Effects of temperature alteration on viscosity, polymerization, and in-vivo arterial distribution of N-butyl cyanoacrylate-iodized oil mixtures.

PURPOSE: Temperature alteration can modify the polymerization of n-butyl cyanoacrylate (NBCA)-iodized oil mixtures during vascular embolization; its effects on viscosity, polymerization time, and intra-arterial distribution of the NBCA-iodized oil mixture were investigated. MATERIALS AND METHODS: In vitro, the viscosities of NBCA, iodized oil, and NBCA-iodized oil mixtures (ratio, 1:1-8) were measured at 4-60 ºC using a rotational rheometer. The polymerization times (from contact with blood plasma to stasis) were recorded at 0-60 ºC using a high-speed video camera. In vivo, the 1:2 mixture was injected into rabbit renal arteries at 0, 20, and 60 ºC; intra-arterial distribution of the mixture was pathologically evaluated. RESULTS: The mixtures' viscosities decreased as temperature increased; those at 60 ºC were almost four to five times lower than those at 4 ºC. The polymerization time of NBCA and the 1:1-4 mixtures increased as temperature decreased in the 0-30 ºC range; the degree of time prolongation increased as the percentage of iodized oil decreased. The 0 ºC group demonstrated distributions of the mixture within more peripheral arterial branches than the 20 and 60 ºC groups. CONCLUSION: Warming reduces the mixture's viscosity; cooling prolongs polymerization. Both can be potential factors to improve the handling of NBCA-iodized oil mixtures for lesions requiring peripheral delivery. Temperature alteration influences the polymerization time, viscosity, and intra-arterial distribution of NBCA-iodized oil mixtures. Warming reduces the viscosity of the mixture, while cooling prolongs polymerization.

In vivo evaluation of a monodisperse solid-in-oil-in-water miriplatin/ lipiodol emulsion in transcatheter arterial chemoembolization using a rabbit VX2 tumor model.

Transcatheter arterial chemoembolization (TACE) is a standard treatment for unresectable hepatocellular carcinoma; however, it does not always result in tumor control. Nevertheless, treatment outcome can be improved with monodisperse emulsions of anticancer agents. In this study, the distribution of a monodisperse miriplatin-Lipiodol emulsion in the tumor and its safety were evaluated in ten Japanese white rabbits. VX2 tumor was implanted into the left liver lobe. The animals were divided into control and experimental groups (of five animals each) and respectively administered a conventional miriplatin suspension or the emulsion via the left hepatic artery. Computed tomography (CT) was performed before, immediately after, and two days following TACE. All rabbits were sacrificed two days after the procedure. Each tumor was removed and cut in half for assessment of iodine concentration in one half by mass spectroscopy and evaluation of Lipiodol accumulation and adverse events in the other half. Mean Hounsfield unit (HU) values were measured using plain CT images taken before and after TACE. Iodine concentration was higher in the experimental group [1100 (750-1500) ppm, median (range)] than in the control group [840 (660-1800) ppm], although statistically not significant. Additionally, the HU value for the experimental group was higher than that for the control group immediately after [199.6 (134.0-301.7) vs. 165.3 (131.4-280.5)] and two days after [114.2 (56.1-229.8) vs. 58.3 (42.9-132.5)] TACE, although statistically not significant. Cholecystitis was observed in one rabbit in the control group. Ischemic bile duct injury was not observed in any group. The results show that Lipiodol accumulation and retention in VX2 tumor can possibly be improved with a monodisperse emulsion; however, it should be verified with a larger study. Moreover, no significant adverse events are associated with the use of the emulsion.

Embolization using warmed glue via the triaxial microballoon occlusion system for various vascular disorders.

PURPOSE: We aimed to illustrate the benefits of using warmed glue for viscosity reduction via the triaxial microballoon system for the treatment of various vascular disorders. METHODS: Seven patients who underwent 10 treatment sessions for hemoptysis, type II endoleak, post-pancreatic surgical bleeding, spontaneous retroperitoneal bleeding, or ovarian tumor bleeding were evaluated based on technical and clinical outcomes. In the procedure, the triaxial system, consisting of a 4.5-Fr guiding catheter, a 2.8-Fr microballoon catheter, and a 1.9-Fr no-taper microcatheter, was advanced into the target lesion. Glue (33% n-butyl cyanoacrylate mixed with Lipiodol) warmed to 40°C was injected under balloon occlusion. RESULTS: The common hepatic, right bronchial, intercostals, internal mammary, costocervical, lateral thoracic, superior thoracic, thoracoacromial, inferior thyroid, iliolumbar, lumbar, internal pudendal arteries, and branch of the inferior mesenteric artery were successfully embolized; 100% technical success and 100% clinical success were obtained after each session. CONCLUSION: Our modified balloon-occluded glue embolization may lead to better handling with more distal glue penetration capability.

Evaluation of the relationship between hepatocellular carcinoma location and transarterial chemoembolization efficacy.

AIM: To evaluate the relationship between the location of hepatocellular carcinoma (HCC) and the efficacy of transarterial chemoembolization (TACE). METHODS: We evaluated 115 patients (127 nodules), excluding recurrent nodules, treated with TACE between January 2011 and June 2014. TACE efficacy was evaluated according to mRECIST. The HCC location coefficient was calculated as the distance from the central portal portion to the HCC center (mm)/liver diameter (mm) on multiplanar reconstruction images rendered (MPR) to visualize bifurcation of the right and left branches of the portal vein and HCC center. The HCC location coefficient was compared between complete response (CR) and non-CR groups in Child-Pugh grade A and B patients. RESULTS: The median location coefficient of HCC among all nodules, the right lobe, and the medial segment was significantly higher in the CR group than in the non-CR group in the Child-Pugh grade A patients (0.82 vs 0.62, P < 0.001; 0.71 vs 0.59, P < 0.01; 0.81 vs 0.49, P < 0.05, respectively). However, there was no significant difference in the median location coefficient of the HCC in the lateral segment between in the CR and in the non-CR groups (0.67 vs 0.65, P > 0.05). On the other hand, in the Child-Pugh grade B patients, the HCC median location coefficient in each lobe and segment was not significantly different between in the CR and in the non-CR groups. CONCLUSION: Improved TACE efficacy may be obtained for HCC in the peripheral zone of the right lobe and the medial segment in Child-Pugh grade A patients.

Negative-balance isolated pelvic perfusion in patients with incurable symptomatic rectal cancer: results and drug dose correlation to adverse events.

BACKGROUND: Drug leakage and lack of a drug-removal system have prevented clinical application of isolated pelvic perfusion (IPP). These barriers were overcome with negative-balance IPP (NIPP) in experimental pig models. Here, a phase 1 clinical study of NIPP was performed in patients with incurable symptomatic rectal cancer. PURPOSE: To establish a safe regimen of high-dose regional chemotherapy with NIPP using cisplatin in patients with incurable rectal cancer. MATERIAL AND METHODS: Between June 2004 and January 2007, NIPP therapy was performed for 23 patients (11 women, 12 men; mean age, 58 years). NIPP was routinely performed twice over a 4-week interval. Dose-limiting toxicities (DLTs) were defined using a 5 + 3 design, and cisplatin doses were escalated from 170 mg/m(2), with a fixed 5-fluorouracil dose of 1000 mg/m(2). The grade of adverse events (AEs) at the first and second sessions of NIPP therapy, pharmacokinetics, and antitumor response were evaluated. RESULTS: No DLTs were observed during the first session of NIPP. However, at the second session, two patients experienced the DLT of neuropathy after administration of 200 mg/m(2) cisplatin. Therefore, 190 mg/m(2) cisplatin was indicated as the maximum tolerated dose (MTD). The plasma pelvic-to-systemic exposure ratio was 18.4 based on the maximum concentration and 19.0 based on the concentration-time curve. Solid tumor responses included complete response in two patients, partial response in five patients, stable disease in 15 patients, and progressive disease in one patient. CONCLUSION: NIPP may offer the safe delivery of high-dose regional chemotherapy (MTD of 190 mg/m(2) cisplatin) with negligible AEs and effective control of tumor growth in patients with incurable rectal cancer.

Comparison of epirubicin-iodized oil suspension and emulsion for transcatheter arterial chemoembolization in VX2 tumor.

To compare the antitumor efficacy and safety of transcatheter arterial chemoembolization (TACE) by epirubicin suspension (epirubicin suspension: epirubicin-iodized oil mixture without solution) to that by epirubicin emulsion (epirubicin emulsion: epirubicin-iodized oil mixture with solution), the efficacy of treatment by administration of either an epirubicin suspension or emulsion was examined in an animal model. Changes in plasma epirubicin concentration were compared over 24 h immediately after treatment, and enhanced ultrasonographic and histopathological analysis subsequently conducted 7 days after treatment to determine the growth ratio and proportion of viable tumor cells. The growth ratio and proportion of viable tumor cells were found to be significantly lower in the suspension group than in the emulsion group while the plasma epirubicin concentration was found to be significantly higher in the suspension group than in the emulsion group. These results indicate that administration of an epirubicin suspension is a superior form of TACE compared to that of administration of an epirubicin emulsion.

Oily chemoembolization combined with degradable starch microspheres for HCC with cirrhosis.

BACKGROUND/AIMS: To assess efficacy of transcatheter arterial chemoembolization (TACE) combined with degradable starch microspheres (DSM) for patients with liver cirrhosis and hepatocellular carcinoma (HCC). METHODOLOGY: Our studied population was 19 patients with unresectable HCC and liver dysfunction due to repeated TACE, in whom we were unable to selectively advance a microcatheter into the feeding arteries because of tortuous or complex feeding arteries to the HCC. To avoid embolization of an extended non-tumorous area, we conducted Lipiodol-TACE after DSM-embolization (TACE-DSM) of the tumor-free parenchyma. Embolization data and clinical parameters were prospectively assessed. RESULTS: TACE-DSM was performed 21 times in the 19 patients, and the overall technical success rate was 81%. The TACE-DSM method did not induce severe liver dysfunction. A favorable response involving necrosis of more than 80% or 50% of the tumor was seen in 62% and 90% of cases, respectively. In the follow-up period (8 to 36 months), complete necrosis of the targeted tumors was observed in 26% of cases. The 2-year survival rates calculated as starting from the date of TACE-DSM therapy was 32.6%. CONCLUSIONS: From these results we conclude that TACE-DSM therapy is useful for protecting liver function in patients with cirrhosis and unresectable HCC.