miRNAs in precancerous lesions of the gastrointestinal tract

In spite of the well-established understanding of the phenotypic lesions occurring in the shift from native epithelia to invasive (adeno) carcinoma, the molecular typing of the precancerous changes in the gastrointestinal tract remains unreliable. In recent years, no biomarkers have aroused as much interest as the miRNAs,a class of non-coding RNA molecules that function as endogenous silencers of numerous target genes. Aberrant miRNA expression is a hallmark of human disease,including cancer. Unlike most mR...     

共聚焦激光显微内镜对胃非隆起型病变的诊断价值

目的探讨共聚焦激光显微内镜检查（CLE）对胃非隆起性病变良、恶性的鉴别诊断价值。方法对37例常规内镜发现的胃非隆起型病变患者行CLE检查。静脉注射荧光素钠后对病变区域进行观察,然后进行靶向活检。对CLE或靶向活检病理诊断为恶性病变者进行内镜或手术治疗,术后对整块标本进行病理学检查;对良性患者予规范药物治疗并每隔3个月复查胃镜,直至病变愈合。结果CLE诊断癌性病变11例,良性病变26例。靶向活检病理证实CLE诊断的11例癌变者中10例为癌,1例为良性;26例良性者中1例为癌,余皆为良性。共12例接受切除治疗（3例内镜治疗,9例外科手术）,术后病理学证实与靶向活检病理诊断完全一致。良性者随访中未发现有恶变,经平均3．16（3．58±1．20）个月的内镜随访,病变均愈合。CLE对胃非隆起性病变癌变诊断的灵敏度、特异度和准确度分别为90．9％、96．2％和90．9％,阳性预测值和阴性预测值分别为90．9％和96．2％;CLE与组织学检查的Kappa值为0．871。结论CLE对胃非隆起型病变具有较高的诊断价值,将有望替代活检病理做出实时组织学诊断。     

In vivo characterisation of superficial colorectal neoplastic lesions with high-resolution probe-based confocal laser endomicroscopy in combination with video-mosaicing: A feasibility study to enhance routine endoscopy

Background

Recent technological advances in miniaturisation have allowed for a confocal scanning microscope to be integrated into trans-endoscopic probes enabling endoscopists to collect in vivo virtual biopsies of the gastrointestinal mucosa during endoscopy.

Aims

The aim of the present study was to assess prospectively the clinical applicability and predictive power of a probe-based confocal laser endomicroscopy for the in vivo diagnosis of colorectal neoplasia.

Methods

Patients with evidence of colorectal superficial neoplasia at routine endoscopy, were included prospectively in this study. Lesions were identified using white-light endoscopy followed by pCLE imaging recorded by a Coloflex UHD-type probe. The images were interpreted as either neoplastic or not according to vascular and cellular changes. pCLE readings were then compared with histopathological results from endoscopically resected lesions and/or targeted biopsy specimens.

Results

A total of 32 lesions were identified in 20 consecutive patients. Histopathology diagnosis was of adenomas in 19 cases, hyperplastic polyps in 11 cases and adenocarcinoma in 2 cases. For the detection of neoplastic tissue pCLE had a sensitivity of 100%, a specificity of 84.6%, an accuracy of 92.3, a PPV of 90.5% and a NPV of 100%.

Conclusions

pCLE permits high-quality imaging, enabling prediction of intraepithelial neoplasia with a high level of accuracy.     

微探头共聚焦显微内镜诊断胃黏膜病变的初步应用

目的:探讨Cellvizio微探头式共聚焦内镜诊断胃黏膜病变的能力。方法:收集门诊6例胃黏膜病变患者行Cellvizio微探头式共聚焦内镜检查术。检查中静脉注射荧光素钠作为荧光剂。每例患者均经内镜直视诊断、共聚焦微探头诊断并获取靶向活组织行病理检查。符合手术指征者行外科手术。结果:6例患者共7处病灶,其中息肉2处,黏膜粗糙、发红2处,浅表凹陷灶1处,隆起伴凹陷灶1处,深溃疡1处。所有患者均完成共聚焦内镜检查,共获得连续视频图像32段。微探头共聚焦内镜易于操作其诊断正确者为6例(6/7),未发生明显不良反应。结论:Cellvizio微探头式共聚焦内镜操作简便,即时成像,是有效的胃黏膜病变诊断手段。     

Diagnosis of gastric intraepithelial neoplasia by narrow-band imaging and confocal laser endomicroscopy

AIM: To evaluate the diagnosis of different differentiated gastric intraepithelial neoplasia (IN) by magnification endoscopy combined with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE).METHODS: Eligible patients with suspected gastric IN lesions previously diagnosed by endoscopy in secondary hospitals and scheduled for further diagnosis and treatment were recruited for this study. Excluded from the study were patients who had liver cirrhosis, impaired renal function, acute gastrointestinal (GI) bleeding, coagulopathy, esophageal varices, jaundice, and GI post-surgery. Also excluded were those who were pregnant, breastfeeding, were younger than 18 years old, or were unable to provide informed consent. All patients had all mucus and bile cleared from their stomachs. They then received upper GI endoscopy. When a mucosal lesion is found during observation with white-light imaging, the lesion is visualized using maximal magnification, employing gradual movement of the tip of the endoscope to bring the image into focus. Saved images are analyzed. Confocal images were evaluated by two endoscopists (Huang J and Li MY), who were familiar with CLE, blinded to the related information about the lesions, and asked to classify each lesion as either a low grade dysplasia (LGD) or high grade dysplasia (HGD) according to given criteria. The results were compared with the final histopathologic diagnosis. ME-NBI images were evaluated by two endoscopists (Lu ZS and Ling-Hu EQ) who were familiar with NBI, blinded to the related information about the lesions and CLE images, and were asked to classify each lesion as a LGD or HGD according to the “microvascular pattern and surface pattern” classification system. The results were compared with the final histopathologic diagnosis.RESULTS: The study included 32 pathology-proven low grade gastric IN and 26 pathology-proven high grade gastric IN that were detected with any of the modalities. CLE and ME-NBI enabled clear visualization of the vascular microsurface patterns and microvascular structures of the gastric mucosa. The accuracy of the CLE and the ME-NBI diagnosis was 88% (95% CI: 78%-98%) and 81% (95% CI: 69%-93%), respectively. The kappa coefficient of agreement between the histopathology and the in vivo CLE imaging was 0.755; between the histopathology and the in vivo CLE imaging was 0.615. McNemar’s test (binomial distribution used) indicated that the agreement was significant (P < 0.05). When patients were diagnosed by ME-NBI with CLE, the overall accuracy of the diagnosis was 86.21% (95% CI: 73%-96%), and the kappa coefficient of agreement was 0.713, according to McNemar’s test (P < 0.05).CONCLUSION: Higher diagnostic accuracy, sensitivity and specificity of CLE over ME-NBI indicate the feasibility of these two techniques for the efficacious diagnostic classification of gastric IN.     

Uses of probe-based confocal laser endomicroscopy: responses to a question to practitioners

Confocal laser endomicroscopy is a novel imaging technology,which allows realtime visualization and inter-pretation of microscopic details in live tissues. Although several potential uses have been identified for this technology,no data are available regarding its real-worlduses. We report the results of an email-based surveyof experts in North America regarding their use of the technology.     

Evaluation of the updated confocal laser endomicroscopy criteria for Barrett's esophagus among gastrointestinal pathologists

Previously developed novel probe‐based confocal laser endomicroscopy (pCLE) criteria have been found to have high accuracy and substantial interobserver agreement (IOA) for diagnosing dysplasia in Barrett's esophagus (BE) when used by endoscopists. These updated criteria are: (i) epithelial surface: saw toothed, (ii) cells: enlarged, (iii) cells: pleomorphic, (iv) glands: not equidistant, (v) glands: unequal in size and shape, and (vi) goblet cells: not easily identified. The accuracy and IOA among pathologists in the diagnosis of dysplasia using the novel pCLE criteria is not known. The primary objective of the study was to evaluate the accuracy, overall IOA and learning curve among three gastrointestinal (GI) pathologists in diagnosing dysplasia in BE using the updated pCLE criteria. The secondary aim was to compare the accuracy and IOA between GI pathologists and gastroenterology endoscopists. Ninety pCLE videos and respective histology were retrieved from a previously conducted multicenter, prospective, randomized, controlled trial evaluating the utility of pCLE in BE patients. Videos were obtained from 101 BE patients previously enrolled for surveillance or endoscopic treatment of high‐grade dysplasia or early esophageal adenocarcinoma. Three GI pathologists reviewed 90 pCLE video clips for dysplasia versus no dysplasia, confidence in their diagnosis, and image quality. The overall accuracy for the diagnosis of dysplasia (low‐grade dysplasia/high‐grade dysplasia/esophageal adenocarcinoma) was 77.8% (95% confidence interval [CI]: 72.4–82.3). The accuracy was higher when pathologists had ‘high confidence’ in their assessment of the videos (93.8% vs. 69.3%, P < 0.001). There was no significant difference in accuracy between the first set of 30 and second set of 60 videos (84% vs. 74%, P = 0.065). IOA among GI pathologists was substantial, k = 0.65 (95% CI: 0.53–0.73). The sensitivity for detecting dysplasia was 85% (95% CI: 78.1–90.7) and the specificity was 70% (95% CI: 61.91–77.92). These results were comparable with the evaluation of the same set of videos by endoscopists. GI pathologists have high accuracy and substantial IOA for diagnosing BE dysplasia with pCLE. Pathologists appear to have similar accuracy and IOA as endoscopists. These results provide further support of endoscopists accurately interpreting the in vivo optical histology provided by pCLE.     

Current application of confocal endomicroscopy in gastrointestinal disorders

Confocal endomicroscopy (CEM) is a recent advancement in imaging technology that incorporates a confocal laser microscope into the tip of a flexible endoscope. The 1000-fold magnification and high resolution allows for real time in vivo histology or "virtual biopsies" of the gastrointestinal tract mucosa. CEM has the capability to instantaneously diagnose intra-epithelial neoplasia during endoscopy, alone or in combination with a "red-flag" technique, such as chromoendoscopy. Therefore, there is clinical utility in the surveillance or diagnosis of Barrett's esophagus, gastric intestinal metaplasia and cancer, longstanding ulcerative colitis, and colonic neoplasia. Furthermore, CEM also appears to be useful in the evaluation of coeliac disease, microscopic colitis, and in diagnosing Helicobacter pylori chronic gastritis. This review examines the current available data on the utility of this new technology in clinical gastroenterology and its potential impact in the future.     

共聚焦显微内镜对临床难以确诊的皮革胃的诊断价值

目的探索共聚焦显微内镜（CLE）对临床难以确诊的皮革胃病例的诊断价值。方法收集2009年-2011年因胃黏膜病变行CLE检查的患者317例。CLE检查过程中使用经静脉注射的10％荧光素钠溶液作为荧光剂,术后行导向病理活检。对CLE无法确诊的病例行腹部薄层增强CT扫描,对符合手术指征者行外科手术。将普通胃镜、CLE检查及活检病理结果进行比较分析。结果总共13例临床确诊为皮革胃的患者接受了CLE检查,所有患者术前均曾接受包括常规内镜及活检病理在内的辅助检查,病理均未确诊胃癌。单纯根据CLE图像诊断皮革胃的准确率为76．9％（10／13）,CLE导向活检阳性率84．6％（11／13）。对皮革胃患者的CLE图像分析显示,腺体排列紊乱伴明显炎症反应、荧光素钠大量渗出、高度异型腺体或成片排列的大型暗色细胞、腺上皮或间质中大型浅色细胞、间质中异常扭曲异型的阳性率分别为84．6％、76．9％、76．9％、46．1％与7．7％。结论CLE检查及CLE导向活检术是提高皮革胃诊断正确性的有效方法。     

数字染色内镜及共聚焦激光显微内镜在Barrett食管诊断中的价值研究

目的探讨数字染色内镜（I-Scan）及共聚焦激光显微内镜（CLE）对Barrett食管（BE）的诊断价值。方法878例患者行普通内镜和I-Scan模式下检查,部分筛查出的疑似BE患者行CLE检查及活检,比较普通内镜和I-Scan模式下疑似BE检出率及图象特点,对比分析活检病理及CLE诊断BE结果。结果普通胃镜模式下筛查出疑似BE患者46例（5．2％）,I-Scan筛查出52例（5．9％）,两者比较差异无统计学意义（x2=0．533,P〉0．05）;普通胃镜模式下SCJ与CEJ间距间可观察到栅栏状血管者21例（45．7％）,I-Scan可观察到35例（67．3％）,两者比较差异有统计学意义（X2=0．031,P〈0．05）。19例疑似BE患者进行了CLE检查及活检,CLE诊断BE的敏感度、特异度分别为93％和100％。结论I-Scan对SCJ与GEJ间距间栅栏状血管的观察具有重要意义,可提高疑似BE检出率;CLE使实时在体组织学诊断成为可能,诊断BE的敏感度和特异度均较高。     

In-vivo characterization of DALM in ulcerative colitis with high-resolution probe-based confocal laser endomicroscopy

Recently,the use of confocal laser endomicroscopy(CLE) in the diagnosis of chronic ulcerative colitis(CUC) was reported.In this brief report we aimed to assess the application of probe-based CLE to characterize colonic mucosa and dysplasia in CUC.The study involved a patient presenting long-standing CUC.Confocal imaging of both the inflamed mucosa,a circumscribed lesion(dysplasiaassociated lesional mass),and adjacent colonic mucosa are demonstrated and the correlation between the CLE and histological images...     

Poor agreement between endoscopists and gastrointestinal pathologists for the interpretation of probe-based confocal laser endomicroscopy findings

AIM: To compare the interpretation of probe-based confocal laser endomicroscopy (pCLE) findings between endoscopists and gastrointestinal (GI)-pathologists.METHODS: All pCLE procedures were undertaken and the endoscopist rendered assessment. The same pCLE videos were then viewed offline by an expert GI pathologist. Histopathology was considered the gold standard for definitive diagnosis. The sensitivity, specificity and accuracy for diagnosis of dysplastic/ neoplastic GI lesions and interobserver agreement between endoscopists and experienced gastrointestinal pathologist for pCLE findings were analyzed.RESULTS: Of the 66 included patients, 40 (60.6%) had lesions in the esophagus, 7 (10.6%) in the stomach, 15 (22.7%) in the biliary tract, 3 (4.5%) in the ampulla and 1 (1.5%) in the colon. The overall sensitivity, specificity and accuracy for diagnosing dysplastic/neoplastic lesions using pCLE were higher for endoscopists than pathologist at 87.0% vs 69.6%, 80.0% vs 40.0% and 84.8% vs 60.6% (P = 0.0003), respectively. Area under the ROC curve (AUC) was greater for endoscopists than the pathologist (0.83 vs 0.55, P = 0.0001). Overall agreement between endoscopists and pathologist was moderate for all GI lesions (K = 0.43; 95%CI: 0.26-0.61), luminal lesions (K = 0.40; 95%CI: 0.20-0.60) and those of dysplastic/neoplastic pathology (K = 0.55; 95%CI: 0.37-0.72), the agreement was poor for benign (K = 0.13; 95%CI: -0.097-0.36) and pancreaticobiliary lesions (K = 0.19; 95%CI: -0.26-0.63).CONCLUSION: There is a wide discrepancy in the interpretation of pCLE findings between endoscopists and pathologist, particularly for benign and malignant pancreaticobiliary lesions. Further studies are needed to identify the cause of this poor agreement.     

Endoscopic imaging of Barrett’s esophagus

The incidence of esophageal adenocarcinoma(EAC) has dramatically increased in the United States as well as Western European countries. The majority of esophageal adenocarcinomas arise from a backdrop of Barrett’s esophagus(BE),a premalignant lesion that can lead to dysplasia and cancer. Because of the increased risk of EAC,GI society guidelines recommend endoscopic surveillance of patients with BE. The emphasis on early detection of dysplasia in BE through surveillance endoscopy has led to the development of advanced endoscopic imaging technologies. These techniques have the potential to both improve mucosal visualization and characterization and to detect small mucosal abnormalities which are difficult to identify with standard endoscopy. This review summarizes the advanced imaging technologies used in evaluation of BE.