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Deep learning methods have been shown to achieve excellent performance on diagnostic tasks, but how to optimally combine them with expert knowledge and existing clinical decision pathways is still an open challenge. This question is particularly important for the early detection of cancer, where high-volume workflows may benefit from (semi-)automated analysis. Here we present a deep learning framework to analyze samples of the Cytosponge-TFF3 test, a minimally invasive alternative to endoscopy, for detecting Barrett's esophagus, which is the main precursor of esophageal adenocarcinoma. We trained and independently validated the framework on data from two clinical trials, analyzing a combined total of 4,662 pathology slides from 2,331 patients. Our approach exploits decision patterns of gastrointestinal pathologists to define eight triage classes of varying priority for manual expert review. By substituting manual review with automated review in low-priority classes, we can reduce pathologist workload by 57% while matching the diagnostic performance of experienced pathologists. A clinician-in-the-loop deep learning system streamlines the workflow of pathologists for detection of Barrett's esophagus and retains the diagnostic accuracy of full manual review., Author(s): Marcel Gehrung [sup.1] [sup.2] , Mireia Crispin-Ortuzar [sup.1] , Adam G. Berman [sup.1] , Maria O'Donovan [sup.3] [sup.4] , Rebecca C. Fitzgerald [sup.3] , Florian Markowetz [sup.1] Author Affiliations: [...]

Esophageal cancer is increasing in frequency in the United States faster than any other cancer. Barrett's esophagus, an otherwise benign complication of esophageal reflux, affects approximately three million Americans and precedes almost all cases of esophageal cancer. If detected as high-grade dysplasia (HGD), most esophageal cancers can be prevented. Standard-of-care screening for dysplasia uses visual endoscopy and a prescribed pattern of biopsy. This procedure, in which a tiny fraction of the affected tissue is selected for pathological examination, has a low probability of detection because dysplasia is highly focal and visually indistinguishable. We developed a system called endoscopic polarized scanning spectroscopy (EPSS), which performs rapid optical scanning and multispectral imaging of the entire esophageal surface and provides diagnoses in near real time. By detecting and mapping suspicious sites, guided biopsy of invisible, precancerous dysplasia becomes practicable. Here we report the development of EPSS and its application in several clinical cases, one of which merits special consideration., Previously we demonstrated that spectroscopic information in light scattered by nuclei could reveal precancer cellular changes (1). The first application of light-scattering spectroscopy successfully detected dysplasia in Barrett's esophagus (1-5) [...]

A case-study of an old man is used to explain the causes, symptoms and effects of BarrettEs esophagus, a premalignant lesion detected in patients with esophagus. The various steps to be taken for the management and treatment of the disorder are also discussed.

We have constructed a high-speed, two-dimensional capillary electrophoresis system with a compact and high-sensitivity fluorescence detector. This instrument is used for the rapid and reproducible separations of Barrett's esophagus tissue homogenates. Proteins and biogenic amines are labeled with the fluorogenic reagent 3-(2furoyl)quinoline-2-carboxaldehyde. Labeled biomolecules are separated sequentially in two capillaries. The first capillary employs capillary sieving electrophoresis using a replaceable sieving matrix. Fractions are successively transferred to a second capillary where they undergo additional separation by micellar electrokinetic capillary chromatography. The comprehensive two-dimensional separation requires 60 min. Within-day migration time reproducibility is better than 1% in both dimensions for the 50 most intense features. Between-day migration time precision is 1.3% for CSE and better than 0.6% for MECC. Biopsies were obtained from the squamous epithelium in the proximal tubular esophagus, Barrett's epithelium from the distal esophagus, and fundus region of the stomach from each of three Barrett's esophagus patients with informed consent. We identified 18 features from the homogenate profiles as biogenic amines and amino acids. For each of the patients, Barrett's biopsies had more than 5 times the levels of phenylalanine and alanine as compared to squamous tissues. The patient with high-grade dysplasia shows the highest concentrations for 13 of the amino acids across all tissue types. Concentrations of glycine are 40 times higher in squamous biopsies compared to Barrett's and fundal biopsies from the patient with high-grade dysplasia. These results suggest that two-dimensional capillary electrophoresis may be of value for the rapid characterization of endoscopic and surgical biopsies.

Background and aims: Specialised intestinal metaplasia and its dysplastic transformation, which precedes cancer in Barrett's oesophagus cannot be differentiated in standard gastroscopy. The aim of this study was to investigate [...]

Background and aims: Endoscopic surveillance including stepwise four quadrant biopsies (4QB) is still regarded as the standard approach in patients with Barrett's oesophagus (BO). Several methods such as dye staining [...]

Background: The presence of intestinal metaplasia (IM) in the columnar lined distal oesophagus defines Barrett's oesophagus with the risk of future malignant transformation. The distribution of both IM and dysplasia [...]

Even though gastroesophageal reflux disease (GERD) increases the risk of esophageal cancer, the risk of cancer is still low in most people and does not justify regular endoscopy in these patients. GERD occurs when acid in the stomach backs up into the esophagus, causing heartburn., Context Gastroesophageal reflux disease (GERD) is a risk factor for adenocarcinoma of the esophagus, a rare cancer whose incidence is increasing. Adenocarcinoma may develop from Barrett esophagus, a metaplastic change of the esophageal epithelium from squamous to intestinalized columnar mucosa, which is associated with chronic reflux. Some have recommended that patients with chronic reflux symptoms undergo upper endoscopy to assess for Barrett esophagus and to screen for cancer. Objectives To review the evidence linking GERD and Barrett esophagus to esophageal adenocarcinoma and, to examine the utility of upper endoscopy as a screening tool in adenocarcinoma of the esophagus among individuals with GERD. Data Sources A MEDLINE search was performed to identify all pertinent English-Janguage reports about GERD, adenocarcinoma, and Barrett esophagus from 1968 through 2001. Reports were of randomized controlled clinical trials if available, case-control data if trials were unavailable, and cohort studies if case-control data were unavailable. Pertinent bibliographies were also reviewed to find reports not otherwise identified. Study Selection and Data Extraction Studies were selected by using the search terms gastroesophageal reflux, adenocarcinoma, and Barrett's esophagus, with subheadings for classification, complications, drug therapy, economics, epidemiology, mortality, surgery, and prevention and control. Clinical guidelines for the care of subjects with GERD and Barrett esophagus were retrieved and abstracted. Data Synthesis Cohort studies demonstrate that symptoms of GERD occur monthly in almost 50% of US adults and weekly in almost 20%. Three large case-control studies demonstrate a positive association between reflux symptoms and risk of adenocarcinoma of the esophagus, with more prolonged and severe symptoms accentuating this risk. However, because of the low incidence of adenocarcinoma of the esophagus and the ubiquity of reflux symptoms, the risk of cancer in any given individual with reflux symptoms is low. No randomized trial data are available to demonstrate either decreased cancer incidence or increased life expectancy in subjects with GERD who undergo screening endoscopy. Conclusions Strong evidence supports the association of GERD and adenocarcinoma of the esophagus; however, the risk of cancer in any given individual with GERD is low. Barrett esophagus appears to be a common precursor lesion to this cancer. Given the low absolute risk of cancer in those with GERD and the lack of demonstrated efficacy of endoscopic screening, insufficient evidence exists to endorse routine endoscopic screening of patients with chronic GERD symptoms.

Context.--Pathologists frequently assess esophageal biopsy specimens to 'rule out Barrett esophagus,' as well as to assess for the presence or absence of dysplasia. Objective.--To review some of the recent controversies in the diagnosis of Barrett esophagus and Barrett-related dysplasia. Data Sources.--Sources were the author's experience and review of the English literature from 1978 to 2009. Conclusions.--Although goblet cells are required by the American College of Gastroenterology to confirm a diagnosis of Barrett esophagus, this definition might expand to include columnar-lined esophagus without goblet cells. The recognition of dysplasia in Barrett esophagus remains a difficult task for the surgical pathologist, with difficulties in distinguishing reactive epithelium from dysplasia, low-grade dysplasia from high-grade dysplasia, and even high-grade dysplasia from intramucosal adenocarcinoma., One of the more common specimens encountered by both general surgical pathologists and gastrointestinal pathologists are esophageal biopsy specimens to 'rule out Barrett esophagus (BE),' as well as to assess [...]

Adenocarcinoma and dysplasias are recognized complications of Barrett mucosa. In the past, the treatment for this carcinoma was esophagectomy. However, new techniques, including endoscopic mucosal resection, sometimes replace esophagectomy and are becoming standard procedures in clinical practice, not just in major medical centers. Pathologists must learn to handle these specimens, which have extensive artifacts. Also, Barrett mucosa has duplicated stromal layers beneath the mucosa that include a new lamina propria and a new muscularis mucosae. We must be aware of these peculiarities because of staging implications. Regardless of new technology, the diagnostic approach to dysplasia depends on the light microscopic interpretation, which is not as reliable or consistent as one would wish. Hopefully, better diagnostic criteria will arise, and perhaps a new histologic stain or a molecular or genetic test will emerge that complements "our eyeballs.", This case report has 3 discussion items: the diagnosis of dysplasia in Barrett mucosa, the altered anatomy in Barrett mucosa with its staging implications, and the peculiarities of endoscopic mucosal [...]

* Context.--At present, Barrett esophagus is the most common cause of esophageal adenocarcinoma. In the past 20 years, the incidence of esophageal adenocarcinoma in white males has exceeded that of tumors of the colorectum, lung, prostate, and skin. Objectives.--To (1) provide an evidence-based review of the diagnosis, classification, and histologic differentiation of Barrett esophagus from gastric carditis, (2) provide a summary of the key pathologic features of precursor lesions, such as dysplasia, and (3) evaluate adjunctive markers of dysplasia and predictive markers for the development of cancer. The natural history and risk of cancer in patients with Barrett esophagus is also reviewed. Data Sources.--For this review, selected published peer reviewed articles were chosen from a search through PubMed between the years 1970 and 2007. Conclusions.--The current definition of Barrett esophagus is partially flawed because not all cases are endoscopically recognizable, nongoblet epithelium is biologically intestinalized, and determination of the presence or absence of goblet cells is susceptible to sampling error. Differentiation of ultrashort segment Barrett esophagus from chronic gastric carditis can be accomplished, in a minority of cases, by evaluating for the presence or absence of histologic features that are known to be associated with Barrett esophagus. Dysplasia in Barrett esophagus begins in the crypt bases and then extends more superficially to include the upper portions of the crypts and surface epithelium. Low-and high-grade dysplasia are distinguished by the presence of marked cytologic and/or architectural abnormalities in the latter compared with the former. There are few, if any, reliable adjunctive diagnostic techniques that can help differentiate nondysplastic from dysplastic epithelium. However, a-methylacyl coenzyme A racemase staining has been shown to be useful in 2 separate studies. Both low- and high-grade dysplasia are progressive lesions, and in general, the extent of dysplasia, particularly low grade, is a strong risk factor for progression to carcinoma. Of all the biologic and genetic biomarkers studied to date, evaluation of DNA content is the most reliable and specific. The management of patients with dysplasia is variable among institutions and ranges from aggressive surveillance, endoscopic mucosal resection, mucosal ablation, or total esophagectomy., In the past 20 years, the incidence of esophageal adenocarcinoma in white males has exceeded that of tumors of the colorectum, lung, prostate, and skin (melanoma). (1,2) In the United [...]