La principale limite en chirurgie hépatobiliaire est représentée par l’insuffisance hépatocellulaire (IHC) posthépatectomie (Hx) ou la dysfonction du greffon (EAD) après transplantation (TH). Peu d’études ont évalué le métabolisme du foie dans son ensemble, du fait du manque de technique utilisable en clinique. La métabolomique HR-MAS-RMN pourrait pallier à ce manque. Le but de cette thèse était d’évaluer l’apport de cette technique en chirurgie hépatobiliaire.En TH (n=42), le profil métabolique (PM) prédisait le risque d’EAD et identifiait le lactate et la phosphocholine comme biomarqueurs permettant d’envisager un matching métabolique. Après Hx majeure (n=45), le PM prédisait la survenue d’un décès par IHC. Ce PM différait du profil cirrhotique en décompensation et était compatible avec celui de système cellulaire prolifératif. Une étude préliminaire montrait que le PM prédisait la récidive à 1 an après hépatectomie. Ce travail montre l’intérêt de la métabolomique par HR MAS RMN pour prédire l’issue d’une Hx ou d’une TH dans un temps compatible avec la clinique. Ces données orientent vers la piste de l’intervention métabolique en chirurgie hépatique. / One of the main limits in liver surgery is the risk of liver failure (LF) after hepatectomy (Hx) or graft dysfunction (EAD) after liver transplantation (LT). Few studies have evaluated global liver metabolism, probably due to the lack of clinically relevant techniques. HR-MAS-NMR metabolomics may fulfill this lack and the goal of this work was to evaluate its capacity to predict early outcomes after hepatectomy and LT. In LT (n=42), metabolic profile predicted EAD and lactate and phosphocholine were potent biomarkers providing means for metabolic matching. In liver biopsies harvested at the end of major Hx (n=45), metabolic profile predicted PHLF. The profile at risk of LF differed from that of decompensated cirrhosis but correlated to that of proliferative multicellular systems. A preliminary study showed that the metabolic profile predicted the risk of liver metastases recurrence at 1 year. This work underlines the potential value of HR-MAS-NMR metabolomics in the prediction of short-term outcomes in liver surgery. It provides clues to be further investigated for future evaluation of metabolic intervention in the field of liver surgery.

Le principal frein au développement de la transplantation hépatique à donneur vivant est le risque de complication et de décès encourus par le donneur. Nous proposons une préparation du donneur par la réalisation d'un rétrécissement (sténose) de 20% de la veine d'un coté de son foie afin de faire grossir ce dernier sans altérer la viabilité du futur greffon. Pour cela, sur 32 porcs, nous avons recherché la plus petite sténose capable de déclencher le maintien du débit portal et étudié les déclenchements de la prolifération cellulaire et de l'atrophie. Des scanners associés à des scintigraphies hépatobiliaires à la mebrofénine ont été réalisés afin d'étudier les changements morphologiques et fonctionnels du foie. Nous démontrons que la sténose de 20% d'un coté du foie déclenche la régénération hépatique de l'autre coté et permet le gain d'une masse hépatique fonctionnelle. Conclusion : Notre pré-conditionnement est capable de préparer le foie d'un patient à l'hépatectomie majeure. / The main hindrance in promoting living donor liver transplantation remains the morbidity and mortality risk for the donor. We propose the realization of a 20% stenosis of the left portal vein (LPV) in order to induce an increase of the functional liver mass without altering the viability of the future graft.Materials and Methods: Thirty-two pigs were included in this program. The hemodynamic study identified the smallest stenosis capable of triggering mechanisms of maintenance of the hepatic blood flow. Cell proliferation and atrophy were studied. Scanners associated with Mebrofenin hepatobiliary scintigraphy were performed to study the morphological and functional changes of the liver.Results: A 20% LPV stenosis trigger liver regeneration in the contralateral lobe inducing a gain in hepatic functional hepatic mass.Conclusion: A 20% LPV stenosis is the effective preconditioning in order to get the remnant liver of living donor ready to take on graft harvesting.

Orientadores: Raquel Silveira Bello Stucchi, Ilka de Fátima Santana Ferreira Boin / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T08:25:01Z (GMT). No. of bitstreams: 1 Santos_DanieleCostados_M.pdf: 1085243 bytes, checksum: f6d71bd9d53ba2ba29df2a153ac0ae0a (MD5) Previous issue date: 2014 / Resumo: Introdução: Fatores como perda de massa e função muscular, alterações mecânicas da mobilidade da caixa torácica e diafragma secundárias a ascite e fraqueza muscular juntamente com desnutrição podem induzir à deficiência motora global e à inatividade física, interferindo negativamente nas atividades de vida diária e na qualidade de vida dos indivíduos que possuem doença hepática crônica em fase avançada. Objetivos: Avaliar a capacidade funcional, composição corporal, qualidade de vida e eletromiografia de pacientes hepatopatas crônicos candidatos a transplante de fígado; verificar se existe correlação entre as variáveis funcionais dos indivíduos testados por meio do Teste de Caminhada de 6 minutos (TC6) e as co-variáveis: prova de função pulmonar (PFP), qualidade de vida, eletromiografia de superfície dos músculos reto abdominal e diafragma e composição corporal total. Métodos: Este estudo foi realizado no Ambulatório de Transplante de Fígado da Universidade Estadual de Campinas (UNICAMP) no período de agosto de 2012 a novembro de 2013. Foram incluídos 54 pacientes com doença hepática crônica que possuíam condições clínicas e funcionais de realizarem os testes a serem propostos. Foram submetidos às seguintes avaliações: anamnese, questionário de qualidade de vida "Short Form 36" (SF-36), eletromiografia de superfície (sEMG) dos músculos diafragma e reto abdominal, avaliação da composição corporal por meio da Bioimpedância Elétrica (BIA), TC6 e PFP. Resultados: Foram encontrados scores médios inferiores a 65 no questionário SF-36, bem como a média da distância percorrida no TC6 também foi abaixo dos valores preconizados para população saudável. A distância percorrida no TC6 teve correlação com qualidade de vida e com ângulo de fase da BIA. Foram encontradas também correlações das variáveis respiratórias do TC6 com índice de massa corpórea, PFP e qualidade de vida. Conclusão: Conclui-se que a capacidade funcional e qualidade de vida encontram-se diminuídos em pacientes hepatopatas crônicos em lista de transplante hepático. Adicionalmente, a capacidade funcional apresentou correlações com alterações na qualidade de vida, função pulmonar e composição corporal / Abstract: Introduction: Loss of muscle mass and function, mechanic alterations of chest mobility and the diaphragm due to ascitis and muscular weakness in combination with malnutrition can induce a global motor impairment and physical inactivity, adversely impairing the daily living activities and quality of life in end-stage liver disease patients, candidates for liver transplantation. Objectives: To evaluate functional status, pulmonary function, body composition and quality of life in end-stage liver disease patients, candidates for liver transplantation; to verify if there is a correlation between the functional variables of the individuals tested through the 6-minute walk test (6MWT) and covariables: pulmonary function test (PFP), quality of life, surface electromyography (sEMG) of the diaphragm and rectus abdominis muscles and body composition. Methods: This study was carried out at the Liver Transplant Unit of the State University of Campinas (UNICAMP) from August, 2012 until November, 2013. Fifty four patients with end-stage liver disease were included. The patients underwent the following evaluations: medical history, quality of life questionnaire "Short Form 36" (SF-36), surface electromyography (sEMG) of the diaphragm and rectus abdominis muscles, body composition assessment by Electrical Bioimpedance (BIA), 6MWT and PFP. Results: Scores below to 65 at SF-36 were founded and the distance walked on 6MWT was below to recommended for heathy population. The walked distance was correlated with quality of life and BIA (phase angle). Correlations were found between respiratory variables of 6MWT and body mass index, PFP and quality of life. Conclusion: Functional status and quality of life are impaired in patients with chronic liver disease and candidates for liver transplantation. Additionally, functional status is related to changes in quality of life, pulmonary capacity and body composition / Mestrado / Fisiopatologia Cirúrgica / Mestra em Ciências

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22303号 / 医博第4544号 / 新制||医||1040(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 福原 俊一, 教授 川口 義弥, 教授 松村 由美 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23421号 / 医博第4766号 / 新制||医||1053(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 小濱 和貴, 教授 妹尾 浩, 教授 川口 義弥 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

121 9. Summárý Purpose: This study was designed to evaluate the role of interventional radiology in liver transplantation programme. The aim is to present our experience, technical outcomes and long-term clinical results with chemoembolization of hepatocellular carcinoma in patients before liver transplantation and with percutaneous treatment of vascular and biliary complication after orthotopic liver transplantation. Methods: Twenty five patients (17 men, 8 women, mean age 57.76 years) with HCC were scheduled for TACE prior to liver transplantation from 2008 to 2012. Twenty three procedures were performed, 7 c-TACE in 2008 and 16 DEB TACE in next years. Thirty patients (13 men, 17 women, mean age 46.4 years) with biliary strictures after liver transplantation without endoscopic access possibility were treated with balloon dilatation and biliary duct drainage from 1996 and 2010. Twenty patients (13 men, 7 women, mean age 45.25 years) were treated with PTA/stent due to hepatic artery stenosis after liver transplantation between 1996 and 2011. Stents were placed to the hepatic/celiac artery in 16 PTAs, balloon dilatation alone was performed in 7 stenosis due to tortuosity of the vessel. Results: Liver transplantation was performed to 20 patients after TACE. Only one patient (4.5 %) was excluded from waiting...

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20225号 / 医博第4184号 / 新制||医||1019(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 Shohab YOUSSEFIAN, 教授 川村 孝 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20620号 / 医博第4269号 / 新制||医||1023(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 坂井 義治, 教授 小西 靖彦, 教授 川口 義弥 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Laparoscopic liver resection (LLR) is an increasingly relevant treatment option for patients with resectable hepatocellular carcinoma (HCC). Orthotopic liver transplantation (OLT) has been considered optimal treatment for HCC in cirrhosis, but is challenged by rising organ scarcity. While health-related quality of life (HRQoL) and mental health are well-documented after OLT, little is known about HRQoL in HCC patients after LLR. We identified all HCC patients who underwent LLR at our hospital between 2014 and 2018. HRQoL and mental health were assessed using the Short Form 36 and the Hospital Anxiety and Depression Scale, respectively. Outcomes were compared to a historic cohort of HCC patients after OLT. Ninety-eight patients received LLR for HCC. Postoperative morbidity was 25% with 17% minor complications. LLR patients showed similar overall HRQoL and mental health to OLT recipients, except for lower General Health (p = 0.029) and higher anxiety scores (p = 0.010). We conclude that LLR can be safely performed in patients with HCC, with or without liver cirrhosis. The postoperative HRQoL and mental health are comparable to that of OLT recipients in most aspects. LLR should thus always be considered an alternative to OLT, especially in times of organ shortage.