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1.
Ann Surg ; 273(1): 96-108, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33332874

RESUMO

OBJECTIVE: The Expert Consensus Guidelines initiative on MIDH for LDLT was organized with the goal of safe implementation and development of these complex techniques with donor safety as the main priority. BACKGROUND: Following the development of minimally invasive liver surgery, techniques of MIDH were developed with the aim of reducing the short- and long-term consequences of the procedure on liver donors. These techniques, although increasingly performed, lack clinical guidelines. METHODS: A group of 12 international MIDH experts, 1 research coordinator, and 8 junior faculty was assembled. Comprehensive literature search was made and studies classified using the SIGN method. Based on literature review and experts opinions, tentative recommendations were made by experts subgroups and submitted to the whole experts group using on-line Delphi Rounds with the goal of obtaining >90% Consensus. Pre-conference meeting formulated final recommendations that were presented during the plenary conference held in Seoul on September 7, 2019 in front of a Validation Committee composed of LDLT experts not practicing MIDH and an international audience. RESULTS: Eighteen Clinical Questions were addressed resulting in 44 recommendations. All recommendations reached at least a 90% consensus among experts and were afterward endorsed by the validation committee. CONCLUSIONS: The Expert Consensus on MIDH has produced a set of clinical guidelines based on available evidence and clinical expertise. These guidelines are presented for a safe implementation and development of MIDH in LDLT Centers with the goal of optimizing donor safety, donor care, and recipient outcomes.


Assuntos
Hepatectomia/métodos , Hepatectomia/normas , Transplante de Fígado , Coleta de Tecidos e Órgãos/normas , Humanos , Doadores Vivos , Procedimentos Cirúrgicos Minimamente Invasivos
2.
Int J Med Sci ; 18(9): 1953-1959, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33850464

RESUMO

Nowadays, liver transplantation is the most effective treatment for end-stage liver disease. However, the increasing imbalance between growing demand for liver transplantation and the shortage of donor pool restricts the development of liver transplantation. How to expand the donor pool is a significant problem to be solved clinically. Many doctors have devoted themselves to marginal grafting, which introduces livers with barely passable quality but a high risk of transplant failure into the donor pool. However, existing common methods of preserving marginal grafts lead to both high risk of postoperative complications and high mortality. The application of machine perfusion allows surgeons to make marginal livers meet the standard criteria for transplant, which shows promising prospect in preserving and repairing donor livers and improving ischemia reperfusion injury. This review summarizes the progress of recent researches on hepatic machine perfusion.


Assuntos
Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Traumatismo por Reperfusão/prevenção & controle , Humanos , Transplante de Fígado/normas , Transplante de Fígado/tendências , Preservação de Órgãos/instrumentação , Preservação de Órgãos/tendências , Perfusão/instrumentação , Perfusão/tendências , Coleta de Tecidos e Órgãos/normas
3.
Int J Mol Sci ; 21(16)2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32824744

RESUMO

While liver transplantation remains the sole treatment option for patients with end-stage liver disease, there are numerous limitations to liver transplantation including the scarcity of donor livers and a rise in livers that are unsuitable to transplant such as those with excess steatosis. Fatty livers are susceptible to ischaemia-reperfusion (IR) injury during transplantation and IR injury results in primary graft non-function, graft failure and mortality. Recent studies have described new cell death pathways which differ from the traditional apoptotic pathway. Necroptosis, a regulated form of cell death, has been associated with hepatic IR injury. Receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL) are thought to be instrumental in the execution of necroptosis. The study of hepatic necroptosis and potential therapeutic approaches to attenuate IR injury will be a key factor in improving our knowledge regarding liver transplantation with fatty donor livers. In this review, we focus on the effect of hepatic steatosis during liver transplantation as well as molecular mechanisms of necroptosis and its involvement during liver IR injury. We also discuss the immune responses triggered during necroptosis and examine the utility of necroptosis inhibitors as potential therapeutic approaches to alleviate IR injury.


Assuntos
Transplante de Fígado/efeitos adversos , Necroptose , Hepatopatia Gordurosa não Alcoólica/metabolismo , Disfunção Primária do Enxerto/metabolismo , Coleta de Tecidos e Órgãos/efeitos adversos , Animais , Humanos , Fígado/irrigação sanguínea , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Disfunção Primária do Enxerto/etiologia , Coleta de Tecidos e Órgãos/normas
4.
Zhonghua Wai Ke Za Zhi ; 58(5): 345-349, 2020 May 01.
Artigo em Zh | MEDLINE | ID: mdl-32393000

RESUMO

The quality control of coronary artery bypass grafting (CABG) is an important prerequisite to the graft patency and the long-term outcomes. The evaluation of target vessel is the basis, the choice of surgical types is the means, the high-quality acquisition of graft harvesting is the guarantee, and the anastomotic method and quality is the core. As the most commonly used quality control tool, intraoperative transit time flow measurement can effectively detect the coronary graft failure caused by anastomotic stenosis and guide to repair of the graft. However, some studies showed that the positive predictive value is low, and the evidence is insufficient for the relationship with the long-term patency rate of grafts. Intraoperative instantaneous flow measurement combined with high-resolution epicardial ultrasound can improve the quality, safety and effectiveness of CABG, which should be an important recommendation for CABG quality control. Once the shape of the grafts and anastomotic ports is abnormal and the blood flow is not satisfied, it needs to adjust or re-anastomose immediately. The quality control of CABG requires comprehensive judgment and individualized measures to ensure the safety and long-term outcome of patients.


Assuntos
Ponte de Artéria Coronária/normas , Doença das Coronárias/cirurgia , Controle de Qualidade , Anastomose Cirúrgica/normas , Ponte de Artéria Coronária/métodos , Humanos , Coleta de Tecidos e Órgãos/normas , Grau de Desobstrução Vascular
5.
Am J Transplant ; 19(3): 737-751, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30091857

RESUMO

Kidneys from donation after circulatory death (DCD) are highly sensitive to ischemia-reperfusion injury and thus require careful reconditioning, such as normothermic regional perfusion (NRP). However, the optimal NRP protocol remains to be characterized. NRP was modeled in a DCD porcine model (30 minutes of cardiac arrest) for 2, 4, or 6 hours compared to a control group (No-NRP); kidneys were machine-preserved and allotransplanted. NRP appeared to permit recovery from warm ischemia, possibly due to an increased expression of HIF1α-dependent survival pathway. At 2 hours, blood levels of ischemic injury biomarkers increased: creatinine, lactate/pyruvate ratio, LDH, AST, NGAL, KIM-1, CD40 ligand, and soluble-tissue-factor. All these markers then decreased with time; however, AST, NGAL, and KIM-1 increased again at 6 hours. Hemoglobin and platelets decreased at 6 hours, after which the procedure became difficult to maintain. Regarding inflammation, active tissue-factor, cleaved PAR-2 and MCP-1 increased by 4-6 hours, but not TNF-α and iNOS. Compared to No-NRP, NRP kidneys showed lower resistance during hypothermic machine perfusion (HMP), likely associated with pe-NRP eNOS activation. Kidneys transplanted after 4 and 6 hours of NRP showed better function and outcome, compared to No-NRP. In conclusion, our results confirm the mechanistic benefits of NRP and highlight 4 hours as its optimal duration, after which injury markers appear.


Assuntos
Função Retardada do Enxerto/prevenção & controle , Transplante de Rim/efeitos adversos , Preservação de Órgãos/métodos , Perfusão/métodos , Temperatura , Doadores de Tecidos/provisão & distribuição , Coleta de Tecidos e Órgãos/normas , Animais , Isquemia Fria , Função Retardada do Enxerto/etiologia , Masculino , Suínos , Fatores de Tempo , Isquemia Quente
6.
Am J Transplant ; 19(3): 752-762, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30171799

RESUMO

The aims of this study were to determine the most optimal timing to start machine perfusion during kidney preservation to improve early graft function and to evaluate the impact of temperature and oxygen supply during machine perfusion in a porcine ischemia-reperfusion autotransplant model. The left kidney of an approximately 40-kg female Belgian Landrace pig was exposed to 30 minutes of warm ischemia via vascular clamping and randomized to 1 of 6 study groups: (1) 22-hour static cold storage (SCS) (n = 6), (2) 22-hour hypothermic machine perfusion (HMP) (n = 6), (3) 22-hour oxygenated HMP (n = 7), (4) 20-hour HMP plus 2-hour normothermic perfusion (NP) (n = 6), (5) 20-hour SCS plus 2-hour oxygenated HMP (n = 7), and (6) 20-hour SCS plus 2-hour NP (n = 6). Graft recovery measured by serum creatinine level was significantly faster for continuous HMP preservation strategies compared with SCS alone and for all end-ischemic strategies. The active oxygenated 22-hour HMP group demonstrated a significantly faster recovery from early graft function compared with the 22-hour nonactive oxygenated HMP group. Active oxygenation was also found to be an important modulator of a faster increase in renal flow during HMP preservation. Continuous oxygenated HMP applied from the time of kidney procurement until transplant might be the best preservation strategy to improve early graft function.


Assuntos
Isquemia Fria , Função Retardada do Enxerto/prevenção & controle , Transplante de Rim/efeitos adversos , Preservação de Órgãos/métodos , Perfusão/métodos , Traumatismo por Reperfusão/cirurgia , Doadores de Tecidos/provisão & distribuição , Isquemia Quente , Animais , Autoenxertos , Função Retardada do Enxerto/etiologia , Feminino , Testes de Função Renal , Preservação de Órgãos/normas , Soluções para Preservação de Órgãos , Suínos , Coleta de Tecidos e Órgãos/normas
7.
J Surg Res ; 244: 50-56, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31279263

RESUMO

BACKGROUND: Living kidney donors (LKDs) with obesity have increased perioperative risks and risk of end-stage renal disease after donation. Consequently, obesity serves as a barrier to donation, as many transplant centers encourage or require weight loss before donation for obese LKD candidates. Therefore, this study sought to assess patients' perspectives on weight management strategies before donation among obese LKD candidates. We hypothesized that willingness to participate in a weight loss program may be associated with donor-recipient relationship. MATERIALS AND METHODS: Obese (BMI ≥30 kg/m2) LKD candidates evaluated at a single institution from September 2017 to August 2018 were recruited. A survey was administered to assess LKD candidates' baseline exercise and dietary habits and their interest in weight management strategies for the purpose of donation approval. Participants were grouped by relationship to the recipient (close relatives: first-degree relatives or spouses [n = 29], compared with all other relationships [n = 21]). Descriptive statistics were used to summarize the data. RESULTS: 50 of 51 obese LKD candidates who were approached completed the survey. 90% of participants expressed willingness to lose weight if necessary to become eligible for donor nephrectomy. Compared with all other LKD candidates, close relatives were more likely to be interested in combined diet and exercise programs at our institution (P = 0.01). CONCLUSIONS: Among obese LKD candidates, there was an interest in weight loss for the purposes of living kidney donation approval, particularly among close relatives of potential recipients. Future programs designed to promote weight management efforts for obese LKD candidates should be considered.


Assuntos
Doadores Vivos/psicologia , Nefrectomia/efeitos adversos , Obesidade/reabilitação , Coleta de Tecidos e Órgãos/efeitos adversos , Programas de Redução de Peso , Adulto , Dieta Saudável/psicologia , Exercício Físico/fisiologia , Exercício Físico/psicologia , Relações Familiares/psicologia , Feminino , Humanos , Rim/cirurgia , Falência Renal Crônica/etiologia , Falência Renal Crônica/prevenção & controle , Transplante de Rim/métodos , Transplante de Rim/normas , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Participação do Paciente/psicologia , Período Pré-Operatório , Pesquisa Qualitativa , Inquéritos e Questionários/estatística & dados numéricos , Coleta de Tecidos e Órgãos/psicologia , Coleta de Tecidos e Órgãos/normas , Redução de Peso/fisiologia
8.
Clin Transplant ; 33(11): e13724, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31585486

RESUMO

INTRODUCTION: Many transplant centers utilize a hard cutoff of 2 hours of warm ischemic time (WIT), defined as the time from withdrawal of life-sustaining measures to cold organ flush, to exclude donation after circulatory determination of death (DCD) kidney donation. As a result, almost a quarter of withdrawals to retrieve DCD organs fail to produce kidney transplants in Ontario. In order to assess our ability to increase organ yield, we wanted to characterize WIT and functional WIT (fWIT, time from systolic blood pressure <50 mm Hg to cold organ flush), as well as determine the time at which potential donors eventually die in those that did not become organ donors. METHODS: A retrospective review of all DCD kidney donors in Ontario was performed utilizing the Trillium Gift of Life Database from April 2013 to February 2018. RESULTS: Of 350 DCD kidney donors analyzed, 46.9% had < 0.5 hours, 51.7% between 0.5 and 2 hours, and 1.4% >2 hours of WIT. In each of these categories (WIT <0.5 hours, 0.5-2 hours and >2 hours), the percentage of patients with fWIT <30 minutes was 100%, 94.4%, and 100%, respectively (P = NS). There were 106 potential donors who did not end up donating due to WIT >2 hours. Of these, 20.8% died between 2 and 4 hours, 10.4% between 4 and 6 hours, and 68.8% beyond 6 hours. DISCUSSION: The percentage of donors with fWIT >30 minutes did not increase with increasing WIT in DCD donors that went on to donate organs. These data support assessment of waiting up to 4 hours for DCD kidney donation as long as fWIT remains low.


Assuntos
Transplante de Rim/métodos , Doadores de Tecidos/provisão & distribuição , Coleta de Tecidos e Órgãos/normas , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Isquemia Quente/normas , Morte , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
9.
Clin Transplant ; 33(10): e13716, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31541478

RESUMO

Recent evidence suggests that hypothermic machine perfusion of donor kidneys reduces delayed graft function (DGF). This study addresses the effect of machine perfusion (MP) on allograft rejection in the United States. We assembled a retrospective cohort of patients undergoing kidney-alone transplants in the UNOS database from June 30, 2004 to May 31, 2017. DGF was defined as dialysis requirement in the first week post-transplant; graft rejection was defined at 6 months and 1 year. Multivariable logistic regression adjusted for recipient and donor factors evaluated the effect of MP on DGF and graft rejection. Records for 79 300 kidney transplants meeting inclusion criteria were abstracted, 42% of which underwent MP. MP kidneys came from older donors, were more likely to have been obtained following donation after cardiac death, and had longer cold ischemic times. Rates of DGF and rejection were similar between MP and static storage kidneys. Following adjustment, recipients of MP kidneys were less likely to experience rejection at 1 year (OR 0.91 [95% CI 0.86-0.97] P = .002), but not at 6 months post-transplantation (OR 0.94 [0.88-1.02] P = .07). This effect persisted following adjustment for cold ischemic time. This study adds to the accumulating evidence demonstrating improved outcomes following MP of kidneys. We encourage protocolized consideration of MP for kidney grafts.


Assuntos
Função Retardada do Enxerto/prevenção & controle , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/métodos , Preservação de Órgãos/instrumentação , Perfusão/instrumentação , Doadores de Tecidos/provisão & distribuição , Coleta de Tecidos e Órgãos/normas , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/métodos , Prognóstico , Estudos Retrospectivos
10.
Can J Surg ; 62(1): 44-51, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30484989

RESUMO

Background: Outcomes in liver transplantation with organs obtained via donation after cardiocirculatory death (DCD) have been suboptimal compared to donation after brain death, attributed mainly to the high incidence of ischemic cholangiopathy (IC). We evaluated the effect of a 10-year learning curve on IC rates among DCD liver graft recipients at a single centre. Methods: We analyzed all DCD liver transplantation procedures from July 2006 to July 2016. Patients were grouped into early (July 2006 to June 2011) and late (July 2011 to July 2016) eras. Those with less than 6 months of follow-up were excluded. Primary outcomes were IC incidence and IC-free survival rate. Results: Among the 73 DCD liver transplantation procedures performed, 70 recipients fulfilled the selection criteria, 32 in the early era and 38 in the late era. Biliary complications were diagnosed in 19 recipients (27%). Ischemic cholangiopathy was observed in 8 patients (25%) in the early era and 1 patient (3%) in the late era (p = 0.005). The IC-free survival rate was higher in the late era than the early era (98% v. 79%, p = 0.01). The warm ischemia time (27 v. 24 min, p = 0.049) and functional warm ischemia time (21 v. 17 min, p = 0.002) were significantly lower in the late era than the early era. Conclusion: We found a significant reduction in IC rates and improvement in ICfree survival among DCD liver transplantation recipients after a learning curve period that was marked by more judicious donor selection with shorter procurement times.


Contexte: L'issue des greffes de foie suite à un don d'organe après décès cardiocirculatoire (DDC) a été sous-optimale comparativement aux dons suivant la mort cérébrale. Cela serait surtout attribuable à une forte incidence de cholangiopathie ischémique (CI). Nous avons évalué l'effet d'une courbe d'apprentissage échelonnée sur 10 ans sur les taux de CI chez des receveurs de greffe de foie après DDC dans un seul centre. Méthodes: Nous avons analysé toutes les greffes de foie consécutives à des DDC entre juillet 2006 et juillet 2016. Les patients ont été regroupés en 2 époques, la première, de juillet 2006 à juin 2011, et la seconde, de juillet 2011 à juillet 2016. Ceux pour lesquels on disposait de moins de 6 mois de suivi ont été exclus. Les paramètres principaux étaient l'incidence de CI et le taux de survie sans CI. Résultats: Parmi les 73 greffes de foie par suite de DDC, 70 receveurs répondaient aux critères de sélection, 32 pour la première époque et 38 pour la seconde époque. Des complications biliaires ont été diagnostiquées chez 19 receveurs (27 %). La cholangiopathie ischémique a été observée chez 8 patients (25 %) de la première époque et 1 patient (3 %) de la seconde (p = 0,005). Le taux de survie sans CI a été plus élevé pendant la seconde époque que pendant la première (98 % c. 79 %, p = 0,01). Le temps d'ischémie chaude (27 minutes c. 24, p = 0,049) et le temps d'ischémie chaude fonctionnelle (21 minutes c. 17, p = 0,002) ont été significativement plus courts durant la seconde époque que durant la première. Conclusion: Nous avons observé une réduction significative des taux de CI et une amélioration de la survie sans CI chez les receveurs de greffes de foie par DDC après une courbe d'apprentissage qui a été marquée par une sélection plus judicieuse des donneurs et des délais d'obtention plus courts.


Assuntos
Doenças dos Ductos Biliares/prevenção & controle , Morte , Doença Hepática Terminal/cirurgia , Isquemia/prevenção & controle , Transplante de Fígado/efeitos adversos , Isquemia Quente/normas , Adulto , Idoso , Doenças dos Ductos Biliares/etiologia , Canadá , Bases de Dados Factuais , Feminino , Sobrevivência de Enxerto , Humanos , Isquemia/etiologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Doadores de Tecidos , Coleta de Tecidos e Órgãos/normas , Obtenção de Tecidos e Órgãos/normas , Transplantados , Resultado do Tratamento
11.
Am J Transplant ; 18(3): 580-589, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28889600

RESUMO

Normothermic ex vivo kidney perfusion (NEVKP) represents a novel approach for graft preservation and functional improvement in kidney transplantation. We investigated whether NEVKP also allows graft quality assessment before transplantation. Kidneys from 30-kg pigs were recovered in a model of heart-beating donation (group A) after 30 minutes (group B) or 60 minutes (group C) (n = 5/group) of warm ischemia. After 8 hours of NEVKP, contralateral kidneys were resected, grafts were autotransplanted, and the pigs were followed for 3 days. After transplantation, renal function measured based on peak serum creatinine differed significantly among groups (P < .05). Throughout NEVKP, intrarenal resistance was lowest in group A and highest in group C (P < .05). intrarenal resistance at the initiation of NEVKP correlated with postoperative renal function (P < .001 at NEVKP hour 1). Markers of acid-base homeostasis (pH, HCO3- , base excess) differed among groups (P < .05) and correlated with posttransplantation renal function (P < .001 for pH at NEVKP hour 1). Similarly, lactate and aspartate aminotransferase were lowest in noninjured grafts versus donation after circulatory death kidneys (P < .05) and correlated with posttransplantation kidney function (P < .001 for lactate at NEVKP hour 1). In conclusion, assessment of perfusion characteristics and clinically available perfusate biomarkers during NEVKP allows the prediction of posttransplantation graft function. Thus, NEVKP might allow decision-making regarding whether grafts are suitable for transplantation.


Assuntos
Transplante de Rim/métodos , Preservação de Órgãos/métodos , Garantia da Qualidade dos Cuidados de Saúde/normas , Medição de Risco/métodos , Doadores de Tecidos/provisão & distribuição , Coleta de Tecidos e Órgãos/normas , Obtenção de Tecidos e Órgãos/normas , Animais , Masculino , Modelos Animais , Perfusão , Suínos , Temperatura , Coleta de Tecidos e Órgãos/métodos
12.
Liver Transpl ; 24(7): 908-921, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29729104

RESUMO

The prevalence of obesity-associated nonalcoholic fatty liver disease has significantly increased over the past decade, and end-stage liver disease secondary to nonalcoholic steatohepatitis has become 1 of the most common indications for liver transplantation. This both increases the demand for organs and decreases the availability of donor livers deemed suitable for transplantation. Although in the past many steatotic livers were discarded due to concerns over enhanced susceptibility to ischemia/reperfusion injury (IRI) and organ failure, the discrepancy between supply and demand has resulted in increasing use of expanded criteria donor organs including steatotic livers. However, it remains controversial whether steatotic livers can be safely used for transplantation and how best to improve the performance of steatotic grafts. We aimed to evaluate the impact of diet-induced hepatic steatosis in a murine model of IRI. Using a diet of high trans-fat, fructose, and cholesterol (HTF-C) and a diet high in saturated fats, sucrose, and cholesterol (Western diet), we were able to establish models of mixed macrovesicular and microvesicular steatosis (HTF-C) and microvesicular steatosis (Western). We found that the presence of hepatic steatosis, whether it is predominantly macrovesicular or microvesicular, significantly worsens IRI as measured by plasma alanine aminotransferase levels and inflammatory cytokine concentration, and histological evaluation for necrosis. Additionally, we report on a novel finding in which hepatic IRI in the setting of steatosis results in the induction of the necroptosis factors, receptor interacting protein kinase (RIPK) 3, RIPK1, and mixed-lineage kinase domain-like. These data lay the groundwork for additional experimentation to test potential therapeutic approaches to limit IRI in steatotic livers by using a genetically tractable system. Liver Transplantation 24 908-921 2018 AASLD.


Assuntos
Transplante de Fígado/efeitos adversos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/patologia , Traumatismo por Reperfusão/patologia , Animais , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Humanos , Fígado/irrigação sanguínea , Fígado/cirurgia , Testes de Função Hepática , Transplante de Fígado/normas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/etiologia , Traumatismo por Reperfusão/etiologia , Coleta de Tecidos e Órgãos/normas
13.
Liver Transpl ; 24(11): 1589-1602, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30120877

RESUMO

Cold storage (CS) remains the gold standard for organ preservation worldwide, although it is inevitably associated with ischemia/reperfusion injury (IRI). Molecular hydrogen (H2 ) is well known to have antioxidative properties. However, its unfavorable features, ie, inflammability, low solubility, and high tissue/substance permeability, have hampered its clinical application. To overcome such obstacles, we developed a novel reconditioning method for donor organs named hydrogen flush after cold storage (HyFACS), which is just an end-ischemic H2 flush directly to donor organs ex vivo, and, herein, we report its therapeutic impact against hepatic IRI. Whole liver grafts were retrieved from Wistar rats. After 24-hour CS in UW solution, livers were cold-flushed with H2 solution (1.0 ppm) via the portal vein (PV), the hepatic artery (HA), or both (PV + HA). Functional integrity and morphological damages were then evaluated by 2-hour oxygenated reperfusion at 37°C. HyFACS significantly lowered portal venous pressure, transaminase, and high mobility group box protein 1 release compared with vehicle-treated controls (P < 0.01). Hyaluronic acid clearance was significantly higher in the HyFACS-PV and -PV + HA groups when compared with the others (P < 0.01), demonstrating the efficacy of the PV route to maintain the sinusoidal endothelia. In contrast, bile production and lactate dehydrogenase leakage therein were both significantly improved in HyFACS-HA and -PV + HA (P < 0.01), representing the superiority of the arterial route to attenuate biliary damage. Electron microscopy consistently revealed that sinusoidal ultrastructures were well maintained by portal HyFACS, while microvilli in bile canaliculi were well preserved by arterial flush. As an underlying mechanism, HyFACS significantly lowered oxidative damages, thus improving the glutathione/glutathione disulfide ratio in liver tissue. In conclusion, HyFACS significantly protected liver grafts from IRI by ameliorating oxidative damage upon reperfusion in the characteristic manner with its route of administration. Given its safety, simplicity, and cost-effectiveness, end-ischemic HyFACS may be a novel pretransplant conditioning for cold-stored donor organs.


Assuntos
Antioxidantes/administração & dosagem , Hidrogênio/administração & dosagem , Preservação de Órgãos/métodos , Traumatismo por Reperfusão/prevenção & controle , Coleta de Tecidos e Órgãos/métodos , Aloenxertos/efeitos dos fármacos , Aloenxertos/patologia , Animais , Modelos Animais de Doenças , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Transplante de Fígado , Masculino , Preservação de Órgãos/normas , Estresse Oxidativo/efeitos dos fármacos , Perfusão/instrumentação , Perfusão/métodos , Perfusão/normas , Ratos , Ratos Wistar , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Coleta de Tecidos e Órgãos/efeitos adversos , Coleta de Tecidos e Órgãos/normas
14.
Cytotherapy ; 20(4): 564-575, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29429941

RESUMO

BACKGROUND: Umbilical cord (UC) tissue can be collected in a noninvasive procedure and is enriched in progenitor cells with potential therapeutic value. Mesenchymal stromal cells (MSCs) can be reliably harvested from fresh or cryopreserved UC tissue by explant outgrowth with no apparent impact on functionality. A number of stem cell banks offer cryopreservation of UC tissue, alongside cord blood, for future cell-based applications. In this setting, measuring and monitoring UC quality is critical. MATERIALS AND METHODS: UC explants were evaluated using a plating and scoring system accounting for cell attachment and proliferation. Explant scores for fresh and cryopreserved-then-thawed tissue from the same UC were compared. Metabolic activity of composite UC tissue was also assayed after exposure of the tissue to conditions anticipated to affect UC quality and compared with explant scores within the same UC. RESULTS: All fresh and cryopreserved tissues yielded MSC-like cells, and cryopreservation of the tissue did not prevent the ability to isolate MSCs by the explant method. Thawed UC tissue scores were 91% (±0.6%; P = 0.0009) that of the fresh, biologically identical tissue. Within the same UC, explant scores correlated well to both cell yield (R2 = 0.85) and tissue metabolic activity (R2 = 0.69). DISCUSSION: A uniform explant scoring assay can provide information about the quality of composite UC tissue. Such quantitative measurement is useful for analysis of tissue variability and process monitoring. Additionally, a metabolic assay of UC tissue health provides results that correlate well to explant scoring results.


Assuntos
Bioensaio , Coleta de Tecidos e Órgãos , Cordão Umbilical , Bioensaio/métodos , Bioensaio/normas , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Criopreservação/métodos , Criopreservação/normas , Estudos de Avaliação como Assunto , Sangue Fetal/química , Sangue Fetal/citologia , Sangue Fetal/metabolismo , Saúde , Humanos , Recém-Nascido , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Metaboloma , Controle de Qualidade , Padrões de Referência , Bancos de Tecidos/normas , Coleta de Tecidos e Órgãos/métodos , Coleta de Tecidos e Órgãos/normas , Cordão Umbilical/química , Cordão Umbilical/citologia , Cordão Umbilical/metabolismo , Cordão Umbilical/cirurgia
15.
Clin Transplant ; 32(3): e13204, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29345387

RESUMO

BACKGROUND: All living kidney donors are counseled about the possible surgical and medical risks associated with donation. Only a minority of transplant centers discuss the potential benefit of discovering undiagnosed medical conditions in the donor during evaluation, as part of their consent process. METHODS: We retrospectively investigated all potential living kidney donors evaluated over a 10-year period at a single center to characterize incidentally diagnosed serious medical conditions. RESULTS: Sixty-five of the 762 potential donors (8.5%) were not approved for donation because of a newly diagnosed serious medical condition discovered during their evaluation. This included six patients diagnosed with malignancies, five of which required operative intervention, six patients diagnosed with transmittable diseases requiring follow-up and treatment, four patients were found to have bilateral renal stones with significant stone burden, and two patients diagnosed with IgA nephropathy. Additionally, four patients were diagnosed with significant heart disease, and one of those patients subsequently required a coronary artery bypass surgery. CONCLUSIONS: The evaluation process can diagnose serious medical conditions in a significant minority of donors that would have otherwise been unrecognized. The benefit associated with the donor evaluation should be considered an important part of the consent process.


Assuntos
Seleção do Doador/normas , Transplante de Rim/métodos , Rim/fisiopatologia , Doadores Vivos/estatística & dados numéricos , Medição de Risco/métodos , Índice de Gravidade de Doença , Coleta de Tecidos e Órgãos/normas , Adulto , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Humanos , Consentimento Livre e Esclarecido , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
16.
Clin Transplant ; 32(10): e13387, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30133026

RESUMO

The use of donation after circulatory death (DCD) has increased significantly to face the persistent mismatch between supply and demand of organs for transplantation. While controlled (c) DCDs have warm ischemic time (WIT) that can be estimated, the WIT is often inexact and extended in uncontrolled DCD (uDCD), making assessment of injury difficult. We aimed at investigating the effects of cold ischemia on potential donor organ damage in the course of nRP by assessing the dynamic variations of transaminases and creatinine values in 17 uDCD donors. In our series, lactate values did not show significant changes during the study period (P = 0.147). Creatinine values did not significantly changed while transaminases progressive increased throughout the study period, even if it was significant only for AST (P = 0.035). According to our data, nRP duration affects splanchnic organs, being the liver sensitive to hypoperfusion, and serial biochemical measurements could help in detecting organ functional status.


Assuntos
Morte Encefálica , Creatinina/metabolismo , Preservação de Órgãos/normas , Transplante de Órgãos , Doadores de Tecidos/provisão & distribuição , Coleta de Tecidos e Órgãos/normas , Transaminases/metabolismo , Adolescente , Adulto , Idoso , Isquemia Fria , Oxigenação por Membrana Extracorpórea , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Perfusão , Projetos Piloto , Estudos Prospectivos , Estudos Retrospectivos , Isquemia Quente , Adulto Jovem
17.
Cell Tissue Bank ; 19(2): 175-186, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29022196

RESUMO

Under the auspices of the IAEA tissue banking programme on "Radiation Sterilisation of Tissue Graft" conducted from 1985 to 2004, many scientists and surgeons were involved in various regional research and development (R&D) projects mainly in dealing with radiation dose selection, radiation effects on human tissues and quality system in radiation sterilisation. New findings on radiation effects, tissue processing and preservation were shared during the regional and interregional meetings and workshops. Many tissue banks started to use radiation (25 kGy) to sterilize tissue grafts for tissue safety and efficacy and still continue to use it. The IAEA Code of Practice for Radiation Sterilization of Tissues Allografts developed in 2007 offered simpler methods to conduct radiation dose setting and dose validation experiments for tissue grafts. Advances in dose selection and dose mapping are continued under the quality management system when banks need to be certified to continue their operation. The combination of good tissue processing and preservation as well as good radiation practice will ensure the tissue products are properly sterilised thus safe and of high quality. Experience in meeting challenges in using radiation sterilisation and achievements reported by the tissue bankers are shared here.


Assuntos
Agências Internacionais/normas , Radiação , Bancos de Tecidos/normas , Coleta de Tecidos e Órgãos/normas , Humanos , Transplante Homólogo , Transplantes/normas
18.
Orv Hetil ; 159(42): 1695-1699, 2018 10.
Artigo em Húngaro | MEDLINE | ID: mdl-30334486

RESUMO

The author concludes lessons learned from Hungary joining Eurotransplant five years ago through the more than half a century history of the Hungarian organ transplantation. The result of the stepwise evolution is that today's transplantation activity can be measured by a European benchmark. In comparison to the era before the membership, there are 40% more transplantations in the country. First the numbers of the living donor kidney transplantations significantly raised, followed by the organs transplanted from brain-dead donors: kidney, heart, pancreas, then liver and finally also lung. The ratio of the multiorgan donors changed from about 40% to more than 70%. A reassuring solution was found for the high urgent cases, for the paediatric transplants and for the highly immunized patients, who would have been in a desperate situation without Eurotransplant, but now every Hungarian end-stage organ failure patient has similar chances for getting a potential life-saving organ as their former luckier West-European counterparts. Orv Hetil. 2018; 159(42): 1695-1699.


Assuntos
Transplante de Órgãos/tendências , Coleta de Tecidos e Órgãos/tendências , Obtenção de Tecidos e Órgãos/tendências , União Europeia , Transplante de Coração/estatística & dados numéricos , Transplante de Coração/tendências , Humanos , Hungria , Transplante de Rim/estatística & dados numéricos , Transplante de Fígado/estatística & dados numéricos , Transplante de Fígado/tendências , Transplante de Pulmão/estatística & dados numéricos , Transplante de Pulmão/tendências , Transplante de Órgãos/normas , Transplante de Pâncreas/estatística & dados numéricos , Transplante de Pâncreas/tendências , Coleta de Tecidos e Órgãos/normas , Obtenção de Tecidos e Órgãos/normas
19.
Am J Transplant ; 17(4): 957-969, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27647696

RESUMO

Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) versus short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS versus prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 min of warm ischemia, kidneys were removed from 30-kg Yorkshire pigs and preserved for 16 h with (A) 16 h SCS, (B) 15 h SCS + 1 h NEVKP, (C) 8 h SCS + 8 h NEVKP, and (D) 16 h NEVKP. After contralateral kidney resection, grafts were autotransplanted and pigs followed up for 8 days. Perfusate injury markers such as aspartate aminotransferase and lactate dehydrogenase remained low; lactate decreased significantly until end of perfusion in groups C and D (p < 0.001 and p = 0.002). Grafts in group D demonstrated significantly lower serum creatinine peak when compared to all other groups (p < 0.001) and 24-h creatinine clearance at day 3 after surgery was significantly higher (63.4 ± 19.0 mL/min) versus all other groups (p < 0.001). Histological assessment on day 8 demonstrated fewer apoptotic cells in group D (p = 0.008). In conclusion, prolonged, continuous NEVKP provides superior short-term outcomes following DCD kidney transplantation versus SCS or short additional NEVKP following SCS.


Assuntos
Morte Encefálica , Temperatura Baixa , Transplante de Rim/métodos , Preservação de Órgãos/métodos , Perfusão , Coleta de Tecidos e Órgãos/normas , Animais , Masculino , Sus scrofa , Coleta de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos
20.
Liver Transpl ; 23(10): 1305-1311, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28734130

RESUMO

The evidence is insufficient for safe use of elderly donors in adult-to-adult living donor liver transplantation (LDLT). The aim of this study was to evaluate the outcomes of right lobe LDLT by donor age (≥55 versus < 55 years). All living donors who underwent right hepatectomy at the authors' institution between March 2008 and December 2015 were divided into 2 groups: group A with an age ≥ 55 years and group B with an age of <55 years. The selection criteria for elderly donor were preservation of middle hepatic vein, remnant liver volume ≥30%, and no or mild fatty liver. The matching criteria of recipients for the elderly donor grafts were Model for End-Stage Liver Disease score of <25, graft-to-recipient weight ratio of >0.8%, and body mass index of <25 kg/m2 . Perioperative data, complications by the Clavien classification, and the outcomes with at least 12 months follow-up were compared. A total of 42 donors were enrolled in group A and 498 in group B. No significant differences in operative parameters were observed between the 2 groups. The peak postoperative aspartate aminotransferase, alanine aminotransferase, and total bilirubin levels made no difference between the 2 groups. The peak international normalized ratio level was significantly lower in group A than in group B (P = 0.001). All donors recovered completely with no significant differences in overall complications between the 2 groups. All recipients of grafts from donors in group A showed good initial function with no significant differences in 1-year graft and patient survival or biliary complications between 2 groups. These results provide clinical evidence for feasibility of right hepatectomy in living donors aged ≥ 55 years without compromising donor safety or recipient outcomes. Liver Transplantation 23 1305-1311 2017 AASLD.


Assuntos
Doença Hepática Terminal/cirurgia , Hepatectomia/métodos , Transplante de Fígado/métodos , Doadores Vivos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Coleta de Tecidos e Órgãos/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Doença Hepática Terminal/mortalidade , Estudos de Viabilidade , Feminino , Seguimentos , Sobrevivência de Enxerto , Hepatectomia/efeitos adversos , Hepatectomia/normas , Humanos , Fígado/fisiologia , Fígado/cirurgia , Testes de Função Hepática , Transplante de Fígado/efeitos adversos , Transplante de Fígado/normas , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida , Coleta de Tecidos e Órgãos/efeitos adversos , Coleta de Tecidos e Órgãos/normas , Resultado do Tratamento , Adulto Jovem
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