McKinley, Matthew

INTRODUCTION: Studies have shown that dysplasia in Barrett's esophagus (BE) has a predilection for the right hemisphere. There is limited information on the longitudinal distribution. The aim was to determine both the longitudinal and circumferential distributions of dysplasia and early neoplasia from 3 prospective studies. METHODS: This is a pooled analysis from 3 prospective studies of patients with treatment-naive BE. Both circumferential and longitudinal locations (for BE segments greater than 1 cm) of dysplastic and early neoplastic lesions were recorded. RESULTS: A total of 177 dysplastic and early neoplastic lesions from 91 patients were included in the pooled analysis; of which 59.3% (n = 105) were seen on high-definition white light endoscopy, 29.4% (n = 52) on advanced imaging, and 11.2% (n = 20) with random biopsies. The average Prague score was C3M5. Of 157 lesions within BE segments greater than 1 cm, 49 (34.8%) lesions were in the proximal half, whereas 92 lesions (65.2%) were in the distal half ( P < 0.001). The right hemisphere of the esophagus contained 55% (86/157) of the total lesions compared with 45% (71/157) for the left hemisphere ( P = 0.02). This was because of the presence of high-grade dysplasia being concentrated in the right hemisphere compared with the left hemisphere (60% vs 40%, P = 0.002). DISCUSSION: In this pooled analysis of prospective studies, both low-grade dysplasia and high-grade dysplasia are more frequently found in the distal half of the Barrett's segment. This study confirms that the right hemisphere is a hot spot for high-grade dysplasia. Careful attention to these locations is important during surveillance endoscopy.

INTRODUCTION: Ablation of Barrett's esophagus (BE) is the preferred approach for the treatment of neoplasia without visible lesions. Limited data on cryoballoon ablation (CBA) suggest its potential clinical utility. We evaluated the safety and efficacy of CBA in a multicenter study of patients with neoplastic BE. METHODS: In a prospective clinical trial, 11 academic and community centers recruited consecutive patients with BE of 1–6 cm length and low-grade dysplasia, high-grade dysplasia (HGD), or intramucosal adenocarcinoma (ImCA) confirmed by central pathology. Patients with symptomatic pre-existing strictures or visible BE lesions had dilation or endoscopic mucosal resection (EMR), respectively, before enrollment. A nitrous oxide cryoballoon focal ablation system was used to treat all visible columnar mucosa in up to 5 sessions. Study end points included complete eradication of all dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1 year. RESULTS: One hundred twenty patients with BE with ImCA (20%), HGD (56%), or low-grade dysplasia (23%) were enrolled. In the intention-to-treat analysis, the CE-D and CE-IM rates were 76% and 72%, respectively. In the per-protocol analysis (94 patients), the CE-D and CE-IM rates were 97% and 91%, respectively. Postablation pain was mild and short lived. Fifteen subjects (12.5%) developed strictures requiring dilation. One patient (0.8%) with HGD progressed to ImCA, which was successfully treated with EMR. Another patient (0.8%) developed gastrointestinal bleeding associated with clopidogrel use. One patient (0.8%) had buried BE with HGD in 1 biopsy, not confirmed by subsequent EMR. DISCUSSION: In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted (clinicaltrials.gov registration NCT02514525).

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 Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291

83 Background: Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries significant morbidity and mortality. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study was to assess the safety, efficacy, and tolerability of spray cryotherapy of esophageal cancer. Methods: This study includes patients enrolled retrospectively and prospectively in an open-label registry and patients in a retrospective cohort from twelve academic and community practices. Endoscopic spray cryotherapy was performed until local tumor eradication was confirmed by biopsy or until treatment was halted due to progression of disease, patient withdrawal or co-morbidities. Results: One-hundred and eight patients (median age 75.5, 79.6% male, 93.5% adenocarcinoma, mean length 5.2 cm) underwent 442 treatments (mean 4.2 per patient). Tumor stages included 40 with T1a, 27 with T1b, 10 with unspecified T1, 15 with T2, and 16 with no T stage reported. One-hundred and six patients completed treatment with complete response of intraluminal disease in 54.7%, including complete response in 74.4% for T1a, 50% for T1b, 65.3% for all T1, 6.7% for T2, and 50% for those with no T stage reported. Mean follow-up was 17.3 months. There were no deaths or perforations related to spray cryotherapy. Strictures developed in 11 of 108 patients (10.2%) but were present before spray cryotherapy in 3 of 11. Conclusions: This study suggests that endoscopic spray cryotherapy is safe, well tolerated and effective for early esophageal cancer in patients who are not candidates for conventional therapy.