Specialized Intestinal Metaplasia Research Articles

S402 Voice Enabled Artificial Intelligence for Detection of Pathologic Gastroesophageal Reflux Disease and Barrett’s Esophagus

Introduction: Gastroesophageal reflux disease (GERD) can lead to voice alterations, including hoarseness. The study aim was to identify specific voice biomarkers associated with pathologic GERD using advanced machine learning tools. Detection of pathologic GERD, including Barrett’s esophagus (BE), with voice biomarkers can serve as a simple non-invasive screening tool. Methods: Voice recordings were obtained from patients undergoing clinically indicated esophagogastroduodenoscopy (EGD) and/or ambulatory pH monitoring studies. Patients were excluded if they had another condition (pulmonary, cardiac, neurologic, etc) associated with voice disturbance. Voice recording consisted of a 6-sentence standard script read over 25-45 seconds. GERD(+) patients were defined as those with erosive esophagitis (LA grade B-D) or peptic stricture or acid exposure time >6%. BE was defined as columnar mucosa >1 cm with confirmed specialized intestinal metaplasia. Patients without these findings were considered GERD(-). A vocally normal group consisting of individuals with normal voice as judged by speech pathology evaluation was used as an independent control group. Random forest models were trained using a balanced number of subjects per condition using random participant selection from the majority class. Using a 5-fold nested cross validation strategy, features were selected and ranked within fold, and a series of models were trained within each fold using recursive feature elimination. The average F1 score, a harmonic mean of precision and recall (range 0-100), across all folds was reported to assess performance. Results: The study sample consisted of 245 patients (vocally normal, n=98; GERD(-), n=78; GERD(+), n=34; BE, n=35) (Table). Feature rankings suggested voice quality differences between groups relating to voice signal periodicity. The model demonstrated excellent ability to discern BE and GERD(+) from the vocally normal group with F1 scores 82 (males) and 89 (females) and 80 (males) and 80 (females) for BE and GERD(+) respectively. There was also a good voice signal distinguishing BE and GERD(+) groups from GERD(-) with F1 scores ranging from 60-70. Figure shows model Receiver Operating Characteristics. Conclusion: These results suggest that voice biomarkers may be useful as a non-invasive tool in the detection of pathologic GERD/BE. A deep learning diagnostic model will be developed using the identified voice biomarkers.Figure 1.: Receiver Operating Characteristics for a Random Forest (RF) Model for males a) BE vs. Normal Voice b) BE vs. GERD(-) c) GERD(+) vs. Normal Voice d) GERD(+) vs. GERD(-); females e) BE vs. Normal Voice f) BE vs. GERD(-) g) GERD(+) vs. Normal Voice h) GERD(+) vs. GERD(-). Table 1. - Baseline patient characteristics in study subgroups Subgroup Sex Number of patients Mean age in years (SD) Barrett's esophagus FemaleMale 1322 65 (15)67 (9) Gastroesophageal reflux disease (+) FemaleMale 2311 51 (14)53 (19) Gastroesophageal reflux disease (-) FemaleMale 4830 55 (15)59 (15) Vocally normal FemaleMale 6434 28 (11)34 (15)

Barrett's Esophagus

Barrett’s esophagus (BE) is caused by metaplasia of squamous epithelium into columnar epithelium, mainly in the lower esophagus. Updates have been made in the etiology, diagnosis and treatment of BE since its first report as an ulcerative lesion in the lower esophagus. Columnar metaplasia of the lower esophagus has been reported as a result of gastroesophageal reflux, rather than genetic factors. When specialized intestinal metaplasia (SIM) is confirmed on biopsy, it is diagnosed as BE; otherwise, it is described as columnar line esophagus (CLE). Recent recommendations state that the following two conditions must be satisfied to diagnose BE: CLE with a length ≥1 cm proximal to the gastroesophageal junction, or SIM, with goblet cells confirmed on biopsy. BE is a key risk factor for esophageal adenocarcinoma. Early detection and treatment of BE, dysplasia, and early esophageal adenocarcinoma arising from BE has become a critical issue in the USA and Europe. The prevalence of BE in Korea is likely to increase because of the increasing prevalence of gastroesophageal reflux diseases. However, there are few reports on the diagnosis and treatment of BE in Korea. In this narrative review, important historical discoveries related to BE, the anatomical structures and endoscopic findings around the gastroesophageal junction required for diagnosing CLE and BE, and a brief review of the guidelines for the diagnosis and treatment of BE are summarized.

516 THE CHARACTERIZATION OF DYSPLASIA IN BARRETT’S ESOPHAGUS—A PROSPECTIVE NATIONWIDE REGISTRY FROM THE RIBBON NETWORK

Abstract Barrett’s Esophagus is the main pathological precursor to esophageal adenocarcinoma (EAC), dysplasia is known to be one of the principal predictors of progression to malignancy. The RIBBON Registry was established with six academic medical centers in the Republic of Ireland to identify and manage high risk Barrett’s Esophagus (BE) patients. From our database of over 4,000 patients our aim was to establish characteristics of those patients who progressed to dysplasia and furthermore to malignancy. Methods Data was gathered prospectively from December 2007—December 2019. Ethical approval was sought for the database at the time of establishment. Detailed endoscopic, pathological and clinical data was collected via a web-based data capture system at time of initial diagnosis and at each subsequent encounter. A data manager was appointed at each site and a national lead coordinating the project. The Vienna Grading system was used to grade histology. Patients were included if they had an initial or subsequent diagnosis of Specialized intestinal metaplasia (SIM), Indefinite for dysplasia (IND) or Low-Grade Dysplasia (LGD). Results 860 patients were included with a total of 3792 patient years, a male to female ratio of 2.9:1 and a median age at diagnosis of 63. 50 patients had an initial diagnosis of SIM with subsequent episodes of dysplasia while 510 patients had IND or LGD at diagnosis. 158 (18.37%) progressed to High grade dysplasia (HGD) and EAC. The overall incidence of EAC was 1.7% per year, HGD 2.4% per year and a combined rate of 4.2% per year. Median time to progression in SIM was 4.7 years, 1.1 years for IND and 9 months for LGD. Conclusion The overall progression of the group was much higher compared to looking at those who had SIM alone without dysplasia from the same registry (0.9% per year). Time to progression was significantly faster in the groups with initial dysplasia be that IND or LGD. In our centers those patients were followed up with repeat endoscopy as per international guidelines, the above results highlight the importance of this practice given the potential for malignancy.

Barrett's Registry Collaboration of academic centers in Ireland reveals high progression rate of low-grade dysplasia and low risk from nondysplastic Barrett's esophagus: report of the RIBBON network.

Barrett's esophagus (BE) is the main pathological precursor of esophageal adenocarcinoma (EAC). Progression to high-grade dysplasia (HGD) or EAC from nondysplastic BE (NDBE), low-grade dysplasia (LGD) and indefinite for dysplasia (IND) varies widely between population-based studies and specialized centers for many reasons, principally the rigor of the biopsy protocol and the accuracy of pathologic definition. In the Republic of Ireland, a multicenter prospective registry and bioresource (RIBBON) was established in 2011 involving six academic medical centers, and this paper represents the first report from this network. A detailed clinical, endoscopic and pathologic database registered 3,557 patients. BE was defined strictly by both endoscopic evidence of Barrett's epithelium and the presence of specialized intestinal metaplasia (SIM). A prospective web-based database was used to gather information with initial and follow-up data abstracted by a data manager at each site. A total of 2,244 patients, 1,925 with no dysplasia, were included with complete follow-up. The median age at diagnosis was 60.5 with a 2.1:1 male to female ratio and a median follow-up time of 2.7years (IQR 1.19-4.04), and 6609.25 person years. In this time period, 125 (5.57%) progressed to HGD/EAC, with 74 (3.3%) after 1year of follow-up and 38 (1.69%) developed EAC, with 20 (0.89%) beyond 1year. The overall incidence of HGD/EAC was 1.89% per year; 1.16% if the first year is excluded. The risk of progression to EAC alone overall was 0.57% per year, 0.31% excluding the first year, and 0.21% in the 1,925 patients who had SIM alone at diagnosis. Low-grade dysplasia (LGD) progressed to HGD/EAC in 31% of patients, a progression rate of 12.96% per year, 6.71% with the first year excluded. In a national collaboration of academic centers in Ireland, the progression rate for NDBE was similar to recent population studies. Almost one in two who progressed was evident within 1year. Crucially, LGD diagnosed and confirmed by specialist gastrointestinal pathologists represents truly high-risk disease, highlighting the importance of expertise in diagnosis and management, and providing indirect support for ablative therapies in this context.

FA02.05: PROGRESSION RATE OF BARRETT’S ESOPHAGUS FROM NATIONAL REGISTRY OF EXPERT CENTERS IS MUCH GREATER THAN ANTICIPATED FROM POPULATION STUDIES

Abstract Background Barrett's Esophagus (BE) is well established as the main pathological precursor for esophageal adenocarcinoma (EAC). Progression to high grade dysplasia (HGD) or EAC varies widely between population based studies and specialized BE registries from high volume centers. No such data existed from the Republic of Ireland until 2011 when a multicenter registry was established involving three centers to more accurately determine the risk of progression to EAC in the Irish population. Methods A detailed clinical, endoscopic and pathological database includes 3397 patients from January 2008 to July 2017, with BE defined by the presence of specialized intestinal metaplasia (SIM). A prospective web based database was used to gather information from three designated esophageal centers with initial and follow up data abstracted by a data manager and overseen by a project manager. Results 325 were excluded following a diagnosis of HGD or EAC at index biopsy, or being a tertiary referral, leaving 3072 with a median age of 61 and a 2.1:1 male to female ratio and a median follow up of 3 years, and 5024 person years. 127 (4%) cases progressed to HGD/EAC, 65 after one year of follow up. 55 (2%) developed EAC were identified, 30 of those within one year. The overall incidence HGD/EAC was 2.53% per year, 1.3% if the first year is excluded. The risk of progression to EAC alone was 1.09% per year, 0.5% excluding the first year. Low grade dysplasia (LGD) on index biopsy was associated with a progression rate of 11.7% per year, 4.2% with the first year excluded. Conclusion With strict data entry and pathologic quality assurance, progression rates for non-dysplastic BE was several fold higher than population studies, highlighting caution in abstracting from population data. True LGD, as evidenced in a recent report by Kestens et al.1 represent high risk disease, with most of the risk evident within the first year. Reference: 1. Kestens C, Offerhaus G, van Baal J, Siersema PD. Patients wtih Barrett's esophagus and persistent low-grade dysplasia have an increased risk for high- grade dysplasia and cancer. Clin Gastroenterol Hepatol. 2016;14:956–962 Disclosure All authors have declared no conflicts of interest.

A Multicenter Study of a Fluorescence In Situ Hybridization Probe Set for Diagnosing High-Grade Dysplasia and Adenocarcinoma in Barrett's Esophagus.

Preliminary single-institution data suggest that fluorescence in situ hybridization (FISH) may be useful for detecting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EA) in patients with Barrett's esophagus (BE). This multicenter study aims to validate the measurement of polysomy (gain of at least two loci) by FISH as a way to discriminate degrees of dysplasia in BE specimens. Tissue specimens were collected from four different hospitals and read by both the local pathology department ("Site diagnosis") and a single central pathologist ("Review diagnosis") at a separate institution. The specimens then underwent FISH analysis using probes 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) for comparison. A total of 46 non-BE, 42 non-dysplastic specialized intestinal metaplasia (SIM), 23 indefinite-grade dysplasia (IGD), 10 low-grade dysplasia (LGD), 29 HGD, and 42 EA specimens were analyzed. We found that polysomy, as detected by FISH, was the predominant chromosomal abnormality present as dysplasia increased. Polysomy was also the best predictor for the presence of dysplasia or EA when comparing its area under the curve to that of other FISH abnormalities. We observed that if at least 10% of cells had polysomy within a specimen, the FISH probe was able to differentiate between EA/HGD and the remaining pathologies with a sensitivity of 80% and a specificity of 88%. This study demonstrates that using FISH to determine the percentage of cells with polysomy can accurately and objectively aid in the diagnosis of HGD/EA in BE specimens.

Endoscopic management of Barrett's esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

Current practices for the management of Barrett's esophagus (BE) vary across Europe, as several national European guidelines exist. This Position Statement from the European Society of Gastrointestinal Endoscopy (ESGE) is an attempt to homogenize recommendations and, hence, patient management according to the best scientific evidence and other considerations (e.g. health policy). A Working Group developed consensus statements, using the existing national guidelines as a starting point and considering new evidence in the literature. The Position Statement wishes to contribute to a more cost-effective approach to the care of patients with BE by reducing the number of surveillance endoscopies for patients with a low risk of malignant progression and centralizing care in expert centers for those with high progression rates.Main statements MS1 The diagnosis of BE is made if the distal esophagus is lined with columnar epithelium with a minimum length of 1 cm (tongues or circular) containing specialized intestinal metaplasia at histopathological examination. MS2 The ESGE recommends varying surveillance intervals for different BE lengths. For patients with an irregular Z-line/columnar-lined esophagus of < 1 cm, no routine biopsies or endoscopic surveillance is advised. For BE ≥ 1 cm and < 3 cm, BE surveillance should be repeated every 5 years. For BE ≥ 3 cm and < 10 cm, the interval for endoscopic surveillance should be 3 years. Patients with BE with a maximum extent ≥ 10 cm should be referred to a BE expert center for surveillance endoscopies. Patients with limited life expectancy and advanced age should be discharged from endoscopic surveillance. MS3 The diagnosis of any degree of dysplasia (including "indefinite for dysplasia") in BE requires confirmation by an expert gastrointestinal pathologist. MS4 Patients with visible lesions in BE diagnosed as dysplasia or early cancer should be referred to a BE expert center. All visible abnormalities, regardless of the degree of dysplasia, should be removed by means of endoscopic resection techniques in order to obtain optimal histopathological staging MS5 All patients with a BE ≥ 10 cm, a confirmed diagnosis of low grade dysplasia, high grade dysplasia (HGD), or early cancer should be referred to a BE expert center for surveillance and/or treatment. BE expert centers should meet the following criteria: annual case load of ≥10 new patients undergoing endoscopic treatment for HGD or early carcinoma per BE expert endoscopist; endoscopic and histological care provided by endoscopists and pathologists who have followed additional training; at least 30 supervised endoscopic resection and 30 endoscopic ablation procedures to acquire competence in technical skills, management pathways, and complications; multidisciplinary meetings with gastroenterologists, surgeons, oncologists, and pathologists to discuss patients with Barrett's neoplasia; access to experienced esophageal surgery; and all BE patients registered prospectively in a database.

Risk Profiles for Barrett’s Esophagus Differ between New and Prevalent, and Long- and Short-Segment Cases

BackgroundPrevious studies on Barrett’s esophagus (BE) risk factors have had differing case definitions and control groups. The purpose of this study was to examine differences in risk factors between newly diagnosed vs. prevalent BE, long- vs. short-segment BE, and endoscopy-only BE without specialized intestinal metaplasia (SIM).MethodsWe conducted a cross-sectional study among eligible patients scheduled for elective esophagogastroduodenoscopy (EGD) and patients eligible for screening colonoscopy, recruited from primary care clinics at a Veterans Affairs center. All participants completed a survey on demographics, gastroesophageal reflux disease (GERD) symptoms and medication use prior to undergoing study EGD. We compared BE cases separately to two control groups: 503 primary care controls and 1353 endoscopy controls. Associations between risk factors and differing BE case definitions were evaluated with multivariate logistic regression models.ResultsFor comparisons with primary care controls, early onset frequent GERD symptoms were more strongly associated with risk of long-segment BE (OR 19.9; 95% CI 7.96–49.7) than short-segment BE (OR 8.54; 95% CI 3.85–18.9). Likewise, the inverse association with H. pylori infection was stronger for long-segment BE (OR, 0.45; 95% CI, 0.26–0.79) than short-segment BE (OR, 0.71; 95% CI, 0.48–1.05). GERD symptoms and H. pylori infection was also more strongly associated with prevalent BE than newly diagnosed BE. Few differences were observed between BE cases and endoscopy controls. Endoscopy-only BE was associated with GERD symptoms (OR 2.25, 95% CI 1.32–3.85) and PPI/H2RA use (OR 4.44; 95% CI 2.61–7.54) but to a smaller degree than BE with SIM.ConclusionWe found differences in the strength and profiles of risk factors for BE. The findings support that epidemiological studies of BE should make a distinction between long and short, new and prevalent, endoscopy-only and BE with SIM as well as type of controls.

The value of NBI-ME for targeting biopsy in the follow-up of Barrett esophagus

Objective To assess the value of NBI-ME for targeting biopsy in the follow-up of Barrett esophagus. Methods A total of 96 patients with Barrett esophagus were enrolled and biopsied between September 2012 and May 2015. With paired crossover design, the patients were randomly allocated to receive a WLI or NBI-ME, who received the other examination in 1-3 months. Outcomes of NBI-ME and WLI were compared with histology of biopsy specimen, and the biopsy quantities were also compared. Results A total of 88 patients completed the study, 4 cases with non-specialized intestinal metaplasia, 55 cases with specialized intestinal metaplasia (SIM), 23 cases with low grade intraepithelial neoplasia(LGIN) and 6 cases with high grade intraepithelial neoplasia(HGIN)were detected. The biopsy number of WLI group was higher than that of NBI-ME group(5.3 VS 3.1, P<0.05). The incidence of intraepithelial neoplasia of WLI was lower than that of NBI-ME[21.6%(19/88)VS 31.8%(28/88), P<0.05]. Diagnostic accuracy of WLI was lower than that of NBI-ME[58.6%(17/26) VS 93.1%(27/29), P<0.05)]. Conclusion NBI-ME can detect more lesions of intraepithelial neoplasia than WLI in the follow-up of Barrett esophagus, and fewer biopsy specimens are needed. Key words: Barrett esophagus; Endoscopy; Follow-up studies; Narrow-band imaging

Localization of specialized intestinal metaplasia and the molecular alterations in Barrett esophagus in a Japanese population: an analysis of biopsy samples based on the “Seattle” biopsy protocol

It remains unclear why Barrett esophagus (BE)-associated adenocarcinoma (EAC) frequently occurs in the 0 to 3 o'clock area of the BE. The aims of this study were to clarify the localization of specialized intestinal metaplasia (SIM) as a precancerous lesion and of molecular alterations among different locations using 4-quadrant biopsies based on the "Seattle" protocol. We prospectively evaluated microsatellite instability; methylation status at the APC, CDKN2A, hMLH1, RUNX3, and MGMT genes; the immunoreactivity of the monoclonal antibody Das-1 for the colonic phenotype; and Ki-67 staining in 10 early EACs and 128 biopsy samples from 32 BE patients. Among the molecular changes, only APC gene hypermethylation was an independent predictive marker of EAC (odds ratio, 24.4; P = .01). SIM was more frequently identified in the 0 to 3 o'clock quadrant than in the 6 to 9 o'clock quadrant (P = .08). The Ki-67 index was higher in SIM than in the columnar-lined epithelium (CLE) without goblet cells (P < .0001) and in both SIM and CLE with Das-1 reactivity than in those without (P = .04 and P = .06, respectively). Furthermore, the index was relatively higher in the 0 to 3 o'clock quadrant than in the 6 to 9 o'clock quadrant in cases with Das-1 reactivity. RUNX3 methylation was more frequently found in SIM than in CLE (P = .04), whereas the incidence of the other biomarkers did not show a significant difference between the 0 to 3 o'clock and 6 to 9 o'clock areas, nor between SIM and CLE. SIM with Das-1 reactivity, but not molecular alterations, in the 0 to 3 o'clock quadrant may have higher proliferative activity compared to the other areas of the BE.

Sa1895 The Accuracy of Acetic Acid Chromoendoscopy for the Diagnosis of Specialized Intestinal Metaplasia (SIM) and Early Neoplasia (EN) in Patients With Barrett's Esophagus. Systematic Review and Meta-Analysis

Sa1895 The Accuracy of Acetic Acid Chromoendoscopy for the Diagnosis of Specialized Intestinal Metaplasia (SIM) and Early Neoplasia (EN) in Patients With Barrett's Esophagus. Systematic Review and Meta-Analysis

Meta-analysis of the effects of endoscopy with narrow band imaging in detecting dysplasia in Barrett's esophagus.

Narrow band imaging (NBI) is a real-time imaging technique. The aim of this meta-analysis was to estimate the sensitivity, specificity, and diagnostic accuracy on the role of NBI in the detection and characterization of specialized intestinal metaplasia (SIM), high-grade dysplasia (HGD) in the Barrett's esophagus. We identified studies by performing a literature search of Medline, EMBASE, and the Cochrane Library databases up to May 2013. We performed data analysis using Meta-DiSc (version 1.4) software. To assess study quality and potential for bias, we used the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). Overall, seven eligible studies including over 3988 lesions of 502 patients were retrieved. The results showed that endoscopic diagnosis of dysplasia performed using NBI has a high diagnostic performance, with an area under the summary receiver operating characteristic (SROC) curve near 0.90 both in HGD lesions and SIM lesions. We also found that NBI has a sensitive and specificity of 0.91 (95% confidence interval [CI] = 0.86-0.94) and 0.85 (95% CI = 0.76-0.92) on a per-patient element, and 0.97 (95% CI = 0.95-0.98) and 0.64 (95% CI = 0.59-0.68) on a per-lesion element for SIM diagnosis, respectively. The pooled per-patient sensitivity and specificity for identifying HGD are 0.91 (95% CI = 0.75-0.98) and 0.95 (95% CI = 0.91-0.97). The pooled per-lesion sensitivity and specificity for identifying HGD are 0.69 (95% CI = 0.63-0.74) and 0.90 (95% CI = 0.88-0.91). In conclusion, we found that endoscopic diagnosis with NBI is an accurate test to diagnosis dysplasia of Barrett's esophagus.

Carcinogenesis of Barrett's esophagus: a review of the clinical literature.

Barrett's esophagus (BE) is a premalignant condition of esophageal adenocarcinoma (EAC). Although the incidence of BE has risen rapidly in the West, it is rare in Asia despite a recent increase in the prevalence of gastroesophageal reflux disease. Controversies over the definition of BE are presented because most cases show short-segment BE, especially ultra-short BE, in Asia. Here we review possible risk factors for the development of EAC, particularly possible roles of ethnicity, specialized intestinal metaplasia (SIM), BE length, and environmental factors, such as Helicobacter pylori infection and obesity. Additionally, we summarize recent studies on the effect of chemoprevention including proton pump inhibitors, nonsteroidal anti-inflammatory drugs or aspirin in order to reduce the risk of neoplastic progression in BE patients. Although substantial knowledge of risk factors of dysplasia/EAC in BE is shown, the risk for neoplastic development may be influenced by geographic variation, study population, the presence or absence of SIM or dysplasia at baseline, and the small number of BE patients investigated. Recently, the efficiency of surveillance for BE patients has been discussed from the standpoint of cost-effectiveness. It may be too difficult to draw conclusions because no randomized clinical trials of BE surveillance have been performed.

Predictable Marker for Regression of Barrett's Esophagus by Proton Pump Inhibitor Treatment in Korea

Background/AimsThere has been no report regarding the regression of Barrett's esophagus (BE) by continuous treatment of proton pump inhibitor (PPI). The aim of this study was to determine the regression rate of BE by PPI and predictable markers related to regression.MethodsThirty-five patients diagnosed as BE were consecutively enrolled and most of them took continuous PPI. The 25 patients underwent endoscopic surveillance and received biopsy. If the specialized intestinal metaplasia (SIM) was lost at any point of surveillance and did not recur, the case was regarded as the regression group. The proportion of SIM was graded and the mucin phenotype was decided using immunohistochemistry for MUC2, MUC5AC and MUC6. To assess the cell proliferation indexes and the degree of intestinal maturation, immunohistochemistry for Ki67 and CDX2 were performed.ResultsThe regression of BE occurred in the 11 (44%) patients. The clinical and demographic factors showed no difference between the regression (n = 11) and persistence group (n = 14). The lower grade of SIM (P < 0.001) and gastric predominant mucin phenotype (P = 0.018) were more frequent, and the number of Ki67 positive cell per gland (P = 0.008) and the mean extent of CDX2 (P = 0.022) were lower in the regression group than in the persistence group.ConclusionsThe regression of BE by PPI treatment was frequent in Korea. The immunohistochemical detection of mucin phenotype, grade of SIM, Ki67 and CDX2 expression in Barrett's mucosa could be useful as a predictable marker for regression of SIM in BE.

Magnifying endoscopy for the diagnosis of specialized intestinal metaplasia in short-segment Barrett’s esophagus

To determine whether magnified observation of short-segment Barrett's esophagus (BE) is useful for the detection of specialized intestinal metaplasia (SIM). Thirty patients with suspected short-segment BE underwent magnifying endoscopy up to × 80. The magnified images were analyzed with respect to their pit-patterns, which were simultaneously classified into five epithelial types [I (small round), II (straight), III (long oval), IV (tubular), V (villous)] by Endo's classification. Then, a 0.5% solution of methylene blue (MB) was sprayed over columnar mucosa. The patterns of the magnified image and MB staining were analyzed. Biopsies were obtained from the regions previously observed by magnifying endoscopy and MB chromoendoscopy. Three of five patients with a type V (villous) epithelial pattern had SIM, whereas 21 patients with a non-type V epithelial patterns did not have SIM. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of pit-patterns in detecting SIM were 100%, 91.3%, 92.3%, 60% and 100%, respectively (P = 0.004). Three of the 12 patients with positive MB staining had SIM, whereas 14 patients with negative MB staining did not have SIM. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MB staining in detecting SIM were 100%, 60.9%, 65.4%, 25% and 100%, respectively (P = 0.085). The specificity and accuracy of pit-pattern evaluation were significantly superior compared with MB staining for detecting SIM by comparison with the exact McNemar's test (P = 0.0391). The magnified observation of a short-segment BE according to the mucosal pattern and its classification can be predictive of SIM.

Aberrant expression of Wnt and Notch signal pathways in Barrett's esophagus

Specialized intestinal metaplasia (SIM) mucosa observed in Barrett's esophagus (BE) has been a hot research topic due to the close relationship with adenocarcinoma of esophagus (ACE). Earlier studies found that SIM mucosa was similar to normal intestinal epithelium on morphology and histology. The signal pathway involved in conformation of intestinal epithelium may be a critical initiator for BE. The expressions of key regulators (Tcf4, Cdx2, Hes1 and Math1) in Wnt and Notch signal pathways were measured in 41 paired esophageal biopsies. Cell morphological changes in normal esophagus were compared among groups treated by acid, bile acid and the mixture of both media. The expression levels of regulators (Tcf4, Cdx2, Hes1 and Math1) were found significantly increased in SIM, C ≥ 3Mn and high-grade dysplasia (HGD) groups. Distinct ultrastructure changes and highly expressed key regulators were also detected at the seventh day for group treated by 400 μmol bile acid. Aberrant expressed regulators in Wnt and Notch pathways were observed in BE tissue and normal esophageal cells treated by acid, bile acid and the mixture of both media. This study provided preliminary data to understand the mechanism of BE conformation.

Usefulness of endoscopic brushing and magnified endoscopy with narrow band imaging (ME-NBI) to detect intestinal phenotype in columnar-lined esophagus

Barrett's esophagus with specialized intestinal metaplasia (SIM), which is at high risk of progressing to esophageal adenocarcinoma, has been identified by obtaining biopsy specimens randomly. Magnified endoscopy with narrow band imaging (ME-NBI) is reported to be useful for detecting SIM or the intestinal phenotype. We aimed to evaluate the usefulness of endoscopic brushing followed by ME-NBI for the detection of the intestinal phenotype. Biopsy and brushing samples were taken following endoscopic observation by ME-NBI. Total RNA was extracted from the whole sample and microdissected samples, and quantitative reverse transcription-polymerase chain reaction (PCR) analysis of SHH, CDX2, and mucin mRNA expression was performed. Fifty patients (32 men, 18 women, average age 67.3 years) with metaplastic columnar epithelium of the lower esophagus were studied. MUC2 (85 vs. 65 %) and CDX2 (95 vs. 75 %) were detected more frequently in the brushing samples than in the biopsy samples. MUC2 expression levels were significantly higher in the brushing samples than those in the biopsy samples. CDX2 and MUC2 expression levels in the brushing samples were significantly higher in the mucosa with tubular/villous pattern observed by ME-NBI than the levels in mucosae with other patterns. Endoscopic brushing in mucosa of columnar epithelium with a tubular/villous pattern visualized by ME-NBI is useful to detect the intestinal phenotype.

The Prevalence of Barrett's Esophagus and the Comparison of Barrett's Esophagus with Cardiac Intestinal Metaplasia in the Health Screening at a Secondary Care Hospital

The purpose of this study was to estimate the prevalence of Barrett's esophagus (BE) and its association with reflux esophagitis (RE) and peptic ulcer disease detected by free charge endoscopy which was covered by the National Health Insurance at a secondary care hospital, and to compare the results of the biopsy of BE with that of cardiac intestinal metaplasia (CIM). A total of 4,002 patients underwent endoscopy from March 2010 to December 2012. BE was diagnosed if there was histologically proven specialized intestinal metaplasia, and CIM was diagnosed if intestinal metaplasia was accompanied with chronic gastritis. Four hundred twenty four patients underwent endoscopic biopsy, and the prevalence of BE was 1.0% (42/4,002). The mean age and the proportion of males in BE were significantly higher than those of the rest of study population, and BE had slight tendency related to RE than the rest of study population. CIM was observed in 34 patients and BE and CIM showed similar results, regarding age, sex and association with RE. The mean length of endoscopic Barrett's mucosa of BE group was 9.2±5.1 mm, and it was similar to that of CIM. The prevalence of BE in the secondary care hospital was not low, and old age and male sex were significantly associated with BE. Because BE was observed in about 10% of biopsied patients and CIM was observed in a similar percentage with BE, the precise targeted biopsy is warranted and the biopsy method should be reestablished through the large prospective study of multiple secondary care hospitals.

Detailed esophageal function and morphological analysis shows high prevalence of gastroesophageal reflux disease and Barrett's esophagus in patients with cervical inlet patch

Although the pathogenesis of cervical inlet patch (CIP) is not fully understood, most authors consider it as a congenital abnormality, whereas others surmise it to be related to gastroesophageal reflux disease (GERD). We aimed to evaluate esophageal function and the prevalence of GERD and Barrett's esophagus in patients with CIP. GERD is defined by the presence of erosive esophagitis or an abnormal pH monitoring. Seventy-one consecutive patients with endoscopic and histological evidence of CIP were prospectively evaluated. Esophageal symptom analysis, 24-hour simultaneous biliary reflux and double-channel pH-monitoring, and esophageal manometry were carried out in 65/71 (92%) patients and in 25 matched controls. Six patients were not suitable for testing and were, therefore, excluded. The histological evaluation of the heterotopic islands showed cardia and/or oxyntic mucosa in 64/65 (98%) patients and specialized intestinal metaplasia (SIM) in one patient (2%). The cardia and/or oxyntic mucosa was accompanied by focally appearing pancreatic acinar metaplasia and pancreatic ductal metaplasia in 7/64 (11%) and in 1/64 (2%), superficial mucous glands in 6/64 (9%), and SIM in 2/64 (3%) cases. In total, SIM was present in three patients (5%), and one of them had low-grade dysplasia. At the gastroesophageal junction, 28 (43%) patients had columnar metaplasia, including nine (14%) patients with SIM. Erosive esophagitis was present in 37 (57%) cases. Thirty-two patients (49%) had abnormal acid reflux in the distal and 25 (38%) in the proximal esophagus. Abnormal biliary reflux was present in 25 (38%) cases. On the basis of endoscopic and pH studies, GERD was established in 44/65 (68%) patients. Typical reflux symptoms were common (33/65, 51%). The combined 24-hour biliary and double-channel pH-monitoring detected significantly more significant acidic reflux at both measurement points and significantly longer bile exposure time in the distal esophagus in patients with CIP. Acid secretion in the CIP was detected in three (5%) cases. Esophageal manometry revealed decreased LES pressure and prolonged relaxation with decreased peristaltic wave amplitude, and an increased number of simultaneous contractions in the esophageal body. The detailed evaluation of the esophageal morphology and function in subjects with CIP showed a high prevalence of GERD and Barrett's esophagus. Further studies are needed to evaluate whether combined acidic and biliary reflux is able to promote similar histomorphological changes in the CIP, as it is shown distally in patients with Barrett's esophagus.

A renewed insight into Barrett's esophagus: comparative histopathological analysis of esophageal columnar metaplasia

Specialized intestinal metaplasia (SIM) is considered as a premalignant condition of the esophagus, but other types of esophageal metaplasia are commonly neglected. A standardized histopathological analysis was focused not only on SIM but also on the presence of metaplastic processes typical of additional glands. A morphological study using standardized histopathological tests was carried out between 2004 and 2007, with biopsies taken from esophageal mucosa of 826 consecutive patients. Mean age and male : female ratio of patients were 55.6 ± 14.7 and 1.1 : 1, respectively. Only 4.1% (n = 34) of all cases proved to have SIM. The remainder of the cases (n = 615; 74.4%) contained cardiac-fundic mucosa without SIM. Some samples exhibited superficial mucous glands, pancreatic acinar metaplasia (PAM), and ciliated metaplasia accounting for 24% (n = 198), 14.9% (n = 123), and 0.2% (n = 2), respectively. SIM was colocalized with superficial mucous glands (103/198 superficial mucous gland cases; P < 0.001). Low-grade dysplasia (n = 51; 6.2%) and high-grade dysplasia (n = 9; 1.1%) were found mainly in SIM (37/51; 9/9; P = 0.071) with male preponderance (3 : 1 at low-grade and 2 : 1 at high-grade dysplasia). PAM was found mainly in cases without dysplasia (103 of 123 pancreatic metaplasias; P < 0.001). SIM alone in the esophagus is rare, and its frequent association with cardiac mucosa-type metaplasia testifies to transition of mucinous-goblet cell through pseudogoblet cells. PAM rather indicates absence of dysplasia, but superficial mucous glands predicts that SIM follows dysplasia.