Antonino Cavallaro

Leiomyosarcoma of the inferior vena cava: Analysis and search of world literature on 141 patients and report of three new cases

Leiomyosarcoma of the inferior vena cava is a rare and potentially curable tumor. Uncertainty about the results of treatment derives from lack of a large series in the same center and of a long-term follow-up of the published cases. A review of the world literature from 1871 to 1989 allowed us to collect information on 141 patients with inferior vena cava leiomyosarcoma to which our three cases have to be added. The tumor arose from the lower segment of the inferior vena cava (infrarenal portion) in 49 patients, from the middle segment (from the renal veins to the hepatic veins) in 59, and from the upper segment (from the hepatic veins to the right atrium) in 34 patients. Complete clinical, pathologic, and therapeutic data and up-to-date follow-up have been obtained through personal correspondence with several authors. All data have been examined with both univariate and multivariate analyses as predictive factors for outcome. Variables, associated with an increased risk of death from disease, included the involvement of inferior vena cava upper segment and a high-grade tumor. Patients who underwent a radical resection of the tumor (82 patients, 56.9%) had a significantly better survival (27.9% and 14.2%, 5- and 10-year survival rates, respectively). Of these patients, those with tumor of the inferior vena cava middle segment fared better than those with lower segment tumor (5- and 10-year survival rates were 48.3% and 34.4%, respectively, for middle segment tumor and 9.3% and 0.0% for lower segment tumor). Variables associated with a good outcome and longer survival were the presence of abdominal pain and the absence of a palpable abdominal mass. Despite the high rate of recurrence (52.4% of patients undergoing radical operation; median time, 25 months), radical resection of inferior vena cava leiomyosarcoma is the only chance for a long-term cure. An earlier and more accurate preoperative diagnosis, by means of modern diagnostic techniques (echography, CT scanning, magnetic resonance imaging) will allow a higher rate of radical resection to be performed with an increase in patient survival.

Percutaneous transluminal angioplasty versus surgery for subclavian artery occlusive disease

Twenty-one patients who underwent percutaneous transluminal angioplasty (PTA) for proximal stenosis of the subclavian artery were compared with 15 patients who underwent carotid subclavian reconstruction. This represents the first attempt to directly compare the two procedures. All patients had routine Doppler examination during follow-up. Mean follow-up was 30 +/- 24 months after PTA and 40 +/- 25 months after surgery. The incidences of procedural complications were similar (PTA one complication, surgery two complications). Although better early results were achieved in patients who underwent PTA (actuarial patency: PTA 91 percent, surgery 87 percent), after dilatation, we observed a continuous deterioration of the hemodynamic status of the artery, which led to a high rate of late restenosis (actuarial patency: PTA 54 percent, surgery 87 percent). There were no significant changes postoperatively. The specific role of each procedure is analyzed in view of the new acknowledgment of the clinical importance of proximal subclavian artery disease.

Shear stress induces transforming growth factor–beta1 release by arterial endothelial cells ☆

BACKGROUND Myointimal hyperplasia is a common complication after vascular reconstruction. Increasing shear stress has been shown to reduce formation of myointimal hyperplasia. The aims of our study were (1) to analyze the correlation between shear stress and release of transforming growth factor (TGF)-beta 1 by endothelial cells and (2) to determine the effect of TGF-beta 1 on smooth muscle cell proliferation. METHODS Bovine arterial endothelial cells were subjected to increasing shear stress in an in vitro serum-free system. The release of TGF-beta 1 by endothelial cells was assessed by enzyme-linked immunosorbent assay and Western blot analysis. The effect of TGF-beta 1 on the proliferation of the subconfluent monolayer of bovine smooth muscle cells was determined by tritiated thymidine uptake. RESULTS Shear stress induced a significant increase of the release of TGF-beta 1 by endothelial cells (p < 0.001). This phenomenon was proportional to the level of shear stress. The amount of TGF-beta 1 released by endothelial cells subjected to shear stress had a significant inhibitory effect on growth rate and tritiated thymidine uptake of smooth muscle cells. CONCLUSIONS On the basis of the results of our study, we conclude that increasing shear stress induces release of TGF-beta 1 by arterial endothelial cells in a concentration that has a clear inhibitory effect on smooth muscle cell proliferation. This phenomenon could explain the inhibitory effect of increasing shear stress on the formation of myointimal hyperplasia.

Surgical treatment of popliteal artery entrapment syndrome: A ten-year experience

Popliteal artery entrapment syndrome is increasingly described in the world literature as a cause of lower limb arterial impairment. It is caused by the anomalous interrelationship between the popliteal artery and its surrounding muscular and/or tendineous structures. The first case surgically treated was reported in 1959 and since then more than 300 cases have been reported including our personal experience (31 cases in 23 patients). We have treated surgically 19 males and four females with symptoms which were moderate (cramping after intensive physical training, paraesthesia, etc.) in 14 limbs, intermittent claudication in 16 and necrosis (first toe) in one. Preoperative arteriography showed arterial occlusion in eight limbs, stenosis in eight and aneurysms in two. In 11 limbs stenosis or occlusion was only shown after active plantar hyperextension and in two arteriography was not done because surgical indications were established on the basis of a venogram positive for popliteal vein entrapment syndrome. Ten different anatomical variants were seen and the medial head of gastrocnemius muscle was involved in 74.2%. Surgical treatment consisted of division of the aberrant musculotendinous tissue in 18 cases (in two of these balloon angioplasty was also used). In 12 cases a vascular reconstruction was also required, while one case was explored without a specific procedure being warranted. Optimal results were obtained when the syndrome was treated at an early stage by simple division of musculotendinous tissue (94.4% long-term patency rate, mean follow-up 46.0 months, min 2, max 120 months). When arterial grafting was required the long-term patency rate was only 58.3% (mean follow-up 43.5 months, min 1, max 100 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular endothelial growth factor increases the migration and proliferation of smooth muscle cells through the mediation of growth factors released by endothelial cells

BACKGROUND Vascular endothelial growth factor (VEGF), a highly specific chemotactic and mitogenic factor for vascular endothelial cells (EC), appears to be involved in the development of atherosclerosis. The purpose of our study was to assess if VEGF might indirectly stimulate SMC migration and proliferation in a EC-SMC coculture system, through the mediation of growth factors released by EC. METHODS Bovine aortic SMC were cocultured with bovine aortic EC treated with hrVEGF, to assess SMC proliferation and migration. The release and mRNA expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta(1) (TGFbeta(1)) were assessed by ELISA and PCR analysis. RESULTS hrVEGF (10 ng/ml), added to EC cocultured with SMC, induced a significant increase in tritiated thymidine uptake by SMC as compared to controls (P < 0.01) and a significant increase in SMC migration in respect to control (27%; P < 0.01). EC stimulated with hrVEGF increased the release and the expression of bFGF and decreased the release and the expression of TGFbeta(1) with a statistically significant difference in respect to controls (P < 0.001). CONCLUSIONS VEGF indirectly stimulates SMC proliferation and migration through the modulation of bFGF and TGFbeta(1) released by EC.

Shear stress induces changes in the morphology and cytoskeleton organisation of arterial endothelial cells

OBJECTIVES The aim of this study was to determine the changes in the morphology and cytoskeleton organisation of endothelial cells (EC) determined by exposure to a laminar flow. Cultured EC were exposed to a wall shear stress of 6 dyne/cm2 for 24 hours. CHIEF OUTCOME MEASURES The morphology of EC was analysed by light and scanning electron microscopy. The organisation of the cytoskeleton was determined by double fluorescence labeling with antibody anti-vimentin, anti-vinculin, anti-tubulin, and with rhodamine-labeled phalloidin. RESULTS EC exposed to laminar flow become round-shaped with decreased area of adhesion to the substrate. There was a clear reorganisation of the cytoskeleton after exposure to shear stress; the distribution of actin changed from a stress fibre pattern to a more diffuse membrane-associated distribution. These changes in shape and cytoskeleton organisation were reversible after a 48-hour resting period. CONCLUSIONS EC respond to laminar flow in a predictable manner and these findings may be correlated to the functional changes of EC observed after exposure to shear stress.

Modulation of arterial smooth muscle cell growth by haemodynamic forces

To define the correlation between flow dynamics and the proliferation of arterial smooth muscle cells (SMCs), bovine arterial SMC were subjected to increasing laminar flow shear stress in an in vitro system. Smooth muscle cells were seeded in a fibronectin-coated polystyrene cylinder at 5 x 10(5) cells/tube. The experimental groups were subjected to increasing shear stress (3, 6, 9 dyn cm-2) for a 24-h period. The control group was subjected to similar incubation conditions without flow. Shear stress reduced significantly (p less than 0.01) the 24-h incorporation of tritiated thymidine and cell proliferation. This effect was proportional to the level of shear stress and was still evident 24 h after flow cessation. Flow cytometry demonstrated a lower percentage of SMCs in S-phase with increasing shear stress. Extrapolation of these findings to the clinical setting might explain how unphysiological shear stress can predispose to the abnormal proliferation rate of SMCs and early plaque formation.

Shear Stress Influences the Release of Platelet Derived Growth Factor and Basic Fibroblast Growth Factor by Arterial Smooth Muscle Cells

OBJECTIVES To determine the correlation between haemodynamic forces and the release of two mitogens for smooth muscle cells (SMC): Platelet Derived Growth Factor (PDGF) and basic Fibroblast Growth Factor (bFGF). METHODOLOGY Bovine aortic smooth muscle cells were seeded on fibronectin coated polystyrene cylinders and allowed to reach confluence. The cells were subjected to a laminar flow of 50 cc/min (3 dyne/cm2), 100 cc/min (6 dyne/cm2) and 150 cc/min (9 dyne/cm2) in an in vitro system. Control cells were subjected to similar incubation conditions without flow. PRINCIPAL RESULTS Shear stress increased the release of mitogens by SMC. The release of mitogens was proportional to the level of shear stress and was still evident 24 hours after flow cessation. Conditioned serum-free medium from SMC subjected to shear stress increased tritiated thymidine uptake in Swiss 3T3 fibroblasts 13-fold as compared to conditioned serum-free medium from control SMC not subjected to shear stress (p < 0.01) and threefold as compared to standard control (p < 0.001). Addition of an excess of anti-PDGF antibody reduced the mitogenic activity of the conditioned medium by 30% (p < 0.01). Addition of an excess of anti-bFGF antibody reduced the mitogenic activity of the conditioned medium by 60% (p < 0.01). CONCLUSIONS Increasing shear stress promotes the release of both PDGF and bFGF from arterial SMC in culture and is a possible explanation for atherosclerosis formation.

Popliteal artery entrapment syndrome: The role of early diagnosis and treatment

BACKGROUND The purpose of this study was to evaluate whether certain factors could influence arterial impairment at presentation for treatment of popliteal artery entrapment syndrome (PAES) and whether its early diagnosis could optimize long-term results. METHODS Between 1979 and 1995, 30 patients were treated for PAES at our institution. Patients were characterized by age, risk factors, associated diseases, preoperative symptoms, affected side, dominant limb, duration of symptoms, musculotendinous structure causing the compression, arteriographic findings, arterial status at presentation, type of operation, postoperative complications, and long-term follow-up. RESULTS Twenty-nine (65%) limbs underwent musculotendinous section (MTS), 15 (33%) limbs underwent vascular reconstruction, and 1 (2%) was surgically explored. Patients submitted to MTS were younger (mean, 31 +/- 3 years) than patients who underwent vascular reconstruction (mean, 41 +/- 4 years; p < 0.05). MTS limbs had a greater number of minor symptoms compared with those that underwent vascular reconstruction (62% versus 20%; p < 0.02). Arteriogram showed that MTS limbs had a greater number of normal findings at rest when compared with limbs that underwent conventional reconstruction (85% versus 0%; p < 0.001). No specific factors influenced the arterial status at presentation. During follow-up, treadmill examination revealed that MTS limbs had a better response (96%) than limbs that had undergone vascular procedures (67%; p < 0.02). MTS limbs had a better long-term patency rate (mean, 87 +/- 7 months) compared with limbs that were submitted to vascular reconstruction (mean, 107 +/- 8 months) (95% versus 65%; p < 0.02). CONCLUSIONS Because PAES is a progressive disease that can create serious vascular obstructive disease and no specific factors seem to influence the degree of vascular impairment, the detection and treatment of PAES at an early stage permit better long-term results.

Formation of myointimal hyperplasia and cytokine production in experimental vein grafts.

BACKGROUND The purpose of this study was to determine the correlation between progression and regression of myointimal hyperplasia (MH) and cytokine production in experimental vein grafts. Although the autologous vein is the best suitable bypass conduit for reconstruction of peripheral arteries, at the end of the first year thrombosis in the coronary and lower extremity circulation ranges from 20% to 50%. Many of these failures are caused by MH. METHODS In 76 inbred Lewis rats, a 1 cm long segment of inferior vena cava was inserted at the level of the abdominal aorta. The segments of inferior vena cava were obtained from syngeneic Lewis rats. In 56 animals the arterial vein graft was explanted 3 days (n = 10), 7 days (n = 10), 4 weeks (n = 26), and 12 weeks (n = 10) after operation. In 20 animals the vein graft was explanted 4 weeks after being in the arterial system and reimplanted as iliac venovenous bypass in syngeneic Lewis rats. These grafts were explanted 2 weeks (n = 10) and 8 weeks (n = 10) later. Grafts were analyzed by light and electron microscopy, morphometric study, and histochemical analysis and were put in an organ culture to assess cytokine production. RESULTS We observed MH formation in arterial vein grafts and MH regression in reimplanted vein grafts (p < 0.001). MH formation was correlated with production of platelet-derived growth factor, basic fibroblast growth factor, interleukin-1, and tumor necrosis factor-alpha. MH regression was correlated with transforming growth factor-beta 1 production. CONCLUSIONS On the basis of the results of our study, we conclude that MH formation in experimental vein grafts depends on production of platelet-derived growth factor, basic fibroblast growth factor, interleukin-1, and tumor necrosis factor-alpha, and MH regression depends on transforming growth factor-beta 1 production. Cytokine therapy may represent a valuable new treatment to prevent vein bypass failures caused by MH.