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Biomedical subjects

P Macchiarini

Publications and source records attributed to P Macchiarini.

At least 19 recordsLinked to original sources

Radical resection of radiation-induced sarcoma of the chest wall: report of 15 cases.

BACKGROUND: Surgical management of radiation-induced sarcoma of the chest wall remains difficult because of its impressive local aggressiveness. METHODS: Between 1987 and 1995, 15 patients (median age, 58 years) underwent radical resection of radiation-induced sarcoma of the chest wall. This type of tumor was defined as a metachronous, histologically different neoplasm in the irradiated field of the original tumor. Ten patients had a history of primary breast cancer and 5 patients, Hodgkin's disease. The median delivered radiation dose to the primary tumor area was 45 Gy, and the median interval between radiotherapy and diagnosis of sarcoma was 14 years. Seven tumors were located on the sternum, three on the lateral chest wall, and five in the thoracic outlet. Four total and three partial sternectomies, three lateral chest wall resections and five resections of tumors in the thoracic outlet (three first-rib resections) were performed. Seven patients required stabilization of the chest wall with prosthetic material. Soft tissue reconstruction was carried out with either muscle flaps and skin advancement in 9, musculocutaneous flaps in 4, or skin flaps alone in 2 patients. RESULTS: One patient died 3 months after total sternectomy of respiratory failure. Two patients (13.3%) had a local complication: sepsis after sternectomy in 1 and cutaneous necrosis in 1. Local recurrence occurred in 7 patients after a median interval of 10 months. Two of them died, and 4 underwent a repeat resection, 3 of whom are still alive. Four patients died of systemic recurrence. With a median follow-up of 30 months, overall 5-year survival and 5-year disease-free survival rates were 48% and 27%, respectively. CONCLUSION: Despite poor long-term disease-free survival, radical resection of radiation-induced sarcoma of the chest wall is justified on the basis of low postoperative morbidity and the lack of other available therapies.

Female

Tracheal growth after slide tracheoplasty.

OBJECTIVE: Our goal was to investigate the effects of slide tracheoplasty on tracheal growth in newborn piglets. METHODS: Slide tracheoplasty was performed on normal trachea (n = 6) and a model of tracheal stenosis resembling that seen in infants (n = 6). After division of the trachea at its midportion between the second cartilaginous ring above and the right upper lobe takeoff below (around 23 rings), the proximal and distal segments were incised vertically on opposite anterior and posterior surfaces and reconstructed together. RESULTS: The reconstructed tracheas lengthened and their cross-sectional areas enlarged linearly at a rate of 0.94 cm per month and 1.55 mm2/kg, respectively, as the piglets grew over a 6-month period from 4.7 +/- 0.6 to 64.4 +/- 5.7 kg (+/- standard deviation). Growth was not different between the two studied groups. There was no narrowing or late restenosis. The mean anastomotic cross-sectional area was overall 1.63 +/- 0.28 times larger (range 1.2 to 2.7) than the cross-sectional area of the unreconstructed trachea. When the animals were put to death, all tracheal lumina were completely lined with normal respiratory epithelium and all layers were histologically intact; anastomotic trachealis muscles contracted less (p < 0.001) but relaxed similarly to those muscles lining normal tracheas. Tracheal blood supply was macroscopically and microscopically normal in both groups; however, newborn piglets had an almost twofold increased number of intramural capillary vessels as opposed to adult pigs (p < 0.001). CONCLUSIONS: Results suggest that slide tracheoplasty is not limited by the length of stenosis, provides a permanent enlargement of the cross-sectional airway diameter, does not compromise tracheal vascular supply, and does not impair tracheal growth as somatic growth continues.

Animals

[Intrathoracic goiters. 62 surgically treated patients].

OBJECTIVES: Intrathoracic goitres present as tumors of the upper mediastinum. Malignancy is uncommon, but sudden or progressive development often leads to compression of the trachea. We report here our experience with surgical exeresis. METHODS: From 1980 to 1995, we operated 62 patients with intrathoracic goitre. There were 23 men and 39 women (mean age 63 years). The main manifestations leading to diagnosis were dyspnea (n = 20; 32%) and identification of a mediastinal formation on routine chest x-rays (n = 19; 30%). RESULTS: Antevascular goitre was seen in 24 patients (39%) and retrovascular goitre in 38 (61%). The retrovascular goitres were located anteriorly and laterally to the trachea in 21 patients (34%) and posteriorly in 17 (27%). Simple cervicotomy was used in 57 patients (92%). Manubriotomy (n = 1) and total sternotomy (n = 4) were also required. All intrathoracic goitres removed were benign. Post-operative mortality was nul and morbidity was 11%: 2 cases of hypocalcemia and 2 tracheomalacias including 1 with recurrent nerve palsy and one with hematoma and pulmonary infection. CONCLUSION: Surgical exeresis of intrathoracic goitre is essentially required in case of respiratory distress due to compression of the trachea. Morbidity is low with simple cervicotomy.

Adult

Thymic neuroendocrine carcinoma (carcinoid): a clinicopathologic study of fourteen cases.

The medical records and histologic documents of 14 patients treated at our institution for a thymic carcinoid tumor were reviewed. There were 3 women and 11 men with an age range from 35 to 71 years. One patient had a multiple endocrine neoplasia syndrome; another had a neurofibromatosis. Twelve tumors were revealed by local symptoms and two were asymptomatic. One patient had Cushing's syndrome that appeared secondarily and was related to metastases. Tumors ranged from 6 to 20 cm and had the characteristic histologic appearance of atypical carcinoid tumor. Immunohistochemical evaluations were done. Tumors were positive for cytokeratin (92%), neuroendocrine markers (100%), and p53 oncoprotein (29%). S-100 protein antibody revealed numerous sustentacular cells in one case. Overall survival was 46% and 31% at 3 and 5 years, respectively. However, all patients died of the disease within 109 months as a result of local progression (n = 5), local relapse (n = 3), distant metastases (n = 8), or a combination of these reasons. Median survival was 71, 30, and 5 months for patients who had total resection (n = 4), partial resection (n = 5), or simple biopsy (n = 4), respectively (p = 0.023). In conclusion, thymic carcinoid tumors can be considered thymic neuroendocrine carcinomas because of their malignant behavior and histologic appearance of atypical carcinoid tumors. Complete surgical resection offers the best hope for long-term survival.

Adult

Large bilateral pulmonary artery aneurysms in Behçet's disease: rupture of the contralateral lesion after aneurysmorrhaphy.

An 18-year-old man presented with Behçet's disease and two large bilateral pulmonary artery aneurysms. The day following aneurysmorrhaphy of the right aneurysm, a massive hemoptysis led to death. Postmortem examination disclosed rupture of the left aneurysm in a segmental bronchus. The aneurysms had inflammatory walls and were associated with organized pulmonary arterial thromboses and endomyocardial fibrosis of the right ventricle. Our case report highlights the surgical risk of rupture of associated arterial lesions, certainly related to per- and postoperative pulmonary arterial pressure variations.

Adolescent

Carinal resection for bronchogenic cancer.

Traditionally, high technical morbidity and mortality and uncertain long-term survival have been associated with carinal surgery for bronchogenic carcinoma. However, growing evidence exists that judicious indications, meticulous surgery, and also perioperative management can decrease surgical mortality. Contraindications include patients whose tumors are so extensive that reconstruction would be under tension and those with involved precarinal and paratracheal nodes. Patients with diseased subcarinal nodes might benefit from surgery. Right carinal pneumonectomy is the most common carinal procedure, and the safe limit of resection is approximately 4 cm between the lower trachea and contralateral main bronchus. Small lesions involving the carina only may be resected without pulmonary resection with somewhat greater resectional limits. Right upper lobe tumors involving the carina may also be completely resected by saving the right middle and lower lobes and fashioning a new carina. Fatal early (noncardiogenic pulmonary edema) and late (anastomotic dehiscence or separation) complications after carinal pneumonectomy may be preventable by limiting mediastinal lymphatic dissection and perioperative intravascular fluid overload. A limited tailored thoracoplasty and transposition of the latissimus and serratus muscles into the postpneumonectomy pleural space can mitigate anastomotic complications. If these recommendations are respected, the technical mortality rates of carinal pneumonectomy can equal those observed after conventional pneumonectomy, and 5-year survival rates in excess of 40% can be expected for NO-1 patients. Invasion of the carina by bronchogenic carcinoma should not be considered by itself a surgical contraindication because the potential for cure is not elusive.

Anesthesia, Inhalation

Management of acquired tracheoesophageal fistula.

Acquired, nonmalignant tracheoesophageal fistulae usually result from erosion of the tracheal and esophageal walls by endotracheal or tracheostomy tube cuffs, especially when a rigid nasogastric tube is in place. This has become an infrequent occurrence with the use of high-volume, low-pressure cuffs, but it still represents a life-threatening condition. Spontaneous recovery is exceptional. Most are diagnosed while patients still are mechanically ventilated and, due to the negative effects of positive pressure ventilation on tracheal suture lines, repair should be delayed until patients are weaned. After the patients is weaned from the ventilator, a one-staged anterior approach including esophageal closure, segmental tracheal resection, and primary reconstruction definitely corrects the fistula and removes concurrent tracheal disease and should be preferred to simple division and closure of the fistula.

Anastomosis, Surgical

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

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

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

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

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

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

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

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

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