Engineering aspects of stents design and their translation into clinical practice

The implantation of coronary stents is a relevant part of interventional procedures for percutaneous revascularization. The wide acceptance of coronary stenting was based on the results of two highly significant trials which have shown the superiority of stenting over balloon angioplasty in terms of reduction of angiographic restenosis and need for repeated intervention in focal lesions and large coronary arteries. Since then, the growing use of stent market was impressive. A rapidly increasing number of different stent type with different material and designs has been introduced in the market both for bare metal stent and drug eluting stent. This review will summarize the different components of stent design that are important in term of biological response of the arterial wall and clinical outcome. In addition, new stent platforms, mainly represented by the biodegradable stent will be shortly reviewed since it may provide in the near future a more "physiological" answer to stent implantation, reducing vascular injury and accelerating vessel healing with consequent improving in clinical outcome.     

新型前列腺放疗支架的研制

目的:研制一种能够具备针对性放射治疗手段的新型前列腺放疗支架,实施时可在现有的普通支架基础上结合近距离放射治疗的技术,采用与放射性粒子相同的放射性同位素,设计一种可以将放射性同位素覆盖在普通支架一端形成照射源然后植入人体实现体内放疗的支架产品。方法:通过对NiTi材料的医学基础研究、NiTi支架的临床应用现状、支架的设计因素、放射性同位素的选择、支架的结构设计、支架的制造工艺六个分析步骤,确定新型前列腺放疗支架使用的材料是金属材料,选用的放射性同位素结合生产周期和临床治疗效果两个因素确定为同位素125I,放疗支架的结构确定为一端覆盖放射性高分子膜,另一端设置可回收支架的高强度手术缝合线,当放射性同位素在其活度趋于零的时候,可将本品从人体植入部位取出,使用溶剂溶解掉失效的放射性高分子材料后,可再次制造放疗支架。结论:虽然同位素125I用于治疗前列腺癌已有十几年的历史,且临床疗效已被医患双方广泛认可;虽然本文研制的一端带有放射源的新型前列腺放疗支架目前还没有检索到公开的临床研究数据和相关报道,且本产品已经通过国家食品药品监督管理局医疗器械专业检验机构的型式检验,但其如果正式应用于临床还需要制定严格规范的研究方案,确定适应症及禁忌症,规定入选标准、排除标准、退出标准、剔除标准,设置普通前列腺支架为对照组,对两组支架的临床应用安全性和有效性进行统计学综合分析。     

带定位中心的介入用支架输送器研究

现阶段涂药支架或放射性支架在临床使用的频率越来越高,但初期的支架雏形均是在支架外表面采用特殊的工艺将药物均匀的涂在支架表面,但临床使用效果表明某些药物支架与人体管腔正常组织接触后,带来了不确定的组织损伤。临床要求该种药物支架在进行工艺改进后能够只针对管腔病变位置实施治疗而不涉及正常管腔组织,但如何将该种药物支架的涂药部位在手术时准确定位在人体管腔病变位置是个急需解决的问题。目前临床介入科及腔镜科均使用普通的支架输送器或预置支架的球囊扩张导管将支架置入到人体病变部位。如果需要将局部涂药的支架置入到人体病变部位就需要研究一种带定位中心的输送器,该输送器除了具备普通输送器在生物相容性等方面的要求外还必须具备可实施定位置入支架的要求。由于X射线不能透过金属材料,所以可以考虑将金属线加入到导管材料中,并在导管的径向和轴向加工定型一个十字靶心,在支架出厂时可以将支架局部涂药的部位对准导管的十字靶心进行预置,这样在临床放置支架时只需在X射线的观察下将十字靶心定位于已实施影像检查的人体管腔病变部位即可。实验结果表明将带定位中心的介入用支架输送器置于X射线人体测试模拟体模内在70kV、3mA曝光条件下实施透视及70kV、200mA曝光条件下实施摄影,其影像非常清晰能够使临床医生能够准确地将局部涂药支架定位于人体管腔病变位置。     

腹腔镜胆总管探查改良胆道支架引流术

目的:探讨腹腔镜胆总管探查术中放置自行脱落胆道支架的可行性。方法:在腹腔镜胆总管探查术清除结石后,将斑马导丝经胆道镜操作孔置入十二指肠。退出胆道镜,将改良支架套住导丝,用推送管将支架的猪尾巴端送入十二指肠。支架上端用快吸收线固定于胆管壁。一期缝合关闭胆总管切口。结果:该法治疗33例患者。术后平均住院时间4.3(3~8)d,术后支架均随粪便排出,排出时间13.6(9~21)d。4例(12.1%)术后血清淀粉酶短暂升高。发生堵管并黄疸加深1例(3%),经保守治疗后黄疸消退。无胆漏、提前脱管、导管滞留、导管退入胆道等并发症。术后随访3-20个月,全部病例无胆系炎症、残余结石及胆管狭窄。结论:在腹腔镜胆总管探查术中放置胆道自行脱落J型引流支架较放置其它支架操作更方便、更安全。因支架能自行脱落排出,该法更具成本效益并符合微创原则。     

金属食管支架置入结合放疗治疗食管癌性狭窄的临床应用研究

目的 探讨X射线下国产食管支架置入的技术、方法、带"架"放疗的可行性以及两者结合治疗食道癌性狭窄的临床应用价值。方法 总结X射线下放置的较完整的158例病人的临床X射线资料,着重分析其中86例带"架"病人进行常规分割照射放疗的可行性及疗效。结果 158例病人放置食管支架162个,除一例严重狭窄导丝难以插入不能放置外,其余均一次成功。所有病人支架置入后吞咽困难立即缓解,特别是结合放疗病人,生活质量明显提高,生存期延长,无一例出现大出血及穿孔等并发症。结论 国产食管支架X射线下放置安全,疗效快捷;带"架"不影响病人放疗;两者结合可明显提高疗效。此方法应成为晚期食道癌性狭窄病人首选的治疗手段。     

Palliation in cancer of the oesophagus – what passes down an oesophageal stent?

Introduction: Self‐expanding metal stents are becoming an increasingly popular method of palliation of dysphagia in advanced oesophageal carcinoma. Approximately 10% require intervention post‐placement because of blockage ( Angorn, 1981 ). This could be prevented by effective dietary advice. We set out to write evidence‐based dietary guidelines for patients undergoing oesophageal stent insertion. A comprehensive literature search failed to identify evidence to support the present guidelines used by manufacturers and dietitians on foods allowed or to avoid and the use of fizzy drinks to ‘clean’ the stent. Only reference on the ability to consume a semi‐solid or solid diet was made ( Nedin, 2002 ). We therefore tested the ability of 50 foods to pass through a stent and the efficacy of fizzy water in unblocking an occluded stent. Method: Normal mouthfuls of raw and cooked, peeled/unpeeled fruit and vegetables, casseroles, griddle or grilled plain meat, poultry or fish, eggs, nuts, dried fruit and bread in various forms were tested. An adult female chewed a ‘normal’ mouthful of each test food and at the point of swallowing the bolus of food was passed into an expanded Ultraflex metal covered stent (internal diameter 18 mm). If occlusion occurred, water was dribbled through the stent, simulating swallowing fluid, in an attempt to unblock the stent. If the occlusion remained, the stent was agitated to mimic advice given about moving around to unblock a stent in a patient. If it remained occluded, a smaller amount of food, approximately half a mouthful, was chewed for twice as long and re‐tested. To test the efficacy of fizzy water to clear an occlusion, we compared the ability of water, warm water and fizzy water to unblock a stent artificially occluded with a bolus of bread. Results: Foods that occluded the stent but passed through if eaten in half mouthfuls and chewed for twice normal chewing time included sandwiches, dry toast, apple, tinned pineapple, fresh orange segments with pith removed, up to six sultanas, chopped dried apricot, boiled egg, muesli, meat and poultry. Dry meat, fruit with pith, skins of capsicum peppers and tomatoes, more than seven sultanas and dried apricots caused occlusion. Nuts and vegetables such as lettuce, which are cited in many diet sheets as items to avoid ( Nedin, 2002 ), passed through the stent when chewed to a normal level. The volumes of fluid required to unblock a stent occluded with bread were 5 l of fizzy water, 3.5 l of cold water or 1 l of warm water. Conclusion: If a patient has good dentition and can chew well and take small mouthfuls and prepare and cook food appropriately, it is likely that they can enjoy a wide variety of solid foods. The use of fizzy drinks to maintain the patency of the stent in patients prone to reflux is questionable, warm fluids may be more efficacious. Based on these initial findings we are updating our dietary guidelines for patients undergoing oesophageal stent insertion and hope to audit stent occlusion following implementation.     

携带bFGF-siRNA质粒表达载体的生物降解支架防治兔颈动脉再狭窄的初步实验研究

目的初步探讨携带bFGF-siRNA质粒表达载体的生物降解支架防治兔颈动脉再狭窄的作用。方法经股动脉入路建立球囊损伤兔颈动脉狭窄模型,实验动物分组后分别植入裸生物降解支架和携带bFGF-siRNA质粒表达载体的生物降解支架,分别以光镜和电镜观察狭窄段血管病理形态学变化,计算血管中膜和内膜厚度。结果裸支架组和siRNA支架组血管内膜厚度明显较对照组小,且siRNA支架组和裸支架组相比,血管内膜厚度明显减小,但三组之间中膜变化不明显。结论携带bFGF-siRNA质粒表达载体的生物降解支架能有效防治兔颈动脉再狭窄的发生,其具体分子机制尚需进一步的检测。     

携带bFGF-siRNA质粒表达载体的生物降解支架防治兔颈动脉再狭窄的初步实验研究

目的 初步探讨携带bFGF-siRNA质粒表达载体的生物降解支架防治兔颈动脉再狭窄的作用。方法经股动脉入路建立球囊损伤兔颈动脉狭窄模型,实验动物分组后分别植入裸生物降解支架和携带bFGF-siRNA质粒表达载体的生物降解支架,分别以光镜和电镜观察狭窄段血管病理形态学变化,计算血管中膜和内膜厚度。结果裸支架组和siRNA支架组血管内膜厚度明显较对照组小。且siRNA支架组和裸支架组相比,血管内膜厚度明显减小,但三组之间中膜变化不明显。结论携带bFGF-siRNA质粒表达载体的生物降解支架能有效防治兔颈动脉再狭窄的发生,其具体分子机制尚需进一步的检测。     

内镜下双侧塑料支架植入治疗肝门部胆管恶性梗阻的疗效分析

目的：评估双侧塑料支架植入治疗肝门部胆管恶性梗阻的临床疗效,探讨肝门部胆管癌内镜治疗的最佳模式。方法：回顾性分析南京地区2家内镜中心近2年来38例采用经内镜双侧塑料支架植入治疗肝门部胆管癌的临床资料,包括支架放置成功率、有效引流率、早期并发症发生率、支架通畅时间及生存时间。结果：双支架组操作成功率为89.4%,有效引流率为86.8%,术后早期并发症为18.4%,支架通畅率为15.8%,患者中位生存期29周。结论：双侧塑料支架植入治疗肝门部胆管恶性梗阻安全可行并有较高成功率,可有效降低黄疸,提高生活质量。     

扫描电镜观察体内留置双J管表面生物膜的形成

目的观察植入人体内的双J管表面生物膜的形成情况。方法对42例泌尿外科手术后植入人体内的双J管分成4段分别作细菌学检验,然后用扫描电镜观察其表面生物膜的形成。结果42份双J管标本中,4段双J管均有同种细菌生长20例(47.6%),各段双J管细菌培养阳性率分别为:肾盂段81.0%、输尿管上段64.3%、输尿管下段71.4%和膀胱内段83.3%,共培养出18种126株细菌,以大肠埃希菌(23.0%)、铜绿假单胞菌(15.9%)、棒杆菌属(15.1%)和表皮葡萄球菌(13.5%)多见;电镜扫描双J管表面观察到未经使用过的双J管表面呈凹凸不平,但干净无任何附着物或结晶体,植入体内的双J管表面均有数量不等的炎性附着物或结晶体,可观察到细菌结构,生物膜的细菌被包裹在大量的纤维膜之中。结论植入体内的双J管表面易形成细菌生物膜,这可能是导管相关感染的因素之一。     

进口雷帕霉素洗脱支架治疗冠心病合并糖尿病患者的疗效观察

[目的]评价进口雷帕霉素洗脱支架（Cypher）在冠心病合并糖尿病患者中的治疗效果。[方法]192例冠心病合并糖尿病患者随机分为两组,分别植入雷帕霉素涂层支架及普通支架,普通支架组（Vision）80例,均成功进行经皮冠状动脉介入治疗（PCI）。两组患者术后均正规应用抗凝、抗血小板及调脂治疗。随访6-8个月,观察并记录再狭窄、主要心血管事件（泵衰竭、急性心肌梗死）、心脏性猝死等心脏事件。[结果]6~8月中Cypher支架组发生心脏性猝死1例,急性心肌梗死0例,2例泵衰竭;其中70例复查冠状动脉造影发现支架再狭窄5例,占7.14%。普通支架组发生心脏性猝死1例,急性心肌梗死1例,2例泵衰竭;其中53例复查冠状动脉造影发现支架再狭窄7例,占13.2%。Cypher支架组再狭窄率明显少于普通支架组,且不增加主要心血管事件的风险。[结论]与普通支架组相比,Cypher支架对糖尿病合并冠心病的患者效果更好。     

雷帕霉素洗脱支架置入动物体内后的支架内皮化进程

目的研究雷帕霉素洗脱支架(CypherTM)对血管内皮再生的影响。方法杂种犬6只,经麻醉后行血管造影,选择动脉血管直径为2.25 mm的直血管段在远端及近端分别置入直径为2.25 mm的CypherTM支架及Bx son ic支架。术后仍继续给予抗血小板治疗,分别在术后1月、3月时行再次血管造影后取标本行扫描电镜检查。结果术后1月、3月血管造影CypherTM支架及Bx son ic支架均无管腔丢失。1月时扫描电镜显示CypherTM支架内皮覆盖不完整,有一定的血小板黏附、聚集;Bx son ic支架内皮覆盖完整,未见血小板黏附聚集。3月时CypherTM支架及Bx son ic支架内皮覆盖均较完整,无血小板黏附、聚集。结论CypherTM支架内皮再生较裸金属支架缓慢,有一定的血小板激活。3个月时才能完全实现内皮化。置入CypherTM支架的患者应进行更为严格的抗血小板治疗。     

抗菌型胆道支架的研究进展

胆道支架已普遍应用于胆道狭窄和胆道梗阻的治疗并能有效缓解患者痛苦,但术后细菌感染及支架堵塞依旧是一大难题.介绍胆道支架植入后由细菌入侵引发的感染和支架堵塞机制,阐述细菌生物膜和胆汁污泥的形成机理.抗菌型胆道支架是抑制胆道感染的有效途径,综述国内外采用不同抗菌方式对胆道支架抗菌改性的相关文献,总结并展望抗菌型胆道支架的研...     

Immediate and six months clinical and angiographic results of intracoronary paclitaxel-coated stent implantation - the Meo:DrugStar-1 study

The study was conducted to evaluate the clinical and angiographic results of the implantation of the paclitaxel-eluting stent Meo:DrugStar ST in patients with symptomatic coronary artery disease. The Meo:DrugStar ST stent has a stainless steel stent platform with a homogenous non-biodegradable coating of paclitaxel mixed with a polyether-based biostable, monophase, and hemocompatible coating. Sixty patients with native coronary artery disease were included in the study. The Meo:DrugStar ST stents were implanted in 60 de novo lesions detected in these patients. Immediate and long-term clinical and angiographic follow-up results were evaluated. There was a high proportion of patients with hypertension (55%) according to JNC-VII. Mean stenosis ratio was 78 +/- 13 %, mean implanted stent diameter was 3.0 +/- 0.4 mm and mean length was 22 +/- 5 mm. Restenosis was detected in 4 (10%) of those patients and 11 (27.5%) of 40 patients had insignificant amount of restenosis. The results of this study indicate a potential benefit of the Meo:DrugStar ST stent for the prevention of stent thrombosis and restenosis in these relatively high-risk patients.     

Thrombosis of a coronary stent after discontinuing treatment with clopidogrel

A drug-eluting stent was implanted in four patients, a man aged 67 and a woman aged 42 with acute myocardial infarction, a woman aged 41 with unstable angina pectoris and a man aged 41 with stable angina pectoris. All suffered stent thrombosis after discontinuation (in three cases prematurely) of clopidogrel therapy. Reasons for discontinuation included allergic reaction, a dental procedure and refusal of reimbursement by the insurer. In order to restore stent patency they were treated by percutaneous coronary intervention and all patients suffered irreversible myocardial damage. Combination therapy using acetylsalicylic acid and clopidogrel during and after angioplasty for the prevention of long- and short-term complications is necessary. Stent thrombosis after drug-eluting stent implantation usually occurs within 1-4 weeks following discontinuation ofantiplatelet medication. These cases stress the importance of antiplatelet therapy after stent implantation. Physicians, dentists and patients must be aware of the risk of the early discontinuation ofantiplatelet therapy.     

内镜下自膨式无覆膜结肠金属支架置入治疗左侧结肠恶性梗阻

目的 探讨经内镜自膨式无覆膜金属支架置入治疗左侧结肠癌性梗阻的临床价值.方法 根据梗阻情况进行不同术前肠道准备后,经内镜放置金属支架治疗左侧结肠癌性梗阻患者21例,术后进行常规处理并随访.结果 21例结肠癌性梗阻中,放置金属支架成功率为100％,术后1～2d肠梗阻症状均得到缓解或消除;支架术后均有少量的便血6例,无大出血、穿孔及支架移位等并发症发生;21例患者术后均能恢复经口进食,生存期4 ～ 22月,平均生存期为7月.结论 经内镜放置自膨式无覆膜金属支架治疗左侧结肠癌性梗阻,操作简单、经济有效、术后并发症少,有效缓解患者的梗阻症状,提高其生活质量.     

Portal vein stenting to treat portal vein tumor thrombus in hepatocellular carcinoma

Tumor thrombus in the portal vein is refractory to therapy and a serious negative prognostic factor in hepatocellular carcinoma. We describe herein the case of a patient in whom an expandable metallic stent was successfully employed to treat portal vein tumor thrombus by restoring blood flow. An expandable metallic stent was implanted in a patient with severe main portal vein stenosis caused by tumor thrombus protruding from the left portal vein branch. Immediately after stent placement, the stenotic lesion was effectively dilated, the portal blood flow restored, and portal hypertension relieved. Angiography, computed tomography, and doppler ultrasonography done 2 months after the stent placement revealed continued patency of the portal vein. Thus, intraportal placement of an expandable metallic stent appears to be an effective treatment for major portal vein tumor     

血管吻合用中空支架壁双层结构的研究

目的：研制一种血管吻合用支架，使其外表面光滑柔软，内层又具有快速溶解的特性。方法：选用高纯度低分子量明胶和色谱纯分子量为20000的聚乙二醇为原料制备血管吻合用中空支架，使前者构成支架壁的表层，后者构成支架壁的内层，并观察在类吻合环境下支架表面结构的改变。结论：双层血管吻合用支架在吻合环境中具有光滑柔软的外表面，能够快速溶解，适于血管吻合。     

电子气管镜用于食管严重狭窄支架置入的效果观察

目的：探讨气管镜用于食管严重狭窄病例支架置入的可行性与优越性。方法：将胃镜无法通过的食管严重狭窄的患者共34例,分为实验组12例在Olympus-BF260电子气管镜直视下置入食管支架;对照组22例用普通胃镜在X线透视下行食管支架置入术。结果：实验组12例患者均一次性成功放置食管支架,成功率100%,操作时间相对短,并发症少,支架位置准确;对照组22例,成功置入16例,成功率72.7%,出现并发症4例。结论：电子气管镜代胃镜行食管支架置入术,操作时间短,成功率高,并发症少,支架定位精确;且无需在X光机,不对医务人员造成辐射损害,因此电子气管镜代胃镜用于食管严重狭窄支架置入优点多,有气管镜的医院均可开展此项工作。     

Abdominal pain following placement of an endoprosthesis in the biliary duct

A 76-year-old man presented with diffuse progressive abdominal pain. He had undergone endoscopic retrograde pancreaticocholangiography (ERCP) 5 weeks earlier for jaundice and increased levels of liver enzymes. A dilated biliary duct with multiple concrements had been seen, and a plastic endoprosthesis was placed. During a follow-up ERCP the stent was not found, and the obstruction was still present. Another stent was placed. Abdominal x-ray revealed migration of the first endoprosthesis to the distal jejunum and signs of ileus and free gas. CT showed that the stent was stuck in a perforated diverticulum of the sigmoid, surrounded by an abscess mass. The stent was removed by laparotomy, the perforation was closed, and a double-loop stoma was made. Two weeks after initial recovery, abdominal pain recurred. CT revealed a second dislocated stent with a perforation of the jejunum. Laparotomy was performed again with removal of the stent and repair of the perforation. Migration is a known complication of biliary endoprosthesis placement, and should be considered in cases of abdominal pain after ERCP. Perforations rarely occur and mostly affect areas of the bowel that are fixed or that present obstacles to normal elimination. Two perforations within a short period of time is an extremely rare complication of migration.