title: Reappraisal of the risks and benefits of major liver resection in patients with initially unresectable colorectal liver metastases.
abstract: OBJECTIVE
  To determine short- and long-term outcomes of major hepatectomy in patients with downstaged colorectal liver metastases considered initially unresectable (IU).
  
  
  BACKGROUND
  Improvements in both surgical technique and efficacy of chemotherapy have increased the rate of resection for IU colorectal liver metastases. The outcome of these patients needs to be reassessed.
  
  
  METHODS
  From 2000 to 2011, 257 patients underwent major hepatectomy for colorectal liver metastases. Of these, 87 (34%) IU patients required portal vein occlusion after chemotherapy downstaging. Patients requiring less than 12 cycles and 12 or more cycles of chemotherapy before resection were defined as fast responders and slow responders, respectively.
  
  
  RESULTS
  Compared with fast responders, slow responders had increased mortality (0% vs 19%, P = 0.003) and major morbidity rates (20% vs 55%, P < 0.001) despite almost identical tumor characteristics and similar procedures. In multivariate analysis, the only factor associated with increased major morbidity was the existence of a number of chemotherapy cycles of 12 or more (hazard ratio [HR]: 5.32, confidence interval [CI]: 1.69-16.7, P = 0.004). One-, 3-, and 5-year disease-free survival rates for the entire population were 48%, 17.5%, and 13%, respectively. Multivariate analysis found that slow responders (HR: 2.89, CI: 1.67-5.04, P < 0.001) and patients without adjuvant chemotherapy (HR: 2.38, CI: 1.33-4.35, P = 0.004) had a significantly decreased disease-free survival. All slow responders postoperatively recurred within 3 years.
  
  
  CONCLUSIONS
  Liver resection in slow responders, that is, IU patients requiring 12 or more chemotherapy cycles and portal vein occlusion to achieve resectability, is associated with poor short- and long-term outcomes. These patients would probably benefit from more conservative strategies.
authors.affiliation: Department of HPB Surgery & Liver Transplantation, Beaujon Hospital, Clichy, France.
authors.forename: François
authors.initials: F
authors.lastname: Cauchy
authors.forename: Béatrice
authors.initials: B
authors.lastname: Aussilhou
authors.forename: Safi
authors.initials: S
authors.lastname: Dokmak
authors.forename: David
authors.initials: D
authors.lastname: Fuks
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gaujoux
authors.forename: Olivier
authors.initials: O
authors.lastname: Farges
authors.forename: Sandrine
authors.initials: S
authors.lastname: Faivre
authors.forename: Daniel
authors.initials: D
authors.lastname: Lepillé
authors.forename: Jacques
authors.initials: J
authors.lastname: Belghiti
mesh_terms: D000368:Aged; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome