共聚焦激光显微内镜对非糜烂性反流病微观变化的诊断价值  

Microalterations of esophagus in patients with non-erosive reflux disease: in vivo diagnosis by confocal laser endomicroscopy and its relationship with gastroesophageal reflux

作　　者：褚传莲[1] 李长青[2] 李真[2] 顾晓萌[2] 于涛[2] 戚庆庆 周成军[3] 李延青[2] 

机构地区：[1]山东大学附属济南市中心医院消化科,济南250013 [2]山东大学齐鲁医院消化科 [3]山东大学第二医院病理科

出　　处：《胃肠病学和肝病学杂志》2014年第2期131-137,共7页Chinese Journal of Gastroenterology and Hepatology

基　　金：卫生部临床学科重点项目(2007年度);山东省科技发展计划项目(2010GSF10247);济南市科技发展计划项目(201121001)

摘　　要：目的探讨非糜烂性反流病(NERD)患者电镜下微观结构的改变,研究食管下端黏膜的微观变化及其与反流的关系,为NERD的诊断及治疗提供依据。方法选取具有烧心、反酸≥3个月、反流性疾病问卷(RDQ)≥12分的患者纳入本研究。据内镜下表现将无黏膜破损者定为NERD患者组。选择同期的健康志愿者作为对照组。用共聚焦激光显微内镜(CLE)测量上皮乳头内毛细血管襻(IPCLs)数目、直径及鳞状上皮细胞间隙等,并与病理学资料相比较。同时行24 h食管多通道腔内阻抗-pH监测。按照反流物的组成成分(液体、混合及气体反流)及反流物的pH值(酸、弱酸及无酸反流)分别分析。结果共有67例患者纳入CLE检查,其中NERD患者46例[平均年龄(48.9±13.6)岁,男24例,女22例],对照者21例[平均年龄(35.0±12.3)岁,男11例,女9例]。NERD组IPCLs的数目、直径(μm)均大于对照组(8.29±3.52 vs 5.69±2.31,P=0.010)(19.48±3.13 vs 15.87±2.21,P=0.041),对于鳞状上皮细胞间隙,NERD组的平均值(μm)明显大于对照组(3.40±0.82 vs 1.90±0.53,P=0.042);ROC曲线显示两组间IPCLs数目的最佳工作点为6.0/FOV(AUC 0.722,95%CI:0.592~0.853),IPCLs直径的最佳工作点为17.20μm(AUC0.847,95%CI:0.747~0.947),细胞间隙的最佳工作点为2.40μm(AUC 0.935,95%CI:2.895~0.995)。IPCLs数目增多、扩张与存在DIS诊断NERD的敏感性最高,为100%。酸反流与IPCLs数目增多(β=0.059,t=2.017,P=0.030)及IPCLs扩张(β=0.047,t=2.236,P=0.045)有关。按照体位分析,则以卧位下明显,酸反流与IPCLs数目增多和扩张的β值、t值及P值分别为0.063、2.895、0.038和0.156、1.023、0.040。Bland-Altman plot分析结果显示CLE与透射电镜测得的细胞间隙数值有良好的一致性。结论CLE可清晰地观察到食管黏膜IPCLs形态、管径的变化及细胞间隙增宽,CLE在体测得的DIS与透射电镜一致,CLE可以作为快速、方便诊断NERD微观变化的实用工具。Objective To examine the microalterations of the esophagus in patients with non-erosive reflux disease （NERD） and its relationship with reflux episodes monitored by multiple intraluminal impedance-pH （MII-pH）. Methods NERD patients was determined by negative gastroseopy and questionnaires. Patients without reflux symptoms were recruited as controls. All subjects were examined by white-light mode of the endoscopy followed by the standard CLE mode and then MII-pH monitoring. Results On CLE images, NERD patients had more intrapapillary capillary loops （IPCLs） per image than did controls （8.29±3.52 vs 5.69 ± 2.31, P = 0. 010）, as well as the diameter of IPCLs （μm） （ 19.48 ＋ 3.13 vs 15.87 ± 2.21, P = 0.041 ） and intercellular spaces of squamous cells （μm） （3.40 ± 0.82 vs 1.90 ± 0.53, P = 0.042）. The receiver operating characteristic analysis indicated that IPCLs number [optimal cut-off〉 6 per image, area under the curve （AUC） 0.722, 95% confidence interval （CI）：0.592 ～ 0.853, sensitivity 67.7% , specificity 71.6%], IPCLs diameter （optimal cutoff 〉 17.2 p^m, AUC 0. 847, 95% CI： 0.747～0.947,sensitivity 81.0% , specificity 76.0%） , and the intercellular spaces of squamous cells （optimal cutoff 〉 2.40 Ixm, AUC 0. 935, 95% CI：0.875～0.995, sensitivity 85.7% , specificity 90.5% ） diagnosed NERD with reasonable accuracy. Combined features of dilatation of intercellular space plus increased IPCLs provided 100% specificity in the diagnosis of NERD patients. The intercellular spaces of squamous cells observed on CLE were highly related to that on TEM findings （r = 0.75, P 〈0.001）. Multivariate progressive regression analysis showed that acidic reflux, especially in the supine position, was related to the increased number and dilation of IPCLs in the squamous epithelium （β = 0.063, t = 2.895, P = 0.038 and β = 0.156, t = 1.023, P = 0.040）. Conclusion CLE represents a useful and potentially significant improvement over standard endoscopy to exam

关 键 词：共聚焦激光显微内镜 食管多通道腔内阻抗 非糜烂性反流病 胃食管反流病 诊断 

分 类 号：R57[医药卫生—消化系统]