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P Macchiarini

Publications and source records attributed to P Macchiarini.

At least 19 recordsLinked to original sources
PubMed2006

Generation of a bioartificial fibromuscular tissue with autoregenerative capacities for surgical reconstruction.

INTRODUCTION: Anecdotal clinical reports denote first tissue engineering applications entering medical practice. Currently it is still unknown, if these new types of implants will tolerate the specific needs in cancer patients undergoing postoperative chemo- and radiotherapy. METHODS: We implemented a radiotherapy protocol (cumulative dosis 40 Gy) on generated human bioartificial fibromuscular tissues in vitro. We monitored tissue vitality during radiotherapy and tissue recovery (8 weeks follow up period) applying histological methods. RESULTS: The biopsy procedure and seeding techniques yielded a viable 3 dimensional bioartificial human tissue. Radiation resulted in immediate devitalization without destroying tissue integrity. The bioartificial tissue recovered entirely in vitro within 6 weeks. CONCLUSION: Bioartificial human implants appear applicable for surgical reconstruction in oncologic patients potentially facing postoperative radiotherapy.

Animals↗
PubMed2006

Early immunological changes associated with laryngeal transplantation in a major histocompatibility complex-matched pig model.

Laryngeal transplantation is an increasingly viable proposition for patients with irreversible diseases of the larynx. One human transplant has been performed successfully, but many questions remain before routine transplantation can begin. In order to measure the immunological changes in mismatched transplants, it is first necessary to know the immediate combined effects of ischaemia-reperfusion injury (IRI) plus the added insult of major surgery in a fully matched setting. We measured the changes in immunologically active mucosal cells following 3 h of cold ischaemia and 8 h of in situ reperfusion in a major histocompatibility complex (MHC)-matched minipig model (n = 4). Biopsies were prepared for quantitative, multiple-colour immunofluorescence histology. The number of immunologically active cells was significantly altered above (supraglottis) and below (subglottis) the vocal cords following transplantation and reperfusion (P < 0.05, P < 0.001, respectively). However, the direction of the change differed between the two subsites: cell numbers decreased post-transplant in the supraglottis and increased in the subglottis. Despite the statistical evidence for IRI, these changes were less than the large normal inter- and intrapig variation in cell counts. Therefore, the significance of IRI in exacerbating loss of function or rejection of a laryngeal allograft is open to question. Longer-term studies are required.

Animals↗
PubMed2002

Model for experimental revascularized laryngeal allotransplantation.

BACKGROUND: Although a human laryngeal transplant has been undertaken successfully, important questions remain that require a suitable animal model. METHODS: A pig model for allotransplantation has been developed. Organ perfusion was studied in nine animals before four transplants were performed in congenic (unrecovered) animals and eight in unmatched (recovered) animals. Larynges were regularly examined endoscopically until death at 14 days. Immunosuppression included the use of tacrolimus. Revascularization was achieved by anastomosing the donor right cervical vascular tree to the recipient common carotid. In recovered animals, four allografts were placed orthotopically and four heterotopically. RESULTS: The pig larynx was perfused adequately via the right cervical vascular tree and congenic grafts were well tolerated. Of eight allografts, seven were well tolerated and remained healthy for the duration of the study (14 days). One allograft became infected between days 4 and 7 after operation. Median operating time was 6 h, with a median cold ischaemia time of 3 h. CONCLUSION: Revascularized allotransplants of the larynx can be undertaken reliably in pigs and this provides a preclinical model for studies of laryngeal transplantation.

Animals↗
PubMed2001

Low molecular weight dextran sulfate prevents complement activation and delays hyperacute rejection in pig-to-human xenotransplantation models.

Dextran sulfate of 5000 molecular weight (DXS 5000) is known to block complement activation as well as the intrinsic coagulation cascade by potentiation of C inhibitor. The effect of DXS 5000 on hyperacute rejection (HAR) was tested in pig-to-human xenotransplantation models. For in vitro testing, a cytotoxicity assay was used with the pig kidney cell line PK15 as target cells and fresh, undiluted human serum as antibody and complement source. Ex vivo pig lung perfusion was chosen to assess DXS 5000 in a physiologic model. Pig lungs were perfused with fresh, citrate-anticoagulated whole human blood to which 1 or 2 mg/ml DXS 5000 were added; the lungs were ventilated and the blood de-oxygenated. Pulmonary vascular resistance (PVR) and blood oxygenation (deltapO2) were monitored throughout the experiment. Autologous pig blood and human blood without DXS 5000 served as controls. In the PK 15 assay DXS 5000 led to a complete, dose-dependent inhibition of human serum cytotoxicity with an average IC50 of 43 +/- 18 microg/ml (n=8). Pig lungs perfused with untreated human blood (n=2) underwent HAR within 105 +/- 64 min, characterized by increased PVR, decrease of deltapO2, and generalized edema. Microscopically, capillary bleeding as well as deposition of human antibodies, complement and fibrin could be observed. Addition of DXS 5000 (n=4) prolonged lung survival to 170 +/- 14 min for 1 mg/ml and 250 +/- 42 min for 2 mg/ml. and PVR values as well as edema formation were comparable to control lungs that were perfused with autologous pig blood (n=2). Activation of complement (activation products in serum, deposition on lung tissue) and the coagulation system (fibrin monomers) were significantly diminished as compared to human blood without DXS 5000. Binding of anti-Gal antibodies was not influenced, and in vitro experiments showed no evidence of complement depletion by DXS 5000. In conclusion, DXS 5000 is an efficient complement inhibitor in pig-to-human xenotransplantation models and therefore a candidate for complement-inhibitory/anti-inflammatory therapy either alone or in combination with other substances and warrants further investigation.

Animals↗
PubMed2001

Partial cricoidectomy with primary thyrotracheal anastomosis for postintubation subglottic stenosis.

OBJECTIVE: We describe a Pearson-type technique and evaluate its results for postintubation subglottic stenosis. METHODS: Forty-five patients underwent a partial cricoidectomy with primary thyrotracheal anastomosis, and 5 underwent simultaneous repair of a tracheoesophageal fistula as well. Twenty-four (53%) patients were referred to us after initial conservative (n = 21) or operative (n = 3) management. There were 27 cuff lesions, 7 stomal lesions, and 11 at both levels. The upper limit of the stenosis was 1.5 cm (range, 1-2.5 cm) below the cords, and the subglottic diameter was reduced by 60% in 38 (84%) of the patients. The length of airway resection ranged from 2 to 6 cm (median, 3 cm). Despite 23 thyrohyoid or suprahyoid releases, 8 anastomoses were under tension. RESULTS: Thirty-seven (82%) patients were extubated after the operation (n = 30) or within 24 hours (n = 7). Six patients required postoperative airway stenting (median, 5.5 days). Early (<30 days) complications occurred in 18 (41%) patients, mainly as transient airway and voice complaints, aspiration, and dysphagia. One (2%) patient died of myocardial infarction. Late morbidities were 2 failures occurring as bilateral recurrent nerve paralysis and restenosis requiring definitive tracheostomy. Patients had excellent or good anatomic (n = 42 [96%]), functional (n = 41 [93%]), or both types of long-lasting results, with no stenotic relapse. CONCLUSIONS: Partial cricoidectomy with primary thyrotracheal anastomosis can be applied in patients with postintubation stenosis extending up to 1 cm below the cords and measuring up to 6 cm in length with excellent-to-good definitive results. The association with a tracheoesophageal fistula does not contraindicate surgical repair.

Adolescent↗
PubMed2000

Use of embryonic human trachea grown in nude mice to patch-repair congenital tracheal stenosis.

BACKGROUND: Long congenital tracheal stenosis is a life-threatening condition, and the available surgical treatments do not give satisfactory long-term results. METHODS: Human embryonic tracheas were implanted in the abdominal cavities of nude mice until their differentiation was completed. These differentiated tracheas were used to patch-repair surgically induced tracheal stenosis in piglets. The human, mouse, or pig origin, of all the cells in the two successive xenotransplants in the nude mouse and the pig, was determined on tissue sections by in situ hybridization with species-specific DNA probes. RESULTS: The transplanted pigs thrived and reached normal adulthood, irrespective of the administration of immunosuppressive treatment. The human tracheal tissue developed in nude mice conserved human structures, with the exception of feeding capillaries, which were of mouse origin. The tracheal patch in the adult healthy pigs comprised only pig cells organized into a fibrous scar, which was covered by normal pig epithelium. CONCLUSIONS: Results suggest that human embryonic trachea grown in nude mice can be successfully used as patch tracheoplasty for long congenital tracheal stenosis without conventional immunosuppression.

Animals↗
PubMed2000

Transcervical-transtracheal endoluminal repair of membranous tracheal disruptions.

Tracheal lacerations are rare and potentially hazardous complications of tracheal intubation. Surgical repair is the treatment of choice of tracheal injuries although nonoperative management is occasionally appropriate for well-selected patients. We describe our personal technique of anterior transcervical-transtracheal endoluminal suture of iatrogenic lacerations of the membranous trachea and our results with this approach in 8 patients. This method is less invasive than conventional cervical or transthoracic approaches.

Humans↗
PubMed2000

Surgical treatment of pulmonary aspergilloma: current outcome.

OBJECTIVE: This retrospective study was designed to confirm that aggressive pulmonary resection can provide effective long-term palliation of disease for patients with pulmonary aspergilloma. METHODS AND RESULTS: From 1959 to 1998, 84 patients underwent a total of 90 operations for treatment of pulmonary aspergilloma in the Marie-Lannelongue Hospital. The mean follow-up period was 9 years, and 83% of the patients were followed up for 5 years or until death, if the latter occurred earlier. The median age was 44 years. The most common indications were hemoptysis (66%) and sputum production (15%). Fifteen patients (18%) had no symptoms. Tuberculosis and lung abscess were the most common underlying causes of lung disease (65%). The procedures were 70 lobar or segmental resections, 8 cavernostomies, and 7 pneumonectomies. Five thoracoplasties were required after lobectomy (3 patients) or pneumonectomy (2 patients). The operative mortality rate was 4%. The major complications were bleeding (23 patients), prolonged air leak (31 patients), respiratory failure (10 patients), and empyema (5 patients). The actuarial survival curve showed 84% survival at 5 years and 74% survival at 10 years. During the first 2 years, death was related to the surgical procedure and the underlying disease. In contrast, 85% of the survivors had a good late result. CONCLUSION: Lobar resection in both the symptomatic and the asymptomatic patients was conducted in low-risk settings. For patients whose condition is unfit for pulmonary resection, cavernostomy may need to be undertaken despite the high operative risk. The better survival rate in this study may have been due to the selection of patients with better lung function and localized pulmonary disease.

Adult↗
PubMed2000

Evaluation and outcome of different surgical techniques for postintubation tracheoesophageal fistulas.

OBJECTIVE: We evaluated the outcome of different surgical techniques for postintubation tracheoesophageal fistula. METHODS: Thirty-two consecutive patients aged 51 +/- 23 years had tracheoesophageal fistulas resulting from a median of 30 days of mechanical ventilation via endotracheal (n = 12) or tracheostomy (n = 20) tubes. Tracheoesophageal fistulas were 2.5 +/- 1.2 cm long and were associated with a tracheal (n = 10) or subglottic (n = 3) stenosis in 13 patients. RESULTS: All but 3 patients were weaned from respirators before repair. All operations were done through cervical incisions and included direct division and closure (n = 9), esophageal diversion (n = 3), muscle interposition (n = 6), or, more recently, tracheal or laryngotracheal resection and anastomosis with primary esophageal closure (n = 14). Nine thyrohyoid and two supralaryngeal releases reduced anastomotic tension. Twenty-three patients (74%) were extubated after the operation (n = 16) or within 24 hours (n = 7), and 7 required a temporary tracheotomy tube. One postoperative death (3%) was associated with recurrent tracheoesophageal fistula. Seven complications (22%) included recurrent tracheoesophageal fistula (n = 1), delayed tracheal stenosis (n = 2), dysphagia (n = 2), and recurrent nerve palsy (n = 2). Complications necessitated reoperation (n = 1), dilation (n = 2), definitive tracheostomy (n = 1), Montgomery T tubes (n = 1), and Teflon injection of the vocal cords (n = 1). Twenty-nine patients (93%) had excellent (n = 24) or good (n = 5) anatomic and functional long-term results. Complications have been less common (7% vs 38%) and long-term results better (93% vs 65%) recently with tracheal or laryngotracheal resection and anastomosis with primary esophageal closure as compared with previous procedures. CONCLUSIONS: Postintubation tracheoesophageal fistula is usually best treated with tracheal or laryngotracheal resection and anastomosis with primary esophageal closure even in the absence of tracheal damage.

Adult↗
PubMed2000

Factors affecting long-term survival after en-bloc resection of lung cancer invading the chest wall.

OBJECTIVE: Several reports emphasize the importance of en-bloc resection as the optimal surgical treatment of lung cancer with chest wall invasion. We investigated possible factors which could affect long-term survival following radical resection of these tumors. METHODS: Between 1981 and 1998, 100 patients (90 male; ten female), with a median age of 60 years (36-84), underwent radical en-bloc resection of non-small cell lung cancer (NSCLC) with chest wall involvement. Patients with superior sulcus tumors invading the thoracic inlet were excluded from this series. There were 43 squamous and 57 non-squamous tumors. The median number of resected ribs was three (1-5). Lung resection included 73 lobectomies, two bilobectomies, 18 pneumonectomies and seven segmentectomies. Chest wall resection also extended to the sternum in one patient, the transverse process in one, the costotransverse foramen and hemivertebrae in two. All patients had a complete resection. Sixty-three patients received postoperative radiotherapy and 12 received chemotherapy. Histological data, including differentiation and depth of chest wall invasion, were carefully reviewed. The effect of various factors on survival were studied. RESULTS: There were four in-hospital deaths. Lymph node involvement was negative on surgical specimens in 65 patients, and 28 patients had positive N1 nodes; the final histology revealed seven N2 diseases. Chest wall invasion was limited to the parietal pleura in 29 patients and included intercostal muscles, bones and extrathoracic muscles in 67, 24 and seven cases, respectively. The overall 2-year survival rate was 41%. The 5-year survival for patients with N0, N1 and N2 disease was 22, 9 and 0%, respectively. A local recurrence occurred in 13 patients, with four having a new resection and 45 patients developing systemic metastases. The nodal status (N0-1 vs. N2; P=0. 026) and the number of resected ribs(<2 vs. >2; P=0.03) were survival predictors in univariate analysis. By multivariate analysis, the two independent factors affecting long-term survival were the histological differentiation (well vs. poorly differentiated; P=0. 01) and the depth of chest wall invasion (parietal pleura vs. others; P=0.024). CONCLUSIONS: Histological differentiation and depth of chest wall involvement were the main factors affecting long-term survival in this series. The role of induction chemotherapy for tumors with poor prognosis should be investigated.

Adenocarcinoma↗
PubMed1999

A preclinical model for laryngeal transplantation: anatomy and mucosal immunology of the porcine larynx.

BACKGROUND: A major step in translating work on laryngeal transplantation into clinical practice is the establishment of a preclinical model. We have investigated the anatomy and mucosal immunology of the porcine larynx in eight Minnesota Minipigs (12-37 weeks). METHODS: Neck dissections were carried out and the vascular tree was mapped. Snap-frozen biopsies from epiglottis, supraglottis, glottis, and subglottis were prepared for conventional histology, immunohistochemistry (CD45), and single and two-color immunofluorescence (CD3, MHC-II, CD45). RESULTS: The anatomy of the laryngeal skeleton was broadly similar to that of the human larynx. The blood supply is predominantly via the caudal thyroid vessels, with assistance from the cranial laryngeal artery. The porcine larynx is clearly highly immunologically active. Structured collections of leukocytes were found in the mucosal epithelium, around tubuloacinar glands, and occasionally in the submucosa. MHC-II and CD 3 cells were predominantly found within the epithelium. The highest densities of all cell types were observed in the epiglottis, tailing off caudally. The lowest densities were seen in the vocal cords. CONCLUSIONS: The porcine larynx is both anatomically and immunologically similar to the human larynx and contains a high level of immunological organization. It presents an ideal preclinical model for laryngeal transplantation.

Animals↗
PubMed1999

Characterization of a pig-to-goat orthotopic lung xenotransplantation model to study beyond hyperacute rejection.

BACKGROUND: A pig-to-goat orthotopic lung xenograft model was developed to test whether depletion of goat xenoreactive antibodies against pig red blood cells would prolong pig lung xenograft survival. METHODS: Adult goats with anti-pig xenoreactive antibodies underwent left pneumonectomy followed by orthotopic transplantation of pig left lung (group 1) or immunodepletion of their xenoreactive antibodies by extracorporeal right pig lung perfusion before transplantation without (group 2) or with (group 3) complete clampage of the right pulmonary artery. In group 4, goat left lungs were orthotopically transplanted into pigs and served as negative controls (pig serum does not have anti-goat xenoreactive antibodies). Each study group included 5 animals. Immunosuppression in surviving recipients included cyclosporine and azathioprine. RESULTS: Group 1 recipients died 7 +/- 3 hours after xenograft reimplantation of severe pulmonary hypertension and dysfunction and vasogenic shock, with little evidence of histologic xenograft injury. Group 2 xenografts had a stable circulatory and respiratory function on reperfusion and survived 9 +/- 4 days. Group 3 animals also tolerated complete occlusion of the right pulmonary artery, and xenografts assured the total respiratory support for 4 +/- 1 days. After immunodepletion, goat serum showed no detectable titers of xenoreactive antibodies, which began to reappear by postoperative day 2, where xenografts showed histologic stigmata of acute (humoral and cellular-mediated) rejection that evolved to a complete xenograft necrose at death. Group 4 xenografts showed scattered features of acute rejection 5 +/- 1 days after the operation. CONCLUSIONS: Pig left lung xenografts can provide prolonged and complete respiratory support after depletion of goat xenoreactive antibodies, but they ultimately necrose once recipient xenoreactive antibodies return to pretransplantation values.

Animals↗
PubMed1999

Experimental and clinical evaluation of a new synthetic, absorbable sealant to reduce air leaks in thoracic operations.

BACKGROUND: Air leaks after pulmonary resections may contribute to increased patient morbidity, delayed removal of chest drainage tubes, and prolonged hospitalization. OBJECTIVE: The purpose of this study was to investigate the effects of a new synthetic, absorbable sealant on the healing of healthy bronchial and lung tissues (experimental study) and its safety and efficacy to stop air leaks after lung resection (clinical study). METHODS: Fifteen large white pigs underwent a left upper lobectomy. All parenchymal surgical sites were sealed; the bronchial stump was either stapled, sealed, or both (n = 5 each). In the clinical study, 26 consecutive patients were prospectively randomized, intraoperatively, to standard closure of parenchymal surgical sites with (n = 15) or without (n = 11) the sealant. RESULTS: In the experimental study, no postoperative air leaks occurred, with intact bronchial closures and normal tissues at death. In the clinical study, 100% of intraoperative leaks were sealed versus 18% of control patients (P =.001). Although 77% (n = 10) of treated patients remained leak-free from the end of the operation to chest tube removal versus 9% (n = 1) of control patients (P =.001), there was no statistical difference in the duration of postoperative chest tube time, hospital stay, or cost. There were no acute or late undesirable side-effects related to the sealant application. CONCLUSIONS: The surgical adhesive investigated here demonstrated a compelling safety profile and significant clinical efficacy to stop air leaks after lung resections.

Animals↗
PubMed1999

Subclavian artery resection and reconstruction for thoracic inlet cancers.

PURPOSE: We previously described an original transcervical approach to resect primary or secondary malignant diseases that invade the thoracic inlet (TI). The purpose of this study was to evaluate the technical aspects and long-term results of the resection and revascularization of the subclavian artery (SA). METHODS: Between 1986 and 1998, 34 patients (mean age, 49 years) underwent en bloc resection of TI cancer that had invaded the SA. The surgical approach was an L-shaped transclavicular cervicotomy in 33 patients. In 14 of these patients, this approach was associated with a posterolateral thoracotomy (n = 10) or a posterior midline approach (n = 4). In one patient, the procedure was achieved with a single posterolateral thoracotomy approach. An end-to-end anastomosis was performed in 16 patients. In one patient, a subclavian-left common carotid artery transposition was performed. In one other patient, an end-to-end anastomosis was performed between the proximal innominate artery and the SA. The right carotid artery was transposed into the SA in an end-to-side fashion. In 16 patients, prosthetic revascularization with a polytetrafluoroethylene graft was performed. Thirty-three patients underwent postoperative radiation therapy. RESULTS: There were no cases of perioperative death, neurologic sequelae, graft infections or occlusions, or limb ischemia. There were two delayed asymptomatic polytetrafluoroethylene graft occlusions at 12 and 31 months. The 5-year patency rate was 85%. During this study, 20 patients died: 18 died of tumor recurrence (5 local and systemic and 13 systemic), one of respiratory failure, and one of an unknown cause at 74 months. The overall 5-year survival rate was 36%, and the 5-year disease-free survival rate was 18%. CONCLUSION: Tumor arterial invasion per se should not be a contraindication to TI cancer resection. This study shows that cancers that invade the SA can be resected through an L-shaped transclavicular cervicotomy, with good results with a concomitant revascularization of the SA.

Adult↗
PubMed1999

Clamshell or sternotomy for double lung or heart-lung transplantation?

OBJECTIVE: To evaluate the influence of either incision on the lungs and chest wall. METHODS: Ninety-two double lung (DLT) or heart-lung (HLT) transplantations were done since January 1990. There were 22 (24%) hospital deaths, leaving 70 patients with complete data for evaluation. We did 38 DLT and 32 HLT for end-stage chronic respiratory failure (n = 22) and primary (n = 34) or secondary (n = 14) pulmonary hypertension, using 37 fourth or fifth interspace clamshell incisions and 33 median sternotomies. RESULTS: The clamshell group included a higher percentage of DLTs (73 vs. 33%, P = 0.001) but recipient age, gender, preoperative diagnosis, bronchial anastomotic complications, number of cytomegalovirus infection, episode of acute rejection per patient-months and incidence of bronchiolitis obliterans were not statistically different between the two groups. At a follow-up time of 3.7 +/- 2 years, the overall 5-year survival of 57% was not influenced by the type of incision. The clamshell incision caused sternal over-riding in 12 (32%) patients, and eight surgical clamshell revision were necessary as compared with one median sternotomy (P = 0.02). The clamshell incision was associated with a significantly higher incidence of postoperative chronic pain (27 vs. 6%, P = 0.02). Postoperative mechanical properties of the chest wall were significantly (P < 0.0001) worse in the clamshell-group patients while the intrinsic properties of the airways were not different. CONCLUSIONS: The clamshell incision results in more postoperative deformity, chronic pain, and impaired function as compared with median sternotomy. A bilateral anterolateral thoracotomy without division of the sternum is proposed for the sequential bilateral lung transplantation technique.

Adult↗