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Simultaneous hepatic and portal vein ligation induces rapid liver hypertrophy: A study in pigs


Schadde, Erik; Guiu, Boris; Deal, Rebecca; Kalil, Jennifer; Arslan, Bulent; Tasse, Jordan; Olthof, Pim B; Heil, Jan; Schnitzbauer, Andreas A; Jakate, Shriram; Breitenstein, Stefan; Schläpfer, Martin; Schimmer, Beatrice Beck; Hertl, Martin (2019). Simultaneous hepatic and portal vein ligation induces rapid liver hypertrophy: A study in pigs. Surgery, 165(3):525-533.

Abstract

Background Liver hypertrophy induced by partial portal vein occlusion (PVL) is accelerated by adding simultaneous parenchymal transection (“ALPPS procedure”). This preclinical experimental study in pigs tests the hypothesis that simultaneous ligation of portal and hepatic veins of the liver also accelerates regeneration by abrogation of porto-portal collaterals without need for operative transection. Methods A pig model of portal vein occlusion was compared with the novel model of simultaneous portal and hepatic vein occlusion, where major hepatic veins draining the portal vein–deprived lobe were identified with intraoperative ultrasonography and ligated using pledgeted transparenchymal sutures. Kinetic growth was compared, and the portal vein system was then studied after 7 days using epoxy casts of the portal circulation. Portal vein flow and portal pressure were measured, and Ki-67 staining was used to evaluate the proliferative response. Results Pigs were randomly assigned to portal vein occlusion (n = 8) or simultaneous portal and hepatic vein occlusion (n = 6). Simultaneous portal and hepatic vein occlusion was well tolerated and led to mild cytolysis, with no necrosis in the outflow vein–deprived liver sectors. The portal vein–supplied sector increased by 90 ± 22% (mean ± standard deviation) after simultaneous portal and hepatic vein occlusion compared with 29 ± 18% after PVL (P < .001). Collaterals to the deportalized liver developed after 7 days in both procedures but were markedly reduced in simultaneous portal and hepatic vein occlusion. Ki-67 staining at 7 days was comparable. Conclusion This study in pigs found that simultaneous portal and hepatic vein occlusion led to rapid hypertrophy without necrosis of the deportalized liver. The findings suggest that the use of simultaneous portal and hepatic vein occlusion accelerates liver hypertrophy for extended liver resections and should be evaluated further. Introduction Portal vein occlusion by ligation (PVL) or embolization is a well-established method to improve the safety of extended liver resections by inducing liver hypertrophy before resection.1, 2, 3 The novel procedure associating liver partition and portal vein ligation (ALPPS) indicated that kinetic growth of the future liver remnant can be increased by adding a parenchymal transection between the portal vein–supplied and portal vein–deprived part of the liver.4 A recent pig study from our laboratory suggested that the parenchymal transection in ALPPS leads to an abrogation of extensive porto-portal neocollaterals between the portal vein–supplied and the portal vein–deprived side of the liver.5 Porto-portal collaterals are common in PVL and also occur in portal vein embolization; these collaterals are known to blunt hypertrophy, and their complete abrogation may well be the cause for the astounding effectiveness of parenchymal transection in ALPPS. Based on the concept that abrogation of collaterals is a key requirement for rapid hypertrophy, we postulated that simultaneous occlusion of hepatic and portal veins may abrogate the formation of porto-portal collaterals to the deportalized side of the liver and thereby accelerate hypertrophy compared with PVL. This study tested whether simultaneous ligation of portal veins and hepatic veins (PLV+HVL) to the deportalized side of the liver would accelerate the increase in liver volume of the contralateral nondeportalized liver in a pig model. Methods Ethical statement Approval for the experiments was obtained from the Internal Animal Care and Use Committee of Rush University Medical Center (No. 15-025). The experiments were performed in compliance with the Guide for the Care and Use of Laboratory Animals by the National Research Council, 2011 edition (https://www.nap.edu/download/12910), and the ARRIVE guidelines.6

Abstract

Background Liver hypertrophy induced by partial portal vein occlusion (PVL) is accelerated by adding simultaneous parenchymal transection (“ALPPS procedure”). This preclinical experimental study in pigs tests the hypothesis that simultaneous ligation of portal and hepatic veins of the liver also accelerates regeneration by abrogation of porto-portal collaterals without need for operative transection. Methods A pig model of portal vein occlusion was compared with the novel model of simultaneous portal and hepatic vein occlusion, where major hepatic veins draining the portal vein–deprived lobe were identified with intraoperative ultrasonography and ligated using pledgeted transparenchymal sutures. Kinetic growth was compared, and the portal vein system was then studied after 7 days using epoxy casts of the portal circulation. Portal vein flow and portal pressure were measured, and Ki-67 staining was used to evaluate the proliferative response. Results Pigs were randomly assigned to portal vein occlusion (n = 8) or simultaneous portal and hepatic vein occlusion (n = 6). Simultaneous portal and hepatic vein occlusion was well tolerated and led to mild cytolysis, with no necrosis in the outflow vein–deprived liver sectors. The portal vein–supplied sector increased by 90 ± 22% (mean ± standard deviation) after simultaneous portal and hepatic vein occlusion compared with 29 ± 18% after PVL (P < .001). Collaterals to the deportalized liver developed after 7 days in both procedures but were markedly reduced in simultaneous portal and hepatic vein occlusion. Ki-67 staining at 7 days was comparable. Conclusion This study in pigs found that simultaneous portal and hepatic vein occlusion led to rapid hypertrophy without necrosis of the deportalized liver. The findings suggest that the use of simultaneous portal and hepatic vein occlusion accelerates liver hypertrophy for extended liver resections and should be evaluated further. Introduction Portal vein occlusion by ligation (PVL) or embolization is a well-established method to improve the safety of extended liver resections by inducing liver hypertrophy before resection.1, 2, 3 The novel procedure associating liver partition and portal vein ligation (ALPPS) indicated that kinetic growth of the future liver remnant can be increased by adding a parenchymal transection between the portal vein–supplied and portal vein–deprived part of the liver.4 A recent pig study from our laboratory suggested that the parenchymal transection in ALPPS leads to an abrogation of extensive porto-portal neocollaterals between the portal vein–supplied and the portal vein–deprived side of the liver.5 Porto-portal collaterals are common in PVL and also occur in portal vein embolization; these collaterals are known to blunt hypertrophy, and their complete abrogation may well be the cause for the astounding effectiveness of parenchymal transection in ALPPS. Based on the concept that abrogation of collaterals is a key requirement for rapid hypertrophy, we postulated that simultaneous occlusion of hepatic and portal veins may abrogate the formation of porto-portal collaterals to the deportalized side of the liver and thereby accelerate hypertrophy compared with PVL. This study tested whether simultaneous ligation of portal veins and hepatic veins (PLV+HVL) to the deportalized side of the liver would accelerate the increase in liver volume of the contralateral nondeportalized liver in a pig model. Methods Ethical statement Approval for the experiments was obtained from the Internal Animal Care and Use Committee of Rush University Medical Center (No. 15-025). The experiments were performed in compliance with the Guide for the Care and Use of Laboratory Animals by the National Research Council, 2011 edition (https://www.nap.edu/download/12910), and the ARRIVE guidelines.6

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Anesthesiology
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Surgery
Language:English
Date:1 March 2019
Deposited On:28 Nov 2018 15:32
Last Modified:23 Feb 2019 02:03
Publisher:Elsevier
ISSN:0039-6060
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.surg.2018.09.001

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