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Biomedical subjects

Marc de Perrot

Publications and source records attributed to Marc de Perrot.

At least 19 recordsLinked to original sources

Role of lung transplantation in the treatment of bronchogenic carcinomas for patients with end-stage pulmonary disease.

PURPOSE: To determine the role of lung transplantation in the treatment of patients presenting with bronchogenic carcinoma and end-stage lung disease. METHODS: An international survey was conducted to determine the outcome of patients with bronchogenic carcinoma in the explanted lung at the time of transplantation. A group of 69 patients was collected from 33 centers. RESULTS: Twenty-six patients underwent 29 lung transplantations for advanced multifocal bronchioloalveolar carcinoma (BAC) as the primary indication for transplantation, and 13 developed a recurrence, with an overall 5-year actuarial survival of 39%. Incidental bronchogenic carcinomas classified as stage I (n = 22), II (n = 12), and III (n = 2), or as incidental multifocal BAC (n = 7), were found in the explanted lung of the remaining 43 patients. The 5-year actuarial survival was 51% in patients with stage I carcinomas, and was significantly better than for patients with stage II and III carcinomas (survival of 14%) or with incidental multifocal BAC (survival of 23%). Time from transplantation to recurrence and from recurrence to death was significantly longer in patients with multifocal BAC than in patients with other types of bronchogenic carcinoma. In addition, the site of recurrence was limited to the transplanted lung in 88% of the patients with multifocal BAC, whereas it was always widespread in patients with other types of bronchogenic carcinoma. CONCLUSION: This study demonstrates that long-term survival can be achieved after lung transplantation in patients with stage I bronchogenic carcinoma or with advanced multifocal BAC.

Adenocarcinoma, Bronchiolo-Alveolar↗

Twenty-year experience of lung transplantation at a single center: Influence of recipient diagnosis on long-term survival.

OBJECTIVES: The objective of this study was to examine the long-term patient outcomes of lung transplantation in a single center. METHODS: Between 1983 and 2003, 521 lung transplants were performed in 501 patients. Major indications were cystic fibrosis (n = 124), chronic obstructive pulmonary disease (n = 88), alpha-1 antitrypsin deficiency (n = 63), pulmonary fibrosis (n = 97), primary pulmonary hypertension (n = 35), Eisenmenger syndrome (n = 21), and miscellaneous end-stage lung diseases (n = 93). RESULTS: The 5-, 10-, and 15-year survivals for all recipients were 55.1% (95% confidence interval: +/-5%), 35.3% (+/-6%), and 26.5% (+/-11%), respectively. The most common causes of death were sepsis and bronchiolitis obliterans syndrome. Despite an increased postoperative mortality rate, patients with primary pulmonary hypertension achieved the best long-term survival (10-year survival: 59%). Recipients with cystic fibrosis without Burkholderia cepacia infection achieved significantly better long-term survival (10-year survival: 52%) than those with Burkholderia cepacia infection (10-year survival: 15%). The 10-year survival was also significantly better in recipients with chronic obstructive pulmonary disease (43%) than in recipients with alpha-1 antitrypsin deficiency (23%). Although the incidence of bronchiolitis obliterans syndrome was similar between recipients with chronic obstructive pulmonary disease (39%) and alpha-1 antitrypsin deficiency (46%), recipients with alpha-1 antitrypsin deficiency died of sepsis more frequently than recipients with chronic obstructive pulmonary disease (27% vs 6%, respectively; P =.0003). CONCLUSIONS: Although bronchiolitis obliterans syndrome and sepsis still limit the durability of the benefit, lung transplantation returns many patients with end-stage lung disease to active and productive lives. Differences in the complications and long-term survival show the important contribution of the recipient diagnosis to the success of lung transplantation.

Adolescent↗

15 years single center experience with surgical resection of the superior vena cava for non-small cell lung cancer.

OBJECTIVES: To examine our results with surgery for locally advanced non-small cell lung cancer (NSCLC) invading the superior vena cava (SVC). METHODS: A retrospective analysis of patients who underwent resection between 1988 and 2003 was performed. Postoperative morbidity, long-term survival, including risk factors for overall and disease-free survival were examined. RESULTS: Median age of the 15 operated patients was 60 years (28-78). All had direct SVC invasion by tumor. All underwent mediastinoscopy. Seven patients with N2 disease, and one with a bulky right upper lobe tumor received induction therapy. Eight underwent lobectomy (three sleeve), and seven had pneumonectomy (two carinal). The SVC was replaced by interposition graft in nine patients, whereas six had partial resection. There were two postoperative deaths (14%) and three major morbidities (23%). There was one late graft thrombosis. Mean follow-up was 25 months (3-132, median 11). Overall 1 and 3-year survival was 68 and 57% and disease-free survival was 55 and 27%, respectively. All late deaths were due to recurrence. Survival of patients with N2 disease was not significantly worse than those with localized (N0/N1) nodal disease. There was a trend towards later recurrence in patients who had induction therapy (median disease-free interval of 29 months versus 5 months in the untreated group, P = 0.3), but there was no significant effect on overall survival. The extent of lung resection and type of SVC procedure did not influence long-term survival. CONCLUSIONS: Carefully selected patients with NSCLC and SVC involvement can be operated upon with acceptable postoperative morbidity and mortality. Induction therapy appears to delay recurrence.

Adult↗

Risk quantification of early outcome after lung transplantation: donor, recipient, operative, and post-transplant parameters.

BACKGROUND: Because there is no reliable evaluation system of recipient acuity after lung transplantation, comparing patients among centers is difficult. The purpose of our study was to identify risk factors for 30-day mortality and prolonged intensive care unit stay and to develop a scoring system to evaluate the severity of impairment and to predict surgical outcomes. METHODS: We prospectively collected data from 122 lung transplant recipients and from 119 donors from January 1997 to June 2000. We assessed donor, recipient, and operative factors; ischemic time; and immediate post-operative physiologic parameters to identify risk factors for 30-day mortality and prolonged intensive care unit stay. Furthermore, we sub-classified these factors into grades to develop a scoring system for predicting surgical outcomes. RESULTS: Cardiopulmonary bypass use, body mass index >25 kg/m2, immediate post-operative systolic pulmonary arterial pressure, trend of oxygenation index from 12 to 24 hours after transplantation, and the Acute Physiology and Chronic Health Evaluation II score correlated significantly with outcomes, and the sum of these 5 scores correlated strongly with outcomes (p < 0.0001). CONCLUSIONS: We conclude that the total score of these 5 risk factors could be used to predict 30-day mortality and prolonged intensive care unit stay. This scoring system also will facilitate standardization among transplant centers in evaluating post-transplant severity of illness.

Female↗

Recipient T cells mediate reperfusion injury after lung transplantation in the rat.

Leukocytes have been implicated in ischemia-reperfusion (IR) injury of the lung, but the individual role of T cells has not been explored. Recent evidence in mice suggests that T cells may play a role in IR injury. Using a syngeneic (Lewis to Lewis) rat lung transplant model, we observed that recipient CD4(+) T cells infiltrated lung grafts within 1 h of reperfusion and up-regulated the expression of CD25 over the ensuing 12 h. Nude rats (rnu/rnu) and heterozygous rats (rnu/+) were used to determine the role of T cells in IR injury. No significant difference in lung function was observed between nude and heterozygous recipient rats after 2 h of reperfusion. However, after 12 h of reperfusion, recipient nude rats had significantly higher oxygenation and lower peak airway pressure than recipient heterozygous rats. This was associated with significantly lower levels of IFN-gamma in transplanted lung tissue of recipient nude rats. Reconstitution of recipient nude rats with T cells from heterozygous rats restored IR injury after 12 h of reperfusion. The effect of T cells was independent of neutrophil recruitment and activation in the transplanted lung. These results demonstrate that recipient T cells are activated and mediate IR injury during lung transplantation in rats.

Adoptive Transfer↗

Accommodation after lung xenografting from hamster to rat.

BACKGROUND: Long-term xenograft survival can be achieved in hamster hearts transplanted into rats treated with cobra venom factor (CVF) and cyclosporine A (CsA). This phenomenon of "accommodation" is associated with expression of protective genes such as bcl-2, bcl-X(L), and heme-oxygenase-1. We examined whether accommodation could be induced in hamster-to-rat lung xenografts and whether the pattern of protective genes is similar to cardiac xenografts. METHODS: We used hamster-to-rat cardiac and lung xenotransplantation models. Cardiac xenotransplants were treated with CVF+CsA and compared with untreated controls. Lung xenotransplants were treated with either CVF+CsA or FK506 and cyclophosphamide (Cp) and compared with untreated controls. All recipients were killed by 21 days after transplantation. We examined graft survival and protein expression of protective genes, and we performed histologic and immunohistologic analyses. RESULTS: Rejection occurred rapidly in untreated rats. CVF+CsA or FK506+Cp treatment significantly influenced graft survival. Eight of 12 CVF+CsA-treated heart transplants survived 21 days. Seven of 16 CVF+CsA-treated lung grafts and five of 12 FK506+Cp-treated lung xenografts survived 21 days. We observed significant protein expression of bcl-2, bcl-X(L), and heme-oxygenase-1 in cardiac xenografts treated with CVF+CsA at 2, 14, and 21 days after transplantation, compared with normal hamster hearts. We also observed significant expression of these proteins in lung xenografts treated with either CVF+CsA or FK506+Cp at 21 days after transplantation, compared with normal lungs. CONCLUSIONS: Accommodation may be a general phenomenon for all organs, mediated through protective genes. Induction of accommodation does not require disruption of the complement system.

Adaptation, Physiological↗

Ischemia-reperfusion-induced lung injury.

Ischemia-reperfusion-induced lung injury is characterized by nonspecific alveolar damage, lung edema, and hypoxemia occurring within 72 hours after lung transplantation. The most severe form may lead to primary graft failure and remains a significant cause of morbidity and mortality after lung transplantation. Over the past decade, better understanding of the mechanisms of ischemia-reperfusion injury, improvements in the technique of lung preservation, and the development of a new preservation solution specifically for the lung have been associated with a reduction in the incidence of primary graft failure from approximately 30 to 15% or less. Several strategies have also been introduced into clinical practice for the prevention and treatment of ischemia-reperfusion-induced lung injury with various degrees of success. However, only three randomized, double-blinded, placebo-controlled trials on ischemia-reperfusion-induced lung injury have been reported in the literature. In the future, the development of new agents and their application in prospective clinical trials are to be expected to prevent the occurrence of this potentially devastating complication and to further improve the success of lung transplantation.

Graft Rejection↗

Impact of minimally invasive trans-cervical thymectomy on outcome in patients with myasthenia gravis.

OBJECTIVE: To study the impact of minimally invasive trans-cervical thymectomy on the incidence of remission of patients with myasthenia gravis (MG) in a single institution over a 10-year period. METHODS: A total of 120 consecutive patients referred for video-assisted trans-cervical thymectomy between 1991 and 2000 were included in the analysis. Complete remission was defined as no symptoms and no treatment for 6 months, and remission as minimal ocular symptoms (slight ptosis) or treatment with pyridostigmine only for 6 months. RESULTS: There were 86 females and 34 males with a median age of 33 (range 14-79) and 36 years (range 12-68), respectively. Symptoms of MG lasted between 2 months and 17 years before thymectomy (median 10 months). Surgery was converted to a partial upper sternotomy in 23 cases (19%). The median hospital stay decreased from 2 days (range 1-8) before 1994 to 1 day (range 1-8) thereafter (p<0.0001). Postoperative complications occurred in four patients (3.3%). After a median follow-up of 48 months (range 6-117 months), 50% of the patients were in complete remission (41%) or in remission (9%). Kaplan-Meier estimates rate of complete remission were 30% after 5 years of follow-up and 91% after 10 years. CONCLUSIONS: Minimally invasive trans-cervical thymectomy can be performed with short hospital stay and low morbidity, and achieve excellent durable results at 10 years.

Adult↗

Bronchogenic carcinoma after solid organ transplantation.

BACKGROUND: This study assesses the risk of bronchogenic carcinoma after solid organ transplantation. Although the overall incidence of malignancy is increased after solid organ transplantation, the risk of bronchogenic carcinoma in the transplant population has not been systematically studied. METHODS: Among a cohort of 3,374 patients transplanted in our institution between 1985 and 2000 (1,735 kidney recipients, 930 liver, 313 heart, and 396 lung recipients), 9 patients (0.3%) had a bronchogenic carcinoma develop. Lung carcinoma occurred in 3 kidney recipients, 3 liver recipients, 2 heart recipients, and 1 lung recipient. RESULTS: Time to diagnosis after the transplant procedure ranged from 9 to 126 months (mean, 63 months). Aside from the lung transplant candidate, all recipients had a smoking history. Seven patients underwent thoracotomy and 6 had a complete resection. Tumors were classified as stage IA (n = 1), IB (n = 2), IIB (n = 2), IIIA (n = 2), IIIB (n = 1), and IV (n = 1). Genotyping demonstrated that the carcinoma arising in the lung transplant recipient originated from the donor and may have been transmitted at the time of transplantation. Two patients were alive without recurrence 21 and 42 months after the operation. CONCLUSIONS: The risk of bronchogenic carcinoma is low and occurs mainly in recipients with a smoking history. However, bronchogenic carcinoma can also be transmitted from donor lungs at the time of transplantation. Hence careful examination of chest roentgenograms, and computed tomographic chest scan if available, as well as meticulous assessment of the lung, and biopsy of any suspicious lesions, are important to limit the risk of lung cancer transmission, especially with the liberalization of donor criteria.

Aged↗

Lung transplantation. Lung preservation.

Over the past decade, improvements in the technique of lung preservation have led to significant reduction in the incidence of ischemia-reperfusion-induced lung injury after lung transplantation. The challenge remains to improve the number of donor lungs available for transplantation. While the number of patients on the waiting list is constantly increasing, only 10% to 30% of donor lungs are currently being used for transplantation. Hence, the development of new strategies to assess, repair, and improve the quality of the lungs could have a tremendous impact on the number of transplants performed. In addition, an improved understanding of the mechanisms involved in lung preservation might help elucidate the potential link between acute lung injury and chronic graft dysfunction. In the future, genetic analysis using novel technologies such as microarray analysis will help researchers determine which genes control the injury seen in the transplantation process. Hopefully, this information will provide new insights into the mechanisms of injury and reveal potential new strategies and targets for therapies to improve lung preservation.

Graft Rejection↗

De novo pulmonary capillary hemangiomatosis occurring rapidly after bilateral lung transplantation.

A 45-year-old woman experienced diffuse bilateral pulmonary capillary hemangiomatosis within 3 months after bilateral lung transplantation. The donor was a 41-year-old man with excellent lung function and without histologic or macroscopic pulmonary lesions at the time of retrieval. This case supports the theory that persistent infection or inflammation may be an inciting factor in uncontrolled angiogenesis, leading ultimately to diffuse pulmonary capillary hemangiomatosis.

Adult↗

Impact of human interleukin-10 on vector-induced inflammation and early graft function in rat lung transplantation.

This study was undertaken to examine the time course of human interleukin (hIL)-10 gene expression after transtracheal administration of adenoviral (Ad)hIL-10 and its effect on the early adenoviral proinflammatory cytokine response and on post-transplant lung function. Using a rat lung transplant model, we observed that lungs retrieved 12 h after the administration of AdhIL-10 were associated with significant improvement in post-transplant lung function. Shorter periods of transfection were associated with significantly elevated levels of tumor necrosis factor-alpha and macrophage inflammatory protein-2 in lung tissue, leading to an increased degree of injury. The release of proinflammatory cytokines secondary to the adenoviral vector was reduced by high-dose methylprednisolone (30 mg/kg) administered 3 h before transfection. Reduction in the early adenoviral inflammatory response was associated with significant improvement in post-transplant lung function when lungs were retrieved 6 or 12 h after transtracheal administration of AdhIL-10. Transtracheal administration of adenoviral-mediated hIL-10 to donor lungs is associated with a significant early inflammatory response that may enhance ischemia-reperfusion injury if insufficient hIL-10 is expressed in lung tissue before retrieval. The period between delivery of AdhIL-10 and lung retrieval can be reduced if the early inflammatory response is suppressed with methylprednisolone.

Adenoviridae↗

Risk factors for acute lung injury after thoracic surgery for lung cancer.

UNLABELLED: Acute lung injury (ALI) may complicate thoracic surgery and is a major contributor to postoperative mortality. We analyzed risk factors for ALI in a cohort of 879 consecutive patients who underwent pulmonary resections for non-small cell lung carcinoma. Clinical, anesthetic, surgical, radiological, biochemical, and histopathologic data were prospectively collected. The total incidence of ALI was 4.2% (n = 37). In 10 cases, intercurrent complications (bronchopneumonia, n = 5; bronchopulmonary fistula, n = 2; gastric aspiration, n = 2; thromboembolism, n = 1) triggered the onset of ALI 3 to 12 days after surgery, and this was associated with a 60% mortality rate (secondary ALI). In the remaining 27 patients, no clinical adverse event preceded the development of ALI-0 to 3 days after surgery-that was associated with a 26% mortality rate (primary ALI). Four independent risk factors for primary ALI were identified: high intraoperative ventilatory pressure index (odds ratio, 3.5; 95% confidence interval, 1.7-8.4), excessive fluid infusion (odds ratio, 2.9; 95% confidence interval, 1.9-7.4), pneumonectomy (odds ratio, 2.8; 95% confidence interval, 1.4-6.3), and preoperative alcohol abuse (odds ratio, 1.9; 95% confidence interval, 1.1-4.6). In conclusion, we describe two clinical forms of post-thoracotomy ALI: 1). delayed-onset ALI triggered by intercurrent complications and 2). an early form of ALI amenable to risk-reducing strategies, including preoperative alcohol abstinence, lung-protective ventilatory modes, and limited fluid intake. IMPLICATIONS: In an observational study including all patients undergoing lung surgery, we describe two clinical forms of acute lung injury (ALI): a delayed-onset form triggered by intercurrent complications and an early form associated with preoperative alcohol consumption, pneumonectomy, high intraoperative pressure index, and excessive fluid intake over the first 24 h.

Acute Disease↗

Neuroendocrine carcinoma (carcinoid) of the thymus associated with Cushing's syndrome.

Neuroendocrine carcinoma (carcinoid) of the thymus associated with Cushing's syndrome is a rare disease. Recent evidence suggests that these tumors form part of a continuous spectrum ranging from well-differentiated carcinomas to small cell carcinomas. We report two new cases and review the 23 cases reported in the literature since 1972. The different diagnostic modalities are discussed, and an algorithm for the diagnosis of ectopic secretion of adrenocorticotropin (ACTH) is presented. In the future, the advent of radiologic and nuclear imaging as well as more accurate workup should help to diagnose these tumors at an earlier stage and improve the long-term outcome.

ACTH Syndrome, Ectopic↗

Bilateral lung transplantation using a donor with a tracheal right upper lobe bronchus.

We report on a case of successful bilateral sequential lung transplantation using a donor with the right upper lobe bronchus arising from the trachea. After en-bloc donor lung retrieval, the right bronchial stump was fashioned to create one lumen including the bronchus intermedius and the aberrant right upper lobe bronchus. A carinoplasty was performed in the recipient with resection of a portion of the lateral wall of trachea. The anastomosis was completed using a telescoping technique without any complication. This case demonstrates the possibility of successfully using donor lungs with such anatomic abnormality for transplantation.

Adult↗

Solitary fibrous tumors of the pleura.

Solitary fibrous tumor of the pleura is a mesenchymal tumor that has been increasingly recognized over the past few years. The tumor was initially described in the pleura, but it has been reported in many other sites lately. Although the majority of these tumors have a benign course, the malignant form still remains enigmatic. Indeed, the behavior of these tumors is often unpredictable and does not always correlate with histologic findings. In addition, benign tumors may remain unproblematic for several years before changing into a malignant form. In order to define more precisely the clinical behavior of solitary fibrous tumors of the pleura, we reviewed the literature with particular attention to the clinical presentation, histopathologic characteristics, and cytogenetic differentiation of these tumors. A staging system and an algorithm for the management and follow-up of these patients are proposed.

Algorithms↗