The commonest carotid artery lesions observed after cervical or mediastinal irradiation are steno-occlusive. The increasing incidence of ENT cancers, the treatment of which is essentially by radiotherapy alone or associated with surgery, explain the rising number of carotid lesions. The histopathological effects of radiation on the arterial wall are an acceleration of atherosclerosis and secondary ischaemic lesions due to radio-induced occlusion of the vasa vasorum. Irradiation acts in synergy with other sources of arterial aggression such as hyperlipidaemia, hypertension, and smoking. The diagnosis and evaluation of carotid stenosis are based on echo-Doppler ultrasonography and MRI angiography. The imputability of ionising radiation is retained on a series of arguments, none of which is specific, and remains very theoretical because of the common intrication of preexisting atheromatous disease. Arteriography of the supraaortic vessels is essential for the management of these patients because of the multifocal and extensive nature of the lesions. A previous history of irradiation increases the risk of usually transient cranial nerve paralysis and of cervical wound healing. Nevertheless, the incidence of morbi-mortality reported in series of carotid artery surgery for post-irradiation lesions, conforms to expert recommendations. Angioplasty and stenting probably have a role to plays in the management of these patients. Prospective studies are required to determine its place with respect to conventional surgery which remains the reference treatment at present.
Introduction: Forkhead Box F1 (FOXF1 ) is an ontogenic transcription factor expressed in fetal lung mesenchyme. We hypothesised that altered FOXF1 expression may contribute to the profibrotic phenotype of lung fibroblasts in Idiopathic Pulmonary Fibrosis (IPF). Methods: FOXF1 expression was determined in normal (n=8) and IPF (n=17) lung biopsies. FOXF1 expression was induced or repressed in human normal (n=6) and IPF (n=6) lung fibroblasts by transfection of plasmids, siRNAs or lentiviral vectors. Proliferation, migration, collagen-1 (COL1) synthesis and gene expression were determined. Results: In normal lungs, FOXF1 was detected in smooth muscle, endothelium, and 42% of alveolar septal cells. Confocal microscopy of alveolar septa showed FOXF1 restricted to cells lacking epithelial (cytokeratin) and leucocyte (CD45) markers; 80% of FOXF1+ cells expressed CD31, an endothelial marker. A similar pattern was observed in normal regions of IPF lungs, whereas fibroblastic foci often lacked FOXF1; FOXF1 mRNA was lower in IPF lung homogenate compared to normal lungs. In normal fibroblasts, FOXF1 knockdown induced proliferation and COL1 expression; FOXF1 expression induced migration and repressed COL1. mRNA microarrays identified ARPC2 as a putative FOXF1 target. In IPF fibroblasts, FOXF1 knockdown and expression repressed and induced migration. Conclusion: In adult lung, FOXF1 was expressed in cell types consistent with mesenchymal specificity. In normal fibroblasts, FOXF1 acted as a tumor suppressor and regulated migration and COL1 expression. In IPF, reduced FOXF1 levels may confer cells of fibroblastic foci a trophic advantage and derepress collagen synthesis.
The aim of this study was to assess the influence of preservation solution type and extra- or intracellular composition on the occurrence of early graft dysfunction after clinical lung transplantation. For 170 patients who underwent a single (n = 124) or bilateral (n = 46) lung transplantation in two centers in Paris between 1988 and 1999, the preservation technique applied to the donor lung was single-flush perfusion of the pulmonary artery with one of several solutions of intracellular (Euro-Collins, n = 61; University of Wisconsin, n = 24) or extracellular composition (Cambridge, n = 64; Celsior, n = 21). The early postoperative outcome of these patients was reviewed. Reimplantation edema occurred in 48% of all patients, and the overall 1-mo survival rate was 84%. No significant difference in the incidence of edema, duration of mechanical ventilation, and 1-mo survival rate was observed between the four groups or between intra- and extracellular groups. After adjustment for graft ischemic time by means of multivariate analysis, the use of extracellular preservation fluid was associated with a lower incidence of reimplantation edema without effect on 1-mo mortality. Graft ischemic time was associated with both edema occurrence and 1-mo survival rate (p = 0.02 and p = 0.01, respectively). We conclude that extracellular-type solutions are associated with better lung preservation than intracellular-type solutions in clinical transplantation.
Aim: Bronchioloalveolar carcinomas (BACs) are rare primitive lung adenocarcinomas growing along the alveolar septum without stromal, vascular or pleural invasion. We report an immunohistochemical study of their vascular microenvironment. Methods and results: In three mucinous BACs (M‐BAC) and three non‐mucinous BACs (NM‐BAC) we examined the following parameters in comparison with the normal lung: (i) constituents of the alveolar extracellular matrix; (ii) qualitative and quantitative changes of alveolar capillaries; and (iii) expression of vascular endothelial growth factor (VEGF) by tumour cells. In M‐BAC, the alveolar matrix was unchanged compared with the normal parenchyma. Capillaries expressed normal alveolar endothelial markers and their average surface was calculated, as in normal lung, as 8%. VEGF was negative in tumour cells. In NM‐BAC, the alveolar wall was thickened by deposits of fibronectin and type III collagen containing myofibroblasts and the basement membrane was disrupted. Capillaries did not retain alveolar endothelial markers and their surface was calculated as 19%. Tumour cells expressed high levels of VEGF. Conclusions: In contrast to NM‐BAC, M‐BAC do not modify the alveolar structure and seem to exploit the normal alveolar vascular bed to grow, without inducing neoangiogenesis. A better understanding of the mechanisms of growth of lung cancers may have implications for future anti‐angiogenic therapeutic strategies.
