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• W3119707882 abstract "We read with great interest the article by Hatta et al. highlighting the impact of KRAS mutational status on survival after surgical resection in patients with colorectal liver metastases (CRLM).1Hatta A.A.Z. Pathanki A.M. Hodson J. Sutcliffe R.P. Marudanayagam R. Roberts K.J. et al.The effects of resection margin and KRAS status on outcomes after resection of colorectal liver metastases.HPB. 2020 May 13; (S1365-182X(20)30143-X)https://doi.org/10.1016/j.hpb.2020.04.016Abstract Full Text Full Text PDF Scopus (3) Google Scholar The results show that patients with mutated KRAS (mKRAS) have a significantly worse prognosis than wild type KRAS (wt-KRAS) in terms of both overall survival and recurrence free survival. The KRAS gene encodes for a G protein that participates in the transduction of the cellular signal induced by the epidermis growth factor receptor (EGFR). The mutations of the KRAS gene cause the RAS proteins to remain permanently in the active form, perpetuating the signal transduction mechanisms in the absence of any upstream stimulation of EGFR/HER receptors leading to cell growth, unstoppable proliferation and abnormal differentiation of the cell.2Andreyev H.J. Norman A.R. Cunningham D. Oates J. Dix B.R. Iacopetta B.J. et al.Kirsten ras mutations in patients with colorectal cancer: the KRASCAL II study.Br J Canc. 2001 Sep 1; 85: 692-696https://doi.org/10.1054/bjoc.2001.1964Crossref PubMed Scopus (715) Google Scholar This pathophysiological mechanism significantly affects surgical outcomes with a negative impact on the prognosis.3Margonis G.A. Sasaki K. Gholami S. Kim Y. Andreatos N. Rezaee N. et al.Genetic and Morphological Evaluation (GAME) score for patients with colorectal liver metastases.Br J Surg. 2018 Aug; 105: 1210-1220https://doi.org/10.1002/bjs.10838Crossref PubMed Scopus (56) Google Scholar,4Adam R. de Gramont A. Figueras J. Kokudo N. Kunstlinger F. Loyer E. et al.Of the EGOSLIM (Expert Group on OncoSurgery management of LIver Metastases) group. Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus.Canc Treat Rev. 2015 Nov; 41 (Epub 2015 Jun 30. PMID: 26417845): 729-741https://doi.org/10.1016/j.ctrv.2015.06.006Abstract Full Text Full Text PDF PubMed Scopus (256) Google Scholar Therefore, it would be interesting to re-evaluate the option of liver transplantation in the different mutational patterns of KRAS. It could be hypothesized in fact that considering the high rate of post-resection recurrences in mKRAS patients, liver transplantation could be ideally a better choice in order to obtain a real oncological clearance. At the same time, the question is whether this radical, but aggressive, surgical strategy is really helpful for patients affected by such an aggressive metastatic disease, in a context of chronic shortage of organs. Favorable outcomes after liver transplantation in selected patients affected by CRLM are derived from the SECA II study, which encourages us to reconsider with more evidence this rare indication of transplantation, forgotten and forbidden for a longtime.5Dueland S. Syversveen T. Solheim J.M. Solberg S. Grut H. Bjørnbeth B.A. et al.Survival following liver transplantation for patients with nonresectable liver-only colorectal metastases.Ann Surg. 2020 Feb; 271 (PMID: 31188200): 212-218https://doi.org/10.1097/SLA.0000000000003404Crossref PubMed Scopus (71) Google Scholar Considering the recent evolution of individual medicine in the treatment of colorectal liver metastases, the role of transplantation could find a wider space after analyzing the outcomes of different molecular KRAS mutation patterns. Maybe in the near future when regenerative medicine and whole organ engineering will allow to overcome the shortage of organs and immunosuppression, surgical strategy will radically change.6Mazza G. Al-Akkad W. Rombouts K. Pinzani M. Liver tissue engineering: from implantable tissue to whole organ engineering.Hepatol Commun. 2017 Dec 21; 2: 131-141https://doi.org/10.1002/hep4.1136Crossref PubMed Scopus (58) Google Scholar This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare that they do not have any conflicts of interest." @default.
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• W3119707882 title "Can the mutational status of KRAS drive the treatment of colorectal liver metastases?" @default.
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