Epithelial-Fibroblast Crosstalk in Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an emerging form of food allergy that exerts a significant clinical and financial burden worldwide. EoE is clinically characterized by eosinophil-rich inflammatory infiltrates in esophageal mucosa and esophageal dysfunction. Remodeling events in esophageal epithelium and lamina propria also frequently occur in patients with EoE. Because subepithelial fibrosis is associated with esophageal stricture, the most severe consequence of EoE, there exists an urgent need for a deeper understanding of the molecular mechanisms mediating fibrosis in EoE. Here, we review emerging evidence from experimental model systems that implicates crosstalk between esophageal epithelial cells and underlying stromal cells in EoE fibrosis. We further discuss implications for epithelial-stromal interaction with regard to EoE patient care and propose future directions that may be pursued to further the understanding of epithelial-stromal crosstalk in EoE pathobiology.

Esophageal intramural pseudodiverticulosis.

Esophageal intramural pseudodiverticulosis (EIPD) is a disease of unknown pathogenesis characterized by usually systemic, cystic dilatation of the excretory ducts of esophageal submucosal glands. In this article, I review the epidemiology, clinical manifestations, endoscopic findings, esophagographic findings, and histopathology of EIPD. I also discuss the etiology and possible pathogenesis of EIPD based on my experiences with this disease and a review of the literature. EIPD usually presents with dysphagia in middle-aged individuals. It is often complicated with secondary infections, most commonly candidiasis. On esophagography, EIPD is delineated as small, multiple, flask-shaped outward projections within the esophageal wall. In recent years, EIPD has been mainly diagnosed by endoscopic findings of multiple, localized, small mucosal depressions. The orifices of the "pseudodiverticula" periodically open and close, and excrete mucus onto the mucosal surface. On histopathological examination, the luminal surface of dilated ducts in EIPD is covered by multilayered, hyperplastic epithelial cells, but myoepithelial cells in the glandular acini are well preserved. Treatment of EIPD is usually symptomatic therapy, and prevention of the infectious complications is important. The etiology and pathogenesis of EIPD are largely unknown, but functional abnormalities of autonomic nerve fibers innervating the esophageal glands likely play an important role, since the structures of the glands are basically preserved in this disease.

The utility of balloon-based and standard impedance technology to diagnose esophageal mucosal diseases in children.

BACKGROUND: Standard impedance catheters and balloon-based mucosal impedance catheters (BBMI) have been used to assess mucosal integrity and diagnose mucosal diseases. The goal of this study was to determine the age-related technical issues associated with mucosal balloon inflation, validate the BBMI measurement against a standard impedance probe, and compare software-generated diagnoses to histologic diagnoses. METHODS: We prospectively recruited patients undergoing endoscopy, during which patients underwent standard mucosal impedance catheters and BBMI measurements. Measurements were compared to each other, to the histologic diagnoses, and to the number of eosinophils per high power field. We then compared the patients' diagnosis to that assigned by the BBMI software. KEY RESULTS: Sixty-two patients (mean age: 62 ± 62 months) were recruited, including non-GERD (N = 40), GERD (N = 15), and EoE (N = 7) patients. There were significant differences between the impedance values measured by the two technologies at each esophageal height (p < 0.003). There were significant correlations between the mean impedance values taken by the two catheters in the distal (r2 = 0.272, p = 0.04), mid (r2 = 0.371, p < 0.001), and proximal (r2 = 0.259, p = 0.05) esophagus. There were significant differences in BBMI impedance values across diagnoses in the mid and proximal esophagus (p = 0.024 and 0.025, respectively). While not statistically significant (p = 0.061-0.073), the standard catheter showed similar trends by diagnosis. Using the BBMI diagnostic prediction software, 33%-72% of patients were misclassified. CONCLUSION AND INFERENCES: While there was significant variability in impedance values between technologies within patients, regional measurements were consistent across catheters. Automated analyses lacked the sensitivity to diagnose inflammatory disorders.

Benign esophageal stricture model construction and mechanism exploration.

Esophageal stricture is a debilitating condition that negatively impacts patients' quality of life after undergoing endoscopic mucosal resection (EMR). Despite its significance, this disease remains underexplored due to the lack of a stable animal model. Under direct visualization with choledochoscopy, we retrogradely damaged the esophageal mucosal layer through the gastrostomy to create a rat model of esophageal stricture. The development of histological defects in the mucosal layer was assessed over a 2-week period after model induction. Then the models were evaluated using X-ray barium radiography, Hematoxylin-Eosin, Masson's trichrome, Sirius red, and Victoria blue staining, multiphoton microscopic imaging. Additionally, the molecular mechanisms of esophageal stricture were explored by conducting RNA transcriptome sequencing, PCR, immunohistochemistry, and immunofluorescence staining. We successfully established fifteen rat models of esophageal stricture by injuring the mucosal layer. In the model group, the mucosal defect initially occurs and subsequently repaired. The epithelium was absent and was plastically remodeled by collagen during the acute inflammatory phase (Day 1), proliferation phase (Day 7), anaphase of proliferation (Day 10), and plastic remodeling phase (Day 14). We observed increased expression of COL1A1, acta2, FGF, IL-1, and TGF-ß1 pathway in the model group. We established a highly repeatable rat model of esophageal stricture, and our results suggest that the mucosal defect of the esophagus is a critical factor in esophageal stricture development, rather than damage to the muscularis layer. We identified Atp4b, cyp1a2, and gstk1 as potential targets for treating esophageal stricture, while the TGF-ß pathway was found to play an important role in its development.

Complete Circumferential Endoscopic Submucosal Dissection for Esophageal Cancer Leaving an Island of Normal Mucosa.

Esophageal stricture caused by complete circumferential endoscopic submucosal dissection (ESD) of extensive esophageal squamous cell carcinoma (ESCC) is a major concern and can result in a low quality of life. Normal mucosa may remain within a complete circumferential lesion of ESCC in some cases. We herein report a case of ESCC in which a complete circumferential lesion was treated with ESD while leaving an island of normal mucosa within it. This case demonstrates that preserving areas of normal mucosa within lesions during complete circumferential ESD is not technically difficult and may be an effective measure for preventing esophageal stricture.

Challenges in Inter-rater Agreement on Lamina Propria Fibrosis in Esophageal Biopsies.

BACKGROUND: Mucosal biopsies in eosinophilic esophagitis (EoE) can exhibit lamina propria (LP) fibrosis, which may portend stenotic complications; however, the histologic diagnosis of LP fibrosis is subjective. We sought to assess and improve the consistency of LP fibrosis diagnosis among our pathologist group. METHODS: At a large pediatric hospital, 25 esophageal biopsy slides from 19 patients (16 with EoE) exhibiting a wide spectrum of LP area, artifacts, and fibrosis severity were scanned into whole-slide images. Staff pediatric pathologists (n = 8) separate from the authors classified each biopsy by LP adequacy and fibrosis severity 1 month before and after completion of an educational tutorial. Consensus was defined as >70% agreement. RESULTS: At baseline, 16/25 (64%) cases reached consensus for no fibrosis (n = 3), fibrosis (n = 7), or inadequate LP (n = 6); agreement was fair (α = 0.34). Post-tutorial, 13/25 (52%) cases reached consensus for no fibrosis (n = 2), fibrosis (n = 7), or inadequate LP (n = 4); agreement was again fair (α = 0.33). There was moderate agreement in grading of fibrosis severity (α = 0.54). CONCLUSION: We document only fair-to-moderate agreement in the diagnosis of esophageal LP fibrosis and adequacy in a large pediatric pathologist group despite targeted education, highlighting a challenge in incorporating this feature into EoE research and clinical decision-making.

Submucosal Tunneling Techniques for Tumor Resection.

The concept of third space endoscopy is based on the principle that the deeper layers of the gastrointestinal tract can be accessed by tunneling in the submucosal space and maintaining the integrity of the overlying mucosa. The mucosal flap safety valve enabled endoscopists to use submucosal space securely. The era of third space endoscopy started with peroral endoscopic myotomy for treatment of achalasia and has expanded to treat various other gastrointestinal disorders, such as mucosal lesions, submucosal tumors, extraluminal tumors, and refractory gastroparesis, Zenker diverticulum, and restoration of the completely obstructed esophageal lumen. Third space endoscopy rapidly emerged as a minimally invasive alternative to conventional surgery. Many studies discovered that this technique is safe and effective with excellent outcomes. Our review focused on the indications, techniques, clinical management, and adverse events of submucosal tunneling techniques for tumor resection.

Risk factors and pathological characteristics for intraductal tumor spread of submucosal gland in early esophageal squamous cell neoplasia.

The esophageal gland duct may serve as a pathway for the spread of early esophageal squamous cell neoplasia (ESCN) to a deeper layer. Deep intraductal tumor spreading cannot be completely eradicated by ablation therapy. However, the risk factors of ductal involvement (DI) in patients with ESCNs have yet to be investigated. We consecutively enrolled 160 early ESCNs, which were treated with endoscopic submucosal dissection. The resected specimens were reviewed for the number, morphology, resected margin, distribution and extension level of DI, which were then correlated to clinical factors. A total of 317 DIs (median:3, range 1-40 per-lesion) in 61 lesions (38.1%) were identified. Of these lesions, 14 have DIs maximally extended to the level of lamina propria mucosa, 17 to muscularis mucosae, and 30 to the submucosa. Multivariate logistic regression analysis showed that tumors located in the upper esophagus (OR = 2.93, 95% CI, 1.02-8.42), large tumor circumferential extension (OR = 5.39, 95% CI, 1.06-27.47), deep tumor invasion depth (OR = 4.12, 95% CI, 1.81-9.33) and numerous Lugol-voiding lesions in background esophageal mucosa (OR = 2.65, 95% CI, 1.10-6.37) were risk factors for DI. The maximally extended level of ducts involved were significantly correlated with the cancer invasion depth (P < 0.05). Notably, 245 (77%) of the involved ducts were located at the central-trisection of the lesions, and 52% of them (165/317) revealed dilatation of esophageal glandular ducts. Five (1.6%) of the involved ducts revealed cancer cell invasion through the glandular structures. In conclusion, DI is not uncommon in early ESCN and may be a major limitation of endoscopic ablation therapy.

Early prediction of complex benign anastomotic stricture after esophagectomy using early postoperative endoscopic findings.

BACKGROUND: Benign anastomotic stricture after esophagectomy and reconstruction adversely affects oral intake and can increase the risk of aspiration pneumonia. Some patients experience relapse that requires frequent endoscopic dilatations. This study aimed to investigate whether the endoscopic appearance of anastomosis during the early postoperative period is associated with the complexity of subsequent anastomotic strictures. METHODS: Data of 213 patients who underwent esophagectomy with gastric tube reconstruction and early postoperative endoscopy between July 2008 and September 2018 were prospectively collected. Relationships among various risk factors, including the severity of mucosal degeneration of the anastomosis and complexity of anastomotic stricture, were studied using multivariate logistic regression analysis. RESULTS: Fifty-three patients (25%) developed anastomotic strictures at a median of 55 days after surgery, requiring a median of 5 endoscopic dilations. In multivariate analysis, severe mucosal degeneration was the only significant risk factor for any type of anastomotic stricture (P < 0.001). Twenty-seven patients (51%) developed refractory anastomotic strictures. In multivariate analysis, younger age (< 65 years) (P = 0.01), lack of neoadjuvant therapy (P = 0.02), severe mucosal degeneration (P = 0.03), and stricture development within 55 days (P = 0.01) were the risk factors for refractory stricture. The analysis of the risk factors for severe mucosal degeneration revealed that comorbidities and anastomotic techniques were independently correlated (P < 0.01). CONCLUSIONS: Early postoperative severe mucosal degeneration of esophagogastrostomy was the only predictor of strictures, regardless of their type. Mucosal degeneration, early postoperative stricture, younger age, and front surgery were associated with refractory anastomotic strictures.

Clinical relevance of esophageal subepithelial activity in eosinophilic esophagitis.

Esophageal subepithelial activity (ESEA) is an important determinant of disease severity and complications in eosinophilic esophagitis (EoE). Inflammation and fibrosis of the lamina propria and muscularis propria result in esophageal dysfunction and stricture formation that are clinically manifest by symptoms of dysphagia and food impaction as well as the need for esophageal dilation. Esophageal biopsies that are limited to the evaluation of the esophageal epithelium are an inadequate means to assess overall, clinical disease severity in EoE. Instruments for the assessment of subepithelial activity in EoE are both limited and/or underutilized and thus represent an important unmet clinical need. Studies using endoscopic features, endoscopic ultrasonography, and barium esophagography have demonstrated improvement in ESEA parameters with topical steroid therapy. Impedance planimetry is being evaluated as an objective and quantifiable measure of esophageal distensibility that is a consequence of ESEA. In conjunction with symptom and histologic assessment, evaluation of ESEA provides a more complete evaluation of disease activity in EoE that will enhance clinical care as well as provide insights into the strengths and limitations of therapeutic interventions.

Acute dysphagia presentation and its association with esophagitis dissecans and concomitant diseases. A diagnostic challenge.

Esophagitis dissecans (ESD) is an uncommon disease that is associated with eosinophilic esophagitis (EoE), candidiasis and/or drugs. We aim to characterize the clinical, endoscopic and histological damage of the mucosal in subjects with dysphagia, its relation to concomitant entities and the treatment response. This is a retrospective observational study in patients with dysphagia and esophageal mucosal damage We included 23 patients (mean age = 55 years) who had GERD symptoms, dysphagia and/or odynophagia. There were 10, 9 and 4 cases of esophagitis dissecans, desquamative/esfacelante (ESD/ES) and fibrostenotic, respectively. ESD/SE is a rare entity with variable clinical, endoscopic and histological spectrum. The association with GERD was frequent.

La esofagitis disecante (ESD) es una enfermedad rara que puede asociarse a esofagitis eosinofílica, candidiásica o medicamentos. Se analizaron las características clinico-endoscópicas e histopatológicas en sujetos con disfagia de corta evolución asociada a afecciones concurrentes. Estudio observacional de cohorte retrospectiva con disfagia y daño mucoso. Se ingresaron 23 pacientes con edad media de 55 años. Todos tuvieron síntomas de reflujo gastroesofágico (ERGE), disfagia y odinofagia. Fueron 10, 9 y 4 casos de ESD, descamativa/esfacelante (ESD/ES) y fibroestenosis, respectivamente. La ESD/SE es una afección rara, con un espectro clínico, endoscópico e histológico variable.

Epithelial-stromal crosstalk and fibrosis in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a food allergen-induced inflammatory disorder. EoE is increasingly recognized as a cause of swallowing dysfunction, food impaction and esophageal stricture. Inflammation of the esophageal mucosa involves immune cell infiltrate, reactive epithelial changes and fibroblast activation, culminating in robust tissue remodeling toward esophageal fibrosis characterized by excess collagen deposition in the subepithelial lamina propria. Fibrosis contributes to a unique mechanical property of the EoE-affected esophagus that is substantially stiffer than the normal esophagus. There is a great need to better understand the processes behind esophageal fibrosis in order to foster improved diagnostic tools and novel therapeutics for EoE-related esophageal fibrosis. In this review, we discuss the role of esophageal inflammatory microenvironment that promotes esophageal fibrosis, with specific emphasis upon cytokines-mediated functional epithelial-stromal interplays, recruitment and activation of a variety of effector cells, and tissue stiffness. We then explore the current state of clinical methodologies to detect and treat the EoE-related esophageal stricture.

GERD: Presence and Size of Hiatal Hernia Influence Clinical Presentation, Esophageal Function, Reflux Profile, and Degree of Mucosal Injury.

A hiatal hernia (HH) is a frequent finding in patients with gastroesophageal reflux disease (GERD). We examined a consecutive series of patients with GERD diagnosed by a 24-hour pH monitoring. Based on the presence and size of HH on barium swallow, patients were divided into the following groups: no HH, HH <3 cm, HH 3-5 cm and HH >5 cm. A total of 175 patients were included: 43 with no HH, 86 with HH <3 cm, 34 with HH 3-5 cm, and 12 with HH >5 cm. Patients with larger HH had more frequent episodes of coughing and wheezing associated with episodes of reflux. High-resolution manometry showed that the increasing size of the HH was associated with decreasing pressure of the lower esophageal sphincter and weaker peristalsis. Ambulatory pH monitoring revealed that patients with larger HH had more acid reflux, in both the distal and proximal esophagus. Endoscopy showed that patients with larger HH had more severe esophagitis. Fifty per cent of patients with HH >5.0 cm had Barrett's esophagus. These findings should guide gastroenterologists and surgeons in choosing the appropriate therapy in patients with GERD and large HH.

Obtaining adequate lamina propria for subepithelial fibrosis evaluation in pediatric eosinophilic esophagitis.

BACKGROUND AND AIMS: Subepithelial fibrosis in eosinophilic esophagitis (EoE) can be detected only in esophageal biopsy specimens with adequate amounts of lamina propria (LP). We investigated how often pediatric esophageal biopsy specimens contain adequate LP, and whether esophageal eosinophilia influences the acquisition rates. METHODS: We evaluated 284 esophageal biopsy specimens from 39 patients with EoE, and 87 biopsy specimens from 32 patients without esophageal eosinophilia or other esophageal abnormalities for the presence of adequate LP and fibrosis. RESULTS: On a per biopsy specimen basis, there was no significant difference in the rate of procuring adequate amounts of LP between patients with EoE and patients without esophageal eosinophilia (43% vs 31%, P = .14). Eighty-five percent of patients with EoE had fibrosis. Fibrosis in patients with EoE was patchy and more likely to be detected in the middle or distal esophagus (odds ratio, 19.93; 95% confidence interval, 4.12-91.52). Among patients with fibrosis, the probability of its detection reached >95% with 7 middle-distal esophageal biopsy specimens. Most children with newly diagnosed EoE already had subepithelial fibrosis despite exhibiting only inflammatory endoscopic features. CONCLUSIONS: Most individual esophageal biopsy specimens in children are inadequate for assessing subepithelial fibrosis, and the rates of procuring adequate LP per biopsy specimen are similar in patients with and without EoE. To reliably detect fibrosis in patients with EoE, at least 7 biopsy specimens should be taken from the middle-distal esophagus. The finding of fibrosis in children with newly diagnosed EoE and only inflammatory endoscopic features suggests that fibrosis can occur early in this disease.

Endoscopic Submucosal Tunnel Dissection for Upper Gastrointestinal Submucosal Tumors Originating from the Muscularis Propria Layer: A Single-Center Study.

BACKGROUND/AIMS: In recent years, endoscopic submucosal tunnel dissection (ESTD) has gained popularity worldwide. The aim of this study was to evaluate the safety and efficacy of ESTD in treating upper gastrointestinal submucosal tumors (SMTs) in a large-volume endoscopic center. METHODS: Patients with SMTs were enrolled in this study between January 2012 and January 2015. Demographic data, clinical data, and treatment outcome were collected and analyzed. RESULTS: Seventy SMTs originating from the muscularis propria (MP) layer were identified in 69 patients. All patients successfully underwent the ESTD procedure. The mean procedure time was 49.0±29.5 minutes, and the mean tumor size was 18.7±7.2 mm. Among all lesions, the majority (70.0%) were located in the esophagus, 12.9% in the cardia, and 17.1% in the stomach. Complete resection was achieved in 67 lesions (95.7%). Perforation occurred in three patients (4.3%), who were treated by endoclips. Pneumothorax occurred in two patients (2.9%) and was successfully managed by thoracic drainage. During a median follow-up of 18.1 months, patients were free of local recurrence or distant metastasis. CONCLUSIONS: Our results demonstrated the feasibility and safety of ESTD in treating upper gastrointestinal SMTs originating from the MP layer. Large-scale comparative studies with other treatment methods should be conducted in the future.

Risk factors for intraoperative perforation during endoscopic submucosal dissection of superficial esophageal squamous cell carcinoma.

AIM: To identify the risk factors and clarify the subsequent clinical courses. METHODS: This study retrospectively analyzed consecutive patients with esophageal squamous cell carcinoma (ESCC) treated using endoscopic submucosal dissection (ESD) between April 2008 and October 2012. We divided the ESCC lesions into perforation cases and non-perforation cases, and compared characteristics and endoscopic findings between the two groups. "Intraoperative perforation" was defined as the detection of a perforation site during ESD and the presence of mediastinal emphysema. RESULTS: In total, 147 patients with 156 ESCC lesions were treated by ESD. Intraoperative perforation was recorded for nine lesions (5.8%) from nine patients. Multivariate analysis identified mucosal deficiency larger than 75% of the circumference of the esophagus as an independent risk factor for intraoperative perforation (OR = 7.37, 95%CI: 1.45-37.4, P = 0.016). The predominant site of perforation was the left wall [6/9 (67%)]. Six of nine perforation sites were successfully closed by clips during the procedures. Two of nine cases required drainage for pleural effusions; however, all nine cases recovered with conservative treatment and without surgical intervention. At the median follow up of 42 mo after ESD, no cases of local recurrence or distant organ metastasis had been observed. CONCLUSION: This study suggests that mucosal deficiency larger than 75% of the luminal circumference is a risk factor for intraoperative perforation during ESD for ESCC.

Mallory Weiss syndrome is not associated with hiatal hernia: a matched case-control study.

BACKGROUND/OBJECTIVE: Hiatal hernia is considered to be a predisposing factor to develop Mallory-Weiss Syndrome (MWS). No large case-control studies verifying this hypothesis have been conducted. METHODS: We reviewed all esophagogastroduodenoscopies with findings of MWS (n = 2342) in a national database and compared with age and gender-matched controls (n = 9368). Demographics, endoscopic characteristics and presence of a hiatal hernia were compared between both groups. Average age was 56.7 ± 18.6 years, and 72.4% were male. RESULTS: Hiatal hernia was more common in controls, and no significant difference was seen in a multivariate analysis. CONCLUSION: Dynamic changes inducing mucosal tension are more relevant determinants to develop MWS than gastro-esophageal junction location alone.

Hiatus hernia in healthy volunteers is associated with intrasphincteric reflux and cardiac mucosal lengthening without traditional reflux.

BACKGROUND AND AIMS: Hiatus hernia (HH) is a key mediator of gastro-oesophageal reflux disease but little is known about its significance in the general population. We studied the structure and function of the gastro-oesophageal junction in healthy volunteers with and without HH. METHODS: We compared 15 volunteers with HH, detected by endoscopy or MRI scan, but without gastro-oesophageal reflux disease with 15 controls matched for age, gender and body weight. Jumbo biopsies were taken across the squamocolumnar junction (SCJ). High-resolution pH metry (12 sensors) and manometry (36 sensors) were performed upright and supine, before and after a meal. The SCJ was marked with an endoscopically placed clip and visualised fluoroscopically. RESULTS: Cardiac mucosa was longer in volunteers with HH (3.5 vs 2.5 mm, p=0.01). There was no excessive acid reflux 5 cm above the upper border of the lower oesophageal sphincter (LOS) in either group but those with HH had short segment reflux 11 mm above the pH transition point after the meal when supine (pH<4 for 5.5% vs 0.3% of time, p=0.01). The SCJ and pH transition point were proximally displaced within the gastro-oesophageal junction in those with HH versus controls (p<0.05). The pH transition point was proximal to the peak LOS pressure point in HH subjects but distal to it in controls after the meal (p<0.05). When supine, the postprandial pH transition point crossed the SCJ in those with HH (p=0.03). CONCLUSIONS: Healthy volunteers with HH have increased intrasphincteric reflux and lengthening of cardiac mucosa in the absence of traditional transsphincteric reflux.

Swallowed Fluticasone Propionate Is an Effective Long-Term Maintenance Therapy for Children With Eosinophilic Esophagitis.

OBJECTIVES: Although effective in the treatment of eosinophilic esophagitis (EoE) in children, limited data exist on long-term safety and efficacy of swallowed topical corticosteroids. We investigated whether long-term use of swallowed fluticasone in children with EoE leads to sustained reduction in esophageal eosinophils, and endoscopic and clinical improvement. METHODS: In an open-label, prospective, single-center study, we offered pediatric patients with active EoE fluticasone 2 puffs to swallow twice a day (strengths in µg/puff: 2-4 years: 44, 5-11 years: 110, ≥12 years: 220). Clinical, endoscopic, and histological assessments were performed at baseline and shortly after therapy. If histological remission was seen, fluticasone was continued with clinical follow-ups every 4 months and endoscopic and histological follow-ups yearly. Clinical scores were derived from eight symptoms (abdominal pain, nausea, vomiting, regurgitation, chest pain, dysphagia, food impaction, and early satiety). Endoscopic scores were derived from six features (rings, exudates, furrows, edema, stricture, and shearing). Scores were expressed as ratio (features present/total). In addition to peak eosinophils/high power field (HPF) (primary outcome), histological features (eosinophilic microabscesses, degranulation, superficial layering, basal zone hyperplasia, dilated intercellular spaces, and lamina propria fibrosis) were assessed. Median clinical and endoscopic scores and individual histologic features were compared over 4 time intervals: <4 months, 4-12 months, 13-24 months, and >24 months. Growth and adverse effects were monitored. RESULTS: We enrolled 54 patients, 80% male, median age 6.5 years (range 2-17 years), 85% atopic (57% asthma, 68% allergic rhinitis, and 31% atopic dermatitis), and 74% with food allergy. Mean follow-up was 20.4 months, the longest being 68 months (5.7 years). Esophageal eosinophil counts significantly decreased (median peak eosinophils/HPF at baseline 72, <4 months: 0.5, 4-12 months: 1.75, 13-24 months: 10, and >24 months: 12, all P<0.01). All histological features significantly decreased from baseline to all follow-up time points (all P<0.01). Lamina propria fibrosis significantly decreased (% patients with fibrosis at baseline 92, <4 months: 41, 4-12 months: 50, 13-24 months: 45, and >24 months: 39, all P<0.01). Endoscopic features improved (score at baseline 0.37, <4 months: 0.17, 4-12 months: 0.17, 13-24 months: 0, and >24 months: 0.1, all P<0.01, except at >24 months: P<0.05). Symptoms improved (score at baseline 0.22, <4 months: 0, 4-12 months: 0.11, 13-24 months: 0.11, and >24 months: 0.11, all P<0.05 except at >24 months: P=0.05). In a mixed linear regression model that accounts for correlation of repeated observations in the patient in a per-patient analysis, we found that treatment with swallowed fluticasone led to a statistically significant and sustained decrease in peak esophageal eosinophil counts. Asymptomatic esophageal candidiasis was seen in three children but resolved with anti-fungal therapy. Height and weight z-scores followed expected growth curves. CONCLUSIONS: We demonstrate that swallowed fluticasone is effective as a long-term maintenance therapy for children with EoE, without growth impediment or serious side effects.

Long-term outcomes of endoscopic multiband mucosectomy for early esophageal squamous cell neoplasia: a retrospective, single-center study.

BACKGROUND AND AIMS: Endoscopic multiband mucosectomy (EMBM) has been used to treat early Barrett's esophagus and esophagogastric junction neoplasia, yet it is seldom reported for the treatment of early esophageal squamous cell neoplasia. Here we retrospectively evaluated the feasibility, safety, and efficacy of EMBM for early esophageal squamous cell neoplasia. METHODS: A total of 125 patients were included in the study. Lesions were delineated using electrocoagulation and resected using the EMBM technique. The primary outcomes were local recurrence and adverse events. Secondary outcomes were histology of the endoscopic resection specimens, specimen area, and speed of resection. All patients were followed up endoscopically. RESULTS: There were 135 esophageal lesions, of which 40 were pathologically diagnosed as low-grade intraepithelial neoplasia, 57 as high-grade intraepithelial neoplasia, 34 as early esophageal cancer, and 4 as squamous epithelium without neoplasia. No severe adverse events were observed, except for 1 perforation, which was treated by application of clips. The median follow-up was 27.75 months. Three patients had local recurrence and were endoscopically treated again. Local recurrence rate was 2.4% (3/125). No deaths occurred during the follow-up. All specimens were visible with a dividing rule, and the mean specimen area was 4.63 cm2. Mean operation time was 31.2 ± 17.4 minutes. Mean speed of resection was 6.74 min/cm2. CONCLUSIONS: EMBM seems to be effective and safe for patients with early esophageal squamous cell neoplasia. The long-term recurrence rate is low.