title: Reversal of attachment to or invasion of major intrahepatic vessels by colorectal liver metastases according to prehepatectomy chemotherapy regimen.
abstract: BACKGROUND
  Tumor reduction by present-day prehepatectomy chemotherapy can render initially unresectable disease resectable. However, little is known about whether effects on liver metastases with radiologically defined "attachment to or invasion of" major intrahepatic vessels differ between chemotherapy regimens with or without monoclonal antibodies. We compared histologically the relationships between liver tumors and major intrahepatic vessels after chemotherapy according to regimens used to treat colorectal liver metastasis.
  
  
  METHODS
  In 38 patients who underwent chemotherapy and hepatectomy with pretreatment images showing metastases attached to or invading major intrahepatic vessels, 62 metastases showed attachment to or invasion of 88 vessels. After resection, attachment, invasion, and separation were determined histopathologically in resected specimens.
  
  
  RESULTS
  Thirteen patients received cytotoxic drug combinations alone, whereas 25 were treated with regimens including a monoclonal antibody (bevacizumab in 15 and cetuximab in 10). By imaging, 16% (5/32) of vessels in patients receiving cytotoxic drugs alone, 23% (8/35) of vessels in those also receiving bevacizumab, and 48% (10/21) of vessels in those also receiving cetuximab showed detachment after chemotherapy (P = .015 for cetuximab versus cytotoxic and P = .039 for cetuximab versus bevacizumab). Excluding 8 vessels not evaluated histologically, 23 of 31 vessels in the cytotoxic group remained attached or invaded, as did 16 of 29 in the bevacizumab group and 8 of 20 vessels in the cetuximab group (P = .05 versus cytotoxic).
  
  
  CONCLUSIONS
  Prehepatectomy chemotherapy regimens including monoclonal antibodies, particularly anti-epidermal growth factor receptor antibodies, eradicated attachment or invasion between vessels and metastases more frequently. Individualized strategies for prehepatectomy chemotherapy based on intrahepatic location of metastases may offer advantages according to proximity of the metastases to the major intrahepatic vessels.
authors.affiliation: Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan; Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. Electronic address: U17-92TS@med.teikyo-u.ac.jp.
authors.forename: Kuniya
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yabushita
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Clinical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ichikawa
authors.affiliation: Department of Biostatistics and Epidemiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Taguri
authors.affiliation: Division of Diagnostic Pathology, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tanabe
authors.affiliation: Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Koda
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000068258:Bevacizumab; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000473:pathology*; D066246:ErbB Receptors / Q000276:immunology; D005260:Female; D006498:Hepatectomy; D006499:Hepatic Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D006503:Hepatic Veins / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000601:surgery; D008113:Liver Neoplasms / Q000098:blood supply* / Q000556:secondary* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000000981:diagnostic imaging; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology; D011859:Radiography; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D066246:ErbB Receptors; D000068818:Cetuximab