High dose-rate brachytherapy for the treatment of lower extremity in-stent restenosis.

OBJECTIVE: Historically, edge stenosis and late thrombosis limited the effectiveness of adjunctive endovascular brachytherapy (EVBT) for in-stent restenosis (ISR) after percutaneous transluminal angioplasty (PTA) and stenting. We evaluated an updated protocol of PTA and EVBT for ISR among patients with lower extremity occlusive disease. METHODS: This is a retrospective, single-center review of patients treated with PTA and EVBT for ISR in the iliac and femoropopliteal segments between 2004 and 2012. A dose of 20 Gy was given at a depth of 0.5 mm beyond the radius of the largest PTA balloon using iridium 192, with at least 2-cm-long margins of radiation coverage proximal and distal to the injured area. Stents were assessed for patency by duplex ultrasound imaging at 1, 3, 6, 9, 12, and 18 months and then yearly. The primary end point was freedom from ≥50% restenosis in the treated segment at 6 months, 1 year, and 2 years. Patency data were estimated using the Kaplan-Meier method. Secondary end points were early and late thrombotic occlusion. RESULTS: Among 42 consecutive cases in 35 patients of EVBT for ISR in common or external iliac (9 [20.8%]) and superficial femoral or popliteal (33 [76.7%]) arteries, or both, 21 patients (50%) had claudication, asymptomatic hemodynamically significant stenoses were identified on duplex ultrasound imaging in 16 (38.1%), and 4 (9.8%) had critical limb ischemia. Mean treated length was 23.5 ± 12.3 cm over a mean duration of 16.1 ± 9.6 minutes. There was one technical failure (2.3%). Median post-EVBT follow-up time was 682 days (range, 1-2262 days). There were two (4.9%) and five (11.9%) cases of early and late thrombotic occlusions, respectively. There was one death, believed to be secondary to acute coronary syndrome. Primary, assisted primary, and secondary patency in the entire cohort was 75.2%, 89.1%, and 89.1%, respectively, at 1 year and 63.7%, 80.6%, and 85.6%, respectively, at 2 years. CONCLUSIONS: This contemporary protocol of PTA and adjunctive EVBT for lower extremity ISR, which is updated from those used in prior trials and includes a surveillance strategy that identifies at-risk stents for reintervention before occlusion, may be a promising treatment for lower extremity ISR at institutions where a close collaboration between vascular surgeons and radiation oncologists is feasible.

Endovascular brachytherapy in the femoropopliteal segment using 192Ir and 188Re.

This report presents a review of the literature on endovascular brachytherapy (EVBT) after percutaneous transluminal angioplasty (PTA) in the femoropopliteal segment. We summarize the pathophysiological changes induced by PTA and EVBT within the vessel wall, technical considerations regarding various radiation sources and their application, the impact of stents on the radial dose profile, recommendations for dosimetry of beta and gamma sources, results of experimental and clinical trials, and the medication required before, during, and after EVBT. We aim to help to identify patients who are eligible for EVBT, to choose an appropriate technical approach, and to initiate adequate antiplatelet and anticoagulant therapy.

Effects of percutaneous transluminal angioplasty and endovascular brachytherapy on vascular remodeling of human femoropopliteal artery: 2 years follow-up by noninvasive magnetic resonance imaging.

OBJECTIVES: We aimed to assess in vivo the long-term effects of percutaneous transluminal angioplasty (PTA) and endovascular brachytherapy (EVBT) on vessel wall by serial MRI. METHODS: Twenty patients with symptomatic stenosis of the femoropopliteal artery were randomly assigned to PTA (n=10) or PTA+EVBT (n=10, 14Gy by gamma-source). High-resolution MRI was performed prior, at 24-hours, 3-months, and 24-months after intervention. MRI data were analyzed by an independent, blinded observer. RESULTS: The effects of both procedures on vessel wall at 24-hours and 3-months have been reported. Despite similar percent decrease in lumen area between 3- and 24-months in both groups (-8% for PTA and -11% for PTA+EVBT), at 24-months lumen area gain compared to baseline was +30% in PTA versus +82% in PTA+EVBT (p<0.05). Total vessel area, which was increased at 24-hours and 3-months, returned to pre-treatment value in both groups. CONCLUSIONS: We demonstrated non-invasively that restenosis and inward remodeling after PTA are delayed by EVBT. At 24-months, patients treated with brachytherapy have larger lumen than those treated with PTA alone. The decrease in luminal and total vessel area between 3- and 24-months after EVBT indicates that the restenotic and remodeling process is not abolished but delayed with this therapy.

Endovascular gamma irradiation for the prevention restenosis after angioplasty of femoropopliteal de novo stenoses.

The purpose of this study was to investigate the effectiveness and detect side effects of centered, overlapped endovascular gamma irradiation after angioplasty of de novo femoropopliteal stenoses. Thirty patients (age 65.3+/-9.2 years) with arterial occlusive disease were prospectively enrolled to receive endovascular gamma irradiation (192-iridium, 14 Gy centered at 2 mm vessel wall) immediately after percutaneous transluminal angioplasty (PTA) of femoropopliteal stenoses. Irradiation overlapped dilatation by 1-2 cm at each end. Follow-up involved angiography after 12 months; duplex sonography; and interviews before and after PTA and at 1, 6, and 12 months follow-up. PTA and centered endovascular irradiation were performed successfully in all patients. Three thromboembolic complications occurred during irradiation. Angiographic and clinical follow-up was possible in 28 patients. The angiographic degree of stenosis was 73.8%+/-16.3% before and 3.6%+/-23.5% after PTA and was 3.5%+/-43.7% at the 1-year follow-up. Restenosis (>50%) of the target lesion developed in three patients (10.7%) and edge stenoses (>30%) in nine patients (32.1%). An aneurysm of the irradiated segment in one patient was treated by stenting. The rate of retreatment was 17.9%. The vessel diameter after endovascular gamma irradiation and PTA of femoropopliteal stenoses remained stable. Restenosis, induction of edge stenoses, and aneurysm were reasons for reinterventions.

Association of subclinical wall changes of carotid, femoral, and popliteal arteries with obstructive coronary artery disease in patients undergoing coronary angiography.

STUDY OBJECTIVES: To examine the association of occult atherosclerosis of carotid, femoral, and popliteal arteries with the presence and severity of obstructive coronary artery disease (CAD) in patients without a history or presence of cerebrovascular or peripheral arterial disease using ultrasound examination of peripheral arteries. PATIENTS/METHODS: One hundred eighty-four such individuals underwent routine coronary angiography. Obstructive CAD was found in 103 cases, which comprised the patient group. The remaining 81 individuals comprised the control group. All were blindly examined by duplex ultrasonography in order to assess occult atherosclerosis, as indicated by the estimation of intima-media thickness of the carotid artery (IMTC), intima-media thickness of the femoral artery (IMTF), intima-media thickness of the popliteal artery (IMTP), and ultrasonic biopsy (UB) of the carotid and femoral arteries. For the individuals with positive coronary angiography findings, the severity of CAD was estimated by the number of the diseased vessels. RESULTS: IMTC, IMTF, IMTP, and UB showed significant correlation with the presence of obstructive CAD, but only IMTC and IMTF were independent predictive factors, with specificity of 74% and 60% and sensitivity of 76% and 70%, respectively. Additionally, our analysis yielded a regression model that, for a given value of IMTC and IMTF, may estimate the probability of CAD: p (CAD) = e((- 4.765 + 3.36 IMTC + 1.91 IMTF))/1 + e((- 4.765 + 13.36 IMTC + 1.91 IMTF)). Patients with one-vessel disease had significantly lower IMTC (p < 0.001) and UB (p = 0.011) and lower IMTF (p = 0.057) than those with three-vessel disease. CONCLUSIONS: The assessment of occult atherosclerosis by duplex ultrasonography in both the carotid and the femoral arteries is significantly associated with the presence and severity of CAD.

Effects of probucol versus aspirin and versus brachytherapy on restenosis after femoropopliteal angioplasty: the PAB randomized multicenter trial.

PURPOSE: To evaluate the effect of probucol and/or of endovascular brachytherapy (EVBT) on restenosis after percutaneous transluminal angioplasty (PTA) of femoropopliteal arteries. METHODS: A total of 335 patients (206 men; mean age 72+/-9 years) with intermittent claudication were randomized according to a 2x2 factorial design to 1 of the 4 groups: probucol, placebo, EVBT, and EVBT+probucol. Probucol (1 g/d) or placebo were given in double-blinded fashion 1 month before and for 6 months after PTA. Gamma irradiation (192Iridium, 14 Gy, 5-mm reference depth) was randomly applied in an unblinded manner from a noncentered endoluminal catheter. All patients received aspirin (100 mg/d). Primary endpoint was restenosis (>50% diameter reduction) detected by duplex ultrasound 6 months after PTA. Secondary endpoints included clinical and hemodynamic assessment. RESULTS: Restenosis in patients undergoing EVBT was 17% (23/133) versus 35% (50/142) in patients without EVBT (p<0.001); in patients treated with probucol versus placebo, the rates were 23% (31/135) and 30% (43/140, p<0.001). Three quarters (77%, 102/133) of patients were free of claudication after EVBT therapy versus 61% (87/142) without EVBT (p<0.05). Need for target vessel revascularization was 6% (8/133) with EVBT versus 14% (20/142) without EVBT (p<0.01). Late thrombotic occlusions occurred in 4% (6/133), exclusively in patients treated with EVBT after stent implantation. CONCLUSIONS: Endovascular brachytherapy significantly reduces restenosis, improves symptoms, and reduces reinterventions after PTA of femoropopliteal arteries. Probucol reduces restenosis but has no additive effect when combined with brachytherapy.

Effects of percutaneous transluminal angioplasty and endovascular brachytherapy on vascular remodeling of human femoropopliteal artery by noninvasive magnetic resonance imaging.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) of severely stenotic peripheral vascular lesions is hampered by a higher restenosis rate. The effects of PTA on vascular wall as well as the effects of the antirestenotic properties of endovascular brachytherapy (EVBT) remain unclear. MRI allows in vivo noninvasive assessment of the vascular effects of such treatment strategies. We sought to elucidate the vascular effect of PTA and PTA+EVBT by serial MRI. METHODS AND RESULTS: Twenty symptomatic patients with severe stenosis of the femoropopliteal artery were randomly assigned to PTA (n=10) or PTA+EVBT (n=10; 14 Gy by gamma-irradiation source) and imaged by high-resolution MRI before and 24 hours and 3 months after intervention. An independent observer blinded to the procedure analyzed the MRI data. At 24 hours, cross-sectional MRI revealed that lumen area (86% and 67%) and total vessel area (47% and 34%) increased similarly in the PTA and PTA+EVBT groups, respectively. All patients showed severe splitting of the atherosclerotic plaque, resulting in an irregularly shaped lumen. At 3 months, MRI revealed a significant difference in lumen area change between the PTA and PTA+EVBT groups (40% and 106%, respectively; P=0.026) and in the total vessel area (14% and 39%, respectively; P=0.018). At 3 months, plaque disruption was still present in 50% of the patients treated with PTA+EVBT. CONCLUSIONS: After PTA, there is deep disruption of the atherosclerotic plaques and an extensive remodeling process of the arterial wall. Luminal loss after PTA is partially due to inward vessel remodeling. Brachytherapy prevents inward remodeling and induces an increase in lumen area but partially prevents healing of disrupted vessel surface.

Endovascular brachytherapy after percutaneous transluminal angioplasty of recurrent femoropopliteal obstructions.

PURPOSE: To test the preventive effect of endovascular brachytherapy (EVBT) on restenosis following secondary angioplasty in patients with presumed neointimal restenosis in the femoropopliteal segment. METHODS: From March 1997 through May 2000, 100 patients (58 men; mean age 70 years, range 45-87) with postangioplasty femoropopliteal segment restenoses were enrolled and randomized to treatment with repeat angioplasty and EVBT (n=51) or to angioplasty alone (n=49) as control. The groups were similar with regard to demographics and lesion characteristics. High-dose-rate EVBT was performed with (192)Ir irradiation without a centering device (12 Gy for a reference vessel radius of 3 mm and a 2-mm reference depth). Primary endpoint in the 1-year follow-up was recurrent obstruction >50% documented by duplex ultrasound; the secondary endpoint was clinical improvement. RESULTS: Only 44 (86%) of 51 patients received adequate EVBT due to technical failure, so the 7 failures were included with the controls in the per-protocol adherence analysis. At 1 year, the patients receiving EVBT had a restenosis rate of 23% (10/44), which differed significantly (p<0.028) from the 42% (23/56) rate in controls. Clinical results tended to be better with EVBT, but differences did not achieve statistical significance. CONCLUSIONS: EVBT without a centering device reduced restenosis significantly in patients with recurrent stenosis after angioplasty, which confirms previous results in primary long-segment femoropopliteal obstructions.

Endovascular brachytherapy in peripheral arteries.

Increasing knowledge about the pathophysiology of the process leading to restenosis has given the rationale to investigate the potential role of radiation in the prevention of restenosis. Compared to the rapidly increasing experience in the coronary circulation, there is until now only a limited number of studies concerning the use of brachytherapy (BT) in the peripheral circulation. The-Vienna 2-Trial was the first randomized study to demonstrate the efficacy of endovascular BT for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty. The cumulative patency rates at 12 months of follow-up were 63.6% in the PTA + BT-group and 35.3% in the PTA-group (p < 0.005), and the significant improvement in patency was also maintained after two years. The results of two ongoing randomized, double-blinded multicenter trials (PARIS; Vienna 3) have to be awaited before definitive recommendations can be given. The rather high incidence of late thrombotic occlusion after long-segment femoropopliteal stenting and endovascular BT requires optimization of the antithrombotic regimen.

Late acute thrombotic occlusion after endovascular brachytherapy and stenting of femoropopliteal arteries.

OBJECTIVES: The aim of this article is to underline the importance of this complication after endovascular brachytherapy (EVBT) and intravascular stenting of the femoropopliteal arteries occurring in a running randomized trial. BACKGROUND: Endovascular brachytherapy has been proposed as a promising treatment modality to reduce restenosis after angioplasty. However, the phenomenon of late acute thrombotic occlusion (LATO) in patients receiving EVBT after stenting is of major concern. METHODS: In an ongoing prospective multicenter trial, patients were randomized to undergo EVBT (iridium 192; 14 Gy at a depth of the radius of the vessel +2 mm) after percutaneous recanalization of femoropopliteal obstructions. Of the 204 patients who completed the six months follow-up, 94 were randomized to EVBT. RESULTS: Late acute thrombotic occlusion occurred exclusively in 6 of 22 patients (27%) receiving EVBT after intravascular stenting and always in concomitance with reduction of antithrombotic drug prevention (clopidogrel). Conversely, none of the 13 patients with stents and without EVBT (0%; p < 0.05) and none of the 72 patients (0%; p < 0.01) undergoing EVBT after simple balloon angioplasty presented LATO. CONCLUSIONS: Late thrombotic occlusion occurs not only in patients undergoing EVBT after percutaneous coronary recanalization but also after stenting of the femoropopliteal arteries and may compromise the benefits of endovascular radiation. The fact that all our cases with LATO occurred concomitantly with stopping clopidogrel may indicate a possible rebound mechanism. An intensive and prolonged antithrombotic prevention is probably indicated in these patients.

Gamma radiation induces positive vascular remodeling after balloon angioplasty: a prospective, randomized intravascular ultrasound scan study.

BACKGROUND: Endovascular brachytherapy (EBT) has been shown to prevent restenosis after percutaneous transluminal coronary angioplasty (PTA) in both animal and clinical studies. However, as yet, the effect of EBT on peripheral arteries is unknown. OBJECTIVE: This intravascular ultrasound scan (IVUS) study evaluates the effect of EBT on the extent of plaque growth and vascular remodeling after PTA of the femoropopliteal artery. METHODS: Twenty-four patients with obstructive disease of the femoropopliteal artery underwent standard PTA. Patients were randomized to receive no additional therapy or additional EBT (192-Iridium) after PTA. IVUS investigation was performed after PTA and at 6-month follow-up. A comparison was made between patients without EBT (n = 16) and with EBT (n = 8) in the change in lumen, vessel, and plaque area and plaque dissections seen with IVUS at 6-month follow-up. RESULTS: At follow-up, IVUS revealed a significant difference in lumen area change between patients without and with EBT (-9% and +23%, respectively; P =.03). This difference was the result of a significant difference in vessel area change (+2% and +19%, respectively; P =.05). In both groups of patients, a similar increase in plaque area (+12% and +16%, respectively; P =.80) was encountered. Plaque dissections encountered immediately after PTA were absent at follow-up in patients without EBT, whereas in four of the eight patients with EBT, a persistent dissection was encountered. CONCLUSION: This randomized IVUS study showed that gamma-radiation after PTA has a positive effect on lumen dimensions at 6-month follow-up by inducing positive vascular remodeling (ie, vascular dilatation); gamma-radiation seemed not to affect plaque growth. In addition, gamma-radiation has an effect on the healing process of dissections after PTA.

Endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal angioplasty : results of a prospective randomized study.

BACKGROUND: Inasmuch as endovascular brachytherapy (BT) has gained recent interest because of its inhibitory effect on mechanisms leading to restenosis after percutaneous transluminal angioplasty (PTA), we performed this randomized study to determine its efficacy for prophylaxis of restenosis after femoropopliteal PTA. METHODS AND RESULTS: One hundred thirteen patients (63 men, 50 women; mean age 71 years) with de novo or recurrent femoropopliteal lesions were included in this randomized trial comparing the restenosis rate after PTA plus BT (57 patients, PTA+BT group) versus PTA (56 patients, PTA group) without stent implantation. The mean treated length was 16.7 cm (PTA+BT group) versus 14.8 cm (PTA group). In patients randomized to PTA plus BT, a dose of 12 Gy was applied by an (192)Ir source 3 mm from the source axis. Follow-up examinations included measurement of the ankle-brachial index, color-flow duplex sonography, and angiography. The primary end point of the study was patency after 6 months. The overall recurrence rate after 6 months was 15 (28.3%) of 53 in the PTA+BT group versus 29 (53.7%) of 54 in the PTA group (chi(2) test, P<0.05). The cumulative patency rates at 12 months of follow-up were 63.6% in the PTA+BT group and 35.3% in the PTA group (log-rank test, P<0.005). CONCLUSIONS: This is the first randomized study to demonstrate the efficacy of endovascular BT for prophylaxis of restenosis after femoropopliteal PTA. The value of this approach should now be improved by modification of the BT procedure and by combination with stent implantation.

Brachytherapy for prophylaxis of restenosis after long-segment femoropopliteal angioplasty: pilot study.

PURPOSE: To evaluate in a pilot study the feasibility and efficacy of endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA) without stent implantation in a group of patients with a high risk of restenosis. MATERIALS AND METHODS: Ten patients (six women, four men; mean age, 68 years) with long-segment (mean length, 16 cm; range, 9-22 cm) restenosis underwent PTA followed by endovascular irradiation with high-dose-rate afterloading of an iridium-192 rod. A dose of 12 Gy was targeted to the inner intimal layer of the vessel. Follow-up examinations until 12 months after PTA included measurement of the ankle-brachial index, color duplex ultrasonography (US) with calculation of the peak velocity ratio, and intraarterial angiography when recurrence was suspected. RESULTS: Irradiation was technically feasible in all patients without complications. In six patients, the dilated and irradiated segment remained widely patent at color US, with corresponding excellent hemodynamic and clinical results after 12 months. In four patients, clinical and laboratory findings indicated recurrence and arteriography demonstrated restenosis with a diameter reduction of 60%, 70%, 80%, or 90%. CONCLUSION: Considering the negative selection of patients with a high risk of restenosis, the results of our pilot study are promising concerning the possibility of reduction of restenosis by means of endovascular brachytherapy after long-segment femoropopliteal PTA without stent implantation. The value of this approach should now be determined definitively in randomized trials.

Simple look-up table of optimized dwell time intervals using a high-dose-rate remote afterloader for endovascular irradiation.

PURPOSE: This article's objective is to develop a simple methodology deliver a uniform radiation dose to the wall of a narrow peripheral artery for preventing restenosis using a high-dose-rate (HDR) 192Ir remote afterloader. METHODS AND MATERIALS: Based upon published two-dimensional data such as anisotropy factors of an HDR 192Ir source calculated from the Monte-Carlo method, arterial wall doses at a close range from an HDR source may be easily calculated using the special formula suggested in Task Group Report No. 43 published by the American Association of Physicists in Medicine. An optimization procedure was used to calculate the optimized dwell times for delivering a uniform dose along arterial walls for various arterial diameters and lengths of lesions. RESULTS: Based on lengths of the stenosis and diameters of arteries or angioplasty balloons, a set of simple look-up tables for optimal dwell time intervals of endovascular radiation treatment have been developed for the MicroSelectron HDR remote afterloader. CONCLUSION: Doses for endovascular irradiation have been accurately calculated with anisotropy factors. For delivering uniform doses along the arterial wall, a set of look-up tables listed for optimal dwell times is available for the HDR remote afterloader.

[Clinical aspects of using extremely high frequency electromagnetic radiation in the complex treatment of occlusive vascular diseases of the lower extremities]. / Klinicheskie aspekty primeneniia élektromagnitnogo izlucheniia kraine vysokoi chastoty v kompleksnom lechenii obliteriruiushchikh zabolevanii sosudov nizhnikh konechnostei.

A method of local influencing with the extremely high frequency electromagnetic irradiation on the points of acupuncture was used in the complex treatment of 44 patients with obliterative diseases of the vessels of the lower extremities at the age of 34-75 years. Obliterative atherosclerosis was diagnosed in 15 of them, obliterative endarteritis --in 29. A high effectiveness of the method even in late stages of vascular pathology was noted. No complications were observed.

Radiation-induced occlusion of the artery in the distal lower extremity--a case report.

In a 54 year-old man, a symptomatic occlusion of the popliteal artery and its trifurcation occurred following radiotherapy. Three years following curative radiotherapy to the upper tibia for metastatic renal cell carcinoma, he began experiencing intermittent claudication of the calf, which suddenly progressed to severe rest pain and coldness of the foot, and eventually to ischemic ulcer. Angiogram revealed an atherosclerotic occlusion well localized within the field of the previous irradiation. The significance of this rare entity is discussed from various aspects.