与开放手术(open surgery repair,OSR)相比,腹主动脉瘤(abdominal aortic aneurysm,AAA)腔内治疗(endovascular aortic repair,EVAR)患者早期生存优势明显,但晚期生存并无显著优势,且长期随访结果显示EVAR术后并发症和再干预的风险更高[1-2]。基于此,如何有效识别与EVAR相关的危险因素显得尤为重要。目前形态学特征(如短瘤颈、宽瘤颈、扭曲瘤颈、瘤体直径、瘤腔血栓负荷、髂动脉扭曲等)在EVAR中起着至关重要的作用,已被广泛用于评估EVAR术后的风险。但对不良形态学特征的综述比较少见,为此本文就影响EVAR术后相关死亡、移植物相关并发症和EVAR术后再干预的不良形态学特征研究进展进行总结,旨在为临床医师评估EVAR风险提供依据。
EVAR术后相关死亡 相较于OSR,尽管EVAR患者术后死亡率已显著下降,尤其是早期死亡率[1],但是EVAR术后相关死亡仍是EVAR术后风险预测的一个主要方面。目前AAA的直径仍为EVAR术后相关死亡风险的最主要预测因素,Khashram等[3]发现AAA直径每增加1 cm,集合危险比为1.14(95%CI:1.09~1.18)。至于AAA直径的临界值,几项研究有些许差异。Kim等[4]发现直径为5.0~5.5 cm比直径≥5.5 cm的AAA患者EVAR术后有更高的5年生存率,而与直径为4.0~5.0 cm的AAA患者相比5年生存率无显著差异。Jeon-Slaughter等[5]的研究以5.6 cm为临界值,结果显示EVAR术后患者中期死亡率与AAA大小有关,而晚期死亡率与AAA大小无关。Huang等[6]发现当AAA直径≥6.0 cm时EVAR患者有更高的全因死亡率。Oliveira等[7]发现AAA直径 > 7 cm、近端瘤颈直径≥30 mm为EVAR术后患者心血管疾病相关死亡的危险因素,而近端瘤颈血栓周长 > 25%为保护性因素。除AAA直径外,也有研究聚焦于扭曲瘤颈,Mathlouthi等[8]发现严重肾上成角(> 60°)与EVAR术后死亡率有关(30天死亡率和长期死亡率)。AbuRahma等[9]的研究同样发现当瘤颈角度 > 60°、瘤颈长度 < 10 mm时EVAR术后有更高的死亡率。不同于传统的形态学特征,Kwon等[10]发现主动脉"shaggy"综合征与EVAR术后30天死亡率有关。而Khan等[11]用直径-高度指数(diameter-to-height index,DHI)来评估EVAR术后30天和5年的死亡率,DHI定义为中心线处AAA直径/高度。结果显示其预测结果明显优于AAA直径,此结果尚需进一步验证。
移植物相关并发症 移植物相关并发症定义为:主动脉相关并发症(Ⅰ型内漏;Ⅱ型内漏伴瘤腔增大 > 5 mm;Ⅲ型内漏;任何原因引起的瘤腔增大 > 5 mm;支架移位 > 5 mm)和髂支相关并发症(有干预指征的髂支狭窄或闭塞)。有研究探讨了形态学特征与移植物相关并发症的关系,也有研究探讨了具体并发症(Ⅰ型内漏、Ⅱ型内漏、髂支闭塞等)与形态学特征的关系,在此分别论述。
移植物相关并发症 Oliveira-Pinto等[12]发现AAA主动脉腔体积与移植物相关并发症的发生有关。Antoniou等[13]一项meta分析结果显示宽瘤颈更易出现并发症(死亡,与动脉瘤有关的再干预,Ⅰa型内漏,瘤腔扩大,动脉瘤破裂,和瘤颈有关的不良事件)。而对于宽瘤颈的定义不同研究有所差异,Gargiulo等[14]发现瘤颈直径≥28 mm的患者EVAR术后易发生近端瘤颈相关并发症(近端瘤颈扩张,Ⅰa型内漏,瘤颈相关的再干预)。Kouvelos等[15]发现瘤颈直径≥29 mm易发生瘤颈相关并发症。Oliveira等[16]发现近端瘤颈直径≥30 mm易发生瘤颈相关并发症(Ⅰa型内漏,瘤颈相关的再干预,4年免于瘤颈相关不良事件)。Laczynski等[17]一项meta分析中结果显示宽瘤颈(25~30 mm或更大)易发生Ⅰa型内漏,再干预和支架移位。此外,Pitoulias等[18]发现在不良近端瘤颈患者标准EVAR术后,锥形瘤颈更易发生近端瘤颈相关并发症。
Ⅰ/Ⅲ型内漏 Ⅰ型内漏为血流经移植物近端锚定区(Ⅰa)或远端锚定区(Ⅰb)的空隙进入瘤腔。Ⅲ型内漏为血液因移植物结构故障或覆膜支架各部分连接处脱节而使得血流进入瘤腔。近年来由于手术医师经验积累和支架产品的更新换代,围手术期及早中期的Ⅰa型内漏已显著降低。关于围手术期及早中期的Ⅰa型内漏相关风险的报道较少。Schuurmann等[19]发现和主动脉钙化一样,主动脉曲率(近肾主动脉、瘤腔、主动脉远端)是发生术中Ⅰa型内漏的相关形态学特征。近年来大量研究聚焦于晚期Ⅰa型内漏,发现不良近端瘤颈是晚期Ⅰa型内漏的主要危险因素。对不良近端瘤的定义几项研究有所不同,Oliveira等[20]对严重瘤颈扭曲的定义为:(1)瘤颈长度 > 15 mm,肾下成角(β) > 75°或者肾上成角(α) > 60°;(2)瘤颈长度10~15 mm,β > 60°或者α > 45°;结果显示尽管早期和中期的结果令人满意,但从长期结果来看,在严重瘤颈扭曲患者中有较高的Ⅰa型内漏发生率。O'Donnell等[21]发现近端瘤颈直径 > 28 mm,瘤颈长度 < 20 mm,瘤颈角度 > 60°与晚期Ⅰa型内漏的发生有关。此外Schuurmann等[22]发现动脉瘤最大曲率(47 m-1)与晚期Ⅰa型内漏和支架移位的发生有关。Ⅰb内漏的发生多与髂支锚定区的形态学特征有关,Mascoli等[23]发现髂总动脉长度 < 4 cm,直径 > 15 mm和 > 50%的血栓周长,远端锚定位置在髂内动脉起始处以上 > 1 cm的患者EVAR术后易发生Ⅰb型内漏。Choi等[24]研究同样显示早期Ⅰb型内漏的患者髂动脉更扭曲、更短,髂支远端锚定的长度更短。而晚期Ⅰb型内漏的患者有更大的AAA直径,髂动脉更短,髂支远端锚定的长度更短。Ⅲ型内漏相关的报道较少,有研究以Ⅰb型内漏或者Ⅲ型内漏作为主要终点事件。Roos等[25]的研究结果显示髂动脉直径大,锚定区短易发生Ⅰb或者Ⅲ型内漏。Chen等[26]发现主动脉扭曲的患者易发生Ⅰb或者Ⅲ型内漏。
Ⅱ型内漏 Ⅱ型内漏为血液经与瘤腔相通的侧支动脉反流进入瘤腔,侧支动脉包括肠系膜下动脉(inferior mesenteric artery,IMA)和腰动脉(lumbar artery,LA)等。Ⅱ型内漏是EVAR的主要并发症,发病率可高达44%,大多数Ⅱ型内漏能够自发消失。当持续时间≥6个月(持续性Ⅱ型内漏),自行消失的概率降低[27]。目前仍有研究关注IMA和LA的形态学特征,Chew等[28]的研究发现当术前影像学评估结果显示IMA闭塞或严重狭窄时,会显著降低Ⅱ型内漏的发生率。近年来更多的研究关注瘤腔血栓在Ⅱ型内漏发生中所起的作用,Fujii等[29]发现瘤腔血栓体积与Ⅱ型内漏及瘤腔增大有关。Müller-Wille等[30]进一步证实低瘤腔血栓体积比患者易发生Ⅱ型内漏及瘤腔增大。Piazza等[31]发现在IMA通畅(且直径 > 3 mm)、至少3对LA通畅、2对LA和骶动脉通畅(或者附属肾动脉、任何直径的IMA通畅)的高危组中瘤腔血栓体积比 < 35%为Ⅱ型内漏及再干预的独立危险因素。一项meta分析[32]结果显示:血栓量、AAA最大直径平面的血栓厚度、环形血栓和IMA水平处出现血栓与Ⅱ型内漏的发生有关。Whaley等[33]发现瘤腔血栓形态与Ⅱ型内漏发生有关,管腔后外侧和环形血栓为Ⅱ型内漏发生的保护性因素。此外,Huh等[34]研究结果显示当AAA最大直径≥7 cm时易发生Ⅱ型内漏。
近年来也有研究开始关注持续性Ⅱ型内漏,Otsu等[35]研究结果显示当IMA直径≥2.6 mm、LA直径≥1.9 mm时Ⅱ型内漏易成为持续性Ⅱ型内漏,而环形血栓为持续性Ⅱ型内漏的保护性因素。Seike等[36]的研究结果显示,当LA的数量≥4时易发生持续性Ⅱ型内漏。Gallitto等[37]发现AAA侧枝数量≥6,瘤腔血栓体积比 < 40%与持续性Ⅱ型内漏的发生有关。
髂支闭塞、远端移位、延迟破裂 Daoudal等[38]发现如果髂支锚定在髂外动脉或存在窄瘤颈的患者,EVAR术后易发生髂支闭塞38。Ihara等[39]发现远端锚定区 < 10 mm的患者易发生远端移位。Zacharias等[40]发现超出IFU标准的EVAR中出现延迟破裂的患者其AAA直径较大,近端瘤颈形态为宽瘤颈、短瘤颈、扭曲瘤颈。
EVAR术后再干预 EVAR术后并发症中指南建议积极干预Ⅰ/Ⅲ型内漏,而对于Ⅱ型内漏,需要结合瘤体增大的直径、导致Ⅱ型内漏的动脉形态学特征等因素[41-42]。单独以再干预作为主要终点事件研究其不良形态学特征的研究较少。Ferrel等[43]发现AAA最大直径≥6.5 cm时二次干预的时间缩短。
结语 尽管目前EVAR是AAA治疗的首选,但是EVAR术后相关死亡、并发症和再干预仍需引起临床医师的重视。本文通过系统综述影响EVAR术后风险的不良形态学特征,将更加有助于有效识别与EVAR相关的危险因素,为临床医师评估EVAR风险提供依据,这可能会影响手术方式的选择和术后随访。
作者贡献声明 王永刚 文献收集,研究构思,综述撰写。史振宇 综述指导和修订。符伟国 综述审校和修订。
利益冲突声明 所有作者均声明不存在利益冲突。
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