Cooling Techniques and Ex Situ Liver Surgery

Part of the Updates in Surgery book series (UPDATESSURG)


Hypothermic preservation is a strategy to reduce ischemia-reperfusion injury in both liver transplantation and liver resection procedures and has been successfully used in liver transplantation setting since the early 1960s to prolong the viability of harvested liver grafts. Static cold storage is able to reduce cellular metabolism by 10- to 12-fold and to slow down energy demand. Hypothermic perfusion is used also during complex liver resection in order to protect the liver parenchyma from ischemia-reperfusion injury during total vascular exclusion.

Ex situ liver resection is a complex kind of surgery burdened by a high morbidity and mortality rate and feasible only for a strictly selected category of patients affected by primary and metastatic liver cancer considered unresectable by conventional surgery. Surgical expertise in liver transplant is required due to the several similarities with the transplant techniques.


Liver transplantation Hypothermic perfusion Cold storage Liver harvesting Ischemia-reperfusion injury Liver preservation Total vascular exclusion Ex situ liver resection Extreme resection Machine perfusion 

Supplementary material

Video 4.1

(MP4 1886244 kb)


  1. 1.
    Starlz TE, Kaupp HA Jr, Brock DR, et al. Reconstructive problems in canine liver homotransplantation with special reference to the postoperative role of hepatic venous flow. Surg Gynecol Obstet. 1960;111:733–43.PubMedGoogle Scholar
  2. 2.
    van Golen RF, Reiniers MJ, van Gulik TM, Heger M. Organ cooling in liver transplantation and resection: how low should we go? Hepatology. 2015;61:395–9.CrossRefGoogle Scholar
  3. 3.
    Dutkowski P, Krug A, Krysiak M, et al. Detection of mitochondrial electron chain carrier redox status by transhepatic light intensity during rat liver reperfusion. Cryobiology. 2003;47:125–42.CrossRefGoogle Scholar
  4. 4.
    Petrat F, de Groot H, Sustmann R, Rauen U. The chelatable iron pool in living cells: a methodically defined quantity. Biol Chem. 2002;383:489–502.CrossRefGoogle Scholar
  5. 5.
    Chang WJ, Chehab M, Kink S, Toledo-Pereyra LH. Intracellular calcium signaling pathways during liver ischemia and reperfusion. J Investig Surg. 2010;23:228–38.CrossRefGoogle Scholar
  6. 6.
    Malhi H, Gores GJ. Cellular and molecular mechanisms of liver injury. Gastroenterology. 2008;134:1641–54.CrossRefGoogle Scholar
  7. 7.
    Chouchani ET, Pell VR, Gaude E, et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014;515:431–5.CrossRefGoogle Scholar
  8. 8.
    Martins RM, Teodoro JS, Furtado E, et al. Recent insights into mitochondrial targeting strategies in liver transplantation. Int J Med Sci. 2018;15:248–56.CrossRefGoogle Scholar
  9. 9.
    Teoh NC, Farrell GC. Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection. J Gastroenterol Hepatol. 2003;18:891–902.CrossRefGoogle Scholar
  10. 10.
    Jaeschke H, Mitchell JR. Use of isolated perfused organs in hypoxia and ischemia/reperfusion oxidant stress. Methods Enzymol. 1990;186:752–9.CrossRefGoogle Scholar
  11. 11.
    Lentsch AB, Kato A, Yoshidome H, et al. Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion injury. Hepatology. 2000;32:169–73.CrossRefGoogle Scholar
  12. 12.
    Chen ZH, Zhang XP, Wang K, et al. Liver resection versus transcatheter arterial chemoembolization for the treatment of patients with hepatocellular carcinoma and hepatic vein or inferior vena cava tumor thrombus: a propensity score matching analysis. Hepatol Res. 2018; [Epub ahead of print].
  13. 13.
    Hosokawa I, Allard MA, Gelli M, et al. Long-term survival benefit and potential for cure after r1 resection for colorectal liver metastases. Ann Surg Oncol. 2016;23:1897–905.CrossRefGoogle Scholar
  14. 14.
    Margonis GA, Buettner S, Andreatos N, et al. Association of BRAF mutations with survival and recurrence in surgically treated patients with metastatic colorectal liver cancer. JAMA Surg. 2018;153:e180996. Scholar
  15. 15.
    Huguet C, Gallot D, Offenstadt G, Coloigner M. Total vascular exclusion of the liver in extensive hepatic exeresis. Value and limits. Nouv Press Med. 1976;5:1189–92. [Article in French].Google Scholar
  16. 16.
    Bismuth H, Castaing D, Garden OJ. Major hepatic resection under total vascular exclusion. Ann Surg. 1989;210:13–9.CrossRefGoogle Scholar
  17. 17.
    Azoulay D, Eshkenazy R, Andreani P, et al. In situ hypothermic perfusion of the liver versus standard total vascular exclusion for complex liver resection. Ann Surg. 2005;241:277–85.CrossRefGoogle Scholar
  18. 18.
    Raab R, Schlitt HJ, Oldhafer KJ, et al. Ex-vivo resection techniques in tissue-preserving surgery for liver malignancies. Langenbeck's Arch Surg. 2000;385:179–84.CrossRefGoogle Scholar
  19. 19.
    Park J, Kim MH, Kim KP, et al. Natural history and prognostic factors of advanced cholangiocarcinoma without surgery, chemotherapy, or radiotherapy: a large-scale observational study. Gut Liver. 2009;3:298–305.CrossRefGoogle Scholar
  20. 20.
    Gringeri E, Polacco M, D’Amico FE, et al. A new liver autotransplantation technique using subnormothermic machine perfusion for organ preservation in a porcine model. Transplant Proc. 2011;43:997–1000.CrossRefGoogle Scholar
  21. 21.
    Oldhafer KJ, Lang H, Schlitt HJ, et al. Long-term experience after ex situ liver surgery. Surgery. 2000;127:520–7.CrossRefGoogle Scholar
  22. 22.
    Hannoun L, Panis Y, Balladur P, et al. Ex-situ in-vivo liver surgery. Lancet. 1991;337:1616–7.CrossRefGoogle Scholar
  23. 23.
    Hannoun L, Balladur P, Delva E, et al. “Ex situ-in vivo” surgery of the liver: a new technique in liver surgery. Principles and preliminary results. Gastroenterol Clin Biol. 1991;15:758–61. [Article in French].PubMedGoogle Scholar
  24. 24.
    Vaillant JC, Borie DC, Hannoun L. Hepatectomy with hypothermic perfusion of the liver. Hepato-Gastroenterology. 1998;45:381–8.PubMedGoogle Scholar
  25. 25.
    Belghiti J, Dousset B, Sauvanet A, et al. Preliminary results with “ex situ” surgery for hepatic tumors: an alternative between palliative treatment and liver transplantation? Gastroenterol Clin Biol. 1991;15:449–53. [Article in French].PubMedGoogle Scholar
  26. 26.
    Mehrabi A, Fonouni H, Golriz M, et al. Hypothermic ante situm resection in tumors of the hepatocaval confluence. Dig Surg. 2011;28:100–8.CrossRefGoogle Scholar
  27. 27.
    Hemming AW, Reed AI, Fujita S, et al. Role for extending hepatic resection using an aggressive approach to liver surgery. J Am Coll Surg. 2008;206:870–5.CrossRefGoogle Scholar
  28. 28.
    Hemming AW, Reed AI, Langham MR, et al. Hepatic vein reconstruction for resection of hepatic tumors. Ann Surg. 2002;235:850–8.CrossRefGoogle Scholar
  29. 29.
    Hemming AW, Reed AI, Langham MR Jr, et al. Combined resection of the liver and inferior vena cava for hepatic malignancy. Ann Surg. 2004;239:712–9.CrossRefGoogle Scholar
  30. 30.
    Malde DJ, Khan A, Prasad KR, et al. Inferior vena cava resection with hepatectomy: challenging but justified. HPB (Oxford). 2011;13:802–10.CrossRefGoogle Scholar
  31. 31.
    Forni E, Meriggi F. Bench surgery and liver autotransplantation. Personal experience and technical considerations. G Chir. 1995;16:407–13.PubMedGoogle Scholar
  32. 32.
    Tomimaru Y, Eguchi H, Wada H, et al. Liver resection combined with inferior vena cava resection and reconstruction using artificial vascular graft: a literature review. Ann Gastroenterol Surg. 2018;2:182–6.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Surgery, Oncology and GastroenterologyUniversity of PaduaPaduaItaly
  2. 2.Hepatobiliary Surgery and Liver Transplant UnitPadua University HospitalPaduaItaly

Personalised recommendations