Image enhanced endoscopy and molecular biomarkers vs Seattle protocol to diagnose dysplasia in Barrett's esophagus

BACKGROUND: Dysplasia in Barrett's esophagus (BE) is often invisible on high-resolution white-light endoscopy (HRWLE). We compared the diagnostic accuracy for inconspicuous dysplasia of the combination of autofluorescence (AFI)-guided probe-based confocal laser endomicroscopy (pCLE) and molecular biomarkers versus HRWLE with Seattle protocol biopsies. METHODS: BE patients with no dysplastic lesions were block randomized to standard endoscopy (HRWLE with Seattle protocol) or AFI-guided pCLE with targeted biopsies for molecular biomarkers (p53 and cyclin A by immunohistochemistry; aneuploidy by image cytometry), with crossover to the other arm after 6-12 weeks. Histological endpoint was diagnosis from all study biopsies (trial histology). Sensitivity analysis was performed for overall histology, which included diagnoses within 12 months from first study endoscopy. Endoscopists were blinded to the referral endoscopy and histology results. Primary outcome was diagnostic accuracy for dysplasia by real-time pCLE versus HRWLE biopsies. RESULTS: Of 154 patients recruited, 134 completed both arms. In the primary outcome analysis (trial histology analysis), AFI-guided pCLE had similar sensitivity for dysplasia compared to standard endoscopy [74.3% (95%CI, 56.7-87.5) vs 80.0% (95%CI 63.1-91.6), p=0.48]. Multivariate logistic regression showed pCLE optical dysplasia, aberrant p53 and aneuploidy had strongest correlation with dysplasia (secondary outcome). This 3-biomarker panel had higher sensitivity for any grade of dysplasia than Seattle protocol (81.5% vs 51.9%, p<0.001) in the overall histology analysis, but not in the trial histology analysis (91.4% vs 80.0%; p=0.16) with an area under receiver operating curve of 0.83. CONCLUSIONS: Seattle protocol biopsies miss dysplasia in approximately half of patients with inconspicuous neoplasia. AFI-guided pCLE has similar accuracy to the current gold standard. Addition of molecular biomarkers could improve diagnostic accuracy

Use of Cytosponge as a triaging tool to upper gastrointestinal endoscopy during the COVID-19 pandemic.

During the COVID-19 pandemic, endoscopy services have been severely curtailed—eg, in England, UK, a 30% reduction of diagnostic endoscopies has been reported for the period between January and April, 2020, compared with the same period in 2019, with an estimated 750 oesophagogastric cancers going undiagnosed. A delay in oesophageal cancer diagnosis could adversely affect outcomes, such as has previously been seen with low endoscopy referral rates being linked with poor outcomes from oesophageal cancer

The effect of procedural time on dysplasia detection rate during endoscopic surveillance of Barrett's esophagus.

BACKGROUND : Endoscopic surveillance of Barrett's esophagus (BE) with Seattle protocol biopsies is time-consuming and inadequately performed in routine practice. There is no recommended procedural time for BE surveillance. We investigated the duration of surveillance procedures with adequate tissue sampling and effect on dysplasia detection rate (DDR). METHODS : We performed post hoc analysis from the standard arm of a crossover randomized controlled trial recruiting patients with BE (≥C2 and/or ≥M3) and no clearly visible dysplastic lesions. After inspection with white-light imaging, targeted biopsies of subtle lesions and Seattle protocol biopsies were performed. Procedure duration and biopsy number were stratified by BE length. The effect of endoscopy-related variables on DDR was assessed by multivariable logistic regression. RESULTS : Of 142 patients recruited, 15 (10.6 %) had high grade dysplasia/intramucosal cancer and 15 (10.6 %) had low grade dysplasia. The median procedural time was 16.5 minutes (interquartile range 14.0-19.0). Endoscopy duration increased by 0.9 minutes for each additional 1 cm of BE length. Seattle protocol biopsies had higher sensitivity for dysplasia than targeted biopsies (86.7 % vs. 60.0 %; P = 0.045). Longer procedural time was associated with increased likelihood of dysplasia detection on quadrantic biopsies (odds ratio [OR] 1.10, 95 %CI 1.00-1.20, P = 0.04), and for patients with BE > 6 cm also on targeted biopsies (OR 1.21, 95 %CI 1.04-1.40; P = 0.01). CONCLUSIONS : In BE patients with no clearly visible dysplastic lesions, longer procedural time was associated with increased likelihood of dysplasia detection. Adequate time slots are required to perform good-quality surveillance and maximize dysplasia detection.Infrastructure support was received by the Experimental Cancer Medicine Centre and NIHR Cambridge Biomedical Research Centre (BRC-1215-20014)

Development and Validation of Confocal Endomicroscopy Diagnostic Criteria for Low-Grade Dysplasia in Barrett's Esophagus.

OBJECTIVES: Low-grade dysplasia (LGD) in Barrett's esophagus (BE) is generally inconspicuous on conventional and magnified endoscopy. Probe-based confocal laser endomicroscopy (pCLE) provides insight into gastro-intestinal mucosa at cellular resolution. We aimed to identify endomicroscopic features and develop pCLE diagnostic criteria for BE-related LGD. METHODS: This was a retrospective study on pCLE videos generated in 2 prospective studies. In phase I, 2 investigators assessed 30 videos to identify LGD endomicroscopic features, which were then validated in an independent video set (n = 25). Criteria with average accuracy >80% and interobserver agreement κ > 0.4 were taken forward. In phase II, 6 endoscopists evaluated the criteria in an independent video set (n = 57). The area under receiver operating characteristic curve was constructed to find the best cutoff. Sensitivity, specificity, interobserver, and intraobserver agreements were calculated. RESULTS: In phase I, 6 out of 8 criteria achieved the agreement and accuracy thresholds (i) dark nonround glands, (ii) irregular gland shape, (iii) lack of goblet cells, (iv) sharp cutoff of darkness, (v) variable cell size, and (vi) cellular stratification. The best cutoff for LGD diagnosis was 3 out of 6 positive criteria. In phase II, the diagnostic criteria had a sensitivity and specificity for LGD of 81.9% and 74.6%, respectively, with an area under receiver operating characteristic of 0.888. The interobserver agreement was substantial (κ = 0.654), and the mean intraobserver agreement was moderate (κ = 0.590). CONCLUSIONS: We have generated and validated pCLE criteria for LGD in BE. Using these criteria, pCLE diagnosis of LGD is reproducible and has a substantial interobserver agreement.Financial support: the Addenbrookes Charitable Trust and the Kathy Shaw Memorial (Oesophageal Cancer) Fund funded the endoscopy equipment at Cambridge University Hospital. This study received infrastructure support from the Experimental Cancer Medicine Center and from the Cambridge Cancer Centre