Antonio V. Sterpetti

Optimization of staging of the neck with prophylactic central and lateral neck dissection for papillary thyroid carcinoma.

Objective:To analyze the yield and rate of node metastases (pN1) for prophylactic central (CND) and lateral neck dissection (LND) for papillary thyroid carcinoma, the risk factors for pN1, and outcomes.Background:Prophylactic CND and LND are not routinely employed. Adjuvant radioiodine treatment may

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.

Abdominal aortic aneurysm in elderly patients. Selective management based on clinical status and aneurysmal expansion rate.

The records of 125 patients 75 years of age or older with a diagnosis of unruptured abdominal aortic aneurysm were reviewed. Operative mortality was 4.3 percent in 69 patients considered at low risk and 39.8 percent in 13 patients at high risk who underwent aneurysmectomy shortly after diagnosis. Forty-three patients with an asymptomatic abdominal aortic aneurysm initially measuring 3.5 to 6 cm did not undergo aneurysmal resection and were followed for 6 to 72 months (mean 24 months) with serial echography. The mean enlargement rate was 0.48 cm/year. In the 43 patients, resection of the abdominal aortic aneurysm was performed for aneurysmal expansion to greater than 6 cm, development of symptoms, or a sudden change in aneurysmal diameter. Two patients were lost to follow-up, 21 underwent elective resection, aneurysms ruptured in 2, 9 died from other causes, and 9 were alive and asymptomatic at last follow-up. An aggressive surgical approach seems appropriate, even in the asymptomatic elderly patient with a small aneurysm of 4.5 to 6 cm. Serial echographic measurement appears useful in determining which patients with a very small aneurysm of less than 4.5 cm or who are considered to be high risk surgical candidates require elective aneurysmectomy.

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.

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.

Palliative management for patients with subacute obstruction and stage IV unresectable rectosigmoid cancer: colostomy versus endoscopic stenting: final results of a prospective randomized trial

BACKGROUND Survival in patients with stage IV unresectable rectosigmoid cancer is significantly reduced, and when patients are seen with symptoms of obstruction, it is advisable to perform a diverting colostomy before acute obstruction occurs. The aim of this study was to compare the results of endoscopic stent placement with diverting proximal colostomy in patients with stage IV rectosigmoid cancer and symptoms of chronic subacute obstruction. METHODS In a prospective randomized trial, 22 patients with stage IV unresectable rectosigmoid cancer and symptoms of chronic subacute obstruction were randomized to either endoscopic placement of an expandable stent or diverting proximal colostomy. Patients were followed until death. RESULTS There was no case of mortality or major postoperative complications. Oral feeding and bowel function were restored within 24 hours after endoscopic stent placement and within 72 hours after diverting colostomy. Hospital stays were shorter (mean, 2.6 days) in patients with endoscopic stent placement than in those with diverting stomas (mean, 8.1 days) (P < .05). Mean long-term survival was 297 days (range, 125-612 days) in patients who had stents and 280 days (range, 135-591 days) in patients with stomas (P = NS). No case of mortality during follow-up was related to the procedures. All patients with stomas found them quite unacceptable. The same feelings were present in family members. None of the patients with stents or their family members found any inconvenience about the procedure. CONCLUSIONS Endoscopic expandable stent placement offers a valid solution in patients with stage IV unresectable cancer and symptoms of chronic subacute obstruction, with shorter hospital stays. The procedure is much better accepted, psychologically and practically, by patients and their family members.

Progression and regression of myointimal hyperplasia in experimental vein grafts depends on platelet-derived growth factor and basic fibroblastic growth factor production

PURPOSE The factors that lead to myointimal hyperplasia (MH) in arterial vein grafts (AVGs) are unknown. Platelet-derived growth factor (PDGF) and basic fibroblastic growth factor (bFGF) are two powerful mitogens for smooth muscle cells that have been implicated in the genesis of MH. The aim of this study was to analyze the correlation between progression and regression of MH and production of PDGF and bFGF in experimental vein grafts. MATERIALS In 64 inbred Lewis rats, a 1-cm segment of inferior vena cava was inserted at the level of the abdominal aorta. The segments of inferior vena cava were obtained from syngenic rats. In 48 rats, the AVG was explanted 3 days (n = 8), 7 days (n = 8), 4 weeks (n = 24), and 12 weeks (n = 8) after surgery. In 16 rats the vein graft was explanted after being in the arterial system for 4 weeks and was reimplanted as a venous-venous bypass in syngenic Lewis rats. Reimplanted vein grafts (RVGs) were explanted 2 weeks (n = 8) and 8 weeks (n = 8) later. Grafts were analyzed by light and electron microscopy, morphometry, and histochemistry, and were put in organ culture to assess PDGF and bFGF production and mitogenic activity. RESULTS We observed MH formation in AVGs and MH regression in RVGs (p < 0.001).PDGF and bFGF production correlated with the degree of MH (p < 0.01). Histochemistry showed PDGF and bFGF in the area of MH in AVG, which disappeared in RVG. Conditioned media from AVG had greater mitogenic activity than RVG or control veins. CONCLUSION MH formation and regression in experimental vein grafts correlate with PDGF and bFGF production.

Growth factor production by arterial and vein grafts : Relevance to coronary artery bypass grafting

BACKGROUND Occlusion caused by myointimal hyperplasia, atherosclerosis, or both is the main reason for late failure of saphenous vein coronary artery bypass grafts. On the other hand, internal mammary artery grafts are usually spared from atherosclerosis. Evidence exists that platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) are involved in the genesis of myointimal hyperplasia and atherosclerosis. The aim of this study was to assess the production of PDGF and bFGF by arterial and vein grafts. METHODS In 20 inbred Lewis rats alpha 1 cm long segment of arterial graft was interposed at the level of the abdominal aorta. In a control group of 20 Lewis rats alpha 1 cm long segment of vein graft was implanted at the level of the abdominal aorta. Animals were killed 4 weeks after operation, and the grafts were studied in serum-free organ culture to assess the production of PDGF and bFGF. RESULTS. Arterial grafts produced a smaller quantity of PDGF and bFGF than vein grafts (p < 0.01) Higher mitogenic activity was present in the conditioned media from vein grafts than in the conditioned media from arterial grafts (p < 0.001). A large amount of myointimal hyperplasia was present in all vein grafts. CONCLUSIONS This phenomenon could explain the rarity of atherosclerotic changes in internal mammary coronary bypass grafts.