title: Genetic and histological assessment of surgical margins in resected liver metastases from colorectal carcinoma: minimum surgical margins for successful resection.
abstract: OBJECTIVE
  There have been few reports on the minimum surgical margins (SMs) required for successful liver resection in patients with colorectal metastases. This minimum requirement may be narrower than the previously recommended margin of 10 mm.
  
  
  OBJECTIVE
  To identify the minimum margins by assessing the presence of micrometastases around the tumor using genetic and histological techniques, and to investigate whether SMs are associated with patterns of tumor recurrence or patient survival.
  
  
  METHODS
  Prospective and retrospective studies.
  
  
  METHODS
  Tertiary referral cancer center.
  
  
  METHODS
  Fifty-eight patients who underwent 62 liver resections for hepatic metastasis from colorectal cancer between December 1, 1996, and November 30, 2000, were included in the study. Tissue samples taken from the tumor, surrounding liver parenchyma, and Glisson pedicle near the tumor were tested for K-ras and p53 mutations using the mutant allele-specific amplification method. For the retrospective study on patient outcomes, 194 patients who had undergone liver resections between 1980 and 2000 were analyzed according to their SMs.
  
  
  RESULTS
  Of the 62 sets of samples from liver metastases, 39 were positive for K-ras and p53 gene mutations or both. Micrometastases in the liver parenchyma surrounding colorectal metastases were present in 2.0% (4/199) of tested samples and were located within 4 mm of the tumor border. Micrometastases via Glisson pedicle were more common (14.3% [3/21]), but these were also confined to a short distance from the tumor edge (</=5 mm). Of the 5 micrometastases detected by genetic analysis, only 2 were confirmed by histopathological examination. The analysis of patient outcomes demonstrated that the incidence of cut-end recurrence (relapse in the bed of resection) decreased from 20.0% to a range of 5.6% to 7.5% when the SM is 2 mm or more. The incidence of definite cut-end recurrence in patients with SMs less than 2 m, 2 to 4 mm, and 5 mm or wider was 13.3% (6/45), 2.8% (1/36), and 0% (0/102), respectively. The SM was not a significant prognostic factor in patient survival.
  
  
  CONCLUSIONS
  Micrometastases around liver tumors are not common, and most are confined to the immediate vicinity of the tumor border. We propose an SM of 2 mm as a clinically acceptable minimum requirement, which carries approximately a 6% risk of margin-related recurrence. Because liver resection provides the only chance of cure, complete removal of the tumor with a minimum margin is justified when technically unavoidable because of the size, location, number of tumors, or successive resections.
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan 113-8655. kokudo-2su@h.u-tokyo.ac.jp
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Miki
authors.forename: Sachiko
authors.initials: S
authors.lastname: Sugai
authors.forename: Akio
authors.initials: A
authors.lastname: Yanagisawa
authors.forename: Yo
authors.initials: Y
authors.lastname: Kato
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Junji
authors.initials: J
authors.lastname: Yamamoto
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Tetsuichiro
authors.initials: T
authors.lastname: Muto
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Makuuchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006498:Hepatectomy / Q000379:methods / Q000592:standards; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D012189:Retrospective Studies; D016019:Survival Analysis