The authors have no acknowledgements.

All experiments in this protocol were approved by the Veterinary Authorities of the Canton of Z&#252;rich, Switzerland (number 60/2014). Furthermore, all experimental steps were performed in strict compliance with the Guidelines on Experiments with Animals by the Swiss Academy of Medical Sciences (SAMS) and Guidelines of the Federation of European Laboratory Animal Science Associations (FELASA).
1. Animal Husbandry, Operating Room Equipment and Instruments, Anesthesia
<ol>
	<li>Keep male Wistar rats with a weight of 250-300 g in ventilated cages under standard pathogen-free conditions in a 12/12 h light/dark cycle. Give animals free access to food and water at an ambient temperature of 22 &#177; 1 &#176;C.</li>
	<li>Induce anesthesia in a box, where isoflurane is flushed in with 5 vol% for 30 s (Figure 1A), followed by an isoflurane concentration of 3 vol% until the animal is under deep anesthesia. Confirm the level of anesthesia by the toe-pinch reflex.</li>
	<li>Provide analgesia using subcutaneously applied buprenorphine (0.01 mg/kg) during the surgical intervention, followed by 0.02 mg/kg every 12 h in the postoperative phase for 48 h.</li>
	<li>Transfer the animal to the working place, where they are spontaneously breathing exposed to a gas mixture of 1.0 - 2.5 vol% isoflurane in oxygen (flow: 600 mL/min).</li>
	<li>Close the eyes of the animal and use an ointment to protect the eyes. Inject 5 mL saline subcutaneously, half of it on each side of the abdomen, followed by 0.1 mg atropine.</li>
	<li>Perform surgery using a surgical microscope in a microsurgery room.</li>
	<li>Keep the animal under volatile anesthesia using a ventilation mask consisting of a latex membrane (Figure 1B), through which the rat&#39;s snout is pushed. Fix the extremities with tape (Figure 1B).</li>
	<li>Lay out the surgical instruments in sterile fashion on a side table: saline- and Betadine-soaked sponges (Figure 2A), abdominal wall retractors (Figure 2B) as well as 3-0 sutures for retraction of the abdominal wall and xiphoid, scissors, Adson forceps, fine tips microforceps straight and curved and pre-cut 6-0 silk ties for the ligation procedure (Figure 2C).</li>
	<li>Use non-sticking bipolar microforceps for transection of the hepatic parenchyma. Close the abdominal wall and skin using 3-0 silk sutures with SH-1 needles and 5-0 Maxon (Figure 2D). Use a bipolar forceps for hemostasis.</li>
</ol>
2. Start of Surgery
<ol>
	<li>Shave the abdomen of the animal with a small animal hair clipper from the xiphoid to the genitals with a 2-cm area lateral of the midline. Thoroughly remove the hair.</li>
	<li>Disinfect this area 3 times with betadine soaked sponges.</li>
	<li>Perform a midline incision using a scalpel for the skin, and then use surgical scissors to open the abdomen.</li>
	<li>Retract the right and left abdominal wall and the xiphoid with 3-0 silk sutures (Figure 3A).</li>
	<li>Retract the stomach, colon and small bowel from the hepatoduodenal ligament of the rat with self-made small wire retractors (Figure 3B).</li>
</ol>
3. Portal Vein Ligation (PVL)
<ol>
	<li>Access the portal vein and its branches by lateral retraction of the stomach and the small bowel (Figure 3B).</li>
	<li>Dissect the portal vein bluntly by picking up the peritoneum with the microforceps and slowly peeling it medially.</li>
	<li>Dissect the portal vein branches out (Figure 3C) in the following sequence: (1) right posterior branch, (2) left lateral and left median branch together, and (3) caudate branch.
	<ol>
		<li>First, peel off the peritoneum with small, not too energetic moves to avoid tearing the small arterial branches to the liver lobes that run directly under the peritoneal coverage.</li>
		<li>Once the main portal vein is denuded, encircle the branches with slow forward pushing and spreading movements and then pull a 1-cm piece of 6-0 silk tie around the respective portal vein branch and ligate it.</li>
	</ol>
	</li>
	<li>Ligate the right posterior lobe branch. (Figure 3C) The technical difficulty of the right posterior branch consists in the fact that the artery to the right posterior lobe is running across the right posterior portal vein branch.
	<ol>
		<li>Pull the artery cranially together with the peritoneum to expose the right portal vein branch with the curved microforceps.</li>
		<li>Ligate the right posterior lobe branch with the pre-cut 6-0 silk tie. The right posterior lobe turns visibly pale once the portal vein is ligated.</li>
		<li>Avoid pushing against resistance during the circling to prevent tearing the artery or the portal vein. In case of bleeding, apply pressure for at least one minute with a sterile cotton swab and then reassess. If bleeding does not stop, sacrifice the animal.</li>
	</ol>
	</li>
	<li>Ligate the left lateral (LLL) and left median lobe (LML) branches. These branches have one common trunk. (Figure 3C). The left median lobe branch arises from the portal vein within the parenchyma of the LLL.
	<ol>
		<li>Ligate the portal vein leading to both LLL and also the LML branch together using the pre-cut 6-0 silk tie.</li>
		<li>Avoid injuries to the arteries leading to LLL and LML, running within the peritoneal layer. As long as the peritoneum is peeled back carefully, they stay intact. The LLL and LML turn visibly pale once the branches are ligated.</li>
	</ol>
	</li>
	<li>Ligate the caudate lobe branch (Figure 3C). The portal vein leading to the somewhat separate caudate lobes in rats takes off from the main portal vein, distally and medially to the takeoff of the right lobe branch from the main portal vein (not strictly inferiorly like in humans or larger animals).
	<ol>
		<li>Dissect it out and encircle it by lifting up the peritoneum plus bile duct and arteries from the main portal vein.</li>
		<li>Encircle the caudate portal vein branch with a curved microforceps coming from laterally. The two caudate lobes turn visibly pale, once the caudate lobe branch is ligated with 6-0 silk.</li>
	</ol>
	</li>
	<li>Tying these three portal vein branches leads to exclusive portal vein perfusion of the right median lobe (RML), which is visible by a distinct demarcation line between the right and left median lobe.</li>
</ol>
4. Portal Vein Ligation with Transection (PVL+T)
<ol>
	<li>Perform the transection along the demarcation line between RML and LML after PVL (Figure 3D).</li>
	<li>Use a non-sticking bipolar silver forceps with a very fine neurosurgical tip to precauterize the liver tissue creating a 1-mm cauterization strip along the demarcation line.</li>
	<li>Use scissors to carefully cut the precauterized tissue. It is quite difficult to properly assess the depth of the transection. The goal is to get as close to the vena cava as possible, which runs intrahepatically in rats. Injury of the vena cava is accompanied by extensive bleeding, which can usually not be stopped.</li>
	<li>In case of injury apply gentle pressure using a cotton-swab, but if the bleeding does not stop within 3 - 4 min, sacrifice the animal. Attempts at repairing the vena cava using sutures have generally been unsuccessful. Rats are very sensitive to air embolism, which may occur on occasion and lead to cardiac arrest.</li>
</ol>
5. Intraoperative Measurement of Portal Vein Pressure and Volume Flow
<ol>
	<li>Assess portal vein pressure by direct cannulation with a G30 needle connected to a pressure monitor (Figure 4A).</li>
	<li>Use the 2-mm volume flow probe placed laterally connected to the flow device for direct measurement of portal volume flow over 2 min (Figure 4B). Only record data with stable measurement quality as indicated on the machine display.</li>
	<li>Assess portal vein flow and pressure separately after the group of steps that define the respective procedure, i.e. the tying off of three portal vein branches or the tying off of the three portal vein branches plus performing the parenchymal transection between the RML and the LML.</li>
</ol>
6. Final Steps of Surgery
<ol>
	<li>Make sure that the small bowel is placed properly in the abdominal cavity before closing.</li>
	<li>Close the peritoneum and the abdominal wall with 3-0 silk sutures with SH-1 needles.</li>
	<li>Finally suture the skin using Maxon 5-0.</li>
	<li>Disinfect the skin again.</li>
	<li>Apply again 5 mL saline subcutaneously into the subcutaneous tissue lateral to the abdomen.</li>
</ol>
7. Liver Volumetry in Rats Using Small Animal CT
<ol>
	<li>24 h prior to the first CT imaging inject 200 &#956;L of the contrast agent into the tail vein through a G26 intravenous catheter.</li>
	<li>Use a micro CT to scan the rats. Place the animal in a plexiglas box to induce general anesthesia (first flush in with 5 vol% for 30 s, followed by an isoflurane concentration of 2 - 3 vol% until the animal is under anesthesia and maintain it throughout scanning via a tubing system). For optimal image quality, synchronize the CT scan with the respiration of the animal.</li>
	<li>Export the digital imaging and communications in medicine (DICOM) files and analyze them using the public domain imaging platform OsiriX 8.0. Use the &#34;closed polygon&#34; tool to draw the lobe borders based on the radiodensitiy of the nanoparticle contrast in the liver and use the region of interest (ROI) menu to calculate partial liver volumes (see Figure 2A in Schadde et al.17)</li>
	<li>In the standard model, allow the liver to grow over 3 days and obtain daily CT scans to assess volume increase.</li>
</ol>

<ol>
	<li>She, W. H., Chok, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Strategies+to+increase+the+resectability+of+hepatocellular+carcinoma.">Strategies to increase the resectability of hepatocellular carcinoma.</a> World J Hepatol. 7 (18), 2147-2154 (2015).</li><li>Vauthey, J. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standardized+measurement+of+the+future+liver+remnant+prior+to+extended+liver+resection:+methodology+and+clinical+associations.">Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical associations.</a> Surgery. 127 (5), 512-519 (2000).</li><li>Kinoshita, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preoperative+portal+vein+embolization+for+hepatocellular+carcinoma.">Preoperative portal vein embolization for hepatocellular carcinoma.</a> World J Surg. 10 (5), 803-808 (1986).</li><li>van Lienden, K. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Portal+Vein+Embolization+Before+Liver+Resection:+A+Systematic+Review.">Portal Vein Embolization Before Liver Resection: A Systematic Review.</a> Cardiovasc Intervent Radiol. , (2012).</li><li>Kianmanesh, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Right+portal+vein+ligation:+a+new+planned+two-step+all-surgical+approach+for+complete+resection+of+primary+gastrointestinal+tumors+with+multiple+bilateral+liver+metastases.">Right portal vein ligation: a new planned two-step all-surgical approach for complete resection of primary gastrointestinal tumors with multiple bilateral liver metastases.</a> J Am Coll Surg. 197 (1), 164-170 (2003).</li><li>Nadalin, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volumetric+and+functional+recovery+of+the+liver+after+right+hepatectomy+for+living+donation.">Volumetric and functional recovery of the liver after right hepatectomy for living donation.</a> Liver Transpl. 10 (8), 1024-1029 (2004).</li><li>Michalopoulos, G. K., DeFrances, M. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liver+regeneration.">Liver regeneration.</a> Science. 276 (5309), 60-66 (1997).</li><li>Fulop, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alterations+in+hepatic+lobar+function+in+regenerating+rat+liver.">Alterations in hepatic lobar function in regenerating rat liver.</a> J Surg Res. 197 (2), 307-317 (2015).</li><li>Schnitzbauer, A. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Right+portal+vein+ligation+combined+with+in+situ+splitting+induces+rapid+left+lateral+liver+lobe+hypertrophy+enabling+2-staged+extended+right+hepatic+resection+in+small-for-size+settings.">Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings.</a> Ann Surg. 255 (3), 405-414 (2012).</li><li>de Santibanes, E., Clavien, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Playing+Play-Doh+to+prevent+postoperative+liver+failure:+the+&amp;#34;ALPPS&amp;#34;+approach.">Playing Play-Doh to prevent postoperative liver failure: the &amp;#34;ALPPS&amp;#34; approach.</a> Ann Surg. 255 (3), 415-417 (2012).</li><li>Schadde, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Monosegment+ALPPS+hepatectomy:+extending+resectability+by+rapid+hypertrophy.">Monosegment ALPPS hepatectomy: extending resectability by rapid hypertrophy.</a> Surgery. 157 (4), 676-689 (2015).</li><li>Dokmak, S., Belghiti, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Which+limits+to+the+&amp;#34;ALPPS&amp;#34;+approach?.">Which limits to the &amp;#34;ALPPS&amp;#34; approach?.</a> Ann Surg. 256 (3), e6 (2012).</li><li>Aloia, T. A., Vauthey, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Associating+liver+partition+and+portal+vein+ligation+for+staged+hepatectomy+(ALPPS):+what+is+gained+and+what+is+lost?.">Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): what is gained and what is lost?.</a> Ann Surg. 256 (3), e9 (2012).</li><li>Yao, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Establishment+of+a+rat+model+of+portal+vein+ligation+combined+with+in+situ+splitting.">Establishment of a rat model of portal vein ligation combined with in situ splitting.</a> PLoS One. 9 (8), e105511 (2014).</li><li>Schlegel, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ALPPS:+from+human+to+mice+highlighting+accelerated+and+novel+mechanisms+of+liver+regeneration.">ALPPS: from human to mice highlighting accelerated and novel mechanisms of liver regeneration.</a> Ann Surg. 260 (5), 839-846 (2014).</li><li>Croome, K. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+a+porcine+model+for+associating+liver+partition+and+portal+vein+ligation+for+a+staged+hepatectomy.">Characterization of a porcine model for associating liver partition and portal vein ligation for a staged hepatectomy.</a> HPB (Oxford). 17 (12), 1130-1136 (2015).</li><li>Schadde, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hypoxia+of+the+growing+liver+accelerates+regeneration.">Hypoxia of the growing liver accelerates regeneration.</a> Surgery. 161 (3), 666-679 (2017).</li><li>Moris, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanistic+insights+of+rapid+liver+regeneration+after+associating+liver+partition+and+portal+vein+ligation+for+stage+hepatectomy.">Mechanistic insights of rapid liver regeneration after associating liver partition and portal vein ligation for stage hepatectomy.</a> World J Gastroenterol. 22 (33), 7613-7624 (2016).</li><li>Garcia-Perez, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Associated+Liver+Partition+and+Portal+Vein+Ligation+(ALPPS)+vs+Selective+Portal+Vein+Ligation+(PVL)+for+Staged+Hepatectomy+in+a+Rat+Model.+Similar+Regenerative+Response?.">Associated Liver Partition and Portal Vein Ligation (ALPPS) vs Selective Portal Vein Ligation (PVL) for Staged Hepatectomy in a Rat Model. Similar Regenerative Response?.</a> PLoS One. 10 (12), e0144096 (2015).</li><li>Shi, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+preliminary+study+of+ALPPS+procedure+in+a+rat+model.">A preliminary study of ALPPS procedure in a rat model.</a> Sci Rep. 5, 17567 (2015).</li><li>Almau Trenard, H. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+an+experimental+model+of+portal+vein+ligation+associated+with+parenchymal+transection+(ALPPS)+in+rats.">Development of an experimental model of portal vein ligation associated with parenchymal transection (ALPPS) in rats.</a> Cir Esp. 92 (10), 676-681 (2014).</li><li>Dhar, D. K., Mohammad, G. H., Vyas, S., Broering, D. C., Malago, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+rat+model+of+liver+regeneration:+possible+role+of+cytokine+induced+neutrophil+chemoattractant-1+in+augmented+liver+regeneration.">A novel rat model of liver regeneration: possible role of cytokine induced neutrophil chemoattractant-1 in augmented liver regeneration.</a> Ann Surg Innov Res. 9, 11 (2015).</li><li>Wei, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Establishment+of+a+rat+model:+Associating+liver+partition+with+portal+vein+ligation+for+staged+hepatectomy.">Establishment of a rat model: Associating liver partition with portal vein ligation for staged hepatectomy.</a> Surgery. 159 (5), 1299-1307 (2016).</li><li>Tschuor, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Salvage+parenchymal+liver+transection+for+patients+with+insufficient+volume+increase+after+portal+vein+occlusion+-+an+extension+of+the+ALPPS+approach.">Salvage parenchymal liver transection for patients with insufficient volume increase after portal vein occlusion - an extension of the ALPPS approach.</a> Eur J Surg Oncol. 39 (11), 1230-1235 (2013).</li><li>Schadde, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+survival+and+safety+of+ALPPS:+first+report+of+the+International+ALPPS+Registry.">Early survival and safety of ALPPS: first report of the International ALPPS Registry.</a> Ann Surg. 260 (5), 829-836 (2014).</li><li>Harnoss, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prolyl+Hydroxylase+Inhibition+Enhances+Liver+Regeneration+Without+Induction+of+Tumor+Growth.">Prolyl Hydroxylase Inhibition Enhances Liver Regeneration Without Induction of Tumor Growth.</a> Ann Surg. , (2016).</li><li>Olthof, P. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparable+liver+function+and+volume+increase+after+portal+vein+embolization+in+rabbits+and+humans.">Comparable liver function and volume increase after portal vein embolization in rabbits and humans.</a> Surgery. 161 (3), 658-665 (2017).</li><li>Olthof, P. B., van Gulik, T. M., Bennink, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimal+use+of+hepatobiliary+scintigraphy+before+liver+resection.">Optimal use of hepatobiliary scintigraphy before liver resection.</a> HPB (Oxford). 18 (10), 870 (2016).</li><li>Lau, L., Christophi, C., Muralidharan, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraoperative+functional+liver+remnant+assessment+with+indocyanine+green+clearance:+another+toehold+for+climbing+the+&amp;#34;ALPPS&amp;#34;.">Intraoperative functional liver remnant assessment with indocyanine green clearance: another toehold for climbing the &amp;#34;ALPPS&amp;#34;.</a> Ann Surg. 261 (2), e43-e45 (2015).</li><li>Cieslak, K. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+Liver+Function+Using+(99m)Tc-Mebrofenin+Hepatobiliary+Scintigraphy+in+ALPPS+(Associating+Liver+Partition+and+Portal+Vein+Ligation+for+Staged+Hepatectomy).">Assessment of Liver Function Using (99m)Tc-Mebrofenin Hepatobiliary Scintigraphy in ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy).</a> Case Rep Gastroenterol. 9 (3), 353-360 (2015).</li><li>Truant, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drop+of+Total+Liver+Function+in+the+Interstages+of+the+New+Associating+Liver+Partition+and+Portal+Vein+Ligation+for+Staged+Hepatectomy+Technique:+Analysis+of+the+&amp;#34;Auxiliary+Liver&amp;#34;+by+HIDA+Scintigraphy.">Drop of Total Liver Function in the Interstages of the New Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Technique: Analysis of the &amp;#34;Auxiliary Liver&amp;#34; by HIDA Scintigraphy.</a> Ann Surg. 263 (3), e33-e34 (2016).</li></ol>

The authors have nothing to disclose.

This protocol presents an animal model of ALPPS with its rapid hypertrophy induced by PVL+T, that roughly doubles volume increase within 3 days compared to PVL alone.17 The right middle hepatic lobe is used as a model for the growing liver lobe because the middle hepatic lobe is one contiguous parenchymal mass supplied by two separate portal veins to its left and to its right side, as shown in Figure 1 in a recently published work.17 Compared t...

The size of the liver remnant limits the resectability of liver tumors.1 In general, when less than 25% liver tissue is left behind, the patient is at increased risk of death from acute liver failure due to the lack of metabolic function for the entire organism (&#34;too small for size syndrome&#34;).2 This post-hepatectomy liver failure is the most devastating complication after liver resection. Therefore clinicians have tried to induce liver regeneration prior to resection of the liver by manipulating the flow of the portal vein.3 It was found that, once the portal vein is occluded, the remaining part with portal vein flow starts to grow at a slow rate, and can thereby increase up to 60% in size.4 Surgical ligation5 or interventional portal vein occlusion have both been clinically established.4 The increase in volume and function of the liver is reliable, but the growth rate of the liver after portal occlusion is only about one fifth compared to the growth of the remnant liver after partial hepatectomy.6
The time necessary for the liver to grow is weeks to months even though the liver can regenerate at a much faster rate after resection. As such, the liver is the only organ that grows back to normal function after removal of a part of it.7 A novel procedure inducing liver regeneration at a similar pace as after partial hepactectomy was developed by a group of surgeons who discovered that adding a transection between the occluded and the non-occluded part of the liver induces liver hypertrophy at the same growth rate as after liver resection, but prior to resection.9 The procedure initiates rapid hypertrophy of 80% within a week in the future liver remnant, which allows the resection of extensive, primarily unresectable, liver tumors within a week. The procedure was called &#34;Associating Liver Partition and Portal vein ligation for Staged hepatectomy = ALPPS&#34; and became rapidly popular across the world.10 Multiple reports supported an expansion of the resectability of borderline resectable liver tumors achieved by the new technique,11 while the complex surgical procedure was also criticized for its high complication rate.12,13
The development of a rodent and also large animal models of slow and rapid hypertrophy has been attempted since the publication of ALPPS in 2012 to allow a better histological characterization and understanding of the mechanisms and to test drug effects on the different growth rates of liver tissue in animals. The first animal model developed was a rat model. In this model, rapid hypertrophy after parenchymal transection between the right and the left part of the median lobe accelerated regeneration of the right median lobe.14 A different model was introduced later in the mouse. In this model the left lateral lobe was resected and the portal vein branches to every lobe of the liver except the left median lobe were tied.15 In the meantime, large animal models of ALPPS in pigs have been described as well.16
For the study of physiological mechanisms like flow changes and pressure in the portal vein, perfusion and oxygenation of liver tissue, the rat model is superior to the model of ALPPS in mice. Another advantage of the rat over the murine model is that in the rat model there is no necessity for a resection of the left lateral lobe,15 which may contaminate the effects of liver resection with those of ALPPS. The rat model in contrast does not reduce the liver cell mass. A pig model uses the right posterior lobe as the growing lobe, but the pig liver is highly lobulated. Therefore, it is difficult to create a transection plane in the already thin tissue bridge between the right posterior and the right anterior lobe. In contrast, the median lobe in rats consist of two parts that are separately supplied by a portal vein each and a parenchymal transection plane can easily be created between the two using microsurgical techniques. The availability of small animal computer tomography (CT) and/or magnet resonance imaging (MRI) allows the very exact quantification of volumetric growth between portal vein ligation alone and portal vein ligation and the added transection, which is important for the validation of any rapid liver hypertrophy model.
The protocol presented here describes the surgical technique and procedures used for volumetric validation and physiological characterization of the model of slow and rapid hypertrophy after portal vein ligation and portal vein ligation with transection, respectively, in rats.

<table><tbody><tr><td>Isoflurane, 250 mL bottles</td><td>Attane, Piramal, Mumbai, India</td><td>LDNI 22098</td><td>Standard vet. equipment</td></tr><tr><td>Tec-3 Isofluorane Vaporizer</td><td>Ohmeda, GE-Healthcare, Chicago, IL</td><td>not available anymore</td><td>Standard vet. equipment&amp;nbsp;</td></tr><tr><td>Buprenorphine (Temgesic)</td><td>Indivior, Baar, Switzerland</td><td>7680419310353</td><td>GTIN-number</td></tr><tr><td>Vitamine A ointment</td><td>Bausch&amp;amp;Lomp, Zug, Switzerland</td><td>7680223980247</td><td>GTIN-number</td></tr><tr><td>Atropine sulfate 0.5 mg/mL</td><td>Sintetica SA, Mendrisio, Switzerland</td><td>7680565330045</td><td>GTIN-number</td></tr><tr><td>Microsurgery microscope</td><td>Olympus, Tokio, Japan</td><td>SZX10</td><td>Standard vet. equipment</td></tr><tr><td>Betadine</td><td>Mundipharma, Basel, Switzerland</td><td>7680342821377</td><td>GTIN-number</td></tr><tr><td>Sponges</td><td>Carl Roth GmbH, Karlsruhe, Germany</td><td>NK83.1</td><td>Mini-sponges</td></tr><tr><td>Abdominal Wall retractors</td><td>N/A</td><td>N/A</td><td>Self-made from paper clips and Q-Tips</td></tr><tr><td>3-0 silk&amp;nbsp;</td><td>Ethicon, Sommerville, NJ</td><td>K872H</td><td>Standard surgical</td></tr><tr><td>Scissors&amp;nbsp;</td><td>World precision instruments (WPI), Sarasota, FL</td><td>503371</td><td>Standard microsurgical</td></tr><tr><td>Adson forceps</td><td>World precision instruments (WPI), Sarasota, FL</td><td>501244-G</td><td>Standard microsurgical</td></tr><tr><td>Fine tips microforceps</td><td>World precision instruments (WPI), Sarasota, FL</td><td>501976</td><td>Tips need to be polished regularly</td></tr><tr><td>Curved fine tips microforceps</td><td>World precision instruments (WPI), Sarasota, FL</td><td>504513</td><td>Essential to go around the portal vein branches&amp;nbsp;</td></tr><tr><td>6-0 LOOK black braided silk</td><td>Surgical Specalities Corporation, Wyomissing, PA&amp;nbsp;</td><td>SP114</td><td>Spool, precut prior to the procedure</td></tr><tr><td>2-0 silk sutures</td><td>Ethicon, Sommerville, NJ</td><td>K833</td><td>Standard surgical</td></tr><tr><td>5-0 maxon sutures</td><td>Covidien, Dublin, Ireland</td><td>6608-21</td><td>Standard surgical</td></tr><tr><td>Bipolar microforceps</td><td>Sutter, Freiburg, Germany</td><td>780148SGS</td><td>Essential for parenchymal transection</td></tr><tr><td>Q-tips small</td><td>Carl Roth GmbH, Karlsruhe, Germany</td><td>EH11.1</td><td>Standard surgical</td></tr><tr><td>Q-tips big</td><td>Carl Roth GmbH, Karlsruhe, Germany</td><td>XL54.1</td><td>Standard surgical</td></tr><tr><td>G30 needle&amp;nbsp;</td><td>Terumo, Tokyo, Japan</td><td>NN-3013R&amp;nbsp;</td><td>Standard anesthesia equipment</td></tr><tr><td>2 mm volume flow probe&amp;nbsp;</td><td>Transonic Systems, Ithaca, NY</td><td>MA-2PS</td><td>Smallest available probe for HAT-311 flow meter</td></tr><tr><td>Transonic flow meter</td><td>Transonic Systems, Ithaca, NY</td><td>HAT-311 Transsonic flow QC meter</td><td>One of the&amp;nbsp; first generation flow flow meters for surgery</td></tr><tr><td>ExiTron nano 12,000&amp;nbsp;</td><td>Miltenyi Biotech, Bergisch Gladbach, Germany</td><td>130-095-698</td><td>Nanomoloecular contrast medium that opacifies liver and spleen</td></tr><tr><td>G26 intravenous catheter</td><td>Becton Dickinson, Franklin Lakes, NJ</td><td>391349</td><td>Standard anesthesia equipment</td></tr><tr><td>Quantum FX MicroCT&amp;nbsp;</td><td>Perkin Elmer, Waltham, MA</td><td>N/A</td><td>Standard small animal CT scanner at the institute of physiology, University of Z&amp;uuml;rich</td></tr><tr><td>OsiriX 8.0</td><td>Pixmeo Sarl, Geneva, Switzerland</td><td>N/A</td><td>Public domain software : www.pixmeo.com</td></tr></tbody></table>

rat model of the associating liver partition and portal vein ligation for staged hepatectomy (alpps) procedure

Recent clinical data support an aggressive surgical approach to both primary and metastatic liver tumors. For some indications, like colorectal liver metastases, the amount of liver tissue left behind after liver resection has become the main limiting factor of resectability of large or multiple liver tumors. A minimal amount of functional tissue is required to avoid the severe complication of post-hepatectomy liver failure, which has high morbidity and mortality. Inducing liver growth of the prospective remnant prior to resection has become more established in liver surgery, either in the form of portal vein embolization by interventional radiologists or in the form of portal vein ligation several weeks prior to resection. Recently, it was shown that liver regeneration is more extensive and rapid, when the parenchymal transection is added to portal vein ligation in a first stage and then, after only one week of waiting, resection performed in a second stage (Associating Liver Partition and Portal vein ligation for Staged hepatectomy = ALPPS). ALPPS has rapidly become popular across the world, but has been criticized for its high perioperative mortality. The mechanism of accelerated and extensive growth induced by this procedure has not been well understood. Animal models have been developed to explore both the physiological and molecular mechanisms of accelerated liver regeneration in ALPPS. This protocol presents a rat model that allows mechanistic exploration of accelerated regeneration.

The two different surgical procedures portal vein ligation (PVL) and PVL with transection (PVL+T) result in distinctly different growth kinetics. PVL induces moderate volume increase within 3 days, whereas in PVL+T a much larger right median lobe (RML) can be seen (Figure 5). This can be verified by daily volumetry. The volume of the RML roughly doubles within 3 days in PVL, while it triples in PVL+T.17
<p class="jove_content" fo:k...

Watch this Scientific Journal Video about Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy ALPPS Procedure at JoVE.com

Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy ALPPS Procedure

Inducing rapid liver hypertrophy using Associating Liver Partition and Portal vein ligation for a Staged hepatectomy (ALPPS) has been proposed for resection of borderline resectable liver tumors. This model may elucidate mechanisms involved in rapid hypertrophy and allows testing of drugs that promote or block the acceleration of regeneration.

Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Procedure

Recent clinical data support an aggressive surgical approach to both primary and metastatic liver tumors. For some indications, like colorectal liver ...

rat-model-associating-liver-partition-portal-vein-ligation-for-staged

Research

JoVE Journal

Medicine

14.6K Views.  University of Zurich. Snelle lever hypertrofie associëren lever partitie en Portal vein afbinding gebruiken voor een Staged hepatectomy inducerende (ALPPS) voorgesteld voor resectie van borderline resectable lever tumoren. Dit model kan verhelderen mechanismen die betrokken zijn in snelle hypertrofie en kunt testen van drugs die bevorderen of blokkeren van de versnelling van de regeneratie.

Video: Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy ALPPS Procedure

Cecal Ligation Puncture Procedure

Human sepsis is characterized by a set of systemic reactions in response to intensive and massive infection that failed to be locally contained by the host. Currently, sepsis ranks among the top ten causes of mortality in the USA intensive care units 1. During sepsis there are two established haemodynamic phases that may overlap. The initial phase (hyperdynamic) is defined as a massive production of proinflammatory cytokines and reactive oxygen species by macrophages and neutrophils that affects vascular permeability (leading to hypotension), cardiac function and induces metabolic changes culminating in tissue necrosis and organ failure. Consequently, the most common cause of mortality is acute kidney injury. The second phase (hypodynamic) is an anti-inflammatory process involving altered monocyte antigen presentation, decreased lymphocyte proliferation and function and increased apoptosis. This state known as immunosuppression or immune depression sharply increases the risk of nocosomial infections and ultimately, death. The mechanisms of these pathophysiological processes are not well characterized. Because both phases of sepsis may cause irreversible and irreparable damage, it is essential to determine the immunological and physiological status of the patient. This is the main reason why many therapeutic drugs have failed. The same drug given at different stages of sepsis may be therapeutic or otherwise harmful or have no effect 2,3. To understand sepsis at various levels it is crucial to have a suitable and comprehensive animal model that reproduces the clinical course of the disease. It is important to characterize the pathophysiological mechanisms occurring during sepsis and control the model conditions for testing potential therapeutic agents. 
To study the etiology of human sepsis researchers have developed different animal models. The most widely used clinical model is cecal ligation and puncture (CLP). The CLP model consists of the perforation of the cecum allowing the release of fecal material into the peritoneal cavity to generate an exacerbated immune response induced by polymicrobial infection. This model fulfills the human condition that is clinically relevant. As in humans, mice that undergo CLP with fluid resuscitation show the first (early) hyperdynamic phase that in time progresses to the second (late) hypodynamic phase. In addition, the cytokine profile is similar to that seen in human sepsis where there is increased lymphocyte apoptosis (reviewed in 4,5). Due to the multiple and overlapping mechanisms involved in sepsis, researchers need a suitable sepsis model of controlled severity in order to obtain consistent and reproducible results.

The mouse model of cecal ligation and puncture as a valuable tool for the study of human sepsis.

Human sepsis is characterized by a set of systemic reactions in response to intensive and massive infection that failed to be locally contained by the ...

Surgical Procedures for a Rat Model of Partial Orthotopic Liver Transplantation with Hepatic Arterial Reconstruction

Orthotopic liver transplantation (OLT) in rats using a whole or partial graft is an indispensable experimental model for transplantation research, such as studies on graft preservation and ischemia-reperfusion injury 1,2, immunological responses 3,4, hemodynamics 5,6, and small-for-size syndrome 7. The rat OLT is among the most difficult animal models in experimental surgery and demands advanced microsurgical skills that take a long time to learn. Consequently, the use of this model has been limited. Since the reliability and reproducibility of results are key components of the experiments in which such complex animal models are used, it is essential for surgeons who are involved in rat OLT to be trained in well-standardized and sophisticated procedures for this model.
While various techniques and modifications of OLT in rats have been reported 8 since the first model was described by Lee et al. 9 in 1973, the elimination of the hepatic arterial reconstruction 10 and the introduction of the cuff anastomosis technique by Kamada et al. 11 were a major advancement in this model, because they simplified the reconstruction procedures to a great degree. In the model by Kamada et al., the hepatic rearterialization was also eliminated. Since rats could survive without hepatic arterial flow after liver transplantation, there was considerable controversy over the value of hepatic arterialization. However, the physiological superiority of the arterialized model has been increasingly acknowledged, especially in terms of preserving the bile duct system 8,12 and the liver integrity 8,13,14.
In this article, we present detailed surgical procedures for a rat model of OLT with hepatic arterial reconstruction using a 50% partial graft after ex vivo liver resection. The reconstruction procedures for each vessel and the bile duct are performed by the following methods: a 7-0 polypropylene continuous suture for the supra- and infrahepatic vena cava; a cuff technique for the portal vein; and a stent technique for the hepatic artery and the bile duct.

Orthotopic liver transplantation in rats is an indispensable experimental model for biomedical research. Here we present our surgical procedures for orthotopic rat liver transplantation with hepatic arterial reconstruction using a 50% partial graft.

Orthotopic liver transplantation (OLT) in rats using a whole or partial graft is an indispensable experimental model for transplantation research, such as ...

Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure

In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2).
A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.&#160; The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor&#8217;s portal vein was carried out via the recipient&#8217;s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient&#8217;s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7
In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3&#177;0.8 g to 9.8&#177;1 g. At this time, the graft&#8217;s weight decreased from 3.3&#177;0.8 g to 2.3&#177;0.8 g.
We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure until the native liver regenerates.

Auxiliary liver transplantation provides a temporary support in acute hepatic failure, until regeneration of the failing liver. The heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) renders sufficient liver function. We developed an analogous technique in the rat, to examine the influence of the portal vein arterialization on the morphology and function of the graft.

In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the ...

Application of the En Bloc Concept Combined with Anatomic Resection in Laparoscopic Hepatectomy

Laparoscopic hepatectomy has been reported in many studies, and it is the mainstream method of liver resection. In some particular cases, such as when there are tumors adjacent to the cystic bed, surgeons cannot palpate the surgical margins through the laparoscopic approach, which leads to uncertainty about R0 resection. Conventionally, the gallbladder is resected first, and the hepatic lobes or segments are resected second. However, tumor tissues can be disseminated in the above cases. To address this issue, based on the recognition of the porta hepatis and intrahepatic anatomy, we propose a unique approach to hepatectomy combined with gallbladder resection by en bloc anatomic resection in situ. Firstly, after dissecting the cystic duct, without cutting the gallbladder primarily, the porta hepatis is pre-occluded by the single lumen ureter; secondly, the left hepatic pedicle is made free by the gap of the Laennec membrane and Hilar plate; thirdly, the assistant is asked to drag the fundus of the gallbladder, and the liver parenchyma tissue is resected using a harmonic scalpel along the ischemia line on the liver surface and intraoperative ultrasound. The whole middle hepatic vein (MHV) and its tributaries appear completely; lastly, the left hepatic vein (LHV) is disconnected, and the specimen is taken out from the abdominal cavity. The tumor, gallbladder, and other surrounding tissues are resected en bloc, which meets the tumor-free criterion, and a wide incisal margin and R0 resection are achieved. Therefore, the laparoscopic hepatectomy with the combination of the en bloc concept and anatomic resection is a safe, effective, and radical method with low postoperative recurrence and metastasis.

Numerous studies have demonstrated the advantages of anatomic resection. Nonetheless, whether anatomic resection can increase R0 resection rates remains controversial. Consequently, the present study describes an innovative procedure involving the en bloc concept combined with anatomic resection in laparoscopic hepatectomy, which can reduce postoperative recurrence and metastasis.

Laparoscopic hepatectomy has been reported in many studies, and it is the mainstream method of liver resection. In some particular cases, such as when ...

Cancer Research

Re-Arterialized Rat Partial Liver Transplantation with an in vivo Vessel-Oriented 70% Hepatectomy

Split liver transplantation and living liver donor liver transplantation were developed in the clinic to utilize liver organs in a more efficient manner. To better understand the mechanism behind these surgical procedures, a rat partial liver transplantation (PLTx) model was established for relevant surgical studies. Because of the complexity of the rat PLTx model, a protocol with detailed descriptions is required. An article published previously reported a protocol in which ex vivo hepatectomy was used to achieve 50% rat PLTx. In contrast to this protocol, we introduced a re-arterialized PLTx with an in vivo 70% hepatectomy. An updated vessel-oriented hepatectomy was incorporated into the rat PLTx to refine the microsurgical procedure. The portal veins and hepatic arteries of the left lateral lobe and the median lobe were individually dissected and ligated before removal of the liver parenchyma, thereby decreasing the probability of bleeding in the remnant liver stump. Furthermore, an end-to-side vessel anastomosis between the common hepatic artery and the enlarged proper hepatic artery was introduced to re-arterialize the hepatic artery. By using this end-to-side vessel anastomosis technique, the diameter of the anastomosis was enlarged, thereby decreasing the difficulty of hand suture and maintaining a high rate of anastomotic patency. Moreover, the cuff anastomosis of the infrahepatic vena cava was slightly modified. A section of circumferential liver parenchyma around the vena cava of a recipient was preserved during cuff anastomosis to maintain the three-dimensional shape of the vascular lumen. This section of liver parenchyma was removed after completing the anastomosis. With this modification, the step involving placement of stay sutures was omitted, thereby further shortening the cuff anastomosis time. By using this protocol of rat PLTx, a low liver enzyme level, an intact liver lobular architecture and a high survival rate were achieved after microsurgery.

Re-Arterialized Rat Partial Liver Transplantation with an in vivo Vessel-Oriented 70% Hepatectomy

Here, a protocol involving re-arterialized rat partial liver transplantation is presented. Specifically, 70% liver was resected in vivo by using an updated technique of vessel-oriented hepatectomy. The hepatic artery was reconstructed in an end-to-side manner. The cuff technique was modified to shorten the anastomosis time of the infrahepatic vena cava.

Split liver transplantation and living liver donor liver transplantation were developed in the clinic to utilize liver organs in a more efficient manner. ...

Reduced Complications after Arterial Reconnection in a Rat Model of Orthotopic Liver Transplantation

The rat orthotopic liver transplantation (OLT) model is a powerful tool to study acute and chronic rejection. However, it is not a complete representation of human liver transplantation due to the absence of arterial reconnection. Described here is a modified transplantation procedure that includes the incorporation of hepatic artery (HA) reconnection, leading to a marked improvement in transplant outcomes. With a mean anhepatic time of 12 min and 14 s, HA reconnection results in improved perfusion of the transplanted liver and an increase in long-term recipient survival from 37.5% to 88.2%. This protocol includes the use of 3D-printed cuffs and holders to connect the portal vein and infrahepatic inferior vena cava. It can be implemented for studying multiple aspects of liver transplantation, from immune response and infection to technical aspects of the procedure. By incorporating a simple and practical method for arterial reconnection using a microvascular technique, this modified rat OLT protocol closely mimics aspects of human liver transplantation and will serve as a valuable and clinically relevant research model.

The goal of this study is to modify the rat orthotopic liver transplant model to better represent human liver transplantation and improve recipient survival. The presented method reestablishes hepatic arterial inflow by connecting the donor liver&#39;s common hepatic artery to the recipient liver&#39;s proper hepatic artery.

The rat orthotopic liver transplantation (OLT) model is a powerful tool to study acute and chronic rejection. However, it is not a complete representation ...

Studying Liver Regeneration of ALLPS in Animal Models for Staged Hepatectomy

A Mouse Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Procedure Aided by Microscopy

Hepatectomy is widely regarded as the primary treatment for hepatic malignancies; yet, postoperative liver failure remains a major cause of perioperative mortality, severely impacting patient outcomes. In a robust hepatic environment, the future liver remnant (FLR) must exceed 25%, and in cases of cirrhosis, this requirement increases to over 40%. The inadequacy of FLR is currently a major obstacle in the progression of hepatic surgery.
Traditional methods to enhance FLR hypertrophy mainly focus on portal vein embolization (PVE), but its effectiveness is considerably limited. In recent years, there have been numerous reports on a novel biphasic hepatectomy method involving hepatic partitioning and portal vein ligation, known as associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). ALPPS surpasses PVE in efficiently and considerably inducing FLR hypertrophy. However, the detailed mechanisms driving ALPPS-facilitated hepatic regeneration are not fully understood. Thus, replicating ALPPS in animal models is crucial to thoroughly investigate the molecular mechanisms of hepatic regeneration, offering valuable theoretical and practical insights.

Author Spotlight: Advancing Liver Regeneration Research through ALPPS Mouse Model

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has been shown to result in remarkable liver regeneration after several weeks post first-stage surgery. Animal models that have undergone ALPPS have been developed to explore potential liver regeneration ability and achieve favorable clinical outcomes.

Hepatectomy is widely regarded as the primary treatment for hepatic malignancies; yet, postoperative liver failure remains a major cause of perioperative ...

Liver Transplantation in Rats and Analyzing Allograft Patency

Heterotopic Auxiliary Whole Liver Rat Transplant Model Utilizing a Hepaticoureterostomy for Allograft Rejection Studies

Small animal transplant models are indispensable for organ tolerance studies investigating feasible therapeutic interventions in preclinical studies. Rat liver transplantation (LTx) protocols typically use an orthotopic model where the recipients&#39; native liver is removed and replaced with a donor liver. This technically demanding surgical procedure requires advanced micro-surgical skills and is further complicated by lengthy anhepatic and lower body ischemia times. This prompted the development of a less complicated heterotopic method that can be performed faster with no anhepatic or lower body ischemia time, reducing post-surgery stress for the recipient animal.
This heterotopic LTx protocol includes two main steps: excising the liver from the donor rat and transplanting the whole liver into the recipient rat. During the excision of the donor liver, the surgeon ligates the supra-hepatic vena cava (SHVC) and hepatic artery (HA). On the recipient side, the surgeon removes the left kidney and positions the donor liver with the portal vein (PV), infra-hepatic vena cava (IHVC), and bile duct facing the renal vessels. Further, the surgeon anastomoses the recipient&#39;s renal vein end to end with the IHVC of the liver and arterializes the PV with the renal artery using a stent. A hepaticoureterostomy is utilized for biliary drainage by anastomosing the bile duct to the recipient&#39;s ureter, permitting the discharge of bile via the bladder.
The average duration of the transplantation was 130 min, cold ischemia duration was around 35 min, and warm ischemia duration was less than 25 min. Hematoxylin and eosin histology of the auxiliary liver from syngeneic transplants showed normal hepatocyte structure with no significant parenchymal alterations 30 days post-transplant. In contrast, 8-day post-transplant allogeneic graft specimens demonstrated extensive lymphocytic infiltration with a Banff Schema rejection activity index score of 9. Therefore, this LTx method facilitates a low morbidity rejection model alternative to orthotopic LTx.

The rat heterotopic auxiliary liver transplant protocol described here offers a practical investigational tool for exploring mechanisms of hepatic allograft rejection. This model helps to alleviate the surgical hurdles and animal stress of orthotopic liver transplantation in rats.

Small animal transplant models are indispensable for organ tolerance studies investigating feasible therapeutic interventions in preclinical studies. Rat ...

Laparoscopic Sectionectomy Using Ligamentum Teres for Bloodless Hepatectomy

Laparoscopic Left Lateral Sectionectomy: Guided by the Ligamentum Teres Hepatis and the Umbilical Fissure Vein

Laparoscopic left lateral sectionectomy (LLLS), a mainstream procedure in liver surgery, often utilizes controlled low central venous pressure (CLCVP) to reduce bleeding in the hepatic venous system. However, anesthesiologists may avoid the use of CLCVP in patients with concurrent cardiovascular and cerebrovascular diseases to prioritize the maintenance of vital organ perfusion. In this report, we present an LLLS guided by the ligamentum teres hepatis (LTH) for dissection of the Glissonian pedicles for segments 2/3 outside the liver, followed by hepatic parenchymal dissection along the falciform ligament and umbilical fissure vein (UFV) while approaching the left hepatic vein root. Guided by LTH and UFV, this LLLS procedure effectively controlled intraoperative bleeding, even in the absence of CLCVP. Additionally, hepatectomy guided by extrahepatic and intrahepatic anatomical landmarks prevents loss of direction during liver dissection and ensures precise hepatic resection. These attributes suggest that the potential benefits extend beyond patients with cardiovascular or cerebrovascular conditions, making it applicable in a wide range of LLLS cases.

Author Spotlight: Advancing Hepatobiliary and Pancreatic Tumor Treatment with Minimally Invasive Surgical Techniques

Laparoscopic left lateral sectionectomy guided by the ligamentum teres hepatis and umbilical fissure vein effectively controls intraoperative bleeding even without controlled low central venous pressure and prevents loss of direction during parenchymal dissection.

Laparoscopic left lateral sectionectomy (LLLS), a mainstream procedure in liver surgery, often utilizes controlled low central venous pressure (CLCVP) to ...

Mouse Extended Hepatectomy Model for Liver Regeneration Studies

Extended 78&#37; Hepatectomy in a Mouse Surgical Model

Partial 2/3 hepatectomy in mice is used in research to study the liver's regenerative capacity and explore outcomes of liver resection in a number of disease models. In the classical partial 2/3 hepatectomy in mice, two of the five liver lobes, namely the left and median lobes representing approximately 66% of the liver mass, are resected en bloc with an expected postoperative survival of 100%. More aggressive partial hepatectomies are technically more challenging and hence, have seldom been used in mice. Our group has developed a mouse model of an extended hepatectomy technique in which three of the five liver lobes, including the left, median, and right upper lobes, are resected separately to remove approximately 78% of the total liver mass. This extended resection, in otherwise healthy mice, leaves a remnant liver that cannot always sustain adequate and timely regeneration. Failure to regenerate ultimately results in 50% postoperative lethality within 1 week due to fulminant hepatic failure. This procedure of extended 78% hepatectomy in mice represents a unique surgical model for the study of small-for-size syndrome and the evaluation of therapeutic strategies to improve liver regeneration and outcomes in the setting of liver transplantation or extended liver resection for cancer.

Author Spotlight: Evaluating Therapeutic Strategies to Enhance Liver Regeneration

The mouse model of partial 2/3 (66%) hepatectomy is well described in the literature, but more extended hepatectomies mimicking small-for-size syndrome after liver transplantation have seldom been used. We describe an extended 78% hepatectomy procedure in a mouse model that results in approximately 50% postoperative lethality in healthy mice.

Partial 2/3 hepatectomy in mice is used in research to study the liver's regenerative capacity and explore outcomes of liver resection in a number of ...

Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Procedure

Samenvatting

Meer video's verkennen

Hoofdstukken in deze video