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We report 4 cases of breast cancer transmission to transplant recipients from a single organ donor that occurred years after donation. The diagnosis of breast cancer was occult at the time of donation. All of the recipients developed a histologically similar type of breast cancer within 16 months to 6 years after transplantation. Three out of 4 recipients died as a result of widely metastasized disease. One of the recipients survived after transplant nephrectomy followed by cessation of immunosuppression and chemotherapy. This extraordinary case points out the often fatal consequences of donor-derived breast cancer and suggests that removal of the donor organ and restoration of immunity can induce complete remission.
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Neoplasias de la Mama/etiología , Trasplante de Riñón/efectos adversos , Trasplante de Hígado/efectos adversos , Trasplante de Pulmón/efectos adversos , Donantes de Tejidos , Adulto , Neoplasias de la Mama/fisiopatología , Neoplasias de la Mama/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Receptores de TrasplantesRESUMEN
RATIONALE: Altered pulmonary hemodynamics and fluid flow-induced high shear stress (HSS) are characteristic hallmarks in the pathogenesis of pulmonary arterial hypertension (PAH). However, the contribution of HSS to cellular and vascular alterations in PAH is unclear. OBJECTIVES: We hypothesize that failing shear adaptation is an essential part of the endothelial dysfunction in all forms of PAH and tested whether microvascular endothelial cells (MVECs) or pulmonary arterial endothelial cells (PAECs) from lungs of patients with PAH adapt to HSS and if the shear defect partakes in vascular remodeling in vivo. METHODS: PAH MVEC (n = 7) and PAH PAEC (n = 3) morphology, function, protein, and gene expressions were compared with control MVEC (n = 8) under static culture conditions and after 24, 72, and 120 hours of HSS. MEASUREMENTS AND MAIN RESULTS: PAH MVEC showed a significantly delayed morphological shear adaptation (P = 0.03) and evidence of cell injury at sites of nonuniform shear profiles that are critical loci for vascular remodeling in PAH. In clear contrast, PAEC isolated from the same PAH lungs showed no impairments. PAH MVEC gene expression and transcriptional shear activation were not altered but showed significant decreased protein levels (P = 0.02) and disturbed interendothelial localization of the shear sensor platelet endothelial cell adhesion molecule-1 (PECAM-1). The decreased PECAM-1 levels were caused by caspase-mediated cytoplasmic cleavage but not increased cell apoptosis. Caspase blockade stabilized PECAM-1 levels, restored endothelial shear responsiveness in vitro, and attenuated occlusive vascular remodeling in chronically hypoxic Sugen5416-treated rats modeling severe PAH. CONCLUSIONS: Delayed shear adaptation, which promotes shear-induced endothelial injury, is a newly identified dysfunction specific to the microvascular endothelium in PAH. The shear response is normalized on stabilization of PECAM-1, which reverses intimal remodeling in vivo.
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Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Microvasos/fisiopatología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Remodelación Vascular/fisiología , Adulto , Animales , Western Blotting , Células Cultivadas , Niño , Modelos Animales de Enfermedad , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Masculino , Microvasos/metabolismo , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Arteria Pulmonar/metabolismo , Arteria Pulmonar/fisiopatología , Ratas , Adulto JovenRESUMEN
Combined lung-liver transplantation is a logistically challenging procedure hampered by shortage of organ donors. We describe the case of a young patient with end-stage lung disease due to of cystic fibrosis and liver cirrhosis who needed combined lung-liver transplantation. The long waiting for this caused an interesting clinical dilemma. We decided to change our policy in this situation by listing him only for the lung transplantation and to apply for a high urgent liver transplantation if the liver failed after the lung transplantation. This strategy enabled us to use lungs treated with ex vivo lung perfusion (EVLP) from an unsuitable donor after circulatory death. After conditioning for 4 h via EVLP, the pO2 was 59.7 kPa. The lungs were transplanted successfully. He developed an acute-on-chronic liver failure for which he received a successful liver transplantation 19 days after the lung transplantation.
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Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/métodos , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón/métodos , Adulto , Fibrosis Quística/cirugía , Edema/patología , Femenino , Humanos , Cirrosis Hepática/cirugía , Pulmón/patología , Masculino , Perfusión/métodos , Donantes de Tejidos , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal fibrosing lung disease with a median survival of approximately 3 years after diagnosis. The only medical option to improve survival in IPF is lung transplantation (LTX). The purpose of this study was to evaluate trajectory data of IPF patients listed for LTX and to investigate the survival after LTX. METHODS AND RESULTS: Data were retrospectively collected from September 1989 until July 2011 of all IPF patients registered for LTX in the Netherlands. Patients were included after revision of the diagnosis based on the criteria set by the ATS/ERS/JRS/ALAT. Trajectory data, clinical data at time of screening, and donor data were collected. In total, 98 IPF patients were listed for LTX. During the waiting list period, 30 % of the patients died. Mean pulmonary artery pressure, 6-min walking distance, and the use of supplemental oxygen were significant predictors of mortality on the waiting list. Fifty-two patients received LTX with a median overall survival after transplantation of 10 years. CONCLUSIONS: This study demonstrated a 10-year survival time after LTX in IPF. Furthermore, our study demonstrated a significantly better survival after bilateral LTX in IPF compared to single LTX although bilateral LTX patients were significantly younger.
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Fibrosis Pulmonar Idiopática/cirugía , Trasplante de Pulmón , Estudios de Cohortes , Prueba de Esfuerzo , Femenino , Humanos , Hipertensión Pulmonar/epidemiología , Fibrosis Pulmonar Idiopática/epidemiología , Fibrosis Pulmonar Idiopática/mortalidad , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Terapia por Inhalación de Oxígeno/estadística & datos numéricos , Presión Esfenoidal Pulmonar , Estudios Retrospectivos , Tasa de Supervivencia , Listas de Espera/mortalidadRESUMEN
Several diagnostic imaging methodologies are available for the clinical evaluation of sarcoidosis, but all have their limitations. FDG PET/CT is frequently used, but this technique does not provide optimal results in all cases. Novel radiopharmaceuticals aimed at other disease targets may be helpful, particularly in cardiac sarcoidosis when FDG PET/CT has a low diagnostic accuracy, due to difficulties in preparing the patients who should use a specific diet combined with prolonged fasting. 68Ga-labeled somatostatin based receptor hybrid imaging is a potential alternative to FDG PET/CT. This short communication provides a rapid overview of initial findings concerning the application of 68Ga-labeled somatostatin based receptor hybrid imaging in the diagnosis of (cardiac) sarcoidosis activity.
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OBJECTIVE: To describe patients diagnosed with idiopathic pulmonary fibrosis (IPF) registered for lung transplantation and to evaluate the current referral guidelines for lung transplantation in the Netherlands. DESIGN: Retrospective study. METHOD: All patients diagnosed with interstitial lung disease and registered for lung transplantation from September 1989-June 2010 were included in this study. Patients who had been diagnosed with IPF according to the American Thoracic Society-European Respiratory Society criteria were included. Clinical data of these patients at the time of screening for lung transplantation and survival data were collected. RESULTS: In total, 289 patients with IPF were registered for lung transplantation. After a first waiting list. During the waiting period, 30 patients (33%) died, 7 were taken off the list due to newly developed comorbidity and excessive physical deterioration, 51 underwent transplantation and 2 were still on the waiting list at the time of study closure. At the time of screening, the mean FVC% predicted of these patients was 51% (SD: 19.0) and the mean diffusing capacity was 27% of predicted (SD: 9.3). CONCLUSION: One-third of the IPF patients on the waiting list died before donor lungs became available. The mean diffusing capacity of 27% of predicted at the time of screening was considerably lower than advised in the international guidelines for placement on the waiting list. This study, therefore, shows that the timing of screening IPF patients for lung transplantation can be improved in the Netherlands.
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Fibrosis Pulmonar Idiopática/mortalidad , Trasplante de Pulmón , Listas de Espera/mortalidad , Femenino , Humanos , Fibrosis Pulmonar Idiopática/terapia , Trasplante de Pulmón/mortalidad , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Países Bajos , Terapia por Inhalación de Oxígeno , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo , Capacidad Pulmonar Total/fisiologíaRESUMEN
OBJECTIVE: The use of non-heart-beating (NHB) lung donors has been propagated as an alternative besides heart-beating (HB) lung donors to overcome organ shortage. We evaluated the effectiveness of NHB lung transplantation. METHODS: The donor and recipient data of all 35 NHB category III lung transplantations (LTx) between January 2005 and December 2009 were reviewed. For comparison, we collected recipient and donor data of a cohort of 77 HB lung transplantations. In both groups, we assessed survival, primary graft dysfunction (PGD), forced expiratory volume in 1s (FEV(1)), acute rejection, and bronchiolitis obliterans syndrome (BOS). RESULTS: Thirty-five NHB lung transplantations were performed, five single LTx and 30 bilateral LTx in 12 male and 23 female patients. The donor oxygenation capacity was 61 kPa (interquartile range (IQR), 56-64). Warm ischemia time in the donor was 29 min (IQR, 24-30). Cold ischemic time of the last implanted lung was 458 min (IQR, 392-522). Cardiopulmonary bypass was used 13 times. PGD (1-3) was observed in 45% of the patients at T0, in 42% at T24, in 53% at T48, and in 50% at T72. PGD 3 decreased from 24% at T0 to 6% at T72. The use of nitric oxide (NO) within 24h after transplantation was necessary in three patients with successful weaning in all. There was no significant difference for donor and recipient characteristics between NHB and HB lung transplantations. Survival, occurrence of PGD, and acute rejection was equal to the HB cohort. The incidence of BOS was lower in the NHB group. The measured FEV(1) tended to be better in the NHB group. CONCLUSION: Lungs from nonheparinized category III NHB donors are well suited for transplantation and can safely increase the donor pool.
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Selección de Donante/métodos , Paro Cardíaco , Trasplante de Pulmón/métodos , Recolección de Tejidos y Órganos/métodos , Enfermedad Aguda , Adulto , Bronquiolitis Obliterante/etiología , Femenino , Volumen Espiratorio Forzado/fisiología , Rechazo de Injerto , Humanos , Estimación de Kaplan-Meier , Trasplante de Pulmón/efectos adversos , Trasplante de Pulmón/fisiología , Masculino , Persona de Mediana Edad , Preservación de Órganos/métodos , Estudios Retrospectivos , Obtención de Tejidos y Órganos/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of the study was to investigate the impact of the lung allocation score (LAS) on mortality among highly urgent (HU) and urgent (U) lung transplant (LTx) candidates in Eurotransplant (ET) and to identify useful additional parameters (LASplus). METHODS: All adult LTx candidates for whom a first request for HU or U status was made in 2008 in ET were included (N = 317). Patients were followed until LTx, death on the waiting list (WL), delisting, or closure date (i.e., January 10, 2010). The relationship between the LAS/LASplus and waiting list, post-transplant, and overall mortality was assessed with a multivariate regression model. The LAS and LASplus were decomposed into their basic waitlist and post-transplant components. RESULTS: Waiting list mortality rate was 22% and 1-year post-transplant mortality rate was 34%. The waitlist component of the LASplus was significantly associated with waiting list mortality (hazard ratio [HR] 1.91, p = 0.021), whereas the LAS was not (p = 0.063). The post-transplant components of both scores were significantly associated with 1-year post-transplant mortality (LAS: HR 2.69, p = 0.005; LASplus: HR 2.55, p = 0.004). Both scores strongly predicted overall mortality (LAS: HR 1.65, p = 0.008; LASplus: HR 1.72, p = 0.005). CONCLUSION: LAS accurately predicts overall mortality in critically ill transplant candidates and should therefore be considered as the basis for a new lung allocation policy in ET. An adjustment of the original LAS may be indicated to accurately predict waiting list mortality.
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Enfermedad Crítica/mortalidad , Asignación de Recursos para la Atención de Salud/métodos , Trasplante de Pulmón , Selección de Paciente , Adolescente , Adulto , Anciano , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Trasplante de Pulmón/mortalidad , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Resultado del Tratamiento , Listas de Espera/mortalidad , Adulto JovenRESUMEN
Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing and transplantation on the patient's quality of life. Although recent population-based analyses of the US lung allocation system for the CF population have raised controversies about the survival benefits of transplantation, studies from the United Kingdom and Canada have suggested a definite survival advantage for those receiving transplants. In response to these and other controversies, leaders in transplantation and CF met together in Lansdowne, Virginia, to consider the state of the art in lung transplantation for CF in an international context, focusing on advances in surgical technique, measurement of outcomes, use of prognostic criteria, variations in local control over listing, and prioritization among the United States, Canada, the United Kingdom, and The Netherlands, patient adherence before and after transplantation and other issues in the broader context of lung transplantation. Finally, the conference members carefully considered how efforts to improve outcomes for lung transplantation for CF lung disease might best be studied. This Roundtable seeks to communicate the substance of our discussions.