Simultaneous Examination of Eosinophil Infiltration in Esophageal Mucosa and Muscle in Patients with Achalasia: Direct Biopsy of the Esophageal Muscle at Per-oral Endoscopic Myotomy.

BACKGROUND: The relationship between eosinophilic esophagitis (EoE) and achalasia is not completely understood. There have been reports of eosinophilic infiltration of all esophageal layers in patients with achalasia. However, a routine endoscopic biopsy of the muscular layer is usually not feasible. We evaluate the safety and efficacy of muscle layer biopsy during per-oral endoscopic myotomy (POEM) as well as the prevalence of eosinophilic infiltration of the esophageal mucosa and muscular layer in patients with achalasia. PATIENTS AND METHODS: All enrolled patients had diagnosed achalasia and had simultaneous biopsies of the muscular layer at the middle esophagus and distal esophageal sphincter as well as the mucosal layer of the proximal and distal esophagus during POEM. All POEM procedures took place from August 2018 to December 2018 or September 2019 to November 2019. Various demographic, disease-related, and procedure-related data were collected from chart review. Eosinophilic infiltration in the biopsy specimen was examined. KEY RESULTS: Twenty consecutive patients (65% female, age range: 21-84) with a pre-procedure Eckardt score of >6 were enrolled during the study period, with the duration of their achalasia ranging from 1 to 32 years. Eighteen patients had clinical symptomatic improvement after POEM, as defined by an Eckardt score <3. Endoscopic examination did not reveal any signs of eosinophilic esophagitis. Pathologic examination of biopsies revealed eosinophilic infiltration in three of 20 patients (15%) in the distal esophageal mucosa (all <15 eosinophils/HPF) and none in the proximal esophageal mucosa. There was no eosinophilic infiltration in the distal esophageal sphincter and the middle esophageal muscle. No complication was noted due to muscle biopsy. CONCLUSIONS AND INFERENCES: Submucosal tunneling during POEM provides a safe access for direct esophageal muscle biopsy. This is the first report of the simultaneous biopsy of the esophageal mucosa and muscle in patients with achalasia. Contrary to all previously published studies, the association of esophageal eosinophilic infiltration and achalasia was not observed in this small sample study. Based on our findings, immune or autoimmune reaction rather than direct eosinophilic infiltration in the muscle is more likely the cause of achalasia.

Use of the Functional Lumen Imaging Probe in Clinical Esophagology.

The functional lumen imaging probe (FLIP) measures luminal dimensions using impedance planimetry, performed most often during sedated upper endoscopy. Mechanical properties of the esophageal wall and opening dynamics of the esophagogastric junction (EGJ) can be objectively evaluated in esophageal motor disorders, eosinophilic esophagitis, esophageal strictures, during esophageal surgery and in postsurgical symptomatic states. Distensibility index, the ratio of EGJ cross sectional area to intraballoon pressure, is the most useful FLIP metric. Secondary peristalsis from balloon distension can be displayed topographically as repetitive anterograde or retrograde contractile activity in the esophageal body, similar to high-resolution manometry. Real-time interpretation and postprocessing of FLIP metadata can complement the identification of esophageal outflow obstruction and achalasia, especially when findings are inconclusive from alternate esophageal tests in symptomatic patients. FLIP can complement the diagnosis of achalasia when manometry and barium studies are inconclusive or negative in patients with typical symptoms. FLIP can direct adequacy of disruption of the EGJ in achalasia when used during and immediately after myotomy and pneumatic dilation. Lumen diameter measured using FLIP in eosinophilic esophagitis and in complex strictures can potentially guide management. An abbreviated modification of the Grading of Recommendations Assessment, Development, and Evaluation was used to determine the quality of available evidence and recommendations regarding FLIP utilization. FLIP metrics that are diagnostic or suggestive of an abnormal motor pattern and metrics that define normal esophageal physiology were developed by consensus and are described in this review.

Loss to follow-up after food impaction among patients with and without eosinophilic esophagitis.

Symptoms of esophageal dysfunction such as food impaction are consistent with, but not diagnostic for eosinophilic esophagitis (EoE) without obtaining histology. We conducted a retrospective study to characterize patients with food impaction at a tertiary center. We hypothesized that many patients with food impaction may be lost to follow-up and that many have features suggestive of EoE. Adult patients presenting to the emergency department with esophageal food impaction were identified from an endoscopic database. Electronic medical records were manually abstracted. We examined associations between demographics, comorbid conditions, and follow-up with biopsy findings. Of 220 patients who presented to the emergency department for food impaction, 74.1% were men. Adequate follow-up was not documented in 120 (54.5%). Those lost to follow-up did not differ significantly by gender, age at symptom onset, or distance from hospital compared to those with follow-up. Esophageal biopsies were obtained in 158 (71.8%), and those with ≥15 eos/HPF were more likely to be lost to follow-up than those with <15 eos/HPF (52.8% vs. 34.8%, P < 0.05). Of those never biopsied, 79.0% were lost to follow-up and had intermediate proportions of males, food allergy, and asthma when compared to those with and without eosinophilic inflammation. Patients with food impaction commonly have EoE but are often lost to follow-up. Among those never biopsied, demographic and clinical features suggest that many may have undiagnosed EoE. Strategies for increasing use of biopsies in patients with food impaction and improving follow-up are needed to diagnose and manage EoE.

Propensity score methods to control for confounding in observational cohort studies: a statistical primer and application to endoscopy research.

BACKGROUND AND AIMS: Confounding is a major concern in nonexperimental studies of endoscopic interventions and can lead to biased estimates of the effects of treatment. Propensity score methods, which are commonly used in the pharmacoepidemiology literature, can effectively control for baseline confounding by balancing measured baseline confounders and risk factors and creating comparable populations of treated and untreated patients. METHODS: We propose the following 5-step checklist to guide the use and evaluation of propensity score methods: (1) select covariates, (2) assess "Table 1" balance in risk factors before propensity score implementation, (3) estimate and implement the propensity score in the study cohort, (4) reassess "Table 1" balance in risk factors after propensity score implementation, and (5) critically evaluate differences between matched and unmatched patients after propensity score implementation. We then applied this checklist to an endoscopy example using a study cohort of 411 adults with newly diagnosed eosinophilic esophagitis (EoE), some of whom were treated with esophageal dilation. RESULTS: We identified 156 patients, aged 18 and older, who were treated with esophageal dilation, and 255 patients who were nondilated. We successfully matched 148 (95%) dilated patients to nondilated patients who had a propensity score within 0.1, based on patient age, sex, race, self-reported food allergy, and presence of narrowing at baseline endoscopy. Crude imbalances were observed before propensity score matching in several baseline covariates, including age, sex, and narrowing; however, propensity score matching was successful in achieving balance across all measured covariates. CONCLUSIONS: We provide an introduction to propensity score methods, including a straightforward checklist for implementing propensity score methods in nonexperimental studies of treatment effectiveness. Moreover, we demonstrate the advantage of using "Table 1" as a simple but effective diagnostic tool for evaluating the success of propensity score methods in an applied example of esophageal dilation in EoE.

Comparative Analysis of Adverse Events After Esophageal Balloon and Bougie Dilations in Children.

BACKGROUND: Pneumatic balloon and bougie dilation are widely used methods for pediatric esophageal dilation. There are no studies directly comparing the safety of these techniques in pediatric patients. This study compared adverse events (AEs) of balloon and bougie dilation in children at a single institution. METHODS: AEs were identified by means of a prospective clinical registry of all procedure related AEs from 2012 to 2015 at a single institution. Identified AEs underwent retrospective review of procedural and clinical details. The category of each AE was recorded and severity was assigned using a 5-point scoring system. AEs were compared between balloon and bougie dilation for different severities. RESULTS: There were 105 patients who underwent 246 dilation sessions. Balloon dilation was performed more commonly (n = 190, 77%) as compared to Maloney dilators (n = 56, 23%). Patients with balloon dilation were younger (3.0 vs 14.5 years, P = 0.0001) and more likely to have strictures from caustic ingestion (42% vs 2%, P < 0.0001) or surgical anastomoses (34% vs 5% P < 0.0001). Bougie dilation was used more commonly in patients with eosinophilic esophagitis (77% vs 7%, P < 0.0001)). In multivariate analysis, each year of increasing age was associated with a 12% increase in any AEs (P = 0.015), but no difference in clinically significant AEs (grade 2 or higher) was identified between dilation methods. CONCLUSIONS: Bougie and balloon dilation did not have significant differences in AE rates, but the patient populations differed between the 2 methods. The dilation method should depend on stricture characteristics and endoscopist expertise with each method.

Unsedated In-office Transgastrostomy Esophagoscopy to Monitor Therapy in Pediatric Esophageal Disease.

Monitoring therapy in esophageal inflammatory disorders such as eosinophilic esophagitis and reflux esophagitis often requires frequent endoscopic evaluation. We recently reported the effective use of unsedated in-office transnasal esophagoscopy that significantly decreased costs and anesthetic exposure associated with pediatric esophagoscopy in eosinophilic esophagitis. Here we report a series of pediatric patients with esophagitis with gastrostomy tubes who underwent unsedated transgastrostomy esophagoscopy (TGE) in an office setting. Nine patients (ages 16 months-21 years) tolerated TGE without significant adverse events. Biopsy specimens were adequate for evaluation. This series confirms that unsedated in-office TGE can be used to successfully obtain mucosal biopsies to monitor esophageal inflammatory conditions in children without the use of sedation.

Esophageal dilation with either bougie or balloon technique as a treatment for eosinophilic esophagitis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Esophageal dilation is a now recognized to be an important therapeutic modality in eosinophilic esophagitis (EoE). We aimed to evaluate the safety of esophageal dilation in EoE, especially regarding perforation risk, and to examine perforation risk by dilator type. METHODS: We conducted a systematic review of the published literature from January 1, 1950 to June 30, 2016 using PubMed, EMBASE, and Web of Science. Studies were included if they described patients with EoE who underwent elective esophageal dilation and also reported the presence or absence of at least 1 adverse event (eg, perforation, bleeding, pain, or hospitalization). We used random-effects meta-analysis to estimate the frequency of each adverse event. RESULTS: Of 923 identified articles, 37 met inclusion criteria and represented 2034 dilations in 977 patients. On meta-analysis, postprocedure hospitalization occurred in .689% of dilations (95% confidence interval [CI], 0%-1.42%), clinically significant GI hemorrhage in .028% (95% CI, 0%-.217%), and clinically significant chest pain in 3.64% (95% CI, 1.73%-5.55%). Nine perforations were documented, at a rate of .033% (95% CI, 0%-.226%) per procedure after meta-analysis. None of the perforations resulted in surgical intervention or mortality. Most (5/9) were reported before 2009 (rate, .41% [95% CI, 0%-2.75%]); from 2009 forward the rate was .030% (95% CI, 0%-.225%). Dilation method was described in 30 studies (1957 dilations), in which 4 perforations were detected. The estimated perforation rate for bougies was .022% (95% CI, 0%-.347%) and for balloons was .059% (95% CI, 0%-.374%). CONCLUSIONS: Perforation from esophageal dilation in EoE is rare, and there is no evidence of a significant difference in perforation risk related to dilator type. Esophageal dilation should be considered a safe procedure in EoE.

Systematic review with meta-analysis: endoscopic dilation is highly effective and safe in children and adults with eosinophilic oesophagitis.

BACKGROUND: Oesophageal dilation is frequently used as an adjunct treatment to alleviate symptoms that develop from fibrostenotic remodelling in eosinophilic oesophagitis (EoE). Earlier reports described an increased risk of complications associated with dilation. AIM: Perform a systematic review and meta-analysis to assess the efficacy and safety of endoscopic dilation in children and adults with EoE. METHODS: Professional librarians searched MEDLINE, EMBASE, the Cochrane library, Scopus, and Web of Science for articles in any language describing studies of dilation in EoE through December 2016. Studies were selected and data were abstracted independently and in duplicate. Random effects modelling was used to generate summary estimates for clinical improvement and complications (haemorrhage, perforation, hospitalisation, and death). RESULTS: The search resulted in 3495 references, of which 27 studies were included in the final analysis. The studies described 845 EoE patients, including 87 paediatric patients, who underwent a total of 1820 oesophageal dilations. The median number of dilations was 3 (range: 1-35). Clinical improvement occurred in 95% of patients (95% CI: 90%-98%, I2 : 10%, 17 studies). Perforation occurred in 0.38% (95% CI: 0.18%-0.85%, I2 : 0%, 27 studies), haemorrhage in 0.05% (95% CI: 0%-0.3%, I2 : 0%, 18 studies), and hospitalisation in 0.67% (95% CI: 0.3%-1.1%, I2 : 44%, 24 studies). No deaths occurred (95% CI: 0%-0.2% I2 : 0%, 25 studies). CONCLUSIONS: Endoscopic dilation is consistently effective in children and adults with EoE, resulting in improvement in 95% of patients with very low rates (<1%) of major complications.

The Endoscopic Reference Score shows modest accuracy to predict histologic remission in adult patients with eosinophilic esophagitis.

BACKGROUND: The relationship between the severity of endoscopic signs scored according to the Endoscopic Reference Score (EREFS) and histopathologic signs of eosinophilic esophagitis (EoE) has not been sufficiently explored. We aimed to determine if the EREFS system predicts histopathologic activity in EoE patients. METHODS: We included 69 patients with EoE (age 35 [IQR 29-48] years; 80% male) who, between 2006 and 2014, underwent esophagogastroduodenoscopy (EGD) during which high-quality endoscopic images were taken and esophageal biopsy specimens were obtained. Per EGD, three or more depersonalized images were scored by an expert endoscopist, and histopathologic signs were scored by a pathologist with gastrointestinal expertise; both in a blinded fashion. The predictive values of endoscopic signs for disease activity (peak eosinophil count) were calculated. In addition, we measured the utility of the EREFS in the follow-up of 35 EoE patients. KEY RESULTS: Individual endoscopic signs did not correspond to the peak eosinophil count or other histopathologic signs. Although the composite fibrotic signs score, inflammatory signs score, and total EREFS correlated weakly to moderately with the peak eosinophil count, none of these scores had both high positive and negative predictive values for histopathologic disease activity. In the follow-up of 35 patients, lower peak eosinophil counts were not associated with a decrease in endoscopic abnormalities. CONCLUSIONS & INFERENCES: In adult patients with EoE, the EREFS system correlates with peak eosinophil counts, but their predictive value for disease activity is insufficient for clinical use. Therefore, biopsies remain indispensable for the assessment of disease activity.

Spontaneous intramural esophageal dissection: an unusual onset of eosinophilic esophagitis

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Eosinophilic Esophagitis Dilation in the Community--Try It--You will Like It--But Start Low and Go Slow.

The saga of esophageal dilation for patients with eosinophilic esophagitis and strictures reads like a historical novel. Currently, data from over 500 eosinophilic esophagitis (EoE) patients now convincingly prove that esophageal dilation is effective for prolonged relief and safe. It can easily be performed in the gastroenterologists community but follow the basic tenets of starting low with small diameter bougies/balloons and progressing slowly as you gradually dilate these strictures to 16-18 mm. Table 1 outlines my approach.

Outcomes of Esophageal Dilation in Eosinophilic Esophagitis: Safety, Efficacy, and Persistence of the Fibrostenotic Phenotype.

OBJECTIVES: Esophageal dilation is commonly performed in eosinophilic esophagitis (EoE), but there are few long-term data. The aims of this study were to assess the safety and long-term efficacy of esophageal dilation in a large cohort of EoE cases, and to determine the frequency and predictors of requiring multiple dilations. METHODS: We conducted a retrospective cohort study in the University of North Carolina EoE Clinicopathological Database from 2002 to 2014. Included subjects met consensus diagnostic criteria for EoE. Clinical, endoscopic, and histologic features were extracted, as were dilation characteristics (dilator type, change in esophageal caliber, and total number of dilations) and complications. Patients with EoE who had undergone dilation were compared with those who did not and also stratified by whether they required single or multiple dilations. RESULTS: Of 509 EoE patients, 164 were dilated a total of 486 times. Those who underwent dilation had a longer duration of symptoms before diagnosis (11.1 vs. 5.4 years, P<0.001). Ninety-five patients (58%) required >1 dilation (417 dilations total, mean of 4.4±4.3 per patient). The only predictor of requiring multiple dilations was a smaller baseline esophageal diameter. Dilation was tolerated well, with no major bleeds, perforations, or deaths. The overall complication rate was 5%, primarily due to post-procedural pain. Of 164 individuals dilated, a majority (58% or 95/164) required a second dilation. Of these individuals, 75% required repeat dilation within 1 year. CONCLUSIONS: Dilation in EoE is well-tolerated, with a very low risk of serious complications. Patients with long-standing symptoms before diagnosis are likely to require dilation. More than half of those dilated will require multiple dilations, often needing a second procedure within 1 year. These findings can be used to counsel patients with fibrostenotic complications of EoE.

Role of Endoscopy in Diagnosis and Management of Pediatric Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergic (immune-mediated) disease that leads to esophageal dysfunction and feeding disorders in children. Foods, and possibly environmental triggers, cause an inflammatory response in the esophagus, leading to esophageal inflammation, eosinophilic infiltration, and esophageal dysmotility, which may progress to dysphagia, food impaction, and esophageal stricture. Endoscopy with biopsy and histologic evaluation is currently the only method to diagnose EoE. Once diagnosed with EoE, children undergo follow-up endoscopy after therapy initiation and adjustments to ensure remission. Furthermore, children with food impactions or strictures may require endoscopic intervention such as foreign body removal and/or esophageal dilation.

Unsedated transnasal esophagoscopy for monitoring therapy in pediatric eosinophilic esophagitis.

BACKGROUND AND AIMS: Unsedated transnasal endoscopy (TNE) is safer and less costly than sedated EGD. The aim of this study was to evaluate the performance of TNE with biopsies in monitoring the esophageal mucosa of pediatric patients with eosinophilic esophagitis. METHODS: Patients between 8 and 17 years of age with eosinophilic esophagitis and their parents were enrolled. Unsedated TNE was performed. A 2.8-mm (1.2-mm channel) or a 4-mm flexible bronchoscope (2-mm channel) was used, and esophageal biopsy specimens were obtained. Biopsy specimen analysis, duration, adverse events, and billing charges of TNE were assessed. Immediately after TNE and a minimum of 2 weeks later, a modified Group Health Association of America 9 survey and a preference questionnaire were completed, respectively. RESULTS: Twenty-one of 22 enrolled patients underwent TNE. TNE was performed with no serious adverse events. Histopathological analysis revealed 0 eosinophils per high-power field (n = 12), fewer than 15 eosinophils per high-power field (n = 4), and more than 15 eosinophils per high-power field (n = 5). The total epithelial surface area of mucosal biopsy samples from either TNE Forceps (1.2 mm or 2 mm biopsy channel forceps) compared with those obtained during the subject's previous EGD by using standard endoscopic forceps was not statistically different (P = .308 [1.2 mm]/P = .492 [2 mm]). All parents and 76.2% of subjects would undergo the TNE again. TNE was preferred over EGD by 85.7% of parents and 52.4% of subjects. The modified Group Health Association of America 9 survey revealed a high degree of satisfaction (average, 43.19 ± 2.6; maximum score, 45). Charges associated with TNE were 60.1% lower than for previous EGDs. CONCLUSIONS: Unsedated TNE is an effective, lower-cost procedure for monitoring the esophageal mucosa of children with eosinophilic esophagitis.

Two-stage Surgery for an Aortoesophageal Fistula Caused by Tuberculous Esophagitis.

An aortoesophageal fistula (AEF) is an extremely rare, potentially fatal condition, and aortic surgery is usually performed together with extracorporeal circulation. However, this surgical method has a high rate of surgical complications and mortality. This report describes an AEF caused by tuberculous esophagitis that was treated successfully using a two-stage operation. A 52-yr-old man was admitted to the hospital with severe hematemesis and syncope. Based on the computed tomography and diagnostic endoscopic findings, he was diagnosed with an AEF and initially underwent thoracic endovascular aortic repair. Esophageal reconstruction was performed after controlling the mediastinal inflammation. The patient suffered postoperative anastomotic leakage, which was treated by an endoscopic procedure, and the patient was discharged without any further problems. The patient received 9 months of anti-tuberculosis treatment after he was diagnosed with histologically confirmed tuberculous esophagitis; subsequently, he was followed as an outpatient and has had no recurrence of the tuberculosis or any further issues.

Eosinophilic esophagitis as paraneoplastic syndrome in a patient with ganglioneuroblastoma.

A 16-month-old boy presented with failure to thrive despite sufficient caloric intake, hypersalivation, abdominal pain, chronic diarrhea and blepharitis. An eosinophilic esophagitis (EoE) was diagnosed by esophageal biopsy. Dietary restrictions and topical steroid treatment lead to no improvement. Further diagnostic work-up revealed an intrathoracal, paraspinal ganglioneuroblastoma. After operative extirpation of the tumour, all initial symptoms resolved. An esophageal control biopsy 4 weeks after tumour resection was normal. This is the first report of eosinophilic esophagitis as part of a paraneoplastic syndrome in a patient with a malignant disease other than a carcinoma.

First successful treatment of a circumferential intramural esophageal dissection with perforation in a patient with eosinophilic esophagitis using a partially covered self-expandable metal stent.

Intramural esophageal dissection (IED) is a rare disease characterized by a partial (PIED) or circumferential (CIED) mucosal rupture. Whereas PIED responds well to nonoperative treatment, complicated courses have been reported necessitating surgery, up to the point of esophagectomy despite complex endoscopic interventions, in CIED. We report the first case of an iatrogenic CIED with perforation in a young patient with underlying eosinophilic esophagitis treated successfully by endoscopy alone, using a partially covered self-expandable metal stent.

Otolaryngologic surgeries are frequent in children with eosinophilic esophagitis.

OBJECTIVE: The aim was to study the prevalence of otolaryngologic surgeries in pediatric patients with eosinophilic esophagitis (EoE). METHODS: Retrospective cohort study at a tertiary care center. The type of otolaryngologic surgeries performed in patients with diagnosis of EoE was recorded during a 5-year period. RESULTS: Seventy-five percent of patients were male, with average age of EoE diagnosis at 7.5 years with an 83% incidence of atopy. Cohort analysis revealed that 33% (119/362) had a total of 275 otolaryngologic surgeries. Surgeries performed on 119 patients are as follows: 20% bilateral myringotomy with tubes, 14% tonsillectomy, 18.5% adenoidectomy, 1.4% sinus irrigation, 3.3% bronchoscopy, and 1.4% laryngotracheoplasty (LTP); 63% of patients underwent multiple procedures. Thirty percent of patients undergoing bilateral myringotomy with tube placement (BMT) needed additional tubes. Four of 5 LTP patients had successful operations. Twelve percent of patients had EoE diagnosis prior to an otolaryngologic surgery. CONCLUSION: Thirty-three percent of children with EoE required otolaryngologic surgical intervention and nearly one-third who underwent BMT required additional ear tubes. A large fraction of children with EoE will undergo an otolaryngologic surgery, only a minority with a preoperative EoE diagnosis. Until the nature of this relationship is clarified, the high coincidence with otolaryngologic surgeries dictates that otolaryngologists should be familiar with diagnosis of EoE in patients.