Desarrollo de un modelo experimental de ligadura portal asociada a transección parenquimatosa (ALPPS) en ratas

Trenard, Héctor M. Almau; Moulin, L.; Padín, Juan Manuel; Stringa, Pablo; Gondolesi, Gabriel; Schelotto, Pablo Barros

doi:10.1016/j.ciresp.2013.11.005

Cited by 21 publications

(15 citation statements)

References 16 publications

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“…From this viewpoint, we prefer the right-sided ALPPS model (right median lobe as the FRL) for further evaluation. Also when we were about to submit this article, we noticed a brief report on right sided rat ALPPS model mentioning significant increase in liver regeneration of the FRL at day 3, 7 and 14 but lacking any comparison with the PVL group [ 10 ]. AS far as we aware, this is the first study showing the liver images of the ALPPS regenerated lobes in an animal model.…”

Section: Discussionmentioning

confidence: 99%

A novel rat model of liver regeneration: possible role of cytokine induced neutrophil chemoattractant-1 in augmented liver regeneration

et al. 2015

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BackgroundLiver resection is the mainstay of treatment for most of the liver tumors. Liver has a unique capability to restore the lost volume following resection, however, most of the primary tumors grow in a liver with preexisting parenchymal diseases and secondary tumors often present in multiple liver lobes precluding a safe curative resection. Two-stage hepatectomy and portal vein ligation (PVL) are used to achieve a safer future remnant liver volume (FRLV), however, these procedures take several weeks to achieve adequate FRLV. A recently introduced faster alternative two-stage hepatectomy, also know as associated liver partitioning and portal vein ligation for staged hepatectomy (ALPPS), produces a desirable FRLV in days.MethodsTo have an insight into the mechanism of ALPPS associated liver regeneration, we reproduced a rat model of ALPPS and compared the results with the PVL group.ResultsOur results convincingly showed an advantage of the ALPPS procedure over PVL group in terms of early regeneration, however, in 1-week time the amount of regeneration was comparable. An early regeneration in the ALPPS group coincided with an early entry of hepatocytes into the cell proliferation phase, a significant increase in portal pressure and increase in hepatic enzymes in the ALPPS group compared with the PVL group. According to the protein array evaluation of 29 cytokines/chemokines, cytokine induced neutrophil chemoattractant-1 had the highest expression whereas IL-6 had the highest fold (>6 vs PVL group) expression at the early phase of regeneration in the ALPPS group.ConclusionsThis unique rat model of ALPPS would help to improve our understanding about the liver generation process and also will help in further refinement of the ALPPS procedure for the clinical benefit.Electronic supplementary materialThe online version of this article (doi:10.1186/s13022-015-0020-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

A novel rat model of liver regeneration: possible role of cytokine induced neutrophil chemoattractant-1 in augmented liver regeneration

et al. 2015

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“…Subsequently, various research groups created their own, rat-based ALPPS models with minor changes to the primary concepts of Yao or Schlegel [36,64,65]. …”

Section: Rodent 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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“…Although it is clear that ALPPS can induce accelerated liver regeneration, the underlying mechanisms remain unclear, and they need well-designed animal studies to clarify. To the best of our knowledge, there are only few studies on animal models for the ALPPS procedure 11 12 13 . Schlegel et al developed a reproducible mouse model mimicking ALPPS and explored the underlying mechanisms.…”

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confidence: 99%

A preliminary study of ALPPS procedure in a rat model

Shi

Yang

Zheng

et al. 2015

Sci Rep

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Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been reported to be a novel surgical technique that provides fast and effective growth of liver remnant. Despite occasional reports on animal studies, the mechanisms of rapid liver regeneration in ALPPS remains unclear. In the present study, we intend to develop a reproducible rat model to mimick ALPPS and to explore the underlying mechanisms. Rats assigned to the portal vein ligation (PVL), left lateral lobe (LLL) resection, transection and sham groups served as controls. Results indicated that the regeneration rate in the remnant liver after ALPPS was two times relative to PVL, whereas rats with transection alone showed minimal volume increase. The expression levels of Ki-67 and PCNA were about ten-fold higher after ALPPS compared with the transection and LLL resection groups, and four-fold higher compared with the PVL group. The levels of TNF-α, IL-6 and HGF in the regenerating liver remnant were about three-fold higher after ALPPS than the controls. There was a more significant activation of NF-κB p65, STAT3 and Yap after ALPPS, suggesting synergistic activation of the pathways by PVL and transection, which might play an important role in liver regeneration after ALPPS.

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Desarrollo de un modelo experimental de ligadura portal asociada a transección parenquimatosa (ALPPS) en ratas

Cited by 21 publications

References 16 publications

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

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

A preliminary study of ALPPS procedure in a rat model

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