Assuntos
Índice de Massa Corporal , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores Sexuais , Prognóstico , Fatores de Risco , Adulto , Resultado do Tratamento , Obesidade/complicações , Obesidade/cirurgia , Obesidade/diagnósticoRESUMO
INTRODUCTION: Creatinine, bilirubin, and fibrinolysis resistance are associated with multi-organ dysfunction and likely risk factors for prolonged intensive care unit (pICU) stay following liver transplantation (LT). We hypothesize postoperative day-1 (POD-1) labs will predict pICU. METHODS: LT recipients had clinical laboratories and viscoelastic testing with tissue plasminogen activator thrombelastography (tPA TEG) to quantify fibrinolysis resistance (LY30) on POD-1. pICU was defined as one week or longer in the ICU. Logistic regression was used to identify the relationship between POD-1 labs and pICU. RESULTS: Of 304 patients, 50% went to the ICU, with 15% experiencing pICU. Elevated creatinine (OR 6.6, P â< â0.001) and low tPA TEG LY30 (OR 3.7, P â= â0.004) were independent predictors of pICU after controlling for other risk factors. A 9-fold increase in the rate of 90-day graft loss (19% vs 2% p â< â0.001) was observed patients who had these risk factors for pICU. CONCLUSION: Elevated creatine and fibrinolysis resistance are associated with pICU and poor outcomes following LT.
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Transplante de Fígado , Ativador de Plasminogênio Tecidual , Humanos , Creatinina , Fibrinólise , Cuidados CríticosRESUMO
A gap exists between the demand for pediatric liver transplantation and the supply of appropriate size-matched donors. We describe our center's experience with pediatric liver transplantation using anonymous nondirected living liver donors (ND-LLD). First-time pediatric liver transplant candidates listed at our center between January 2012 and June 2020 were retrospectively reviewed and categorized by donor graft type, and recipients of ND-LLD grafts were described. A total of 13 ND-LLD pediatric liver transplantations were performed, including 8 left lateral segments, 4 left lobes, and 1 right lobe. Of the ND-LLD recipients, 5 had no directed living donor evaluated, whereas the remaining 8 (62%) had all potential directed donors ruled out during the evaluation process. Recipient and graft survival were 100% during a median follow-up time of 445 (range, 70-986) days. Of ND-LLDs, 69% were previous living kidney donors, and 1 ND-LLD went on to donate a kidney after liver donation. Of the ND-LLDs, 46% were approved prior to the recipient being listed. Over time, the proportion of living donor transplants performed, specifically from ND-LLDs, increased, and the number of children on the waiting list decreased. The introduction of ND-LLDs to a pediatric liver transplant program can expand the benefit of living donor liver transplantation to children without a suitable directed living donor while achieving excellent outcomes for both the recipients and donors.
Assuntos
Transplante de Fígado , Criança , Sobrevivência de Enxerto , Humanos , Fígado , Transplante de Fígado/efeitos adversos , Doadores Vivos , Estudos RetrospectivosRESUMO
Despite an increasing demand for liver transplantation in older patients, our understanding of posttransplant outcomes in older recipients is limited to basic recipient and graft survival. Using National Surgical Quality Improvement Program Transplant, we tracked early outcomes after liver transplantation for patients >65. METHODS: We conducted a retrospective analysis of patients in National Surgical Quality Improvement Program Transplant between March 1, 2017 and March 31, 2019. Recipients were followed for 1 y after transplant with follow-up at 30, 90, and 365 d. Data were prospectively gathered using standard definitions across all sites. RESULTS: One thousand seven hundred thirty-one adult liver transplants were enrolled; 387 (22.4%) were >65 y old. The majority of older recipients were transplanted for hepatocellular carcinoma. The older cohort had a lower lab Model for End-Stage Liver Disease and was less likely to be hospitalized at time of transplant. Overall, older recipients had higher rates of pneumonia but no difference in intensive care unit length of stay (LOS), total LOS, surgical site infection, or 30-d readmission. Subgroup analysis of patients with poor functional status revealed a significant difference in intensive care unit and total LOS. Pneumonia was even more common in older patients and had a significant impact on overall survival. CONCLUSIONS: By targeting patients with hepatocellular carcinoma and lower Model for End-Stage Liver Diseases, transplant centers can achieve nearly equivalent outcomes in older recipients. However, older recipients with poor functional status require greater resources and are more likely to develop pneumonia. Pneumonia was strongly associated with posttransplant survival and represents an opportunity for improvement. By truly understanding the outcomes of elderly and frail recipients, transplant centers can improve outcomes for these higher-risk recipients.
RESUMO
There are limited data to guide the use of anticoagulation in cirrhotic patients prior to liver transplantation especially when using direct oral anticoagulants. In this article, we present 2 cases. The first is a 42-year-old male with cirrhosis complicated by portal vein thrombosis (PVT) treated with dabigatran who underwent orthotopic liver transplantation without complication. The second case is a 65-year-old man with alcoholic cirrhosis complicated by PVT treated with dabigatran who underwent orthotopic liver transplantation and required reoperation for surgical bleeding. Both patients were treated with dabigatran's reversal agent idarucizumab prior to incision. In this case series, we discuss the treatment of cirrhotic patients with various anticoagulants, considerations for anticoagulant selection and reversal prior to liver transplant, and questions for future investigation.
Assuntos
Transplante de Fígado , Trombose Venosa , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Anticoagulantes , Dabigatrana , Humanos , Masculino , Veia Porta/cirurgia , Trombose Venosa/tratamento farmacológicoRESUMO
Burnout among surgeons has been attributed to increased workload and decreased autonomy. Although prior studies have examined burnout among transplant surgeons, no studies have evaluated burnout in abdominal transplant surgery fellows. The objective of our study was to identify predictors of burnout and understand its impact on personal and patient care during fellowship. A survey was sent to all abdominal transplant surgery fellows in an American Society of Transplant Surgeons-accredited fellowship. The response rate was 59.2% (n = 77) and 22.7% (n = 17) of fellows met criteria for burnout. Fellows with lower grit scores were more likely to exhibit burnout compared with fellows with higher scores (3.6 vs 4.0, P = .026). Those with burnout were more likely to work >100 hours per week (58.8% vs 27.6%, P = .023), have severe work-related stress (58.8% vs 22.4%, P = .010), consider quitting fellowship (94.1% vs 20.7%, P < .001), or make a medical error (35.3% vs 5.2%, P = .003). This national analysis of abdominal transplant fellows found that burnout rates are relatively low, but few fellows engage in self-care. Personal and program-related factors attribute to burnout and it has unacceptable effects on patient care. Transplant societies and fellowship programs should develop interventions to give fellows tools to prevent and combat burnout.
Assuntos
Esgotamento Profissional , Cirurgiões , Esgotamento Profissional/etiologia , Bolsas de Estudo , Humanos , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Obesity has been associated with both increased progression of chronic kidney disease (CKD) as well as with a paradoxical improvement in survival among end-stage renal disease patients undergoing hemodialysis. As such, the optimal weight management strategy for obese CKD patients remains unclear. OBJECTIVE: To estimate the outcomes of obese, CKD stage 3b patients after 3 weight loss interventions, including medical weight management, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB), were followed to determine which strategy optimizes long-term survival. SETTING: University hospital, Aurora, Colorado. METHODS: A decision analytic Markov state transition model was created to simulate the life of 30,000 obese patients with CKD stage 3b, as they progressed to end-stage renal disease, transplantation, and death. Life expectancy after conservative medical weight management, RYGB, and SG were estimated. Base case patients were defined as being 50 years old and having a preintervention BMI of 40 kg/m2. Sensitivity analysis of initial BMI was performed. All Markov parameters were extracted from literature review. RESULTS: RYGB and SG were associated with improved survival for patients with preintervention body mass index of >38 kg/m2. Compared with conservative weight management, base case patients who underwent RYGB gained 10.6 months of life, and gained 8.3 months of life after SG. CONCLUSIONS: Balancing progression of CKD with improved survival on end-stage renal disease for obese patients requires selective use of weight management strategies. RYGB and SG improved survival for CKD patients with Class II and III obesity, but not for patients with Class I obesity. As such, aggressive weight loss interventions should be reserved for patients with Class II and III obesity, while more conservative methods should be offered to those with Class I obesity.
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Derivação Gástrica , Obesidade Mórbida , Gastrectomia , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Redução de PesoRESUMO
INTRODUCTION: The use of bariatric surgery has increased for morbidly obese patients with end stage renal disease (ESRD) for whom listing on the waitlist is often restricted until a certain BMI threshold is achieved. Effective weight loss for this population improves access to life-saving renal transplantation. However, it is unclear whether sleeve gastrectomy (SG) vs Roux-en-Y gastric bypass (RYGB) is a more effective therapy for these patients. METHODS: A decision analytic Markov state transition model was created to simulate the life of morbidly obese patients with ESRD who were deemed ineligible to be waitlisted for renal transplantation unless they achieved a BMI less than 35 kg/m2. Life expectancy following weight management (MWM), RYGB, and SG were estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. Markov parameters were extracted from literature review. RESULTS: RYGB improved survival compared with SG and MWM. RYGB patients had higher rates of transplantation, leading to improved mean long-term survival. Base case patients who underwent RYGB gained 1.3 additional years of life compared with patient's who underwent SG and 2.6 additional years of life compared with MWM. CONCLUSIONS: RYGB improves access to renal transplantation and thereby increases long-term survival compared with SG and MWM. The use of SG may be incongruent with the goal of improving access to renal transplantation for morbidly obese patients.
Assuntos
Derivação Gástrica , Falência Renal Crônica , Obesidade Mórbida , Técnicas de Apoio para a Decisão , Gastrectomia , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgiaRESUMO
BACKGROUND: Offspring (donor) to parent (recipient) transplant is the most common form of living donor liver transplant in the United States. In kidney transplantation, it has been suggested that female recipients of offspring living donor kidney allografts have inferior outcomes. It is unknown whether such a phenomenon also occurs following living donor liver transplantation. METHODS: A retrospective analysis was completed of recipients of a living donor liver transplant from January 1998 to January 2018 in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Patients were grouped as having received a living donor liver allograft from either an offspring or a nonoffspring, with exactly 3 HLA matches, as would be expected between an offspring and parent. Graft and patient survival were analyzed using Cox proportional hazards modeling. RESULTS: A total of 279 offspring to parent and 241 nonoffspring donor liver transplants were included in the analysis. Female recipients of offspring liver allografts had both inferior 10-year graft (52% versus 72%; P < 0.001) and patient survival (52% versus 81%; P < 0.001) compared with female recipients of nonoffspring allografts. No such difference in outcomes was discovered among male recipients. A stratified analysis of sex of offspring donors to female recipients demonstrated that donor male gender was associated with graft failure (HR = 2.87; P = 0.04) and mortality (hazard ratio = 3.89; P = 0.03). Again, this association was not seen with male recipients. CONCLUSIONS: Among female recipients, offspring to parent living donor liver transplantation yields inferior long-term graft and patient survival. Furthermore, among offspring donors, male sex was strongly associated with inferior outcomes. These findings have significant implications for donor selection.
Assuntos
Seleção do Doador/métodos , Rejeição de Enxerto/epidemiologia , Transplante de Fígado/métodos , Doadores Vivos , Pais , Sistema de Registros , Obtenção de Tecidos e Órgãos/métodos , Adulto , Doença Hepática Terminal/cirurgia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Transplantados , Transplante Homólogo , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: Vascular anastomoses are complex surgical procedures, performed in time-sensitive circumstances, making intraoperative teaching more challenging. We sought to evaluate whether a vascular anastomosis simulation was effective in developing resident skills. DESIGN, SETTING, PARTICIPANTS: General surgery residents participated in a vascular anastomosis simulation for 1 to 2hours during their transplant rotation. An attending transplant surgeon at the University of Colorado guided the resident through end-to-end and end-to-side anastomoses using bovine carotid artery (Artegraft). The residents completed a presimulation and postsimulation survey which quantitated their confidence. They also completed the MiSSES scale, which assessed the validity of the simulation. RESULTS: Twenty residents participated in the simulation and completed the surveys. The residents reported increased understanding in how to set up an end-to-end anastomosis and an end-to-side anastomosis (p = 0.001 and p = 0.009, respectively). They reported increased ability to suture, forehand and backhand with a Castro-Viejo needle driver (both p < 0.001). The residents reported increased ability to manipulate the needle (p = 0.006), and increased ability to manipulate tissue without causing trauma (p = 0.021). They reported increased confidence in tying a surgical knot with 6-0 Prolene and in operating while wearing loupes (p = 0.002, and p < 0.001, respectively). Overall, the residents reported increased confidence when asked to perform part of a vascular anastomosis in the operating room (p < 0.001). Seventeen residents completed the MiSSES scale with median scores of "somewhat agree" to "strongly agree" on all domains of the scale. CONCLUSIONS: The use of a simple, inexpensive vascular anastomosis simulation is an effective and safe environment to improve residents' surgical skills and the residents felt that the simulation was valid.
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Competência Clínica , Educação de Pós-Graduação em Medicina/métodos , Cirurgia Geral/educação , Treinamento por Simulação/métodos , Procedimentos Cirúrgicos Vasculares/educação , Anastomose Cirúrgica/educação , Feminino , Humanos , Internato e Residência/métodos , Masculino , Inquéritos e QuestionáriosAssuntos
Cirrose Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Veia Porta/patologia , Complicações Pós-Operatórias/prevenção & controle , Trombose Venosa/complicações , Aloenxertos/irrigação sanguínea , Aloenxertos/patologia , Anticoagulantes/uso terapêutico , Doenças Assintomáticas/epidemiologia , Feminino , Humanos , Achados Incidentais , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Cirrose Hepática/patologia , Masculino , Assistência Perioperatória/métodos , Flebografia , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Prevalência , Fatores Sexuais , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia Doppler , Estados Unidos/epidemiologia , Trombose Venosa/diagnóstico , Trombose Venosa/epidemiologia , Trombose Venosa/terapia , Listas de Espera/mortalidadeRESUMO
AIM: To evaluate donation after circulatory death (DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy (HC) and patient/graft survival] and donor risk-conditions. METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS DonorNet included preoperative systolic and diastolic blood pressure, heart rate, pH, SpO2, PaO2, FiO2, and hemoglobin. Mean arterial blood pressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O2 content was computed as [hemoglobin (gm/dL) × 1.37 (mL O2/gm) × SpO2%) + (0.003 × PaO2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure < 60 mmHg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry < 80% until clamping. Donor hypoxia score was (ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin. RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age (33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion (9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin (10.7 ± 2.2 gm/dL vs 12.3 ± 2.1 gm/dL, P = 0.017), lower preoperative arterial oxygen content (14.8 ± 2.8 mL O2/100 mL blood vs 16.8 ± 3.3 mL O2/100 mL blood, P = 0.049), greater hypoxia score >2.0 (69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure (92.7 ± 16.2 mmHg vs 83.8 ± 18.5 mmHg, P = 0.10). HC was independently associated with age, multi-pressor/red-cell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure (r(2) = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2 (7.1/year)], compared to our early experience [era 1 (2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1 (P = 0.03). Era 2 donors had longer times for extubation-to-asystole (14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia (13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia (16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score > 2.0 rate (73.1% vs 28.6%, P = 0.006). CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.
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Extubação , Colestase/etiologia , Seleção do Doador , Hipóxia/etiologia , Transplante de Fígado/métodos , Oxigenoterapia , Doadores de Tecidos , Adolescente , Adulto , Extubação/efeitos adversos , Extubação/mortalidade , Biomarcadores/metabolismo , Causas de Morte , Criança , Colestase/diagnóstico , Colestase/mortalidade , Colestase/cirurgia , Transfusão de Eritrócitos , Feminino , Sobrevivência de Enxerto , Hemoglobinas/metabolismo , Humanos , Hipóxia/sangue , Hipóxia/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Oxigenoterapia/efeitos adversos , Oxigenoterapia/mortalidade , Reoperação , Estudos Retrospectivos , Fatores de Risco , Choque/sangue , Choque/mortalidade , Choque/fisiopatologia , Choque/terapia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The effects of obesity in liver transplantation remain controversial. Earlier institutional data demonstrated no significant difference in postoperative complications or 1-year mortality. This study was conducted to test the hypothesis that obesity alone has minimal effect on longterm graft and overall survival. METHODS: A retrospective, single-institution analysis of outcomes in patients submitted to primary adult orthotopic liver transplantation was conducted using data for the period from 1 January 2002 to 31 December 2012. Recipients were divided into six groups by pre-transplant body mass index (BMI), comprising those with BMIs of <18.0 kg/m(2) , 18.0-24.9 kg/m(2) , 25.0-29.9 kg/m(2) , 30.0-35.0 kg/m(2) , 35.1-40.0 kg/m(2) and >40 kg/m(2) , respectively. Pre- and post-transplant parameters were compared. A P-value of <0.05 was considered to indicate statistical significance. Independent predictors of patient and graft survival were determined using multivariate analysis. RESULTS: A total of 785 patients met the study inclusion criteria. A BMI of >35 kg/m(2) was associated with non-alcoholic steatohepatitis (NASH) cirrhosis (P < 0.0001), higher Model for End-stage Liver Disease (MELD) score, and longer wait times for transplant (P = 0.002). There were no differences in operative time, intensive care unit or hospital length of stay, or perioperative complications. Graft and patient survival at intervals up to 3 years were similar between groups. Compared with non-obese recipients, recipients with a BMI of >40 kg/m(2) showed significantly reduced 5-year graft (49.0% versus 75.8%; P < 0.02) and patient (51.3% versus 78.8%; P < 0.01) survival. CONCLUSIONS: Obesity increasingly impacts outcomes in liver transplantation. Although the present data are limited by the fact that they were sourced from a single institution, they suggest that morbid obesity adversely affects longterm outcomes despite providing similar short-term results. Further analysis is indicated to identify risk factors for poor outcomes in morbidly obese patients.
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Doença Hepática Terminal/cirurgia , Transplante de Fígado/efeitos adversos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/mortalidade , Transplantados/estatística & dados numéricos , Adulto , Índice de Massa Corporal , Estudos de Coortes , Doença Hepática Terminal/complicações , Doença Hepática Terminal/mortalidade , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Hospitais Universitários , Humanos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/fisiopatologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Ischemia-reperfusion injury (IRI) to the liver continues to be a source of significant morbidity, especially in patients with hepatic steatosis. This is a growing problem given the increase in nonalcoholic fatty liver disease. B-cell lymphoma-2 homology3-only members of the B-cell lymphoma-2 protein family are known mediators of cellular apoptosis, although their role in hepatic IRI is still emerging. The goal of this study was to investigate the effect of Bim and Bid on warm hepatic IRI in the setting of steatosis. METHODS: Lean and obese Bim and/or Bid wild-type (WT) and double knockout (DKO) mice underwent 60 min of warm hepatic ischemia using a 70% segmental occlusion technique. Obesity and hepatic steatosis were induced using a high fat diet. Hepatocellular injury patterns were compared among lean and steatotic mice after reperfusion. Differences were analyzed using a Student t-test and reported as mean ± standard error of the mean. RESULTS: DKO mice were protected from IRI relative to WT. A high fat diet created equal degrees of steatosis in both WT and DKO mice. The IRI was increased in steatotic WT livers; however, DKO mice remained protected relative to WT despite hepatic steatosis. CONCLUSIONS: The B-cell lymphoma-2 homology3-only proteins are important mediators of hepatic IRI in both lean and steatotic livers. These mechanisms have been underappreciated in steatotic liver injury and may be leveraged as targets for intervention in clinical scenarios such as transplant and hypovolemic shock.
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Proteínas Reguladoras de Apoptose/metabolismo , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Fígado Gorduroso/complicações , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/genética , Proteína 11 Semelhante a Bcl-2 , Fígado Gorduroso/metabolismo , Fígado/irrigação sanguínea , Fígado/metabolismo , Proteínas de Membrana/genética , Camundongos Knockout , Proteínas Proto-Oncogênicas/genéticaRESUMO
BACKGROUND: The molecular basis of the increased susceptibility of steatotic livers to warm ischemia/reperfusion (I/R) injury during transplantation remains undefined. Animal model for warm I/R injury was induced in obese Zucker rats. Lean Zucker rats provided controls. Two dimensional differential gel electrophoresis was performed with liver protein extracts. Protein features with significant abundance ratios (p < 0.01) between the two cohorts were selected and analyzed with HPLC/MS. Proteins were identified by Uniprot database. Interactive protein networks were generated using Ingenuity Pathway Analysis and GRANITE software. RESULTS: The relative abundance of 105 proteins was observed in warm I/R injury. Functional grouping revealed four categories of importance: molecular chaperones/endoplasmic reticulum (ER) stress, oxidative stress, metabolism, and cell structure. Hypoxia up-regulated 1, calcium binding protein 1, calreticulin, heat shock protein (HSP) 60, HSP-90, and protein disulfide isomerase 3 were chaperonins significantly (p < 0.01) down-regulated and only one chaperonin, HSP-1 was significantly upregulated in steatotic liver following I/R. CONCLUSION: Down-regulation of the chaperones identified in this analysis may contribute to the increased ER stress and, consequently, apoptosis and necrosis. This study provides an initial platform for future investigation of the role of chaperones and therapeutic targets for increasing the viability of steatotic liver allografts.
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Fígado Gorduroso/metabolismo , Chaperonas Moleculares/metabolismo , Proteômica , Traumatismo por Reperfusão/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Bases de Dados de Proteínas , Regulação para Baixo , Eletroforese em Gel Bidimensional , Estresse do Retículo Endoplasmático , Fígado Gorduroso/patologia , Masculino , Espectrometria de Massas , Proteoma/metabolismo , Ratos , Ratos Zucker , Regulação para Cima , Isquemia QuenteRESUMO
BACKGROUND: Although inflow occlusion techniques have given surgeons the ability to carry out increasingly complex liver resections, ischemia-reperfusion (IR) injury continues to be a source of morbidity. Efforts to ameliorate IR injury have been hindered in absence of adequate preclinical models. The goal of the present study was to develop a simple, efficient, and cost-effective means of studying hepatic IR injury. METHODS: Liver cubes were procured from normal (C57BL/6) mice. After hepatectomy, 4-mm punch biopsies were taken for individual placement in culture wells containing hepatocyte media. Experimental cubes underwent hypoxia for 60 minutes, whereas controls remained normoxic. Supernatants were collected from individual wells after 0, 6, and 12 hours of rediffusion for transaminase and cytokine measurement. Histologic examination was performed on individual cubes. RESULTS: Extensive histologic injury was seen in the experimental cubes compared with controls with greater staining for activated caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling at 6 and 24 hours, respectively. Changes consistent with ischemic injury occurred more centrally in liver cubes, whereas markers for rediffusion injury were appreciated along the periphery. Transaminases were significantly higher at 6 hours after rediffusion in experimental cubes compared with controls (P = .02). tumor necrosis factor-α and interleukin-1ß were significantly higher in the media of experimental cubes compared with controls at 12 hours rediffusion (P = .05 and .03 respectively). CONCLUSION: In vitro IR of cubes produces a significant injury with a pattern reflective of hepatic lobular architecture. This novel technique may open new avenues for uncoupling the mechanisms of IR while facilitating rapid screening of potential therapies.
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Modelos Animais de Doenças , Hepatopatias , Traumatismo por Reperfusão , Animais , Caspase 3/metabolismo , Citocinas/metabolismo , Fígado/enzimologia , Fígado/patologia , Hepatopatias/enzimologia , Hepatopatias/patologia , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Técnicas de Cultura de Tecidos , Transaminases/metabolismoRESUMO
BACKGROUND: A strategy to increase the number of size- and weight-appropriate organs and decrease the paediatric waiting list mortality is wider application of sectional orthotopic liver transplantation (OLT). These technical variants consist of living donor, deceased donor reduced and split allografts. However, these grafts have an increased risk of biliary complications. An unusual and complex biliary complication which can lead to graft loss is inadvertent exclusion of a major segmental bile duct. We present four cases and describe an algorithm to correct these complications. METHODS: A retrospective review of the paediatric orthotopic liver transplantation database (2000-2010) at Washington University in St. Louis/St. Louis Children's Hospital was conducted. RESULTS: Sixty-eight patients (55%) received technical variant allografts. Four complications of excluded segmental bile ducts were identified. Percutaneous cholangiography provided diagnostic confirmation and stabilization with external biliary drainage. All patients required interval surgical revision of their hepaticojejunostomy for definitive drainage. Indwelling biliary stents aided intra-operative localization of the excluded ducts. All allografts were salvaged. DISCUSSION: Aggressive diagnosis, percutaneous decompression and interval revision hepaticojejunostomy are the main tenets of management of an excluded bile duct. Careful revision hepaticojejunostomy over a percutaneous biliary stent can result in restoration of biliary continuity and allograft survival.