[摘要]"炎症性肠病(inflammatory"bowel"disease,IBD)是一组慢性复发性疾病,病程中可出现肠外表现,给患者日常生活造成困扰。近年来,IBD治疗目标已从最初的临床缓解逐渐演变为生化缓解、内镜缓解及病理缓解等,但相关指南并未解决IBD诊断缺乏金标准的问题。目前,IBD的诊断仍结合其临床症状、内镜下表现、活组织病理及影像学检查等综合判断。值得关注的是,相较于普通内镜,超声内镜在IBD诊断和鉴别、监测疾病活动和复发、评估疾病预后和治疗应答等方面发挥重要作用。现就超声内镜在IBD诊治中的应用价值进行综述。
[关键词]"超声内镜;炎症性肠病;克罗恩病;溃疡性结肠炎;诊治
[中图分类号]"R573""""""[文献标识码]"A""""""[DOI]"10.3969/j.issn.1673-9701.2024.31.021
炎症性肠病(inflammatory"bowel"disease,IBD)是一组免疫异常导致的慢性非特异性肠道炎症性疾病,包括克罗恩病(Crohn’s"disease,CD)和溃疡性结肠炎(ulcerative"colitis,UC),其特点是病情反复且累及全身多部位,内科治疗效果不佳或出现肠道穿孔及癌变时须手术治疗[1-2]。相关数据显示,IBD的发病率不断上升,发病年龄多为15~30岁[3]。IBD是多因素、多基因导致的疾病,致病基因类型较多,涉及黏膜屏障完整性、先天免疫和适应性免疫等。目前多数学者认为部分IBD由异常免疫和炎症反应引起[4]。近年来,IBD的治疗目标已从控制症状转向持续且深度缓解。因此,早期引入有效治疗,增加评估频率、监测疾病活动、根据评估结果调整治疗成为主要的管理策略[5]。
小肠CT造影、磁共振小肠成像(magnetic"resonance"enterography,MRE)和超声内镜(endoscopic"ultrasonography,EUS)等技术在IBD的诊断和鉴别诊断、监测疾病活动和复发、评估疾病预后和治疗应答等方面发挥重要作用[6]。EUS是近年来广泛应用于临床的一种辅助检查方法,该方法综合消化内镜和超声检查的优点,可提供清晰的胃肠道黏膜皱襞及其内部结构图像,准确定位、测量并评价黏膜下水肿及肠壁增厚[7-8]。在观察胃肠道黏膜的基础上,EUS还可监测受累肠壁的层次结构及周围系膜、淋巴结特征,在IBD的诊断和评估病情活动性方面作用显著。
1""EUS在UC诊断中的应用价值
UC的临床诊断和治疗效果评估主要通过组织病理学检查、临床表现和内镜表现等确定。组织病理学研究和常规内镜检查只能评估肠黏膜表面病变,很难准确判断肠壁各层结构的损伤程度及结构变化,这在一定程度上影响临床医生对UC严重程度的判断[9-10]。EUS在诊断UC时具有独特优势。EUS可准确定位UC病变的位置及活动度。影像学表现为肠壁异常增厚、肠壁分层结构异常、肠壁各层间界限不规则或不清。部分UC患者存在黏膜下血管扩张和肠外淋巴结肿大[11-12]。也有学者指出,EUS可借助肠镜清晰评估肛管及全结肠状况,并对潜在病变区域进行细胞学和病理学检查[13-14]。""Jin等[15]研究发现EUS可准确检测出UC患者的病变范围及深度,为疾病严重程度的评估提供客观参考。另有研究指出即使UC患者的临床症状完全缓解、内镜下病变得到改善,但体内仍存在持续组织学炎症,影响疾病预后。EUS可精确评估UC患者的病变深度[16-17]。
2""EUS在CD诊断中的应用价值
CD是一种慢性炎症性疾病,可累及整个胃肠道,主要受累部位为小肠和回肠末端。CD在其自然病程中进展较快,因此早期诊断和发现并发症至关重要。内镜在CD中的应用包括初步诊断、病变范围评估、疾病活动度评估、治疗应答评估、术后复发预测、癌变监测和治疗干预等。CD在内镜下通常表现为黏膜红斑、水肿、黏膜易碎、溃疡、蛇形溃疡、跳跃性病变和狭窄。慢性炎症的组织学表现包括隐窝结构扭曲和非干酪化肉芽肿[18]。CD的EUS主要有以下表现:①肠壁明显增厚;②肠壁脂肪浸润、水肿或纤维化导致肠壁分层消失;""③管腔纤维化可导致蠕动变慢,甚至出现肠腔狭窄;④病变不局限于肠壁,肠系膜外侧的脂肪也可出现改变;⑤病变周围可见多个肿大淋巴结[19]。Tarján等[20]报道EUS诊断CD的敏感度为88.4%,特异性为93.3%,准确率为90.4%。邱恩祺[21]通过对436例内镜下疑似CD患者行EUS检查,发现EUS诊断CD的敏感度、特异性和准确率分别为87.5%、87.8%和87.6%;EUS发现黏膜下层血管扩张40例、瘘道13例、脓肿5例,探及管壁外肿大淋巴结75例。该研究表明EUS可对CD的消化道层次进行清晰观察,诊断准确率较高;同时,EUS能很好地发现瘘道、脓肿等肠外并发症,从而为并发症治疗提供有价值的信息。
3""EUS在UC及CD鉴别诊断中的应用价值
考虑到UC的炎症过程仅限于黏膜和黏膜下层,而CD的炎症可能影响到肠壁全层,在临床检查、实验室检查、结肠镜检查和组织病理学检查无法明确诊断的情况下,EUS可用于两种疾病的鉴别诊断。Ellrichmann等[22]研究表明,结合一系列特征(黏膜或黏膜下层厚度、肠壁总厚度和淋巴结的存在),EUS区分活动期UC和活动期CD的敏感度为93%,特异性为100%。Roushan等[12]根据平均黏膜厚度区分UC和CD的敏感度和特异性分别为92.3%和88.6%,截断值为1.1mm;平均黏膜下层厚度区分CD和UC的敏感度和特异性分别为100%和86.1%,截断值为1.08mm。研究发现UC患者EUS的超声改变主要涉及肠壁的前三层,而CD患者出现与固有肌层对应的第四层明显增厚[23]。上述研究均证实总肠壁厚度与用于评估临床和内镜活动的评分之间的相关性。研究表明无直肠受累的CD患者和对照组之间的直肠壁厚度存在显著差异,表明经直肠EUS在识别可能发生直肠受累或肛周疾病的CD患者方面具有潜在预测作用[22]。虽然上述研究取得一定成果,但目前还没有明确区分UC和CD的EUS标准。
4""EUS在IBD评估中的应用价值
IBD活动性的评估主要基于临床表现、实验室检查或内镜严重程度评分。肠壁厚度可区分活动期疾病和非活动期疾病。Rasmussen等[23]发现UC患者直肠壁厚度的增加与临床、内镜和组织学严重程度成正比。为确定结直肠EUS在评估UC严重程度中的作用,Dağli等[24]提出一系列肠壁总厚度和黏膜及黏膜下层厚度的临界值,以便区分缓解期患者与活动期患者。活动性UC的临界值总壁厚≥5.36mm,黏膜厚度≥2.23mm,黏膜下层厚度≥2.34mm。黏膜下层是否存在动脉或静脉流动是鉴别诊断的另一个有价值的参数。与黏膜下层增厚相比,该参数在区分活动期UC与缓解期UC方面显示出较高的特异性和敏感度[25]。研究发现黏膜下层的反应最敏感,当未达到内镜下缓解或内镜下改善时,黏膜下层仍显著增厚;黏膜的改变与组织学缓解显著相关;该研究明确内镜下缓解(≤2.8mm)、内镜下改善(≤3.9mm)和内镜下应答(减少32%)的准确临界值[26]。
从Tsuga提出的分类开始,Yan等[27]提出用于评估UC严重程度的EUS评分,该评分通过评估肠壁的厚度、炎症过程的深度和由肠壁血管化所定义的肠壁充血程度进行综合判断。研究表明EUS评分与临床和内镜下严重程度评分呈显著正相关,证实其也可用于监测治疗应答[15]。在缓解期UC患者中,EUS检查时其黏膜和黏膜下层厚度越厚,复发风险越高。Watanabe等[28]观察发现,在一组激素治疗无效的UC患者中,EUS直肠黏膜厚度越厚的患者对环孢素A治疗的反应越好。这与其他研究结果一致,即EUS可帮助预测活动性UC患者对药物治疗的应答,并确定是否需要手术干预[29]。
CD通常以透壁损伤为特征。越来越多的证据表明透壁愈合与CD患者长期预后较好有关[30]。EUS是一种无创的、高度精确的成像方式,可提供实时结果,并可评估CD的透壁愈合。研究表明在接受抗肿瘤坏死因子治疗的CD患者中,与不完全缓解患者相比,经EUS评定为透壁愈合的患者可降低住院率、手术次数,减少类固醇激素的使用[31]。CD患者经生物制剂治疗1年后,EUS评定为透壁愈合患者预后优于未愈合或仅黏膜愈合的患者[32]。越来越多的研究证实EUS在评估CD活动性方面的有效性及可靠性,EUS越来越多地被用于CD诊断、确定其病变范围和疾病活动度及疗效评定[33-35]。Horsthuis等[36]进行的一项Meta分析表明,EUS评估疾病活动的平均每肠段敏感度约73.5%,平均每肠段特异性约92.9%。Panés等[37]研究发现EUS评估疾病活动性的敏感度为84%,特异性为92%,EUS对评估近端回肠疾病的准确率较低。此外,在评估CD相关并发症时,EUS可准确检测瘘及狭窄,但易漏诊深部脓肿,EUS对CD相关并发症的检测敏感度较低。这可能与横断面检查中肠袢的遮挡、造影剂的使用、患者相关因素(EUS在有探头压力的疼痛区检查表现困难等情况)有关[38]。
综上所述,EUS在IBD的诊断、鉴别诊断CD和UC、监测疾病活动等方面发挥重要作用。但EUS操作对医生要求较高,中国专职承担EUS检查的医生较少。随着新技术的出现和内镜器械的不断更新,未来EUS在IBD的诊断和疗效评估过程中将发挥更重要的作用。
利益冲突:所有作者均声明不存在利益冲突。
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(收稿日期:2024–07–15)
(修回日期:2024–10–15)