Esophageal Patients Research Articles

Switch from Off-Label Swallowed Topical Corticosteroids to Budesonide Orodispersible Tablets in Eosinophilic Esophagitis patients.

Switch from Off-Label Swallowed Topical Corticosteroids to Budesonide Orodispersible Tablets in Eosinophilic Esophagitis patients.

Association between serum alder-specific immunoglobulin E positivity and seasonal onset of eosinophilic esophagitis.

Pollen exposure may induce seasonal onset of eosinophilic esophagitis. However, whether serum pollen-specific immunoglobulin E positivity can predict such seasonal eosinophilic esophagitis onset remains unclear. Here, we aimed to evaluate the association between pollen-specific immunoglobulin E positivity and the seasonal onset of eosinophilic esophagitis during the pollen dispersal period. We seasonally classified eosinophilic esophagitis patients and compared their clinical and endoscopic findings. Seasonal trends with respect to the positivity rate of serum pollen-specific immunoglobulin E were examined. Pollens such as alder, cedar, cypress, birch, orchard grass, timothy, ragweed, and mugwort were evaluated. We classified patients into two groups: tested positive or negative for each pollen-specific immunoglobulin E. We then evaluated whether the positivity of each pollen-specific immunoglobulin E was associated with the seasonal onset of eosinophilic esophagitis during the pollen dispersal period. We included 122 patients diagnosed with eosinophilic esophagitis between 2010 and 2019. Among them, 31 (25.4%), 42 (34.4%), 29 (23.8%), and 20 (16.4%) patients were diagnosed during spring, summer, fall, and winter, respectively. No significant differences were observed in clinical and endoscopic findings across seasons. No significant seasonal trends were observed in the positivity rate of each pollen-specific immunoglobulin E. The positivity rate of alder-specific immunoglobulin E was significantly associated with the seasonal onset of eosinophilic esophagitis (P < 0.01). However, the positivity rates of other pollen-specific immunoglobulin E were not associated with the seasonal onset of eosinophilic esophagitis. Serum alder-specific immunoglobulin E positivity was associated with the seasonal onset of eosinophilic esophagitis.

S1106 Comparative Outcomes of Eosinophilic Esophagitis in Patients With and Without Inflammatory Bowel Disease: A Propensity-Matched Cohort Study

S1106 Comparative Outcomes of Eosinophilic Esophagitis in Patients With and Without Inflammatory Bowel Disease: A Propensity-Matched Cohort Study

S590 Comparative Outcomes of Gastroesophageal Reflux Disease, Nonerosive Reflux Disease, and Erosive Esophagitis in Patients Undergoing Roux-en-Y Gastric Bypass versus Sleeve Gastrectomy for Weight Loss

S590 Comparative Outcomes of Gastroesophageal Reflux Disease, Nonerosive Reflux Disease, and Erosive Esophagitis in Patients Undergoing Roux-en-Y Gastric Bypass versus Sleeve Gastrectomy for Weight Loss

Clinicopathological Study of Herpes Simplex Esophagitis in a Tertiary Centre in India

Introduction and objectives: Herpes Simplex Virus (HSV) is a common viral pathogen, known to cause symptomatic disease in the immunocompromised hosts; however, it may occur in healthy individuals as well. Among the varied manifestations of the disease, involving skin, central nervous system and gastrointestinal systems, HSV esophagitis is a less studied entity from the Indian perspective. The aim of the study is to compare clinical, histologic and serologic data of HSV esophagitis patients. Materials and methods: 27 cases, proved to have HSV esophagitis on endoscopic biopsy were included, and the pertinent clinical and serologic characteristics were studied. Results: We found a male preponderance (p&lt;0.01), which has been a well-established risk factor. Other risk factors are retroviral coinfection, Type 2 Diabetes Mellitus, immunosuppression, chemoradiation etc. among others. Eleven patients had retroviral coinfection, with CD4 counts of &gt; 200/μL in all. Anti HSV 1 IgM antibody was most commonly detected on serology. HSV esophagitis affects immunocompromised patients more often than immunocompetent ones. Odynophagia and dysphagia are the most common symptoms. Histological evaluation for the characteristic inclusions helps in early diagnosis. The novelty of this study rests on the clinicopathological and serologic correlation, for a better understanding of the disease process, to prompt future large scale studies on the same. Conclusion: Herpes simplex esophagitis is most seen in immunocompromised patients. Apart from retroviral illness, other risk factors include diabetes mellitus, patients undergoing chemotherapy and other malignancy. CD4 counts in our series was &gt;200/μL, in contrast to the cutoff of &lt;200/μL described in literature.

Gastrointestinal dysmotility is associated with proton pump inhibitor refractory esophagitis in patients with systemic sclerosis.

Patients with systemic sclerosis present with severe gastroesophageal reflux disease, often refractory to proton-pump inhibitors (PPI) treatment. The aim of the present study was to identify factors associated with PPI-refractory esophagitis. We performed a cross-sectional study in a single-center cohort of patients diagnosed with systemic sclerosis. We included patients who underwent an esophagogastroduodenoscopy while on PPI treatment. Patients with PPI-refractory erosive esophagitis were compared with those with endoscopically normal esophageal mucosa. A total of 69 patients were included, from these, 23 patients (33%) had PPI-refractory esophagitis (Grade A, n = 11; Grade B, n = 7; Grade C, n = 2; Grade D, n = 3) and 46 (67%) had an endoscopically normal esophageal mucosa. On univariate analysis, patients with PPI-refractory esophagitis were more frequently diffuse SSc subset (43% vs 17%; p= 0.041). Evaluating gastrointestinal motility tests, neither absent esophageal contractility (39% vs 25%, p= 0.292) nor hypotensive lower esophageal sphincter (47% vs 44%, p= 0.980) were significantly associated with PPI-refractory esophagitis. Gastrointestinal dysmotility, defined as abnormal gastric emptying and/or small bowel dilated loops, was significantly associated with PPI-refractory esophagitis (66 vs 8%, p = <0.001). On a multivariate regression model to evaluate the association between motility test results adjusted for the diffuse subset, gastrointestinal dysmotility (β = 0.751, p= 0.010) was independently associated with PPI-refractory esophagitis, while absent esophageal contractility (β = 0.044, p= 0.886) or a hypotensive LES were not (β=-0.131, p= 0.663). Our findings suggest that gastric and small intestinal motor dysfunction may be an important contributor to the development of PPI-refractory esophagitis in patients with systemic sclerosis.

Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response.

Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.

Distal gastrectomy and Roux-en-Y reconstruction for refractory reflux esophagitis after proximal gastrectomy and esophagogastric anastomosis reconstruction.

Refractory gastroesophageal reflux disease can develop after proximal gastrectomy and esophagogastrostomy. We introduce a new method that combines distal gastrectomy and Roux-en-Y reconstruction to treat refractory reflux esophagitis in patients who have undergone proximal gastrectomy and esophagogastric anastomosis reconstruction. This novel method may be useful not only for alleviating the symptoms of gastroesophageal reflux disease but also for preventing future esophageal malignancies arising from long-term reflux esophagitis.

Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age

BackgroundDupilumab is a human monoclonal antibody that blocks interleukin-4 and interleukin-13 pathways and has shown efficacy in five different atopic diseases marked by type 2 inflammation, including eosinophilic esophagitis in adults and adolescents.MethodsIn this phase 3 trial, we randomly assigned, in a 2:2:1:1 ratio, patients 1 to 11 years of age with active eosinophilic esophagitis who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups) (Part A). At the end of Part A, eligible patients in each dupilumab group continued the same regimen and those in the placebo groups were assigned to higher-exposure or lower-exposure dupilumab for 36 weeks (Part B). At each level of exposure, dupilumab was administered in one of four doses tiered according to baseline body weight. The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤6 per high-power field) at week 16. Key secondary end points were tested hierarchically.ResultsIn Part A, histologic remission occurred in 25 of the 37 patients (68%) in the higher-exposure group, in 18 of the 31 patients (58%) in the lower-exposure group, and in 1 of the 34 patients (3%) in the placebo group (difference between the higher-exposure regimen and placebo, 65 percentage points [95% confidence interval {CI}, 48 to 81; P<0.001]; difference between the lower-exposure regimen and placebo, 55 percentage points [95% CI, 37 to 73; P<0.001]). The higher-exposure dupilumab regimen led to significant improvements in histologic, endoscopic, and transcriptomic measures as compared with placebo. The improvements in histologic, endoscopic, and transcriptomic measures between baseline and week 52 in all the patients were generally similar to the improvements between baseline and week 16 in the patients who received dupilumab in Part A. In Part A, the incidence of coronavirus disease 2019, nausea, injection-site pain, and headache was at least 10 percentage points higher among the patients who received dupilumab (at either dose) than among those who received placebo. Serious adverse events were reported in 3 patients who received dupilumab during Part A and in 6 patients overall during Part B.ConclusionsDupilumab resulted in histologic remission in a significantly higher percentage of children with eosinophilic esophagitis than placebo. The higher-exposure dupilumab regimen also led to improvements in measures of key secondary end points as compared with placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; EoE KIDS ClinicalTrials.gov number, NCT04394351.)

Dosimetric risk factors for radiation esophagitis in patients with breast cancer following regional nodal radiation

BACKGROUND Radiation esophagitis (RE) is one of the most common clinical symptoms of regi-onal lymph node radiotherapy for breast cancer. However, there are fewer studies focusing on RE caused by hypofractionated radiotherapy (HFRT). AIM To analyze the clinical and dosimetric factors that contribute to the development of RE in patients with breast cancer treated with HFRT of regional lymph nodes. METHODS Between January and December 2022, we retrospectively analysed 64 patients with breast cancer who met our inclusion criteria underwent regional nodal intensity-modulated radiotherapy at a radiotherapy dose of 43.5 Gy/15F. RESULTS Of the 64 patients in this study, 24 (37.5%) did not develop RE, 29 (45.3%) developed grade 1 RE (G1RE), 11 (17.2%) developed grade 2 RE (G2RE), and none developed grade 3 RE or higher. Our univariable logistic regression analysis found G2RE to be significantly correlated with the maximum dose, mean dose, relative volume 20-40, and absolute volume (AV) 20-40. Our stepwise linear regression analyses found AV30 and AV35 to be significantly associated with G2RE (P &lt; 0.001). The optimal threshold for AV30 was 2.39 mL [area under the curve (AUC): 0.996; sensitivity: 90.9%; specificity: 91.1%]. The optimal threshold for AV35 was 0.71 mL (AUC: 0.932; sensitivity: 90.9%; specificity: 83.9%). CONCLUSION AV30 and AV35 were significantly associated with G2RE. The thresholds for AV30 and AV35 should be limited to 2.39 mL and 0.71 mL, respectively.

The spectrum of esophagitis in patients living with HIV - a scoping review.

Esophageal lesions are common findings in disorders of the digestive tract in patients living with HIV, the most typical symptoms being odynophagia and/or dysphagia. This article provides a narrative review of the spectrum of esophagitis in patients living with HIV, focusing on fungal, viral, bacterial and non-infectious etiologies, as well as co-infections with viral hepatitis viruses. The article provides a comprehensive approach to the strategy of diagnosis and the role of upper digestive endoscopy and histopathological examination in the evaluation of esophageal pathology in patients living with HIV.

Eosinophil specialization is regulated by exposure to the esophageal epithelial microenvironment.

Distinct subsets of eosinophils are reported in inflammatory and healthy tissues, yet the functions of uniquely specialized eosinophils and the signals that elicit them, particularly in eosinophilic esophagitis, are not well understood. Herein, we report an ex vivo system wherein freshly isolated human eosinophils were cocultured with esophageal epithelial cells and disease-relevant proinflammatory (IL-13) or profibrotic (TGF-β) cytokines. Compared with untreated cocultures, IL-13 increased expression of CD69 on eosinophils, whereas TGF-β increased expression of CD81, CD62L, and CD25. Eosinophils from IL-13-treated cocultures demonstrated increased secretion of GRO-α, IL-8, and macrophage colony-stimulating factor and also generated increased extracellular peroxidase activity following activation. Eosinophils from TGF-β-treated cocultures secreted increased IL-6 and exhibited increased chemotactic response to CCL11 compared with eosinophils from untreated or IL-13-treated coculture conditions. When eosinophils from TGF-β-treated cocultures were cultured with fibroblasts, they upregulated SERPINE1 expression and fibronectin secretion by fibroblasts compared with eosinophils that were cultured with granulocyte macrophage colony-stimulating factor alone. Translational studies revealed that CD62L was heterogeneously expressed by eosinophils in patient biopsy specimens. Our results demonstrate that disease-relevant proinflammatory and profibrotic signals present in the esophagus of patients with eosinophilic esophagitis cause distinct profiles of eosinophil activation and gene expression.

Nonepithelial Gene Expression Correlates With Symptom Severity in Adults With Eosinophilic Esophagitis

BackgroundThe mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood. ObjectiveWe examined the correlation of a validated, patient-reported outcome (PRO) metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis. MethodsData were extracted from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Patients were subgrouped by esophageal dilation history. We compared a validated PRO metric, the EoE Activity Index (EEsAI), with a set of transcripts expressed in the esophagus of patients with EoE, the EoE Diagnostic Panel (EDP). We utilized single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms. ResultsThe EEsAI correlated with the EDP total score, especially in patients without recent esophageal dilation (r = -0.31, P = .003). We identified 14 EDP genes that correlated with EEsAI scores (r ≥ 0.3, P < .05). Of these, 11 were expressed in non-epithelial cells and 3 in epithelial cells; during histologic remission, only 4/11 (36%) non-epithelial versus 3/3 (100%) epithelial genes had decreased expression to <50% of that in active EoE. Fibroblasts expressed 5/11 (45%) non-epithelial EEsAI-associated EDP genes. A subset of non-epithelial (8/11, 73%), but not EoE-representative (0/4, 0%; CCL26, CAPN14, DSG1, SPINK7), genes was upregulated in patients with EoE with the highest versus lowest symptom burden. ConclusionThe correlation of symptoms and non-epithelial esophageal gene expression substantiates that non-epithelial cells (e.g., fibroblasts) likely contribute to symptom severity.

Long-term risk factors for developing Barrett’s oesophagus in patients with gastro-oesophageal reflux disease: a longitudinal cohort study

Background and aimsSeveral characteristics are known to affect the risk of Barrett’s oesophagus (BO) in the general population, with symptomatic gastro-oesophageal reflux disease (GORD) being a critical risk factor. In...

A Multicenter Long-Term Cohort Study of Eosinophilic Esophagitis Variants and Their Progression to Eosinophilic Esophagitis Over Time.

Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined. Patients from 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)histological, and molecular features were determined and compared with EoE and healthy controls. We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression, indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months). Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis.

Clinical practices and adherence to guidelines for eosinophilic esophagitis: A European survey

BackgroundWe aimed to assess the clinical practices and adherence to guidelines for adult Eosinophilic Esophagitis (EoE) patients in Europe. MethodsA cross-sectional web survey containing 23 questions was distributed to members of the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract (EUREOS) and the Italian Association of Hospital Gastroenterologists and digestive endoscopists (AIGO). We conducted a subgroup analysis to assess the impact of EoE expertise and practice setting on clinical practices. Results228 physicians from 18 European countries participated. Adherence to guidelines varied from 72% to 98.6%. 83.4% of total respondents obtained ≥ 6 esophageal biopsies in suspected EoE. 42% of total respondents, 82.5% of EoE experts (vs. non-experts 33%; P < 0.0001), and 55% of academics (vs. 29.1 non-academics; P < 0.0001) routinely used the EREFS score. Regarding first-line therapy, 82.9% of total respondents prescribed proton pump inhibitors, 41.6% topical steroids, 20.6% elimination diets, and 9.2% combination therapies. Only 72% of respondents used symptoms and endoscopy with <15 Eosinophils/HPF to define treatment response. 21.5% of all respondents did not prescribe maintenance therapies and 12.7% discontinued therapy before response evaluation endoscopy. ConclusionOur findings revealed significant heterogeneity in practice patterns and suboptimal adherence to EoE guidelines across Europe. Expertise in EoE and working in an academic hospital positively influenced clinical practices and adherence to guidelines.

Prevalence and risk factors for medication-refractory reflux esophagitis in patients with systemic sclerosis in Japan.

Patients with systemic sclerosis (SSc) often have esophageal motility abnormalities and weak esophago-gastric junction (EGJ) barrier function, which causes proton pump inhibitor (PPI)-refractory reflux esophagitis (RE). The aims of this study were to clarify the current management of RE and prevalence and risk factors of medication-refractory RE in patients with SSc in Japan. A total of 188 consecutive patients with SSc who underwent both esophageal high-resolution manometry (HRM) and esophagogastroduodenoscopy (EGD) were reviewed. The presence of RE and grades of the gastroesophageal flap valve (GEFV) were assessed. Esophageal motility was assessed retrospectively according to the Chicago classification v3.0. When RE was seen on a standard dose of PPI or any dose of vonoprazan (VPZ), it was defined as medication-refractory RE. Approximately 80% of patients received maintenance therapy with acid secretion inhibitors regardless of esophageal motility abnormalities. Approximately 50% of patients received maintenance therapy with PPI, and approximately 30% of patients received VPZ. Medication-refractory RE was observed in 30 patients (16.0%). In multivariable analyses, the number of EGD and absent contractility were significant risk factors for medication-refractory RE. Furthermore, combined absent contractility and GEFV grade III or IV had higher odds ratios than did absent contractility alone. Patients with persistent reflux symptoms and those with absent contractility and GEFV grade III or IV should receive maintenance therapy with strong acid inhibition to prevent medication-refractory RE.

In Vivo Raman Spectroscopy Reveals Biochemical Composition of the Esophageal Tissue in Pediatric Eosinophilic Esophagitis.

Biochemical alterations in the esophagus of patients with eosinophilic esophagitis (EoE) are poorly understood. We used Raman spectroscopy through a pediatric endoscope to identify key Raman features reflective of the esophageal biochemical composition to differentiate between children with EoE from non-EoE controls and between children with active (aEoE) and inactive EoE (iEoE). Spectral measurements were obtained using a customized pediatric endoscope-compatible fiber-optic Raman probe in real time during an esophagogastroduodenoscopy. Chemometric analysis was performed to identify key Raman features associated with EoE. Pearson correlation analysis was used to assess relationship between the key Raman features and EoE activity indices. Their diagnostic utility was ascertained using the receiver operator characteristic curve analysis. Forty-three children were included in the study (EoE = 32 [74%] and non-EoE control = 11 [26%]; aEoE = 20 [63%] and iEoE = 12 [37%]). Raman intensities assigned to lipids, proteins, and glycogen:protein ratio accurately distinguished children with EoE from those without EoE and aEoE from iEoE. They significantly correlated with EoE activity indices. The Raman peak ratio for lipids had 90.6% sensitivity, 100% specificity, and an area under the curve of 0.95 to differentiate children with EoE from non-EoE controls. The glycogen:protein ratio had 70% sensitivity, 91.7% specificity, and an area under the curve of 0.75 to distinguish children with aEoE from iEoE. Real-time intraendoscopy Raman spectroscopy is an effective method for identifying spectral markers reflective of the esophageal biochemical composition in children with EoE. This technique may aid in the diagnosis and monitoring of EoE and help to elucidate EoE pathogenesis.

Long-gap esophageal atresia: is native esophagus preservation always possible?

Esophageal atresia (EA) is a congenital defect that causes esophageal discontinuity, often with an associated tracheo-esophageal fistula (TEF) in 70%-90% of cases. When the distance between esophageal ends precludes primary anastomosis, it results in long gap esophageal atresia (LGEA), complicating the surgical management. This study retrospectively reviewed LGEA cases from the past decade, treated with the goal of preserving the native esophagus, comparing surgical techniques and outcomes with current literature. The data of patients treated for LGEA between 2013 and 2024 were collected from medical charts, focusing on patients treated with the preservation of their native esophagus. Ten patients were enrolled for this study. All of them had a gap between the esophageal ends equal to or greater than three vertebral bodies. Four patients (40%) underwent a delayed primary anastomosis (DPA) procedure, while the remaining six (60%) underwent a traction staged repair. All patients were treated with open surgery. The follow-up period extended from 3 months to 10 years. Preserving the native esophagus in patients with LGEA is a challenging but feasible goal, with delayed primary anastomosis and traction techniques playing key roles. We advocate for the preservation of the native esophagus as the preferred approach for ensuring a high quality of life for patients, as it helps to avoid severe long-term complications associated with esophageal substitution.

Comorbid disorders of esophagus in patients with irritable bowel disease

Comorbid disorders of esophagus in patients with irritable bowel disease