Balloon-Assisted Portal Vein Embolization Using n-Butyl-2-Cyanoacrylate-Lipiodol-Iopamidol Mixture in Swine: A Comparison of 2 Formulations.

PURPOSE: To compare 2 ratios of n-butyl-2-cyanoacrylate (nBCA)-ethiodized oil (Lipiodol)-iopamidol (NLI) in balloon-assisted portal vein embolization (PVE) in swine. MATERIALS AND METHODS: In an in vitro study, NLI prepared at a ratio of 2:3:1 (NLI231) or 1:4:1 (NLI141) was injected into 2.5- or 10-mL syringes filled with swine blood, and the viscosity of NLI was measured to determine an appropriate balloon occlusion time. Two portal vein branches in 8 female swine (n = 16 vein branches) were embolized with NLI231 (n = 8) or NLI141 (n = 8) under balloon occlusion. Portal venography was performed before, immediately after, and 3 days after PVE to evaluate the migration of NLI and the recanalization of embolized portal vein branches. Then, the livers were removed for histopathologic evaluation. RESULTS: The times to peak viscosity of NLI231 in the 2.5- and 10-mL syringes were 55.8 seconds (SD ± 7.0) and 85.2 seconds (SD ± 6.3), and those to peak viscosity of NLI141 were 129.2 seconds (SD ± 11.8) and 254.0 seconds (SD ± 21.8), respectively. No migration of NLI231 was observed in all 8 procedures immediately or 3 days after PVE. Migration of NLI141 was observed in 6 of 8 procedures within 3 days after PVE. The migration frequency of the embolic material was lower in the NI231 group than in the NLI141 group (0/8 vs 6/8; P = .051). Histologically, NLI231 occupied the portal veins without any thrombi, whereas NLI141 was accompanied by thrombi in the portal veins. CONCLUSIONS: NLI231 may be more suitable than NLI141 for balloon-assisted PVE in swine.

Usefulness of ethiodized oil and gelatin sponge particles for delaying the washout of indocyanine green from the liver in swine.

PURPOSE: To assess the effect of ethiodized oil (EO) and gelatin sponge particles (GS) on delaying the washout of indocyanine green (ICG) from the liver in swine. METHODS: Fifteen swine were divided into 3 groups: injection of a mixture of ICG and water-soluble contrast medium (CM) followed by embolization with GS (group A), injection of a mixture of ICG and EO (group B) and injection of a mixture of ICG and EO followed by embolization with GS (group C). The liver surface was observed using an infrared camera system during and at 1, 2, 3, and 6 h after the procedure to measure ICG contrast. Livers were removed at 6 h for histopathological examination. RESULTS: The contrast ratio between injected and non-injected regions at 6 h was 1.45 ± 0.44 in group A, 1.89 ± 0.37 in group B, and 3.62 ± 0.76 in group C. The contrast ratio in group C was significantly greater than that in groups A and B (P = 0.032 and 0.033, respectively). CONCLUSIONS: EO and GS delayed the washout of ICG from the liver in swine and may extend intraoperative navigation in clinical use. Indocyanine green (ICG) mixed with ethiodized oil (EO) was injected into the left hepatic artery in swine, and the artery was embolized with gelatin sponge particles (GS). We confirmed that ICG remained in the liver parenchyma up to 6 h after the procedure. EO and GS delayed the washout of ICG from the liver in swine.

Determination of the Optimal Ratio and the Relationship Between Viscosity and Adhesion of n-Butyl Cyanoacrylate-Lipiodol-Iopamidol for Balloon-Assisted Embolization of Wide-Neck Aneurysms in Swine.

PURPOSE: To determine the optimal ratio of n-butyl cyanoacrylate-Lipiodol-iopamidol (NLI) for balloon-assisted embolization of wide-neck aneurysms in swine. MATERIALS AND METHODS: Sixteen NLI mixtures were prepared for in vitro studies. The viscosity of each mixture was measured for 30 min. We evaluated whether the mixtures could be injected through a microcatheter and whether they adhered to the microcatheter. In vivo, 15 wide-neck aneurysms were created on the arteries in 4 female swine. Under balloon occlusion, 7 aneurysms were embolized with NLI141 (NBCA:Lipidol:iopamidol = 1:4:1) and 8 were embolized with NLI231. We performed angiography to evaluate adhesion of NLI to the balloons or microcatheters and NLI migration. RESULTS: In vitro, the iopamidol content needed to comprise at least 1/6 of the mixture in order for NLI to be non-adhesive with increased viscosity. NLI could not be injected through a microcatheter if the iopamidol content exceeded 1/6 of the mixture. Only NLI141 and NLI231 did not adhere to the microcatheter with increased viscosity, and could be injected through a microcatheter. In vivo, neither NLI mixture adhered to the balloons or microcatheters. The migration of NLI was observed in 6 of 7 aneurysms embolized with NLI141 and in none of 8 aneurysms embolized with NLI231. CONCLUSION: Our in vitro study revealed that the ratios of NLI that were non-adhesive and could be injected through a microcatheter were 1:4:1 and 2:3:1. The optimal ratio of NLI for balloon-assisted embolization of wide-neck aneurysms in swine was considered to be 2:3:1.

Feasibility and Safety of n-Butyl Cyanoacrylate-Lipiodol-Iopamidol as an Alternative Liquid Embolic Material.

PURPOSE: To evaluate the feasibility and safety of n-butyl cyanoacrylate (NBCA)-Lipiodol-Iopamidol (NLI) as a liquid embolic material. MATERIALS AND METHODS: In vitro, the ratio of NLI components was adjusted and the configuration of the mixtures was assessed visually in saline. In vivo, 14 wide-necked aneurysms were created on the common carotid and external iliac arteries of four female swine. Under balloon occlusion, 12 aneurysms were embolized with NLI prepared at a NBCA-Lipidol-Iopamidol ratio of 2:3:1 (NLI231), and two were embolized with NBCA-Lipiodol (NL) prepared at a NBCA-Lipiodol ratio of 1:2 (NL12) as a trial group. We performed angiography to evaluate the effectiveness of embolization and adhesion of the embolic material to the balloons or microcatheters. RESULTS: In vitro, NLI231 (33% NBCA) was considered to be the optimal ratio for aneurysm embolization based on its configuration and stability. In vivo, embolization using NLI231 was successful and no adhesion between the embolic material and the balloons or microcatheters was observed in all 12 aneurysms. Embolization with NL12 was impossible in the other two aneurysms due to leakage and adhesion of NL. CONCLUSION: The configuration of NLI changed at each ratio. NLI231 is a feasible and safe liquid embolic material for balloon-assisted embolization of wide-necked aneurysms in swine.

Balloon-Assisted Embolization of Wide-Neck Aneurysms Using a Mixture of n-Butyl Cyanoacrylate, Lipiodol, and Ethanol in Swine: A Comparison of Four n-Butyl Cyanoacrylate Concentrations.

PURPOSE: To determine the optimal ratio of n-butyl cyanoacrylate (NBCA)-Lipiodol-ethanol (NLE) mixture for balloon-assisted embolization of wide-neck aneurysms. MATERIALS AND METHODS: We created 32 wide-neck aneurysms on both the common carotid arteries and external iliac arteries in eight female swine. Eight aneurysms were randomly assigned to four groups. Under balloon occlusion, the aneurysms were packed using NLE at one of four ratios of NLE: 2:2:1 (NLE221; 40%NBCA); 3:6:1 (NLE361; 30%NBCA); 2:7:1 (NLE271; 20%NBCA); and 1:5:1 (NLE151; 14.3%NBCA). We performed angiography before and after embolization to assess the aneurysms, and we compared adhesion between NLE and the balloon and assessed NLE migration. Three days after embolization, the aneurysms were removed for histopathologic evaluation. RESULTS: Embolization was performed in 27 aneurysms. Adhesion between NLE and the balloon was not observed in any group. NLE migration was found in 0/7 aneurysms in the NLE221 group, 0/6 in the NLE361 group, 5/6 in the NLE271 group, and 7/8 in the NLE151 group. NLE migration was significantly lower in the NLE221 group than in the NLE271 and NLE151 groups (P = 0.0047 and 0.0014, respectively) and was significantly lower in the NLE361 group than in the NLE271 and NLE151 groups (P = 0.0152 and 0.0047, respectively). Media necrosis of the arterial wall close to the aneurysms was observed in all groups. CONCLUSION: NLE with an NBCA concentration of ≥ 30% is a safe and feasible embolic material for balloon-assisted embolization of wide-neck aneurysms in swine in the short term up to 3 days after embolization.

Prophylactic Intraoperative Embolization of Abdominal Aortic Aneurysm Sacs Using N-Butyl Cyanoacrylate/Lipiodol/Ethanol Mixture with Proximal Neck Aortic Balloon Occlusion during Endovascular Abdominal Aortic Repair.

PURPOSE: To determine the feasibility of prophylactic intraoperative abdominal aortic aneurysm (AAA) sac embolization using a mixture of N-butyl cyanoacrylate/Lipiodol/ethanol (NLE) with proximal neck aortic balloon occlusion during endovascular aneurysm repair (EVAR) to prevent the occurrence of endoleak and aneurysm sac expansion. MATERIALS AND METHODS: Prophylactic intraoperative AAA sac embolization was performed in 24 patients with an infrarenal neck angulation > 60° (n = 16) or AAA sac diameter > 60 mm (n = 17). AAA sac pressure was continuously measured with a 3-F catheter inserted into the AAA sac. The systolic sac pressure index (SPI) was calculated as the ratio of systolic AAA sac pressure to the simultaneously measured systolic aortic pressure, and was measured with and without proximal neck aortic balloon occlusion. The aneurysm sac was embolized with NLE during proximal neck aortic balloon occlusion immediately after EVAR. Endoleak and AAA sac diameter were evaluated by enhanced computed tomography and subtraction magnetic resonance imaging at 6 months and yearly after EVAR. RESULTS: Mean SPIs after EVAR with and without proximal neck aortic balloon occlusion were 0.36 and 0.57, respectively. There were no adverse events related to intraoperative sac embolization. Follow-up imaging (mean, 12.1 mo) revealed three minor endoleaks (12.5%) and no aneurysm sac expansion. CONCLUSIONS: Prophylactic intraoperative sac embolization with NLE during proximal neck aortic balloon occlusion was safe and feasible and may reduce endoleaks and prevent sac expansion after EVAR in patients with unfavorable anatomic factors.

Clinical evaluation of transcatheter arterial chemoembolization with 2-day-soluble gelatin sponge particles for hepatocellular carcinoma-comparison with insoluble gelatin sponge particles.

PURPOSE: To compare therapeutic effect, adverse events, and embolized hepatic artery impairment in transcatheter arterial chemoembolization between Lipiodol plus insoluble gelatin sponge particles (Gelpart) and Lipiodol plus 2-day-soluble gelatin sponge particles (2DS-GSPs). MATERIALS AND METHODS: In a single-center, prospective, randomized controlled trial, patients with hepatocellular carcinoma were assigned to the 2DS-GSP group or the Gelpart group. Radiographic response at 3 months per modified Response Evaluation Criteria In Solid Tumors was evaluated as the primary endpoint; secondary endpoints were safety (per Common Terminology Criteria for Adverse Events, version 4.0) within 3 months and hepatic branch artery impairment at the time of repeat chemoembolization (grade 0, no damage; grade I, mild vessel wall irregularity; grade II, overt stenosis; grade III, occlusion of more peripheral branch artery than subsegmental artery; grade IV, occlusion of subsegmental artery). Grade II, III, or IV indicated significant hepatic artery impairment. RESULTS: Thirty-seven patients with 143 nodules were randomized to the 2DS-GSP group and 36 patients with 137 nodules were randomized to the Gelpart group. No significant differences in patient background existed between groups. Target lesion response and overall tumor response in the 2DS-GSP and Gelpart groups were 77.7% versus 76.9% and 78.3% versus 77.8%, respectively, with no significant differences. No significant difference in adverse events existed between groups. Hepatic artery impairment was observed in 5% of patients in the 2DS-GSP group (n = 32) and in 16% in the Gelpart group (n = 33; P< .001). CONCLUSIONS: Transcatheter arterial chemoembolization with 2DS-GSPs resulted in the same therapeutic and adverse effects as chemoembolization with Gelpart while causing significantly less hepatic artery impairment.

Basic study of a mixture of N-butyl cyanoacrylate, ethanol, and lipiodol as a new embolic material.

PURPOSE: To clarify the configuration change of N-butyl cyanoacrylate (NBCA) polymerization with increasing proportion of ethanol, the properties of a mixture of NBCA with lipiodol plus ethanol (NLE), and the feasibility of use of NLE for aneurysm packing in a swine model. MATERIALS AND METHODS: The polymerization configuration of NLE was explored using ratios of 1-4 parts NBCA and 1-3 parts ethanol per 1 part of lipiodol; a 1:1 ratio of NBCA to lipiodol (NLE110) was used as a control. The distance that NLE migrated into saline flowing in a tube was measured. A carotid artery aneurysm was created in each of 18 swine. Aneurysmal packing with three configurations--NLE110, NLE at a ratio of 1:1:2 (NLE112), and NLE at a ratio of 1:1:3 (NLE113)--was attempted in six swine for each configuration. RESULTS: Regardless of NBCA composition, medium-sized droplets, a single large droplet, and a noodle-shaped extrusion were observed in NLE with lipiodol versus ethanol ratios of 1:1, 1:2, and 1:3. NLE110 migrated as viscous fluid to 190 cm from the injection site, whereas NLE112 migrated for 81 cm ± 11 and NLE113 migrated for 74 cm ± 9. Instant outflow of NLE110 from the six aneurysms caused occlusion of the parent artery, with adhesion to the microcatheter. Packing was achieved with minimal adhesion for all six of the aneurysms packed with NLE112 or with NLE113. CONCLUSIONS: With high ratios of ethanol, the NLE polymerization configuration acquired solid-like properties with potent occlusive ability and negligible adhesion to the microcatheter, suggesting its feasibility for packing of aneurysms.

Pathologic evaluation of damage to bronchial artery, bronchial wall, and pulmonary parenchyma after bronchial artery embolization with N-butyl cyanoacrylate for massive hemoptysis.

Histologic evidence of safety after bronchial arterial embolization (BAE) with N-butyl cyanoacrylate (NBCA) should be assured. The present report describes a 78-year-old man with massive hemoptysis from lung cancer who underwent surgical lobectomy 23 days after hemostasis had been achieved via BAE with NBCA. Pathologic examination revealed that NBCA filled the lumen of bronchial branch arteries 143-1,094 µm in diameter from the lobar bronchus to subsegmental bronchus but was not seen in the lumen of the pulmonary artery or pulmonary vein. NBCA induced occlusion of bronchial branch arteries but no necrosis of the bronchial wall or pulmonary parenchyma.

Prospective comparison of transcatheter arterial chemoembolization with Lipiodol-epirubicin and Lipiodol-cisplatin for treatment of recurrent hepatocellular carcinoma.

PURPOSE: The aim of this study was to compare the safety and short-term efficacy of transcatheter arterial chemoembolization (TACE) using cisplatin-Lipiodol suspension (CP/Lp) with that using epirubicin-Lipiodol emulsion (EP/Lp) in patients with recurrent hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 28 HCC patients were enrolled prospectively and assigned to the CP/Lp group or EP/Lp group. Adverse effects related to TACE were graded; and the treatment effect (TE) on HCC nodules at 3 months and overall tumor response at 6 months were assessed as the endpoint. RESULTS: No significant difference was observed between the groups regarding the frequency of adverse effects of grade 3 or less. The TE rates for 100% necrosis plus >50% necrosis in 62 HCC nodules in the CP/Lp group and 75 HCC nodules in the EP/Lp group were 72.6% and 66.7%, respectively (P = 0.894). Overall tumor response revealed that six patients (50.0%) in the CP/Lp group and six patients (37.5%) in the EP/Lp group had a partial response plus a complete response, with no significant difference (P = 0.615). TACE-free control curves for both groups revealed no significant difference (P = 0.513). CONCLUSION: No significant difference was found with regard to adverse effects, the treatment effect on HCC nodules, or overall tumor response between the CP/Lp and EP/Lp groups.

Triple-phase computed tomography during arterial portography with bolus tracking for hepatic tumors.

PURPOSE: The purpose of this study was to assess the usefulness of triple-phase computed tomography during arterial portography (CTAP) using a bolus-tracking technique. MATERIAL AND METHODS: The subjects were 60 patients with hepatic tumors: 20 patients with metastatic liver tumors with a normal liver and 40 with hypervascular hepatocellular carcinoma (HCC) with liver cirrhosis. The region of interest was set in the portal vein, and CTAP was automatically started after the triggering threshold (180 HU) was reached. Three scans were performed: early phase (E), hepatic parenchymal phase (HP), and late phase (L). The scan start time of E-CTAP was measured. The detection rates of the HCC nodules were evaluated during each CTAP phase. RESULTS: CTAP was performed by bolus tracking without failure in any of the patients. The mean scan start times in the normal liver group and liver cirrhosis group were 14.3 +/- 1.34 s and 18.5 +/- 2.46 s, respectively, which were significantly different from each other. The detection rates of HCC nodules for E-CTAP, HP-CTAP, and L-CTAP were 29.6%, 100%, and 83.3%, respectively. CONCLUSION: The bolus-tracking technique enabled us to perform CTAP with optimal timing regardless of the portal blood flow dynamics.