1. In Situ Hypothermic Perfusion with Retrograde Outflow During Right Hemihepatectomy: First Experiences with a New Technique 
Megan J. Reiniers, MS, Rowan F. van Golen, MS, Michal Heger, PhD, Banafsche Mearadji, MD, PhD, Roelof J. Bennink, MD, PhD, Joanne Verheij, MD, PhD, Thomas M. van Gulik, MD, PhD 
Journal of the American College of Surgeons 
Volume 218, Issue 1, Pages e7-e16 (January 2014)
DOI: /j.jamcollsurg
Copyright © 2014 American College of Surgeons Terms and Conditions

2. Figure 1
The liver during in situ hypotermic perfusion (with retrograde outflow) (IHP-R). The right hepatic artery and the right portal vein branch were cut, after which the right hepatic artery stump was cannulated and connected to the perfusion setup (Fig. 3). Subsequently, vascular inflow occlusion (VIO) was applied and the left and middle hepatic vein (or the confluence thereof) were occluded (depicted above). This situation allows for IHP-R, in which pressurized (<100 mmHg) 4°C lactated Ringer's solution enters the liver via the right hepatic artery stump, the solution courses through the left hemiliver (dashed arrows), and drainage occurs in a retrograde fashion via the cut end of the right portal vein branch.
Journal of the American College of Surgeons  , e7-e16DOI: ( /j.jamcollsurg )
Copyright © 2014 American College of Surgeons Terms and Conditions

3. Figure 2
Photographic images of in situ hypotermic perfusion (with retrograde outflow) (IHP-R). The different phases of IHP-R are depicted. (A) The right hepatic artery (RHA) and portal vein (PV) were dissected free and the hepatic pedicle was looped with a Mersilene sling as a tourniquet (pedicle sling). (B) The situation after cutting and cannulation of the RHA with an arterial cannula. (C) The middle and left hepatic vein (MHV and LHV, respectively) were secured with Mersilene slings and the line of transection, which follows the demarcation that resulted from severing the RHA and right PV branch, was marked on the liver surface using diathermy. (D) The final phase of parenchymal transection, during which the hepatic pedicle, MHV, and LHV were occluded and IHP-R was applied. Blanching of the left liver segments was apparent and a needle temperature probe was inserted into segment 4 to monitor the liver core temperature. (E) The liver remnant shortly after reperfusion, in which the normal color of the liver was restored.
Journal of the American College of Surgeons  , e7-e16DOI: ( /j.jamcollsurg )
Copyright © 2014 American College of Surgeons Terms and Conditions

4. Figure 3
Schematic overview of the perfusion setup of in situ hypotermic perfusion with retrograde outflow (IHP-R). The right hepatic artery was cannulated with an 8-Fr wire-bound arterial cannula (center right) that was connected to the perfusion setup (center left). The perfusion setup consisted of 2 bags of chilled lactated Ringer's solution that were placed in a dual pressure chamber and connected to the arterial cannula via a dual infusion system (depicted on the left). Efflux of the perfusion fluid occurred in a retrograde fashion through the right portal vein branch and the perfusate was subsequently removed from the surgical field by suction (right upper corner). During IHP-R, the pressure in the perfusion setup as well as the liver (TLIVER) and body temperature (TBODY) were monitored on the anesthesia workstation, indicated by the top and bottom graph, respectively (right lower corner). The liver core temperature was measured using a needle temperature probe that was inserted into the liver tissue (depicted on the right).
Journal of the American College of Surgeons  , e7-e16DOI: ( /j.jamcollsurg )
Copyright © 2014 American College of Surgeons Terms and Conditions

5. Figure 4
Body and liver core temperature during in situ hypotermic perfusion with retrograde outflow (IHP-R). The median and range (n = 3 participants) body (TBODY, blue line) and liver core (TLIVER, red line) temperature during IHP-R are plotted over time. The bars depicted above indicate the median and range in the duration of ischemia and IHP-R (perfusion). Three phases are distinguished: an active cooling phase during which the liver core temperature was reduced to the target temperature of 28°C, a maintenance phase during which the liver core temperature was maintained at 28°C, and a rewarming phase during which the liver core temperature was allowed to recover to body temperature.
Journal of the American College of Surgeons  , e7-e16DOI: ( /j.jamcollsurg )
Copyright © 2014 American College of Surgeons Terms and Conditions

6. Figure 5
Histology of the nontumorous tissue of 2 patients. Representative images of hematoxylin and eosin-stained nontumorous sections from the resected liver specimens of 2 patients. (A) Liver tissue from patient 5 (Tables 1 and 3) with grade 1 sinusoidal dilation33 (yellow arrowheads) and minimal portal inflammation (green arrowheads). (B) Liver tissue from patient 4 (Tables 1 and 3) with 15% to 20% steatosis (blue arrowheads) and some intracellular bilirubinostasis (inset, black arrowheads).
Journal of the American College of Surgeons  , e7-e16DOI: ( /j.jamcollsurg )
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7. Figure 6
Functional and volumetric liver regeneration after in situ hypotermic perfusion with retrograde outflow. Function and volume of the (future) remnant liver ([F]RL) were determined preoperatively and on postoperative day 3. (A) A box-and-whisker plot of the calculated (F)RL function, suggesting an increase in remnant liver function on postoperative day 3 compared with the preoperatively calculated values. (B) A box-and-whisker plot of the (F)RL volume at both time points with a trend towards an increase in liver volume on postoperative day 3 compared with the preoperatively calculated values.
Journal of the American College of Surgeons  , e7-e16DOI: ( /j.jamcollsurg )
Copyright © 2014 American College of Surgeons Terms and Conditions

8. Figure 7
Relative increase in postoperative liver function and volume in patients who underwent in situ hypotermic perfusion with retrograde outflow (IHP-R) and in an historic cohort. The relative increase in (future) remnant liver ([F]RL) function and volume compared to preoperatively determined values was calculated (in %) for the IHP-R group as well as for a historic cohort of 12 patients that had undergone a major hepatectomy. (A) The relative increase in (F)RL function in the IHP-R group on postoperative day 3 and in the historic cohort on postoperative days 1 and 90. The relative increase in liver function is significantly greater in the IHP-R group on postoperative day 3 compared to the historic cohort on postoperative day 1 (p = , Mann-Whitney U test), but not compared to the historic cohort on postoperative day 90 (p = , Mann-Whitney U test). (B) The relative increase in (F)RL volume in the IHP-R group on postoperative day 3 and in the historic cohort on postoperative day 90, which are not significantly different (p = , Mann-Whitney U test).
Journal of the American College of Surgeons  , e7-e16DOI: ( /j.jamcollsurg )
Copyright © 2014 American College of Surgeons Terms and Conditions