Leggett, Cadman L.

Objective Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used in Barrett’s oesophagus (BE) to help identify dysplasia in the oesophagus. VLE criteria exist for oesophageal dysplasia but not for dysplasia in the gastric cardia. The aim of this study was to determine if there are in vivo VLE features that can predict gastric cardia dysplasia in BE. Design This was a single-centre observational cohort study from August 2016 to August 2018. Patients were included if they had BE, were undergoing a VLE exam as standard of care, and had a suspicious target laser marked at the gastric cardia. The following VLE features were correlated to histology to determine if an association existed between histology subtype and VLE feature: wide crypts, irregular surface, one large isolated gland, multiple glands, and complex glands. Results A total of 110 in vivo gastric cardia targets in 77 patients with BE were analysed. The following abnormalities were identified: 61 wide crypts, 34 isolated glands, 16 irregular surfaces, 15 multiple glands, and 11 complex glands. Complex glands were the only VLE feature that correlated to any histology subtype. They were present in 71% of targets with high-grade dysplasia (HGD), T1a cancer or T1b cancer and had a sensitivity, specificity, and accuracy of 71%, 99%, and 85%, respectively. Of the 10 patients with complex glands on VLE and HGD/cancer on histology, 4 had a normal-appearing mucosa (40%) on endoscopy. Conclusion Identification of complex glands on VLE may aid in detection of HGD or early cancer in the gastric cardia in BE. This is particularly important, as dysplasia at the gastric cardia can be difficult to see endoscopically.

INTRODUCTION: Volumetric laser endomicroscopy (VLE) is a high-resolution imaging modality used in Barrett’s esophagus (BE) surveillance. Established VLE scoring systems use a combination of features to guide BE dysplasia diagnosis but it remains unclear whether these features are sufficient to reach optimal VLE diagnostic performance. This study explores an exhaustive list of VLE features using one-to-one imaging to pathology correlation to develop optimal VLE diagnostic models for BE dysplasia. METHODS: In this prospective, multi-center (5 sites) study, patients with dysplastic BE underwent VLE with laser targeted regions of interest (ROIs), followed by standard surveillance endoscopy and biopsy directed to laser-marked sites. Histology was reviewed by two GI pathologists (MV, RO) who achieved a consensus diagnosis (gold-standard). ROIs were dysplastic if low-grade dysplasia (LGD), high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC) was present. Two VLE experts (CLL, GJT) reviewed ROIs and corresponding endoscopic images to identify and define a set of VLE features associated with BE dysplasia. A multi-variable logistic regression model based on least absolute shrinkage and selection operator (LASSO) method was developed to determine the optimal diagnostic performance of these features. A decision tree model with high clinical usability also was developed to evaluate VLE diagnostic performance for real-time image interpretation. RESULTS: A total of 461 VLE ROIs with matching histology were obtained from 150 patients (Table 1). A final dataset of 55 neoplastic (LGD, 12; HGD, 24; IMC, 19) and 56 randomly selected non-dysplastic ROIs were reviewed. Twenty-eight VLE features were identified describing layering, signal intensity, surface topography, and glandular characteristics. LASSO logistic regression modeling identified 5 VLE features which when utilized optimized diagnostic performance with an area under the curve (AUC) for BE dysplasia of 0.95 (Figure 1). To improve clinical usability, a decision tree model was optimized to three levels with an AUC of 0.90 (Figure 2). CONCLUSION: This study represents the most comprehensive review of VLE features associated with BE dysplasia to date. The proposed high-performing diagnostic models suggest that VLE can be used efficiently and effectively to enhance BE surveillance by identifying ROIs for targeted biopsy. Further validation of the proposed VLE models will determine their clinical utility.

SUMMARY Image interpretation of Barrett's esophagus (BE) with volumetric laser endomicroscopy (VLE) can be enhanced by image processing software that highlights established features using a color-graded scale (intelligent real-time image segmentation, IRIS). This study aims to provide a description of IRIS features of various gastroesophageal tissue types using histologic correlation. A database of 80 VLE laser-marked targets with histologic correlation was reviewed for various tissue types. IRIS was applied off-line to the VLE scans, laser-marked targets were identified, and feature review was performed. Squamous epithelium targets (N = 7) showed IRIS layered architecture with lack of surface hyper-reflectivity and epithelial glands. Gastric cardia targets (N = 10) showed absent layering (100%) and surface hyper-reflectivity with epithelial glands (40%). Nondysplastic BE targets (N = 39) showed surface hyper-reflectivity (64%), epithelial glands (51%), and lack of layering (74%). Targets of BE with early neoplasia (N = 24), showed surface hyper-reflectivity (96%), epithelial glands (67%), and lack of layering (96%). IRIS features that characterize each tissue type appear to mirror the nonenhanced VLE counterparts that define them.

Abstract Background and study aims Precise staging in T1 esophageal adenocarcinoma (EAC) is critical in determining candidacy for curative endoscopic resection. High-frequency endoscopic ultrasound (EUS) has demonstrated suboptimal accuracy in T1 EAC staging due to insufficient spatial resolution. Volumetric laser endomicroscopy (VLE) allows for high-resolution wide-field visualization of the esophageal microstructure. We aimed to investigate the role of VLE in staging T1 EAC. Patients and methods Patients undergoing endoscopic mucosal resection (EMR) were prospectively enrolled and only T1 EAC cases were included. EMR specimens were imaged using second-generation VLE immediately after resection. VLE images were analyzed for signal intensity by depth and signal attenuation (dB/mm) in both cross-sectional and en-face orientation. A decision tree model was constructed to combine measured VLE parameters and delineate diagnostic thresholds. Results Thirty EMR scans were obtained – 15 T1a specimens from 9 patients and 15 T1b specimens from 11 patients. T1b specimen VLE scans exhibited higher signal intensity (P < 0.0001) and higher signal attenuation compared to T1a specimens (P = 0.03). A combination of signal attenuation and signal intensity at 150 µm depth yielded optimal diagnostic thresholds and an area under the curve (AUC) of 0.77. VLE signal attenuation was significantly associated with grade of differentiation, irrespective of EAC stage. Conclusions VLE signal intensity and signal attenuation are quantitatively distinct in T1a and T1b EAC and associated with grade of differentiation. This is the first study examining the role of VLE for staging of T1 EAC and demonstrates promising diagnostic performance. With further in vivo validation, VLE may serve a role in staging superficial EAC.

Background Esophageal food impaction is relatively common and increasing over time. Treatment ranges from medications to invasive endoscopic therapies. The endoscopic push technique has been advised against in favor of endoscopic retrieval for safety concerns. We sought to assess use patterns and safety of treatments for food impaction in a population‐based retrospective review. Methods A database of recorded esophageal food impactions in Olmsted County, MN, USA, from 1975–2011 was reviewed for patient demographics, treatment, and complications. Results A total of 645 impactions occurred, with increasing incidence over time, peaking at 23.2 per year (2000–2004). Medications (almost exclusively glucagon) were successful in relieving impactions 34.5% of the time when trialed. Urgent endoscopy was common (74.0%), as was the need for endoscopic therapy (67.1%). Endoscopic therapy increased over time, with the endoscopic push technique becoming most common. Esophageal complications (deep mucosal injury or perforation) increased over time but remained rare (peak 11%). There was no difference in complications between push and retrieval techniques. Conclusions The endoscopic push technique is safe in comparison to endoscopic retrieval in esophageal food impactions. While complications surrounding impaction have increased, they remain rare. Medication trials are reasonable, as long as they do not delay endoscopy, and may prevent the need for emergent endoscopy in one‐third of cases.

Objective Surveillance interval protocols after complete remission of intestinal metaplasia (CRIM) post radiofrequency ablation (RFA) in Barrett’s oesophagus (BE) are currently empiric and not based on substantial evidence. We aimed to assess the timeline, location and patterns of recurrence following CRIM to inform these guidelines. Design Data on patients undergoing RFA for BE were obtained from prospectively maintained databases of five (three USA and two UK) tertiary referral centres. RFA was performed until CRIM was confirmed on two consecutive endoscopies. Results 594 patients achieved CRIM as of 1 May 2017. 151 subjects developed recurrent BE over a median (IQR) follow-up of 2.8 (1.4–4.4) years. There was 19% cumulative recurrence risk of any BE within 2 years and an additional 49% risk over the next 8.6 years. There was no evidence of a clinically meaningful change in the recurrence hazard rate of any BE, dysplastic BE or high-grade dysplasia/cancer over the duration of follow-up, with an estimated 2% (95% CI −7% to 12%) change in recurrence rate of any BE in a doubling of follow-up time. 74% of BE recurrences developed at the gastro-oesophageal junction (GOJ) (24.1% were dysplastic) and 26% in the tubular oesophagus. The yield of random biopsies from the tubular oesophagus, in the absence of visible lesions, was 1% (BE) and 0.2% (dysplasia). Conclusions BE recurrence risk following CRIM remained constant over time, suggesting that lengthening of follow-up intervals, at least in the first 5 years after CRIM, may not be advisable. Sampling the GOJ is critical to detecting recurrence. The requirement for random biopsies of the neosquamous epithelium in the absence of visible lesions may need to be re-evaluated.

Abstract Background Endoscopic mucosal resection (EMR) can be performed en-bloc in Barrett's esophagus (BE) lesions that are ≤2 cm in size. The true size of a BE lesion may be underestimated under white light endoscopy, limiting the rate of en-bloc resection. Volumetric laser endomicroscopy (VLE) provides high-resolution cross-sectional imaging of BE. A greater number of VLE glands are associated with BE dysplasia and may help predict lesion size. The aim of this study was to determine the association between VLE gland count and outcome of resection. Methods EMR specimens from patients with a history of dysplastic BE were imaged with VLE. EMRs performed on BE lesions ≤2cm in size with intent at en-bloc resection were included. Manual quantification of epithelial glands was performed in blinded fashion. Image visualization enhancement software was used to quantify the surface area occupied by epithelial glands on en-face VLE. Histologic en-bloc (R0) and incomplete (R1) resection of the targeted lesion was defined by the absence and presence of dysplasia and/or cancer at the specimen margins respectively. Results The study sample consisted of 37 EMRs from 31 patients. The mean (SD) size of EMRs was 1.04 (0.37) cm. Pathology showed low-grade dysplasia (N = 12), high-grade dysplasia (N = 19), and intramucosal cancer (N = 6). The en-bloc resection rate was 37.8% (R0: N = 14; R1: N = 23). The mean (SD) number of epithelial glands was 13.0 (6.7) and 28.8 (23.9) for R0 and R1 specimens, respectively, with a statistically significant mean difference of 15.8 glands (95% CI: 2–29, P = 0.02) between the two groups. A gland count of 28 or higher per EMR specimen predicted R1 with 100% sensitivity and 39% specificity (ROC: 0.69). The mean (SD) surface area occupied by epithelial glands in R0 and R1 specimens was 0.98 (1.1) mm2 and 2.3 (2.4) mm2, respectively. There was strong correlation between manual gland counts and epithelial gland surface area (R2: 0.81, P < 0.001). Conclusion A higher number of VLE glands in EMR specimens is associated with a lower en-bloc resection rate suggesting that white-light endoscopy underestimates lesion size and that VLE may have a potential role in lesion margin assessment. Disclosure All authors have declared no conflicts of interest.