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OBJECTIVE: To analyse outcomes after adult right ex-situ split graft liver transplantations (RSLT) and compare with available outcome benchmarks from whole liver transplantation (WLT). SUMMARY BACKGROUND DATA: Ex-situ SLT may be a valuable strategy to tackle the increasing graft shortage. Recently established outcome benchmarks in WLT offer a novel reference to perform a comprehensive analysis of results after ex-situ RSLT. METHODS: This retrospective multicenter cohort study analyzes all consecutive adult SLT performed using right ex-situ split grafts from 01.01.2014 to 01.06.2022. Study endpoints included 1 year graft and recipient survival, overall morbidity expressed by the comprehensive complication index (CCI©) and specific post-LT complications. Results were compared to the published benchmark outcomes in low-risk adult WLT scenarii. RESULTS: In 224 adult right ex-situ SLT, 1y recipient and graft survival rates were 96% and 91.5%, within the WLT benchmarks. The 1y overall morbidity was also within the WLT benchmark (41.8 CCI points vs. <42.1). Detailed analysis, revealed cut surface bile leaks (17%, 65.8% Grade IIIa) as a specific complication without a negative impact on graft survival. There was a higher rate of early hepatic artery thrombosis (HAT) after SLT, above the WLT benchmark (4.9% vs. ≤4.1%), with a significant impact on early graft but not patient survival. CONCLUSION: In this multicentric study of right ex-situ split graft LT, we report 1-year overall morbidity and mortality rates within the published benchmarks for low-risk WLT. Cut surface bile leaks and early HAT are specific complications of SLT and should be acknowledged when expanding the use of ex-situ SLT.
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Optimizing graft preservation is key for ex-situ split grafts in pediatric liver transplantation (PSLT). Hypothermic Oxygenated Perfusion (HOPE) improves ischemia-reperfusion injury (IRI) and post-operative outcomes in adult LT. This study compares the use of HOPE in ex-situ partial grafts to static cold storage ex-situ partial grafts (SCS-Split) and to the gold standard living donor liver transplantation (LDLT). All consecutive HOPE-Split, SCS-Split and LDLT performed between 2018-2023 for pediatric recipients were included. Post-reperfusion syndrome (PRS, drop ≥30% in systolic arterial pressure) and reperfusion biopsies served as early indicators of IRI. We included 47 pediatric recipients (15 HOPE-Split, 17 SCS-Split, and 15 LDLT). In comparison to SCS-Split, HOPE-Split had a significantly shorter cold ischemia time (CIT) (470min vs. 538 min; p =0.02), lower PRS rates (13.3% vs. 47.1%; p = 0.04) and a lower IRI score (3 vs. 4; p = 0.03). The overall IRI score (3 vs. 3; p = 0.28) and PRS (13.3% vs. 13.3%; p = 1) after HOPE-Split were comparable to LDLT, despite a longer CIT (470 min vs. 117 min; p < 0.001). Surgical complications, one-year graft, and recipient survival did not differ among the groups. In conclusion, HOPE-Split mitigates early IRI in pediatric recipients in comparison to SCS-Split, approaching the gold standard of LDLT.
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Transplante de Fígado , Doadores Vivos , Preservação de Órgãos , Perfusão , Traumatismo por Reperfusão , Humanos , Transplante de Fígado/métodos , Transplante de Fígado/efeitos adversos , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/etiologia , Masculino , Feminino , Criança , Pré-Escolar , Preservação de Órgãos/métodos , Perfusão/métodos , Adolescente , Lactente , Isquemia Fria , Sobrevivência de Enxerto , Estudos Retrospectivos , Fígado/irrigação sanguíneaRESUMO
Bile acids (BA) are key for liver regeneration and injury. This study aims at analyzing the changes in the BA pool induced by ischemia-reperfusion (IRI) and investigates the impact of hypothermic oxygenated perfusion (HOPE) on the BA pool compared to static cold storage (SCS). In a porcine model of IRI, liver grafts underwent 30 min of asystolic warm ischemia followed by 6 h of SCS (n = 6) ± 2 h of HOPE (n = 6) and 2 h of ex-situ warm reperfusion. The BA pool in bile samples was analyzed with liquid chromatography coupled with tandem mass spectrometry. We identified 16 BA and observed significant changes in response to ischemia-reperfusion, which were associated with both protective and injury mechanisms. Second, HOPE-treated liver grafts exhibited a more protective BA phenotype, characterized by a more hydrophilic BA pool compared to SCS. Key BA, such as GlycoCholic Acid, were identified and were associated with a decreased transaminase release and improved lactate clearance during reperfusion. Partial Least Square-Discriminant Analysis revealed a distinct injury profile for the HOPE group. In conclusion, the BA pool changes with liver graft IRI, and preservation with HOPE results in a protective BA phenotype compared to SCS.
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Ácidos e Sais Biliares , Traumatismo por Reperfusão , Suínos , Animais , Preservação de Órgãos/métodos , Perfusão/métodos , Fígado/fisiologia , IsquemiaRESUMO
BACKGROUND: Hypothermic oxygenated perfusion (HOPE) improves outcomes of marginal liver grafts. However, to date, no preservation solution exists for both static cold storage (SCS) and HOPE. METHODS: After 30 min of asystolic warm ischemia, porcine livers underwent 6 h of SCS followed by 2 h of HOPE. Liver grafts were either preserved with a single preservation solution (IGL2) designed for SCS and HOPE (IGL2-Machine Perfusion Solution [MPS] group, n = 6) or with the gold-standard University of Wisconsin designed for for SCS and Belzer MPS designed for HOPE (MPS group, n = 5). All liver grafts underwent warm reperfusion with whole autologous blood for 2 h, and surrogate markers of hepatic ischemia-reperfusion injury (IRI) were assessed in the hepatocyte, cholangiocyte, vascular, and immunological compartments. RESULTS: After 2 h of warm reperfusion, livers in the IGL2-MPS group showed no significant differences in transaminase release (aspartate aminotransferase: 65.58 versus 104.9 UI/L/100 g liver; P = 0.178), lactate clearance, and histological IRI compared with livers in the MPS group. There were no significant differences in biliary acid composition, bile production, and histological biliary IRI. Mitochondrial and endothelial damage was also not significantly different and resulted in similar hepatic inflammasome activation. CONCLUSIONS: This preclinical study shows that a novel IGL2 allows for the safe preservation of marginal liver grafts with SCS and HOPE. Hepatic IRI was comparable with the current gold standard of combining 2 different preservation solutions (University of Wisconsin + Belzer MPS). These data pave the way for a phase I first-in-human study and it is a first step toward tailored preservation solutions for machine perfusion of liver grafts.
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Transplante de Fígado , Soluções para Preservação de Órgãos , Suínos , Humanos , Animais , Preservação de Órgãos/métodos , Perfusão/métodos , Transplante de Fígado/métodos , Fígado/patologia , Soluções para Preservação de Órgãos/farmacologia , Hepatócitos/patologiaRESUMO
Liver graft-recipient matching remains challenging, and both morphologic and hemodynamic characteristics have been shown to be relevant indicators of post-transplant outcomes. However, no combined analysis is available to date. To study the impact of both morphologic and hemodynamic characteristics of liver grafts on transplantation outcomes, we retrospectively evaluated all consecutive 257 liver transplantations with prospective hemodynamic measurements from 2017 to 2020 in a single-center perspective. First, a morphologic analysis compared recipients with or without large-for-size (LFS), defined by a graft/recipient weight ratio >2.5% and excluding extreme LFS. Second, a hemodynamic analysis compared recipients with or without low portal flow (LPF; <80 mL/min per 100 g of liver tissue). Third, an outcome analysis combining LPF and LFS was performed, focusing on liver graft-related morbidity (LGRM), graft and patient survival. LGRM was a composite endpoint, including primary nonfunction, high-risk L-Graft7 category, and portal vein thrombosis. Morphologic analysis showed that LFS (n=33; 12.9%) was not associated with an increased LGRM (12.1% vs 9.4%; p =0.61) or impaired graft and patient survival. However, the hemodynamic analysis showed that LPF (n=43; 16.8%) was associated with a higher LGRM (20.9% vs 7.5%, p = 0.007) and a significantly impaired 90-day graft and patient survival. Multivariable analysis identified LPF but not LFS as an independent risk factor for LGRM (OR: 2.8%; CI:1.088-7.413; and p = 0.03), 90-day (HR: 4%; CI: 1.411-11.551; and p = 0 .01), and 1-year patient survival. LPF is a significant predictor of post-liver transplantation morbi-mortality, independent of LFS when defined as a morphologic metric alone. Consequently, we propose the novel concept of large-for-flow, which may guide graft selection and improve perioperative management of LPF.
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Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Estudos Prospectivos , Fígado/cirurgia , Fígado/irrigação sanguínea , Fatores de Risco , Sobrevivência de Enxerto , Resultado do TratamentoRESUMO
In this report, we discuss several technical and anatomical details of ex-situ H67 reduction of liver grafts during hypothermic oxygenated perfusion to prevent large-for-size syndrome in the case of anthropometric graft-recipient mismatch.
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Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Preservação de Órgãos , Sobrevivência de Enxerto , Perfusão , FígadoRESUMO
BACKGROUND: Graft-recipient size matching is a major challenge in pediatric liver transplantation, especially for adolescent recipients. Indeed, adolescents have the lowest transplantation rate among pediatric recipients, despite prioritization policies and the use of split grafts. In case of an important graft-recipient size mismatch, ex situ graft reduction with right posterior sectionectomy (RPS) may optimize the available donor pool to benefit adolescent recipients. METHODS: We present three cases of liver graft reduction with ex situ RPS for adolescent recipients. The surgical strategy was guided by GRWR (graft/recipient weight ratio), GW/RAP (right anteroposterior distance ratio), and CT-scan volumetric and anthropometric evaluation. RESULTS: Recipients were 12, 13, and 14-year-old and weighed 32, 47, and 35 kg, respectively. All liver grafts were procured from brain-dead donors with a donor/recipient weight ratio >1.5. RPS was performed ex situ, removing 20% of the total liver volume leading to a decrease of the GRWR <4% and the GW/RAP <100 g/cm in each case. All three reduced grafts were successfully transplanted with a static cold storage time ranging from 390 to 510 min without the need for delayed abdominal closure. We did not observe any primary non-function, vascular complication, or delayed graft function with a median follow-up of 6 months. One biliary anastomotic stenosis occurred which required surgical treatment. CONCLUSION: Ex situ liver graft reduction with RPS allowed for successful transplantation in case of anthropometric graft-recipient size mismatch in adolescent liver transplant candidates. Although the use of split grafts remains the gold standard, RPS should be acknowledged as a way to optimize the donor pool, especially for adolescent recipients.
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Colestase , Transplante de Fígado , Humanos , Adolescente , Criança , Fígado/cirurgia , Doadores de Tecidos , Hepatectomia , Colestase/cirurgia , Doadores Vivos , Sobrevivência de Enxerto , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Liver graft utilization rates are a hot topic due to the worldwide organ shortage and the increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially enable the assessment of livers before use. METHODS: Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht type III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, the UK, and the US. Initial type-III DCD liver offers were correlated with accepted, recovered and implanted livers. RESULTS: A total number of 34,269 DCD livers were offered, resulting in 9,780 liver transplants (28.5%). The discard rates were highest in the UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g. between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, we observed large differences in the use of various machine perfusion techniques, as well as in graft and donor risk factors. For example, the median donor age and functional donor warm ischemia time were highest in Italy, e.g. >40 min, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in 5-year graft survival rates, which ranged between 60-82% in this analysis. CONCLUSIONS: Overall, DCD liver discard rates across the eight countries were high, although this primarily reflects the situation in the Netherlands, the UK and the US. Countries where in situ and ex situ machine perfusion strategies were used routinely had better DCD utilization rates without compromised outcomes. IMPACT AND IMPLICATIONS: A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5% but varies significantly between 18.9% and 74.2%. For example, the median DCD-III liver utilization in five countries, e.g. Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, 1- and 5-year graft survival rates remain fairly similar among all participating countries. A highly varying experience with modern machine perfusion technology was observed. In situ and ex situ liver perfusion concepts, and application of assessment tools for type-III DCD livers before transplantation, may be a key explanation for the observed differences in DCD-III utilization.
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Sistema Cardiovascular , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Humanos , Fígado , Doadores de Tecidos , Transplante de Fígado/métodos , Sobrevivência de Enxerto , Preservação de Órgãos/métodos , Perfusão/métodosRESUMO
BACKGROUND: Brazil is one of the world's largest pesticide consumers, but information on pesticide poisoning among workers is scarce. OBJECTIVE: To evaluate acute pesticide poisoning among tobacco growers, according to different criteria. METHODS: This was a two-step cross-sectional study with 492 pesticide applicators. It used a 25 question pesticide-related symptoms (PRS) questionnaire and medical diagnosis for comparison with toxicological assessment. Associations were evaluated using Poisson regression. RESULTS: 10.6% reported two or more PRS, while 8.1% reported three or more. Furthermore, 12.2% received a medical diagnosis of poisoning. According to toxicologists, possible cases accounted for 14.2% and probable cases for 4.3%. PRS increased during the period of greater exposure. Those exposed to dithiocarbamates, sulfentrazone, pyrethroids, fipronil and iprodione exhibited more PRS. The number of exposure types, multi-chemical exposure, clothes wet with pesticides and spillage on the body/clothes were associated with acute poisonings. All criteria showed sensitivity greater than 79% for probable cases but only greater than 70% for medical diagnosis when compared to possible cases, presenting substantial Kappa agreement. CONCLUSION: The prevalence of acute pesticide poisoning is much higher than officially recorded. Trained physicians can screen for pesticide poisoning. It is necessary to improve workers' education to reduce pesticide use and exposure to them.
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Doenças dos Trabalhadores Agrícolas , Exposição Ocupacional , Praguicidas , Intoxicação , Humanos , Nicotiana , Estudos Transversais , Doenças dos Trabalhadores Agrícolas/epidemiologia , Agricultura , Intoxicação/epidemiologiaRESUMO
BACKGROUND & AIMS: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. METHODS: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. RESULTS: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). CONCLUSIONS: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. IMPACT AND IMPLICATIONS: This randomized controlled phase III trial is the first to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation. Compared to conventional cold storage, HOPE did not have a significant effect on the number of patients with at least one Clavien ≥III complication. However, we believe that HOPE may have a beneficial effect on the quantity of complications per patient, based on its application leading to fewer severe liver graft-related complications, and to a lower risk of liver-related graft loss. The HOPE approach can be applied easily after organ transport during recipient hepatectomy. This appears fundamental for wide acceptance since concurring perfusion technologies need either perfusion at donor sites or continuous perfusion during organ transport, which are much costlier and more laborious. We conclude therefore that the post hoc findings of this trial should be further validated in future studies.
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Transplante de Fígado , Preservação de Órgãos , Humanos , Preservação de Órgãos/métodos , Perfusão/métodos , Fígado , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Morte Encefálica , Complicações Pós-Operatórias , Sobrevivência de EnxertoRESUMO
BACKGROUND: Pulmonary metastases (PM) are the most frequent extra-abdominal metastases from colorectal cancer. Lung resection and imaging-guided thermal ablation (IGTA) are used as curative-intent treatment. We compared the outcomes of patients with PM, treated with resection or ablation. METHODS: We retrospectively analyzed data from patients who underwent surgery or IGTA for colorectal PM between April 2011 and November 2020. Surgery was performed for peripheral PM and IGTA for deep-located PM not in contact with major vessels. Patients who had both procedures were excluded. Patients were compared using propensity score matching (PSM) analysis, stratified according to number, size, and unilaterality of PM. RESULTS: One hundred and fourty-six patients were included, 65 (44.5%) underwent surgery and 81 (55.5%) underwent IGTA. After PSM analysis, each group contained 46 patients. IGTA patients had a lower morbidity rate (13.1% vs. 15.2%, p = 0.028) and a shorter length of stay (5.13 vs. 2.63 days, p < 0.001). Oncological outcomes were similar in both groups with 5-year OS of 80% and 5-year progression-free survival (PFS) of 30% (p = 0.657 and p = 0.504, respectively) with similar recurrence patterns. CONCLUSION: Lung resection and IGTA seem to have similar oncologic outcomes for both OS and PFS. IGTA could be an alternative effective treatment for small PM, whenever technically feasible.
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Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia , Hepatectomia/métodos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/secundário , Resultado do Tratamento , Neoplasias Hepáticas/cirurgiaRESUMO
Resumo Introdução: a produção agrícola no Brasil tem crescido nas últimas décadas e os trabalhadores rurais estão expostos a vários riscos ocupacionais. Estudos epidemiológicos sobre o tema ainda são limitados, especialmente pela complexidade metodológica. Objetivos: apresentar os principais desafios metodológicos para a realização de estudos epidemiológicos ocupacionais rurais. Métodos: as considerações apresentadas neste artigo têm como base a literatura e a experiência dos autores como pesquisadores desta temática. Resultados: foram abordados conceitos sobre população alvo, local de moradia e trabalho, classificação dos trabalhadores e caracterização do contexto da produção agrícola. Foram exploradas as estratégias de amostragem; a caracterização dos indicadores econômicos, incluindo produção agrícola e nível de mecanização; a exposição aos agrotóxicos, como tipos químicos, formas e frequência de exposição; a intoxicação por agrotóxicos; e a disponibilidade e o uso de Equipamentos de Proteção Individual. Foram descritos os cuidados com amostras biológicas, bem como aspectos envolvendo entrevistadores, treinamentos, trabalho de campo, questões climáticas e logísticas. Conclusão: apesar dos desafios metodológicos e logísticos, com o planejamento adequado é possível realizar com êxito pesquisas de grande complexidade e de alto nível científico sobre a relação saúde-trabalho na atividade agropecuária.
Abstract Introduction: agricultural production in Brazil has grown in recent decades, and rural workers are exposed to many occupational risks. Epidemiological studies on the topic remain limited, especially regarding methodological complexity. Objectives: to present the main methodological challenges to carrying out occupational epidemiological studies in rural areas. Methods: the considerations presented in this article are based on the literature and on the experience of the authors as researchers of this thematic. Results: we approached concepts about target population, living and working place, workers classification, and agricultural production context characterization. We discussed sampling strategies, characterization of economic indicators, including agricultural production and mechanization level, pesticide exposure, such as chemical types, forms, and frequency of exposure, pesticide poisonings, and availability and use of personal protective equipment. We described the necessary care with biological samples and aspects involving interviewers, training, field work, and clinical and logistical issues. Conclusion: despite the methodological and logistical challenges, adequate planning enables successful research studies, of great complexity and high scientific level, about the health-work relationship in agricultural activity.
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OBJECTIVE: To define benchmark cutoffs for redo liver transplantation (redo-LT). BACKGROUND: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. METHODS: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. RESULTS: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks. CONCLUSION: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.
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Doença Hepática Terminal , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Benchmarking , Doença Hepática Terminal/cirurgia , Sobrevivência de Enxerto , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.
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Carcinoma Hepatocelular , Doença Hepática Terminal , Neoplasias Hepáticas , Transplante de Fígado , Aspartato Aminotransferases , Doença Hepática Terminal/cirurgia , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Índice de Gravidade de DoençaRESUMO
Partial liver grafts from ex situ splitting are considered marginal due to prolonged static cold storage. The use of ex situ hypothermic oxygenated perfusion (HOPE) may offer a strategy to improve preservation of ex situ split grafts. In this single-center pilot study, we prospectively performed ex situ liver splitting during HOPE (HOPE-Split) for adult and pediatric partial grafts over a 1-year period (November 1, 2020 to December 1, 2021). The primary safety endpoint was based on the number of liver graft-related adverse events (LGRAEs) per recipient, including primary nonfunction, biliary complications, hepatic vascular complications, and early relaparotomies and was compared with consecutive single-center standard ex situ split transplantations (Static-Split) performed from 2018 to 2020. Secondary endpoints included preservation characteristics and early outcomes. Sixteen consecutive HOPE-Split liver transplantations (8 HOPE-Split procedures) were included and compared with 24 Static-Splits. All HOPE-Split grafts were successfully transplanted, and no graft loss nor recipient death was encountered during the median follow-up of 7.5 months (interquartile range, 5.5-12.5). Mean LGRAE per recipient was similar in both groups (0.31 ± 0.60 vs. 0.46 ± 0.83; p = 0.78) and split duration was not significantly increased for HOPE-Split (216 vs. 180 min; p = 0.45). HOPE-Split grafts underwent perfusion for a median of 125 min, which significantly shortened static cold storage (472 vs. 544 min; p = 0.001), whereas it prolonged total ex vivo preservation (595 vs. 544 min; p = 0.007) and reduced neutrophil infiltration on reperfusion biopsies (p = 0.04) compared with Static-Split. This clinical pilot study presents first feasibility and safety data for transplantation of partial liver grafts undergoing ex situ split during HOPE and suggests improved preservation compared with static ex situ splitting. These preliminary results will allow to set up large-scale trials on the use of machine perfusion in pediatric and split-liver transplantation.
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Transplante de Fígado , Adulto , Criança , Sobrevivência de Enxerto , Humanos , Fígado/cirurgia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Preservação de Órgãos/efeitos adversos , Preservação de Órgãos/métodos , Perfusão/efeitos adversos , Perfusão/métodos , Projetos PilotoRESUMO
BACKGROUND: Ex vivo split liver transplantation in pediatric recipients has shown inferior results compared with whole grafts. One factor among others contributing to split grafts being considered as marginal is the prolonged static cold storage time related to ex vivo liver splitting. End ischemic hypothermic oxygenated perfusion is a validated strategy to improve outcomes of marginal whole grafts and may thus also benefit split liver grafts. METHOD: We present the first case of full left/full right split procedure performed during hypothermic oxygenated perfusion. RESULTS: We present a standardized surgical two-step approach where parenchymal transection was performed during end ischemic hypothermic oxygenated perfusion via the portal vein to shorten static cold storage duration. Both split grafts were successfully transplanted in a 4-year-old pediatric and a 38-year-old adult recipient. Despite high-risk procedure (retransplantation), extended donor criteria including a prolonged cardiac arrest and high donor risk index (2,25), both grafts showed early recovery of hepatic function and low serum transaminase release. At 6 months, both recipients were alive with a normal liver biology and a functioning graft. CONCLUSION: Although challenging, full left/full right liver split procedure during end ischemic hypothermic oxygenated perfusion can be successfully performed and is a promising strategy to improve post-transplant outcomes.