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

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

Advanced imaging in surveillance of Barrett's esophagus: Is the juice worth the squeeze?

Esophageal cancer is on the rise. The known precursor lesion is Barrett's esophagus (BE). Patients with dysplasia are at higher risk of developing esophageal cancer. Currently the gold standard for surveillance endoscopy involves taking targeted biopsies of abnormal areas as well as random biopsies every 1-2 cm of the length of the Barrett's. Unfortunately studies have shown that this surveillance can miss dysplasia and cancer. Advanced imaging technologies have been developed that may help detect dysplasia in BE. This opinion review discusses advanced imaging in BE surveillance endoscopy and its utility in clinical practice.

Economic value of narrow-band imaging versus white light endoscopy for the diagnosis and surveillance of Barrett's esophagus: Cost-consequence model.

Barrett's esophagus (BE) is an abnormality arising from gastroesophageal reflux disease that can progressively evolve into a sequence of dysplasia and adenocarcinoma. Progression of Barrett's esophagus into dysplasia is monitored with endoscopic surveillance. The current surveillance standard requests random biopsies plus targeted biopsies of suspicious lesions under white-light endoscopy, known as the Seattle protocol. Recently, published evidence has shown that narrow-band imaging (NBI) can guide targeted biopsies to identify dysplasia and reduce the need for random biopsies. We aimed to assess the health economic implications of adopting NBI-guided targeted biopsy vs. the Seattle protocol from a National Health Service England perspective. A decision tree model was developed to undertake a cost-consequence analysis. The model estimated total costs (i.e. staff and overheads; histopathology; adverse events; capital equipment) and clinical implications of monitoring a cohort of patients with known/suspected BE, on an annual basis. In the simulation, BE patients (N = 161,657 at Year 1; estimated annual increase: +20%) entered the model every year and underwent esophageal endoscopy. After 7 years, the adoption of NBI with targeted biopsies resulted in cost reduction of £458.0 mln vs. HD-WLE with random biopsies (overall costs: £1,966.2 mln and £2,424.2 mln, respectively). The incremental investment on capital equipment to upgrade hospitals with NBI (+£68.3 mln) was offset by savings due to the reduction of histological examinations (-£505.2 mln). Reduction of biopsies also determined savings for avoided adverse events (-£21.1 mln). In the base-case analysis, the two techniques had the same accuracy (number of correctly identified cases: 1.934 mln), but NBI was safer than HD-WLE. Budget impact analysis and cost-effectiveness analyses confirmed the findings of the cost-consequence analysis. In conclusion, NBI-guided targeted biopsies was a cost-saving strategy for NHS England, compared to current practice for detection of dysplasia in patients with BE, whilst maintaining at least comparable health outcomes for patients.

Endosheath ultrathin transnasal endoscopy is a cost-effective method for screening for Barrett's esophagus in patients with GERD symptoms.

BACKGROUND AND AIMS: Barrett's esophagus (BE) screening is currently not considered to be cost effective in the general population but may be effective in high-risk subgroups, such as 50-year-old white men with chronic reflux disease (GERD). A new modality for screening is unsedated transnasal endoscopy using endosheath technology (uTNE), which has been shown to be safe and effective in clinical practice. In this study, we determined the cost-utility of uTNE in a high-risk subgroup compared with no screening or screening with standard endoscopy. METHODS: A Markov model was used to simulate screening of 50-year-old white men with symptoms of GERD with either uTNE or standard endoscopy compared with no screening, over a lifetime horizon. Input variables were based on the literature and recent data on uTNE screening for BE. The study was designed from a healthcare payer perspective by using direct costs. Primary outcome measures were costs, quality-adjusted life years (QALYs), and the incremental cost-utility ratio (ICUR) of uTNE and standard endoscopy compared with no screening. Sensitivity analysis was performed for several factors, such as prevalence of BE. RESULTS: Costs of uTNE, standard endoscopy, and no screening were estimated at, $2495, $2957, and $1436, respectively. Compared with no screening, uTNE screening resulted in an overall QALY increase of 0.039 (95% percentile 0.018; 0.063) and an ICUR of $29,446 per QALY gained (95% confidence interval [CI], 18.516-53.091), whereas standard endoscopy compared with no screening resulted in a QALY increase of 0.034 (95% CI, 0.015-0.056) and an ICUR of $47,563 (95% CI, 31,036-82,970). CONCLUSION: Both uTNE and standard endoscopy seem to be cost-effective screening methods in a screening cohort of 50-year-old white men with GERD at a willingness-to-pay cutoff of $50,000.

How to get the most out of costly Barrett's oesophagus surveillance.

Current endoscopic surveillance protocols for Barrett's oesophagus have several limitations, mainly the poor cost-effectiveness and high miss rate. However, there is sufficient evidence that patients enrolled in a surveillance program have better survival chances of oesophageal cancer due to earlier tumor stages at diagnosis compared to patients with de novo diagnosed oesophagus cancer. Risk stratifications aim to identify patients at highest risk of developing adenocarcinoma of the oesophagus; most of them base on the length of the Barrett's segment and the presence of dysplasia. This review discusses prognostic factors and provides practical guidance on how to improve the efficacy and outcome in Barrett's surveillance programs.

Performance characteristics of optical coherence tomography in assessment of Barrett's esophagus and esophageal cancer: systematic review.

Optical coherence tomography (OCT) can generate high-resolution images of the esophagus that allows cross-sectional visualization of esophageal wall layers. We conducted a systematic review to assess the utility of OCT for diagnosing of esophageal intestinal metaplasia (IM; Barrett's esophagus BE)), dysplasia, cancer and staging of early esophageal cancer. English language human observational studies and clinical trials published in PubMed and Embase were included if they assessed any of the following: (i) in-vivo features and accuracy of OCT at diagnosing esophageal IM, sub-squamous intestinal metaplasia (SSIM), dysplasia, or cancer, and (ii) accuracy of OCT in staging esophageal cancer. Twenty-one of the 2,068 retrieved citations met inclusion criteria. In the two prospective studies that assessed accuracy of OCT at identifying IM, sensitivity was 81%-97%, and specificity was 57%-92%. In the two prospective studies that assessed accuracy of OCT at identifying dysplasia and early cancer, sensitivity was 68%-83%, and specificity was 75%-82%. Observational studies described significant variability in the ability of OCT to accurately identify SSIM. Two prospective studies that compared the accuracy of OCT at staging early squamous cell carcinoma to histologic resection specimens reported accuracy of >90%. Risk of bias and applicability concerns was rated as low among the prospective studies using the QUADAS-2 questionnaire. OCT may identify intestinal metaplasia and dysplasia, but its accuracy may not meet recommended thresholds to replace 4-quadrant biopsies in clinical practice. OCT may be more accurate than EUS at staging early esophageal cancer, but randomized trials and cost-effective analyses are lacking.

Systematic assessment with I-SCAN magnification endoscopy and acetic acid improves dysplasia detection in patients with Barrett's esophagus.

Background and study aims Enhanced endoscopic imaging with chromoendoscopy may improve dysplasia recognition in patients undergoing assessment of Barrett's esophagus (BE). This may reduce the need for random biopsies to detect more dysplasia. The aim of this study was to assess the effect of magnification endoscopy with I-SCAN (Pentax, Tokyo, Japan) and acetic acid (ACA) on dysplasia detection in BE using a novel mucosal and vascular classification system. Methods BE segments and suspicious lesions were recorded with high definition white-light and magnification endoscopy enhanced using all I-SCAN modes in combination. We created a novel mucosal and vascular classification system based on similar previously validated classifications for narrow-band imaging (NBI). A total of 27 videos were rated before and after ACA application. Following validation, a further 20 patients had their full endoscopies recorded and analyzed to model use of the system to detect dysplasia in a routine clinical scenario. Results The accuracy of the I-SCAN classification system for BE dysplasia improved with I-SCAN magnification from 69 % to 79 % post-ACA (P = 0.01). In the routine clinical scenario model in 20 new patients, accuracy of dysplasia detection increased from 76 % using a "pull-through" alone to 83 % when ACA and magnification endoscopy were combined (P = 0.047). Overall interobserver agreement between experts for dysplasia detection was substantial (0.69). Conclusions A new I-SCAN classification system for BE was validated against similar systems for NBI with similar outcomes. When used in combination with magnification and ACA, the classification detected BE dysplasia in clinical practice with good accuracy.Trials registered at ISRCTN (58235785).

Volumetric laser endomicroscopy in the management of Barrett's esophagus.

PURPOSE OF REVIEW: The incidence of esophageal adenocarcinoma is on the rise despite widespread appreciation that the precursor lesion is Barrett's esophagus. Studies have shown that some patients known to have Barrett's esophagus develop cancer despite their enrollment in conventional endoscopic surveillance programs. This highlights the need for advanced endoscopic imaging to help identify early neoplasia and prevent its progression to esophageal cancer. Recently, a wide-field, second-generation optical coherence tomography endoscopic platform called volumetric laser endomicroscopy (VLE) was cleared by the Food and Drug Administration and made commercially available for advanced imaging in Barrett's esophagus. RECENT FINDINGS: The current review discusses current literature on VLE imaging in Barrett's esophagus. Based on ex-vivo studies, criteria have been established for identifying Barrett's esophagus-associated neoplasia. In addition, recent studies, case series, and case reports have demonstrated that VLE is well tolerated, efficacious, and can target neoplasia. SUMMARY: VLE is a new advanced imaging platform for Barrett's esophagus with considerable promise to target Barrett's esophagus-associated neoplasia. The following are needed to establish VLE's clinical role: studies showing incremental yield of dysplasia detection using VLE, studies to determine VLE's in-vivo diagnostic accuracy for identifying and classifying Barrett's esophagus-associated neoplasia, and studies on the cost-efficacy of VLE.

Image assessment of Barrett's esophagus using the simplified narrow band imaging classification.

BACKGROUND: A simplified narrow band imaging (NBI) classification has been proposed with the objective of integrating multiple classifications of NBI surface patterns in Barrett's esophagus (BE). Little is known about the impact of the simplified NBI classification on the diagnosis of BE when using high-definition magnification endoscopy with NBI (HM-NBI). This study aimed to evaluate (a) the reproducibility of NBI surface patterns and predicted histology and (b) the diagnostic accuracy of interpreting HM-NBI images by using the simplified NBI classification. METHODS: Two hundred and forty-eight HM-NBI images from macroscopically normal areas in patients with BE were retrieved from endoscopy databases and randomized for review by four endoscopists (two experts, two non-experts). We evaluated inter- and intra-observer agreement of the interpretation of NBI surface patterns and the predicted histology (dysplasia vs. non-dysplasia), as calculated by using κ statistics, and diagnostic values of the prediction. RESULTS: The overall inter-observer agreements were substantial for mucosal pattern (κ = 0.73) and vascular pattern (κ = 0.71), and almost perfect for predicting dysplastic histology (κ = 0.80). The overall intra-observer agreements were almost perfect for mucosal (κ = 0.84) and vascular patterns (κ = 0.86), and predicting dysplastic histology (κ = 0.89). The mean accuracy in predicting dysplastic histology for all reviewers was 95 % (experts: 96.8 %, non-experts: 93.1 %). CONCLUSIONS: The simplified NBI classification has the potential to provide high diagnostic reproducibility and accuracy when using HM-NBI.

Miniprobe EUS in the pretherapeutic assessment of early esophageal neoplasia.

BACKGROUND AND STUDY AIMS: The high-frequency endosonography miniprobe has been advocated prior to endoscopic treatment of superficial esophageal neoplasm. We conducted a retrospective study, which summarized our clinical experience with various miniprobe techniques in the assessment of early squamous cell carcinoma (SCC) and superficial adenocarcinoma on Barrett's mucosa (SAB). PATIENTS AND METHODS: A total of 106 superficial and naive esophageal lesions were included in this series (52 SAB, 54 SCC). The results of the miniprobe staging were compared with pathology in order to determine the accuracy of this technique in differentiating mucosal from submucosal infiltration. Secondary aims were a comparison between the frequencies (20- vs. 30-MHz) and coupling methods (water-filled lumen vs. balloon-sheathed catheter) used. RESULTS: Overall accuracy, sensitivity, and specificity to differentiate T1sm from T1 m tumors were 73.5 %, 62 %, and 76.5 %, respectively. Overdiagnosis occurred in 18.6 % of the lesions. No statistically significant difference was found in the accuracy of the miniprobe staging between the two lesion types (SCC and SAB) ( P = 0.65), and results were significantly poorer in the distal part of the esophagus ( P = 0.00039). No significant difference was found between the two frequencies ( P = 0.51). Water-filled lumen proved to be superior to the balloon-sheathed catheter ( P = 0.015). CONCLUSION: High-frequency miniprobe examination has a limited accuracy in the detection of submucosal invasion in early esophageal cancer. Further improvements in acoustic coupling and ultrasound technique are required to improve the miniprobe accuracy before its implementation into clinical routine.

Clinical impact of conventional endosonography and endoscopic ultrasound-guided fine-needle aspiration in the assessment of patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma who have been referred for endoscopic ablation therapy.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection and photodynamic therapy are exciting, minimally invasive curative techniques that represent an alternative to surgery in patients with Barrett's esophagus and high-grade dysplasia or intramucosal adenocarcinoma. However, there is lack of uniformity regarding which staging method should be used prior to therapy, and some investigators even question whether staging is required prior to ablation. We report our experience with a protocol of conventional endoscopic ultrasound staging prior to endoscopic therapy. PATIENTS AND METHODS: A total of 25 consecutive patients with a diagnosis of high-grade dysplasia or intramucosal adenocarcinoma in Barrett's esophagus who had been referred to the University of Chicago for staging in preparation for endoscopic therapy between March 2002 and November 2004 were included in the study. All 25 patients underwent repeat diagnostic endoscopy and conventional endosonography with a radial echo endoscope. Any suspicious lymph nodes that were detected were sampled using endoscopic ultrasound-guided fine-needle aspiration. RESULTS: Baseline pathology in the 25 patients (mean age 70, range 49-85) revealed high-grade dysplasia in 12 patients and intramucosal carcinoma in 13 patients. Five patients were found to have submucosal invasion on conventional endosonography. Seven patients had suspicious adenopathy, six regional (N1) and one metastatic to the celiac axis (M1a). Fine-needle aspiration confirmed malignancy in five of these seven patients. Based on these results, five patients (20%) were deemed to be unsuitable candidates for endoscopic therapy. CONCLUSIONS: By detecting unsuspected malignant lymphadenopathy, conventional endosonography and endoscopic ultrasound with fine-needle aspiration dramatically changed the course of management in 20% of patients referred for endoscopic therapy of Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma. Based on our results, we believe that conventional endosonography and endoscopic ultrasound with fine-needle aspiration when nodal disease is present should be performed routinely in all patients referred for endoscopic therapy in this setting.

Barrett's esophagus: current and future role of endosonography and optical coherence tomography.

This paper reviews the role of endosonography and optical coherence tomography (OCT) for imaging of Barrett's esophagus (BE). The routine use of endoscopic ultrasound (EUS) to screen patients with BE is neither justified nor cost effective. EUS does appear to have a role in patients who have BE and high-grade dysplasia or intramucosal carcinoma, in whom a non-operative therapy is being contemplated. For patients with a diagnosis of esophageal cancer with or without BE, EUS is superior to computed tomography or magnetic resonance imaging for assessing esophageal wall penetration and for detecting regional lymph node involvement. In its current state, OCT is not yet ready for application in clinical practice. However, given its superior resolution compared with other modalities such as EUS, OCT has great potential as a powerful adjunct to standard endoscopy in surveillance of BE and may enhance the ability of endoscopists to detect high-grade dysplasia at an early stage. With further technical refinement, this technique may become a mainstay in the surveillance of BE and other premalignant conditions of the gastrointestinal tract.

The reticular pattern as a radiographic sign of the Barrett esophagus: an assessment.

A two-part retrospective study was conducted to assess the value of a reticular pattern as a sign of columnar-lined esophagus. Radiographic, endoscopic, and histologic findings were reviewed in 124 patients with known Barrett esophagus; then all barium esophagrams done at our institution during a 3 1/2 month period were reviewed and presence of a reticular pattern was correlated with available endoscopic and histologic data. In patients with known Barrett esophagus, the reticular pattern was found in 26% of double-contrast examinations. Twelve of these patients underwent careful esophageal mapping biopsies: the pattern was in squamous mucosa with ulceration in two, in columnar epithelium with ulceration in six, and in columnar epithelium without ulceration in four. In the group of 314 unselected patients who had double-contrast examinations, the reticular pattern was found in 26 (8%). Thirteen of the 26 had had endoscopy and biopsy: the site of the pattern was located in a squamous carcinoma in one, in squamous epithelium adjacent to squamous carcinoma in three, in squamous epithelium with esophagitis in five (two of whom had columnar mucosa distally), in normal squamous mucosa in one, and in columnar epithelium with esophagitis in three. The reticular pattern is a strong indicator of important esophageal disease, but is not specific for Barrett esophagus.