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1.
Ann Oncol ; 35(3): 317-326, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38048850

RESUMO

BACKGROUND: Tebentafusp demonstrated a superior overall survival (OS) benefit [hazard ratio (HR) 0.51] compared to investigator's choice (82% pembrolizumab) in a randomized, phase III trial (IMCgp100-202; N = 378) in untreated metastatic uveal melanoma (mUM). The 1-year OS rates for tebentafusp and pembrolizumab were 73% and 59%, respectively. In the single-arm GEM1402 (N = 52), the 1-year OS rate for nivolumab plus ipilimumab (N+I) in mUM was 52%. Due to limitations in conducting randomized trials in mUM, we compared OS on tebentafusp or pembrolizumab (IMCgp100-202) to N+I (GEM1402) in untreated mUM using propensity scoring methods. PATIENTS AND METHODS: Analyses were adjusted using propensity score-based inverse probability of treatment weighting (IPTW), balancing age, sex, baseline lactate dehydrogenase (LDH), baseline alkaline phosphatase, disease location, Eastern Cooperative Oncology Group status, and time from primary diagnosis to metastasis. OS was assessed using IPT-weighted Kaplan-Meier and Cox proportional hazard models. Sensitivity analyses using alternative missing data and weights methods were conducted. RESULTS: The primary IPTW analysis included 240 of 252 patients randomized to tebentafusp from IMCgp100-202 and 45 of 52 N+I-treated patients from GEM-1402. Key baseline covariates, including LDH, were generally well balanced before weighting. The IPTW-adjusted OS favored tebentafusp, HR 0.52 [95% confidence interval (CI) 0.35-0.78]; 1-year OS was 73% for tebentafusp versus 50% for N+I. Sensitivity analyses showed consistent superior OS for tebentafusp with all IPTW HRs ≤0.61. IPTW analysis of pembrolizumab versus N+I showed no significant difference in OS (HR 0.72; 95% CI 0.50-1.06). CONCLUSIONS: Tebentafusp was previously shown to provide an OS benefit compared to checkpoint inhibitors or chemotherapy in untreated mUM. Propensity score analysis demonstrated a similar OS benefit for tebentafusp compared with N+I. These data further support tebentafusp as the standard of care in previously untreated human leukocyte antigen (HLA)-A∗02:01+ adult patients with mUM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Melanoma , Nivolumabe , Proteínas Recombinantes de Fusão , Neoplasias Uveais , Adulto , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ipilimumab , Pontuação de Propensão
2.
Transplant Proc ; 48(9): 3064-3066, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27932147

RESUMO

The growing disparity between organ supply and demand has become the greatest hurdle facing transplant professionals and life-saving transplants. Because the organ shortage has become the rate-limiting step to effective transplants, it is critical for the transplant community to identify viable mechanisms to expand the donor pool and use every available allograft. Although using kidneys from deceased donors whose demise was secondary to ethylene glycol (EG) toxicity requires great deliberation and precise timing as described by Barbas et al [5], using hepatic allografts in this setting involves far less risk. The following is a discussion of a 61-year-old male who was diagnosed with end-stage liver disease secondary to non-alcoholic steatohepatitis and ultimately underwent a life-saving transplant with a liver recovered from a donor with EG-induced brain death and allocated nationally due to trepidation by local and regional centers to use the liver from a donor after EG toxicity.


Assuntos
Morte Encefálica , Doença Hepática Terminal/cirurgia , Transplante de Fígado/métodos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Adulto , Etilenoglicol/intoxicação , Humanos , Masculino , Pessoa de Meia-Idade , Suicídio , Transplante Homólogo/métodos , Transplantes/fisiologia
3.
Anal Biochem ; 429(1): 32-8, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22796501

RESUMO

We report the use of resazurin (AlamarBlue) dye in a robust assay for cell viability of primary cells. Human mononuclear cells were used here for immunological studies, but the method can be applied to monitor reduction potential of any living cell. Reduction of AlamarBlue dye is widely used in several commercial assays of cell viability. Although it is fast and easy with immortal cell lines, the method is impractical for the primary cells due to their slower metabolic activity. We propose that the viability of human primary cells can be determined with AlamarBlue by monitoring the increase in fluorescence intensity in a matter of a few hours. In the presence of AlamarBlue, the dynamic increase in cellular reduction capacity is linear for several hours or, alternatively, the assay can be repeated to monitor the viability at any time point of cell culture. In addition to testing cellular growth rates and cytotoxicity, the application can be used to compare sample quality of cells that have been frozen or represent a pool of multiple donors. This application of the AlamarBlue cell viability assay is simple, rapid, and cost-effective, and therefore it is also well suited for high-throughput studies.


Assuntos
Leucócitos Mononucleares/citologia , Espectrometria de Fluorescência/métodos , Sobrevivência Celular , Células Cultivadas , Corantes/metabolismo , Humanos , Oxazinas/metabolismo , Fatores de Tempo , Xantenos/metabolismo
4.
Am J Transplant ; 12(2): 428-37, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22008552

RESUMO

Donor livers are precious resources and it is, therefore, ethically imperative that we employ optimally sensitive and specific transplant selection criteria. Current selection criteria, the Milan criteria, for liver transplant candidates with hepatocellular carcinoma (HCC) are primarily based on radiographic characteristics of the tumor. Although the Milan criteria result in reasonably high survival and low-recurrence rates, they do not assess an individual patient's tumor biology and recurrence risk. Consequently, it is difficult to predict on an individual basis the risk for recurrent disease. To address this, we employed microarray profiling of microRNA (miRNA) expression from formalin fixed paraffin embedded tissues to define a biomarker that distinguishes between patients with and without HCC recurrence after liver transplant. In our cohort of 64 patients, this biomarker outperforms the Milan criteria in that it identifies patients outside of Milan who did not have recurrent disease and patients within Milan who had recurrence. We also describe a method to account for multifocal tumors in biomarker signature discovery.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Transplante de Fígado , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , RNA Neoplásico/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Biópsia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos
5.
Oncogene ; 30(42): 4327-38, 2011 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-21532617

RESUMO

Prostate cancer and breast cancer are the most common malignancies in the western world. Androgen receptor (AR) and PTEN both have been well documented to have important roles in prostate carcinogenesis. In contrast, AR and PTEN in breast carcinogenesis have not been well studied. Furthermore, the crosstalk and connection between those two pathways remain unclear. Increased AR expression in prostate cancers, combined with decreased PTEN expression, portends a poor clinical outcome. Paradoxically, both high AR and high PTEN levels, detected by immunohistochemistry, in primary breast carcinomas have been associated with better disease-free survival. Here, we performed in silico analysis of publicly available microarray data sets from prostate or breast carcinomas. We found an inverse correlation between AR and PTEN transcript expression in prostate cancer tissues in contrast to the positive correlation in breast cancer. These data led us to hypothesize that AR may directly affect PTEN transcriptional regulation in prostate and breast cancer cells. Here, we show for the first time that AR inhibits PTEN transcription in prostate cancer cells, whereas AR upregulates PTEN transcription in breast cancer cells, which mechanistically explains both the immunohistochemical PTEN-AR expressional data noted in clinical trials and in our in silico analysis of the transcriptomes of breast and prostate cancers. In addition, we have fine-mapped the AR-binding motif within the PTEN promoter. Here we show that, in patients with Cowden syndrome, an inherited cancer syndrome caused by germline mutations scattered throughout PTEN, point variants affecting the 3' end of the AR-binding motif result in abrogation of androgen-mediated transcriptional regulation of PTEN expression. We may speculate that the differential AR effect on PTEN may begin to explain organ-specific and perhaps sex-specific neoplasia predisposition in Cowden syndrome, as well as why only a fraction of women with germline PTEN mutations develop breast cancer, depending on the androgen steroid milieu and levels.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Sequência de Bases , Neoplasias da Mama/genética , Carcinoma/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Síndrome do Hamartoma Múltiplo/genética , Síndrome do Hamartoma Múltiplo/metabolismo , Humanos , Masculino , Dados de Sequência Molecular , PTEN Fosfo-Hidrolase/genética , Mutação Puntual , Regiões Promotoras Genéticas , Neoplasias da Próstata/genética , Fatores Sexuais
6.
Int J Psychiatry Med ; 41(4): 295-308, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22238836

RESUMO

OBJECTIVE: The donation of livers by living donors entails complex processes, both surgically and psychosocially, potentially involving risks in both domains. Thorough psychosocial evaluation is necessary to minimize those risks, yet little has been written about the donor assessment process. This article describes one such process, utilized by a transplant program in upstate New York. METHOD: Donor candidates undergo multiple psychosocial interviews early in the overall transplant evaluation process. Evaluators subsequently meet as a group, along with an independent ethicist, to determine psychosocial candidacy prior to final medical/surgical clearance. RESULTS: Between 2003 and 2007, 416 donor candidates initiated and/or underwent full evaluation, resulting in a 17.5% surgery and 55.5% exclusion rate among those individuals. Of those ruled out, 20.8% were for (medical or psychosocial) reasons associated with the recipient, and 8.7% were for donor-related psychosocial issues. CONCLUSION: Given the primacy ofpsychosocial and ethical issues in living liver donor candidate evaluation, the multiple interview process, followed by team discussion and overseen by an ethicist removed from other transplant program functions, has advantages as a donor assessment model.


Assuntos
Transplante de Fígado/psicologia , Doadores Vivos/psicologia , Programas de Rastreamento/psicologia , Determinação da Personalidade/estatística & dados numéricos , Adulto , Comportamento Cooperativo , Definição da Elegibilidade/ética , Ética Médica , Família/psicologia , Feminino , Hospitais Universitários , Humanos , Comunicação Interdisciplinar , Transplante de Fígado/ética , Doadores Vivos/ética , Masculino , Programas de Rastreamento/ética , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , New York , Equipe de Assistência ao Paciente
7.
Transplant Proc ; 42(10): 4101-8, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21168637

RESUMO

BACKGROUND: Bleeding esophageal varices (BEV) in cirrhosis has been considered an indication for liver transplantation (LT). This issue was examined in a randomized controlled trial (RCT) of unselected, consecutive patients with advanced cirrhosis and BEV that compared endoscopic sclerotherapy (EST; n = 106) to emergency direct portacaval shunt (EPCS; n = 105). METHODS: Diagnostic work-up and treatment were initiated within 8 hours. Patients were evaluated for LT on admission and repeatedly thereafter; 96% underwent over 10 years of regular follow-up. The analysis was supplemented by 1300 unrandomized cirrhotic patients who previously underwent portacaval shunt (PCS) with 100% follow-up. RESULTS: In the RCT long-term bleeding control was 100% following EPCS, only 20% following EST. Also, 3-, 5-, 10-, and 15-year survival rates were 75%, 73%, 46%, and 46%, respectively, following EPCS compared with 44%, 21%, 9%, and 9% following EST, respectively (P < .001). Only 13 RCT patients (6%) were ultimately referred for LT mainly because of progressive liver failure; only 7 (3%) were approved for LT and only 4 (2%) underwent LT. The 1- and 5-year LT survival rates were 0.68% and 0, respectively, compared with 81% and 73%, respectively, after EPCS. In the 1300 unrandomized PCS patients, 50 (3.8%) were referred and 19 (1.5%) underwent LT. The 5-year survival rate was 53% compared with 72% for all 1300 patients. CONCLUSIONS: If bleeding is permanently controlled, as occurred invariably following EPCS, cirrhotic patients with BEV seldom require LT. PCS is effective first-line and long-term treatment. Should LT be required in patients with PCS, although technically more demanding, numerous studies have shown that PCS does not increase mortality or complications. EST is not effective emergency or long-term therapy.


Assuntos
Tratamento de Emergência , Varizes Esofágicas e Gástricas/cirurgia , Cirrose Hepática/cirurgia , Transplante de Fígado , Doença Aguda , Humanos , Taxa de Sobrevida , Resultado do Tratamento
8.
Oncogene ; 27(41): 5387-97, 2008 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-18794875

RESUMO

Germline PTEN (Phosphatase and TENsin homologue deleted on chromosome TEN) mutations predispose to phenotypically diverse disorders that share several overlapping clinical features: Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome and Proteus-like syndrome, collectively classified as PTEN hamartoma tumour syndrome (PHTS). The meticulous acquisition and documentation of PHTS phenotypic data at different levels and the profiling of the plethora of genetic changes in PTEN and other genes within the same or related pathways are important in resolving the challenge of discriminating heritable cancers from sporadic PHTS-mimicking clinical features. The characterization of PTEN and PTEN-related pathways from a multidisciplinary perspective underscores the importance of incorporating data from different -omics, which is crucial for the advancement of personalized medicine.


Assuntos
Heterogeneidade Genética , Síndrome do Hamartoma Múltiplo/genética , PTEN Fosfo-Hidrolase/genética , Animais , Genômica/tendências , Mutação em Linhagem Germinativa/fisiologia , Síndrome do Hamartoma Múltiplo/diagnóstico , Humanos , Camundongos , Camundongos Knockout , Modelos Biológicos , Fenótipo , Proteômica/tendências , Fatores de Transcrição/genética
9.
Am J Transplant ; 7(10): 2344-9, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17845568

RESUMO

Donor safety has been scrutinized by both the medical community and the media. Variability exists in reported donor complications and associated risk factors are ill defined. Use of administrative data can overcome the bias of single-center studies and explore variables associated with untoward events. A retrospective cohort study identifying living liver donors in two large healthcare registries yielded 433 right and left lobe donors from 13 centers between 2001 and 2005. Perioperative complications were identified using International Classification of Diseases, 9th Revision (ICD-9) coding data and classified according to the Clavien system. Logistic regression models identified factors associated with complications. There was one perioperative death (0.23%). The overall complication rate was 29.1% and major complication rate defined by a Clavien grade >or=3 was 3.5%. Center living-donor volume (OR = 0.97, 95% CI = 0.95-0.99) and the ratio of living-donors to all donors (living and deceased) (OR = 0.94, 95% CI = 0.92-0.96) were associated with a lower risk of all complications. Donor age >50 years (OR = 4.25, 95% CI = 1.22-14.87) was associated with a higher risk of major complications. Living liver donation is currently performed with a low risk of major morbidity. Use of administrative data represents an important tool to facilitate a better understanding of donor risk factors.


Assuntos
Hepatectomia/efeitos adversos , Complicações Intraoperatórias/epidemiologia , Transplante de Fígado/estatística & dados numéricos , Doadores Vivos/estatística & dados numéricos , Coleta de Tecidos e Órgãos/efeitos adversos , Distribuição de Qui-Quadrado , Hepatectomia/mortalidade , Humanos , Complicações Intraoperatórias/mortalidade , Análise Multivariada , Seleção de Pacientes , Fatores de Risco , Segurança , Coleta de Tecidos e Órgãos/mortalidade , Estados Unidos
10.
Clin Exp Immunol ; 149(1): 186-93, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17511774

RESUMO

The immune tolerance induced by the liver as an allograft is difficult to reconcile with the evidence that the liver selectively accumulates activated T cells from the circulation. However, much of this information is based on murine liver lymphocytes that were isolated using enzymatic digestion. In the present study we made use of a novel resource, the lymphocytes isolated during the perfusion of living donor liver lobe prior to transplantation. These healthy human liver lymphocytes displayed surface markers indicating a high degree of activation of natural killer cells, CD56(+) T cells, CD4(+) T cells and CD8(+) T cells. These properties were independent of enzymatic treatment or the details of cell isolation. We conclude that the healthy human liver is a site of intense immunological activity.


Assuntos
Fígado/imunologia , Ativação Linfocitária/imunologia , Linfócitos T CD4-Positivos/imunologia , Antígeno CD56/análise , Linfócitos T CD8-Positivos/imunologia , Células Cultivadas , Humanos , Tolerância Imunológica , Imunofenotipagem , Células Matadoras Naturais/imunologia , Doadores Vivos
11.
Am J Transplant ; 6(9): 2212-7, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16780542

RESUMO

Nephrogenic systemic fibrosis (NSF) is a recently characterized systemic fibrosing disorder developing in the setting of renal insufficiency. NSF's rapidly progressive nature resulting in disability within weeks of onset makes early diagnosis important. Two reports of NSF after liver transplantation are known of. We present three cases of NSF developing within a few months after liver transplantation and review the current literature. Loss of regulatory control of the circulating fibrocyte, its aberrant recruitment, in a milieu of renal failure and a recent vascular procedure appear important in its development. Known current therapies lack consistent efficacy. Only an improvement in renal function has the greatest likelihood of NSF's resolution. Delayed recognition may pose a significant barrier to functional recovery in the ubiquitously deconditioned liver transplant patient. Early recognition and implementation of aggressive physical therapy appear to have the greatest impact on halting its progression.


Assuntos
Nefropatias/etiologia , Transplante de Fígado/efeitos adversos , Dermatopatias/etiologia , Idoso , Fibrose/etiologia , Humanos , Nefropatias/patologia , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Dermatopatias/patologia , Dermatopatias/terapia , Resultado do Tratamento
12.
Transplant Proc ; 37(7): 3159-61, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16213336

RESUMO

INTRODUCTION: Hepatitis C virus (HCV)-related liver disease is the most common indication for liver transplantation in the United States. Recurrence of HCV infection in these recipients is almost uniform. The currently available antiviral treatment is known to cause significant side effects, and the rate of sustained viral response is low. There is still controversy about whether such patients should undergo subsequent transplantations for HCV disease. This study compared outcomes for hepatic retransplantation performed in HCV(+) and HCV(-) recipients at a single center. PATIENTS AND METHODS: From December 1994 through November 2003, 68 patients at our institution received a second liver allograft. Nineteen of the recipients were HCV(+) (group A) and 49 were HCV(-) (group B). All patients were followed until January 2004. The mean follow-up time after initial retransplantation was 37 +/- 29 months. Patient and graft survival for the two groups were compared. RESULTS: Seven recipients in group A (36.8%) and 22 recipients in group B (44.9%) died during follow-up. The actuarial 3-year patient survival after initial retransplantation for groups A and B were 61.7% and 51.6%, respectively. Nine patients required a second retransplantation, 3 (15.8%) in group A and 6 (12.2%) in group B. The actuarial 3-year graft survival from initial retransplantation for groups A and B were 56.3% and 45.7%, respectively. CONCLUSION: We observed slightly better patient and graft survivals at 3 years from initial retransplantation in HCV(+) recipients compared to HCV(-) recipients. This may be due to younger donor age and better selection of HCV(+) recipients in this series.


Assuntos
Hepatite C/cirurgia , Transplante de Fígado/fisiologia , Adulto , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Reoperação/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo
13.
Transplant Proc ; 37(7): 3162-4, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16213337

RESUMO

INTRODUCTION: Older donor allografts are being accepted for liver transplantation (LTx) due to shortage of organs. Hepatitis C virus (HCV) infection-related disease is presently the most common indication of LT in the United States. We studied the impact of donor age on patient and graft survivals in patients with HCV infection. PATIENTS AND METHODS: One hundred fifty four consecutive HCV(+) LTx recipients (117 men, 37 women) were studied. The mean follow-up period was 41.0 +/- 30.2 months. The population was divided into four groups according to donor age: group I (< or =20 years); group II (21 to 40 years); group III (41 to 60 years); group IV (>60 years). RESULTS: Thirty-two (20.8%) patients died during follow-up and 16 patients (10.4%) required retransplantation. The actuarial 7-year patient survivals for groups I, II, III, and IV were 87.1%, 73.7%, 69.3%, and 68.5%, respectively (P = .4). Patient survivals for donor age groups III + IV (n = 95) and groups I + II (n = 59) were 68.9% and 77.2%, respectively (P = .19). The 7-year graft survivals for groups I, II, III, and IV were 82.7%, 71.8%, 65.8%, and 62.5%, respectively (P = .17). Graft survivals for groups III + IV and groups I + II were 58.4% and 76.2%, respectively (P = .03). CONCLUSION: Patient and graft survivals for HCV-positive liver transplant recipients in this study decreased progressively as the donor age increased. Patient and graft survivals were best for group I recipients. There were significant differences in graft survivals when recipients were grouped with a cutoff donor age of 40 years.


Assuntos
Hepatite C/transmissão , Transplante de Fígado/estatística & dados numéricos , Doadores de Tecidos , Adulto , Fatores Etários , Cadáver , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/mortalidade , Transplante de Fígado/fisiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/virologia , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo
14.
Transplant Proc ; 37(7): 3165-7, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16213338

RESUMO

INTRODUCTION: Jejunoileal bypass (JIB) was, at one time, a popular surgical technique for the treatment of morbid obesity. However, this operation was also associated with major complications. Consequently, many such procedures were eventually reversed. One of the most serious of these complications was liver failure. For those patients who developed cirrhosis, liver transplantation was one therapeutic alternative. Tacrolimus is one of the primary immunosuppressive agents used in liver transplantation. It is effective to prevent acute rejection episodes, but shows a narrow therapeutic index and can cause nephrotoxicity and neurotoxicity. This report describes the change in tacrolimus absorption that was observed after JIB reversal in a 57-year-old female liver transplant recipient. RESULTS: Prior to JIB reversal, the mean tacrolimus dose was 7 mg twice daily with a whole-blood tacrolimus concentration ranging from 5.2 to 6.4 ng/mL. There was no appreciable peak in tacrolimus concentration, and the area under the concentration-time curve (AUC) was 10.9 ng/mL/h. After reversal, the daily tacrolimus dose was decreased to 5 mg twice daily, with a now-discernable peak concentration at 3 hours postdose. Furthermore, the AUC increased 90% to 20.7 ng/mL/h. CONCLUSION: After JIB reversal, the patient showed higher systemic levels of tacrolimus and required lower steady-state doses. It is therefore imperative that such patients be monitored closely to avoid tacrolimus-related toxicity.


Assuntos
Derivação Jejunoileal , Transplante de Fígado/imunologia , Tacrolimo/farmacocinética , Tacrolimo/uso terapêutico , Administração Oral , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Absorção Intestinal , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Reoperação , Tacrolimo/administração & dosagem
15.
Transplant Proc ; 37(7): 3182-6, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16213344

RESUMO

INTRODUCTION: Cytomegalovirus (CMV) infection after solid organ transplantation is one of the most common viral infections, causing significant morbidity and mortality if not treated promptly. Ganciclovir has proven to be effective for the prophylaxis and treatment of CMV. However, oral absorption of ganciclovir is poor. Recently, oral administration of valganciclovir hydrochloride (Valcyte) has been observed to display 10-fold better absorption than oral ganciclovir. Valganciclovir has increasingly been used as prophylaxis against CMV after solid organ transplantation. The purpose of this study was to examine the efficacy of valganciclovir prophylaxis therapy after primary liver transplantation. PATIENTS AND METHODS: Between July 2001 and May 2003, 203 consecutive liver transplant recipients, including 129 men and 74 women of overall mean age 53 +/- 11 years, received valganciclovir (900 mg/d or 450 mg every other day depending on renal function) for 3 to 6 months after primary liver transplantation. All patients were followed up for a minimum of 6 months. Mean follow-up was 19 +/- 5.8 months. CMV DNA in peripheral blood was tested using polymerase chain reaction (PCR) amplification. Symptomatic CMV was stratified according to the CMV immunoglobulin (Ig)G status of the donor and recipient at the time of liver transplantation. Donors and recipients were classified preoperatively into groups according to the presence or absence of CMV as follows: group 1 (n = 73; donor CMV+, recipient CMV+); group 2 (n = 41; donor CMV-, recipient CMV+); group 3 (n = 54; donor CMV+, recipient CMV-; high-risk group); and group 4 (n = 35; donor CMV-, recipient CMV-). RESULTS: Twenty-nine patients (14.3%) developed symptomatic CMV disease at 169 +/- 117 days after liver transplantation: group 1, 16.4% versus group 2, 7.3% versus group 3, 25.9% versus group 4, 0%. Of these patients, 5 also had invasive CMV on liver biopsy, which was performed owing to abnormal liver functions. All 29 patients were treated with intravenous ganciclovir. One patient died owing to disseminated CMV, whereas the remaining 28 patients responded to treatment. Interestingly, 8 patients, including 1 who had invasive CMV hepatitis, developed symptomatic CMV within 90 days of liver transplantation even while on prophylactic valganciclovir. CONCLUSION: Valganciclovir failed to provide adequate prophylaxis following liver transplantation in our patients. The overall rate of CMV in seropositive donors and/or recipients was 17%, and in the high-risk group was 26%. Further prospective studies with measurement of ganciclovir concentrations are needed to elucidate the reasons for this unexpected failure.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/análogos & derivados , Adulto , Anticorpos Antivirais/sangue , Biópsia , Citomegalovirus/isolamento & purificação , DNA Viral/sangue , Feminino , Ganciclovir/uso terapêutico , Hepatite Viral Humana/prevenção & controle , Humanos , Imunoglobulina G/sangue , Transplante de Fígado/efeitos adversos , Transplante de Fígado/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Valganciclovir
16.
Transplant Proc ; 37(7): 3187-9, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16213345

RESUMO

INTRODUCTION: With the shortage of donor organs, increasing number of hepatitis B core antibody (HBcAb)-positive [HBcAb(+)] liver allografts are being used for liver transplantation (LTx) in patients who are HBcab-negative [HBsAb(-)]. This study was aimed at assessing outcomes for hepatitis C virus (HCV)-positive [HCV(+)] and HCV-negative [HCV(-)] patients who received HBcAb(+) liver grafts from deceased donors and also received a short course of hepatitis B immunoglobulin (HBIg) with long-term lamivudine therapy after LTx. MATERIALS AND METHODS: From February 1995 through February 2003, 28 patients (mean age 53.8 +/- 10.2 years, 19 men and nine women, 16 HCV[-]; 12 HCV[+]) received HbcAb(+) liver allografts. All recipients received a short course of HBIg prophylaxis (10,000 units/day for 4 days) and long-term lamivudine 100 mg/d after LTx in addition to a tacrolimus-based immunosuppressive regimen. RESULTS: Seven (25%) of the 28 recipients died during follow-up and three recipients required retransplantation. Three recipients (10.7%) developed HBV infection during follow-up, one of whom died 36 months after LTx and the other two had YMDD mutant HBV. The overall 6-year actuarial patient survival after transplantation was 74.4% and those for HCV(-) and HCV(+) recipients were 81.3% and 66.6%, respectively (P = .46). The overall 6-year actuarial graft survival was 63.9% and those for HCV(+) and HCV(-) recipients were 68.8% and 57.1%, respectively (P = .6). CONCLUSION: We conclude that HBcAb(+) liver grafts can be used for both HCV(+) patients and HCV(-) patients who are critically ill, have early hepatocellular carcinoma, or have been exposed to HBV in the past. A short course of HBIg-lamivudine combination therapy provides effective prophylaxis against HBV infection in 89% of recipients of HBcAb(+) grafts.


Assuntos
Antivirais/uso terapêutico , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Hepatite C/diagnóstico , Hepatite C/prevenção & controle , Imunoglobulinas/uso terapêutico , Lamivudina/uso terapêutico , Transplante de Fígado/imunologia , Adulto , Feminino , Sobrevivência de Enxerto , Hepacivirus/imunologia , Hepacivirus/isolamento & purificação , Anticorpos Anti-Hepatite B/uso terapêutico , Hepatite C/imunologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Imunização Passiva , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida
17.
Pediatr Transplant ; 6(5): 419-22, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12390430

RESUMO

We report a case of arterio-portal fistulae in a 12-month-old-child following a segmental liver transplantation. The fistula, probably the result of mass ligature of a vascular pedicle during back table allograft reduction, is to our knowledge the first such case reported. Diagnosed on the third post-operative day, the fistula was successfully managed with transcatheter coil embolization. The child is well and asymptomatic, 33 months after transplantation. In addition to those seen in whole organ transplantation, there are a few complications specifically related to segmental transplantation. These complications, although infrequent, are a direct consequence of the back table liver partition, as in the case herein reported.


Assuntos
Fístula Arteriovenosa/etiologia , Complicações Intraoperatórias , Transplante de Fígado/efeitos adversos , Fístula Arteriovenosa/diagnóstico , Fístula Arteriovenosa/terapia , Embolização Terapêutica , Feminino , Artéria Hepática , Humanos , Lactente , Transplante de Fígado/métodos , Veia Porta
18.
Liver Transpl ; 7(10): 845-52, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11679981

RESUMO

Right-lobe living donor liver transplantation has emerged as an alternative to cadaveric transplantation. An appreciation of the unique anatomy and behavior of the right lobe has emerged and has precipitated technical modifications. Living donors underwent right lobectomy, including preservation of significant inferior hepatic veins. The parenchyma was divided following a plane approximating the right border of the posterior two thirds of the midhepatic vein (MHV), but deviating anteriorly to include the distal one third of the MHV with the graft. Large venous tributaries from segment VIII were preserved. Anastomosis in the recipient was accomplished by means of complete cavoplasty. Significant inferior veins, tributaries to the MHV, and the distal portion of the MHV were reconstructed when technically possible. Forty-eight right-lobe resections and transplantations were performed in the manner described. There were no donor complications attributable to the technique. Forty-six of the 48 recipients are alive, and 44 of the 46 surviving patients have their original graft. Venous tributaries from segment VIII and/or the distal portion of the MHV were reconstructed in only 3 patients. Outflow obstruction was recognized intraoperatively in 2 patients; 1 patient had a caval web excised and the other patient required revision of the main anastomosis. Neither organ was lost. There were no other significant venous complications. The incidence of ascites was the same as that in recipients of whole organs. These methods of parenchymal transection and venous reconstruction resulted in a low rate of complications. The wide anastomosis and collateral pathways between the MHV and right hepatic vein seem to be more critical than reconstruction of tributaries from segment VIII or the distal MHV.


Assuntos
Hepatectomia/métodos , Transplante de Fígado/métodos , Fígado/irrigação sanguínea , Doadores Vivos , Adulto , Anastomose Cirúrgica , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Veias Hepáticas/diagnóstico por imagem , Humanos , Fígado/anatomia & histologia , Circulação Hepática , Transplante de Fígado/mortalidade , Masculino , Prognóstico , Radiografia , Regeneração/fisiologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
19.
Liver Transpl ; 7(8): 673-9, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11510010

RESUMO

Double hepatic arterial and portal venous branches are common anatomic variations of the isolated right hepatic lobe. Reconstruction of these vessels during transplantation can be challenging because of their small caliber, close proximity to other hilar structures, and abnormal alignment with the native vasculature. Practical techniques for the creation of these anastomoses would simplify the recipient surgery and might minimize the incidence of vascular complications. Alternative methods for management of these structures are summarized. The recipient's proper hepatic artery and its bifurcation are resected for use as an arterial Y-type graft. The donor arteries are individually anastomosed at the bifurcation of the recipient's hepatic artery at the back table. The free end of the Y graft is then replaced at the origin of the gastroduodenal artery using standard branch-patch technique. Reconstruction of a second donor portal branch is similarly facilitated by ex situ placement of a Y-type vascular conduit derived from the recipient's portal vein. Surgical management of these vessels and reconstruction of other hilar structures are noticeably less cumbersome. There have been no short-term vascular complications. The use of autologous vascular conduits with ex situ reconstruction facilitates management of double donor arterial and portal venous branches. The incidence of complications attributable to these methods is expected to be low.


Assuntos
Artéria Hepática/cirurgia , Transplante de Fígado/métodos , Doadores Vivos , Veia Porta/cirurgia , Angiografia , Humanos , Veia Porta/diagnóstico por imagem , Complicações Pós-Operatórias , Análise de Sobrevida , Resultado do Tratamento
20.
J Clin Microbiol ; 39(9): 3360-1, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11526178

RESUMO

Tests of the survival of Candida spp., Aspergillus spp., a Fusarium sp., a Mucor sp., and a Paecilomyces sp. on hospital fabrics and plastics indicated that viability was variable, with most fungi surviving at least 1 day but many living for weeks. These findings reinforce the need for appropriate disinfection and conscientious contact control precautions.


Assuntos
Equipamentos e Provisões Hospitalares , Fungos Mitospóricos/crescimento & desenvolvimento , Micoses/microbiologia , Plásticos , Têxteis , Roupas de Cama, Mesa e Banho/microbiologia , Vestuário , Contaminação de Equipamentos , Humanos
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