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Multiscale Study of the Hepatic Volume Evolution After Major Hepatectomie in a Porcine Model Mohamed Bekheit

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Multiscale Study of the Hepatic Volume Evolution After Major Hepatectomie in a Porcine Model Mohamed Bekheit Multiscale study of the hepatic volume evolution after major hepatectomie in a porcine model Mohamed Bekheit To cite this version: Mohamed Bekheit. Multiscale study of the hepatic volume evolution after major hepatectomie in a porcine model. Surgery. Université Paris Saclay (COmUE), 2018. English. NNT : 2018SACLS033. tel-01753156 HAL Id: tel-01753156 https://tel.archives-ouvertes.fr/tel-01753156 Submitted on 29 Mar 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Etude multi-échelle de l`évolution du volume du foie après hépatectomie majeure chez un modèle porcine Multiscale study of the hepatic volume evolution after 2018SACLS033 major hepatectomy in a porcine model : NNT Thèse de doctorat de l'Université Paris-Saclay préparée à l'Université Paris-Sud et l`INSERM U1193, CHB, Paul Brousse École doctorale n°569 : innovation thérapeutique: du fondamental à l'appliqué (ITFA) et sigle Spécialité de doctorat: SC Thèse présentée et soutenue à Villejuif, le 26-1-2018, par Mohamed Bekheit Composition du Jury : Iréne VIGNON-CLEMENTEL Dir Rech, Établissement : INRIA & UPMC, Paris Président Stéphanie TRUANT Pr, Établissement : Université de Lille Rapporteur Ewen HARRISON Dr, Établissement: Université d`Edinburgh Rapporteur Emilie GREGOIRE Dr, Établissement APHM Université de Marseille Examinateur Eric VIBERT Pr, Établissement Université Paris Saclay Examinateur Titre : Etude multi-échelle de l`évolution du volume du foie après hépatectomie majeure chez un modèle porcine Mots clés : Hepatectomie majeure, porc, modulation de flux, modelisation, architecture, regeneration. Résumé : L’ablation partielle du foie est une Des mesures expétimentales sont nécessaires chirurgie qui intervient dans le traitement des pour la construction et la validation de ces lésions du foie ainsi que lors d’une modèles. Des ablations du foie de différentes transplantation partielle de foie (donneur tailles sont effectuées sur des porcs et pendant vivant). Grâce à la capacité de régénération du ces chirurgies plusieurs pressions et débits sont foie, quelques mois après la chirurgie il retrouve mesurés. De plus, un colorant fluorescent est sa masse initiale. Les complications de cette injecté avant ou après l’ablation partielle, et la chirurgie sont l’insufisance hépatique et après fluorescence de ce composé est mesurée. Dans une transplantation le syndrome du trop petit une première partie, la procédure chirurgicale, foie. Ces deux complications sont liées à une les conditions expérimentales ainsi que les fonction hépatique post-opératoire faible. Les mesures obtenues sont détaillées. Ensuite, les relations entre l’hémodynamique du foie, son changements hémodynamiques, conséquence volume et ses fonctions restent à élucider pour de l’ablation partielle du foie. Le modèle permet mieux comprendre les causes de ces de prendre en compte les changements de complications. Lors de la chirurgie, volume sanguins qui peuvent se produire l’hémodynamique du foie est alterée suite à (saignements) lors de la chirurgie. Par l’augmentation de la résistance au flux sanguin conséquent, ce modèle propose une explication de l’organe. Les conséquences de cette chirurgie de la variabilité des mesures acquises lors de ces sur l’hémodynamique sont difficiles à analyser chirurgies. du fait de la double perfusion sanguine du foie. Puis, le transport dans le sang d’un composé En effet, le foie reçoit du sang oxygéné via ainsi que son traitement par le foie sont l’artère hépatique et du sang riche en nutriment modélisés. La dynamique d’un composé depuis via la veine porte. De plus, la régénération du l’injection intraveineuse jusqu’au moment où il foie semble dépendante des changements de atteint les vaisseaux du foie est analysé avec débit et de pression dans la veine porte. Dans ce des modèles. contexte, le objectif de cette thèse est de mieux Le contrôle des changements de débit et de comprendre, grâce à des modèles pression de la veine porte après une mathématiques, l’influence de l’hépatectomie hepatectomie pourrait protèger le foie restant sur l’hémodynamique. L`objectif est l’analyse de (ou le greffon) et améliorer sa régénération la perfusion et de la fonction du foie. Un modèle post-opératoire. Les deux sujets abordés dans de transport dans le sang d’un composé ainsi cette thèse ont pour but d’améliorer l’efficacité que la modélisation du traitement de ce d’un dispositif médical (anneau ajustable MID- composé par le foie sont développés. AVRTM) permettant ce contrôle. Université Paris-Saclay Espace Technologique / Immeuble Discovery Route de l’Orme aux Merisiers RD 128 / 91190 Saint-Aubin, France Title : Multiscale Study of Hepatic Volume Evolution after Major Hepatectomy in a Porcine Model Keywords : Liver, resection, regeneration, mathematical model, hemodynamics, flow modulation Abstract : The liver is a unique organ with a The observations made during the surgical multitude of characteristics. One of these, is the procedures and information gathered through remarkable ability to regenerate. In the context other parameters were integrated into multiscale of secondary liver cancers and given the simulations to understand the interactions extensive bilobar disease that we often see in the between the change of the hemodynamics and clinical practice, most of the patients are deemed the change of the hepatic volume that result from inoperable. One of the major reasons is that this resection or regeneration. Subsequently, a category of patients, if subjected to curative modulation device was used to test the effect of resection, will leave them with insufficient liver hemodynamic adjustments on the regenration for survival. The mechanisms by which the and survival. This was done primarly in a 75% resultant syndrome; small for size; is not fully resection model then on a smaller scale in a 94% understood. resection model. In the former model, the effect The beforehand work addressed certain was more seen on the level of the function, some translational aspects regarding the histological parameters but not the volume nor pathophysiology of the syndrome, the prediction the survival. On the other hand, the experiments of its occurrence prior to surgery. The setting with the ring (modulation device) lead to a and design involved the major and ultra-major surviving animal as opposed to no survival of resection in a porcine model. Along with animals without the ring. At the moment, this continuous hemodynamic monitoring and ICG shows a promising path for researchers to take dynamic assessment, the present work lead to a forward to help reducing the significant few steps forward in the knowledge and mortality that could potentially follow such understanding of the interaction between the major resection. Not only that but this sould hepatic, systemic circulation, and the hepatic allow more patient s to have access to the regeneration. The experimentations involved curative treatment they would other not have it. CT scanning prior to the operation to gain a comprehensive knowledge on the anatomy and volume, which was repeated in a temporal fashion following a strict protocol to monitor the volume changes as well. This was accompanied by 2D and 3D histological analysis and quantification of various regeneration parameters. Université Paris-Saclay Espace Technologique / Immeuble Discovery Route de l’Orme aux Merisiers RD 128 / 91190 Saint-Aubin, France Synthèse de la Thèse : L’ablation partielle du foie est une chirurgie qui intervient dans le traitement des lésions du foie ainsi que lors d’une transplantation partielle de foie (donneur vivant). Grâce à la capacité de régénération du foie, quelques mois après la chirurgie il retrouve sa masse initiale. Les complications de cette chirurgie sont l’insufisance hépatique et après une transplantation le syndrome du trop petit foie. Ces deux complications sont liées à une fonction hépatique post-opératoire faible. Les relations entre l’hémodynamique du foie, son volume et ses fonctions restent à élucider pour mieux comprendre les causes de ces complications. Lors de la chirurgie, l’hémodynamique du foie est alterée suite à l’augmentation de la résistance au flux sanguin de l’organe. Les conséquences de cette chirurgie sur l’hémodynamique sont difficiles à analyser du fait de la double perfusion sanguine du foie. En effet, le foie reçoit du sang oxygéné via l’artère hépatique et du sang riche en nutriment via la veine porte. De plus, la régénération du foie semble dépendante des changements de débit et de pression dans la veine porte. Dans ce contexte, le objectif de cette thèse est de mieux comprendre, grâce à des modèles mathématiques, l’influence de l’hépatectomie sur l’hémodynamique. L`objectif est l’analyse de la perfusion et de la fonction du foie. Un modèle de transport dans le sang d’un composé ainsi que la modélisation du traitement de ce composé par le foie sont développés. Des mesures expétimentales sont nécessaires pour la construction et la validation de ces modèles. Des ablations du foie de différentes tailles sont effectuées sur des porcs
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