The ALPPS Approach for Colorectal Liver Metastases: Impact of KRAS Mutation Status in Survival

Dig Surg. 2018;35(4):303-310. doi: 10.1159/000471930. Epub 2017 Oct 14.


Background/aims: Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations influence survival after hepatectomy for colorectal liver metastases (CRLM). However, their prognostic significance has never been evaluated in patients who undergo Associating Liver Partition and Portal vein occlusion for Staged hepatectomy (ALPPS).

Methods: Between June 2011 and March 2016, 26 patients underwent ALPPS for CRLM. Complications were classified according to the Clavien-Dindo classification. Bi- and multivariate cox analyses were performed to evaluate variables potentially associated with survival.

Results: Overall, morbidity grade ≥3a and 90-day mortality were 38.5 and 0%, respectively. The median follow-up from the time of discharge was 21.5 months (interquartile range 9.6-35.6). One- and 3-year overall survival (OS) was 83.4 and 48.9%, respectively. Patients with mutated (MT) KRAS had a median OS of 15.3 vs. 38.3 months for those with wild-type (WT) KRAS (p < 0.0001). Median disease-free survival was 7.9, 5.6 vs. 12.3 months for MT and WT KRAS, respectively (p = 0.023). KRAS mutation was found to be an independent risk factor for OS (hazard ratio 7.15, 95% CI 1.50-34.11; p = 0.014).

Conclusion: KRAS mutation is an independent predictor of poor survival after ALPPS. This finding will help to optimize patient selection, both avoiding futile surgical indication and maximizing the benefit for patients with extensive disease who are otherwise subjected to high-risk aggressive surgery.

Keywords: Associating liver partition and portal vein occlusion for staged hepatectomy; Colorectal liver metastases; Genetic mutations; Kirsten rat sarcoma viral oncogene homolog; Posthepatectomy liver failure; Survival.

MeSH terms

  • Adult
  • Aged
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / secondary
  • Colorectal Neoplasms / surgery
  • Female
  • Hepatectomy / methods*
  • Humans
  • Liver / surgery*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Mutation
  • Patient Selection
  • Portal Vein / surgery*
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / blood
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Retrospective Studies


  • KRAS protein, human
  • Proto-Oncogene Proteins p21(ras)