Embolization of hepatocellular carcinoma with drug-eluting beads: Doxorubicin tissue concentration and distribution in patient liver explants

Background & Aims To follow the local tissue delivery of doxorubicin in HCC explants from patients embolized with drug-eluting beads and to compare it with histologic modifications. Methods Six patients with HCC underwent chemoembolization with doxorubicin-eluting beads (caliber 100–300 μm, dose...

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Bibliographic Details
Published in:Journal of hepatology 2011-12, Vol.55 (6), p.1332-1338
Main Authors: Namur, Julien, Citron, Steven J, Sellers, Marty T, Dupuis, Mark H, Wassef, Michel, Manfait, Michel, Laurent, Alexandre
Format: Article
Language:English
Subjects:
Adult
Aged
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - pharmacokinetics
Biological and medical sciences
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Carcinoma, Hepatocellular - surgery
Carcinoma, Hepatocellular - therapy
Chemoembolization, Therapeutic
Delayed-Action Preparations
Doxorubicin
Doxorubicin - administration & dosage
Doxorubicin - pharmacokinetics
Drug-eluting beads
Female
Gastroenterology and Hepatology
Gastroenterology. Liver. Pancreas. Abdomen
Hepatocellular carcinoma
Histologic modifications
Humans
Liver - blood supply
Liver - metabolism
Liver - pathology
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Liver Neoplasms - surgery
Liver Neoplasms - therapy
Liver Transplantation
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Microspheres
Middle Aged
Necrosis
Tissue concentration
Tissue Distribution
Tumors
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Summary:Background & Aims To follow the local tissue delivery of doxorubicin in HCC explants from patients embolized with drug-eluting beads and to compare it with histologic modifications. Methods Six patients with HCC underwent chemoembolization with doxorubicin-eluting beads (caliber 100–300 μm, dose 75–150 mg) followed by liver transplantation at different time points (8 h to 36 days). On sections of the explanted liver, the tissue concentration of doxorubicin was determined radially around bead-occluded vessels with microspectrofluorimetry. The intra/peritumoral location of the beads and the modifications of the surrounding tissue were determined on an adjacent hematein–eosin–saffron-stained section and compared to drug measurements. Results Doxorubicin was detected in the tissue surrounding the beads at all times of explantation. The drug impregnates an area of at least 1.2 mm in diameter around the occluded vessel. The tissue concentration of drug ranges from 5 μM at 8 h to 0.65 μM at 1 month. In patient transplanted at 8 h, no major tissue modification was observed and we found 42% of the beads occluding intratumoral vessels. Drug concentration was not different around intratumoral and peritumoral occluded vessels. After 9–14 days, necrosis was present around 37% of vessels and at 32–36 days, around 40% of vessels. Necrotic tissue was associated with a deeper penetration and a higher concentration of the drug than non necrotized areas, though statistically significant only at 32–36 days. Conclusions Doxorubicin-eluting beads provide a sustained delivery of drug for a period of 1 month and local tissue concentrations above cytotoxic threshold in HCC-bearing livers.
ISSN:0168-8278
1600-0641
DOI:10.1016/j.jhep.2011.03.024