Barrett's Esophagus-related Neoplasia Research Articles

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.

Real-world upper endoscopy utilization patterns among patients with gastroesophageal reflux disease, Barrett esophagus, and Barrett esophagus-related esophageal neoplasia in the United States.

This study fills a gap in literature by providing contemporary real-world evidence on the prevalence of patients with gastroesophageal reflux disease (GERD), Barrett esophagus (BE), and Barrett esophagus-related neoplasia (BERN) and their upper endoscopy utilization patterns in the United States. A retrospective cohort study design was used: adults with GERD, nondysplastic Barrett esophagus (NDBE), and BERN (indefinite for dysplasia [IND], low-grade dysplasia [LGD], high-grade dysplasia [HGD], or esophageal adenocarcinoma [EAC]) were identified from the MarketScan databases (January 01, 2015-December 31, 2019). For each disease stage, prevalence of adults in commercial claims by calendar year, annual number of upper endoscopies per patient and time between upper endoscopies were reported. In 2019, in commercial claims (N = 12,363,227), the annual prevalence rate of GERD was 13.7% and 0.70% for BE/BERN, among which, 87.1% had NDBE, 6.8% had IND, 2.3% had LGD, 1.0% had HGD, and 2.8% had EAC. From 2015-2019, the study included 3,310,385 patients with GERD, 172,481 with NDBE, 11,516 with IND, 4332 with LGD, 1549 with HGD, and 11,676 with EAC. Annual mean number of upper endoscopies was 0.20 per patient for GERD, 0.37 per patient for NDBE, 0.43 for IND, 0.58 for LGD, and 0.87 for HGD. Median time (months) to second upper endoscopy was 38.10 for NDBE, 36.63 for IND, 22.63 for LGD, and 11.90 for HGD. Upper endoscopy utilization increased from GERD to BE to BERN, and time between upper endoscopies decreased as the disease stage progressed from BE to BERN, with less frequent utilization in BERN than what would be expected from guideline recommendations for surveillance.

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.

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.

Multimodal imaging for detection and segmentation of Barrett's esophagus-related neoplasia using artificial intelligence.

Multimodal imaging for detection and segmentation of Barrett's esophagus-related neoplasia using artificial intelligence.

Artificial Intelligence in Surveillance of Barrett's Esophagus.

A study by Waterhouse and colleagues in a previous issue of Cancer Research describes the development and prospective validation of an artificial intelligence approach in conjunction with spectral imaging to enhance endoscopic detection of Barrett's esophagus-related neoplasia. The authors developed a novel spectral endoscope with external optics suitable for routine Barrett's esophagus surveillance with diffuse tissue reflectance to define multispectral data correlated with histopathology. A convolutional neural network was trained on the absis of the spectral signatures acquired as part of a small, prospective clinical trial to distinguish Barrett's esophagus from Barrett's esophagus neoplasia. The results from the study suggest the utility of artificial intelligence for diagnosis of Barrett's esophagus.See related article by Waterhouse et al., Cancer Res 2021;81:3415-25.

Endoscopists' diagnostic accuracy in detecting upper gastrointestinal neoplasia in the framework of artificial intelligence studies.

Estimates on miss rates for upper gastrointestinal neoplasia (UGIN) rely on registry data or old studies. Quality assurance programs for upper GI endoscopy are not fully established owing to the lack of infrastructure to measure endoscopists' competence. We aimed to assess endoscopists' accuracy for the recognition of UGIN exploiting the framework of artificial intelligence (AI) validation studies. Literature searches of databases (PubMed/MEDLINE, EMBASE, Scopus) up to August 2020 were performed to identify articles evaluating the accuracy of individual endoscopists for the recognition of UGIN within studies validating AI against a histologically verified expert-annotated ground-truth. The main outcomes were endoscopists' pooled sensitivity, specificity, positive and negative predictive value (PPV/NPV), and area under the curve (AUC) for all UGIN, for esophageal squamous cell neoplasia (ESCN), Barrett esophagus-related neoplasia (BERN), and gastric adenocarcinoma (GAC). Seven studies (2 ESCN, 3 BERN, 1 GAC, 1 UGIN overall) with 122 endoscopists were included. The pooled endoscopists' sensitivity and specificity for UGIN were 82 % (95 % confidence interval [CI] 80 %-84 %) and 79 % (95 %CI 76 %-81 %), respectively. Endoscopists' accuracy was higher for GAC detection (AUC 0.95 [95 %CI 0.93-0.98]) than for ESCN (AUC 0.90 [95 %CI 0.88-0.92]) and BERN detection (AUC 0.86 [95 %CI 0.84-0.88]). Sensitivity was higher for Eastern vs. Western endoscopists (87 % [95 %CI 84 %-89 %] vs. 75 % [95 %CI 72 %-78 %]), and for expert vs. non-expert endoscopists (85 % [95 %CI 83 %-87 %] vs. 71 % [95 %CI 67 %-75 %]). We show suboptimal accuracy of endoscopists for the recognition of UGIN even within a framework that included a higher prevalence and disease awareness. Future AI validation studies represent a framework to assess endoscopist competence.

Standalone performance of artificial intelligence for upper GI neoplasia: a meta-analysis

ObjectiveArtificial intelligence (AI) may reduce underdiagnosed or overlooked upper GI (UGI) neoplastic and preneoplastic conditions, due to subtle appearance and low disease prevalence. Only disease-specific AI performances have been reported,...

Endoscopic submucosal dissection (ESD) for Barrett's esophagus (BE)-related early neoplasia after standard endoscopic management is feasible and safe.

Background and study aims There is little data on the feasibility and safety of endoscopic submucosal dissection (ESD) as a salvage treatment for Barrett’s esophagus (BE)-related neoplasia after standard endoscopic treatments. Patients and methods A multicenter retrospective analysis on patients who underwent ESD for BE was performed. The primary endpoint was effectiveness of obtaining en-bloc resection in salvage as compared to non-salvage treatments. Results Median age was 71 (IQR 55 – 79) years. Twelve (37%) of 32 patients underwent salvage ESD. Median resection time was 100 (IQR 60 – 136) minutes. En-bloc resection was achieved in 31 patients (97 %). Complete R0 resection was obtained in 75 % in the salvage group and 80 % in the non-salvage group ( P = 1.00). In seven patients (22 %), the pre-ESD diagnosis was upgraded on post-ESD histopathology (1 low-grade dysplasia to high grade dysplasia [HGD], 4 HGD to early esophageal carcinoma (EAC), and 2 intramucosal EAC to invasive EAC). No perforations occurred in either group. Two late adverse events occurred, both in the salvage group ( P = 0.133). Delayed bleeding occurred in a patient who had just resumed warfarin and stricture occurred in a patient who had a circumferential resection requiring serial dilation and stent placement. Conclusions Our cohort study demonstrated that ESD as salvage therapy for BE related neoplasia is feasible and safe, achieving similar high rates of en-bloc resection and complete R0 resection as in treatment-naïve patients. Referral to an expert center performing ESD should be considered for patients with recurrence or progression following endoscopic mucosal resection or ablation therapy.

Minichromosomal Maintenance Component Complex 5 (MCM5) as a Marker of Barrett's Esophagus-Related Neoplasia: A Feasibility Study.

The endoscopic detection of esophageal cancer is suboptimal in both patients referred with dyspeptic symptoms and those enrolled in Barrett's surveillance programs. MCM5 expression in cells collected from gastric fluid may be correlated with the presence of dysplasia or adenocarcinoma. Analysis of this biomarker may improve the detection of cancer. Sixty-one patients were enrolled at a single UK referral center. From each patient, 5-10ml of gastric fluid was aspirated endoscopically. Patients were categorized according to their histology, normal, non-dysplastic Barrett's (NDBE), high-grade dysplastic Barrett's (HGD), and esophageal adenocarcinoma (EAC). All histology was confirmed by Seattle protocol biopsies or endoscopic mucosal resection. Samples were centrifuged, and the cell pellet was lysed. MCM5 expression levels were quantified using a proprietary immunoassay. The mean MCM5 expression was compared between groups by Kruskal-Wallis test. ROC curves were also used to assess diagnostic utility. The mean expression of MCM5 increases as patients progress from a normal esophagus to NDBE, HGD, and EAC (14.4; 49.8; 112.3; and 154.1, respectively). There was a significant difference in the MCM5 expression of patients with a normal esophagus compared to those with EAC (p = 0.04). There was a trend toward higher MCM5 expression in patients with EAC compared to those with NDBE (p = 0.34). MCM5 expression was a fair discriminator (AUC 0.70 [95% CI 0.57-0.83]) between patients without neoplasia (normal and NDBE) and those with early neoplasia (HGD and EAC). MCM5 expression in gastric fluid samples can differentiate patients with a histologically normal esophagus compared to those with early adenocarcinoma. Larger, powered studies are needed to assess whether it can be used to differentiate those with HGD from NDBE.

An Interactive Web-Based Educational Tool Improves Detection and Delineation of Barrett’s Esophagus–Related Neoplasia

Endoscopic detection of early Barrett's esophagus-related neoplasia (BORN) is a challenge. We aimed to develop a web-based teaching tool for improving detection and delineation of BORN. We made high-definition digital videos during endoscopies of patients with BORN and non-dysplastic Barrett's esophagus. Three experts superimposed their delineations of BORN lesions on the videos using special tools. In phase one, 68 general endoscopists from 4 countries assessed 4 batches of 20 videos. After each batch, mandatory feedback compared the assessors' interpretations with those from experts. These data informed the selection of 25 videos for the phase 2 module, which was completed by 121 new assessors from 5 countries. A 5-video test batch was completed before and after scoring of the four 5-video training batches. Mandatory feedback was as in phase 1. Outcome measures were scores for detection, delineation, agreement delineation, and relative delineation of BORN. A linear mixed-effect model showed significant sequential improvement for all 4 outcomes over successive training batches in both phases. In phase 2, median detection rates of BORN in the test batch increased by 30% (P < .001) after training. From baseline to the end of the study, there were relative increases in scores of 46% for detection, 129% for delineation, 105% for agreement delineation, and 106% for relative delineation (all, P < .001). Scores improved independent of assessors' country of origin or level of endoscopic experience. We developed a web-based teaching tool for endoscopic recognition of BORN that is easily accessible, efficient, and increases detection and delineation of neoplastic lesions. Widespread use of this tool might improve management of Barrett's esophagus by general endoscopists.

PS02.062: CONFOCAL LASER ENDOMICROSCOPY IN THE ASSESSMENT OF PERSISTENT/RECURRENT INTESTINAL METAPLASIA/NEOPLASIA AFTER ENDOSCOPIC TREATMENT OF BORN

Abstract Background Patients after endoscopic treatment of Barrett's esophagus related neoplasia (BORN) should undergo regular endoscopic surveillance with biopsies to detect recurrent intestinal metaplasia (IM) or neoplasia (N). Probe-based confocal laser endomicroscopy (pCLE) offers detailed examination of cellular structures and may examine larger areas compared to standard biopsy. Methods A single center, prospective, controlled and pathologist-blinded (still ongoing) study in patients undergoing surveillance endoscopy after endoscopic treatment of BORN. pCLE images were obtained from the neo-Z-line (in few cases including macroscopically visible tongues), the cardia and the esophagus. Thereafter, standard biopsies were taken and sent for histopathological analysis (minimally 4 biopsies from macroscopically normal neo-Z-line, 2 biopsies from the cardia and the esophagus and targeted biopsies from visible abnormalities, if present). Results We examined 34 patients, from these 14 patients (41%) had the initial diagnosis of low-grade intraepithelial neoplasia (LGIN), 8 patients (24%) had high-grade intraepithelial neoplasia (HGIN) and 12 patients (35%) had an early adenocarcinoma (EAC). Three patients (9%) underwent endoscopic resection (ER), in 18 patients (53%) we performed ER or dissection of all visible lesions followed by radiofrequency ablation (RFA), and 13 patients (38%) had RFA as a single treatment modality. Persistent/recurrent IM was detected only at the level of neo-Z-line in 8 patients (24%, 8/34 pts) by both methods. pCLE but not biopsies detected persistent/recurrent IM in 2 patients (6%, 2/34), another 2 patients had IM present in biopsies but not in pCLE. pCLE diagnosed one patient with recurrent LGIN in a macroscopic visible tongue arising from neo-Z-line, which was not confirmed in biopsies (there was only agreement in persistent IM detected by both methods). Sensitivity and specificity of pCLE in detection of persistent/recurrent IM was 80% (95% CI 44–98) and 92% (95% CI 73–99), respectively, with a positive predictive value of 80% (95% CI 51–94) and a negative predictive value of 92% (95% CI 76–98). Agreement of pCLE and histopathological findings was 88%. Conclusion pCLE seems comparable to standard biopsies in detection of persistent/recurrent IM after endoscopic treatment of BORN. Nevertheless, these results need to be confirmed in a larger cohort of patients. Disclosure All authors have declared no conflicts of interest.

Radiofrequency ablation for Barrett's esophagus-related neoplasia.

Barrett's esophagus (BE) is a premalignant condition associated with increased risk of developing esophageal adenocarcinoma. In the past, BE patients with high-grade intraepithelial neoplasia (IEN) or early adenocarcinoma (EAC) were indicated for esophagectomy. With the recent advance in endoscopy, endoscopic techniques have surpassed esophagectomy in the treatment of Barrett's esophagus-related neoplasia and minimized the treatment-related morbidity. Patients with IEN are candidates for endoscopic treatment - endoscopic mucosal resection (ER) of visible lesions and/or ablation therapy of flat Barrett's mucosa. ER combined with radiofrequency ablation (RFA) is now considered as a gold standard for treatment of patients with early Barrett's cancer. RFA is currently the most effective method of ablation used in the treatment of low-grade intraepithelial neoplasia/high-grade intraepithelial neoplasia without visible lesions and for ablation of residual Barrett's mucosa following ER/ESD of EAC or HGIN aiming to achieve complete eradication of Barrett's surface and thus, decreasing the risk of recurrent dysplasia or cancer. The rates of complete remission of neoplasia and metaplasia after completion of endoscopic treatment are 81-92.6% and 75-88.2%, respectively. The aim of this article is to review the principles, techniques, indications, efficacy and safety of this ablative method and surveillance of patients after successful treatment with RFA.

Role of confocal laser endomicroscopy in patients with early esophageal neoplasia.

Probe-based confocal laser endomicroscopy (pCLE) enables real-time histopathological assessment during endoscopic procedures to evaluate epithelial and subepithelial structures with a 1000x magnification. It may be used in various localizations not only in the digestive tract, but its role in clinical practice is still a matter of discussion. The main advantages of pCLE compared to standard biopsies may be: 1) real-time diagnosis; 2) which may be done by the endoscopist; and 3) a larger evaluated area compared to standard biopsies. In theory, pCLE has the potential to eliminate the need for biopsy. However, pCLE cannot replace standard biopsies at this time, among others, standard forceps biopsies are presently more cost-effective. pCLE may be used to enhance the diagnostic arsenal and improve mucosal visualization and evaluation in patients with Barrett's esophagus (BE), with visible esophageal lesions and in patients undergoing surveillance endoscopy after endoscopic treatment of BE related neoplasia. pCLE requires sufficient training and use of validated classifications systems. At present, the majority of endoscopic centers do not use pCLE routinely and no guidelines recommend its routine use for patients with different esophageal diseases, although pCLE is (in selected indications) reimbursed in some countries. This article describes the principle and performance of pCLE and reviews its use in patients with BE and early esophageal neoplasia.

Quality indicators for EUS.

EUS has become integral to the diagnosis and staging of GI and mediastinal mass lesions and conditions. EUS-guided FNA (EUS-FNA) allows the endoscopist to obtain tissue or fluid for cytologic and chemical analysis, adding to the procedure's utility. Furthermore, the recent development of EUS-guided core biopsy techniques enables his-tologic sampling in selected cases and for obtaining tissue for molecular analysis in neoadjuvant and palliative settings. The clinical effectiveness of EUS and EUS-FNA depends on the judicious use of these techniques.

P-0132 - Is a Complete Remission of Intestinal Metaplasia a Suitable Endpoint in Patients Undergoing Radiofrequency Ablation (RFA)? Long-Term Results of RFA Treatment in 62 Consecutive Patients

Introduction: Radiofrequency ablation (RFA) in combination with endoscopic resection (ER) is a method of choice for treatment of early esophageal neoplasia. Complete remission of intestinal metaplasia (CR-IM) and complete remission of dysplasia (CR-D) are commonly used as the endpoints of successful treatment. The relevance of CR-IM (in patients with macroscopically normal neo-Z-line) has recently been challenged. Methods: The aim of this prospective, single center study was to assess the long-term efficacy of RFA. Main outcome measurements were complete remission of intestinal metaplasia (CR-IM) or dysplasia (CR-D) in patients with/without a complete macroscopic eradication of Barrett's esophagus and recurrence rate of IM and dysplasia. Conover one-way analysis was used to calculate the risk factors for recurrence of intestinal metaplasia. Results: The study involved 62 consecutive patients (mean age 62, range 25-86; 55 males and 7 females) undergoing endoscopic treatment for esophageal neoplasia in our center during 2009–2013. Sixty patients were diagnosed with Barrett's esophagus related neoplasia, the remaining 2 patients had squamous neoplasia. The median follow-up was 25 months (range 3-60). In 19 patients (31%), RFA was a single treatment modality while in 43 patients (69%), RFA was combined with endoscopic resection or dissection of a visible lesion The indications for endoscopic treatment were as follows: early adenocarcinoma (EAC): 23 (37,1%), early squamous carcinoma (ESC): 2 (3,2%), high-grade intraepithelial neoplasia (HGIN): 20 (32,3%), low-grade intraepithelial neoplasia (LGIN): 17 (27,4%). A total of 117 RFA treatment sessions were performed (37 with HALO 360, 80 with HALO 90). The median number of treatment sessions per patient (ER + RFA) was 2 (1-6). CR-IM and CR-D were achieved in 69% (95% CI 61-81%) and 89% (95% CI 85-97%), respectively. In 80% of patients without CR-IM, the neo-Z-line was completely normal without macroscopically visible islands or tongues of metaplastic mucosa. During the follow-up, there were 6 recurrences at the level of neo-Z-line (out of 33 patients with BE with follow up of at least 18 months after finishing the treatment; 18%) of intestinal metaplasia. In 5 of these patients, the neo-Z-line was macroscopically normal. Low-grade dysplasia (within the Z-line) recurred in 2 patients (5%). High-grade dysplasia and/or carcinoma have not recurred. The risk factors for recurrence of intestinal metaplasia were male sex, younger age and diagnosis of cancer. We did not detect buried glands beneath the new neosquamous epithelium in any patient. Conclusion: Treatment of BE with RFA results in CR-D and CR-IM in a high proportion of patients with a low recurrence rate. A majority of patients without CR-IM or with a recurrence of IM have macroscopically normal neo-Z-line. CR-IM and a recurrence of IM might not be clinically relevant endpoints in patients with macroscopically normal neo-Z-line.

Tu1340 Recurrence After Successful Radiofrequency Ablation for Barrett's Related Neoplasia Is More Likely in Males: Data From the United Kingdom Patient Registry

Barrett's esophagus (BE) is the pre-cursor to eosophageal adenocarcinoma (EAC). BE is more prevalent in males. Combined endoscopic mucosal resection (EMR) for visible lesions followed by Radiofrequency ablation (RFA) have become first line treatments for patients with BE related neoplasia. Recurrence after successful treatment can occur in up to 25% of cases.

In vivo endomicroscopy improves detection of Barrett's esophagus–related neoplasia: a multicenter international randomized controlled trial (with video)

Confocal laser endomicroscopy (CLE) enables in vivo microscopic imaging of the GI tract mucosa. However, there are limited data on endoscope-based CLE (eCLE) for imaging Barrett's esophagus (BE). To compare high-definition white-light endoscopy (HDWLE) alone with random biopsy (RB) and HDWLE + eCLE and targeted biopsy (TB) for diagnosis of BE neoplasia. Multicenter, randomized, controlled trial. Academic medical centers. Adult patients with BE undergoing routine surveillance or referred for early neoplasia. Patients were randomized to HDWLE + RB (group 1) or HDWLE + eCLE + TB (group 2). Real-time diagnoses and management plans were recorded after HDWLE in both groups and after eCLE in group 2. Blinded expert pathology diagnosis was the reference standard. Diagnostic yield, performance characteristics, clinical impact. A total of 192 patients with BE were studied. HDWLE + eCLE + TB led to a lower number of mucosal biopsies and higher diagnostic yield for neoplasia (34% vs 7%; P < .0001), compared with HDWLE + RB but with comparable accuracy. HDWLE + eCLE + TB tripled the diagnostic yield for neoplasia (22% vs 6%; P = .002) and would have obviated the need for any biopsy in 65% of patients. The addition of eCLE to HDWLE increased the sensitivity for neoplasia detection to 96% from 40% (P < .0001) without significant reduction in specificity. In vivo CLE changed the treatment plan in 36% of patients. Tertiary-care referral centers and expert endoscopists limit generalizability. Real-time eCLE and TB after HDWLE can improve the diagnostic yield and accuracy for neoplasia and significantly impact in vivo decision making by altering the diagnosis and guiding therapy. ( NCT01124214.).

Esophageal resection for high-grade dysplasia and intramucosal carcinoma: When and how?

High-grade dysplasia (HGD) and intramucosal carcinoma (IMC) in the setting of Barrett's esophagus have traditionally been treated with esophagectomy. However, with the advent of endoscopic mucosal resection and endoscopic ablative therapies, endoscopic therapy at centers with expertise is now an established treatment of Barrett's-esophagus-related neoplasia, including HGD and IMC. Esophagectomy is today reserved for more selected cases with submucosal invasion, evidence for lymph node metastasis, or unsuccessful endoscopic therapy.

Total Barrett eradication: Is it ready for prime time?

This special issue of Endoscopy is dedicated to the subject of total Barrett eradication, that is the complete removal of Barrett esophagus and asso− ciated neoplasia by endoscopic resection and/or endoscopic ablation techniques. Many leading experts in the field have contributed to this im− portant issue. Drs. Shaheen and Spechler discuss the relevant methodological issues and pitfalls in studies of Barrett esophagus eradication [1], Drs. Curvers and Bansal offer recommendations for the endoscopic work−up of patients with Barrett esophagus−related neoplasia (BERN) [2], and Drs. Odze and Lauwers clearly describe how pre− and post−treatment histology should be evaluat− ed [3]. Subsequently, leaders in the field of thera− peutic endoscopy discuss the different available endoscopic treatment modalities for BERN: en− doscopic resection, argon plasma coagulation (APC), cryotherapy, photodynamic therapy (PDT), and radiofrequency ablation (RFA) [4 ± 7]. Finally, Drs. Peters [8] and Falk [9] look into the crystal ball to predict the future of endoscopic treatment of BERN from a surgeon’s and an en− doscopist’s viewpoint, respectively. Why has a special issue of Endoscopy been dedi− cated to this topic? The evidence is now accumu− lating that endoscopic treatment of BERN is safe and effective, suggesting that this approach should be preferred over esophagectomy in se− lected patients [10 ±12]. New endoscopic tools, most recently endoscopic resection and RFA, ap− pear to be effective not only in removing BERN but also in completely eradicating all associated Barrett mucosa in the majority of treated patients [13 ± 16]. As a result, many expert centers have adopted advanced imaging, endoscopic resec− tion, and ablation as their management strategy for BERN. In our opinion, the past five years have yielded a number of very promising advances for our field in the endoscopic diagnosis, staging, and man− agement of BERN. We have moved from an era of “survey most lesions and operate on those with high grade dysplasia and cancer,” to an era where we have the option to “survey all lesions, endoscopically treat selected lesions, and reserve surgery only for patients with invasive cancers involving the submucosa.” We are witnessing a significant paradigm shift ± one that is accompa− nied by new challenges that we must be prepared to address. These challenges include: maintain− ing technical excellence and safety with all pro− cedures, via robust training programs; ensuring that visible lesions are detected and properly staged prior to initiation of an endoscopic treat− ment regimen; preparing the patient for endo− scopic management; evaluating the evidence cri− tically to determine ideal patient selection crite− ria, and which disease states should be treated; and evaluating the financial realities of cost−ef− fectiveness and reimbursement. Regarding technical excellence, endoscopic re− section and ablative therapies for BERN generally encompass multiple endoscopic modalities for diagnosis, staging, and treatment. Done properly, we believe they are highly effective and quite safe for the patient. We need to develop training pro− grams for physicians and our advanced trainees so that currently reported efficacy and safety pro− files are maintained. Extracurricular training courses (see www.endosurgery.eu for examples) aimed at the entire spectrum of endoscopic man− agement are being developed to achieve these objectives. Endoscopic detection and proper staging of pa− tients with BERN prior to therapy, are essential. Most available studies come from expert centers with standardized endoscopic staging algo− rithms, high quality therapeutic interventions, rigorous endoscopic follow−up, and expert histo− pathological evaluation. Respectfully, a general endoscopist may not see as many cases of BERN as endoscopists in expert centers and therefore may not be as likely to recognize the subtle