Endovascular brachytherapy for the prevention of restenosis after angioplasty

Restenosis is an unsolved clinical and financial limitation of angioplasty. Local irradiation is a new approach for the reduction of restenosis. Several animal studies have demonstrated the effective inhibition of arterial neointimal proliferation by percutaneous or endovascular irradiation. High-dose-rate irradiation from gamma and beta sources can be applied from radioactive wires or seeds and from liquid beta-emitter-filled balloon catheters. Dosimetric calculations have been performed for all relevant radionuclides. An effective dose can be applied within 10 min to the treated arteries. Beta-emitters are characterized by a low tissue penetration, which simplifies radiation protection but complicates the achievement of a homogeneous dose distribution without centring of the irradiation source. Gamma-emitters are characterized by deep tissue penetration and delivery of almost the same dose to all vessel layers; however, considerable care with regard to radiation protection of the environment is required if gamma-emitters are used. The liquid-filled balloon ensures a homogeneous dose delivery due to the self-centring irradiation source but entails the possibility of radioactivity incorporation in the event of balloon rupture. The most attractive radionuclide for this purpose is rhenium-188, which is available from the ¹⁸⁸W/¹⁸⁸Re generator system. Radiation exposure after accidental incorporation can be limited by chelation with mercaptoacetyltriglycine or by subsequent oral administration of perchlorate. Initial clinical trials have demonstrated the feasibility of the various irradiation techniques and yielded encouraging results. The use of unsealed radioactivity in a balloon catheter involves the nuclear medicine physician in this new field of therapy. This review discusses the concepts, the radiotracers and the results of animal experiments and early clinical trials in the field of endovascular irradiation employed as a possible means to prevent restenosis after angioplasty.     

血管内照射防治血管成形术后再狭窄

PTCA(经皮穿刺冠状动脉成形术)是治疗冠状动脉狭窄最常用的方法,但术后6个月内再狭窄的发生率达40%~60%,始终是困绕医学界的一个难题。核素内照射治疗是目前解决这一难题最有前景的方法,最近几年来在血管核素内照射的机制、剂量、动物和临床实验及安全性等方面取得了一些进展。     

Endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal angioplasty: five-year follow-up--prospective randomized study

PURPOSE: To report the 5-year results from the prospective randomized Vienna-2 trial, which was designed to evaluate the safety and effectiveness of adjunctive endovascular brachytherapy (EBT) compared with no further treatment after successful revascularization in patients with long-segment femoropopliteal lesions. MATERIALS AND METHODS: Each patient gave written informed consent to participate in the study, which was approved by the hospital's ethics committee. One hundred two patients (men, 53.9%; mean age, 72.1 years +/- 8.7 [standard deviation]; lesion length, 8.1 cm +/- 4.9) underwent percutaneous transluminal angioplasty (PTA) without further stent implantation. Patients were then assigned to either receive EBT (n = 51) by using an iridium 192 source, with a prescribed dose of 12 Gy at 3 mm from the source axis, or no further treatment (n = 51). Radiation was delivered without a centering catheter. Data were analyzed by using a Student t test for continuous values and a chi(2) test to compare categorical values. A Cox proportional hazards regression analysis was performed to evaluate predictors of recurrence at follow-up. RESULTS: After 6 months, the restenosis rate for the 102 patients with completed 5-year follow-up was significantly reduced for the PTA plus EBT group versus the PTA alone group (29.4% vs 56.9%, P < .05). During follow-up we observed a late catch-up phenomenon, and after 5 years the recurrence rate was comparable in both groups (72.5% vs 72.5%, P > .99). Time to recurrence, however, was significantly delayed in the PTA plus EBT group (17.5 months +/- 14.7 vs 7.4 months +/- 6.8 for the PTA alone group, P < .05). CONCLUSION: At 5-year follow-up, PTA followed by gamma radiation EBT with a dose of 12 Gy resulted in a delay but not an inhibition of restenosis when compared with that of PTA alone.     

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.     

188 Re液体血管内照射防治血管内膜损伤后再狭窄的实验研究

目的　研究1 88Re液体充盈球囊导管对兔血管再狭窄模型用不同剂量内照射后对增生内膜不同的剂量效应。方法　 16只新西兰白兔分成 2组 ,一侧下肢髂动脉行内膜剥脱术后 ,通过直径 2 5mm液体1 88Re充盈球囊导管分别给以 0、8和 15Gy剂量的血管内照射治疗。其中 8只兔的另一侧髂动脉仅行内膜剥脱术作为对照。 4周后处死动物 ,取出血管。组织经HE染色、VanGieson胶原染色、α 肌动蛋白免疫组化染色 ,通过图像分析系统分析 ,测定狭窄指数和增殖指数。结果　对照组、8和 15Gy组的狭窄指数分别为 0 49± 0 0 6、0 65± 0 0 5和 0 82± 0 0 5 ,增殖指数分别为 0 5 4±0 0 9、0 48± 0 0 6和 0 3 3± 0 0 4。 15Gy组增生的内膜明显下降 (P <0 0 5 ) ,而 8Gy组与对照组比较差异无显著性 (P >0 0 5 )。免疫组化显示增生的内膜主要是平滑肌细胞 (SMCs)。结论　在兔血管再狭窄模型中 ,用1 88Re液体充盈球囊导管内照射治疗 ,当接近血管内表面的吸收剂量达到 15Gy时能安全有效地抑制内膜平滑肌的增生     

β射线局部照射对冠状动脉弥漫性支架内再狭窄的疗效

目的：探讨β射线(^90Sr/^90Y)对冠状动脉(简称冠脉)弥漫性支架内再狭窄的疗效。方法:39例经皮冠脉介入术(PCI)及支架置入术后支架内再狭窄患者，随机分为支架内放射治疗组(治疗组)18例及单纯球囊组(对照组)21例。2组患者再狭窄病变先经充分球囊扩张，治疗组用Beta-Cath系统进行冠脉内放射治疗。术后随访9个月。结果:治疗组1例(5．6％)研究段血管再狭窄，对照组有8例(38．1％)再狭窄，两组间差异有显著性(P=0．006)。结论:β射线治疗冠脉弥漫性支架内再狭窄安全、有效、可行。     

Endovascular brachytherapy for prophylaxis against restenosis after long-segment femoropopliteal placement of stents: initial results

PURPOSE: To evaluate the feasibility, safety, and effectiveness of endovascular brachytherapy for the prevention of restenosis after long-segment femoropopliteal percutaneous transluminal angioplasty (PTA) and stent implantation. MATERIALS AND METHODS: Thirty-three patients (23 men, 10 women; mean age, 66 years) with femoropopliteal lesions (mean treated length, 17 cm; range, 4-30 cm) underwent PTA and stent implantation followed by brachytherapy with a centering catheter. A dose of 14 Gy was delivered to the adventitia by using an iridium 192 source. Long-term pharmacotherapy with acetylsalicylic acid was combined with clopidogrel for 1 month. Follow-up examinations included measurement of the ankle-brachial index, color-coded duplex ultrasonography, and angiography. RESULTS: The overall 6-month recurrence rate was 30% (10 of 33 arteries). Seven patients developed sudden late thrombotic occlusion of the segment with the stent 3.5-6 months after stent implantation. Considering the overall results after successful local thrombolysis in six of these seven patients, only four (12%) of 33 arteries with a stent had in-stent restenosis caused by neointimal hyperplasia. CONCLUSION: The study results are promising concerning the possibility of reducing in-stent restenosis by means of brachytherapy after long-segment femoropopliteal placement of stents. The high incidence of late thrombotic occlusion requires optimization of the antithrombotic regimen.     

90Sr血管内照射防治内膜损伤后再狭窄

目的研究常规治疗剂量和高剂量99Sr照射对血管壁平滑肌的生物学效应.方法18只新西兰兔分为3组,行髂动脉内膜剥脱术后,12只用90Sr后装技术行血管内照射,距放射源中心轴线2 mm深度血管壁吸收剂量分别为16和50Gy,6只未行血管内照射治疗作为对照组.28 d后处死动物进行组织病理学分析.结果50Gy组血管中层组织为类内皮样细胞所覆盖,其血栓发生率(3/6只)高于对照组(0/6只)和16Gy组(1/6只).16Gy组狭窄指数、增殖指数、增殖细胞核抗原阳性率和凋亡细胞阳性率与对照组比较差异有显著性.50Gy组狭窄指数、增殖指数与对照组和16Gy组比较,差异均有显著性.结论16Gy组血管内膜增生受到明显抑制,剂量增加到50Gy时,内膜增生现象完全受到抑制,除血栓发生率较高外,未见其他如假性动脉瘤等血管严重并发症.     

Interventional nuclear medicine in the prevention of restenosis following angioplasty

Restenosis is an unsolved clinical and economic limitation of angioplasty. Local irradiation is a new concept to overcome this problem. The magnitude of this health problem becomes apparent when one recognizes that 166132 percutaneous transluminal coronary angioplasty (PTCA) procedures were performed in Germany in 1999. Each angioplasty has subsequent costs of 6384 DM, which can be reduced to 2161 DM by 50% restenosis reduction due to irradiation [1]. The number of diagnostic and therapeutic procedures is growing by at least 10% per year.     

基质金属蛋白酶与血管成形术后再狭窄

基质金属蛋白酶(MMPs)为一蛋白酶家族,激活后能降解细胞外基质(ECM)的所有组成成分,参与细胞向内膜迁移形成新生内膜和血管重塑.综述MMPs家族的组成、活性的调节和MMPs与血管成形术后再狭窄的关系,并针对这些途径的干预治疗进行展望.     

High dose rate endovascular brachytherapy in aorto-iliac lesion for the prevention of restenosis

This study examined the applicability of endovascular brachytherapy to larger del arteries such as the abdominal aorta and iliac artery. Endovascular brachytherapy using an Ir-192 HDR source was administered 11 times to nine patients who had undergone percutaneous transluminal angioplasty (PTA) between 1995 and 1999. The follow-up lasted 13 to 55 months after treatment (median, 24 months). Eight of the 11 lesions have been controlled so far. Although one case developed thrombus inside the stent five months later, recanalization was achieved by means of retreatment. One patient who underwent low-dose irradiation (6 Gy) without stent implantation showed restenosis five months after treatment. We used a centering catheter that did not block the blood stream for exact centering of the radiation source in larger vessels such as the abdominal aorta. Although endovascular brachytherapy is a promising and safe procedure, careful follow-up is needed to detect untoward reactions such as thrombosis.     

Carotid angioplasty and stent placement for restenosis after endarterectomy

Introduction Recurrent carotid stenosis following endarterectomy is a common complication, and reoperation may be associated with increased morbidity. The goal of this study was to determine the procedural safety and long-term complication rates of carotid angioplasty and stenting for recurrent stenosis. Methods Of 248 consecutive carotid angioplasty and/or stenting procedures performed at our institution between March 1996 and November 2005, 83 procedures for recurrent stenosis following endarterectomy were performed in 75 patients (mean age 68 years; 43 men, 32 women) without cerebral protection devices. The patients’ medical records were retrospectively reviewed for vascular imaging reports and available clinical follow-up. Procedural and long-term complication rates were calculated. Results Recurrent stenosis was reduced from a mean of 80.6% to no significant stenosis in 82 of 83 procedures. The procedural stroke rate was 3 out of 83 procedures (3.6%). The procedural transient ischemic attack (TIA) rate was 2 out of 83 procedures (2.4%). Mean follow-up was 22.4 months (range 0.1 to 86.7 months) with at least 6 months follow-up for 54 of 83 procedures (65%). There were five TIAs and no strokes on follow-up (new TIAs at 25.5 and 43.4 months; recurrent TIAs at 1, 11.1, and 12 months, all with normal angiograms). The composite 30-day stroke, myocardial infarction, or death rate was 5 of 83 procedures (6.0%). Conclusion In this series, angioplasty and stenting were effective in relieving stenosis secondary to recurrent carotid disease after endarterectomy, and have low rates of ischemic complications.     

Endovascular radiotherapy for stenosis after percutaneous transluminal coronary angioplasty

The rate of restenosis after percutaneous transluminal coronary angioplasty ranges from 30% to 60%. Despite numerous trials, no effective pharmacological therapy has been found. This late effect can be reduced by endovascular radiotherapy. In animal models of restenosis after balloon injury, there is marked reduction of neointimal proliferation when the injured vessel is irradiated, using a variety of radiation sources and delivery systems. Early human trials did not focus on the importance of source selection and calibration. Other aspects which should be carefully determined are source selection and responsibilities of the treatment team. These matters are reviewed and discussed.     

核素内照射防治血管成形术后再狭窄

血管介入术后的再狭窄严重影响术后远期疗效。在各种防治再狭窄的方法中 ,放射性核素血管内照射逐渐成为一种极有前途的新方法 ,与之相关的设备 ,剂量以及随之而来的并发症也逐渐为人们所认识。目前看来 ,此法仍较为可行。     

Endovascular brachytherapy: restenosis in de novo versus recurrent lesions of femoropopliteal artery--the Vienna experience

PURPOSE: To determine the effectiveness of endovascular brachytherapy in the prevention of restenosis in recurrent versus de novo femoropopliteal lesions. MATERIALS AND METHODS: Ethics committee approval and patient informed consent were obtained. After they had undergone femoropopliteal angioplasty, 199 patients (mean age, 71.9 years +/- 9.6; 115 men, 84 women) were treated with either percutaneous transluminal angioplasty (PTA) and brachytherapy (n = 100) or PTA alone (n = 99). The patients were part of prospective randomized trials, the Vienna 2 and 3 trials, and were evaluated according to the stratification criterion of de novo or recurrent disease. Sixty-six of 134 patients with a de novo lesion and 34 of 65 patients with a recurrent lesion were randomly assigned to the PTA and brachytherapy arm; the remaining patients were treated with PTA alone. Outcomes were compared between the groups. The Student t test or one-way analysis of variance was used to compare continuous variables, and the chi2 test or Fisher exact test was used to assess dichotomous variables. Kaplan-Meier curves were calculated, and the log-rank test was performed to determine freedom from recurrence at 12 months in both groups. A multivariate Cox proportional hazard regression analysis was performed to evaluate the multivariate predictors of recurrence at 12-month follow-up. RESULTS: For patients with de novo lesions, the frequency of recurrence at 12 months was not significantly different between those who underwent brachytherapy and PTA and those who underwent PTA alone (24 [36%] of 66 patients vs 30 [44%] of 68 patients, P = .32). For patients with recurrent lesions, however, the 12-month recurrence rate was significantly lower in those who received brachytherapy than in those who did not (nine [26%] of 34 patients vs 22 [71%] of 31 patients, P = .004). CONCLUSION: Endovascular brachytherapy with gamma radiation significantly reduces the restenosis rate after femoropopliteal angioplasty of recurrent but not de novo lesions.     

经皮腔内血管成形术后再狭窄的炎症预测因子

大量的实验室及临床研究表明,经皮腔内血管成形术(PTA)后发生血管再狭窄主要与以下几个因素有关:炎症反应、血管壁的损伤、血小板聚集、血栓形成、血管内膜细胞过度增生等,其相应的反应参数可以作为PTA术后发生再狭窄的预测因子.本文就对儿种与炎症反应相关的预测因子做一综述.     

32P液体球囊血管内照射预防血管成形术后再狭窄

目的 探讨^32P液体球囊血管内近距离照射治疗对防止血管成形术后再狭窄的量效关系及其抑制再狭窄发生的可能机制。方法 27只雌性大白兔据动脉球囊扩张损伤后，实验组(18只)分别给予3、9、18和36Gy^32P液体球囊行内照射治疗，对照组(9只)灌注生理盐水。术后于不同时间点取材，行HE染色、增殖细胞核抗原(PCNA)免疫组织化学染色以及电镜观察血管组织形态学的改变，用计算机图像分析法测量管腔面积和内膜面积。结果 对照组血管内膜明显增生，管腔变狭窄。18Gy组血管壁平滑肌细胞增殖明显受抑，细胞凋亡增加，管腔面积无明显丢失；36GY组血栓形成明显；3和9Gy组均未观察到明显的生物效应。结论 ^32P液体球囊血管内照射可防止血管成形术后再狭窄发生，其机制可能为抑制血管壁平滑肌细胞增殖，促进其凋亡及改善血管重塑形。     

血管腔内近距离照射预防介入治疗后再狭窄的研究现状

血管成形术后发生再狭窄影响手术的远期疗效。血管腔内近距离照射治疗可有效抑制血管内膜的过度增生,促进细胞凋亡,同时还可引起管壁正性重建,增加管腔面积。大量的临床资料证实,该方法有效且安全可行,是介入心脏病学的一大突破。