Early Barrett's Esophagus Neoplasia Research Articles

Computer-aided diagnosis improves characterization of Barrett’s neoplasia by general endoscopists (with video)

Characterization of visible abnormalities in patients with Barrett's esophagus (BE) can be challenging, especially for inexperienced endoscopists. This results in suboptimal diagnostic accuracy and poor interobserver agreement. Computer-aided diagnosis (CADx) systems may assist endoscopists. We aimed to develop, validate, and benchmark a CADx system for BE neoplasia. The CADx system received pretraining with ImageNet and then consecutive domain-specific pretraining with GastroNet, which includes 5 million endoscopic images. It was subsequently trained and internally validated using 1758 narrow-band imaging (NBI) images of early BE neoplasia (352 patients) and 1838 NBI images of nondysplastic BE (173 patients) from 8 international centers. CADx was tested prospectively on corresponding image and video test sets with 30 cases (20 patients) of BE neoplasia and 60 cases (31 patients) of nondysplastic BE. The test set was benchmarked by 44 general endoscopists in 2 phases (phase 1, no CADx assistance; phase 2, with CADx assistance). Ten international BE experts provided additional benchmark performance. Stand-alone sensitivity and specificity of the CADx system were 100% and 98% for images and 93% and 96% for videos, respectively. CADx outperformed general endoscopists without CADx assistance in terms of sensitivity (P= .04). Sensitivity and specificity of general endoscopists increased from 84% to 96% and 90% to 98% with CAD assistance (P< .001). CADx assistance increased endoscopists' confidence in characterization (P< .001). CADx performance was similar to that of the BE experts. CADx assistance significantly increased characterization performance of BE neoplasia by general endoscopists to the level of expert endoscopists. The use of this CADx system may thereby improve daily Barrett surveillance.

Clinical Relevance of Random Biopsies From the Esophagogastric Junction After Complete Eradication of Barrett’s Esophagus is Low

Although random histological sampling from the esophagogastric junction (EGJ) after complete eradication of Barrett's esophagus (BE) is recommended, its clinical relevance is questionable. This study aimed to assess the incidence and long-term outcomes of findings from random EGJ biopsies in a nationwide cohort with long-term follow-up. We included all patients with successful endoscopic eradication therapy (EET), defined as complete endoscopic eradication of all visible BE (CE-BE), for early BE neoplasia from the Dutch registry. Patients were treated and followed-up in 9 expert centers according to a joint protocol. Outcomes included the incidence of intestinal metaplasia (IM) at the EGJ (EGJ-IM) and the association between IM and visible (dysplastic) BE recurrence. A total of 1154 patients were included with a median follow-up of 43 months (interquartile range, 22-69 months). At the time of CE-BE, persisting EGJ-IM was found in 7% of patients (78/1154), which was reproduced during further follow-up in 46% of patients (42/78). No significant association existed between persisting EGJ-IM at CE-BE and recurrent non-dysplastic or dysplastic BE (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.63-2.13 and HR, 0.73; 95% CI, 0.17-3.06, respectively). Among patients with no EGJ-IM at the time of CE-BE (1043/1154; 90%), EGJ-IM recurred in 7% (72/1043) after a median of 21 months (interquartile range, 15-36 months), and was reproduced during further follow-up in 26% of patients (19/72). No association was found between recurrent EGJ-IM and non-dysplastic or dysplastic recurrence (HR, 1.18; 95% CI, 0.67-2.06 and HR, 0.27; 95% CI, 0.04-1.96, respectively). Because EGJ-IM was not associated with a higher risk for recurrent disease, we recommend to consider abandoning random EGJ sampling after successful EET, under the condition that care is provided in expert centers, and the esophagus, including the EGJ, is carefully inspected (Netherlands Trial Register, NL7309).

Development and External Validation of a Model to Predict Complex Treatment After Radiofrequency Ablation for Barrett’s Esophagus With Early Neoplasia

Endoscopic eradication therapy for Barrett's esophagus (BE)-related neoplasia is safe and leads to complete eradication in the majority of patients. However, a subgroup will experience a more complex treatment course with a risk for failure or disease progression. Early identification of these patients may improve patient counseling and treatment outcomes. We aimed to develop a prognostic model for a complex treatment course. We collected data from a nationwide registry that captures outcomes for all patients undergoing endoscopic eradication therapy for early BE neoplasia. A complex treatment course was defined as neoplastic progression, treatment failure, or the need for endoscopic resection during the radiofrequency ablation treatment phase. We developed a prognostic model using logistic regression. We externally validated our model in an independent registry. A total of 1386 patients were included, of whom 78 (6%) had a complex treatment course. Our model identified patients with a BE length of 9 cm or longer with a visible lesion containing high-grade dysplasia/cancer, and patients with less than 50% squamous conversion after radiofrequency ablation were identified as high risk for a complex treatment. This applied to 8% of the study population and included 93% of all treatment failures and 76% of all patients with advanced neoplastic progression. The model appeared robust in multiple sensitivity analyses and performed well in external validation (area under the curve, 0.84). We developed a prognostic model that identified patients with a BE length of 9 cm or longer and high-grade dysplasia/esophageal adenocarcinoma and those with poor squamous regeneration as high risk for a complex treatment course. The good performance in external validation suggests that it may be used in clinical management (Netherlands Trial Register: NL7039).

Comparative Study of Conventional and Ultrahigh-resolution Optical Coherence Tomography Imaging in Esophageal Neoplasia

Early diagnosis of esophageal cancer can be enhanced by the application of optical coherence tomography (OCT) to gastrointestinal endoscopy. One of the most salient examples is the use of OCT to augment the detection of dysplasia during Barrett's esophagus (BE) surveillance, the established precursor to esophageal adenocarcinoma (EAC). 1 Reid BJ Li X Galipeau PC et al. Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis. Nat Rev Cancer. 2010; 10: 87-101https://doi.org/10.1038/nrc2773 Crossref PubMed Scopus (303) Google Scholar , 2 Pohl H Welch HG The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005; 97: 142-146https://doi.org/10.1093/jnci/dji024 Crossref PubMed Scopus (1069) Google Scholar A previously commercially available balloon-based imaging catheter system, also known as volumetric laser endomicroscopy (VLE), was designed to provide circumferential esophageal imaging at the time of endoscopy. The VLE system uses a 1300 nm wavelength-swept laser and provides images with an axial resolution of 7 µm up to a depth of 3 mm. VLE is capable of resolving microarchitectural features associated with early neoplasia in BE including irregular glandular morphology and increased surface signal intensity. 3 Leggett CL Gorospe EC Chan DK et al. Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus. Gastrointest Endosc. 2016; 83: 880-888.e2https://doi.org/10.1016/j.gie.2015.08.050 Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Scoring systems that incorporate these features are associated with a sensitivity of 76-83% and specificity of 71-79% in the diagnosis of BE neoplasia. 3 Leggett CL Gorospe EC Chan DK et al. Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus. Gastrointest Endosc. 2016; 83: 880-888.e2https://doi.org/10.1016/j.gie.2015.08.050 Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar , 4 Swager AF Tearney GJ Leggett CL et al. Identification of volumetric laser endomicroscopy features predictive for early neoplasia in Barrett’s esophagus using high-quality histological correlation. Gastrointest Endosc. 2017; 85: 918-926.e7https://doi.org/10.1016/j.gie.2016.09.012 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Similarly, esophageal OCT has been used in the diagnosis and staging of squamous cell carcinoma (ESCC) where layer effacement predicts the depth of invasion. 5 Trindade AJ Benias PC Inamdar S et al. Use of volumetric laser endomicroscopy for determining candidates for endoscopic therapy in superficial esophageal squamous cell carcinoma. United European Gastroenterol J. 2018; 6: 838-845https://doi.org/10.1177/2050640618761701 Crossref PubMed Scopus (5) Google Scholar In the last decade, ultra-high resolution (UHR) OCT systems that operate at 800 nm and achieve an axial resolution closer to 2.5 µm have been developed. Our group previously described a super-achromatic OCT capsule designed for UHR esophageal imaging. 6 Li K Liang W Mavadia-Shukla J et al. Super-achromatic optical coherence tomography capsule for ultrahigh-resolution imaging of esophagus. J Biophotonics. 2019; 12e201800205https://doi.org/10.1002/jbio.201800205 Crossref PubMed Scopus (16) Google Scholar In the present study, we compare the imaging capability of UHR OCT to VLE in distinguishing microarchitectural features associated with esophageal neoplasia by imaging ex vivo esophageal resection specimens obtained from patients undergoing clinical endoscopy.

Endoscopic submucosal dissection vs. endoscopic mucosal resection for early Barrett's neoplasia in the West: a retrospective study.

The difference in clinical outcomes after endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for early Barrett's esophagus (BE) neoplasia remains unclear. We compared the recurrence/residual tissue rates, resection outcomes, and adverse events after ESD and EMR for early BE neoplasia. We included patients who underwent EMR or ESD for BE-associated high grade dysplasia (HGD) or T1a esophageal adenocarcinoma (EAC) at eight academic hospitals. We compared demographic, procedural, and histologic characteristics, and follow-up data. A time-to-event analysis was performed to evaluate recurrence/residual disease and a Kaplan-Meier curve was used to compare the groups. 243 patients (150 EMR; 93 ESD) were included. EMR had lower en bloc (43 % vs. 89 %; P < 0.001) and R0 (56 % vs. 73 %; P = 0.01) rates than ESD. There was no difference in the rates of perforation (0.7 % vs. 0; P > 0.99), early bleeding (0.7 % vs. 1 %; P > 0.99), delayed bleeding (3.3 % vs. 2.1 %; P = 0.71), and stricture (10 % vs. 16 %; P = 0.16) between EMR and ESD. Patients with non-curative resections who underwent further therapy were excluded from the recurrence analysis. Recurrent/residual disease was 31.4 % [44/140] for EMR and 3.5 % [3/85] for ESD during a median (interquartile range) follow-up of 15.5 (6.75-30) and 8 (2-18) months, respectively. Recurrence-/residual disease-free survival was significantly higher in the ESD group. More patients required additional endoscopic resection procedures to treat recurrent/residual disease after EMR (EMR 24.2 % vs. ESD 3.5 %; P < 0.001). ESD is safe and results in more definitive treatment of early BE neoplasia, with significantly lower recurrence/residual disease rates and less need for repeat endoscopic treatments than with EMR.

A prospective multicenter study using a new multiband mucosectomy device for endoscopic resection of early neoplasia in Barrett’s esophagus

Early neoplasia in Barrett's esophagus (BE) can be effectively and safely removed by endoscopic resection (ER) using multiband mucosectomy (MBM). This study aimed to document performance of a novel MBM device designed for improved visualization, easier passage of accessories, and better suction power compared with other marketed MBM devices. This international, single-arm, prospective registry in 14 referral centers (Europe, 10; United States, 3; Canada, 1) included patients with early BE neoplasia scheduled for ER. The primary endpoint was successful ER defined as complete resection of the delineated area in 1 procedure. Secondary outcomes were adverse events and procedure time. A total of 332 lesions was included in 291 patients (248 men; mean age, 67 years [standard deviation, 9.6]). ER indication was high-grade dysplasia in 64%, early adenocarcinoma in 19%, lesion with low-grade dysplasia in 11%, and a lesion without definite histology in 6%. Successful ER was reached in 322 of 332 lesions (97%; 95% confidence interval [CI], 94.6%-98.4%). A perforation occurred in 3 of 332 procedures (.9%; 95% CI, .31%-2.62%), all were managed endoscopically, and patients were admitted with intravenous antibiotics during days 2, 3, and 9. Postprocedural bleeding requiring an intervention occurred in 5 of 332 resections (1.5%; 95% CI, .65%-3.48%). Dysphagia requiring dilatation occurred in 11 patients (3.8%; 95% CI, 2.1%-6.6%). Median procedure time was 16 minutes (interquartile range, 12.0-26.0). In expert hands, the novel MBM device proved to be effective for resection of early neoplastic lesions in BE, with successful ER in 97% of procedures. Severe adverse events were rare and were effectively managed endoscopically or conservatively. (Clinical trial registration number: NCT02482701.).

Abstract 3600: Early detection of esophageal adenocarcinoma using near-infrared lectin-based imaging

Abstract Background: Long procedure times and sampling error frequently limit the efficacy of endoscopic surveillance for Barrett's esophagus (BE). Near-infrared (NIR) fluorescence imaging minimizes optical scattering and tissue autofluorescence. We assessed, in an ex vivo setting, the feasibility of using a topically applied NIR dye-labeled lectin for the detection of early neoplasia in BE. Methods: We recruited consecutive patients undergoing endoscopic mucosal resection (EMR) for BE-related early neoplasia. EMR specimens were freshly collected and sprayed at the bedside with a fluorescent lectin and then imaged ex vivo. A maximum of two punch biopsies were collected from each EMR under NIR light guidance. Fluorescence intensity from dysplastic and nondysplastic areas within EMRs were compared and from punch biopsies with different histological grades. Results: We analyzed 29 EMR specimens from 17 patients. Dysplastic regions showed significantly lower fluorescence across whole EMR specimens (P &amp;lt; 0.001). A 41% reduction in fluorescence was found for dysplastic compared to nondysplastic punch biopsies (P &amp;lt; 0.001), with a sensitivity and specificity for dysplasia detection of 80% and 82.9%, respectively. Conclusion: NIR imaging using fluorescently-labeled lectins can distinguish dysplastic from nondysplastic Barrett's mucosa ex vivo. We are currently planning a first-in-human study to validate this imaging platform. Citation Format: Andre A. Neves, Massimiliano Di Pietro, Maria O'Donovan, Dale J. Waterhouse, Sarah E. Bohndiek, Kevin M. Brindle, Rebecca C. Fitzgerald. Early detection of esophageal adenocarcinoma using near-infrared lectin-based imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3600.

Expanding Role of Third Space Endoscopy in the Management of Esophageal Diseases.

OPINION STATEMENT: "Third space" endoscopy, also commonly referred as submucosal endoscopy, is founded on the principle that the deeper layers of the gastrointestinal (GI) tract can be accessed by tunneling in the submucosal space without compromising the integrity of the overlying mucosa. Peroral endoscopic myotomy (POEM), endoscopic submucosal dissection (ESD), and submucosal tunneling endoscopic resection (STER) are innovative techniques within the field of third space endoscopy in the management of esophageal disorders. POEM has become an accepted minimally invasive therapy for achalasia and related motility disorders with excellent short-term results, with early studies yielding similar efficacy to surgical myotomy and increased durability when compared to pneumatic balloon dilation (PBD). Data are needed to establish long-term outcomes with POEM, with particular interest on the incidence of gastroesophageal reflux, which appears to be higher than initially anticipated. ESD, a mature endoscopic resection technique in Asia, has recently gained traction in the West as a viable option for the management of early Barrett's esophagus (BE) neoplasia. Compared to standard endoscopic mucosal resection (EMR), ESD allows the en bloc resection of lesions irrespective of size, which may facilitate histological interpretation and reduce recurrence rates. Large prospective randomized controlled trials are needed to validate the efficacy and safety of this technique and to further define its role in the endoscopic armamentarium in early BE neoplasia. STER is an attractive technique that theoretically permits the resection of subepithelial esophageal tumors (SETs) arising from the deeper GI layers. Initial studies from highly experienced endoscopic centers support its technical feasibility and safety, although these results should be interpreted with caution due to variability arising from small numbers and heterogeneity among studies. Overall, third space endoscopy is an expanding field within endoscopic therapeutics for the treatment of esophageal diseases. While initial results have been very promising, large prospective studies, long-term data, and structured training programs with the establishment of competency parameters are needed before third space endoscopy can be advocated outside of highly specialized centers.

Computer-aided detection of early Barrett’s neoplasia using volumetric laser endomicroscopy

Volumetric laser endomicroscopy (VLE) is an advanced imaging system that provides a near-microscopic resolution scan of the esophageal wall layers up to 3-mm deep. VLE has the potential to improve detection of early neoplasia in Barrett's esophagus (BE). However, interpretation of VLE images is complex because of the large amount of data that need to be interpreted in real time. The aim of this study was to investigate the feasibility of a computer algorithm to identify early BE neoplasia on exvivo VLE images. We used 60 VLE images from a database of high-quality exvivo VLE-histology correlations, obtained from BE patients ± neoplasia (30 nondysplastic BE [NDBE] and 30 high-grade dysplasia/early adenocarcinoma images). VLE features from a recently developed clinical VLE prediction score for BE neoplasia served as input for the algorithm: (1) higher VLE surface than subsurface signal and (2) lack of layering. With this input, novel clinically inspired algorithm features were developed, based on signal intensity statistics and grayscale correlations. For comparison, generic image analysis methods were examined for their performance to detect neoplasia. For classification of the images in the NDBE or neoplastic group, several machine learning methods were evaluated. Leave-1-out cross-validation was used for algorithm validation. Three novel clinically inspired algorithm features were developed. The feature "layering and signal decay statistics" showed the optimal performance compared with the other clinically features ("layering" and "signal intensity distribution") and generic image analyses methods, with an area under the receiver operating characteristic curve (AUC) of .95. Corresponding sensitivity and specificity were 90% and 93%, respectively. In addition, the algorithm showed a better performance than the clinical VLE prediction score (AUC .81). This is the first study in which a computer algorithm for BE neoplasia was developed based on VLE images with direct histologic correlates. The algorithm showed good performance to detect BE neoplasia in exvivo VLE images compared with the performance of a recently developed clinical VLE prediction score. This study suggests that an automatic detection algorithm has the potential to assist endoscopists in detecting early neoplasia on VLE. Future studies on invivo VLE scans are needed to further validate the algorithm.

Endoscopic submucosal dissection for Barrett’s early neoplasia: a multicenter study in the United States

The role of endoscopic submucosal dissection (ESD) in Barrett's early neoplasia is not well defined, with most studies originating from Asia and Europe. We aimed to assess the efficacy, safety, and results of ESD in Barrett's esophagus (BE) with high-grade dysplasia (HGD) and early adenocarcinoma (EAC) across centers in the United States. Multicenter retrospective analysis on 46 patients with BE who underwent ESD for BE-HGD or EAC, or both, between January 2010 and April 2015. The primary endpoint was the rate of en bloc resection. Secondary aims included rate of R0 (complete) and curative resection, a comparison of pre- and post-ESD histology, procedure-related adverse events, and rate of remission at follow-up. Median age was 69 years (range, 42-82 years). The median resected specimen size was 45mm (range, 13-125mm). En bloc and curative resection rates were 96% (44/46) and 70% (32/46), respectively. Most lesions (11/20; 55%) diagnosed as BE-HGD on biopsy were upstaged to intramucosal or invasive EAC on post-ESD histopathology. There were 4 early (<48 hours) adverse events (3 bleeding and 1 perforation), and all were treated endoscopically. Seven patients (15%) developed esophageal strictures that were managed endoscopically. Complete remission of BE neoplasia was found in 100% (32/32) of patients with curative resection at median follow-up of 11 months (range, 2-25 months). This is the largest multicenter series of ESD for early neoplastic BE from the United States. ESD appears to be safe and effective, with high en bloc and curative resection rates in the treatment of early BE neoplasia.

Identification of volumetric laser endomicroscopy features predictive for early neoplasia in Barrett’s esophagus using high-quality histological correlation

Volumetric laser endomicroscopy (VLE) provides a circumferential scan that enables visualization of the subsurface layers of the esophageal wall at 7 μm resolution. The aims of this study were to identify VLE features of Barrett's esophagus (BE) neoplasia and to develop a VLE prediction score. A database of VLE images from endoscopic resection specimens, precisely correlated with histology, from patients with BE with and without neoplasia was used. Features potentially predictive for early BE neoplasia were identified by unblinded evaluation of 25 VLE-histology images. In a learning phase, 20 VLE images with or without BE neoplasia were scored by 2 VLE experts, blinded to histology. A prediction score was created by using multivariable logistic regression analyses and validated by scoring 40 VLE images (50% neoplastic) by using area under receiver operating characteristic (ROC) curve (AUC) analysis. Three VLE features independently predictive for BE neoplasia were identified: (1) lack of layering; (2) higher surface than subsurface signal; (3) presence of irregular, dilated glands/ducts. A VLE neoplasia prediction score was developed with the following: (1) 6 points; (2) 6 or 8 points for equal or higher surface signal; and (3) 5 points. The ROC curve of this prediction score showed an AUC of 0.81 (95% confidence interval, 0.71-0.90). A cut-off value of≥8 was associated with sensitivity and specificity of 83% and 71%, respectively. When high-quality exvivo VLE-histology correlation was used, the VLE features of layering, surface signal, and irregular glands/ducts were independently and significantly associated with BE neoplasia. A VLE prediction score for BE neoplasia was developed and validated, with promising accuracy. (Clinical trial registration number: NCT01862666.).

Single-session endoscopic resection and focal radiofrequency ablation for short-segment Barrett’s esophagus with early neoplasia

The management of early neoplasia in Barrett's esophagus (BE) requires endoscopic resection of visible lesions, followed by radiofrequency ablation (RFA) of the remaining BE. We evaluated the safety and efficacy of combining endoscopic resection and focal RFA in a single endoscopic session in patients with early BE neoplasia. This was a retrospective analysis of patients with early BE neoplasia and a visible lesion undergoing combined endoscopic resection and focal RFA in a single session. Consecutive ablation procedures were performed every 8 to 12 weeks until complete endoscopic and histologic eradication of dysplasia and intestinal metaplasia were reached. Forty patients were enrolled, with a median C1M2 BE segment, a visible lesion with a median diameter of 15mm, and invasive carcinoma in 68% of cases. Endoscopic resection was performed by using the multiband mucosectomy technique in 80% of cases, and the Barrx(90) catheter (Barrx Medical, Sunnyvale, Calif) was used for focal ablation. When an intention-to-treat analysis was used, both complete remission of all neoplasia and intestinal metaplasia were 95% after a median follow-up of 19 months. Stenoses occurred in 33% of cases and were successfully managed with a median number of 2 dilations. In 43% of patients, 1 single-session treatment resulted in complete histologic remission of intestinal metaplasia. Combining endoscopic resection and focal RFA in a single session appears to be effective. Less-aggressive RFA regimens could limit the adverse event rates.

Volumetric laser endomicroscopy in Barrett's esophagus: a feasibility study on histological correlation.

Volumetric laser endomicroscopy (VLE) is a novel balloon-based optical coherence tomography (OCT) imaging technique that may improve detection of early neoplasia in Barrett's esophagus (BE). Most OCT studies lack a direct correlation between histology and OCT images. The aim is to investigate the optimal approach for achieving one-to-one correlation of ex-vivo VLE images of endoscopic resection (ER) specimens with histology. BE patients with and without early neoplasia underwent ER after delineating areas with electrocoagulation markers (ECM). After ER, specimens underwent additional ex-vivo marking with several different markers (ink, pin, Gold Probe) followed by ex-vivo VLE scanning. ER specimens were carefully sectioned into tissue blocks guided by the markers. Histology and VLE slides were considered a match if ≥ 2 markers were visible on both modalities and mucosal patterns aside from these markers matched on both histology and VLE. From 16 ER specimens 120 tissue blocks were sectioned of which 23 contained multiple markers. Fourteen histology-VLE matches were identified. ECMs and ink markers proved to be the most effective combination for matching. The last 6/16 ER specimens yielded 9/14 matches, demonstrating a learning curve due to methodological improvements in marker placement and tissue block sectioning. One-to-one correlation of VLE and histology is complex but feasible. The groundwork laid in this study will provide high-quality histology-VLE correlations that will allow further research on VLE features of early neoplasia in BE.

Third-generation autofluorescence endoscopy for the detection of early neoplasia in Barrett's esophagus: a pilot study

In Barrett's esophagus (BE), second-generation autofluorescence imaging (AFI-II) improves targeted detection of high-grade intra-epithelial neoplasia (HGIN) and early cancer (EC), yet suffers from high false-positive (FP) rates. The newest generation AFI (AFI-III) specifically targets fluorescence in malignant cells and may therefore improve detection of early neoplasia and reduce FP rate. The aim was to compare AFI-III with AFI-II for endoscopic detection of early neoplasia in BE. BE patients with endoscopically inconspicuous neoplasia underwent two diagnostic endoscopies (AFI-II/AFI-III) in a single session. End-points: number of patients and lesions with HGIN/EC detected with AFI-II and AFI-III after white-light endoscopy (WLE) and the value of reinspection of AFI-positive areas with WLE and narrow-band imaging. Forty-five patients were included (38 males, age 65 years). Nineteen patients showed HGIN/EC. AFI-II inspection after WLE increased detection of HGIN/EC from 9 to 15 patients (47 to 79%); AFI-III increased detection from 9 to 17 patients (47 to 89%). WLE plus random biopsies diagnosed 13/19 (68%) HGIN/EC patients. One hundred and four abnormal AFI areas were inspected; 23 (22%) showed HGIN/EC. AFI-II increased detection of HGIN/EC from 10 to 18 lesions (43 to 78%). AFI-III increased detection from 10 to 20 lesions (43-87%). FP rate was 86% for AFI-II and AFI-III. Reinspection with WLE or narrow-band imaging reduced FP rate to 21% and 22%, respectively, but misclassified HGIN/EC lesions as unsuspicious in 54% and 31%, respectively. This first feasibility study on third-generation AFI again showed improved targeted detection of HGIN/EC in BE. However, the results do not suggest AFI-III performs significantly better than conventional AFI-II.

Endoscopic TriModal imaging and biomarkers for neoplasia conjoined: a feasibility study in Barrett's esophagus

In Barrett's esophagus (BE), the normal squamous lining of the esophagus is replaced by specialized columnar epithelium. Endoscopic surveillance with autofluorescence imaging (AFI) and molecular biomarkers have been studied separately to detect early neoplasia (EN) in BE. The combination of advanced-imaging modalities and biomarkers has not been investigated; AFI may help detecting biomarkers as a risk-stratification tool. We retrospectively evaluated a cohort of patients undergoing endoscopy for EN in BE with AFI and correlated five biomarkers (HPP1, RUNX3, p16, cyclin A, and p53) in tissue samples with AFI and dysplasia status. Fifty-eight samples from a previous prospective study were selected: 15 true-positive (TP: AFI-positive, EN), 21 false-positive (FP: AFI-positive, no EN), 12 true-negative (TN1; AFI-negative, no EN in sample), 10 true-negative (TN2: AFI-negative, no EN in esophagus). Methylation-specific RT-PCR was performed for HPP1, RUNX3, p16, and immunohistochemistry for cyclin A, p53. P < 0.05 was considered statistically significant. Bonferroni correction was used for multiple comparisons. P16, cyclin A, p53 correlated with dysplasia (P < 0.01, P = 0.003, P < 0.001, respectively). Increased p16 methylation was observed between TP versus TN2 (P = 0.003) and TN1 versus TN2 (P = 0.04) subgroups, suggesting a field defect. Only p53 correlated with AFI-status (P = 0.003). After exclusion of EN samples, significance was lost. Although correlation with dysplasia status was confirmed for p16, cyclin A and p53, underlining the importance of these biomarkers as an early event in neoplastic progression, none of the investigated biomarkers correlated with AFI status. A larger prospective study is needed to assess the combination of AFI and a larger panel of biomarkers to improve risk stratification in BE.

How Adequate Is Endoscopic Inspection of a Barrett's Esophagus with Early Neoplasia By Expert Endoscopists? An International Multi-Center Study with Complete Histological Correlation of the Whole Barrett's Segment

Background: Endoscopic treatment of high-grade dysplasia (HGD) or intramucosal cancer (IMC) in Barrett's esophagus (BE) is a valid alternative to surgery. Submucosal cancer (SMC), however, has a high risk of lymphatic involvement and should be treated surgically. Many centers treat early BE neoplasia by endoscopic resection (ER) of the most involved area followed by ablation therapy (AT) of the remaining BE. Proper endoscopic work-up is of crucial importance here: SMCs that are not resected but ablated will be missed since AT lacks histological correlation.

Accuracy of Hyperband EUS in the Assessment of Early Neoplasia in Barrett's Esophagus: A Prospective Cohort Study

Rationale: Routine radial EUS has been felt to be inadequate to stage early neoplasia in Barrett's Esophagus (BE). The hyperband (Olympus GF-UM 160) echoendoscope using composite piezo-electric material provides broadband scanning using four different frequencies, resulting in high-resolution ultrasound images. The yield and accuracy of this instrument in the assessment of early neoplasia in BE has not been reported previously. Aim: To assess the accuracy of the GF-UM 160 echoendoscope in the staging of neoplastic lesions arising in BE using endoscopic resection (EMR) specimen pathology as the gold standard in a prospective study. Methods: A prospective cohort of 77 patients with HGD/Carcinoma and BE seen at the Mayo Clinic was studied. All patients underwent a standard protocol assessment with EGD, 4 quadrant biopsies every centimeter. Visible lesions were resected using either the Olympus EMR kit (70%) or the Wilson-Cook Duette Multi-Band mucosectomy system (30%). Staging was performed prior to resection in all patients using the Olympus GF-UM 160 instrument by a single experienced endosonographer. Results: 77 patients were studied. 58 (75%) were males. The median age was 69 years (IQR 61, 76). The pre-procedure diagnosis was HGD in 49 patients (64%) and cancer in the remainder (36%). The median BE segment length was 3 cm (IQR 1, 7). 73% of patients had a visible nodule/mucosal irregularity on EGD. Staging with EUS revealed no abnormality (uT0) in 61 (77%) patients, uT1 disease in 15 (9%) patients (mucosal [uT1a] in 8 patients and submucosal [uT1b] in 7 patients), and uT2 disease in 3 patients (4%). No patients had metastatic lymph nodes. EMR pathology revealed carcinoma in 20 patients (submucosal in 7; mucosal in 13). 44% of the resected lesions contained HGD. 3 of the 13 (23%) mucosal cancers and 2 of 7 (28%) submucosal cancers were correctly staged, with the remaining being under or over staged. 4 patients with submucosal cancer underwent esophagectomy, 2 continued with endoscopic therapy alone and one patient opted for comfort care only. Conclusions: The sensitivity of Hyperband EUS in detecting cancers was 70% with a specificity of 93%. This compares favorably with prior reports of endosonographic identification and staging of early neoplasia in Barrett's esophagus. Hyperband EUS accurately predicted EMR respectability of lesions in all patients. However accuracy of staging superficial cancers as mucosal or submucosal remained limited, when compared to staging following EMR.

Stepwise Radical Endoscopic Resection Is Effective for Complete Removal of Barrett's Esophagus with Early Neoplasia: A Prospective Study

Endoscopic therapy for early neoplasia in Barrett's esophagus (BE) is evolving rapidly. Aim of this study was to prospectively evaluate safety and efficacy of stepwise radical endoscopic resection (ER) of BE containing early neoplasia. Patients with early neoplasia (i.e., high-grade intraepithelial neoplasia or early cancer) in BE < or = 5 cm, without signs of submucosal infiltration or lymph node/distant metastases, were included. Patients underwent resection sessions (cap technique after submucosal lifting) with intervals of 6 wk. Between January 2003 and December 2004, 39 consecutive patients were included. Therapy was discontinued in two patients due to unrelated comorbidity. Complete eradication of early neoplasia was achieved in all 37 treated patients in a median number of three sessions. Complete removal of all Barrett's mucosa was achieved in 33 (89%) patients: 4 patients (all had undergone APC [argon plasma coagulation]) were found to have small isles of Barrett's mucosa underneath neosquamous mucosa. Complications occurred in two out of 88 (2%) ER procedures: one asymptomatic perforation, one delayed bleeding. Symptomatic stenosis occurred in 10 of 39 (26%) patients and was effectively treated by endoscopic bougienage. During a median follow-up of 11 months, no patients died and none had recurrence of neoplasia or Barrett's mucosa. Stepwise radical ER is effective for selected patients with early neoplasia in BE; provides optimal histopathological diagnosis; and may reduce recurrence rate, since all mucosa at risk is effectively removed. Use of APC should be limited to prevent buried Barrett's mucosa. Methods for prevention of stenosis should be developed.

Inter- and Intraobserver Variability in High Resolution Chromoendoscopy with Acetic Acid for the Detection of Intestinal Metaplasia and Early Neoplasia in Barrett's Esophagus

Specialized intestinal metaplasia (SIM) in Barrett's esophagus (BE) embodies the risk of malignant transformation. Optically guided, “smart” biopsies using chromoendoscopy with acetic acid (AA) are a fascinating option in surveillance procedures for BE. Methods: Consecutive patients with GERD, suspicious of SIM or early neoplasia in BE referred to our center were enclosed in this prospective study. They were studied using Fujinon high resolution endoscopes (EG HR485ZW5, EG HR490ZW5). The distal esophagus was sprayed with a solution of 1.5% acetic acid. Esophageal columnar mucosal patterns were characterized after AA spraying: Dotted round pits representing cardiac mucosa (pattern I), villous and ridged surface pattern (pattern II) for SIM and an irregular, distorted mucosal pattern (pattern III) representing neoplasia in SIM. The observed surface patterns were digitally stored on PC. All digitally stored images were reassessed by 6 blinded endoscopists. Intra- and interobserver variations of the investigators were evaluated by using kappa statistics. Results: 394 endoscopic pictures of 96 patients were studied. SIM could be predicted with a sensitivity of 92%, high-grade intraepithelial neoplasia (HGIN) or early mucosal cancer in 89% respectively. The mean kappa for interobserver agreement was 0.959, whereas intraobserver agreement showed a mean kappa of 1.0. Conclusions: High resolution endoscopy with acetic acid is an accurate method for visually predicting SIM and early neoplasia in BE with very low inter- and intraobserver variability.