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Title: Temporary Arterial Embolization of Liver Parenchyma with Degradable Starch Microspheres (EmboCept{sup ®}S) in a Swine Model

Abstract

BackgroundThis study aimed to evaluate the embolic properties, time to reperfusion, and histologic changes in temporary embolization of liver tissue with degradable starch microspheres (DSM) in a swine model.MethodsIn four adult minipigs, DSMs were injected into the right or left hepatic artery on the lobar level until complete stasis of the blood flow was detectable angiographically. The time required to complete angiographically determined reperfusion was noted. The animals were killed 3 h after complete reperfusion, and samples were taken from the liver. Histologic examinations of the embolized liver parenchyma and untreated tissue were performed.ResultsHepatic arterial embolization using DSMs was technically successful in all cases, with complete blood flow stasis shown by control angiography. A single vial of DSMs (450 mg/7.5 ml) was sufficient to embolize a whole liver lobe in all cases. Angiography showed complete reconstitution of hepatic arterial perfusion after a mean time to reperfusion of 32 ± 6.1 min (range, 26–39 min). Hematoxylin and eosin staining showed no histologically detectable differences between untreated tissue and parenchyma embolized with DSMs except for mild sinusoidal congestion in one case. Indirect in situ DNA nick end labeling staining (TUNEL) showed only single positive hepatocytes, indicating apoptosis.ConclusionTemporary embolization of the hepatic artery using DSMs is feasible with complete reperfusion aftermore » 30 min in pigs. Even after complete arterial blood flow stasis, no extensive tissue damage to the embolized liver parenchyma was observed at histologic examinations in this short-term study.« less

Authors:
;  [1];  [2];  [3];  [1];  [4]
  1. University of Bonn, Department of Radiology (Germany)
  2. University of Rostock, Institute for Experimental Surgery (Germany)
  3. University of Rostock, Department of Diagnostic and Interventional Radiology (Germany)
  4. Johanniter Hospital, Evangelische Kliniken Bonn (Germany)
Publication Date:
OSTI Identifier:
22469999
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cardiovascular and Interventional Radiology; Journal Volume: 38; Journal Issue: 2; Conference: BSIR 2014: Britisch Society of Interventional Radiology 2014 annual meeting, Liverpool (United Kingdom), 12-14 Nov 2014; Other Information: Copyright (c) 2015 Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE); http://www.springer-ny.com; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANIMAL TISSUES; APOPTOSIS; ARTERIES; BIOMEDICAL RADIOGRAPHY; BLOOD FLOW; DAMAGE; DNA; EOSIN; HEMATOXYLIN; LABELLING; LIVER; LIVER CELLS; MICROSPHERES; PLANT TISSUES; STARCH; SWINE; VASCULAR DISEASES

Citation Formats

Pieper, Claus C., E-mail: claus.christian.pieper@ukb.uni-bonn.de, Meyer, Carsten, E-mail: Carsten.Meyer@ukb.uni-bonn.de, Vollmar, Brigitte, E-mail: brigitte.vollmar@med.uni-rostock.de, Hauenstein, Karlheinz, E-mail: karlheinz.hauenstein@med.uni-rostock.de, Schild, Hans H., E-mail: Hans.Schild@ukb.uni-bonn.de, and Wilhelm, Kai E., E-mail: Kai.Wilhelm@ek-bonn.de. Temporary Arterial Embolization of Liver Parenchyma with Degradable Starch Microspheres (EmboCept{sup ®}S) in a Swine Model. United States: N. p., 2015. Web. doi:10.1007/S00270-014-0966-2.
Pieper, Claus C., E-mail: claus.christian.pieper@ukb.uni-bonn.de, Meyer, Carsten, E-mail: Carsten.Meyer@ukb.uni-bonn.de, Vollmar, Brigitte, E-mail: brigitte.vollmar@med.uni-rostock.de, Hauenstein, Karlheinz, E-mail: karlheinz.hauenstein@med.uni-rostock.de, Schild, Hans H., E-mail: Hans.Schild@ukb.uni-bonn.de, & Wilhelm, Kai E., E-mail: Kai.Wilhelm@ek-bonn.de. Temporary Arterial Embolization of Liver Parenchyma with Degradable Starch Microspheres (EmboCept{sup ®}S) in a Swine Model. United States. doi:10.1007/S00270-014-0966-2.
Pieper, Claus C., E-mail: claus.christian.pieper@ukb.uni-bonn.de, Meyer, Carsten, E-mail: Carsten.Meyer@ukb.uni-bonn.de, Vollmar, Brigitte, E-mail: brigitte.vollmar@med.uni-rostock.de, Hauenstein, Karlheinz, E-mail: karlheinz.hauenstein@med.uni-rostock.de, Schild, Hans H., E-mail: Hans.Schild@ukb.uni-bonn.de, and Wilhelm, Kai E., E-mail: Kai.Wilhelm@ek-bonn.de. Wed . "Temporary Arterial Embolization of Liver Parenchyma with Degradable Starch Microspheres (EmboCept{sup ®}S) in a Swine Model". United States. doi:10.1007/S00270-014-0966-2.
@article{osti_22469999,
title = {Temporary Arterial Embolization of Liver Parenchyma with Degradable Starch Microspheres (EmboCept{sup ®}S) in a Swine Model},
author = {Pieper, Claus C., E-mail: claus.christian.pieper@ukb.uni-bonn.de and Meyer, Carsten, E-mail: Carsten.Meyer@ukb.uni-bonn.de and Vollmar, Brigitte, E-mail: brigitte.vollmar@med.uni-rostock.de and Hauenstein, Karlheinz, E-mail: karlheinz.hauenstein@med.uni-rostock.de and Schild, Hans H., E-mail: Hans.Schild@ukb.uni-bonn.de and Wilhelm, Kai E., E-mail: Kai.Wilhelm@ek-bonn.de},
abstractNote = {BackgroundThis study aimed to evaluate the embolic properties, time to reperfusion, and histologic changes in temporary embolization of liver tissue with degradable starch microspheres (DSM) in a swine model.MethodsIn four adult minipigs, DSMs were injected into the right or left hepatic artery on the lobar level until complete stasis of the blood flow was detectable angiographically. The time required to complete angiographically determined reperfusion was noted. The animals were killed 3 h after complete reperfusion, and samples were taken from the liver. Histologic examinations of the embolized liver parenchyma and untreated tissue were performed.ResultsHepatic arterial embolization using DSMs was technically successful in all cases, with complete blood flow stasis shown by control angiography. A single vial of DSMs (450 mg/7.5 ml) was sufficient to embolize a whole liver lobe in all cases. Angiography showed complete reconstitution of hepatic arterial perfusion after a mean time to reperfusion of 32 ± 6.1 min (range, 26–39 min). Hematoxylin and eosin staining showed no histologically detectable differences between untreated tissue and parenchyma embolized with DSMs except for mild sinusoidal congestion in one case. Indirect in situ DNA nick end labeling staining (TUNEL) showed only single positive hepatocytes, indicating apoptosis.ConclusionTemporary embolization of the hepatic artery using DSMs is feasible with complete reperfusion after 30 min in pigs. Even after complete arterial blood flow stasis, no extensive tissue damage to the embolized liver parenchyma was observed at histologic examinations in this short-term study.},
doi = {10.1007/S00270-014-0966-2},
journal = {Cardiovascular and Interventional Radiology},
number = 2,
volume = 38,
place = {United States},
year = {Wed Apr 15 00:00:00 EDT 2015},
month = {Wed Apr 15 00:00:00 EDT 2015}
}
  • PurposeThe purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI).Materials and MethodsEighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused.ResultsThe platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those inmore » the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006).ConclusionsTACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution.« less
  • Temporary small intestinal ischemia was induced by mesenteric arteriolar embolization of degradable starch microspheres in cats. During ischemia, the small intestine received a surface dose of 7 Gy 200 kV x-ray irradiation. One group of animals also had received 7 Gy to the intact abdomen 72 hr earlier. The risk of thrombosis in small intestinal vessels during or after starch microsphere-induced ischemia combined with irradiation was evaluated by monitoring superior mesenteric arterial blood flow, by determination of blood platelets, fibrinogen, and factor VIII consumed across the mesenteric vascular bed, and by histologic examination of small intestinal vessels. Vascular integrity wasmore » inferred from intact response to isoproterenol and vasopressin after the combined trauma of ischemia and irradiation. No signs of thrombosis were detected in small intestinal vessels after temporary ischemia and irradiation. Hypoxic radioprotection of the small intestine in the cat can thus be achieved by mesenteric arterial microembolization of degradable starch spheres without evidence of thrombotic complications of significant vascular damage.« less
  • Temporary small intestinal ischemia was induced by mesenteric arteriolar embolization of degradable starch microspheres in cats. During ischemia, the small intestine received a surface dose of 7 Gy 200 kV x-ray irradiation. One group of animals also had received 7 Gy to the intact abdomen 72 hr earlier. The risk of thrombosis in small intestinal vessels during or after starch microsphere-induced ischemia combined with irradiation was evaluated by monitoring superior mesenteric arterial blood flow, by determination of blood platelets, fibrinogen, and factor VIII consumed across the mesenteric vascular bed, and by histologic examination of small intestinal vessels. Vascular integrity wasmore » inferred from intact response to isoproterenol and vasopressin after the combined trauma of ischemia and irradiation. No signs of thrombosis were detected in small intestinal vessels after temporary ischemia and irradiation. Hypoxic radioprotection of the small intestine in the cat can thus be achieved by mesenteric arterial microembolization of degradable starch spheres without evidence of thrombotic complications or significant vascular damage.« less
  • Objectives: The pharmacokinetic profile after hepatic arterial embolization with superabsorbent microspheres (QuadraSpheres) loaded with doxorubicin was studied. Methods: Rabbits with hepatic VX2 tumors were treated with intra-arterial administration of QuadraSpheres loaded with doxorubicin, or transarterial chemoembolization (TACE) using doxorubicin, Lipiodol and Embospheres, or hepatic arterial infusion (HAI) of doxorubicin. Tumor specimens were evaluated by fluorescence microscopy, and plasma and tumor concentrations of doxorubicin were measured. Results: The peak plasma concentration of doxorubicin was lower in the QuadraSphere group (309.9 ng/ml) than in the HAI (673.4 ng/ml) or TACE (360.5 ng/ml) groups, suggesting higher tumor retention in the QuadraSphere group. Intratumoralmore » doxorubicin levels declined to negligible levels at 1 and 3 days after treatment, respectively, in the HAI and TACE groups. In the QuadraSphere groups, intratumoral doxorubicin level declined after day 1, but was still detectable at 14 days after treatment and was higher than that in the other groups at 1, 3, and 7 days. Intratumoral doxorubicin fluorescence was detected at all time points in the QuadraSphere group, but only at 1 day after treatment in the TACE group. Conclusions: Hepatic arterial administration of doxorubicin-loaded QuadraSpheres enables the sustained release of doxorubicin to hepatic tumors.« less
  • PurposeThis phase II prospective study investigates possible benefits of radiofrequency ablation (RFA) combined with hepatic arterial chemoembolization using degradable starch microsphere (DSM) mixed with mitomycin C (MMC) in non-surgical candidates with colorectal liver metastases.Materials and MethodsThis study, approved by the respective institutional review board, included non-surgical candidates with 3 or fewer liver tumors of 3 cm or smaller, or a single lesion 5 cm or smaller. Percutaneous RFA was performed immediately after chemoembolization using DSM-MMC. Primary and secondary endpoints were the local tumor control rate, safety, and 2-year recurrence-free and overall survival rates.ResultsThis study examined 25 patients (22 males, 3 females) withmore » 38 tumors of mean maximum diameter of 2.2 ± 0.9 cm (standard deviation) (range 1.0–4.2 cm). Their mean age was 70.2 ± 8.2 years (range 55–82 years). Local tumor progression developed in 3 tumors (7.9%, 3/38) of 3 patients (12%, 3/25) during the mean follow-up of 34.9 ± 9.2 months (range 18.3–50.1 months). The 2-year local tumor control rates were 92.0% [95% confidence interval (CI), 81.4–100%] on a patient basis and 94.6% (95% CI, 87.3–100%) on a tumor basis. The respective 2-year overall and recurrence-free survival rates were 88.0% (95% CI, 75.3–98.5%) and 63.3% (95% CI, 44.2–82.5%), with median survival time of 48.4 months. Fever was the only adverse event requiring treatments in 2 patients (8%).ConclusionsThis combination therapy is safe, exhibiting strong anticancer effects on colorectal liver metastasis, which might contribute to patient survival.« less