Rabih A. Chaer

Basic Science Review: Current Insights on the Biology and Clinical Aspects of VEGF Regulation

Vascular endothelial growth factor (VEGF) is a key molecule that orchestrates the formation and function of vascular networks. Impaired regulation of angiogenesis is implicated in a number of pathologic states. For instance, neoplasias exhibit uncontrolled angiogenesis, whereas ischemia and states of vascular insufficiency involve reduced VEGF activity. As the role of VEGF has been elucidated in these disease processes, its therapeutic role has been developed. The Food and Drug Administration has approved several anti-VEGF agents for treating colorectal, lung, and kidney cancer. VEGF-inducing agents have also been used experimentally to induce angiogenesis in patients with critical limb ischemia. As more knowledge is gathered about the biology of VEGF and its receptors, there is greater promise for therapeutic modulation of VEGF expression. The purpose of this review is to describe the various therapeutic and biologic factors that regulate the expression of VEGF.

Primary neuroendocrine tumors of the thymus

Primary neuroendocrine tumors of the thymus are highly aggressive tumors that rarely occur. A little more than 200 cases have been reported, many of which were single case reports. Only a few articles contained modest series from single centers for analysis. A review of 157 cases collected from the major series reported to-date show a clinical pattern with male preponderance (male:female ratio, 3:1) and a mean age of 54 years. Most patients presented with symptoms and signs of local compression. Almost 50% of these tumors were functionally active and were associated with endocrinopathies. Several histologic variants have been described, all with similar ultrastructural features. The biologic behavior of these tumors shows a direct relation to the degree of differentiation. Whenever possible, surgical resection is the treatment of choice as adjuvant therapy is controversial and has been used with variable success. Potential therapies exploit the presence of somatostatin receptors on a variety of these tumors. Use of radiolabeled Octreotide for radionuclide therapy has yielded tumor inhibition in animal models and may have clinical application. Fifty-one percent of the patients survived 3 years, 27% survived 5 years, and less than 10% survived beyond 10 years. Histologic grade, tumor extension, and early detection are the most important factors affecting survival. Other prognostic factors that impact outcome include presence of endocrinopathy, incomplete resectability, nodal status, and presence of distant metastasis.

Current Management of Extracranial Carotid Artery Disease

Stroke is the third most common cause of death in the United States. There are approximately 700,000 strokes/year; 80% are ischemic, and 20-30% of ischemic strokes are secondary to carotid disease. Carotid stenosis is traditionally treated by carotid endarterectomy (CEA). Multicenter, randomized, controlled trials have shown that surgery significantly reduces the risk of ipsilateral stroke in patients with severe symptomatic and asymptomatic carotid stenosis. Endovascular techniques for treating carotid stenosis have been developed over recent years. Carotid angioplasty and stenting (CAS) with cerebral protection has become an alternative to CEA for high-surgical-risk patients and the procedure of choice for stenoses inaccessible by surgery. In this review we summarize the existing data regarding the traditional state of management of extracranial carotid artery stenosis and compare these data to a critical analysis of the recent results of CAS.

Genetics and Gene Manipulation Therapy of Premature Coronary Artery Disease

Despite the notable recent scientific advances, our ability to detect and prevent premature coronary artery disease (CAD) remains limited, and the identification of patients at risk is yet to be based on objective scientific testing. Eliciting a family history of CAD currently remains the only available screening tool to identify patients with a genetic predisposition. The risk of CAD attributable to genes appears to be most significant at younger ages, and this may explain the lack of definite markers for the disease. Candidate gene association studies focusing on young patients with CAD will, therefore, be more likely to identify a true genetic risk. In this report, we review the known genetic risk factors for premature CAD. We also discuss the potential gene manipulation therapy of CAD as well as of vein graft atherosclerosis following coronary artery bypass surgery.

Endovascular Repair of 2 Iliac Pseudoaneurysms and Arteriovenous Fistula Following Spine Surgery

Purpose: To describe endovascular repair of traumatic iliac pseudoaneurysm and arteriovenous fistula (AVF) following spinal surgery. Case Report: A 48-year-old male underwent minimally invasive L5-S1 hemilaminectomy, foraminotomy, and microdiscectomy spinal surgery for trauma related to a motor-vehicle accident. Postoperative angiogram demonstrated pseudoaneurysm of the right internal iliac artery and AVF at the common iliac bifurcation with the right iliac vein with prompt filling of the iliac vein and vena cava. The second patient, a 25-year-old female, underwent minimally invasive L4-S1 hemilaminectomy, foraminotomy, and microdiscectomy spinal surgery for intractable pain and was complicated with postoperative symptoms of congestive heart failure. Postoperative angiogram demonstrated AVF between the right common iliac artery and vein with associated pseudoaneurysm formation. Endovascular repair was performed in both cases. Follow-up imaging revealed no endoleak and complete pseudoaneurysm and AVF exclusion. Conclusions: Endovascular repair of iliac injuries following spine surgery can be successfully performed with minimal morbidity.

Closed chest hypothermic circulatory arrest for complex intracranial aneurysms

BACKGROUNDnRecent advances in techniques of cardiopulmonary bypass permitted hypothermic circulatory arrest (HCA) using groin cannulation with the chest closed (CC-HCA) and without direct access to the heart. Herein we describe our experience with this technique for complex intracranial aneurysms.nnnMETHODSnBetween 1992 and 1999, 16 patients (4 men and 12 women) with a mean age of 52 years (range 32 to 61 years) with complex intracranial aneurysms underwent resection or clipping of their aneurysms at our institution using the technique of CC-HCA and groin cannulation. Groin access was obtained with 16F to 19F arterial and 18F to 20F venous cannulas placing the tips at the aortoiliac and atriocaval junctions, respectively. Patients were cooled to a nasopharyngeal temperature of 16 degrees C.nnnRESULTSnMean circulatory arrest time was 32 minutes. No patient required conversion to standard sternotomy and central cannulation. There were no intraoperative deaths. The 30-day hospital mortality was 2 of 16 patients (12%). Of the 14 surviving patients (88%), 1 developed bilateral third nerve palsy and another left hemiparesis that improved on follow-up. Both were discharged to an extended care facility and continued to do well at home after discharge. Two patients developed deep venous thrombosis postoperatively and required anticoagulation. All patients continued to do well at a mean follow-up of 42 months.nnnCONCLUSIONSnThe less invasive technique of CC-HCA through groin cannulation avoids complications associated with a sternotomy, is safe and is associated with little morbidity, reduced operative time, and early hospital discharge and rehabilitation.

Vascular Wall Invasion in Neurofibromatosis-Induced Aortic Rupture

Neurofibromatosis type 1 (NF-1) is an autosomal dominant disease primarily characterized by cutaneous café au lait macules, benign neurofibromas, and iris hamartomas. A spectrum of vascular abnormalities is associated with NF-1. We present a case of a 49-year-old female with NF-1 and spontaneous rupture of the infrarenal aorta caused by invasion of a neurofibroma and treated with endovascular stent grafting.

Bilateral asymmetric popliteal entrapment syndrome treated with successful surgical decompression and adjunctive thrombolysis.

Popliteal artery entrapment syndrome (PAES) is the most common cause of lower leg claudication in patients younger than 50 years. The different types of PAES can result in different rates of arterial damage, leading to aneurysmal degeneration or occlusion. We report a rare case of a young patient presenting with asymmetrical bilateral popliteal artery entrapment. Type III PAES on the right resulted in severe limb ischemia and was treated by division of the accessory tendon and replacement of damaged artery with vein graft. On the left, the medial head of gastrocnemius was resected to release a type I PAES.

Current management of extracranial carotid artery disease.

Stroke is the third most common cause of death in the United States. There are approximately 700,000 strokes/year, eighty percent are ischemic, and 20-30% of ischemic strokes are secondary to carotid disease. Carotid stenosis is traditionally treated by carotid endarterectomy (CEA). Multicenter randomized controlled trials have shown that surgery significantly reduces the risk of ipsilateral stroke in patients with severe symptomatic and asymptomatic carotid stenosis. Endovascular techniques for treating carotid stenosis have been developed over recent years. Carotid angioplasty and stenting (CAS) with cerebral protection has become an alternative to CEA for high-surgical-risk patients and the procedure of choice for stenoses inaccessible by surgery. In this review we summarize the existing data regarding the traditional state of management of extracranial carotid artery stenosis, and compare these data to a critical analysis of the recent results of CAS.

Late presentation of retained intracardiac ice pick with papillary muscle injury

An unusual case of a penetrating intracardiac injury is described in a 16-year-old boy who presented with a retained 14-cm segment of an ice pick that went unnoticed by the patient for 4 days. The ice pick had lacerated the anterior papillary muscle of the left ventricle causing avulsion of its tip and prolapse of the anterior leaflet of the mitral valve resulting in severe mitral regurgitation. The urgency for surgical correction of the traumatic mitral valve injury at the time of extraction of the intracardiac foreign body through a single-stage approach versus a two-stage approach is discussed.