Esophageal Biopsies Research Articles

230. ENDOSCOPIC REFERENCE SCORE REMODELING SUBSCORE AND ESOPHAGEAL EOSINOPHIL COUNT DO NOT CORRELATE IN PLACEBO-TREATED EOSINOPHILIC ESOPHAGITIS PATIENTS FROM DUPILUMAB STUDIES

Abstract Although eosinophils are the hallmark of eosinophilic esophagitis (EoE) with threshold levels required for diagnosis, their exact role in EoE is unclear. The EoE-Endoscopic Reference Score (EREFS) assesses endoscopic inflammatory (edema/exudate/furrows) and remodeling (rings/strictures) features. We assessed the correlations between peak esophageal intraepithelial eosinophil count (eos/high-power field [hpf]) and EREFS in placebo-treated EoE patients from two clinical trials: phase 2 proof-of-concept (POC; NCT02379052; n = 24) and part A of phase 3 TREET (Phase3-PartA; NCT03633617; n = 39). POC was a 12-week trial in adults and Phase3-PartA was a 24-week trial in adults and adolescents. Endoscopic examination of the esophagus was performed at baseline (BL) and end of treatment (EOT) and scored for inflammatory and remodeling subscores and total score using EREFS (higher scores indicate greater severity). Peak eos/hpf was measured from pinch biopsies of proximal, mid, and distal esophagus at BL and EOT. Pearson correlations were performed between total/proximal/mid/distal eos/hpf and EREFS total, subscores, and components at BL, EOT, and for change from BL at EOT. Some strong correlations (r > 0.5) were observed between total peak eos/hpf and EREFS at BL in both studies and at EOT in Phase3-Part A (Table). Moderate-to-strong correlations (r > 0.3) were observed between total peak eos/hpf and EREFS inflammation subscore and edema/exudates/furrows individual components (some P > 0.5) in both studies. Correlations of total peak eos/hpf with EREFS remodeling subscore and rings/stricture components were not significant (P = 0.07–0.94). Peak eos/hpf in the proximal, mid, or distal esophagus were more strongly associated with EREFS inflammation subscore (majority moderate-to-strong correlations; P = 0.001–0.66) than EREFS remodeling subscore (weak correlations, P = 0.22–0.99) at BL/EOT for both studies. In these EoE patients, moderate-to-strong correlations were observed between eos/hpf and endoscopic markers of inflammation. No strong correlations were observed between total, proximal, mid, or distal peak eos/hpf and endoscopic parameters of remodeling. These data support a role for intact eosinophils in inflammatory changes in the esophagus in EoE and demonstrate the need for both histology and endoscopic evaluation. Further study, with larger sample sizes, is required to verify these findings in other contexts.

An Unusual Cause of Esophagitis

An Unusual Cause of Esophagitis

Eosinophil Peroxidase Staining Enhances the Diagnostic Utility of the Cytosponge in Eosinophilic Esophagitis.

We aimed to assess the diagnostic utility of eosinophil peroxidase (EPX) staining on Cytosponge (CS) samples in eosinophilic esophagitis (EoE). Esophageal biopsy (BX) samples from adult subjects with EoE were assessed using peak eosinophils per high-power field (eos/hpf), EPX, and the EoE histologic scoring system. EPX staining and eos/hpf were compared (BX vs CS). CS EPX positivity correlated with eos/hpf (CS [ r = 0.82, P < 0.0001]; BX [ r = 0.65, P < 0.0001]) and EoE histologic scoring system (grade [ r = 0.62, P < 0.00001]; stage [ r = 0.61, P < 0.0001]). CS EPX identified subjects with active EoE (area under the curve = 0.86, P < 0.0001). The correlation of CS EPX with eosinophilic inflammation and histologic disease severity supports its diagnostic utility in EoE.

Eosinophilic oesophagitis in Denmark: Population‐based incidence and prevalence in a nationwide study from 2008 to 2018

BackgroundEosinophilic oesophagitis (EoE) is a chronic immune‐mediated or antigen‐mediated oesophageal disease characterised by symptoms related to oesophageal dysfunction and eosinophil‐predominant inflammation.ObjectiveWe aimed to estimate the incidence and prevalence of EoE in Denmark during the period 2008–2018.MethodsBased on data from nationwide registers we identified cases of EoE using two definitions: a broad definition based solely on oesophageal biopsies registered in the Danish Pathology Register and a narrow definition also including symptoms of oesophageal dysfunction registered in the Danish National Patient Registry. The annual incidence and prevalence were standardised by sex and age in 5‐year intervals to the 2013 study population.ResultsFrom 2008 to 2011, the standardised incidence of EoE was stable, but from 2011 to 2018 it increased from 3.9 (95% CI 3.3–4.4) to 11.7 (95% CI 10.8–12.6) per 100,000 person‐years. Similar temporal trends were observed when using the narrow EoE definition. The increase in incidence was most pronounced in men and in individuals above 40 years of age. In children, the EoE incidence was a fourth of the incidence in adults aged 40–64 years: 4.4 (95% CI 3.2–5.6) versus 17.6 (95% CI 15.7–19.5) per 100,000 person‐years. The EoE incidence varied substantially across the five regions in Denmark. Overall, the biopsy rate as well as the proportion of oesophageal biopsies with detected eosinophilia increased during the study period.ConclusionThis study of the entire population of Denmark during the period 2008 to 2018 shows that the incidence and prevalence of EoE is not yet plateauing and that EoE could be severely underdiagnosed, especially in children.

Pre-endoscopy Symptoms and Age, But Not Esophageal Biopsy Number Are Associated With Post-endoscopy Adverse Events.

Esophagogastroduodenoscopy (EGD) is a frequently utilized investigative tool in the management of gastrointestinal conditions in children. Biopsies obtained during EGD may pose risk for post-operative adverse events (AEs), and further understanding of risk is imperative to provide informed consent to families and safe patient care. In particular, the impact of biopsy number and location on the development of AEs has not been studied in pediatric patients. We prospectively assessed for AEs by telephone survey 3-7 days after 209 EGDs performed on patients ages 1-21 years over a 1-year period. Demographic, endoscopic, and histologic data were collected. The most common symptoms reported were throat pain (61%), chest pain (26%), and dysphagia (26%). Binary regression models identified age and pre-operative symptoms as factors that influenced the likelihood of post-operative morbidity. Multiple biopsies from 3 different locations of the esophagus did not impact the risk of post-operative AEs.

A six-year hospital-based surveillance study on burden of esophageal candidiasis in Gangtok, Sikkim.

Esophageal candidiasis once thought to be restricted amongst immunocompromised patients is being increasingly reported among non-immunocompromised individuals. It is debilitating and if not treated well may cause chronic long-lasting infections. The objective of this study was to identify the various species of Candida causing esophageal candidiasis and analyse their antifungal susceptibility pattern. This was an observational, prospective study. Total of 108 patients who attended the Gastroenterology Department of Sir Thutob Namgyal Memorial Hospital, Govt of Sikkim, Gangtok, India between July 2012 - May 2018 were included in the study. They had complaints of upper gastrointestinal disturbances and chronic dyspeptic symptoms that required an endoscopy. Esophageal biopsy and brushings were taken and were transported to Microbiology Department. They were subjected to microscopic observation, fungal culture on Sabourauds dextrose agar. Preliminary species identification was done by chlamydospore formation and growth characteristics on CHROMagar Candida. Species confirmation and antifungal susceptibility testing was done on VITEK 2 system at Microbiology Department, Kasturba Medical College and Hospital, MAHE, Manipal, Karnataka, India. A total of 108 patients were screened among which 73 samples were positive for Candida species and species identification and antifungal susceptibility was performed. Forty fiveisolates were found to be C. albicans, 8 were C. glabrata, 4 were C. tropicalis, 3 were C. lusitaniae 2 were C. krusei, 2 were C. lipolyticaand 1 was C. parapsilosis. Eight isolates could not be identified and were recorded as Candida spp. C. albicans isolates were predominantly sensitive strain with susceptibility of 95% for both amphotericin B and fluconazole and 100% for caspofungin. C. glabrata showed high resistance to fluconazole with one isolate showing intermediate resistance to caspofungin. Upper gastrointestinal symptoms even in non-immunocompromised patients need to be screened by endoscopy to rule out esophageal candidiasis. With the emergence of drug resistant non albicans Candida species diagnostic testing laboratories should include Candida species identification and antifungal susceptibility testing facility to provide effective patient care.

An Unusual Case of Refractory Peptic Ulcer Disease

An Unusual Case of Refractory Peptic Ulcer Disease

An Endoscopic and Histologic Study on Healing of Radiofrequency Ablation Wounds in Patients With Barrett's Esophagus.

Radiofrequency ablation (RFA) of Barrett's esophagus (BE) inflicts a wound spanning 3 epithelial types (stratified squamous, Barrett's metaplasia, gastric epithelium), yet the esophageal injury heals almost completely with squamous epithelium. Knowledge of how this unique wound heals might elucidate mechanisms underlying esophageal metaplasia. We aimed to prospectively and systematically characterize the early endoscopic and histologic features of RFA wound healing. Patients with nondysplastic BE had endoscopy with systematic esophageal photographic mapping, biopsy, and volumetric laser endomicroscopy performed before and at 1, 2, and 4 weeks after RFA. Seven patients (6 men; mean age 56.1 ± 10.9 years) completed this study. Squamous re-epithelialization of RFA wounds did not only progress exclusively through squamous cells extending from the proximal wound edge but also progressed through islands of squamous epithelium sprouting throughout the ablated segment. Volumetric laser endomicroscopy revealed significant post-RFA increases in subepithelial glandular structures associated with the squamous islands. In 2 patients, biopsies of such islands revealed newly forming squamous epithelium contiguous with immature-appearing squamous cells arising from esophageal submucosal gland ducts. Subsquamous intestinal metaplasia (SSIM) was found in biopsies at 2 and/or 4 weeks after RFA in 6 of 7 patients. RFA wounds in BE are re-epithelialized, not just by squamous cells from the proximal wound margin but by scattered squamous islands in which esophageal submucosal gland duct cells seem to redifferentiate into the squamous progenitors that fuel squamous re-epithelialization. SSIM can be found in most patients during the healing process. We speculate that this SSIM might underlie Barrett's recurrences after apparently successful eradication.

Exploring the use of p53 protein expression as an indicator of oesophageal cancer severity from a high incidence rural area of Africa

The expression of p53 has been associated with the severity of other types of cancer. There is scanty information when it comes to oesophageal cancer. This study aimed to explore the use of p53 protein expression as an indicator of oesophageal cancer severity from a high-risk incidence in the African rural population. Fifty-one patients newly diagnosed with oesophageal cancer were recruited from the endoscopic unit at Nelson Mandela Academic Hospital in Mthatha, South Africa. The serological expression of p53 was measured using the ELISA method and the severity of oesophageal cancer expressed in grade was obtained from the histopathology report from patient's oesophageal biopsies. We found that the expression of p53 was equally distributed among the histological grades of cancer with the value of 2495 pg/mL ± 1736 pg/ mL for lower grades and 2520 ± 1539 pg/mL for higher grades. Furthermore, we found that the level of p53 expression was equally distributed in patients from grade 1, 2, 3, and 4. The expression of p53 protein does not vary according to the histological grade of oesophageal cancer in the given population, therefore may not be helpful as a prognostic factor.

Eosinophilic esophagitis auxiliary diagnosis based on a peptide ligand to eosinophil cationic protein in esophageal mucus of pediatric patients

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus characterized by increased number of eosinophils. Currently, EoE diagnosis is based on endoscopic procedures for histopathological examination, eosinophils’ counting and, often, in clinical practice, the challenge is the differentiation between EoE and gastroesophageal reflux disease (GERD). Our aim was to develop novel peptide ligand to Eosinophil cationic protein (ECP) present in EoE biopsies of patients with potential to be used for detection. We performed a comparative proteomic analysis using liquid chromatography-tandem mass spectrometry (LC–MS/MS) of esophageal biopsies from pediatric patients with eosinophilic esophagitis, gastroesophageal reflux disease and control individuals. Then, phage display technology was used to select peptides against specific up-regulated protein from EoE patients. Twelve phage clones were selected after three biopanning rounds, and the best phage clone reactivity was evaluated by phage-ELISA assay using esophageal mucus samples from 94 pediatric patients. Mass spectrometry showed that eosinophil cationic protein (ECP) was one of the most up-regulated proteins in EoE patients, which is an eosinophil granule protein usually deposited on tissues to mediate remodeling, but in excess may cause fibrosis and hypertrophy, especially in allergic responses. A highly reactive ECP-ligand peptide (E5) was able to distinguish reactive mucus of EoE patients from GERD and the control individuals by Phage-ELISA, achieving a sensitivity of 84.62%, and a specificity of 82.72%. This is the first study that successfully demonstrated an antibody-like peptide targeting ECP at the esophagus mucus as a useful auxilliary tool for EoE diagnosis with a significant association with atopic disorders and dysphagia.ClinicalTrials.gov no.: NCT03069573.

A Deep Multi-Label Segmentation Network For Eosinophilic Esophagitis Whole Slide Biopsy Diagnostics.

Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus associated with elevated numbers of eosinophils. Disease diagnosis and monitoring require determining the concentration of eosinophils in esophageal biopsies, a time-consuming, tedious and somewhat subjective task currently performed by pathologists. Here, we developed a machine learning pipeline to identify, quantitate and diagnose EoE patients' at the whole slide image level. We propose a platform that combines multi-label segmentation deep network decision support system with dynamics convolution that is able to process whole biopsy slide. Our network is able to segment both intact and not-intact eosinophils with a mean intersection over union (mIoU) of 0.93. This segmentation enables the local quantification of intact eosinophils with a mean absolute error of 0.611 eosinophils. We examined a cohort of 1066 whole slide images from 400 patients derived from multiple institutions. Using this set, our model achieved a global accuracy of 94.75%, sensitivity of 94.13%, and specificity of 95.25% in reporting EoE disease activity. Our work provides state-of-the-art performances on the largest EoE cohort to date, and successfully addresses two of the main challenges in EoE diagnostics and digital pathology, the need to detect several types of small features simultaneously, and the ability to analyze whole slides efficiently. Our results pave the way for an automated diagnosis of EoE and can be utilized for other conditions with similar challenges.

Barrier proteins and eosinophilic esophagitis in children: the role of E-cadherin and filaggrin.

This study aimed to assess the protein expression of E-cadherin and filaggrin (FLG) in the oesophagus of paediatric and adolescent patients diagnosed with eosinophilic esophagitis (EoE). It is a cross-sectional study conducted with 24 patients with EoE and 17 control patients, from June 2015 to June 2018. The histological analyses were performed by a trained pathologist. The protein expression of E-cadherin and FLG in oesophageal biopsy fragments was determined using an immunohistochemical technique. The epidemiological data were retrieved from medical records. There were no statistical differences in age and sex between case-patients and control patients. Food allergy was significantly higher in patients with EoE, as was the number of eosinophils present in the oesophageal biopsy materials. The immunohistochemical studies did not indicate FLG expression in any patient from the two groups. E-cadherin showed significantly reduced expression in patients with EoE. We concluded that FLG did not seem to play an important role in the mucosal alteration in EoE and that E-cadherin under expression could be a promising marker of epithelial damage in these patients.

Acute Esophageal Necrosis: A Retrospective Cohort Study Highlighting the Mayo Clinic Experience

ObjectiveTo describe the clinical, endoscopic, and histologic features in patients with acute esophageal necrosis (AEN). Patients and MethodsIn this retrospective cohort study, patients who were diagnosed as having AEN at Mayo Clinic sites in Minnesota, Florida, and Arizona between January 1, 1996, and January 31, 2021, were included. Data were collected on patient clinical characteristics and endoscopic and pathologic findings. ResultsThe study included 79 patients with AEN with a median (range) age of 64 years (12 to 91 years); 53 (67.1%) were men. Predominant presenting symptoms were hematemesis (49 of 79 [62.0%]), abdominal pain (29 [36.7%]), and melena (20 [25.3%]). Shock was the triggering event for AEN in 49 (62.0%). The 30- and 90-day mortality were 24.0% (19 of 79) and 31.6% (25), respectively. The presence of coexisting infection or bacteremia was significantly associated with 90-day mortality (P<.01). Endoscopically, involvement of the distal third only, distal two-thirds only, and entire esophagus was observed in 31.6% (24 of 76), 39.5% (30), and 29.0% (22), respectively. The length of esophageal involvement correlated with duration of hospitalization (P=.05). The endoscopic appearance of the esophageal mucosa ranged from predominantly white (21 of 44 [47.7%]) to mixed white and black (13 [29.6%]) to predominantly black (10 [22.7%]), and sloughing was present in 18 (40.9%). In the 26 patients with histopathologic findings available for review, 25 (96.1%) had necrosis and/or ulceration with abundant pigmentation. Among the 79 patients, 39 (49.4%) had a follow-up esophagogastroduodenoscopy; 26 of these 39 patients (66.7%) had resolution while 5 had persistent AEN, 4 of whom had improvement. Esophageal strictures developed in 7 of the 39 patients (18.0%). ConclusionAcute esophageal necrosis is a serious condition observed in critically ill patients. Its endoscopic appearance can be highly variable. In patients with an unclear diagnosis, esophageal biopsies may be helpful given the characteristic histologic findings.

Salivary microbiota composition may discriminate between patients with eosinophilic oesophagitis (EoE) and non-EoE subjects.

Data on the role of the microbiome in adult patients with eosinophilic oesophagitis (EoE) are limited. To prospectively collect and characterise the salivary, oesophageal and gastric microbiome in patients with EoE, further correlating the findings with disease activity. Adult patients with symptoms of oesophageal dysfunction undergoing upper endoscopy were consecutively enrolled. Patients were classified as EoE patients, in case of more than 15 eosinophils per high-power field, or non-EoE controls, in case of lack of eosinophilic infiltration. Before and during endoscopy, saliva, oesophageal and gastric fundus biopsies were collected. Microbiota assessment was performed by 16 s rRNA analysis. A Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was implemented to identify biomarkers. Saliva samples were collected from 29 EoE patients and 20 non-EoE controls;, biopsies from 25 EoE and 5 non-EoE controls. In saliva samples, 23 Amplicon Sequence Variants (ASVs) were positively associated with EoE and 27 ASVs with controls, making it possible to discriminate between EoE and non-EoE patients with a classification error (CE) of 24%. In a validation cohort, the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of this model were 78.6%, 80%, 75%, 80% and 60%, respectively. Moreover, the analysis of oesophageal microbiota samples observed a clear microbial pattern able to discriminate between active and inactive EoE (CE=8%). Our preliminary data suggest that salivary metabarcoding analysis in combination with machine learning approaches could become a valid, cheap, non-invasive test to segregate between EoE and non-EoE patients.

Novel DNA Methylation Biomarker Panel for Detection of Esophageal Adenocarcinoma and High-Grade Dysplasia.

Current endoscopy-based screening and surveillance programs have not been proven effective at decreasing esophageal adenocarcinoma (EAC) mortality, creating an unmet need for effective molecular tests for early detection of this highly lethal cancer. We conducted a genome-wide methylation screen to identify novel methylation markers that distinguish EAC and high-grade dysplasia (HGD) from normal squamous epithelium (SQ) or nondysplastic Barrett's esophagus (NDBE). DNA methylation profiling of samples from SQ, NDBE, HGD, and EAC was performed using HM450 methylation arrays (Illumina) and reduced-representation bisulfate sequencing. Ultrasensitive methylation-specific droplet digital PCR and next-generation sequencing (NGS)-based bisulfite-sequencing assays were developed to detect the methylation level of candidate CpGs in independent esophageal biopsy and endoscopic brushing samples. Five candidate methylation markers were significantly hypermethylated in HGD/EAC samples compared with SQ or NDBE (P < 0.01) in both esophageal biopsy and endoscopic brushing samples. In an independent set of brushing samples used to construct biomarker panels, a four-marker panel (model 1) demonstrated sensitivity of 85.0% and 90.8% for HGD and EACs respectively, with 84.2% and 97.9% specificity for NDBE and SQ respectively. In a validation set of brushing samples, the panel achieved sensitivity of 80% and 82.5% for HGD and EAC respectively, at specificity of 67.6% and 96.3% for NDBE and SQ samples. A novel DNA methylation marker panel differentiates HGD/EAC from SQ/NDBE. DNA-methylation-based molecular assays hold promise for the detection of HGD/EAC using esophageal brushing samples.

Abstract 2616: Stemness factors nanog and oct4 contribute to epithelial-to-mesenchymal transition and are predictive for outcome in esophageal adenocarcinoma

Abstract Background and Aims: The incidence of esophageal adenocarcinoma (EAC) has increased six-fold in Western countries over the last decades, and 5-year survival rates remain low at 5-20%. While multimodality treatment strategies for curative treatment of esophageal cancer, including the CROSS regimen (chemoradiotherapy followed by surgery) have increased median overall survival, the majority of patients develop recurrences after several months. Epithelial to mesenchymal transition (EMT) has been recently shown by our group to be one of the major underlying mechanisms of resistance to therapy. Paradoxically, therapeutic pressure of effective therapies such as the CROSS regimen are found to instruct a mesenchymal, resistant phenotype in models for EAC. In this study, the aim was to delineate the heterogeneity for the propensity to undergo EMT after chemoradiation and which mechanisms underpin this propensity. Methods: A panel of 8 EAC cell lines (5 primary and 3 ATCC cell lines) were treated with chemoradiotherapy and ranked by their propensity to undergo EMT, based on morphology when EMT occurred and protein marker expression. Next, the cell line panel as well as 44 pre-treated esophageal biopsies were RNA-sequenced. Expression data of the cell line panel were linked to their ranked in vitro EMT response. By means of Leave-one-out cross validation with Ridge Regression, EMT score prediction in pre-treated biopsies was validated. Gene expression profiles were related to clinical outcome data to identify markers that associated with propensity for EMT in patients. Results: In the panel of in vitro EAC models, a strong heterogeneity was observed for the propensity to EMT after chemoradiation. For each marker, Ridge regression analysis identified the top 50 highly correlating genes. Combining all positively correlating genes of days to EMT, NCAD and ZEB1, known key transcription factors of pluripotency including NANOG and OCT4 emerged. Expression of NANOG and OCT4 in pre-treatment biopsies was highly predictive for response to neoadjuvant chemoradiation, occurrence of recurrences, and survival in patients. Genetic perturbation by knockout and inhibition of NANOG and OCT4 reduced the onset of EMT and sensitized cells for chemoradiation. Conclusions: In conclusion, we were able to identify patients who are disproportionally prone to develop EMT in response to chemoradiation. Moreover, stemness factors NANOG and OCT4 are crucial regulators in plasticity of EAC and are promising predictive markers in pre-treatment biopsies of patients. By targeting NANOG and OCT4 in vitro, cells were sensitized to chemoradiation, holding promise for stemness inhibition to prevent therapy resistance in EAC. Citation Format: Amber Perenna van der Zalm, Mark P. Dings, Reimer Janssen, Peter Bailey, Jan Koster, Danny Zwijnenburg, Richard Volckmann, Cynthia Waasdorp, Jeroen Blokhuis, César Oyarce, Gerrit Hooijer, Sybren L. Meijer, Jan Paul Medema, Hanneke W. van Laarhoven, Maarten F. Bijlsma. Stemness factors nanog and oct4 contribute to epithelial-to-mesenchymal transition and are predictive for outcome in esophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2616.

Multicenter Randomized Controlled Trial of Surveillance Versus Endoscopic Therapy for Barrett’s Esophagus With Low-grade Dysplasia: The SURVENT Trial: Study Rationale, Methodology, Innovation, and Implications

Multicenter Randomized Controlled Trial of Surveillance Versus Endoscopic Therapy for Barrett’s Esophagus With Low-grade Dysplasia: The SURVENT Trial: Study Rationale, Methodology, Innovation, and Implications

Global variations in diagnostic guidelines for Barrett's esophagus.

Endoscopic diagnosis of gastroesophageal junction and Barrett's esophagus is essential for surveillance and early detection of esophageal adenocarcinoma and esophagogastric junction cancer. Despite its small size, the gastroesophageal junction has many inherent problems, including marked differences in diagnostic methods for Barrett's esophagus in international guidelines. To define Barrett's esophagus, gastroesophageal junction location should be clarified. Although gastric folds and palisade vessels are landmarks for identifying this junction, they are sometimes difficult to observe due to air entry or reflux esophagitis. The possibility of diagnosing a malignancy associated with Barrett's esophagus <1 cm, identified using palisade vessels, should be re-examined. Nontargeted biopsies of Barrett's esophagus are commonly used to detect intestinal metaplasia, dysplasia, and cancer as described in the Seattle protocol. Barrett's esophagus with intestinal metaplasia has a high risk of becoming cancerous. Furthermore, the frequency of cancer in patients with Barrett's esophagus without intestinal metaplasia is high, and the guidelines differ on whether to include the presence of intestinal metaplasia in the diagnosis of Barrett's esophagus. Use of advanced imaging technologies, including narrow-band imaging with magnifying endoscopy and linked color imaging, is reportedly valid for diagnosing Barrett's esophagus. Furthermore, artificial intelligence has facilitated the diagnosis of Barrett's esophagus through its deep learning and image recognition capabilities. However, it is necessary to first use the endoscopic definition of the gastroesophageal junction, which is common in all countries, and then elucidate the characteristics of Barrett's esophagus in each region, for example, length differences in the risk of carcinogenesis with and without intestinal metaplasia.

Prevalence of Eosinophilic Esophagitis in Patients with Gastroesophageal Reflux Symptoms: A Cross-Sectional Study

Objective:Prevalence of eosinophilic esophagitis in patients with gastroesophageal reflux symptoms. Study Design:A Cross-sectional Study Place and Duration:The study was conducted at Gastroenterology department of DHQ Teaching Hospital, Timargarafor six months from August 2021 to January 2022. Methods: There were 300 patients of both genders presented in this study. Individuals who agreed to participate, their personal information such as age, gender, height and weight was recorded with their informed permission. Included patients were had gastroesophageal reflux symptoms. Esophageal biopsies of all the patients were underwentesophagogastroduodenoscopy (EGD). Prevalence of eosinophilic esophagitis was recorded among all cases. SPSS 23.0 was used to analyze all data. Results: The mean age of the patients was 41.9±8.21 years and had mean BMI 25.7±6.31 kg/m2. Majority of the patients were males 190 (63.3%) and 110 (36.7%) were females. We found that frequency of eosinophilic esophagitis among all cases were 27 (9%). Among 27 cases of EoE, males were higher in number 19 (70.4%) than females 8 (29.6%). Among these cases, heartburn was the most common symptom found in 10 (37.03%) cases, followed by dysphagia in 6 (22.2%), epigastric pain in 5 (18.5%). Lower esophagus found in 12 (44.4%) cases and mid in 15 (55.6%) cases. Mean eosinophils was 24.4±7.29 per HPF. As per histological findings,eosinophilicmicroabscess was found in 20 (70.1%) cases. Conclusion:Patients with refractory GERD are at risk of developing eosinophilic esophagitis, which can be life-threatening. Dysphagia, heartburn, and food impaction are all possible symptoms. The EoE screening of elderly patients with prolonged GERD, atopy, and non-response to stomach acid inhibitors must be evaluated. Keywords: Refractory GERD, Eosinophilic Esophagitis, Dysphagia, Heartburn

Esophageal epithelial immunoglobulin G is an important marker for the diagnosis and management of pediatric eosinophilic esophagitis

Background and AimOur primary aim was to describe the prevalence of immunoglobulin G (IgG) and its subclass IgG4 in immunohistochemistry staining in esophageal biopsy specimens of children with eosinophilic esophagitis (EoE) compared with that of specimens from children with gastroesophageal reflux disease (GERD).MethodsEsophageal biopsy specimens from children with EoE or GERD were stained prospectively for IgG and IgG4 antibodies. Subjects with EoE were divided into cohorts with either active EoE or EoE in remission. Active EoE cases were further divided into proton pump inhibitor responsive (PPI‐r) and PPI‐nonresponsive (PPI‐nr) subgroups. Demographic, clinical, and histologic data were compared among groups, including quantified IgG and IgG4 staining, peak eosinophil count, eosinophil‐derived neurotoxin levels, and EoE endoscopic reference score.ResultsSeventy‐nine children (aged 10.6 ± 5.6 years; 68% male) were enrolled. IgG‐positive cell counts were significantly elevated in those with active EoE (n = 29, 3 [interquartile range, IQR: 2–6]/high‐powered field [HPF]), compared with those having EoE remission (n = 25, 1 [IQR: 0–2]/HPF; P = 0.002) and those with GERD (n = 25, 0 [IQR: 0–0.25]/HPF, P = <0.0001). IgG‐positive cell counts were significantly higher in the PPI‐r (n = 15, 5 [IQR: 2.5–11]/HPF) subgroup, compared with the PPI‐nr subgroup (n = 11, 3 [IQR: 1.5–3.5]/HPF; P = 0.041) at baseline endoscopy.ConclusionInitial esophageal tissue biopsy specimens from pediatric subjects with active EoE showed a significant increase in IgG‐positive staining compared with tissue from subjects in EoE remission or with GERD. There was higher positivity of IgG‐stained cells in the PPI‐r subgroup compared with the PPI‐nr subgroup.