title: Hepatic atrophy following preoperative chemotherapy predicts hepatic insufficiency after resection of colorectal liver metastases.
abstract: For patients with colorectal liver metastases (CLM) undergoing major hepatectomy, extensive preoperative chemotherapy has been associated with increased morbidity and mortality. The impact of extensive chemotherapy on total liver volume (TLV) change is unclear. The aims of the current study were twofold: (1) to determine the change of TLV following preoperative chemotherapy in patients undergoing resection for CLM and (2) to investigate the correlations among TLV change, postoperative hepatic insufficiency (PHI), and death from liver failure.
  
  
  
  Clinicopathological features of patients with CLM who underwent preoperative chemotherapy and curative resection were reviewed (2008-2015). TLV change (degree of atrophy) was defined as the percentage difference of TLV (estimated by manual volumetry)/standardized liver volume (SLV) ratio: ([Pre-chemotherapy TLV]-[Post-chemotherapy TLV])×100÷SLV (%). Receiver operating characteristic (ROC) analysis was performed to decide the accurate cut-off value of degree of atrophy to predict PHI. The Cox proportional hazard model was performed to identify the predictors of severe degree of atrophy and PHI.
  
  
  
  The study cohort consisted of 459 patients, of which 154 patients (34%) underwent extensive preoperative chemotherapy (≥7 cycles). ROC analysis identified the degree of atrophy ≥10% as an accurate cut-off to predict PHI, which was significantly correlated with ≥7 cycles of preoperative chemotherapy. Four factors independently predicted PHI: standardized future liver remnant ≤30% (odds ratio [OR] 4.03, p=0.019), high aspartate aminotransferase-to-platelet ratio index (OR 5.27, p=0.028), degree of atrophy ≥10% (OR 43.5, p<0.001), and major hepatic resection (OR 5.78, p=0.005). Degree of atrophy ≥10% was associated with increased mortality from liver failure (0% [0/374] vs. 15% [13/85], p<0.001).
  
  
  
  Extensive preoperative chemotherapy induced significant atrophic change of TLV. Degree of atrophy ≥10% is an independent predictor of PHI and death in patients with CLM undergoing preoperative chemotherapy and resection.
  
  
  
  Extensive preoperative chemotherapy for patients with colorectal liver metastases (CLM) could induce hepatic atrophy. A higher degree of atrophy is an independent predictor of postoperative hepatic insufficiency and death in patients with CLM undergoing preoperative chemotherapy and resection.
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Hepatobiliary-Pancreatic, Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Shindoh
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mizuno
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yun Shin
authors.initials: YS
authors.lastname: Chun
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Claudius
authors.initials: C
authors.lastname: Conrad
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Aloia
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jvauthey@mdanderson.org.
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Vauthey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects*; D048550:Hepatic Insufficiency / Q000209:etiology*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology*; D011446:Prospective Studies; D055815:Young Adult
keywords: Colorectal liver metastases; Postoperative hepatic insufficiency; Preoperative chemotherapy; Total liver volume