Specificity Of pCLE Research Articles

Probe-based confocal laser endomicroscopy in the evaluation of dominant strictures in patients with primary sclerosing cholangitis: results of a U.S. multicenter prospective trial

Patients with primary sclerosing cholangitis (PSC) and dominant biliary strictures carry increased risk for the development of cholangiocarcinoma. Although ERCP-based techniques including brush cytology and intraductal biopsy sampling represent first-line tissue sampling methods for dominant strictures, sensitivity is low. Probe-based confocal laser endomicroscopy (pCLE) offers microscopic-level imaging of subepithelial biliary mucosa. Because data regarding the use of pCLE in PSC are limited, we aimed to investigate its diagnostic performance in dominant strictures. This was a multicenter prospective study involving PSC patients with dominant strictures. ERCP with pCLE was performed with use of the Miami classification (2+ criteria for malignant diagnosis) and Paris classification. Final malignant diagnoses required histopathologic confirmation, and benign diagnoses required a minimum of 1 year of follow-up without development of cancer. Fifty-nine patients (mean age, 49 years; 59% men) with 63 strictures were included in the study. Stricture locations included the common bile duct (31.7%), bifurcation (22.2%), and common hepatic duct (19%). Seven patients (11.9%) were found to have cholangiocarcinoma. The sensitivity and specificity of pCLE was 85.7% (95% confidence interval [CI], 42.1-99.6) and 73.1% (95% CI, 58.9-84.4), respectively. Within specific stricture locations, the highest sensitivity was seen at the bifurcation (100%; 95% CI, 2.5-100) and the right hepatic duct (100%; 95% CI, 29.2-100). The lowest sensitivities were seen at the common bile duct (25%; 95% CI, 5.5-57.2) and the left hepatic duct (28.6%; 95% CI, 3.7-70.9). In this prospective multicenter study, pCLE had a high sensitivity in detecting cholangiocarcinoma, but technical aspects of the probe may limit evaluation in the common bile duct and left hepatic duct. Further evaluation is needed to elucidate the role of pCLE in the algorithm of excluding neoplasia in biliary strictures associated with PSC. (Clinical trial registration number: NCT02736708.).

Morphometric Assessment of Confocal Laser Endomicroscopy for Pancreatic Ductal Adenocarcinoma, an Ex-Vivo Pilot Study.

Ex-vivo freshly surgical removed pancreatic ductal adenocarcinoma (PDAC) specimens were assessed using pCLE and then processed for paraffin embeding and histopathological diagnostic in an endeavour to find putative image analysis algorithms that might recognise adenocarcinoma. Methods: Twelve patients diagnosed with PDAC on endoscopic ultrasound and FNA confirmation underwent surgery. Removed samples were sprayed with acriflavine as contrast agent, underwent pCLE with an experimental probe and compared with previous recordings of normal pancreatic tissue. Subsequently, all samples were subjected to cross-sectional histopathology, including surgical resection margins for controls. pCLE records, as well as corespondant cytokeratin-targeted immunohistochemistry images were processed using the same morphological classifiers in the Image ProPlus AMS image analysis software. Specific morphometric classifiers were automatically generated on all images: Area, Hole Area (HA), Perimeter, Roundness, Integrated Optical Density (IOD), Fractal Dimension (FD), Ferret max (Fmax), Ferret mean (Fmean), Heterogeneity and Clumpiness. Results: After histopathological confirmation of adenocarcinoma areas, we have found that the same morphological classifiers could clearly differentiate between tumor and non-tumor areas on both pathology and correspondand pCLE (area, roundness, IOD, ferret and heterogeneity (p < 0.001), perimeter and hole area (p < 0.05). Conclusions: This pilot study proves that classical morphometrical classifiers can clearly differentiate adenocarcimoma on pCLE data, and the implementation in a live image-analysis algorithm might help in improving the specificity of pCLE in vivo diagnostic.

PS02.062: CONFOCAL LASER ENDOMICROSCOPY IN THE ASSESSMENT OF PERSISTENT/RECURRENT INTESTINAL METAPLASIA/NEOPLASIA AFTER ENDOSCOPIC TREATMENT OF BORN

Abstract Background Patients after endoscopic treatment of Barrett's esophagus related neoplasia (BORN) should undergo regular endoscopic surveillance with biopsies to detect recurrent intestinal metaplasia (IM) or neoplasia (N). Probe-based confocal laser endomicroscopy (pCLE) offers detailed examination of cellular structures and may examine larger areas compared to standard biopsy. Methods A single center, prospective, controlled and pathologist-blinded (still ongoing) study in patients undergoing surveillance endoscopy after endoscopic treatment of BORN. pCLE images were obtained from the neo-Z-line (in few cases including macroscopically visible tongues), the cardia and the esophagus. Thereafter, standard biopsies were taken and sent for histopathological analysis (minimally 4 biopsies from macroscopically normal neo-Z-line, 2 biopsies from the cardia and the esophagus and targeted biopsies from visible abnormalities, if present). Results We examined 34 patients, from these 14 patients (41%) had the initial diagnosis of low-grade intraepithelial neoplasia (LGIN), 8 patients (24%) had high-grade intraepithelial neoplasia (HGIN) and 12 patients (35%) had an early adenocarcinoma (EAC). Three patients (9%) underwent endoscopic resection (ER), in 18 patients (53%) we performed ER or dissection of all visible lesions followed by radiofrequency ablation (RFA), and 13 patients (38%) had RFA as a single treatment modality. Persistent/recurrent IM was detected only at the level of neo-Z-line in 8 patients (24%, 8/34 pts) by both methods. pCLE but not biopsies detected persistent/recurrent IM in 2 patients (6%, 2/34), another 2 patients had IM present in biopsies but not in pCLE. pCLE diagnosed one patient with recurrent LGIN in a macroscopic visible tongue arising from neo-Z-line, which was not confirmed in biopsies (there was only agreement in persistent IM detected by both methods). Sensitivity and specificity of pCLE in detection of persistent/recurrent IM was 80% (95% CI 44–98) and 92% (95% CI 73–99), respectively, with a positive predictive value of 80% (95% CI 51–94) and a negative predictive value of 92% (95% CI 76–98). Agreement of pCLE and histopathological findings was 88%. Conclusion pCLE seems comparable to standard biopsies in detection of persistent/recurrent IM after endoscopic treatment of BORN. Nevertheless, these results need to be confirmed in a larger cohort of patients. Disclosure All authors have declared no conflicts of interest.

Probe-based confocal laser endomicroscopy for indeterminate biliary strictures: refinement of the image interpretation classification.

Background. Accurate diagnosis and clinical management of indeterminate biliary strictures are often a challenge. Tissue confirmation modalities during Endoscopic Retrograde Cholangiopancreatography (ERCP) suffer from low sensitivity and poor diagnostic accuracy. Probe-based confocal laser endomicroscopy (pCLE) has been shown to be sensitive for malignant strictures characterization (98%) but lacks specificity (67%) due to inflammatory conditions inducing false positives. Methods. Six pCLE experts validated the Paris Classification, designed for diagnosing inflammatory biliary strictures, using a set of 40 pCLE sequences obtained during the prospective registry (19 inflammatory, 6 benign, and 15 malignant). The 4 criteria used included (1) multiple thin white bands, (2) dark granular pattern with scales, (3) increased space between scales, and (4) thickened reticular structures. Interobserver agreement was further calculated on a separate set of 18 pCLE sequences. Results. Overall accuracy was 82.5% (n = 40 retrospectively diagnosed) versus 81% (n = 89 prospectively collected) for the registry, resulting in a sensitivity of 81.2% (versus 98% for the prospective study) and a specificity of 83.3% (versus 67% for the prospective study). The corresponding interobserver agreement for 18 pCLE clips was fair (k = 0.37). Conclusion. Specificity of pCLE using the Paris Classification for the characterization of indeterminate bile duct stricture was increased, without impacting the overall accuracy.

PTU-156 The Combination of Autofluorescence Imaging and Probe-Based Confocal Laser Endomicroscopy has an Excellent Diagnostic Accuracy for Dysplasia in Barrett’S Esophagus

IntroductionEndoscopic surveillance in Barrett’s oesophagus (BO) has major limitations including sampling error due to inconspicuous dysplasia, need for multiple biopsies and subjectivity of pathological assessment of dysplasia. Probe-based confocal laser...

Diagnostic Accuracy of Probe-based Confocal Laser Endomicroscopy and Narrow Band Imaging in Detection of Dysplasia in Duodenal Polyps

To estimate the accuracy of probe-based confocal laser endomicroscopy (pCLE) and narrow band imaging (NBI), individually and in combination, for classification of duodenal polyps. Ex vivo pathologic diagnosis of duodenal polyps causes time delay, requiring separate procedures for diagnosis and therapy. It also involves small risk of pancreatitis in ampullary adenomas and can make subsequent endoscopic mucosal resection more difficult by "tacking down" mucosa. In vivo diagnosis with pCLE and NBI may avoid these complications and may guide immediate therapy. During high-definition white light endoscopy, 1 endoscopist (M.B.W.) performed NBI and then, pCLE of duodenal sites. Matched tissue sampling or endoscopic mucosal resection was performed. Confocal videos were recorded, de-identified, and reviewed by same endoscopist, blinded to histopathology, 1 month later. Confocal features of dysplasia in Barrett esophagus were applied for detection of duodenal dysplasia. Of 65 sites from 36 participants, 24 lesions showed dysplasia, whereas 41 polyps and control sites were nondysplastic on histopathology, used as standard reference. The accuracy, sensitivity, and specificity of pCLE were 83%, 92%, and 78%, whereas that of NBI were 80%, 83%, and 78%, respectively. In subset of 49 lesions with similar pCLE and NBI diagnosis, the accuracy, sensitivity, and specificity, improved significantly and was found to be 92%, 95%, and 90%, respectively. Our study suggests that pCLE has superior sensitivity as compared with NBI for detection of dysplasia in duodenal polyps. Combined accuracy of pCLE and NBI approaches that of ex vivo pathology, which may help in avoiding biopsy sampling.

Real-time increased detection of neoplastic tissue in Barrett's esophagus with probe-based confocal laser endomicroscopy: final results of an international multicenter, prospective, randomized, controlled trial

Probe-based confocal laser endomicroscopy (pCLE) allows real-time detection of neoplastic Barrett's esophagus (BE) tissue. However, the accuracy of pCLE in real time has not yet been extensively evaluated. To compare the sensitivity and specificity of pCLE in addition to high-definition white-light endoscopy (HD-WLE) with HD-WLE alone for the detection of high-grade dysplasia (HGD) and early carcinoma (EC) in BE. International, prospective, multicenter, randomized, controlled trial. Five tertiary referral centers. A total of 101 consecutive BE patients presenting for surveillance or endoscopic treatment of HGD/EC. All patients were examined by HD-WLE, narrow-band imaging (NBI), and pCLE, and the findings were recorded before biopsy samples were obtained. The order of HD-WLE and NBI was randomized and performed by 2 independent, blinded endoscopists. All suspicious lesions on HD-WLE or NBI and 4-quadrant random locations were documented. These locations were examined by pCLE, and a presumptive diagnosis of benign or neoplastic (HGD/EC) tissue was made in real time. Finally, biopsies were taken from all locations and were reviewed by a central pathologist, blinded to endoscopic and pCLE data. Diagnostic characteristics of pCLE. The sensitivity and specificity for HD-WLE were 34.2% and 92.7%, respectively, compared with 68.3% and 87.8%, respectively, for HD-WLE or pCLE (P = .002 and P < .001, respectively). The sensitivity and specificity for HD-WLE or NBI were 45.0% and 88.2%, respectively, compared with 75.8% and 84.2%, respectively, for HD-WLE, NBI, or pCLE (P = .01 and P = .02, respectively). Use of pCLE in conjunction with HD-WLE and NBI enabled the identification of 2 and 1 additional HGD/EC patients compared with HD-WLE and HD-WLE or NBI, respectively, resulting in detection of all HGD/EC patients, although not statistically significant. Academic centers with enriched population. pCLE combined with HD-WLE significantly improved the ability to detect neoplasia in BE patients compared with HD-WLE. This may allow better informed decisions to be made for the management and subsequent treatment of BE patients. ( NCT00795184.).