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1.
Int J Artif Organs ; : 0, 2017 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-29027193

RESUMO

BACKGROUND: Studies have shown that survival after lung transplantation is impaired if extracorporeal membrane oxygenation (ECMO) support is implemented. We investigated the outcome and potential independent risk factors on survival in recipients undergoing lung transplantation with intraoperative ECMO support. MATERIALS AND METHODS: Medical records of recipients were retrospectively evaluated (January 2000-December 2014). Retransplantation and bridge to transplantation on ECMO were excluded. Recipients (n = 291) were divided into 2 groups: those who needed intraoperative ECMO support (Group 1, n = 134) and those who did not receive intraoperative ECMO support (Group 2, n = 157). Independent risk factors were identified by a stepwise backward regression analysis. RESULTS: 1-year survival was 84.2% in Group 1 vs. 90.4% in Group 2, and 5-year survival was 52.8% in Group 1 vs. 70.5% in Group 2 (p = 0.002). Multivariate analysis indicated that recipient age (p = 0.001), renal replacement therapy (p = 0.001) and intraoperative ECMO support (p = 0.03) were significant risk factors for overall survival. The rate of postoperative early surgical complications was comparable between the two groups (p = 0.09). The number of patients requiring renal replacement therapy and experiencing late pulmonary complications was significantly higher in Group 1 (p = 0.02). CONCLUSIONS: Our data showed that lung transplantation with intraoperative ECMO support is associated with poor outcomes.

2.
Biomed Res Int ; 2015: 635748, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25756049

RESUMO

INTRODUCTION: We investigated the expression of microRNAs and mRNAs in pleural tissues from patients with either malignant pleural mesothelioma or benign asbestos-related pleural effusion. METHODS: Fresh frozen tissues from a total of 18 malignant pleural mesothelioma and 6 benign asbestos-related pleural effusion patients were studied. Expression profiling of mRNA and microRNA was performed using standard protocols. RESULTS: We discovered significant upregulation of multiple microRNAs in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Hsa-miR-484, hsa-miR-320, hsa-let-7a, and hsa-miR-125a-5p were able to discriminate malignant from benign disease. Dynamically regulated mRNAs were also identified. MET was the most highly overexpressed gene in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Integrated analyses examining microRNA-mRNA interactions suggested multiple altered targets within the Notch signaling pathway. CONCLUSIONS: Specific microRNAs and mRNAs may have diagnostic utility in differentiating patients with malignant pleural mesothelioma from benign asbestos-related pleural effusion. These studies may be particularly helpful in patients who reside in a region with a high incidence of mesothelioma.


Assuntos
Neoplasias Pulmonares/genética , Mesotelioma/genética , MicroRNAs/biossíntese , Derrame Pleural/genética , RNA Mensageiro/biossíntese , Idoso , Idoso de 80 Anos ou mais , Amianto/toxicidade , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/patologia , Mesotelioma Maligno , MicroRNAs/genética , Pessoa de Meia-Idade , Derrame Pleural/induzido quimicamente , Derrame Pleural/patologia , Proteínas Proto-Oncogênicas c-met/biossíntese , Proteínas Proto-Oncogênicas c-met/genética , RNA Mensageiro/genética
3.
J Thorac Oncol ; 9(12): 1763-71, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25226425

RESUMO

INTRODUCTION: Pulmonary carcinoid tumors account for approximately 5% of all lung malignancies in adults, and comprise 30% of all carcinoid tumors. There are limited reagents available to study these rare tumors, and consequently no major advances have been made for patient treatment. We report the generation and characterization of human pulmonary carcinoid tumor cell lines to study underlying biology, and to provide models for testing novel chemotherapeutic agents. METHODS: Tissue was harvested from three patients with primary pulmonary typical carcinoid tumors undergoing surgical resection. The tumor was dissociated and plated onto dishes in culture media. The established cell lines were characterized by immunohistochemistry, Western blotting, and cell proliferation assays. Tumorigenicity was confirmed by soft agar growth and the ability to form tumors in a mouse xenograft model. Exome and RNA sequencing of patient tumor samples and cell lines was performed using standard protocols. RESULTS: Three typical carcinoid tumor lines grew as adherent monolayers in vitro, expressed neuroendocrine markers consistent with the primary tumor, and formed colonies in soft agar. A single cell line produced lung tumors in nude mice after intravenous injection. Exome and RNA sequencing of this cell line showed lineage relationship with the primary tumor, and demonstrated mutations in a number of genes related to neuronal differentiation. CONCLUSION: Three human pulmonary typical carcinoid tumor cell lines have been generated and characterized as a tool for studying the biology and novel treatment approaches for these rare tumors.


Assuntos
Tumor Carcinoide/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Animais , Tumor Carcinoide/patologia , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Feminino , Xenoenxertos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus
4.
Eur J Cardiothorac Surg ; 43(2): 288-92, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22851662

RESUMO

OBJECTIVES: The resection of thymic tumours requires completeness and may be technically challenging due to the anatomical proximity of the delicate mediastinal structures. An open approach by sternotomy is still recommended in all cases with locally extended disease. Video-assisted thoracoscopic surgery is feasible, but limited by the two-dimensional vision and the impaired mobility of the instruments. We evaluated the da Vinci® Surgical System for the resection of various mediastinal pathologies, particularly thymomas. METHODS: Among 105 patients operated on by robotic assisted thoracoscopic surgery (RATS) for mediastinal tumours between 27 August 2004 and 12 July 2011, 20 patients with thymomas were studied prospectively. Of these, 10 males with a median age of 53 years, with a well-circumscribed thymic lesion on computed tomography (CT) and a diameter of <6 cm were resected by RATS alone, and selected ones (n = 3), with a diameter of >6 cm, underwent a hybrid procedure with a contralateral thoracotomy on the side of the main tumour extension. A regular follow-up with chest CT scans was performed every 6 months. RESULTS: Thymoma resection was complete in all patients. Partial pericardial resection was needed in five and pulmonary resection in two patients. Eighty-five percent of patients had an R0 resection. Histological classifications included thymoma WHO type A (n = 3), AB (n = 8), B1-2 (n = 5) and B3 (n = 4). All B3 thymomas received adjuvant radiotherapy. No intraoperative complications occurred. The median hospitalization time was 5 days (range 2-14 days). There were no local, but two pleural, recurrences. After a median observation time of 26 months, 19 patients (95%) are alive. CONCLUSIONS: Well-circumscribed thymomas can be safely and completely resected with the da Vinci® Surgical System with excellent short- and mid-term outcomes. Selected tumours with large diameters may be resectable using a hybrid procedure combining RATS with a thoracotomy.


Assuntos
Robótica , Cirurgia Torácica Vídeoassistida/métodos , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Estudos de Coortes , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Testes de Função Respiratória , Timoma/patologia , Neoplasias do Timo/patologia , Resultado do Tratamento
5.
BMC Cancer ; 12: 615, 2012 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-23259649

RESUMO

BACKGROUND: Asbestos is the main cause of MPM in industrialized countries. Even since asbestos is banned in most developed countries, the peak wave of MPM incidence is anticipated for the next years due to the long latency of asbestos induced MPM. MPM patients not eligible for surgical procedures like decortication or pleuro-pneumectomie have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation. METHODS/DESIGN: This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x106 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor recognizing FAP which serves as target structure in MPM. At day 0 of the protocol, re-directed T cells will be injected in the pleural effusion and patients will be monitored for 48h under intermediate care conditions. AE, SAE, SADR and SUSAR will be monitored for 35 days and evaluated by an independent safety board to define any dose limiting toxicity (DLT). No further patient can be treated before the previous patient passed day 14 after T cell transfer. The protocol will be judged as save when no DLT occurred in the first 3 patients, or 1 DLT in 6 patients. Secondary objectives are feasibility and immune monitoring. DISCUSSION: Adoptive T cell transfer is a new and rapidly expanding branch of immunotherapies focusing on cancer treatment. Recently, objective responses could be observed in patients with chronic lymphatic leukemia treated with adoptively transferred CD19-specific re-directed T cells. The choice of the target antigen determines the possible on-target off-tissue toxicity of such approaches. There are reports of severe toxicity in patients who received T cells intravenously due to unexpected expression of the target antigen (on-target) in other tissues than the tumor (off-tissue). To minimize the risk of on-target off-tissue toxicity and to maximize the on-target anti-tumor effect we propose a clinical protocol with loco-regional administration of re-directed T cells. FAP-specific T cells will be directly injected in the pleural effusion of patients with MPM. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01722149).


Assuntos
Gelatinases/metabolismo , Imunoterapia Adotiva/métodos , Proteínas de Membrana/metabolismo , Mesotelioma/terapia , Neoplasias Pleurais/terapia , Serina Endopeptidases/metabolismo , Linfócitos T/imunologia , Adolescente , Transferência Adotiva , Adulto , Idoso , Citocinas/metabolismo , Endopeptidases , Feminino , Humanos , Masculino , Mesotelioma/imunologia , Mesotelioma/metabolismo , Pessoa de Meia-Idade , Derrame Pleural , Derrame Pleural Maligno , Neoplasias Pleurais/imunologia , Neoplasias Pleurais/metabolismo , Adulto Jovem
6.
BMC Genomics ; 13: 204, 2012 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-22646479

RESUMO

BACKGROUND: Bronchopulmonary dysplasia is a chronic lung disease of premature neonates characterized by arrested pulmonary alveolar development. There is increasing evidence that microRNAs (miRNAs) regulate translation of messenger RNAs (mRNAs) during lung organogenesis. The potential role of miRNAs in the pathogenesis of BPD is unclear. RESULTS: Following exposure of neonatal mice to 80% O2 or room air (RA) for either 14 or 29 days, lungs of hyperoxic mice displayed histological changes consistent with BPD. Comprehensive miRNA and mRNA profiling was performed using lung tissue from both O2 and RA treated mice, identifying a number of dynamically regulated miRNAs and associated mRNA target genes. Gene ontology enrichment and pathway analysis revealed that hyperoxia modulated genes involved in a variety of lung developmental processes, including cell cycle, cell adhesion, mobility and taxis, inflammation, and angiogenesis. MiR-29 was prominently increased in the lungs of hyperoxic mice, and several predicted mRNA targets of miR-29 were validated with real-time PCR, western blotting and immunohistochemistry. Direct miR-29 targets were further validated in vitro using bronchoalveolar stem cells. CONCLUSION: In newborn mice, prolonged hyperoxia induces an arrest of alveolar development similar to that seen in human neonates with BPD. This abnormal lung development is accompanied by significant increases in the levels of multiple miRNAs and corresponding decreases in the levels of predicted mRNA targets, many of which have known or suspected roles in pathways altered in BPD. These data support the hypothesis that dynamic regulation of miRNAs plays a prominent role in the pathophysiology of BPD.


Assuntos
Hiperóxia , Lesão Pulmonar/genética , Lesão Pulmonar/metabolismo , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/patologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo
7.
Eur J Cardiothorac Surg ; 40(5): 1151-6, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21450488

RESUMO

OBJECTIVE: Complete surgical resection with pathologic negative margin is associated with the best prognosis in early-stage non-small-cell lung cancer (NSCLC). However, the impact of the length of the bronchial margin remains unknown. This study aimed to determine whether an increased bronchial resection margin length is correlated with an improved disease-free and overall survival rate. METHODS: A total of 3936 consecutive pulmonary resections were performed between 25 June 1992 and 31 December 2007 at Mayo Clinic Rochester. A subset consisting of 496 patients with completely resected lesions (R0-resection), and a documented bronchial margin length was analyzed retrospectively. RESULTS: There were 340 men (68.5%) and 156 women (31.5%), with a mean age of 65.9±10.6 years. All patients underwent anatomic lobectomy or larger resection. Final pathology confirmed complete resection without microscopic residual tumor (R0-resection) in all patients. Mean length of the bronchial resection margin was 23.3±15.9mm. Overall, 190 patients (38.3%) suffered from disease recurrence with local recurrence in 35 patients, distant recurrence in 101, and both local and distant recurrence in 54 patients. Overall 5-year and 10-year local recurrence-free survival was 72.5% (95% confidence interval (CI): 67.3-78.1) and 68.0% (95% CI: 62.1-74.4), distant recurrence free survival 61.0% (95% CI: 55.8-66.6) and 52.9% (95% CI: 46.7-60.1) and overall survival 50.0% (95% CI: 45.1-55.3) and 28.8% (95% CI: 23.8-34.7). Tumor size and N-stage were associated with a worse prognosis in terms of local and distant recurrence, as well as survival (p<0.05). Histology was not significantly associated with local recurrence (p=0.28), though adenocarcinoma relative to squamous cell carcinoma was associated with an increased risk of distant recurrence (p<0.01). There was no significant association between type of surgical resection and local (p=0.37) or distant recurrence (p=0.37). Neither local (p=0.56) or distant recurrence (p=0.46), nor survival (p=0.54) was associated with the bronchial margin length. In multivariate models including age, N-stage, and gender there were no significant overall associations of margin length (≤5, 6-10, 11-15, 16-20, >20mm) and local recurrence (p=0.51), distant recurrence (p=0.33), or survival (p=0.75). CONCLUSIONS: When complete surgical resection is achieved, the extent of the bronchial margin has no clinically relevant impact on disease-free and overall survival in NSCLC.


Assuntos
Brônquios/cirurgia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Métodos Epidemiológicos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasia Residual , Pneumonectomia/métodos , Prognóstico , Resultado do Tratamento
8.
Semin Respir Crit Care Med ; 32(1): 69-77, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21500126

RESUMO

Lung cancer continues to be the most frequent cancer-related cause of death in the United States and throughout the world. Surgical resection is currently the most effective treatment in early-stage non-small-cell lung cancer, and historically the only treatment approach achieving significant cure rates. In advanced disease, therapeutic approaches involving chemotherapy and/or radiation therapy are utilized to improve prognosis, either as part of a neoadjuvant treatment approach followed by surgical resection or as definitive treatment alone. The role of surgery in locally advanced or metastatic non-small-cell lung cancer remains controversial, with more studies required to further refine the application of modern surgical techniques. For any treatment approach, thorough preoperative staging as well as careful patient selection are essential to assess the benefits and risks involved for the patient. Surgical management of early-stage non-small-cell lung cancer and its role in more advanced disease are discussed in this review.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante/métodos , Metástase Neoplásica , Estadiamento de Neoplasias , Seleção de Pacientes , Prognóstico , Estados Unidos/epidemiologia
9.
Cancer J ; 17(1): 11-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21263261

RESUMO

Optimal management of non-small cell lung cancer requires treatment approach to be tailored to both the particular disease stage and the overall health and functional status of the patient. Even though surgical resection by means of an anatomic lobectomy remains the treatment of choice with the goal of cure for early-stage lung cancer, it is an invasive procedure with associated morbidity and mortality. Although these risks continue to decrease in the modern era with improvements in surgical technique and perioperative management, the risks are elevated in patients with associated medical comorbidities. As a consequence, patients at potentially increased or high risk for surgical lobectomy need to be identified by a structured preoperative assessment. This has gained increasing importance, given the emergence of alternative treatment approaches such as minimally invasive surgery, less extensive pulmonary resection, and stereotactic body radiation therapy. We review the clinical approach to suspected early-stage lung cancer based on a tumor and patient-centered stratification of risk and benefit.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Assistência Centrada no Paciente , Cuidados Pré-Operatórios
10.
Innovations (Phila) ; 6(4): 237-42, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22437981

RESUMO

OBJECTIVE: Robotic-assisted surgery is not widely accepted for general thoracic surgical procedures, and the technical advantages, cost effectiveness, and patient benefit are in question. Few reports have been published to date regarding clinical experience with this technology. We describe our first consecutive case experience with robotic-assisted lung resection. METHODS: A total of 23 robotic-assisted lung resections were performed from December 1, 2008, to September 30, 2010. Patients were selected on the basis of being candidates for a minimally invasive approach to their lung resection, including criteria such as known or suspected early-stage nonsmall-cell lung cancer, no prior thoracotomy, no neoadjuvant therapy, and a body mass index (BMI) less than 40 kg/cm². Data on patient characteristics and perioperative results were collected retrospectively. RESULTS: Overall 90-day mortality was 0%. The total postoperative complication rate was 39%. Conversion of the robotic-assisted procedure to a video-assisted procedure was necessary in four patients (17%), and to a thoracotomy in one patient (4%). We assessed operative time, chest tube duration, and length of hospital stay. Comparison to published outcomes from the Society of Thoracic Surgeons database demonstrated comparable outcomes to standard approaches. CONCLUSIONS: Robotic-assisted lung resection is safe and feasible, with comparable short-term outcomes to published results from video-assisted or open approaches.

11.
Eur J Cardiothorac Surg ; 39(5): 726-31, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21084198

RESUMO

OBJECTIVE: Lung transplantation is a standard treatment option for patients with end-stage lung disease. Lung transplantation in the elderly is controversial due to concerns over anticipated increased surgical risks, inferior long-term outcomes and proper stewardship in allocating limited donor organs. With demographic trends showing an increasing proportion of patients over 60 years old, we evaluated our outcomes with lung transplantation in this older cohort. METHODS: Between January 1990 and July 2009, 142 patients underwent lung transplantation at our institution. A total of 15 patients receiving heart/lung transplantation and one patient declining research participation were excluded. As many as 126 patients were analyzed in two groups: <60 and ≥ 60 years old. RESULTS: There were 65 females (52%) and 61 males (48%). A total of 53 patients (42%) underwent bilateral sequential lung transplantation and 73 patients single-lung transplantation (58%). Median age at transplantation was 55.3 years (range, 21.6-73.1 years) with 94 patients <60 years (75%) and 32 patients ≥ 60 years (25%). Median follow-up was 4.3 years (range, 0-17.8 years). Overall survival at 30 days was 93.7% with no difference between age groups (p=0.95). There was no difference between the groups for in-hospital, postoperative complications (p=0.86), or unplanned readmission rates within 90 days of the hospitalization (p=0.26). Postoperative pulmonary function (forced expiratory volume in 1s (FEV1) % predicted) at transplant, 4 weeks, 3 months, and 6 months after transplantation was not different between groups (p=0.93). No difference in long-term survival was observed (p=0.59), with 5-year survival of 52.2% for patients <60 years and 47.3% for patients ≥ 60 years. Overall, 20 patients developed bronchiolitis obliterans syndrome and 13 posttransplant lymphoproliferative disease, which was not statistically different between age groups (p=0.87, p=0.37, respectively). CONCLUSION: Increased age of 60 years and greater, in highly selected patients, does not appear to have a significant impact on the short- or long-term outcome in patients undergoing lung transplantation. Judicious selection of older patients, who are otherwise excellent candidates for lung transplantation, remains a reasonable option.


Assuntos
Pneumopatias/cirurgia , Transplante de Pulmão , Adulto , Fatores Etários , Idoso , Bronquiolite Obliterante/etiologia , Creatinina/sangue , Volume Expiratório Forçado/fisiologia , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Rim/fisiologia , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/fisiologia , Pessoa de Meia-Idade , Seleção de Pacientes , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
12.
Expert Rev Respir Med ; 4(4): 499-508, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20658911

RESUMO

Genomic technology continues to advance, and data derived from non-small-cell lung cancer (NSCLC) tumor specimens in conjunction with clinical information are accumulating at an exponential rate. Application of this information to clinical practice for the treatment of patients with NSCLC lags behind the promise of individualized patient management based on genomic medicine. Testing treatment decisions based on genomic information in cancer clinical trials is only now being addressed. How best to incorporate the myriad of potentially available molecular diagnostics into treatment algorithms is not yet clear. Many hurdles and much work remain for the development of true, individualized treatment strategies for NSCLC based on molecular staging. Here we review some of the successes, frustrations and obstacles that exist to further progress in the field.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Testes Genéticos , Genômica , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Estadiamento de Neoplasias , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico
13.
PLoS One ; 5(5): e10854, 2010 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-20520778

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are known to be important regulators of both organ development and tumorigenesis. MiRNA networks and their regulation of messenger RNA (mRNA) translation and protein expression in specific biological processes are poorly understood. METHODS: We explored the dynamic regulation of miRNAs in mouse lung organogenesis. Comprehensive miRNA and mRNA profiling was performed encompassing all recognized stages of lung development beginning at embryonic day 12 and continuing to adulthood. We analyzed the expression patterns of dynamically regulated miRNAs and mRNAs using a number of statistical and computational approaches, and in an integrated manner with protein levels from an existing mass-spectrometry derived protein database for lung development. RESULTS: In total, 117 statistically significant miRNAs were dynamically regulated during mouse lung organogenesis and clustered into distinct temporal expression patterns. 11,220 mRNA probes were also shown to be dynamically regulated and clustered into distinct temporal expression patterns, with 3 major patterns accounting for 75% of all probes. 3,067 direct miRNA-mRNA correlation pairs were identified involving 37 miRNAs. Two defined correlation patterns were observed upon integration with protein data: 1) increased levels of specific miRNAs directly correlating with downregulation of predicted mRNA targets; and 2) increased levels of specific miRNAs directly correlating with downregulation of translated target proteins without detectable changes in mRNA levels. Of 1345 proteins analyzed, 55% appeared to be regulated in this manner with a direct correlation between miRNA and protein level, but without detectable change in mRNA levels. CONCLUSION: Systematic analysis of microRNA, mRNA, and protein levels over the time course of lung organogenesis demonstrates dynamic regulation and reveals 2 distinct patterns of miRNA-mRNA interaction. The translation of target proteins affected by miRNAs independent of changes in mRNA level appears to be a prominent mechanism of developmental regulation in lung organogenesis.


Assuntos
Redes Reguladoras de Genes/genética , Pulmão/embriologia , Pulmão/metabolismo , MicroRNAs/genética , Organogênese/genética , Animais , Cromossomos de Mamíferos/genética , Análise por Conglomerados , Regulação da Expressão Gênica no Desenvolvimento , Genoma/genética , Camundongos , MicroRNAs/metabolismo , Análise de Componente Principal , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Fatores de Tempo
14.
Eur J Cardiothorac Surg ; 37(4): 807-13, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19900819

RESUMO

OBJECTIVE: As part of our ongoing quality improvement effort, we evaluated our conventional approach to post-oesophagectomy management by comparing it to an alternative postoperative management pathway. METHODS: Medical records from 386 consecutive patients undergoing oesophagectomy with gastric conduit for oesophageal cancer or Barrett's oesophagus with high-grade dysplasia were analysed retrospectively (July 2004 to August 2008). The conventional pathway involved a routine radiographic contrast swallow study at 5-7 days after oesophagectomy with initiation of oral intake if no leak was detected. In the alternative pathway, a feeding jejunostomy was placed for enteral feeding and used exclusively until oral intake was gradually initiated at home at 4 weeks after oesophagectomy. No contrast swallow was obtained in the alternative pathway group unless indicated by clinical suspicion of an anastomotic leak. Each group was analysed on an intention-to-treat basis with respect to anastomotic leak rates, length of hospitalisation, re-admission and other complications. RESULTS: A total of 276 (72%) patients underwent conventional postoperative management, 110 (28%) followed the alternative pathway. Patient characteristics were similar in both the groups. The anastomotic leak rate was lower in the alternative pathway with three clinically significant leaks (2.7%) versus 33 in the conventional pathway (12.0%; p=0.01). Among patients undergoing a radiographic contrast swallow examination, a false-negative rate of 5.8% was observed. The swallow study of 14 patients (5.9%) was complicated by aspiration of oral contrast. Postoperatively, 7.3% of patients suffered from pneumonia. There were no significant differences overall in postoperative pulmonary or cardiac complications associated with either pathway. Median length of hospitalisation was 2 days shorter for the alternative pathway (7 days) than the conventional pathway (9 days; p<0.001). There was no significant difference in unplanned re-admission rates. CONCLUSION: An alternative postoperative pathway following oesophagectomy involving delayed oral intake and avoidance of a routine contrast swallow study is associated with a shortened length of hospitalisation without a higher risk of complication after hospital discharge.


Assuntos
Esôfago de Barrett/cirurgia , Neoplasias Esofágicas/cirurgia , Cuidados Pós-Operatórios/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/efeitos adversos , Procedimentos Clínicos , Nutrição Enteral , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos
15.
Interact Cardiovasc Thorac Surg ; 9(5): 780-3, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19671580

RESUMO

Commonly used extracorporeal membrane oxygenation (ECMO) systems for cardiac support are limited by bleeding complications, especially after surgery in the adult patient. Recently, we have switched from the use of a conventional ECMO system to a miniature-circuit including a centrifugal pump and the Novalung membrane ventilator (iLA). This system allows us to administer less heparin compared to the conventional system. Between January and August 2007, 1469 patients underwent cardiac surgery at our center, of which 18 patients (1.2%) required temporary postoperative ECMO system support. Surgical procedures in these patients included coronary artery bypass grafting (CABG) surgery (n=5), valvular replacement (n=2), aortic surgery (n=2), cardiac transplantation (n=5), and other procedures (n=3). The mean age of the 18 patients was 50+/-15 years (n=13 male) with a mean duration of ECMO system support of 4.3 days (range: <1 to 14 days). Twelve patients (67%) were successfully weaned from ECMO system. The 30-day survival was 44% with a hospital mortality of 61%. Re-thoracotomy for bleeding was necessary in six patients (33%) under ECMO system support. In summary, the miniature ECMO system circuit seems to be suitable for middle-term cardiac support and is associated with a low rate of bleeding complications.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Oxigenação por Membrana Extracorpórea/instrumentação , Insuficiência Cardíaca/terapia , Coração Auxiliar , Adulto , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Desenho de Equipamento , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Insuficiência Cardíaca/etiologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Miniaturização , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/cirurgia , Reoperação , Estudos Retrospectivos , Toracotomia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Mayo Clin Proc ; 84(6): 509-13, 2009 06.
Artigo em Inglês | MEDLINE | ID: mdl-19483167

RESUMO

OBJECTIVE: To review our experience with video-assisted thoracoscopic (VATS) lobectomy with respect to morbidity, mortality, and short-term outcome. PATIENTS AND METHODS: VATS lobectomies were performed in 56 patients between July 6, 2006, and February 26, 2008. Two patients declined consent for research participation and were excluded. Clinical data for 54 patients were collected from medical records and analyzed retrospectively. RESULTS: The studied cohort included 19 men (35%) and 35 women (65%) with a median age of 67.5 years (minimum-maximum, 21-87 years; interquartile range [IQR], 59-74 years). Median duration of operation for VATS lobectomy was 139 minutes (minimum-maximum, 78-275 minutes; IQR, 121-182 minutes). Two cases (4%) required conversion to open lobectomy. Median time to chest tube removal was 2 days (minimum-maximum, 1-12 days; IQR, 1.3-3.8 days). Median length of stay was 4 days (minimum-maximum, 1-12 days; IQR, 4-7 days). There was no operative mortality. CONCLUSION: VATS lobectomy is safe and feasible for pulmonary resection. This minimally invasive approach may allow patients to benefit from lobectomy with shorter recovery times and hospital stays compared with conventional open thoracotomy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Resultado do Tratamento , Adulto Jovem
17.
Ann Thorac Surg ; 87(6): 1973-80, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19463649

RESUMO

Thymomas are the most common tumors of the mediastinum. The introduction of multimodality treatment strategies, as well as novel approaches to the diagnosis of these tumors, has led to changes in the clinical management of thymomas. Here we review the literature for current clinical practice in the diagnosis, management, and treatment of thymomas.


Assuntos
Timoma/diagnóstico , Timoma/terapia , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/terapia , Humanos
18.
Gastroenterol Clin North Am ; 38(1): 169-81, x, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19327574

RESUMO

Esophageal cancer is an aggressive disease with an overall poor prognosis. Esophagectomy remains a key therapeutic option in treating patients who have this disease. Tailoring the surgical approach to the patient and the nature of his or her malignancy is essential. Over time, advances in staging, preoperative assessment, operative techniques, and postoperative care have resulted in decreased operative mortality and better long-term outcomes.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Cuidados Pré-Operatórios
19.
J Plast Reconstr Aesthet Surg ; 62(7): 920-6, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18468503

RESUMO

BACKGROUND: Radial artery forearm flaps are used for reconstruction of soft tissue defects. However, the functional consequences of removal of the radial artery for hand perfusion remain unclear at rest. We hypothesised that baseline microcirculation at rest is different following removal of the radial artery in a long-term perspective. METHODS: 114 atherosclerotic patients (100 males, 61.7+/-6.7 years) were included undergoing elective coronary revascularisation using the radial artery of the non-dominant forearm with non-pathological Allen's Test. Resting palmar microcirculatory mapping was applied at 25+/-5 months following removal of the radial artery regarding capillary flow, finger tip oxygenation as well as postcapillary venous filling pressures at both hands using combined non-invasive real-time laser Doppler flowmetry and spectrophotometry. RESULTS: 54/56 positions, more than 2 years following radial artery removal, did not reveal a difference beyond a 5% threshold at rest. No clinical signs of malperfusion were found following radial artery removal. No patient was impaired in his daily palmar motor activity or suffered exercise-related signs of malperfusion. Superficial and deep oxygen saturation decreased with age. In the non-donor hand, oxygen saturation declined in the first and second digits. Postcapillary venous filling pressure in both thenars increased with age. CONCLUSIONS: The hypothesis was rejected. Pedicled removal of the radial artery does not compromise superficial or deep palmar capillary blood flow, finger tip oxygenation or postcapillary venous filling pressures among atherosclerotic patients at rest in a clinically significant way.


Assuntos
Doença da Artéria Coronariana/fisiopatologia , Antebraço/irrigação sanguínea , Microcirculação/fisiologia , Artéria Radial , Coleta de Tecidos e Órgãos/efeitos adversos , Idoso , Velocidade do Fluxo Sanguíneo/fisiologia , Índice de Massa Corporal , Capilares/fisiopatologia , Feminino , Mãos/irrigação sanguínea , Humanos , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/métodos , Resultado do Tratamento
20.
Asian Cardiovasc Thorac Ann ; 15(6): 486-92, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18042773

RESUMO

The effect of age as a risk factor for deterioration of palmar microcirculation after radial artery harvesting for coronary revascularization is unknown. In 114 patients aged 61.7 +/- 6.7 years undergoing radial artery harvesting, superficial and deep tissue oxygen saturation, postcapillary venous filling, and capillary blood flow were determined using a combined laser Doppler spectrophotometry system 25 +/- 5 months after surgery. Superficial and deep oxygen saturation at the harvested thenar eminence decreased with age. In the nondonor hand, oxygen saturation declined in the first and second digits. Postcapillary venous filling pressure in both thenars increased with age. It was concluded that neurological complications do not correlate with age. Palmar tissue oxygen saturation, palmar capillary blood flow, and blood velocity decrease, while postcapillary venous filling pressure significantly increases with age. Radial artery harvesting for coronary revascularization does not compromise palmar microcirculation to the same extent as age. A cut-off value of

Assuntos
Envelhecimento , Mãos/irrigação sanguínea , Artéria Radial/transplante , Coleta de Tecidos e Órgãos/efeitos adversos , Doenças Vasculares/etiologia , Distribuição por Idade , Fatores Etários , Idoso , Velocidade do Fluxo Sanguíneo , Ponte de Artéria Coronária , Seguimentos , Humanos , Fluxometria por Laser-Doppler , Microcirculação , Pessoa de Meia-Idade , Oxigênio/sangue , Seleção de Pacientes , Fluxo Sanguíneo Regional , Fatores de Risco , Fatores de Tempo , Ultrassonografia , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/fisiopatologia , Pressão Venosa
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