Clinical Outcomes After Endoscopic Management of Low-Risk and High-Risk T1a Esophageal Adenocarcinoma: A Multicenter Study.

INTRODUCTION: Endoscopic eradication therapy (EET) is standard of care for T1a esophageal adenocarcinoma (EAC). However, data on outcomes in high-risk T1a EAC are limited. We assessed and compared outcomes after EET of low-risk and high-risk T1a EAC, including intraluminal EAC recurrence, extraesophageal metastases, and overall survival. METHODS: Patients who underwent EET for T1a EAC at 3 referral Barrett's esophagus endotherapy units between 1996 and 2022 were included. Patients with submucosal invasion, positive deep margins, or metastases at initial diagnosis were excluded. High-risk T1a EAC was defined as T1a EAC with poor differentiation and/or lymphovascular invasion, with low-risk disease being defined without these features. All pathology was systematically assessed by expert gastrointestinal pathologists. Baseline and follow-up endoscopy and pathology data were abstracted. Time-to-event analyses were performed to compare outcomes between groups. RESULTS: One hundred eighty-eight patients with T1a EAC were included (high risk, n = 45; low risk, n = 143) with a median age of 70 years, and 84% were men. Groups were comparable for age, sex, Barrett's esophagus length, lesion size, and EET technique. Rates of delayed extraesophageal metastases (11.1% vs 1.4%) were significantly higher in the high-risk group ( P = 0.02). There was no significant difference in the rates of intraluminal EAC recurrence ( P = 0.79) and overall survival ( P = 0.73) between the 2 groups. DISCUSSION: Patients with high-risk T1a EAC undergoing successful EET had a substantially higher rate of extraesophageal metastases compared with those with low-risk T1a EAC on long-term follow-up. These data should be factored into discussions with patients while selecting treatment approaches. Additional prospective data in this area are critical.

Long-term outcomes following successful endoscopic treatment of T1 esophageal adenocarcinoma: a multicenter cohort study.

BACKGROUND AND AIMS: Endoscopic eradication therapy (EET) is guideline endorsed for management of early-stage (T1) esophageal adenocarcinoma (EAC). Patients with baseline high-grade dysplasia (HGD) and EAC are at highest risk of recurrence after successful EET, but limited data exist on long-term (>5 year) recurrence outcomes. Our aim was to assess the incidence and predictors of long-term recurrence in a multicenter cohort of patients with T1 EAC treated with EET. METHODS: Patients with T1 EAC achieving successful endoscopic cancer eradication with a minimum of 5 years' clinical follow-up were included. The primary outcome was neoplastic recurrence, defined as dysplasia or EAC, and it was characterized as early (<2 years), intermediate (2-5 years), or late (>5 years). Predictors of recurrence were assessed by time to event analysis. RESULTS: A total of 84 T1 EAC patients (75 T1a, 9 T1b) with a median 9.1 years (range, 5.1-18.3 years) of follow-up were included. The overall incidence of neoplastic recurrence was 2.0 per 100 person-years of follow-up. Seven recurrences (3 dysplasia, 4 EAC) occurred after 5 years of EAC remission. Overall, 88% of recurrences were treated successfully endoscopically. EAC recurrence-related mortality occurred in 3 patients at a median of 5.2 years from EAC remission. Complete eradication of intestinal metaplasia was independently associated with reduced recurrence (hazard ratio, .13). CONCLUSIONS: Following successful EET of T1 EAC, neoplastic recurrence occurred after 5 years in 8.3% of cases. Careful long-term surveillance should be continued in this patient population. Complete eradication of intestinal metaplasia should be the therapeutic end point for EET.

Barrett's Epithelial Thickness, Assessed by Volumetric Laser Endomicroscopy, Is Associated With Response to Radiofrequency Ablation.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) is the most common treatment for flat Barrett's esophagus (BE), but reasons for varying outcomes are poorly understood. A recently developed contrast-enhancement algorithm allows reliable measurement of Barrett's epithelial thickness (BET) from volumetric laser endomicroscopy (VLE) images and correlation with response to RFA. Using this algorithm, we investigated whether patients with thicker Barrett's mucosa are less likely to respond to RFA. In the future, this algorithm may guide choice of RFA dosing or endoscopic resection. METHODS: We performed a retrospective analysis on all patients with BE who received a baseline VLE scan between May 2015 and October 2016, followed by RFA and 1 follow-up exam, from 14 institutions participating in the United States VLE registry. We measured BET on equidistant locations by estimating the distance between the esophageal surface and the superficial edge of the deepest lamina propria. The primary outcome variable was the percentage reduction in Prague length; secondary outcome variables were complete remission of intestinal metaplasia (CRIM) and presence of strictures after 12 months. RESULTS: Images from 61 patients were included in our final analysis. Mean BET per patient ranged from 224 µm to 705 µm. A 100 µm thicker mean BET per patient resulted in a 12% lower response to treatment, measured by a reduction of Prague length (P = .03), after adjustment for confounders. We found an association between mean BET and CRIM, but not with stricture formation. CONCLUSIONS: Based on measurements on contrast-enhanced VLE images, we found that BET correlates with response to RFA. For clinical implementation, larger studies with a standardized follow-up and development of computer-aided image analysis systems are needed.

Impact of topical budesonide on prevention of esophageal stricture after mucosal resection.

BACKGROUND AND AIMS: EMR and endoscopic submucosal dissection (ESD) are treatment modalities for Barrett's esophagus involving high-grade dysplasia or early cancer. Injectional corticosteroid therapy decreases the risk of procedure-related esophageal stricture (ES) formation. Our aim was to assess the efficacy of topical budesonide on the rate of ES formation after EMR or ESD. METHODS: Patients included prospectively from 3 tertiary endoscopy centers received 3 mg budesonide orally twice a day for 8 weeks after esophageal EMR or ESD of 50% or more of the esophageal circumference between January 1, 2014 and June 30, 2018. These patients were matched (1:3 ratio) retrospectively with a consecutive patient cohort who underwent EMR or ESD of 50% or more of the esophageal circumference without concomitant corticosteroid therapy. The primary endpoint was the presence of ES at the 12-week follow-up. RESULTS: Twenty-five patients (budesonide) were matched with 75 patients (no budesonide). Most underwent EMR for Barrett's esophagus with biopsy-proven high-grade dysplasia or suspected T1a cancer. Although most baseline characteristics did not differ significantly, patients in the budesonide cohort tended to have a higher proportion of circumferential EMR. The proportion of patients with ES was not significantly lower in the budesonide cohort (16% vs 28%). On logistic regression analysis, budesonide remained associated with a lower incidence of ES (P = .023); however, when controlling for baseline characteristics with a propensity score weighted logistic regression model, there was no significant effect on ES formation (P = .176). CONCLUSIONS: Topical budesonide might be associated with a reduction of ES after EMR or ESD; however, further studies are needed to verify our results.

Validation of a methylated DNA marker panel for the nonendoscopic detection of Barrett's esophagus in a multisite case-control study.

BACKGROUND AND AIMS: We previously identified a 5 methylated DNA marker (MDM) panel for the detection of nonendoscopic Barrett's esophagus (BE). In this study, we aimed to recalibrate the performance of the 5 MDM panel using a simplified assay in a training cohort, validate the panel in an independent test cohort, and explore the accuracy of an MDM panel with only 3 markers. METHODS: Participants were recruited from 3 medical centers. The sponge on a string device (EsophaCap; CapNostics, Concord, NC, USA) was swallowed and withdrawn, followed by endoscopy, in BE cases and control subjects. A 5 MDM panel was blindly assayed using a simplified assay. Random forest modeling analysis was performed, in silico cross-validated in the training set, and then locked down, before test set analysis. RESULTS: The training set had 199 patients: 110 BE cases and 89 control subjects, and the test set had 89 patients: 60 BE cases and 29 control subjects. Sensitivity of the 5 MDM panel for BE diagnosis was 93% at 90% specificity in the training set and 93% at 93% specificity in the test set. Areas under the receiver operating characteristic curves were .96 and .97 in the training and test sets, respectively. Model accuracy was not influenced by age, sex, or smoking history. Multiple 3 MDM panels achieved similar accuracy. CONCLUSIONS: A 5 MDM panel for BE is highly accurate in training and test sets in a blinded multisite case-control analysis using a simplified assay. This panel may be reduced to only 3 MDMs in the future. (Clinical trial registration number: NCT02560623.).

Outcomes of radiofrequency ablation by manual versus self-sizing circumferential balloon catheters for the treatment of dysplastic Barrett's esophagus: a multicenter comparative cohort study.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) is the preferred ablative modality for treating dysplastic Barrett's esophagus. The recently introduced self-sizing circumferential ablation catheter eliminates the need for a sizing balloon. Although it enhances efficiency, outcomes have not been compared with the previous manual-sizing catheter. We evaluated the comparative safety and efficacy of these 2 ablation systems in a large, multicenter cohort. METHODS: Patients undergoing RFA at 3 tertiary care centers from 2005 to 2018 were included. Circumferential RFA was performed in a standard fashion, followed by focal RFA as needed. Outcomes were compared between the self-sizing and manual-sizing groups. The primary outcome was the rate of adverse events, including strictures, perforation, and bleeding. Secondary outcomes were procedure time and treatment efficacy, as assessed by rates and time to complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM). RESULTS: Three hundred eighteen patients were included, 90 (28.3%) treated with the self-sizing catheter and 228 (71.7%) with the manual-sizing catheter. Twenty-one patients (6.6%) developed strictures (8 [8.9%] in the self-sizing group and 13 [5.7%] in the manual-sizing group, P = .32). Of the self-sizing strictures, 75% occurred at the 12J dose before widespread adoption of the current 10J treatment standard. One patient developed bleeding, and no perforations were encountered. Procedure time was significantly shorter in the self-sizing group. No significant differences were observed in rates of and time to CE-D and CE-IM. CONCLUSIONS: These findings suggest that both systems are comparable in safety and efficacy. The use of the self-sizing system may enhance the efficiency of RFA for treating dysplastic Barrett's esophagus.

Prospective development and validation of a volumetric laser endomicroscopy computer algorithm for detection of Barrett's neoplasia.

BACKGROUND AND AIMS: Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used to detect Barrett's esophagus (BE) dysplasia. However, real-time interpretation of VLE scans is complex and time-consuming. Computer-aided detection (CAD) may help in the process of VLE image interpretation. Our aim was to train and validate a CAD algorithm for VLE-based detection of BE neoplasia. METHODS: The multicenter, VLE PREDICT study, prospectively enrolled 47 patients with BE. In total, 229 nondysplastic BE and 89 neoplastic (high-grade dysplasia/esophageal adenocarcinoma) targets were laser marked under VLE guidance and subsequently underwent a biopsy for histologic diagnosis. Deep convolutional neural networks were used to construct a CAD algorithm for differentiation between nondysplastic and neoplastic BE tissue. The CAD algorithm was trained on a set consisting of the first 22 patients (134 nondysplastic BE and 38 neoplastic targets) and validated on a separate test set from patients 23 to 47 (95 nondysplastic BE and 51 neoplastic targets). The performance of the algorithm was benchmarked against the performance of 10 VLE experts. RESULTS: Using the training set to construct the algorithm resulted in an accuracy of 92%, sensitivity of 95%, and specificity of 92%. When performance was assessed on the test set, accuracy, sensitivity, and specificity were 85%, 91%, and 82%, respectively. The algorithm outperformed all 10 VLE experts, who demonstrated an overall accuracy of 77%, sensitivity of 70%, and specificity of 81%. CONCLUSIONS: We developed, validated, and benchmarked a VLE CAD algorithm for detection of BE neoplasia using prospectively collected and biopsy-correlated VLE targets. The algorithm detected neoplasia with high accuracy and outperformed 10 VLE experts. (The Netherlands National Trials Registry (NTR) number: NTR 6728.).

Expert assessment on volumetric laser endomicroscopy full scans in Barrett's esophagus patients with or without high grade dysplasia or early cancer.

BACKGROUND: Volumetric laser endomicroscopy (VLE) allows for near-microscopic imaging of the superficial esophageal wall and may improve detection of early neoplasia in Barrett's esophagus (BE). Interpretation of a 6-cm long, circumferential VLE "full scan" may however be challenging for endoscopists. We aimed to evaluate the accuracy of VLE experts in correctly diagnosing VLE full scans of early neoplasia and non-dysplastic BE (NDBE). METHODS: 29 VLE full scan videos (15 neoplastic and 14 NDBE) were randomly evaluated by 12 VLE experts using a web-based module. Experts were blinded to the endoscopic BE images and histology. The 15 neoplastic cases contained a subtle endoscopically visible lesion, which on endoscopic resection showed high grade dysplasia or cancer. NDBE cases had no visible lesions and an absence of dysplasia in all biopsies. VLE videos were first scored as "neoplastic" or "NDBE." If neoplastic, assessors located the area most suspicious for neoplasia. Primary outcome was the performance of VLE experts in differentiating between non-dysplastic and neoplastic full scan videos, calculated by accuracy, sensitivity, and specificity. Secondary outcomes included correct location of neoplasia, interobserver agreement, and level of confidence. RESULTS: VLE experts correctly labelled 73 % (95 % confidence interval [CI] 67 % - 79 %) of neoplastic VLE videos. In 54 % (range 27 % - 66 %) both neoplastic diagnosis and lesion location were correct. NDBE videos were consistent with endoscopic biopsies in 52 % (95 %CI 46 % - 57 %). Interobserver agreement was fair (kappa 0.28). High level of confidence was associated with a higher rate of correct neoplastic diagnosis (81 %) and lesion location (73 %). CONCLUSIONS: Identification of subtle neoplastic lesions in VLE full scans by experts was disappointing. Future studies should focus on improving methodologies for reviewing full scans, development of refined VLE criteria for neoplasia, and computer-aided diagnosis of VLE scans.

Hiatal Hernia Associated with Higher Odds of Dysplasia in Patients with Barrett's Esophagus.

BACKGROUND: Patients with Barrett's esophagus (BE) are more likely to have associated hiatal hernia (HH) compared to the general population. Studies show that HH are typically longer and wider in patients with BE. AIMS: To determine whether patients with HH have associated increased odds of coexistence of BE by examining inpatient prevalence, as well as determining other inpatient outcomes. METHODS: This was a case-control study using the NIS 2016, the largest public inpatient database in the USA. All patients with ICD10CM codes for BE were included. None were excluded. The primary outcome was determining the association between BE and HH in hospitalized patients, stratified by grade of dysplasia. Secondary outcomes included measuring use of endoscopic ablation in patients with BE and HH compared to patients with BE and no HH, determining the degree of association between HH and esophagitis in patients with or without BE, as well as the association between esophagitis and dysplasia in patients with BE and HH. RESULTS: A total of 118,750 patients with BE were identified, of which 24,030 had associated HH. Adjusted odds of having associated BE in patients with HH was 10.9 (p < 0.01) compared to patients without HH. Patients with HH also displayed significantly higher odds of both low-grade dysplasia (aOR 34.5, p < 0.01) and high-grade dysplasia (aOR 14.7, p < 0.01). For secondary outcomes, the odds of undergoing ablation for BE was higher 4.77 (p < 0.01) in patients with HH. CONCLUSIONS: Patients with HH have significantly higher odds of having associated BE, regardless of the level of dysplasia. Furthermore, the odds of undergoing ablation are much higher, likely reflecting higher odds of dysplasia. This highlights the importance of BE in patients with HH, and potentially consider these patients as higher risk.

Molecular biomarker identification for esophageal adenocarcinoma using endoscopic brushing and magnified endoscopy.

BACKGROUND: Barrett's esophagus (BE) is a predisposing factor for esophageal adenocarcinoma (EAC); however, the precise mechanism underlying this association remains unclear. The identification of biomarkers that are associated with an increased risk of BE progression to EAC would facilitate diagnosis and early treatment. Toward this goal, we aimed to identify biomarkers associated with BE and EAC in patients. METHODS: In conjunction with high-resolution magnified endoscopy with narrow-band imaging (ME-NBI), we obtained brushing samples from the long-segment BE (LSBE) or short-segment BE (SSBE) of patients with EAC or without EAC (control). To identify candidate biomarker genes, microarray analysis was performed for a training set of 28 American samples. To confirm the microarray results, expression levels of the 16 candidate biomarkers were evaluated by real-time polymerase chain reaction analysis, using samples collected from an additional 53 American patients. In addition, we also performed a functional analysis for these genes using Gene Ontology (GO) enrichment analysis. RESULTS: Among the 16 genes identified as differentially expressed by microarray analysis, the GO analysis indicated matrix metalloproteinase (MMP) family associated with 'collagen metabolic process' and 'multicellular organismal macromolecule metabolic process' as the two top biological processes. Brushing samples of patients with EAC showed up-regulated expression of decay-accelerating factors (DAF and CD55) and topoisomerase type Iiα (TOP2A), and down-regulated expression of the sodium channel epithelial 1 beta subunit (SCNN1B). CONCLUSIONS: The up-regulation of CD55 and TOP2A, and the down-regulation of SCNN1B were common to the brushing samples and might serve as molecular biomarkers for identifying EAC in patients with SSBE. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) (000004004).

Accurate Nonendoscopic Detection of Barrett's Esophagus by Methylated DNA Markers: A Multisite Case Control Study.

INTRODUCTION: Nonendoscopic Barrett's esophagus (BE) screening may help improve esophageal adenocarcinoma outcomes. We previously demonstrated promising accuracy of methylated DNA markers (MDMs) for the nonendoscopic diagnosis of BE using samples obtained from a capsule sponge-on-string (SOS) device. We aimed to assess the accuracy of these MDMs in an independent cohort using a commercial grade assay. METHODS: BE cases had ≥ 1 cm of circumferential BE with intestinal metaplasia; controls had no endoscopic evidence of BE. The SOS device was withdrawn 8 minutes after swallowing, followed by endoscopy (the criterion standard). Highest performing MDMs from a previous study were blindly assessed on extracted bisulfite-converted DNA by target enrichment long-probe quantitative amplified signal (TELQAS) assays. Optimal MDM combinations were selected and analyzed using random forest modeling with in silico cross-validation. RESULTS: Of 295 patients consented, 268 (91%) swallowed the SOS device; 112 cases and 89 controls met the pre-established inclusion criteria. The median BE length was 6 cm (interquartile range 4-9), and 50% had no dysplasia. The cross-validated sensitivity and specificity of a 5 MDM random forest model were 92% (95% confidence interval 85%-96%) and 94% (95% confidence interval 87%-98%), respectively. Model performance was not affected by age, gender, or smoking history but was influenced by the BE segment length. SOS administration was well tolerated (median [interquartile range] tolerability 2 [0, 4] on 10 scale grading), and 95% preferred SOS over endoscopy. DISCUSSION: Using a minimally invasive molecular approach, MDMs assayed from SOS samples show promise as a safe and accurate nonendoscopic test for BE prediction.

Late Recurrence of Barrett's Esophagus After Complete Eradication of Intestinal Metaplasia is Rare: Final Report From Ablation in Intestinal Metaplasia Containing Dysplasia Trial.

BACKGROUND & AIMS: The goal of treatment for Barrett's esophagus (BE) with dysplasia is complete eradication of intestinal metaplasia (CEIM). The long-term durability of CEIM has not been well characterized, so the frequency and duration of surveillance are unclear. We report results from a 5-year follow-up analysis of patients with BE and dysplasia treated by radiofrequency ablation (RFA) in the randomized controlled Ablation of Intestinal Metaplasia Containing Dysplasia (AIM) trial. METHODS: Participants for the AIM Dysplasia trial (18-80 years old) were recruited from 19 sites in the United States and had endoscopic evidence of non-nodular dysplastic BE ≤8 cm in length. Subjects (n = 127) were randomly assigned (2:1 ratio) to receive either RFA (entire BE segment ablated circumferentially) or a sham endoscopic procedure; patients in the sham group were offered RFA treatment 1 year later, and all patients were followed for 5 years. We collected data on BE recurrence (defined as intestinal metaplasia in the tubular esophagus) and dysplastic BE recurrence among patients who achieved CEIM. We constructed Kaplan-Meier estimates and applied parametric survival analysis to examine proportions of patients without any recurrence and without dysplastic recurrence. RESULTS: Of 127 patients in the AIM Dysplasia trial, 119 received RFA and met inclusion criteria. Of those 119, 110 (92%) achieved CEIM. Over 401 person-years of follow-up (mean, 3.6 years per patient; range, 0.2-5.8 years), 35 of 110 (32%) patients had recurrence of BE or dysplasia, and 19 (17%) had dysplasia recurrence. The incidence rate of BE recurrence was 10.8 per 100 person-years overall (95% CI, 7.8-15.0); 8.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI, 4.9-14.0), and 13.5 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 8.8-20.7). The incidence rate of dysplasia recurrence was 5.2 per 100 person-years overall (95% CI 3.3-8.2); 3.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI 1.5-7.2), and 7.3 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 4.2-12.5). Neither BE nor dysplasia recurred at a constant rate. There was a greater probability of recurrence in the first year following CEIM than in the following 4 years combined. CONCLUSIONS: In this analysis of prospective cohort data from the AIM Dysplasia trial, we found BE to recur after CEIM by RFA in almost one third of patients with baseline dysplastic disease; most recurrences occurred during the first year after CEIM. However, patients who achieved CEIM and remained BE free at 1 year after RFA had a low risk of BE recurrence. Studies are needed to determine when surveillance can be decreased or discontinued; our study did not identify any BE or dysplasia recurrence after 4 years of surveillance.

Highly Discriminant Methylated DNA Markers for the Non-endoscopic Detection of Barrett's Esophagus.

BACKGROUND: Minimally invasive methods have been described to detect Barrett's esophagus (BE), but are limited by subjectivity and suboptimal accuracy. We identified methylated DNA markers (MDMs) for BE in tissue and assessed their accuracy on whole esophagus brushings and capsule sponge samples. METHODS: Step 1: Unbiased whole methylome sequencing was performed on DNA from BE and normal squamous esophagus (SE) tissue. Discriminant MDM candidates were validated on an independent patient cohort (62 BE cases, 30 controls) by quantitative methylation specific PCR (qMSP). Step 2: Selected MDMs were further evaluated on whole esophageal brushings (49 BE cases, 36 controls). 35 previously sequenced esophageal adenocarcinoma (EAC) MDMs were also evaluated. Step 3: 20 BE cases and 20 controls were randomized to swallow capsules sponges (25 mm, 10 pores or 20 pores per inch (ppi)) followed endoscopy. DNA yield, tolerability, and mucosal injury were compared. Best MDM assays were performed on this cohort. RESULTS: Step 1: 19 MDMs with areas under the ROC curve (AUCs) >0.85 were carried forward. Step 2: On whole esophageal brushings, 80% of individual MDM candidates showed high accuracy for BE (AUCs 0.84-0.94). Step 3: The capsule sponge was swallowed and withdrawn in 98% of subjects. Tolerability was superior with the 10 ppi sponge with minimal mucosal injury and abundant DNA yield. A 2-marker panel (VAV3 + ZNF682) yielded excellent BE discrimination (AUC = 1). CONCLUSIONS: Identified MDMs discriminate BE with high accuracy. BE detection appears safe and feasible with a capsule sponge. Corroboration in larger studies is warranted. ClinicalTrials.gov number NCT02560623.

Volumetric laser endomicroscopy in the biliary and pancreatic ducts: a feasibility study with histological correlation.

BACKGROUND: Volumetric laser endomicroscopy (VLE) provides circumferential images 3 mm into the biliary and pancreatic ducts. We aimed to correlate VLE images with the normal and abnormal microstructure of these ducts. METHODS: Samples from patients undergoing hepatic or pancreatic resection were evaluated. VLE images were collected using a low-profile VLE catheter inserted manually into the biliary and pancreatic ducts ex vivo. Histological correlation was assessed by two unblinded investigators. RESULTS: 25 patients (20 liver and 5 pancreatic samples) and 111 images were analyzed. VLE revealed three histological layers: epithelium, connective tissue, and parenchyma. It identified distinctive patterns for primary sclerosing cholangitis (PSC), pancreatic cysts, neuroendocrine tumor, and adenocarcinoma adjacent to the pancreatic duct or ampulla. VLE failed to identify dysplasia in a dominant stricture and inflammatory infiltrates in PSC. Reflectivity measurements of the liver parenchyma diagnosed liver cirrhosis with high sensitivity. CONCLUSIONS: VLE can identify histological changes in the biliary and pancreatic ducts allowing real-time diagnosis. Further studies are needed to measure the accuracy of VLE in a larger sample and to validate our findings in vivo.

Volumetric laser endomicroscopy interpretation and feature analysis in dysplastic Barrett's esophagus.

BACKGROUND AND AIM: Volumetric laser endomicroscopy (VLE) is used to identify Barrett's esophagus (BE) dysplasia. Selection of a dysplastic region of interest (ROI) can be challenging due to feature variability across a large amount of data. The degree of agreement among VLE users in selecting a ROI has not been studied. METHODS: High-definition videos that divided a VLE scan from 18 patients with biopsy-proven BE dysplasia into 1-cm segments were reviewed using a four-quadrant grid superimposed for systematic interpretation. VLE scans were selected based on image quality and appropriate visualization of BE epithelium. Four experienced VLE users rated each quadrant as dysplastic or non-dysplastic. For quadrants rated as dysplastic, reviewers selected a single timeframe with representative features. A high-degree of agreement among reviewers was defined as ≥75% agreement on the quadrant diagnosis and ≥50% agreement on selected timeframe (±2 s). RESULTS: Thirty-one videos, each 32 s in length, comprising 124 quadrants were reviewed. There was high-agreement among reviewers in 99 (80%) quadrants, of which 68 (69%) were rated as dysplastic. Compared with quadrants rated as non-dysplastic, ROIs of quadrants rated as dysplastic contained a higher number of epithelial glands (12.7 vs 1.2, P < 0.001) with atypical architecture (54 vs 1, P < 0.001). A statistically significant difference was observed between the signal intensity profiles of quadrants rated as dysplastic and quadrants rated as non-dysplastic (P = 0.004). CONCLUSION: This study highlights that experienced VLE users can identify ROIs with high-degree of agreement. Selected ROIs contained VLE features associated with BE dysplasia.

Predictors of Progression in Barrett's Esophagus with Low-Grade Dysplasia: Results from a Multicenter Prospective BE Registry.

OBJECTIVES: Low-grade dysplasia (LGD) is a risk factor for progression in Barrett's esophagus (BE). Progression estimates however vary and predictors of progression are not well established. We aimed to assess predictors of progression in a multicenter BE-LGD cohort. METHODS: All subjects with LGD (diagnosed by a GI pathologist) in a prospective BE registry were identified. Progression was defined development of HGD/EAC more than 12 months after index date of LGD diagnosis. Clinical, endoscopic factors and impact of histologic review by an independent panel of two GI pathologists were assessed as predictors of progression. Cox proportional hazard models were used to assess their association with risk of progression. RESULTS: 244 BE-LGD subjects met inclusion criteria. Their mean age was 63.2 years. 205 (84%) were males. The median follow up was 4.8 years. Fifty six patients were diagnosed with HGD/EAC in less than 12 months, while 14 progressed to HGD/EAC after 12 months, with an overall annual risk of progression of 1.2%. 29% of LGD subjects were downgraded to non-dysplastic and the remaining re-confirmed as LGD or indefinite dysplasia. The risk of progression in the reconfirmed LGD group was eight fold higher (hazards ratio: 7.6, 95% CI: 1.5-139.4) in a propensity score stratified model. CONCLUSIONS: In this large BE-LGD cohort, progression risk increased substantially when an additional panel of two expert GI pathologists re-confirmed a LGD diagnosis. These BE subjects may be candidates for endoscopic therapy. LGD was a marker of prevalent HGD/EAC in 18% of patients.

Role of EUS in patients with suspected Barrett's esophagus with high-grade dysplasia or early esophageal adenocarcinoma: impact on endoscopic therapy.

BACKGROUND AND AIMS: Endoscopic therapy is the standard treatment for high-grade dysplasia and some cases of T1a esophageal adenocarcinoma (EAC), but it is not appropriate for deeply invasive disease. Data on the value of EUS for patient selection for endoscopic or surgical resection are conflicting. We investigated the outcome of esophageal EUS for the staging and treatment selection of patients with treatment-naive, premalignant Barrett's esophagus (BE) and suspected superficial EAC. METHODS: We retrospectively reviewed consecutive patients who underwent EUS for staging of treatment-naive, suspected premalignant BE and superficial EAC from January 2006 to June 2014. All patients referred for endoscopic therapy routinely underwent EUS. Patients with esophageal masses, squamous cell cancers, previous neoadjuvant therapy, or unrelated pathologies were excluded. Each patient's final diagnosis was verified by EMR, esophagectomy, or forceps biopsy sampling. Test characteristics of EUS were calculated. RESULTS: Three hundred thirty-five patients (mean age, 68 years; 86% male) with BE, a Prague C mean of 2.8 cm, and a Prague M mean of 4.5 cm were staged (pT0, 78% [6% nondysplastic, 24% low-grade dysplasia, 42% high-grade dysplasia]; pT1a, 14%; pT1b, 7%; and pT2, 1%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for patient selection to endoscopic (T1aN0 or less) or surgical therapy with EUS TN staging were 50%, 93%, 40%, 95%, and 90%, respectively. Comparable rates were achieved for patients with nodular BE. Overstaging occurred in 7% of patients, and EUS selected 11% for incorrect treatment modalities compared with pathologic staging. CONCLUSIONS: This study confirms the limited value of EUS suggested in the latest American College of Gastroenterology guidelines for BE management.

Effects of the Learning Curve on Efficacy of Radiofrequency Ablation for Barrett's Esophagus.

BACKGROUND & AIMS: Complete eradication of Barrett's esophagus (BE) often requires multiple sessions of radiofrequency ablation (RFA). Little is known about the effects of case volume on the safety and efficacy of RFA or about the presence or contour of learning curves for this procedure. METHODS: We collected data from the US RFA Patient Registry (from 148 institutions) for patients who underwent RFA for BE from July 2007 to July 2011. We analyzed the effects of the number of patients treated by individual endoscopists and individual centers on safety and efficacy outcomes of RFA. Outcomes, including stricture, bleeding, hospitalization, and complete eradication of intestinal metaplasia (CEIM), were assessed using logistic regression. The effects of center and investigator experience on numbers of treatment sessions to achieve CEIM were examined using linear regression. RESULTS: After we controlled for potential confounders, we found that as the experience of endoscopists and centers increased with cases, the numbers of treatment sessions required to achieve CEIM decreased. This relationship persisted after adjusting for patient age, sex, race, length of BE, and presence of pretreatment dysplasia (P < .01). Center experience was not significantly associated with overall rates of CEIM or complete eradication of dysplasia. We did not observe any learning curve with regard to risks of stricture, gastrointestinal bleeding, perforation, or hospitalization (P > .05). CONCLUSIONS: Based on analysis of a large multicenter registry, efficiency of the treatment, as measured by number of sessions needed to achieve CEIM, increased with case volume, indicating a learning curve effect. This trend began to disappear after treatment of approximately 30 patients by the center or individual endoscopist. However, there was no significant association between safety or efficacy outcomes and previous case volume.

Safety and feasibility of volumetric laser endomicroscopy in patients with Barrett's esophagus (with videos).

BACKGROUND: Volumetric laser endomicroscopy (VLE) produces high-resolution, cross-sectional surface, and subsurface images for detecting neoplasia, targeting biopsies, and guiding real-time treatment. OBJECTIVE: To evaluate the safety and feasibility of the Nvision VLE system. DESIGN: Prospective, multicenter study. SETTING: Tertiary-care medical centers. PATIENTS: One hundred patients with suspected Barrett's esophagus, including 52 patients with prior endotherapy. INTERVENTIONS: The first-generation Nvision VLE Imaging System, a balloon-centered, rotating optical probe provided images of the mucosa and submucosa through a 6-cm segment length and 360° scan of the distal esophagus. MAIN OUTCOME MEASUREMENTS: Acquisition of a complete, 6-cm scan from the distal esophagus, demographic and procedural data, and final histologic diagnosis. RESULTS: VLE imaging was successfully performed in 87 cases. After VLE imaging, biopsy specimens were obtained in 77 patients and mucosal resection was performed in 20 patients. The final pathologic diagnoses of the patients studied were adenocarcinoma (4 patients), high-grade dysplasia (10 patients), low-grade dysplasia (11 patients), indefinite (5 patients), intestinal metaplasia (29 patients), and normal squamous cells (18 patients). VLE was not completed in 13 of 100 (13%) because of optical probe and console issues. There were 2 minor adverse events (mucosal lacerations not requiring therapy). LIMITATIONS: This was a feasibility study with a first-generation device. There was no direct histopathologic correlation with the VLE images or any comparative analysis with white-light endoscopy or narrow-band imaging findings. CONCLUSION: VLE is a safe procedure for patients with suspected or confirmed Barrett's esophagus. Real-time VLE images enabled visualization of the mucosa and submucosa in 87% of cases. Further studies are needed to evaluate the in vivo diagnostic accuracy and clinical utility of VLE.

Comparison of endoscopic treatment modalities for Barrett's neoplasia.

BACKGROUND: There are few data comparing endoscopic treatment outcomes for Barrett's esophagus (BE). OBJECTIVE: To compare treatment outcomes in BE patients treated with radiofrequency ablation (RFA), RFA after EMR, and porfimer sodium photodynamic therapy (Ps-PDT). DESIGN: Retrospective, observational study. SETTING: Single tertiary center between 2001 and 2013. PATIENTS: A total of 342 BE patients treated with RFA (n = 119), EMR+RFA (n = 98), and Ps-PDT (n = 125). MAIN OUTCOME MEASUREMENTS: Rates of complete remission of intestinal metaplasia (CRIM), BE recurrence, and adverse events. RESULTS: Baseline BE high-grade dysplasia (HGD) and adenocarcinoma were more common in the Ps-PDT group (89%) compared with the EMR-RFA (70%) and RFA (37%) groups. At a median follow-up of 14.2 months, 173 patients (50.6%) achieved CRIM. CRIM was significantly more common in Ps-PDT patients compared with RFA (P < .001) and EMR-RFA (P < .001) patients on multivariable analysis. In patients who achieved CRIM, the rates of subsequent BE recurrence were relatively similar among the 3 groups. Although the rates of bleeding were similar, strictures were less common in RFA patients (2.4%) compared with EMR-RFA (13.3%, P = .001) and Ps-PDT (10.4%, P =.043) patients. CONCLUSION: This study of endoscopic treatment for Barrett's dysplasia and neoplasia found that complete remission was achieved more often and more rapidly after Ps-PDT with similar disease recurrence rates compared with EMR or RFA. Adverse events were more common after EMR and Ps-PDT. Further studies are required to determine which ablation and resection techniques are ideally suited for each BE patient.