title: Sinusoidal dilation increases the risk of complications in hepatectomy for CRCLM - Protective effect of bevacizumab and diabetes mellitus, serum gamma-glutamyltranspeptidase as predictive factor.
abstract: BACKGROUND
  Advances in neoadjuvant chemotherapy (NCT) have allowed surgical treatment in otherwise unresectable patients with colorectal liver metastases (CRLM). It is well known that NCT induces liver lesions such as sinusoidal obstruction syndrome (SOS) and steatohepatitis (SH). However, whether it affects postoperative morbidity remains controversial. The aim of this study was both to evaluate the impact of NCT on liver parenchyma and postoperative morbidity, and to identify preoperative predictive markers for liver injury.
  
  
  METHODS
  Among 140 patients undergoing liver resection for CRLM between 2010 and 2013, 70 underwent systemic NCT. Liver function tests, pathology, postoperative morbidity and mortality were compared between the two groups.
  
  
  RESULTS
  Univariate analysis revealed NCT as a cause of sinusoidal dilation (p = 0.09), peliosis (p = 0.028) and moderate and severe SOS (p = 0.004) and bevacizumab as a protective agent against moderate and severe SOS (p = 0.045). Diabetic patients were identified as having a lower incidence of sinusoidal dilation (p = 0.034) and a higher incidence of steatosis (p = 0.003). Multivariate analysis confirmed sinusoidal dilation as an independent cause for morbidity (p = 0.02) and liver-specific complications (p = 0.016). Preoperative level of GGT was identified as predictive factor for moderate and severe SOS and peliosis (p < 0.001 and p = 0.004, respectively).
  
  
  CONCLUSIONS
  The administration of NCT induces SOS-lesions, but can be partially prevented by bevacizumab and diabetes. Sinusoidal dilation is associated with increased postoperative morbidity. Preoperative GGT levels can be useful to predict the presence of SOS.
authors.affiliation: Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Martins
authors.affiliation: Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Electronic address: halexandrino123@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Alexandrino
authors.affiliation: Department of Pathology, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Oliveira
authors.affiliation: Department of Pathology, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: M A
authors.initials: MA
authors.lastname: Cipriano
authors.affiliation: Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Falcão
authors.affiliation: Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Ferreira
authors.affiliation: Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Martins
authors.affiliation: Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Serôdio
authors.affiliation: Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Martins
authors.affiliation: Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: J G
authors.initials: JG
authors.lastname: Tralhão
authors.affiliation: Department of Pathology, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Prado e Castro
authors.affiliation: Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Castro E Sousa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D003920:Diabetes Mellitus; D005260:Female; D006498:Hepatectomy / Q000379:methods*; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology* / Q000517:prevention & control*; D006801:Humans; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D015996:Survival Rate; D016896:Treatment Outcome; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D005723:gamma-Glutamyltransferase
keywords: Colorectal neoplasms; Hepatectomy; Neoadjuvant therapy; Sinusoidal obstruction syndrome