Neuroprotective effects of dodecafluoropentane ...

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Conclusion: Irreversible electroporation of liver tumors is safe even when adjacent to bowel or other vital structures. It demonstrates high efficacy based on ...
JVIR



Scientific Session

Monday

2:50 PM

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their effect on outcomes. LTP-free survival and OS were calculated using Kaplan-Meier methodology. Factors affecting oncologic outcome were assessed in univariate and multivariate analysis. Results: Median tumor size was 1.9 cm (range 0.5 to 5.7 cm). Complete ablation was demonstrated in 209 cases (technique effectiveness rate: 96%). Median overall survival was 35.43 months. One-, 3-, and 5-year overall survival rates were: 91%, 47% and 33%, respectively. On univariate analysis, as well as multivariate analysis tumor size over 3 cm (HR: 2.58, 95% CI: 1.47, 4.53; p¼0.001) and not receiving systemic chemotherapy following RFA (HR: 0.63, 95% CI: 0.4, 0.98; p¼0.04) were independent predictors for shorter OS. Median LTP-free survival was 25 months. Size (p¼0.01), prior systemic (p¼0.02) and prior intraarterial chemotherapy (p¼0.03) were independent factors for LTP-free survival in the univariate model, however only size retained its significance in the multivariate model (p¼0.01). Conclusion: Size of ablated tumor and post-ablation chemotherapy are associated with better oncologic outcomes after RFA of colorectal liver metastases.

Scientific Session 10 Basic Science: Vascular and Other Topics

MONDAY: Scientific Sessions

advantage of IRE over thermal ablation techniques includes the ability to ablate tissue adjacent to blood vessels or other critical structures. This study assessed the safety and efficacy of IRE for the treatment of liver malignancies. Materials and Methods: In this institutional review boardapproved retrospective study, 15 patients were treated with IRE for 17 tumors in the liver. Eight patients were diagnosed with hepatocellular carcinoma, 6 had metastatic liver tumors from colorectal cancer, and one patient had cholangiocarcinoma. Median patient age was 58 years. Nine of 15 (60%) were male, and 11/15 (73%) were Eastern Cooperative Performance Status (ECOG) performance status of 0. Median number of tumors was 1 (range 1-2), with a median diameter of 1.8 cm (range 0.7-4.1 cm). IRE was chosen due to proximity of the tumor to large vessels (hepatic vein, n¼5; portal vein, n¼3), bile duct (n¼3), or bowel (stomach, n¼2; colon, n¼4). Results: IRE was performed in standard fashion under general anesthesia using 2-4 probes (median 3). Eleven were performed percutaneously and four surgically. Follow up assessment was performed on all patients. Sixteen of 17 (94%) ablations were technically successful, as defined by complete overlap of the ablation zone with the tumor. Median hospital stay was one day (range 0-34 days). Median follow-up was 219 days. Complications included one case of self-limiting rectus sheath hematoma and one case of acute liver dysfunction (which was transient and resolved). There were no injuries to adjacent bowel. No hepatic or malignancy related deaths have occurred. Imaging follow-up was available for 12/17 (71%) tumors. Ten tumors demonstrated complete response and two demonstrated partial response. Following complete ablation, there was one case of tumor recurrence at the ablation site. Conclusion: Irreversible electroporation of liver tumors is safe even when adjacent to bowel or other vital structures. It demonstrates high efficacy based on imaging response criteria, even for lesions adjacent to large blood vessels.



Monday, April 15, 2013 1:30 PM – 3:00 PM Room: 289

Abstract No. 91

Factors affecting oncologic outcome after radiofrequency ablation of colorectal liver metastasis 1

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W. Shady , C.T. Sofocleous , E.N. Petre , N.E. Kemeny , S.B. Solomon1, K.T. Brown1, W. Alago, Jr.1, R.H. Thornton1, J.P. Erinjeri1, R.H. Siegelbaum1; 1 Interventional Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; 2Medicine, Memorial Sloan-Kettering Cancer Center, NY, NY Purpose: To assess factors affecting oncologic outcomes of percutaneous radiofrequency ablation (RFA) in the management of colorectal liver metastases. Materials and Methods: One-hundred-forty-nine patients (86 men and 63 women, median age: 61 years) underwent a total of 198 RF ablation sessions for the treatment of 218 lesions from January 2003 to March 2012. Technique effectiveness per lesion was evaluated at the 4-6-week post ablation CT and local tumor progression (LTP) at the ablation site was assessed reviewing subsequent scans. The endpoints of the study were: LTP-free survival and overall survival (OS) from the time of the ablation. Clinical factors such as: tumor size, prior hepatic resection, node positivity of the primary, time interval from primary resection to liver metastasis, number of tumors, presence of extrahepatic disease, pre and post ablation systemic and intraarterial chemotherapy were analyzed for

Abstract No. 92

’Dr. Constantin Cope Medical Student Research Award

Neuroprotective effects of dodecafluoropentane emulsion in an angiographic model of acute ischemic stroke in rabbits S.D. Woods1, M.L. Winter1, R.D. Skinner2, A. Brown1, J.D. Lowery3, M.J. Borrelli1, W.C. Culp1; 1Radiology, University of Arkansas for Medical Sciences, Little Rock, AR; 2Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR; 3Laboratory Animal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR Purpose: Interventional treatments for acute ischemic stroke are critically limited by a time window that restricts safety and efficacy to a period before large areas of brain have died. The purpose of this study was to assess the potential for emergency use of the oxygen-transporting dodecafluoropentane emulsion (DDFPe) to protect the brain from acute ischemic damage and reduce infarct volume without lysis of arterial obstructions. Materials and Methods: New Zealand white rabbits (N¼55) received cerebral angiography from a femoral artery approach.

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Monday

Scientific Session

JVIR



Neuroprotective Effects of Dodecafluoropentane Emulsion in an Angiographic Model of Acute Ischemic Stroke in Rabbits Group no.

MONDAY: Scientific Sessions

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DDFPe dosage

Sacrifice time (h)

N

Infarct volume (%) ⫾ SE

P-value (vs. control)

Serum S-100B (ng/ml)

P-value (vs. control)

7 7 7 7 24 24

6 7 9 8 16 9

3.88⫾1.41 0.58⫾0.21 0.59⫾0.25 1.03⫾0.69 3.39⫾0.94 0.51⫾0.14

– 0.004 0.003 0.009 – 0.008

0.65⫾0.16 0.69⫾0.13 0.53⫾0.11 0.27⫾0.12 0.79⫾0.08 0.25⫾0.11

– 0.854 0.549 0.067 – 0.004

Control 0.1 ml/kg 0.3 ml/kg 0.6 ml/kg Control 0.1 ml/kg

Embolic microspheres (diameter¼700-900mm) were injected into the internal carotid artery occluding the middle cerebral and/or anterior cerebral arteries. Rabbits were randomly assigned to treatment groups and sacrifice times as in theTable. In all treated groups, intravenous DDFPe dosing with a 2% w/v emulsion began at 60 min post-embolization and was repeated every 90 min until sacrifice at either 7 or 24 hrs post-embolization. Serum levels of S-100B protein, a marker for blood-brain barrier disruption, were measured in blood samples taken before sacrifice by ELISA. Following sacrifice, infarcts were measured as a percent of brain volume using vital stains on brain sections. Results: Percent infarct volume means decreased for all DDFPe treated groups compared with controls, and S-100B concentrations were decreased at 24 hrs with DDFPe treatment compared to controls (Table 1). Concentrations of S-100B at 24 hrs were positively correlated with percent infarct volume (r¼0.70, P¼0.0002). Conclusion: Intravenous DDFPe protects brain from ischemic injury in the rabbit model of permanent embolic stroke. S-100B data at 7 hours indicate that higher DDFPe doses may provide earlier neuroprotection. Decreased infarct volumes and serum S100B levels indicate improved brain status, which can persist for 24 hours with repeated doses

1:38 PM

Abstract No. 93

Doxorubicin, irinotecan and sunitinib: loading and release with a resorbable embolization microsphere (REM) L. Bedouet1, V. Verret1, S. Louguet1, E. Servais1, L. Moine2, A. Laurent3; 1Occlugel, Jouy-en-Josas, France; 2UMR CNRS 8612, IFR 141-ITFM, Universite´ Paris-Sud, Faculte´ de Pharmacie, Chatenay-Malabry,  ˆ France; 3AP-HP hopital Lariboisiere, Paris, France

Purpose: Today no temporary material can provide a progressive release of drug as non-resorbable drug eluting microspheres (Non-REM) DC-beads and Quadrasphere. We modified a resorbable embolization microsphere (REM) by grafting ionic functions to enable its loading with ionic drugs like doxorubicin (DOX), irinotecan (IRI) and sunitinib (SUN). The ionic functions (sulphonate, carbonate) used for non-REM are not convenient for REM since they would be toxic if released during resorption. We added small amounts of a biocompatible function, methacrylate, to REM and evaluated their performances in terms of cytotoxicity, drug loading and release. Materials and Methods: REM were made of a hydrolytic resorbable crosslinker and an acrylic monomer by suspension polymerization and methacrylate was added at 0% (REM-0), 10% (REM-10), 20% (REM-20) and 50% (REM-50). The toxicity was assessed by direct contact on L929 fibroblasts. REM were incubated with DOX, IRI and SUN for 1h, and the loaded content was determined. REM were incubated in saline buffer and the release kinetics was assessed. Results: REM-0, REM-10 and REM-20 were not cytotoxic, whereas REM-50 caused an inhibition of cell proliferation by half after 3 days. Thus, REM-50 was not tested for loading and release. REM-0 loaded very small amount of the three drugs, and released them in a burst. The addition of ionic functions in REM-10 and REM- 20 increased significantly the drug loading of REM vs. REM-0 for the three drugs, although the maximal loading capacity was not investigated here. The release was slowed down significantly for REM-10 and REM-20 vs. REM-0 for DOX and SUN but not IRI. Conclusion: The addition of ionic functions enabled the loading of REM with the three drugs and slowed down their release, making them efficient for local drug delivery and comparable to non-REM.

Doxorubicin, Irinotecan and Sunitinib: Loading and Release with a Resorbable Embolization Microsphere (REM)

Doxorubicin (35 mg/mL of REM) Irinotecan (40 mg/mL of REM) Sunitinib (50 mg/mL of REM)

Drug loading (mg/mL of sediment)

Drug release in saline buffer (% of loading)

REM-0

REM-10 2–5 min

5 18 4

REM-10 31 34 37

REM-20 34 37 40

22 37 7

1h 74 73 25

6h 81 82 52

REM-20 2-5 min 13 37 5

1h 49 75 18

6h 64 87 39