Chemoembolization with Vascular Disrupting Agent CKD-516 Dissolved in Ethiodized Oil in Combination with Doxorubicin: A VX2 Tumor Model Study.

PURPOSE: To assess feasibility and efficacy of CKD-516, a vascular disrupting agent, in transarterial chemoembolization in a liver tumor model. MATERIALS AND METHODS: A VX2 carcinoma strain was implanted in rabbit liver (n = 40) and incubated for 2 weeks. After confirmation of tumor growth using computed tomography, transarterial chemoembolization was performed. CKD-516 was dissolved in ethiodized oil, and animals were allocated to 4 treatment groups (n = 10 in each): group A, ethiodized oil; group B, ethiodized oil/CKD-516; group C, ethiodized oil + doxorubicin; group D, ethiodized oil/CKD-516 + doxorubicin. To assess hepatic damage, serum aspartate transaminase and alanine transaminase levels were measured on day 1, 3, and 7 after delivery. To assess tumor necrosis, animals were euthanized on day 7, and explanted tumors were stained with hematoxylin and eosin and a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay. Percentage areas of viable tumors were calculated using digitalized histopathologic specimen images. RESULTS: Tumor viability rates were 47.1% ± 11.4%, 27.5% ± 13.6%, 14.4% ± 12.5%, and 0.7% ± 1.0% in groups A, B, C, and D (P < .001). Liver enzyme levels were elevated after drug delivery but recovered during follow-up. Significant between-group differences were observed on days 1, 3, and 7 (aspartate transaminase and alanine transaminase: P = .0135 and P = .0134, P = .0390 and P = .0084, and P = .8260 and P = .0440). CONCLUSIONS: Treatment with a combination of CKD-516 and conventional transarterial chemoembolization showed therapeutic benefit in a liver tumor model.

Early Experience in the Management of Postoperative Lymphatic Leakage Using Lipiodol Lymphangiography and Adjunctive Glue Embolization.

PURPOSE: To evaluate the safety and efficacy of Lipiodol lymphangiography and 3 adjunctive N-butyl cyanoacrylate (NBCA) glue embolization techniques for the management of postoperative lymphatic leakage. MATERIALS AND METHODS: This retrospective study included 27 patients with postoperative lymphatic leakage (17 with ascites, 3 with chylothorax, 6 with lymphoceles, and 1 with a skin fistula) who underwent Lipiodol lymphangiography for diagnostic and therapeutic purposes in 3 tertiary referral centers between August 2010 and January 2016. Adjunctive glue embolization was performed as needed by using 3 different techniques: "lymphopseudoaneurysm" embolization, closest upstream lymph node embolization, or direct upstream lymphatic vessel embolization. RESULTS: Sixteen patients were observed to determine the therapeutic effect of lymphangiography, and 8 patients (50%) recovered without further embolization. In 16 patients, including 11 who underwent immediate embolization after lymphangiography and 5 who underwent delayed embolization, a total of 28 embolizations (12 lymphopseudoaneurysms, 14 lymph nodes, and 2 lymphatic vessels) were performed. The technical and clinical success rates of the adjunctive embolizations were 89% (25 of 28) and 94% (15 of 16), respectively. The overall clinical success rate was 85% (23 of 27). The median time from initial lymphangiography to recovery was 5 days. No procedure-related major complications were reported. CONCLUSIONS: Lipiodol lymphangiography and adjunctive glue embolization techniques appear safe and provide promising efficacy for the management of postoperative lymphatic leakage.

Improved drug targeting to liver tumors after intra-arterial delivery using superparamagnetic iron oxide and iodized oil: preclinical study in a rabbit model.

PURPOSE: The purpose of this study was to evaluate the feasibility and the therapeutic efficacy of a novel drug-delivery system that uses superparamagnetic iron oxide (SPIO) and iodized oil (IO) to improve the selective intra-arterial (IA) drug delivery to an experimentally induced hepatic tumor. MATERIALS AND METHODS: This animal study was approved by our institutional animal care and use committee. Fifteen rabbits with hepatic VX2 carcinomas were treated with IA delivery of 4 different agents: doxorubicin alone (group A, n = 3), doxorubicin/IO (group B, n = 3), a doxorubicin/SPIO complex (group C, n = 4), and a doxorubicin/SPIO/IO complex (group D, n = 5). The infused doxorubicin dose was 1 mg for all groups. The serum doxorubicin concentration was measured at 0, 5, 30, 60, and 120 minutes after the delivery. To assess the distribution of the SPIO, magnetic resonance (MR) scans were performed at day 7 after the delivery, when computed tomographic scans were performed in addition to MR in group B and D to assess the distribution of IO. After the completion of follow-up imaging, all the animals were euthanized to measure the intratumoral doxorubicin concentration and to assess tumor viability through pathologic examination. RESULTS: Groups C and D demonstrated significantly lower MR signal intensities, which inversely corresponded to SPIO deposition, in the tumor areas than did groups A and B. Group D exhibited the lowest serum doxorubicin concentration at all time points up to 180 minutes after the delivery, suggesting minimal passage of doxorubicin into the systemic circulation. The intratumoral doxorubicin concentrations were 72.4 ng/g for group A, 142.0 ng/g for group B, 264.1 ng/g for group C, and 679.6 ng/g for group D. The proportion of viable tumor cells were 65.3% for group A, 1.3% for group B, 17.0% for group C, and 0.1% for group D. CONCLUSIONS: The drug-delivery system developed using SPIO and IO can result in better drug targeting when it is used for IA delivery to liver cancer. The results of this study warrant further investigation of this potential clinical treatment of advanced liver cancer.

Chemoembolization via branches from the splenic artery in patients with hepatocellular carcinoma.

PURPOSE: This study was designed to evaluate the radiologic findings and imaging response of chemoembolization via branches of the splenic artery in patients with hepatocellular carcinoma (HCC). METHODS: From January 2001 to July 2010, we observed tumor staining supplied by branches of the splenic artery in 34 (0.6%) of 5,413 patients with HCC. Computed tomography (CT) scans and digital subtraction angiograms of these patients were retrospectively reviewed in consensus by two investigators. RESULTS: A total of 39 tumor feeding-vessels in 34 patients were identified: omental branches from the left gastroepiploic artery (n = 5), branches from the short gastric artery (n = 9), and omental branches directly from the splenic artery (n = 25). Branches of the splenic artery that supplied tumors were revealed on the celiac angiogram in 29 (85%) of 34 patients and were detected on pre-procedure CT images in 27 (79%) of 34 patients. Selective chemoembolization was achieved in 38 of 39 tumor-feeding vessels. Complete or partial response of the tumor fed by branches of the splenic artery, as depicted on follow-up CT scans, was achieved in 21 (62%) patients. No patient developed severe complications directly related to chemoembolization via branches of the splenic artery. CONCLUSIONS: Omental branches directly from the splenic artery are common tumor-feeding vessels of the splenic artery in cases of advanced HCC with multiple previous chemoembolizations. Tumor-feeding vessels of the splenic artery are usually visualized on the celiac angiogram or CT scan, and chemoembolization through them can be safely performed in most patients.