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Biomedical subjects

A R Chapelier

Publications and source records attributed to A R Chapelier.

14 recordsLinked to original sources

Surgery for invasive primary mediastinal tumors.

BACKGROUND: There have been few reports on results after extended radical resection for primary mediastinal tumors invading neighboring organs. METHODS: A retrospective analysis of 89 patients who underwent total or subtotal resection of a primary mediastinal tumor with resection of at least part of an adjacent structure between 1979 and 1995 was performed. Clinical data were collected from the medical records. RESULTS: There were 35 invasive thymomas, 12 thymic carcinomas, 17 germ cell tumors, 16 lymphomas, 3 neurogenic tumors, 3 thyroid carcinomas, 2 radiation-induced sarcomas, and 1 mediastinal mesothelioma. The tumor was located in the anterior mediastinum in 74% of patients. Residual masses after chemotherapy were excised in 14 patients with germ cell tumor and 8 with lymphoma. A median sternotomy was the most frequently used approach (79% of patients). Total resection was achieved in 79% and significantly improved survival (p < 0.01). Adjacent resected structures included 38 phrenic nerves, 21 superior venae cavae, 16 upper lobes, and 13 innominate veins, in 5 patients, a pneumonectomy was required. The complication rate was 17% and the mortality rate, 6%. With follow-up available for 86 patients, the overall 5-year survival rate was 69% for patients with thymoma, 42% for patients with thymic carcinoma, 48% for patients with germ cell tumor, and 83% for patients with lymphoma. CONCLUSIONS: Malignant mediastinal tumors can be safely resected even if they have invaded other mediastinal structures. Complete resection is important to achieve satisfactory long-term survival. A median sternotomy is an excellent approach, and a preoperative diagnosis by biopsy is desirable. Residual masses after chemotherapy for lymphoma or germ cell tumor should be resected. Extensive resection without a preoperative diagnosis is not indicated.

Adolescent

Inhaled nitric oxide attenuates reperfusion injury in non-heartbeating-donor lung transplantation. Paris-Sud University Lung Transplantation Group.

BACKGROUND: Non-heartbeating-donor (NHBD) lung transplantation could help reduce the current organ shortage. Polymorphonuclear neutrophil (PMN) activation plays a pivotal role in ischemia-reperfusion injury (I-R), and can be inhibited by nitric oxide (NO). We hypothesized that inhaled NO might be beneficial in NHBD lung transplantation. METHODS: The effect of inhaled NO on PMNs was studied by measuring in vivo PMN lung sequestration (myeloperoxidase activity) and adhesion of recipient circulating PMNs to cultured pulmonary artery endothelial cells (PAECs) in vitro. Pigs were randomly assigned to an NO or a control group (n=9 each). In the NO group, cadavers and recipients were ventilated with oxygen and 30 parts per million of NO. After 3 hr of postmortem in situ warm ischemia and 2 hr of cold ischemia, left allotransplantation was performed. The right pulmonary artery was ligated, and hemodynamic and gas exchange data were recorded hourly for 9 hr. Recipient PMN adherence to tumor necrosis factor-alpha- and calcium ionophore-stimulated PAECs was measured before and after reperfusion, and lung PMN sequestration was determined after death. RESULTS: NO-treated animals exhibited lowered pulmonary vascular resistance (P<0.01), as well as improved oxygenation (P<0.01) and survival (P<0.05). Adhesion of PMNs to PAECs was inhibited in the NO group before (P<0.001) and after reperfusion (P<0.0001). Lung PMN sequestration was reduced by NO (P<0.05). CONCLUSIONS: Inhaled NO attenuates I-R injury after NHBD lung transplantation. This is likely due to the prevention of I-R-induced pulmonary vasoconstriction and to the direct effect on peripheral blood PMN adhesion to endothelium, which results in reduced sequestration and tissue injury.

Administration, Inhalation

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

Inhaled nitric oxide and pentoxifylline in rat lung transplantation from non-heart-beating donors. The Paris-Sud University Lung Transplantation Group.

BACKGROUND: In non-heart-beating donor lung transplantation, postmortem warm ischemia poses a special challenge. Inhaled nitric oxide and pentoxifylline have been shown to attenuate ischemia-reperfusion injury after lung transplantation. We hypothesized that concomitant administration of inhaled nitric oxide and pentoxifylline would result in a synergistic effect on ischemia-reperfusion lung injury. METHODS: Lungs were harvested from non-heart-beating donors after 30 minutes of in situ warm ischemia, flushed, and stored for 2 hours at 4 degrees C before left lung transplantation in rats. Inhaled nitric oxide (30 ppm) was added during cadaver ventilation and reperfusion; pentoxifylline was given intravenously throughout reperfusion. The following groups were studied (n = 8 each): control, pentoxifylline, nitric oxide, and nitric oxide+pentoxifylline. Hemodynamic indices and arterial blood gases were obtained after ligation of the right pulmonary artery. Lung myeloperoxidase and wet/dry ratio were measured after death. RESULTS: All rats that did not receive nitric oxide died within 10 minutes after ligation. Inhaled nitric oxide significantly decreased pulmonary vascular resistance and improved recipient survival. Nitric oxide + pentoxifylline improved pulmonary vascular resistance, arterial oxygen tension, and survival even further and reduced lung myeloperoxidase as compared with the group that received nitric oxide only. Preservation solution flush time was significantly decreased in both groups receiving nitric oxide, suggesting that inhaled nitric oxide used during cadaver ventilation allows for a more even distribution of the preservation solution. CONCLUSIONS: We conclude that treatment with inhaled nitric oxide + pentoxifylline results in a synergistic protection from ischemia-reperfusion injury after non-heart-beating donor lung transplantation. This is likely the result of a dual action on the graft vasculature and neutrophil sequestration.

Animals

Prevention of reperfusion injury by inhaled nitric oxide in lungs harvested from non-heart-beating donors. Paris-Sud University Lung Transplantation Group.

BACKGROUND: In lung transplantation using non-heart-beating donors (NHBD), the postmortem period of warm ischemia exacerbates lung ischemia-reperfusion injury. We hypothesized that inhaled nitric oxide (NO) would reduce ischemia-reperfusion injury, and thus ameliorate the viability of the lung graft. METHODS: A blood-perfused, isolated rat lung model was used. Lungs were flushed and harvested from non-heart-beating donors after 30 minutes of in situ warm ischemia. The lung was then stored for 2 hours at 4 degrees C. Inhaled NO at 30 ppm was given either during the period of warm ischemia, during reperfusion, or during both periods. Lung ischemia-reperfusion injury was assessed after 1 hour of reperfusion by measuring pulmonary vascular resistance, coefficient of filtration, wet-to-dry lung weight ratio, and myeloperoxidase activity. RESULTS: A severe IR injury occurred in lungs undergoing ischemia and reperfusion without NO as evidenced by high values of pulmonary vascular resistance (6.83 +/- 0.36 mm Hg. mL-1.min-1), coefficient of filtration (3.02 +/- 0.35 mL.min-1.cm H2O-1 x 100 g-1), and wet-to-dry lung weight ratio (8.07 +/- 0.45). Lower values (respectively, 3.31 +/- 0.44 mm Hg.mL-1.min-1, 1.49 +/- 0.34 mL.min-1.cm H2O-1 x 100 g-1, and 7.44 +/- 0.43) were observed when lungs were ventilated with NO during ischemia. Lung function was further improved when NO was given during reperfusion only. All measured variables, including myeloperoxidase activity were significantly improved when NO was given during both ischemia and reperfusion. Myeloperoxidase activity was significantly correlated with coefficient of filtration (r = 0.465; p < 0.05). CONCLUSIONS: These data suggest that inhaled NO significantly reduces ischemia-reperfusion injury in lungs harvested from non-heart-beating donors. This effect might be mediated by inhibition of neutrophil sequestration in the reperfused lung.

Administration, Inhalation

L-arginine and pentoxifylline attenuate endothelial dysfunction after lung reperfusion injury in the rabbit. The Paris-Sud University Lung Transplant Group.

BACKGROUND: Among the factors involved in the early complications of lung transplantation is the ischemia-reperfusion syndrome related to a warm reperfusion in ischemic lungs. METHODS: Using an isolated rabbit lung preparation perfused with whole blood, we studied the effects of cold ischemia followed by a warm reperfusion on pulmonary vascular responses to reproduce experimentally the conditions encountered during lung transplantation. RESULTS: Pulmonary vascular responses to acetylcholine were rapidly altered by warm ischemia (relaxation of 7% versus 60% in controls). Conversely, relaxation was maintained even after a prolonged cold ischemic storage (maximal relaxation of 57% at 48 hours). Warm reperfusion in ischemic lungs induced major alteration of endothelium-dependent relaxation (maximal relaxation of 13% at 4 hours). The addition of L-arginine or pentoxifylline during reperfusion prevented the pulmonary endothelial alteration resulting from warm reperfusion. CONCLUSION: These data suggest that treatments aimed at maintaining intact functional endothelium reduce ischemia-reperfusion injury in transplanted lungs.

Acetylcholine

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

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

Lung preservation with Euro-Collins, University of Wisconsin, Wallwork, and low-potassium-dextran solution. Université++ Paris-Sud Lung Transplant Group.

Using isolated rat lungs, we compared prevention of ischemia-reperfusion injury provided by flushing the lungs with modified Euro-Collins solution (EC), University of Wisconsin solution (UW), low-potassium-dextran solution (LPD), or Wallwork solution (WA). After 4 hours' and 6 hours' cold ischemia, reperfusion injury was assessed on the basis of changes in filtration coefficients (Kfc) and pressure-flow curves, characterized by the slope of the curves (incremental resistance) and the extrapolation of this slope to zero flow (pulmonary pressure intercept [Ppi]). After 4 hours, Kfc and Ppi were higher with EC than with UW, LPD, and WA, and the incremental resistance was higher with EC and UW. After 6 hours, Kfc and incremental resistance Ppi were higher with LPD than with WA. Because ischemia-reperfusion injury is associated with decreased endothelial synthesis of prostacyclin and nitric oxide, we tested whether the addition of prostacyclin or the nitric oxide precursor L-arginine to WA would improve preservation. The Kfc and Ppi were lower with both treatments. In conclusion, ischemia-reperfusion injury was best prevented by using WA. The favorable effect of prostacyclin or L-arginine emphasizes the role played by endothelial dysfunction in ischemia-reperfusion injury.

Adenosine

Extramedullary hematopoietic tumors of the posterior mediastinum related to asymptomatic refractory anemia.

Two asymptomatic paravertebral thoracic masses occurred in a 65-year-old patient with isolated macrocytosis. The largest one measured 8 cm and was surgically resected with a presumptive diagnosis of schwannoma. This thoracic mass was hemorrhagic, encapsulated, and composed of fat and hematopoietic tissue. While extramedullary hematopoietic tumors usually occur in patients with severe chronic hemolytic anemia, our report suggests that such lesions must be considered in the differential diagnosis of posterior mediastinal mass in patients without clinical evident anemia.

Adipose Tissue

Anterior transcervical-thoracic approach for radical resection of lung tumors invading the thoracic inlet.

We describe an original anterior transcervical-thoracic approach required for a safe exposure and radical resection of non-small-cell lung cancer that has invaded the cervical structures of the thoracic inlet. Through a large L-shaped anterior cervical incision, after the removal of the internal half of the clavicle, the following steps may be performed: (1) dissection or resection of the subclavian vein; (2) section of the anterior scalenus muscle and resection of the cervical portion of the phrenic nerve, if invaded; (3) exposure of the subclavian and vertebral arteries; (4) dissection of the brachial plexus up to the spinal foramen; (5) section of invaded ribs; and (6) en bloc removal of chest wall and lung tumor, either directly or through an extension of the cervical incision into the deltopectoral groove. An additional posterior thoracotomy may be required for resection of the chest wall below the second rib. Between 1980 and 1991, 29 patients underwent radical en bloc resection of the inlet tumor, chest wall (ribs 1 and 2), and underlying lung, either through the anterior transcervical approach alone (n = 9) or with an additional posterior thoracotomy (n = 20). The inferior root of the brachial plexus, either alone (n = 11) or with the phrenic nerve (n = 4), was involved and resected in 15 patients (52%). Twelve patients (41%) had a vascular involvement that included the subclavian artery alone (n = 3); subclavian artery and subclavian vein (n = 3); subclavian artery, subclavian vein, and vertebral artery (n = 2); subclavian artery and vertebral artery (n = 1); subclavian vein alone (n = 1); vertebral artery alone (n = 1), or subclavian artery and vertebral artery (n = 1). The subclavian artery was revascularized either with a prosthetic replacement (n = 7) or an end-to-end anastomosis (n = 2), and the median graft patency was 18.5 months (range, 6 to more than 73 months); only 1 patient had postradiotherapy graft occlusion in the revascularized artery 6 months after operation. We performed 14 wedge resections, 14 lobectomies, and 1 pneumonectomy. There were no operative or hospital deaths. Postoperative radiotherapy (median, 56 Gy) was given to 25 (86%) patients, either alone (n = 14) or in combination with adjuvant systemic chemotherapy (n = 11). With a median follow-up time of 2.5 years, overall 2- and 5-year survivals were 50% and 31%, respectively. This transcervical-thoracic approach affords a safe exposure and radical resection of non-small-cell lung cancer involving the thoracic inlet and results in encouraging long-term survival.

Adult

Long-term follow-up after prosthetic replacement of the superior vena cava combined with resection of mediastinal-pulmonary malignant tumors.

The contraindication to curative excision of mediastinal and pulmonary cancers because of invasion of the superior vena cava is now challenged by the existence of vascular prostheses that are suitable for venous replacement. Between 1979 and 1990 22 patients underwent resection of lung cancer (n = 6) or malignant mediastinal tumors (n = 16) involving the superior vena cava. Resection was done with concomitant venous reconstruction, and polytetrafluorethylene grafts were used. All bronchogenic carcinomas necessitated right pneumonectomy, whereas the excision of mediastinal tumors had to include pulmonary resections in nine patients (five lobectomies and four sublobar resections) and the right phrenic nerve in 12 patients. Venous reconstruction was performed by interposition of a large polytetrafluoroethylene graft between the proximal and cardiac ends of the superior vena cava (n = 8), or between one (n = 10) or both brachiocephalic veins (n = 4) and the right atrium. One patient died postoperatively (4.5%), and another had mediastinitis that was successfully treated by omentopexy. Chemotherapy was administered preoperatively to five patients and postoperatively to seven patients; radiotherapy was administered to two and 10 patients, respectively. The overall actuarial survival rate is 48% at 5 years, with 11 patients presently alive. The survival rate of patients with mediastinal tumors is 60% at 5 years. Among the patients with lung cancer, two with N1 disease are alive at 16 and 51 months, and one died at 38 months; the two patients with N2 disease died at 6 and 8 months. Only one graft occlusion occurred in the postoperative period; another occurred 14 months after operation and was precipitated by insertion of a central venous catheter. The patency of all remaining grafts was demonstrated after an average time of 23 (1 to 98) months. On the basis of these results, polytetrafluoroethylene graft replacement of the superior vena cava should be part of the planning and execution of radical excision with curative intent of mediastinal and right pulmonary malignant tumors that are not present with other contraindications, such as pleural or distant metastasis and severe systemic disease.

Adult