Safety, tolerability, and bioavailability of topical SAR 1118, a novel antagonist of lymphocyte function-associated antigen-1: a phase 1b study.

PURPOSE: A growing body of evidence points to a role for inflammation mediated by lymphocyte function-associated antigen-1 (LFA-1) and its ligand intercellular adhesion molecule-1 in the pathogenesis of diabetic macular oedema. This phase 1b clinical trial assessed the safety, tolerability, and pharmacokinetics of topically administered SAR 1118, a novel LFA-1 antagonist, in human subjects. METHODS: In this prospective, randomized, double-masked trial, 13 subjects scheduled for vitrectomy received one of three concentrations of topical SAR 1118 (0.1, 1.0, or 5.0%) twice daily for 1 week before surgery. Undiluted aqueous and vitreous samples were collected at surgery and analysed for the concentration of the medication. RESULTS: All subjects completed the entire course of medication. The only adverse events reported were instillation site irritation (4/13, 31%) and dysgeusia (3/13, 23%). These were mild and transient, occurring at the highest dose. Mean concentrations (ng/ml) of SAR 1118 in the aqueous humour were 0.25, 37.2, and 101.1 for the 0.1%, 1.0%, and 5.0% dose groups, respectively. SAR 1118 was below the level of detection (0.5 ng/ml) for all vitreous samples except in a single subject who had a history of prior vitrectomy and a dislocated intraocular lens. CONCLUSIONS: Topical SAR 1118 was safe and well tolerated, and dose-dependent levels of drug were detected in aqueous. However, vitreous levels were below the threshold of detection with the concentrations tested. Further investigation of this medication for posterior segment applications would require intravitreal delivery or chemical modification of the drug.

Phase I trial on the safety of topical rhVEGF on chronic neuropathic diabetic foot ulcers.

OBJECTIVE: To assess the safety/tolerability and perform a preliminary efficacy evaluation of a multiple-dosing regimen of recombinant human vascular endothelial growth factor (VEGF165 or rhVEGF; telbermin) applied topically to chronic diabetic neuropathic foot ulcers. METHOD: Subjects with type 1 or 2 diabetes mellitus were randomised to receive either topical applied telbermin (72 microg/cm2) (n=29) or placebo (n=26) treatment to the foot ulcer surface in conjunction with standard ulcer care. Subjects received treatment every 48 hours (maximum three doses per week) for up to six weeks. Weekly 35mm photography, quantitative planimetry and physical examinations documented the ulcer appearance, surface area and stage. Safety endpoints included incidence of clinically significant hypotension, adverse events and ulcer infection. Exploratory efficacy endpoints included percentage reduction in total ulcer surface area, incidence of complete ulcer healing and time to complete ulcer healing. RESULTS: Incidence of adverse events was comparable in the two treatment groups. None of the adverse events were attributed to study drug, and no hypotension was observed as a result of telbermin treatment. Occurrence of infected study ulcers appeared to be balanced between the treatment groups. Positive trends suggestive of potential signals of biological activity were observed for incidence of complete ulcer healing (41.4% telbermin versus 26.9% placebo at day 43 [P=0.39]) and time to complete ulcer healing (25th percentile of 32.5 days telbermin versus 43.0 days placebo [log-rank P=0.13]). CONCLUSION: The topical application of telbermin 72 microg/cm2 three times a week for up to six weeks appeared to be well tolerated. Further studies are required to characterise the safety/efficacy of telbermin more completely.

Transcatheter interventions for the treatment of peripheral atherosclerotic lesions: part I.

Transcatheter endovascular procedures are increasingly used to treat symptomatic peripheral atherosclerosis. This two-part review identifies the existing evidence supportive of the application of transcatheter treatments for peripheral atherosclerotic lesions. The first part addresses the treatment of obstructive lesions that cause limb claudication and critical ischemia, renovascular hypertension and azotemia, and mesenteric ischemia. Studies were identified via a search of MEDLINE (January 1993 through April 1999) and reference lists of identified articles. When multicenter prospective randomized trials or other high-quality studies were unavailable, a preference was given to studies with at least 50 patients per treated group and a minimum mean follow-up duration of 6 months. Data presented in tables are proportionally weighted averages from included studies. For each application, the authors assessed the quality of evidence (QOE; efficacy, safety, and, where available, cost-effectiveness) and made recommendations with appropriate caveats. There is higher QOE supporting the more established treatments such as lower limb percutaneous transluminal angioplasty (PTA) with stent placement and thrombolysis. Treatments such as renal artery PTA and stent placement and mesenteric and brachiocephalic PTA are in wide use, but high QOE supporting general application is lacking. Blanket recommendations based on established efficacy and cost-effectiveness cannot be made. However, the use of transcatheter therapies can be supported in specific circumstances based on an expected reduction in procedure-related morbidity and/or mortality rates. It is hoped that the identification of deficiencies in the literature will inform and inspire critically needed research in this area.

Alteplase and tenecteplase: applications in the peripheral circulation.

Alteplase (t-PA), a recombinant analogue of human tissue plasminogen activator, became the first genetically engineered thrombolytic approved by the Food and Drug Administration in 1987 for acute myocardial infarction (AMI). In addition to AMI, alteplase is currently approved for the treatment of acute ischemic stroke and pulmonary embolism, and we anticipate approval for catheter clearance in late 2001 in a 2-mg vial configuration. With the withdrawal of human neonatal kidney cell-derived urokinase, alteplase has become an alternative agent in peripheral vascular applications. Because few interventionalists had prior experience with the handling and dosage of alteplase, the Advisory Panel to the Society of Cardiovascular and Interventional Radiology established practice guidelines for use in noncoronary applications. Emerging clinical experience with contemporary dosing regimens shows a safety and efficacy profile similar to urokinase but with significantly reduced drug costs. Tenecteplase (TNK) is a genetically modified version of alteplase. TNK is the only plasminogen activator available that has shown a significantly enhanced safety profile versus alteplase in AMI. Approved for a 5-second, single-bolus injection in AMI, TNK possesses a longer half-life, increased resistance to plasminogen activator inhibitor, and improved fibrin specificity compared with alteplase. Because of its enhanced safety profile, TNK may be a desirable agent for peripheral vascular applications. Initial clinical studies with TNK in acute arterial and venous disease are ongoing. This article outlines the Advisory Panel guidelines for using alteplase and highlights features of tenecteplase.

Endovascular management of iliac vein compression (May-Thurner) syndrome.

PURPOSE: To evaluate the feasibility of endovascular techniques in treating venous outflow obstruction resulting from compression of the iliac vein by the iliac artery of the left lower extremity (May-Thurner syndrome). MATERIALS AND METHODS: A retrospective analysis of 39 patients (29 women, 10 men; median age, 46 years) with iliac vein compression syndrome (IVCS) was performed. Nineteen patients presented with acute deep vein thrombosis (DVT) and 20 patients presented with chronic symptoms. All patients presented with leg edema or pain. In the acute group, patients were treated with catheter-directed thrombolysis (120,000-180,000 IU urokinase/h) and angioplasty followed by stent placement. In the chronic group, patients were treated with use of angioplasty and stent placement alone (n = 8), or in combination with thrombolysis (n = 12). Patients were then followed-up with duplex ultrasound and a quality-of-life assessment. RESULTS: Initial technical success was achieved in 34 of 39 patients (87%). The overall patency rate at 1 year was 79%. Symptomatically, 85% of patients were completely or partially improved compared with findings before treatment. Thirty-five of 39 patients received stents. The 1-year patency rate for patients with acute symptoms who received stents was 91.6%; for patients with chronic symptoms who received stents, the 1-year patency rate was 93.9%. Five technical failures occurred. Major complications included acute iliac vein rethrombosis (< 24 hours) requiring reintervention (n = 2). Minor complications included perisheath hematomas (n = 4) and minor bleeding (n = 1). There were no deaths, pulmonary embolus, cerebral hemorrhage, or major bleeding complications. CONCLUSION: Endovascular reconstruction of occluded iliac veins secondary to IVCS (May-Thurner) appears to be safe and effective.

Surgical intervention is not required for all patients with subclavian vein thrombosis.

PURPOSE: The role of thoracic outlet decompression in the treatment of primary axillary-subclavian vein thrombosis remains controversial. The timing and indications for surgery are not well defined, and thoracic outlet procedures may be associated with infrequent, but significant, morbidity. We examined the outcomes of patients treated with or without surgery after the results of initial thrombolytic therapy and a short period of outpatient anticoagulation. METHODS: Patients suspected of having a primary deep venous thrombosis underwent an urgent color-flow venous duplex ultrasound scan, followed by a venogram and catheter-directed thrombolysis. They were then converted from heparin to outpatient warfarin. Patients who remained asymptomatic received anticoagulants for 3 months. Patients who, at 4 weeks, had persistent symptoms of venous hypertension and positional obstruction of the subclavian vein, venous collaterals, or both demonstrated by means of venogram underwent thoracic outlet decompression and postoperative anticoagulation for 1 month. RESULTS: Twenty-two patients were treated between June 1996 and June 1999. Of the 18 patients who received catheter-directed thrombolysis, complete patency was achieved in eight patients (44%), and partial patency was achieved in the remaining 10 patients (56%). Nine of 22 patients (41%) did not require surgery, and the remaining 13 patients underwent thoracic outlet decompression through a supraclavicular approach with scalenectomy, first-rib resection, and venolysis. Recurrent thrombosis developed in only one patient during the immediate period of anticoagulation. Eleven of 13 patients (85%) treated with surgery and eight of nine patients (89%) treated without surgery sustained durable relief of their symptoms and a return to their baseline level of physical activity. All patients who underwent surgery maintained their venous patency on follow-up duplex scanning imaging. CONCLUSION: Not all patients with primary axillary-subclavian vein thrombosis require surgical intervention. A period of observation while patients are receiving oral anticoagulation for at least 1 month allows the selection of patients who will do well with nonoperative therapy. Patients with persistent symptoms and venous obstruction should be offered thoracic outlet decompression. Chronic anticoagulation is not required in these patients.

Internal iliac artery embolization in the stent-graft treatment of aortoiliac aneurysms: analysis of outcomes and complications.

PURPOSE: To analyze the complications of internal iliac artery (IIA) embolization in conjunction with stent-graft treatment of aortoiliac aneurysms. MATERIALS AND METHODS: Seventy-one patients with aortoiliac (n = 47) or iliac (n = 24) aneurysms were treated with endoluminal placement of stent-grafts. Thirty-two patients (31 men, one woman; mean age, 73 years; range, 56-88 years) had embolization or occlusion of one (n = 27) or both (n = 5) IIAs. Status of the IIAs and the collateral circulation was assessed by retrospective review of angiographic images. Follow-up consisted of a standardized patient questionnaire and review of radiologic and medical records. RESULTS: The mean follow-up time was 35 months (range, 5-64 months). Eleven of the 47 patients with abdominal aortic aneurysms (AAA) (23%) and 19 of the 24 patients with iliac aneurysms (79%) required IIA embolization. One patient with AAA and another with iliac aneurysm had unintentional occlusion of an IIA by extension of the stent-graft over their origins. A total of seven patients had bilateral occlusion of the IIAs after the procedure. Additionally, the inferior mesenteric arteries (IMAs) of two other patients with AAA were also embolized. In six patients, all three vessels were occluded after placement of the stent-grafts. Symptoms were reported in nine of the 20 (45%) patients with iliac aneurysms and in three of the 12 (25%) patients with AAA. Symptoms consisted of buttock claudication (nine of 32, 28%), new sexual dysfunction (two of 16, 12%), and transient urinary retention (3%). Seven of the claudicants had resolution of symptoms after a mean interval of 14 months (range, 1-36 months). There were no instances of bowel ischemia, neurologic sequelae, or buttock necrosis related to these procedures. CONCLUSION: Embolization of the IIA is associated with symptoms in a significant number of patients. While symptoms are transient in most patients, they can be problematic. Efforts should be made to preserve the pelvic circulation if possible.

Stent-graft therapy for subclavian artery aneurysms and fistulas: single-center mid-term results.

PURPOSE: To evaluate the potential of covered stents to replace surgery in the treatment of subclavian artery aneurysms and traumatic injuries. MATERIALS AND METHODS: Nine patients (five men, four women; age range, 20-83 years; mean, 54 years) with subclavian artery aneurysms (n = 5) or fistulas (n = 4) were treated with stent-grafts. All devices used were custom-made, consisting of polytetrafluoroethylene (PTFE)-covered Palmaz (n = 5), Wallstent (n = 2), Z stents (n = 8), or a polyester-covered Z stent (n = 1). One patient was lost to follow-up after 2 months. All others were followed up with clinical evaluation, computed tomography (CT), and/or ultrasound. RESULTS: All devices were deployed successfully with exclusion of the aneurysms and fistulas. There were two procedure-related complications (22%), consisting of groin pseudoaneurysms requiring surgical repair 3 and 9 days after the procedure. One of those patients required additional oral antibiotic therapy for a postsurgical groin wound infection. One patient developed a stenosis at 12 months, which required angioplasty. The stent-graft thrombosed in one patient because of a kink 2 months after placement, which was successfully treated by thrombolysis and placement of a Wallstent. The primary and secondary patencies are 89% and 100%, respectively, after a mean follow-up of 29 months (2-66 mo). CONCLUSION: Mid-term results of stent-graft therapy of subclavian artery aneurysms and fistulas are encouraging, with low morbidity and excellent clinical outcome.

Thrombolytic therapy with use of alteplase (rt-PA) in peripheral arterial occlusive disease: review of the clinical literature. The Advisory Panel.

PURPOSE: The clinical literature describing the use of alteplase in the treatment of peripheral arterial occlusive (PAO) disease is reviewed. MATERIALS AND METHODS: The literature database was acquired by a MEDLINE search using the Boolean keyword string: tissue plasminogen activator and/or rt-PA and peripheral not animal. A review was performed to identify the dose range of alteplase, technique of infusion, use of anticoagulation, clinical success rates, and risk of complications. RESULTS: Forty-six clinical studies were identified. There are few prospective, randomized clinical trials and a lack of standardized protocols and endpoints. Use of catheter-directed infusions of recombinant tissue plasminogen activator (rt-PA) may be beneficial versus surgery in the initial management of acute limb ischemia (< 14 days) and in reducing the magnitude of subsequent surgical or percutaneous revascularization. For patients with chronic limb ischemia (> 14 days), irreversible acute limb ischemia, or advanced diabetic arteriopathy, catheter-directed infusion of rt-PA or other plasminogen activators may be unsuitable. The risk of adverse bleeding appears related to the overall dose and duration of infusion. These risks appear similar to those of urokinase. The role of heparin in increasing adverse bleeding during rt-PA therapy is unclear. CONCLUSIONS: There is no generally accepted dose or technique for administering catheter-directed thrombolysis using alteplase; however, several studies have demonstrated its clinical safety and efficacy. Formal studies will be required to determine the optimal dose, technique of infusion, the role of anticoagulation, and complication rates when alteplase is used for PAO disease.

True-lumen collapse in aortic dissection: part I. Evaluation of causative factors in phantoms with pulsatile flow.

PURPOSE: To investigate the causative factors in true-lumen collapse in a model of aortic dissection. MATERIALS AND METHODS: Phantoms with an aortic arch, true and false lumina with abdominal branch vessels, and a distal bifurcation were used to model a Stanford type B aortic dissection. The effects of anatomic factors (entry-tear size, branch-vessel flow distribution, fenestrations, distal reentry communication) and physiologic factors (peripheral resistance in the branch vessels, pump output and rate, vascular compliance) on true-lumen collapse were investigated. The morphology of the true lumen was observed. Branch pressures and flow rates were measured. RESULTS: True-lumen collapse was induced and was exacerbated by an increase in the size of the entry tear, a decrease in the false-lumen outflow caused by occluding the false-lumen branch vessels, and an increase in the true-lumen outflow caused by lowering the peripheral resistance in true-lumen branch vessels. Two kinds of true-lumen collapse depended on pump output. With low pump output and low outflow resistance from the true lumen, the true lumen collapsed. With high pump output and low inflow resistance in the false lumen, the true lumen was compressed. Distal reentry communication between the true and false limbs was more effective than aortic fenestrations in preventing true-lumen collapse. CONCLUSION: True-lumen collapse in this dissection model strongly depends on the difference in the ratios of inflow capacity to outflow capacity in the true and false lumina. Both anatomic and physiologic factors can affect true-lumen collapse.

True-lumen collapse in aortic dissection: part II. Evaluation of treatment methods in phantoms with pulsatile flow.

PURPOSE: To discover and evaluate the effective treatment methods to prevent or relieve true-lumen collapse in models of aortic dissection. MATERIALS AND METHODS: Two phantoms were built to simulate type B aortic dissection. After true-lumen collapse was induced, experiments were conducted to evaluate the effectiveness of clinically relevant variables in relieving the collapse. Variables included entry-tear size, branch-vessel flow distribution, distal reentry communication between the true and false limbs, aortic fenestrations, and pump output. To test the effect of closing the entry tear, a stent-graft was deployed over the entry tear under physiologic conditions in a mock-flow loop. The difference in the effect of each variable on the prevention and relief of true-lumen collapse was also investigated. RESULTS: It was more difficult to relieve true-lumen collapse than it was to prevent it. Placement of a stent-graft over the entry tear was the most effective method of relieving true-lumen collapse. Less-effective procedures included opening a false-lumen outflow branch and opening the distal reentry branch. Opening the fenestration-branch loops, meant to simulate the creation of artificial fenestrations in the intimal flap, did not relieve true-lumen collapse. CONCLUSION: The definitive treatment for true-lumen collapse in aortic dissection is direct repair of the entry tear to decrease false-lumen inflow. Otherwise, increasing the false-lumen outflow and/or creating distal fenestrations between the true and false lumina distal to the level of the compromised aortic branch are less-effective alternatives.

Chronically occluded inferior venae cavae: endovascular treatment.

PURPOSE: To report the results of endoluminal recanalization and stent placement in patients with chronic occlusions of the inferior vena cava (IVC). MATERIALS AND METHODS: Seventeen consecutive patients (12 male, five female patients; mean age, 40.6 years; age range, 15-77 years) with chronic IVC occlusions were treated during a 6-year period. The mean duration of symptoms was 32 months. Underlying active malignancy was the cause of occlusion in four patients. Five patients with superimposed acute thrombus underwent catheter-directed thrombolysis prior to IVC recanalization. Clinical patency was defined as absence or improvement of symptoms. Clinical follow-up was supplemented with ultrasonography, vena cavography, or both in 10 patients. RESULTS: Technical success was achieved in 15 (88%) patients. Additional thrombolytic therapy and stent placement was needed in two patients to maintain patency at 4 and 6 months after the procedure. Twelve patients had IVCs that remained patent after a mean follow-up of 19 months for a primary patency rate of 80%. The primary assisted patency rate was 87% (13 of 15). There were four deaths owing to underlying disease 6-21 months after the procedures. There were no procedure-related complications. CONCLUSION: Endoluminal recanalization and stent placement in chronically occluded IVCs has a good intermediate-term outcome and should be considered in patients who have symptoms and who often do not have adequate alternative therapy.

Aortic aneurysmal disease: assessment of stent-graft treatment-CT versus conventional angiography.

PURPOSE: To compare computed tomographic (CT) angiography and conventional angiography for determining the success of endoluminal stent-graft treatment of aortic aneurysms. MATERIALS AND METHODS: Forty patients underwent conventional angiography and CT angiography following treatment of aortoiliac aneurysms with endoluminal stent-grafts. Six additional sets of conventional angiographic-CT angiographic examinations were performed in five patients after placement of additional stent-grafts or coil embolization to treat perigraft leakage. Three faculty CT radiologists who were blinded to patient clinical data and outcome independently interpreted the CT angiograms, and three faculty angiographers, who were not involved in the stent-graft deployment, interpreted the conventional angiograms. Images were assessed for the presence of postdeployment complications. A reference standard was developed by experienced radiologists using all available images and clinical data. Sensitivities, specificities, and kappa values were calculated. RESULTS: Perigraft leakage was the most commonly identified complication. Twenty perigraft leaks were detected in the results of 46 examinations. Sensitivities and specificities for detecting perigraft leakage were 63% and 77% for conventional angiography and 92% and 90% for CT angiography, respectively. The kappa value was 0. 41 for conventional angiography and 0.81 for CT angiography. CONCLUSION: CT angiography is the preferred method for establishing the presence of perigraft leakage following treatment of aortoiliac aneurysms with stent-grafts.

Diagnostic yield of MR-guided liver biopsies compared with CT- and US-guided liver biopsies.

PURPOSE: To compare diagnostic yield and complication rates of magnetic resonance (MR)-guided versus computed tomography (CT)- and ultrasound (US)-guided liver biopsies. MATERIALS AND METHODS: MR-, CT-, and US-guided liver biopsies performed between 9/96 and 9/98 were compared. Sixty patients (21 men and 39 women, mean age 60 years) underwent MR-guided biopsy of liver lesions. Thirty patients (16 men and 14 women, mean age 59 years) underwent CT-guided biopsy. Eighteen patients (seven men and 11 women, mean age 50 years) underwent US-guided biopsy. MR procedures were performed in an open-configuration 0.5-T Signa SP MR unit. Lesion localization used standard T1 and T2 sequences, whereas biopsies were performed with multiplanar spoiled gradient recalled echo and fast gradient recalled echo sequences. A coaxial system with an MR-compatible 18-gauge stabilizing needle and a 21-gauge aspiration needle was used to obtain all samples. In CT and US procedures, a 19-gauge stabilizing needle and a 21-gauge aspiration or a 20-gauge core biopsy needle were used. A cytotechnologist was present to determine the adequacy of samples. RESULTS: MR had a diagnostic yield of 61%. CT and US had diagnostic yields of 67% and 61%, respectively. No serious complications were reported for MR and US procedures. Two CT biopsies resulted in postprocedural hemorrhage. One patient required surgical exploration and died. CONCLUSIONS: MR-guided biopsy of liver lesions with use of a 0.5-T open-configuration magnet is safe and accurate when compared with CT and US. No statistical difference was observed between the diagnostic yield of biopsies performed with MR, CT, and US guidance. MR enabled biopsy of a number of lesions in the hepatic dome and lesions with low contrast, which would normally be difficult to sample safely with use of CT or US.

Management of misplaced or migrated endovascular stents.

PURPOSE: To report experience with techniques for management of misplaced or migrated endovascular stents. MATERIALS AND METHODS: During a 5-year period, percutaneous management of 27 misplaced or migrated endovascular stents (16 Palmaz, 11 Wallstents) in 25 patients was attempted. The 17 venous and 10 arterial stents were rescued from the aorta (n = 9), inferior vena cava (IVC) (n = 4), transjugular intrahepatic portosystemic shunt/IVC (n = 2), right atrium (n = 3), right ventricle (n = 2), pulmonary artery (n = 2), iliac vein (n = 2), iliac artery (n = 1), superior vena cava (n = 1), and superior mesenteric vein (n = 1). RESULTS: Stent management was successful in 26 of 27 cases (96%). Eleven stents were removed percutaneously, two were repositioned and removed with a minor surgical procedure, and 13 were repositioned and deployed in a stable alternate location. The only complication was the development of tricuspid insufficiency in the single case in which the procedure failed (4% complication rate). This patient's stent was eventually surgically removed from the right ventricle. CONCLUSION: Misplaced or migrated endovascular Palmaz and Wallstents can be effectively managed with few complications by using a variety of percutaneous techniques.

Endovascular treatment of hepatic venous outflow obstruction after piggyback technique liver transplantation.

BACKGROUND: The piggyback technique of orthotopic liver transplantation is an attractive alternative that preserves the recipient inferior vena cava and allows uninterrupted venous blood return during the anhepatic phase. As with other transplantation techniques, the vascular anastomoses required by the piggyback technique can develop strictures. METHODS: Review of records of 264 piggyback transplantations revealed two cases of delayed-onset hepatic venous obstruction from anastomotic strictures. Both patients also had symptoms of inferior vena cava obstruction, with azotemia and lower extremity edema. Both patients were treated percutaneously with balloon-expandable stents. RESULTS: Rapid, dramatic resolution of symptoms was achieved in both patients. Patients remain completely asymptomatic at 39 and 3 months of follow-up. CONCLUSIONS: Hepatic venous anastomotic strictures in recipients of piggyback technique transplants are a very uncommon complication. They may be easily and effectively treated by minimally invasive endovascular intervention.

Recurrent TIPS failure associated with biliary fistulae: treatment with PTFE-covered stents.

PURPOSE: To evaluate the efficacy of covered stents for the treatment of transjugular intrahepatic portosystemic shunt (TIPS) obstruction in human subjects with identified or suspected biliary fistulae. METHODS: Five patients were treated for early failure of TIPS revisions. All had mid-shunt thrombus, and four of these had demonstrable biliary fistulae. Three patients also propagated thrombus into the native portal venous system and required thrombolysis. TIPS were revised in four patients using a custom-made polytetrafluoroethylene (PTFE)-covered Wallstent, and in one patient using a custom-made PTFE-covered Gianturco Z-stent. RESULTS: All identified biliary fistulae were successfully sealed. All five patients maintained patency and function of the TIPS during follow-up ranging from 2 days to 21 months (mean 8.4 months). No patient has required additional revision. Thrombosis of the native portal venous system was treated with partial success by mechanical thrombolysis. CONCLUSION: Early and recurrent failure of TIPS with mid-shunt thrombosis, which may be associated with biliary fistulae, can be successfully treated using covered stents. Stent-graft revision appears to be safe, effective, and potentially durable.

Thoracic aortic aneurysm repair with an endovascular stent graft: the "first generation".

OBJECTIVE: The feasibility and efficacy trial of an endovascular stent-grafting system for the treatment of aneurysms of the descending thoracic aorta was investigated. METHODS: After Institutional Review Board approval, 103 patients (mean age 69 years) underwent stent graft repair of a descending thoracic aortic aneurysm between July 1992 and November 1997. The stent graft was fabricated using self-expanding "Z" stents covered by a woven Dacron tube graft. Follow-up, which averaged 22 months, was 100% complete. Simultaneous open abdominal aortic aneurysm repair was performed in 19 patients. RESULTS: Complete aneurysm thrombosis was achieved in 86 patients (83%). Early mortality, defined as a death during the same hospitalization or in less than 30 days, was 9 +/- 3%, and was significantly associated with preoperative cerebrovascular accident (CVA) or myocardial infarction. Major perioperative morbidity occurred in 31 patients, and included paraplegia in 3, CVA in 7, and respiratory insufficiency in 12 patients each. Actuarial survival was 81 +/- 4% at 1 year, and 73 +/- 5% at 2 years. Treatment failure (including all late, sudden, unexplained deaths) occurred in 38 patients, and only 53 +/- 10% of patients were free of treatment failure at 3.7 years. Five patients required late operative therapy for endoleaks associated with aneurysm enlargement. CONCLUSIONS: Satisfactory results were achieved using this "first-generation" homemade stent graft device. Mortality and morbidity occurred frequently, but may have been associated with the high-risk character of this patient population. Medium-term results were acceptable, but continued aortic enlargement, with the late development of endoleaks, is a significant concern. Second-generation devices with commercial development, coupled with this initial experience, should allow improved clinical results in the future. Longer term follow-up is still necessary to fully define the efficacy of this endovascular approach.