Volumetric laser endomicroscopy and its application to Barrett's esophagus: results from a 1,000 patient registry.
ABSTRACT: Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.
Project description:Methods and study aims: The incidence of esophageal cancer is rising despite increased surveillance efforts. Volumetric laser endomicroscopy (VLE) is a new endoscopic imaging tool that can allow for targeted biopsy of neoplasia in Barrett's esophagus. We report a series of 6 patients with long-segment Barrett's esophagus ( > 3 cm), who underwent a session of endoscopy with volumetric laser endomicroscopy, after a separate prior session of standard high-definition endoscopy with narrow band imaging (NBI) and random biopsies that did not reveal neoplasia. In all six patients, the first endoscopy was the index endoscopy diagnosing the Barrett's esophagus. All VLE exams were performed within 6 months of the previous endoscopy. In five patients, VLE-targeted biopsy resulted in upstaged disease/diagnosed dysplasia that then qualified the patient for endoscopic ablation therapy. In one patient, VLE localized a focus of intramucosal cancer that allowed for curative endoscopic mucosal resection. This case series shows that endoscopy with VLE can target neoplasia that cannot be localized by high-definition endoscopy with NBI and random biopsies.
Project description:Biopsy surveillance protocols for the assessment of Barrett's esophagus can be subject to sampling errors, resulting in diagnostic uncertainty. Optical coherence tomography is a cross-sectional imaging technique that can be used to conduct volumetric laser endomicroscopy (VLE) of the entire distal esophagus. We have developed a biopsy guidance platform that places endoscopically visible marks at VLE-determined biopsy sites.The objective of this study was to demonstrate in human participants the safety and feasibility of VLE-guided biopsy in vivo.A pilot feasibility study.Massachusetts General Hospital.A total of 22 participants were enrolled from January 2011 to June 2012 with a prior diagnosis of Barrett's esophagus. Twelve participants were used to optimize the laser marking parameters and the system platform. A total of 30 target sites were selected and marked in real-time by using the VLE-guided biopsy platform in the remaining 10 participants.Volumetric laser endomicroscopy.Endoscopic and VLE visibility, and accuracy of VLE diagnosis of the tissue between the laser cautery marks.There were no adverse events of VLE and laser marking. The optimal laser marking parameters were determined to be 2 seconds at 410 mW, with a mark separation of 6 mm. All marks made with these parameters were visible on endoscopy and VLE. The accuracies for diagnosing tissue in between the laser cautery marks by independent blinded readers for endoscopy were 67% (95% confidence interval [CI], 47%-83%), for VLE intent-to-biopsy images 93% (95% CI, 78%-99%), and for corrected VLE post-marking images 100% when compared with histopathology interpretations.This is a single-center feasibility study with a limited number of patients.Our results demonstrate that VLE-guided biopsy of the esophagus is safe and can be used to guide biopsy site selection based on the acquired volumetric optical coherence tomography imaging data. (NCT01439633.).
Project description:BACKGROUND:Dysplastic Barrett's esophagus (BE) lesions ?2 cm in size can be targeted for en-bloc endoscopic mucosal resection (EMR). White-light endoscopy can underestimate the size of a lesion, limiting complete resection. Volumetric laser endomicroscopy (VLE) provides high-resolution cross-sectional imaging of BE. Epithelial glands are a VLE feature associated with BE dysplasia. We study the association between VLE gland quantification and outcome of resection. METHODS:EMR specimens of BE lesions targeted for en-bloc resection were imaged with VLE using an established protocol. Manual and automated quantification of epithelial glands was performed blinded to resection outcome. The presence of epithelial glands at the resection margins was recorded. Histologic en-bloc (R0) resection of the targeted lesion was defined by the absence and incomplete (R1) resection by the presence of dysplasia/neoplasia at specimen margins. RESULTS:Thirty-seven EMRs with a mean (standard deviation) size of 1.04 (0.37) cm were imaged with VLE. The highest grade of dysplasia found was low-grade dysplasia (n = 12), high-grade dysplasia (n = 19), and intramucosal cancer (n = 6). The en-bloc resection rate was 37.8% (R0, n = 14; R1, n = 23). The mean (standard deviation) number of epithelial glands quantified with VLE was 13.0 (6.7) and 28.8 (23.9) for R0 and R1 specimens, respectively, with a significant mean difference of 15.8 glands (95% confidence interval, 2-29; P = .02). The presence of glands at the specimen margin was associated with incomplete resection (P < .001). CONCLUSION:Systematic quantification of BE epithelial glands using VLE can determine the outcome of endoscopic resection. VLE may have a potential role in assessment of lesion margins.
Project description:BACKGROUND AND STUDY AIMS:Barrett's esophagus (BE)?-?associated neoplasia can be treated endoscopically, but accurate assessment before intervention is challenging. This study aimed to investigate the role of confocal laser endomicroscopy (CLE) as an adjunct in the endoscopic treatment of BE-associated neoplasia by assessing lateral tumor and subsquamous tumor (SST) extension. PATIENTS AND METHODS:In the context of a prospective, single-arm pilot clinical trial, patients referred for endoscopic resection of BE-associated neoplasia (high grade dysplasia and esophageal adenocarcinoma) underwent high definition, white light endoscopy with narrow-band imaging (NBI). Then, CLE mapping of suspected neoplastic lesions was performed by another endoscopist, partially blinded to the previous findings, before the patients underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), depending on lesion size and anticipated histology. RESULTS:In 7 of 38 patients (18?%), CLE revealed additional neoplastic tissue compared with prior white light endoscopy and NBI: 2 concomitant lesions, 2 cases of lateral tumor extension within the Barrett's epithelium, and 3 cases of previously undetected SST extension. Overall, en bloc resection (tumor-free lateral margin) was achieved in 28 of 34 neoplastic lesions (82?%), and complete resection (tumor-free lateral and basal margins) in 21 of 34 neoplastic lesions (62?%). CONCLUSIONS:CLE-assisted endoscopic resection of BE-associated neoplasia was safe and effective in this study, as proved by a high additional diagnostic yield of CLE (including visualization of occult SST extension) and a favorable rate of en bloc resection. The clinical value of CLE for assisting endoscopic therapy of BE-associated neoplasia deserves further evaluation in randomized controlled trials.
Project description:Probe-based confocal laser endomicroscopy (pCLE) and volumetric laser endomicroscopy (VLE) (also known as frequency domain optical coherence tomography) are advanced endoscopic imaging modalities that may be useful in the diagnosis of dysplasia associated with Barrett's esophagus (BE). We performed pCLE examination in ex-vivo EMR specimens and compared the diagnostic performance of using the current VLE scoring index (previously established as OCT-SI) and a novel VLE diagnostic algorithm (VLE-DA) for the detection of dysplasia.A total of 27 patients with BE enrolled in a surveillance program at a tertiary-care center underwent 50 clinically indicated EMRs that were imaged with VLE and pCLE and classified into neoplastic (N = 34; high-grade dysplasia, intramucosal adenocarcinoma) and nonneoplastic (N = 16; low-grade dysplasia, nondysplastic BE), based on histology. Image datasets (VLE, N = 50; pCLE, N = 50) were rated by 3 gastroenterologists trained in the established diagnostic criteria for each imaging modality as well as a new diagnostic algorithm for VLE derived from a training set that demonstrated association of specific VLE features with neoplasia. Sensitivity, specificity, and diagnostic accuracy were assessed for each imaging modality and diagnostic criteria.The sensitivity, specificity, and diagnostic accuracy of pCLE for detection of BE dysplasia was 76% (95% confidence interval [CI], 59-88), 79% (95% CI, 53-92), and 77% (95% CI, 72-82), respectively. The optimal diagnostic performance of OCT-SI showed a sensitivity of 70% (95% CI, 52-84), specificity of 60% (95% CI, 36-79), and diagnostic accuracy of 67%; (95% CI, 58-78). The use of the novel VLE-DA showed a sensitivity of 86% (95% CI, 69-96), specificity of 88% (95% CI, 60-99), and diagnostic accuracy of 87% (95% CI, 86-88). The diagnostic accuracy of using the new VLE-DA criteria was significantly superior to the current OCT-SI (P < .01).The use of a new VLE-DA showed enhanced diagnostic performance for detecting BE dysplasia ex vivo compared with the current OCT-SI. Further validation of this algorithm in vivo is warranted.
Project description:Esophageal adenocarcinoma is rising rapidly in incidence and usually develops from Barrett's esophagus, a precursor condition commonly found in patients with chronic acid reflux. Premalignant lesions are challenging to detect on conventional screening endoscopy because of their flat appearance. Molecular changes can be used to improve detection of early neoplasia. We have developed a peptide that binds specifically to high-grade dysplasia and adenocarcinoma. We first applied the peptide ex vivo to esophageal specimens from 17 patients to validate specific binding. Next, we performed confocal endomicroscopy in vivo in 25 human subjects after topical peptide administration and found 3.8-fold greater fluorescence intensity for esophageal neoplasia compared with Barrett's esophagus and squamous epithelium with 75% sensitivity and 97% specificity. No toxicity was attributed to the peptide in either animal or patient studies. Therefore, our first-in-human results show that this targeted imaging agent is safe and may be useful for guiding tissue biopsy and for early detection of esophageal neoplasia and potentially other cancers of epithelial origin, such as bladder, colon, lung, pancreas, and stomach.
Project description:The detection of high-grade dysplasia and cancer in Barrett's esophagus (BE) can be challenging. Confocal laser endomicroscopy (CLE) allows in vivo visualization of mucosal histology during endoscopy.To determine whether CLE with optical biopsy and targeted mucosal biopsy improves the diagnostic yield of endoscopically inapparent, BE-associated neoplasia compared to standard endoscopy with a 4-quadrant, random biopsy protocol.Prospective, double-blind, randomized, crossover study.Single, tertiary-care academic center.This study involved patients with BE undergoing routine surveillance or referred for treatment of nonlocalized, endoscopically inapparent, BE-associated neoplasia.All participants underwent both a confocal endomicroscopy with a targeted biopsy procedure and standard endoscopy with a 4-quadrant biopsy procedure in a randomized order.Increase in diagnostic yield for neoplasia, reduction in mucosal biopsy number, final pathologic diagnosis.CLE with targeted biopsy almost doubled the diagnostic yield for neoplasia and was equivalent to the standard protocol for the final diagnosis of neoplasia. Two thirds of patients in the surveillance group did not need any mucosal biopsies at all.Single-center study.CLE with targeted biopsy significantly improves the diagnostic yield for endoscopically inapparent BE neoplasia compared to a standard endoscopy with a random-biopsy protocol. CLE with targeted biopsy also greatly reduces the number of biopsies needed per patient and allows some patients without neoplasia to completely forgo mucosal biopsy.
Project description:In the gastroenterology field, the impact of artificial intelligence was investigated for the purposes of diagnostics, risk stratification of patients, improvement in quality of endoscopic procedures and early detection of neoplastic diseases, implementation of the best treatment strategy, and optimization of patient prognosis. Computer-assisted diagnostic systems to evaluate upper endoscopy images have recently emerged as a supporting tool in endoscopy due to the risks of misdiagnosis related to standard endoscopy and different expertise levels of endoscopists, time-consuming procedures, lack of availability of advanced procedures, increasing workloads, and development of endoscopic mass screening programs. Recent research has tended toward computerized, automatic, and real-time detection of lesions, which are approaches that offer utility in daily practice. Despite promising results, certain studies might overexaggerate the diagnostic accuracy of artificial systems, and several limitations remain to be overcome in the future. Therefore, additional multicenter randomized trials and the development of existent database platforms are needed to certify clinical implementation. This paper presents an overview of the literature and the current knowledge of the usefulness of different types of machine learning systems in the assessment of premalignant and malignant esophageal lesions via conventional and advanced endoscopic procedures. This study makes a presentation of the artificial intelligence terminology and refers also to the most prominent recent research on computer-assisted diagnosis of neoplasia on Barrett's esophagus and early esophageal squamous cell carcinoma, and prediction of invasion depth in esophageal neoplasms. Furthermore, this review highlights the main directions of future doctor-computer collaborations in which machines are expected to improve the quality of medical action and routine clinical workflow, thus reducing the burden on physicians.
Project description:BACKGROUND & AIMS:Barrett's esophagus (BE) recurs in 25% or more of patients treated successfully with radiofrequency ablation (RFA), so surveillance endoscopy is recommended after complete eradication of intestinal metaplasia (CEIM). The frequency of surveillance is informed only by expert opinion. We aimed to model the incidence of neoplastic recurrence, validate the model in an independent cohort, and propose evidence-based surveillance intervals. METHODS:We collected data from the United States Radiofrequency Ablation Registry (US RFA, 2004-2013) and the United Kingdom National Halo Registry (UK NHR, 2007-2015) to build and validate models to predict the incidence of neoplasia recurrence after initially successful RFA. We developed 3 categories of risk and modeled intervals to yield 0.1% risk of recurrence with invasive adenocarcinoma. We fit Cox proportional hazards models assessing discrimination by C statistic and 95% confidence limits. RESULTS:The incidence of neoplastic recurrence was associated with most severe histologic grade before CEIM, age, endoscopic mucosal resection, sex, and baseline BE segment length. In multivariate analysis, a model based solely on most severe pre-CEIM histology predicted neoplastic recurrence with a C statistic of 0.892 (95% confidence limit, 0.863-0.921) in the US RFA registry. This model also performed well when we used data from the UK NHR. Our model divided patients into 3 risk groups based on baseline histologic grade: non-dysplastic BE; indefinite for dysplasia, low-grade dysplasia, and high-grade dysplasia; or intramucosal adenocarcinoma. For patients with low-grade dysplasia, we propose surveillance endoscopy at 1 and 3 years after CEIM; for patients with high-grade dysplasia or intramucosal adenocarcinoma, we propose surveillance endoscopy at 0.25, 0.5, and 1 year after CEIM, then annually. CONCLUSION:In analyses of data from the US RFA and UK NHR for BE, a much-attenuated schedule of surveillance endoscopy would provide protection from invasive adenocarcinoma. Adherence to the recommended surveillance intervals could decrease the number of endoscopies performed yet identify unresectable cancers at rates less than 1/1000 endoscopies.
Project description:Achalasia and Treatment of esophageal Adenocarcinoma are commonly associated to surgical resection. Newer technologies in interventional endoscopy gave way to a substantial paradigm shift in the management of these conditions. In the case of achalasia, endoscopic myotomy is rapidly displacing Heller's myotomy as the gold standard in many centers. Early stage neoplasia in Barrett's esophagus (BE) comprising high-grade dysplasia (HGD), intramucosal and, in some cases, submucosal carcinoma is now being treated without the need of esophagectomy. This review presents a summary of the most relevant endoscopic techniques for both achalasia and esophageal cancer. Endoscopic advances in diagnostic and therapeutic arenas allow for minimally invasive therapies and organ preservation in most settings of achalasia and early stage neoplasia of the esophagus provided that the clinical setting and physician's expertise are prepared for this approach.