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 journalArticle

Abstract

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
Volume258
Issue number5
DOIs
Publication statusPublished - Nov 2013

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Neoplasm Micrometastasis
Neoplasm Metastasis
Drug Therapy
Hepatic Veno-Occlusive Disease
Survival
Liver
Wounds and Injuries
Neoplasms
oxaliplatin
irinotecan
Survival Rate
Blood Vessels
Fatty Liver
Multivariate Analysis

Keywords

  • 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

Cite this

Liver resection for colorectal metastases after chemotherapy : Impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival. / Viganò, Luca; Capussotti, Lorenzo; De Rosa, Giovanni; De Saussure, Wassila Oulhaci; Mentha, Gilles; Rubbia-Brandt, Laura.

In: Annals of Surgery, Vol. 258, No. 5, 11.2013, p. 731-742.

Research output: Contribution to journalArticle

Viganò, Luca ; Capussotti, Lorenzo ; De Rosa, Giovanni ; De Saussure, Wassila Oulhaci ; Mentha, Gilles ; Rubbia-Brandt, Laura. / Liver resection for colorectal metastases after chemotherapy : Impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival. In: Annals of Surgery. 2013 ; Vol. 258, No. 5. pp. 731-742.
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title = "Liver resection for colorectal metastases after chemotherapy: Impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival",
abstract = "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.",
keywords = "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",
author = "Luca Vigan{\`o} and Lorenzo Capussotti and {De Rosa}, Giovanni and {De Saussure}, {Wassila Oulhaci} and Gilles Mentha and Laura Rubbia-Brandt",
year = "2013",
month = "11",
doi = "10.1097/SLA.0b013e3182a6183e",
language = "English",
volume = "258",
pages = "731--742",
journal = "Annals of Surgery",
issn = "0003-4932",
publisher = "Lippincott Williams and Wilkins",
number = "5",

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TY - JOUR

T1 - Liver resection for colorectal metastases after chemotherapy

T2 - Impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival

AU - Viganò, Luca

AU - Capussotti, Lorenzo

AU - De Rosa, Giovanni

AU - De Saussure, Wassila Oulhaci

AU - Mentha, Gilles

AU - Rubbia-Brandt, Laura

PY - 2013/11

Y1 - 2013/11

N2 - 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.

AB - 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.

KW - Adjuvant chemotherapy

KW - Body mass index

KW - Chemotherapy-related liver injuries

KW - Colorectal liver metastases

KW - Liver surgery

KW - Long-term outcome

KW - Micrometastases

KW - Microscopic biliary invasion

KW - Microvascular invasion

KW - Neoadjuvant chemotherapy

KW - Nodular regenerative hyperplasia

KW - Pathological tumor response to chemotherapy

KW - Preoperative chemotherapy

KW - Prognostic factors

KW - Sinusoidal dilatation

KW - Sinusoidal obstruction syndrome

KW - Steatohepatitis

KW - Steatosis

KW - Survival

KW - Tumor regression grade

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