title: Intrahepatic lymphatic invasion but not vascular invasion is a major prognostic factor after resection of colorectal cancer liver metastases.
abstract: BACKGROUND
  Despite advances in diagnosis and surgical strategies, up to 70% of patients will develop recurrence of the disease after resection of colorectal cancer liver metastases (CRCLM). The purpose of our study was to determine the frequency of four different mechanisms of intrahepatic dissemination, and to evaluate the impact of each mechanism on patient outcomes.
  
  
  METHODS
  The medical records of 118 patients who underwent a first resection of CRCLM during the period between 2000 and 2010 were reviewed. Clinicopathologic variables and outcome parameters were examined. Resected specimens were submitted to routine histological evaluation, and immunohistochemical staining with D2-40 (lymphatic vessels), CD34 (blood vessels), CK-7 (biliary epithelium), and CK-20 (CRC cells).
  
  
  RESULTS
  The mean follow-up after resection was 38 months. Tumor recurrence was observed in 76 patients, with a median interval of 13 months after resection. Overall survival and disease-free survival (DFS) rates after hepatectomy were 62 and 56%, and 26 and 24% at 3 and 5 years, respectively. Intrahepatic microscopic invasion included portal venous in 49 patients, sinusoidal in 43 patients, biliary in 20 patients, and lymphatic in 33 patients. Intra-hepatic lymphatic invasion was the only mechanism of dissemination independently associated with the risk of hepatic recurrence (odds ratio 2.75) and shorter DFS (p = 0.006).
  
  
  CONCLUSIONS
  Intrahepatic lymphatic invasion is a significant prognostic factor. Other mechanisms of invasion, although frequently observed, are not related to recurrence or survival, suggesting that the lymphatic system is the main route for dissemination of CRCLM. Furthermore, immunohistochemical detection of intrahepatic lymphatic invasion might be of value in clinical practice.
authors.affiliation: Liver Surgery Unit, Department of Gastroenterology, University of São Paulo Medical School, Av. Dr Enéas de Carvalho Aguiar, 155 05403-000, São Paulo, Brazil, rmlupinacci@gmail.com.
authors.forename: Renato Micelli
authors.initials: RM
authors.lastname: Lupinacci
authors.forename: Evandro Sobrosa
authors.initials: ES
authors.lastname: Mello
authors.forename: Rafael S
authors.initials: RS
authors.lastname: Pinheiro
authors.forename: Gilton
authors.initials: G
authors.lastname: Marques
authors.forename: Fabrício Ferreira
authors.initials: FF
authors.lastname: Coelho
authors.forename: Jaime Arthur Pirolla
authors.initials: JA
authors.lastname: Kruger
authors.forename: Marcos Vinícius
authors.initials: MV
authors.lastname: Perini
authors.forename: Paulo
authors.initials: P
authors.lastname: Herman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology; D002272:Carcinoembryonic Antigen / Q000097:blood; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology* / Q000556:secondary / Q000628:therapy*; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D012189:Retrospective Studies; D015996:Survival Rate; D047368:Tumor Burden
chemical_list: D002272:Carcinoembryonic Antigen