Liver resection for colorectal metastases after chemotherapy: Impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival

Luca Viganò, Lorenzo Capussotti, Giovanni De Rosa, Wassila Oulhaci De Saussure, Gilles Mentha, Laura Rubbia-Brandt

Research output: Contribution to journalArticlepeer-review


Objectives: 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.

Original languageEnglish
Pages (from-to)731-742
Number of pages12
JournalAnnals of Surgery
Issue number5
Publication statusPublished - Nov 2013


  • Adjuvant chemotherapy
  • Body mass index
  • Chemotherapy-related liver injuries
  • Colorectal liver metastases
  • Liver surgery
  • Long-term outcome
  • Micrometastases
  • Microscopic biliary invasion
  • Microvascular invasion
  • Neoadjuvant chemotherapy
  • Nodular regenerative hyperplasia
  • Pathological tumor response to chemotherapy
  • Preoperative chemotherapy
  • Prognostic factors
  • Sinusoidal dilatation
  • Sinusoidal obstruction syndrome
  • Steatohepatitis
  • Steatosis
  • Survival
  • Tumor regression grade

ASJC Scopus subject areas

  • Surgery


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