1,721,002 research outputs found
Sviluppo di un modello murino di perfusione ex vivo dei polmoni per la ricerca in Trapiantologia
No full textIntroduzione. La perfusione ex vivo dei polmoni (EVLP) è un’alternativa al trasporto in cella frigorifera (static cold storage, SCS) per la preservazione degli organi ai fini di trapianto. I suoi vantaggi includono la possibilità di valutare, ricondizionare e preservare più a lungo i polmoni prima del trapianto. Questa tecnologia è stata introdotta nei primi anni 2000, e, da allora, diversi dispositivi e protocolli per l’EVLP sono entrati a far parte della pratica clinica internazionale. Tuttavia, alcuni aspetti legati all’EVLP sono ancora controversi; inoltre, le potenzialità dell’EVLP nel ricondizionare e rigenerare gli organi rimangono ancora in larga parte da esplorare.
Per dare risposta a questi quesiti, diversi investigatori hanno creato dei modelli animali di EVLP. Il modello murino di EVLP costituisce uno strumento estremamente utile per la ricerca in trapiantologia, poiché, rispetto all’animale di grande taglia, tramite esso è possibile realizzare un maggior numero di esperimenti, e testare un ampio ventaglio di approcci terapeutici. Lo scopo di questo progetto è creare una piattaforma sperimentale di EVLP nel ratto, e valutare il ruolo dell’albumina come componente di una soluzione di perfusione acellulare.
Metodi. Blocchi cuore-polmone di ratto sono stati prelevati da ratti Sprague-Dawley dopo un’ora di ischemia calda. Gli organi sono stati immersi per un’ora in soluzione di preservazione, a 4°C, e successivamente connessi alla piattaforma EVLP per 3 ore e perfusi con una soluzione acellulare, a basso contenuto di potassio e a base di destrano, a cui sono stati aggiunti oppure no 70 gr/L di albumina, a seconda del gruppo sperimentale (EVLP e EVLP+albumina). Ogni 30 minuti i polmoni sono stati valutati per l’efficienza degli scambi gassosi, la compliance polmonare dinamica (Cdyn), e le resistenze vascolari polmonari (PVR). Il grado di danno polmonare è stato valutato istologicamente attraverso il rapporto wet/dry, istologia, immunoistochimica, e test TUNEL.
Risultati. Tra i minuti 30 e 60 di EVLP è stata osservata una significativa riduzione delle PVR, mentre gli altri parametri di funzionalità polmonare sono rimasti stabili nell’arco delle 3 ore. Non sono state osservate differenze significative nei parametri di funzionalità polmonare o nella valutazione patologica tra i gruppi EVLP e EVLP+albumina. I campioni di tessuto dei polmoni sottoposti a EVLP, con o senza albumina, sono risultati caratterizzati da un grado significativamente maggiore di edema e da un maggior indice apoptotico (p<0.05), rispetto ai polmoni del gruppo SCS.
Conclusioni. Questo Progetto descrive la prima esperienza istituzionale con un modello di EVLP murino, il quale consente la preservazione di polmoni di ratto per 3 ore in uno stato fisiologicamente attivo, con parametri di funzionalità polmonare stabili. Dopo una fase iniziale di apprendimento, la sperimentazione ha dato luogo a risultati affidabili e riproducibili. L’albumina non si è rivelata una componente indispensabile per la corretta riuscita della perfusione ex-vivo; tuttavia, questo risultato necessita di ulteriori test per periodi più lunghi e su differenti modelli animali. I risultati anatomopatologici suggeriscono che, a confronto con la preservazione in cella frigorifera, l’EVLP potrebbe dare luogo ad un danno polmonare di maggior entità, che, se confermato, dovrebbe essere tenuta in considerazione come un limite intrinseco del modello murino.Background. Ex vivo lung perfusion (EVLP) is an alternative to static cold storage (SCS) for lung preservation in clinical lung transplantation. Its advantages include the possibility of assessing, reconditioning, and preserving for longer time the lungs prior to transplantation. This technology was introduced in the early years of 2000, and, since then, different devices and protocols were introduced into widespread clinical practice. However, several aspects of EVLP are still controversial; moreover, the potential of EVLP for organ reconditioning and regeneration is still largely unexplored. For these purposes, several investigators have created animal models of EVLP. Rat models of EVLP constitute a potentially invaluable tool for transplantation research, since they allow a higher number of experiments to be performed than with a large animal model, and a wide array of experimental treatments to be investigated. The aim of this project is to create a reliable experimental rat ELVP protocol for transplantation research, and to assess the role of albumin as an additive of EVLP perfusion solution.
Methods. Rat heart-lung blocks were harvested from Sprague-Dawley rats after 1 hour of warm ischemia. Grafts were kept immersed for 1 hour in low-potassium dextran solution and then placed on EVLP for 3 hours and perfused with a low-potassium dextran solution, additioned or not with 70 g/L of albumin (EVLP and EVLP+albumin groups). Every 30 minutes perfused lungs were evaluated for gas exchange, dynamic lung compliance (Cdyn), and pulmonary vascular resistance (PVR). Control lungs, after harvest, were kept in low-potassium dextran solution at 4°C for 4 hours (SCS group). Lung injury was evaluated by wet/dry ratio, histology, immunohistochemistry and TUNEL assay.
Results. A significant decrease in PVR was observed from 30 to 60 minutes of EVLP, while other lung function parameters remained stable throughout the 3 hours. No significant differences were observed in lung function parameters or in pathologic assessment between EVLP and EVLP+albumin groups. Pathologic specimens of lungs treated by EVLP, with or without albumin, were characterized by significantly higher edema score and apoptotic index (p <0.05), as compared to lungs preserved by SCS.
Conclusions. This project describes the first institutional experience with a rat EVLP model which allows for safe preservation of rat lungs for 3 hours with stable lung function parameters. After an initial learning phase, consistent and reliable results were obtained. Albumin did not demonstrate to be an essential component of the perfusion solution; however, this result needs further testing for longer perfusion times and on different animal models. Pathologic findings suggest that, compared to SCS, EVLP may cause a higher extent of lung injury; which, if confirmed, should be acknowledged as an inherent limitation of this model
Impact of lymph node occult metastases in stage I non-small cell lung cancer (NSCLC): What is the evidence?
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An alternative surgical access for posterior tracheal defects or fistulae situated between the cervical and thoracic region
No full textPosterior tracheal lesion defects between the cervical and the thoracic region represent a surgical challenge. Cervicotomy or median sternotomy might not allow a satisfactory exposure of the defect, and a history of prior neck surgeries could further complicate the procedure. We propose a high posterior right thoracotomic approach, by which the entire posterior aspect of the trachea is visible, up to the cervical region. We describe our experience with this approach, which is best suited for cases where a non-circumferential repair of the trachea is attempted
Human tracheal transplantation: A systematic review of case reports
No full textBackgroundPatients with long-segment airway stenosis not amenable to conventional surgery may benefit from tracheal transplantation. However, this procedure has been only anecdotally reported, and its indications, techniques, and outcomes have not been extensively reviewed.MethodsWe conducted a systematic Literature search to identify all original articles reporting attempts at tracheal transplantation in humans.ResultsOf 699 articles found by the initial search, 11 were included in the systematic review, describing 14 cases of tracheal transplantation. Patients underwent transplantation for benign stenosis in nine cases, and for malignancies in five cases. In 12 cases blood supply to the trachea was provided by wrapping the graft in a vascularized recipient's tissue, while in 2 cases the trachea was directly transplanted as a vascularized composite allograft. The transplantation procedure was aborted before orthotopic transplantation in two patients. Among the remaining 12 patients, there was 1 operative mortality, while 4 patients experienced complications. Immunosuppressants drugs were administered to the majority of patients postoperatively, and only one group of authors attempted their withdrawal, in five patients. At the end of follow-up, all 11 patients surviving the operation were alive, but 2 had a recurrent tracheal stenosis requiring an airway appliance for breathing.ConclusionHuman tracheal transplantation is still at an embryonic phase. Studies available in the Literature report different surgical techniques, and information on long-term outcomes is still limited. Future research is needed in order to understand the clinical value of this procedure
Complex lobectomy in a patient with lung cancer and pulmonary artery sling
No full textPulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. This condition typically presents with respiratory failure in young infancy, while asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required
Non-intubated tracheal surgery: Is it worthwhile?
No full textThe birth of modern thoracic surgery coincided with the development of double-lumen endobronchial tubes permitting single-lung ventilation, which allowed surgeons to operate on a totally collapsed lung. So far, this type of anesthesia is considered mandatory for most thoracic surgery procedure
Survival and prognostic factors following pulmonary metastasectomy for sarcoma
Full text linkSarcomas are a heterogeneous group of malignancies with a marked propensity to metastasize to the lungs. Chemotherapy offers only a limited benefit in metastatic disease, whereas lung metastasectomy, in selected cases, can lead to long-term survival. Other local ablative techniques and hybrid therapies have been proposed. A multidisciplinary setting is of paramount importance for choosing the most appropriate treatment for each case. There is no randomized controlled trial providing formal evidence of the effectiveness of lung metastasectomy. Main areas of controversy concern the selection of surgical candidates, the operative approach and the role of chemotherapy. Five-year survival rates range from 15% to 50.9%, as reported mainly in retrospective case-series in which several prognostic factors were identified. In this article, the authors review the surgical management of sarcoma metastases to the lung, with a particular focus on the outcomes and prognostic factors associated with long-term survival after resection. The role of chemotherapy and other adjunctive therapies is also discussed
Tracheal Tissue Engineering: Principles and State of the Art
Full text linkPatients affected by long-segment tracheal defects or stenoses represent an unsolved surgical issue, since they cannot be treated with the conventional surgery of tracheal resection and consequent anastomosis. Hence, different strategies for tracheal replacement have been proposed (synthetic materials, aortic allografts, transplantation, autologous tissue composites, and tissue engineering), each with advantages and drawbacks. Tracheal tissue engineering, on the other hand, aims at recreating a fully functional tracheal substitute, without the need for the patient to receive lifelong immunosuppression or endotracheal stents. Tissue engineering approaches involve the use of a scaffold, stem cells, and humoral signals. This paper reviews the main aspects of tracheal TE, starting from the choice of the scaffold to the type of stem cells that can be used to seed the scaffold, the methods for their culture and expansion, the issue of graft revascularization at the moment of in vivo implantation, and experimental models of tracheal research. Moreover, a critical insight on the state of the art of tracheal tissue engineering is also presented
Laser-assisted lung metastasectomy: a systematic review
No full textLaser-assisted resection (LAR) of pulmonary metastases offers several potential advantages compared to conventional surgical techniques. However, the technical details, indications and outcomes of LAR have not been extensively reviewed. We conducted a systematic literature search to identify all original articles reporting on LAR of pulmonary metastases. All relevant outcomes, including morbidity rate, R0 rate, pulmonary function tests, overall- (OS) and relapse-free survival (RFS) rates were collected. Additionally, a comparison between outcomes obtained by laser-assisted and conventional resection techniques was provided. Of 2629 articles found by the initial search, 12 were selected for the systematic review. Following LAR, the R0 rate ranged between 72 and 100% and the morbidity rate ranged from 0 to 27.5%. The postoperative decline in forced expiratory volume in 1 s varied between 3.4 and 11%. Median OS and RFS were 42-77.6 months and 9-34.1 months, respectively. Compared with patients treated by other resection techniques, patients treated by LAR frequently had a higher number of metastases and a higher rate of bilateral disease. Despite this, no significant differences were observed in R0 rate, morbidity rate, and median OS rate, while only 1 study found a lower RFS rate in the LAR cohort. Although selection bias limits the comparability of outcomes, the findings of this review suggest that LAR is a valid alternative to conventional procedures of lung metastasectomy. The main difficulties of this technique consist in the adoption of a video-assisted thoracoscopic approach, and in the pathologic assessment of resection margins
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