Subtotal hepatectomy in swine for studying small-for-size syndrome and portal inflow modulation: is it reliable?

Darnis, Benjamin; Mohkam, Kayvan; Schmitt, Z.; Ledochowski, Stanislas; Vial, J.P.; Duperret, S.; Vogt, Catherine; Demian, H.; Golse, Nicolas; Mezoughi, Salim; Ducerf, C.; Mabrut, Jean‐Yves

doi:10.1111/hpb.12434

Cited by 25 publications

(26 citation statements)

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“…The right medial or left lateral section, which had been initially proposed as partial grafts for LT, were further abandoned given the associated need for demanding and timeconsuming reconstructions. Besides, the cut-off value of remnant-to-initial liver volume ratio for obtaining the setting of SFS syndrome appears to be approximately 20% after partial LT [9], and the right lateral section including segment 1, which represents approximately 30% of the whole liver volume, appears to be too large for inducing a significant increase in portal vein pressure and creating the setting of SFS [7]. Therefore, the use of a right lateral section with segment 1 transplanted in a 2-3-fold larger recipient as initially described by Kelly et al without the use of venovenous bypass as described by Fondevila et al could be considered as the best possible choice for studying the SFS syndrome after partial LT in swine [13,[16][17][18].…”

Section: Optimal Model Of Small-for-size Liver Transplantationmentioning

confidence: 97%

“…Due to the various terms used in the literature regarding the porcine anatomy of the liver, we propose herein a standardized nomenclature based on previous studies on the porcine liver anatomy [5,6] and our own findings [7]. In brief, the porcine liver is similar to human liver and could be divided in four sections of two segments each ( Fig.…”

Section: Proposed Standardized Anatomical Nomenclaturementioning

confidence: 99%

“…Darnis et al [7] Left trisectionectomy (n = Whole liver small-for-size grafts Instead of using a split liver graft, Boillot et al reported the use of a whole liver transplanted in 4-fold larger animals, which allowed a SFS graft with GRWR of 0.6% [12]. The graft was transplanted heterotopically beneath the native liver.…”

Section: )mentioning

confidence: 99%

“…Court et al reported the first porcine model of posthepatectomy SFS, which consisted of a left trisectionectomy without portal clamping in order to avoid ischemia of the liver remnant [20]. The same model was further reproduced in several other studies on portal hyperperfusion [7,[21][22][23][24][25][26][27][28][29][30]. However, despite inducing portal hyperperfusion (as defined by an increase of portal vein flow above 250 ml/min per 100 g of liver tissue), the left trisectionectomy model does not seem suitable for studying the SFS syndrome.…”

Section: Porcine Models Of Small-for-size Hepatectomymentioning

confidence: 99%

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Porcine models for the study of small‐for‐size syndrome and portal inflow modulation: literature review and proposal for a standardized nomenclature

Mohkam

Darnis

Mabrut

2016

J Hepato Biliary Pancreat

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Porcine models of extended hepatectomy and liver transplantation (LT) of reduced graft have been widely used for studying the small-for-size (SFS) syndrome and the various modalities of portal inflow modulation (PIM). However, considerable heterogeneity exists among the studies and their results. The aim of this review was to assess the main advantages and drawbacks of the different porcine models of SFS LT and SFS hepatectomy, and propose a standardized anatomical nomenclature for the various models. The MEDLINE database was searched for articles reporting porcine models of reduced graft LT or hepatectomy of more than 65%. Nineteen articles on SFS LT matched our inclusion criteria, including 10 articles reporting a model of PIM. Twenty-seven articles reporting a model of posthepatectomy SFS were identified, of which 16 reported a model of PIM. Subtotal hepatectomy (i.e. resection of all segments except segment 1) without inflow occlusion, left trisectionectomy with inflow occlusion, and LT of a right lateral section including the caudate lobe in a larger recipient appeared to be the most suitable porcine models for studying the SFS syndrome. All three models were appropriate for assessing the surgical and pharmaceutical PIM modalities, except for those involving the splenic flow.

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Section: Optimal Model Of Small-for-size Liver Transplantationmentioning

confidence: 97%

Section: Proposed Standardized Anatomical Nomenclaturementioning

confidence: 99%

Section: )mentioning

confidence: 99%

Section: Porcine Models Of Small-for-size Hepatectomymentioning

confidence: 99%

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Porcine models for the study of small‐for‐size syndrome and portal inflow modulation: literature review and proposal for a standardized nomenclature

Mohkam

Darnis

Mabrut

2016

J Hepato Biliary Pancreat

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“…Their alimentary tract more or less resembles that of the human, and the overall physiology of these animals is very similar to ours. Pigs as liver surgery models have previously been used to explore the effects of liver transplantation, resection as well as PVO [69,70,71]. However, the anatomy of the pig liver strongly differs from the human organ.…”

Section: Large Animal Modelsmentioning

confidence: 99%

Animal Models for Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS): Achievements and Future Perspectives

et al. 2017

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Background: Since 2012, Associated Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been standing in the limelight of modern liver surgery and numerous questions have been raised regarding this novel approach. On the one hand, ALPPS has proved to be a valuable method in the treatment of hepatic tumors, while on the other hand, there are many controversies, such as high mortality and morbidity rates. Further surgical research is essential for a better understanding of underlying mechanisms and for enhancing patient safety. Summary: Until recently, only 8 animal models have been created with the purpose to mimic ALPPS-induced liver regeneration. From these 7 are rodent (6 rat and 1 mouse) models, while only 1 is a large animal model, which uses pigs. In case of rodent models, portal flow deprivation of 75-90% is achieved via portal vein ligation leaving only the right (20-25%) or left median (10-15%) lobes portally perfused, while liver splitting in general is carried out positioned according to the falciform ligament. As for the swine model, the left lateral and medial lobes (70-75% of total liver volume) are portally ligated, and the right lateral lobe (accounting for 20-24% of the parenchyma) is partially resected in order to reach critical liver volume. Each model is capable of reproducing the accelerated liver regeneration seen in human cases. However, all species have significantly different liver anatomy compared with the human anatomic situation, making clinical translation somewhat difficult. Key Messages: Unfortunately, there are no perfect animal models available for ALPPS research. Small animal models are inexpensive and well suited for basic research, but may only provide limited translational potential to humans. Clinically large animal models may provide more relevant data, but currently no suitable one exists.

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Re: Porcine models for the study of small‐for‐size syndrome

Mohkam

Mabrut

2017

J Hepato Biliary Pancreat

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Dear Editor,We would like to thank Athanasiou and Spartalis [1] for their interest in our recently published work [2]. In their letter, the authors stated that 80% hepatectomy was the only porcine model suitable for studying the small-forsize syndrome. We agree that such a model is of interest, as it has been shown that it creates the small-for-size setting. However, to obtain a 20% liver remnant in swine, it is necessary to perform a transection within the right posterior lobe, which may be complex, and as a consequence, it may require the use of some complex and expansive transection devices to reduce blood loss, as this has been suggested by Athanasiou et al. themselves [3]. Conversely, other teams have proposed subtotal hepatectomy [4][5][6][7][8][9][10] or left trisectionectomy + remnant warm ischemia [11][12][13][14][15][16][17] as alternative and more simple models, which could be performed by transecting the liver parenchyma along deep interlobular fissures, thus avoiding excessive blood loss.Further, Athanasiou and Spartalis [1] stated that there is no publication by our team reporting that splenic artery ligation and splenectomy are not appropriate for portal inflow modulation in pigs. We would like to recall that on several occasions in the review, we cited our published work [9] in which we studied the intraoperative effects of splenectomy and splenic artery ligation on splanchnic hemodynamics after extended hepatectomy: we found that those two procedures did not induce any significant changes in portal vein flow, pressure and hepatic venous pressure gradient. In that same work, we also studied the ratio between splenic and portal blood flows in both swine and humans, and we found that in swine, the splenic blood flow consisted of only 9% of the total portal flow received by the liver, whereas in humans, the splenic venous flow accounted for 31% of total portal flow. This could explain the absence of effectiveness of portal inflow modulation involving the splenic blood flow in swine.Surprisingly, Athanasiou and Spartalis [1] mentioned that Hisakura et al. [18] showed similar results after 80% hepatectomy and splenectomy as compared to their recently published work [19]: we do not agree with this statement. In fact, in their work, Hisakura et al. clearly stated that "there was no significant differences in portal venous pressure after hepatectomy between the splenectomy group and the control group," which is actually consistent with our findings [9], and not with the ones by Athanasiou et al. [19]. Besides, in the study by Hisakura et al., the favorable effects of splenectomy observed in animals undergoing 80% hepatectomy were similar to those observed in animals having an intramuscular injection of thrombopoietin 5 days before 80% hepatectomy. Thus, Hisakura et al. concluded that the positive effects of splenectomy (which was performed 7 days prior to hepatectomy) were linked to thrombocytosis (induced after both splenectomy and thrombopoietin injection), and not to any reduction in portal pressure. R...

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Subtotal hepatectomy in swine for studying small-for-size syndrome and portal inflow modulation: is it reliable?

Abstract: Subtotal hepatectomy of 90% in swine is a reliable model for SFSS inducing a significant increase in HVPG. However, in view of the relevant differences between swine and human splanchnic anatomy, this model is inadequate for studying the effects of PIM by SAL and splenectomy.

Cited by 25 publications

References 24 publications

Porcine models for the study of small‐for‐size syndrome and portal inflow modulation: literature review and proposal for a standardized nomenclature

Porcine models for the study of small‐for‐size syndrome and portal inflow modulation: literature review and proposal for a standardized nomenclature

Animal Models for Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS): Achievements and Future Perspectives

Re: Porcine models for the study of small‐for‐size syndrome

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