Barrett's Neoplasia Research Articles

Recurrence following successful eradication of neoplasia with endoscopic mucosal resection compared with endoscopic submucosal dissection in Barrett's esophagus: a retrospective comparison.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are effective treatments for Barrett's neoplasia. However, little is known about recurrence rates following these techniques. We compared long-term neoplasia recurrence rates following EMR and ESD. This study included patients with Barrett's neoplasia (high grade dysplasia/adenocarcinoma) treated between July 2019 and December 2023 at a tertiary referral center in Canada. Outcomes were residual neoplasia at first follow-up, complete remission of neoplasia (CRN), and neoplasia recurrence following CRN. 157 patients were included (87 EMR, 70 ESD). Compared with EMR, the ESD group had larger lesions (median 2 vs. 3 cm, P<0.05), more adenocarcinoma (85.1% vs. 94.3%, P = 0.07), and deeper submucosal invasion (T1a: 71.6% vs. 75.8%; T1b-SM1: 25.7% vs. 6.1%; T1b≥SM2: 2.7% vs. 18.2%; P<0.05). Among 124 patients with follow-up (71 EMR, 53 ESD), 84.9% of ESD-treated patients had curative resections (i.e. R0 resection with low risk for lymph node metastasis), whereas 94.4% of EMR-treated patients had deep margin R0 resection of low risk lesions. At first follow-up, residual neoplasia (14.1% vs. 11.3%) and CRN (97.2% vs. 100%) were similar in the EMR and ESD groups, but neoplasia recurrence following CRN was significantly higher with EMR (13% vs. 1.9%, P<0.05), with cumulative probability of recurrence at 3 years of 18.3% vs. 4.2%, respectively. Neoplasia recurrence following CRN was significantly higher following EMR compared with ESD, suggesting that ESD may be superior to EMR in preventing neoplasia recurrence in Barrett's esophagus.

Endoscopic submucosal dissection vs. endoscopic mucosal resection in the treatment of early Barrett's neoplasia: Systematic review and meta-analysis.

Endoscopic resection is the preferred approach to treat early Barrett's neoplasia, reducing the need for surgical interventions. However, the best choice between endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) remains unclear. The study aimed to compare the efficacy and safety of EMR vs. ESD for early Barrett's neoplasia. An electronic search was conducted in MEDLINE, Central Cochrane, EMBASE, and LILACS until November 2023. Studies comparing ESD vs. EMR in the treatment of patients with early Barrett's neoplasia were included. This study was performed according to the Preferred Report Items for Systematic Reviews and Meta-Analyses guidelines. The ROBIN-I tool was used to analyze the risk of bias and GRADE to measure the quality of the evidence. A total of 9352 patients from 15 observational studies were included. Patients undergoing ESD had significantly higher rates of en-bloc (odds ratio [OR] 25.96, 95% confidence interval [CI] 13.82, 48.74; I2 = 52%; P < 0.00001) and R0 (OR 5.10, 95% CI 3.29, 7.91; I2 = 73%; P < 0.00001) with a higher risk of adverse events, including bleeding, stricture formation, and perforation. In a subgroup analysis of patients who did not receive radiofrequency ablation, ESD had a lower recurrence rate than EMR (OR 0.22, 95% CI 0.05, 0.94; I2 = 88%; P = 0.04). Endoscopic submucosal dissection is more effective than EMR in treating early Barrett's neoplasia at the expense of higher adverse events rates.

Reasons for fear of cancer recurrence after endoscopic treatment of T1 esophageal adenocarcinoma. A semi-structured interview study.

Prior research has shown that patients with early Barrett's neoplasia treated endoscopically report at least the same level of fear for cancer recurrence as patients treated surgically for a more advanced disease stage. The aim of this qualitative study was to gain insight into the reasons why endoscopically treated patients fear or not fear cancer recurrence. Patients treated endoscopically for T1 esophageal adenocarcinoma participated in a semi-structured interview. Patients were asked open questions about their fear of cancer recurrence and presented an a priori list of possible reasons for experiencing or not experiencing fear of cancer recurrence. Data saturation was reached with 12 patients who added 7 new reasons. Reasons that induced fear of cancer recurrence were related to physical symptoms, if cancer was diagnosed as an accidental finding and experiences with cancer in close relations. Endoscopic surveillance was mentioned as a reason for not experiencing fear of cancer recurrence. Patients reduced their fear of cancer recurrence by talking to close relations and seeking distraction. Caregivers reduced patients fear of cancer recurrence by giving adequate information and by showing photo of the treatment and the results of the treatment. According to patients with early Barrett's neoplasia, receiving comprehensible information about the risk of recurrence and potential symptoms that may or may not be indicative of cancer recurrence, and continuing endoscopic surveillance, reduced fear of cancer recurrence. We recommend that healthcare providers discuss fear of cancer recurrence with their patients to enable tailoring information provision to their needs.

Endoscopic Resections for Barrett's Neoplasia: A Long-Term, Single-Center Follow-Up Study.

Background and Objectives: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are both well-established and effective treatments for dysplasia and early cancer in Barrett's esophagus (BE). This study aims to compare the short- and long-term outcomes associated with these procedures in treating Barrett's neoplasia. Materials and Methods: This single-center retrospective cohort study included 95 patients, either EMR (n = 67) or ESD (n = 28), treated for Barrett's neoplasia at Sahlgrenska University Hospital between 2004 and 2019. The primary outcome was the complete (en-bloc) R0 resection rate. Secondary outcomes included the curative resection rate, additional endoscopic resections, adverse events, and overall survival. Results: The complete R0 resection rate was 62.5% for ESD compared to 16% for EMR (p < 0.001). The curative resection rate for ESD was 54% versus 16% for EMR (p < 0.001). During the follow-up, 22 out of 50 patients in the EMR group required additional endoscopic resections (AERs) compared to 3 out of 21 patients in the ESD group (p = 0.028). There were few adverse events associated with both EMR and ESD. In both the stratified Kaplan-Meier survival analysis (Log-rank test, Chi-square = 2.190, df = 1, p = 0.139) and the multivariate Cox proportional hazards model (hazard ratio of 0.988; 95% CI: 0.459 to 2.127; p = 0.975), the treatment group (EMR vs. ESD) did not significantly impact the survival outcomes. Conclusions: Both EMR and ESD are effective and safe treatments for BE neoplasia with few adverse events. ESD resulted in higher curative resection rates with fewer AERs, indicating its potential as a primary treatment modality. However, the survival analysis showed no difference between the methods, highlighting their comparable long-term outcomes.

Safety and efficacy of salvage endoscopic submucosal dissection for Barrett's neoplasia recurrence after radiofrequency ablation.

This study evaluated the safety and efficacy of salvage endoscopic submucosal dissection (ESD) for Barrett's neoplasia recurrence after radiofrequency ablation (RFA). Data from patients at 16 centers were collected for a multicenter retrospective study. Patients who underwent at least one RFA treatment for Barrett's esophagus and thereafter underwent further esophageal ESD for neoplasia recurrence were included. Data from 56 patients who underwent salvage ESD between April 2014 and November 2022 were collected. Immediate complications included one muscular tear (1.8%) treated with stent (Agree classification: grade IIIa). Two transmural perforations (3.6%; treated with clips) and five muscular tears (8.9%; two treated with clips) had no clinical impact and were not considered as adverse events. Seven patients (12.5%) developed strictures (grade IIIa), which were treated with balloon dilation. Histological analysis showed 36 adenocarcinoma, 17 high grade dysplasia, and 3 low grade dysplasia. En bloc and R0 resection rates were 89.3% and 66.1%, respectively. Resections were curative in 33 patients (58.9%), and noncurative in 22 patients (39.3%), including 11 "local risk" (19.6%) and 11 "high risk" (19.6%) resections. At the end of follow-up with a median time of 14 (0-75) months after salvage ESD, and with further endoscopic treatment if necessary (RFA, argon plasma coagulation, endoscopic mucosal resection, ESD), neoplasia remission ratio was 37/53 (69.8%) and the median remission time was 13 (1-75) months. In expert hands, salvage ESD was a safe and effective treatment for recurrence of Barrett's neoplasia after RFA treatment.

Approach to patients with positive vertical margins after endoscopic resection of Barrett's neoplasia.

Approach to patients with positive vertical margins after endoscopic resection of Barrett's neoplasia.

Influence of artificial intelligence on the diagnostic performance of endoscopists in the assessment of Barrett's esophagus: a tandem randomized and video trial.

This study evaluated the effect of an artificial intelligence (AI)-based clinical decision support system on the performance and diagnostic confidence of endoscopists in their assessment of Barrett's esophagus (BE). 96 standardized endoscopy videos were assessed by 22 endoscopists with varying degrees of BE experience from 12 centers. Assessment was randomized into two video sets: group A (review first without AI and second with AI) and group B (review first with AI and second without AI). Endoscopists were required to evaluate each video for the presence of Barrett's esophagus-related neoplasia (BERN) and then decide on a spot for a targeted biopsy. After the second assessment, they were allowed to change their clinical decision and confidence level. AI had a stand-alone sensitivity, specificity, and accuracy of 92.2%, 68.9%, and 81.3%, respectively. Without AI, BE experts had an overall sensitivity, specificity, and accuracy of 83.3%, 58.1%, and 71.5%, respectively. With AI, BE nonexperts showed a significant improvement in sensitivity and specificity when videos were assessed a second time with AI (sensitivity 69.8% [95%CI 65.2%-74.2%] to 78.0% [95%CI 74.0%-82.0%]; specificity 67.3% [95%CI 62.5%-72.2%] to 72.7% [95%CI 68.2%-77.3%]). In addition, the diagnostic confidence of BE nonexperts improved significantly with AI. BE nonexperts benefitted significantly from additional AI. BE experts and nonexperts remained significantly below the stand-alone performance of AI, suggesting that there may be other factors influencing endoscopists' decisions to follow or discard AI advice.

The use of a real-time computer-aided detection system for visible lesions in the Barrett’s esophagus during live endoscopic procedures: a pilot study (with video)

This pilot study evaluated the performance of a recently developed computer-aided detection (CADe) system for Barrett's neoplasia during live endoscopic procedures. Fifteen patients with a visible lesion and 15 without were included in this study. A CAD-assisted workflow was used that included a slow pullback video recording of the entire Barrett's segment with live CADe assistance, followed by CADe-assisted level-based video recordings every 2 cm of the Barrett's segment. Outcomes were per-patient and per-level diagnostic accuracy of the CAD-assisted workflow, in which the primary outcome was per-patient invivo CADe sensitivity. In the per-patient analyses, the CADe system detected all visible lesions (sensitivity 100%). Per-patient CADe specificity was 53%. Per-level sensitivity and specificity of the CADe-assisted workflow were 100% and 73%, respectively. In this pilot study, detection by the CADe system of all potentially neoplastic lesions in Barrett's esophagus was comparable to that of an expert endoscopist. Continued refinement of the system may improve specificity. External validation in larger multicenter studies is planned. (Clinical trial registration number: NCT05628441.).

Rates of Recurrent Intestinal Metaplasia and Dysplasia After Successful Endoscopic Therapy of Barrett's Neoplasia by Endoscopic Mucosal Resection vs Endoscopic Submucosal Dissection and Ablation: A Large North American Multicenter Cohort.

Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort. Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis. A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51-1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56-1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence. Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques.

A deep learning system for detection of early Barrett's neoplasia: a model development and validation study.

Computer-aided detection (CADe) systems could assist endoscopists in detecting early neoplasia in Barrett's oesophagus, which could be difficult to detect in endoscopic images. The aim of this study was to develop, test, and benchmark a CADe system for early neoplasia in Barrett's oesophagus. The CADe system was first pretrained with ImageNet followed by domain-specific pretraining with GastroNet. We trained the CADe system on a dataset of 14 046 images (2506 patients) of confirmed Barrett's oesophagus neoplasia and non-dysplastic Barrett's oesophagus from 15 centres. Neoplasia was delineated by 14 Barrett's oesophagus experts for all datasets. We tested the performance of the CADe system on two independent test sets. The all-comers test set comprised 327 (73 patients) non-dysplastic Barrett's oesophagus images, 82 (46 patients) neoplastic images, 180 (66 of the same patients) non-dysplastic Barrett's oesophagus videos, and 71 (45 of the same patients) neoplastic videos. The benchmarking test set comprised 100 (50 patients) neoplastic images, 300 (125 patients) non-dysplastic images, 47 (47 of the same patients) neoplastic videos, and 141 (82 of the same patients) non-dysplastic videos, and was enriched with subtle neoplasia cases. The benchmarking test set was evaluated by 112 endoscopists from six countries (first without CADe and, after 6 weeks, with CADe) and by 28 external international Barrett's oesophagus experts. The primary outcome was the sensitivity of Barrett's neoplasia detection by general endoscopists without CADe assistance versus with CADe assistance on the benchmarking test set. We compared sensitivity using a mixed-effects logistic regression model with conditional odds ratios (ORs; likelihood profile 95% CIs). Sensitivity for neoplasia detection among endoscopists increased from 74% to 88% with CADe assistance (OR 2·04; 95% CI 1·73-2·42; p<0·0001 for images and from 67% to 79% [2·35; 1·90-2·94; p<0·0001] for video) without compromising specificity (from 89% to 90% [1·07; 0·96-1·19; p=0·20] for images and from 96% to 94% [0·94; 0·79-1·11; ] for video; p=0·46). In the all-comers test set, CADe detected neoplastic lesions in 95% (88-98) of images and 97% (90-99) of videos. In the benchmarking test set, the CADe system was superior to endoscopists in detecting neoplasia (90% vs 74% [OR 3·75; 95% CI 1·93-8·05; p=0·0002] for images and 91% vs 67% [11·68; 3·85-47·53; p<0·0001] for video) and non-inferior to Barrett's oesophagus experts (90% vs 87% [OR 1·74; 95% CI 0·83-3·65] for images and 91% vs 86% [2·94; 0·99-11·40] for video). CADe outperformed endoscopists in detecting Barrett's oesophagus neoplasia and, when used as an assistive tool, it improved their detection rate. CADe detected virtually all neoplasia in a test set of consecutive cases. Olympus.

The impact of endoscopic treatment on health-related quality of life in patients with Barrett's neoplasia: a scoping review.

The objective of this scoping review is to understand the extent, type of evidence, and overall findings in relation to the impact of endoscopic treatment (ET) on health-related quality of life (HR-QoL) in patients with Barrett's dysplasia and early oesophageal cancer. A comprehensive search was conducted for literature between 2001 and 2022 in computerised databases (PubMed, Embase, Cochrane Library, and CINAHL Complete). Additionally, sources of unpublished literature were searched in Google Advanced Search. After title and abstract checking, full-text papers were retrieved. Data were extracted, synthesised, key information tabulated, and a narrative synthesis completed. Six studies were included in the final analysis. Twelve different survey tools were utilised across all studies. Study designs included three randomised controlled studies, two prospective observational studies, and a single retrospective observational study. The average age of study participants ranged from 60.3 to 71.0years. Two studies evaluated HR-QoL as primary outcome measures, but most research evaluated HR-QoL as a secondary outcome. Health domains evaluated in the studies focussed on the biophysical and psychosocial aspects of quality of life. A small number of research studies have been conducted in this area. Due to the heterogeneity and small number of included studies, it was difficult to draw conclusions about the impact of specific ET types on HR-QoL. Overall, there were perceived psychological benefits while undergoing ET. Future research could target specific ET subtypes and measure HR-QoL at baseline and post-procedures in the short and long term.

Quality indicators in Barrett's endoscopy: Best is yet to come.

There is growing interest in establishing quality indicators (QIs) for endoscopic screening and surveillance in Barrett's esophagus (BE). QIs are objective, measurable, and evidence-based metrics that are applicable in a health-care setting to monitor a process and identify key performance indicators (KPIs) to achieve defined goals. In the Barrett's endoscopy setting, QIs can offer a standardized approach to monitor and maintain high-quality endoscopy for BE screening and surveillance that will allow measuring performance of an endoscopist as an individual, a group, or a facility. Since BE is an endoscopically identifiable premalignant condition with histological corroboration, adherence to QIs is paramount for the early and accurate detection of dysplasia and neoplasia. It is the holy grail for BE screening and surveillance. Although several suggested QIs for Barrett's endoscopy exist, issues remain in determining the most appropriate ones. These issues include inconsistent use of terminology, unclear definitions, and a scarcity of studies linking these QIs with relevant patient outcomes, making it difficult for clinicians to understand the concept and clinical importance. Hence, there is an urgent need to determine what should constitute appropriate QIs for Barrett's endoscopy, clearly define items used in the QIs, and identify ways to measure these KPIs. Ultimately, well-defined and validated QIs will contribute to clinically effective, safe, timely, and patient-focused care. In this review, we summarize recent literature and discuss four proposed QIs: (i) neoplasia detection rate; (ii) postendoscopy Barrett's neoplasia; (iii) Barrett's inspection time; and (iv) adherence to the Seattle biopsy protocol.

Healthcare Resource Utilization and Costs Among Patients With Gastroesophageal Reflux Disease, Barrett's Esophagus, and Barrett's Esophagus-Related Neoplasia in the United States.

Background: Gastroesophageal reflux disease (GERD) is a risk factor for Barrett's esophagus (BE) and BE-related neoplasia (BERN). Objectives: This study aimed to evaluate healthcare resource utilization (HRU) and costs associated with GERD, BE, and BERN in the United States. Methods: Adult patients with GERD, nondysplastic BE (NDBE), and BERN (including indefinite for dysplasia [IND], low-grade dysplasia [LGD], high-grade dysplasia [HGD] or esophageal adenocarcinoma [EAC]), were identified from a large US administrative claims database, the IBM Truven Health MarketScan® databases (Q1/2015-Q4/2019). Patients were categorized into the corresponding mutually exclusive EAC-risk/diagnosis cohorts based on the most advanced stage from GERD to EAC using diagnosis codes in medical claims. Disease-related HRU and costs (2020 USD) were calculated for each cohort. Results: Patients were categorized into the following EAC-risk/diagnosis cohorts: 3 310 385 into GERD, 172 481 into NDBE, 11 516 into IND, 4332 into LGD, 1549 into HGD, and 11 676 into EAC. Disease-related annual mean number of inpatient admissions, office visits, and emergency department visits by cohort were 0.09, 1.45, and 0.19 for GERD; 0.08, 1.55, and 0.10 for NDBE; 0.10, 1.92, and 0.13 for IND; 0.09, 2.05, and 0.10 for LGD; 0.12, 2.16, and 0.14 for HGD; and 1.43, 6.27, and 0.87 for EAC. Disease-related annual mean total healthcare costs by cohort were $6955 for GERD, $8755 for NDBE, $9675 for IND, $12 241 for LGD, $24 239 for HGD, and $146 319 for EAC. Discussion: Patients with GERD, BE, and BERN had important HRU and costs, including inpatient admissions and office visits. As patients progressed to more advanced stages, there was substantially higher disease-related resource utilization, with associated costs being 16 times higher in patients with EAC than those with NDBE. Conclusions: Findings suggest the need for early identification of high-risk individuals prior to progression to EAC to potentially improve clinical and economic outcomes in this population.

OGC P03 Staging of Barrett's neoplasia using artificial neural networks, proof of concept study

Abstract Background Endoscopic differentiation between intramucosal and submucosal Barrett's neoplasia has several important implications but remains challenging even for expert endoscopists. Recent studies demonstrated promising results on AI-assisted detection of Barrett's neoplasia, but data on AI-assisted staging is limited. We aimed to develop and validate an AI system for classification of Barrett's neoplasia into intramucosal or submucosal, and compare its performance to expert endoscopists. Methods The model, based on VGG-16 architecture, was trained on 117 images of prospectively collected and annotated Barrett's neoplastic lesions. Rotation and random flip were used for data augmentation. The ground truth was the histological staging of endoscopically resected specimens performed by two pathologists with expertise in Barrett's neoplasia. Images comprised of WLI, enhanced imaging, and magnification views. The model was designed to classify images as either intramucosal (pT1a) or submucosal (pT1b). Performance of the AI system was compared to a group of three experts. Results The AI model was tested on an independent dataset of 90 images. The accuracy, sensitivity and specificity and AUC of the AI model in differentiating between intramucosal and submucosal neoplasia was 70.9%, 72.5%, 65.7%, and 0.781 respectively. Mean accuracy, sensitivity and specificity of experts were 73.3%, 63.3% and 83.3% respectively. Processing speed of the AI system was 5 ms/image. Conclusions This study demonstrates the feasibility of AI-assisted staging of Barrett's neoplasia on endoscopic images. The AI model's performance was comparable to that of experts. More work is needed to further develop this early model and validate its use on real-time video sequences.

OGC P15 Outcomes of Endoscopic Submucosal Dissection for Neoplasia in Barrett's Oesophagus at a Single Tertiary UK Centre

Abstract Background Endoscopic therapies for dysplasia or early cancer in Barrett's Oesophagus have become well established over recent years. Endoscopic Submucosal Dissection (ESD) offers the benefit of en bloc resection and accurate histological staging of lesions which is particularly advantageous in cancers and may eliminate the need for major surgery in selected patients. However, ESD is not widely available in the United Kingdom (UK) and it remains a high risk procedure in Western settings with complication rates of up to 12–27% reported in the literature. Here we report our outcomes at a single tertiary referral centre in the UK. Methods Retrospective review of prospectively maintained database. Results 244 consecutive ESD were carried out in patients with Barrett's neoplasia with visible lesions. The mean age was 69.8 years and 201 patients were male. Median Prague classification was C2M5. The median lesion size was 30mm (range 5–120mm). En bloc resection was achieved in 95.5% of cases. Bleeding, perforation and strictures occurred in 0.82%, 0.82% and 6.97% of cases respectively. These were all managed endoscopically. Histology showed low grade dysplasia in 12 cases, high grade dysplasia in 37 cases, and adenocarcinoma in 192 cases. In the cases of adenocarcinoma, 131 were intramucosal (stage pT1a) and 60 were submucosally invasive (pT1b). Of the submucosally invasive cancers, 36 were SM1 and 24 &amp;gt;SM1. R0 resection was achieved in 74% of cancer cases. Following ESD, 93 patients underwent ablation of residual Barrett's, 25 underwent further endoscopic resection, 21 entered endoscopic surveillance only and 25 patients underwent oesophagectomy. Of the patients who underwent oesophagectomy, 9 were for T1b &amp;gt;SM1 disease, 8 for poor prognostic factors (including poorly differentiated adenocarcinoma, lymphovascular invasion or signet ring cells), 4 for R1 resection at deep margin, 3 for patient choice and 2 for difficult recurrence. Conclusions Our data demonstrates that ESD can be effectively targeted for cancers in patients based on endoscopic assessment by experienced endoscopists with 78.7% of procedures being carried out for early cancers. ESD is safe and effective in the majority of patients and informed the need for surgery in the appropriate group of individuals.

Development and validation of artificial neural networks model for detection of Barrett’s neoplasia: a multicenter pragmatic nonrandomized trial (with video)

The aim of this study was to develop and externally validate a computer-aided detection (CAD) system for the detection and localization of Barrett's neoplasia and assess its performance compared with that of general endoscopists in a statistically powered multicenter study by using real-time video sequences. In phase 1, the hybrid visual geometry group 16-SegNet model was trained by the use of 75,198 images and videos (96 patients) of neoplastic and 1,014,973 images and videos (65 patients) of nonneoplastic Barrett's esophagus. In phase 2, image-based validation was performed on a separate dataset of 107 images (20 patients) of neoplastic and 364 images (14 patients) of nonneoplastic Barrett's esophagus. In phase 3 (video-based external validation) we designed a real-time video-based study with 32 videos (32 patients) of neoplastic and 43 videos (43 patients) of nonneoplastic Barrett's esophagus from 4 European centers to compare the performance of the CAD model with that of 6 nonexpert endoscopists. The primary endpoint was the sensitivity of CAD diagnosis of Barrett's neoplasia. In phase 2, CAD detected Barrett's neoplasia with sensitivity, specificity, and accuracy of 95.3%, 94.5%, and 94.7%, respectively. In phase 3, the CAD system detected Barrett's neoplasia with sensitivity, specificity, negative predictive value, and accuracy of 93.8%, 90.7%, 95.1%, and 92.0%, respectively, compared with the endoscopists' performance of 63.5%, 77.9%, 74.2%, and 71.8%, respectively (P< .05 in all parameters). The CAD system localized neoplastic lesions with accuracy, mean precision, and mean intersection over union of 100%, 0.62, and 0.54, respectively, when compared with at least 1 of the expert markings. The processing speed of the CAD detection and localization were 5 ms/image and 33 ms/image, respectively. To our knowledge, this is the first study describing external (multicenter) validation of AI algorithms for the detection of Barrett's neoplasia on real-time endoscopic videos. The CAD system in this study significantly outperformed nonexpert endoscopists on real-time video-based assessment, achieving >90% sensitivity for neoplasia detection. This result needs to be validated during real-time endoscopic assessment.

Development of Advanced Imaging and Molecular Imaging for Barrett's Neoplasia.

Barrett esophagus (BE) is a precursor to a life-threatening esophageal adenocarcinoma (EAC). Surveillance endoscopy with random biopsies is recommended for early intervention against EAC, but its adherence in the clinical setting is poor. Dysplastic lesions with flat architecture and patchy distribution in BE are hardly detected by high-resolution endoscopy, and the surveillance protocol entails issues of time and labor and suboptimal interobserver agreement for diagnosing dysplasia. Therefore, the development of advanced imaging technologies is necessary for Barrett’s surveillance. Recently, non-endoscopic or endoscopic technologies, such as cytosponge, endocytoscopy, confocal laser endomicroscopy, autofluorescence imaging, and optical coherence tomography/volumetric laser endomicroscopy, were developed, but most of them are not clinically available due to the limited view field, expense of the equipment, and significant time for the learning curve. Another strategy is focused on the development of molecular biomarkers, which are also not ready to use. However, a combination of advanced imaging techniques together with specific biomarkers is expected to identify morphological abnormalities and biological disorders at an early stage in the surveillance. Here, we review recent developments in advanced imaging and molecular imaging for Barrett’s neoplasia. Further developments in multiple biomarker panels specific for Barrett’s HGD/EAC include wide-field imaging systems for targeting ‘red flags’, a high-resolution imaging system for optical biopsy, and a computer-aided diagnosis system with artificial intelligence, all of which enable a real-time and accurate diagnosis of dysplastic BE in Barrett’s surveillance and provide information for precision medicine.

Multicenter Randomized Controlled Trial of Surveillance Versus Endoscopic Therapy for Barrett’s Esophagus With Low-grade Dysplasia: The SURVENT Trial: Study Rationale, Methodology, Innovation, and Implications

Multicenter Randomized Controlled Trial of Surveillance Versus Endoscopic Therapy for Barrett’s Esophagus With Low-grade Dysplasia: The SURVENT Trial: Study Rationale, Methodology, Innovation, and Implications

Agrin Loss in Barrett's Esophagus-Related Neoplasia and Its Utility as a Diagnostic and Predictive Biomarker.

There is an unmet need for identifying novel biomarkers in Barrett's esophagus that could stratify patients with regards to neoplastic progression. We investigate the expression patterns of extracellular matrix (ECM) molecules in Barrett's esophagus and Barrett's esophagus-related neoplasia, and assess their value as biomarkers for the diagnosis of Barrett's esophagus-related neoplasia and to predict neoplastic progression. Gene-expression analyses of ECM matrisome gene sets were performed using publicly available data on human Barrett's esophagus, Barrett's esophagus-related dysplasia, esophageal adenocarcinoma (ADCA) and normal esophagus. Immunohistochemical expression of basement membrane (BM) marker agrin (AGRN) and p53 was analyzed in biopsies of Barrett's esophagus-related neoplasia from 321 patients in three independent cohorts. Differential gene-expression analysis revealed significant enrichment of ECM matrisome gene sets in dysplastic Barrett's esophagus and ADCA compared with controls. Loss of BM AGRN expression was observed in both Barrett's esophagus-related dysplasia and ADCA. The mean AGRN loss in Barrett's esophagus glands was significantly higher in Barrett's esophagus-related dysplasia and ADCA compared with non-dysplastic Barrett's esophagus (NDBE; P < 0.001; specificity = 82.2% and sensitivity = 96.4%). Loss of AGRN was significantly higher in NDBE samples from progressors compared with non-progressors (P < 0.001) and identified patients who progressed to advanced neoplasia with a specificity of 80.2% and sensitivity of 54.8%. Moreover, the combination of AGRN loss and abnormal p53 staining identified progression to Barrett's esophagus-related advanced neoplasia with a specificity and sensitivity of 86.5% and 58.7%. We highlight ECM changes during Barrett's esophagus progression to neoplasia. BM AGRN loss is a novel diagnostic biomarker that can identify patients with NDBE at increased risk of developing advanced neoplasia.

Identification of Barrett's neoplasia: Beyond Seattle protocol

Identification of Barrett's neoplasia: Beyond Seattle protocol