Hypothermic perfusion with retrograde outflow during right hepatectomy is safe and feasible.
In situ hypothermic perfusion during liver resection performed under vascular inflow occlusion decreases hepatic ischemia-reperfusion injury, but technical limitations have restricted its widespread use. In situ hypothermic perfusion with retrograde outflow circumvents these impediments and thus could extend the applicability of in situ hypothermic perfusion. The safety and feasibility of in situ hypothermic perfusion with retrograde outflow were analyzed in selected patients undergoing right (extended) hepatectomy and compared to intermittent vascular inflow occlusion, the gold standard method, in this randomized pilot study.



Patients were first screened for parenchymal liver disease (exclusion criteria: steatosis ≥30%, cirrhosis, or cholestasis). Study participants were randomized intraoperatively to undergo in situ hypothermic perfusion with retrograde outflow (n = 9) or intermittent vascular inflow occlusion (n = 9). The target liver core temperature during in situ hypothermic perfusion with retrograde outflow was 28°C. The primary end point was ischemia-reperfusion injury (expressed by peak postoperative transaminase levels). Secondary outcomes included functional liver regeneration (assessed by hepatobiliary scintigraphy) and clinical outcomes.



Peak transaminase levels, total bilirubin, and the international normalized ratio were similar between both groups, although a trend toward more rapid normalization of bilirubin levels was noted for the in situ hypothermic perfusion with retrograde outflow group. Functional liver regeneration as evaluated by hepatobiliary scintigraphy was improved on postoperative day 3 fafter in situ hypothermic perfusion with retrograde outflow but not after intermittent vascular inflow occlusion. Furthermore, in situ hypothermic perfusion with retrograde outflow (requiring continuous ischemia) was comparable to intermittent vascular inflow occlusion for all clinical outcomes, including postoperative complications and hospital stay.



The use of in situ hypothermic perfusion with retrograde outflow appears to be safe and feasible in selected patients with healthy liver parenchyma and may benefit early functional liver regeneration. Future applications of in situ hypothermic perfusion with retrograde outflow include patients with damaged liver parenchyma who would require major hepatic resection with a prolonged vascular inflow occlusion duration.
Department of Surgery, Surgical Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Megan J
MJ
Reiniers
Department of Surgery, Surgical Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Pim B
PB
Olthof
Department of Surgery, Surgical Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Rowan F
RF
van Golen
Department of Surgery, Surgical Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Michal
M
Heger
Department of Cell Biology and Immunology, Wageningen University, Wageningen, The Netherlands.
Adriaan A
AA
van Beek
Department of Cell Biology and Immunology, Wageningen University, Wageningen, The Netherlands.
Ben
B
Meijer
Laboratory Genetic Metabolic Diseases, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
René
R
Leen
Laboratory Genetic Metabolic Diseases, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
André B P
ABP
van Kuilenburg
Department of Radiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Banafsche
B
Mearadji
Department of Nuclear Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Roelof J
RJ
Bennink
Department of Pathology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Joanne
J
Verheij
Department of Surgery, Surgical Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: t.m.vangulik@amc.uva.nl.
Thomas M
TM
van Gulik
D000368:Aged; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D005240:Feasibility Studies; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D008107:Liver Diseases / Q000601:surgery*; D008115:Liver Regeneration; D008297:Male; D008875:Middle Aged; D010477:Perfusion / Q000379:methods*; D010865:Pilot Projects; D015427:Reperfusion Injury / Q000517:prevention & control*; D000637:Transaminases / Q000378:metabolism; D016896:Treatment Outcome
D000637:Transaminases