title: Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival.
abstract: OBJECTIVE
  We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy.
  
  
  BACKGROUND
  CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear.
  
  
  METHODS
  Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases.
  
  
  RESULTS
  A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%.The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032).After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival rate of 23.3% vs 45.7% if absent, P = 0.017; 0% vs 42.3%, P = 0.032, respectively).
  
  
  CONCLUSIONS
  TRG was confirmed to be a crucial prognostic determinant. CALI do not negatively impact long-term prognosis, but the tumor response is reduced in patients with grade 2-3 SOS. Steatosis was found to have a protective effect on survival. Micrometastases significantly impacted prognosis assessment.
authors.affiliation: Departments of *HPB and Digestive Surgery and †Pathology, Ospedale Mauriziano Umberto I, Torino, Italy; and Departments of ‡Visceral and Transplantation Surgery and §Clinical Pathology, University Hospitals, Geneva, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Viganò
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Capussotti
authors.forename: Giovanni
authors.initials: G
authors.lastname: De Rosa
authors.forename: Wassila Oulhaci
authors.initials: WO
authors.lastname: De Saussure
authors.forename: Gilles
authors.initials: G
authors.lastname: Mentha
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000068258:Bevacizumab; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D005234:Fatty Liver / Q000139:chemically induced; D005260:Female; D006498:Hepatectomy / Q000379:methods*; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery*; D008297:Male; D009361:Neoplasm Invasiveness; D061206:Neoplasm Micrometastasis; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000009:adverse effects; D000077150:Oxaliplatin; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin