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Biomedical subjects

Paolo Macchiarini

Publications and source records attributed to Paolo Macchiarini.

At least 19 recordsLinked to original sources

Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: is deep hypothermia required?

OBJECTIVE: To investigate whether deep (<20 degrees C) hypothermia is necessary in patients undergoing pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. METHODS: Between January 2004 and February 2005, 30 patients (New York Heart Association (NYHA) class III or IV) were randomly assigned to increasing (1 degrees C) levels of moderate (28-32 degrees C) hypothermic cardiopulmonary bypass (CPB), each study group including six patients. Primary study endpoint was adverse neurological outcome. Overall preoperative total pulmonary vascular resistance was 1110+/-192 dynes cm(-5). RESULTS: Mean CPB and cross-clamp times, and core temperature at the time of circulatory arrests were 129+/-39 min and 92+/-24 min, and 30.1+/-1.5 degrees C, respectively. Circulatory arrest was induced 2+/-0.7 times and its mean total duration was 10.3+/-5.2 min (range, 2-19 min). Postoperatively, three patients (10%) belonging to the 31 degrees C (n=1) and 32 degrees C (n=2) groups suffered from temporary neurological dysfunction. Postoperative mechanical ventilatory support and ICU stay were 26.3+/-18.9 h and 6.6+/-8.5 days, respectively, and uninfluenced by degree of hypothermia. There were no lung reperfusion injuries or any other major complications. All patients had a significant hemodynamic improvement. CONCLUSION: Results suggest that pulmonary endarterectomy can be safely performed with moderate hypothermia and short periods of circulatory arrests without the need of profound hypothermia.

Adult↗

Self-made tracheal stomal stent using a tracheal T-tube.

Adapting a silicone tracheal safe T-tube is a simple method to guarantee upper airway permeability. Its making and availability ease offers a cheap and valid option to avoid the complications of the tracheostomy tube.

Airway Obstruction↗

Technical innovations of carinal resection for nonsmall-cell lung cancer.

BACKGROUND: We present our perioperative management of operable nonsmall-cell lung cancer invading the tracheobronchial bifurcation and the results obtained. METHODS: Fifty consecutive patients undergoing carinal surgery with radical lymphadenectomy over a 5-year period were studied. RESULTS: Eighteen patients (36%) were N2 and had chemoradiation (48 +/- 6 Gy) preoperatively. Surgery included 34 carinal pneumonectomies (24 right, 10 left), 11 carinal lobectomies (n = 6) or bilobectomies (n = 5), and 5 carinal resections, with (n = 3) and without (n = 2) reconstructions. Patients were ventilated through low tidal volume controlled techniques except during airway resection and reconstruction, during which the apneic (hyper) oxygenation techniques were used. High inspiratory oxygen concentrations, multiple collapse and reexpansions, hypoperfusion of the ipsilateral lung, and fluid overload were avoided. All patients but 1 were extubated in the operating room, 7 +/- 5 minutes after skin closure. Operative mortality (less than 30 days) and morbidity were 4% (n = 2) and 37% (n = 18), respectively. All resections but 1 (98%) R1 were complete. The number of resected nodes per patient was 9 +/- 2, and 7 (22%) of the 32 patients who had negative preoperative positron emission tomography results had micrometastatic mediastinal nodes. With a median follow-up of 38 months, actuarial 5-year and disease-free survivals were 51% and 47%, respectively. Disease-free survival was significantly affected by endobronchial extension (tracheobronchial angle invasion versus less than 0.5 cm from carina, p = 0.03) and nodal status (N0 versus N1-2, p = 0.02) in the multivariate analysis. CONCLUSIONS: Preoperative chemoradiation, carinal lobectomy, or left pneumonectomy, and radical lymphadenectomy do not worsen the therapeutic index of carinal surgery. The high incidence of micrometastatic nodes in positron emission tomography-negative patients justifies routine mediastinoscopy and radical lymphadenectomy.

Adult↗

Primary tracheal tumours.

Primary tumours of the trachea can be benign or malignant and account for fewer than 0.1% of tumours. However, they are a diagnostic and therapeutic challenge. Benign tumours are usually misdiagnosed as asthma or chronic lung disease, and can delay diagnosis for months or years. Because of their rapid growth and onset of haemoptysis, malignant tumours are often diagnosed earlier than benign tumours and patients thus often present with locally advanced disease. Inappropriate treatment is an equally frustrating issue. Modern techniques for tracheal surgery-laryngotracheal, tracheal, or carinal resection-combined with radiotherapy, can be offered curatively with low perioperative risks. Nevertheless, the low numbers of patients undergoing resection and the associated poor survival in epidemiological studies over the past two decades have shown that surgery is rarely considered outside referral centres, with radiotherapy or another form of local treatment (eg, endotracheal stents, debridement, brachytherapy) generally preferred. The liberal use of these other techniques should be avoided because surgery has the potential to cure all patients with benign and low-grade tumours and most patients with malignant primary tracheal tumours, and other techniques are usually palliative at best.

Brachytherapy↗

Extended pulmonary resections of advanced thoracic malignancies with support of cardiopulmonary bypass.

OBJECTIVE: Complete resection of advanced pulmonary malignancies infiltrating the heart or the great vessels may require the application of cardiopulmonary bypass (CPB). Extracorporal circulation, however, is known to cause lung injury and may be harmful especially in pneumonectomies. METHODS: Over a period of 10 years extended pulmonary resections requiring cardiopulmonary bypass were analyzed in a retrospective study. RESULTS: From August 1993 to August 2003, 13 patients underwent an extended pulmonary resection for curative indications, requiring support by CPB. Underlying diseases were sarcomas (n=8), non-small cell lung carcinomas (n=3), and others (n=2). Pneumonectomies were performed in nine and lobectomies in four cases. In the majority of cases, several cardiac structures, predominantly the left atrium (n=9), were affected. In four patients (31%), the indication for a CPB-supported procedure was not electively planned, but made intraoperatively. Complete en-bloc resection (R0) was achieved in 12 of 13 cases (92%). The 30-day mortality rate was 15% (n=2). Major complications observed were acute lung injury (n=4), right heart failure (n=1), and multi-organ failure (n=1). The cumulative survival at 1, 3, and 5 years in patients presenting with sarcomas was 62.5% compared to 33%, 0%, and 0%, respectively, in patients with non-small cell carcinoma (n=3). CONCLUSIONS: Our results encourage the application of CPB in extended pulmonary resections to achieve complete resections. In carefully selected patients, especially those with sarcomas, the radical surgical procedure associated with increased pulmonary complications allows for significantly prolonged survival and quality of life.

Adult↗

An ex vivo model for reperfusion of laryngotracheal grafts.

OBJECTIVE: To describe the development of an ex vivo model to facilitate the study of ischemia-reperfusion injury in laryngotracheal grafts taken from Minnesota minipigs. STUDY DESIGN: This is a descriptive study. METHODS: Laryngotracheal grafts from Minnesota minipigs were harvested and placed in cold storage for 3 hours. Autologous blood was used to reperfuse the graft for up to 8 hours using the described reperfusion model. RESULTS: By altering retrieval technique and pressures within the graft, we demonstrated healthy grafts after 8 hours of reperfusion. CONCLUSIONS: Ex vivo reperfusion offers a range of experimental advantages over in vivo reperfusion including close control of interventions, ease of outcome measurement, and reduction in animal use. This model is now ready to be used for further studies of interventions to reduce ischemia-reperfusion injury in these grafts.

Animals↗

Expansion of chondrocytes in a three-dimensional matrix for tracheal tissue engineering.

BACKGROUND: The generation of autologous tracheal implants by tissue-engineering techniques is a promising concept for otherwise untreatable patients. A functional cartilaginous backbone represents a prerequisite for any bioartificial tracheal graft. The aim of this study was to define suitable cell types and culture conditions for the generation of tracheal cartilage. METHODS: We obtained tracheal, costal, and auricular cartilage from porcine donor animals (n = 10). The chondrocytes were cultured two-dimensionally in cell flasks or mixed with a liquid collagen solution forming a three-dimensional culture system. Labeling with carboxy fluorescein diacetate succinimidyl ester (CFDA SE) and biochemical reduction of formazan served to determine cell viability and proliferation. The extracellular matrix produced by the chondrocytes was characterized by Western blot. RESULTS: The CFDA SE labeling proved viability and the MTT assays documented a proliferation of the chondrocytes over time in vitro. While the chondrocytes in the three-dimensional cell culture system produced hyaline cartilage composed of collagen II, the two-dimensional culture conditions resulted in nonspecific collagen synthesis. CONCLUSIONS: Chondrocytes grown in a three-dimensional matrix can effectively proliferate and produce cartilage and are viable for more than 2 weeks. Costal chondrocytes are suitable for tracheal cartilage tissue engineering.

Animals↗

Experimental generation of a tissue-engineered functional and vascularized trachea.

OBJECTIVE: We sought to grow in vitro functional smooth muscle cells, chondrocytes, and respiratory epithelium on a biologic, directly vascularized matrix as a scaffold for tracheal tissue engineering. METHODS: Ten- to 15-cm-long free jejunal segments with their own vascular pedicle were harvested and acellularized from donor pigs (n = 10) and used as a vascular matrix. Autologous costal chondrocytes, smooth muscle cells, and respiratory epithelium and endothelial progenitor cells were first cultured in vitro and then disseminated on the previously acellularized vascular matrix. Histologic, immunohistologic, molecular imaging, and Western blotting studies were then performed to assess cell viability. RESULTS: The endothelial progenitor cells re-endothelialized the matrix to such an extent that endothelial cell viability was uniformly documented through 2-(18F)-fluoro-2'-deoxyglucose positron emission tomography. This vascularized scaffold was seeded with functional (according to Western blot analysis) smooth muscle cells and successfully reseeded with viable ciliated respiratory epithelium. Chondrocyte growth and production of extracellular cartilaginous matrix was observed as soon as 2 weeks after their culture. CONCLUSIONS: The fundamental elements for a bioartificial trachea were successfully engineered in vitro in a direct vascularized 10- to 15-cm-long bioartificial matrix. Future experimental work will be directed to give them a 3-dimensional aspect and a biomechanical profile of a functioning trachea.

Animals↗

Uncommon primary mediastinal tumours.

The mediastinum is a unique anatomic area containing several structures and pluripotent cells that allow for the development of a range of tumours. Uncommon neoplasms of the mediastinum account for less than 10% of all mediastinal masses and include primary thymic carcinomas, neuroendocrine carcinomas, germ-cell tumours (GCTs), lymphomas, and neurogenic, endocrine, and mesenchymal tumours. Primary thymic carcinomas and neuroendocrine carcinomas, although rare, are highly malignant lesions. GCTs are thought to derive from primitive germ cells and can be classified in seminomatous and non-seminomatous GCTs. They are located predominantly in the anterior mediastinum, as are the primary mediastinal lymphomas that include Hodgkin lymphoma, large B cell lymphoma, and lymphoblastic lymphoma. Neurogenic tumours may arise from peripheral nerves, sympathetic ganglia, or rarely parasympathetic ganglia and are located predominantly in the posterior mediastinum. Endocrine tumours are the ectopic thyroid and parathyroid tumours. Mesenchymal tumours are rare tumours and no less problematic than they are in peripheral sites. The clinical, radiological, and therapeutic aspects of these tumours are reviewed.

Humans↗