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Idiopathic pulmonary fibrosis (IPF) is a severe health problem characterized by progressive fibroblast proliferation and aberrant vascular remodeling. However, the lack of a suitable in vitro model that replicates cell-specific changes in IPF tissue is a crucial issue. Three-dimensional (3D) cell cultures allow the mimicking of cell-specific functions, facilitating development of novel antifibrosis drugs. We have established a layer-by-layer (LbL) cell coating technique that enables the construction of 3D tissue and also vascularized 3D tissue. This study evaluated whether this technique is beneficial for constructing an in vitro IPF-3D model using human lung fibroblasts and microvascular endothelial cells. We fabricated an in vitro IPF-3D model to provide IPF-derived fibroblasts-specific function and aberrant microvascular structure using the LbL cell coating technique. We also found that this in vitro IPF-3D model showed drug responsiveness to two antifibrosis drugs that have recently been approved worldwide. This in vitro IPF-3D model constructed by a LbL cell coating technique would help in the understanding of fibroblast function and the microvascular environment in IPF and could also be used to predict the efficacy of novel antifibrosis drugs. Impact statement We established a novel in vitro model mimicking idiopathic pulmonary fibrosis. Three-dimensional culture was constructed by layer-by-layer cell coating technique. This novel model provides a visualization of fibroblast-specific function. This assay allows for the assessment of pulmonary microvascular environment. Our model may be useful for predicting the efficacy of novel antifibrosis drugs.
Assuntos
Células Endoteliais , Fibrose Pulmonar Idiopática , Fibroblastos , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , PulmãoRESUMO
BACKGROUND: Although complete surgical resection of thymic carcinoma is a prognostic factor, it is not always an option for advanced tumors because of locoregional invasion. Extended surgery combined with a major blood vessel procedure remains controversial because of the increased risk of mortality. CASE PRESENTATION: Chest computed tomography (CT) uncovered an abnormal shadow in the mediastinum of a 74-year-old man. An irregularly shaped tumor obstructed the left innominate vein, and invasion of the aortic arch was suspected. A CT-guided percutaneous needle biopsy revealed squamous cell carcinoma of the thymus, which was considered unresectable. The patient underwent chemotherapy elsewhere, then was referred to us for surgical resection. We combined extended surgery with total aortic arch replacement under a cardiopulmonary bypass. Complete resection was achieved, and the patient remains alive without recurrence at 3 years after surgery CONCLUSION: Resection including aortic arch replacement might be an option that can achieve complete resection of local advanced thymic carcinoma.
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BACKGROUND: Treatment strategies for brain metastasis from lung cancer have been making progress. The aim of this retrospective analysis was to investigate the post-recurrent prognostic factors in patients with brain metastasis after complete resection of non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed the medical records of 40 patients found to have postoperative brain metastasis from NSCLC in our institution from 2002 to 2008. All patients had undergone radical pulmonary resection for the lung cancer. The impact of numerous variables on survival were assessed, including gender, age, carcinoembryonic antigen (CEA), tumor size, N status, histological type, number of brain metastases, tumor size of brain metastasis, presence of symptoms from the brain tumor(s), and use of perioperative chemotherapy. RESULTS: The median follow-up was 20.6 months (range, 3.4-66 months). The five-year survival rate from the diagnosis of brain recurrence was 22.5%. In univariate analysis, the favorable prognostic factors after brain recurrence included a normal range of CEA, no extracranial metastasis, no symptoms from the brain metastasis, brain metastasis (less than 2 cm), and radical treatment (craniotomy or stereotactic radiosurgery [SRS]). The multivariate Cox model identified that a small brain metastasis and radical treatment were independent favorable prognostic factors. CONCLUSIONS: This study found that the implementation of radical therapy for metastatic brain tumor(s) when the tumor is still small contributed to an increase in patients' life expectancy.
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According to a recent report by the Committee for Scientific Affairs of the Japanese Association for Thoracic Surgery, pulmonary metastasectomy accounted for as many as 10.2 % of all entry cases of general thoracic surgery, and its use is increasing year by year. Accordingly, many studies have examined the surgical procedures used during pulmonary metastasectomy for metastases from primary tumors affecting various organs as well as the outcomes of and indications for such procedures, but some problems remain. In this article, the following questions related to the surgical approach and the type of resection used during pulmonary metastasectomy are reviewed: (1) Wedge resection--what is a safe margin for preventing local recurrence? (2) What is the clinical significance of node sampling/dissection during pulmonary metastasectomy? and (3) When is segmentectomy necessary? In addition, we discuss: (4) open thoracotomy vs. video-assisted thoracoscopic surgery (VATS), (5) repeated metastasectomy for pulmonary metastases, (6) the surgical approach for bilateral pulmonary metastasectomy, (7) pneumonectomy, and (8) pulmonary metastasectomy combined with resection of the neighboring organs.
Assuntos
Neoplasias Pulmonares/cirurgia , Metastasectomia/métodos , Desenho de Equipamento , Humanos , Pulmão/cirurgia , Neoplasias Pulmonares/secundário , Metastasectomia/instrumentação , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/cirurgia , Pneumonectomia/instrumentação , Pneumonectomia/métodos , Reoperação , Cirurgia Torácica Vídeoassistida/métodos , Toracotomia/instrumentação , Toracotomia/métodosRESUMO
PURPOSE: Several reports have described extended survival after aggressive surgical treatment for non-small cell lung cancer (NSCLC) and synchronous brain metastasis. This retrospective analysis assesses the prognostic factors in this population. METHODS: We reviewed retrospectively the medical records of 29 patients with synchronous brain metastasis from NSCLC, who underwent surgical treatment in our institution between 1980 and 2008. All patients underwent chest surgery to remove the primary lesion. The impact of several variables on survival was assessed. RESULTS: The median follow-up period was 9.6 months and the 5-year survival rate from the time of lung cancer resection was 20.6 %. Univariate analysis demonstrated that the carcinoembryonic antigen (CEA) level, primary tumor size, and the presence of lymph node involvement were predictive of overall survival (p < 0.05). Multivariate analysis also identified those factors to be independent favorable prognostic factors. CONCLUSIONS: Although the survival of patients with brain metastasis from non-small cell lung cancer remains poor, surgical resection may benefit a select group of patients, particularly those with a normal CEA level, small tumor size, and node-negative status.