Faculty Bibliography

BACKGROUND: The published results of carotid endarterectomy (CEA) in chronic renal insufficiency (CRI) patients are contradictory, mostly because of the relatively small number of patients in these studies. To better assess the neurologic complications and mortality, we reviewed a recent and substantially larger series of CRI patients who underwent CEAs. METHODS: From March 2000 to March 2003, 675 consecutive primary CEAs were performed in 609 patients (346 men, 57%) under general anesthesia. Asymptomatic carotid artery stenosis accounted for 71% of cases. CRI (serum creatinine level > or = 1.5 mg/dL) was detected in 166 patients (27%) who underwent 184 CEAs. The remaining 443 patients (73%) had 491 CEAs. RESULTS: Patients with CRI were different in age (76 +/- 8 years vs 72 +/- 9 years, P < .001), male gender (73% vs 51%, P < .001), coronary artery disease (50% vs 28%, P < .001), and diabetes mellitus incidence (38% vs 27%, P < .02). No significant difference in stroke rates was observed between the CRI patients and the control group (1.2% vs 0.5%). The mortality rate for CRI patients was 3%, whereas it was 0% for the control group ( P < .002). The 143 CRI patients with serum creatinine levels from 1.5 to 2.9 mg/dL had a 0.7% mortality rate, whereas it was 17% for 23 patients with serum creatinine levels of 3 mg/dL or more ( P < .001). The stroke rate for the former group was 0.7% and 4.3% for the latter group (NS). Asymptomatic (16) and symptomatic (7) patients with serum creatinine levels of 3 mg/dL or more had mortality rates of 13% and 28%, respectively, with P = .6. CONCLUSION: The high mortality rate observed in patients with serum creatinine levels of 3 mg/dL or more after CEA calls for a nonoperative approach in the management of asymptomatic patients.

The objective of this study was to investigate the role of inflammation, programmed cell death, its molecular modulators, and proteolysis in the pathogenesis of iliac artery aneurysms (IAAs). Nineteen IAA specimens were obtained from patients undergoing elective surgical repair. All were males with ages ranging from 55 to 85 years (mean 73 years). Controls were iliac arteries (n=6) retrieved from surgical patients without aneurysmal disease. Standard histochemical techniques were used to assess elastic lamellae fragmentation and inflammatory infiltrate in aneurysmal and normal tissues Identification of different types of cells in the aneurysm wall and detection of death-pro molecules, Fas, p53, perforin, apoptosis-mediating bcl-2 family proteins, apoptotic death substrate, and poly(adenosine diphosphate-ribose) polymerase were performed immunohistochemically. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick end-labeling (TUNEL) assay and caspase activity. Proteolytic activity was determined by 10% gelatin gel zymography. There is a conspicuous disruption and fragmentation of elastic lamellae in IAAs compared with normal arteries. Increased gelatinolytic activity was observed at 92, 72, and 67 kDa in the aneurysmal tissues. There was a significant loss of vascular smooth muscle cells (VSMCs) in the IAA walls compared with normal arteries (p < .02). Large numbers of inflammatory cells were observed in the IAA specimens (p = .01). Only aneurysmal arteries showed CD8+ T cells expressing death-promoting molecules. CD3+, CD8+, CD20+, CD30+, and CD68+ immunoreactive cells were significantly more prominent in the aneurysmal tissues than in the control arteries. There was a significant increase in the number of cells undergoing apoptosis in aneurysmal tissue than in the normal vessels (p < .02), as well as in the expression of bax, p53, CPP-32, and Fas. Apoptotic cells and proapoptotic molecules predominantly localized to the inflammatory infiltrate. VSMC apoptosis was significant in IAAs. The data confirm the architectural disruption of the IAA wall and illustrate an apparent biologic response involving inflammatory infiltrate, apoptosis, and signaling molecules capable of initiating cell death. In addition to compromising the mechanical integrity of the vessel wall, VSMC loss may contribute to imbalance in the protein profile, accelerating extracellular matrix degradation that could favor IAA development.

Although ultrasonography (US) advantageously portrays lumen and wall thickness, velocity criteria have been used primarily to interpret carotid artery stenosis. The relationship of US and velocity measurements was investigated. Peak-systolic and end-diastolic velocities (PSV, EDV) increase exponentially as the lumen of the internal carotid artery narrows and the percent stenosis (%S) increases. We tested the consistency of the, relationship between carotid velocities and US %S in two distinct data sets. One data set was used to obtain regression equations relating velocity parameters and %S based on US. Validation of these equations was conducted using a separate, independent data set. US measurements were classified in 12 %S intervals, PSV, EDV, the ratio of the internal carotid artery to the common carotid artery PSV, and %S were entered consecutively until 10 records for each %S interval were obtained. Regression equations obtained in the first data set were used to predict %S in the second data set. Predicted %S was then compared with actual US %S. The highest correlation in the first data set (r = .89) was between %S and the natural logarithm (In) of PSV. This In PSV -%S equation was then applied to a second data set of an additional 120 carotid duplex images. In the second data set, actual %S and PSV-predicted %S differed by >10% in 38 cases (32%). When all velocity-%S regression equations were used for comparison, differences between actual and at least one velocity-predicted %S were >10% in 19% of the arteries. Conversely, actual %S matched at least one prediction of %S based on velocity data in 81% of the cases. US %S differed significantly from single velocity-based estimates of %S in at least one-third of the cases. On the other hand, four of five US measurements were confirmed by at least one velocity parameter. Emphasis on US, in addition to velocity data, is recommended for the interpretation of duplex US carotid examinations.

Von Hippel-Lindau (VHL) gene is a tumor suppressor gene that plays a genome "gatekeeper'' role and controls several downstream effector genes. We have previously demonstrated that both in vivo and in vitro adenovirus-mediated gene transfer of tumor suppressor genes into the vascular endothelium is effective in decreasing neointimal hyperplasia and abnormal cell proliferation. The degree of apoptosis induced by these genes is critical in mediating the in vivo responses to gene therapy and the maintenance of the crucial balance between cell death and viability. Since VHL gene is known to regulate vascular endothelial growth factor (VEGF) as well as other angiogenic factors, it may exhibit a greater potential in the attenuation of vascular disorders in comparison to other tumor suppressor genes. This study focused on whether adenovirus-mediated VHL gene transfer into human vascular smooth muscle cells has an effect on cell proliferation and induction of apoptosis. Human aortic smooth muscle cells (HASMC) were grown as monolayers and transfected with varying titers of adenovirus containing the VHL cDNA (AdVHL). The negative controls were adenovirus containing green fluorescent protein (AdGFP), vector alone (AdNull), and virus-free infection medium. Adenovirus encoding wild-type p53 (Adp53) was used as positive control. Cell viability and proliferation were determined by using trypan blue exclusion and MTS-based CellTiter 96 AQ Proliferation Assay. Apoptosis was evaluated by TUNEL assay, morphologic changes, and nucleosomal DNA degradation. Following AdVHL transfection HASMCs demonstrated a dose-dependent decrease in viability as compared to negative controls (p < 0.05). AdVHL-transfected cells exhibited a decrease in their proliferative ability by 40.21 +/-1.66 (SEM)%. In cultures transfected with the positive control, Adp53, the cell viability as well as proliferation was highly reduced (p < 0.001). AdGFP and AdNull did not increase HASMC apoptosis above baseline levels. The cells exposed to adenoviruses expressing tumor suppressor genes underwent apoptosis, with Adp53 demonstrating a very high magnitude of cell death (75.27 +/-3.52 [SEM]%). AdVHL expression caused 45.36 +/-2.55 (SEM)% apoptosis in HASMC. Recombinant adenovirus-mediated VHL expression is efficacious in limiting vascular smooth muscle cell growth in vitro. Overexpression of VHL suppresses HASMC proliferation and regulates apoptosis. Further experiments are indicated to examine whether VHL may be a useful adjunct in limiting myointimal hyperplasia.

The clinical significance of lower extremity deep vein thrombus (DVT) propagation in the setting of anticoagulation therapy remains unclear. The purpose of this study is to compare results of thrombus outcome found with repeat duplex ultrasonography to the incidence of pulmonary embolism and mortality. During a recent 18-month period, 457 patients were diagnosed with lower extremity DVT with duplex ultrasonography and their data were retrospectively analyzed. Repeat examinations were available for review in 118 patients (51 men, 67 women). Results of repeat duplex exams were divided into 4 groups: resolved, improved, unchanged, or extended proximally. All patients received heparin and warfarin therapy. Ventilation-perfusion (V/ Q) scans were obtained only for signs and symptoms of pulmonary embolism (n=30). Mortality, the prevalence of high-probability V/ Q scans, frequency of intracaval filter insertion, gender, mean age, mean prothrombin time (PT), mean partial thromboplastin time (PTT), mean number of repeat ultrasounds per patient, and mean time over which the repeat ultrasounds took place were compared among the 4 groups. Patients who had proximal extension of DVT (19%) on repeat duplex ultrasound had an increased prevalence of pulmonary embolism (p<0.05). Also, patients whose DVT resolved were younger (p<0.05). There was no difference among the 4 groups in mortality, placement of Greenfield filters, mean PT, mean PTT, mean number of ultrasound exams per patient, or mean follow-up time over which the exams took place. Proximal extension of DVT documented by repeat duplex ultrasound is a significant risk factor for pulmonary embolism. Repeat duplex ultrasound can identify a group of patients who may benefit from insertion of an intracaval filter device.

PURPOSE: Radiofrequency ablation (RFA) of the greater saphenous vein (GSV; "closure") is a relatively new option for treatment of venous reflux. However, our initial enthusiasm for this minimally invasive technique has been tempered by our preliminary experience with its potentially lethal complication, deep venous thrombosis (DVT). METHODS: Seventy-three lower extremities were treated in 66 patients with GSV reflux, between April 2003 and February 2004. There were 48 (73%) female patients and 18 (27%) male patients, with ages ranging from 26 to 88 years (mean, 62 +/- 14 years). RFA was combined with stab avulsion of varicosities in 55 (75%) patients and subfascial ligation of perforator veins in 6 (8%) patients. An ATL HDI 5000 scanner with linear 7-4 MHz probe and the SonoCT feature was used for GSV mapping and procedure guidance in all procedures. GSV diameter determined the size of the RFA catheter used. Veins less than 8 mm in diameter were treated with a 6F catheter (n = 54); an 8F catheter was used for veins greater than 8 mm in diameter (n = 19). The GSV was cannulated at the knee level. The tip of the catheter was positioned within 1 cm of the origin of the inferior epigastric vein (first GSV tributary). All procedures were carried out according to manufacturer guidelines. RESULTS: All patients underwent venous duplex ultrasound scanning 2 to 30 days (mean, 10 +/- 6 days) after the procedure. The duplex scans documented occlusion of the GSV in 70 limbs (96%). In addition, DVT was found in 12 limbs (16%). Eleven patients (92%) had an extension of the occlusive clot filling the treated proximal GSV segment, with a floating tail beyond the patent inferior epigastric vein into the common femoral vein. Another patient developed acute occlusive clots in the calf muscle (gastrocnemius) veins. Eight patients were readmitted and received anticoagulation therapy. Four patients were treated with enoxaparin on an ambulatory basis. None of these patients had pulmonary embolism. Initially 3 patients with floating common femoral vein clots underwent inferior vena cava filter placement. Of the 19 limbs treated with the 8F RFA catheter, GSV clot extension developed in 5 (26%), compared with 7 of 54 (13%) limbs treated with the 6F RFA catheter (P =.3). No difference was found between the occurrence of DVT in patients who underwent the combined procedure (RFA and varicose vein excision) compared with patients who underwent GSV RFA alone (P =.7). No statistically significant differences were found in age or gender of patients with or without postoperative DVT (P = NS). CONCLUSION: Patients who underwent combined GSV RFA and varicose vein excision did not demonstrate a higher occurrence of postoperative DVT compared with patients who underwent RFA alone. Early postoperative duplex scans are essential, and should be mandatory in all patients undergoing RFA of the GSV.

The standard preoperative duplex arteriography (DA) from the aorta to the pedal vessels is time consuming and may be unnecessary in patients presenting with calf claudication alone. The feasibility of a shortened protocol was evaluated. Of 286 femoral-popliteal reconstruction based on DA during the last 4A years, 79 (28%) were primary operations for calf claudication. Eliminating the aortoiliac portion of the test except for the distal external iliac artery and limiting the scanning of the infrapopliteal vessels to one or two arteries in the leg would significantly shorten the exam. To confirm the adequacy of the inflow tract, we relied on the common femoral artery Doppler waveform analysis and the intraoperative graft pressure upon completion of the bypass. Of the 79 primary femoral-popliteal bypasses, 53 (67%) had triphasic common femoral artery waveform and the remaining 26 had monophasic or biphasic waveforms. Three (6%) of the 53 femoral-popliteal bypasses in the former group had significant pressure gradients measured intraoperatively and were treated with iliac angioplasties and stents for unsuspected stenoses in 2 cases and a covered stent for a common iliac aneurysm in 1 case. Three, two, and one infrapopliteal vessel runoff was observed in 24 (45%), 16 (30%), and 9 (17%) extremities, respectively. Four patients (8%) had significant stenoses (>50%) or occlusion of all three infrapopliteal arteries. Eighty-one percent of the patients would have completed the short protocol had we scanned the peroneal artery initially. An additional 8% would have required scanning of a second vessel (anterior tibial) and only 11%, scanning of all three infrapopliteal vessels. The time interval for completion of short-protocol DA was significantly less than the time for the standard DA (16.2 A+/- 5.2A min vs. 35.1 A+/- 10.6 min) ( p < 0.01). We believe that the proposed short DA protocol combined with intraoperative graft pressure measurements can be used in 94% of the patients who have a patent popliteal artery (>/= 7 cm). It is a totally noninvasive approach that is particularly suitable for vascular technologists and surgeons who wish to start utilizing DA instead of contrast arteriography prior to infrainguinal reconstructions. However, the short protocol does not avert the need for completion arteriography of the inflow arteries and readiness to perform endovascular procedures to correct lesions not suspected by common femoral artery waveform analysis.

Venography is rarely available for comparison with ultrasonography (US) as a means for quality assurance (QA) in the detection of lower extremity venous thrombosis. New QA methods must be implemented. We compared results of multiple serial studies performed in the same extremity as a QA indicator. From a 3-year sample of close to 9,000 venous tests, we obtained a subset of 44 patients who had 331 tests in 71 lower extremities throughout the years. A positive or negative study preceded or followed by another positive or negative study was considered as a confirmed study. A negative or positive study not preceded or followed by a negative or positive study was considered as unconfirmed. Explanations were then sought to explain unconfirmed results. There were 169 (51%) and 124 (37%) confirmed positive and negative studies, respectively, and 13 (4%) and 25 (8%) unconfirmed positive and negative studies, respectively. Of the 13 unconfirmed positive tests, 2 were preceded by negative tests, 3 were preceded and followed by negative tests, and 8 were followed by negative tests. Of these 13 tests, 4 documented extensive venous thrombosis. Of the 25 unconfirmed negative tests, 11 followed treatment for venous thrombosis, 6 had recurrent thrombosis with intermittent lysis, and 8 were followed by positive tests. Considering the low probability of extensive thrombosis being a false-positive test, positive predictive value was 95% (173/182). Excluding 11 negative tests following treatment for venous thrombosis, negative predictive value was 90% (124/138) and accuracy was 93% (297/320). US versus US and literature US versus venography comparisons of these statistics were similar.

The limitations and complications associated with contrast angiography (CA) prior to lower extremity revascularization have led to an increased interest in duplex arteriography (DA) as a potential replacement. We report our experience with DA in patients with diabetes and/or chronic renal insufficiency (CRI) that would particularly benefit from a noninvasive approach to preoperative evaluation of the arterial tree. From January 1998 to November 2000, DA was performed in 145 patients with diabetes mellitus and/or CRI prior to 180 arterial reconstructions. One hundred twenty-one procedures were performed on 91 patients with diabetes alone, 41 on 33 patients with diabetes and CRI, and 18 on 15 patients with CRI alone. Patient ages ranged from 36 to 98 years (mean 72 +/- 12 years). Indications for surgery were severe claudication in 33 (18%), rest pain in 37 (21%), nonhealing ischemic ulcers in 52 (29%), and limb gangrene in 58 (32%). Optimal inflow and outflow anastomotic sites were selected according to a diagram based on DA that included arterial tree imaging from mid-aorta to the pedal vessels. Preoperative contrast arteriography was performed in 16 cases (9%) because of extremely poor runoff based on DA and limited visualization of outflow vessels. The distal anastomosis was to the popliteal artery in 89 cases (49%) and to the tibial and pedal arteries in 91 (51%). Intraoperative findings confirmed the preoperative DA results with the exception of one (0.6%) where the distal anastomosis was placed proximal to a significant stenosis requiring an extension graft. The use of DA presents a safe and reliable option to prebypass CA for many patients with diabetes or CRI. The ease of use and favorable patient outcomes achieved by this imaging modality may rival the use of CA for these patients.