title: Hepatocellular necrosis, apoptosis, and proliferation after transcatheter arterial embolization or chemoembolization in a standardized rabbit model.
abstract: OBJECTIVE
  To evaluate the effect of transcatheter arterial chemoembolization versus transcatheter arterial embolization on hepatocellular damage, apoptosis, proliferation, and proinflammatory response in a rabbit VX2 tumor model.
  
  
  METHODS
  Rabbits implanted with VX2 tumors in left liver lobes were randomly divided into three groups: a control group (n = 9) that underwent infusion of distilled water into the left hepatic artery, an embolization group (n = 15) that underwent left hepatic artery embolization with polyvinyl alcohol (PVA) particles, and a chemoembolization group (n = 15) that underwent left hepatic artery infusion of a mixture of 10-hydroxycamptothecin and iodized oil followed by PVA embolization. Serum and liver samples were collected at 6 hours, 3 days, and 7 days postoperatively. Liver damage was measured by liver function tests and histologic analysis. Ki-67 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling were performed to quantify proliferating and apoptotic cells. Serum tumor necrosis factor (TNF)-α levels were measured to assess proinflammatory response.
  
  
  RESULTS
  Compared with embolization, chemoembolization caused liver injury with a greater increase in serum alanine aminotransferase and aspartate aminotransferase levels on days 3 and 7; histologic analysis showed increased hepatic necrosis in adjacent liver tissue beginning at day 3 and increased serum levels of TNF-α at 6 hours. By contrast, chemoembolization resulted in a slower increase in hepatocyte proliferation. Additionally, increased apoptotic hepatocytes were observed after embolization and chemoembolization.
  
  
  CONCLUSIONS
  In contrast to embolization, nonsuperselective transcatheter arterial chemoembolization increased hepatocellular damage and stimulated systemic proinflammatory cytokine release, but inhibited hepatocyte proliferation.
authors.affiliation: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie-fang Rd., Wuhan 430022, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Zheng
authors.forename: Bin
authors.initials: B
authors.lastname: Liang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.forename: Huimin
authors.initials: H
authors.lastname: Liang
authors.forename: Gansheng
authors.initials: G
authors.lastname: Feng
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D015901:Angiography, Digital Subtraction; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation / Q000187:drug effects*; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects; D004621:Embolization, Therapeutic / Q000009:adverse effects; D006499:Hepatic Artery; D020287:In Situ Nick-End Labeling; D007459:Iodized Oil / Q000008:administration & dosage; D019394:Ki-67 Antigen / Q000378:metabolism; D008111:Liver Function Tests; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008115:Liver Regeneration / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D009336:Necrosis; D011142:Polyvinyl Alcohol / Q000008:administration & dosage; D011817:Rabbits; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019394:Ki-67 Antigen; D014409:Tumor Necrosis Factor-alpha; D007459:Iodized Oil; D011142:Polyvinyl Alcohol; C028098:10-hydroxycamptothecin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002166:Camptothecin