Real-Time Increased Detection of Neoplastic Tissue in Barrett’s Esophagus with Probe-Based Confocal Laser Endomicroscopy: Final Results of an International Multicenter, Prospective, Randomized, Controlled Trial

BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) allows real-time detection of neoplastic Barrett's esophagus (BE) tissue. However, the accuracy of pCLE in real time has not yet been extensively evaluated. OBJECTIVE: To compare the sensitivity and specificity of pCLE in addition to high-definition white-light endoscopy (HD-WLE) with HD-WLE alone for the detection of high-grade dysplasia (HGD) and early carcinoma (EC) in BE. DESIGN: International, prospective, multicenter, randomized, controlled trial. SETTING: Five tertiary referral centers. PATIENTS: A total of 101 consecutive BE patients presenting for surveillance or endoscopic treatment of HGD/EC. INTERVENTIONS: All patients were examined by HD-WLE, narrow-band imaging (NBI), and pCLE, and the findings were recorded before biopsy samples were obtained. The order of HD-WLE and NBI was randomized and performed by 2 independent, blinded endoscopists. All suspicious lesions on HD-WLE or NBI and 4-quadrant random locations were documented. These locations were examined by pCLE, and a presumptive diagnosis of benign or neoplastic (HGD/EC) tissue was made in real time. Finally, biopsies were taken from all locations and were reviewed by a central pathologist, blinded to endoscopic and pCLE data. MAIN OUTCOME MEASUREMENTS: Diagnostic characteristics of pCLE. RESULTS: The sensitivity and specificity for HD-WLE were 34.2% and 92.7%, respectively, compared with 68.3% and 87.8%, respectively, for HD-WLE or pCLE (P = .002 and P < .001, respectively). The sensitivity and specificity for HD-WLE or NBI were 45.0% and 88.2%, respectively, compared with 75.8% and 84.2%, respectively, for HD-WLE, NBI, or pCLE (P = .01 and P = .02, respectively). Use of pCLE in conjunction with HD-WLE and NBI enabled the identification of 2 and 1 additional HGD/EC patients compared with HD-WLE and HD-WLE or NBI, respectively, resulting in detection of all HGD/EC patients, although not statistically significant. LIMITATIONS: Academic centers with enriched population. CONCLUSIONS: pCLE combined with HD-WLE significantly improved the ability to detect neoplasia in BE patients compared with HD-WLE. This may allow better informed decisions to be made for the management and subsequent treatment of BE patients. (Clinical trial registration number: NCT00795184.)

Position paper: The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction

Environmental enteric dysfunction (EED) is a disease of the small intestine affecting children and adults in low and middle income countries. Arising as a consequence of repeated infections, gut inflammation results in impaired intestinal absorptive and barrier function, leading to poor nutrient uptake and ultimately to stunting and other developmental limitations. Progress towards new biomarkers and interventions for EED is hampered by the practical and ethical difficulties of cross-validation with the gold standard of biopsy and histology. Optical biopsy techniques — which can provide minimally invasive or noninvasive alternatives to biopsy — could offer other routes to validation and could potentially be used as point-of-care tests among the general population. This Consensus Statement identifies and reviews the most promising candidate optical biopsy technologies for applications in EED, critically assesses them against criteria identified for successful deployment in developing world settings, and proposes further lines of enquiry. Importantly, many of the techniques discussed could also be adapted to monitor the impaired intestinal barrier in other settings such as IBD, autoimmune enteropathies, coeliac disease, graft-versus-host disease, small intestinal transplantation or critical care

The Argos project: The development of a computer‐aided detection system to improve detection of Barrett's neoplasia on white light endoscopy

Background: Computer-aided detection (CAD) systems might assist endoscopists in the recognition of Barrett's neoplasia. Aim: To develop a CAD system using endoscopic images of Barrett's neoplasia. Methods: White light endoscopy (WLE) overview images of 40 neoplastic Barrett's lesions and 20 non-dysplastic Barret's oesophagus (NDBO) patients were prospectively collected. Experts delineated all neoplastic images. The overlap area of at least four delineations was labelled as the ‘sweet spot’. The area with at least one delineation was labelled as the ‘soft spot’. The CAD system was trained on colour and texture features. Positive features were taken from the sweet spot and negative features from NDBO images. Performance was evaluated using leave-one-out cross-validation. Outcome parameters were diagnostic accuracy of the CAD system per image, and localization of the expert soft spot by CAD delineation (localization score) and its indication of preferred biopsy location (red-flag indication score). Results: Accuracy, sensitivity and specificity for detection were 92, 95 and 85%, respectively. The system localized and red-flagged the soft spot in 100 and 90%, respectively. Conclusion: This uniquely trained and validated CAD system detected and localized early Barrett's neoplasia on WLE images with high accuracy. This is an important step towards real-time automated detection of Barrett's neoplasia

The Argos project: The development of a computer-aided detection system to improve detection of Barrett's neoplasia on white light endoscopy

Background: Computer-aided detection (CAD) systems might assist endoscopists in the recognition of Barrett's neoplasia. Aim: To develop a CAD system using endoscopic images of Barrett's neoplasia. Methods: White light endoscopy (WLE) overview images of 40 neoplastic Barrett's lesions and 20 non-dysplastic Barret's oesophagus (NDBO) patients were prospectively collected. Experts delineated all neoplastic images.The overlap area of at least four delineations was labelled as the 'sweet spot'. The area with at least one delineation was labelled as the 'soft spot'. The CAD system was trained on colour and texture features. Positive features were taken from the sweet spot and negative features from NDBO images. Performance was evaluated using leave-one-out cross-validation. Outcome parameters were diagnostic accuracy of the CAD system per image, and localization of the expert soft spot by CAD delineation (localization score) and its indication of preferred biopsy location (red-flag indication score). Results: Accuracy, sensitivity and specificity for detection were 92, 95 and 85%, respectively. The system localized and red-flagged the soft spot in 100 and 90%, respectively. Conclusion: This uniquely trained and validated CAD system detected and localized early Barrett's neoplasia on WLE images with high accuracy. This is an important step towards real-time automated detection of Barrett's neoplasia.status: publishe

The Argos project:the development of a computer-aided detection system to improve detection of Barrett's neoplasia on white light endoscopy

\u3cp\u3eBackground: Computer-aided detection (CAD) systems might assist endoscopists in the recognition of Barrett's neoplasia. Aim: To develop a CAD system using endoscopic images of Barrett's neoplasia. Methods: White light endoscopy (WLE) overview images of 40 neoplastic Barrett's lesions and 20 non-dysplastic Barret's oesophagus (NDBO) patients were prospectively collected. Experts delineated all neoplastic images. The overlap area of at least four delineations was labelled as the ‘sweet spot’. The area with at least one delineation was labelled as the ‘soft spot’. The CAD system was trained on colour and texture features. Positive features were taken from the sweet spot and negative features from NDBO images. Performance was evaluated using leave-one-out cross-validation. Outcome parameters were diagnostic accuracy of the CAD system per image, and localization of the expert soft spot by CAD delineation (localization score) and its indication of preferred biopsy location (red-flag indication score). Results: Accuracy, sensitivity and specificity for detection were 92, 95 and 85%, respectively. The system localized and red-flagged the soft spot in 100 and 90%, respectively. Conclusion: This uniquely trained and validated CAD system detected and localized early Barrett's neoplasia on WLE images with high accuracy. This is an important step towards real-time automated detection of Barrett's neoplasia.\u3c/p\u3

Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and lymph node metastasis of carcinogen-induced colorectal tumors

Loss of p53 is considered to allow progression of colorectal tumors from the adenoma to the carcinoma stage. Using mice with an intestinal epithelial cell (IEC)-specific p53 deletion, we demonstrate that loss of p53 alone is insufficient to initiate intestinal tumorigenesis but markedly enhances carcinogen-induced tumor incidence and leads to invasive cancer and lymph node metastasis. Whereas p53 controls DNA damage and IEC survival during the initiation stage, loss of p53 during tumor progression is associated with increased intestinal permeability, causing formation of an NF-κB-dependent inflammatory microenvironment and the induction of epithelial-mesenchymal transition. Thus, we propose a p53-controlled tumor-suppressive function that is independent of its well-established role in cell-cycle regulation, apoptosis, and senescence