Esophageal Biopsies Research Articles

S3679 Development of Eosinophilic Esophagitis Following Adalimumab Treatment in Two Adolescents With Crohn's Disease

Introduction: Adalimumab is an anti-tumor necrosis factor-alpha (TNF-alpha) used in the treatment of Crohn’s disease (CD). There have been reported associations of CD and Eosinophilic Esophagitis (EoE); A recent study found that the prevalence of Inflammatory Bowel Disease (IBD) in the EoE population was 2.2% and the prevalence of EoE in the IBD population was 1.5%. A second study found that patients with IBD are four times more likely to develop EoE than the general population. In a small case series, 10 children with CD were diagnosed with EoE while on biologic therapy with infliximab. We describe two adolescents who developed EoE while on adalimumab therapy for CD. Case Description/Methods: Case 1: A 16-year-old male with CD and Down’s syndrome underwent an upper endoscopy and colonoscopy for monitoring of IBD activity. On gross examination, the esophagus appeared erythematous and biopsies of the mid and distal esophagus revealed 50-100 eos/hpf consistent with EoE. He had initiated adalimumab therapy three years prior to EoE diagnosis when esophageal biopsies were normal. Adalimumab level at this time was 6.79 ug/mL. He had no issues with dysphagia, but his weight gain was sub-optimal. After initiation of topical esophageal steroid therapy his weight gain improved and adalimumab therapy has been continued. Due to the current pandemic, follow up biopsies have been postponed. Case 2: A 14-year-old female with CD underwent an upper endoscopy and colonoscopy for monitoring of IBD activity. On gross examination, the esophagus had furrowing and biopsies of the mid and distal esophagus revealed 25-50 eos/hpf consistent with EoE. She had initiated adalimumab therapy one year prior to EoE diagnosis when esophageal biopsies showed mild chronic esophagitis (0-2 eos/hpf). Colonic biopsies showed active disease. Adalimumab level at this time was 17 ug/mL. She reported symptoms of dysphagia. Adalimumab therapy was changed to infliximab due to insufficient disease control and she was started on a high dose proton pump inhibitor to treat EoE with resolution of dysphagia. Due to the current pandemic, follow up biopsies have been postponed. Discussion: These two cases highlight the development of EoE in children with IBD on anti-TNF therapy. To our knowledge, based on a PubMed search, this is the first case report of children developing EoE while on adalimumab therapy for CD.

S2114 IgG4-Related Disease: An Uncommon Location

Introduction: Granular cell tumors (GCTs) of the esophagus are rare and benign neoplasms of neural cell origin. The lesions are often incidentally identified during upper endoscopic evaluation for other indications. We report a case of esophageal GCT in a young patient who presented with heartburn. Case Description/Methods: A 29-year-old white woman with a history of bulimia nervosa, gastroesophageal reflux disease, and chronic diarrhea following a recent COVID-19 infection presented to the clinic with heartburn and regurgitation that had been ongoing for years. She recently switched her omeprazole to famotidine to prepare for conception, which made her symptoms worse. Her physical examination and laboratory investigations were unremarkable. Esophagogastroduodenoscopy showed a single 6 mm yellowish, firm, submucosal nodule in the distal esophagus (Fig. 1A) and chronic gastritis. The nodule was biopsied with cold forceps and proved to be a granular cell tumor (Fig. 1B). The granular cell tumor cells were negative for pan-cytokeratin and positive for S100 (Fig 1C). They were negative for CD45 and Synaptophysin by immunohistochemistry staining. Biopsy of the distal esophagus also confirmed a short segment of Barrett's esophagus without dysplasia. Gastric body and antrum biopsy showed mild chronic gastritis negative for Helicobacter pylori. She was scheduled for an endoscopic ultrasound followed by possible endoscopic mucosal resection. Discussion: Even though esophageal GCTs are benign incidental findings, they have malignant potential (1-4%). Mortality is related to the size, growth, and invasiveness of the tumor. Indications for endoscopic or surgical resection are large size ≥ 1 cm, rapid growth, high suspicion of malignancy, transmural infiltration, and persistent symptoms. Endoscopic resection techniques include endoscopic mucosal resection and submucosal tunnel endoscopic resection. The later is more preferred in lesions < 3 cm. One study reported no recurrence of esophageal GCTs after resection in 14 cases at a median of 4-year follow-up.

S381 Esophageal Eosinophil Count Does Not Correlate With the Endoscopic Reference Score Remodeling Subscore in Placebo-Treated Eosinophilic Esophagitis Patients in the Phase 2 Proof-of-Concept and Phase 3 TREET Studies

Introduction: Eosinophilic esophagitis (EoE) is a chronic type 2 inflammatory disease of the esophagus. Although eosinophils (eos) are the hallmark of EoE diagnosis, their exact role in disease is unclear. The EoE-Endoscopic Reference Score (EREFS) assesses severity of endoscopically identified inflammatory (edema, exudate, furrows) and remodeling (rings, strictures) aspects of disease activity. To examine the relationship between eosinophilic inflammation and endoscopic disease activity, correlations were assessed between esophageal intraepithelial eos count (eos/high-power field [hpf]) and EREFS in EoE patients (pts) receiving placebo (PBO) in 2 clinical trials: the 12-week phase 2 proof-of-concept study (POC; NCT02379052) in adults and the 24-week Part A of the 3-part, phase 3 TREET study (P3PA; NCT03633617), in adolescents and adults. Methods: Endoscopies of the proximal and distal esophagus were 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). Eos/hpf was measured from pinch biopsies of proximal, mid, and distal esophagus at BL and EOT. Pearson correlations were performed between eos/hpf and EREFS total, subscores, and components at BL, EOT, and change from BL at EOT. Results: Few strong correlations (correlation coefficient > 0.5) were observed at BL between eos/hpf and EREFS in pts receiving PBO of both studies (Table 1). Moderate-to-strong correlations were observed between EREFS total score and eos/hpf in P3PA, but not POC. Moderate-to-strong correlations were observed in both studies between eos/hpf and the EREFS inflammation subscore and inflammatory components of edema, exudates, and furrows (some of which reached statistical significance). All correlations of eosinophil levels to the EREFS remodeling subscore and rings/stricture components were weak-to-moderate and not statistically significant (P values ranged from 0.07 to 0.94). Conclusion: In these EoE pts, no strong correlations were observed between eos/hpf and endoscopic remodeling as assessed by EREFS. Moderate to strong correlations were observed between eos/hpf and endoscopic markers of inflammation. Combined with histology, endoscopic assessment of remodeling aspects of EoE provides a more comprehensive characterization of disease activity. Further study, with larger sample sizes, is required to verify and validate these findings in other populations, duration of observation, and treatment contexts.Table 1.: Correlations between esophageal intraepithelial eosinophil count (eos/hpf) and EREFS total score, inflammation and remodeling subscores, and individual components scores in patients with EoE receiving placebo in the phase 2 POC study and part A of the phase 3 LIBERTY TREET study.

S2051 Primary Esophageal Lymphoma or Lymphoma Presenting as an Esophageal Mass: Rare Disease or Rare Presentation of a Disease?

Introduction: GI tract is the most common site of extra nodal non Hodgkin lymphoma (NHL) with the usual sites being stomach, small intestine and colon. Esophageal involvement has been reported in < 1% of cases and mostly occurs as an extension of mediastinal or gastric lymphoma. Here, we present a case of diffuse large B cell lymphoma (DLBCL) presenting with obstructive esophageal symptoms and diagnosed on esophageal ulcer biopsy. Case Description/Methods: A 72-year-old White male with history of 84 pack years smoking, GERD, presented with a month of shortness of breath, dysphagia to solids, odynophagia, loss of appetite, and 20 lbs. weight loss. Labs revealed WBC count 7000/µL. CT chest without contrast showed a large mediastinal mass with hilar extension, causing esophageal obstruction and two masses within the right lobe of liver. Endoscopy showed a mid-esophageal ulcer without bleeding, and atypical lymphoid cells on biopsy. Immunohistochemistry was positive for CD20, PAX5, BCL2 and BCL6, MUM1 and negative for CD10, cyclinD1 with MIB1 90%, thus consistent with DLBCL. Biopsy of liver mass showed similar histology and immunohistochemistry. HIV testing was negative. He was started on EPOCH based chemotherapy for the DLBCL. On chart review, CT Lung screening a year ago showed several filling defects in mid esophagus, however the filling defects were not evaluated as he was lost to follow up. Discussion: Primary esophageal DLBCL is a rare NHL with only handful of cases reported in literature to date. Our patient did not satisfy Dawson’s criteria for diagnosis of primary GI lymphoma which requires absence of peripheral and mediastinal lymphadenopathy, lack of liver and spleen involvement, and normal peripheral blood count. However, the utility of Dawson’s criteria for diagnosis of primary esophageal lymphoma has been questioned. Esophagus is a mediastinal structure and has rich lymphatic network, thus, predisposing to early mediastinal lymph nodes involvement. Also, esophageal cancers have been known to spread to liver via venous channels. Our patient had several mid esophageal filling defects a year ago and now presented with a large mediastinal mass encasing esophagus, thus, supporting the diagnosis of primary esophageal lymphoma. This case highlights the importance of endoscopic evaluation of esophageal filling defects seen on imaging.Figure 1.: Low dose CT lung screening performed a year prior shows filling defects in mid esophagus (red arrow) as seen in (A) axial section and (B) sagittal section. (C) CT chest without contrast on presentation showing large mediastinal mass, at the same level as image A causing esophageal obliteration. (D) Endoscopic biopsy of esophageal ulcer showing atypical lymphoid cells.

S466 Use of Immunoglobulin G and Immunoglobulin G4 as a Diagnostic Marker for Pediatric Eosinophilic Esophagitis

Introduction: Eosinophilic esophagitis (EoE) is a chronic esophageal disease that is clinically characterized by esophageal dysfunction and histologically by eosinophil-predominate inflammation. Our aim is to study the use of IgG and IgG4 as a diagnostic marker for pediatric eosinophilic esophagitis and further help predicting responsiveness to proton-pump specific to EoE. Methods: We prospectively enrolled pediatric patients who are known to have EoE, and gastroesophageal reflux disease (GERD) and performed IgG and IgG4 immunostaining on esophageal epithelial biopsies. Enrolled patients were divided into 3 different groups: active EoE, remission EoE, and GERD. Active EoE was then subdivided into PPI-responsiveness (PPI-r) and PPI-non-responsiveness, based on the proceedings of the AGREE conference published in 2018. Demographic, clinical, histopathological data, IgG, IgG4 staining, Peak Eosinophil Count (PEC), EDN (eosinophil derived neurotoxin) level, endoscopic (EREFS) were collected and compared between the different groups using fisher t-test and Pearson correlation between the groups. Results: We enrolled 79 subjects (median age of 11, range 1-20 years with 72% were males). Patients’ characteristics shown in Table 1. IgG was significantly elevated in active EoE (n = 29, mean IgG staining 4.52 ± 4.50 per hpf) compared to EoE in remission, (n = 25, mean IgG staining 1.32 ± 1.72 P-value = 0.002), and GERD (n = 25, mean IgG staining 1.08 ± 2.87 per hpf, P-value = 0.000) (Figure 1). Within the active EoE group, IgG staining (hpf) was significantly higher in the PPI-responsiveness subgroup (n = 15, mean 6.4 ±4.9 )vs nonresponsive group (n = 11, mean IgG staining 3 ±2.6, P-value = 0.041). IgG staining correlated with peak eosinophil count (PEC) in active EoE patients (Pearson correlation of 0.56 with r2 of 0.314 with P-value of 0.002). Additionally, in the remission EoE group, there was a significant correlation between IgG staining and PEC with Pearson correlation of 0.55 (n = 25), P-value = 0.004. The EoE remission and GERD patients were not statistically different from each other for IgG staining. Prevalence of IgG4 positive staining in active EoE group was 24%, significantly higher than EoE in remission 8%, P-value = 0.04 and in subjects with GERD 3.8%, P-value = 0.01. Conclusion: IgG and IgG4 staining is higher in pediatric patients with active EoE compared to patients with EoE in remission and GERD. IgG staining might predict PPI-responsiveness in pediatric patients with active EoE.Table 1.: Demographics of active EoE, EoE in remission and GERDFigure 1.: IgG was significantly elevated in active EoE (n = 29, mean IgG staining 4.52 ± 4.50 per hpf) compared to EoE in remission, (n = 25, mean IgG staining 1.32 ± 1.72 P-value = 0.002), and GERD (n = 25, mean IgG staining 1.08 ± 2.87 per hpf, P-value = 0.000).

S2134 Pulmonary Artery Sling—An Extremely Rare Etiology of Dysphagia

Introduction: Pulmonary artery sling (PAS) is a rare anomaly created when the left pulmonary artery originates from the posterior aspect of the right pulmonary artery and courses over from right to left, posterior to the trachea or carina and anterior to the esophagus, to reach the hilum of the left lung. While coursing, it can compress the trachea or the esophagus resulting in airway or esophageal obstruction. Case Description/Methods: 43-year-old man with history of Down’s syndrome was evaluated for esophageal dysphagia for solid food of 2-month duration. EGD was unrevealing except for mild distal esophagitis. Mid and distal esophageal biopsies were negative for eosinophilic esophagitis. Barium esophagogram revealed extrinsic impression on the right side of esophagus just inferior to the aortic arch. CT thorax revealed showed presence of left pulmonary artery (PAS) corresponding to the above-mentioned extrinsic impression seen on esophagogram. Due to complexity and high mortality associated with the required corrective surgery it was decided to manage this condition conservatively with dietary modifications. Discussion: Vascular rings are congenital anomalies that can present with a variety of pulmonary and gastroesophageal symptoms. PAS is a rare vascular anomaly first described by Glaevecke and Doehle in 1897. PAS can be associated with congenital cardiac anomalies like ASD, VSD or PDA or airway anomalies like tracheal stenosis. Majority of patients are symptomatic and 2/3rd of patients presents within their first 2 months of life mainly with respiratory symptoms of stridor, respiratory distress, cyanosis, wheezing, and/or pneumonia. Presentation in adulthood is extremely rare as only one other case of adult-onset dysphagia caused by PAS has been reported in English literature in 1966 by Dumler. Arteriosclerotic dilatation of the anomalous pulmonary artery can account for late onset of dysphagia in previously asymptomatic individuals. Corrective surgery is mainstay of treatment for life-limiting symptoms after failure of conservative management.Figure 1.: Cartoon depiction of Pulmonary sling (A), Esophagram (B), CT (C, D) showing aberrant pulmonary artery.

S3707 Pancreatic Acinar Metaplasia at the Gastroesophageal Junction in a Patient With Chronic Reflux

Introduction: Pancreatic acinar metaplasia (PAM) is defined as pancreatic glandular tissue forming acini outside of the pancreas. Recent studies have shown a possible association between chronic use of proton pump inhibitors (PPIs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Here, we present a case of PAM in a patient with chronic reflux on PPIs without a history of NSAID use. Case Description/Methods: A 41-year-old female with a longstanding history of gastroesophageal reflux disease (GERD) presented to clinic for evaluation of chronic reflux. The patient reported having symptoms of reflux for over 20 years. Over this time, she trialed multiple medications such as PPIs and antacids, but denied the use of NSAIDs. She also underwent multiple esophagogastroduodenoscopies (EGDs) for evaluation of her reflux, the last being 5 years ago, which showed mild gastric erythema but was otherwise unremarkable. Due to persistent symptoms despite medical management, she was scheduled for repeat EGD. EGD showed salmon-colored mucosa and gastric erythema. Pathology from esophagus biopsies revealed junctional mucosa with focal pancreatic acinar metaplasia (PAM). The patient was transitioned to Dexlansoprazole for symptomatic management and was scheduled for repeat EGD in 1 year for surveillance of PAM. Discussion: Pancreatic acinar metaplasia (PAM) is a term used to describe pancreatic glandular tissue organized in nests found outside of the pancreas. It is most commonly found in the gastric antrum, but can be found elsewhere in the gastrointestinal tract such as at the gastroesophageal junction (GEJ). While endoscopic findings of PAM differ, one study showed that the most commonly found appearance is salmon-colored mucosa. PAM is diagnosed histologically by pancreatic acinar-like cells that have a prominent cytoplasm with eosinophilic apical areas and basophilic basal areas. The exact pathogenesis of PAM is unknown; studies have shown that PAM may be associated with chronic NSAID or PPI use. While our patient used PPIs for years, she denies a history of NSAID usage. Another study by Schneider et al. showed that there was no association between PAM and reflux or gastritis, suggesting that PAM be have a congenital component. Further research is needed to determine the etiology of PAM. It can be found in patients with Barrett’s esophagus and may be associated with Helicobacter pylori. Therefore, it is important that these patients undergo routine surveillance.

S2113 Eosinophilic Esophagitis in a Patient With Oral Allergy Syndrome: Is There an Overlap?

Introduction: Food allergies can trigger systemic manifestations outside of the GI tract, most notably anaphylaxis. Eosinophilic esophagitis (EoE) is a chronic, immune-mediated eosinophilic infiltration of the esophagus with a higher prevalence in patients with food allergy than the general population (1 in 20 vs 1 in 2500). Oral allergy syndrome (OAS) is a clinical diagnosis describing symptoms including swelling and itching of the oral mucosa and may serve as a surrogate to identify patients with EoE. Case Description/Methods: A 49-year-old female with a history of OAS, esophageal hypersensitivity and non-erosive acid reflux presented with nausea and abdominal discomfort. Endoscopic esophageal biopsies revealed eosinophilic infiltrate confirming EoE. Omeprazole therapy provided incomplete symptom control with persistent episodic retrosternal burning and globus sensation, which responded to carafate. Repeat endoscopy three years later, showed persistent esophageal mucosal changes consistent with EoE and erythematous mucosa in the gastric body and antrum. She continued to abstain from seafood but was reluctant to initiate elimination diets and will likely require localized steroid treatment. Discussion: Allergic disease of the GI tract can occur in an IgE-dependent (OAS), IgE-independent or mixed fashion (EoE). The culprit antigen in OAS is birch pollen Betv1, sharing up to 70% homology with amino acids in certain fruits. Food and airborne allergens play a pivotal role in EOE. OAS and EoE both have a strong association with atopic conditions. However, common food allergens tested in EoE are dairy and wheat which differ from OAS. In a study of 186 patients with EoE, approximately 50% of patients were found to have concomitant OAS. Sensitization to at least 1 pollen and 1 aeroallergen was noted in 82.4% and 90.4% respectively. The authors proposed the inciting factor in EoE may be sensitization to pollen allergens resulting in subsequent cross-reactivity with food proteins. A novel syndrome coined Food-Induced immediate Response of the Esophagus (FIRE) representing retrosternal pain with ingestion of certain foods has been associated with EoE with known overlap with OAS. The treatment for OAS is avoidance and heat-treatment whereas elimination diets and steroids form the mainstay of management for EoE. In summary, with increasing diagnosis of allergic GI tract disease, OAS may serve as a screening tool for EoE. Concomitant OAS may contribute to a more aggressive course of EoE as was seen in our patient.Figure 1.: esophageal web/stricture from initial EGD.

S440 Clinical Characteristics and Endoscopic Features in Patients With Esophageal Graft versus Host Disease

Introduction: Graft versus host disease (GVHD) is an immunologic disorder most commonly following hematopoietic stem cell transplantation (HSCT) that frequently involves the gastrointestinal tract but not the esophagus. The aim of this study was to describe the clinical characteristics and endoscopic features in patients with esophageal GVHD. Methods: In this retrospective cohort study, we identified all patients with esophageal GVHD at Mayo Clinic between January 1, 2000 and June 3, 2021. Patients were included if they had a histologic diagnosis of GVHD from esophageal biopsies interpreted by an expert gastrointestinal pathologist (C.E.H). Retrospective chart review was performed to gather data on clinical characteristics and endoscopic features. Numerical and categorical data were reported as median (range) and proportions. Results: Forty-three patients with esophageal GVHD were included with median age 59 (5-75) years and 29 (67%) were men (Table 1). Forty-2 (98%) had received HSCT and 1 liver transplant. The median time from transplant to esophageal GVHD was 3 (0-39) months. Twenty-5 (58%) patients had known GVHD prior to esophageal involvement. Other organ involvement with GVHD was common at esophageal GVHD diagnosis, most commonly involving skin (72%). Clinical symptoms at esophageal GVHD diagnosis included nausea/vomiting (63%), anorexia (51%), diarrhea (44%), weight loss >5% (37%), and dysphagia (26%). Odynophagia (5%) and heartburn (5%) were less common. EGD showed no abnormalities in the esophagus in 13 (30%) patients. Where esophageal endoscopic abnormalities were present, 20 (67%) were diffuse and 10 (33%) were focal, and included erosive esophagitis in 10 (23%) patients, ulceration 7 (16%), desquamation 6 (14%), rings/furrows 6 (14%), and erythema/edema 5 (12%) (Figure 1). Concurrent endoscopic abnormalities were present in the stomach in 24 (56%) patients, duodenum 16 (37%), and colon 15 (35%). All patients were treated with steroids and 16 (37%) had recurrent gastrointestinal symptoms with steroid discontinuation. Twenty-one (49%) patients had a follow-up EGD at median 4.5 (0-29) months with 11 (52%) having persistent esophageal GVHD and 3 (14%) requiring dilation. Conclusion: As esophageal GVHD is associated with gut and other organ involvement and clinical and/or endoscopic findings are non-specific or absent, there should be a low threshold for biopsy when esophageal GVHD is suspected in the presence of other gastrointestinal involvement.Figure 1.: Endoscopic findings seen with esophageal graft versus host disease include A) erosive esophagitis, B) ulceration, C) desquamation, and D) rings.Table 1.: Clinical characteristics in patients with esophageal graft versus host disease.

S475 Racial and Ethnic Disparity of Esophageal Biopsy in Patients With Dysphagia

S475 Racial and Ethnic Disparity of Esophageal Biopsy in Patients With Dysphagia

COMPARISON OF HEMATOXYLIN &amp; EOSIN (H&amp;E) STAINING AND PERIODIC ACID SCHIFF-ALCIAN BLUE (PAS-AB) HISTOCHEMISTRY IN ESOPHAGEAL BIOPSIES IN TERMS OF INTESTINAL METAPLASIA

Barret esophagus is considered as a precursor lesion for esophageal adenocarcinomas. Histopathological examination is required for the barret esophagus, where endoscopic examination takes an important place. Intestinal metaplasia is revealed with hematoxylin &amp;amp; eosin (H&amp;amp;E) and alcian blue (AB) in histopathological examinations. There are 2 different opinions on this issue. One of them is to perform histochemical examination for AB or PAS-AB when intestinal metaplasia is suspected in routine H&amp;amp;E staining, while the other is to perform histochemical examination for routine AB or Periodic acid schiff alcian blue (PAS-AB) in all esophageal biopsies with H&amp;amp;E section. This study aims to reveal the roles of H&amp;amp;E and AB staining methods in the assessment of intestinal metaplasia. 200 esophageal endoscopic biopsies were included in the study. Sections of the biopsies were re-evaluated blindly by two pathologists. H&amp;amp;E and PAS-AB stains were compared in terms of sensitivity, specificity, positive predictivity. In statistical analysis, a strong correlation was found between H&amp;amp;E and AB in the evaluation of intestinal metaplasia (Kendall, p = 0.00; r = 0, 81). In H&amp;amp;E evaluation, sensitivity is 79%, specificity 100%, positive predictivity 100%, negative predictivity 82.6%, while sensitivity is 100%, specificity 100%, positive predictivity 100%, negative predictivity 100% in PAS-AB stained sections. The main goal in the histopathological evaluation of intestinal metaplasia is to detect positive cases. Since absence of intestinal metaplasia means less importance, higher sensitivity and negative predictivity values should be preferred rather than 100% specificity and positive predictivity values observed in H&amp;amp;E sections. Considering these conditions, it seems rational to use an auxiliary histochemistry containing AB.

Clinical pathological features of 180 cases with primary esophageal malignant melanoma

Objective: To investigate the clinical pathological and epidemiological characteristics of primary esophageal malignant melanoma (PMME). Methods: The clinical pathology data of 180 PMME patients in the esophageal cancer database of the key laboratory of esophageal cancer research in Henan Province from 1973 to 2016 were collected, of which 136 were male, aged (58.5±9.0) years, 44 were female, aged (56.7±12.2) years. Kaplan-Meier and Log rank test were used for survival analysis, Cox regression scale model was used for risk factor analysis. Results: The incidence of PMME is 0.036% (180/500, 000), mostly were male (about 3∶1 for men: female). The common sites of PMME were the lower part of the esophagus (48.9%, 85/174), followed by the middle section of the esophagus (46.0%, 80/174) and the upper part of the esophagus (5.2%, 9/174). No black particles were seen in the PMME cells of 3 patients under microscope, and strong positive expressions of Melan-A and HMB453 were observed in these 3 patients by immunohistochemical results. Of the 129 patients who had a routine preoperative esophageal biopsy, 69 were undiagnosed with PMME (53.5%). The medium survival time of the whole group was 7.9 months, and the survival rates of 1, 2, 3, 5 years were 25.0%, 7.9%, 6.6% and 1.3%, respectively. The univariate analysis showed that N, M, TNM phase and radiotherapy were related to the overall survival of patients (P<0.05). Multivariate analysis showed that TNM phase and radiotherapy were the independent risk factors for overall survival of patients (P<0.05). Conclusions: PMME is more common in men, the common site of the disease is the lower part of the esophagus. The preoperatively missed diagnosis rate of Chinese PMME is high. TNM phase and radiotherapy are the independent risk factors for overall survival of patients.

Association of celiac disease with eosophageal eosinophilia and eosinophilic eosophagitis

Aim of the study was to evaluate the association between celiac disease and eosinophilic oesophagitis/oesophageal eosinophilia in children. A total of 278 patients with celiac disease (mean age: 7.12±4.64years, M/F: 0.77) were involved in the study. The patients were evaluated retrospectively in terms of clinical, endoscopic and histopathological findings. The association between celiac disease and eosinophilic oesophagitis/oesophageal eosinophilia was determined. According to Marsh classification system 6 (2.1%) of the patients were graded type 3A, 10 (3.5%) were type 3B, 262 (94.4%) were type 3C. The histopathological examination of oesophageal biopsy specimens of the patients revealed <15 eosinophils per high power field in only 4 (1.4%) patients. Two of these patients were positive for HLA DQ8, one was DQ2, and the other one was both DQ8 and DQ2. Tissue transglutaminase IgA level was above 300U/mL in these patients. None of them had elevated serum total IgE levels, peripheral eosinophilia and history of atopic diseases. The gastrointestinal symptoms resolved and tissue transglutaminase IgA level of the patients were declined after 3months of gluten-free diet. Although an association between celiac disease and eosinophilic oesophagitis/oesophageal eosinophilia have been postulated in recent years, no exact relationship was established in this study. This is the first study reporting the performance of follow-up GI endoscopy with biopsies revealing the resolution of oesophageal eosinophilia.

244 MICROBIOME ANALYSIS OF UPPER DIGESTIVE TRACT BIOPSY SAMPLES FROM INDIVIDUALS ALONG THE METAPLASIA-DYSPLASIA-ADENOCARCINOMA SEQUENCE.

Abstract The human microbiota, the collection of microbes that inhabit the human body, is increasingly being appreciated as playing a role in human health. A seminal example of this relationship is Helicobacter pylori and gastric cancer oncogenesis. The drop in H.pylori infections and non-cardia gastric cancer incidences has coincided with the rise in oesophageal adenocarcinoma (OAC) incidences. We sought to explore the relationship between the upper digestive tract microbiome and OAC oncogenesis. Methods Pinch biopsies were taken from individual’s oesophagus and stomach who were along the metaplasia-dysplasia-adenocarcinoma sequence (GERD, Barrett's oesophagus, dysplasia, OAC, metastatic OAC) as well as healthy controls. We carried out 16 s rRNA gene DNA sequencing protocols on these samples. DNA extraction and library preparation was performed with consideration to the low mass nature of oesophageal biopsies. Raw reads were processed and amplicon sequence variants (ASVs) were generated using the DADA2. We dissected ecological differences between sample site and clinical classification using a variety of approaches including examining differentially abundant taxa and inferred metabolic pathways, alpha diversity and beta-diversity. Results The upper digestive tract was found to be dominated by the genera Streptococcus, Prevotella, and Haemophilus. There was no statistically significant shift in beta diversity with respect to biopsy location. Alpha diversity was reduced in gastric biopsies compare to oesophageal biopsies. A slight yet significant shift was seen in beta diversity (Bray–Curtis Dissimilarity) with respect to clinical classification in biopsies derived from the gastroesophageal junction (GEJ) and stomach. Various taxa were found to be differentially abundant between biopsy site and with regard to clinical classification. Conclusion OAC primarily occurs at the GEJ. Community structure was shifted in samples derived from the GEJ and the stomach. Fusobacterium nucleatum was overrepresented in oesophageal biopsies from individuals with diseased oesophagus compared to individuals with a histologically normal oesophagus. This bacterium has been implicated in oncogenesis of various cancers most notably colorectal cancer. Serval ASVs assigned to the genus Prevotella were depleted in stomachs of individuals with metastatic OAC compared to all other groups.

224 A RETROSPECTIVE CASE–CONTROL STUDY ASSESSING THE CLINICAL AND ENDOSCOPIC CHARACTERISTICS OF EOSINOPHILIC ESOPHAGITIS IN JAPAN

Abstract Eosinophilic esophagitis (EoE) is an allergy-associated clinicopathologic condition gaining an increasing amount of recognition in various areas of the world. While the clinical definition and characteristics may differ depending on country and region, sufficient studies have not yet been performed in Japan. To assess the prevalence of EoE among the Japanese population and the clinical features and the prognosis associated with the disease. Methods Medical data from January 2012 to October 2018 was gathered from nine Japanese clinical institutes. EoE, defined as more than 15 intraepithelial eosinophils per high power field, was determined based on esophageal biopsies. Clinical and endoscopic patterns in the cases with EoE were investigated and compared with 186 age- and sex-matched controls. We also analyzed the treatment and prognosis of an individual patient. Results From 130,013 upper endoscopic examinations, 66 cases of EoE were identified (0.051%; mean age: 45.2 years (range 7-79); 45 males). Patients with EoE had more symptoms (69.7 vs. 10.8%; P &amp;lt; 0.01) such as dysphagia and food impaction, and more allergies (63.6 vs. 23.7%; P &amp;lt; 0.01) compared with the controls. The prevalence of atrophic gastritis was lower in EoE patients than in the controls (20.0% vs. 33.3%). In 55 patients analyzed, 32 patients (78.0%) received proton pump inhibitors with or without swallowed topical corticosteroids. During the follw-up period (mean 23 months), no patient got worse regarding clinical and endoscopic findings. Conclusion The prevalence of EoE in the Japanese population was 0.051% which was comparable with previous reports in Japan. Male predominance, a history of allergies, and the absence of Helicobacter pylori infection might be risk factors for EoE. Our study also indicated that the prognosis of EoE might be relatively good in Japanese populations.

619 HIGH DISCOVERY RATE OF GASTRODUODENAL EOSINOPHILIA BUT NOT EOSINOPHILIC ESOPHAGITIS IN PATIENTS WITH CHRONIC GASTROINTESTINAL SYMPTOMS

Abstract Although the prevalence of eosinophilic gastrointestinal disorders (EGIDs) is increasing, there is evidence that eosinophilic gastritis and/or duodenitis (EG/EoD) are underdiagnosed. Patients with EG/EoD often present with chronic, non-specific gastrointestinal (GI) symptoms, similar to patients with functional GI disorders. We hypothesized that systematic evaluation, including multiple esophageal, gastric and duodenal biopsies, of patients with chronic GI symptoms might reveal a high rate of gastroduodenal eosinophila, with or without eosinophilic esophagitis (EoE). Methods We performed a prospective multi-center study of patients with non-specific GI symptoms for ≥6 months, from 20 sites. Patients completed a questionnaire assessing abdominal pain, abdominal cramping, early satiety, bloating, nausea, vomiting, diarrhea, and loss of appetite. Those with daily average symptom severity scores ≥3/10 for any single symptom underwent esophagogastroduodenoscopy (EGD) with collection of 4 esophageal (EoE), 8 gastric, and 4 duodenal biopsies, analyzed by central pathologists. Histologic criteria for EoE was ≥15eos/hpf in ≥1 esophageal site and for EG/EoD was peak eosinophil counts ≥30/hpf in ≥5 gastric hpfs and/or 3 duodenal hpfs—criteria used in randomized trials. Results Of 556 patients screened, 405 (73%) met symptom criteria and underwent EGD; 181 patients (45%, mean age 45, 73% female) who underwent EGD met the histologic criteria for EG/EoD, and of these, 7% also had EoE diagnosed. Overall 2% met histologic criteria for EoE alone. Of patients who met the histologic criteria for EG/EoD, 93% were previously diagnosed with gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), or functional dyspepsia (FD) (Figure 1). The average duration of GI symptoms in the screened population as well as those that met histologic criteria for EG/EoD was 11 years. Conclusion Forty-five percent of patients with moderate-to-severe GI symptoms who underwent EGD met histologic criteria for EG/EoD. Over 90% of these patients had previously been diagnosed with GERD, IBS, and/or FD, and had minimal overlap with EoE. EGD with systematic gastroduodenal biopsies, and intentional evaluation for tissue eosinophilia, should be performed in patients with chronic GI symptoms. Accurate diagnosis of EG/EoD is required for appropriate, targeted treatment and improved outcomes of patients with moderate-to-severe GI symptoms.

Correlation of clinical symptoms, endoscopic features and density of oesophageal eosinophilia in children with newly-diagnosed eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an inflammatory immune-mediated oesophageal disease of growing prevalence. The aim of this study is to characterise the clinical symptoms, endoscopic features and histological findings, as well as their possible correlations, in newly-diagnosed EoE paediatric patients. Between 2009-2018, the clinical records of patients diagnosed with EoE at the Paediatric Hospital in Warsaw, Poland, were retrospectively reviewed. Inclusion criteria were upper gastrointestinal tract symptoms in association with oesophageal mucosal biopsy specimens containing not less than 15 intraepithelial eosinophils per hpf. The prevalence and the possible correlations between symptoms, endoscopic features and the density of eosinophilic infiltration were analysed; the medical history of the comorbidities were also assessed. The study included 47 children (median age 9.5 years). The most common clinical symptoms were abdominal pain (53%) and GERD-like symptoms (26%). The most common macroscopic changes were white plaques and exudates in 47% and furrows in 34%. A macroscopically normal oesophagus was observed in 28% of the children. The median number of eosinophils was estimated to be 45 eosinophils/hpf (IQR: 30-60), and no significant differences were found between the density of eosinophil infiltration and clinical symptoms or endoscopic features. Moreover, 70% of the children had a history of an allergy disease, older children (>3 years) tended to have pollen allergy more often than younger children (p<0.05). The density of oesophageal eosinophilia does not correlate with symptoms or endoscopic findings in children with newl-diagnosed EoE.

Морфологічна діагностика ерозивного езофагіту при гастроезофагеальній рефлюксній хворобі

Досліджено біоптати стравоходу 79 хворих із клінічно підтвердженою гастроезофагеальною рефлюксною хворобою. За допомогою комп’ютерної морфометрії виміряно та проаналізовано ширину міжклітинних просторів плоского епітелію стравоходу, а також особливості міграції клітин запалення у випадках розвитку неерозивного, ерозивного й еозинофільного езофагіту залежно від тонуса сфінктера Одді та жовчного міхура.

Histologic Findings in Mucosa and Muscularis Propria Biopsied During Peroral Endoscopic Myotomy in Patients With Achalasia

BackgroundPeroral endoscopic myotomy (POEM) has been increasingly used to treat achalasia. Previous studies have reported high frequency of muscular eosinophilic infiltration in achalasia. Esophageal mucosal changes in achalasia have only been studied in esophagectomy specimens. Cardia mucosal changes in achalasia have not been reported previously. We aimed to further characterize the esophageal, gastric cardia, and muscularis propria changes in achalasia.MethodsThis was a pilot study. Patients with clinically and radiographically confirmed achalasia who underwent POEM were enrolled in the study. Mucosal biopsies were taken 1 cm proximal and 1 cm distal to the gastroesophageal junction, and muscularis propria biopsies were taken from the mid esophagus. Tissues were submitted for histological evaluation.ResultsEighteen patients (10 male and eight female, mean age: 60.7 (standard deviation (SD): 13) years) were enrolled in this pilot study. Nine patients had type II achalasia, two type III, one type I, five esophageal gastric outlet obstruction, and one unspecific type achalasia. The mean duration of symptoms prior to POEM was 79 (range 1 - 480) months. All patients had a dilated esophagus on examination, but no endoscopic evidence of Barrett’s esophagus. Esophageal, gastric cardia, and muscular biopsies were performed in 17, 13, and 17 patients, respectively. Basal hyperplasia, spongiosis, ballooning, and parakeratosis were seen in 92.3%, 100%, 100%, and 76.5% of cases, respectively. Intraepithelial lymphocytosis was seen in 70.5% of cases, and active esophagitis was seen in 23.5% of case. Six (35.3%) cases had few intraepithelial eosinophils, but none of them had > 15 eosinophils per high power field. Histologic findings in gastric cardia mucosa included carditis (69.2%), H. pylori gastritis (7.6%), and reactive gastropathy (15.4%). One case (7.6%) showed low-grade dysplasia arising from intestinal metaplasia in the cardia. Absence of ganglion cells in the muscular biopsies was noted in 88.2% of cases, and the remaining two showed rare residual ganglion cells with ganglionitis in one case (5.8%). Muscular atrophy and interstitial fibrosis were observed in 52.9% and 82.3% of the cases, respectively. Two cases (11.7%) had eosinophilic inflammation in the muscularis propria and one of them was accompanied by lymphocytic inflammation.ConclusionsMuscular biopsies in our study revealed loss of ganglion cells, supporting the view that achalasia is a primary esophageal disease with ganglion cell depletion. Squamous mucosa in achalasia showed changes mimicking reflux and lymphocytic esophagitis. Cardia mucosa in achalasia patients often were inflamed and uncommonly showed intestinal metaplasia and glandular dysplasia.

Biological correlates before esophageal cancer screening and after diagnosis

Almost 50% of the world’s esophageal cancer (EC) cases occur in China, and the impact of cancer screening has long been a controversial topic. The study was designed to evaluate the biological correlates of EC screening and subsequent diagnosis in China. Based on the national cohort of esophageal cancer program, a prospective multicenter study in high-risk regions was conducted from 2017 to 2019. 61 participants received twice esophageal endoscopy screening and pathological biopsy successively (with a mean follow-up of 14.03 months). Box–Cox-power transformation and two-way repeated measures ANOVA were used to evaluate hormone cortisol and immunoglobulin (IgA, IgG, IgM) levels in plasma, reflecting their stress, immune function, and biological correlates before screening and after knowing the diagnosis. The median of cortisol, IgA, IgG, and IgM in pre-screening was 15.46 ug/dL, 1.86 g/L, 12.14 g/L, and 0.91 g/L, corresponding value at post-diagnosis was 15.30 ug/dL, 2.00 g/L, 12.79 g/L, and 0.94 g/L, respectively. No significant differences in biological indicators were found between normal and esophagitis and low-grade intraepithelial neoplasia before screening and after diagnosis. After normality transformation, cortisol, IgA, IgG and IgM levels were (0.25 ± 0.04) U/mL, (0.72 ± 0.13) (g/L), (2.44 ± 0.22) (g/L) and (0.98 ± 0.25) (g/L) before screening, (0.25 ± 0.05) U/mL, (0.70 ± 0.13) (g/L), (2.48 ± 0.21) (g/L) and (1.00 ± 0.25) (g/L) after diagnosis, respectively. Repeated Measures ANOVA showed that the main effects were significant on IgA levels between pre-screening and post-diagnosis (P = 0.019). No interaction effects on biological levels between pre-post screening and esophageal pathology, anxiety states (all P > 0.05). Little biological correlates were found both before screening and after diagnosis. Cortisol and IgA dropped less significantly, while IgM and IgA were increased slightly after diagnosis. Further multi-round longitudinal studies are needed to validate these results.