Endoscopic ultrasound features of distal biliary stricture
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摘要:
目的 回顾性分析胆总管远端狭窄患者的超声内镜(EUS)特征,为EUS评估胆总管远端狭窄提供临床依据。 方法 收集安徽医科大学第一附属医院2016年4月—2020年3月行EUS检查的175例胆总管远端狭窄的患者临床资料,分析患者的临床表现、实验室、影像学及EUS检查结果,并进行随访,总结胆总管远端狭窄的EUS特征。计数资料两组间比较采用χ2检验,计量资料两组间比较采用t检验。 结果 175例胆总管远端狭窄患者中,良性胆总管远端狭窄85例(85/175,48.57%),恶性胆总管远端狭窄90例(90/175,51.43%)。在恶性胆总管远端狭窄的患者中,EUS显示狭窄长度高于良性胆总管远端狭窄患者[(14.1±3.0) mm vs (7.9±3.0) mm, t=13.358,P<0.001],同时EUS发现恶性胆总管远端狭窄患者的管腔低回声占位(57.8% vs 34.1%, χ2=9.843,P=0.002)、周围淋巴结肿大(26.7% vs 12.9%, χ2=5.147,P=0.023)及胰管扩张(51.1% vs 28.2%, χ2=9.532,P=0.002)等特征性改变发生率高于良性胆总管远端狭窄患者。EUS和MRCP两者联合诊断良性胆总管远端狭窄的敏感性为70.6%,诊断恶性胆总管远端狭窄的敏感性为92.2%。 结论 胆总管远端狭窄具有如较长狭窄、低回声、周围淋巴结肿大及胰管扩张等EUS图像特征,有助于临床中胆总管远端狭窄的鉴别诊断作用。 Abstract:Objective To investigate the endoscopic ultrasound (EUS) features of distal biliary stricture (DBS), and to provide a clinical basis for the evaluation of DBS by EUS. Methods Related clinical data were collected from 175 patients with DBS who underwent EUS examination in The First Affiliated Hospital of Anhui Medical University from April 2016 to March 2020 to analyze their clinical manifestation, laboratory examination results, imaging findings, and EUS findings, and the patients were followed up to summarize the EUS features of DBS. The chi-square test was used for comparison of categorical data between groups, and the t-test was used for comparison of continuous data between groups. Results Among the 175 patients with DBS, 85(48.57%) had benign DBS and 90(51.43%) had malignant DBS. Compared with the patients with benign DBS, the patients with malignant DBS had a significantly longer length of stricture on EUS (14.1±3.0 mm vs 7.9±3.0 mm, t=13.358, P < 0.001) and significantly higher incidence rates of the characteristic changes on EUS such as hypoechoic space-occupying lesions in lumen (57.8% vs 34.1%, χ2=9.843, P=0.002), peripheral lymph node enlargement (26.7% vs 12.9%, χ2=5.147, P=0.023), and pancreatic duct dilatation (51.1% vs 28.2%, χ2=9.532, P=0.002). EUS combined with magnetic resonance cholangiopancreatography had a sensitivity of 70.6% in the diagnosis of benign DBS and a sensitivity of 92.2% in the diagnosis of malignant DBS. Conclusion The characteristic EUS features of DBS, such as long length of stricture, hypoechoic lesion, peripheral lymph node enlargement, and pancreatic duct dilatation, may help with the differential diagnosis of DBS in clinical practice. -
胆管狭窄是由于胆管内容物通过受阻引起的胆道疾病[1],可由胆管腔内或腔外病变压迫引起,临床上可引起肝酶升高、黄疸、腹痛、发热等表现,按病因分为良性和恶性胆管狭窄[2]。良性胆管狭窄常见于医源性因素如胆囊切除和原位肝移植,以及感染、炎症及自身免疫性疾病等。恶性胆管狭窄通常由局部恶性肿瘤引起,如胆管癌、胰腺癌、肝细胞癌、壶腹癌或胆囊癌等[3-4]。鉴别良性和恶性胆管狭窄有助于选择合适的治疗方法,虽然大多数术前恶性胆管狭窄多为胰腺癌和胆管癌等,但高达30%是良性狭窄,多达1/4的可疑恶性狭窄在手术切除时被确定为良性狭窄。由于内镜辅助的细胞学检查的低敏感度(0.37~0.56)及低阴性预测值,临床上常难以早期获得准确诊断胆管狭窄所需的病理资料[2],因此,综合患者症状和体征、影像学以及内镜检查等临床资料,是目前胆管狭窄定性诊断和评估的主要方法[5]。磁共振胰胆管造影(MRCP)是临床常用的影像学方法,但对于胆总管远端的狭窄病变,因胆管远端管径纤细,常存在十二指肠乳头周围憩室以及肠腔内气体的干扰,严重影响胆总管远端狭窄的准确评估。近年来,超声内镜(EUS)可以克服上述影响因素,将超声探头靠近胆总管近距离扫查,动态观察目标病变的图像特征,在胆总管远端狭窄的诊断中发挥重要作用[6-8],研究[9]表明,EUS诊断恶性胆管狭窄的敏感性和特异性分别为80%和97%,对恶性胆总管远端狭窄的诊断敏感性更高。因此,本研究通过回顾胆总管远端狭窄患者的临床资料,分析胆总管远端狭窄的EUS图像特征,为EUS有效和准确诊断胆总管远端狭窄提供临床依据。
1. 资料与方法
1.1 研究对象
选择2016年4月—2020年3月于本院进行EUS检查并经临床确诊的胆总管远端狭窄患者175例。定义远端1/3胆管狭窄为胆总管远端狭窄[8],分为良性胆总管远端狭窄和恶性胆总管远端狭窄。
1.2 诊断标准
良性胆总管远端狭窄诊断标准:结合临床症状、实验室检查、影像学及内镜检查结果综合判断,必要时行胆管细胞学或病理检查,且临床随访至少6个月仍为良性病程[8, 10]。恶性胆总管远端狭窄诊断标准:结合临床症状、实验室检查、影像学及内镜检查结果及胆管细胞学或病理检查结果综合判断,或临床随访至少6个月表现出恶性进展证据[8, 10]。
1.3 研究方法
对胆总管远端狭窄患者病历资料进行回顾性分析,详细登记符合入选标准患者的一般资料、临床症状、实验室检查、MRCP及EUS检查结果、治疗经过和转归等,整理归纳并进行统计学分析。EUS与MRCP检查结果诊断为胆总管远端狭窄任一阳性即为两者联合阳性,二者均为阴性则为阴性。EUS检查包括狭窄段长度、管壁不规则不均匀增厚、管腔低回声占位、周围淋巴结肿大、胰管扩张、十二指肠乳头占位和胰腺占位等图像特征。
1.4 伦理学审查
本研究经安徽医科大学第一附属医院伦理委员会批准,批号:PJ2018-12-17,所有研究对象均签署知情同意书。
1.5 统计学方法
用SPSS 16.0软件进行数据分析。计数资料两组间比较采用χ2检验;计量资料以x±s表示,两组间比较采用t检验。P<0.05为差异有统计学意义。
2. 结果
2.1 胆总管远端狭窄患者的临床资料
共收集175例胆总管远端狭窄患者,其中良性胆总管远端狭窄85例,男40例,女45例,平均(63.4±11.6)岁;恶性胆总管远端狭窄90例,男45例,女45例,平均(63.1±9.6)岁。85例良性胆总管远端狭窄患者的病因构成中,感染、良性肿瘤和先天性因素等占63.5%,其次为炎症(20.0%)和医源性因素(10.6%),病因未明确占5.9%。90例恶性胆总管远端狭窄患者的病因构成中,胰头癌、壶腹癌或十二指肠癌占61.1%,其次为胆管癌(30.0%)、胆囊癌(5.6%),转移癌(3.3%)较少见。良性胆总管远端狭窄患者中,43例(50.6%)患者选择对症治疗,20例(23.5%)患者行内镜逆行胰胆管造影(ERCP)支架引流,外科手术11例(12.9%),另有11例(12.9%)无症状或症状轻微患者未接受治疗。恶性胆总管远端狭窄患者中,59例(65.6%)患者行外科手术治疗,12例(13.3%)患者行ERCP支架引流,5例(5.6%)行经皮经肝胆管引流术引流,11例(12.2%)患者对症治疗,2例(2.2%)患者接受化疗,1例(1.1%)患者放弃治疗。对所有纳入的患者进行了6个月以上的随访,进行生存曲线分析发现,恶性胆总管远端狭窄患者生存中位数为48个月,良恶性胆总管远端狭窄组间差异均有统计学意义(χ2=17.9,P<0.05)。
2.2 胆总管远端狭窄患者的EUS特征分析
EUS发现恶性胆总管远端狭窄的狭窄段长度显著高于良性胆总管远端狭窄患者,差异有统计学意义(P<0.05)。与良性胆总管远端狭窄患者相比,恶性胆总管远端狭窄患者的EUS特征包括更多的管腔低回声占位、周围淋巴结肿大及胰管扩张等,差异均有统计学意义(P值均<0.05)。良恶性胆总管远端狭窄其余EUS特征比较,差异均无统计学意义(P值均>0.05)(表 1)。
表 1 胆总管远端狭窄的EUS特征分析EUS特征 良性胆总管远端狭窄(n=85) 恶性胆总管远端狭窄(n=90) 统计值 P值 狭窄段长度(mm) 7.9±3.0 14.1±3.0 t=13.358 <0.001 不规则不均匀增厚[例(%)] 15(17.6) 25(27.8) χ2=2.544 0.111 管腔低回声占位[例(%)] 29(34.1) 52(57.8) χ2=9.843 0.002 周围淋巴结肿大[例(%)] 11(12.9) 24(26.7) χ2=5.147 0.023 胰管扩张[例(%)] 24(28.2) 46(51.1) χ2=9.532 0.002 十二指肠乳头占位[例(%)] 13(15.3) 18(20.0) χ2=0.664 0.415 壶腹部占位[例(%)] 16(18.8) 19(21.1) χ2=0.143 0.705 2.3 EUS对胆总管远端狭窄的诊断效能
EUS诊断良性胆总管远端狭窄的敏感性、阳性预测值及阴性预测值均高于MRCP。两者联合应用诊断良性胆总管远端狭窄的敏感性和阴性预测值均高于单独检测。EUS诊断恶性胆总管远端狭窄的敏感性及阴性预测值均高于MRCP。两者联合应用诊断恶性胆总管远端狭窄的敏感性和阴性预测值均高于单独检测(表 2)。
表 2 EUS、MRCP对胆总管远端狭窄的诊断效能疾病分类 诊断方法 敏感度(%) 特异度(%) 阳性预测值(%) 阴性预测值(%) 良性胆总管远端狭窄 EUS 52.9 80.0 71.4 64.3 MRCP 34.1 81.1 63.0 56.6 两者联合 70.6 65.6 66.7 70.2 恶性胆总管远端狭窄 EUS 72.2 74.1 74.7 71.6 MRCP 60.0 95.3 93.1 69.2 两者联合 92.2 71.8 77.6 89.7 3. 讨论
EUS和MRCP是鉴别良恶性胆总管远端狭窄的重要辅助诊断工具。MRCP是广泛应用于临床的一种非介入性胰胆管成像技术,通过加权技术提高胆汁信号来间接显示胆管,但容易受呼吸伪影、肠腔内气体等因素的影响[11-12]。与CT相比,MRCP的优点是提供胆管造影,检查胆管狭窄部位和范围,尤其适用于胆管近端狭窄。研究[2, 5]发现,MRCP确定是否存在胆管梗阻的敏感度和特异度分别为0.97和0.98,判断梗阻程度分别为0.98和0.98,鉴别良恶性胆管狭窄的敏感度和特异度分别为0.88和0.95。MRCP可用于判断是否存在胆管狭窄,但难以区分肿瘤和良性疾病引起的胆管狭窄[13]。
EUS的优点是能够提供胃肠道和邻近器官的实时成像,由于超声探头在十二指肠部位靠近胆管,EUS可对肝外胆道树进行详细检查[14-15]。除此之外,EUS还可以进行细针穿刺获取组织病理[16-19]。EUS诊断胆管狭窄的总体敏感度为0.88,特异度为0.90。在没有胰腺和胆管肿块时进行EUS检查,可以在CT漏诊的病变中识别高达40%的微小病变[2]。但对于非肿块性的胆管狭窄,EUS下细针穿刺和ERCP细胞刷检价值有限[20],此时诊断更依赖于EUS的特征[2, 21-22]。本研究发现,EUS中恶性胆总管远端狭窄患者的狭窄长度显著高于良性胆总管远端狭窄患者,恶性胆总管远端狭窄患者中可见更多的管腔低回声、周围淋巴结肿大等特征性改变[22]。研究[5, 23]表明,EUS图像特征可能为不明原因胆管狭窄的诊断提供重要线索,胰腺肿块和/或不规则胆管壁增厚鉴别良恶性胆管狭窄的敏感度为0.88,特异度为1.00。另有研究[2]发现EUS中胰腺肿块或胆管壁厚度>3 mm与胆管狭窄的恶性程度相关,敏感度和特异度分别为0.79、0.88和0.79、1.00。本研究未能发现胆管壁厚度在良恶性胆管狭窄中的显著差别,可能与管壁炎症活动的影响有关。
Spyglass检查可以通过直视下获取胆管组织进行病理学检查,明显提高胆总管狭窄的诊断效能。一项涉及283个病例的荟萃分析[24]显示,Spyglass诊断胆道恶性肿瘤的敏感度和特异度分别为94%(95%CI:89%~97%)和95%(95%CI:90%~98%)。Korrapati等[25]发现Spyglass对恶性胆管狭窄诊断准确率为0.89(95%CI:0.84~0.93),组织学诊断的准确率为0.79(95%CI:0.74~0.84)。Nishikawa等[26]研究发现Spyglass诊断胆道恶性狭窄的敏感度、特异度和准确度分别为1.00、0.91和0.97,胆道镜引导下的病理活检的敏感度、特异度和准确度分别为0.38、1.00和0.60。但Spyglass属于有创检查,常用于EUS和MRCP等方法不能明确诊断的胆总管狭窄。
在本研究中,EUS对恶性胆总管远端狭窄的诊断敏感性高于MRCP,同Mcmahon等[27]研究结果一致,但特异性较差,两者联合使用可提高诊断效能。如能联合实验室检查及EUS特征等有助于提高诊断准确性,在恶性胆总管远端狭窄的早期筛查中发挥重要作用[28]。EUS检查胆总管狭窄的图像特征优于肝门部狭窄[7]。同时发现对远端胆管狭窄的敏感性显著高于近端胆管狭窄(83% vs 76%),但诊断优势比分别为33.88和47.78,因此,胆管狭窄部位对EUS诊断准确性的影响有待进一步研究。
综上所述,胆总管远端狭窄临床表现多样,联合临床表现、实验室检查、影像学及EUS检查结果有助于提高胆总管远端狭窄的诊断效能。
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表 1 胆总管远端狭窄的EUS特征分析
EUS特征 良性胆总管远端狭窄(n=85) 恶性胆总管远端狭窄(n=90) 统计值 P值 狭窄段长度(mm) 7.9±3.0 14.1±3.0 t=13.358 <0.001 不规则不均匀增厚[例(%)] 15(17.6) 25(27.8) χ2=2.544 0.111 管腔低回声占位[例(%)] 29(34.1) 52(57.8) χ2=9.843 0.002 周围淋巴结肿大[例(%)] 11(12.9) 24(26.7) χ2=5.147 0.023 胰管扩张[例(%)] 24(28.2) 46(51.1) χ2=9.532 0.002 十二指肠乳头占位[例(%)] 13(15.3) 18(20.0) χ2=0.664 0.415 壶腹部占位[例(%)] 16(18.8) 19(21.1) χ2=0.143 0.705 表 2 EUS、MRCP对胆总管远端狭窄的诊断效能
疾病分类 诊断方法 敏感度(%) 特异度(%) 阳性预测值(%) 阴性预测值(%) 良性胆总管远端狭窄 EUS 52.9 80.0 71.4 64.3 MRCP 34.1 81.1 63.0 56.6 两者联合 70.6 65.6 66.7 70.2 恶性胆总管远端狭窄 EUS 72.2 74.1 74.7 71.6 MRCP 60.0 95.3 93.1 69.2 两者联合 92.2 71.8 77.6 89.7 -
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