title: Nodular Regenerative Hyperplasia in Patients Undergoing Liver Resection for Colorectal Metastases After Chemotherapy: Risk Factors, Preoperative Assessment and Clinical Impact.
abstract: BACKGROUND
  Nodular regenerative hyperplasia (NRH) is a severe form of chemotherapy-related liver injury (CALI) that may worsen the short-term outcome of liver resection (LR) for colorectal metastases (CRLM). The present study aimed to clarify the incidence, risk factors, preoperative assessment, and clinical impact of NRH.
  
  
  METHODS
  Overall, 406 patients undergoing 478 LRs for CRLM after chemotherapy between 2000 and 2012 were studied. All resection specimens were reviewed. After Gomori staining, NRH was graded according to the Wanless score.
  
  
  RESULTS
  NRH was diagnosed in 87 (18.2 %) patients, grades 2-3 in 14 (2.9 %) patients. At multivariate analysis, the prevalence of NRH was increased after oxaliplatin administration (21.4 vs. 8.4 %; p = 0.003), and reduced by the addition of bevacizumab (11.7 vs. 19.8 %; p = 0.020). Two parameters predicted the presence of NRH: the APRI score (AST to platelet ratio index: 25.5 % if >0.36 vs. 9.8 % if ≤0.36; p = 0.004), and the platelet count (63.6 % if <100 × 10(3)/mm(3) vs. 25.3 % if 100-200 × 10(3)/mm(3) vs. 11.9 % if >200 × 10(3)/mm(3); p = 0.032). Ninety-day mortality and liver failure rates were 0.6 and 3.6 %. NRH was an independent predictor of postoperative liver failure (9.2 % if present vs. 2.3 % if not present; p = 0.021). In patients with grades 2-3 NRH, the rate of liver failure was 14.3 %, 25.0 % after major hepatectomy. No other forms of CALI impacted short-term outcomes.
  
  
  CONCLUSIONS
  NRH was the most relevant form of CALI, increasing the risk of postoperative liver failure. Oxaliplatin increased the incidence of NRH, while bevacizumab decreased it. The APRI score and platelet count were useful tools for predicting NRH.
authors.affiliation: Department of Hepatobiliary and General Surgery, Humanitas Research Hospital, Humanitas University, Rozzano, MI, Italy. lvigano@ymail.com.|Department of HPB and Digestive Surgery, Ospedale Mauriziano Umberto I, Turin, Italy. lvigano@ymail.com.
authors.forename: Luca
authors.initials: L
authors.lastname: Viganò
authors.affiliation: Department of Clinical Pathology, University Hospitals, Geneva, Switzerland.|Hepato-Pancreato-Biliary Centre, University Hospitals, Geneva, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.affiliation: Department of Pathology, Ospedale Mauriziano Umberto I, Turin, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: De Rosa
authors.affiliation: Department of Visceral and Transplantation Surgery, University Hospitals, Geneva, Switzerland.|Hepato-Pancreato-Biliary Centre, University Hospitals, Geneva, Switzerland.
authors.forename: Pietro
authors.initials: P
authors.lastname: Majno
authors.affiliation: Department of HPB and Digestive Surgery, Ospedale Mauriziano Umberto I, Turin, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Langella
authors.affiliation: Department of Visceral and Transplantation Surgery, University Hospitals, Geneva, Switzerland.|Hepato-Pancreato-Biliary Centre, University Hospitals, Geneva, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Toso
authors.affiliation: Department of Visceral and Transplantation Surgery, University Hospitals, Geneva, Switzerland.|Hepato-Pancreato-Biliary Centre, University Hospitals, Geneva, Switzerland.
authors.forename: Gilles
authors.initials: G
authors.lastname: Mentha
authors.affiliation: Department of HPB and Digestive Surgery, Ospedale Mauriziano Umberto I, Turin, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Capussotti
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000601:surgery*; D003131:Combined Modality Therapy; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000175:diagnosis / Q000209:etiology*; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D008115:Liver Regeneration; D008297:Male; D009367:Neoplasm Staging; D011183:Postoperative Complications; D011300:Preoperative Care; D011379:Prognosis; D012307:Risk Factors