Accuracy of probe-based confocal laser endomicroscopy (pCLE) compared to random biopsies during endoscopic surveillance of Barrett’s esophagus

Abstract Background For surveillance of Barrett’s esophagus (BE), the current standard of random 4-quadrant biopsies misses 10 – 50 % of esophageal neoplasms, and does not permit real-time decision-making. Probe-based confocal laser endomicroscopy (pCLE) permits real-time in vivo histologic assessment of esophageal mucosa during upper endoscopy. Prospective studies comparing the accuracy of pCLE to 4-quadrant biopsies in routine clinical practice are lacking. Methods Consecutive patients with BE underwent high definition white light and narrow-band imaging followed by pCLE and targeted biopsy or mucosal resection. Four-quadrant biopsies were obtained during the same session. Baseline variables, real-time pCLE interpretation, and histology results were prospectively recorded. Blinded expert review of pCLE sequences and histology specimens was performed. A sample size of 64 patients was calculated a priori based on 3 % estimated prevalence of high grade dysplasia (HGD) or cancer. Results In total, 66 patients were included in the study. The prevalence of HGD or cancer was 4.55 %. Both real-time and blinded pCLE correctly identified all cases of cancer. For the primary outcome, real-time pCLE was 98 % specific but only 67 % sensitive for HGD/cancer compared to non-blinded pathologist interpretation. For HGD and cancer, inter-observer agreement was substantial between real-time and blinded endomicroscopists (kappa = 0.6). pCLE identified dysplasia in 75 % of cases where both blinded and unblinded pathology interpretation was low grade dysplasia. Conclusions pCLE demonstrates high specificity for detecting dysplasia and cancer, but lower sensitivity may limit its utility in routine BE surveillance. pCLE may have a role in confirming LGD in real-time before eradication therapy.

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Probe-based confocal laser endomicroscopy and Barrett's esophagus – just a scientific toy or significant improvement in diagnosis?

Digestive Diseases ◽

10.1159/000516257 ◽

2021 ◽

Author(s):

Luka Vranić ◽

Tin Nadarević ◽

Davor Štimac

Keyword(s):

Diagnostic Accuracy ◽

Real Time ◽

Barrett’S Esophagus ◽

Predictive Value ◽

Barrett's Esophagus ◽

High Reliability ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Imaging Method ◽

Increased Risk

Background: Barrett’s esophagus (BE) requires surveillance to identify potential neoplasia at early stage. Standard surveillance regimen includes random four-quadrant biopsies by Seattle protocol. Main limitations of random biopsies are high risk of sampling error, difficulties in histology interpretation, common inadequate classification of pathohistological changes, increased risk of bleeding and time necessary to acquire the final diagnosis. Probe-based confocal laser endomicroscopy (pCLE) has emerged as a potential tool with an aim to overcome these obvious limitations. Summary: pCLE represents real-time microscopic imaging method that offers evaluation of epithelial and subepithelial structures with 1000-fold magnification. In theory, pCLE has potential to eliminate the need for biopsy in BE patient. The main advantages would be real-time diagnosis and decision making, greater diagnostic accuracy and to evaluate larger area compared to random biopsies. Clinical pCLE studies in esophagus show high diagnostic accuracy and its high negative predictive value offers high reliability and confidence to exclude dysplastic and neoplastic lesions. However, it still cannot replace histopathology due to lower positive predictive value and sensitivity. Key messages: Despite promising results, its role in routine use in patients with Barrett’s esophagus remains questionable primarily due to lack of well-organized double-blind randomized trials.

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Su1997 - Generation and Validation of New Confocal Laser Endomicroscopy Criteria for the Diagnosis of Low-Grade Dysplasia in Barrett's Esophagus

Gastroenterology ◽

10.1016/s0016-5085(18)32341-2 ◽

2018 ◽

Vol 154 (6) ◽

pp. S-660

Author(s):

Massimiliano Di Pietro ◽

Helga Bertani ◽

Maria O'Donovan ◽

Patricia Santos ◽

Jacobo Ortiz Fernández-Sordo ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Low Grade ◽

Low Grade Dysplasia

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Accuracy and Inter-Observer Agreement of Experts for Probe-Based Confocal Laser Endomicroscopy Detection of Dysplasia in Barrett's Esophagus

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2009.03.1033 ◽

2009 ◽

Vol 69 (5) ◽

pp. AB351 ◽

Cited By ~ 5

Author(s):

Michael B. Wallace ◽

Julian A. Abrams ◽

Monther Bajbouj ◽

Ajay Bansal ◽

Anna M. Buchner ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Observer Agreement ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser

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Real-time diagnosis of Barrett’s esophagus: a prospective, multicenter study comparing confocal laser endomicroscopy with conventional histology for the identification of intestinal metaplasia in new users

Surgical Endoscopy ◽

10.1007/s00464-018-6420-9 ◽

2018 ◽

Vol 33 (5) ◽

pp. 1585-1591 ◽

Cited By ~ 7

Author(s):

Cory Richardson ◽

Paul Colavita ◽

Christy Dunst ◽

John Bagnato ◽

Peter Billing ◽

...

Keyword(s):

Intestinal Metaplasia ◽

Real Time ◽

Barrett’S Esophagus ◽

Multicenter Study ◽

Barrett's Esophagus ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Prospective Multicenter Study ◽

Conventional Histology ◽

Time Diagnosis

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Confocal Laser Endomicroscopy vs Biopsies in the Assessment of Persistent or Recurrent Intestinal Metaplasia/Neoplasia after Endoscopic Treatment of Barrett’s Esophagus related Neoplasia

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld-2467 ◽

2020 ◽

Vol 29 (3) ◽

pp. 305-312

Author(s):

Jana Krajciova ◽

Marek Kollar ◽

Jana Maluskova ◽

Martin Janicko ◽

Zuzana Vackova ◽

...

Keyword(s):

Intestinal Metaplasia ◽

Barrett’S Esophagus ◽

Endoscopic Treatment ◽

Barrett's Esophagus ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Low Grade ◽

Predictive Values ◽

Early Adenocarcinoma ◽

Sensitivity Specificity

Background and Aims: Patients after endoscopic treatment of Barrett‘s esophagus (BE) related neoplasia (BORN) should enter endoscopic surveillance with biopsies to detect persistent or recurrent neoplasia or intestinal metaplasia (IM). Probe-based confocal laser endomicroscopy (pCLE) serves as a virtual biopsy and could replace standard biopsies. However, the role of pCLE in patients after endoscopic treatment of BORN has not been systematically assessed. The aim of this study was to compare pCLE with biopsies in detecting persistent/recurrent IM/neoplasia. Methods: A single center, prospective and pathologist-blinded study was performed. Patients after endoscopic treatment of BORN (endoscopic resection or dissection, radiofrequency ablation) underwent surveillance endoscopy with pCLE followed by biopsies. Results: A total of 56 patients were enrolled: initial diagnoses were low-grade dysplasia (LGD) in 24 patients (43%), high-grade dysplasia (HGD) in 12 patients (21%) and early adenocarcinoma (EAC) in 20 patients (36%). Only one patient (2%) experienced recurrent neoplasia (LGD), which was diagnosed by pCLE only. Twenty patients (35.7%) experienced persistent/recurrent IM, diagnosed by both pCLE and biopsies in 17 patients (17/30, 85%) and by pCLE only in 3 pts (3/30, 15%). Sensitivity, specificity, positive and negative predictive values to diagnose recurrent/persistent IM did not differ significantly between pCLE and biopsies; diagnostic accuracy was 100% (95%CI 93.6-100) for pCLE and 94.6 (95%CI 85.1-98.9%) for biopsies, p=0.25. In patients with IM detected by both tested methods, pCLE detected significantly more goblet cells (median 43 per patient) than biopsies (median 12 per patient), p=0.01. Conclusion: pCLE is at least as effective as standard biopsies in the detection of persistent/recurrent IM after endoscopic treatment of BORN.

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Barrett’s esophagus: novel strategies for screening and surveillance

Therapeutic Advances in Chronic Disease ◽

10.1177/2040622319837851 ◽

2019 ◽

Vol 10 ◽

pp. 204062231983785 ◽

Cited By ~ 8

Author(s):

Vedha Sanghi ◽

Prashanthi N. Thota

Keyword(s):

Barrett’S Esophagus ◽

Esophageal Adenocarcinoma ◽

Barrett's Esophagus ◽

Eradication Therapy ◽

Oral Microbiome ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Computer Assisted ◽

Screening And Surveillance ◽

Esophageal Capsule

Barrett’s esophagus is the precursor lesion for esophageal adenocarcinoma. Screening and surveillance of Barrett’s esophagus are undertaken with the goal of earlier detection and lowering the mortality from esophageal adenocarcinoma. The widely used technique is standard esophagogastroduodenoscopy with biopsies per the Seattle protocol for screening and surveillance of Barrett’s esophagus. Surveillance intervals vary depending on the degree of dysplasia with endoscopic eradication therapy confined to patients with Barrett’s esophagus and confirmed dysplasia. In this review, we present various novel techniques for screening of Barrett’s esophagus such as unsedated transnasal endoscopy, cytosponge with trefoil factor-3, balloon cytology, esophageal capsule endoscopy, liquid biopsy, electronic nose, and oral microbiome. In addition, advanced imaging techniques such as narrow band imaging, dye-based chromoendoscopy, confocal laser endomicroscopy, volumetric laser endomicroscopy, and wide-area transepithelial sampling with computer-assisted three-dimensional analysis developed for better detection of dysplasia are also reviewed.

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CONFOCAL LASER ENDOMICROSCOPY IN DIAGNOSING GASTRIC AND ESOPHAGEAL LESIONS AND IN POST-RFA SURVEILLANCE OF PATIENTS WITH BARRETT'S ESOPHAGUS

10.1055/s-0038-1637429 ◽

2018 ◽

Author(s):

J Krajciova ◽

M Kollar ◽

J Maluskova ◽

Z Vackova ◽

J Spicak ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser

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TissueCypher Barrett’s esophagus assay impacts clinical decisions in the management of patients with Barrett’s esophagus

Endoscopy International Open ◽

10.1055/a-1326-1533 ◽

2021 ◽

Vol 09 (03) ◽

pp. E348-E355

Author(s):

David L. Diehl ◽

Harshit S. Khara ◽

Nasir Akhtar ◽

Rebecca J. Critchley-Thorne

Keyword(s):

High Risk ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Clinical Decision Making ◽

Eradication Therapy ◽

Low Risk ◽

Management Approach ◽

Low Grade ◽

Management Decisions ◽

The Impact

Abstract Background and study aims The TissueCypher Barrett’s Esophagus Assay is a novel tissue biomarker test, and has been validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus (BE). The aim of this study was to evaluate the impact of TissueCypher on clinical decision-making in the management of BE. Patients and methods TissueCypher was ordered for 60 patients with non-dysplastic (ND, n = 18) BE, indefinite for dysplasia (IND, n = 25), and low-grade dysplasia (LGD, n = 17). TissueCypher reports a risk class (low, intermediate or high) for progression to HGD or EAC within 5 years. The impact of the test results on BE management decisions was assessed. Results Fifty-two of 60 patients were male, mean age 65.2 ± 11.8, and 43 of 60 had long segment BE. TissueCypher results impacted 55.0 % of management decisions. In 21.7 % of patients, the test upstaged the management approach, resulting in endoscopic eradication therapy (EET) or shorter surveillance interval. The test downstaged the management approach in 33.4 % of patients, leading to surveillance rather than EET. In the subset of patients whose management plan was changed, upstaging was associated with a high-risk TissueCypher result, and downstaging was associated with a low-risk result (P < 0.0001). Conclusions TissueCypher was used as an adjunct to support a surveillance-only approach in 33.4 % of patients. Upstaging occurred in 21.7 % of patients, leading to therapeutic intervention or increased surveillance. These results indicate that the TissueCypher test may enable physicians to target EET for TissueCypher high-risk BE patients, while reducing unnecessary procedures in TissueCypher low-risk patients.

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