title: Safety evaluation of self-expanding metallic biliary stents eluting gemcitabine in a porcine model.
abstract: OBJECTIVE
  Palliative biliary decompression by metal stent is the treatment of choice for unresectable malignant biliary obstruction; however, conventional stents provide only mechanical palliation and exert no anti-tumor effects. Gemcitabine (GEM) has been reported to be more effective in unresectable pancreatic cancer and biliary cancer compared with other chemotherapeutic drugs. We evaluated the safety of a GEM-eluting stent by analyzing histologic responses of the porcine bile duct.
  
  
  METHODS
  Stents containing GEM (0%, 10%, 15%, and 20% [w/v]) were surgically inserted into bile ducts of pigs (each group, n = 2). The animals were euthanized after 4 weeks, and the stented bile duct segment underwent gross and microscopic examination. Laboratory assay was performed for aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin, and gamma-glutamyl transferase (γ-GTP).
  
  
  RESULTS
  Moderate to severe inflammation was observed in the bile ducts in contact with stents containing 15 and 20% GEM, compared with no inflammation with 0% GEM and mild inflammation with 10% GEM. Fibrous reactions observed in the submucosal layer did not differ among groups. Transmural necrosis and perforations were not observed in any animal. No abnormal laboratory test findings were directly caused by GEM.
  
  
  CONCLUSIONS
  Our newly developed GEM eluting stents can be used safely in normal bile ducts. Our results indicated that 10% GEM produced mild histologic changes in the stented segment and adjacent tissue; this concentration may be appropriate for clinical application.
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University Health System, Seoul, Korea.
authors.forename: Moon Jae
authors.initials: MJ
authors.lastname: Chung
authors.forename: Hyunki
authors.initials: H
authors.lastname: Kim
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Kim
authors.forename: Sangsoo
authors.initials: S
authors.lastname: Park
authors.forename: Jae Bock
authors.initials: JB
authors.lastname: Chung
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Park
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D001652:Bile Ducts / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D015415:Biomarkers / Q000097:blood; D003664:Decompression / Q000009:adverse effects / Q000295:instrumentation*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D054855:Drug-Eluting Stents; D004869:Equipment Safety; D008422:Materials Testing; D008670:Metals; D023421:Models, Animal; D010166:Palliative Care; D011474:Prosthesis Design; D018570:Risk Assessment; D012995:Solubility; D013552:Swine; D013997:Time Factors; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D008670:Metals; D003841:Deoxycytidine; D000093542:Gemcitabine