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Biomedical subjects

P Macchiarini

Publications and source records attributed to P Macchiarini.

At least 55 records · Page 3Linked to original sources
PubMed1995

Vascular ring causing symptomatic tracheal compression in adulthood.

A 32-year-old woman was referred for evaluation of a 3-year history of exertion dyspnea. An anomalous vascular ring created by a right aortic arch with mirror-image branching, left descending aorta, and aortic diverticulum narrowed the trachea circumferentially. This feature was surgically approached through a right posterolateral thoracotomy, and simple amputation of the aortic diverticulum resulted in immediate symptomatic relief.

Adult↗
PubMed1995

Maximal preservation time of tracheal allografts. The Paris-Sud University Lung Transplantation Group.

BACKGROUND: Our objective was to study the maximal preservation time of directly revascularized tracheal allografts in immunosuppressed piglets. METHODS: Donor grafts were flushed with Euro-Collins solution (65 mL/kg at 4 degrees C) by simultaneous inferior thyroid artery and bronchial artery perfusion through a 15-cm aortic segment and heterotopically implanted on their own vascular pedicle after 3 (group 1), 6 (group 2), 15 (group 3), and 24 (group 4) hours of static storage in Euro-Collins solution at 4 degrees C (n = 5 each). The animals were observed for 4 weeks after transplantation and then sacrificed. Histologic evaluation of the tracheal allografts was routinely done using specimens from open biopsies. RESULTS: The overall length of tracheal grafts was 12.4 +/- 0.6 cm, and this variable was not significantly different between the four groups. Graft exocrine (mucous secretion) function began 1.3 +/- 0.5 days after transplantation in groups 1 through 3 but was absent in all group 4 grafts (p < 0.0001). All grafts in groups 1 through 3 were viable at the time of sacrifice and showed little discernible intergroup and intragroup histologic and functional (tracheal smooth muscle contraction and relaxation) variations except for a significantly higher (p < 0.001) incidence of rejection in group 3 allografts. In contrast, all grafts in group 4 became completely necrotic 4 days after transplantation (p < 0.001) despite full patency of all the vascular anastomoses. CONCLUSIONS: These results demonstrate that tracheal allografts may be safely preserved for as long as 15 hours and that longer periods of ischemia are likely to result in irreversible allograft damage.

Animals↗
PubMed1995

Experimental tracheal and tracheoesophageal allotransplantation. Paris-Sud University Lung Transplantation Group.

We investigated the effects of allograft perfusion with a preservative technique and of combined thyrotracheoesophageal implantation on airway epithelium of long segments of thyrotracheal grafts allotransplanted on their own vascular pedicles into immunosuppressed pigs. Four groups of five animals each underwent heterotopic (into the neck) thyrotracheal (group 1) and thyrotracheoesophageal (group 2) and orthotopic thyrotracheal (group 3) and thyrotracheoesophageal (group 4) allotransplantation. Allograft revascularization included (1) interposition of donor right subclavian artery--incorporating the inferior thyroid artery--to recipient right carotid artery (end-to-end fashion) and (2) end-to-side anastomosis of donor anterior vena cava to recipient right external jugular vein. All thyrotracheoesophageal blocks were harvested after inferior thyroid artery perfusion with 4 degrees C Euro-Collins solution. The overall lengths of tracheal and esophageal grafts were 10.7 +/- 2.7 cm and 13.4 +/- 3.6 cm, respectively. In the heterotopic groups, all allografts were viable and histologically normal at postmortem examination and the incidence and severity of airway ischemia and rejections (at equal residual levels of cyclosporine) were not different between groups 1 and 2. In the orthotopic groups, the first two pigs died of airway collapse with histologically normal grafts. In the remaining pigs, temporary airway stenting was inserted and allografts remained viable and histologically intact for their entire length 30 days after transplantation. Transplanted tracheal smooth muscles had concentration-dependent contractions and relaxations similar to those of nontransplanted (native) tracheas. This study documents the feasibility of allotransplanting long tracheal and esophageal segments on their own vascular pedicles and demonstrates that allograft preservation and thyrotracheoesophageal transplantation are equally effective in minimizing airway ischemia. Thyrotracheoesophageal transplantation does not enhance recipient alloimmune response compared with thyrotracheal transplantation alone.

Animals↗
PubMed1995

Prognostic significance of peritumoural blood and lymphatic vessel invasion by tumour cells in T4 non-small cell lung cancer following induction therapy.

We investigated the impact of new biological prognostic factors is in 28 patients receiving a median of two courses of cisplatin-based chemotherapy with (n = 14) or without (n = 14) radiation and operation for stage IIIB (T4) non-small cell lung cancer (NSCLC). After induction therapy, 5 patients had a complete and 21 a partial response; 2 had a stable disease. A complete resection was made in 26 patients (93%). Five patients (18%) had their primary tumour and involved vestiges completely sterilized. In the remaining 23, the majority of the tumours showed abnormalities in the p53 gene expression (56%), harboured proliferating cells (91%) and induced angiogenesis (91%). Peritumoural blood and lymphatic vessel invasion (PBLVI) by tumour emboli was observed in 6 tumours. With a median follow-up of 25 months, overall 3-year survival was 48%; disease-free survival (DFS) has not been reached yet. The only significant factor influencing DFS in multivariate analysis was PBLVI by tumour cells; PBLVI-positive patients had a significantly higher likelihood ratio (P = 0.000001) of developing metastasis than their PBLVI-negative counterparts. This study documents the prognostic implication of PBLVI by tumour cells in T4 NSCLC.

Adult↗
PubMed1995

Technique of superior vena cava resection and reconstruction.

Superior vena cava (SVC) resection and reconstruction is a technically demanding procedure associated with several concerns. During operation, continuous arterial and venous pressure measurements are essential to monitor and maintain the physiologic arterial-venous brain parenchymal gradient. Technical details mitigating this hemodynamic compromise include intraluminal shunt procedures, pharmacologic agents and fluid implementation, short venous clamping time, and anticoagulation therapy. SVC replacement is usually afforded using a normal or ringed polytetrafluoroethylene graft.

Anastomosis, Surgical↗
PubMed1995

Operative technique of bullectomy.

The exact indications and long-term results of surgical bullectomy are still not completely clear. Patients with large-sized, compressive bullae with a normal or near-normal underlying lung parenchyma may benefit from surgical bullectomy (when carefully performed) because it relieves symptoms of dyspnea and improves exercise tolerance. By contrast, the value of surgical bullectomy in patients with diffuse, noncompressive bullous disease is less satisfactory and clear, although bilateral pneumectomy (volume reduction) has been proposed recently as an alternative to lung transplantation.

Humans↗
PubMed1994

Angiogenesis: an indicator of metastasis in non-small cell lung cancer invading the thoracic inlet.

We have attempted to identify a biologic rationale for the local aggressiveness and late treatment failure of resected non-small cell lung cancer involving the thoracic inlet. Tumor specimens from 28 patients who underwent a new transcervical approach were analyzed for the expression of tumor proliferative activity, suppressor-gene p53, intratumoral and peritumoral blood vessel invasion by tumor cells, the presence and degree of angiogenesis (induction of new capillaries and venules), and other biologic variables. Eighty-nine percent of the neoplasms were moderately or poorly differentiated, 89% expressed either an intermediate or high proliferative activity, 39% showed p53 aberrations, 71% exhibited induction of angiogenesis, and 39% had tumors that were positive for blood vessel invasion. With a median follow-up time of 3.5 years (range, 8 to 145+ months), the overall projected 5-year survival was 29% and the median disease-free interval was 23 months. Results of univariate and multivariate analysis of survival and the disease-free interval identified the degree of angiogenesis (density less than 1 versus more than 1 and number of neovessels less than 6 versus more than 6) as the only independent and significant predictors of the disease-free interval. Patients whose tumor showed a density of angiogenesis of 1 or greater and a number of neovessels of 6 or greater faced a significantly (p = 0.0001) higher relative risk of suffering systemic recurrence of their primary tumor than did their low-risk counterparts. Results demonstrate that angiogenesis significantly correlates with late treatment failure (metastasis), and this is acquired at a critical density and number of vessels.

Adenocarcinoma↗
PubMed1994

Extended operations after induction therapy for stage IIIb (T4) non-small cell lung cancer.

Twenty-three patients with stage IIIb (T4) non-small cell lung cancer received induction chemotherapy (median, 2 cycles) with (n = 12) or without (n = 11) radiation (median, 45 Gy) before operation. Nine tumors involved the carina (n = 8) or lateral tracheal wall (n = 1), 11 were located centrally and invaded the proximal pulmonary artery (n = 6), veins (n = 3), or both (n = 2), three were apical tumors involving T4 structures, and six were associated with histologically diseased mediastinal nodes. Five complete and 18 partial responses were observed after induction treatment. Resection of all residual tumor at the primary site and involved vestiges was possible in 21 patients (91%); in two apical tumors, tumor was left behind. Nine right tracheal sleeve and 11 intrapericardial pneumonectomies and three resections of apical tumors were performed; 11 patients (48%) had radical mediastinal lymph node dissection. Complete sterilization of the primary tumor was observed in 3 patients (13%). Mean operating time was 209.3 +/- 86.8 minutes, and mean blood loss was 896.9 +/- 1031 mL. Major postoperative complications occurred in 6 patients (26%), including hemothorax requiring drainage (n = 1) or reoperation (n = 1), acute distress syndrome (n = 2), and bronchopleural fistula (n = 2), and their incidence was significantly higher (p = 0.0003) among patients receiving induction chemoradiation than among those receiving chemotherapy alone (42 versus 9%). Early (< 1 month) postoperative mortality was 8.6% (n = 2). With a median follow-up of 25 months (range, 12 to more than 39 months), the projected 3-year overall survival was 54%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Chest wall reconstruction following resection of large primary malignant tumors.

Reconstructive procedures following radical resection of large primary malignant chest wall tumors (PMCWT) continue to evolve. Between 1982 and 1993, 32 consecutive patients (18 males/14 females) with a median age of 47 years (range, 12-77) underwent radical resection for large (median 10 +/- 5.4 cm) PMCWTs arising either from the bone (n = 15) or soft tissues (n = 17) of the chest wall. Nine (28%) had previous surgical resection before referral. Sixteen (50%) required extensive skin excision. Twelve sternectomies (5 total and 7 partial) and 20 lateral chest wall resections were performed. In this latter group, 16 patients (80%) had at least three ribs resected. Resection extended to the lung (10 wedge resections, 2 lobectomies and 1 pneumonectomy) in 13 patients, diaphragm in 3, abdominal wall in 2, brachiocephalic and subclavian vessels in 5, superior vena cava in 1 and upper limb in 1. Stability of the chest wall was obtained with prosthetic material in 27 patients, including Marlex (n = 21), polytetrafluoroethylene (PTFE) (n = 4) and polyglactin (n = 2) meshes. After sternectomy, six patients had a methyl methacrylate mesh reinforcement while soft tissue reconstruction was carried out using the pectoralis major muscle (PM), either alone with skin advancement (n = 8) or as a myocutaneous flap in three males (unilateral n = 2, bilateral n = 1) and by a latissimus dorsi (LD) myocutaneous flap in one female. Muscle transposition was used to reconstruct defects of the lateral chest wall and included 10 LD, 6 PM and 2 serratus anterior (SA) muscles, with associated advancement of the diaphragm in two cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Heterotopic pig model for direct revascularization and venous drainage of tracheal allografts. Paris-Sud University Lung Transplantation Group.

A macrosurgical technique of thyrotracheal harvesting and direct revascularization with and without venous drainage in a heterotopic thyrotracheal and immunosuppressed allograft in the pig model is described. Harvesting included en bloc cervicothoracic exenteration of the aortic arch and its supraortic trunks, anterior vena cava, jugular veins, subclavian vessels, thyroid gland, cervicothoracic trachea, and esophagus. This technique conserves the tracheal arterial supply provided by either the right or left subclavian artery, directly or indirectly via the inferior thyroid artery, and venous return provided by the anterior vena cava, directly or indirectly via the descending cervical vein. In recipients, implantation included (1) arterial end-to-end anastomoses of the proximal and postscalenic stumps of donor's subclavian artery to the proximal and prescalenic stumps of recipient's subclavian artery; (2) end-to-side venous anastomosis of the donor's anterior vena cava to the recipient's brachiocephalic venous trunk; and (3) heterotopic implantation of the proximal and distal orifices of the grafted trachea into the neck. Ten adult Large White pigs underwent direct revascularization of a thyrotracheal allograft with (n = 6, group 1) and without (n = 4, group 2) venous drainage. All grafts of group 2 exhibited a venous infarction, extensive inferior thyroid artery thrombosis, and ischemic and suppurative thyrotracheal necrosis 1 to 2 days after transplantation. In group 1, the length of the grafted trachea and number of rings were 9.75 +/- 1.5 cm and 22.1 +/- 3.3, respectively; ischemic time was 236.3 +/- 338.3 minutes. Group 1 pigs were put to death 4 (n = 4) and 3 (n =2) weeks after transplantation. All tracheal grafts had histologically normal airway epithelium; isolated areas of necrotic ischemia of the chorion and submucosa lasted for the first 7 days after transplantation but disappeared after epithelial regeneration. Premortem angiograms showed that all vascular anastomoses were patent. Grafts were histologically normal at postmortem examinations and all but one had no rejection. This large animal model demonstrates that long tracheal allografts might be transplanted by means of this direct revascularization and venous drainage technique.

Animals↗
PubMed1994

Double lung transplantation in situs inversus with Kartagener's syndrome. Paris-Sud University Lung Transplant Group.

En bloc double lung transplantation with bilateral bronchial anastomoses was successfully performed in three patients with complete situs inversus and end-stage Kartagener's syndrome. Dextrocardia was not a technical problem for institution of cardiopulmonary bypass, but a large azygos vein draining the systemic venous return was systematically preserved. The major technical difficulty was restoration of airway continuity, because patients with situs inversus have an inverse direction and length of the main stem bronchi. The right and left main bronchi of the recipients were approached in the aortocaval sinus and transected approximately at 1.5 cm from the carina. The donor right main stem bronchus was divided at its origin and the donor left main stem bronchus was divided proximal to the upper lobe takeoff. The different bronchial angulation was not an obstacle, and airway continuity was reestablished twice with an end-to-end anastomosis and once with a telescopic technique. Because of the midline position of the left atrium and pulmonary artery, the anastomoses with the respective recipient's structures were made as in patients with situs solitus. One patient required a right lower lobectomy because the position of the right side of the heart interfered with lobar expansion. One patient died of obliterative bronchiolitis 36 months after the operation. The remaining two are alive and doing well after 48 and 6 months, respectively.

Adult↗
PubMed1993

Germ cell tumors of the mediastinum. A 30-year experience.

BACKGROUND: The records of 98 consecutive patients (58 males and 40 females; median age, 27 years; age range, 2-64 years) who presented with a primary germ cell tumor (GCT) of the mediastinum between January 1960 and December 1990 were reviewed. There were 45 mature teratomas, 8 immature teratomas, 16 pure seminomas, and 24 malignant nonseminomatous GCT (MNSGCT). RESULTS: All patients with mature teratomas were cured by radical resection alone, except one patient who died intraoperatively. Among the eight patients with immature teratomas, five were treated before the advent of cisplatin treatment (two children younger than 15 years were cured by surgery alone and three adults died within 7 months after operation). Three patients underwent surgery followed by cisplatin-based chemotherapy (two are still alive and one died of an associated rhabdomyosarcoma). Thirteen of 16 patients with seminomas (81%) were cured by surgery either alone (5 patients) or with adjuvant radiation therapy (8 patients). Among the 24 MNSGCT, 10 were treated before 1980 without cisplatin and all but 1 died of disease progression. Fourteen patients were treated by initial high-dose cisplatin combination chemotherapy and 8 (57%) achieved complete remission (2 died of systemic mastocytosis development). CONCLUSIONS: Results indicate the benignity of mature teratomas of the mediastinum, the age-dependent clinical course of immature teratomas, and the excellent prognosis of seminomas. The improved survival advantage resulting from cisplatin-based chemotherapy in MNSGCT is impaired by the propensity to nongerminal solid tumor development and hematologic malignancies.

Adolescent↗
PubMed1993

p53 alterations in non-small cell lung cancers correlate with metastatic involvement of hilar and mediastinal lymph nodes.

Alterations of p53 are one of the most common molecular changes found in all types of lung tumors, suggesting a crucial role for p53 in bronchial carcinogenesis. However, the prognostic significance of p53 abnormalities in lung cancer patients is still unclear. By using genetic and immunohistochemical methods we have found p53 alterations in 40 of 53 (75%) primary, resected non-small cell lung cancer. A strong association (P = 0.0015) was found between deletions on chromosome region 17p13.3 and p53 mutations suggesting that loss of the wild-type p53 allele might be necessary for tumorigenesis. Correlations to clinicopathological parameters showed that p53 alterations (structural aberration of the gene and/or nuclear accumulation of the protein) are significantly linked with metastatic involvement of hilar and mediastinal lymph nodes (P < 0.01). Since the latter are well established prognostic factors for non-small cell lung cancer, p53 aberrations may also be a predictor of tumor aggressiveness.

Aged↗
PubMed1993

Technique for resecting primary and metastatic nonbronchogenic tumors of the thoracic outlet.

Although primary or metastatic nonbronchogenic tumors infrequently arise in or involve the thoracic outlet, they represent a major surgical challenge because of their tendency to encapsulate outlet structures. Fourteen patients with a histologically proven primary (n = 8) or metastatic (n = 6) nonbronchogenic outlet tumor were treated by an anterior transcervical approach, including an L-shaped cervicotomy extended into the deltopectoral groove, resection of the internal half of the clavicle, and, in the case of tumor involvement, resection of the jugular and subclavian veins, phrenic nerve, subclavian artery, brachial plexus, and ribs. All patients underwent a radical resection. Tumors extended to bony (usually the first rib), muscular (usually the anterior scalenus muscle), and nerve (usually the phrenic nerve) outlet structures in 8, 10, and 7 patients, respectively. Ten patients had involvement of outlet vessels: 6 had simple ligature (n = 5) or wedge resection (n = 1) of the subclavian vein and related branches, 1 had revascularization of both the subclavian vein by an end-to-end anastomosis and the subclavian artery by a ringed polytetrafluoroethylene graft, 1 had revascularization of the subclavian artery alone, and 2 had revascularization between the left brachiocephalic vein and superior vena cava (ringed polytetrafluoroethylene graft). Follow-up venograms showed complete patency of the anastomoses. There was one postoperative death (7%) due to multiorgan system failure. Other complications were mild and short-lasting. With a median follow-up of 3.4 years, all patients but 1 (who had systemic progression) are alive and disease free 3 to 127 months postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Tracheoesophageal fistula caused by mycobacterial tuberculosis adenopathy.

Tracheoesophageal fistulas resulting from a Mycobacterium tuberculosis infection are uncommon. We describe a patient with such a lesion that had the radiologic and clinic appearance of a malignant tracheoesophageal fistula. Use of an anterior cervical approach with one-stage esophageal repair along with tracheal resection and anastomosis allowed definitive diagnosis and treatment of this life-threatening complication.

Aged↗
PubMed1993

Laryngotracheal resection and reconstruction for postintubation subglottic stenosis. Lessons learned.

Between 1981 and June 1992, 26 consecutive patients with a postintubation subglottic stenosis (21 circumferential, 2 anterolateral) underwent the Pearson operation. Subglottic stenosis resulted from a complication of mechanical ventilation with endotracheal intubation with (n = 14) or without (n = 12) tracheostomy (median placement: 25 days). One patient had an associated laryngopharyngeal and tracheoesophageal fistula. Overall, the upper limit of the stenoses lay 1.8 +/- 0.3 cm below the vocal cords, falling in the range of 1 to 2 cm in 88% of patients; they measured 2.9 +/- 0.8 cm in length and the diameter at the level of the maximum stenotic process was 0.5 +/- 0.1 cm. Operations were performed without dissection of the recurrent nerves and plicature of the membranous trachea. Because of scarred mucosa at a higher level, one vertical section of the posterior cricoid plate with interposition of autogenous costal cartilage and 2 subtotal cricoid plate resections with stenting were necessary. The mean length of resection was 3.6 +/- 0.8 cm (range: 2-5 cm) and 88% of them ranged within 2.8 and 5 cm. Twelve thyrohyoid and 3 supralaryngeal releases were performed. Six patients required postoperative tracheostomy, but all were extubated within 24 h. Good results were obtained in 24 (96%) surviving patients; 1 failure and 1 postoperative death (sudden myocardial infarction) occurred. The results confirm that the Pearson operation is an adequate treatment for subglottic stenosis extending up to 1 cm below the vocal cords and measuring up to 6 cm in length. Dissection of both the recurrent nerves, plicature of the membranous trachea, postoperative decompressive tracheostomy and stenting are not necessary.

Adult↗