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3.
Transplant Proc ; 51(1): 90-91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30655144

RESUMO

Herein we report a case of liver dysfunction caused by consumption of vitamin A supplements leading to liver transplantation. The patient was a 48-year-old male with a medical history of congenital ichthyosiform erythroderma in treatment with vitamin A until 12 years of age, at which point he discontinued the supplements because he had developed ascites. Liver cirrhosis was diagnosed as secondary to hypervitaminosis A on the basis of histologic examination of liver biopsy and the absence of other potential causes of chronic liver disease. Despite interruption of administration of vitamin A, the patient continued to deteriorate over the years, with development of portal hypertension signs. His medical conditions were aggravated with the development of hepatic insufficiency manifested by refractory ascites, renal insufficiency, and severe encephalopathy and he underwent orthotopic liver transplantation, followed by disappearance of all signs of portal hypertension. This case highlights the need to take a careful history of consumption of vitamin A when evaluating a patient with liver failure.


Assuntos
Suplementos Nutricionais/envenenamento , Hipervitaminose A/complicações , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/cirurgia , Transplante de Fígado , Humanos , Hipertensão Portal/induzido quimicamente , Eritrodermia Ictiosiforme Congênita/complicações , Fígado/patologia , Masculino , Pessoa de Meia-Idade
4.
Pancreatology ; 19(2): 367-371, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30683515

RESUMO

INTRODUCTION: Pancreatic neuroendocrine neoplasms (PNEN) are rare tumours and well differentiated PNEN are associated with relatively indolent physiological behaviour. For this reason, only few studies have investigated those factors associated with recurrence in this group of patients. The aim of this study is to analyse whether it is possible to predict tumour recurrence in World Health Organization (WHO) 2017 G1-G2 PNEN patients. METHODS: This is a retrospective multi-institutional study. Patients submitted to pancreatic resection from 7 Spanish centres were reviewed. Only patients with WHO G1-G2 PNEN were included. Demographic and clinicopathological variables were analysed. RESULTS: Data from 137 patients were reviewed. Median age was 59.2 (25-84) years. Recurrence of disease occurred in 19 (13.9%) patients. Median DFS was 55 months. At multivariate analysis, tumour size >20 mm, lymphnode metastasis and a new tumour grade 2 incorporating Ki-67 labelling index (LI) > 5% and mitotic index (MI) > 2 were independently associated with recurrence. We developed a risk score model with these three factors. High-risk patients had a significantly lower 5-year disease-specific survival compared to low-risk patients (70% vs 100%). CONCLUSION: We propose a novel risk score for recurrence based on lymphnode metastasis, tumour size > 20 mm and a new grade 2 based on Ki-67 LI >5% and MI > 2. If 2 factors are present, patients have a higher risk for recurrence and a significantly poorer DSS, and therefore they should be closely monitored during follow-up. The role of adjuvant chemotherapy in these patients needs to be evaluated in clinical trials.


Assuntos
Recidiva Local de Neoplasia/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Espanha , Organização Mundial da Saúde
5.
Transplant Proc ; 50(2): 610-612, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29579866

RESUMO

OBJECTIVE: The aim of this work was to find out whether thinking frequently about the donor influences post-traumatic growth of liver transplant recipients. METHODS: The sample of 240 patients selected was made up of 185 men and 55 women with an overall mean age of 60.21 (SD 9.3) years. All of them had received liver transplants from cadaver donors. Transplant recipients were asked whether they thought frequently about the donor (yes or no) and filled out the Post-traumatic Growth Inventory. The t test for unpaired samples was applied to analyze how thinking frequently about the donor or not influenced post-traumatic growth. We also calculated the effect sizes by means of Cohen d or Cohen w depending on the nature of the variables analyzed (quantitative or qualitative). RESULTS: The liver transplant recipients who thought frequently about the donor, compared with those who did not, had higher total scores on post-traumatic growth (P = .000; d = 0.57; medium effect size). Furthermore, considering the effect sizes, the differences between the subgroups were more relevant on the following subscales: new possibilities (P = .000; d = 0.53; medium effect size), appreciation of life (P = .000; d = 0.60; medium effect size), and spiritual change (P = .000; d = 0.54; medium effect size). CONCLUSIONS: Patients who think frequently about the donor have more post-traumatic growth than those who do not.


Assuntos
Transplante de Fígado , Estresse Psicológico/psicologia , Transplantados/psicologia , Adulto , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos
6.
Transplant Proc ; 50(2): 613-616, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29579867

RESUMO

BACKGROUND: The purpose of this study was to determine the morbidity and survival in patients with polycystic liver disease (PLD) undergoing liver transplantation (LT) in 4 Spanish hospitals. METHODS: A multicentric retrospective study using a prospective database was designed including 19 LTs after PLD diagnosis performed from January 1, 1990, to December 31, 2016. Pediatric patients were excluded from the analysis. RESULTS: Of the included patients, 63.2% were female, the overall average age was 52.16 ± 11.276 years, median time on the waiting list was 394 days (interquartile range [IQR], 96.25-464.50) and most of them were classified with Model for End-Stage Liver Disease scores of ≤17. Eleven patients received isolated LT, 1 patient had a previous kidney transplantation (KT), and 7 patients received combined liver-kidney transplantation, 4 of them with a previous nephrectomy. Complications include hepatopulmonary syndrome in 10.5%, paralytic ileus in 10.5%, transient renal dysfunction in 10.5%, and hepatorenal syndrome in 5.3%. The most common surgical complication was bleeding (15.8%). Three patients presented graft rejection, which was treated by means of immunosuppressive optimization (15.8%), with corticosteroid addition needed in 1 of them. Thrombosis of the hepatic artery occurred in 3 patients, requiring retransplantation in 2 of them. Most of the patients had improved renal function after the procedure. The mortality rate was 15.8%, related to tumors or sepsis, with an estimated 86% 5-year graft survival. CONCLUSIONS: PLD as indication of LT presents a low complications rate and better graft survival and renal function, especially when KT is associated with LT.


Assuntos
Cistos/epidemiologia , Cistos/cirurgia , Hepatopatias/epidemiologia , Hepatopatias/cirurgia , Transplante de Fígado , Adolescente , Adulto , Criança , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Transplante de Rim , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Reoperação , Estudos Retrospectivos , Espanha , Listas de Espera
7.
Transplant Proc ; 50(2): 646-649, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29579877

RESUMO

OBJECTIVE: Analyze the influence of 2 variables (post-traumatic growth and time since liver transplantation) on coping strategies used by the transplant recipient's family members. METHODS: In all, 218 family members who were their main caregivers of liver transplant recipients were selected. They were evaluated using the Posttraumatic Growth Inventory and the Brief COPE. A 3 × 3 factorial analysis of variance was used to analyze the influence that post-traumatic growth level (low, medium, and high) and time since transplantation (≤3.5 years, >3.5 to ≤9 years, and >9 years) exerted on caregiver coping strategies. RESULTS: No interactive effects between the two factors in the study were found. The only significant main effect was the influence of the post-traumatic growth factor on the following variables: instrumental support (P = .007), emotional support (P = .005), self-distraction (P = .006), positive reframing (P = .000), acceptance (P = .013), and religion (P = <.001). According to the most relevant effect sizes, low post-traumatic growth compared with medium growth was associated with less use of self-distraction (P = .006, d = -0.52, medium effect size), positive reframing (P = .001, d = -0.62, medium effect size), and religion (P = .000, d = -0.66, medium effect size), and in comparison with high growth, it was associated with less use of positive reframing (P = .002, d = -0.56, medium effect size) and religion (P = .000, d = 0.87, large effect size). CONCLUSION: Regardless of the time elapsed since the stressful life event (liver transplantation), family members with low post-traumatic growth usually use fewer coping strategies involving a positive, transcendent vision to deal with transplantation.


Assuntos
Adaptação Psicológica , Cuidadores/psicologia , Família/psicologia , Transplante de Fígado/psicologia , Transplantados/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Religião
8.
Transplant Proc ; 48(9): 2973-2976, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27932122

RESUMO

The goal of this work has been to analyze the first 1000 liver transplantations (LTs) performed in the Virgen del Rocío Hospital of Seville and to evaluate the changes in that time. We included 916 patients who had 1000 LTs. We distinguish 2 stages in the follow-up: the first stage, between 1990 and 2002, and the second, from 2003 to 2013 (Model for End-stage Liver Disease [MELD] stage). We analyzed recipient features, LT indications, donation criteria, surgical technique, complications, and survival both for patients and grafts. The median age of recipients was 53.50 ± 46.49 years old, with a noticeable increase after 2000. There were 3 times as many men as women. The most frequent indications for LT were hepatocellular disease (48.8%), followed by hepatocarcinoma (17.8%), retransplantation (8.1%), and cholestatic diseases (3.6%). Donors of Andalusian centers accounted for 88.2% of LTs, and 8.3% of LTs presented some arterial or venous complication. Biliary complications occurred in 15.6%. Patient survival at 1, 5, and 10 years was 77%, 63.5%, and 51.3%, respectively. In conclusion, some of the factors that negatively influenced survival of the patient were stage of the LT, hepatitis C virus-positive recipient, emergency cases, hepatocarcinoma, high consumption of blood products, and second transplantations.


Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Reoperação , Estudos Retrospectivos , Espanha , Resultado do Tratamento , Adulto Jovem
9.
Transplant Proc ; 48(9): 2983-2986, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27932125

RESUMO

Recently, there has been a large discrepancy between the number of patients on the waiting list for a liver transplant and the availability of deceased donors, with an increase in annual wait list mortality rates. Elderly donor livers are thought to be marginal grafts; however, in recent years, their utilization has constantly increased. The aim of this study is to evaluate the utilization of elderly donors in Andalusia and post-transplant outcomes. This retrospective observational study of 2408 liver transplants, performed in Andalusia between 2000 and 2014, analyzes the outcomes from donors aged 70 plus (n = 423) in terms of survival rates of the graft and the recipient, the type of transplant, donor age, and D-MELD score (product of donor age and preoperative Model for End-stage Liver Disease score). The most frequent indications for transplant were alcoholic cirrhosis (49.2%), hepatitis C cirrhosis (13%), and hepatocellular carcinoma (12.5%). The overall survival at 5 years was 64%, with a significant fall in survival for recipients with a D-MELD greater than 1500 (57%; P = .045). In the 70-year-old-plus donor group, the overall patient survival was 58.4%. The retransplant rate increased proportionately with donor age. In the alcoholic cirrhosis recipient subgroup, the overall survival at 5 years was 67.6% (P < .05) compared with 33.5% in patients with hepatitis C. Use of elderly donors is a safe strategy to reduce the scarcity of donors, provided that a D-MELD score below 1500 is obtained. Retransplant rates increase progressively with donor age. It is necessary to carefully screen recipients of older organs, taking into account that the best results are obtained for alcoholic cirrhosis, negative viral load hepatitis C, and a D-MELD score below 1500.


Assuntos
Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/cirurgia , Transplante de Fígado/mortalidade , Doadores de Tecidos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Doença Hepática Terminal/patologia , Feminino , Sobrevivência de Enxerto , Hepatite C/complicações , Hepatite C/mortalidade , Humanos , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/mortalidade , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Espanha , Análise de Sobrevida , Taxa de Sobrevida , Listas de Espera
10.
Transplant Proc ; 48(9): 2990-2993, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27932127

RESUMO

BACKGROUND: Survival after orthotopic liver transplantation (LT) for hepatocellular carcinoma (HCC) is influenced by tumor recurrence. This study examines the survival of patients who underwent LT for HCC and developed recurrence of tumor after transplantation. METHODS: A retrospective analysis was performed of the 200 patients who underwent LT secondary to HCC from 1990 to 2014. We excluded 19 patients from the study owing to early postoperative deaths in the 1st month. We divided our sample into 2 groups according to the presence of recurrence. We performed a univariate analysis to identify variables that are significantly associated with the risk of recurrence. Afterward we use multivariate analysis regression analysis to find independent significance. RESULTS: Univariate analysis shows significant relationship between high Edmondson-Steiner grades (G3-G4) and the development of tumor recurrence. Tumor size, vascular invasion, and capsular invasion were found to be independent risk factors of tumor recurrence in the multivariate analysis. CONCLUSIONS: Tumor recurrence defines survival of patients who underwent LT for HCC. In this study we discuss which histologic factor are associated with higher risk of tumor recurrence, and therefore a negative the impact on patient's survival.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Recidiva Local de Neoplasia/etiologia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Fatores de Risco
11.
Adv Exp Med Biol ; 924: 25-28, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27753013

RESUMO

p53 is the most commonly mutated gene in malignant human cancers. To detect p53 mutations in circulating DNA (cirDNA) of transplanted hepatocellular carcinoma (HCC) patients could be an interesting approach to know of any tumor recurrence. In this study, our objective was to determine the utility of this method in the diagnosis and the prognosis of HCC tumor recurrence.Twenty four liver transplanted HCC patients were included in the study together with a group of healthy controls. Detection of the specific p53 mutation in cirDNA was performed by high-resolution melting PCR (HRM-PCR) and COLD-PCR immediately before the transplantation. Serum anti-p53 was also determined using a p53-autoantibody ELISA kit.The results of the HRM-PCR and COLD-PCR showed two well-differentiated groups of transplanted patients after normalization by healthy controls. These data allow us to distinguish between patients with p53 mutated cirDNA and those with wild type cirDNA. Moreover, we have found that most of p53 mutated patients also presented elevated anti-p53 antibodies. The present results indicate that it is possible to detect mutated p53 genes with the cirDNA and that this could be used as a biomarker of tumor recurrence during the clinical evolution of the transplanted patients.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , DNA de Neoplasias/genética , Neoplasias Hepáticas/genética , Mutação , Proteína Supressora de Tumor p53/genética , Autoanticorpos/sangue , Autoanticorpos/imunologia , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , DNA de Neoplasias/sangue , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Transplante de Fígado , Recidiva Local de Neoplasia , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Proteína Supressora de Tumor p53/imunologia
12.
Adv Exp Med Biol ; 924: 113-116, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27753030

RESUMO

The evaluation of the transplanted liver health by non-invasive approaches may offer an improvement in early clinical intervention. As transplanted organs have genomes that are distinct from the host's genome, the quantification of the specific DNA of the donated liver in the patient serum will allow us to obtain information about its damage. We evaluated the state of transplanted liver health by monitoring the RH gene in serum circulating DNA (cirDNA) from 17 recipient and donor mismatched for this gene. cirDNA RH gene was quantified by RT- PCR before, at the moment of transplantation (day 0) and during the stay at the intensive care unit. Beta-globin cirDNA was quantified as a general cellular damage marker. Patients were grouped based on clinical outcomes: (A) patients with no complication; (B) patients that accepted the organ but suffered other complications; (C) patients that suffered organ rejection. All patients showed an increased cirDNA levels at day 0 that decreased until patient stabilization. Patients from groups A and B showed low levels of the RH gene cDNA during the follow-up, with an increase of beta-globin gene at the moment of any clinical complication. Patients from group C showed an increase in the RH gene during rejection.


Assuntos
DNA/genética , Genômica/métodos , Transplante de Fígado/métodos , Fígado/metabolismo , Biomarcadores/sangue , DNA/sangue , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Humanos , Especificidade de Órgãos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sistema do Grupo Sanguíneo Rh-Hr/genética , Fatores de Tempo , Doadores de Tecidos , Globinas beta/genética
13.
Gene Ther ; 23(1): 67-77, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26204498

RESUMO

Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO) synthase type III (NOS-3) overexpression induces cell death in hepatoblastoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. The first-generation adenoviruses were designed to overexpress NOS-3 or green fluorescent protein, and luciferase complementary DNA under the regulation of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters, respectively. Both adenovirus and Hepa 1-6 cells were used for in vitro and in vivo experiments. Adenoviruses were administered through the tail vein 2 weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8, -9 and -3 activities in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by Nω-nitro-l-arginine methyl ester hydrochloride, p53 and CD95 small interfering RNA. AFP-NOS-3/RSV-luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.


Assuntos
Carcinoma Hepatocelular/terapia , Regulação Neoplásica da Expressão Gênica , Terapia Genética/métodos , Neoplasias Hepáticas/terapia , Óxido Nítrico Sintase Tipo III/genética , Adenoviridae/genética , Animais , Carcinoma Hepatocelular/genética , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Dano ao DNA , DNA Complementar/genética , DNA Complementar/metabolismo , Modelos Animais de Doenças , Proteína Ligante Fas/genética , Proteína Ligante Fas/metabolismo , Vetores Genéticos , Fígado/citologia , Fígado/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/terapia , Neoplasias Hepáticas/genética , Camundongos , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Vírus do Sarcoma de Rous/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/metabolismo
14.
Transplant Proc ; 47(9): 2643-4, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26680059

RESUMO

Biliary atresia (BA) is a neonatal progressive cholangiopathy of unknown etiology and one of the most common reasons for liver transplantation (LT) in children. Kasai portoenterostomy (KP) improves survival of the native liver, although LT remains the only ultimate treatment. In some cases KP makes it possible to defer the ultimate LT until adulthood. We report our experience regarding 5 cases of BA treated with LT during adulthood. KP was performed in all patients at an average age of 176 days (range, 60-280), which allowed an average survival of the native liver of 19.01 years (range, 14.06-22.32). Five-year survival rate was 100%. Ten-year survival rate did not reach 100% because of a death 9.55 years after LT due to chronic graft rejection, in a patient who was already prepared for a new LT. Our results corroborate that KP remains the first-line treatment of BA. Early performance of the KP provides children with the best chance of survival, allowing the delay of the LT to adulthood. LT during adulthood in these patients achieves good post-LT survival rate; we have not found any data regarding this group of patients in the literature.


Assuntos
Atresia Biliar/cirurgia , Transplante de Fígado/mortalidade , Portoenterostomia Hepática/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Fígado/cirurgia , Transplante de Fígado/métodos , Masculino , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
Redox Biol ; 6: 174-182, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26233703

RESUMO

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.


Assuntos
Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Transdução de Sinais , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Morte Celular/efeitos dos fármacos , Cisteína/análogos & derivados , Cisteína/química , Cisteína/farmacologia , Células Hep G2 , Humanos , Niacinamida/farmacologia , Óxido Nítrico/química , Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , S-Nitrosotióis/química , S-Nitrosotióis/farmacologia , Sorafenibe
16.
Transplant Proc ; 47(1): 104-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25645783

RESUMO

OBJECTIVES: We aimed to compare the affective symptomatology in two medical conditions under immunotherapy (cadaveric liver transplantation [G1] and multiple sclerosis [G2]), considering their functional impairment, and to assess the clinical significance of the results regarding a representative age-adjusted sample of the general Spanish population (G3). METHODS: Using a cross-sectional design, 164 patients (82 per clinical group) were selected, matched for gender, and homogenized regarding age and functional impairment according to the Physical functioning subscale from the SF-36 Health Survey. The criterion variables were the Mental health and Role-emotional SF-36 subscales and the Hospital Anxiety and Depression Scale. An analysis of covariance was conducted, controlling for age and the Physical functioning score as covariates. Cohen's d was reported as an effect size index and to analyze the clinical significance regarding a representative age-adjusted sample of the general Spanish population (n = 7881). RESULTS: No statistically significant differences were found between conditions in any affective dimension (P > .05; ds1₋2 from 0.08 to 0.30) or in the percentage of clinical cases regarding the anxious (P = .628) or depressive spectrum (P = .716). The neurological patients showed clinically significant impairment in both SF-36 subscales (ds2₋3 = 0.55 and 0.52, respectively), but transplant recipients only differed from the general population in Role-emotional (d1₋3 = 0.81). CONCLUSIONS: Despite having controlled for functional impairment, important deterioration in daily functioning was still found in liver recipients due to emotional problems, and no relevant differences were observed even when compared with a neurodegenerative condition such as multiple sclerosis.


Assuntos
Ansiedade/etiologia , Depressão/etiologia , Transplante de Fígado/psicologia , Esclerose Múltipla/psicologia , Transplantados/psicologia , Adulto , Idoso , Ansiedade/diagnóstico , Estudos Transversais , Depressão/diagnóstico , Avaliação da Deficiência , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Espanha , Inquéritos e Questionários
17.
Transplant Proc ; 47(1): 100-3, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25645782

RESUMO

BACKGROUND: The objective of this study was to analyze the influence of two variables (acute cellular rejection and depressive symptomatology) on liver transplant recipients' quality of life. METHODS: Using a 2 × 2 factorial design, two groups were selected: 44 patients who had acute cellular rejection and 44 patients without this medical complication. After an average of 6 years since the transplant, patients were assessed with the Hospital Anxiety and Depression Scale and the SF-36 Health Survey. Analysis of variance, t test for unpaired samples, and Cohen's d effect size index were applied. RESULTS: The presence of clinical depressive symptomatology negatively affected all dimensions of quality of life (P < .001; large effect sizes); and interactive effects between factors acute cellular rejection and depressive symptomatology were found in the dimensions role-physical (P = .049) and bodily pain (P = .017). Transplant recipients with clinical depressive symptomatology scored lower on both dimensions (role-physical, P = .110, d = 0.52, medium effect size; bodily pain, P = .001, d = 1.25, large effect size) if they had an acute cellular rejection. In contrast, if they did not exceed the clinical threshold for depressive symptomatology, there were no differences in these dimensions (role-physical, P = .239, d = -0.33, small effect size; bodily pain, P = .555, d = 0.16, null effect size) between transplant recipients with and without acute cellular rejection. CONCLUSIONS: Clinical depressive symptomatology is associated with poorer quality of life in liver transplant recipients; and the long-term differences in the dimensions role-physical and bodily pain between liver transplant recipients with and without acute cellular rejection depend on patients' mental health.


Assuntos
Depressão/etiologia , Rejeição de Enxerto/psicologia , Transplante de Fígado/psicologia , Complicações Pós-Operatórias/psicologia , Qualidade de Vida , Transplantados/psicologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários
18.
Transplant Proc ; 46(9): 3092-4, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25420831

RESUMO

Domino liver transplantation (DLT) is a strategy used to increase the number of available grafts. In this procedure, the transplant recipient is a living donor of her own liver. It is mandatory that the graft should be fully functional and the genetic defect should recur with sufficient latency period in the new recipient. Corino-Andrade disease, or familial amyloidotic polyneuropathy (FAP), satisfies these conditions. We retrospectively reviewed our prospective database of DLT. From July 2004 to April 2013, we performed 12 DLTs. We assessed age, sex, real Model for End-Stage Liver Disease (MELD) score, waiting list time, cold and warm ischemia times, intraoperative transfusion requirements, hospital stay, early peritransplantation morbidity (post-reperfusion syndrome, intraoperative cardiac arrest, post-transplantation thrombotic events, and biliary morbidity), acute cellular rejection, retransplantation, mortality, patient and graft survivals. With the intention to study the effect of the learning curve in the global survival results (including both donors and recipients of livers with FAP), we divided our series into 2 periods: the early period (from 2004 to 2008) and the present period (from 2009 to 2013). The crude mortality was 40% vs 0% (P = .042) in the early and present periods, respectively. The cumulative patient survival was also significantly in favor of the present period (P = .049). The graft loss prevalence was 60% vs 7.1% (P = .019) in the early and present periods, respectively. The cumulative graft survival was also significantly in favor of the present period (P = .030; Fig 2). In conclusion, we consider DLT to be a complex procedure, whose initial results are conditioned by the learning curve.


Assuntos
Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/epidemiologia , Curva de Aprendizado , Transplante de Fígado/métodos , Doadores Vivos/psicologia , Educação de Pacientes como Assunto , Feminino , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Masculino , Prevalência , Estudos Retrospectivos , Espanha/epidemiologia , Taxa de Sobrevida/tendências , Fatores de Tempo
19.
Am J Transplant ; 14(6): 1391-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24730359

RESUMO

The prevalence of hepatopulmonary syndrome (HPS) and its influence on survival before and after liver transplantation (LT) remain controversial. Additionally, the chronology of post-LT reversibility is unclear. This study prospectively analyzed 316 patients with cirrhosis who were evaluated for LT in 2002-2007; 177 underwent LT at a single reference hospital. HPS was defined by a partial pressure of arterial oxygen (PaO2 ) <70 mmHg and/or an alveolar-arterial oxygen gradient (A-a PO2 ) ≥20 mmHg in the supine position and positive contrast echocardiography. The prevalence of HPS was 25.6% (81/316 patients), and most patients (92.6%) had mild or moderate HPS. High Child-Pugh scores and the presence of ascites were independently associated with HPS. Patients with and without HPS did not significantly differ in LT waiting list survival (mean 34.6 months vs. 41.6 months, respectively; log-rank, p = 0.13) or post-LT survival (mean 45 months vs. 47.6 months, respectively; log-rank, p = 0.62). HPS was reversed in all cases within 1 year after LT. One-fourth of the patients with cirrhosis who were evaluated for LT had HPS (mostly mild to moderate); the presence of HPS did not affect LT waiting list survival. HPS was always reversed after LT, and patient prognosis did not worsen.


Assuntos
Síndrome Hepatopulmonar/complicações , Cirrose Hepática/cirurgia , Transplante de Fígado , Feminino , Síndrome Hepatopulmonar/mortalidade , Síndrome Hepatopulmonar/fisiopatologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de Doença , Análise de Sobrevida , Listas de Espera
20.
Transplant Proc ; 45(10): 3656-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24314987

RESUMO

OBJECTIVE: The objective of this study was to compare the evolution (hospitalization in the transplantation unit and at 12 months post-transplantation) of anxious and depressive symptomatology in cadaveric transplant recipients as a function of type of organ implanted (liver or kidney). METHODS: Using a 2 × 2 mixed factorial design, 2 groups were selected: 34 liver transplant recipients and 41 kidney transplant recipients. Both groups were assessed in 2 phases: (1) in the transplantation unit after discharge from the intensive care unit; and (2) 12 months after discharge from the hospital following implantation surgery. The Hospital Anxiety and Depression Scale and the Scale for the Assessment of Social Support were administered. A mixed analysis of covariance was used to assess the influence on transplant recipients' anxious-depressive symptomatology of 2 independent factors: phase (hospitalization in the transplantation unit and at 12 months post-transplantation) and organ (liver and kidney). Perceived social support and age were included as covariates in the analyses. We also calculated d and w as effect size indexes. RESULTS: Interactive effects of the factors phase and organ were found in the variable anxiety (P = .005). Specifically, the following simple effects were significant: (1) kidney transplant recipients presented more anxious symptomatology while hospitalized in the transplantation unit than at 12 months post-transplantation (P = .001; d = 0.52; medium effect size); and (2) kidney transplant recipients presented more anxious symptomatology than liver transplant recipients while hospitalized in the transplantation unit (P = .013; d = -0.59; medium effect size). No statistically significant effect was obtained for the variable depression. CONCLUSION: Worse mental health (anxious symptoms) was associated with kidney transplant recipients but not with liver recipients while recovering from the implantation surgery in the transplantation unit.


Assuntos
Ansiedade/psicologia , Depressão/psicologia , Hospitalização , Transplante de Rim/psicologia , Transplante de Fígado/psicologia , Saúde Mental , Adulto , Ansiedade/diagnóstico , Ansiedade/etiologia , Cadáver , Depressão/diagnóstico , Depressão/etiologia , Humanos , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Percepção , Escalas de Graduação Psiquiátrica , Fatores de Risco , Apoio Social , Inquéritos e Questionários , Fatores de Tempo , Doadores de Tecidos , Resultado do Tratamento
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