Phillip J. Bendick

Penetrating atherosclerotic ulcers of the aorta

PURPOSE This study investigates the natural history and optimal imaging modality of penetrating atherosclerotic ulcers of the aorta. METHODS We reviewed our experience with 29 penetrating ulcers in 18 patients. Computed tomography (17 patients), magnetic resonance imaging (nine patients), and aortography (five patients) were used for diagnosis and follow-up. Patients were typically elderly (average age 74 years) and had hypertension and coronary artery disease. Ulcers were most common in the distal descending thoracic aorta (31%) and were characterized by a discrete ulcer crater (100%) and thickened aortic wall (89%). Modes of presentation included chest or back pain in four patients, distal embolization in two patients, and abnormal chest radiography results in one; the remaining were incidental findings. RESULTS Follow-up was available in ten patients with 17 ulcers from 1 to 7 years. Recurrent pain occurred in two patients, recurrent embolization occurred in one patient, and seven patients remained symptom free. Progression to saccular pseudoaneurysm occurred in five ulcers, and fusiform aneurysm occurred in two ulcers. Two ulcers were associated with an increase in aortic diameter, and nine ulcers did not change. There were no cases of aortic dissection or rupture in the follow-up period. There were no deaths and only one patient underwent resection. CONCLUSION The natural history of penetrating atherosclerotic ulcers is one of progressive aortic enlargement, with saccular and fusiform aneurysms the result if follow-up is sufficient. Aortic dissection, aortic rupture, and embolization can also occur but are less common. Contrast-enhanced computed tomography is the primary imaging modality.

Isolation of endothelial cells and their progenitor cells from human peripheral blood.

PURPOSE We have developed techniques to isolate endothelial cell (EC) progenitors from human peripheral and umbilical cord blood. METHODS Human adult peripheral and umbilical cord blood monocytes were isolated by centrifugation, and progenitor cells were separated with the use of magnetic polystyrene beads that were coated with a monoclonal antibody specific for the CD34 cell-membrane antigen. Cells were propagated in selective media, and developing cultures were immunostained for CD31, CD34, factor VIII, and vascular endothelial growth factor cell receptors. ECs that developed were transfected with a gene for prourokinase and used to line ePTFE grafts, which were evaluated in vitro in a pulsatile flow system. RESULTS Umbilical cord monocyte cultures demonstrated colonies that resembled ECs at approximately 2 weeks, with growth being best supported by EC growth media plus 20% calf serum with iron. Immunostaining of colonies was positive for CD31 and factor VIII. After 18 days in culture, CD34(+) cells from adult peripheral blood were noted, which had the typical cobblestone appearance of ECs and immunostained positively for CD31 and factor VIII-related antigens. Cultures of umbilical cord-derived cells and adult peripheral blood-derived cells developed complex line formations within 1 week in culture that stained positively for vascular endothelial growth factor receptor-2. Urokinase-transfected ECs were shown to overexpress urokinase. Prosthetic grafts lined with transfected cells showed 87.33% +/- 4.97% cell adherence after 2 hours in a pulsatile flow system at clinically relevant shear stress. CONCLUSION We conclude that endothelial progenitor cells can be isolated from human adult peripheral and umbilical cord blood and developed into EC cultures as a source of cells for vascular graft seeding and gene therapy.

Progression of superficial venous thrombosis to deep vein thrombosis

PURPOSE We have evaluated the progression of isolated superficial venous thrombosis to deep vein thrombosis in patients with no initial deep venous involvement. METHODS Patients with thrombosis isolated to the superficial veins with no evidence of deep venous involvement by duplex ultrasound examination were evaluated by follow-up duplex ultrasonography to determine the incidence of disease progression into the deep veins of the lower extremities. Initial and follow-up duplex scans evaluated the femoropopliteal and deep calf veins in their entirety; follow-up studies were done at an average of 6.3 days, ranging from 2 to 10 days. RESULTS From January 1992 to January 1996, 263 patients were identified with isolated superficial venous thrombosis. Thirty (11%) patients had documented progression to deep venous involvement. The most common site of deep vein involvement was progression of disease from the greater saphenous vein in the thigh into the common femoral vein (21 patients, 70%), with 18 of these extensions noted to be nonocclusive and 12 having a free-floating component. Three patients had extended above-knee saphenous vein thrombi through thigh perforators to occlude the femoral vein in the thigh, three patients had extended below-knee saphenous disease into the popliteal vein, and three patients had extended below-knee thrombi into the tibioperoneal veins with calf perforators. At the time of the follow-up examination all 30 patients were being treated without anticoagulation. CONCLUSIONS Proximal saphenous vein thrombosis should be treated with anticoagulation or at least followed by serial duplex ultrasound evaluation so that definitive therapy may be initiated, if progression is noted. More distal superficial venous thrombosis should be carefully followed clinically and repeat duplex ultrasound scans performed, if progression is noted or patient symptoms worsen.

Penetrating atherosclerotic ulcers of the thoracic aorta

Penetrating ulcer of the thoracic aorta is defined as an atherosclerotic lesion of the descending thoracic aorta with ulceration that penetrates the internal elastic lamina, allowing hematoma formation in the media. There is controversy whether this lesion differs from classic acute type III aortic dissection, based on its location, radiographic findings, natural history, and recommended therapeutic approach. Of 47 patients with a diagnosis of aortic dissection seen at our hospital during a 2-year period, five patients had clinical and radiographic findings of penetrating ulcer. Each of the five patients had characteristic computerized tomographic (CT) findings and two patients had angiographic confirmation. In all patients CT showed subintimal hemorrhage, aortic wall enhancement, absence of a double lumen, and contrast extravasation through the ulceration. In both patients who underwent angiography, ulceration, subintimal hematoma, and absence of a false lumen were demonstrated. The clinical presentation in four patients simulated acute aortic dissection or expanding thoracic aneurysm. The other patient, who was normotensive, did not have symptoms referable to the thoracic aorta but was studied because of an abnormal chest x-ray film. None of these five patients required surgical intervention. All five patients were alive and free of symptoms at 6 months, 8 months, 14 months (two patients), and 30 months after the original diagnosis. Follow-up CT scans in four patients showed resolution of subintimal hematoma and some dilatation of the lumen but no progression to rupture or aneurysm. Other authors stress the importance of differentiating symptomatic penetrating atherosclerotic ulcers from acute type III aortic dissection because of the higher incidence of rupture of penetrating ulcers and therefore recommend early surgical intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Predictors of mortality in trauma patients with intracranial hemorrhage on preinjury aspirin or clopidogrel.

BACKGROUND The mortality risk in elderly patients who sustained head trauma resulting in intracranial hemorrhage (ICH) while taking the antiplatelet agents aspirin (ASA) or clopidogrel or both (Plavix) was evaluated. METHODS A retrospective review identified trauma patients, age 50 or greater, who had computed tomography (CT) evidence of ICH and were taking ASA, clopidogrel, or a combination of both. Patient demographics, type of medication, mechanism of injury, Glasgow Coma Score (GCS), grading of head CT scans, and outcomes were characterized. RESULTS One hundred nine patients including 61 men and 48 women were identified; the mean age was 77 years +/- 10 years. Injury was due to level fall (73), fall from height (21), motor vehicle crash (11), and other (4). Twenty (18%) patients died; age, gender, type of medication, and mechanism of injury were not predictive of death. The initial GCS for survivors was 14.2 +/- 1.9 versus 11.3 +/- 4.9 for nonsurvivors (p < 0.007). Deaths based on initial CT grade were: grade 1, 5 of 70; grade 2, 4 of 17; grade 3, 5 of 10; grade 4, 6 of 12 (p = 0.002). Follow-up CT scans were performed in 81 patients who were not taken to surgery and had grade 1 or 2 hemorrhage initially. Of 4 patients with hemorrhage progression, there was 1 death (25%) versus 6 deaths in 77 patients without progression (8%; p = 0.70). CONCLUSIONS There is high mortality rate associated with ASA or clopidogrel or both in elderly patients who have head trauma resulting in ICH. The presenting GCS and initial grade of CT scan are most predictive of death. Progression of hemorrhage after admission is unusual. The risk of brain injury, particularly from falls, should be explained to elderly patients taking these medications.

Complications of preinjury warfarin use in the trauma patient.

BACKGROUND The frequency of use of warfarin anticoagulation increases significantly in the elderly population. It remains controversial whether this puts these patients at increased risk for hemorrhagic complications after trauma. METHODS We prospectively evaluated consecutive trauma patients who were taking warfarin and compared their outcomes to a group of age-matched patients with head injuries but not taking warfarin. RESULTS One hundred fifty-nine trauma patients on warfarin were evaluated, 94 (59%) with some type of head trauma; 25 of these 94 patients (27%) had documented intracranial trauma. Fifteen patients died (9.4%); they had an international normalized ratio of 3.3 +/- 1.6 versus 3.0 +/- 2.1 for survivors in the warfarin group (p = 0.585). Twelve deaths were in the group of 25 patients with intracranial injuries (48%). Three patients without head injury died (5%) of other causes not related to warfarin or hemorrhage at a mean of 13 days after admission. Ten of 12 patients on warfarin with intracranial injuries who died had documented loss of consciousness (LOC); two patients who died secondary to an isolated intracranial injury had no LOC. Of 70 age-matched patients with head trauma not taking warfarin, 47 (67%) had intracranial injury and 5 of these died (10%) (p < 0.001 for both values compared with study patients). There were no significant differences for patients with intracranial injury comparing those on warfarin and those who were not in terms of age, gender, mechanism of injury, Injury Severity Score, or Glasgow Come Scale score. CONCLUSION We conclude that the preinjury use of warfarin does not place the trauma patient at increased risk for fatal hemorrhagic complications in the absence of head trauma. Furthermore, the presence of a head trauma alone is not predictive of mortality. However, the presence of intracranial injury is strongly associated with a mortality rate that is significantly higher than patients with head trauma who are not taking warfarin. LOC is also associated with mortality, but the absence of loss of consciousness does not reliably indicate the absence of intracranial injury or risk of death.

The use of thermal knives in surgery: Electrosurgery, lasers, plasma scalpel

Summary In this monograph we have tried to describe the three different-thermal knives available today, to trace their development, to compare their effects on tissues, to report their hazards and to give our opinions about appropriate uses and proper techniques. Each surgeon concentrates on developing and continually refining an operative technique that is unique to himself. Some assiduously avoid electrosurgery whereas others have made it an essential part of their armamentarium, preferring a certain manufacturers unit, handpiece or even a particular setting for the current. We urge the latter group to examine their prejudices in the light of known effects on tissue and to become acutely aware of the hazard of electrosurgery. We urge the former to consider taking the time to learn the technique of its proper use. Both groups need to be aware of the areas in which our knowledge is deficient so that meaningful research may be initiated; and all surgeons need to be aware that there probably will be a proper place for all three thermal knives, since there are some situations in which each offers the best chance for the patient to benefit from the slightest but most effective “attack of surgery” our skills can supply.

a Randomized, Prospective, Double-blind, Placebo-controlled Trial of the Effect of a Calcium Channel Blocker Ointment on Pain After Hemorrhoidectomy

PURPOSESpasm of the internal sphincter plays a role in hemorrhoidal disease and may be a source of anal pain after hemorrhoid surgery. We have evaluated the effects of topical diltiazem, a calcium channel blocker, in reducing pain after hemorrhoidectomy.METHODSAfter hemorrhoidectomy, 18 patients were randomly assigned to receive 2 percent diltiazem ointment (n = 9) or a placebo ointment (n = 9). Ointments were applied to the perianal region three times daily for seven days. Patients were prescribed hydrocodone bitartrate (Vicodin ®) to take as needed. The type and number of prescribed or nonprescribed medications taken during the postoperative period were recorded. Patients maintained a log to measure postoperative pain daily and perceived benefit of the ointment, using a Visual Analog Scale ranging from 0 to 10. Any postoperative morbidity noted during the follow-up period was recorded.RESULTSPatients using the diltiazem ointment had significantly less pain and greater benefit than those in the placebo group throughout the first postoperative week. Postoperative pain scores in the placebo group averaged 8.8 ± 1.2 early and diminished to 5.2 ± 1.7 at the end of one week, compared to the diltiazem group of 5.2 ± 2.4 early and 2.3 ± 1.2 at the end of one week (P < 0.001, both time periods). Perceived benefit in the placebo group averaged 2.7 ± 1.2 vs. 5.6 ± 1.4 in the diltiazem group (P < 0.001). Total and daily narcotic use was higher in the placebo group, but this was not statistically significant (P = 0.13). No differences in the frequency of use of nonsteroidal anti-inflammatory drugs and acetaminophen were seen between the two groups, and there were no differences in morbidity between the two groups.CONCLUSIONSPerianal application of 2 percent diltiazem ointment after hemorrhoidectomy significantly reduces postoperative pain and is perceived as beneficial, with no increase in associated morbidity. Patients using a placebo ointment tend to take more prescription narcotics for pain relief postoperatively, with a similar usage of nonsteroidal anti-inflammatory drugs and acetaminophen, although differences were not significant.

Evaluation of the vertebral arteries with duplex sonography

Using duplex sonography, we have routinely evaluated the vertebral arteries as part of the carotid artery examination in 453 consecutive patients over a 6-month period. Sixty-two of these 906 vessels could not be adequately evaluated, primarily because these vessels lay too deep within the vertebral structures, resulting in a technical failure rate of 6.8%. For the remaining 844 vessels, 74.4% were considered normal by Doppler flowmeter spectral analysis. Angiographic correlation was available for 224 vessels; of 155 judged normal by duplex sonography, 144 (93%) were shown to be normal or have only mild atherosclerotic disease. Eleven vessels were considered either occluded or to have severe disease by duplex sonography, and angiography showed this to be the case in 10 (91%) vessels. Unusually strong vertebral artery flow was associated with hemodynamically significant carotid or contralateral vertebral atherosclerotic disease or subclavian steal 82% of the time. Twelve cases of subclavian steal, only one of which was symptomatic, were identified by duplex sonography; four of these were confirmed by angiography. Angiographic correlation was available for 229 vessels in which duplex evaluation showed vertebral artery flow to be moderately damped. In 11 of these (38%), angiography showed greater than 50% stenosis. Angiography judged the remaining 18 vessels in this group normal; these vessels may represent a small subgroup of patients with normal anatomy or only mild atherosclerotic disease, but with hemodynamic dysfunction that can be identified with the duplex technique.

Improved adherence of genetically modified endothelial cells to small-diameter expanded polytetrafluoroethylene grafts in a canine model

PURPOSE A significant limitation to using genetically modified endothelial cells (ECs) to seed prosthetic grafts before implantation has been poor cell adherence to the graft lumen. Methodologic changes to improve cell adherence were evaluated in a canine carotid interposition graft model using 4 mm interior diameter expanded polytetrafluoroethylene. METHODS ECs harvested from external jugular veins were grown in culture, with 80% of the cells from each culture transduced by incubation with an LXSN-type retroviral vector carrying a gene for human prourokinase and a neomycin resistance gene for selection in antibiotic G418. Control grafts had passive luminal coating with fibronectin and were seeded with transduced ECs immediately after G418 selection; these grafts were incubated for 2 days before implantation. Experimental grafts had fibronectin forcefully squeezed through the interstices and were seeded with ECs that had recovered in culture for 5 days after G418 selection; these grafts were incubated for 4 days before implantation. For each control (n = 9) and experimental (n = 12) graft, a graft prepared in the same fashion but seeded with the remaining autologous nontransduced cells was placed in the contralateral carotid artery. Grafts were explanted after 30 days and were evaluated for patency, thrombus-free surface area, and cell-free surface area. RESULTS No significant differences in patency rates were seen between any groups. The thrombus-free surface area was improved for experimental grafts (90%) compared with control grafts (76%), but this improvement did not achieve statistical significance. The cell-free surface area for transduced cells on experimental grafts was 65% compared with 96% for control grafts (p = 0.021) and was comparable with that for nontransduced cells on both control grafts (62%) and experimental grafts (51%; p = 0.201). CONCLUSIONS Adherence of genetically modified endothelial cells to small-diameter expanded polytetrafluoroethylene grafts in an in vivo physiologic flow model is significantly improved when cells have a more prolonged recovery from G418 selection, when the graft lumen is more uniformly coated with fibronectin before EC seeding, and when seeded grafts are left longer in culture before implantation to develop cell lining stability. The short-term patency rate of these seeded grafts is not affected by increased cell retention; long-term graft patency data and luminal healing require further evaluation.