the clinical benefit, such as lower rates of TACE re-intervention achieved using B-TACE. MATERIAL AND METHODS: The B-TACE procedures (n = 96 patients) were compared with a control group of non-B-TACE treatments (n = 434 pts), performed with conventional (cTACE) or drug-eluting microspheres TACE (DEM-TACE). Data were collected from six European centres from 2015 to 2019. Objective responses (OR) and complete response (CR) rates after the first session and the number of TACE re-interventions were evaluated using PSM (91 patients per arm). RESULTS: The best target OR after PSM were similar for both B-TACE and non-B-TACE (90.1% and 86.8%, p = 0.644); however, CR at 1-6 months was significantly higher for B-TACE (59.3% vs. 41.8%, p = 0.026). Patients treated with B-TACE had a significantly lower retreatment rate during the first 6 months (9.9%% vs. 22.0%, p = 0.041). Post-embolisation syndrome (PES) rates were 8.8% in non-B-TACE and 41.8% in B-TACE (p < 0.001), with no significant differences between groups regarding major adverse events. CONCLUSION: B-TACE is safe and effective, achieving higher CR rates than non-B-TACE. Patients undergoing B-TACE had a significantly lower retreatment rate within the first 6 months but higher PES rates. LEVEL OF EVIDENCE III: Level 3, retrospective study.

Balloon-Occluded Transcatheter Arterial Chemoembolization (b-TACE) for Hepatocellular Carcinoma Performed with Polyethylene-Glycol Epirubicin-Loaded Drug-Eluting Embolics: Safety and Preliminary Results.

PURPOSE: To report technical success, safety profile and oncological results of balloon-occluded transcatheter arterial chemoembolization using a balloon micro-catheter and epirubicin-loaded polyethylene-glycol (PEG) microsphere (100 ± 25 µm and 200 ± 50 µm) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This is a single-centre, single-arm, retrospective study with 6-month follow-up. Twenty-two patients (Child-Pugh A 68% [15/22], B in 32% [7/22]; age 67.05 ± 14 years) with 29 HCC were treated in 24 procedures. Technical success is defined: ability to place the balloon micro-catheter within the required vascular segment, balloon-occluded arterial stump pressure drops and assessment of microsphere deposition. Laboratory assessment pre/post-procedural and complications were analysed, respectively, according to Common Terminology Criteria for Adverse Events (CTCAEv5) and CIRSE system. Postembolization syndrome (PES) was defined as fever and/or nausea and/or pain onset. Oncological results were evaluated using m-RECIST criteria with CT/MRI imaging at 1 and 3-6 months. In partial responder patients, pre/post-procedural tumour volume was compared. RESULTS: Pre-planned feeder was reached in all cases. Pressure drop average was 51.1 ± 21.6 mmHg. Exclusive target embolization was achieved in 14/24 procedures (58.3%). Laboratory test modifications were all grade 1. 4/24 adverse events occurred (17%): pseudo-aneurysm of the feeder (grade 3), liver abscess (grade 2) and 2 asymptomatic segmentary biliary tree dilatations (grade 2). PES occurred in 8/24 (33%). The complete response at 1 and 3-6 months was 44.8% (13/29) and 52.9% (9/17), respectively. The partial response at 1 and 3-6 months was 55% (16/29) and 4/17 (23.5%), respectively. Among partial responder patients, the average percentage of tumour volume reduction was 64.9 ± 27.3%. CONCLUSION: Epirubicin-loaded PEG microsphere b-TACE is technically feasible, safe and effective procedure for HCC treatment.

Balloon-occluded transcatheter arterial chemoembolization for hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is widely accepted as a treatment for patients with hepatocellular carcinoma (HCC) in the intermediate stage according to the Barcelona Clinic Liver Cancer (BCLC) guidelines. Recently, balloon-occluded TACE (B-TACE) was developed in Japan. Despite the lack of a clear definition, B-TACE is generally defined as the infusion of emulsion of chemotherapeutic agents with lipiodol followed by gelatin particles under the occlusion of feeding arteries by a microballoon catheter, which leads to the dense lipiodol emulsion (LE) accumulation in HCC nodules. This phenomenon cannot be explained only by the prevention of proximal migration and leakage of embolization materials; it further involves causing local changes in the hemodynamics of the surrounding occlusion artery and targeted HCC nodules. Balloon-occluded arterial stump pressure plays an important role in the dense LE accumulation in targeted HCC nodules. Although randomized controlled trials comparing the therapeutic effect and the prognosis of B-TACE to those of the other TACE procedures, such as conventional-TACE and drug-eluting beads TACE, are still lacking, B-TACE is thought to be a promising treatment. The purpose of this review is to summarize the mechanism, therapeutic effect, indication, prognosis and complications of B-TACE.

Change in Imaging Findings on Angiography-Assisted CT During Balloon-Occluded Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma.

PURPOSE: To evaluate changes in imaging findings on CT during hepatic arteriography (CTHA) and CT during arterial portography (CTAP) by balloon occlusion of the treated artery and their relationship with iodized oil accumulation in the tumor during balloon-occluded transcatheter arterial chemoembolization (B-TACE). METHODS: Both B-TACE and angiography-assisted CT were performed for 27 hepatocellular carcinomas. Tumor enhancement on selective CTHA with/without balloon occlusion and iodized oil accumulation after B-TACE were evaluated. Tumorous portal perfusion defect size on CTAP was compared with/without balloon occlusion. Factors influencing discrepancies between selective CTHA with/without balloon occlusion and the degree of iodized oil accumulation were investigated. RESULTS: Among 27 tumors, tumor enhancement on selective CTHA changed after balloon occlusion in 14 (decreased, 11; increased, 3). In 18 tumors, there was a discrepancy between tumor enhancement on selective CTHA with balloon occlusion and the degree of accumulated iodized oil, which was higher than the tumor enhancement grade in all 18. The tumorous portal perfusion defect on CTAP significantly decreased after balloon occlusion in 18 of 20 tumors (mean decrease from 21.9 to 19.1 mm in diameter; p = 0.0001). No significant factors influenced discrepancies between selective CTHA with/without balloon occlusion. Central area tumor location, poor tumor enhancement on selective CTHA with balloon occlusion, and no decrease in the tumorous portal perfusion defect area on CTAP after balloon occlusion significantly influenced poor iodized oil accumulation in the tumor. CONCLUSIONS: Tumor enhancement on selective CTHA frequently changed after balloon occlusion, which did not correspond to accumulated iodized oil in most cases.

Transarterial chemoembolization for hepatocellular carcinoma: A review of techniques.

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide. While curative therapies, including resection, liver transplantation, and percutaneous ablation (percutaneous ethanol injection and radiofrequency ablation), are applicable for only a portion of the HCC population, transcatheter arterial chemoembolization (TACE) has been recognized as an effective palliative treatment option for patients with advanced HCC. TACE is also used even for single HCCs in which it is difficult to perform surgical resection or locoregional treatment due to systemic co-morbidities or anatomical problems. TACE has become widely adopted in the treatment of HCC. By using computed tomography-angiography, TACE is capable of performing diagnosis and treatment at the same time. Furthermore, TACE plays an important role in the multidisciplinary treatment for HCC when combined with other treatment. In this review, we first discuss the history of TACE, and then review the previous findings about techniques of achieving a locoregional treatment effect (liver infarction treatment, e.g., ultra-selective TACE, balloon-occluded TACE), and the use of TACE as a drug delivery system for anti-cancer agents (palliative, e.g., platinum complex agents, drug-eluting beads) for multiple lesions.