Barrett's Mucosa Research Articles

Endoscopic Characteristics of Early Gastroesophageal Junction Adenocarcinomas and Assessment for Invasion Depth: A Case Series Study.

Early-stage gastroesophageal junction (GEJ) adenocarcinoma can be challenging to diagnose and treat promptly using endoscopy. This study aims to summarize the endoscopic characteristics of early GEJ adenocarcinoma and investigate their correlation with pathological grade and invasion depth. This retrospective case series study evaluated patients with early GEJ adenocarcinoma who underwent endoscopic or surgical resection at First Affiliated Hospital of Dalian Medical University between January 2016 and December 2022. A total of 71 patients were included in the analysis, with 59 males and a median age of 67 years. The majority of the lesions were located on the posterior side of the GEJ (40.8%) or the lesser curvature side (29.6%). Siewert II lesions accounted for 71.8% of cases, with most occurring on the posterior side (49.0%) and Siewert III lesions mostly occurring on the lesser curvature side (42.9%). Siewert I lesions accounted for only 7.0%, and all originated from Barrett mucosa. Paris classification of Is (P = .015) or IIc (P = .015), lesion size ≥12 mm (P = .017), red color with subsquamous extension (P = .038), and disordered microsurface with local fusion (P < .001) were independently and positively correlated with pathological grade and invasion depth by multivariable ordinal logistic regression. The posterior side and lesser curvature of the GEJ are the high-incidence sites of GEJ adenocarcinoma. Both forward and backward views during endoscopy should be combined to detect the lesion. Endoscopic characteristics such as Is or IIc morphology, larger size, red color with subsquamous extension, and disordered microsurface with local fusion may indicate a higher pathological grade and deeper invasion.

A Case of a Granular Cell Tumor Arising in a Patient with Long-segment Barrett's Esophagus.

Esophageal cell tumors are rare. Esophagogastroduodenoscopy performed on a 48-year-old woman revealed an elevated esophageal lesion and the presence of long-segment Barrett's esophagus. Endoscopic ultrasonography showed a 15 mm homogeneous hypoechoic tumor extending from the lamina propria mucosa to the submucosa. Pathological examination of the biopsy tissue revealed a sheet-like cluster of histiocytoid cells with an abundant eosinophilic granular cytoplasm. Immunohistochemical examination revealed S-100 (+) and CD68 (+), thus suggesting the diagnosis of a granular cell tumor. The tumor was resected by endoscopic submucosal dissection. Pathologically, the background mucosa was Barrett's mucosa. This is the first reported case of an esophageal granular cell tumor in long-segment Barrett's esophagus.

Intestinal metaplasia in follow-up endoscopies among Asian patients with short-segment Barrett's esophagus: Regression, sampling error, and associated factors

The percentage of and factors associated with the regression of Barrett's esophagus (BE) or its characteristic intestinal metaplasia (IM) remain unclear, and conflicting results have been reported because of diverse regression and sampling error definitions. Thus, we investigated the rates of IM regression, sampling error, and associated factors. Forty-two patients with proven short-segment BE with IM who underwent two follow-up endoscopies with biopsies of Barrett's mucosa were retrospectively analyzed. Additional Alcian blue and MUC2 staining were done on the biopsy specimens without IM in hematoxylin-eosin staining. Only patients with negative hematoxylin-eosin, Alcian blue, and MUC2 staining for IM in both follow-up endoscopies were considered to have true regression. When all three stains were negative for IM in the first, but positive in the second follow-up endoscopy, we considered IM persisting and declared sampling error. Among the 18 patients without IM at the first follow-up endoscopy, only five (11.9%) were judged to have true regression. Prolonged proton-pump inhibitor use was significantly associated with regression. Limited experience of the endoscopist, and insufficient biopsy number were significantly related to sampling error. Receiver operating characteristic (ROC) curve analysis showed the best cut-off value of the biopsy number/maximal-length (cm) ratio to predict sampling error was 2.25. In our patients with short-segment BE, 11.9% experienced regression of IM. Prolonged proton-pump inhibitors treatment was associated with regression. An insufficient biopsy number was related to a missed IM, which may be eliminated by maintaining biopsy number/maximal-length (cm) ratio ≥2.25.

Demarcating Z-line and Gastric Folds Boundary Based on the Segmentation of the Lower Esophageal Sphincter Images.

The endoscopic diagnosis of pathological changes in the gastroesophageal junction including esophagitis and Barrett's mucosa is based on the visual detection of two boundaries: mucosal color change between esophagus and stomach, and top endpoint of gastric folds. The presence and pattern of mucosal breaks in the gastroesophageal mucosal junction (Z line) classify esophagitis in patients and the distance between the two boundaries points to the possible columnar lined epithelium. Since visual detection may suffer from intra- and interobserver variability, our objective was to define the boundaries automatically based on image processing algorithms, which may enable us to measure the detentions of changes in future studies. To demarcate the Z-line, first the artifacts of endoscopy images are eliminated. In the second step, using SUSAN edge detector, Mahalanobis distance criteria, and Gabor filter bank, an initial contour is estimated for the Z-line. Using region-based active contours, this initial contour converges to the Z-line. Finally, by applying morphological operators and Gabor Filter Bank to the region inside of the Z-line, gastric folds are segmented. To evaluate the results, a database consisting of 50 images and their ground truths were collected. The average dice coefficient and mean square error of Z-line segmentation were 0.93 and 3.3, respectively. Furthermore, the average boundary distance criteria are 12.3 pixels. In addition, two other criteria that compare the segmentation of folds with several ground truths, i.e., Sweet-Spot Coverage and Jaccard Index for Golden Standard, are 0.90 and 0.84, respectively. Considering the results, automatic segmentation of Z-line and gastric folds are matched to the ground truths with appropriate accuracy.

S2389 The Odd Couple: Active H. pylori Infection Within Long Segment Barrett’s Esophagus

Introduction: Barrett’s esophagus (BE) is a consequence of poorly-controlled GERD leading to intestinal metaplasia, which predisposes to esophageal cancer. Similarly, there is a well-established link between Helicobacter pylori and development of gastric cancer. However, there is a negative association between H. pylori and risk of BE. Here, we present a rare case of H. pylori infection within Barrett's mucosa. Case Description/Methods: A 54-year-old woman was referred for one month of dysphagia to solids. She described food sticking in her mid-esophagus without difficulty swallowing pills or liquids. She also endorsed significant heartburn and belching but denied systemic symptoms, regurgitation, abdominal pain, or weight loss. EGD demonstrated a 5 cm segment of circumferential salmon-colored mucosa suspicious for Barrett’s esophagus, a small esophageal ulcer, and a normal stomach and duodenum. Gastric biopsies revealed mild gastritis with H. pylori organisms. Esophageal biopsies showed intestinal metaplasia consistent with Barrett’s esophagus as well as H. pylori organisms. Quadruple therapy was initiated with metronidazole, tetracycline, omeprazole, and bismuth (Figure). Discussion: We describe a rare case of H. pylori discovered within long-segment Barrett’s esophagus. Evidence suggests an inverse association between H. pylori and BE. However, a recent meta-analysis demonstrated that this association disappeared in patients with GERD. One proposed mechanism for H. pylori’s protectiveness against BE is decreased gastric acid production. Together, this suggests H. pylori protects against BE by preventing development of GERD but once GERD is present, H. pylori is no longer protective. Thus, our simultaneous diagnosis of BE and H. pylori could be explained by long-standing GERD and BE prior to H pylori infection. While it is uncommon to diagnose H. pylori and BE together, it is even rarer to see H. pylori within Barrett’s mucosa, given the organism’s proclivity for gastric epithelium. One potential explanation is that this patient’s significant GERD allowed reflux of H. pylori organisms into the esophagus, leading to colonization of the metaplastic epithelium. Furthermore, there may be microscopic satellites of gastric mucosa within the segment of BE, providing a friendlier environment in which the organisms could grow. More observation is needed to determine the significance and long-term effects of active H. pylori infection in Barrett's mucosa and if this facilitates progression to dysplasia or carcinoma.Figure 1.: 1. A. Esophagoduodenoscopy (EGD) image of 5 cm circumferential salmon mucosa consistent with Barrett’s esophagus. B. Hematoxylin and eosin (H&E) stain of esophageal mucosa demonstrating intestinal metaplasia and H pylori organisms.

S2363 Pagetoid Spread of Esophageal Adenocarcinoma

Introduction: Pagetoid spread refers to the “upward spreading” of cancer cells into the upper dermis from below. In the esophagus, it is a rare finding seen with poorly differentiated adenocarcinomas and is associated with deeper invasion. Case Description/Methods: A 75-year-old male with history of diabetes, hypertension, and hyperlipidemia presented to the gastroenterology clinic for dysphagia to solids. He reported that his symptoms started intermittently approximately 3 weeks prior and had gradually progressed. He denied a history of acid reflux, heartburn, or prior episodes of dysphagia. He also reported an unintentional loss of 10 pounds over the past 5 months. His medications included lisinopril, metformin, pioglitazone, and simvastatin. He denied a history of tobacco or alcohol use and had no family history of gastrointestinal malignancy. Physical exam was unremarkable. To further evaluate his dysphagia, an esophagogastroduodenoscopy was performed, revealing a small fungating mass in the distal esophagus near the gastroesophageal junction. Superior to this in the distal and mid-esophagus, there was a long segment of circumferential induration with irregular, reticulated erosions (Figure). Biopsies of the lesion revealed esophageal adenocarcinoma with pagetoid spread into overlying squamous epithelium, arising in Barrett mucosa with high-grade dysplasia. Endoscopic ultrasound was subsequently performed, revealing a mass measuring 12 mm in thickness with sonographic evidence of invasion into the adventitia and one malignant appearing lymph node in the lower paraoesophageal mediastinum (staged T3, N1). Discussion: Upper endoscopy is highly sensitive and specific for diagnosing esophageal cancer. However, in cases where there may not be an obvious fungating tumor, the presence of indurated mucosa with reticular erosions should alert the endoscopist to the presence of malignancy, possibly with pagetoid spread and deep invasion, as was seen in this patient.Figure 1.: Circumferential induration with irregular, reticulated erosions found in the mid esophagus during upper endoscopy.

Clinical Endoscopic and Histologic Findings of a Long-Term Follow-Up (10.7 Years) After Roux-en-Y Laparoscopic Gastric Bypass: a Prospective Study.

Bariatric surgery, with laparoscopic Roux-en-Y gastric bypass (LYGB), is one of the most effective treatments for long-term weight loss. However, there are few publications concerning endoscopic evaluations at late control. The purpose was to evaluate the macroscopic and histological findings at the distal esophagus, gastric pouch, jejunal limb and the evolution of Barrett's esophagus (BE) in the long term. Cohort of 110 patients with obesity underwent LYGB in a university hospital. Several clinical, endoscopic and histological evaluations were performed after surgery. Exclusion criteria were previous bariatric procedure, hiatal hernia > 4cm, BE with histological dysplasia and body mass index (BMI) > 50kg/m2. Average age was 38.7 ± 9years with 70% females. BMI averaged 39.6 ± 6kg/m2. Follow-up was 10.7 ± 2years, and 18 patients (16.4%) were lost. The total weight loss was 23.4 ± 7kg. Erosive esophagitis, present in 33% of patients, decreased to 5%. After surgery, intestinal metaplasia regressed to cardial mucosa in 5 of 8 patients. One patient developed a short-segment BE. The level of control to gastroesophageal reflux disease (GERD) symptom control was 87% to responders (Visick I-II) and 13% to non-responders (Visick III-IV). An increase in dilated cardia type III was observed (p < 0.001). The length of the gastric pouch increased significantly after surgery (p < 0.001). Anastomotic ulcers healed at 6months with proton pump inhibitor (PPI) use, without recurrence. LYGB is a very effective surgical procedure to control symptoms of GERD and/or endoscopic erosive esophagitis. Besides, regression of Barrett's mucosa to carditis occurred in 62%.

Editors' Selections from Relevant Scientific Publications.

Editors' Selections from Relevant Scientific Publications.

Linked-color Imaging May Help Improve the Visibility of Superficial Barrett's Esophageal Adenocarcinoma by Increasing the Color Difference.

Objective Linked-color imaging (LCI), a new technology for image-enhanced endoscopy, emphasizes the color of the mucosa, and its practicality in the detection of early gastric and colon cancers has been reported. However, whether or not LCI is useful for the diagnosis of Barrett's adenocarcinoma (BA) has been unclear. In this study, we explored whether or not LCI enhances the color difference between a BA lesion and the surrounding mucosa. Methods Twenty-one lesions from 20 consecutive patients with superficial BA who underwent endoscopic submucosal dissection between November 2014 and September 2017 were retrospectively examined. The color differences (ΔE*) between the inside and outside of the lesion were evaluated retrospectively using white-light imaging (WLI), blue-light imaging (BLI), and LCI objectively, based on a Commission Internationale de l'Eclairage (CIE) lab color system. Furthermore, we compared the morphology, color, and circumferential location of the lesion. Results The median values of the color difference (ΔE*) in WLI and BLI were 9.1 and 5.8, respectively, and no difference was observed. In LCI, the median color difference was 17.6, which was higher than that of WLI and BLI. Regardless of the morphology, color, and circumferential location of BA lesions, the color difference was larger in LCI than in WLI. Conclusion LCI increases the color difference between the BA and the surrounding Barrett's mucosa.

2020 Seoul Consensus on the Diagnosis and Management of Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

CA19-9-producing esophageal adenocarcinoma originating from the esophageal cardia of the mid-thoracic esophagus: a case report

BackgroundAlthough there are many studies on primary esophageal adenocarcinoma arising from Barrett's esophagus or ectopic gastric mucosa, reports on adenocarcinoma arising from esophageal cardiac glands are extremely rare. Herein, we report a case of mid-thoracic cancer antigen 19-9 (CA 19-9)-producing primary esophageal adenocarcinoma, which presumably originated from the cardiac glands.Case presentationA 74-year-old man was referred to our department with advanced esophageal cancer, which initially presented with dyspepsia. Serum levels of cancer antigen 19-9 (CA 19-9) were elevated (724.89 U/ml). Upper gastrointestinal endoscopy revealed a type 2 tumor on the posterior wall of the mid-thoracic esophagus approximately 29–32 cm from the incisor. Mucosal biopsy was consistent with a diagnosis of adenocarcinoma. Contrast-enhanced computed tomography showed a circumferential wall thickening in the mid-thoracic esophagus without enlarged lymph nodes or distant metastasis. Positron emission tomography–computed tomography showed accumulation in the primary tumor, but no evidence of lymph node or distant metastasis. According to these findings, the adenocarcinoma was staged as cT3N0M0, thereby, requiring subtotal esophagectomy with lymph node dissection. Postoperative course was uneventful. Histopathologic analysis revealed a 50 × 40 mm moderately differentiated adenocarcinoma with invasion to the thoracic duct and lymph node metastasis at #108(1/4), #109R(1/3), and #109L(1/3). After surgery, the stage was revised to moderately differentiated pT4apN2pM0 (pStage III). Immunostaining revealed expression of CA19-9 and suggested esophageal cardiac gland origin of the tumor. Three months after the surgery, the patient showed no recurrence and is undergoing outpatient observation.ConclusionsWe experienced a case of mid-thoracic CA19-9-producing primary esophageal adenocarcinoma, which was presumed to have originated in the esophageal cardiac glands. Due to the scarcity of studies regarding this condition, specific management needs to be further clarified.

Therapeutic effect of laparoscopic fundoplication for patients with GERD from the viewpoint of Lyon Consensus.

The Lyon Consensus was conducted in 2017, leading to a revision of the diagnostic criteria of GERD. Conclusive GERD was defined as cases in which the distal esophageal acid exposure time (AET) is greater than 6% and there exists either peptic esophagitis, constriction, or long-segment Barrett's mucosa with a Los Angeles classification of grade C or D. Borderline GERD is defined as cases in which AET is between 4 and 6% and there exists peptic esophagitis with a Los Angeles classification of either grade A or B. All other cases were defined as Inconclusive GERD. We conducted a retrospective investigation of the treatment results of laparoscopic fundoplication (LF) for GERD according to the Lyon Consensus and evaluated whether or not it is an effective treatment predictor. From among the cases of primary LF conducted on patients with GERD-related illnesses at our university hospital from June 2008 to March 2020, the subjects included 215 individuals who underwent upper gastrointestinal endoscopy and 24h multichannel intraluminal impedance pH (MII-pH) testing prior to surgery. We compared the pathophysiology of the Conclusive GERD Group (Group A), Borderline GERD Group (Group B), and Inconclusive GERD Group (Group C), and then investigated the treatment results of each group. We used AFP classification for pathophysiological evaluation. For the acid reflux evaluation, we conducted MII-pH measurements using Sleuth, manufactured by Sandhill. The postoperative evaluation period was set to 3 months following surgery. The data are expressed using median values, with a statistical significance defined as p < 0.05 using the Kruskal-Wallis, Mann-Whitney, Wilcoxon signed-rank, and Chi-squared tests. Group A: 92 cases (43%, male 69 cases, age 57), Group B: 48 cases (22%, male 20 cases, age 52), and Group C: 75 cases (35%, male 69 cases, age 57). Regarding the patient backgrounds, while there were no significant differences in terms of gender or disease duration, those in Group A were significantly older than the other two groups, and there was a significant difference in Body Mass Index (BMI) between Group A and Group C. The results of each factor were: A factor (1 vs.1 vs. 1, p < 0.001), F factor (2 vs. 0 vs. 0, p < 0.001), and P factor (2 vs. 1 vs. 0, p < 0.001), with AET of 10.0 vs. 2.9 vs. 0.6, p < 0.001, and the disease had progressed more in Group A. There were also no differences in terms of surgical methods, hemorrhage volume, and intraoperative/postoperative complications; however, the use of mesh was higher and surgery duration was longer in Group A. There were obvious improvements in the A, F, and P factors and AET of each group following surgery (other than F and P of Group C, p < 0.001). The rate of recurrence was 15% in Group A, 8% in Group B, and 6% in Group C. It tended to be higher in Group A, but this was not statistically significant. The classification of GERD pathophysiology based on the Lyon Consensus is satisfactory, with no significant differences in the rate of effect of LF. The Lyon Consensus is effective for ascertaining the severity and pathophysiology of GERD; however, we were unable to forecast the treatment results of LF.

Toward improved endoscopic surveillance with multidiameter single fiber reflectance spectroscopy in patients with Barrett's esophagus.

Patients with Barrett's esophagus are at an increased risk to develop esophageal cancer and, therefore, undergo regular endoscopic surveillance. Early detection of neoplasia enables endoscopic treatment, which improves outcomes. However, early Barrett's neoplasia is easily missed during endoscopic surveillance. This study investigates multidiameter single fiber reflectance spectroscopy (MDSFR) to improve Barrett's surveillance. Based on the concept of field cancerization, it may be possible to identify the presence of a neoplastic lesion from measurements elsewhere in the esophagus or even the oral cavity. In this study, MDSFR measurements are performed on non-dysplastic Barrett's mucosa, squamous mucosa, oral mucosa, and the neoplastic lesion (if present). Based on logistic regression analysis on the scattering parameters measured by MDSFR, a classifier is developed that can predict the presence of neoplasia elsewhere in the Barrett's segment from measurements on the non-dysplastic Barrett's mucosa (sensitivity 91%, specificity 71%, AUC = 0.77). Classifiers obtained from logistic regression analysis for the squamous and oral mucosa do not result in an AUC significantly different from 0.5.

Endoscopic features of buried Barrett’s mucosa

Buried Barrett's mucosa is defined as intestinal metaplasia that is "buried" under the normal-appearing squamous epithelium. This can occur in Barrett's esophagus with or without previous endoscopic therapy. Dysplasia and neoplasia within buried Barrett's mucosa have also been reported. However, endoscopic features of buried Barrett's mucosa have not been described. At our tertiary referral center for Barrett's esophagus, several endoscopic features have been observed in patients who were found to have buried Barrett's mucosa on histology. These features are squamous epithelium which is (1) darker pink on white-light and darker brown on narrow-band imaging and/or (2) has a slightly raised or nodular appearance. It was also observed that either of these 2 features is frequently seen adjacent to a Barrett's mucosa island. This study aimed to (1) evaluate the diagnostic accuracy of these endoscopic features, and (2) evaluate the frequency of endoscopically identifiable buried Barrett's mucosa in patients with dysplastic Barrett's esophagus, before and after endoscopic eradication therapy. This was a retrospective analysis of a prospectively observed cohort of all cases of dysplastic Barrett's esophagus referred to St Vincent's Hospital, Melbourne. Endoscopy documentation software and histopathology reports of esophageal biopsy and EMR specimens between March 2013 and March 2019 were searched for terms "buried" or "subsquamous" Barrett's mucosa. Endoscopic reports, images, and histopathology reports of suspected buried Barrett's mucosa were then reviewed to apply the endoscopic features and correlate with the histologic diagnosis. In a cohort of 506 patients with dysplastic Barrett's esophagus, 33 (7%) patients (73% male, median age at referral 70.5 years) had buried Barrett's mucosa on histology. Twenty-seven (82%) patients had previous treatment for dysplastic Barrett's esophagus; radiofrequency in 2 (6%), EMR in 4 (12%), and both modalities in 21 (64%). Six (18%) had no previous treatment. Histologically confirmed buried Barrett's mucosa was suspected at endoscopy in 26 patients (79%). Endoscopic features were (1) darker pink or darker brown mucosa underneath squamous epithelium (24%), (2) raised areas underneath squamous mucosa (27%), and both features present concurrently (27%). These features were associated with adjacent islands of Barrett's esophagus in 48%. Forty-four cases of buried Barrett's mucosa were suspected endoscopically, and these were sampled by biopsy (50%) and EMR (50%). Buried Barrett's mucosa was confirmed in 26 cases, with a positive predictive value of endoscopic suspicion of 59%. Eighteen cases of endoscopically suspected buried Barrett's mucosa had no buried Barrett's mucosa on histology; inflammation or reflux was identified in 12 (67%) patients. Dysplasia was identified within buried Barrett's mucosa in 12 (36%) patients; 5 intramucosal adenocarcinoma, 1 high-grade dysplasia, and 6 low-grade dysplasia. Endoscopic features of buried Barrett's mucosa were observed in 11 of 12 cases harboring dysplasia or neoplasia, compared with 15 of 21 cases of buried Barrett's mucosa without dysplasia. In this retrospective analysis of prospectively observed patients with dysplastic Barrett's esophagus, buried Barrett's mucosa was identified in 7%, including treatment-naive patients. The proposed endoscopic features of buried Barrett's mucosa were seen in 79% of patients with histology confirmed disease. These endoscopic features may predict the presence of buried Barrett's mucosa, which may contain dysplasia or neoplasia. An overlap between the endoscopic features of inflammation, reflux, and buried Barrett's mucosa was observed. Future prospective studies are required to develop and validate endoscopic criteria for identifying buried Barrett's mucosa.

Mucosa-Associated Microbiota in Barrett's Esophagus, Dysplasia, and Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls

INTRODUCTION:Alterations in the composition of the human gut microbiome and its metabolites have been linked to gut epithelial neoplasia. We hypothesized that differences in mucosa-adherent Barrett's microbiota could link to risk factors, providing risk of progression to neoplasia.Methods:Paired biopsies from both diseased and nonaffected esophagus (as well as gastric cardia and gastric juice for comparison) from patients with intestinal metaplasia (n = 10), low grade dysplasia (n = 10), high grade dysplasia (n = 10), esophageal adenocarcinoma (n = 12), and controls (n = 10) were processed for mucosa-associated bacteria and analyzed by 16S ribosomal ribonucleic acid V4 gene DNA sequencing. Taxa composition was tested using a generalized linear model based on the negative binomial distribution and the log link functions of the R Bioconductor package edgeR.Results:The microbe composition of paired samples (disease vs nondisease) comparing normal esophagus with intestinal metaplasia, low grade dysplasia, high grade dysplasia, and adenocarcinoma showed significant decreases in the phylum Planctomycetes and the archaean phylum Crenarchaeota (P < 0.05, false discovery rate corrected) in diseased tissue compared with healthy controls and intrasample controls (gastric juice and unaffected mucosa). Genera Siphonobacter, Balneola, Nitrosopumilus, and Planctomyces were significantly decreased (P < 0.05, false discovery rate corrected), representing <10% of the entire genus community. These changes were unaffected by age, tobacco use, or sex for Crenarcha.DISCUSSSION:There are similar significant changes in bacterial genera in Barrett's esophageal mucosa, dysplasia, and adenocarcinoma compared with controls and intrapatient unaffected esophagus. Further work will establish the biologic plausibility of these specific microbes' contributions to protection from or induction of esophageal epithelial dysplasia.

A computer-assisted algorithm for narrow-band imaging-based tissue characterization in Barrett’s esophagus

The endoscopic evaluation of narrow-band imaging (NBI) zoom imagery in Barrett's esophagus (BE) is associated with suboptimal diagnostic accuracy and poor interobserver agreement. Computer-aided diagnosis (CAD) systems may assist endoscopists in the characterization of Barrett's mucosa. Our aim was to demonstrate the feasibility of a deep-learning CAD system for tissue characterization of NBI zoom imagery in BE. The CAD system was first trained using 494,364 endoscopic images of general endoscopic imagery. Next, 690 neoplastic BE and 557 nondysplastic BE (NDBE) white-light endoscopy overview images were used for refinement training. Subsequently, a third dataset of 112 neoplastic and 71 NDBE NBI zoom images with histologic correlation was used for training and internal validation. Finally, the CAD system was further trained and validated with a fourth, histologically confirmed dataset of 59 neoplastic and 98 NDBE NBI zoom videos. Performance was evaluated using fourfold cross-validation. The primary outcome was the diagnostic performance of the CAD system for classification of neoplasia in NBI zoom videos. The CAD system demonstrated accuracy, sensitivity, and specificity for detection of BE neoplasia using NBI zoom images of 84%, 88%, and 78%, respectively. In total, 30,021 individual video frames were analyzed by the CAD system. Accuracy, sensitivity, and specificity of the video-based CAD system were 83% (95% confidence interval [CI], 78%-89%), 85% (95% CI, 76%-94%), and 83% (95% CI, 76%-90%), respectively. The mean assessment speed was 38 frames per second. We have demonstrated promising diagnostic accuracy of predicting the presence/absence of Barrett's neoplasia on histologically confirmed unaltered NBI zoom videos with fast corresponding assessment time.

Barrett’s Epithelial Thickness, Assessed by Volumetric Laser Endomicroscopy, Is Associated With Response to Radiofrequency Ablation

Radiofrequency ablation (RFA) is the most common treatment for flat Barrett's esophagus (BE), but reasons for varying outcomes are poorly understood. A recently developed contrast-enhancement algorithm allows reliable measurement of Barrett's epithelial thickness (BET) from volumetric laser endomicroscopy (VLE) images and correlation with response to RFA. Using this algorithm, we investigated whether patients with thicker Barrett's mucosa are less likely to respond to RFA. In the future, this algorithm may guide choice of RFA dosing or endoscopic resection. We performed a retrospective analysis on all patients with BE who received a baseline VLE scan between May 2015 and October 2016, followed by RFA and 1 follow-up exam, from 14 institutions participating in the United States VLE registry. We measured BET on equidistant locations by estimating the distance between the esophageal surface and the superficial edge of the deepest lamina propria. The primary outcome variable was the percentage reduction in Prague length; secondary outcome variables were complete remission of intestinal metaplasia (CRIM) and presence of strictures after 12 months. Images from 61 patients were included in our final analysis. Mean BET per patient ranged from 224 μm to 705 μm. A 100 μm thicker mean BET per patient resulted in a 12% lower response to treatment, measured by a reduction of Prague length (P = .03), after adjustment for confounders. We found an association between mean BET and CRIM, but not with stricture formation. Based on measurements on contrast-enhanced VLE images, we found that BET correlates with response to RFA. For clinical implementation, larger studies with a standardized follow-up and development of computer-aided image analysis systems are needed.

Management of Barrett's esophagus with dysplasia refractory to radiofrequency ablation.

Radiofrequency ablation (RFA) is very effective for eradication of flat Barrett’s mucosa in dysplastic Barrett’s esophagus after endoscopic resection of raised lesions. However, in a minority of the time, RFA may be ineffective at eradication of the Barrett’s mucosa. Achieving complete eradication of intestinal metaplasia can be challenging in these patients. This review article focuses on the management of patients with dysplastic Barrett’s esophagus refractory to RFA therapy. Management strategies discussed in this review include optimizing the RFA procedure, optimizing acid suppression (with medical, endoscopic, and surgical management), cryotherapy, hybrid argon plasma coagulation, and EndoRotor resection.

Columnar epithelium morphology after esophagectomy: clinical insight into the development of Barrett's esophagus.

The presence of Barrett's mucosa in the esophageal remnant is a result of post-esophagectomy anastomotic site exposure to gastric acid and is regarded as a human model of Barrett's esophagus onset. Here, we attempted to clarify the relationship between duodenogastric reflux and formation of columnar epithelium by following the changes over time after esophagectomy. A total of 96 patients underwent esophagectomy due to superficial cancer from April 2000 to March 2018 were included in this study. Cases were divided into two groups according to the reconstruction technique after esophagectomy as either the gastric pull-up (Ga) group and ileocolonic interposition (Ic) group. Previously obtained endoscopic pictures of the cases were reviewed retrospectively and chronologically. There were 24 cases of columnar epithelium in the Ga group (42%) and 1 in the Ic group (2.6%) (P < 0.01) with 32 reflux cases (56%) in the Ga group and 1 (2.6%) in the Ic group (P < 0.01). Reflux precedes the development of columnar epithelium in both the Ga- and Ic groups. Multivariate analysis revealed surgical technique (odds ratio 10.6, 95% CI 1.2-97.5, P = 0.037) and reflux (odds ratio 4.5, 95% CI 1.3-15.6, P = 0.0017) as risk factors. The development of columnar epithelium was preceded by reflux comprising principally gastric acid and was strongly associated with a strong inflammatory state.

Esophageal Function Abnormalities in Patients With Barrett's Esophagus.

Various esophageal functional abnormalities have been described in patients with Barrett's esophagus (BE). A significantly higher esophageal acid exposure especially in the supine position has been documented in BE, as compared with the other gastroesophageal reflux disease phenotypes. In addition, weakly acidic reflux and duodenogastroesophageal reflux are more common in BE patients. The presence of Barrett's mucosa reduces esophageal mucosal impedance, occasionally to a level that prevents detection of reflux episodes. Reduced amplitude contractions and lower esophageal sphincter basal pressure are more common in BE patients as compared with the other gastroesophageal reflux disease groups. Ineffective esophageal motility is the most commonly defined motor disorder in BE. Reduced chemoreceptor and mechanoreceptor sensitivity to acid and balloon distention, respectively, have been suggested to explain lack or significantly less reports of reflux-related symptoms by BE patients.