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1.
Am J Transplant ; 21(1): 410-414, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619074

RESUMO

Severe chest wall deformities are considered an absolute contraindication for lung transplantation. The significantly impaired chest compliance associated with pectus excavatum is thought to result in a high risk of postoperative respiratory complications and significant morbidity and mortality. We herein report our pooled institutional experience consisting of 3 patients who underwent bilateral lung transplantation and simultaneous correction of a pectus excavatum. Two of the patients were children and 1 patient had severe asymmetric pectus. All patients received a size-reduced double lung transplant and the deformity was corrected by a Nuss or modified Ravitch procedure. The perioperative course was complicated by prolonged weaning requiring tracheostomy in 2 of the 3 patients. However, long-term results were good and all 3 patients are alive in excellent clinical condition 72, 60, and 12 months after the transplantation. This case series demonstrates that patients with severe chest wall deformities should not a priori be excluded from lung transplantation, and a combined approach is feasible for selected patients.


Assuntos
Tórax em Funil , Transplante de Pulmão , Criança , Tórax em Funil/cirurgia , Humanos , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias
2.
Transpl Int ; 33(5): 544-554, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31984577

RESUMO

The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X-rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO2 /FiO2  ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized.


Assuntos
Transplante de Pulmão , Transplantados , Adulto , Humanos , Pulmão , Estudos Prospectivos , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento
3.
J Pathol ; 245(4): 387-398, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29570800

RESUMO

Deregulated DNA methylation leading to transcriptional inactivation of certain genes occurs frequently in non-small-cell lung cancers (NSCLCs). As well as protein-coding genes, microRNA (miRNA)-coding genes may be targets for methylation in NSCLCs; however, the number of known methylated miRNA genes is still small. Thus, we investigated methylation of miRNA genes in primary tumour (TU) samples and corresponding non-malignant lung tissue (NL) samples of 50 NSCLC patients by using methylated DNA immunoprecipitation followed by custom-designed tiling microarray analyses (MeDIP-chip), and 252 differentially methylated probes between TU samples and NL samples were identified. These probes were annotated, which resulted in the identification of 34 miRNA genes with increased methylation in TU samples. Some of these miRNA genes were already known to be methylated in NSCLCs (e.g. those encoding miR-9-3 and miR-124), but methylation of the vast majority of them was previously unknown. We selected six miRNA genes (those encoding miR-10b, miR-1179, miR-137, miR-572, miR-3150b, and miR-129-2) for gene-specific methylation analyses in TU samples and corresponding NL samples of 104 NSCLC patients, and observed a statistically significant increase in methylation of these genes in TU samples (p < 0.0001). In silico target prediction of the six miRNAs identified several oncogenic/cell proliferation-promoting factors (e.g. CCNE1 as an miR-1179 target). To investigate whether miR-1179 indeed targets CCNE1, we transfected miR-1179 gene mimics into CCNE1-expressing NSCLC cells, and observed downregulated CCNE1 mRNA expression in these cells as compared with control cells. Similar effects on cyclin E1 expression were seen in western blot analyses. In addition, we found a statistically significant reduction in the growth of NSCLC cells transfected with miR-1179 mimics as compared with control cells. In conclusion, we identified many methylated miRNA genes in NSCLC patients, and found that the miR-1179 gene is a potential tumour cell growth suppressor in NSCLCs. Overall, our findings emphasize the impact of miRNA gene methylation on the pathogenesis of NSCLCs. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Metilação de DNA , Neoplasias Pulmonares/genética , MicroRNAs/genética , Células A549 , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Proliferação de Células/genética , Imunoprecipitação da Cromatina/métodos , Ilhas de CpG , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Transdução de Sinais/genética
4.
Transpl Int ; 31(8): 930-937, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29665090

RESUMO

Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine-tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty-three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET.


Assuntos
Transplante de Pulmão , Seleção de Pacientes , Algoritmos , Estudos Transversais , Europa (Continente) , Humanos , Pessoa de Meia-Idade , Estados Unidos
5.
Orv Hetil ; 159(34): 1399-1404, 2018 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-30122061

RESUMO

INTRODUCTION: Nowadays ever smaller, sub-centimetre lung nodules are screened and diagnosed. For these, minimally invasive resection is strongly recommended both with diagnostic and therapeutic purpose. AIM: Despite many advantages of minimally invasive thoracic surgery, thorough palpation of the lung lobes and thus the localization of lung nodules are still limited. There are several options to solve this problem. From the possibilities we have chosen and tried wire- and isotope-guided lung nodule localization. MATERIALS AND METHODS: In 2017, at the Thoracic Surgery Department of the National Institute of Oncology we performed wire- and isotope-guided minimally invasive pulmonary nodule resection in five patients. The diameter of the lung nodules was between 0.5 and 1.2 cm. The age of the patients was between 44 and 65 years and none of them had severe comorbidities, which meant low risk for complications. RESULTS: We successfully performed the minimally invasive atypical resection in all cases. After the wire and isotope placement we found a 2-3 mm pneumothorax in one patient that did not need urgent drainage. In another patient we found that high amount of intraparenchymal bleeding surrounded the channel of the wire. During the operation, two wires were displaced when the lung collapsed, and in another case the mentioned bleeding got into the thoracic cavity and made it difficult to detect the nodule. In one case we resected the wire-guided lung tissue, but the isotope-guided lung nodule was below the resection line. CONCLUSION: Both techniques could help to localize the non-palpable lung nodules. Based on our initial experiences, the isotope-guided method provides more details to estimate the exact depth of the nodule from the visceral surface of the pleura and we can avoid the unpleasantness of wire displacement. On the other hand, the production of the isotope requires a more developed infrastructure and the exact timing of the operation after the isotope injection is more strict. Orv Hetil. 2018; 159(34): 1399-1404.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Tomografia Computadorizada por Raios X/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nódulo Pulmonar Solitário/diagnóstico por imagem
6.
Orv Hetil ; 159(46): 1859-1868, 2018 11.
Artigo em Húngaro | MEDLINE | ID: mdl-30450935

RESUMO

The first lung transplantation in Hungary was performed on 12th of December, 2015. It was a joint effort of the National Institute of Oncology and the Semmelweis University. Hereby we summarise the results and experiences from the first three years. Until August, 2018, 55 lung transplantations were performed in Hungary. This was a retrospective analysis. All patients were listed according to the recommendation of the Lung Transplantation Committee. All implanted lungs have been procured from brain dead donors. Postoperative treatment and rehabilitation of the patients were continued at the Semmelweis University. Between 12. 12. 2015 and 31. 07. 2018, our team performed 76 organ retrievals: out of 45 Hungarian offers, 23 came from Eurotransplant countries and 8 outside of the Eurotransplant region. From these donations, 54 double and 1 single side transplantations were successfully performed. The surgical approach was single side thoracotomy (n = 1), bilateral thoracotomy (n = 1) and in the majority of the cases clamshell incision (n = 53). For the intraoperative veno-arterial extracorporeal membrane oxygenation support was used. The extracorporeal membrane oxygenation support had to be prolonged in 3 patients into the early postoperative period, two other recipients were bridged to transplant with extracorporeal membrane oxygenation. In the same time period, one combined lung-kidney transplantation was also performed. The distribution of recipients according to the underlying disease was: chronic obstructive pulmonary disease (n = 28); idiopathic pulmonary fibrosis (n = 8); cystic fibrosis (n = 12); primary pulmonary hypertension (n = 2); hystiocytosis-X (n = 1); bronchiectasis (n = 2); lymphangioleiomyomatosis (n = 1); and re-transplantation following bronchiolitis obliterans syndrome (n = 1), respectively. The mean age of recipients was 47.5 ± 15.18 years. The youngest recipient was 13 years old. We unfortunately lost 12 patients on our waiting list. The mean intensive care unit stay was 24.6 ± 18.18 days. Two patients were lost in the early postoperative phase. Tracheostomy was necessary in 13 cases due to the need of prolonged ventilation. 1-year survival of the recipients was 82.96% (until 31. 07. 2018). When looking at the first three years of the program, the case numbers elevated quickly throughout the years which is rather unique when compared to other centres in their starting period. Perioperative mortality and morbidity is comparable with high-volume lung transplantation centres. In the future we would like to increase the number of patients on the waiting list, thus increasing the total number of transplantations performed, and we are also planning to implement the use of the ex vivo lung perfusion system (EVLP) in our program. Orv Hetil. 2018; 159(46): 1859-1868.


Assuntos
Transplante de Pulmão/estatística & dados numéricos , Doadores de Tecidos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Feminino , Humanos , Hipertensão Pulmonar/cirurgia , Masculino , Doença Pulmonar Obstrutiva Crônica/cirurgia , Taxa de Sobrevida
7.
Mol Cancer ; 16(1): 1, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-28093071

RESUMO

BACKGROUND: DNA methylation regulates together with other epigenetic mechanisms the transcriptional activity of genes and is involved in the pathogenesis of malignant diseases including lung cancer. In non-small cell lung cancer (NSCLC) various tumor suppressor genes are already known to be tumor-specifically methylated. However, from the vast majority of a large number of genes which were identified to be tumor-specifically methylated, tumor-specific methylation was unknown so far. Thus, the major aim of this study was to investigate in detail the mechanism(s) responsible for transcriptional regulation of the genes SPAG6 and L1TD1 in NSCLCs. METHODS: We analysed publically available RNA-sequencing data and performed gene expression analyses by RT-PCR. DNA methylation analyses were done by methylation-sensitive high-resolution melt analyses and bisulfite genomic sequencing. We additionally investigated protein expression using immunohistochemistry. Cell culture experiments included tumor cell growth, proliferation, viability as well as colony formation assays. Moreover, we performed xenograft experiments using immunodeficient mice. RESULTS: We observed frequent downregulation of SPAG6 and L1TD1 mRNA expression in primary tumor (TU) samples compared to corresponding non-malignant lung tissue (NL) samples of NSCLC patients. We furthermore observed re-expression of both genes after treatment with epigenetically active drugs in most NSCLC cell lines with downregulated SPAG6 and L1TD1 mRNA expression. Frequent tumor-specific DNA methylation of SPAG6 and L1TD1 was detected when we analysed TU and corresponding NL samples of NSCLC patients. ROC curve analyses demonstrated that methylation of both genes is able to distinguish between TU and NL samples of these patients. Immunohistochemistry revealed a close association between SPAG6/L1TD1 methylation and downregulated protein expression of these genes. Moreover, by performing functional assays we observed reduced cell growth, proliferation and viability of pCMV6-L1TD1 transfected NSCLC cells. In addition, reduced volumes of tumors derived from pCMV6-L1TD1 compared to pCMV6-ENTRY transfected NCI-H1975 cells were seen in a xenograft tumor model. CONCLUSIONS: Overall, our results demonstrate that SPAG6 and L1TD1 are tumor-specifically methylated in NSCLCs and that DNA methylation is involved in the transcriptional regulation of these genes. Moreover, in vitro as well as in vivo experiments revealed tumor-cell growth suppressing properties of L1TD1 in NSCLC cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Proteínas dos Microtúbulos/genética , Proteínas/genética , Transcrição Gênica , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/genética , Bases de Dados Genéticas , Modelos Animais de Doenças , Inativação Gênica , Xenoenxertos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Proteínas dos Microtúbulos/metabolismo , Polimorfismo de Nucleotídeo Único , Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Deleção de Sequência , Carga Tumoral , Ensaio Tumoral de Célula-Tronco
8.
Transpl Int ; 28(3): 297-304, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25387861

RESUMO

In patients awaiting lung transplantation (LTX), adequate gas exchange may not be sufficiently achieved by mechanical ventilation alone if acute respiratory decompensation arises. We report on 20 patients with life-threatening hypercapnia who received extracorporeal CO2 removal (ECCO2-R) by means of the interventional lung assist (ILA®, Novalung) as bridge to LTX. The most common underlying diagnoses were bronchiolitis obliterans syndrome, cystic fibrosis, and idiopathic pulmonary fibrosis, respectively. The type of ILA was pumpless arteriovenous or pump-driven venovenous (ILA activve®, Novalung) in 10 patients each. ILA bridging was initiated in 15 invasively ventilated and five noninvasively ventilated patients, of whom one had to be intubated prior to LTX. Hypercapnia and acidosis were effectively corrected in all patients within the first 12 h of ILA therapy: PaCO2 declined from 109 (70-146) to 57 (45-64) mmHg, P < 0.0001; pH increased from 7.20 (7.06-7.28) to 7.39 (7.35-7.49), P < 0.0001. Four patients were switched to extracorporeal membrane oxygenation due to progressive hypoxia or circulatory failure. Nineteen patients (95%) were successfully transplanted. Hospital and 1-year survival was 75 and 72%, respectively. Bridging to LTX with ECCO2-R delivered by arteriovenous pumpless or venovenous pump-driven ILA is feasible and associated with high transplantation and survival rates.


Assuntos
Dióxido de Carbono/metabolismo , Oxigenação por Membrana Extracorpórea/métodos , Hipercapnia/terapia , Transplante de Pulmão , Insuficiência Respiratória/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Hipercapnia/etiologia , Hipercapnia/metabolismo , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/complicações , Insuficiência Respiratória/metabolismo , Estudos Retrospectivos , Adulto Jovem
9.
Ann Surg Oncol ; 21(3): 946-54, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24281417

RESUMO

BACKGROUND: Pulmonary metastasectomy is an integral part of the interdisciplinary treatment of patients with pulmonary metastases (PMs) from colorectal carcinoma (CRC). Although alterations in the epidermal growth factor receptor (EGFR) pathway are common in CRC, there is still insufficient data regarding PM. We hypothesized that EGFR expression and Kirsten rat sarcoma viral oncogene homolog (KRAS)/BRAF mutations (Mts) might be associated with clinicopathological variables and the outcome in patients undergoing pulmonary metastasectomy. METHODS: In this single-center study, 44 patients undergoing pulmonary metastasectomy from primary CRC were included and prospectively followed up. Tissue specimens of resected PMs were assessed. Restriction fragment length analysis was used for BRAF V600E and KRAS codons 12 and 13 Mt analyses. EGFR expression was evaluated by immunohistochemistry. Patients were followed up in 3-6-month intervals. RESULTS: EGFR expression was evident in 49 % of the PMs, whereas Mts in KRAS and BRAF were detected in 48 and 0 %, respectively. Time to lung-specific recurrence after metastasectomy was significantly decreased in patients with KRAS mutated PMs in univariate (p = 0.013) and multivariate analysis (p = 0.035), whereas EGFR expression had no impact on recurrence free survival. Moreover, KRAS Mts were associated with the number of PMs (p = 0.037) and with the lung as first site of recurrence after metastasectomy (p = 0.047). DISCUSSION: This is the first evaluation of EGFR pathway alterations in the setting of pulmonary metastasectomy. Our data suggest that patients with KRAS Mts are at high risk for early pulmonary recurrence and have a more diffuse pattern of metastasis. These findings may have impact on the therapeutic management of CRC patients with pulmonary spreading.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Metastasectomia , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adulto , Idoso , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Proteínas Proto-Oncogênicas p21(ras) , Taxa de Sobrevida
10.
Carcinogenesis ; 34(3): 513-21, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23172663

RESUMO

DNA methylation is part of the epigenetic gene regulation complex, which is relevant for the pathogenesis of cancer. We performed a genome-wide search for methylated CpG islands in tumors and corresponding non-malignant lung tissue samples of 101 stages I-III non-small cell lung cancer (NSCLC) patients by combining methylated DNA immunoprecipitation and microarray analysis. Overall, we identified 2414 genomic positions differentially methylated between tumor and non-malignant lung tissue samples. Ninety-seven percent of them were found to be tumor-specifically methylated. Annotation of these genomic positions resulted in the identification of 477 tumor-specifically methylated genes of which many are involved in regulation of gene transcription and cell adhesion. Tumor-specific methylation was confirmed by a gene-specific approach. In the majority of tumors, methylation of certain genes was associated with loss of their protein expression determined by immunohistochemistry. Treatment of NSCLC cells with epigenetically active drugs resulted in upregulated expression of many tumor-specifically methylated genes analyzed by gene expression microarrays suggesting that about one-third of these genes are transcriptionally regulated by methylation. Moreover, comparison of methylation results with certain clinicopathological characteristics of the patients suggests that methylation of HOXA2 and HOXA10 may be of prognostic relevance in squamous cell carcinoma (SCC) patients. In conclusion, we identified a large number of tumor-specifically methylated genes in NSCLC patients. Expression of many of them is regulated by methylation. Moreover, HOXA2 and HOXA10 methylation may serve as prognostic parameters in SCC patients. Overall, our findings emphasize the impact of methylation on the pathogenesis of NSCLCs.


Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Metilação de DNA , Neoplasias Pulmonares/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Sequência de Bases , Caderinas/genética , Caderinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Mapeamento Cromossômico , Ilhas de CpG , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Neoplásicos , Estudo de Associação Genômica Ampla , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Curva ROC , Análise de Sequência de DNA , Transcriptoma
11.
Orv Hetil ; 154(22): 868-71, 2013 Jun 02.
Artigo em Húngaro | MEDLINE | ID: mdl-23708988

RESUMO

When conservative treatment fails, lung transplantation often remains the only therapeutic option for patients with end stage parenchymal or vascular lung diseases. According to the statistics of the International Society for Heart and Lung Transplantation, in 2010 more than 3500 lung transplantations have been performed worldwide. The Department of Thoracic Surgery at the University of Vienna is considered to be one of the world's leading lung transplantation centres; in the last year 115, since 1989 more than 1500 lung transplantation procedures under the supervision of Prof. Dr. Walter Klepetko. Similar to other Central-European countries, lung transplantation procedures of Hungarian patients have also been performed in Vienna whithin the framework of a twinning aggreement. However, many crucial tasks in the process, such indication and patient selection preoperative rehabilitation organ procurement and long term follow-up care have been stepwise taken over by the Hungarian team. Although the surgery itself is still preformed in Vienna, professional experience is already available in Hungary, since the majority of Hungarian recipients have been transplanted by hungarian surgeons who are authors of this article the professional and personal requirements of performing lung transplantations are already available in Hungary. The demand of performing lung transplantation in Hungary has been raising since 1999 and it soon reaches the extent which justifies launching of an individual national program. Providing the technical requirements is a financial an organisational issue. In order to proceed, a health policy decision has to be made.


Assuntos
Transplante de Pulmão , Obtenção de Tecidos e Órgãos , Áustria , Hospitais Universitários , Humanos , Hungria , Transplante de Pulmão/métodos , Transplante de Pulmão/tendências , Avaliação de Processos e Resultados em Cuidados de Saúde , Seleção de Pacientes , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Obtenção de Tecidos e Órgãos/organização & administração , Obtenção de Tecidos e Órgãos/tendências
12.
Transplant Proc ; 55(3): 697-700, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36935335

RESUMO

BACKGROUND: The main causes of early respiratory failure after lung transplantation include primary graft dysfunction (PGD), acute rejection, and infection. This report describes a case of unclear early respiratory failure after bilateral lung transplantation for extensive COVID-19-induced acute respiratory distress syndrome (ARDS). METHODS: We reviewed the patient file to investigate the course of the functional decline and evaluate reasons for early graft failure. Analyzed data included crossmatching results, biopsy results, HLA antibodies testing, bronchoalveolar lavages, respiratory parameters, and medications. RESULTS: After an initial excellent early postoperative course, the patient developed progressive respiratory failure, making re-implantation of extracorporeal membrane oxygenation (ECMO) support necessary. An extensive diagnostic workup revealed no signs of infection or rejection. Because the patient showed no signs of improvement with any treatment, lung-protective ventilation with the intermittent prone position was initiated. The patient's respiratory situation and bilateral opacities slowly improved over the next few weeks, and ECMO support was eventually discontinued. CONCLUSION: With no evidence of PGD, rejection, or infection, recurrent ARDS caused by a systemic immunologic process was seen as the only plausible cause for the patient's respiratory failure after lung transplantation. The fact that ARDS can develop extrapulmonarily, without direct viral or bacterial damage, makes us conclude that the preceding systemic activation and recruitment of immune cells by the primarily injured lung could potentially lead to the recurrence of ARDS even if the injured organ is removed.


Assuntos
COVID-19 , Transplante de Pulmão , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Humanos , COVID-19/complicações , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Pulmão , Transplante de Pulmão/efeitos adversos , Insuficiência Respiratória/complicações
13.
Eur Respir J ; 40(2): 462-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22362858

RESUMO

Lung transplantation in adults is an accepted therapeutic option, whereas there is ongoing debate on its positive impact on survival in children. We report our experience of the first 20 yrs of paediatric lung transplantation at a single centre in Austria. Patient survival, organ survival and freedom from bronchiolitis obliterans were estimated by Kaplan-Meier curves. Pre- and post-transplant parameters were assessed and their influence on patient and organ survival evaluated by univariate tests and stepwise multivariate analyses. A total of 55 transplantations were performed in 43 patients. 1- and 5-yr patient survival rates were 72.1% and 60.6%, respectively, and 52.6% of patients were found to be free from bronchiolitis obliterans syndrome at 5 yrs post-transplant. Analysing different eras of transplantation suggests an improvement over the years with a 5-yr survival rate of 70.6% in the second decade. A positive effect of pre-transplant diabetes mellitus and immunosuppression was found with the newer drug tacrolimus, and a negative effect of pre-transplant in-hospital admission was reported. A high rate of successful re-transplantation prolonged total patient survival.


Assuntos
Bronquiolite Obliterante/terapia , Fibrose Cística/terapia , Transplante de Pulmão/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Resultado do Tratamento , Adulto Jovem
14.
Ann Thorac Surg ; 114(3): 1050-1054, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35504359

RESUMO

PURPOSE: Dual-lumen extracorporeal membrane oxygenation (ECMO) cannulation is considered technically challenging and harbors the risk of potential life-threatening complications during cannulation. Dual-lumen cannula insertion is performed under either ultrasound or fluoroscopy guidance. Both techniques have significant disadvantages, such as examiner dependence or the necessity for transportation of the patient from the intensive care unit to the operating room. DESCRIPTION: Digital, mobile x-ray devices provide a novel, examiner-independent imaging modality for bedside dual-lumen ECMO cannulation. EVALUATION: From November 2019 to November 2021, 23 dual-lumen cannulations were performed in 20 patients at the Department of Thoracic Surgery, Medical University of Vienna. Twelve of 23 (52.2%) were inserted in the intensive care unit using a mobile x-ray device. The remaining patients (47.8%) were cannulated in the operating room with conventional fluoroscopy guidance. In none of the procedures did cardiovascular injuries occur. Insertion site bleeding was the most common ECMO-related complication (n = 2). CONCLUSIONS: Dual-lumen cannulation using sequential x-rays can be performed safely. Especially for infectious patients or patients who require an awake ECMO, this technique overcomes disadvantages of established imaging modalities.


Assuntos
Cateterismo , Oxigenação por Membrana Extracorpórea , Raios X , Oxigenação por Membrana Extracorpórea/instrumentação , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Estudos Retrospectivos , Ultrassonografia
15.
Ann Thorac Surg ; 112(6): e455-e457, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33811886

RESUMO

Lung transplantation is an established treatment for a variety of end-stage lung diseases; however, chest wall deformities such as an asymmetric pectus excavatum are often considered a contraindication for lung transplantation. Consequently, the published experience of lung transplants and simultaneous chest wall reconstruction is limited to a few case reports. This article aims to provide a detailed description of surgical steps as well as technical challenges and pitfalls of lung transplantation with a simultaneous modified Ravitch procedure. Exemplary technical aspects will be discussed for a pediatric patient in whom such a combined procedure resulted in an excellent outcome.


Assuntos
Tórax em Funil/cirurgia , Transplante de Pulmão , Proteinose Alveolar Pulmonar/cirurgia , Criança , Feminino , Tórax em Funil/complicações , Humanos , Procedimentos Ortopédicos/métodos , Proteinose Alveolar Pulmonar/complicações , Procedimentos de Cirurgia Plástica/métodos
16.
J Heart Lung Transplant ; 40(1): 33-41, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33246712

RESUMO

BACKGROUND: The evaluation of donor lungs heavily depends on the subjective judgment of the retrieval surgeon. As a consequence, acceptance rates vary significantly among transplant centers. We aimed to determine donor ventilation parameters in a prospective study and test if they could be used as objective quality criteria during organ retrieval. METHODS: A prospective evaluation of lung donors was performed in 3 transplant centers. Ventilation parameters were collected at the time of retrieval using a standardized ventilation protocol. Recipient length of mechanical ventilation (LMV) was defined as the primary end point, and collected data was used to build linear models predicting LMV. RESULTS: In total, 166 donors were included in this study. Median LMV after transplantation was 32 hours (interquartile range: 20-63 hours). Peak inspiratory pressure and dynamic compliance (Cdyn) at the time of retrieval, but not the partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio, correlated with recipient LMV in Spearman correlations (r = 0.280, p = 0.002; r = -0.245, p = 0.003; and r = 0.064, p = 0.432, respectively). Linear models were built to further evaluate the impact of donor ventilation parameters on LMV. The first model was based on donor P/F ratio, donor age, donor intubation time, donor smoking history, donor partial pressure of carbon dioxide, aspiration, chest trauma, and pathologic chest X-ray. This model performed poorly (multiple R-squared = 0.063). In a second model, donor ventilation parameters were included, and Cdyn was identified as the strongest predictor for LMV. The third model was extended by recipient factors, which significantly improved the robustness of the model (multiple R-squared = 0.293). CONCLUSION: In this prospective evaluation of donor lung parameters, currently used donor quality criteria poorly predicted recipient LMV. Our data suggest that Cdyn is a strong donor-bound parameter to predict short-term graft performance; however, recipient factors are similarly relevant.


Assuntos
Transplante de Pulmão , Pulmão/fisiopatologia , Respiração Artificial/métodos , Doadores de Tecidos , Adulto , Fatores Etários , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
17.
Transpl Int ; 23(7): e32-4, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20477998

RESUMO

Recently, the applicability of lungs from drowned victims for transplantation has been anecdotically described in literature. However, no data exist about hazards or limitations. Herein, we describe a case of lung transplantation from a submersion victim and the subsequent development of an Aeromonas hydrophila infection in the implanted organ. Based on this case we propose standard procedures, which should be followed when considering drowned donor lungs, in order to minimize risks for infectious complications.


Assuntos
Aeromonas hydrophila , Líquido da Lavagem Broncoalveolar/microbiologia , Afogamento , Infecções por Bactérias Gram-Negativas/etiologia , Transplante de Pulmão/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/cirurgia , Infecções Estafilocócicas/etiologia , Adulto , Aeromonas hydrophila/isolamento & purificação , Seleção do Doador/métodos , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Transplante de Pulmão/métodos , Complicações Pós-Operatórias/etiologia , Infecções Estafilocócicas/tratamento farmacológico , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
18.
Clin Cancer Res ; 15(5): 1741-6, 2009 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-19240177

RESUMO

PURPOSE: The newly identified bone marrow-derived cell population, called lymphatic/vascular endothelial progenitor cells (LVEPC), has been shown to contribute to lymph capillary growth in experimental tumor systems. The clinical significance of these cells has not yet been investigated in a human malignancy. Our aim was to study whether peripheral blood circulating LVEPCs participate in the progression of human small cell lung cancer (SCLC). EXPERIMENTAL DESIGN: A total of 88 patients with limited-stage SCLC and 32 tumor-free control subjects were included. Peripheral blood circulating LVEPC labeled with CD34 and vascular endothelial growth factor receptor-3 (VEGFR3) antibodies and the serum levels of the key lymphangiogenic molecule VEGF-C were measured by flow cytometry and ELISA, respectively. RESULTS: CD34-positive/VEGFR3-positive LVEPC levels were significantly increased in patients (versus controls; P<0.01), and there was also a significant relationship between LVEPC counts and lymph node metastasis (P<0.01). High pretreatment circulating LVEPC numbers correlated with poor overall survival (P<0.01). Although we observed significantly elevated VEGF-C concentrations in patients (versus controls; P<0.01), there was no significant correlation between VEGF-C and LVEPC levels. Moreover, no significant differences in peripheral blood VEGF-C levels were seen between patients subgrouped by clinicopathologic variables including tumor and lymph node stages and survival. CONCLUSIONS: Peripheral blood levels of bone marrow-derived LVEPCs are significantly increased in patients with SCLC and correlate with lymphatic involvement and prognosis. This is the first study that shows evidence of increased numbers of circulating LVEPC in patients with a malignant tumor.


Assuntos
Células Endoteliais/metabolismo , Neoplasias Pulmonares/metabolismo , Vasos Linfáticos/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Células-Tronco/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Medula Óssea/metabolismo , Medula Óssea/patologia , Estudos de Casos e Controles , Progressão da Doença , Células Endoteliais/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Metástase Linfática , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Células-Tronco/patologia , Taxa de Sobrevida , Fator C de Crescimento do Endotélio Vascular/sangue
19.
Wien Klin Mag ; 23(4): 168-173, 2020.
Artigo em Alemão | MEDLINE | ID: mdl-32837601

RESUMO

The pandemic from the SARS-CoV­2 Virus is currently challenging health care systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe work environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develops respiratory or circulatory failure that is refractory to conventional therapies, it is of utmost importance to clearly define criteria for the use of ECMOs in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.

20.
Wien Klin Wochenschr ; 132(21-22): 671-676, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32621065

RESUMO

The pandemic from the SARS-CoV­2 virus is currently challenging healthcare systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe working environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develop respiratory or circulatory failure that is refractory to conventional treatment, it is of utmost importance to clearly define criteria for the use of ECMO in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Oxigenação por Membrana Extracorpórea , Pandemias , Pneumonia Viral , Idoso , COVID-19 , Criança , Humanos , SARS-CoV-2
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