Eosinophilic esophagitis: a bulk of mysteries.

PubMed

Straumann, Alex

2013-01-01

Eosinophilic esophagitis (EoE), which was first described in the early 1990s, has rapidly evolved as a distinctive chronic inflammatory esophageal disease. The diagnosis is based clinically on the presence of symptoms related to esophageal dysfunction and histologically by an eosinophil-predominant inflammation once other conditions leading to esophageal eosinophilia are excluded. This striking male-prevalent disease has an increasing incidence and prevalence in the Westernized countries. Currently, EoE represents the main cause of dysphagia and bolus impaction in adult patients. Despite the fact that EoE often occurs in atopic patients, the value of allergic testing is still under discussion. Topical corticosteroids lead to a rapid improvement of active EoE clinically and histologically; they are therefore regarded as first-line drug therapy. Elimination diets have similar efficacy as topical corticosteroids, but their long-term use is limited by practical issues. Esophageal dilation of EoE-induced strictures can also be effective in improving symptoms, but this therapy has no effect on the underlying inflammation. Neither the diagnostic nor the long-term therapeutic strategies have been fully defined. Currently, the list of unsolved issues--or mysteries--is still long and a concerted effort on behalf of clinicians and scientists is required to improve the understanding and the therapeutic management of this mysterious disease. Copyright © 2013 S. Karger AG, Basel.

Eosinophilic esophagitis in an octogenarian

PubMed Central

Trifan, Anca; Stoica, Oana; Chihaia, Catalin-Alexandru; Danciu, Mihai; Stanciu, Carol; Singeap, Ana-Maria

2016-01-01

Abstract Introduction: Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated disease characterized clinically by symptoms related to esophageal dysfunction and histologically by a marked eosinophilic infiltrate in the esophageal mucosa. What was once considered a rare disease has nowadays become one of the most frequent esophageal diseases in the Western countries, occupying a place just next to the gastroesophageal reflux disease. EoE etiology and pathogenesis remain largely unknown, although most studies consider that allergic and genetic factors play the most important role. Methods: We report the case of EoE in an elderly male (octogenarian), giving a brief review of the current data related to epidemiology, pathogenesis, diagnosis, and treatment of the disease. Results: Dysphagia to solid foods was the leading symptom, and endoscopic findings included white exudates, longitudinal furrows, and concentric mucosal rings, all suggestive for EoE. Diagnosis relied on histological findings in esophageal mucosal biopsies (>30 eosinophils per high power field). He was treated with topical steroids for 8 weeks, symptoms improved gradually and the patient remained in remission at the 8-month follow-up. Conclusion: This case emphasizes that EoE may occur in very old patients and gastroenterologists should have a high index of suspicion of this disorder in any elderly with dysphagia and endoscopic relevant features. PMID:27741150

Eosinophilic Esophagitis: MedlinePlus Health Topic

MedlinePlus

... Esophagitis (EoE) (American Academy of Allergy, Asthma, and Immunology) Also in Spanish Latest News Eosinophilic Esophagitis May ... Pediatric and Adolescent Patients (American College of Gastroenterology) Topic Image Related Health Topics Eosinophilic Disorders Esophagus Disorders ...

Food and aeroallergens in eosinophilic esophagitis: role of the allergist in patient management.

PubMed

Aceves, Seema S

2014-07-01

Eosinophilic esophagitis is a clinicopathologic disease of increasing worldwide prevalence that is triggered by food antigens. The concurrent management of all of the atopic diseases affecting a single individual is likely to be important for successful long-term eosinophilic esophagitis management. This review covers the role of the allergist in eosinophilic esophagitis with a focus on the literature from the past 2  years. Studies in the past 2  years document that testing for immediate and delayed allergic hypersensitivity to foods can be of utility in building elimination diets in children, but that this may not be the case in adults. In addition, it has been shown that a number of cells and interleukins involved in Th2 inflammation such as invariant natural killer T cells, basophils, and interleukin-9 are important in eosinophilic esophagitis pathogenesis. Finally, the role of foods in generating esophageal remodeling has been shown using murine models. Recent studies support the role of the allergist in eosinophilic esophagitis management, especially for food allergen testing, interpretation, and the management of food allergies concurrent atopic diatheses. In addition, allergists have made significant research contributions in our understanding of eosinophilic esophagitis.

Concomitant herpetic and eosinophilic esophagitis--a causality dilemma.

PubMed

Monsanto, P; Almeida, N; Cipriano, M A; Gouveia, H; Sofia, C

2012-09-01

Eosinophilic and herpetic esophagitis are listed as independent causes of dysphagia, especially in young adult males. However, herpetic esophagitis rarely affects immunocompetent individuals. We report the case of a young, not immunocompromised patient, admitted because of severe dysphagia secondary to herpes simplex virus esophagitis. After complete resolution, an endoscopic and histologic reevaluation established the diagnosis of eosinophilic esophagitis. The potential association between the two conditions is discussed.

Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis.

PubMed

Kagalwalla, Amir F; Sentongo, Timothy A; Ritz, Sally; Hess, Therese; Nelson, Suzanne P; Emerick, Karan M; Melin-Aldana, Hector; Li, B U K

2006-09-01

In children, eosinophilic esophagitis (EE) is predominantly, but not exclusively, a food-hypersensitivity disorder. A crystalline amino acid-based elemental diet (ELED) formula currently remains the most effective nutritional treatment in inducing clinical and histologic remission. However, compliance with an exclusive, poor-tasting liquid formulation is difficult. This retrospective observational study assessed the short-term clinical and histologic responses of 2 cohorts of children with EE evaluated during 2 different time periods: one was treated with the standard 6-food elimination diet (SFED) and the other was treated with ELED. Of the 60 children who met the inclusion criteria and were compliant with the dietary protocol, 35 were treated with a diet excluding cow-milk protein, soy, wheat, egg, peanut, and seafood while allowing all other table foods and 25 were treated exclusively with ELED. Repeat esophageal biopsy specimens were obtained at least 6 weeks later. Twenty-six of 35 (74%) in the SFED group and 22 of 25 (88%) in the ELED group achieved significant improvement of esophageal inflammation (

Prevalence of eosinophilic esophagitis in patients with gastroesophageal reflux symptoms: A cross-sectional study from a tertiary care hospital in North India.

PubMed

Baruah, Bhaskarjyoti; Kumar, Tarun; Das, Prasenjit; Thakur, Bhaskar; Sreenivas, Vishnubatla; Ahuja, Vineet; Gupta, Siddhartha Datta; Makharia, Govind K

2017-09-01

Eosinophilic esophagitis (EoE) is being recognized increasingly all over the globe; Indian data is however sparse. We screened patients with symptoms of gastroesophageal reflux disease (GERD) for presence of EoE in them. Consecutive patients with symptoms suggestive of GERD underwent gastroduodenoscopy and esophageal biopsies, obtained from both the upper esophagus (5 cm below the upper esophageal sphincter) and lower esophagus (5 cm above gastroesophageal junction), as well as from any other endoscopically visible abnormal mucosa. Demographic and clinical characteristics, endoscopic findings, peripheral blood eosinophilic count, and history of use of proton-pump inhibitors (PPIs) were analyzed. Stool examination was done to rule out parasitoids. EoE was diagnosed if number of mucosal eosinophil infiltrate was >20 per high-power field. In the latter, Warthin-Starry stain was performed to rule out presence of H elicobacter pylori. Of 190 consecutive patients with symptoms of GERD screened, esophageal biopsies were available in 185 cases. Of them, 6 had EoE, suggesting a prevalence of 3.2% among patients with GERD. On univariate analysis, history of allergy, non-response to PPI, and absolute eosinophil counts and on multivariable analysis, history of allergy and no response to PPIs were significant predictors of EoE. Presence of EOE did not correlate with severity of reflux symptoms. In this hospital-based study from northern part of India, prevalence of EoE in patients with GERD was 3.2%. EoE should be considered as a diagnostic possibility, especially in those with history of allergy, no-response to PPI, and absolute eosinophil count of ≥250/cumm.

Impaired esophageal motor function in eosinophilic esophagitis.

PubMed

Santander, Cecilio; Chavarría-Herbozo, Carlos M; Becerro-González, Irene; Burgos-Santamaría, Diego

2015-10-01

Eosinophilic esophagitis is a chronic immunoallergic inflammatory disease of the esophagus that represents a major cause of digestive morbidity among the pediatric and young adult populations. Despite the fact that key symptoms in adults include dysphagia and food impaction, many patients lack structural changes in the esophagus to account for their complaints, which suggests the presence of underlying motor disorders and esophageal distensibility impairment. In the last few years the esophageal motility of these patients has been studied using various approaches, most particularly high-resolution manometry, ambulatory manometry, and impedance planimetry. This review focuses on the most relevant findings and scientific evidence regarding esophageal motor disorders in eosinophilic esophagitis.

Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity.

PubMed

Simon, D; Cianferoni, A; Spergel, J M; Aceves, S; Holbreich, M; Venter, C; Rothenberg, M E; Terreehorst, I; Muraro, A; Lucendo, A J; Schoepfer, A; Straumann, A; Simon, H-U

2016-05-01

Eosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. EoE is frequently associated with concomitant atopic diseases and immunoglobulin E (IgE) sensitization to food allergens in children as well as to aeroallergens and cross-reactive plant allergen components in adults. Patients with EoE respond well to elemental and empirical food elimination diets. Recent research has, however, indicated that the pathogenesis of EoE is distinct from IgE-mediated food allergy. In this review, we discuss the individual roles of epithelial barrier defects, dysregulated innate and adaptive immune responses, and of microbiota in the pathogenesis of EoE. Although food has been recognized as a trigger factor of EoE, the mechanism by which it initiates or facilitates eosinophilic inflammation appears to be largely independent of IgE and needs to be further investigated. Understanding the pathogenic role of food in EoE is a prerequisite for the development of specific diagnostic tools and targeted therapeutic procedures. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

Muir, Amanda B; Merves, Jamie; Liacouras, Chris A

2016-01-01

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Beneficial effect of Lactococcus lactis NCC 2287 in a murine model of eosinophilic esophagitis.

PubMed

Holvoet, S; Doucet-Ladevèze, R; Perrot, M; Barretto, C; Nutten, S; Blanchard, C

2016-12-01

Eosinophilic esophagitis (EoE) is a severe inflammatory disease of the esophagus which is characterized histologically by an eosinophilic infiltration into the esophageal tissue. The efficacy of probiotics in the context of atopic diseases has been well investigated but, to date, there has been no study which has evaluated probiotic effects on EoE inflammation. This study sought to identify a probiotic which improves esophageal inflammation in experimental EoE. Two candidate probiotics, Lactococcus lactis NCC 2287 and Bifidobacterium lactis NCC 2818, were tested in a murine model of EoE elicited by epicutaneous sensitization with Aspergillus fumigatus protein extract. Administration of bacterial strains in drinking water was used, respectively, as a preventive or treatment measure, or continuously throughout the study. Inflammatory parameters were assessed in the esophagus, skin, and lungs after allergen challenge. In this EoE model, supplementation with L. lactis NCC 2287 significantly decreased esophageal and bronchoalveolar eosinophilia but only when given as a therapeutic treatment. No significant effect on eosinophilia was observed when NCC 2287 was given as a preventive or a continuous intervention. NCC 2287 supplementation had no significant effect on immunoglobulin levels, skin symptom scores, or on transepidermal water loss. Supplementation with another probiotic, B. lactis NCC 2818, had no significant effect on esophageal eosinophilia. We identified a L. lactis strain, able to attenuate esophageal eosinophilic inflammation in a preclinical model of EoE. This effect is strain specific and depends on the timing and duration of bacterial supplementation. Confirmation of these observations in human clinical trials is warranted. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Topical steroids in eosinophilic esophagitis: Systematic review and meta-analysis of placebo-controlled randomized clinical trials.

PubMed

Murali, Arvind R; Gupta, Ashutosh; Attar, Bashar M; Ravi, Venkatesh; Koduru, Pramoda

2016-06-01

Eosinophilic esophagitis (EoE) is a clinicopathologic condition characterized by symptoms of esophageal dysfunction in the presence of eosinophil-predominant inflammation of esophageal mucosa. Topical steroids are recommended as first line pharmacologic therapy in EoE. We aimed to determine the efficacy of topical steroids in inducing histologic and clinical remission in children and adults with EoE. We performed a systematic search of the MEDLINE, EMBASE, Scopus, and Cochrane library databases for studies investigating the efficacy of topical steroids in EoE. We collected data on the number of patients, dose and duration of therapy, complete and partial histological response, and clinical improvement. We performed meta-analysis of placebo-controlled randomized clinical trials using Review Manager version 5.2. We used funnel plots to evaluate for publication bias. Five studies that included 174 patients with EoE were included in the meta-analysis. Topical fluticasone was administered in three studies involving 114 patients, and topical budesonide in two studies involving 60 patients. Patients treated with topical steroids, as compared with placebo, had higher complete histological remission (odds ratio [OR] 20.81, 95% confidence interval [CI] 7.03, 61.63) and partial histological remission (OR 32.20, 95% CI 6.82, 152.04). There was a trend towards improvement in clinical symptoms with topical steroids as compared with placebo but it did not reach statistical significance (OR 2.72, 95 %CI 0.90, 8.23). Topical corticosteroids seem to be effective in inducing histological remission but may not have similar significant impact in improving clinical symptoms of EoE. Studies with large sample size are needed to uniformly validate symptom improvement in EoE. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley & Sons Australia, Ltd.

Determination of esophageal eosinophil counts and other histologic features of eosinophilic esophagitis by pathology trainees is highly accurate

PubMed Central

Rusin, Spencer; Covey, Shannon; Perjar, Irina; Hollyfield, Johnny; Speck, Olga; Woodward, Kimberly; Woosley, John T.; Dellon, Evan S.

2017-01-01

Summary Many studies of eosinophilic esophagitis (EoE) utilize expert pathology review, but it is unknown whether less experienced pathologists can reliably assess EoE histology. We aimed to determine whether trainee pathologists can accurately quantify esophageal eosinophil counts and identify associated histologic features of EoE, as compared to expert pathologists. We used a set of 40 digitized slides from patients with varying degrees of esophageal eosinophilia. Each of six trainee pathologists underwent a teaching session and used our validated protocol to determine eosinophil counts and associated EoE findings. The same slides had previously been evaluated by expert pathologists, and these results comprised the gold standard. Eosinophil counts were correlated, and agreement was calculated for the diagnostic threshold of 15 eosinophils per high-power field (eos/hpf) as well as for associated EoE findings. Peak eosinophil counts were highly correlated between the trainees and the gold standard (Rho ranged from 0.87–0.92; p<0.001 for all). Peak counts were also highly correlated between trainees (0.75–0.91; p<0.001), and results were similar for mean counts. Agreement was excellent for determining if a count exceeded the diagnostic threshold (kappa ranged from 0.83 to 0.89; p<0.001). Agreement was very good for eosinophil degranulation (kappa 0.54 to 0.83; p<0.01) and spongiosis (kappa 0.44–0.87; p<0.01), but was lower for eosinophil microabscesses (kappa 0.37–0.64; p<0.01). In conclusion, using a teaching session, digitized slide set, and validated protocol, the agreement between pathology trainees and expert pathologists for determining eosinophil counts was excellent. Agreement was very good for eosinophil degranulation and spongiosis, but less so for microabscesses. PMID:28041975

Determination of esophageal eosinophil counts and other histologic features of eosinophilic esophagitis by pathology trainees is highly accurate.

PubMed

Rusin, Spencer; Covey, Shannon; Perjar, Irina; Hollyfield, Johnny; Speck, Olga; Woodward, Kimberly; Woosley, John T; Dellon, Evan S

2017-04-01

Many studies of eosinophilic esophagitis (EoE) use expert pathology review, but it is unknown whether less experienced pathologists can reliably assess EoE histology. We aimed to determine whether trainee pathologists can accurately quantify esophageal eosinophil counts and identify associated histologic features of EoE, as compared with expert pathologists. We used a set of 40 digitized slides from patients with varying degrees of esophageal eosinophilia. Each of 6 trainee pathologists underwent a teaching session and used our validated protocol to determine eosinophil counts and associated EoE findings. The same slides had previously been evaluated by expert pathologists, and these results comprised the criterion standard. Eosinophil counts were correlated, and agreement was calculated for the diagnostic threshold of 15 eosinophils per high-power field as well as for associated EoE findings. Peak eosinophil counts were highly correlated between the trainees and the criterion standard (ρ ranged from 0.87 to 0.92; P<.001 for all). Peak counts were also highly correlated between trainees (0.75-0.91; P<.001), and results were similar for mean counts. Agreement was excellent for determining if a count exceeded the diagnostic threshold (κ ranged from 0.83 to 0.89; P<.001). Agreement was very good for eosinophil degranulation (κ = 0.54-0.83; P<.01) and spongiosis (κ = 0.44-0.87; P<.01) but was lower for eosinophil microabscesses (κ = 0.37-0.64; P<.01). In conclusion, using a teaching session, digitized slide set, and validated protocol, the agreement between pathology trainees and expert pathologists for determining eosinophil counts was excellent. Agreement was very good for eosinophil degranulation and spongiosis but less so for microabscesses. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetics of eosinophilic esophagitis

PubMed Central

Kottyan, LC; Rothenberg, ME

2017-01-01

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches. PMID:28224995

Genetics of eosinophilic esophagitis.

PubMed

Kottyan, L C; Rothenberg, M E

2017-05-01

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches.

Eosinophilic esophagitis

MedlinePlus

... of the American Academy of Allergy, Asthma and Immunology. Dietary therapy and nutrition management of eosinophilic esophagitis: ... of the American Academy of Allergy, Asthma, and Immunology. J Allergy Clin Immunol Pract . 2017;5(2): ...

Grade of eosinophilia versus symptoms in patients with dysphagia and esophageal eosinophilia.

PubMed

Larsson, H; Norder Grusell, E; Tegtmeyer, B; Ruth, M; Bergquist, H; Bove, M

2016-11-01

The aim of this study was to assess whether the symptom severity and health-related quality of life (HRQL) of patients with dysphagia and esophageal eosinophilia correlate with disease activity as expressed by the number of eosinophils in the esophageal mucosa. This study included newly diagnosed (n = 58) or relapsed patients (n = 7), where 40% were diagnosed in connection with esophageal bolus impaction. The mean age was 45 years (19-88), and 74% were men. Symptoms and HRQL were recorded using the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Oesophageal Module 18 and the Short Form-36 Questionnaire. Histological samples gathered from the proximal and distal esophageal mucosa were stained using both hematoxylin and eosin (HE) and an immunohistochemical (IHC) technique against 'Eosinophil Major Basic Protein,' and the peak number of eosinophils per high-power field was assessed. More eosinophils were detected after IHC staining than HE staining (P < 0.001). No correlation was found between symptoms or the HRQL and the number of eosinophils. However, higher numbers of eosinophils at the proximal esophagus were found in patients with concomitant bolus impaction (IHC P < 0.05 and HE P < 0.05) and could serve as a risk marker. © 2015 International Society for Diseases of the Esophagus.

Accuracy, safety, and tolerability of tissue collection by Cytosponge vs endoscopy for evaluation of eosinophilic esophagitis.

PubMed

Katzka, David A; Geno, Debra M; Ravi, Anupama; Smyrk, Thomas C; Lao-Sirieix, Pierre; Miremadi, Ahmed; Miramedi, Ahmed; Debiram, Irene; O'Donovan, Maria; Kita, Hirohito; Kephart, Gail M; Kryzer, Lori A; Camilleri, Michael; Alexander, Jeffrey A; Fitzgerald, Rebecca C

2015-01-01

Management of eosinophilic esophagitis (EoE) requires repeated endoscopic collection of mucosal samples to assess disease activity and response to therapy. An easier and less expensive means of monitoring of EoE is required. We compared the accuracy, safety, and tolerability of sample collection via Cytosponge (an ingestible gelatin capsule comprising compressed mesh attached to a string) with those of endoscopy for assessment of EoE. Esophageal tissues were collected from 20 patients with EoE (all with dysphagia, 15 with stricture, 13 with active EoE) via Cytosponge and then by endoscopy. Number of eosinophils/high-power field and levels of eosinophil-derived neurotoxin were determined; hematoxylin-eosin staining was performed. We compared the adequacy, diagnostic accuracy, safety, and patient preference for sample collection via Cytosponge vs endoscopy procedures. All 20 samples collected by Cytosponge were adequate for analysis. By using a cutoff value of 15 eosinophils/high power field, analysis of samples collected by Cytosponge identified 11 of the 13 individuals with active EoE (83%); additional features such as abscesses were also identified. Numbers of eosinophils in samples collected by Cytosponge correlated with those in samples collected by endoscopy (r = 0.50, P = .025). Analysis of tissues collected by Cytosponge identified 4 of the 7 patients without active EoE (57% specificity), as well as 3 cases of active EoE not identified by analysis of endoscopy samples. Including information on level of eosinophil-derived neurotoxin did not increase the accuracy of diagnosis. No complications occurred during the Cytosponge procedure, which was preferred by all patients, compared with endoscopy. In a feasibility study, the Cytosponge is a safe and well-tolerated method for collecting near mucosal specimens. Analysis of numbers of eosinophils/high-power field identified patients with active EoE with 83% sensitivity. Larger studies are needed to establish the efficacy and safety of this method of esophageal tissue collection. ClinicalTrials.gov number: NCT01585103. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Eosinophilic gastroenteritis: A state-of-the-art review.

PubMed

Zhang, MingMing; Li, YanQing

2017-01-01

Eosinophilic gastrointestinal disorders are a series of diseases that include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis. Among these disorders, eosinophilic gastroenteritis is an uncommon and heterogeneous disease characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of secondary causes, presenting with a variety of gastrointestinal manifestations. Up to now, epidemiology and pathophysiology of eosinophilic gastroenteritis are still unclear. Based on clinical manifestations and depth of eosinophilic infiltration into the gastrointestinal tract wall, eosinophilic gastroenteritis is classified into three different patterns including predominantly mucosal pattern, predominantly muscular pattern, and predominantly serosal pattern. For diagnosing eosinophilic gastroenteritis, it is necessary for clinicians to have a high degree of clinical suspicion. In addition to the gastrointestinal symptoms, other evidences such as laboratory results, radiological findings and endoscopy can also provide important diagnostic evidences for eosinophilic gastroenteritis. And these indirect pieces of information together with histological results will lead to a definitive diagnosis of eosinophilic gastroenteritis. To avoid specific allergen, dietary treatments can be considered as initial treatment strategy before drug treatment. Corticosteroids are the main medication for eosinophilic gastroenteritis and have a dramatic therapeutic efficacy. Yet other medications need to further verify their effects in clinical practice, and surgery should be avoided as far as possible. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Dietary Therapy and Nutrition Management of Eosinophilic Esophagitis: A Work Group Report of the American Academy of Allergy, Asthma, and Immunology.

PubMed

Groetch, Marion; Venter, Carina; Skypala, Isabel; Vlieg-Boerstra, Berber; Grimshaw, Kate; Durban, Raquel; Cassin, Alison; Henry, Michelle; Kliewer, Kara; Kabbash, Lynda; Atkins, Dan; Nowak-Węgrzyn, Anna; Holbreich, Mark; Chehade, Mirna

Eosinophilic esophagitis (EoE) is a chronic/immune-antigen-mediated disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. Dietary elimination therapy has been shown to be an effective, drug-free prescription for the treatment of EoE. A range of different dietary elimination therapies have been used. Regardless of the elimination diet chosen, dietary therapy requires in-depth nutrition assessment and management. Elimination diets are not without risk and may impact nutritional status, eating pleasure, and overall quality of life. With adequate guidance, dietary therapy can be effective and nutritionally balanced, and the adverse impact on lifestyle can be minimized. This work group report addresses the potential challenges of implementing an elimination diet for the management of EoE and provides instructions and tools for physicians, dietitians, and other allied health professionals to help guide them in planning elimination diets for both children and adults. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Histopathologic diagnosis of eosinophilic conditions in the gastrointestinal tract.

PubMed

Hurrell, Jennifer M; Genta, Robert M; Melton, Shelby D

2011-09-01

Eosinophils, a constitutive component of the columnar-lined gastrointestinal tract, play an essential role in allergic responses and parasitic infections. The tissue density of these cells also increases in a variety of conditions of uncertain etiology. With the exception of the esophageal squamous epithelium, in which no eosinophils are normally present, the population of normal eosinophils in the remainder of the luminal gut is poorly defined. Therefore, histopathologists must rely on their subjective judgment to determine when a diagnosis of eosinophilic gastritis, enteritis, or colitis should be rendered. Eosinophilic esophagitis is currently the best defined and most studied eosinophilic condition of the digestive tract; therefore, the confidence in accurate diagnosis is increasing. In contrast, the characteristic clinicopathologic features of eosinophilic conditions affecting other parts of the digestive tract remain somewhat elusive. This review was designed to present pathologists with simple and practical information for the biopsy-based histopathologic diagnosis of eosinophilic esophagitis, gastritis, enteritis, and colitis. It was prepared by critically reviewing more than 200 articles on the topic, along with incorporating evidence accumulated through our own collective experience. We anticipate that by increasing pathologists' confidence in reporting these abnormal but often nameless eosinophilic infiltrates, we can help better define and characterize their significance.

Dysmotility in Esophageal Atresia: Pathophysiology, Characterization, and Treatment

PubMed Central

Faure, Christophe; Righini Grunder, Franziska

2017-01-01

Esophageal dysmotility is almost universal after esophageal atresia (EA) repair and is mainly related to the developmental anomaly of the esophagus. Esophageal dysmotility is involved in the pathophysiology of numerous symptoms and comorbidities associated with EA such as gastroesophageal reflux disease, aspiration and respiratory complications, and symptoms of dysphagia and feeding disorders. High-resolution esophageal manometry (HREM) has facilitated the characterization of the dysmotility, but there is an incomplete correlation between symptoms and manometrical patterns. Impedance coupled to HREM should help to predict the clinical outcome and therefore personalize patient management. Nowadays, the management of esophageal dysmotility in patients with EA is essentially based on treatment of associated inflammation related to peptic or eosinophilic esophagitis. PMID:28620599

Increased risk of esophageal eosinophilia and eosinophilic esophagitis in patients with active celiac disease on biopsy

PubMed Central

Jensen, Elizabeth T.; Eluri, Swathi; Lebwohl, Benjamin; Genta, Robert M.; Dellon, Evan S.

2015-01-01

Background and Aims The possible association between eosinophilic esophagitis (EoE) and celiac disease (CD) is controversial as prior results have been contradictory. We aimed to determine the relationship between EoE and CD among patients with concomitant esophageal and duodenal biopsies. Methods We conducted a cross-sectional study in a U.S. national pathology database, using data from January 2009 and June 2012. Our primary case definition was defined by the presence of esophageal eosinophilia with ≥ 15 eosinophils per high-power field. The crude and adjusted (for age and sex) odds of esophageal eosinophilia for patients with active CD were compared to those without CD. Sensitivity analyses were performed using more stringent case definitions and by estimating the associations between CD and reflux esophagitis, and CD and Barrett's esophagus (BE). Results Of 292,621 patients in the source population, 88,517 with both esophageal and duodenal biopsies were studied. 4,101 (4.6%) met criteria for EoE and 1,203 (1.4%) met criteria for CD. Odds of EoE were 26% higher in patients with CD than patients without CD (aOR: 1.26, 95% confidence interval [CI]: 0.98 – 1.60). The magnitude of association varied according to EoE case definition (Table 3), but all definitions showed a weak, positive association between the two conditions. There was no association between CD and reflux esophagitis (aOR 0.95, 95% CI: 0.85 – 1.07) or BE (aOR 0.89, 95% CI: 0.69 – 1.14) and CD. Conclusions There is a weak increase in EoE in patients with CD. This association strengthened with increasingly stringent definitions of EoE, and was not observed for other esophageal conditions. In patients with CD, concomitant EoE should be considered in the correct clinical setting. PMID:25724709

Increased Risk of Esophageal Eosinophilia and Eosinophilic Esophagitis in Patients With Active Celiac Disease on Biopsy.

PubMed

Jensen, Elizabeth T; Eluri, Swathi; Lebwohl, Benjamin; Genta, Robert M; Dellon, Evan S

2015-08-01

The possible association between eosinophilic esophagitis (EoE) and celiac disease is controversial because prior results have been contradictory. We aimed to determine the relationship between EoE and celiac disease among patients with concomitant esophageal and duodenal biopsies. We conducted a cross-sectional study in a U.S. national pathology database by using data from January 2009 through June 2012. Our primary case definition was defined by the presence of esophageal eosinophilia with ≥15 eosinophils per high-power field. The crude and adjusted (for age and sex) odds of esophageal eosinophilia for patients with active celiac disease were compared with those without celiac disease. Sensitivity analyses were performed by using more stringent case definitions and by estimating the associations between celiac disease and reflux esophagitis and celiac disease and Barrett's esophagus. Of 292,621 patients in the source population, 88,517 with both esophageal and duodenal biopsies were studied. Four thousand one hundred one (4.6%) met criteria for EoE, and 1203 (1.4%) met criteria for celiac disease. Odds of EoE were 26% higher in patients with celiac disease than in patients without celiac disease (adjusted odds ratio [aOR], 1.26; 95% confidence interval [CI], 0.98-1.60). The magnitude of association varied according to EoE case definition, but all definitions showed a weak positive association between the 2 conditions. There was no association between celiac disease and reflux esophagitis (aOR, 0.95; 95% CI, 0.85-1.07) or Barrett's esophagus (aOR, 0.89; 95% CI, 0.69-1.14) and celiac disease. There is a weak increase in EoE in patients with celiac disease. This association strengthened with increasingly stringent definitions of EoE and was not observed for other esophageal conditions. In patients with celiac disease, concomitant EoE should be considered in the correct clinical setting. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Esophagitis and its causes: Who is “guilty” when acid is found “not guilty”?

PubMed Central

Grossi, Laurino; Ciccaglione, Antonio Francesco; Marzio, Leonardo

2017-01-01

Esophagitis is mainly a consequence of gastroesophageal reflux disease, one of the most common diseases affecting the upper digestive tract. However the esophageal mucosa can also be targeted by some infectious, systemic or chemical conditions. Eosinophilic esophagitis (EoE) is an immune-mediated inflammatory disease, characterized by eosinophilic infiltration in the mucosa. Esophageal localization of Crohn’s disease is not very common, but it should always be considered in patients with inflammatory bowel disease complaining of upper digestive tract symptoms. There are also forms of infectious esophagitis (e.g., Herpes simplex virus or Candida albicans) occurring in patients with a compromised immune system, either because of specific diseases or immunosuppressive therapies. Another kind of damage to esophageal mucosa is due to drug use (including oncologic chemotherapeutic regimens and radiotherapy) or caustic ingestion, usually of alkaline liquids, with colliquative necrosis and destruction of mucosa within a few seconds. Dysphagia is a predominant symptom in EoE, while infectious, drug-induced and caustic damages usually cause chest pain and odynophagia. Endoscopy can be useful for diagnosing esophagitis, although no specific pattern can be identified. In conclusion when a patient refers upper gastrointestinal tract symptoms and the diagnosis of gastro-esophageal reflux disease is not convincing we should always carefully investigate the patient’s clinical history to consider possibilities other than the gastric refluxate. PMID:28533657

Enhanced activation of eosinophils in peripheral blood and implications for eosinophilic esophagitis diagnosis.

PubMed

Botan, Valéria; Dos Santos Borges, Tatiana Karla; Rocha Alves, Érica Alessandra; Claudino Pereira Couto, Shirley; Bender Kohnert Seidler, Heinrich; Muniz-Junqueira, Maria Imaculada

2017-07-01

Eosinophils are markers of the eosinophilic esophagitis (EoE) disease, and this work aimed to assess whether activation of eosinophils could be a noninvasive test to contribute for EoE diagnosis. The activation state of peripheral blood eosinophils in EoE patients and control subjects was assessed based on the morphological aspects of the eosinophil after adherence to slide. Cyclooxygenase-2 and 5-lipoxygenase expressions were evaluated by means of immunofluorescence microscopy to verify if and which eicosanoid pathway is triggered in eosinophils in blood in EoE. The eosinophils of patients with EoE were significantly more activated than those of control individuals. The lowest percentage of normal eosinophils for control subjects was 40%, while the highest percentage of eosinophils of normal aspect for patients with EoE was 32%. Considering 36% as a cutoff for normal eosinophils, this value differentiated all individuals with EoE from individuals without the disease with a sensitivity of 100%, considering the diagnosis of EoE as currently defined. Eosinophils of EoE patients showed higher expression of cyclooxygenase-2 than those of control subjects. The quantification of morphological changes in eosinophils is a feasible, easy, and reliable manner to identify EoE patients. Therefore, patients with symptoms of esophageal dysfunction showing higher than 36% activated eosinophils in peripheral blood could be a useful way to help definition and diagnostic criterion for EoE. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Cost Utility Analysis of Topical Steroids Compared With Dietary Elimination for Treatment of Eosinophilic Esophagitis.

PubMed

Cotton, Cary C; Erim, Daniel; Eluri, Swathi; Palmer, Sarah H; Green, Daniel J; Wolf, W Asher; Runge, Thomas M; Wheeler, Stephanie; Shaheen, Nicholas J; Dellon, Evan S

2017-06-01

Topical corticosteroids or dietary elimination are recommended as first-line therapies for eosinophilic esophagitis, but data to directly compare these therapies are scant. We performed a cost utility comparison of topical corticosteroids and the 6-food elimination diet (SFED) in treatment of eosinophilic esophagitis, from the payer perspective. We used a modified Markov model based on current clinical guidelines, in which transition between states depended on histologic response simulated at the individual cohort-member level. Simulation parameters were defined by systematic review and meta-analysis to determine the base-case estimates and bounds of uncertainty for sensitivity analysis. Meta-regression models included adjustment for differences in study and cohort characteristics. In the base-case scenario, topical fluticasone was about as effective as SFED but more expensive at a 5-year time horizon ($9261.58 vs $5719.72 per person). SFED was more effective and less expensive than topical fluticasone and topical budesonide in the base-case scenario. Probabilistic sensitivity analysis revealed little uncertainty in relative treatment effectiveness. There was somewhat greater uncertainty in the relative cost of treatments; most simulations found SFED to be less expensive. In a cost utility analysis comparing topical corticosteroids and SFED for first-line treatment of eosinophilic esophagitis, the therapies were similar in effectiveness. SFED was on average less expensive, and more cost effective in most simulations, than topical budesonide and topical fluticasone, from a payer perspective and not accounting for patient-level costs or quality of life. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Muscle layer histopathology and manometry pattern of primary esophageal motility disorders including achalasia.

PubMed

Nakajima, N; Sato, H; Takahashi, K; Hasegawa, G; Mizuno, K; Hashimoto, S; Sato, Y; Terai, S

2017-03-01

Histopathology of muscularis externa in primary esophageal motility disorders has been characterized previously. We aimed to correlate the results of high-resolution manometry with those of histopathology. During peroral endoscopic myotomy, peroral esophageal muscle biopsy was performed in patients with primary esophageal motility disorders. Immunohistochemical staining for c-kit was performed to assess the interstitial cells of Cajal (ICCs). Hematoxylin Eosin and Azan-Mallory staining were used to detect muscle atrophy, inflammation, and fibrosis, respectively. Slides from 30 patients with the following motility disorders were analyzed: achalasia (type I: 14, type II: 5, type III: 3), one diffuse esophageal spasm (DES), two outflow obstruction (OO), four jackhammer esophagus (JE), and one nutcracker esophagus (NE). ICCs were preserved in high numbers in type III achalasia (n=9.4±1.2 cells/high power field [HPF]), compared to types I (n=3.7±0.3 cells/HPF) and II (n=3.5±1.0 cells/HPF). Moreover, severe fibrosis was only observed in type I achalasia and not in other types of achalasia, OO, or DES. Four of five patients with JE and NE had severe inflammation with eosinophilic infiltration of the esophageal muscle layer (73.8±50.3 eosinophils/HPF) with no epithelial eosinophils. One patient with JE showed a visceral myopathy pattern. Compared to types I and II, type III achalasia showed preserved ICCs, with variable data regarding DES and OO. In disorders considered as primary esophageal motility disorders, a disease category exists, which shows eosinophilic infiltration in the esophageal muscle layer with no eosinophils in the epithelium. © 2016 John Wiley & Sons Ltd.

Lymphocytic esophagitis: Report of three cases and review of the literature

PubMed Central

Jideh, Bilel; Keegan, Andrew; Weltman, Martin

2016-01-01

Lymphocytic esophagitis (LyE) is a rare condition characterised histologically by high numbers of esophageal intraepithelial lymphocytes without significant granulocytes infiltration, in addition to intercellular edema (“spongiosis”). The clinical significance and natural history of LyE is poorly defined although dysphagia is reportedly the most common symptom. Endoscopic features range from normal appearing esophageal mucosa to features similar to those seen in eosinophilic esophagitis, including esophageal rings, linear furrows, whitish exudates, and esophageal strictures/stenosis. Symptomatic gastroesophageal reflux disease is an inconsistent association. LyE has been associated in paediatric Crohn’s disease, and recently in primary esophageal dysmotility disorder in adults. There are no studies assessing effective treatment strategies for LyE; empirical therapies have included use of proton pump inhibitor and corticosteroids. Esophageal dilatation have been used to manage esophageal strictures. LyE has been reported to run a benign course; however there has been a case of esophageal perforation associated with LyE. Here, we describe the clinical, endoscopic and histopathological features of three patients with lymphocytic esophagitis along with a review of the current literature. PMID:28035315

Clinical experience using the tethered capsule-based spectrally encoded confocal microendoscopy for diagnosis of eosinophilic esophagitis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Do, Dukho; Alali, Sanaz; Kang, DongKyun; Tabatabaie, Nima; Lu, Weina; Grant, Catriona N.; Soomro, Amna R.; Nishioka, Norman S.; Rosenberg, Mireille; Hesterberg, Paul E.; Yuan, Qian; Garber, John J.; Katz, Aubrey J.; Shreffler, Wayne G.; Tearney, Guillermo J.

2016-03-01

Eosinophilic Esophagitis (EoE) is caused by food allergies, and defined by histological presence of eosinophil cells in the esophagus. The current gold standard for EoE diagnosis is endoscopy with pinch biopsy to detect more than 15 eosinophils/ High power field (HPF). Biopsy examinations are expensive, time consuming and are difficult to tolerate for patients. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology capable of imaging individual eosinophils as highly scattering cells (diameter between 8 µm to 15 µm) in the epithelium. Our lab has developed a tethered SECM capsule that can be swallowed by unsedated patients. The capsule acquires large area confocal images, equivalent to more than 30,000 HPFs, as it traverses through the esophagus. In this paper, we present the outcome of a clinical study using the tethered SECM capsule for diagnosing EoE. To date, 32 subjects have been enrolled in this study. 88% of the subjects swallowed the capsules without difficulty and of those who swallowed the capsule, 95% preferred the tethered capsule imaging procedure to sedated endoscopic biopsy. Each imaging session took about 12 ± 2.4 minutes during which 8 images each spanning of 24 ± 5 cm2 of the esophagus were acquired. SECM images acquired from EoE patients showed abundant eosinophils as highly scattering cells in squamous epithelium. Results from this study suggest that the SECM capsule has the potential to become a less-invasive, cost-effective tool for diagnosing EoE and monitoring the response of this disease to therapy.

Eosinophils in Autoimmune Diseases

PubMed Central

Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

2017-01-01

Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

Treatment with topical steroids downregulates IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression in eosinophilic esophagitis.

PubMed

Lucendo, Alfredo J; De Rezende, Livia; Comas, Carmen; Caballero, Teresa; Bellón, Teresa

2008-09-01

Our aim was to evaluate the changes induced by topical steroid treatment to the esophageal epithelial inflammatory eosinophilic and T-cell infiltrate and to IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 esophageal gene expression levels in patients with eosinophilic esophagitis (EE). Esophageal biopsies were taken from eight adult patients at the moment of diagnosis and after 3-month treatment with fluticasone propionate. Eosinophils, CD8, and CD4 T cells were examined by immunohistochemistry. IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression levels were measured by real-time PCR. Eight control samples were also analyzed. A significant decrease in the eosinophil infiltrate and in CD8(+) T-cell density was observed in the esophageal epithelium from the patients upon steroid treatment. IL-5 was not detected in control samples, and expression levels were variably downregulated after treatment in six of the patients. Gene expression of eotaxin-1/CCL11 showed relevant downregulation in four cases and a modest twofold decrease in three of the patients studied. Mean CCL11 expression values upon steroid treatment were similar to control samples (19.4 +/- 28.6 vs 8.42 +/- 5, P= 0.7). Eotaxin-3/CCL26 gene expression levels were significantly increased in EE. Although they were significantly downregulated upon steroid treatment, control expression levels were not reached in any of the cases analyzed (580.9 +/- 943.9 vs 1.45 +/- 1.0, P= 0.001). Our results confirm that eotaxin-3/CCL26 is significantly increased in EE esophageal samples. However, the individual analysis of IL-5, CCL11, and CCL26 expression data suggests that several cytokines and chemokines could participate in the physiopathology of EE in humans.

Treatment of eosinophilic esophagitis in the pediatric patient: an evidence-based approach.

PubMed

Munoz-Persy, Mery; Lucendo, Alfredo J

2018-05-01

Eosinophilic esophagitis (EoE) is a unique form of non-IgE-mediated food allergy characterized by esophageal eosinophilic infiltration that commonly causes dysphagia and food impaction in children and adolescents. Assessing the efficacy of dietary restrictions or drug therapies to achieve clinical and histologic resolution of EoE through randomized controlled trials and meta-analyses has resulted in new evidence-based guidelines. Avoiding food triggers is the only therapy targeting the cause of the disease. None of the currently available food allergy tests adequately predict food triggers for EoE. Exclusively feeding with an amino acid-based elemental diet and empiric six-food elimination diet (avoiding the six foods most commonly related with food allergy) has consistently provided the best cure rates, but their high level of restriction and need for multiple endoscopies are deterrents for implementation. Simpler and less restrictive empirical methods, like a four-food (milk, gluten-containing cereals, egg, legumes) or a two-food (milk and gluten) elimination diet, show encouraging results. Proton pump inhibitors are currently a first-line treatment, achieving histological remission and improvement of symptoms in 54.1 and 64.9% of pediatric EoE patients, respectively. The efficacy of topical corticosteroids in EoE assessed in several trials and summarized in meta-analyses indicates that budesonide and fluticasone propionate are significantly superior to placebos, both in decreasing eosinophil mucosal infiltration and in relieving symptoms. Owing to differences in drug delivery, viscous budesonide formulas seem to be the best pharmacological therapy for EoE. Applying evidence-based therapies and a practical management algorithm provide an effective control of EoE. What is Known: • Eosinophilic esophagitis (EoE) now constitutes the main cause of dysphagia and food impaction in children, adolescents, and young adults. • Its chronic course and frequent progression to subepithelial fibrosis leading to strictures and narrow-caliber esophagus indicate the need for treatment. What is New: • Therapeutic goals in children with EoE include resolution of esophageal symptoms, to cure esophageal inflammation (mucosal healing) and restore a proper esophageal caliber in case of fibrostenotic endoscopic findings. Avoiding iatrogenic drug effects and nutritional deficiencies, as well as maintaining an adequate quality of life, is also essential. • Novel evidence-based guidelines, endorsed by several European scientific societies, incorporate recent advances in knowledge from several randomized controlled trials and systematic reviews to provide the best standard of care to pediatric patients, by following simple management algorithms.

Eosinophilic esophagitis in children and its relationship with parental allergies: Texas Children's Hospital experience

USDA-ARS?s Scientific Manuscript database

Eosinophilic esophagitis (EoE) is an allergen-mediated, clinicopathological condition affecting all ages. The characteristics of children with EoE in the southwestern USA have not been fully described. Furthermore, very little is known about the relationship between parental allergies and risk of Eo...

Advances in Clinical Management of Eosinophilic Esophagitis

PubMed Central

Dellon, Evan S.; Liacouras, Chris A.

2014-01-01

EoE is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. It is diagnosed based on symptoms of esophageal dysfunction, the presence of at least 15 eosinophils/high-power field in esophageal biopsies, and exclusion of competing causes of esophageal eosinophilia, including proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE). We review what we have recently learned about the clinical aspects of EoE, discussing the clinical, endoscopic, and histologic features of EoE in adults and children. We explain the current diagnostic criteria and challenges to diagnosis, including the role of gastroesophageal reflux disease and PPI-REE. It is also important to consider the epidemiology of EoE (current incidence of 1/10,000 new cases per year and prevalence of 0.5-1/1,000 cases per year) and disease progression. We review the main treatment approaches and new treatment options; EoE can be treated with topical corticosteroids such as fluticasone and budesonide, or dietary strategies, such as amino acid-based formulas, allergy test-directed elimination diets, and non-directed empiric elimination diets. Endoscopic dilation has also become an important tool for treatment of fibrostenostic complications of EoE. There are number of unresolved issues in EoE, including phenotypes, optimal treatment endpoints, the role of maintenance therapy, and treatment of refractory EoE. The care of patients with EoE and the study of the disease span many disciplines—EoE is ideally managed by a multidisciplinary team of gastroenterologists, allergists, pathologists, and dieticians. PMID:25109885

Topical corticosteroids do not revert the activated phenotype of eosinophils in eosinophilic esophagitis but decrease surface levels of CD18 resulting in diminished adherence to ICAM-1, ICAM-2, and endothelial cells.

PubMed

Lingblom, Christine; Bergquist, Henrik; Johnsson, Marianne; Sundström, Patrik; Quiding-Järbrink, Marianne; Bove, Mogens; Wennerås, Christine

2014-12-01

Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.

Augment clinical measurement using a constraint-based esophageal model

NASA Astrophysics Data System (ADS)

Kou, Wenjun; Acharya, Shashank; Kahrilas, Peter; Patankar, Neelesh; Pandolfino, John

2017-11-01

Quantifying the mechanical properties of the esophageal wall is crucial to understanding impairments of trans-esophageal flow characteristic of several esophageal diseases. However, these data are unavailable owing to technological limitations of current clinical diagnostic instruments that instead display esophageal luminal cross sectional area based on intraluminal impedance change. In this work, we developed an esophageal model to predict bolus flow and the wall property based on clinical measurements. The model used the constraint-based immersed-boundary method developed previously by our group. Specifically, we first approximate the time-dependent wall geometry based on impedance planimetry data on luminal cross sectional area. We then fed these along with pressure data into the model and computed wall tension based on simulated pressure and flow fields, and the material property based on the strain-stress relationship. As examples, we applied this model to augment FLIP (Functional Luminal Imaging Probe) measurements in three clinical cases: a normal subject, achalasia, and eosinophilic esophagitis (EoE). Our findings suggest that the wall stiffness was greatest in the EoE case, followed by the achalasia case, and then the normal. This is supported by NIH Grant R01 DK56033 and R01 DK079902.

Lymphocytic Esophagitis: An emerging clinicopathologic disease associated with dysphagia

PubMed Central

Pasricha, Sarina; Gupta, Amit; Reed, Craig C.; Speck, Olga; Woosley, John T.; Dellon, Evan S.

2016-01-01

Background Lymphocytic Esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations. Aim To characterize patients with LyE, compare them to non-LyE controls, and identify risk factors. Methods We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000 and June 1, 2012. Archived pathology slides were re-reviewed and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls. Results 27 adults were diagnosed with LyE, and the majority were female (63%). The most common symptom was dysphagia (70%). 52% had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37%), erosive esophagitis (33%), rings (26%), and hiatal hernia (26%); 33% of patients required dilation. After histology re-review, 78% of LyE patients were found to have more than 20 lymphs/hpf. In comparison to the normal, reflux and EoE controls, patients with LyE tended to be non-white (p<0.01), were more commonly tobacco users (p=0.02), and less likely to have seasonal allergies (p=0.02). Conclusion LyE commonly presents with dysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy. PMID:27343035

Lymphocytic Esophagitis: An Emerging Clinicopathologic Disease Associated with Dysphagia.

PubMed

Pasricha, Sarina; Gupta, Amit; Reed, Craig C; Speck, Olga; Woosley, John T; Dellon, Evan S

2016-10-01

Lymphocytic esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations. The aim of this study was to characterize patients with LyE, compare them to non-LyE controls, and identify risk factors. We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000, and June 1, 2012. Archived pathology slides were re-reviewed, and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls. Twenty-seven adults were diagnosed with LyE, and the majority were female (63 %). The most common symptom was dysphagia (70 %). Fifty-two percentage had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37 %), erosive esophagitis (33 %), rings (26 %), and hiatal hernia (26 %); 33 % of patients required dilation. After histology re-review, 78 % of LyE patients were found to have more than 20 lymphs/hpf. In comparison with the normal, reflux and EoE controls, patients with LyE tended to be nonwhite (p < 0.01), were more commonly tobacco users (p = 0.02) and less likely to have seasonal allergies (p = 0.02). LyE commonly presents with dysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE, whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy.

Comparisons of Fluticasone to Budesonide in the Treatment of Eosinophilic Esophagitis.

PubMed

Albert, Dustin; Heifert, Theresa A; Min, Steve B; Maydonovitch, Corinne L; Baker, Thomas P; Chen, Yen-Ju; Moawad, Fouad J

2016-07-01

Topical steroids are first-line treatment agents for eosinophilic esophagitis; however, some studies have demonstrated modest efficacy in inducing histologic remission. The aim of this study was to determine response to two topical steroids (fluticasone and budesonide), compare their efficacy, and examine patient characteristics which could predict non-response to topical steroids. We performed a retrospective review of an established EoE registry. Inclusion criteria were patients >1 year of age who were diagnosed with EoE as defined by the most recent consensus guidelines. All patients were treated with an 8-week course of either swallowed fluticasone or viscous budesonide. Responders were defined as achieving <15 eosinophils per high-power field (eos/hpf) in both proximal and distal esophageal biopsies. Demographic, clinical, endoscopic, and histologic features were examined. The study cohort included 75 EoE patients with a median age of 33 years (range 2-64 years), 71 % adults, 84 % male, and 76 % Caucasian. Overall histologic response rate to topical steroids was 51 %, while clinical response was 71 %. There was no significant differences in histologic response to treatment between children and adults (68 vs. 44 %, p = 0.111). There was no significant difference in response between males and females (47 vs. 73 %, p = 0.191) and between the two types of steroids (48 vs. 56 %, p = 0.632). Responders and non-responders were similar in clinical presentation and baseline endoscopic findings. Following treatment, responders had significantly less peak proximal (4.0 ± 4.4 vs. 46 ± 53, p < 0.001) and distal eosinophil counts (3.5 ± 3.8 vs. 60 ± 47, p < 0.001) compared to non-responders. There were no predictors of response to steroids identified. Histologic response to treatment was observed in approximately half the cohort, while more than two-thirds experienced clinical response to topical steroids. Response was similar between fluticasone and budesonide. Given the lack of differences in clinical presentation or endoscopic features, predictors of non-response were not seen.

Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis

PubMed Central

Blanchard, Carine; Wang, Ning; Stringer, Keith F.; Mishra, Anil; Fulkerson, Patricia C.; Abonia, J. Pablo; Jameson, Sean C.; Kirby, Cassie; Konikoff, Michael R.; Collins, Margaret H.; Cohen, Mitchell B.; Akers, Rachel; Hogan, Simon P.; Assa’ad, Amal H.; Putnam, Philip E.; Aronow, Bruce J.; Rothenberg, Marc E.

2006-01-01

Eosinophilic esophagitis (EE) is an emerging disorder with a poorly understood pathogenesis. In order to define disease mechanisms, we took an empirical approach analyzing esophageal tissue by a genome-wide microarray expression analysis. EE patients had a striking transcript signature involving 1% of the human genome that was remarkably conserved across sex, age, and allergic status and was distinct from that associated with non-EE chronic esophagitis. Notably, the gene encoding the eosinophil-specific chemoattractant eotaxin-3 (also known as CCL26) was the most highly induced gene in EE patients compared with its expression level in healthy individuals. Esophageal eotaxin-3 mRNA and protein levels strongly correlated with tissue eosinophilia and mastocytosis. Furthermore, a single-nucleotide polymorphism in the human eotaxin-3 gene was associated with disease susceptibility. Finally, mice deficient in the eotaxin receptor (also known as CCR3) were protected from experimental EE. These results implicate eotaxin-3 as a critical effector molecule for EE and provide insight into disease pathogenesis. PMID:16453027

Esophageal stricture - benign

MedlinePlus

Esophageal stricture can be caused by: Gastroesophageal reflux (GERD). Eosinophilic esophagitis. Injuries caused by an endoscope . Long-term use of a nasogastric (NG) tube (tube through the nose into the ...

Prevalence of Eosinophilic Esophagitis and Lymphocytic Esophagitis in Adults with Esophageal Food Bolus Impaction.

PubMed

Truskaite, Kotryna; Dlugosz, Aldona

2016-01-01

Background. The relation of esophageal food bolus impaction (FBI) to eosinophilic esophagitis (EoE) and lymphocytic esophagitis (LyE) is unclear. The aim of this study was to determine the prevalence of EoE and LyE among adults with FBI. Methods. In this retrospective study we analyzed data from all patients referred for gastroscopy during the past 5 years, because of a present or recent episode of FBI. Results. We found 238 patients with FBI (median age 51 (17-96), 71% males). Endoscopic therapy was required in 143 patients. Esophageal biopsies were obtained in 185 (78%) patients. All biopsies were assessed for numbers of eosinophils and lymphocytes. EoE was found in 18% of patients who underwent biopsy. We found 41 patients (22%) who fulfilled the criteria for both EoE and LyE (EoE/LyE). LyE was found in the 9% of patients with FBI. EoE together with EoE/LyE was the leading cause of FBI in patients ≤50 years (64%). GERD was the leading cause of FBI among patients older than 50 years (42%). Conclusions. Our study showed that EoE was the leading cause of FBI in particular among young adults. Our study highlights the need for esophageal biopsies in any patient with FBI.

Esophageal motor disorders in adults with eosinophilic esophagitis.

PubMed

Moawad, Fouad J; Maydonovitch, Corinne L; Veerappan, Ganesh R; Bassett, John T; Lake, Jason M; Wong, Roy K H

2011-05-01

An association between eosinophilic esophagitis (EoE) and esophageal motility disorders has been described in small studies. The aim of this study was to describe the prevalence of esophageal motor disorders in a large cohort of adults with EoE and examine whether an association exists between esophageal dysmotility and dysphagia. A retrospective review of esophageal manometry studies in adult EoE patients was performed. Tracings were reviewed for abnormalities including nutcracker esophagus and ineffective swallows, defined as low amplitude peristalsis (<30 mmHg) or non-propagating contractions. Ineffective esophageal motility (IEM) was categorized as mild (30-40% ineffective swallows), moderate (50-60% ineffective swallows), and severe (≥70% ineffective swallows). Dysphagia was graded on a 0-3 scale for frequency and severity. Seventy-five tracings from EoE patients were reviewed (85% male, mean age 41 ± 12 years). IEM was identified in 25 patients and categorized as mild (n = 13), moderate (n = 6), and severe (n = 6). Nutcracker esophagus was found in three patients. There was no significant difference in eosinophil count among the motility groups: normal 46.5 ± 3.1, mild IEM 56.9 ± 36.9, moderate IEM 45.5 ± 23.7, severe IEM 34.3 ± 12.6 (P = 0.157). In this cohort of EoE patients, the majority had normal esophageal motility studies, although a subset of these patients had some esophageal dysmotility. It is unlikely that esophageal dysmotility is a major contributing factor to dysphagia, although it is reasonable to consider esophageal manometry testing in EoE patients to identify potential abnormalities of the smooth muscle esophagus.

IgE-associated food allergy alters the presentation of paediatric eosinophilic esophagitis.

PubMed

Pelz, B J; Wechsler, J B; Amsden, K; Johnson, K; Singh, A M; Wershil, B K; Kagalwalla, A F; Bryce, P J

2016-11-01

Links between food allergens and eosinophilic esophagitis (EoE) have been established, but the interplay between EoE- and IgE-associated immediate hypersensitivity to foods remains unclear. We sought to determine the prevalence of IgE-associated food allergy at the time of diagnosis of EoE in children and to determine whether differences existed in presentation and disease compared to subjects with EoE alone. Eosinophilic esophagitis patients were stratified based on the diagnosis of IgE-associated immediate hypersensitivity (EoE + IH vs. EoE-IH). Clinical, histologic, pathologic, and endoscopic differences were investigated using a retrospective database. We found that 29% of the 198 EoE patients in our cohort had EoE + IH. These subjects presented at a younger age than those without IH (6.05 vs. 8.09 years, P = 0.013) and were more likely to have comorbid allergic disease. Surprisingly, the EoE + IH group presented with significantly different clinical symptoms, with increased dysphagia, gagging, cough, and poor appetite compared to their counterparts in the EoE-IH group. Male gender, allergic rhinitis, the presence of dysphagia, and younger age were independently associated with having EoE + IH. Specific IgE levels to common EoE-associated foods were higher in EoE + IH, regardless of eliciting immediate hypersensitivity symptoms. In contrast, IgE levels for specific foods triggering EoE were relatively lower in both the groups than IgE levels for immediate reactions. Immediate hypersensitivity is common in children with EoE and identifies a population of EoE patients with distinct clinical characteristics. Our study describes a subtype of EoE in which IgE-mediated food allergy may impact the presentation of paediatric EoE. © 2016 John Wiley & Sons Ltd.

Eosinophilic esophagitis-endoscopic distinguishing findings.

PubMed

Caetano, Ana Célia; Gonçalves, Raquel; Rolanda, Carla

2012-08-21

Eosinophilic esophagitis (EE) is the most frequent condition found in a group of gastrointestinal disorders called eosinophilic gastrointestinal diseases. The hypothetical pathophysiological mechanism is related to a hypersensitivity reaction. Gastroesophageal reflux disease-like complaints not ameliorated by acid blockade or occasional symptoms of dysphagia or food impaction are likely presentations of EE. Due to its unclear pathogenesis and unspecific symptoms, it is difficult to diagnose EE without a strong suspicion. Although histological criteria are necessary to diagnosis EE, there are some characteristic endoscopic features. We present the case of a healthy 55-year-old woman with dysphagia and several episodes of esophageal food impaction over the last six months. This case report stresses the most distinguishing endoscopic findings-mucosa rings, white exudative plaques and linear furrows-that can help in the prompt recognition of this condition.

Diagnosis and treatment of chronic cough in China: an insight into the status quo

PubMed Central

2012-01-01

Chronic cough is a very common complaint in clinics throughout China. Clinical and basic science research on chronic cough started late, but in recent years the effort has yielded promising findings regarding the etiological diagnosis, treatment and pathogenesis. We found that inflammation in nonasthmatic eosinophilic bronchitis has some similarities to cough variant asthma but also a number of distinct differences. Recent evidence has also suggested a mechanistic link between airway neurogenic inflammation and and gastroesophageal reflux cough (GERC). Cough-related animal models have been developed, including models for esophageal reflux, nonasthmatic eosinophilic bronchitis and allergic rhinitis. Normal reference values for differential cell counts in induced sputum, cough sensitivity and esophageal 24-h pH monitoring in Chinese healthy subjects have been established. By using a modified algorithm for the etiological diagnosis of chronic cough, the causes of chronic cough have been investigated across a number of cities in China. The most common causes of chronic cough are cough variant asthma, eosinophilic bronchitis, upper airway cough symptoms, atopic cough and GERC, however, there are some regional variations. The Chinese National Guidelines on Diagnosis and Management of Chronic Cough were drafted in 2005, updated in 2009, and have been widely publicized and disseminated through many channels since their publication. PMID:22839528

Cross-sector sponsorship of research in eosinophilic esophagitis: a collaborative model for rational drug development in rare diseases.

PubMed

Fiorentino, Robert; Liu, Gumei; Pariser, Anne R; Mulberg, Andrew E

2012-09-01

Like many rare diseases, eosinophilic esophagitis (EoE) is a poorly understood disorder, and assessment tools to accurately determine disease activity, remission, and natural history have long been inadequate. Clinical outcome end points able to assess the effectiveness of candidate therapeutic agents in clinical trials have been a particular deficiency and are urgently needed. With no approved therapy available to patients and with the prevalence of EoE on the increase, collaborative approaches to drug development are becoming ever more important. We describe a collaborative effort mobilized across institutions, including both the public and private sectors, that was initiated within the past 18 months expressly to address the need for further clinical research into the cause and treatment of EoE. Collaborators include the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition; the International Gastrointestinal Eosinophilic Researchers; and the US Food and Drug Administration. This effort has resulted in the elucidation of several parameters essential for effective EoE registration trials, including the need for clinically meaningful end points that measure changes in clinical symptoms in addition to the assessment of intraepithelial mucosal eosinophilia. The development and use of biomarkers, particularly in early-phase drug development, have become an important focus for investigations that might reduce clinical reliance on serial invasive monitoring. The concerted efforts described here to develop rational therapeutics and drug development paradigms in EoE also appear to provide a model for effective collaboration in the context of drug development for rare diseases and perhaps more generally for public health initiatives. Published by Mosby, Inc.

Functional heartburn: definition and management strategies.

PubMed

Zerbib, Frank; Bruley des Varannes, Stanislas; Simon, Mireille; Galmiche, Jean Paul

2012-06-01

Functional heartburn (FH) is a functional gastro-intestinal disorder characterized by symptoms of heartburn not related to gastro-esophageal reflux. The absence of evidence of reflux-related symptoms relies on absence of esophagitis at endoscopy (including biopsies to exclude eosinophilic esophagitis), a normal esophageal acid exposure during esophageal pH-monitoring together with a negative symptom-reflux association analysis and an unsatisfactory response to proton pump inhibitor therapy. Addition of impedance measurement to pH-monitoring is likely to increase the number of patients with recognized reflux-related symptoms. The pathophysiology of functional heartburn remains largely unknown but involves disturbed esophageal perception and psychological factors such as depression, anxiety and somatization. The treatment of FH remains largely empirical and an individual approach is therefore recommended. The clinician should provide reassurance and refrain from performing too many invasive tests or therapeutic procedures. The use of pain modulators is recommended by most experts despite the lack of appropriate clinical trials to support it.

High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders

PubMed Central

Abonia, J. Pablo; Wen, Ting; Stucke, Emily M.; Grotjan, Tommie; Griffith, Molly S.; Kemme, Katherine A.; Collins, Margaret H.; Putnam, Philip E.; Franciosi, James P.; von Tiehl, Karl F.; Tinkle, Brad T.; Marsolo, Keith A.; Martin, Lisa J.; Ware, Stephanie M.; Rothenberg, Marc E.

2013-01-01

Background Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease mediated by immune hypersensitization to multiple foods and strongly associated with atopy and esophageal remodeling. Objective We provide clinical and molecular evidence indicating a high prevalence of EoE in patients with inherited connective tissue disorders (CTDs). Methods We examined the rate of EoE among patients with CTDs and subsequently analyzed esophageal mRNA transcript profiles in patients with EoE with or without CTD features. Results We report a cohort of 42 patients with EoE with a CTD-like syndrome, representing 0.8% of patients with CTDs and 1.3% of patients with EoE within our hospital-wide electronic medical record database and our EoE research registry, respectively. An 8-fold risk of EoE in patients with CTDs (relative risk, 8.1; 95% confidence limit, 5.1-12.9; χ21 = 112.0; P < 10−3) was present compared with the general population. Esophageal transcript profiling identified a distinct subset of genes, including COL8A2, in patients with EoE and CTDs. Conclusion There is a remarkable association of EoE with CTDs and evidence for a differential expression of genes involved in connective tissue repair in this cohort. Thus, we propose stratification of patients with EoE and CTDs into a subset referred to as EoE-CTD. PMID:23608731

Management of Esophageal Food Impaction Varies Among Gastroenterologists and Affects Identification of Eosinophilic Esophagitis.

PubMed

Hiremath, Girish; Vaezi, Michael F; Gupta, Sandeep K; Acra, Sari; Dellon, Evan S

2018-06-01

Esophageal food impaction (EFI) is a gastrointestinal emergency requiring immediate evaluation in the emergency room (ER) and an esophagogastroduodenoscopy (EGD) for disimpaction. EFI is also a distinct presenting feature of eosinophilic esophagitis (EoE). This study aimed at understanding the management of EFI among gastroenterologists (GIs) and estimated its impact on identification of EoE in USA. GIs associated with three major gastroenterology societies based in USA were invited to participate in a web-based survey. Information on the resources available and utilized, and the clinical decision-making process related to management of EFI cases was collected and analyzed. Of 428 responses, 49% were from pediatric GIs, 86% practiced in the USA, and 78% practiced in an academic setting. Compared to the pediatric GIs, adult GIs were more likely to perform EGD in the emergency room [OR 87.96 (25.43-304.16)] and advance the food bolus into stomach [5.58 (3.08-10.12)]. Only 34% of respondents obtained esophageal biopsies during EGD, and pediatric GIs were more likely to obtain esophageal biopsies [3.49 (1.12-10.84)] compared to adult GIs. In USA, by our conservative estimates, 10,494 patients presenting to ER with EFI and at risk of EoE are likely being missed each year. EFI management varies substantially among GIs associated with three major gastroenterology societies in USA. Based on their practice patterns, the GIs in USA are likely to miss numerous EoE patients presenting to ER with EFI. Our findings highlight the need for developing and disseminating evidence-based EFI management practice guidelines.

Functional Esophageal Disorders.

PubMed

Aziz, Qasim; Fass, Ronnie; Gyawali, C Prakash; Miwa, Hiroto; Pandolfino, John E; Zerbib, Frank

2016-02-15

Functional esophageal disorders consist of a disease category that present with esophageal symptoms (heartburn, chest pain, dysphagia, globus) not explained by mechanical obstruction (stricture, tumor, eosinophilic esophagitis), major motor disorders (achalasia, EGJ outflow obstruction, absent contractility, distal esophageal spasm, jackhammer esophagus), or gastroesophageal reflux disease (GERD). While mechanisms responsible are unclear, it is theorized that visceral hypersensitivity and hypervigilance play an important role in symptom generation, in the context of normal or borderline function. Treatments directed at improving borderline motor dysfunction or reducing reflux burden to sub-normal levels have limited success in symptom improvement. In contrast, strategies focused on modulating peripheral triggering and central perception are mechanistically viable and clinically meaningful. However, outcome data from these treatment options are limited. Future research needs to focus on understanding mechanisms underlying visceral hypersensitivity and hypervigilance so that appropriate targets and therapies can be developed. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Proton pump inhibitor-responsive esophageal eosinophilia: a historical perspective on a novel and evolving entity.

PubMed

Molina-Infante, Javier; Katzka, David A; Dellon, Evan S

2015-01-01

Eosinophilic esophagitis (EoE) is an emerging chronic esophageal disease, first described in 1993, with a steadily increasing incidence and prevalence in western countries. Over the 80's and early 90's, dense esophageal eosinophilia was mostly associated gastroesophageal reflux disease (GERD). For the next 15 years, EoE and GERD were rigidly considered separate entities: Esophageal eosinophilia with pathological acid exposure on pH monitoring or response to proton pump inhibitor (PPI) therapy was GERD, whereas normal pH monitoring or absence of response to PPIs was EoE. Updated guidelines in 2011 described a novel phenotype, proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE), referring to patients who appear to have EoE clinically, but who achieve complete remission after PPI therapy. Currently, PPI-REE must be formally excluded before diagnosing EoE, since 30-40% of patients with suspected EoE are eventually diagnosed with PPI-REE.Interestingly, PPI-REE and EoE remain undistinguishable based on clinical, endoscopic, and histological findings, pH monitoring, and measurement of tissue markers and cytokines related to eosinophilic inflammation.This review article aims to revisit the relatively novel concept of PPI-REE from a historical perspective, given the strong belief that only GERD, as an acid peptic disorder, could respond to the acid suppressing ability of PPI therapy, is becoming outdated. Evolving evidence suggests that PPI-REE is genetically and phenotypically undistinguishable from EoE and PPI therapy alone can almost completely reverse allergic inflammation. As such, PPI-REE might constitute a subphenotype of EoE and PPI therapy may be the first therapeutic step and diet/ steroids may represent step up therapy. Possibly, the term PPI-REE will be soon replaced by PPI-responsive EoE. The mechanism as to why some patients respond to PPI therapy (PPI-REE) while others do not (EoE), remains to be elucidated.

Eosinophilic esophagitis: A relevant entity for the otolaryngologist.

PubMed

Górriz-Gil, Carmen; Villarreal, Ithzel M; Álvarez-Montero, Óscar; Rodríguez-Valiente, Antonio; Magaz, Marta; García-Berrocal, José R

2016-01-01

Eosinophilic esophagitis (EE) is a recently recognised pathologic entity whose prevalence has risen significantly since it was first described. Its diagnosis represents a challenge for different medical specialties, among which ENT specialists play an important role. Clinical suspicion in a patient with recurrent food impaction or a child with eating disorders and history of hypersensitivity constitutes the first warning sign of a possible EE. The purpose of this review is to highlight EE as a possible differential diagnosis in patients with deglutition disorders and describe the possible clinical symptoms that should alert the ENT specialist to perform appropriate diagnostic tests and procedures. The transnasal esophagoscopy, performed in-office by the ENT, is ideal for reducing possible underdiagnosed cases. Given the fact that an ENT specialist will evaluate a great many patients with deglutition disorders, it is paramount for possible EE cases to be suspected and recognised so that a correct multidisciplinary approach involving not only ENT specialists but also paediatricians, gastroenterologists, allergologists and pathologists can be established. Identifying the dietary component responsible for the esophageal inflammation and removing that food from the patient's diet is the key in the treatment of this immune-mediated disease. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Esophagitis

MedlinePlus

... which irritates the tissue. This problem is called gastroesophageal reflux (GERD). An autoimmune disorder called eosinophilic esophagitis also causes ... Barrett esophagus (BE) can develop after years of GERD. Rarely, BE may lead to cancer of the ...

Eosinophilic esophagitis in children needing emergency endoscopy for foreign body and food bolus impaction.

PubMed

El-Matary, Wael; El-Hakim, Hamdy; Popel, Jillian

2012-07-01

The objective of this study was to examine the prevalence of eosinophilic esophagitis (EoE) in children presenting with esophageal foreign body (FB)/food bolus impaction. A retrospective chart review for all children who underwent endoscopic esophageal FB extraction at the Stollery Children's Hospital between January 2005 and December 2008 was performed. The prevalence of EoE and characteristics of children who had EoE were documented. A total of 140 children (mean age, 4.98 [SD, 4] years; range, 0.3-16.9 years; 81 boys) had esophageal FB/food impaction and needed endoscopic removal over the study period. Eleven children (mean age, 9.38 [SD, 5.35] years; range, 1.9-16.2 years; 8 boys) were diagnosed with EoE (8%). Seven (39%) of 18 children with food impaction were diagnosed with EoE. Four (3%) of 122 children with esophageal foreign bodies other than food had EoE. Considerable number of children with esophageal FB/food bolus impaction may have EoE. Routine sampling of esophageal mucosa at different levels during esophageal FB extraction may be considered. Well-designed prospective studies with multiple-level esophageal biopsies taken from all children with FB/food impaction are needed to confirm our results.

Eosinophilic esophagitis in patients with esophageal atresia and chronic dysphagia.

PubMed

Kassabian, Sirvart; Baez-Socorro, Virginia; Sferra, Thomas; Garcia, Reinaldo

2014-12-21

Esophageal atresia (EA) is defined as a discontinuity of the lumen of the esophagus repaired soon after birth. Dysphagia is a common symptom in these patients, usually related to stricture, dysmotility or peptic esophagitis. We present 4 cases of patients with EA who complained of dysphagia and the diagnosis of Eosinophilic esophagitis (EoE) was made, ages ranging from 9 to 16 years. Although our patients were on acid suppression years after their EA repair, they presented with acute worsening of dysphagia. Esophogastroduodenoscopy and/or barium swallow did not show stricture and biopsies revealed elevated eosinophil counts consistent with EoE. Two of 4 patients improved symptomatically with the topical steroids. It is important to note that all our patients have asthma and 3 out of 4 have tested positive for food allergies. One of our patients developed recurrent anastomotic strictures that improved with the treatment of the EoE. A previous case report linked the recurrence of esophageal strictures in patients with EA repair with EoE. Once the EoE was treated the strictures resolved. On the other hand, based on our observation, EoE could be present in patients without recurrent anastomotic strictures. There appears to be a spectrum in the disease process. We are suggesting that EoE is a frequent concomitant problem in patients with history of congenital esophageal deformities, and for this reason any of these patients with refractory reflux symptoms or dysphagia (with or without anastomotic stricture) may benefit from an endoscopic evaluation with biopsies to rule out EoE.

Empiric 6-food elimination diet induced and maintained prolonged remission in patients with adult eosinophilic esophagitis: a prospective study on the food cause of the disease.

PubMed

Lucendo, Alfredo J; Arias, Ángel; González-Cervera, Jesús; Yagüe-Compadre, José Luis; Guagnozzi, Danila; Angueira, Teresa; Jiménez-Contreras, Susana; González-Castillo, Sonia; Rodríguez-Domíngez, Benito; De Rezende, Livia C; Tenias, José M

2013-03-01

Although empiric exclusion from the diet of the 6 food groups most likely to trigger allergies achieves eosinophilic esophagitis (EoE) remission in children, data on its prolonged efficacy and effects on adults are lacking. We sought to evaluate the efficacy of a 6-food elimination diet in inducing and maintaining prolonged remission in patients with adult EoE. Sixty-seven consecutive patients with adult EoE were prospectively recruited and treated exclusively with a diet avoiding cereals, milk, eggs, fish/seafood, legumes/peanuts, and soy for 6 weeks. Subsequent challenge was undertaken by sequentially reintroducing all excluded single foods, followed by endoscopy and biopsies, which were developed every 6 weeks in case of response (eosinophil peak count reduction to <15/high-power field [hpf]). A food was considered a trigger for EoE and removed from the diet if pathologic eosinophilic infiltration (≥15 eosinophils/hpf) reappeared. Food-specific serum IgE measurements and skin prick tests were performed before initiating the diet. Forty-nine (73.1%) patients exhibited significantly reduced eosinophil peak counts (<15 eosinophils/hpf) before sequential single-food reintroduction. A single offending food antigen was identified in 35.71% of patients, 2 food triggers were identified in 30.95%, and 3 or more food triggers were identified in 33.3%. Cow's milk was the most common food antigen (61.9%), followed by wheat (28.6%), eggs (26.2%), and legumes (23.8%). Prior allergy tests showed no concordance with food-reintroduction challenge results. All patients who continued to avoid the offending foods maintained histopathologic and clinical EoE remission for up to 3 years. An empiric 6-food elimination diet effectively induced remission of active adult EoE, which was maintained for up to 3 years with individually tailored, limited exclusion diets. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Topical Steroid Therapy for the Treatment of Eosinophilic Esophagitis (EoE): A Systematic Review and Meta-Analysis

PubMed Central

Chuang, Ming-yu (Anthony); Chinnaratha, Mohamed A; Hancock, David G; Woodman, Richard; Wong, Geoffrey R; Cock, Charles; Fraser, Robert JL

2015-01-01

OBJECTIVES: Current guidelines recommend topical steroids as first-line treatment for patients with eosinophilic esophagitis (EoE). However, the evidence for this approach has been inconsistent in earlier reports. This meta-analysis aimed to clarify the efficacy of topical steroid treatment in active EoE using updated evidence. METHODS: CENTRAL, MEDLINE and EMBASE databases were searched for randomized controlled trials (RCTs) published up to May 2014 that compared topical steroids with control treatments for active EoE. Study bias was assessed using the Cochrane Collaboration Tool, and outcomes were pooled using random effects models. The primary outcome was the mean change in eosinophil counts. Secondary outcomes were symptom responses and adverse events. RESULTS: In total, seven RCTs (226 patients) were included. Topical steroids were associated with a significant reduction in esophageal mucosal eosinophil counts compared with control therapy although substantial heterogeneity between studies was observed (weighted mean difference (WMD) −27.2, 95% confidence interval (CI) −45.3 to −9.1, I2=56.2%). Subgroup analysis indicated the reduction in eosinophil counts was only present in studies where a proton pump inhibitor (PPI) trial was used to exclude other diagnoses (WMD −46.3, 95% CI −61.3 to −31.4, I2=0.0%). Subdivision of studies on the use of a PPI trial also accounted for the majority of heterogeneity among RCTs. No clear trends in symptom resolution were observed. Eleven out of 127 patients who received topical steroids developed asymptomatic esophageal candidiasis. CONCLUSIONS: These data provide updated high-quality evidence that support current guidelines for first-line EoE treatment with topical steroids after an initial PPI trial to exclude non-EoE pathologies (PROSPERO ID: CRD42014008828). PMID:25809314

Esophageal motor abnormalities in eosinophilic esophagitis identified by high-resolution manometry.

PubMed

Martín Martín, Leticia; Santander, Cecilio; Lopez Martín, Mari Carmen; Espinoza-Ríos, Jorge; Chavarría-Herbozo, Carlos; Gisbert, Javier P; Moreno-Otero, Ricardo

2011-09-01

Esophageal motility abnormalities, as measured by conventional manometry (CM), are non-specific in the majority of patients with eosinophilic esophagitis (EoE). Moreover, the study of CM is limited by poor interobserver agreement. The aims of the present study were: (i) to assess the esophageal patterns in EoE by a topographic analysis of high-resolution manometry (HRM) data; and (ii) to establish a relationship between motility abnormalities and symptoms of EoE, such as dysphagia and bolus impaction. All adult patients with EoE diagnosed according to histological criteria, and controls with gastroesophageal reflux disease symptoms and dysphagia, were included. HRM was done in EoE patients and controls. For the analysis of data, the Chicago classification was followed. HRM was performed in 21 patients with EoE, as well as in 21 controls. Of the 21 patients with EoE, 10 (48%) showed pan-esophageal pressurization, six (28%) showed peristaltic dysfunction, and in five cases (24%), HRM was normal. There was no pan-esophageal pressurization in controls. Nine of 10 patients with pan-esophageal pressurization required endoscopic bolus removal (P < 0.05); none had obstructive endoscopy findings. The most frequent esophageal motor abnormality measured by HRM was a pan-esophageal pressurization. Bolus impaction in patients with EoE was associated with pan-esophageal pressurization. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Etiology of esophageal food impactions in children.

PubMed

Hurtado, Christine Waasdorp; Furuta, Glenn T; Kramer, Robert E

2011-01-01

The aim of the study was to measure clinicopathological features of children presenting to a tertiary care emergency department with esophageal food impaction. A retrospective chart review of children with esophageal food impaction seen between January 1, 2005 and June 30, 2009, including all patients from age 1 month to 18 years with esophageal food impaction at a pediatric emergency department, was performed. Initial screening of International Classification of Disease, 9th Revision, discharge diagnosis identified 698 children with an esophageal foreign body. Of this group, 72 esophageal food impaction events were identified in 65 children (69% boys), 49 of whom required endoscopic intervention. Endoscopic appearances of the esophageal mucosa were abnormal in 40 (82%), revealing evidence of esophagitis (55%) or stricture (27%). Twenty-four of the subjects had biopsies taken at the time of endoscopy. Inflammation, described as increased eosinophils, basilar hyperplasia, rete peg elongation, and/or microabscess, was present in 76% of mucosal samples. Follow-up endoscopy in 12 children identified an etiology in 9, five of whom were found to have eosinophilic esophagitis. The majority of children with esophageal food impaction who underwent endoscopic evaluation and biopsy have an underlying potentially treatable cause. We therefore recommend that all of the children with esophageal food impaction have mucosal biopsies at the time of endoscopic disimpaction with appropriate follow-up to allow for diagnosis and management of the underlying etiology.

Quality assessment of clinical practice guidelines for eosinophilic esophagitis using the AGREE II instrument.

PubMed

Lucendo, Alfredo J; Arias, Ángel; Redondo-González, Olga; Molina-Infante, Javier

2017-04-01

High-quality evidence-based clinical practice guidelines can guide diagnosis and treatment to optimize outcomes. We aimed to systematically review the quality of international guidelines on eosinophilic esophagitis (EoE). MEDLINE and Scopus databases were searched for appropriate guidelines up to 2016. Two gastroenterologists and two methodologists independently evaluated the documents using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Amongst the 25 records initially retrieved, four guidelines developed by recognized scientific organizations met inclusion criteria. AGREE II results varied widely across domains, but none achieved an overall assessment score of over 60%. Scope and purpose (61.82 ± 19.24%), clarity of presentation (57.13 ± 40.56%) and editorial independence (93.75 ± 1.69%) showed the highest mean rating, whereas stakeholder involvement (28.82 ± 11.19%), rigor of development (32.29 ± 12.02%) and applicability (21.62 ± 7.14%) did not reach quality thresholds. Intraclass correlation coefficients for agreement was excellent among appraisers (0.903), between gastroenterologists and methodologists (0.878) and for each individual guideline (0.838 to 0.955). Clinical practice guidelines for EoE vary significantly in quality, are invariably limited and currently, none can be 'strongly recommended'.

Causes and Outcomes of Esophageal Perforation in Eosinophilic Esophagitis.

PubMed

Runge, Thomas M; Eluri, Swathi; Cotton, Cary C; Burk, Caitlin M; Woosley, John T; Shaheen, Nicholas J; Dellon, Evan S

2017-10-01

To characterize patients who suffer perforation in the context of eosinophilic esophagitis (EoE) and to identify predictors of perforation. Esophageal perforation is a serious complication of EoE. We conducted a retrospective cohort study of the University of North Carolina EoE clinicopathologic database from 2001 to 2014. Subjects were included if they had an incident diagnosis of EoE and met consensus guidelines, including nonresponse to a PPI trial. Patients with EoE who had suffered perforation at any point during their course were identified, and compared with EoE cases without perforation. Multiple logistic regression was performed to determine predictors of perforation. Out of 511 subjects with EoE, 10 (2.0%) had experienced an esophageal perforation. Although those who perforated tended to have a longer duration of symptoms before diagnosis (11.4 vs. 7.0 y, P=0.13), a history of food impaction (odds ratio, 14.9; 95% confidence interval, 1.7-129.2) and the presence of a focal stricture (odds ratio, 4.6; 95% confidence interval, 1.1-19.7) were the only factors independently associated with perforation. Most perforations (80%) occurred after a prolonged food bolus impaction, and only half of individuals (5/10) carried a diagnosis of EoE at the time of perforation; none occurred after dilation. Six patients (60%) were treated with nonoperative management, and 4 (40%) required surgical repair. Esophageal perforation is a rare but serious complication of eosinophilic esophagitis, occurring in ∼2% of cases. Most episodes are due to food bolus impaction or strictures, suggesting that patients with fibrostenotic disease due to longer duration of symptoms are at increased risk.

Efficacy of Atopy Patch Testing in Directed Dietary Therapy of Eosinophilic Esophagitis: A Pilot Study.

PubMed

Eckmann, Jason D; Ravi, Karthik; Katzka, David A; Davis, Dawn R; See, Jacalyn A; Geno, Debra R; Kryzer, Lori A; Alexander, Jeffrey A

2018-03-01

Atopy patch testing (APT) has shown potential for predicting dietary food triggers in studies of children and adolescents with eosinophilic esophagitis (EoE). To assess the efficacy of APT in adults with EoE. We conducted a prospective open-label pilot study of patients ≥ 18 years old with diagnosis of EoE at Mayo Clinic in Rochester, Minnesota, from November 2014 to January 2016. All patients underwent patch testing using intact food products, followed by a six food elimination diet and stepwise food reintroduction. Response to elimination diet was assessed with serial endoscopy with biopsies as well as clinical symptoms. APT results were directly compared to elimination diet results for assessment of efficacy. Correlation between clinical symptoms, endoscopic score, and histology was also qualitatively evaluated. Fifty percent of the patients had a positive APT, while only 16% had an APT result confirmed histologically during food reintroduction. Sensitivity of APT was calculated to be 5.9%, with specificity of 92.0%. Furthermore, we found significant qualitative inter-patient heterogeneity in the correlation between clinical symptoms, EREFS score, and histology. APT does not reliably predict food triggers identified by food elimination diet in adult patients with EoE. As a result, APT does not have a clear role in the evaluation of patients with EoE.

Cyclophilin D regulates necrosis, but not apoptosis, of murine eosinophils.

PubMed

Zhu, Xiang; Hogan, Simon P; Molkentin, Jeffery D; Zimmermann, Nives

2016-04-15

Eosinophil degranulation and clusters of free extracellular granules are frequently observed in diverse diseases, including atopic dermatitis, nasal polyposis, and eosinophilic esophagitis. Whether these intact granules are released by necrosis or a biochemically mediated cytolysis remains unknown. Recently, a peptidyl-prolyl isomerase located within the mitochondrial matrix, cyclophilin D (PPIF), was shown to regulate necrotic, but not apoptotic, cell death in vitro in fibroblasts, hepatocytes, and cardiomyocytes. Whether cyclophilin D regulates necrosis in hematopoietic cells such as eosinophils remains unknown. We used PPIF-deficient (Ppif(-/-)) mice to test whether cyclophilin D is required for regulating eosinophil necrosis. PPIF deficiency did not affect eosinophil development or maturation at baseline. After in vitro ionomycin or H2O2 treatment, Ppif(-/-) eosinophils were significantly protected from Ca(2+) overload- or oxidative stress-induced necrosis. Additionally, Ppif(-/-) eosinophils demonstrated significantly decreased necrosis, but not apoptosis, in response to Siglec-F cross-linking, a stimulus associated with eosinophil-mediated processes in vitro and in vivo. When treated with apoptosis inducers, Ppif(+/+) and Ppif(-/-) eosinophils exhibited no significant difference in apoptosis or secondary necrosis. Finally, in a dextran sodium sulfate-induced colitis model, although levels of colitogenic cytokines and eosinophil-selective chemokines were comparable between Ppif(+/+) and Ppif(-/-) mice, the latter exhibited decreased clinical outcomes. This correlated with significantly reduced eosinophil cytolysis in the colon. Collectively, our present studies demonstrate that murine eosinophil necrosis is regulated in vitro and in vivo by cyclophilin D, at least in part, thus providing new insight into the mechanism of eosinophil necrosis and release of free extracellular granules in eosinophil-associated diseases. Copyright © 2016 the American Physiological Society.

Airborne and food sensitization patterns in children and adults with eosinophilic esophagitis.

PubMed

He, Yu Ting; Christos, Paul J; Reisacher, William R

2018-05-01

The pathogenesis of eosinophilic esophagitis (EoE) is currently unknown, but evidence suggests that allergic sensitization to food and airborne allergens may play a key role. This retrospective study examines the rate of sensitization to both food and airborne allergens in EoE patients, and compares their sensitivity patterns to control groups. We identified 103 patients with a diagnosis of EoE via esophageal eosinophilia (≥15 eosinophils/high-power field [hpf]), who had undergone comprehensive food and/or airborne allergen testing through either skin or in vitro methods. Food and airborne allergen sensitization was defined as positive testing in at least 1 food subgroup (milk, peanut, tree nut, seafood/fish, soy, grain, egg) or airborne subgroup (tree, grass, weed, mite/cockroach, animal, mold), respectively. The same sensitization criterion was applied to allergic rhinitis (AR) patients, with and without a clinical suspicion of food allergy (FA), in order to create control groups. Sensitization in the EoE group to at least 1 subgroup of food allergen and airborne allergen was seen in 77.1% (64/83) and 71.7% (38/53), respectively (p = 0.82). There were significant differences in sensitization between EoE and control groups for tree nut, soy, grain, and egg, but no differences noted in any of the other food or airborne allergen subgroups, even after accounting for age and gender. EoE and control groups had similar airborne allergen sensitization patterns, yet dissimilar food allergen sensitization patterns, suggesting that specific allergens may play a more prominent role in the pathogenesis of EoE. The EoE group had a more uniform distribution pattern for food allergens, compared to controls. © 2018 ARS-AAOA, LLC.

[Eosinophilic esophagitis, a pathology on the rise].

PubMed

Miranda García, M; Gutiérrez Teira, B

2013-10-01

The eosinophilic esofagitis is a pathology that consists of an inflammatory condition of the esophagus, which is characterized for having a high percentage of eosinophils. It is a problem of allergic origin and his diagnosis is increasing in the population, especially in children and adult young persons, throughout last decade. The fisiopathology is not completely established nowadays. The diagnosis is confirmed with endoscopia and capture of biopsies. The differential diagnosis is necessary to be done with the disease for reflux gastroesofágico, gastroenteritis eosinofílica, by Crohn's disease, pathology of connective fabric, syndrome hipereosinofílico, infections and response of hypersensitivity to medicaments. Nowadays there is no a treatment that is definitive. We present a clinical case, which was valued initially for the consultation of Primary care. Copyright © 2011 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

How to improve the diagnosis of eosinophilic esophagitis: Experience from a case series in Mexico.

PubMed

Soto-Solís, R; Santana-de Anda, K; González-Uribe, N; Gallegos, C; Romo-Aguirre, C; Remes-Troche, J M; Ballesteros-Amozurrutia, M A

Eosinophilic esophagitis (EoE) is a chronic, immune disorder mediated largely by food antigens. It shares nonspecific symptoms with gastroesophageal reflux disease (GERD). EoE is rarely reported in Mexico, perhaps due to the racial characteristics of the population or because of insufficient diagnostic suspicion. Our aim was to describe a Mexican cohort with EoE and evaluate the usefulness of the clinical history and endoscopy in the EoE diagnosis, in comparison with GERD patients. A retrospective study was carried out on the clinical characteristics and endoscopic and histopathologic findings in patients with EoE, along with a case-control study on patients with GERD. The endoscopic images obtained were interpreted in a blind and randomized manner by 4 gastroenterologists, before and after providing them with information on the characteristic alterations of EoE. The esophageal biopsies were also blinded to 2 pathologists that evaluated their diagnostic correlation. The Fisher's exact test and Mann-Whitney U test were used in the statistical analysis. Fourteen patients with EoE were included in the study. Ten (71%) of them were men and the mean age of the patients was 35 years. There were more subjects with a personal history of asthma (p=0.0023) and food impaction (p=0.04) in the EoE group. The initial evaluation of the endoscopic findings showed 53% correct EoE interpretations and rose to 96% in the second revision (sensitivity 100%, specificity 71%, PPV 65%, NPV 100%). Mexican patients with EoE have similar characteristics to those of patients in western case series. Clinical awareness of the disorder increases endoscopic diagnosis in up to 40% of cases. Copyright © 2016 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Low Prevalence of Biopsy-Proven Eosinophilic Esophagitis in Patients with Esophageal Food Impaction in Mexican Population.

PubMed

García-Compeán, Diego; González-González, José A; Duran-Castro, José J; Herrera-Quiñones, Gilberto; Borjas-Almaguer, Omar D; Maldonado-Garza, Héctor J

2018-06-01

Eosinophilic esophagitis (EoE) is the most common cause of dysphagia and esophageal food impaction (EFI) in the USA, Western Europe, and Australia. In Mexico, the uncomplicated form of this disease is infrequent, and prevalence in patients with EFI is unknown. To determine the prevalence and causes of EFI, endoscopic and therapeutic aspects, and establish the prevalence of biopsy-proven EoE in patients with EFI. Diagnostic upper gastrointestinal endoscopy reports from January 2011 to December 2016 were retrospectively reviewed. Patients with therapeutic procedures, gastrointestinal hemorrhage, or non-food foreign body impaction were excluded. The number of patients with EFI was determined. Additionally, patients with esophageal biopsy were retained for EoE prevalence calculation. The diagnosis of EoE was defined with the presence of eosinophil infiltration count ≥ 15/high-power field with or without typical endoscopic abnormalities. A total of 4700 reports of the same number of patients were selected; 2209 were males (47%) with a mean age of 57.6 ± 12.3 years (range 14-93). We identified 36 patients with EFI (0.76, 95% CI 0.51-1.01), 16 males (44.4%) with a mean age of 54.9 ± 19.7 (range 22-92). Esophageal biopsies were obtained in 17/36 (47.2%) cases. The diagnosis of EoE was confirmed in 2 patients (11.7%). Peptic stenosis was the most frequent cause of EFI. EoE is an infrequent cause of EFI in the Mexican population (11.7%). EoE had the lowest prevalence compared to that reported in Caucasian populations. The prevalence of EFI was also low.

TSLP-elicited basophil responses can mediate the pathogenesis of eosinophilic esophagitis

PubMed Central

Noti, Mario; Tait Wojno, Elia D.; Kim, Brian S.; Siracusa, Mark C.; Giacomin, Paul R.; Nair, Meera G.; Benitez, Alain J.; Ruymann, Kathryn R.; Muir, Amanda B.; Hill, David A.; Chikwava, Kudakwashe R.; Moghaddam, Amin E.; Sattentau, Quentin J.; Alex, Aneesh; Zhou, Chao; Yearley, Jennifer H.; Menard-Katcher, Paul; Kubo, Masato; Obata-Ninomiya, Kazushige; Karasuyama, Hajime; Comeau, Michael R.; Brown-Whitehorn, Terri; de Waal Malefyt, Rene; Sleiman, Patrick M.; Hakonarson, Hakon; Cianferoni, Antonella; Falk, Gary W.; Wang, Mei-Lun; Spergel, Jonathan M.; Artis, David

2014-01-01

Eosinophilic esophagitis (EoE) is a food allergy-associated inflammatory disease characterized by esophageal eosinophilia. EoE has become increasingly common, but current management strategies are nonspecific. Thus, there is an urgent need to identify specific immunological pathways that could be targeted to treat this disease. EoE is associated with polymorphisms in the gene that encodes thymic stromal lymphopoietin (TSLP), a cytokine that promotes allergic inflammation, but how TSLP might contribute to EoE disease pathogenesis remains unknown. Here, we describe a new mouse model of EoE-like disease that developed independently of IgE but was dependent on TSLP-elicited basophils. Therapeutic TSLP neutralization or basophil depletion also ameliorated established EoE-like disease. Critically, in human subjects with EoE, we observed elevated TSLP levels and exaggerated basophil responses in esophageal biopsies, and a gain-of-function TSLP polymorphism was associated with increased basophil responses. Together, these data suggest that the TSLP-basophil axis could be therapeutically targeted to treat EoE. PMID:23872715

Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults.

PubMed

Lucendo, Alfredo J; Molina-Infante, Javier; Arias, Ángel; von Arnim, Ulrike; Bredenoord, Albert J; Bussmann, Christian; Amil Dias, Jorge; Bove, Mogens; González-Cervera, Jesús; Larsson, Helen; Miehlke, Stephan; Papadopoulou, Alexandra; Rodríguez-Sánchez, Joaquín; Ravelli, Alberto; Ronkainen, Jukka; Santander, Cecilio; Schoepfer, Alain M; Storr, Martin A; Terreehorst, Ingrid; Straumann, Alex; Attwood, Stephen E

2017-04-01

Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE. General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes. The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice. Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients' follow up are proposed in the guideline.

Allergen-induced resistin-like molecule-α promotes esophageal epithelial cell hyperplasia in eosinophilic esophagitis

PubMed Central

Mavi, Parm; Niranjan, Rituraj; Dutt, Parmesh; Zaidi, Asifa; Shukla, Jai Shankar; Korfhagen, Thomas

2014-01-01

Resistin-like molecule (Relm)-α is a secreted, cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-β, and Relm-γ. Although resistin was initially defined based on its insulin-resistance activity, the family members are highly induced in various inflammatory states. Earlier studies implicated Relm-α in insulin resistance, asthmatic responses, and intestinal inflammation; however, its function still remains an enigma. We now report that Relm-α is strongly induced in the esophagus in an allergen-challenged murine model of eosinophilic esophagitis (EoE). Furthermore, to understand the in vivo role of Relm-α, we generated Relm-α gene-inducible bitransgenic mice by using lung-specific CC-10 promoter (CC10-rtTA-Relm-α). We found Relm-α protein is significantly induced in the esophagus of CC10-rtTA-Relm-α bitransgenic mice exposed to doxycycline food. The most prominent effect observed by the induction of Relm-α is epithelial cell hyperplasia, basal layer thickness, accumulation of activated CD4+ and CD4− T cell subsets, and eosinophilic inflammation in the esophagus. The in vitro experiments further confirm that Relm-α promotes primary epithelial cell proliferation but has no chemotactic activity for eosinophils. Taken together, our studies report for the first time that Relm-α induction in the esophagus has a major role in promoting epithelial cell hyperplasia and basal layer thickness, and the accumulation of activated CD4+ and CD4− T cell subsets may be responsible for partial esophageal eosinophilia in the mouse models of EoE. Notably, the epithelial cell hyperplasia and basal layer thickness are the characteristic features commonly observed in human EoE. PMID:24994859

Allergen-induced resistin-like molecule-α promotes esophageal epithelial cell hyperplasia in eosinophilic esophagitis.

PubMed

Mavi, Parm; Niranjan, Rituraj; Dutt, Parmesh; Zaidi, Asifa; Shukla, Jai Shankar; Korfhagen, Thomas; Mishra, Anil

2014-09-01

Resistin-like molecule (Relm)-α is a secreted, cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-β, and Relm-γ. Although resistin was initially defined based on its insulin-resistance activity, the family members are highly induced in various inflammatory states. Earlier studies implicated Relm-α in insulin resistance, asthmatic responses, and intestinal inflammation; however, its function still remains an enigma. We now report that Relm-α is strongly induced in the esophagus in an allergen-challenged murine model of eosinophilic esophagitis (EoE). Furthermore, to understand the in vivo role of Relm-α, we generated Relm-α gene-inducible bitransgenic mice by using lung-specific CC-10 promoter (CC10-rtTA-Relm-α). We found Relm-α protein is significantly induced in the esophagus of CC10-rtTA-Relm-α bitransgenic mice exposed to doxycycline food. The most prominent effect observed by the induction of Relm-α is epithelial cell hyperplasia, basal layer thickness, accumulation of activated CD4(+) and CD4(-) T cell subsets, and eosinophilic inflammation in the esophagus. The in vitro experiments further confirm that Relm-α promotes primary epithelial cell proliferation but has no chemotactic activity for eosinophils. Taken together, our studies report for the first time that Relm-α induction in the esophagus has a major role in promoting epithelial cell hyperplasia and basal layer thickness, and the accumulation of activated CD4(+) and CD4(-) T cell subsets may be responsible for partial esophageal eosinophilia in the mouse models of EoE. Notably, the epithelial cell hyperplasia and basal layer thickness are the characteristic features commonly observed in human EoE. Copyright © 2014 the American Physiological Society.

Comparison of 2 delivery vehicles for viscous budesonide to treat eosinophilic esophagitis in children.

PubMed

Rubinstein, Eitan; Lee, John J; Fried, Ari; Logvinenko, Tanya; Ngo, Peter; McDonald, Douglas; Hait, Elizabeth J

2014-09-01

Oral viscous budesonide (OVB) using Splenda as a delivery vehicle has become an attractive therapeutic option for children with eosinophilic esophagitis (EoE). Many families are wary of giving the artificial sweetener in high doses to their children. The aim of the present study was to determine whether OVB mixed with Neocate Nutra, a hypoallergenic nutritional supplement, is at least as efficacious as OVB mixed with Splenda at healing EoE. Our institutional review board approved a retrospective chart review of patients with well-documented EoE treated with OVB at the Boston Children's Hospital Eosinophilic Gastrointestinal Disorder program between June 2008 and June 2013. Primary outcome measured was histologic response defined as change in peak eosinophil count to <15 eosinophils per high-power field (eos/HPF) after at least 10 weeks of OVB therapy. A total of 46 children were treated with OVB mixed with Splenda, and 14 were treated with OVB mixed with Neocate Nutra. The 2 groups were not significantly different in their demographic (race, age, sex) or clinical (initial eosinophil count, proton pump inhibitor use, or concomitant dietary elimination) characteristics. On follow-up endoscopy, 30 of 46 patients on Splenda and 13 of 14 patients on Neocate Nutra achieved histologic response. Mean pretreatment and posttreatment peak eosinophil counts for the children taking Neocate Nutra were 62 eos/HPF ([high-power field] range 20-120 eos/HPF) and 9 eos/HPF (range 0-100 eos/HPF), respectively. Mean pretreatment and posttreatment peak eosinophil counts for the Splenda group were 59.5 eos/HPF (range 20-180 eos/HPF) and 25.5 eos/HPF (range 0-200 eos/HPF), respectively. The odds ratio (OR) of success with Neocate Nutra as compared with Splenda was 6.93 (95% CI 0.83-57.91, P = 0.0728), demonstrating the noninferiority of Neocate Nutra. We demonstrate that OVB mixed with Neocate Nutra is at least as effective as OVB mixed with Splenda at treating children with EoE. Neocate Nutra is an innovative, effective, and palatable mixing agent to create a viscous budesonide slurry for families who prefer not to use the standard recipe with Splenda.

Elimination diets in the management of eosinophilic esophagitis.

PubMed

Wechsler, Joshua B; Schwartz, Sally; Amsden, Katie; Kagalwalla, Amir F

2014-01-01

Eosinophilic esophagitis, an increasingly recognized chronic inflammatory disorder isolated to the esophagus, is triggered by an abnormal allergic response to dietary antigens. Current treatment includes swallowed topical steroids and dietary modification, which aim to resolve symptoms and prevent long-term complications such as formation of strictures. The dietary approach has become more widely accepted because long-term steroid therapy is associated with potential risks. Dietary treatment includes elemental and elimination diets. An exclusive elemental diet, which requires replacement of all intact protein with amino acid-based formula, offers the best response of all available therapies, with remission in up to 96% of subjects proving it to be superior to all other available therapies including topical steroids. However, compliance with this approach is challenging because of poor taste and monotony. The high cost of formula and the associated psychosocial problems are additional drawbacks of this approach. Empiric and allergy test-directed elimination diets have gained popularity given that elimination of a limited number of foods is much easier and as such is more readily acceptable. There is a growing body of literature supporting this type of therapy in both children and adults. This paper reviews the evidence for all types of dietary therapy in eosinophilic esophagitis.

Histological eosinophilic gastritis is a systemic disorder associated with blood and extra-gastric eosinophilia, Th2 immunity, and a unique gastric transcriptome

PubMed Central

Caldwell, Julie M.; Collins, Margaret H.; Stucke, Emily M.; Putnam, Philip E.; Franciosi, James P.; Kushner, Jonathan P.; Abonia, J. Pablo; Rothenberg, Marc E.

2014-01-01

Background The definition of eosinophilic gastritis (EG) is currently limited to histological EG based on the tissue eosinophil count. Objective We aimed to provide additional fundamental information about the molecular, histopathological, and clinical characteristics of EG. Methods Genome-wide transcript profiles and histological features of gastric biopsies as well as blood eosinophil numbers were analyzed in EG and control patients (n = 15 each). Results The peak gastric antrum eosinophil count was 282.7 ± 163.9 eosinophils/400X high-power field (HPF) in EG and 11.0 ± 8.5 eosinophils/HPF in control patients (P = 6.1 × 10−7). EG patients (87%) had co-existing eosinophilic inflammation in multiple gastrointestinal segments; the esophagus represented the most common secondary site. Elevated peripheral blood eosinophil numbers (EG 1.09 ± 0.88 × 103 [K]/μl vs. control 0.09 ± 0.08 K/μl, P = .0027) positively correlated with peak gastric eosinophil counts (Pearson r2 = .8102, P < .0001). MIB-1+ (proliferating), CD117+ (mast cells), and FOXP3+ cells (regulatory and/or activated T cells) were increased in EG. Transcript profiling revealed changes in 8% of the genome in EG gastric tissue. Only 7% of this EG transcriptome overlapped with the eosinophilic esophagitis (EoE) transcriptome. Significantly increased IL4, IL5, IL13, IL17, CCL26 and mast cell-specific transcripts and decreased IL33 were observed. Conclusion EG is a systemic disorder involving profound blood and gastrointestinal tract eosinophilia, Th2 immunity, and a conserved gastric transcriptome markedly distinct from the EoE transcriptome. The data herein define germane cellular and molecular pathways of EG and provide a basis for improving diagnosis and treatment. PMID:25234644

Assessment of fractionated exhaled nitric oxide as a biomarker for the treatment of eosinophilic esophagitis

PubMed Central

Nguyen-Traxler, Ann; Lee, Erika M.; Yip, Jason S.; Weinstock, Joel V.; Chan, Walter W.; Ngo, Peter; Weinstein, Barbara J.; Bonis, Peter A.

2012-01-01

Diagnosis of eosinophilic esophagitis (EoE) and determination of response to therapy is based on histological assessment of the esophagus, which requires upper endoscopy. In children, in whom a dietary approach is commonly used, multiple endoscopies are needed, because foods are eliminated and then gradually reintroduced. Ideally, noninvasive methods could supplement or replace upper endoscopy to facilitate management. Fractionated exhaled nitric oxide (FeNO) has been proposed as a useful measure for monitoring disease activity in studies of patients with eosinophil-predominant asthma and in other atopic disorders. Thus, we evaluated whether FeNO levels could be a useful biomarker to assess the response to therapy in EoE patients. This study was designed to determine whether there is a change in FeNO levels during treatment with topical corticosteroids and whether changes correlated with clinical response. This was a prospective, multicenter study that enrolled nonasthmatic patients with established EoE. FeNO levels and symptom scores were measured at baseline, biweekly during 6-week swallowed fluticasone treatment, and 4 weeks posttreatment. Twelve patients completed the trial. We found a statistically significant difference between median pre- and posttreatment FeNO levels [20.3 ppb (16.0–29.0 ppb) vs 17.6 ppb (11.7–27.3 ppb), p=0.009]. However, neither the pretreatment FeNO level, a change of FeNO level after 2 weeks of treatment, nor the FeNO level at the end of treatment confidently predicted a clinical or histological response. Although our findings suggest nitric oxide possibly has a physiological role in EoE, our observations do not support a role of FeNo determination for management of EoE. PMID:23394511

Intrabolus pressure on high-resolution manometry distinguishes fibrostenotic and inflammatory phenotypes of eosinophilic esophagitis.

PubMed

Colizzo, J M; Clayton, S B; Richter, J E

2016-08-01

The aim of this investigation was to determine the motility patterns of inflammatory and fibrostenotic phenotypes of eosinophilic esophagitis (EoE) utilizing high-resolution manometry (HRM). Twenty-nine patients with a confirmed diagnosis of EoE according to clinicopathological criteria currently being managed at the Joy McCann Culverhouse Swallowing Center at the University of South Florida were included in the retrospective analysis. Only patients who completed HRM studies were included in the analysis. Patients were classified into inflammatory or fibrostenotic subtypes based on baseline endoscopic evidence. Their baseline HRM studies prior to therapy were analyzed. Manometric data including distal contractile integral, integrated relaxation pressure, and intrabolus pressure (IBP) values were recorded. HRM results were interpreted according to the Chicago Classification system. Statistical analysis was performed with SPSS software (Version 22, IBM Co., Armonk, NY, USA). Data were compared utilizing Student's t-test, χ(2) test, Pearson correlation, and Spearman correlation tests. Statistical significance was set at P < 0.05. A total of 29 patients with EoE were included into the retrospective analysis. The overall average age among patients was 40 years. Male patients comprised 62% of the overall population. Both groups were similar in age, gender, and overall clinical presentation. Seventeen patients (58%) had fibrostenotic disease, and 12 (42%) displayed inflammatory disease. The average IBP for the fibrostenotic and inflammatory groups were 18.6 ± 6.0 mmHg and 12.6 ± 3.5 mmHg, respectively (P < 0.05). Strictures were only seen in the fibrostenotic group. Of the fibrostenotic group, 6 (35%) demonstrated proximal esophageal strictures, 7 (41%) had distal strictures, 3 (18%) had mid-esophageal strictures, and 1 (6%) patient had pan-esophageal strictures. There was no statistically significant correlation between the level of esophageal stricture and degree of IBP. Integrated relaxation pressure, distal contractile integral, and other HRM metrics did not demonstrate statistical significance between the two subtypes. There also appeared no statistically significant correlation between patient demographics and esophageal metrics. Patients with the fibrostenotic phenotype of EoE demonstrated an IBP that was significantly higher than that of the inflammatory group. © 2015 International Society for Diseases of the Esophagus.

Tethered SECM endoscopic capsule for the diagnosis of eosinophilic esophagitis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Do, Dukho; Kang, DongKyun; Tabatabaei, Nima; Grant, Catriona N.; Nishioka, Norman S.; Rosenberg, Mireille; Hesterberg, Paul E.; Yuan, Qian; Garber, John J.; Katz, Aubrey J.; Shreffler, Wayne G.; Tearney, Guillermo J.

2017-02-01

Eosinophilic Esophagitis (EoE) is an inflammatory disease caused by inhaled or ingested food allergies, and characterized by the infiltration of eosinophils in the esophagus. The gold standard for diagnosing EoE is to conduct endoscopy and obtain multiple biopsy specimens from different portions of the esophagus; an exam is considered positive if more than 15 eosinophils per high power field (HPF) in any of the biopsies. This method of diagnosis is problematic because endoscopic biopsy is expensive and poorly tolerated and the esophageal eosinophil burden needs to be monitored frequently during the course of the disease. Spectrally encoded confocal microscopy (SECM) is a high-speed confocal microscopy technology that can visualize individual eosinophils in large microscopic images of the human esophagus, equivalent to more than 30,000 HPF. Previously, we have demonstrated that tethered capsule SECM can be conducted in unsedated subjects with diagnosed EoE. However, speckle noise and the relatively low resolution in images obtained with the first capsule prototypes made it challenging to distinguish eosinophils from other cells. In this work, we present a next-generation tethered SECM capsule, which has been modified to significantly improve image quality. First, we substituted the single mode fiber with a dual-clad fiber to reduce speckle noise. A gradient-index multimode fiber was fusion spliced at the tip of the dual-clad fiber to increase the effective numerical aperture of the fiber from 0.09 to 0.15, expanding the beam more rapidly to increase the illumination aperture at the objective. These modifications enabled the new SECM capsule to achieve a lateral resolution of 1.8 µm and an axial resolution of 16.1 µm, which substantially improves the capacity of this probe to visualize cellular features in human tissue. The total size of the SECM capsule remained 6.75 mm in diameter and 31 mm in length. We are now in the process of testing this new SECM capsule in humans. Early results using this new SECM capsule suggest that this technology has the potential to be an effective tool for the diagnosis of EoE.

Esophageal dysmotility in children with eosinophilic esophagitis: a study using prolonged esophageal manometry.

PubMed

Nurko, Samuel; Rosen, Rachel; Furuta, Glenn T

2009-12-01

The pathophysiology of dysphagia in patients with eosinophilic esophagitis (EoE) is unknown but may be related to abnormal esophageal motor function. Symptoms rarely occur during stationary esophageal manometry, so it has been difficult to establish an association between symptoms and motor events. Our aim was to evaluate esophageal motor function in children with EoE with the use of stationary manometry and ambulatory prolonged esophageal manometry and pH-metry (PEMP). PEMP was performed in children with EoE and compared with controls and children with gastroesophageal reflux disease (GERD). Peristalsis was considered effective when the esophageal contractions had a normal amplitude and propagation. Results are expressed as mean+/-s.e. Seventeen patients with EoE, 13 with GERD, and 11 controls were studied. Values are expressed as mean+/-s.e. Stationary manometry identified abnormal peristalsis in 41% of children with EoE. During PEMP, children with EoE had an increased number of isolated (16.7+/-3.8 vs. 9.5+/-1.6 vs. 6.5+/-1.1; P<0.03) and high-amplitude contractions (4.1+/-1.2 vs. 1.8+/-0.8 vs. 0.1+/-0.1; P<0.03), and higher percentage ineffective peristalsis both during fasting (70.5%+/-2.5 vs. 57.8%+/-3.0 vs. 53.8%+/-1.9; P<0.05) and during meals (68.4+/-3.4 vs. 55.3+/-2.8 vs. 48.1+/-2.8; P<0.05) when compared with children with GERD and controls. Thirteen patients with EoE experienced 21 episodes of dysphagia, and all correlated with simultaneous abnormal motor function. PEMP allowed the detection of ineffective peristalsis in children with EoE. Symptoms observed in children with EoE may be related to esophageal motor dysfunction.

Is the etiology of eosinophilic esophagitis in adults a response to allergy or reflux injury? Study of cellular proliferation markers.

PubMed

Lewis, C J; Lamb, C A; Kanakala, V; Pritchard, S; Armstrong, G R; Attwood, S E A

2009-01-01

Recent research suggests that allergy may be the key factor in the etiology of eosinophilic esophagitis (EE); however, historically, the condition was hypothesized as related to reflux injury to the esophageal mucosa. We studied this hypothesis by comparing markers of inflammation and cellular proliferation in EE and reflux esophagitis. Lower esophageal biopsies of adult patients with EE (n = 10), reflux esophagitis (n = 8), and normal controls (n = 13) were assessed quantitatively for the expression of the cyclooxygenase-2 (COX-2) enzyme, cellular proliferation, and oncogenic resistance to apoptosis using monoclonal antibodies for COX-2, Ki-67, and Bcl-2, respectively. Normal esophageal epithelium demonstrated weak diffuse uptake of COX-2 stain in the basal layer. No COX-2 expression was demonstrated in the EE group, significantly less than the control and reflux groups (P < 0.01 and P < 0.001, respectively). Cellular proliferation measured by Ki-67 expression was higher in EE and reflux compared with control (P < 0.001 and P < 0.01). Ki-67 expression, and thus degree of hyperplasia, appeared greater in EE than reflux, but was not statistically significant (P = 0.228). The degree of apoptosis was similar in all study groups. EE and reflux esophagitis are proliferative conditions expressing Ki-67 in higher concentrations than control. Mucosal proliferation in reflux esophagitis is COX-2 dependent. This novel research in EE has demonstrated downregulation of COX-2 expression compared with reflux esophagitis and control. We hypothesize that the allergy-related cytokine IL-13 known to inhibit COX-2 expression and found in high concentrations in EE as responsible for this. The pathogenesis of EE is likely dependent on allergy rather than reflux injury to the esophagus.

Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults

PubMed Central

Molina-Infante, Javier; Arias, Ángel; von Arnim, Ulrike; Bredenoord, Albert J; Bussmann, Christian; Amil Dias, Jorge; Bove, Mogens; González-Cervera, Jesús; Larsson, Helen; Miehlke, Stephan; Papadopoulou, Alexandra; Rodríguez-Sánchez, Joaquín; Ravelli, Alberto; Ronkainen, Jukka; Santander, Cecilio; Schoepfer, Alain M; Storr, Martin A; Terreehorst, Ingrid; Straumann, Alex; Attwood, Stephen E

2017-01-01

Introduction Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE. Methods General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes. Results The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice. Conclusion Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients’ follow up are proposed in the guideline. PMID:28507746

Reliability of symptoms and endoscopic findings for diagnosis of esophageal eosinophilia in a Japanese population.

PubMed

Shimura, Shino; Ishimura, Norihisa; Tanimura, Takashi; Yuki, Takafumi; Miyake, Tatsuya; Kushiyama, Yoshinori; Sato, Shuichi; Fujishiro, Hirofumi; Ishihara, Shunji; Komatsu, Taisuke; Kaneto, Eiji; Izumi, Akio; Ishikawa, Noriyoshi; Maruyama, Riruke; Kinoshita, Yoshikazu

2014-01-01

The clinical characteristics of esophageal eosinophilia (EE), which is essential for diagnosis of eosinophilic esophagitis (EoE), have not been fully clarified in a Japanese population. The aim of this study was to analyze the reliability of symptoms and endoscopic findings for diagnosing EE in Japanese individuals. We prospectively enrolled subjects who complained of esophageal symptoms suggesting EoE and/or those with endoscopic findings of suspected EoE at the outpatient clinics of 12 hospitals. Diagnostic utility was compared between the EE and non-EE groups using logistic regression analysis. A total of 349 patients, including 319 with symptoms and 30 with no symptoms but endoscopic findings suggesting EoE were enrolled. Of those with symptoms, 8 (2.5%) had EE, and 3 were finally diagnosed with EoE. Of those without symptoms but endoscopic findings, 4 had EE. Among 8 symptomatic patients, 7 had abnormal endoscopic findings suspicious of EoE. Although dysphagia was a major symptom in EE, none of the presenting symptoms was useful for diagnosis of EE. Among the endoscopic findings, linear furrow was the most reliable (OR = 41.583). EE is uncommon among patients with esophageal symptoms in Japanese individuals. The most useful endoscopic finding for diagnosis of EE was linear furrow, whereas subjective symptoms were not supportive. © 2014 S. Karger AG, Basel.

Genetic dissection of eosinophilic esophagitis provides insight into disease pathogenesis and treatment strategies

PubMed Central

Sherrill, Joseph D.; Rothenberg, Marc E.

2011-01-01

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus that is compounded by both genetic predisposition and aberrant responses to environmental antigens, particularly those that are food-derived. Data have indicated a unique transcriptional response in vivo that defines EoE and which is partially attributable to the Th2 cytokine interleukin 13 (IL-13). Moreover, a number of genetic risk variants in pro-inflammatory and epithelial cell genes associate with EoE susceptibility, demonstrating novel heritable mechanisms that contribute to disease risk. Here, we discuss recent advances in our understanding of the intrinsic (genetic) and extrinsic (environmental) components that illustrate the complex nature of EoE. PMID:21570716

Expanding and characterizing esophageal epithelial cells obtained from children with eosinophilic esophagitis.

PubMed

Sayej, Wael N; Foster, Christopher; Jensen, Todd; Chatfield, Sydney; Finck, Christine

2018-06-12

The role of epithelial cells in eosinophilic esophagitis (EoE) is not well understood. In this study, our aim was to isolate, culture, and expand esophageal epithelial cells obtained from patients with or without EoE and characterize differences observed over time in culture. Biopsies were obtained at the time of endoscopy from children with EoE or suspected to have EoE. We established patient-derived esophageal epithelial cell (PDEEC) lines utilizing conditional reprogramming methods. We determined integrin profiles, gene expression, MHC class II expression, and reactivity to antigen stimulation. The PDEECs were found to maintain their phenotype over several passages. There were differences in integrin profiles and gene expression levels in EoE-Active compared to normal controls and EoE-Remission patients. Once stimulated with antigens, PDEECs express MHC class II molecules on their surface, and when co-cultured with autologous T-cells, there is increased IL-6 and TNF-α secretion in EoE-Active patients vs. controls. We are able to isolate, culture, and expand esophageal epithelial cells from pediatric patients with and without EoE. Once stimulated with antigens, these cells express MHC class II molecules and behave as non-professional antigen-presenting cells. This method will help us in developing an ex vivo, individualized, patient-specific model for diagnostic testing for causative antigens.

Correlation of High-Resolution Manometric Findings with Symptoms of Dysphagia and Endoscopic Features in Adults with Eosinophilic Esophagitis.

PubMed

von Arnim, Ulrike; Kandulski, Arne; Weigt, Jochen; Malfertheiner, Peter

2017-01-01

Eosinophilic esophagitis (EoE) presents with dysphagia, but data about motility patterns using high-resolution manometry (HRM) are rare. We aimed at evaluating esophageal motility patterns in EoE and their correlation to endoscopic and dysphagia scores. Twenty-six EoE patients and 23 controls were included after 4 weeks of treatment with proton pump inhibitors. Dysphagia and endoscopic scores were evaluated before performing HRM. EoE patients were classified to have fibrostenotic (FS) or inflammatory (IF) type. HRM analysis was performed according to the Chicago classification (CC) system. According to the CC, the HRM findings in EoE and controls were normal in 11 (42%) and 20 (88.5%), p < 0.0001. Weak and failed peristaltic integrity was only seen in EoE patients (failed 1/2.7%, weak 7/26.9%, p = 0.004). Of the EoE patients, 17 had IF and 9 presented with FS type. HRM parameters showed no differences according to the EoE subtype. The endoscopic score in the FS subtype was significantly higher than in EoE with IF subtype (5.33 vs. 3.58, p = 0.001). No significant difference was seen in dysphagia scores in EoE subtypes. HRM findings in EoE are often diagnostic, but they are non-specific and do not correlate with the severity of dysphagia or endoscopic appearance. The clinical impact of HRM in EoE needs further evaluation. © 2017 S. Karger AG, Basel.

Upper GI tract findings in patients with heartburn in whom proton pump inhibitor treatment failed versus those not receiving antireflux treatment.

PubMed

Poh, Choo Hean; Gasiorowska, Anita; Navarro-Rodriguez, Tomas; Willis, Marcia R; Hargadon, Deborah; Noelck, North; Mohler, Jane; Wendel, Christopher S; Fass, Ronnie

2010-01-01

Failure of proton pump inhibitor (PPI) treatment in patients with heartburn is very common. Because endoscopy is easily accessible, it is commonly used as the first evaluative tool in these patients. To compare GERD-related endoscopic and histologic findings in patients with heartburn in whom once-daily PPI therapy failed versus those not receiving antireflux treatment. Cross-sectional study. A Veterans Affairs hospital. Heartburn patients from the GI outpatient clinic. Recording of endoscopic results. Endoscopic findings and association between PPI treatment failure and esophageal mucosal injury by using logistic regression models. A total of 105 subjects (mean age 54.7 +/- 15.7 years; 71 men, 34 women) were enrolled in the PPI treatment failure group and 91 (mean age 53.4 +/- 15.8 years; 68 men, 23 women) were enrolled in the no-treatment group (P = not significant). Anatomic findings during upper endoscopy were significantly more common in the no-treatment group compared with the PPI treatment failure group (55.2% vs 40.7%, respectively; P = .04). GERD-related findings were significantly more common in the no-treatment group compared with the PPI treatment failure group (erosive esophagitis: 30.8% vs 6.7%, respectively; P < .05). Eosinophilic esophagitis was found in only 0.9% of PPI treatment failure patients. PPI treatment failure was associated with a significantly decreased odds ratio of erosive esophagitis compared with no treatment, adjusted for age, sex, and body mass index (adjusted odds ratio 0.11; 95% CI, 0.04-0.30). Heartburn patients in whom once-daily PPI treatment failed demonstrated a paucity of GERD-related findings compared with those receiving no treatment. Eosinophilic esophagitis was uncommon in PPI therapy failure patients. Upper endoscopy seems to have a very low diagnostic yield in this patient population. 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus.

PubMed

Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C; Pasricha, Pankaj J; Li, Xingde; Yu, Shaoyong

2015-03-15

Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE. Copyright © 2015 the American Physiological Society.

Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus

PubMed Central

Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C.; Pasricha, Pankaj J.; Li, Xingde

2015-01-01

Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE. PMID:25591867

Current Diagnosis and Management of Suspected Reflux Symptoms Refractory to Proton Pump Inhibitor Therapy

PubMed Central

2014-01-01

Suspected reflux symptoms that are refractory to proton pump inhibitors (PPIs) are rapidly becoming the most common presentation of gastroesophageal reflux disease (GERD) in patients seen in gastroenterology clinics. These patients are a heterogeneous group, differing in symptom frequency and severity, PPI dosing regimens, and responses to therapy (from partial to absent). Before testing, the physician needs to question the patient carefully about PPI compliance and the timing of drug intake in relation to meals. Switching PPIs or doubling the dose is the next step, but only 20% to 25% of the group refractory to PPIs will respond. The first diagnostic test should be upper gastrointestinal endoscopy. In more than 90% of cases, the results will be normal, but persistent esophagitis may suggest pill esophagitis, eosinophilic esophagitis, or rarer diseases, such as lichen planus, Zollinger-Ellison syndrome, or genotype variants of PPI metabolism. If the endoscopy results are normal, esophageal manometry and especially reflux testing should follow. Whether patients should be tested on or off PPI therapy is controversial. Most physicians prefer to test patients off PPIs to identify whether abnormal acid reflux is even present; if it is not, PPIs can be stopped and other diagnoses sought. Testing patients on PPI therapy allows nonacid reflux to be identified, but more than 50% of patients have a normal test result, leaving the clinician with a conundrum—whether to stop PPIs or continue them because the GERD is being treated adequately. Alternative diagnoses in patients with refractory GERD and normal reflux testing include achalasia, eosinophilic esophagitis, gastroparesis, rumination, and aerophagia. However, more than 50% will be given the diagnosis of functional heartburn, a visceral hypersensitivity syndrome. Treating patients with PPI-refractory GERD–like symptoms can be difficult and frustrating. Any of the following may help: a histamine-2 receptor antagonist at night, baclofen to decrease transient lower esophageal sphincter relaxations, pain modulators, acupuncture, or hypnotherapy. At this time, antireflux surgery should be limited to patients with abnormal acid reflux defined by pH testing and a good correlation of symptoms with acid reflux. PMID:27551249

Etiology and management of esophageal food impaction: a population based study.

PubMed

Gretarsdottir, Helga M; Jonasson, Jon Gunnlaugur; Björnsson, Einar S

2015-05-01

Esophageal food impaction (FI) is a common clinical problem with limited information on incidence. Previous population based studies are lacking. The incidence, main etiological factors, recurrence and outcome of FI was determined in the present study in a population based setting. This was a study of consecutive adult patients who presented with FI from 2008 to 2013 at the National University Hospital of Iceland. The mean crude incidence rate of FI was calculated. Retrospective analysis was undertaken on relevant clinical data such as type of bolus, management, complications, recurrence rate, risk factors for recurrence, and outcome. Overall 308 patients had endoscopically confirmed FI, males 199/308 (65%), median age 62 years. The mean crude incidence was 25 per 100,000 inhabitants per year. The types of FI was meat (68%), fish (12%), vegetable (4%) and other food/objects (16%). Causes for the FI included: esophageal strictures (45%), hiatal hernia (22%), eosinophilic esophagitis (EoE) (16%) and esophageal carcinoma (2%). Recurrence appeared in 21%, in which 24/48 (50%) had EoE vs. 40/260 (15%) in others (p = 0.0001). The removal of the foreign body was successful in 98% of the cases during the first endoscopy. Endoscopic associated complications included four (1.3%) aspirations, one (0.3%) esophageal perforation and one Boerhaave syndrome at presentation (both had EoE). The incidence of FI is the highest reported to date. EoE was strongly associated with recurrence of FI. In a population based setting endoscopy is a safe and effective procedure for removing FI.

1.3 Mb de novo Deletion in Chromosome Band 3q29 Associated with Normal Intelligence in a Child

DTIC Science & Technology

2010-09-01

attention deficit hyperactivity disorder ( ADHD ) of the inattentive type. He also displays some other...learning disabilities and behavioral features consistent with diagnoses of autism and attention deficit hyperactivity disorder ( ADHD ) of the inattentive...esophageal reflux with eosinophilic esophagitis. He was diagnosed with autism at age 3.5 years, attention deficit hyperactivity disorder

Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease.

PubMed

Kottyan, Leah C; Davis, Benjamin P; Sherrill, Joseph D; Liu, Kan; Rochman, Mark; Kaufman, Kenneth; Weirauch, Matthew T; Vaughn, Samuel; Lazaro, Sara; Rupert, Andrew M; Kohram, Mojtaba; Stucke, Emily M; Kemme, Katherine A; Magnusen, Albert; He, Hua; Dexheimer, Phillip; Chehade, Mirna; Wood, Robert A; Pesek, Robbie D; Vickery, Brian P; Fleischer, David M; Lindbad, Robert; Sampson, Hugh A; Mukkada, Vincent A; Putnam, Phil E; Abonia, J Pablo; Martin, Lisa J; Harley, John B; Rothenberg, Marc E

2014-08-01

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in EoE cases of European ancestry and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replicating association of the 5q22 locus (meta-analysis P=1.9×10(-16)), we identified an association at 2p23 spanning CAPN14 (P=2.5×10(-10)). CAPN14 was specifically expressed in the esophagus, was dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to interleukin (IL)-13, and was located in an epigenetic hotspot modified by IL-13. Genes neighboring the top 208 EoE-associated sequence variants were enriched for esophageal expression, and multiple loci for allergic sensitization were associated with EoE susceptibility (4.8×10(-2)

Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease

PubMed Central

Kottyan, Leah C.; Davis, Benjamin P.; Sherrill, Joseph D.; Liu, Kan; Rochman, Mark; Kaufman, Kenneth; Weirauch, Matthew T.; Vaughn, Samuel; Lazaro, Sara; Rupert, Andrew M.; Kohram, Mojtaba; Stucke, Emily M.; Kemme, Katherine A.; Magnusen, Albert; He, Hua; Dexheimer, Phillip; Chehade, Mirna; Wood, Robert A.; Pesek, Robbie D.; Vickery, Brian P.; Fleischer, David M.; Lindbad, Robert; Sampson, Hugh A.; Mukkada, Vince; Putnam, Phil E.; Abonia, J. Pablo; Martin, Lisa J.; Harley, John B.; Rothenberg, Marc E.

2014-01-01

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in European EoE cases and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replication of the 5q22 locus (meta-analysis p = 1.9×10−16), we identified association at 2p23 (encoding CAPN14, p = 2.5×10−10). CAPN14 was specifically expressed in the esophagus, dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to IL-13, and located in an epigenetic hotspot modified by IL-13. There was enriched esophageal expression for the genes neighboring the top 208 EoE sequence variants. Multiple allergic sensitization loci were associated with EoE susceptibility (4.8×10−2 < p < 5.1×10−11). We propose a model that elucidates the tissue specific nature of EoE that involves the interplay of allergic sensitization with an EoE-specific, IL-13–inducible esophageal response involving CAPN14. PMID:25017104

Upper Gastrointestinal Conditions: Nonmalignant Conditions of the Esophagus.

PubMed

Estores, David S; Chang, Ku-Lang

2017-07-01

Eosinophilic esophagitis (EE) is an allergic disorder of the esophagus. This diagnosis requires the presence of specific symptoms and a significantly elevated number of eosinophils in the esophageal lining as determined by endoscopic biopsies. Symptoms tend to be nonspecific among patients younger than 15 years. Among adults, dysphagia is the most common symptom. Comanagement with a gastroenterology subspecialist is essential, particularly for EE patients with a stricture. EE is commonly misdiagnosed as gastroesophageal reflux disease (GERD). The diagnosis of GERD is established by symptom response (eg, postprandial heartburn, regurgitation) to acid suppression, such as administration of a once-daily proton pump inhibitor. Red flag signs and symptoms for esophageal cancer include dysphagia, weight loss, and unexplained anemia. Risk factors include tobacco use, obesity, a long history of heartburn, and a family history of esophageal cancer. Most experts agree that the presence of risk factor(s) signals the need for screening with an upper endoscopy. An abnormal or pathologic pH study result for a patient with negative endoscopy results indicates the presence of nonerosive reflux disease. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors.

PubMed

Gonsalves, Nirmala; Yang, Guang-Yu; Doerfler, Bethany; Ritz, Sally; Ditto, Anne M; Hirano, Ikuo

2012-06-01

Adults with eosinophilic esophagitis (EoE) typically present with dysphagia and food impaction. A 6-food elimination diet (SFED) is effective in children with EoE. We assessed the effects of the SFED followed by food reintroduction on the histologic response, symptoms, and quality of life in adults with EoE. At the start of the study, 50 adults with EoE underwent esophagogastroduodenoscopies (EGDs), biopsies, and skin-prick tests for food and aeroallergens. After 6 weeks of SFED, patients underwent repeat EGD and biopsies. Histologic responders, defined by ≤ 5 eosinophils/high-power field (eos/hpf) (n = 32), underwent systematic reintroduction of foods followed by EGD and biopsies (n = 20). Symptom and quality of life scores were determined before and after SFED. Common symptoms of EoE included dysphagia (96%), food impaction (74%), and heartburn (94%). The mean peak eosinophil counts in the proximal esophagus were 34 eos/hpf and 8 eos/hpf, before and after the SFED, and 44 eos/hpf and 13 eos/hpf in the distal esophagus, respectively (P < .0001). After the SFED, 64% of patients had peak counts ≤ 5 eos/hpf and 70% had peak counts of ≤ 10 eos/hpf. Symptom scores decreased in 94% (P < .0001). After food reintroduction, esophageal eosinophil counts returned to pretreatment values (P < .0001). Based on reintroduction, the foods most frequently associated with EoE were wheat (60% of cases) and milk (50% of cases). Skin-prick testing predicted only 13% of foods associated with EoE. An elimination diet significantly improves symptoms and reduces endoscopic and histopathologic features of EoE in adults. Food reintroduction re-initiated features of EoE in patients, indicating a role for food allergens in its pathogenesis. Foods that activated EoE were identified by systematic reintroduction analysis but not by skin-prick tests. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

A Randomized Controlled Comparison of Esophageal Clearance Times of Oral Budesonide Preparations.

PubMed

Hefner, Jody N; Howard, Robin S; Massey, Robert; Valencia, Miland; Stocker, Derek J; Philla, Katherine Q; Goldman, Matthew D; Nylund, Cade M; Min, Steve B

2016-06-01

Topical steroids prepared as oral viscous slurries have become common in the treatment of eosinophilic esophagitis. Esophageal mucosal contact time correlates with clinical and histologic improvement. To compare the mucosal contact time of alternative oral viscous budesonide (OVB) slurries with the conventional sucralose OVB. A blinded randomized crossover trial investigating esophageal clearance of three OVB slurry preparations was done on healthy adults. Honey and xanthan gum OVB slurries were compared with standard sucralose OVB in 24 randomly assigned subjects. Each subject ingested the sucralose OVB and either the honey or xanthan gum OVB slurries. The esophageal clearance of each slurry was evaluated as an area under the curve (AUC) using 1 millicurie of technetium-99m-sulfur colloid (Tc99) co-administered in each OVB preparation using nuclear scintigraphy. A standardized taste survey was also administered. Xanthan gum had greater mucosal contact time compared to sucralose as measured by a higher AUC at 3 min (P = 0.002), while honey showed no significant difference in esophageal clearance relative to sucralose. Taste scores were significantly higher in the honey group, while scores for xanthan gum were no different from standard sucralose. OVB slurries utilizing xanthan gum may be a superior alternative to a sucralose-based slurry due to its increased mucosal contact time and similar taste tolerance. Honey may be a suitable alternative as well, due to its similar contact time and favorable taste.

Eosinophilic esophagitis prevalence in an adult population undergoing upper endoscopy in southeastern Mexico.

PubMed

De la Cruz-Patiño, E; Ruíz Juárez, I; Meixueiro Daza, A; Grube Pagola, P; Roesch-Dietlen, F; Remes-Troche, J M

2015-01-01

Eosinophilic esophagitis (EoE) prevalence fluctuates according to the population studied and varies from 0.4% in an open population to 6.5% in subjects with esophageal symptoms. Even though this entity has been described in North American and European populations, it is still considered an 'unusual' condition in Latin America. The study aimed to determine EoE prevalence in patients undergoing elective endoscopy in a tertiary referral center in southeastern Mexico. Consecutive patients were evaluated that had been referred to the Medical and Biological Research Institute, Veracruz, Mexico, for upper endoscopy due to gastrointestinal symptoms. Demographic variables and symptoms were analyzed in all the cases. Eight mucosal biopsies of the esophagus (four proximal and four distal) were obtained and were reviewed by a blinded pathologist. Histological diagnosis was established when the mean eosinophil count at a large magnification was ≥15. A total of 235 subjects (137 women, 51.16 years) were evaluated, and EoE prevalence was 1.7% (4/235 95% confidence interval 0.2-3.6%). In all four cases, pH test were normal. Among patients with histological diagnosis of EoE, a greater number of patients with a past history of asthma (50% vs. 19.3%, P = 0.04) and a tendency for a greater frequency of dysphagia (50% vs. 25%, P = 0.10). There were no differences in the endoscopic findings (rings, grooves, plaques, or stricture) when compared with the patients presenting with erosive esophagitis. EoE prevalence among patients undergoing upper endoscopy from southeastern Mexico was 1.7%, which can be regarded as intermediate to low. © 2014 International Society for Diseases of the Esophagus.

The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses.

PubMed

Azouz, Nurit P; Ynga-Durand, Mario A; Caldwell, Julie M; Jain, Ayushi; Rochman, Mark; Fischesser, Demetria M; Ray, Leanne M; Bedard, Mary C; Mingler, Melissa K; Forney, Carmy; Eilerman, Matthew; Kuhl, Jonathan T; He, Hua; Biagini Myers, Jocelyn M; Mukkada, Vincent A; Putnam, Philip E; Khurana Hershey, Gurjit K; Kottyan, Leah C; Wen, Ting; Martin, Lisa J; Rothenberg, Marc E

2018-06-06

Loss of barrier integrity has an important role in eliciting type 2 immune responses, yet the molecular events that initiate and connect this with allergic inflammation remain unclear. We reveal an endogenous, homeostatic mechanism that controls barrier function and inflammatory responses in esophageal allergic inflammation. We show that a serine protease inhibitor, SPINK7 (serine peptidase inhibitor, kazal type 7), is part of the differentiation program of human esophageal epithelium and that SPINK7 depletion occurs in a human allergic, esophageal condition termed eosinophilic esophagitis. Experimental manipulation strategies reducing SPINK7 in an esophageal epithelial progenitor cell line and primary esophageal epithelial cells were sufficient to induce barrier dysfunction and transcriptional changes characterized by loss of cellular differentiation and altered gene expression known to stimulate allergic responses (for example, FLG and SPINK5 ). Epithelial silencing of SPINK7 promoted production of proinflammatory cytokines including thymic stromal lymphopoietin (TSLP). Loss of SPINK7 increased the activity of urokinase plasminogen-type activator (uPA), which in turn had the capacity to promote uPA receptor-dependent eosinophil activation. Treatment of epithelial cells with the broad-spectrum antiserine protease, α1 antitrypsin, reversed the pathologic features associated with SPINK7 silencing. The relevance of this pathway in vivo was supported by finding genetic epistasis between variants in TSLP and the uPA-encoding gene, PLAU We propose that the endogenous balance between SPINK7 and its target proteases is a key checkpoint in regulating mucosal differentiation, barrier function, and inflammatory responses and that protein replacement with antiproteases may be therapeutic for select allergic diseases. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Esophageal eosinophilia is increased in rural areas with low population density: results from a national pathology database.

PubMed

Jensen, Elizabeth T; Hoffman, Kate; Shaheen, Nicholas J; Genta, Robert M; Dellon, Evan S

2014-05-01

Eosinophilic esophagitis (EoE) is an increasingly prevalent chronic disease arising from an allergy/immune-mediated process. Generally, the risk of atopic disease differs in rural and urban environments. The relationship between population density and EoE is unknown. Our aim was to assess the relationship between EoE and population density. We conducted a cross-sectional, case-control study of patients with esophageal biopsies in a US national pathology database between January 2009 and June 2012 to assess the relationship between population density and EoE. Using geographic information systems, the population density (individuals per square mile) was determined for each patient zip code. The odds of esophageal eosinophilia and EoE were estimated for each quintile of population density and adjusted for potential confounders. Sensitivity analyses were conducted with varying case definitions and to evaluate the potential for bias from endoscopy volume and patient factors. Of 292,621 unique patients in the source population, 89,754 had normal esophageal biopsies and 14,381 had esophageal eosinophilia with ≥15 eosinophils per high-power field. The odds of having esophageal eosinophilia increased with decreasing population density (P for trend <0.001). Compared with those in the highest quintile of population density, odds of having esophageal eosinophilia were significantly higher among those in the lowest quintile of population density (adjusted odds ratio (aOR) 1.27, 95% confidence interval (CI): 1.18, 1.36). A similar dose-response trend was observed across case definitions with increased odds of EoE in the lowest population density quintile (aOR 1.59, 95% CI: 1.45-1.76). Estimates were robust to sensitivity analyses. Population density is strongly and inversely associated with esophageal eosinophilia and EoE. This association is robust to varying case definitions and adjustment factors. Environmental exposures that are more prominent in rural areas may be relevant to the pathogenesis of EoE.

Esophageal eosinophilia is increased in rural areas with low population density: Results from a national pathology database

PubMed Central

Jensen, Elizabeth T.; Hoffman, Kate; Shaheen, Nicholas J.; Genta, Robert M.; Dellon, Evan S.

2015-01-01

Objectives Eosinophilic esophagitis (EoE) is an increasingly prevalent chronic disease arising from an allergy/immune-mediated process. Generally, the risk of atopic disease differs in rural and urban environments. The relationship between population density and EoE is unknown. Our aim was to assess the relationship between EoE and population density. Methods : We conducted a cross-sectional, case-control study of patients with esophageal biopsies in a U.S. national pathology database between January 2009 and June 2012 to assess the relationship between population density and EoE. Using Geographic Information Systems (GIS), the population density (individuals/mile2) was determined for each patient zip code. The odds of esophageal eosinophilia and EoE were estimated for each quintile of population density and adjusted for potential confounders. Sensitivity analyses were conducted with varying case definitions and to evaluate the potential for bias from endoscopy volume and patient factors. Results Of 292,621 unique patients in the source population, 89,754 had normal esophageal biopsies and 14,381 had esophageal eosinophilia with ≥15 eosinophils per high-power field (eos/hpf). The odds of esophageal eosinophilia increased with decreasing population density (p for trend < 0.001). Compared to those in the highest quintile of population density, odds of esophageal eosinophilia were significantly higher amongst those in the lowest quintile of population density (aOR 1.27, 95% CI: 1.18, 1.36). A similar dose-response trend was observed across case definitions with odds of EoE increased in the lowest population density quintile (aOR 1.59, 95% CI: 1.45-1.76). Estimates were robust to sensitivity analyses. Conclusions Population density is strongly and inversely associated with esophageal eosinophilia and EoE. This association is robust to varying case definitions and adjustment factors. Environmental exposures more prominent in rural areas may be relevant to the pathogenesis of EoE. PMID:24667575

EoE (Eosinophilic Esophagitis)

MedlinePlus

... Sheet Q & A with Experts Patient Stories Social Security Disability Application Process For Kids For Teens Managing ... Q & A with Experts Health Information Sheet Social Security Disability Application Process For Family and Friends For ...

History and Evolution of the Barium Swallow for Evaluation of the Pharynx and Esophagus.

PubMed

Levine, Marc S; Rubesin, Stephen E

2017-02-01

This article reviews the history of the barium swallow from its early role in radiology to its current status as an important diagnostic test in modern radiology practice. Though a variety of diagnostic procedures can be performed to evaluate patients with dysphagia or other pharyngeal or esophageal symptoms, the barium study has evolved into a readily available, non-invasive, and cost-effective technique that can facilitate the selection of additional diagnostic tests and guide decisions about medical, endoscopic, or surgical management. This article focuses on the evolution of fluoroscopic equipment, radiography, and contrast media for evaluating the pharynx and esophagus, the importance of understanding pharyngoesophageal relationships, and major advances that have occurred in the radiologic diagnosis of select esophageal diseases, including gastroesophageal reflux disease, infectious esophagitis, eosinophilic esophagitis, esophageal carcinoma, and esophageal motility disorders.

Eosinophilic Esophagitis: Symptoms and Causes

MedlinePlus

... Symptoms Signs and symptoms include: Adults: Difficulty swallowing (dysphagia) Food getting stuck in the esophagus after swallowing ( ... eating, in children Vomiting Abdominal pain Difficulty swallowing (dysphagia) Food getting stuck in the esophagus after swallowing ( ...

Advances in mechanisms of asthma, allergy, and immunology in 2010.

PubMed

Broide, David H; Finkelman, Fred; Bochner, Bruce S; Rothenberg, Marc E

2011-03-01

2010 was marked by rapid progress in our understanding of the cellular and molecular mechanisms involved in the pathogenesis of allergic inflammation and asthma. Studies published in the Journal of Allergy and Clinical Immunology described advances in our knowledge of cells associated with allergic inflammation (mast cells, eosinophils, dendritic cells, and T cells), as well as IgE, cytokines, receptors, signaling molecules, and pathways. Studies used animal models, as well as human cells and tissues, to advance our understanding of mechanisms of asthma, eosinophilic esophagitis, food allergy, anaphylaxis and immediate hypersensitivity, mast cells and their disorders, atopic dermatitis, nasal polyposis, and hypereosinophilic syndromes. Additional studies provided novel information about the induction and regulation of allergic inflammation and the genetic contribution to allergic inflammation. Critical features of these studies and their potential effects on human atopic disorders are summarized here. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Effects of eosinophilic oesophagitis on quality of life in an adult UK population: a case control study.

PubMed

Hewett, R; Alexakis, C; Farmer, A D; Ainley, J; Chhaya, V; Hayat, J O; Poullis, A; Kang, J-Y

2017-01-01

Eosinophilic oesophagitis (EoE) is a chronic immune-mediated esophageal disease, characterized by symptoms related to esophageal dysfunction and histologically by eosinophil predominant inflammation. Current evidence for an adverse impact on quality of life (QoL) is conflicting and there are no data from a UK population regarding QoL. We conducted a prospective cross-sectional observational study using the Short Form-36 Health Survey, Hospital Dysphagia/Odynophagia Questionnaire, and the EoE Adult Quality of Life Questionnaire to assess QoL and severity of dysphagia in EoE patients, compared to age and gender matched healthy control subjects. Data were also collected on comorbidity and medication use. Eighty-eight subjects were recruited (44 patients). Patients had higher rates of antihistamine and topical (swallowed) corticosteroid use. Physical QoL did not differ between patients and controls, although patients did report a statistically significant lower mental QoL, with small absolute magnitude of difference. Patients reported higher dysphagia scores and these were negatively correlated with both physical and mental QoL. Higher rates of dysphagia and medication use in patients may among other things account for lower mental QoL. However, a higher rate of dysphagia in patients is not associated with a reduced physical QoL. Our findings are of clinical value, particularly when a new diagnosis of EoE is made, as clinicians can reassure patients that their general physical health should not be greatly affected by the diagnosis. Moreover, it may also be useful for patients to be aware that EoE may have an impact on their mental health, but this effect is likely to be small. We therefore advocate education and reassurance in this respect for all patients at diagnosis. © 2016 International Society for Diseases of the Esophagus.

Eosinophilic Esophagitis in Children and Adolescents with Abdominal Pain: Comparison with EoE-Dysphagia and Functional Abdominal Pain.

PubMed

Gunasekaran, Thirumazhisai; Prabhakar, Gautham; Schwartz, Alan; Gorla, Kiranmai; Gupta, Sandeep; Berman, James

2016-01-01

Aim. Compare EoE-AP with EoE-D for clinical, endoscopy (EGD), histology and outcomes and also with FAP-N. Method. Symptoms, physical findings, EGD, histology, symptom scores, and treatments were recorded for the three groups. Cluster analysis was done. Results. Dysphagia and abdominal pain were different in numbers but not statistically significant between EoE-AP and EoE-D. EGD, linear furrows, white exudates were more in the EoE-D and both combined were significant (p < 0.05). EoE-D, peak and mean eosinophils (p  0.06) and eosinophilic micro abscesses (p  0.001) were higher. Follow-Up. Based on single symptom, EoE-AP had 30% (p  0.25) improvement, EoE-D 86% (p < 0.001) and similar with composite score (p  0.57 and <0.001, resp.). Patients who had follow-up, EGD: 42.8% with EoE-AP and 77.8% with EoE-D, showed single symptom improvement and the eosinophil count fell from 38.5/34.6 (peak and mean) to 31.2/30.4 (p  0.70) and from 43.6/40.8 to 25.2/22.8 (p < 0.001), respectively. FAP-N patients had similar symptom improvement like EoE-D. Cluster Analysis. EoE-AP and FAP-N were similar in clinical features and response to treatment, but EoE-D was distinctly different from EoE-AP and FAP-N. Conclusion. Our study demonstrates that EoE-AP and EoE-D have different histology and outcomes. In addition, EoE-AP has clinical features similar to the FAP-N group.

Eosinophilic Esophagitis in Children and Adolescents with Abdominal Pain: Comparison with EoE-Dysphagia and Functional Abdominal Pain

PubMed Central

Gorla, Kiranmai; Gupta, Sandeep

2016-01-01

Aim. Compare EoE-AP with EoE-D for clinical, endoscopy (EGD), histology and outcomes and also with FAP-N. Method. Symptoms, physical findings, EGD, histology, symptom scores, and treatments were recorded for the three groups. Cluster analysis was done. Results. Dysphagia and abdominal pain were different in numbers but not statistically significant between EoE-AP and EoE-D. EGD, linear furrows, white exudates were more in the EoE-D and both combined were significant (p < 0.05). EoE-D, peak and mean eosinophils (p  0.06) and eosinophilic micro abscesses (p  0.001) were higher. Follow-Up. Based on single symptom, EoE-AP had 30% (p  0.25) improvement, EoE-D 86% (p < 0.001) and similar with composite score (p  0.57 and <0.001, resp.). Patients who had follow-up, EGD: 42.8% with EoE-AP and 77.8% with EoE-D, showed single symptom improvement and the eosinophil count fell from 38.5/34.6 (peak and mean) to 31.2/30.4 (p  0.70) and from 43.6/40.8 to 25.2/22.8 (p < 0.001), respectively. FAP-N patients had similar symptom improvement like EoE-D. Cluster Analysis. EoE-AP and FAP-N were similar in clinical features and response to treatment, but EoE-D was distinctly different from EoE-AP and FAP-N. Conclusion. Our study demonstrates that EoE-AP and EoE-D have different histology and outcomes. In addition, EoE-AP has clinical features similar to the FAP-N group. PMID:27610357

American College of Allergy, Asthma & Immunology

MedlinePlus

... Why Anaphylaxis Types of Allergies: Ragweed Allergy Pine Tree Allergy Hives (Urticaria) Food Allergy Types of Food ... Fish Allergy Eosinophilic Esophagitis Egg Allergy Corn Allergy Tree Nut Allergy Food Allergy Diagnosis Food Allergy Avoidance ...

Eosinophilic Esophagitis (EoE)

MedlinePlus

... the AAAAI Foundation Donate Utility navigation Español Journals Pollen Counts Annual Meeting Member Login / My Membership Search ... allergies to substances such as dust mites, animals, pollen and molds can play a role in EoE. ...

Endoscopic findings and pathologic characteristics of gastric eosinophilic granuloma: A report of 18 patients

PubMed Central

Song, Wen-Chong; Yu, Jie-Ping; Shen, Lei; Xia, Hong; Luo, He-Sheng

2006-01-01

AIM: To investigate the endoscopic findings and patholo-gic characteristics of gastric eosinophilic granuloma (GEG). METHODS: A retrospective study of 18 cases of gastric eosinophilic granulomas was conducted. Gastroscopy was performed and all specimens of biopsies were stained by H&E and observed under light microscopy. RESULTS: Ulcer was the most frequent endoscopic appearance. The others included deformed pylorus and/or duodenal bulb, esophagitis, mucous hyperemia and/or mucosal erosion. Eosinophilic cell infiltration and generous hyperplasia of arterioles, venules and lymph vessels were found in the lesions of the patients. Interstitium had massive eosinophilic infiltrates and was made up of collagen fibers and fibroblasts. Lymphoid follicles were revealed in some sections of biopsies. CONCLUSION: GEG is lack of specific symptoms and physical signs. It can be misdiagnosed as gastric ulcer in most cases before biopsies. Endoscopy and endoscopic multiple deep biopsies in suspected areas are indispensable for correct diagnosis of GEG. PMID:17167848

Incidence and features of eosinophilic esophagitis in dysphagia: a prospective observational study.

PubMed

Murray, Iain Alexander; Joyce, Stephne; Palmer, Joanne; Lau, Michael; Schultz, Michael

2016-03-01

The incidence and symptoms associated with eosinophilic esophagitis (EoE) varies with geographic location, present in 7-15% dysphagic European or North American adults. We aimed to determine incidence and features of EoE in a dysphagic New Zealand population. 101 consecutive patients presenting with dysphagia to a New Zealand teaching hospital completed a questionnaire (demographics and history) before upper gastrointestinal endoscopy and esophageal biopsies. The incidence of EoE was 14.1% in those having esophageal biopsies. Patients with EoE were younger (median age 38 years, cohort 58 years: OR 9.2 for age ≤ 40; p < 0.001), more frequently male (19.1% versus 7.4% of females: OR 4.7; p < 0.05), and had longer symptom duration (median 262 weeks versus 130.6 weeks: p = NS) with non-continuous symptoms (continuous symptoms 8.3% EoE versus 16.2% cohort: p = NS). Progressive symptoms, level of dysphagia and history of allergy/atopy occurred with almost identical frequency in those with and without EoE. Classic endoscopic features of EoE had a sensitivity and specificity of 30.6 and 93.2%, respectively. EoE occurs in an adult dysphagic population in New Zealand with similar frequency to that reported in Europe and North America. Demographics and features of history associated with EoE are described and the need to take esophageal biopsies in this population emphasized by the relatively low sensitivity of endoscopic features for the condition.

Quail egg homogenate alleviates food allergy induced eosinophilic esophagitis like disease through modulating PAR-2 transduction pathway in peanut sensitized mice.

PubMed

Lianto, Priscilia; Han, Shiwen; Li, Xinrui; Ogutu, Fredrick Onyango; Zhang, Yani; Fan, Zhuoyan; Che, Huilian

2018-01-18

The present pharmacotherapy for eosinophilic esophagitis (EoE) fundamentally depend on inhaled corticosteroids. Despite the fact that oral intake of topical steroids can be successful in restricting EoE-related inflammation, there are concerns with respect to the long term utilization of steroids, especially in kids. In the current research, we assess the effect of quail egg, which is reportedly a known serine protease inhibitor, on symptomatology and immune responses in a peanut-sensitized mouse model of food allergy induced EoE. Daily oral treatment with quail egg attenuated mice symptomatology and immune response. Treatment with quail egg inhibited antigen-prompted increments in mouse tryptase and eosinophil cationic protein (ECP) in serum and eosinophil in inflamed tissues like oesophagus, lung, and digestive system. Quail egg treatment resulted in decreased antibody specific IgE and IgG1 and a variety of inflammatory genes that were abnormally expressed in EoE. Other effects included increased IL-10, decreased PAR-2 activation and NF-kB p65 in inflamed tissues. Our results suggest that quail egg treatment may have therapeutic potential in attenuating the symptoms of food allergy induced EoE like disease through regulating PAR-2 downstream pathway by blocking the activation of the transcription factor NF-kB p65 activity.

Minimally-invasive biomarker studies in eosinophilic esophagitis: a systematic review.

PubMed

Hines, Brittany T; Rank, Matthew A; Wright, Benjamin L; Marks, Lisa A; Hagan, John B; Straumann, Alex; Greenhawt, Matthew; Dellon, Evan S

2018-05-10

Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus which currently requires repeated endoscopic biopsies for diagnosis and monitoring as no reliable non-invasive markers have been identified. To identify promising minimally-invasive EoE biomarkers and remaining gaps in biomarker validation. We performed a systematic review of EMBASE, Ovid Medline, PubMed, and Web of Science from inception to June 6, 2017. Studies were included if subjects met the 2007 consensus criteria for EoE diagnosis, a minimally-invasive biomarker was assessed, and the study included at least 1 control for comparison. The search identified 2094 studies, with 234 reviewed at full text level, and 49 included in the analysis (20 adult, 19 pediatric, 7 pediatric and adult, and 3 not stated). The majority (26 of 49) were published after 2014. Thirty-five studies included normal controls, 9 analyzed atopic controls, and 29 compared samples from subjects with active and inactive EoE. Minimally-invasive biomarkers were obtained from peripheral blood (n=41 studies), sponge/string samples (3), oral/throat swab secretions (2), breath condensate (2), stool (2), and urine (2). The most commonly reported biomarkers were peripheral blood eosinophils (16), blood and string eosinophil granule proteins (14), and eosinophil surface or intracellular markers (12). EoE biomarkers distinguished active EoE from normal controls in 23 studies, atopic controls in 2 studies, and inactive EoE controls in 20 studies. Several promising minimally-invasive biomarkers for EoE have emerged; however, few are able to differentiate EoE from other atopic diseases. Copyright © 2018. Published by Elsevier Inc.

The prevalence of eosinophilic esophagitis in pediatric patients with IgE-mediated food allergy

PubMed Central

Hill, David A.; Dudley, Jesse W.; Spergel, Jonathan M.

2017-01-01

BACKGROUND Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that is triggered by food allergens and characterized by progressive esophageal dysfunction. Recently, EoE has been identified in patients undergoing oral immunotherapy (OIT) for IgE-mediated food allergy, suggesting an association. OBJECTIVE We sought to ascertain whether significant associations exist between IgE-mediated food allergies and EoE. METHODS Utilizing analysis of EMR data and manual chart review, we examined our sub-specialty care network of 35,528 children and adolescents to identify and characterize patients with IgE-mediated, and EoE food allergy. The most common food allergens were defined, and the prevalence of EoE in patients with IgE-mediated food allergy was determined. Logistic regression was used to measure the extent to which IgE-mediated food allergy to specific foods is associated with EoE. RESULTS The most common causes of EoE were milk, grains, meats, peanut, tree nuts, egg, and soy, an allergen pattern that is distinct from that of IgE-mediated food allergy. The prevalence of EoE in patients with IgE-mediated food allergy was higher than that reported in the general population (4.7% vs 0.04%). The distribution of IgE-mediated food allergens in patients with EoE was similar to that of the general population, and IgE-mediated allergy to egg (2.27; 1.91–2.64), milk (4.19; 3.52–4.97), or shellfish (1.55; 1.24–1.92) was significantly associated with EoE diagnosis. CONCLUSIONS Our findings support a clinical association between these conditions that has implications for the management of children with food allergy, and particular relevance to patients undergoing OIT. PMID:28042003

Eosinophilic Esophagitis in Pediatric and Adolescent Patients

MedlinePlus

... is allergic to such as specific foods, plants, trees etc. Symptoms Symptoms of EoE are non-specific ... Allergy testing is frequently done for patients to identify potential allergens and other allergic diseases because children ...

How does esophagus look on barium esophagram in pediatric eosinophilic esophagitis?

PubMed

Al-Hussaini, Abdulrahman; AboZeid, Amany; Hai, Abdul

2016-08-01

The clinical, endoscopic, and histologic findings of eosinophilic esophagitis (EoE) are well characterized; however, there have been very limited data regarding the radiologic findings of pediatric EoE. We report on the radiologic findings of pediatric EoE observed on barium esophagram and correlate them with the endoscopic findings. We identified children diagnosed with EoE in our center from 2004 to 2015. Two pediatric radiologists met after their independent evaluations of each fluoroscopic study to reach a consensus on each case. Clinical and endoscopic data were collected by retrospective chart review. Twenty-six pediatric EoE cases (age range 2-13 years; median 7.5 years) had barium esophagram done as part of the diagnostic approach for dysphagia. Thirteen children had abnormal radiologic findings of esophagus (50%): rings formation (n = 4), diffuse irregularity of mucosa (n = 8), fixed stricture formation (n = 3), and narrow-caliber esophagus (n = 10). Barium esophagram failed to show one of 10 cases of narrow-caliber esophagus and 10 of 14 cases of rings formation visualized endoscopically. The mean duration of symptoms prior to diagnosis of EoE was longer (3.7 vs. 1.7 year; p value 0.019), and the presentation with intermittent food impaction was commoner in the group with abnormal barium esophagram as compared to the group with normal barium esophagram (69% vs. 8%; p value 0.04). Barium swallow study is frequently normal in pediatric EoE. With the exception of narrow-caliber esophagus, our data show poor correlation between radiologic and endoscopic findings.

Eosinophils from eosinophilic oesophagitis patients have T cell suppressive capacity and express FOXP3.

PubMed

Lingblom, C; Wallander, J; Ingelsten, M; Bergquist, H; Bove, M; Saalman, R; Welin, A; Wennerås, C

2017-03-01

Eosinophilic esophagitis (EoE) is an antigen-driven T cell-mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin-10 and have T cell suppressive capacity similar to regulatory T cells (T regs ). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell-driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction. In addition, eosinophilic expression of forkhead box protein 3 (FOXP3), the canonical transcription factor of T regs , was determined by conventional and imaging flow cytometry, quantitative polymerase chain reaction (qPCR), confocal microscopy and immunoblotting. It was found that blood eosinophils from EoE patients had T cell suppressive capacity, and that a fraction of the eosinophils expressed FOXP3. A comparison of EoE eosinophils with healthy control eosinophils indicated that the patients' eosinophils had inferior suppressive capacity. Furthermore, a higher percentage of the EoE eosinophils expressed FOXP3 protein compared with the healthy eosinophils, and they also had higher FOXP3 protein and mRNA levels. FOXP3 was found in the cytosol and nucleus of the eosinophils from both the patients and healthy individuals, contrasting with the strict nuclear localization of FOXP3 in T regs . To conclude, these findings suggest that the immunoregulatory function of eosinophils may be impaired in EoE. © 2016 British Society for Immunology.

Eosinophils from eosinophilic oesophagitis patients have T cell suppressive capacity and express FOXP3

PubMed Central

Lingblom, C.; Wallander, J.; Ingelsten, M.; Bergquist, H.; Bove, M.; Saalman, R.; Welin, A.

2016-01-01

Summary Eosinophilic esophagitis (EoE) is an antigen‐driven T cell‐mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin‐10 and have T cell suppressive capacity similar to regulatory T cells (Tregs). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell‐driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction. In addition, eosinophilic expression of forkhead box protein 3 (FOXP3), the canonical transcription factor of Tregs, was determined by conventional and imaging flow cytometry, quantitative polymerase chain reaction (qPCR), confocal microscopy and immunoblotting. It was found that blood eosinophils from EoE patients had T cell suppressive capacity, and that a fraction of the eosinophils expressed FOXP3. A comparison of EoE eosinophils with healthy control eosinophils indicated that the patients' eosinophils had inferior suppressive capacity. Furthermore, a higher percentage of the EoE eosinophils expressed FOXP3 protein compared with the healthy eosinophils, and they also had higher FOXP3 protein and mRNA levels. FOXP3 was found in the cytosol and nucleus of the eosinophils from both the patients and healthy individuals, contrasting with the strict nuclear localization of FOXP3 in Tregs. To conclude, these findings suggest that the immunoregulatory function of eosinophils may be impaired in EoE. PMID:27921303

Eosinophilic Esophagitis

MedlinePlus

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Comparative Dietary Therapy Effectiveness in Remission of Pediatric Eosinophilic Esophagitis

PubMed Central

Henderson, Carol J.; Abonia, J. Pablo; King, Eileen C.; Putnam, Philip E.; Collins, Margaret H.; Franciosi, James P.; Rothenberg, Marc E.

2012-01-01

Background Eosinophilic esophagitis is a chronic, immune-mediated inflammatory disorder that responds to dietary therapy; however, data evaluating the effectiveness of dietary therapeutic strategies is limited. Objective This study compared the effectiveness of three frequently prescribed dietary therapies [elemental, six-food elimination, and skin prick and atopy patch-directed elimination] and assessed the remission predictability of skin tests and their utility in directing dietary planning. Methods A retrospective cohort of proton-pump inhibitor-unresponsive, non-glucocorticoid-treated eosinophilic esophagitis patients who had two consecutive endoscopic biopsies associated with dietary intervention was identified. Biopsy histology and remissions (< 15 eosinophils/high-power field) following dietary therapy and food reintroductions were evaluated. Results Ninety-eight of 513 patients met eligibility criteria. Of these 98, 50% (49), 27% (26), and 23% (23) received elemental, six-food elimination, and directed diets, respectively. Remission occurred in 96%, 81%, and 65% of patients on elemental, six-food elimination, and directed diets, respectively. The odds of post-diet remission vs. non-remission were 5.6-fold higher (P=0.05) on elemental vs. six-food elimination, 12.5-fold higher (P=0.003) on elemental vs. directed, and were not significantly different (P=0.22) on six-food elimination vs. directed diets. Following 116 single-food reintroductions, the negative predictive value of skin testing for remission was 40%–67% (milk 40%, egg 56%, soy 64%, and wheat 67%). Conclusion All three dietary therapies are effective; however, an elemental diet is superior at inducing histologic remission compared with six-food elimination and skin test-directed diets. Notably, an empiric six-food elimination diet is as effective as a skin test-directed diet. The negative predictive values of foods most commonly reintroduced in single-food challenges are not sufficient to support the development of dietary advancement plans solely based on skin tests. PMID:22541246

ESPGHAN-NASPGHAN Guidelines for the Evaluation and Treatment of Gastrointestinal and Nutritional Complications in Children With Esophageal Atresia-Tracheoesophageal Fistula.

PubMed

Krishnan, Usha; Mousa, Hayat; Dall'Oglio, Luigi; Homaira, Nusrat; Rosen, Rachel; Faure, Christophe; Gottrand, Frédéric

2016-11-01

Esophageal atresia (EA) is one of the most common congenital digestive anomalies. With improvements in surgical techniques and intensive care treatments, the focus of care of these patients has shifted from mortality to morbidity and quality-of-life issues. These children face gastrointestinal (GI) problems not only in early childhood but also through adolescence and adulthood. There is, however, currently a lack of a systematic approach to the care of these patients. The GI working group of International Network on Esophageal Atresia comprises members from ESPGHAN/NASPGHAN and was charged with the task of developing uniform evidence-based guidelines for the management of GI complications in children with EA. Thirty-six clinical questions addressing the diagnosis, treatment, and prognosis of the common GI complications in patients with EA were formulated. Questions on the diagnosis, and treatment of gastroesophageal reflux, management of "cyanotic spells," etiology, investigation and management of dysphagia, feeding difficulties, anastomotic strictures, congenital esophageal stenosis in EA patients were addressed. The importance of excluding eosinophilic esophagitis and associated GI anomalies in symptomatic patients with EA is discussed as is the quality of life of these patients and the importance of a systematic transition of care to adulthood. A systematic literature search was performed from inception to March 2014 using Embase, MEDLINE, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Clinical Trials, and PsychInfo databases. The approach of the Grading of Recommendations Assessment, Development and Evaluation was applied to evaluate outcomes. During 2 consensus meetings, all recommendations were discussed and finalized. The group members voted on each recommendation, using the nominal voting technique. Expert opinion was used where no randomized controlled trials were available to support the recommendation.

Eosinophilic Esophagitis (EoE)

MedlinePlus

... the main cause of EoE in a large number of patients. Allergists are experts in evaluating and treating EoE related to food allergies. However the relationship between food allergy and EoE is complex. In many types of food allergy, the triggers ...

Eosinophilic Esophagitis: Diagnosis and Treatment

MedlinePlus

... What you can do Be aware of any pre-appointment restrictions. At the time you make the appointment, be sure to ask if there's anything you need to do in advance, such as restrict your diet. Bring test results. If you are seeing a new specialist ...

Outcomes of children after esophagogastroduodenoscopy for chronic abdominal pain.

PubMed

Thakkar, Kalpesh; Chen, Leon; Tessier, Mary E; Gilger, Mark A

2014-06-01

Chronic abdominal pain is the most common indication for esophagogastroduodenoscopy (EGD) in children. However, little is known about the accuracy of EGD-based diagnosis or the outcomes of the patients who undergo this procedure. We examined the diagnostic yield of EGD and short-term outcomes of children who underwent this procedure for chronic abdominal pain. We conducted a prospective study of 290 children (4-18 years old; mean age, 11.9 ± 3.5 years; 93 girls) who underwent EGD for the primary indication of chronic abdominal pain (216 with at least 1 alarm feature) at a US pediatric gastroenterology referral center. We collected data on demographic features (age, sex), clinical characteristics (alarm features, Rome III criteria), and EGD results for each patient. All subjects with diagnostic lesions were followed for at least 1 year after EGD to determine short-term outcomes. Overall, EGD provided an accurate diagnosis for 109 children (38%). Diagnoses included esophagitis (21.0%), eosinophilic gastroenteritis (4.1%), eosinophilic esophagitis (3.8%), Helicobacter pylori infection (2.0%), celiac disease (0.6%), and Crohn's disease (0.4%). Short-term outcomes were available for 81% of patients with diagnostic findings, and medical therapy was effective in approximately 67% of these children. EGD is valuable for the diagnosis of children with abdominal pain, with a 38% diagnostic yield. EGD identified disorders for which medical therapy was effective in 67% of children during the year after diagnosis. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Development and validation of a registry-based definition of eosinophilic esophagitis in Denmark

PubMed Central

Dellon, Evan S; Erichsen, Rune; Pedersen, Lars; Shaheen, Nicholas J; Baron, John A; Sørensen, Henrik T; Vyberg, Mogens

2013-01-01

AIM: To develop and validate a case definition of eosinophilic esophagitis (EoE) in the linked Danish health registries. METHODS: For case definition development, we queried the Danish medical registries from 2006-2007 to identify candidate cases of EoE in Northern Denmark. All International Classification of Diseases-10 (ICD-10) and prescription codes were obtained, and archived pathology slides were obtained and re-reviewed to determine case status. We used an iterative process to select inclusion/exclusion codes, refine the case definition, and optimize sensitivity and specificity. We then re-queried the registries from 2008-2009 to yield a validation set. The case definition algorithm was applied, and sensitivity and specificity were calculated. RESULTS: Of the 51 and 49 candidate cases identified in both the development and validation sets, 21 and 24 had EoE, respectively. Characteristics of EoE cases in the development set [mean age 35 years; 76% male; 86% dysphagia; 103 eosinophils per high-power field (eos/hpf)] were similar to those in the validation set (mean age 42 years; 83% male; 67% dysphagia; 77 eos/hpf). Re-review of archived slides confirmed that the pathology coding for esophageal eosinophilia was correct in greater than 90% of cases. Two registry-based case algorithms based on pathology, ICD-10, and pharmacy codes were successfully generated in the development set, one that was sensitive (90%) and one that was specific (97%). When these algorithms were applied to the validation set, they remained sensitive (88%) and specific (96%). CONCLUSION: Two registry-based definitions, one highly sensitive and one highly specific, were developed and validated for the linked Danish national health databases, making future population-based studies feasible. PMID:23382628

Mucosal Impedance: a New Approach to Diagnosing Gastroesophageal Reflux Disease and Eosinophilic Esophagitis.

PubMed

Barrett, Caroline; Choksi, Yash; Vaezi, Michael F

2018-06-09

In this review, we discuss current diagnostic testing modalities for both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) and then introduce mucosal impedance (MI), a novel technology that measures epithelial integrity in real time during endoscopy. We describe the advantages and disadvantages of MI as compared with traditional diagnostic testing. We review studies that demonstrate that GERD and EoE have distinct MI patterns, and that physicians can accurately diagnose and distinguish the two during endoscopy with minimal time added to the procedure. We also review studies showing that MI has the capability to assess treatment response in both GERD and EoE and that it can be used to diagnose GERD in patients with extraesophageal reflux symptoms. Mucosal impedance testing is a major advancement in the diagnosis of GERD and EoE. Future studies are planned to assess whether MI can be used as a treatment endpoint in EoE and whether it can be used to predict response to anti-reflux surgery.

Comparison of different biopsy forceps models for tissue sampling in eosinophilic esophagitis.

PubMed

Bussmann, Christian; Schoepfer, Alain M; Safroneeva, Ekaterina; Haas, Nadine; Godat, Sébastien; Sempoux, Christine; Simon, Hans-Uwe; Straumann, Alex

2016-12-01

Background and aims: Eosinophilic esophagitis (EoE) is a mixed inflammatory and fibrostenotic disease. Unlike superficial inflammatory changes, subepithelial fibrosis is not routinely sampled in esophageal biopsies. This study aimed to evaluate the efficacy and safety of deep esophageal sampling with four different types of biopsy forceps. Patients and methods: In this cross-sectional study, esophageal biopsies were taken in 30 adult patients by one expert endoscopist. Biopsies sampled from distal esophagus using a static jaw forceps (Olympus, FB-11K-1) were compared with proximal biopsies sampled with static jaw (Olympus, FB-45Q-1), alligator jaw (Olympus, FB-210K), and large-capacity forceps (Boston Scientific, Radial Jaw 4). One pathologist calculated the surface area of epithelial and subepithelial layers in hematoxylin and eosin (H&E)-stained biopsies. Results: Subepithelial tissue was acquired in 97 % (static jaw FB-11K-1), 93 % (static jaw FB-45Q-1), 80 % (alligator jaw), and 55 % (large-capacity) of samples. Median (interquartile [IQR]) ratios of surface area of epithelial to subepithelial tissue were: static jaw FB-45Q-1, 1.07 (0.65 - 4.465); static jaw FB-11K-1, 1.184 (0.608 - 2.545); alligator jaw, 2.353 (1.312 - 4.465); and large-capacity, 2.71 (1.611 - 4.858). The static jaw models obtained a larger surface area of subepithelial tissue compared with the alligator jaw ( P  < 0.001 and P  = 0.037, for FB-11K-1 and FB-45Q-1, respectively) and the large-capacity forceps ( P  < 0.001, for both static jaw models). No esophageal perforations occurred. Conclusions: The static jaw forceps models allowed sampling of subepithelial tissue in > 90 % of biopsies and appear to be superior to alligator or large-capacity forceps in sampling larger amounts of subepithelial tissue. © Georg Thieme Verlag KG Stuttgart · New York.

Model to Determine the Optimal Dietary Elimination Strategy for Treatment of Eosinophilic Esophagitis.

PubMed

Zhan, Tiannan; Ali, Ayman; Choi, Jin G; Lee, Minyi; Leung, John; Dellon, Evan S; Garber, John J; Hur, Chin

2018-05-03

Elimination diets are effective treatments for eosinophilic esophagitis (EoE), but foods that activate esophagitis are identified empirically, via a process that involves multiple esophagogastroduodenoscopies (EGDs). No optimized approach has been developed to identify foods that activate EoE. We aimed to compare clinical strategies to provide data to guide treatment. We developed a computer-based simulation model to determine the optimal empiric elimination strategy based on reported prevalence values for foods that activate EoE. These were identified in a systematic review, searching PubMed through October 1, 2017 for prospective and retrospective studies of EoE and diet. Each patient in our virtual cohort was assigned profile comprising as many as 12 foods known to induce EoE, including dairy, wheat, eggs, soy, nuts, seafood, beef, corn, chicken, potato, pork, and/or rice. To balance the strategy success rate with the number of EGDs required for food identification, we applied an efficiency frontier approach. Strategies on the frontier were the most efficient, requiring fewer EGDs for higher or equivalent success rates relative to their comparable, neighboring strategies. In all simulations, we found the 1,4,8-food and 1,3-food strategies to be the most efficient in identifying foods that induce EoE, resulting in the highest rate of the correct identification of food triggers balanced by the number of EGDs required to complete the food elimination strategy. Both strategies begin with elimination of dairy; if EoE remission is not achieved, the 1,3 diet proceeds to eliminate wheat and eggs in addition to dairy, and the 1,4,8 strategy removes wheat, eggs, dairy, and soy. In the case of persistent EoE after the second round of food elimination, the 1,3-food strategy terminates, whereas the 1,4,8-food diet eliminates corn, chicken, beef, and pork. The 1,4,8-food resulted in correct identification of foods that activated esophagitis in 76.68% of patients, with a mean 4.13 EGDs and a median 6 EGDs. The 1,3-food strategy identified foods that activated esophagitis in 42.76% of patients, with a mean of 3.36 EGDs and a median 2 EGDs required. In a modeling analysis, we found the 1,4,8-food and 1,3-food elimination strategies to be the most efficient in detection of foods that induce EoE in patients, the 1,4,8-food strategy was optimal, requiring a mean of only 4.13 EGDs for food identification. However, the ideal elimination strategy will vary based on clinical priorities. Additional research on specific foods that induce EoE are needed to confirm the predictions of this model. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

TGF-Beta Gene Polymorphisms in Food Allergic versus Non-Food Allergic Eosinophilic Esophagitis

DTIC Science & Technology

2012-10-01

successful EoE therapy in 60-98% of subjects. Indeed, th e majority of children with EoE have specific IgE to foods but they often continue to ingest...sensitized children with EoE and the TGFb1 genes. W e hypothesize that in EoE there is a gene polymorphism (TGFb1) environment (food) interaction that...esophageal stricture form ation is an im portant complication of remodeling in EoE (6-12% of children ; 33% of adults), identif ying genetic polym orphisms in

The Prevalence of Eosinophilic Esophagitis in Pediatric Patients with IgE-Mediated Food Allergy.

PubMed

Hill, David A; Dudley, Jesse W; Spergel, Jonathan M

Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that is triggered by food allergens and characterized by progressive esophageal dysfunction. Recently, EoE has been identified in patients who underwent oral immunotherapy (OIT) for IgE-mediated food allergy, suggesting an association. We sought to ascertain whether significant associations exist between IgE-mediated food allergies and EoE. Using the analysis of electronic medical record data and manual chart review, we examined our subspecialty care network of 35,528 children and adolescents to identify and characterize patients with IgE-mediated and EoE food allergy. The most common food allergens were defined, and the prevalence of EoE in patients with IgE-mediated food allergy was determined. Logistic regression was used to measure the extent to which IgE-mediated food allergy to specific foods is associated with EoE. The most common causes of EoE were milk, soy, egg, grains, and meats, an allergen pattern that is distinct from that of IgE-mediated food allergy. The prevalence of EoE in patients with IgE-mediated food allergy was higher than that reported in the general population (4.7% vs 0.04%). The distribution of IgE-mediated food allergens in patients with EoE was similar to that of the general population, and IgE-mediated allergy to egg (2.27; 1.91-2.64), milk (4.19; 3.52-4.97), or shellfish (1.55; 1.24-1.92) was significantly associated with an EoE diagnosis. Our findings support a clinical association between these conditions that has implications for the management of children with food allergy, and particular relevance to patients undergoing OIT. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

PedsQL™ Eosinophilic Esophagitis Module: Feasibility, Reliability and Validity

PubMed Central

Franciosi, James P.; Hommel, Kevin A.; Bendo, Cristiane B.; King, Eileen C.; Collins, Margaret H.; Eby, Michael D.; Marsolo, Keith; Abonia, J. Pablo; von Tiehl, Karl F.; Putnam, Philip E.; Greenler, Alexandria J.; Greenberg, Allison B.; Bryson, Ronald A.; Davis, Carla M.; Olive, Anthony P.; Gupta, Sandeep K.; Erwin, Elizabeth A.; Klinnert, Mary D.; Spergel, Jonathan M.; Denham, Jolanda M.; Furuta, Glenn T.; Rothenberg, Marc E.; Varni, James W.

2014-01-01

Objective Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory condition with a paucity of information on health-related quality of life (HRQOL). The objective of the study was to report on the measurement properties of the PedsQL™ EoE Module. Methods The PedsQL™ EoE Module was completed in a multisite study by 196 pediatric EoE patients and 262 EoE parents. Results The PedsQL™ EoE Module scales evidenced excellent feasibility (0.6%–3.1% missing), excellent group comparison reliability across total scale scores (patient α = 0.93; parent proxy α = 0.94), good reliability for the seven individual scales (patient α = 0.75–0.87; parent proxy α = 0.81–0.92), excellent test-retest reliability (patient ICC = 0.88; parent ICC= 0.82), demonstrated no floor effects and low ceiling effects, and demonstrated a high percentage of scaling success for most scales. Intercorrelations with the PedsQL™ Generic Core Scales were in the medium (0.30) to large (0.50) range. PedsQL™ EoE Module scores were worse among patients with active histologic disease (> 5 eos/hpf) compared to those in remission (patient self-report: 63.3 vs. 69.9 [p<0.05]; parent proxy-report: 65.1 vs. 72.3 [p<0.01]), and those treated with dietary restrictions compared to those with no restrictions (patient self-report: 61.6 vs. 74.3 [p< 0.01]; parent proxy-report: 65.5 vs. 74.7 [p<0.01]). Conclusions The results demonstrate excellent measurement properties of the PedsQL™ EoE Module. Patients with active histologic disease and those treated with dietary restrictions demonstrated worse PedsQL™ scores. The PedsQL™ EoE Module may be utilized in evaluation of pediatric EoE disease-specific HRQOL in clinical research and practice. PMID:23478422

Involvement of the iNKT Cell Pathway Is Associated With Early-Onset Eosinophilic Esophagitis and Response to Allergen Avoidance Therapy

PubMed Central

Lexmond, Willem S.; Neves, Joana F.; Nurko, Samuel; Olszak, Torsten; Exley, Mark A.; Blumberg, Richard S.; Fiebiger, Edda

2014-01-01

OBJECTIVES Recent experimental evidence suggests that environmental microbial factors early in life determine susceptibility to allergic diseases through inappropriate chemotaxis and local activation of CD1d-restricted, invariant chain natural killer T (iNKT) cells. In this study, we analyzed the involvement of these pathways in pediatric patients with eosinophilic esophagitis (EoE) before and after dietary allergen elimination. METHODS mRNA expression levels of components of the C-X-C motif chemokine ligand 16 (CXCL16)–iNKT–CD1d axis were compared in esophageal biopsies from EoE patients vs. normal or inflammatory controls and before and after treatment. RESULTS CXCL16, iNKT cell–associated cell marker Vα24, and CD1d were significantly upregulated in esophageal biopsies from EoE patients and correlated with the expression of inflammatory mediators associated with allergy. Upregulation of each of these factors was significantly more pronounced in patients aged < 6 years at diagnosis, and this early-onset EoE subpopulation was characterized by a more prominent food allergic disease phenotype in a cohort-wide analysis. Successful, but not unsuccessful, treatment of early-onset EoE patients with dietary elimination of instigating allergens led to reduction in infiltrating iNKT cells and complete normalization of mRNA expression levels of CXCL16 and CD1d. CONCLUSIONS Our observations place iNKT cells at the center of allergic inflammation associated with EoE, which could have profound implications for our understanding, treatment and prevention of this and other human allergic diseases. PMID:24513807

Misplaced Priorities and Barrett’s Esophagus

Cancer.gov

Nicholas J. Shaheen, MD, MPH is the Bozymski-Heizer Distinguished Professor of Medicine at the University of North Carolina School of Medicine, and Chief of the Division of Gastroenterology and Hepatology at UNC. His research and clinical interests center on gastroesophageal reflux disease, and pre-cancerous and cancerous conditions of the esophagus. He has a clinical and research interest in early detection and treatment of cancerous and precancerous lesions of the esophagus. He has authored greater than 300 publications in these areas. Dr. Shaheen is author of multiple national guidelines in Barrett’s esophagus, GERD and eosinophilic esophagitis. He has served as senior associate editor for the American Journal of Gastroenterology, and on multiple other editorial boards. Dr. Shaheen receives research funding from the National Institutes of Health, multiple societies, and private and public foundations.

Effects of topical steroids on tight junction proteins and spongiosis in esophageal epithelia of patients with eosinophilic esophagitis.

PubMed

Katzka, David A; Tadi, Ravikanth; Smyrk, Thomas C; Katarya, Eesha; Sharma, Anamay; Geno, Deborah M; Camilleri, Michael; Iyer, Prasad G; Alexander, Jeffrey A; Buttar, Navtej S

2014-11-01

The allergic response associated with eosinophilic esophagitis (EoE) occurs when food antigens permeate tight junction-mediated epithelial dilated intercellular spaces. We assessed whether levels of tight junction proteins correlate with the dilation of intercellular spaces (spongiosis) and the effects of topical steroids on these parameters. We assessed esophageal biopsy samples from 10 patients with active EoE treated with topical fluticasone, 10 untreated patients, and 10 patients without esophageal disease (controls) for degree of spongiosis. Immunohistochemical assays were used to determine the levels of the tight junction proteins filaggrin, zonula occludens (ZO)-1, ZO-2, ZO-3, and claudin-1. Histology and immunohistochemistry results were assessed blindly, with levels of tight junction proteins and degree of spongiosis rated on scales of 0 to 3. The mean degrees of spongiosis in untreated and treated patients with EoE were 1.3 and 0.4, respectively (P = .016). Esophageal epithelia did not stain significantly for ZO-1 or ZO-2. Filaggrin was observed in a predominant cytoplasmic pattern, compared with the cytoplasmic and membranous patterns of ZO-3 and claudin-1. In biopsy specimens from patients with active EoE, the mean staining intensities for filaggrin, ZO-3, and claudin-1 were 1.6, 1.4, and 0.7, respectively. In biopsy specimens from patients treated with fluticasone, levels of filaggrin, ZO-3, and claudin-1 were 2.8 (P = .002 compared with untreated patients), 1.7 (P = .46 compared with untreated patients), and 1.3 (P = .25 compared with untreated patients), respectively. The correlation between the level of filaggrin and the degree of spongiosis was r = 0.23, and between ZO-3 staining and the degree of spongiosis was r = .016 (P = .001 for filaggrin vs ZO-3 staining). Filaggrin, ZO-3, and claudin-1 (but not ZO-1 or ZO-2) are detected in the esophageal mucosa of patients with EoE treated with steroids and individuals without esophageal disease. Without treatment, spongiosis increases, corresponding with reduced levels of filaggrin, ZO-3, and claudin-1. Loss of tight junction regulators and dilation of intercellular spaces appear to be involved in the pathophysiology of EoE and could be targets for treatment. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Eosinophilic Esophagitis in Children and Its Relationship with Parental Allergies: Texas Children's Hospital Experience.

PubMed

Hiremath, Girish; Byramji, Darius; Pacheco, Ann; Constantine, Greg; Davis, Carla; Shulman, Robert; Olive, Anthony

2016-02-01

Eosinophilic esophagitis (EoE) is an allergen-mediated, clinicopathological condition affecting all ages. The characteristics of children with EoE in the southwestern USA have not been fully described. Furthermore, very little is known about the relationship between parental allergies and risk of EoE in their offspring in this patient population. To characterize children with EoE and to examine the relationship between prevalence of parental allergies and occurrence of EoE in their offspring at a single referral pediatric center in the southwestern USA. Demographic and clinical information of 126 children (≤18 years of age) with EoE was abstracted in a pre-determined data extraction form and analyzed. The allergy history was collected from biological parents of 61 children (parent-child cluster) with EoE in a standardized questionnaire and analyzed. The median age at presentation was 8 years (interquartile range 4-13). The majority of our patients were male (71 %) and Caucasian (59 %). Overall, 84 % of children reported allergies. Prevalence of food allergy was significantly higher compared to environmental allergies (P = 0.001). At least 46 % of parents reported allergies. A significantly higher proportion of fathers had developed allergies during their childhood compared to adulthood (P = 0.03). The characteristics of EoE in our patients were similar to those reported from other parts of the country. Childhood onset of paternal allergies appears to be a risk factor for occurrence of EoE in their offspring. Additional research to elucidate the relationship between parental allergies and occurrence of EoE in their offspring is warranted.

Eosinophilic esophagitis: dilate or medicate? A cost analysis model of the choice of initial therapy.

PubMed

Kavitt, R T; Penson, D F; Vaezi, M F

2014-07-01

Eosinophilic esophagitis (EoE) is an increasingly recognized clinical entity. The optimal initial treatment strategy in adults with EoE remains controversial. The aim of this study was to employ a decision analysis model to determine the less costly option between the two most commonly employed treatment strategies in EoE. We constructed a model for an index case of a patient with biopsy-proven EoE who continues to be symptomatic despite proton-pump inhibitor therapy. The following treatment strategies were included: (i) swallowed fluticasone inhaler (followed by esophagogastroduodenoscopy [EGD] with dilation if ineffective); and (ii) EGD with dilation (followed by swallowed fluticasone inhaler if ineffective). The time horizon was 1 year. The model focused on cost analysis of initial treatment strategies. The perspective of the healthcare payer was used. Sensitivity analyses were performed to assess the robustness of the model. For every patient whose symptoms improved or resolved with the strategy of fluticasone first followed by EGD, if necessary, it cost an average of $1078. Similarly, it cost an average of $1171 per patient if EGD with dilation was employed first. Sensitivity analyses indicated that initial treatment with fluticasone was the less costly strategy to improve dysphagia symptoms as long as the effectiveness of fluticasone remains at or above 0.62. Swallowed fluticasone inhaler (followed by EGD with dilation if necessary) is the more economical initial strategy when compared with EGD with dilation first. © 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

IgE in the diagnosis and treatment of allergic disease

PubMed Central

Platts-Mills, Thomas A. E.; Schuyler, Alexander J.; Erwin, Elizabeth A.; Commins, Scott P.; Woodfolk, Judith A.

2017-01-01

Traditionally, the concept of allergy implied an abnormal response to an otherwise benign agent (eg, pollen or food), with an easily identifiable relationship between exposure and disease. However, there are syndromes in which the relationship between exposure to the relevant allergen and the “allergic” disease is not clear. In these cases the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy. Good examples include chronic asthma and exposure to perennial indoor allergens and asthma related to fungal infection. Finally, we are increasingly aware of forms of food allergy in which the relationship between exposure and the disease is delayed by 3 to 6 hours or longer. Three forms of food allergy with distinct clinical features are now well recognized. These are (1) anaphylactic sensitivity to peanut, (2) eosinophilic esophagitis related to cow’s milk, and (3) delayed anaphylaxis to red meat. In these syndromes the immunology of the response is dramatically different. Peanut and galactose α-1,3-galactose (alpha-gal) are characterized by high- or very high-titer IgE antibodies for Ara h 2 and alpha-gal, respectively. By contrast, eosinophilic esophagitis is characterized by low levels of IgE specific for milk proteins with high- or very high-titer IgG4 to the same proteins. The recent finding is that patients with alpha-gal syndrome do not have detectable IgG4 to the oligosaccharide. Thus the serum results not only identify relevant antigens but also provide a guide to the nature of the immune response. PMID:27264001

Update on dietary therapy for eosinophilic esophagitis in children and adults.

PubMed

Molina-Infante, Javier; Gonzalez-Cordero, Pedro Luis; Arias, Angel; Lucendo, Alfredo J

2017-02-01

Eosinophilic esophagitis (EoE) is a chronic inflammatory esophageal disease triggered predominantly, but not excusively, by food antigens. Elimination diet thus remains the only therapy targeting the cause of the disease. Importantly, EoE is a unique form of non-IgE mediated food allergy, largely dependant upon delayed, cell-mediated hypersensitivity. Areas covered: A comprehensive review of literature to summarize and update the most relevant advances on dietary therapy for pediatric and adult EoE patients is conducted. Expert commentary: None of the currently available food allergy tests adequately predict food triggers for EoE, especially in adults. Elemental diet (exclusive feeding with aminoacid-based formulas) and empiric six-food elimination diet, withdrawing cow´s milk, wheat, egg, soy, nuts and fish/seafood for 6 weeks, have consistently shown the best cure rates. However, their high level of restriction and need for multiple endoscopies (top-down approach) have been a deterrent for patients and physicians. Less restrictive empiric schemes, like a four-food (animal milk, gluten-containing cereals, egg, legumes) or a two-food (animal milk and gluten-containing cereals) elimination diet have lately shown encouraging results. Therefore, a novel step-up strategy (2-4-6) may enhance patient uptake and promptly identify most responders to empiric diets with few food triggers, besides saving unnecessary dietary restrictions and endoscopic procedures.

BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis

PubMed Central

Jiang, Ming; Ku, Wei-Yao; Zhou, Zhongren; Dellon, Evan S.; Falk, Gary W.; Nakagawa, Hiroshi; Wang, Mei-Lun; Liu, Kuancan; Wang, Jun; Katzka, David A.; Peters, Jeffrey H.; Lan, Xiaopeng; Que, Jianwen

2015-01-01

Tissue homeostasis requires balanced self-renewal and differentiation of stem/progenitor cells, especially in tissues that are constantly replenished like the esophagus. Disruption of this balance is associated with pathological conditions, including eosinophilic esophagitis (EoE), in which basal progenitor cells become hyperplastic upon proinflammatory stimulation. However, how basal cells respond to the inflammatory environment at the molecular level remains undetermined. We previously reported that the bone morphogenetic protein (BMP) signaling pathway is critical for epithelial morphogenesis in the embryonic esophagus. Here, we address how this pathway regulates tissue homeostasis and EoE development in the adult esophagus. BMP signaling was specifically activated in differentiated squamous epithelium, but not in basal progenitor cells, which express the BMP antagonist follistatin. Previous reports indicate that increased BMP activity promotes Barrett’s intestinal differentiation; however, in mice, basal progenitor cell–specific expression of constitutively active BMP promoted squamous differentiation. Moreover, BMP activation increased intracellular ROS levels, initiating an NRF2-mediated oxidative response during basal progenitor cell differentiation. In both a mouse EoE model and human biopsies, reduced squamous differentiation was associated with high levels of follistatin and disrupted BMP/NRF2 pathways. We therefore propose a model in which normal squamous differentiation of basal progenitor cells is mediated by BMP-driven NRF2 activation and basal cell hyperplasia is promoted by disruption of BMP signaling in EoE. PMID:25774506

TGF-Beta Gene Polymorphisms in Food Allergic versus Non-Food Allergic Eosinophilic Esophagitis

DTIC Science & Technology

2013-10-01

our EE subjects are male, Caucasian, and have another atopic disorder (asthma, allergy, eczema and/or food allergy) (n=142, analysis is ongoing...Rhinitis (%) Eczema (%) 43% 66% 30% Table 3: Food IgE Sensitization Pattern Food Antigen IgE Positive (% patients, 95% CI) (n=122-129) Egg 39

An algorithm for the classification of mRNA patterns in eosinophilic esophagitis: Integration of machine learning.

PubMed

Sallis, Benjamin F; Erkert, Lena; Moñino-Romero, Sherezade; Acar, Utkucan; Wu, Rina; Konnikova, Liza; Lexmond, Willem S; Hamilton, Matthew J; Dunn, W Augustine; Szepfalusi, Zsolt; Vanderhoof, Jon A; Snapper, Scott B; Turner, Jerrold R; Goldsmith, Jeffrey D; Spencer, Lisa A; Nurko, Samuel; Fiebiger, Edda

2018-04-01

Diagnostic evaluation of eosinophilic esophagitis (EoE) remains difficult, particularly the assessment of the patient's allergic status. This study sought to establish an automated medical algorithm to assist in the evaluation of EoE. Machine learning techniques were used to establish a diagnostic probability score for EoE, p(EoE), based on esophageal mRNA transcript patterns from biopsies of patients with EoE, gastroesophageal reflux disease and controls. Dimensionality reduction in the training set established weighted factors, which were confirmed by immunohistochemistry. Following weighted factor analysis, p(EoE) was determined by random forest classification. Accuracy was tested in an external test set, and predictive power was assessed with equivocal patients. Esophageal IgE production was quantified with epsilon germ line (IGHE) transcripts and correlated with serum IgE and the T h 2-type mRNA profile to establish an IGHE score for tissue allergy. In the primary analysis, a 3-class statistical model generated a p(EoE) score based on common characteristics of the inflammatory EoE profile. A p(EoE) ≥ 25 successfully identified EoE with high accuracy (sensitivity: 90.9%, specificity: 93.2%, area under the curve: 0.985) and improved diagnosis of equivocal cases by 84.6%. The p(EoE) changed in response to therapy. A secondary analysis loop in EoE patients defined an IGHE score of ≥37.5 for a patient subpopulation with increased esophageal allergic inflammation. The development of intelligent data analysis from a machine learning perspective provides exciting opportunities to improve diagnostic precision and improve patient care in EoE. The p(EoE) and the IGHE score are steps toward the development of decision trees to define EoE subpopulations and, consequently, will facilitate individualized therapy. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Esophageal manifestations of celiac disease.

PubMed

Lucendo, A J

2011-09-01

Celiac disease (CD) may often be associated with various motor disorders affecting the different segments of the digestive tract, including the esophagus. Although it has not been universally reported, some available evidences indicate that pediatric and adult celiac patients could manifest a higher frequency of esophagitis and gastroesophageal reflux disease-related symptoms compared to nonceliac patients. In addition, several published studies have consistently shown the efficacy of a gluten-free diet in rapidly controlling esophageal symptoms and in preventing their recurrence. Since the participation of gluten in the esophageal symptoms of CD seems clear, its intimate mechanisms have yet to be elucidated, and several hypothesis have been proposed, including the specific immune alterations characterizing CD, the reduction in nutrient absorption determining the arrival of intact gluten to distal gastrointestinal segments, and various dysregulations in the function of gastrointestinal hormones and peptides. Recent studies have suggested the existence of a possible relationship between CD and eosinophilic esophagitis, which should be more deeply investigated. © 2011 Copyright the Author. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Esophageal foreign bodies and eosinophilic esophagitis--the need for esophageal mucosal biopsy: a 12-year survey across pediatric subspecialties.

PubMed

Williams, Paul; Jameson, Samuel; Bishop, Phyllis; Sawaya, David; Nowicki, Michael

2013-06-01

Esophageal foreign body impaction (EFBI) is a common problem requiring urgent endoscopy. EFBI may be the first sign of underlying esophageal pathology, yet mucosal biopsies are rarely performed. We report a retrospective analysis of 572 children requiring removal of an EFBI over a 12-year period by pediatric otolaryngologists (ENT), surgeons (PS), and gastroenterologists (PGI). The method of removal [direct laryngoscopy (DL), rigid endoscopy (RE), flexible endoscopy (FE)], type of foreign body (inanimate or food), whether mucosal biopsies were performed, and histologic findings of biopsy samples were recorded for each patient. Foreign body removal was most commonly performed by PGI (298 [52 %]); the remaining were equally distributed between ENT (136 [24 %]) and PS (138 [24 %]). The method of foreign body removal used by ENT was RE (89 %), DL (8 %), and FE (3 %). Pediatric surgery preferred FE (62 %), followed by RE (27 %) and DL (11 %). Pediatric gastroenterology used FE exclusively. Esophageal biopsies were never performed by ENT or PS; PGI performed esophageal biopsies more commonly in children with meat bolus impactions (50 %) than in children with inanimate foreign bodies (12 %). Mucosal pathology was more common in children with meat bolus impaction (100 %) than in children with inanimate foreign bodies (45 %). Esophageal mucosal biopsy should be considered for all children with EFBI not attributed to stricture, particularly those with meat bolus impaction.

Etiology and management of esophageal impaction in children: A review of 11 years.

PubMed

Alrazzak, Baraa Alabd; Al-Subu, Awni; Elitsur, Yoram

2013-04-01

Esophageal impaction in children is a medical emergency that needs an immediate medical attention. In the last years multiple objects have been detected and were removed endoscopically. In the last decade, Eosinophilic Esophagitis (EoE) has been associated with esophageal stenosis, leading to esophageal impaction with various objects including toys, food, coins and other. To determine the various objects and symptoms associated with impactions and to develop algorithm that guides Emergency Department Physicians and Primary care Providers when facing such problem in pediatric patient. A retrospective chart review of all children referred to the pediatric gastroenterology service at Marshall University for FB impaction between 2000 and 2010 was performed. Foreign bodies treated by other specialties were excluded from this review. Clinical and demographic data were retrieved. A total of 291 charts with the diagnosis of foreign body reviewed of which only 126 met the inclusion criteria and considered for final calculation. Male/Female ratio and mean age were 1.17:1.0, and 3.65 ± 0.75 years, respectively. Time of impaction before ER evaluation was: < 24hrs in 75 patients, >24hrs in 17 and in 34 the time of ingestion was not known. Radiology was performed in 118 patients, of whom 1 had pneumo-mediastinum and 1 had pneumothorax. Endoscopic localization of the objects showed: 81- proximal, 23- middle esophagus, and 22- in the distal esophagus. The esophageal mucosa showed non-specific changes in 37 patients, 5 with EoE features, 1 patient with hiatal hernia, 1 patient with candidiasis, and in 5 pts had no mucosal description. Children with foreign body in the esophagus are commonly seen in our Hospital ER. Those children may harbor undiagnosed medical conditions that will need future therapy. Careful endoscopic assessment with mucosal biopsies is needed to diagnose those conditions earlier. Referral to a GI specialist may be warranted.

Eosinophilic Esophagitis in Children and Its Relationship with Parental Allergies: Texas Children’s Hospital Experience

PubMed Central

Hiremath, Girish; Byramji, Darius; Pacheco, Ann; Constantine, Greg; Davis, Carla; Shulman, Robert; Olive, Anthony

2016-01-01

Background Eosinophilic esophagitis (EoE) is an allergen mediated, clinicopathological condition affecting all ages. The characteristics of children with EoE in the southwestern United States (U.S.) have not been fully described. Furthermore, very little is known about the relationship between parental allergies and risk of EoE in their offspring in this patient population. Aims To characterize children with EoE, and to examine the relationship between prevalence of parental allergies and occurrence of EoE in their offspring at a single referral pediatric center in southwestern U.S. Methods Demographic and clinical information of 126 children (≤ 18 years of age) with EoE was abstracted in a pre-determined data extraction form and analyzed. The allergy history was collected from biological parents of 61 children (parent-child cluster) with EoE in a standardized questionnaire and analyzed. Results The median age at presentation was 8 years (interquartile range: 4–13). The majority of our patients were male (71%) and Caucasian (59%). Overall, 84% of children reported allergies. Prevalence of food allergy was significantly higher compared to environmental allergies (P=0.001). At least 46% of parents reported allergies. A significantly higher proportion of fathers had developed allergies during their childhood compared to adulthood (P=0.03). Conclusions The characteristics of EoE in our patients were similar to those reported from other parts of the country. Childhood onset of paternal allergies appears to be a risk factor for occurrence of EoE in their offspring. Additional research to elucidate the relationship between parental allergies and occurrence of EoE in their offspring is warranted. PMID:26441283

The 2010-2015 Prevalence of Eosinophilic Esophagitis in the USA: A Population-Based Study.

PubMed

Mansoor, Emad; Cooper, Gregory S

2016-10-01

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder with increasing prevalence. However, epidemiologic data have mostly been acquired from small studies. We sought to describe the epidemiology of EoE in the USA, utilizing a large database. We queried a commercial database (Explorys Inc, Cleveland, OH, USA), an aggregate of electronic health record data from 26 major integrated US healthcare systems from 1999 to July 2015. We identified an aggregated patient cohort of eligible patients with EoE and a history of proton-pump inhibitor use between July 2010 and July 2015, based on Systematized Nomenclature of Medicine-Clinical Terms. We calculated the prevalence of EoE among different patient groups. Of the 30,301,440 individuals in the database, we identified 7840 patients with EoE with an overall prevalence of 25.9/100,000 persons. Prevalence was higher in males than females [odds ratio (OR) 2.00; 95 % CI 1.92-2.10, p < 0.0001], Caucasians versus African-Americans and Asians (OR 2.00; 95 % CI 1.86-2.14, p < 0.0001), and adults (18-65 years) versus elderly (>65 years) and children (<18 years) (OR 1.63; 95 % CI 1.54-1.71, p < 0.0001). Compared with controls (individuals in database without EoE), individuals with EoE were more likely to have other gastrointestinal diagnoses such as dysphagia and at least one allergic condition. In this large study, we found that the estimated prevalence of EoE in the USA is 25.9/100,000, which is at the lower end of prevalence rates reported in the USA and other industrial countries. We confirmed that EoE has a strong association with allergic and gastrointestinal diagnoses.

Gastrointestinal manifestations of cow's milk allergy.

PubMed

Magazzù, Giuseppe; Scoglio, Riccardo

2002-12-01

To review and discuss the relationship between cow's milk allergy (CMA) and some gastrointestinal manifestations, such as gastroesophageal reflux, constipation, food protein-induced enterocolitis, and food-induced eosinophilic proctocolitis, with respect to diagnostic strategies that might eliminate the need for a double-blind, placebo-controlled oral food challenge (DBPCFC). A review of pertinent PubMed articles, published during the past 10 years, was performed. To obtain positive and negative predictive values known as posterior probabilities and to calculate the likelihood ratio, only those studies including both patients and control subjects were selected for analysis. With respect to gastroesophageal reflux, a typical 24-hour esophageal pH monitoring pattern might obviate the performance of a DBPCFC in patients with symptoms of reflux suspected of having CMA, provided this pH pattern is confirmed in other studies. A relationship between CMA and constipation has been reported in only one prospective controlled study; the clinical and laboratory variables of perianal lesions, histologic abnormalities, and signs of hypersensitivity had likelihood ratios of 2.2, 2.4, and 3.7, respectively, and posttest probabilities of 83, 84, and 88%, respectively. Therefore, a DBPCFC is warranted. In reference to food protein-induced enterocolitis, clinical and laboratory criteria suggested in the literature for defining a food challenge as positive have not been prospectively evaluated in the untreated state. Some simple stool tests, such as fecal tumor necrosis factor-alpha and alpha1-antitrypsin determination, might be candidates for diagnostic studies in patients with food protein-induced enterocolitis, if prospectively evaluated. In infants with food-induced eosinophilic proctocolitis, rectal biopsy invariably shows eosinophilic infiltration and thus makes performance of a DBPCFC unnecessary. Although the current diagnosis of gastrointestinal manifestations of CMA usually depends on a DBPCFC, investigators continue to study other options for confirming the diagnosis.

The Application of the Rome IV Criteria to Functional Esophagogastroduodenal Disorders in Asia

PubMed Central

Suzuki, Hidekazu

2017-01-01

The Rome criteria were amended as Rome IV. For functional esophageal disorders, the exclusion criteria have been more specifically revised based on further understanding of other esophageal disorders, including eosinophilic esophagitis and spastic and hypercontractile motor disorders. Another revised point is the more restrictive definition of gastroesophageal reflux disease, indicating that sensitivity to a physiological reflux burden may be placed more firmly within the functional group. For functional dyspepsia (FD), only minor changes were introduced, mainly to improve specificity. Among the major symptoms of FD, not only postprandial fullness, but also epigastric pain, epigastric burning, and early satiation should be “bothersome.” Investigation on the effect of meal ingestion on symptom generation has indicated that not only postprandial fullness and early satiety, but also epigastric pain, epigastric burning sensation and nausea (not vomiting) may increase after meals. Helicobacter pylori infection is considered a possible cause of dyspepsia if successful eradication leads to sustained resolution of symptoms for more than 6 months, and such status can be termed as “H. pylori–associated dyspepsia.” Prompt esophagogastroduodenoscopy and H. pylori testing and treatment would be more beneficial, especially in Asia, which has a high prevalence of gastric cancer. Acotiamide, tandospirone, and rikkunshito are the newly listed as treatment options for FD. For further therapeutic development, clinical studies based on the strict Rome IV criteria should be performed. PMID:28672431

The notch pathway is activated in neoplastic progression in esophageal squamous cell carcinoma.

PubMed

Lubin, Daniel J; Mick, Rosemarie; Shroff, Stuti G; Stashek, Kristen; Furth, Emma E

2018-02-01

The Notch signaling pathway is integral to normal human development and homeostasis and has a deterministic function on cell differentiation. Recent studies suggest aberrant Notch signaling may contribute to neoplastic progression by an increase in stem cell survival, chemoresistance, and the promotion of epithelial-to-mesenchymal transition. The goals of our study were to determine, utilizing quantitative technologies, the expression of activated Notch 1 in esophageal squamous cell carcinoma (SCC) and to determine the relationship between Notch 1 expression and various clinicopathologic parameters. Immunohistochemical staining for Notch intracellular domain (NICD) was performed on 60 consecutive cases of esophageal squamous cell carcinoma, 42 cases of benign esophageal squamous epithelium, and 13 cases of eosinophilic esophagitis diagnosed in our department from 2007 through 2015, and exact nuclear staining and nuclear characteristics were graded using the Vectra imaging system. Clinicopathologic data (gender, age at diagnosis, smoking status, tumor grade, tumor stage, tumor location, and survival) were collected for each SCC case and these were correlated with NICD staining. Cases of esophageal SCC demonstrated significantly higher NICD staining compared to cases of benign and reactive esophageal epithelium (P=.003 and .005, respectively). Among cases of esophageal SCC, nuclear NICD staining was significantly correlated with both tumor grade and stage. Following classification and regression tree analysis, esophageal SCC patients with increased NICD expression were found to be more likely to die from their disease than those with lower levels of expression. Taken together, the findings suggest that increased Notch 1 may contribute to the development and aggressiveness of esophageal SCC. Copyright © 2017 Elsevier Inc. All rights reserved.

HGF/c-MET Pathway in AIDS-Related Lymphoma

DTIC Science & Technology

2016-09-01

including asthma, atopic dermatitis, inflammatory bowel disease, eosinophilic esophagitis and acute lymphoblastic leukemia [15], but it has never been...2000; 356:2160. 9. Gorsky M, Epstein JB. A case series of acquired immunodeficiency syndrome patients with initial neoplastic diagnoses of intraoral...Acquired Immunodeficiency Syndrome (AIDS) pandemic counties of Africa, KS has become one of the commonest cancers affecting men and children with

Differentiating food allergies from food intolerances.

PubMed

Guandalini, Stefano; Newland, Catherine

2011-10-01

Adverse reactions to foods are extremely common, and generally they are attributed to allergy. However, clinical manifestations of various degrees of severity related to ingestion of foods can arise as a result of a number of disorders, only some of which can be defined as allergic, implying an immune mechanism. Recent epidemiological data in North America showed that the prevalence of food allergy in children has increased. The most common food allergens in the United States include egg, milk, peanut, tree nuts, wheat, crustacean shellfish, and soy. This review examines the various forms of food intolerances (immunoglobulin E [IgE] and non-IgE mediated), including celiac disease and gluten sensitivity. Immune mediated reactions can be either IgE mediated or non-IgE mediated. Among the first group, Immediate GI hypersensitivity and oral allergy syndrome are the best described. Often, but not always, IgE-mediated food allergies are entities such as eosinophilic esophagitis and eosinophilic gastroenteropathy. Non IgE-mediated immune mediated food reactions include celiac disease and gluten sensitivity, two increasingly recognized disorders. Finally, non-immune mediated reactions encompass different categories such as disorders of digestion and absorption, inborn errors of metabolism, as well as pharmacological and toxic reactions.

Endoscopic management of esophageal stenosis in children: New and traditional treatments.

PubMed

Dall'Oglio, Luigi; Caldaro, Tamara; Foschia, Francesca; Faraci, Simona; Federici di Abriola, Giovanni; Rea, Francesca; Romeo, Erminia; Torroni, Filippo; Angelino, Giulia; De Angelis, Paola

2016-02-25

Post-esophageal atresia anastomotic strictures and post-corrosive esophagitis are the most frequent types of cicatricial esophageal stricture. Congenital esophageal stenosis has been reported to be a rare but typical disease in children; other pediatric conditions are peptic, eosinophilic esophagitis and dystrophic recessive epidermolysis bullosa strictures. The conservative treatment of esophageal stenosis and strictures (ES) rather than surgery is a well-known strategy for children. Before planning esophageal dilation, the esophageal morphology should be assessed in detail for its length, aspect, number and level, and different conservative strategies should be chosen accordingly. Endoscopic dilators and techniques that involve different adjuvant treatment strategies have been reported and depend on the stricture's etiology, the availability of different tools and the operator's experience and preferences. Balloon and semirigid dilators are the most frequently used tools. No high-quality studies have reported on the differences in the efficacies and rates of complications associated with these two types of dilators. There is no consensus in the literature regarding the frequency of dilations or the diameter that should be achieved. The use of adjuvant treatments has been reported in cases of recalcitrant stenosis or strictures with evidence of dysphagic symptoms. Corticosteroids (either systemically or locally injected), the local application of mitomycin C, diathermy and laser ES sectioning have been reported. Some authors have suggested that stenting can reduce both the number of dilations and the treatment length. In many cases, this strategy is effective when either metallic or plastic stents are utilized. Treatment complications, such esophageal perforations, can be conservatively managed, considering surgery only in cases with severe pleural cavity involvement. In cases of stricture relapse, even if such relapses occur following the execution of well-conducted conservative strategies, surgical stricture resection and anastomosis or esophageal substitution are the only remaining options.

Lack of Knowledge and Low Readiness for Health Care Transition in Eosinophilic Esophagitis and Eosinophilic Gastroenteritis.

PubMed

Eluri, Swathi; Book, Wendy M; Kodroff, Ellyn; Strobel, Mary Jo; Gebhart, Jessica H; Jones, Patricia D; Menard-Katcher, Paul; Ferris, Maria E; Dellon, Evan S

2017-07-01

A growing population of adolescents/young adults with eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE) will need to transition from pediatric to adult health providers. Measuring health care transition (HCT) readiness is critical, but no studies have evaluated this process in EoE/EGE. We determined the scope and predictors of HCT knowledge in patients and parents with EoE/EGE and measured HCT readiness in adolescents/young adults. We conducted an online survey of patients 13 years or older and parents of patients with EoE/EGE who were diagnosed when 25 years or younger. Parents answered questions regarding their children and their own knowledge of HCT. HCT readiness was assessed in adolescents/young adults aged 13 to 25 years with the Self-Management and Transition to Adulthood with Rx Questionnaire (a 6-domain self-report tool) with a score range of 0 to 90. Four hundred fifty participants completed the survey: 205 patients and 245 parents. Included in the analysis (those diagnosed with EoE/EGE at age 25 years or younger) were 75 of 205 patients and children of 245 parent respondents. Overall, 78% (n = 52) of the patients and 76% (n = 187) of parents had no HCT knowledge. Mean HCT readiness score in adolescents/young adults (n = 50) was 30.4 ± 11.3 with higher scores in domains of provider communication and engagement during appointments. Mean parent-reported (n = 123) score was 35.6 ± 9.7 with higher scores in medication management and disease knowledge. There was a significant deficit in HCT knowledge, and HCT readiness scores were lower than other chronic health conditions. HCT preparation and readiness assessments should become a priority for adolescents/young adults with EoE/EGE and their parents.

Genetics of Eosinophilic Esophagitis

DTIC Science & Technology

2011-03-01

cellular content (total cells, left panel, and differential cell counts , right panel) in bronchoalveolar lavage fluid (BALF) in IL-21R-/- mice compared...group (30%) had multiple sensitivities to foods and pollens (GM total IgE 285 IU/ ml). Tests for IgE to carbohydrate antigens were negative in all...those with multiple pollen allergies. The frequent occurrence of multiple associated sensitivities to grains, legumes, molds, and pollens suggests that

Genes Associated with Food Allergy and Eosinophilic Esophagitis

DTIC Science & Technology

2013-11-01

conserved enzymes present not only in lower life forms but also inmammals that can cleave chitin a nat- urally occurring polysaccharide composed of N...acetylglucosamine re- peats [1,2]. Chitin is highly expressed in insects and crustacean exoskeletons, fungal cell walls, and microfilarial nematode...sheaths [3]. Levels of chitin are regulated by enzymes synthesizing chitin (i.e. chitin synthase) or degrading chitin (i.e. chitinases). Although

Utilization of wireless pH monitoring technologies: a summary of the proceedings from the esophageal diagnostic working group.

PubMed

Richter, J E; Pandolfino, J E; Vela, M F; Kahrilas, P J; Lacy, B E; Ganz, R; Dengler, W; Oelschlager, B K; Peters, J; DeVault, K R; Fass, R; Gyawali, C P; Conklin, J; DeMeester, T

2013-01-01

Gastroesophageal reflux disease (GERD) can be difficult to diagnose - symptoms alone are often not enough, and thus, objective testing is often required. GERD is a manifestation of pathologic levels of reflux into the esophagus of acidic, nonacidic, and/or bilious gastric content. However, in our current evidence-based knowledge approach, we only have reasonable outcome data in regards to acid reflux, as this particular type of refluxate predictably causes symptoms and mucosal damage, which improves with medical or surgical therapy. While there are data suggesting that nonacid reflux may be responsible for ongoing symptoms despite acid suppression in some patients, outcome data about this issue are limited. Therefore, this working group believes that it is essential to confirm the presence of acid reflux in patients with 'refractory' GERD symptoms or extraesophageal symptoms thought to be caused by gastroesophageal reflux before an escalation of antireflux therapy is considered. If patients do not have pathologic acid reflux off antisecretory therapy, they are unlikely to have clinically significant nonacid or bile reflux. Patients who do not have pathologic acid gastroesophageal reflux parameters on ambulatory pH monitoring then: (i) could attempt to discontinue antisecretory medications like proton pump inhibitors and H2-receptor antagonists (which are expensive and which carry risks - i.e. C. diff, etc.); (ii) may undergo further evaluation for other causes of their esophageal symptoms (e.g. functional heartburn or chest pain, eosinophilic esophagitis, gastroparesis, achalasia, other esophageal motor disorders); and (iii) can be referred to an ear, nose, and throat/pulmonary/allergy physician for assessment of non-GERD causes of their extraesophageal symptoms. © 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Changing epidemiology of food bolus impaction: is eosinophilic esophagitis to blame?

PubMed

Mahesh, Venkat N; Holloway, Richard H; Nguyen, Nam Quoc

2013-06-01

Data on the relationship between epidemiological changes in food bolus impaction (FBI) and its relationship to eosinophilic esophagitis (EoE) are limited. The aim of this study was to evaluate changes in the prevalence and etiology of FBI at the Royal Adelaide Hospital over 15 years. Details of all patients who presented with FBI to Royal Adelaide Hospital (1996-2010) were reviewed from a prospective database. Detailed endoscopic and histological findings were examined for patients admitted under the Gastroenterology team. From 1996-2010, 539 patients were admitted. Prevalence of FBI increased overtime, with a male preponderance. The age at presentation was significantly lower in 2006-2010 (56.2 ± 1.6 years) compared with 2001-2005 (61.6 ± 1.9 years, P=0.03). There was a reduction in the proportion of patients with peptic-related stricture (from 75% [1996-2000] to 41% [2006-2010] [P<0.001]) and an increase in the prevalence of EoE (from 0% [1996-2000] to 35% [2006-2010], P<0.001). The proportion of patients who had esophageal biopsies taken at the index endoscopy also increased (8% [1996-2000] vs 28% [2001-2005] and 61% [2006-2010], P<0.01). There were no significant changes in rate of malignancy or post-surgical strictures. Endoscopic removal of food bolus was required in 86% of cases and, of these, 98% were successful with no complication or death. The prevalence of FBI has increased over the last 15 years. This was associated with an increased prevalence of EoE and a reduction in age of presentation and peptic-related strictures. These findings suggest that EoE is an important cause of FBI and that esophageal mucosal biopsy should be performed in all cases of FBI. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Emerging dilemmas in the diagnosis and management of gastroesophageal reflux disease

PubMed Central

Kahrilas, Peter; Yadlapati, Rena; Roman, Sabine

2017-01-01

Gastroesophageal reflux disease (GERD) is common, but less so than widely reported because of inconsistencies in definition. In clinical practice, the diagnosis is usually based on a symptom assessment without testing, and the extent of diagnostic testing pursued should be limited to that which guides management or which protects the patient from the risks of a potentially morbid treatment or an undetected early (or imminent) esophageal adenocarcinoma or which does both. When testing is pursued, upper gastrointestinal endoscopy is the most useful initial diagnostic test because it evaluates for the major potential morbidities (Barrett’s, stricture, and cancer) associated with GERD and facilitates the identification of some alternative diagnostic possibilities such as eosinophilic esophagitis. However, endoscopy is insensitive for diagnosing GERD because most patients with GERD have non-erosive reflux disease, a persistent diagnostic dilemma. Although many studies have tried to objectify the diagnosis of GERD with improved technology, this is ultimately a pragmatic diagnosis based on response to proton pump inhibitor (PPI) therapy, and, in the end, response to PPI therapy becomes the major indication for continued PPI therapy. Conversely, in the absence of objective criteria for GERD and the absence of apparent clinical benefit, PPI therapy is not indicated and should be discontinued. PPIs are well tolerated and safe, but nothing is perfectly safe, and in the absence of measurable benefit, even a miniscule risk dominates the risk-benefit assessment. PMID:29034088

Regulation and dysregulation of esophageal peristalsis by the integrated function of circular and longitudinal muscle layers in health and disease.

PubMed

Mittal, Ravinder K

2016-09-01

Muscularis propria throughout the entire gastrointestinal tract including the esophagus is comprised of circular and longitudinal muscle layers. Based on the studies conducted in the colon and the small intestine, for more than a century, it has been debated whether the two muscle layers contract synchronously or reciprocally during the ascending contraction and descending relaxation of the peristaltic reflex. Recent studies in the esophagus and colon prove that the two muscle layers indeed contract and relax together in almost perfect synchrony during ascending contraction and descending relaxation of the peristaltic reflex, respectively. Studies in patients with various types of esophageal motor disorders reveal temporal disassociation between the circular and longitudinal muscle layers. We suggest that the discoordination between the two muscle layers plays a role in the genesis of esophageal symptoms, i.e., dysphagia and esophageal pain. Certain pathologies may selectively target one and not the other muscle layer, e.g., in eosinophilic esophagitis there is a selective dysfunction of the longitudinal muscle layer. In achalasia esophagus, swallows are accompanied by the strong contraction of the longitudinal muscle without circular muscle contraction. The possibility that the discoordination between two muscle layers plays a role in the genesis of esophageal symptoms, i.e., dysphagia and esophageal pain are discussed. The purpose of this review is to summarize the regulation and dysregulation of peristalsis by the coordinated and discoordinated function of circular and longitudinal muscle layers in health and diseased states.

Regulation and dysregulation of esophageal peristalsis by the integrated function of circular and longitudinal muscle layers in health and disease

PubMed Central

2016-01-01

Muscularis propria throughout the entire gastrointestinal tract including the esophagus is comprised of circular and longitudinal muscle layers. Based on the studies conducted in the colon and the small intestine, for more than a century, it has been debated whether the two muscle layers contract synchronously or reciprocally during the ascending contraction and descending relaxation of the peristaltic reflex. Recent studies in the esophagus and colon prove that the two muscle layers indeed contract and relax together in almost perfect synchrony during ascending contraction and descending relaxation of the peristaltic reflex, respectively. Studies in patients with various types of esophageal motor disorders reveal temporal disassociation between the circular and longitudinal muscle layers. We suggest that the discoordination between the two muscle layers plays a role in the genesis of esophageal symptoms, i.e., dysphagia and esophageal pain. Certain pathologies may selectively target one and not the other muscle layer, e.g., in eosinophilic esophagitis there is a selective dysfunction of the longitudinal muscle layer. In achalasia esophagus, swallows are accompanied by the strong contraction of the longitudinal muscle without circular muscle contraction. The possibility that the discoordination between two muscle layers plays a role in the genesis of esophageal symptoms, i.e., dysphagia and esophageal pain are discussed. The purpose of this review is to summarize the regulation and dysregulation of peristalsis by the coordinated and discoordinated function of circular and longitudinal muscle layers in health and diseased states. PMID:27445346

Pathogenesis of Potassium-Competitive Acid Blocker-Resistant Non-Erosive Reflux Disease.

PubMed

Kawami, Noriyuki; Hoshino, Shintaro; Hoshikawa, Yoshimasa; Takenouchi, Nana; Umezawa, Mariko; Hanada, Yuriko; Kaise, Mitsuru; Iwakiri, Katsuhiko

2018-06-05

The present study examined the pathogenesis of potassium-competitive acid blocker (P-CAB)-resistant non-erosive reflux disease (NERD). Forty-three patients with NERD, who had persistent reflux symptoms despite the administration of P-CAB, were included in this study. After excluding eosinophilic esophagitis and primary esophageal motility disorders, esophageal impedance-pH monitoring was performed. In symptom index (SI)-positive patients, the mechanism of SI-positivity and percent time with intragastric pH > 4 and with esophageal pH < 4 were investigated according to the presence or absence of Helicobacter pylori infection. One (2.3%) of 43 patients had a primary esophageal motility disorder (Jackhammer esophagus). Eighteen (41.9%) and 3 (7%) patients were SI-positive for liquid and gas-only reflux, respectively, and the remaining 21 patients who were SI-negative (48.8%) had functional heartburn. All patients SI-positive for liquid reflux were SI-positive for weakly acidic reflux. Gastric acid was sufficiently suppressed by P-CAB, regardless of the presence or absence of H. pylori infection. The pathogenesis of -P-CAB-resistant NERD was elucidated in 51% of patients. Symptoms in all patients SI-positive for liquid reflux were related to weakly acidic reflux, and symptoms related to acid reflux may be ruled out by the administration of P-CAB. © 2018 S. Karger AG, Basel.

Practice Pattern Variation in Pediatric Eosinophilic Esophagitis in the Carolinas EoE Collaborative: A Research Model in Community and Academic Practices.

PubMed

Huang, Kevin Z; Jensen, Elizabeth T; Chen, Hannah X; Landes, Lisa E; McConnell, Kristen A; Almond, M Angie; Johnston, Douglas T; Durban, Raquel; Jobe, Laura; Frost, Carrie; Donnelly, Sarah; Antonio, Brady; Safta, Anca M; Quiros, J Antonio; Markowitz, Jonathan E; Dellon, Evan S

2018-06-01

Differences in the initial management of pediatric eosinophilic esophagitis (EoE) by practice setting have not been well characterized. We aimed to characterize these differences for sites in the Carolinas EoE Collaborative (CEoEC), a multicenter network of academic and community practices. We performed a retrospective cohort study of pediatric EoE patients at five CEoEC sites: University of North Carolina (UNC) Hospital, Charlotte Asthma and Allergy Specialists, Greenville Health Systems, Wake Forest Baptist Medical Center, and the Medical University of South Carolina Hospital. Cases of EoE were defined by consensus guidelines. Data were extracted from electronic medical records. We tested for differences among sites and used a multinomial model (polytomous regression) to assess associations between treatment and site, adjusting on patient factors. We identified 464 children with EoE across the CEoEC sites. The median age was highest at Wake Forest (11.4 years), the median eosinophil count was highest at UNC (69 eos/hpf), and UNC had the most male patients (82%). UNC used topical steroids for initial treatment in 86% of cases, compared with <1% in Greenville ( P < 0.01). Greenville used dietary elimination more frequently than UNC (81% vs 2%, P < 0.01). Differences in treatment approach held after adjusting for potential baseline confounders. There was no significant association between patient factors and initial treatment approach. Significant differences in EoE patient factors and treatment approaches were identified across CEoEC sites and were not explained by patient or practice factors. This suggests that institutional or provider preferences drive initial treatment approaches, and that more data are needed to drive best practice decisions.

Genetics of Eosinophilic Esophagitis

DTIC Science & Technology

2012-03-01

cells, left panel, and differential cell counts , right panel) in bronchoalveolar lavage fluid (BALF) in IL- 21R-/- mice compared to wild-type (WT). A...positive skin tests. A third group (30%) had multiple sensitivities to foods and pollens (GM total IgE 285 IU/ ml). Tests for IgE to carbohydrate antigens...milk sensitized, and those with multiple pollen allergies. The frequent occurrence of multiple associated sensitivities to grains, legumes, molds, and

Development of a Novel Treatment for Food Allergy Using a New Genetically Defined Mouse Model of the Disease

DTIC Science & Technology

2012-07-01

peanut allergy, and whether treatment with losartan , an angiotensin II (ATII) receptor blocker that inhibits TGFbeta signaling, reduces the development...increased effector responses, or both. We will also examine how treatment with losartan modifies the allergic phenotype in LDS mice. 15...SUBJECT TERMS Loeys Dietz Syndrome, food allergy, eosinophilic esophagitis, anaphylaxis, TGFbeta, losartan 16. SECURITY CLASSIFICATION OF: 17

Physical and Chemical Stability of Budesonide Mucoadhesive Oral Suspensions (MucoLox).

PubMed

Ip, Kendice; Carvalho, Maria; Shan, Ashley; Banov, Daniel

2017-01-01

Budesonide is a corticosteroid that has been shown effective in the treatment of eosinophilic esophagitis, but there are currently no commercial medicines to treat this chronic allergic/immune condition, despite its prevalence in the U.S. Therefore, pharmaceutical compounding is the alternative choice to meet the therapeutic need of eosinophilic esophagitis patients. Two budesonide mucoadhesive oral suspensions (1 mg/10 mL and 2 mg/10 mL) were developed using the compounding vehicle MucoLox, a proprietary mucoadhesive polymer blend that promotes mucosal adhesion. The physical and chemical stability of the oral suspensions was tested over a period of 182 days, at room temperature and refrigerated conditions, in order to determine the corresponding beyond-use date. The physical characterization consisted in observing all samples for color/appearance and odor, and testing for pH and density, whereas the chemical characterization consisted in ultra-performance liquid chromatography assay testing. Both oral suspensions were proven physically and chemically stable, and the ultra-performance liquid chromatography method was proven stability indicating. As a result, the beyond-use date of the budesonide 1-mg/10-mL and 2-mg/10-mL mucoadhesive oral suspensions (MucoLox), in amber plastic bottles, is six months at both room temperature and refrigerated conditions. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Eosinophilic Endotype of Asthma.

PubMed

Aleman, Fernando; Lim, Hui Fang; Nair, Parameswaran

2016-08-01

Asthma is a heterogeneous disease that can be classified into different clinical endotypes, depending on the type of airway inflammation, clinical severity, and response to treatment. This article focuses on the eosinophilic endotype of asthma, which is defined by the central role that eosinophils play in the pathophysiology of the condition. It is characterized by elevated sputum and/or blood eosinophils on at least 2 occasions and by a significant response to treatments that suppress eosinophilia. Histopathologic demonstration of eosinophils in the airways provides the most direct diagnosis of eosinophilic asthma; but it is invasive, thus, impractical in clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD).

PubMed

Khoury, Paneez; Akuthota, Praveen; Ackerman, Steven J; Arron, Joseph R; Bochner, Bruce S; Collins, Margaret H; Kahn, Jean-Emmanuel; Fulkerson, Patricia C; Gleich, Gerald J; Gopal-Srivastava, Rashmi; Jacobsen, Elizabeth A; Leiferman, Kristen M; Francesca, Levi-Schaffer; Mathur, Sameer K; Minnicozzi, Michael; Prussin, Calman; Rothenberg, Marc E; Roufosse, Florence; Sable, Kathleen; Simon, Dagmar; Simon, Hans-Uwe; Spencer, Lisa A; Steinfeld, Jonathan; Wardlaw, Andrew J; Wechsler, Michael E; Weller, Peter F; Klion, Amy D

2018-04-19

Eosinophil-associated diseases (EADs) are rare, heterogeneous disorders characterized by the presence of eosinophils in tissues and/or peripheral blood resulting in immunopathology. The heterogeneity of tissue involvement, lack of sufficient animal models, technical challenges in working with eosinophils, and lack of standardized histopathologic approaches have hampered progress in basic research. Additionally, clinical trials and drug development for rare EADs are limited by the lack of primary and surrogate endpoints, biomarkers, and validated patient-reported outcomes. Researchers with expertise in eosinophil biology and eosinophil-related diseases reviewed the state of current eosinophil research, resources, progress, and unmet needs in the field since the 2012 meeting of the NIH Taskforce on the Research of Eosinophil-Associated Diseases (TREAD). RE-TREAD focused on gaps in basic science, translational, and clinical research on eosinophils and eosinophil-related pathogenesis. Improved recapitulation of human eosinophil biology and pathogenesis in murine models was felt to be of importance. Characterization of eosinophil phenotypes, the role of eosinophil subsets in tissues, identification of biomarkers of eosinophil activation and tissue load, and a better understanding of the role of eosinophils in human disease were prioritized. Finally, an unmet need for tools for use in clinical trials was emphasized. Histopathologic scoring, patient- and clinician-reported outcomes, and appropriate coding were deemed of paramount importance for research collaborations, drug development, and approval by regulatory agencies. Further exploration of the eosinophil genome, epigenome, and proteome was also encouraged. Although progress has been made since 2012, unmet needs in eosinophil research remain a priority. ©2018 Society for Leukocyte Biology.

Genetics Home Reference: eosinophil peroxidase deficiency

MedlinePlus

... an Eosinophil? International Eosinophil Society, Inc.: Patient Support Groups Rare Disease Clinical Research Network: Consortium of Eosinophil Gastrointestinal Disease Researchers Scientific Articles ...

Temporal trends in the relative prevalence of dysphagia etiologies from 1999-2009

PubMed Central

Kidambi, Trilokesh; Toto, Erin; Ho, Nancy; Taft, Tiffany; Hirano, Ikuo

2012-01-01

AIM: To examine the relative prevalence and temporal variation of dysphagia etiologies in patients undergoing upper endoscopy (EGD) over the past decade. METHODS: EGDs with the indication of dysphagia at an urban, university medical center in 1999, 2004 and 2009 were retrospectively identified from the electronic medical record. The entire patient chart, including EGD, pathology, manometry, radiographic and clinician reports, was reviewed for demographic and clinical data and to determine the etiology of dysphagia. The number of EGDs in which an esophageal biopsy was performed was also noted. Gastroesophageal reflux disease (GERD) as a cause of dysphagia independent of peptic stricture was defined by symptoms with erosive esophagitis or symptom response to proton pump inhibition (PPI). Cases of eosinophilic esophagitis (EoE) were defined by an appropriate clinical history and histological criteria of ≥ 15 eosinophils per high powered field. PPI-responsive esophageal eosinophilia was not routinely reported prior to 2008. Statistical analysis was performed using one-way analysis of variance to analyze for trends between 1999, 2004 and 2009 and a post-hoc Tukey analysis was performed following a significant main effect. RESULTS: A total of 1371 cases (mean age 54 years, 43% male) met pre-specified inclusion criteria with 191, 504 and 675 cases in 1999, 2004 and 2009, respectively. Patients were older in 2004 compared to 2009 (mean ± SD, 54.0 ± 15.7 years vs 52.3 ± 16.8 years, P = 0.02) and there were more males in 1999 compared to 2004 (57.5% vs 40.8%, P = 0.005). Overall, GERD (27.6%) and EoE (7.7%) were the most common identifiable causes of dysphagia. An unspecified diagnosis accounted for 21% of overall cases. There were no significant differences in the relative prevalence of achalasia or other motility disorders, peptic stricture, Schatzki’s ring, esophageal cancer or unspecified diagnoses over the 10-year time period. There was, however, a decrease in the relative prevalence of GERD (39.3% vs 24.1%, P < 0.001) and increases in the relative prevalence of EoE (1.6% vs 11.2%, P < 0.001) and oropharyngeal disorders (1.6% vs 4.2%, P = 0.02) from 1999 to 2009. Post-hoc analyses determined that the increase in relative prevalence of EoE was significant between 1999 and 2009 as well as 2004 and 2009 (5.4% vs 11.6%, P < 0.001), but not between 1999 and 2004 (1.6% P 5.4%, P = 0.21). On the other hand, the decrease in relative prevalence of GERD was significant between 1999 and 2009 and 1999 and 2004 (39.3% vs 27.7%, P = 0.006), but not between 2004 and 2009 (27.7% vs 24.1%, P = 0.36). There were also significantly more EGDs in which a biopsy was obtained in 1999 compared to 2009 (36.7% vs 68.7%, P < 0.001) as well as between 2004 and 2009 (37.5% vs 68.7%, P < 0.001). While total EGD volume did increase over the 10-year time period, the percentage of EGDs for the indication of dysphagia remained stable making increasing upper endoscopy an unlikely reason for the observed increased prevalence of EoE. CONCLUSION: EoE has emerged as a dominant cause of dysphagia in adults. Whether this was due to a rise in disease incidence or increased recognition is unclear. PMID:22969196

Temporal trends in the relative prevalence of dysphagia etiologies from 1999-2009.

PubMed

Kidambi, Trilokesh; Toto, Erin; Ho, Nancy; Taft, Tiffany; Hirano, Ikuo

2012-08-28

To examine the relative prevalence and temporal variation of dysphagia etiologies in patients undergoing upper endoscopy (EGD) over the past decade. EGDs with the indication of dysphagia at an urban, university medical center in 1999, 2004 and 2009 were retrospectively identified from the electronic medical record. The entire patient chart, including EGD, pathology, manometry, radiographic and clinician reports, was reviewed for demographic and clinical data and to determine the etiology of dysphagia. The number of EGDs in which an esophageal biopsy was performed was also noted. Gastroesophageal reflux disease (GERD) as a cause of dysphagia independent of peptic stricture was defined by symptoms with erosive esophagitis or symptom response to proton pump inhibition (PPI). Cases of eosinophilic esophagitis (EoE) were defined by an appropriate clinical history and histological criteria of ≥ 15 eosinophils per high powered field. PPI-responsive esophageal eosinophilia was not routinely reported prior to 2008. Statistical analysis was performed using one-way analysis of variance to analyze for trends between 1999, 2004 and 2009 and a post-hoc Tukey analysis was performed following a significant main effect. A total of 1371 cases (mean age 54 years, 43% male) met pre-specified inclusion criteria with 191, 504 and 675 cases in 1999, 2004 and 2009, respectively. Patients were older in 2004 compared to 2009 (mean ± SD, 54.0 ± 15.7 years vs 52.3 ± 16.8 years, P = 0.02) and there were more males in 1999 compared to 2004 (57.5% vs 40.8%, P = 0.005). Overall, GERD (27.6%) and EoE (7.7%) were the most common identifiable causes of dysphagia. An unspecified diagnosis accounted for 21% of overall cases. There were no significant differences in the relative prevalence of achalasia or other motility disorders, peptic stricture, Schatzki's ring, esophageal cancer or unspecified diagnoses over the 10-year time period. There was, however, a decrease in the relative prevalence of GERD (39.3% vs 24.1%, P < 0.001) and increases in the relative prevalence of EoE (1.6% vs 11.2%, P < 0.001) and oropharyngeal disorders (1.6% vs 4.2%, P = 0.02) from 1999 to 2009. Post-hoc analyses determined that the increase in relative prevalence of EoE was significant between 1999 and 2009 as well as 2004 and 2009 (5.4% vs 11.6%, P < 0.001), but not between 1999 and 2004 (1.6% P 5.4%, P = 0.21). On the other hand, the decrease in relative prevalence of GERD was significant between 1999 and 2009 and 1999 and 2004 (39.3% vs 27.7%, P = 0.006), but not between 2004 and 2009 (27.7% vs 24.1%, P = 0.36). There were also significantly more EGDs in which a biopsy was obtained in 1999 compared to 2009 (36.7% vs 68.7%, P < 0.001) as well as between 2004 and 2009 (37.5% vs 68.7%, P < 0.001). While total EGD volume did increase over the 10-year time period, the percentage of EGDs for the indication of dysphagia remained stable making increasing upper endoscopy an unlikely reason for the observed increased prevalence of EoE. EoE has emerged as a dominant cause of dysphagia in adults. Whether this was due to a rise in disease incidence or increased recognition is unclear.

TGF-Beta Gene Polymorphisms in Food Allergic versus Non-Food Allergic Eosinophilic Esophagitis

DTIC Science & Technology

2014-12-01

past reports, the majority of our EE subjects are male, Caucasian, and have another atopic disorder (asthma, allergy, eczema and/or food allergy...or skin prick testing positive Table 2: Co-existent Allergic Characteristics of Pediatric EoE Population Asthma (%) Allergic Rhinitis (%) Eczema ...Consistent with high rates of atopy in the EoE population, 36% had asthma, 53% had allergic rhinitis, 43% had eczema , and 42% had a an immediate

Development and Validation of a Symptom-Based Activity Index for Adults with Eosinophilic Esophagitis

PubMed Central

Schoepfer, Alain M.; Straumann, Alex; Panczak, Radoslaw; Coslovsky, Michael; Kuehni, Claudia E.; Maurer, Elisabeth; Haas, Nadine A.; Romero, Yvonne; Hirano, Ikuo; Alexander, Jeffrey A.; Gonsalves, Nirmala; Furuta, Glenn T.; Dellon, Evan S.; Leung, John; Collins, Margaret H.; Bussmann, Christian; Netzer, Peter; Gupta, Sandeep K.; Aceves, Seema S.; Chehade, Mirna; Moawad, Fouad J.; Enders, Felicity T.; Yost, Kathleen J.; Taft, Tiffany H.; Kern, Emily; Zwahlen, Marcel; Safroneeva, Ekaterina

2015-01-01

BACKGROUND & AIMS Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE), to provide endpoints for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patients’ assessments of disease severity. We also evaluated relationships between patients’ assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings. METHODS We collected information from 186 patients with EoE in Switzerland and the US (69.4% male; median age, 43 years) via surveys (n = 135), focus groups (n = 27), and semi-structured interviews (n = 24). Items were generated for the instruments to assess biologic activity based on physician input. Linear regression was used to quantify the extent to which variations in patient-reported disease characteristics could account for variations in patients’ assessment of EoE severity. The PRO instrument was prospectively used in 153 adult patients with EoE (72.5% male; median age, 38 years), and validated in an independent group of 120 patients with EoE (60.8% male; median age, 40.5 years). RESULTS Seven PRO factors that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia, and pain while swallowing accounted for 67% of the variation in patients’ assessment of disease severity. Based on statistical consideration and patient input, a 7-day recall period was selected. Highly active EoE, based on endoscopic and histologic findings, was associated with an increase in patient-assessed disease severity. In the validation study, the mean difference between patient assessment of EoE severity and PRO score was 0.13 (on a scale from 0 to 10). CONCLUSIONS We developed and validated an EoE scoring system based on 7 PRO items that assesses symptoms over a 7-day recall period. Clinicaltrials.gov number: NCT00939263. PMID:25160980

Randomized controlled trial comparing esophageal dilation to no dilation among adults with esophageal eosinophilia and dysphagia.

PubMed

Kavitt, R T; Ates, F; Slaughter, J C; Higginbotham, T; Shepherd, B D; Sumner, E L; Vaezi, M F

2016-11-01

The role of esophageal dilation in patients with esophageal eosinophilia with dysphagia remains unknown. The practice of dilation is currently based on center preferences and expert opinion. The aim of this study is to determine if, and to what extent, dysphagia improves in response to initial esophageal dilation followed by standard medical therapies. We conducted a randomized, blinded, controlled trial evaluating adult patients with dysphagia and newly diagnosed esophageal eosinophilia from 2008 to 2013. Patients were randomized to dilation or no dilation at time of endoscopy and blinded to dilation status. Endoscopic features were graded as major and minor. Subsequent to randomization and endoscopy, all patients received fluticasone and dexlansoprazole for 2 months. The primary study outcome was reduction in overall dysphagia score, assessed at 30 and 60 days post-intervention. Patients with severe strictures (less than 7-mm esophageal diameter) were excluded from the study. Thirty-one patients were randomized and completed the protocol: 17 randomized to dilation and 14 to no dilation. Both groups were similar with regard to gender, age, eosinophil density, endoscopic score, and baseline dysphagia score. The population exhibited moderate to severe dysphagia and moderate esophageal stricturing at baseline. Overall, there was a significant (P < 0.001) but similar reduction in mean dysphagia score at 30 and 60 days post-randomization compared with baseline in both groups. No significant difference in dysphagia scores between treatment groups after 30 (P = 0.93) or 60 (P = 0.21) days post-intervention was observed. Esophageal dilation did not result in additional improvement in dysphagia score compared with treatment with proton pump inhibitor and fluticasone alone. In patients with symptomatic esophageal eosinophilia without severe stricture, dilation does not appear to be a necessary initial treatment strategy. © 2015 International Society for Diseases of the Esophagus.

Exploration into the Genetics of Food Allergy

DTIC Science & Technology

2012-10-01

3. Green PH, Cellier C. Celiac disease . N Engl J Med 2007; 357:1731-43. 4. Cohen BL, Noone S, Munoz-Furlong A, Sicherer SH. Development of a...Eosinophilic Esophagitis, a non-IgE mediated disease . This work has examined the genetics of food allergy looking at both IgE and non-IgE mediated...atopic dermatitis to another. The understanding that genetics play a role in allergic disease and asthma has been recognized for more than 100

Development of a Novel Treatment for Food Allergy Using a New Genetically Defined Mouse Model of the Disease

DTIC Science & Technology

2013-07-01

goals of this proposal are to examine whether LDS mice are more susceptible to developing peanut allergy, and whether treatment with losartan , an...eosinophilic esophagitis, anaphylaxis, TGFbeta, losartan 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME...susceptible to developing peanut allergy, and whether allergic disease in LDS mice can be prevented or improved by treatment with losartan . Losartan is

Eosinophilic leukocytoclastic vasculitis - a spectrum ranging from Wells' syndrome to Churg-Strauss syndrome?

PubMed

Ratzinger, Gudrun; Zankl, Julia; Eisendle, Klaus; Zelger, Bernhard

2014-01-01

Wells' syndrome is defined as an inflammatory disorder with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Eosinophilic leukocytoclastic vasculitis shows eosinophilic infiltrates in combination with vasculitic changes. And Churg Strauss Syndrome comprises all three characteristics - eosinophilic infiltrates, vasculitis and flame figures. To determine whether these three diseases are distinct entities or different manifestations of a similar clinicopathologic process. Histopathological samples and clinical courses of 17 patients with eosinophilic infiltrates, flame figures and clinical features of Wells' syndrome were re-evaluated. Histopathologically, we focused on the presence or absence of vasculitic features. Clinically, we included only patients who were diagnosed with Wells' syndrome at least once in the course of their disease. 4 patients were finally diagnosed with Wells' syndrome, 5 with eosinophilic leukocytoclastic vasculitis and 6 with Churg Strauss syndrome. Further, we had one case of an overlap between Wells' syndrome and eosinophilic vasculitis and one case of Wegener granulomatosis. Vasculitic features were found in the samples of all patients. Histologically, we find vasculitic features in typical presentations of Wells' syndrome. Clinically, we find typical features of Wells' syndrome in patients finally diagnosed with eosinophilic leukocytoclastic vasculitis or Churg Strauss syndrome. Furthermore, we have observed and formerly reported 3 patients with progression from Wells' syndrome to Churg Strauss syndrome. Thus, we assume that eosinophilic leukocytoclastic vasculitis might form a bridge between Wells' syndrome and Churg Strauss syndrome.

Health care resource utilization and characteristics of patients with eosinophilic asthma in secondary health care in Finland.

PubMed

Mäkelä, Mika J; Christensen, Helene Nordahl; Karlsson, Antti; Rastogi, Sarang; Kettunen, Kirsi

2018-01-01

Background : Eosinophilic airway inflammation is common in asthma patients and appears to be associated with severe exacerbations and loss of asthma control. Objective : To describe the resource utilization and clinical characteristics of patients with eosinophilic asthma. Design : Asthma patients ≥18 years with ≥1 blood eosinophil count in secondary care (South West Finland) during 2003‒2013 were included. Clinical characteristics (age, lung function, body mass index, and comorbidities) and asthma-related resource utilization (hospital admissions, outpatient visits, and emergency room [ER] visits) were retrieved. Resource utilization rates were compared for patients with blood eosinophil ≤ or >300 cells/μL, using adjusted negative binomial regression models. Results : Overall, 4,357 eligible patients were identified (mean age 60 years, females 68%), of which 1,927 (44%) had >300 eosinophil cells/μL blood. Patients with ≤300 and >300 eosinophil counts, exhibited similar clinical characteristics, including advanced age, poor lung function, and overweight. Comorbidities such as pneumonia, sinusitis, and nasal polyps, were more frequent among those with >300 eosinophil cells/μL blood compared with patients with lower counts. Eosinophil counts >300 cells/μL were associated with greater hospital admissions (rate ratio [RR] [95% confidence interval CI]: 1.13 [1.02;1.24]) and outpatient visits (RR [95% CI]: 1.11 [1.03;1.20]) compared with patients with lower eosinophil counts. Rates of ER visits were similar between the patient groups (RR [95% CI]: 0.99 [0.87;1.12]). Conclusions : Hospital admissions and outpatient visits occurred more often for patients with eosinophil counts >300 cells/µL, than for patients with lower eosinophil counts. Routine blood eosinophil screening might be useful to identify patients with an eosinophilic phenotype eligible for more targeted treatments.

CT-assessed large airway involvement and lung function decline in eosinophilic asthma: The association between induced sputum eosinophil differential counts and airway remodeling.

PubMed

Inoue, Hideki; Ito, Isao; Niimi, Akio; Matsumoto, Hisako; Matsuoka, Hirofumi; Jinnai, Makiko; Takeda, Tomoshi; Oguma, Tsuyoshi; Otsuka, Kojiro; Nakaji, Hitoshi; Tajiri, Tomoko; Iwata, Toshiyuki; Nagasaki, Tadao; Kanemitsu, Yoshihiro; Mishima, Michiaki

2016-11-01

Eosinophilic asthma (EA) is a distinct clinical phenotype characterized by eosinophilic airway inflammation and airway remodeling. Few studies have used computed tomography (CT) scanning to assess the association between sputum eosinophil differential counts and airway involvement. We aimed to investigate the clinical characteristics and airway involvement of EA, and to examine the correlation between induced sputum eosinophil differential counts and CT-assessed airway remodeling. We retrospectively divided 63 patients with stable asthma receiving inhaled corticosteroids into 2 groups: 26 patients with EA (sputum eosinophil >3%) and 37 patients with non-eosinophilic asthma (NEA). Clinical measurements such as spirometry, fractional exhaled nitric oxide levels (FeNO), and CT-assessed indices of airway involvement were compared between the groups. Multivariate analysis was performed to identify determinants of the percentage of wall area (WA%). The EA group had significantly longer asthma duration, lower pulmonary function, and higher FeNO than the NEA group. Also, the EA group had higher WA% and smaller airway luminal area than the NEA group. Sputum eosinophil differential counts and WA% were positively correlated. The multivariate linear regression analysis showed that the factors associated with WA% included sputum eosinophil differential counts, age, and body mass index. However, asthma duration was not associated with WA%. Our CT-assessed findings demonstrated large airway involvement in EA, and we observed a positive association between induced sputum eosinophil differential counts and WA%. The findings indicate that induced sputum eosinophil differential counts may be associated with airway remodeling in patients with stable asthma.

Utility of a non-invasive serum biomarker panel for diagnosis and monitoring of eosinophilic esophagitis: A prospective study

PubMed Central

Dellon, Evan S.; Rusin, Spencer; Gebhart, Jessica H.; Covey, Shannon; Higgins, Leana L.; Beitia, RoseMary; Speck, Olga; Woodward, Kimberly; Woosley, John T.; Shaheen, Nicholas J.

2015-01-01

Objectives Non-invasive biomarkers would be valuable for diagnosis and monitoring of eosinophilic esophagitis (EoE). The aim of this study was to determine the utility of a panel of serum biomarkers for the diagnosis and management of EoE. Methods We conducted a prospective cohort study of consecutive adults undergoing outpatient EGD. Incident cases of EoE were diagnosed per consensus guidelines; controls had GERD or dysphagia and did not meet EoE criteria. EoE cases were treated with topical steroids and had repeat endoscopy. Pre- and post-treatment serum samples were analyzed in a blinded fashion for: IL-4, IL-5, IL-6, IL-9, IL-13, TGF-α, TGF-β, TNF-α, eotaxin-1, -2, and -3, TSLP, major basic protein (MBP), and eosinophil-derived neurotoxin (EDN). Cases and controls were compared at baseline, and pre- and post-treatment assays were compared in cases. Results A total of 61 incident EoE cases and 87 controls were enrolled; 51 EoE cases had post-treatment serum analyzed. There were no significant differences in any of the biomarkers between EoE cases and controls at baseline. IL-13 and eotaxin-3 for cases and controls were 85 ±160 vs 43 ±161 pg/mL (p=0.12), and 41 ±159 vs 21 ±73 (p=0.30). There were no significant differences in assay values among cases before and after treatment. There were also no differences after stratification by atopic status or treatment response. Conclusions A panel of inflammatory factors known to be associated with EoE pathogenesis were not increased in the serum, nor were they responsive to therapy. None of these biomarkers are likely candidates for a serum test for EoE. Histologic analysis for diagnosis and management of EoE continues to be necessary, and novel, less invasive, biomarkers are needed. PMID:25781367

Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2-4-6 study.

PubMed

Molina-Infante, Javier; Arias, Ángel; Alcedo, Javier; Garcia-Romero, Ruth; Casabona-Frances, Sergio; Prieto-Garcia, Alicia; Modolell, Ines; Gonzalez-Cordero, Pedro L; Perez-Martinez, Isabel; Martin-Lorente, Jose Luis; Guarner-Argente, Carlos; Masiques, Maria L; Vila-Miravet, Victor; Garcia-Puig, Roger; Savarino, Edoardo; Sanchez-Vegazo, Carlos Teruel; Santander, Cecilio; Lucendo, Alfredo J

2018-04-01

Numerous dietary restrictions and endoscopies limit the implementation of empiric elimination diets in patients with eosinophilic esophagitis (EoE). Milk and wheat/gluten are the most common food triggers. We sought to assess the effectiveness of a step-up dietary strategy for EoE. We performed a prospective study conducted in 14 centers. Patients underwent a 6-week 2-food-group elimination diet (TFGED; milk and gluten-containing cereals). Remission was defined by symptom improvement and less than 15 eosinophils/high-power field. Nonresponders were gradually offered a 4-food-group elimination diet (FFGED; TFGED plus egg and legumes) and a 6-food-group elimination diet (SFGED; FFGED plus nuts and fish/seafood). In responders eliminated food groups were reintroduced individually, followed by endoscopy. One hundred thirty patients (25 pediatric patients) were enrolled, with 97 completing all phases of the study. A TFGED achieved EoE remission in 56 (43%) patients, with no differences between ages. Food triggers in TFGED responders were milk (52%), gluten-containing grains (16%), and both (28%). EoE induced only by milk was present in 18% and 33% of adults and children, respectively. Remission rates with FFGEDs and SFGEDs were 60% and 79%, with increasing food triggers, especially after an SFGED. Overall, 55 (91.6%) of 60 of the TFGED/FFGED responders had 1 or 2 food triggers. Compared with the initial SFGED, a step-up strategy reduced endoscopic procedures and diagnostic process time by 20%. A TFGED diet achieves EoE remission in 43% of children and adults. A step-up approach results in early identification of a majority of responders to an empiric diet with few food triggers, avoiding unnecessary dietary restrictions, saving endoscopies, and shortening the diagnostic process. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Correlation of total serum immunoglobulin E level, sputum, and peripheral eosinophil count in assessing the clinical severity in bronchial asthma.

PubMed

Kumar, Roshan M; Pajanivel, R; Koteeswaran, G; Menon, Surendra K; Charles, Pravin Mv

2017-01-01

Asthma is a chronic inflammatory disorder of the airway with involvement of various cellular populations and release of many inflammatory mediators. Eosinophils and serum immunoglobulin E (IgE) are considered a good marker of airway inflammation in asthma. The correlation of clinical assessment with various markers of airway inflammation in asthma is not well established in the Indian population. This study aims to study the correlation of serum IgE, sputum eosinophil count, and peripheral eosinophil count with clinical severity of Asthma. This is a cross-sectional study involving 76 stable asthmatic patients of 18-60 years of age attending the pulmonary medicine OPD. Spirometry measured at baseline. Participants were categorized according to the GINA criteria based on clinical symptoms and pulmonary function test. Blood samples were collected for peripheral eosinophil count, serum IgE levels, and sputum samples for eosinophil count. All three parameters were compared with severity of asthma. The correlation of sputum eosinophil count, peripheral eosinophil count, and serum IgE with severity of asthma was analyzed by Pearson's Chi-square test, Fisher's exact test, and the correlation coefficient was reported together with standard error of the estimate. The mean age of patients in our study was 37.42 years and 56.6% were male. There was a significant inverse correlation between serum IgE levels and predicted forced expiratory volume 1 s (FEV1). Sputum eosinophilia was significantly seen in severe persistent asthma patients (19.7%). There was a significant inverse correlation between sputum eosinophil count and predicted FEV1and forced vital capacity. We also found there was a significant association between peripheral eosinophil count, sputum eosinophil count, and elevated serum IgE (g100 IU/mL) with severe persistent asthma. The assessment of sputum eosinophil count is simple, inexpensive, noninvasive, and direct measurement of airway inflammation. It could be the preferred method in monitoring airway inflammation and guided management in day-to-day practice.

Most children with eosinophilic esophagitis have a favorable outcome as young adults.

PubMed

Bohm, M; Jacobs, J W; Gupta, A; Gupta, S; Wo, J M

2017-01-01

The disease progression of eosinophilic esophagitis (EoE) from childhood into adulthood is unclear. To determine the clinical outcome of patients who were diagnosed with EoE as children, and who now are young adults. Children (<18 years old) diagnosed with EoE were enrolled in a prospective registry on demographics, presenting symptoms, and endoscopic/histologic findings. Subjects who now are adults (≥18 years old) were identified, and a structured telephone interview was conducted to obtain follow-up data on symptom prevalence (dysphagia to solids and liquids, nausea/vomiting, abdominal pain, and heartburn/regurgitation), food impaction, medication usage, health-care utilization, and resolution of atopy/food allergies. A favorable outcome was defined if EoE symptoms were resolved or improved by subjects' assessment. Unfavorable outcomes was defined as symptoms same or worse. Clinical variables that predicted a favorable outcome as an adult were examined. Mayo Dysphagia Scale (MDQ-30: scored 0-100) was administered to validate the outcome assessment. Mantel-Haenszel odds ratio and unpaired t-test were used. Fifty-eight subjects (64% male) who met study criteria were enrolled. Mean age at diagnosis was 12 years (range 4-17) and mean duration of follow-up was 8.3 years (2-16). As children, the most common presenting symptoms were abdominal pain (54%), dysphagia (33%), and vomiting (24%). As young adults, 47 subjects (81%) had a favorable outcome. Total MDQ-30 scores were 4.6 (0-30) and 14.1 (0-50) in subjects with favorable outcome and unfavorable outcome, respectively (P = 0.015). Two-thirds of subjects did not use steroids or proton pump inhibitors in the preceeding 12 months. Male children with EoE were four times more likely to have a favorable outcome as young adults compared with female children. Females were more likely to report nausea/vomiting as young adults (odds ratio 3.23, CI 0.97-10.60). Of all presenting symptoms in EoE children, dysphagia was the most likely to persist into adulthood (odds ratio 6.29, CI 1.85-21.38). Eighty one percent of EoE children had a favorable outcome as young adults. Most patients with symptom resolution did not require any form of steroid therapy or seek healthcare. © 2016 International Society for Diseases of the Esophagus.

Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort.

PubMed

Hastie, Annette T; Martinez, Fernando J; Curtis, Jeffrey L; Doerschuk, Claire M; Hansel, Nadia N; Christenson, Stephanie; Putcha, Nirupama; Ortega, Victor E; Li, Xingnan; Barr, R Graham; Carretta, Elizabeth E; Couper, David J; Cooper, Christopher B; Hoffman, Eric A; Kanner, Richard E; Kleerup, Eric; O'Neal, Wanda K; Paine, Richard; Peters, Stephen P; Alexis, Neil E; Woodruff, Prescott G; Han, MeiLan K; Meyers, Deborah A; Bleecker, Eugene R

2017-12-01

Increased concentrations of eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with increased frequency of exacerbations, reduced lung function, and corticosteroid responsiveness. We aimed to assess whether high eosinophil concentrations in either sputum or blood are associated with a severe COPD phenotype, including greater exacerbation frequency, and whether blood eosinophils are predictive of sputum eosinophils. We did a multicentre observational study analysing comprehensive baseline data from SPIROMICS in patients with COPD aged 40-80 years who had a smoking history of at least 20 pack-years, recruited from six clinical sites and additional subsites in the USA between Nov 12, 2010, and April 21, 2015. Inclusion criteria for this analysis were SPIROMICS baseline visit data with complete blood cell counts and, in a subset, acceptable sputum counts. We stratified patients on the basis of blood and sputum eosinophil concentrations and compared their demographic characteristics, as well as results from questionnaires, clinical assessments, and quantitative CT (QCT). We also analysed whether blood eosinophil concentrations reliably predicted sputum eosinophil concentrations. This study is registered with ClinicalTrials.gov (NCT01969344). Of the 2737 patients recruited to SPIROMICS, 2499 patients were smokers and had available blood counts, and so were stratified by mean blood eosinophil count: 1262 patients with low (<200 cells per μL) and 1237 with high (≥200 cells per μL) blood eosinophil counts. 827 patients were eligible for stratification by mean sputum eosinophil percentage: 656 with low (<1·25%) and 171 with high (≥1·25%) sputum eosinophil percentages. The high sputum eosinophil group had significantly lower median FEV 1 percentage predicted than the low sputum eosinophil group both before (65·7% [IQR 51·8-81·3] vs 75·7% [59·3-90·2], p<0·0001) and after (77·3% [63·1-88·5] vs 82·9% [67·8-95·9], p=0·001) bronchodilation. QCT density measures for emphysema and air trapping were significantly higher in the high sputum eosinophil group than the low sputum eosinophil group. Exacerbations requiring corticosteroids treatment were more common in the high versus low sputum eosinophil group (p=0·002). FEV 1 percentage predicted was significantly different between low and high blood eosinophil groups, but differences were less than those observed between the sputum groups. The high blood eosinophil group had slightly increased airway wall thickness (0·02 mm difference, p=0·032), higher St George Respiratory Questionnaire symptom scores (p=0·037), and increased wheezing (p=0·018), but no evidence of an association with COPD exacerbations (p=0·35) or the other indices of COPD severity, such as emphysema measured by CT density, COPD assessment test scores, Body-mass index, airflow Obstruction, Dyspnea, and Exercise index, or Global Initiative for Chronic Obstructive Lung Disease stage. Blood eosinophil counts showed a weak but significant association with sputum eosinophil counts (receiver operating characteristic area under the curve of 0·64, p<0·0001), but with a high false-discovery rate of 72%. In a large, well characterised cohort of former and current smoking patients with a broad range of COPD severity, high concentrations of sputum eosinophils were a better biomarker than high concentrations of blood eosinophils to identify a patient subgroup with more severe disease, more frequent exacerbations, and increased emphysema by QCT. Blood eosinophils alone were not a reliable biomarker for COPD severity or exacerbations, or for sputum eosinophils. Clinical trials targeting eosinophilic inflammation in COPD should consider assessing sputum eosinophils. National Institutes of Health, and National Heart, Lung, and Blood Institute. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treatment with a Novel Chemokine-Binding Protein or Eosinophil Lineage-Ablation Protects Mice from Experimental Colitis

PubMed Central

Vieira, Angélica T.; Fagundes, Caio T.; Alessandri, Ana Leticia; Castor, Marina G.M.; Guabiraba, Rodrigo; Borges, Valdinéria O.; Silveira, Kátia Daniella; Vieira, Erica L.M.; Gonçalves, Juliana L.; Silva, Tarcilia A.; Deruaz, Maud; Proudfoot, Amanda E.I.; Sousa, Lirlândia P.; Teixeira, Mauro M.

2009-01-01

Eosinophils are multifunctional leukocytes implicated in numerous inflammatory diseases. The present study was conducted to clarify the precise role of eosinophils in the development of colitis by using eosinophil-depleted mice and a novel chemokine-binding protein that neutralizes CCL11 action. Colitis was induced by administration of dextran sodium sulfate (DSS) to wild-type and eosinophil-deficient ΔdblGATA-1 mice. Accumulation of eosinophils in the gut of mice given DSS paralleled worsening of clinical score and weight loss. In response to DSS, ΔdblGATA-1 mice showed virtual absence of eosinophil recruitment, amelioration of clinical score, weight loss, and tissue destruction, and no lethality. There was a decrease in CXCL1 and CCL3 production and decreased neutrophil influx in the intestine of ΔdblGATA-1 mice. Transfer of bone marrow cells from wild-type mice reconstituted disease manifestation in DSS-treated ΔdblGATA-1 mice, and levels of CCL11 were increased after DSS treatment and localized to inflammatory cells. Treatment with the chemokine-binding protein evasin-4 at a dose that prevented the function of CCL11 greatly ameliorated clinical score, weight loss, overall tissue destruction, and death rates. In conclusion, the influx of eosinophils is critical for the induction of colitis by DSS. Treatment with a novel chemokine-binding protein decreased eosinophil influx and greatly ameliorated colitis, suggesting that strategies that interfere with the recruitment of eosinophils may be useful as therapy for colitis. PMID:19893035

Otolaryngologists may not be doing enough to diagnose pediatric eosinophilic esophagitis.

PubMed

Smith, Lee P; Chewaproug, Linda; Spergel, Jonathan M; Zur, Karen B

2009-11-01

To systematically evaluate the diagnosis of eosinophilic esophagitis (EE). A retrospective review of 657 patients seen at the EE center of a tertiary care children's hospital between 1994 and 2007 was performed. Charts were reviewed for the 144 patients who were also seen by the otolaryngology service. One hundred forty-four patients received 193 otolaryngology-related diagnoses. Eustachian tube dysfunction (27.5%) and sleep disordered breathing (24.9%) were the most common, followed by dysphagia (13.0%), rhinosinusitis/nasal congestion (9.3%) and airway stenosis (5.2%). Seventy-nine patients (54.9%) had a pre-existing diagnosis of EE at the time of their otolaryngology consultation. Twenty-one patients (14.6%) were referred to the gastroenterology service for evaluation for EE. Forty-four patients (30.5%) remained undiagnosed. Twenty-five of these patients presented with dysphagia, 16 of whom were not previously diagnosed with EE; only 4 of these 16 patients were referred for evaluation for EE. In one case, a child with moderate sized tonsils underwent adenotonsillectomy for dysphagia and failure to thrive; this patient was diagnosed with EE 1 month post-operatively. Twenty percent of patients with EE may require care by an otolaryngologist for a myriad of complaints. Even experienced pediatric otolaryngologists may not recognize this condition. Otolaryngologists should consider EE in patients presenting with dysphagia. A careful gastroenterology review of symptoms may also allow otolaryngologists to identify EE in patients with allergy mediated nasal complaints, or laryngeal/airway disorders.

Demographic and Clinical Characteristics of COPD Patients at Different Blood Eosinophil Levels in the UK Clinical Practice Research Datalink.

PubMed

Landis, Sarah; Suruki, Robert; Maskell, Joe; Bonar, Kerina; Hilton, Emma; Compton, Chris

2018-03-20

Blood eosinophil count may be a useful biomarker for predicting response to inhaled corticosteroids and exacerbation risk in chronic obstructive pulmonary disease (COPD) patients. The optimal cut point for categorizing blood eosinophil counts in these contexts remains unclear. We aimed to determine the distribution of blood eosinophil count in COPD patients and matched non-COPD controls, and to describe demographic and clinical characteristics at different cut points. We identified COPD patients within the UK Clinical Practice Research Database aged ≥40 years with a FEV 1 /FVC <0.7, and ≥1 blood eosinophil count recorded during stable disease between January 1, 2010 and December 31, 2012. COPD patients were matched on age, sex, and smoking status to non-COPD controls. Using all blood eosinophil counts recorded during a 12-month period, COPD patients were categorized as "always above," "fluctuating above and below," and "never above" cut points of 100, 150, and 300 cells/μL. The geometric mean blood eosinophil count was statistically significantly higher in COPD patients versus matched controls (196.6 cells/µL vs. 182.1 cells/µL; mean difference 8%, 95% CI: 6.8, 9.2), and in COPD patients with versus without a history of asthma (205.0 cells/µL vs. 192.2 cells/µL; mean difference 6.7%, 95%, CI: 4.9, 8.5). About half of COPD patients had all blood eosinophil counts above 150 cells/μL; this persistent higher eosinophil phenotype was associated with being male, higher body mass index, and history of asthma. In conclusion, COPD patients demonstrated higher blood eosinophil count than non-COPD controls, although there was substantial overlap in the distributions. COPD patients with a history of asthma had significantly higher blood eosinophil count versus those without.

A Review of Clinical and Imaging Findings in Eosinophilic Lung Diseases.

PubMed

Bernheim, Adam; McLoud, Theresa

2017-05-01

The purpose of this article is to review the clinical and imaging findings associated with eosinophilic lung diseases. The spectrum of eosinophilic lung diseases comprises a diverse group of pulmonary disorders that have an association with tissue or peripheral eosinophilia. These diseases have varied clinical presentations and may be associated with several other abnormalities. Characteristic imaging findings are often detected with chest radiography, and CT best shows parenchymal abnormalities. The integration of clinical, radiologic, and pathologic findings facilitates diagnosis and directs appropriate treatment.

Atypical clinical appearance of eosinophilic pustular folliculitis of seborrheic areas of the face.

PubMed

Matsumura, Yumi; Miyachi, Yoshiki

2012-01-01

Eosinophilic pustular folliculitis is a pruritic eruption that preferentially involves the face. It is characterized by well-demarcated erythema, extending peripherally with a central clearing and pigmentation, together with sterile pustules lining the periphery. We describe five cases of eosinophilic pustular folliculitis with pruritic papules and erythema on seborrheic areas of the face, which lacked the typical features of classic eosinophilic pustular folliculitis--pustules and peripheral extension--but showed eosinophilic infiltration of the hair follicles, histologically. The eruption quickly responded to oral indomethacin except for one case that responded to tranilast and one case that was associated with acquired immunodeficiency syndrome, with recurrences in defined areas of the face. Our findings in these cases suggest that eosinophilic pustular folliculitis may vary in clinical appearance.

Component-resolved diagnostics in vernal conjunctivitis.

PubMed

Armentia, Alicia; Sanchís, Eugenia; Montero, Javier A

2016-10-01

Conventional diagnostic tests in allergy are insufficient to clarify the cause of vernal conjunctivitis. Component-resolved diagnostic (CRD) by microarray allergen assay may be useful in detecting allergens that might be involved in the inflammatory process. In a recent trial in patients suffered from eosinophilic esophagitis, after 2 years of the CRD-guided exclusion diet and specific immunotherapy, significant clinical improvement was observed, and 68% of patients were discharged (cure based on negative biopsy, no symptoms, and no medication intake). Our new objective was to evaluate IgE-mediated hypersensitivity by CRD in tears and serum from patients with vernal conjunctivitis and treat patients with identified triggering allergens by specific immunotherapy. Twenty-five patients with vernal conjunctivitis were evaluated. The identified triggering allergens were n Lol p 1 (11 cases), n Cyn d 1 (eight cases), group 4 and 6 grasses (six cases) and group 5 of grasses (five cases). Prick test and pollen IgE were positive in one case. Clinical improvement was observed in 13/25 vernal conjunctivitis patients after 1-year specific immunotherapy. CRD seems to be a more sensitive diagnostic tool compared with prick test and IgE detection. Specific CRD-led immunotherapy may achieve clinical improvements in vernal conjunctivitis patients.

Eosinophilic ascites due to severe eosinophilic ileitis.

PubMed

Setia, Namrata; Ghobrial, Peter; Liron, Pantanowitz

2010-09-17

There is a broad etiology for effusion eosinophilia that includes allergic, reactive, infectious, immune, neoplastic, and idiopathic causes. We report and describe the cytomorphologic findings of a rare case of eosinophilic ascites due to severe eosinophilic ileitis. A 17-year-old male manifested acutely with eosinophilic ascites due to severe biopsy-proven subserosal eosinophilic ileitis. Isolated peritoneal fluid submitted for cytologic evaluation revealed that 65% eosinophils were present in a bloody background. The patient responded to corticosteroids, with complete resolution of his ascites. Eosinophilic gastroenteritis with subserosal involvement should be added to the list of causes for eosinophils in peritoneal fluid. The finding of eosinophilic ascites, with appropriate clinical and laboratory findings, may warrant the need to perform laparoscopic intestinal biopsies to confirm the diagnosis.

Clinical Application of Esophageal High-resolution Manometry in the Diagnosis of Esophageal Motility Disorders.

PubMed

van Hoeij, Froukje B; Bredenoord, Albert J

2016-01-31

Esophageal high-resolution manometry (HRM) is replacing conventional manometry in the clinical evaluation of patients with esophageal symptoms, especially dysphagia. The introduction of HRM gave rise to new objective metrics and recognizable patterns of esophageal motor function, requiring a new classification scheme: the Chicago classification. HRM measurements are more detailed and more easily performed compared to conventional manometry. The visual presentation of acquired data improved the analysis and interpretation of esophageal motor function. This led to a more sensitive, accurate, and objective analysis of esophageal motility. In this review we discuss how HRM changed the way we define and categorize esophageal motility disorders. Moreover, we discuss the clinical applications of HRM for each esophageal motility disorder separately.

Clinical Application of Esophageal High-resolution Manometry in the Diagnosis of Esophageal Motility Disorders

PubMed Central

van Hoeij, Froukje B; Bredenoord, Albert J

2016-01-01

Esophageal high-resolution manometry (HRM) is replacing conventional manometry in the clinical evaluation of patients with esophageal symptoms, especially dysphagia. The introduction of HRM gave rise to new objective metrics and recognizable patterns of esophageal motor function, requiring a new classification scheme: the Chicago classification. HRM measurements are more detailed and more easily performed compared to conventional manometry. The visual presentation of acquired data improved the analysis and interpretation of esophageal motor function. This led to a more sensitive, accurate, and objective analysis of esophageal motility. In this review we discuss how HRM changed the way we define and categorize esophageal motility disorders. Moreover, we discuss the clinical applications of HRM for each esophageal motility disorder separately. PMID:26631942

[Differential diagnosis "non-cardiac chest pain"].

PubMed

Frieling, Thomas

2015-07-01

Non cardiac chest pain (NCCP) are recurrent angina pectoris like pain without evidence of coronary heart diesease in conventional diagnostic evaluation. The prevalence of NCCP is up to 70% and may be detected in this order at all levels of the medical health care system (general practitioner, emergency department, chest pain unit, coronary care). Reduction of quality of life in NCCP is comparable, partially even higher compared to cardiac chest pain. Reasons for psychological strain are symptom recurrence in app. 50%, nonspecific diagnosis with resulting uncertainty and insufficient integration of other medical disciplines in diagnostic work-up. Managing of patients with NCCP has to be interdisciplinary because non cardiac causes of chest pain may be found frequently. This are musculosceletal in app. 40%, gastrointestinal in app. 20%, psychiatric in app. 10% and pulmonary and mediastinal diseases in app. 5% of cases. Also gastroenterological expertise is required because here gastroesophageal reflux disease (GERD) in app. 60%, hypercontractile esophageal motility disorders with nutcracker, jackhammer esophagus or distal esophageal spasmus or achalasia in app. 20% and other esophageal alterations (e. g. infectious esophageal inflammation, drug-induced ulcer, rings, webs, eosinophilic esophagits) in app. 30% of cases may be detected as cause of chest pain may. This implicates that regular interdisciplinary round wards and interdisciplinary management of chest pain units are mandatory. © Georg Thieme Verlag KG Stuttgart · New York.

Pollen-food allergy syndrome is a common allergic comorbidity in adults with eosinophilic esophagitis.

PubMed

Letner, D; Farris, A; Khalili, H; Garber, J

2018-02-01

Eosinophilic esophagitis (EoE) is associated with atopic diseases including asthma, allergic rhinitis, and atopic dermatitis; however, limited data exist on the correlation between pollen-food allergy syndrome (PFAS) and EoE. We analyzed 346 adults with EoE treated at a single center between 2002 and 2016. Demographic and EoE-specific data including clinical features and measures of EoE disease severity and treatments were collected. The presence of other atopic diseases, family history, prevalence of peripheral eosinophilia and elevated IgE, and details of PFAS triggers were collected. Twenty six percent of the 346 subjects in our cohort had both EoE and PFAS (EoE-PFAS). Compared to subjects with EoE alone, subjects with EoE-PFAS had an increased frequency of allergic rhinitis (86.7% vs. 64.2%, P < 0.001) and family history of allergies (71.1% vs. 53.3%, P = 0.003), and comprised a higher proportion of EoE diagnoses made in the spring (Χ2 < 0.001). 43.3% of subjects with concurrent EoE and PFAS opted for treatment with elimination diet, and these measures failed to induce remission in 46.2% of cases. In most cases, elimination diet failed despite strict avoidance of PFAS trigger foods in addition to common EoE triggers including dairy, wheat, and eggs. EoE-PFAS was also associated with higher serum IgE at the time of EoE diagnosis (460.6 vs. 289.9, P < 0.019). Allergic rhinitis and a family history of food allergy were independently associated with having EoE-PFAS. The most common triggers of PFAS in adults with EoE are apples (21.1%), carrots (15.5%), and peaches (15.5%). Along with asthma, allergic rhinitis and atopic dermatitis, PFAS is a common allergic comorbidity that is highly associated with EoE. Further studies aimed at understanding mechanistic similarities and differences of PFAS and EoE may shed light on the pathogenesis of these closely related food allergy syndromes.

Changing roles of eosinophils in health and disease.

PubMed

Furuta, Glenn T; Atkins, F Dan; Lee, Nancy A; Lee, James J

2014-07-01

To review and highlight the unappreciated roles of eosinophils suggested by recent studies. The literature, unpublished observations, and insights by the authors. Basic studies of mouse models and patient-based clinical studies of disease. Eosinophils are often thought of as destructive end-stage effector cells primarily linked to parasite host defense and dysregulated immune responses associated with allergic diseases, such as asthma. However, recent studies (ie, research focused on mechanisms of action and translational studies examining disease/inflammatory pathways) are suggesting far more complex roles for eosinophils. The goal of this review is 3-fold. (1) The authors examine the dynamic history of eosinophils and how physicians over time used this information to formulate defining hypotheses. Particular emphasis is placed on recent studies challenging the parochial view of host defense in favor of roles maintaining homeostasis through immune modulation and tissue remodeling/repair. (2) They discuss diagnostic approaches to assess eosinophils in clinical settings as a means of disease identification and subsequently as a measurement of disease severity. (3) They examine how contemporary views of eosinophils and their perceived roles in diseases have led to specific therapeutic strategies. The emphasis is to review the successes and failures of these strategies as the basis of formulating future clinical studies targeting eosinophils as potential therapies of disease. Despite the complexities of eosinophil-mediated activities and the less than overwhelming success of initial attempts targeting these cells, eosinophils remain a potentially important focal target of disease diagnosis and subsequent treatment strategies. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A Visual Analogue Scale and a Likert Scale are Simple and Responsive Tools for Assessing Dysphagia in Eosinophilic Esophagitis

PubMed Central

Reed, Craig C.; Wolf, W. Asher; Cotton, Cary C.; Dellon, Evan S.

2017-01-01

Background While symptom scores have been developed to evaluate dysphagia in eosinophilic oesophagitis (EoE), their complexity may limit clinical use. Aim We aimed to evaluate a visual analogue scale (VAS) and a 10 point Likert scale (LS) for assessment of dysphagia severity before and after EoE treatment. Methods We conducted a prospective cohort study enrolling consecutive adults undergoing outpatient endoscopy. Incident cases of EoE were diagnosed per consensus guidelines. At diagnosis and after 8 weeks of treatment, symptoms were measured using the VAS, LS, and the Mayo Dysphagia Questionnaire (MDQ). The percentage change in scores before and after treatment were compared overall, in treatment responders (<15 eos/hpf) and non-responders, and in patients without baseline dilation. Results In 51 EoE cases, the median VAS decreased from 3.6 at baseline to 1.4 post-treatment (71% decrease), the LS decreased from 6 to 2 (67%), and the MDQ decreased from 20 to 10 (49%). The VAS correlated with both the LS (R=0.77; p<0.0001) and MDQ (R=0.46, p=0.001). After stratification by histologic response, the LS decreased 70% in responders vs. 13% in non-responders (p=0.02). In patients who did not receive baseline dilation, both the VAS and LS decreased significantly more in the histologic responders. Conclusions Both the VAS and LS were responsive to successful histologic treatment. Because the VAS and LS are simple to administer and are responsive to treatment, they can provide an efficient and objective method for assessing dysphagia severity in EoE in clinical practice. PMID:28370355

Eosinophilic ascites due to severe eosinophilic ileitis

PubMed Central

Setia, Namrata; Ghobrial, Peter; Liron, Pantanowitz

2010-01-01

Background: There is a broad etiology for effusion eosinophilia that includes allergic, reactive, infectious, immune, neoplastic, and idiopathic causes. We report and describe the cytomorphologic findings of a rare case of eosinophilic ascites due to severe eosinophilic ileitis. Case Presentation: A 17-year-old male manifested acutely with eosinophilic ascites due to severe biopsy-proven subserosal eosinophilic ileitis. Isolated peritoneal fluid submitted for cytologic evaluation revealed that 65% eosinophils were present in a bloody background. The patient responded to corticosteroids, with complete resolution of his ascites. Conclusion: Eosinophilic gastroenteritis with subserosal involvement should be added to the list of causes for eosinophils in peritoneal fluid. The finding of eosinophilic ascites, with appropriate clinical and laboratory findings, may warrant the need to perform laparoscopic intestinal biopsies to confirm the diagnosis. PMID:20976207

Upper gastrointestinal bleeding caused by severe esophagitis: a unique clinical syndrome.

PubMed

Guntipalli, Prathima; Chason, Rebecca; Elliott, Alan; Rockey, Don C

2014-12-01

We have recognized a unique clinical syndrome in patients with upper gastrointestinal bleeding who are found to have severe esophagitis. We aimed to more clearly describe the clinical entity of upper gastrointestinal bleeding in patients with severe esophagitis. We conducted a retrospective matched case-control study designed to investigate clinical features in patients with carefully defined upper gastrointestinal bleeding and severe esophagitis. Patient data were captured prospectively via a Gastrointestinal Bleeding Healthcare Registry, which collects data on all patients admitted with gastrointestinal bleeding. Patients with endoscopically documented esophagitis (cases) were matched with randomly selected controls that had upper gastrointestinal bleeding caused by other lesions. Epidemiologic features in patients with esophagitis were similar to those with other causes of upper gastrointestinal bleeding. However, hematemesis was more common in patients with esophagitis 86% (102/119) than in controls 55% (196/357) (p < 0.0001), while melena was less common in patients with esophagitis 38% (45/119) than in controls 68% (244/357) (p < 0.0001). Additionally, the more severe the esophagitis, the more frequent was melena. Patients with esophagitis had less abnormal vital signs, lesser decreases in hematocrit, and lesser increases in BUN. Both pre- and postRockall scores were lower in patients with esophagitis compared with controls (p = 0.01, and p < 0.0001, respectively). Length of hospital stay (p = 0.002), rebleeding rate at 42 days (p = 0.0007), and mortality were less in patients with esophagitis than controls. Finally, analysis of patients with esophagitis and cirrhosis suggested that this group of patients had more severe bleeding than those without cirrhosis. We have described a unique clinical syndrome in patients with upper gastrointestinal bleeding who have erosive esophagitis. This syndrome is manifest by typical clinical features and is associated with favorable outcomes.

Evaluation of esophageal motor function in clinical practice.

PubMed

Gyawali, C P; Bredenoord, A J; Conklin, J L; Fox, M; Pandolfino, J E; Peters, J H; Roman, S; Staiano, A; Vaezi, M F

2013-02-01

Esophageal motor function is highly coordinated between central and enteric nervous systems and the esophageal musculature, which consists of proximal skeletal and distal smooth muscle in three functional regions, the upper and lower esophageal sphincters, and the esophageal body. While upper endoscopy is useful in evaluating for structural disorders of the esophagus, barium esophagography, radionuclide transit studies, and esophageal intraluminal impedance evaluate esophageal transit and partially assess motor function. However, esophageal manometry is the test of choice for the evaluation of esophageal motor function. In recent years, high-resolution manometry (HRM) has streamlined the process of acquisition and display of esophageal pressure data, while uncovering hitherto unrecognized esophageal physiologic mechanisms and pathophysiologic patterns. New algorithms have been devised for analysis and reporting of esophageal pressure topography from HRM. The clinical value of HRM extends to the pediatric population, and complements preoperative evaluation prior to foregut surgery. Provocative maneuvers during HRM may add to the assessment of esophageal motor function. The addition of impedance to HRM provides bolus transit data, but impact on clinical management remains unclear. Emerging techniques such as 3-D HRM and impedance planimetry show promise in the assessment of esophageal sphincter function and esophageal biomechanics. © 2013 Blackwell Publishing Ltd.

[Oesophageal diseases: gastroesophageal reflux disease, Barrett's disease, achalasia and eosinophilic oesophagitis].

PubMed

Calvet, Xavier

2015-09-01

The most important novel findings presented on oesophageal disease in DDW 2015 were the following: 1) GERD: a) hypervigilance seems to be a key pathogenic factor in reflux symptoms refractory to PPI; b) post-reflux swallowing-induced peristaltic waves could be an excellent diagnostic criterion for GERD; c) laryngeal pH-metry is not useful in the diagnosis of extra-oesophageal symptoms; d) the recommendation of weight loss adequately recorded in the clinical reports of patients with GERD and obesity or overweight is an excellent quality indicator and is associated with better outcomes. 2) Barrett's oesophagus: a) persistent low-grade dysplasia in more than one endoscopy and a diagnosis of "indefinite for dysplasia" are associated with a high risk of neoplastic progression; b) narrow-band imaging allows areas of dysplasia on Barrett's oesophagus to be identified with high sensitivity and specificity; c) initial endoscopy fails to identify a high percentage of advanced neoplasms in Barrett's oesophagus. Early re-endoscopy should be considered; d) endoscopists specialized in Barret's oesophagus obtain a much higher yield in the diagnosis of advanced lesions. Patients at high risk-men, older patients, smokers and those with long-segment Barrett's oesophagus-could benefit from follow-up in a referral center. 3) Achalasia: POEM seems safe and effective, independently from patient characteristics (age, comorbidity) and the technical variations used. 4) Eosinophilic esophagitis: topical budesonide and exclusion diets are reasonably effective in PPI non-responders. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Clinical and histopathological differential diagnosis of eosinophilic pustular folliculitis.

PubMed

Fujiyama, Toshiharu; Tokura, Yoshiki

2013-06-01

Eosinophilic pustular folliculitis (EPF) is an inflammatory disease characterized by repeated pruritic follicular papules and pustules arranged in arcuate plaques, and folliculotropic infiltration of eosinophils. The diagnosis of EPF is occasionally difficult and problematic because EPF may share the clinical appearance and histological findings with other diseases. Moreover, EPF has several clinical subtypes, including the classical type, infantile type and immunosuppression-associated type. Because the therapies of EPF are relatively specific as compared to eczematous disorders, accurate diagnosis is essential for the management of EPF. Clinical differential diagnoses include tinea, acne, rosacea, eczematous dermatitis, granuloma faciale, autoimmune annular erythema, infestations and pustular dermatosis. Histologically, cutaneous diseases with eosinophilic infiltrates can be differentially diagnosed. Follicular mucinosis, mycosis fungoides and other cutaneous T-cell lymphomas are the most important differential diagnoses both clinically and histopathologically. It should be kept in mind particularly that the initial lesions of cutaneous T-cell lymphoma resemble EPF. © 2013 Japanese Dermatological Association.

Interactions between gastro-oesophageal reflux disease and eosinophilic oesophagitis.

PubMed

Molina-Infante, Javier; van Rhijn, Bram D

2015-10-01

Gastro-oesophageal reflux disease (GORD) is the most common oesophageal disorder, whereas eosinophilic oesophagitis (EoE) is an emerging disease unresponsive to PPI therapy. Updated guidelines in 2011 described proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE), a novel phenotype in EoE patients who were responsive to PPIs. This article aims to update the complex interplay between GORD, EoE and PPIs. Oesophageal mucosal integrity is diffusely impaired in EoE and PPI-REE patients. PPI-REE might occur with either normal or pathological pH monitoring. The genetic hallmark of EoE is overlapped in PPI-REE, but not in GORD. PPIs can partially restore epithelial integrity and reverse allergic inflammation gene expression in PPI-REE. Acid hypersensitivity in EoE patients may explain symptomatic but not histological response on PPIs. Unsolved issues with PPI-REE are whether oesophageal barrier impairment is the cause or the effect of oesophageal eosinophilia and whether PPIs primarily targets barrier integrity or oesophageal inflammation. Copyright © 2015 Elsevier Ltd. All rights reserved.

The distribution of blood eosinophil levels in a Japanese COPD clinical trial database and in the rest of the world.

PubMed

Barnes, Neil; Ishii, Takeo; Hizawa, Nobuyuki; Midwinter, Dawn; James, Mark; Hilton, Emma; Jones, Paul W

2018-01-01

Blood eosinophil measurements may help to guide physicians on the use of inhaled corticosteroids (ICS) for patients with chronic obstructive pulmonary disease (COPD). Emerging data suggest that COPD patients with higher blood eosinophil counts may be at higher risk of exacerbations and more likely to benefit from combined ICS/long-acting beta 2 -agonist (LABA) treatment than therapy with a LABA alone. This analysis describes the distribution of blood eosinophil count at baseline in Japanese COPD patients in comparison with non-Japanese COPD patients. A post hoc analysis of eosinophil distribution by percentage and absolute cell count was performed across 12 Phase II-IV COPD clinical studies (seven Japanese studies [N=848 available absolute eosinophil counts] and five global studies [N=5,397 available eosinophil counts] that included 246 Japanese patients resident in Japan with available counts). Blood eosinophil distributions were assessed at baseline, before blinded treatment assignment. Among Japanese patients, the median (interquartile range) absolute eosinophil count was 170 cells/mm 3 (100-280 cells/mm 3 ). Overall, 612/1,094 Japanese patients (56%) had an absolute eosinophil count ≥150 cells/mm 3 and 902/1,304 Japanese patients (69%) had a percentage eosinophil ≥2%. Among non-Japanese patients, these values were 160 (100-250) cells/mm 3 , 2,842/5,151 patients (55%), and 2,937/5,155 patients (57%), respectively. The eosinophil distribution among Japanese patients was similar to that among non-Japanese patients. Within multi-country studies with similar inclusion criteria, the eosinophil count was numerically lower in Japanese compared with non-Japanese patients (median 120 vs 160 cells/mm 3 ). The eosinophil distribution in Japanese patients seems comparable to that of non-Japanese patients; although within multi-country studies, there was a slightly lower median eosinophil count for Japanese patients compared with non-Japanese patients. These findings suggest that blood eosinophil data from global studies are of relevance in Japan.

Endoscopic ultrasound as an adjunctive evaluation in patients with esophageal motor disorders subtyped by high-resolution manometry.

PubMed

Krishnan, K; Lin, C-Y; Keswani, R; Pandolfino, J E; Kahrilas, P J; Komanduri, S

2014-08-01

Esophageal motor disorders are a heterogeneous group of conditions identified by esophageal manometry that lead to esophageal dysfunction. The aim of this study was to assess the clinical utility of endoscopic ultrasound (EUS) in the further evaluation of patients with esophageal motor disorders categorized using the updated Chicago Classification. We performed a retrospective, single center study of 62 patients with esophageal motor disorders categorized according to the Chicago Classification. All patients underwent standard radial endosonography to assess for extra-esophageal findings or alternative explanations for esophageal outflow obstruction. Secondary outcomes included esophageal wall thickness among the different patient subsets within the Chicago Classification. EUS identified 9/62 (15%) clinically relevant findings that altered patient management and explained the etiology of esophageal outflow obstruction. We further identified substantial variability in esophageal wall thickness in a proportion of patients including some with a significantly thickened non-muscular layer. EUS findings are clinically relevant in a significant number of patients with motor disorders and can alter clinical management. Variability in esophageal wall thickness of the muscularis propria and non-muscular layers identified by EUS may also explain the observed variability in response to standard therapies for achalasia. © 2014 John Wiley & Sons Ltd.

Endoscopic ultrasound as an adjunctive evaluation in patients with esophageal motor disorders subtyped by high-resolution manometry

PubMed Central

Krishnan, Kumar; Lin, Chen-Yuan; Keswani, Rajesh; Pandolfino, John E; Kahrilas, Peter J; Komanduri, Srinadh

2015-01-01

Background and aims Esophageal motor disorders are a heterogenous group of conditions identified by esophageal manometry that lead to esophageal dysfunction. The aim of this study was to assess the clinical utility of endoscopic ultrasound in the further evaluation of patients with esophageal motor disorders categorized using the updated Chicago Classification. Methods We performed a retrospective, single center study of 62 patients with esophageal motor disorders categorized according to the Chicago Classification. All patients underwent standard radial endosonography to assess for extra esophageal findings or alternative explanations for esophageal outflow obstruction. Secondary outcomes included esophageal wall thickness among the different patient subsets within the Chicago Classification Key Results EUS identified 9/62 (15%) clinically relevant findings that altered patient management and explained the etiology of esophageal outflow obstruction. We further identified substantial variability in esophageal wall thickness in a proportion of patients including some with a significantly thickened non-muscular layer. Conclusions EUS findings are clinically relevant in a significant number of patients with motor disorders and can alter clinical management. Variability in esophageal wall thickness of the muscularis propria and non-muscular layers identified by EUS may also explain the observed variability in response to standard therapies for achalasia. PMID:25041229

Correlation Between Aeroallergen Levels and New Diagnosis of Eosinophilic Esophagitis in New York City.

PubMed

Fahey, Lisa; Robinson, Guy; Weinberger, Kate; Giambrone, Ashley E; Solomon, Aliza B

2017-01-01

The relation between food allergies and eosinophilic esophagitis (EoE) is well established. Aeroallergens may also contribute to the development of EoE; however, there are limited data to support or refute this hypothesis. The objectives of this pilot study were to determine whether there is a seasonal variation in the onset of symptoms and/or diagnosis of EoE and whether these variations correlate with a specific pollen concentration within New York City. We performed a retrospective chart review to identify all pediatric patients at New York Presbyterian Weill Cornell Medical Center diagnosed with EoE between 2002 and 2012. Sixty-six patients were identified and 28 were excluded. Cases were classified by both date of initial symptoms and date of histologic diagnosis. Pollen counts from a certified New York City counting station and the percentage of EoE cases were collated monthly and seasonally and compared. There was a seasonal variation in onset of symptoms and diagnosis of EoE, with the highest number of patients reporting onset of symptoms of EoE in July to September, and those being diagnosed with EoE in October to December. There was a seasonal correlation between peak levels of grass pollen and peak onset of EoE symptoms, which were both highest in July to September. The diagnosis of EoE peaked one season later. The study findings suggest that there is a correlation between specific aeroallergens and both the onset of symptoms and time of diagnosis of patients with EoE.

Clinical Study of Time Optimizing of Endoscopic Photodynamic Therapy on Esophageal and/or Gastric Cardiac Cancer

ClinicalTrials.gov

2015-12-10

Stage I Esophageal Adenocarcinoma; Stage II Esophageal Adenocarcinoma; Stage III Esophageal Adenocarcinoma; Stage I Esophageal Squamous Cell Carcinoma; Stage II Esophageal Squamous Cell Carcinoma; Stage III Esophageal Squamous Cell Carcinoma

Patient-Reported Outcome Measures in Dysphagia: A Systematic Review of Instrument Development and Validation

PubMed Central

Patel, Dhyanesh A.; Sharda, Rohit; Hovis, Kristen L.; Nichols, Erin E.; Sathe, Nila; Penson, David F.; Feurer, Irene D.; McPheeters, Melissa L.; Vaezi, Michael F.; Francis, David O.

2017-01-01

Objective Patient-reported outcome (PRO) measures are commonly used to capture patient experience with dysphagia and to evaluate treatment effectiveness. Inappropriate application can lead to distorted results in clinical studies. A systematic review of the literature on dysphagia-related PRO measures was performed to 1) identify all currently available measures and 2) to evaluate each for the presence of important measurement properties that would affect their applicability. Design MEDLINE via the PubMed interface, the Cumulative Index of Nursing and Allied Health Literature, and the Health and Psychosocial Instrument database were searched using relevant vocabulary terms and key terms related to PRO measures and dysphagia. Three independent investigators performed abstract and full text reviews. Each study meeting criteria was evaluated using an 18-item checklist developed a priori that assessed multiple domains: 1) conceptual model, 2) content validity, 3) reliability, 4) construct validity, 6) scoring and interpretation, and 7) burden and presentation. Results Of 4950 abstracts reviewed, a total of 34 dysphagia-related PRO measures (publication year 1987 – 2014) met criteria for extraction and analysis. Several PRO measures were of high quality (MADS for achalasia, SWAL-QOL and SSQ for oropharyngeal dysphagia, PROMIS-GI for general dysphagia, EORTC-QLQ-OG25 for esophageal cancer, ROMP-swallowing for Parkinson’s disease, DSQ-EoE for eosinophilic esophagitis, and SOAL for total laryngectomy-related dysphagia). In all, 17 met at least one criterion per domain. Thematic deficiencies in current measures were evident including: 1) direct patient involvement in content development, 2) empirically justified dimensionality, 3) demonstrable responsiveness to change, 4) plan for interpreting missing responses, and 5) literacy level assessment. Conclusion This is the first comprehensive systematic review assessing developmental properties of all available dysphagia-related PRO measures. We identified several instruments with robust measurement properties in multiple diseases including achalasia, oropharyngeal dysphagia, post-surgical dysphagia, esophageal cancer, and dysphagia related to neurological diseases. Findings herein can assist clinicians and researchers in making more informed decisions in selecting the most fundamentally sound PRO measure for a given clinical, research, or quality initiative. PMID:28375450

Imaging and Clinicopathologic Features of Esophageal Gastrointestinal Stromal Tumors

PubMed Central

Winant, Abbey J.; Gollub, Marc J.; Shia, Jinru; Antonescu, Christina; Bains, Manjit S.; Levine, Marc S.

2016-01-01

OBJECTIVE The purpose of this article is to describe the imaging and clinicopathologic characteristics of esophageal gastrointestinal stromal tumors (GISTs) and to emphasize the features that differentiate esophageal GISTs from esophageal leiomyomas. MATERIALS AND METHODS A pathology database search identified all surgically resected or biopsied esophageal GISTs, esophageal leiomyomas, and esophageal leiomyosarcomas from 1994 to 2012. Esophageal GISTs were included only if imaging studies (including CT, fluoroscopic, or 18F-FDG PET/CT scans) and clinical data were available. RESULTS Nineteen esophageal mesenchymal tumors were identified, including eight esophageal GISTs (42%), 10 esophageal leiomyomas (53%), and one esophageal leiomyosarcoma (5%). Four patients (50%) with esophageal GIST had symptoms, including dysphagia in three (38%), cough in one (13%), and chest pain in one (13%). One esophageal GIST appeared on barium study as a smooth submucosal mass. All esophageal GISTs appeared on CT as well-marginated predominantly distal lesions, isoattenuating to muscle, that moderately enhanced after IV contrast agent administration. Compared with esophageal leiomyomas, esophageal GISTs tended to be more distal, larger, and more heterogeneous and showed greater IV enhancement on CT. All esophageal GISTs showed marked avidity (mean maximum standardized uptake value, 16) on PET scans. All esophageal GISTs were positive for c-KIT (a cell-surface transmembrane tyrosine kinase also known as CD117) and CD34. On histopathology, six esophageal GISTs (75%) were of the spindle pattern and two (25%) were of a mixed spindle and epithelioid pattern. Five esophageal GISTs had exon 11 mutations (with imatinib sensitivity). Clinical outcome correlated with treatment strategy (resection plus adjuvant therapy or resection alone) rather than risk stratification. CONCLUSION Esophageal GISTs are unusual but clinically important mesenchymal neoplasms. Although esophageal GISTs and esophageal leiomyomas had overlapping imaging features, esophageal GISTs tended to be more distal, larger, more heterogeneous, and more enhancing on CT and were markedly FDG avid on PET. Given their malignant potential, esophageal GISTs should be included in the differential diagnosis of intramural esophageal neoplasms. PMID:25055264

Eosinophilic gastroenteritis with Splendore-Hoeppli material in the ferret (Mustela putorius furo).

PubMed

Fox, J G; Palley, L S; Rose, R

1992-01-01

Eosinophilic gastroenteritis, focal or diffuse with eosinophilic infiltrations of the stomach or intestine, has been described in human beings, cats, dogs, and horses. In this paper, we describe infiltration of the gastrointestinal tract with eosinophils accompanied by a circulating eosinophilia in six ferrets (Mustela putorius furo). Clinical signs included chronic weight loss, anorexia, and diarrhea. The small intestines from five ferrets had diffuse infiltrates of eosinophils. This resulted in focal or multifocal loss of the muscular tunic in three ferrets. Two of these ferrets also had eosinophilic gastritis. Eosinophilic granulomas with Splendore-Hoeppli material were present in mesenteric lymph nodes in four ferrets. Two ferrets had multiple organ involvement; one had eosinophilic granulomas in the liver, mesentery, and choroid plexus as well as moderate parapancreatic segmental arteritis with infiltration of eosinophils and mural thrombosis. The second ferret had, in addition to moderate diffuse gastric and small intestinal eosinophilic mucosal infiltrations, interstitial eosinophilic pulmonary infiltrates. Examination of all tissues failed to reveal an infectious agent.

Novel targeted therapies for eosinophilic disorders

PubMed Central

Wechsler, Michael E.; Fulkerson, Patricia C.; Bochner, Bruce S.; Gauvreau, Gail M.; Gleich, Gerald J.; Henkel, Tim; Kolbeck, Roland; Mathur, Sameer K.; Ortega, Hector; Patel, Jatin; Prussin, Calman; Renzi, Paolo; Rothenberg, Marc E.; Roufosse, Florence; Simon, Dagmar; Simon, Hans-Uwe; Wardlaw, Andrew; Weller, Peter F.; Klion, Amy D.

2013-01-01

Hypereosinophilic syndromes (HESs) are a diverse group of conditions characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. HESs are chronic disorders with significant morbidity and mortality. Although the availability of targeted chemotherapeutic agents, including imatinib, has improved quality of life and survival in some patients with HESs, additional agents with increased efficacy and decreased toxicity are sorely needed. The purpose of this review is to provide an overview of eosinophil biology with an emphasis on potential targets of pharmacotherapy and to provide a summary of potential eosinophil-targeting agents, including those in development, in clinical trials, or approved for other disorders. PMID:22935585

Retrospective Comparison of Fluticasone Propionate and Oral Viscous Budesonide in Children With Eosinophilic Esophagitis.

PubMed

Fable, Jacqueline M; Fernandez, Marina; Goodine, Susan; Lerer, Trudy; Sayej, Wael N

2018-01-01

Eosinophilic esophagitis (EoE) is treated with dietary modification and/or pharmacologic management with swallowed topical steroids. Swallowed fluticasone propionate (FP) and oral viscous budesonide (OVB) have proven to be effective in resolving symptoms and reversing histologic changes in children and adults with EoE. There are minimal comparative studies between the 2 agents. The aim of the study was to retrospectively compare endoscopic and histologic outcomes after FP versus OVB therapy in children with EoE in our center. We performed a retrospective chart review of subjects diagnosed with EoE at a tertiary care center between 2010 and 2015. Inclusion criteria were FP or OVB therapy for ≥8 weeks along with pre- and post-treatment endoscopic evaluation. Demographic and clinical features and endoscopic and histologic assessment were recorded for comparative analysis. Histologic response was defined as <15 eos/hpf and remission as <5 eos/hpf. The study included 68 EoE patients (20 FP and 48 OVB) with a mean age of 10.6 ± 5.2 years (range 1-20 years); 81% were boys and 68% were Caucasian. No significant demographic or clinical differences were noted between the 2 study groups. Overall histologic response to topical steroids was seen in 44 of 68 (65%) patients. A significantly greater number of patients achieved histologic response with OVB (36/48, 75%) than with FP (8/20, 40%) (P = 0.0059). Mean pretreatment peak eos/hpf was 46 ± 19 in the FP group versus 45 ± 23 in the OVB group. Mean post-treatment peak eos/hpf was 20 ± 29 in the FP group versus 12 ± 16 in the OVB group (P = 0.002). There was also a significantly greater difference in the change of absolute eos/hpf from pre- to post-treatment in the OVB group (-33) versus FP (18) (P = 0.047). A greater number of OVB-treated patients without asthma had a histologic response compared to those with asthma (P = 0.031). The response to OVB was not affected by the delivery vehicle, namely sucralose (Splenda) versus Neocate Duocal. Our data suggest that treatment with OVB leads to better endoscopic and histologic outcomes than FP. Adherence to treatment and history of asthma are major determining factors in the response to treatments. Using Neocate Duocal as the OVB delivery vehicle is just as effective as sucralose.

The distribution of blood eosinophil levels in a Japanese COPD clinical trial database and in the rest of the world

PubMed Central

Ishii, Takeo; Hizawa, Nobuyuki; Midwinter, Dawn; James, Mark; Hilton, Emma; Jones, Paul W

2018-01-01

Background Blood eosinophil measurements may help to guide physicians on the use of inhaled corticosteroids (ICS) for patients with chronic obstructive pulmonary disease (COPD). Emerging data suggest that COPD patients with higher blood eosinophil counts may be at higher risk of exacerbations and more likely to benefit from combined ICS/long-acting beta2-agonist (LABA) treatment than therapy with a LABA alone. This analysis describes the distribution of blood eosinophil count at baseline in Japanese COPD patients in comparison with non-Japanese COPD patients. Methods A post hoc analysis of eosinophil distribution by percentage and absolute cell count was performed across 12 Phase II–IV COPD clinical studies (seven Japanese studies [N=848 available absolute eosinophil counts] and five global studies [N=5,397 available eosinophil counts] that included 246 Japanese patients resident in Japan with available counts). Blood eosinophil distributions were assessed at baseline, before blinded treatment assignment. Findings Among Japanese patients, the median (interquartile range) absolute eosinophil count was 170 cells/mm3 (100–280 cells/mm3). Overall, 612/1,094 Japanese patients (56%) had an absolute eosinophil count ≥150 cells/mm3 and 902/1,304 Japanese patients (69%) had a percentage eosinophil ≥2%. Among non-Japanese patients, these values were 160 (100–250) cells/mm3, 2,842/5,151 patients (55%), and 2,937/5,155 patients (57%), respectively. The eosinophil distribution among Japanese patients was similar to that among non-Japanese patients. Within multi-country studies with similar inclusion criteria, the eosinophil count was numerically lower in Japanese compared with non-Japanese patients (median 120 vs 160 cells/mm3). Interpretation The eosinophil distribution in Japanese patients seems comparable to that of non-Japanese patients; although within multi-country studies, there was a slightly lower median eosinophil count for Japanese patients compared with non-Japanese patients. These findings suggest that blood eosinophil data from global studies are of relevance in Japan. PMID:29440882

Widespread Eosinophilic Pustular Folliculitis in a Nonimmunocompromised Patient

PubMed Central

Almodovar-Real, Ana; Molina-Leyva, Alejandro; Espiñeira-Carmona, María Jose; Ríos-Pelegrina, Rosa; Naranjo-Sintes, Ramón; Husein El-Ahmed, Husein

2014-01-01

Objective We present a case of eosinophilic pustular folliculitis, a rare dermatosis which is often associated with HIV infection or internal malignancies. Clinical Presentation and Intervention We report the case of a 66-year-old man with a medical history of hypertension. Histopathological examination showed a dense follicular inflammatory infiltrate with abundant eosinophils. The clinical response to indomethacin was excellent with no recurrence during the follow-up. Conclusion The patient responded well to indomethacin treatment. PMID:24751524

Mammalian milk allergy: clinical suspicion, cross-reactivities and diagnosis.

PubMed

Järvinen, Kirsi M; Chatchatee, Pantipa

2009-06-01

Cow's milk allergy affects 2-3% of young children, the economic impact of which necessitates search for simple diagnostic tools and affordable milk substitutes. This review examines recent studies on the diagnosis of cow's milk allergy as well as on the allergenicity of milk from other mammalian species. Resolution of symptoms during strict milk avoidance and their re-appearance during the double-blind, placebo-controlled milk challenge remains the gold standard for the diagnosis of cow's milk allergy. Allergic eosinophilic esophagitis/gastroenteritis requires confirmatory endoscopic biopsy. There are increasing data in various populations on cut-off points based on positive predictive values for skin prick test and milk-specific IgE measurements to aid in the diagnosis of cow's milk allergy and to decrease the number of unnecessary food challenges. For non-IgE-mediated manifestations, noninvasive diagnostic tests are still largely lacking. The significant homology between milk from cow, sheep and goat results in clinical cross-reactivity. However, mare's or donkey's milk may be tolerated by some individuals. Data have been accumulating on the utility of diagnostic tools for mostly IgE-mediated milk allergy and allergenicity of milk from other mammalian species, although further studies are sought.

Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease.

PubMed

Tashkin, Donald P; Wechsler, Michael E

2018-01-01

COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention. In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13. The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions. We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD.

Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease

PubMed Central

Tashkin, Donald P; Wechsler, Michael E

2018-01-01

COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention. In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13. The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions. We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. PMID:29403271

Eosinophilic and Neutrophilic Airway Inflammation in the Phenotyping of Mild-to-Moderate Asthma and Chronic Obstructive Pulmonary Disease.

PubMed

Górska, Katarzyna; Paplińska-Goryca, Magdalena; Nejman-Gryz, Patrycja; Goryca, Krzysztof; Krenke, Rafał

2017-04-01

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with different inflammatory phenotypes. Various inflammatory mediators play a role in these diseases. The aim of this study was to analyze the neutrophilic and eosinophilic airway and systemic inflammation as the phenotypic characterization of patients with asthma and COPD. Twenty-four patients with asthma and 33 patients with COPD were enrolled in the study. All the patients were in mild-to-moderate stage of disease, and none of them were treated with inhaled corticosteroids. Concentrations of IL-6, neutrophil elastase (NE), matrix metalloproteinase 9 (MMP-9), eosinophil cationic protein (ECP), and IL-33 and IL-17 in serum and induced sputum (IS) were measured by enzyme-linked immunosorbent assay (ELISA). The cellular composition of blood and IS was evaluated. Hierarchical clustering of patients was performed for the combination of selected clinical features and mediators. Asthma and COPD can be differentiated based on eosinophilic/neutrophilic systemic or airway inflammation with unsatisfactory efficiency. Hierarchical clustering of patients based on blood eosinophil percentage and clinical data revealed two asthma clusters differing in the number of positive skin prick tests and one COPD cluster with two subclusters characterized by low and high blood eosinophil concentrations. Clustering of patients according to IS measurements and clinical data showed two main clusters: pure asthma characterized by high eosinophil/atopy status and mixed asthma and COPD cluster with low eosinophil/atopy status. The neutrophilic phenotype of COPD was associated with more severe airway obstruction and hyperinflation.

Clinical significance of the correlation between PLCE 1 and PRKCA in esophageal inflammation and esophageal carcinoma

PubMed Central

Ma, Ming; Zhang, Shanshan; Zhang, Yongmeng; Yuan, Ming; Liu, Bing; Yang, Yiqiong; Cui, Wen; Ansong, Emmanuel; Dong, Huali; Macias, Virgilia; Yang, Wancai

2017-01-01

Esophagitis and Barrett's esophagus are linked to esophageal squamous cell carcinoma and adenocarcinoma, respectively. However, the underlying mechanisms are still unclear. This study analyzed the expression levels of and correlation between PLCE1 and PRKCA in human esophagitis, carcinogen NMBA-induced rat esophagus, PLCE1 genetic deficient mouse esophageal epithelial tissues and human esophageal cancer cell line, integrated with Online oncology data sets. We found that the expression levels of both PLCE1 and PRKCA were significantly elevated in human esophagitis, esophageal squamous cell carcinoma, Barrett's esophagus, esophageal adenocarcinoma and in NMBA-treated rat esophageal epithelia. However, PRKCA and cytokines were significantly downregulated in PLCE1-deficient mouse esophageal epithelia, and knockdown of PLCE1 in human esophageal cancer cells led to reduction of PRKCA and cytokines. Finally, high expression of both PLCE1 and PRKCA is significantly associated with poor outcomes of the patients with esophageal cancers. In conclusion, this study defined the initiation and progression of esophageal inflammation and malignant transformation, in which the positive correlation of PLCE1 and PRKCA exhibits critical clinical significance. PMID:28402280

Leukemia -- Eosinophilic

MedlinePlus

... social workers, and patient advocates. Cancer.Net Guide Leukemia - Eosinophilic Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

General Information about Esophageal Cancer

MedlinePlus

... Research Esophageal Cancer Treatment (PDQ®)–Patient Version General Information About Esophageal Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Asthma Control and Sputum Eosinophils: A Longitudinal Study in Daily Practice.

PubMed

Demarche, Sophie F; Schleich, Florence N; Paulus, Virginie A; Henket, Monique A; Van Hees, Thierry J; Louis, Renaud E

Longitudinal trials have suggested that asthma control may be influenced by fluctuations in eosinophilic inflammation. This association has however never been confirmed in daily practice. To investigate the relationship between asthma control and sputum eosinophils in clinical practice. A retrospective longitudinal study was conducted on 187 patients with asthma with at least 2 successful sputum inductions at our Asthma Clinic. Linear mixed models were used to assess the relationship between asthma control and individual changes in sputum eosinophils. Receiver-operating characteristic curves were constructed to define minimal important differences (MIDs) of sputum eosinophils associated with a change of at least 0.5 in Asthma Control Questionnaire (ACQ) score. Then, a validation cohort of 79 patients with asthma was recruited to reassess this relationship and the accuracy of the MID values. A multivariate analysis showed that asthma control was independently associated with individual fluctuations in sputum eosinophil count (P < .001). In patients with intermittent/persistently eosinophilic asthma, we calculated a minimal important decrease of 4.3% in the percentage of sputum eosinophils (area under the curve [AUC], 0.69; P < .001) or 3.4-fold (AUC, 0.65; P = .003) for a significant improvement in asthma control and a minimal important increase of 3.5% (AUC, 0.67; P = .004) or 1.8-fold (AUC, 0.63; P = .02) for a significant worsening in asthma control. The association between asthma control and sputum eosinophils and the accuracy of the MIDs of sputum eosinophils were confirmed in the validation cohort. At the individual level, asthma control was associated with fluctuations in sputum eosinophil count over time. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Human eosinophils - potential pharmacological model applied in human histamine H4 receptor research.

PubMed

Grosicki, Marek; Kieć-Kononowicz, Katarzyna

2015-01-01

Histamine and histamine receptors are well known for their immunomodulatory role in inflammation. In this review we describe the role of histamine and histamine H4 receptor on human eosinophils. In the first part of article we provide short summary of histamine and histamine receptors role in physiology and histamine related therapeutics used in clinics. We briefly describe the human histamine receptor H4 and its ligands, as well as human eosinophils. In the second part of the review we provide detailed description of known histamine effects on eosinophils including: intracellular calcium concentration flux, actin polymerization, cellular shape change, upregulation of adhesion proteins and cellular chemotaxis. We provide proofs that these effects are mainly connected with the activation of histamine H4 receptor. When examining experimental data we discuss the controversial results and limitations of the studies performed on isolated eosinophils. In conclusion we believe that studies on histamine H4 receptor on human eosinophils can provide interesting new biomarkers that can be used in clinical studies of histamine receptors, that in future might result in the development of new strategies in the treatment of chronic inflammatory conditions like asthma or allergy, in which eosinophils are involved.

Relationship between esophageal clinical symptoms and manometry findings in patients with esophageal motility disorders: a cross-sectional study.

PubMed

FakhreYaseri, Hashem; FakhreYaseri, Ali Mohammad; Baradaran Moghaddam, Ali; Soltani Arabshhi, Seyed Kamran

2015-01-01

Manometry is the gold-standard diagnostic test for motility disorders in the esophagus. The development of high-resolution manometry catheters and software displays of manometry recordings in color-coded pressure plots have changed the diagnostic assessment of esophageal disease. The diagnostic value of particular esophageal clinical symptoms among patients suspected of esophageal motor disorders (EMDs) is still unknown. The aim of this study was to explore the sensitivity, specificity, and predictive accuracy of presenting esophageal symptoms between abnormal and normal esophageal manometry findings. We conducted a cross-sectional study of 623 patients aged 11-80 years. Data were collected from clinical examinations as well as patient questionnaires. The sensitivity, specificity, and accuracy were calculated after high-resolution manometry plots were reviewed according to the most recent Chicago Criteria. The clinical symptoms were not sensitive enough to discriminate between EMDs. Nevertheless, dysphagia, noncardiac chest pain, hoarseness, vomiting, and weight loss had high specificity and high accuracy to distinguish EMDs from normal findings. Regurgitation and heartburn did not have good accuracy for the diagnosis of EMDs. Clinical symptoms are not reliable enough to discriminate between EMDs. Clinical symptoms can, however, discriminate between normal findings and EMDs, especially achalasia.

Clinical application of endoscopic ultrasonography for esophageal achalasia.

PubMed

Minami, Hitomi; Inoue, Haruhiro; Isomoto, Hajime; Urabe, Shigetoshi; Nakao, Kazuhiko

2015-04-01

Endoscopic ultrasonography (EUS) has been widely used for evaluating the nature of diseases of various organs. The possibility of applying EUS for esophageal motility diseases has not been well discussed despite its versatility. At present, peroral endoscopic myotomy (POEM) for esophageal achalasia and related diseases has brought new attention to esophageal diseases because POEM provides a more direct approach to the inner structures of the esophageal wall. In the present study, we discuss the clinical utility of EUS in evaluating and treating esophageal motility diseases such as esophageal achalasia and related diseases. © 2015 The Authors. Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.

Assessment of eosinophil peroxidase as a potential diagnostic and prognostic marker in dogs with inflammatory bowel disease.

PubMed

Bastan, Idil; Robinson, Nicholas A; Ge, Xiao Na; Rendahl, Aaron K; Rao, Savita P; Washabau, Robert J; Sriramarao, P

2017-01-01

OBJECTIVE To evaluate a method for identifying intact and degranulated eosinophils in the small intestine of dogs with inflammatory bowel disease (IBD) by use of a monoclonal antibody (mAb) against eosinophil peroxidase (EPX). ANIMALS 11 untreated dogs with IBD, 5 dogs with IBD treated with prednisolone, and 8 control dogs with no clinical evidence of gastrointestinal tract disease and no immunosuppressive treatment. PROCEDURES 4-μm-thick sections of paraffin-embedded tissues from necropsy specimens were immunostained with EPX mAb. Stained intact and degranulated eosinophils in consecutive microscopic fields (400X magnification) of the upper (villus tips) and lower (between the muscularis mucosae and crypts) regions of the lamina propria of the jejunum were manually counted. RESULTS Compared with control and treated IBD dogs, untreated IBD dogs had a significantly higher number of degranulated eosinophils in the lower region of the lamina propria. However, no significant differences were detected in the number of intact eosinophils in this region among groups. In the upper region of the lamina propria, untreated IBD dogs had a significantly higher number of degranulated and intact eosinophils, compared with control and treated IBD dogs. Number of degranulated and intact eosinophils did not differ significantly between control and treated IBD dogs. CONCLUSIONS AND CLINICAL RELEVANCE Immunohistologic analysis with EPX mAb yielded prominent granule staining that allowed reliable morphological identification of degranulated and intact eosinophils, which may provide a strategy for quantitative and selective evaluation of eosinophils in gastrointestinal biopsy specimens and a potential method to diagnose IBD and evaluate treatment outcome.

An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock.

PubMed

Martillo, Miguel; Abed, Jean; Herman, Michael; Abed, Elie; Shi, Wenjing; Munot, Khushboo; Mankal, Pavan Kumar; Gurunathan, Rajan; Ionescu, Gabriel; Kotler, Donald P

2015-01-01

Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration.

A diagnosis of eosinophilic esophagitis is associated with increased life insurance premiums.

PubMed

Leiman, D A; Kochar, B; Posner, S; Fan, C; Patel, A; Shaheen, O; Keller, C Y; Koutlas, N T; Eluri, S; Dellon, E S

2018-05-24

Eosinophilic esophagitis (EoE) is a chronic disease that can be diagnosed at any age, but is not associated with malignancy and does not shorten lifespan. It remains unknown whether an EoE diagnosis affects insurability or insurance premium costs. We therefore aimed to determine whether a diagnosis of EoE affects the costs of life insurance. Our investigation was a secret shopper audit study whereby we contacted national insurance companies in the United States to evaluate the effect of a diagnosis of EoE on life insurance premiums. We constructed standardized case scenarios for males and females, including a 25-year-old and a 48-year-old without other comorbid conditions, who either had or did not have a diagnosis of EoE. Companies were asked for their best estimate for a $100,000 whole life insurance policy. Comparisons between median premiums were made using the Mann-Whitney U test. There were 20 national life insurance companies contacted and a total of 73 quotes were obtained. The median premium rate was similar for EoE and non-EoE cases at the younger age ($828 [IQR $576-1,020] vs. $756 [IQR $504-$804]; P = 0.10). However, the premium for the older case without EoE was 19% less expensive compared to a case with EoE ($1990 [IQR $1,248-2,350] vs. $2,375 [IQR $2,100-2568; P = 0.02]. This finding was not explained by sex or state of residence. Based on these findings, we conclude that life insurance premiums are significantly more expensive in the older patient case with EoE when compared to the same case without EoE. Patients with EoE and their providers should be aware of the additional cost associated with this diagnosis.

Genetic variations in the TLR3 locus are associated with eosinophilic esophagitis.

PubMed

Ávila-Castellano, Robledo; García-Lozano, José-Raúl; Cimbollek, Stefan; Lucendo, Alfredo J; Bozada, Juan-Manuel; Quiralte, Joaquín

2018-04-01

Eosinophilic esophagitis (EoE) is an antigen-driven disease mediated by an abnormal immune Th2 response. The objective of this article is to investigate genes associated with regulating immune responses leading to disease susceptibility. Twenty-seven tag single nucleotide polymorphisms (tSNPs) selected in five candidate genes ( TLR3, TLR4, FOXP3, FLG and TSLP ) were genotyped in 218 EoE patients and 376 controls. Skin prick tests were carried out in EoE patients with a panel of 17 aeroallergens and 22 plant- and animal-derived foods. Five tSNPs located in the TSLP locus and one tSNP located in the TLR3 locus were significantly associated with EoE. The interactions between TLR3 and TSLP loci were analyzed. TLR3+/TSLP- and TLR3-/TSLP+ individuals showed a significantly reduced susceptibility to EoE compared to TLR3-/TSLP- individuals (OR = 0.66, p  = 0.036 and OR = 0.23, p  = 0.00014, respectively). Likewise, TLR3+/TSLP+ individuals showed the most decreased susceptibility of developing EoE (OR = 0.16, p  = 0.0001). However, the interaction gain attributed to the combination of both genes was negative (IG = -4.52%), which indicated redundancy or independent effect. Additionally, TLR3 locus was found to be associated with aeroallergen and food sensitization in EoE patients (OR = 9.67, p c  = 0.025 and OR = 0.53, p c  = 0.048, respectively). TLR3 constitutes a novel genetic susceptibility locus for developing EoE, and the effects would be independent of TSLP .

The Six-Food Elimination Diet for Eosinophilic Esophagitis Increases Grocery Shopping Cost and Complexity.

PubMed

Asher Wolf, W; Huang, Kevin Z; Durban, Raquel; Iqbal, Zahra J; Robey, Benjamin S; Khalid, Farah J; Dellon, Evan S

2016-12-01

The six-food elimination diet (SFED), where dairy, wheat, eggs, soy, nuts, and seafood are avoided, is an effective treatment for eosinophilic esophagitis (EoE). Patient-related costs of this approach, however, are unknown. We aimed to assess the cost of and ease of shopping for an SFED compared to an unrestricted diet. A dietitian with expertise in EoE generated menus meeting dietary requirements for a week's worth of meals for the SFED and an unrestricted diet. We compared prices and the number of missing items for both diets at standard and specialty grocery stores. The average weekly price of the SFED at a standard supermarket was $92.54 compared to $79.84 for an unrestricted diet (p = 0.0001). A patient shopping at a standard grocery store needed a higher proportion of items from a second store compared to an unrestricted diet (32 vs. 3 %, p = 0.0001). The prices of the SFED and unrestricted diet using a specialty supermarket were comparable ($106.47 vs. $105.96, p = 0.81), as was the percentage of items requiring a trip to a second store (6 vs. 2 % items, p = 0.03). Shopping at a specialty grocery store increased weekly grocery costs by $13.93 (p = 0.04) for the SFED and $26.12 (p = 0.03) for the unrestricted diet. In conclusion, for patients shopping at standard grocery stores, the cost of an SFED is higher, and an SFED requires more items from a second store. These differences disappear at specialty grocery stores, but costs were significantly higher. This cost and logistical burden can inform patients when selecting dietary therapy.

The extremely narrow-caliber esophagus is a treatment-resistant subphenotype of eosinophilic esophagitis.

PubMed

Eluri, Swathi; Runge, Thomas M; Cotton, Cary C; Burk, Caitlin M; Wolf, W Asher; Woosley, John T; Shaheen, Nicholas J; Dellon, Evan S

2016-06-01

Some patients with eosinophilic esophagitis (EoE) have an extremely narrow esophagus, but the characteristics of this group have not been extensively described. We aimed to characterize the narrow-caliber phenotype of EoE, determine associated risk factors, and identify differences in treatment response in this subgroup of patients. This retrospective cohort study from 2001 to 2014 included subjects with a new diagnosis of EoE per consensus guidelines. Demographic, endoscopic, histologic, and treatment response data were extracted from medical records. An extremely narrow-caliber esophagus was defined when a neonatal endoscope was required to traverse the esophagus due to the inability to pass an adult endoscope. Patients with and without an extremely narrow-caliber esophagus were compared. Multivariable logistical regression was performed to assess treatment outcomes. Of 513 patients with EoE, 46 (9%) had an extremely narrow-caliber esophagus. These patients were older (33 vs 22 years; P < .01), had longer symptom duration (11 vs 3 years; P < .01), more dysphagia (98% vs 66%; P < .01), and food impactions (53% vs 31%; P < .01). Dilation was more common with extreme narrowing (69% vs 17%; P < .01). Patients with a narrow-caliber esophagus were more refractory to steroid treatment, with lower symptom (56% vs 85%), endoscopic (52% vs 76%), and histologic (33% vs 63%) responses (P < .01 for all), and these differences persisted after multivariate analysis. The extremely narrow-caliber esophagus is a more treatment-resistant subphenotype of EoE and is characterized by longer symptom duration and the need for multiple dilations. Recognition of an extremely narrow-caliber esophagus at diagnosis of EoE can provide important prognostic information. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Long telomere length predicts poor clinical outcome in esophageal cancer patients.

PubMed

Lv, Yanyan; Zhang, Yong; Li, Xinru; Ren, Xiaojuan; Wang, Meichen; Tian, Sijia; Hou, Peng; Shi, Bingyin; Yang, Qi

2017-02-01

Abnormal telomere length is widely reported in various human cancers, and it is considered to be an important hallmark of cancer. However, there is remarkably little consensus on the value of telomere length in the prognostic evaluation of esophageal cancers. Here, we attempted to determine the association of variable telomere length with clinical outcome of esophageal cancer patients. Using real-time quantitative PCR, we examined relative telomere lengths (RTL) in a cohort of esophageal cancer and normal esophageal tissues, and statistically investigated the association between RTL and clinical outcomes of esophageal cancer patients. The majority of esophageal cancers in this study had longer RTLs as compared to adjacent non-tumor tissues. Enhanced tumor RTL was associated with smoking habit, poor differentiation, advanced tumor stage, lymph node metastasis and cancer related death. In particular, a close relationship between longer RTL and poor survival was fully demonstrated by using cox regression and Kaplan-Maier survival curves. We found frequent telomere elongation in esophageal cancer tissues, and demonstrated longer RTL may be an independent poor prognostic factor for esophageal cancer patients. Copyright © 2016 Elsevier GmbH. All rights reserved.

Esophageal Dysmotility in Patients following Total Laryngectomy.

PubMed

Zhang, Teng; Maclean, Julia; Szczesniak, Michal; Bertrand, Paul P; Quon, Harry; Tsang, Raymond K; Wu, Peter I; Graham, Peter; Cook, Ian J

2018-02-01

Objectives Dysphagia is common in total laryngectomees, with some symptoms suggesting esophageal dysmotility. Tracheoesophageal (TE) phonation requires effective esophagopharyngeal air passage. Hence, esophageal dysmotility may affect deglutition or TE phonation. This study aimed to determine (1) the characteristics of esophageal dysmotility in laryngectomees, (2) whether clinical history is sensitive in detecting esophageal dysmotility, and (3) the relationship between esophageal dysmotility and TE prosthesis dysfunction. Study Design Multidisciplinary cross-sectional study. Setting Tertiary academic hospital. Subjects and Methods For 31 participants undergone total laryngectomy 1 to 12 years prior, clinical histories were taken by a gastroenterologist and a speech pathologist experienced in managing dysphagia. Esophageal high-resolution manometry was performed and analyzed using Chicago Classification v3.0. Results Interpretable manometric studies were obtained in 23 (1 normal manometry). Esophageal dysmotility patterns included achalasia, esophagogastric junction outflow obstruction, diffuse esophageal spasm, and other major (30%) and minor (50%) peristaltic disorders. The sensitivity of predicting any esophageal dysmotility was 28%, but it is noteworthy that patients with achalasia and diffuse esophageal spasm (DES) were predicted. Two of 4 participants with TE puncture leakage had poor esophageal clearance. Of 20 TE speakers, 12 had voice problems, no correlation between poor voice, and any dysmotility pattern. Conclusions Peristaltic and lower esophageal sphincter dysfunction are common in laryngectomees. Clinical history, while not predictive of minor motor abnormalities, predicted correctly cases with treatable spastic motor disorders. Dysmotility was not associated with poor phonation, although TE puncture leakage might be linked to poor esophageal clearance. Esophageal dysmotility should be considered in the laryngectomees with persisting dysphagia or leaking TE puncture.

Eosinophilic oesophagitis: an otolaryngologist's perspective.

PubMed

Gnanasekaran, T; Gnanasekaran, S; Wood, J M; Friedland, P

2017-06-02

Eosinophilic oesophagitis is a diagnosis that is being made more frequently in the assessment of dysphagia in both adults and children. It is unclear whether this is a result of increased prevalence or improved diagnostic methods. Children present commonly to paediatric institutions with foreign body impaction. Research indicates that food impaction may predispose to eosinophilic oesophagitis. This article presents eosinophilic oesophagitis from an otolaryngologist's point of view. It details the clinical features present in the disease as well as how it is diagnosed and managed. It illustrates early signs of eosinophilic oesophagitis so that primary physicians and emergency physicians know when to refer on to otolaryngologists.

Pathogenesis of Double-Dose Proton Pump Inhibitor-Resistant Non-Erosive Reflux Disease, and Mechanism of Reflux Symptoms and Gastric Acid Secretion-Suppressive Effect in the Presence or Absence of Helicobacter pylori Infection.

PubMed

Kawami, Noriyuki; Takenouchi, Nana; Umezawa, Mariko; Hoshino, Shintaro; Hanada, Yuriko; Hoshikawa, Yoshimasa; Sano, Hirohito; Hoshihara, Yoshio; Nomura, Tsutomu; Uchida, Eiji; Iwakiri, Katsuhiko

2017-01-01

Various mechanisms have been suggested to be responsible for contributing to the occurrence of proton pump inhibitor (PPI)-resistant non-erosive reflux disease (NERD). The aims of this study were to clarify the pathogenesis of PPI-resistant NERD. Fifty-three patients with NERD, who had persistent reflux symptoms despite taking double-dose PPI, were included in this study. After excluding eosinophilic esophagitis (EoE) and primary esophageal motility disorder, esophageal impedance-pH monitoring was carried out. In symptom index (SI)-positive patients, the mechanism of SI positivity and the percent time with intragastric pH >4 were investigated according to the presence or absence of Helicobacter pylori infection. One of the 53 patients had EoE, and 4 had primary esophageal motility disorder. Twenty-three and 2 patients were SI-positive for liquid and gas-only reflux respectively. Of 17 SI-positive, H. pylori-negative patients, 5 were SI-positive for acid reflux, whereas all of the H. pylori-positive patients were SI-positive for non-acid reflux. The percent time with intragastric pH >4 was significantly lower in the H. pylori-negative patients than in the H. pylori-positive patients. The pathogenesis of double-dose PPI-resistant NERD was identified in 57%. In some of H. pylori-negative patients, acid-related symptoms were observed. However, in H. pylori-positive patients, these symptoms were excluded by taking double-dose PPI. © 2017 S. Karger AG, Basel.

Blood eosinophil levels as a biomarker in COPD.

PubMed

Brusselle, Guy; Pavord, Ian D; Landis, Sarah; Pascoe, Steven; Lettis, Sally; Morjaria, Nikhil; Barnes, Neil; Hilton, Emma

2018-05-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder and patients respond differently to treatment. Blood eosinophils are a potential biomarker to stratify patient subsets for COPD therapy. We reviewed the value of blood eosinophils in predicting exacerbation risk and response to corticosteroid treatment in the available literature (PubMed articles in English; keywords: "COPD" and "eosinophil"; published prior to May 2017). Overall, clinical data suggest that in patients with a history of COPD exacerbations, a higher blood eosinophil count predicts an increased risk of future exacerbations and is associated with improved response to treatment with inhaled corticosteroids (in combination with long-acting bronchodilator[s]). Blood eosinophils are therefore a promising biomarker for phenotyping patients with COPD, although prospective studies are needed to assess blood eosinophils as a biomarker of corticosteroid response for this. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinical and dosimetric factors of radiation-induced esophageal injury: radiation-induced esophageal toxicity.

PubMed

Qiao, Wen-Bo; Zhao, Yan-Hui; Zhao, Yan-Bin; Wang, Rui-Zhi

2005-05-07

To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during three-dimensional conformal radiotherapy (3D-CRT). We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria. Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus > or =60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, no grade 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P = 0.0001<0.01). Concurrent chemotherapy and the maximal esophageal point dose > or =60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT.

Clinical, endoscopic and manometric features of the primary motor disorders of the esophagus.

PubMed

Martinez, Júlio César; Lima, Gustavo Rosa de Almeida; Silva, Diego Henrique; Duarte, Alexandre Ferreira; Novo, Neil Ferreira; da Silva, Ernesto Carlos; Pinto, Pérsio Campos Correia; Maia, Alexandre Moreira

2015-01-01

Significant incidence, diagnostic difficulties, clinical relevance and therapeutic efficacy associated with the small number of publications on the primary esophageal motor disorders, motivated the present study. To determine the manometric prevalence of these disorders and correlate them to the endoscopic and clinical findings. A retrospective study of 2614 patients, being 1529 (58.49%) women and 1085 (41.51%) men. From 299 manometric examinations diagnosed with primary esophageal motor disorder, were sought-clinical data (heartburn, regurgitation, dysphagia, odynophagia, non-cardiac chest pain, pharyngeal globe and extra-esophageal symptoms) and/or endoscopic (hiatal hernia, erosive esophagitis, food waste) that motivated the performance of manometry. Were found 49 cases of achalasia, 73 diffuse spasm, 89 nutcracker esophagus, 82 ineffective esophageal motility, and six lower esophageal sphincter hypertension. In relation to the correlations, it was observed that in 119 patients clinical conditions were associated with dysphagia, found in achalasia more than in other conditions; in relationship between endoscopic findings and clinical conditions there was no statistical significance between data. The clinical and endoscopic findings have little value in the characterization of the primary motor disorders of the esophagus, showing even more the need for manometry, particularly in the preoperative period of gastroesophageal reflux disease.

An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock

PubMed Central

Martillo, Miguel; Abed, Jean; Herman, Michael; Abed, Elie; Shi, Wenjing; Munot, Khushboo; Mankal, Pavan Kumar; Gurunathan, Rajan; Ionescu, Gabriel; Kotler, Donald P.

2015-01-01

Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration. PMID:26078733

Non-Eosinophilic Nasal Polyps Shows Increased Epithelial Proliferation and Localized Disease Pattern in the Early Stage.

PubMed

Kim, Dong-Kyu; Jin, Hong Ryul; Eun, Kyoung Mi; Mutusamy, Somasundran; Cho, Seong H; Oh, Sohee; Kim, Dae Woo

2015-01-01

Non-eosinophilic nasal polyps (NPs) show less inflammatory changes and are less commonly associated with lower airway inflammatory disorders such as asthma, compared with eosinophilic NPs. However, the development of non-eosinophilic NPs which is a predominant subtype in Asian population still remains unclear. A total of 81 patients (45 with non-eosinophilic NPs and 36 with eosinophilic NPs) were enrolled. Clinical information and computed tomography (CT), endoscopic, and histological findings were investigated. Tissue samples were analyzed for total IgE levels and for mRNA expression levels of interleukin (IL)-4, IL-5, IL-13, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17A, IL-22, IL-23p19, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, and periostin. Immunostaining assessment of Ki-67 as a proliferation marker was performed. We found that epithelial in-growing patterns such as pseudocysts were more frequently observed in histological and endoscopic evaluations of non-eosinophilic NPs, which was linked to increase epithelial staining of Ki-67, a proliferating marker. Eosinophilic NPs were characterized by high infiltration of inflammatory cells, compared with non-eosinophilic NPs. To investigate the developmental course of each subtype, CT was analyzed according to CT scores and subtypes. Non-eosinophilic NPs showed more localized pattern and maxillary sinus involvement, but lesser olfactory involvement in early stage whereas eosinophilic NPs were characterized by diffuse ethmoidal and olfactory involvement. In addition, high ethmoidal/maxillary (E/M) CT scores, indicating ethmoidal dominant involvement, were one of surrogate markers for eosinophilic NP. E/M CT scores was positively correlated with levels of TH2 inflammatory markers, including IL-4, IL-5, periostin mRNA expression and total IgE levels in NPs, whereas levels of the TH1 cytokine, IFN- γ were inversely correlated. Moreover, if the combinatorial algorithm meet the three of the four markers, including IL-5 (<2.379), periostin (<3.889), IFN-γ (>0.316), and E/M ratio (<2.167), non-eosinophilic CRSwNP are diagnosed with a sensitivity of 84.4% and a specificity of 84.8%. Histologic, immunologic and clinical data suggest that non-eosinophilic NPs showed enhanced epithelial alteration and more localized maxillary involvement. Combination of cutoff value on IL-5, periostin, IFN-γ, and E/M scores may be one of surrogate markers for non-eosinophil NP subtype.

Eosinophilic Otitis Media: the Aftermath of Eosinophil Extracellular Trap Cell Death.

PubMed

Ueki, Shigeharu; Ohta, Nobuo; Takeda, Masahide; Konno, Yasunori; Hirokawa, Makoto

2017-05-01

Eosinophilic otitis media (EOM) is a refractory disease characterized by the accumulation of eosinophils in middle ear effusion and mucosa. We summarize current knowledge regarding the clinical characteristics and management of EOM. Although eosinophil activation in inflamed foci is involved in the pathogenesis of EOM, little is known about the fate of the eosinophils and aftermath of their cell death. We discuss the possibility that eosinophils undergo non-apoptotic cell death that worsens tissue damage and increases effusion viscosity. Unlike chronic otitis media, EOM is strongly associated with an allergic background. Corticosteroids are currently the only effective pharmacological treatment, and surgical intervention is often required. Mucosal eosinophils infiltrate extensively into the middle ear cavity where they are stimulated by locally produced activators including interleukin-5 and eotaxin. The eosinophils undergo cytolysis in the effusion, which represents a major fate of activated eosinophils in vivo. Recent data revealed cytolysis could be renamed as extracellular trap cell death (ETosis). ETosis represents suicidal cell death involving total cell degranulation and development of sticky chromatin structures (extracellular traps (ETs)). The characteristics of eosinophil- and neutrophil-derived ET polymers might contribute to the difference in viscosity of secretions between EOM and common chronic otitis media. The extracellular products remaining after eosinophil ETosis are an important aspect of EOM pathology. The concept of ETosis also has novel implications for potential therapeutic modalities in various eosinophilic disorders.

A case report of esophageal perforation: Complication of nasogastric tube placement

PubMed Central

Isik, Arda; Firat, Deniz; Peker, Kemal; Sayar, Ilyas; Idiz, Oguz; Soytürk, Mehmet

2014-01-01

Patient: Male, 70 Final Diagnosis: Esophageal perforation Symptoms: Abdominal pain • nausea • vomiting Medication: — Clinical Procedure: — Specialty: Surgery Objective: Unusual clinical course Background: Esophageal perforation is a well-defined and severe clinical condition. There are several etiologies of esophagus perforation. Case Report: We report the case of a 70-year-old Caucasian man who underwent an emergency cholecystectomy due to acute cholecystitis. Two days after surgery, his condition deteriorated. Thorax computerized tomography revealed an esophageal perforation. Conclusions: Esophageal perforation due to nasogastric application is relatively rare but the consequences are potentially serious. The anatomy of the upper gastrointestinal system should be understood by all healthcare professionals involved in the treatment. PMID:24803977

Presentation and Epidemiology of Gastroesophageal Reflux Disease.

PubMed

Richter, Joel E; Rubenstein, Joel H

2018-01-01

Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder in the United States, and leads to substantial morbidity, though associated mortality is rare. The prevalence of GERD symptoms appeared to increase until 1999. Risk factors for complications of GERD include advanced age, male sex, white race, abdominal obesity, and tobacco use. Most patients with GERD present with heartburn and effortless regurgitation. Coexistent dysphagia is considered an alarm symptom, prompting evaluation. There is substantial overlap between symptoms of GERD and those of eosinophilic esophagitis, functional dyspepsia, and gastroparesis, posing a challenge for patient management. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Drug-, toxin-, and radiation therapy-induced eosinophilic pneumonia.

PubMed

Solomon, Joshua; Schwarz, Marvin

2006-04-01

A significant number of drugs and toxins have been associated with eosinophilic pneumonia. Antibiotics and NSAID, are the most commonly reported drugs. Toxins suspected to cause eosinophilic pneumonia include cigarette smoke and illicit drugs. Drug- or toxin-induced eosinophilic pneumonia is indistinguishable from idiopathic acute or chronic eosinophilic pneumonia by clinical, radiographic, and histopathologic criteria. The diagnosis is supported by a temporal relationship to a drug or toxin. The condition usually resolves with removal from the agent and recurs with rechallenge. Treatment involves discontinuation of the offending drug or toxin and treatment with corticosteroids in severe respiratory failure. There are also mass outbreaks of eosinophilic pneumonia reported, such as the toxic-oil syndrome in 1981 and the eosinophilia-myalgia syndrome related to the ingestion of L-tryptophan in 1989. A recent report has described an outbreak of acute eosinophilic pneumonia found in soldiers in Iraq. Radiation therapy has also been associated with the development of eosinophilic pneumonia in patients receiving this treatment for breast cancer.

Eosinophilic myositis: an updated review.

PubMed

Selva-O'Callaghan, A; Trallero-Araguás, E; Grau, J M

2014-01-01

Eosinophilia-associated myopathies are clinically and pathologically heterogeneous conditions characterized by the presence of peripheral and/or muscle eosinophilia. There are at least three distinct subtypes: focal eosinophilic myositis, eosinophilic polymyositis, and eosinophilic perimyositis. Infiltrating eosinophils are not always identified in conventional muscle histologic examination, but the eosinophil major basic protein, whose extracellular diffusion is considered a hallmark of eosinophilic cytotoxicity, is usually detected by immunostaining in muscle biopsy. Whereas focal eosinophilic myositis seems to be a benign and isolated condition, and perimyositis is usually related with the inflammatory infiltrate due to fasciitis, eosinophilic polymyositis can be associated with muscular dystrophy or be a feature of multiorgan hypereosinophilic syndrome. Muscle biopsy remains the cornerstone for the diagnosis. Parasitic infections, connective tissue disorders, hematologic and non-hematologic malignancies, drugs, and toxic substances are the main etiologic agents of eosinophilia-associated myopathy. However, in some cases, no known etiologic factor is identified, and these are considered idiopathic. Glucocorticoids are the mainstay therapy in idiopathic forms. Imatinib and mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, may be useful in patients with eosinophilic myositis as part of a hypereosinophilic syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

Eosinophilic panniculitis.

PubMed

Samlaska, C P; de Lorimier, A J; Heldman, L S

1995-03-01

Eosinophillic panniculitis is a poorly defined entity with variable clinical features. We report a case of rapidly enlarging, asymptomatic subcutaneous scalp nodules in a 6-year-old black boy with atopic dermatitis. The nodules resolved spontaneously over two to three days. Biopsy specimens were remarkable for eosinophilic panniculitis without evidence of epidermal change or vasculitis. We believe that this is the youngest reported patient with this disorder.

Clinical application of oral meglumine diatrizoate esophagogram in screening esophageal fistula during radiotherapy for esophageal cancer.

PubMed

Geng, Lidan; Wu, Rong; Hu, He; Zhao, Yu; Fan, Lingli; Zhao, Zhenhua; Liao, Dongbiao; Li, Musheng; Xiang, Miao; Ma, Ying; Du, Xiaobo

2018-05-01

Esophageal fistula is a serious and common complication of radiotherapy for esophageal cancer. Therefore, early diagnosis and treatment is necessary. Because of side effect of barium esophagography, it cannot be used to screening esophageal fistula during radiotherapy. Meglumine diatrizoate is an ionic contrast agent, its adverse reactions were rarely seen when it was used in the body cavity. The purpose of this trial is identified the sensitivity and specificity of oral meglumine diatrizoate in an esophagogram for screening esophageal fistula during radiotherapy. This trial was a prospective, multicenter, diagnostic clinical trial. A total of 105 patients with esophageal cancer will swallowed meglumine diatrizoate and underwent a radiographic examination weekly during radiotherapy, medical personnel observed the esophageal lesions to determine whether an esophageal fistula formed. If an esophageal fistula was observed, esophagofiberoscopy and/or computer tomography was used to further confirm the diagnosis. And the sensitivity and specificity of meglumine diatrizoate should be calculated for screening esophageal fistula during radiotherapy. To our knowledge, this study protocol is the first to identify the sensitivity and specificity of oral meglumine diatrizoate in an esophagogram for screening esophageal fistula during radiotherapy. If oral meglumine diatrizoate can be used to screening esophageal fistula, more patients will benefit from early detection and treatment.

Imipenem/cilastatin-induced acute eosinophilic pneumonia.

PubMed

Foong, Kap Sum; Lee, Ashley; Pekez, Marijeta; Bin, Wei

2016-03-04

Drugs, toxins, and infections are known to cause acute eosinophilic pneumonia. Daptomycin and minocycline are the commonly reported antibiotics associated with acute eosinophilic pneumonia. In this study, we present a case of imipenem/cilastatin-induced acute eosinophilic pneumonia. The patient presented with fever, acute hypoxic respiratory distress, and diffuse ground-glass opacities on the chest CT a day after the initiation of imipenem/cilastatin. Patient also developed peripheral eosinophilia. A reinstitution of imipenem/cilastatin resulted in recurrence of the signs and symptoms. A bronchoscopy with bronchoalveolar lavage showed 780 nucleated cells/mm(3) with 15% eosinophil. The patient's clinical condition improved significantly after the discontinuation of imipenem/cilastatin therapy and the treatment with corticosteroid. 2016 BMJ Publishing Group Ltd.

Patient-reported outcome measures in dysphagia: a systematic review of instrument development and validation.

PubMed

Patel, D A; Sharda, R; Hovis, K L; Nichols, E E; Sathe, N; Penson, D F; Feurer, I D; McPheeters, M L; Vaezi, M F; Francis, David O

2017-05-01

Patient-reported outcome (PRO) measures are commonly used to capture patient experience with dysphagia and to evaluate treatment effectiveness. Inappropriate application can lead to distorted results in clinical studies. A systematic review of the literature on dysphagia-related PRO measures was performed to (1) identify all currently available measures and (2) to evaluate each for the presence of important measurement properties that would affect their applicability. MEDLINE via the PubMed interface, the Cumulative Index of Nursing and Allied Health Literature, and the Health and Psychosocial Instrument database were searched using relevant vocabulary terms and key terms related to PRO measures and dysphagia. Three independent investigators performed abstract and full text reviews. Each study meeting criteria was evaluated using an 18-item checklist developed a priori that assessed multiple domains: (1) conceptual model, (2) content validity, (3) reliability, (4) construct validity, (6) scoring and interpretation, and (7) burden and presentation. Of 4950 abstracts reviewed, a total of 34 dysphagia-related PRO measures (publication year 1987-2014) met criteria for extraction and analysis. Several PRO measures were of high quality (MADS for achalasia, SWAL-QOL and SSQ for oropharyngeal dysphagia, PROMIS-GI for general dysphagia, EORTC-QLQ-OG25 for esophageal cancer, ROMP-swallowing for Parkinson's Disease, DSQ-EoE for eosinophilic esophagitis, and SOAL for total laryngectomy-related dysphagia). In all, 17 met at least one criterion per domain. Thematic deficiencies in current measures were evident including: (1) direct patient involvement in content development, (2) empirically justified dimensionality, (3) demonstrable responsiveness to change, (4) plan for interpreting missing responses, and (5) literacy level assessment. This is the first comprehensive systematic review assessing developmental properties of all available dysphagia-related PRO measures. We identified several instruments with robust measurement properties in multiple diseases including achalasia, oropharyngeal dysphagia, post-surgical dysphagia, esophageal cancer, and dysphagia related to neurological diseases. Findings herein can assist clinicians and researchers in making more informed decisions in selecting the most fundamentally sound PRO measure for a given clinical, research, or quality initiative. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Esophageal motor disorders in cirrhotic patients with esophageal varices non-submitted to endoscopic treatment].

PubMed

Flores, Priscila Pollo; Lemme, Eponina Maria de Oliveira; Coelho, Henrique Sérgio Moraes

2005-01-01

The hepatic cirrhosis has as one of the main morbid-mortality causes, the portal hypertension with the development of esophageal varices, the possibility of a digestive hemorrhage and worsening of hepatic insufficiency. It is important to identify causal predictive or aggravating factors and if possible to prevent them. In the last years, it has been observed the association of esophageal motor disorders and gastro-esophageal reflux in cirrhotic patients with esophageal varices. To study the prevalence of the esophageal motility disorders and among them, the ineffective esophageal motility, in patients with hepatic cirrhosis and esophageal varices, without previous endoscopic therapeutic and the predictive factors. Prospectively, it has been evaluate 74 patients suffering from liver cirrhosis and esophagic varices, without previous endoscopic treatment. All of them were submitted to a clinical protocol, esophageal manometry and 55 patients also held the ambulatory esophageal pHmetry. Esophageal motility disorders have been found in 44 patients (60%). The most prevalent was the ineffective esophageal motility, observed in 28%. The abnormal reflux disease was diagnosed through the pHmetry in 35% of the patients. There were no correlation between the manometrical abnormality in general and the ineffective esophageal motility in particular and the esophageal or gastroesophageal reflux disease symptoms, the abnormal reflux, the disease seriousness, the ascites presence and the gauge of the varices. The majority of cirrhotic patients with non-treated esophageal varices present esophageal motor disorders. No predictive factor was found. The clinical relevance of these findings need more researches in the scope to define the real meaning of theses abnormalities.

Canine eosinophilic folliculitis and furunculosis in three cases.

PubMed

Curtis, C F; Bond, R; Blunden, A S; Thomson, D G; McNeil, P E; Whitbread, T W

1995-03-01

The historical, clinical and histopathological features of three dogs with eosinophilic folliculitis and furunculosis are described. The disease was characterised by the rapid development of pruritic, papular, pustular and ulcerative lesions on the dorsum of the muzzle. Skin lesions were confined to the face in two cases. The third dog had more generalised pustular lesions. Skin biopsy specimens showed marked eosinophil infiltration particularly centred on pilosebaceous units. Dermal collagen necrosis was evident in two cases. Similar facial lesions have previously been described as 'nasal pyoderma'. The three dogs failed to respond to initial antibacterial therapy but showed a rapid clinical response when prednisolone was given orally at doses ranging from 1 to 2.2 mg/kg, in addition to the antibacterial therapy, suggesting that glucocorticoids are indicated for the treatment of eosinophilic folliculitis and furunculosis. The aetiology of the disease was not determined.

Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma

PubMed Central

Januskevicius, Andrius; Gosens, Reinoud; Sakalauskas, Raimundas; Vaitkiene, Simona; Janulaityte, Ieva; Halayko, Andrew J.; Hoppenot, Deimante; Malakauskas, Kestutis

2017-01-01

Background: Airway smooth muscle (ASM) remodeling is an important component of the structural changes to airways seen in asthma. Eosinophils are the prominent inflammatory cells in asthma, and there is some evidence that they contribute to ASM remodeling via released mediators and direct contact through integrin–ligand interactions. Eosinophils express several types of outer membrane integrin, which are responsible for cell–cell and cell–extracellular matrix interactions. In our previous study we demonstrated that asthmatic eosinophils show increased adhesion to ASM cells and it may be important factor contributing to ASM remodeling in asthma. According to these findings, in the present study we investigated the effects of suppression of eosinophil integrin on eosinophil-induced ASM remodeling in asthma. Materials and Methods: Individual combined cell cultures of immortalized human ASM cells and eosinophils from peripheral blood of 22 asthmatic patients and 17 healthy controls were prepared. Eosinophil adhesion was evaluated using eosinophil peroxidase activity assay. Genes expression levels in ASM cells and eosinophils were measured using quantitative real-time PCR. ASM cell proliferation was measured using alamarBlue® solution. Eosinophil integrins were blocked by incubating with Arg-Gly-Asp-Ser peptide. Results: Eosinophils from the asthma group showed increased outer membrane α4β1 and αMβ2 integrin expression, increased adhesion to ASM cells, and overexpression of TGF-β1 compared with eosinophils from the healthy control group. Blockade of eosinophil RGD-binding integrins by Arg-Gly-Asp-Ser peptide significantly reduced adhesion of eosinophils to ASM cells in both groups. Integrin-blocking decreased the effects of eosinophils on TGF-β1, WNT-5a, and extracellular matrix protein gene expression in ASM cells and ASM cell proliferation in both groups. These effects were more pronounced in the asthma group compared with the control group. Conclusion: Suppression of eosinophil-ASM interaction via RGD-binding integrins attenuates eosinophil-induced ASM remodeling in asthma. Trial Registration: ClinicalTrials.gov Identifier: NCT02648074. PMID:28119625

An atypical presentation of cardiac tamponade and periorbital swelling in a patient with eosinophilic granulomatosis with polyangiitis: a case report.

PubMed

Keefe, Alexandra C; Hymas, Joseph C; Emerson, Lyska L; Ryan, John J

2017-09-24

Eosinophilic granulomatosis with polyangiitis is a rare, necrotizing systemic vasculitis associated with asthma and hypereosinophilia. Its cause and pathophysiology are still being elucidated. We report a case of eosinophilic granulomatosis with polyangiitis in a 50-year-old Caucasian woman who presented with chest pain, dyspnea at rest, fever, and periorbital swelling. She was found to have significant hypereosinophilia and cardiac tamponade physiology. A biopsy confirmed extensive infiltration of both lungs and pericardium by eosinophils. She did not have any anti-neutrophil cytoplasmic antibodies. Eosinophilic granulomatosis with polyangiitis diagnosis does not require the presence of anti-neutrophil cytoplasmic antibodies. Anti-neutrophil cytoplasmic antibody-positive and anti-neutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis may present with different clinical phenotypes, perhaps suggesting two distinct disease etiologies and distinct pathophysiology.

Point-of-care blood eosinophil count in a severe asthma clinic setting.

PubMed

Heffler, Enrico; Terranova, Giovanni; Chessari, Carlo; Frazzetto, Valentina; Crimi, Claudia; Fichera, Silvia; Picardi, Giuseppe; Nicolosi, Giuliana; Porto, Morena; Intravaia, Rossella; Crimi, Nunzio

2017-07-01

One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers. To evaluate the performance of a point-of-care peripheral blood counter in a patients with severe asthma. The blood eosinophil counts of 76 patients with severe asthma were evaluated by point-of-care and standard analyzers. A significant correlation between blood eosinophils assessed by the 2 devices was found (R 2  = 0.854, P < .001); similar correlations were found also for white blood cells, neutrophils, and lymphocytes. The point-of-care device had the ability to predict blood eosinophil cutoffs used to select patients for biologic treatments for severe eosinophilic asthma and the ELEN index, a composite score useful to predict sputum eosinophilia. The results of our study contribute to the validation of a point-of-care device to assess blood eosinophils and open the possibility of using this device for the management of severe asthma management. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Esophageal leiomyoma in a dog causing esophageal distension and treated by transcardial placement of a self-expanding, covered, nitinol esophageal stent.

PubMed

Robin, Elisabeth M; Pey, Pascaline B; de Fornel-Thibaud, Pauline; Moissonnier, Pierre H M; Freiche, Valérie

2018-02-01

CASE DESCRIPTION A 10-year-old spayed female Rottweiler was referred for evaluation because of a 2-month history of regurgitation and weight loss, despite no apparent change in appetite. The dog had received antiemetic and antacid treatment, without improvement. CLINICAL FINDINGS Physical examination revealed a low body condition score (2/5), but other findings were unremarkable. Diffuse, global esophageal dilatation was noted on plain thoracic radiographs, and normal motility was confirmed through videofluoroscopic evaluation of swallowing. Transhepatic ultrasonographic and CT examination revealed a circumferential, intraparietal lesion in the distal portion of the esophagus causing distal esophageal or cardial subobstruction and no metastases. Incisional biopsy of the lesion was performed, and findings of histologic examination supported a diagnosis of esophageal leiomyoma. TREATMENT AND OUTCOME In view of numerous possible complications associated with esophageal surgery, the decision was made to palliatively treat the dog by transcardial placement of a self-expanding, covered, nitinol esophageal stent under endoscopic guidance. Two weeks after stent placement, radiography revealed complete migration of the stent into the gastric lumen. Gastrotomy was performed, and the stent was replaced and fixed in place. Twenty-four months after initial stent placement, the dog had a healthy body condition and remained free of previous clinical signs. CLINICAL RELEVANCE Diffuse benign muscular neoplasia should be considered as a differential diagnosis for acquired esophageal dilatation in adult and elderly dogs. In the dog of this report, transcardial stent placement resulted in resolution of the clinical signs, with no apparent adverse effect on digestive function. The described procedure could be beneficial for nonsurgical treatment of benign esophageal tumors in dogs.

The significance of eosinophils in predicting the severity of acute ischemic stroke

PubMed Central

Wang, Jun; Ma, Li; Lin, Tao; Li, Shi-Jing; Chen, Lei-Lei; Wang, De-Zhao

2017-01-01

Background Previous studies have shown that tumor-associated tissue eosinophilia have a role in various types of solid tumors. However, the relationship between eosinophil and acute ischemic stroke (AIS) is unclear. We aimed to investigate the diagnostic significance of eosinophil in AIS patients. Methods This study included 300 AIS patients without hypereosinophilic syndrome (HES). The hematologic indices were collected from each patient, including white blood count, eosinophil count, eosinophil percentage, neutrophil count, red blood count, and platelet. The severity of AIS was estimated by national institute of health stroke scale (NIHSS). Logistic regression analyses were performed to confirm the biomarkers for NIHSS and in-hospital non-death among the cases. Moreover, receiver-operating characteristics (ROC) analyses were used to investigate the clinical performances of eosinophils and NIHSS in prediction of non-death. Results The admission NIHSS (P<0.001) and BMI (P<0.001) were predictors to the non-death of the patients. There was a significant correlation between eosinophil counts or eosinophil percentage and NIHSS score (r= -0.451, P < 0.001; r= -0.617, P<0.001, Spearson Correlation). ROC analysis showed that eosinophil counts and eosinophil percentage could predict non-death of the patients in-hospital, with the areas under the curves (AUC) of 0.791 and 0.867, respectively. Conclusions Our study revealed a relationship between eosinophil and NIHSS score in the patients with AIS. Eosinophils might have certain value for predicting the severity of AIS. PMID:29262636

Elevated Systemic Levels of Eosinophil, Neutrophil, and Mast Cell Granular Proteins in Strongyloides Stercoralis Infection that Diminish following Treatment.

PubMed

Rajamanickam, Anuradha; Munisankar, Saravanan; Bhootra, Yukthi; Dolla, Chandra Kumar; Nutman, Thomas B; Babu, Subash

2018-01-01

Infection with the helminth parasite Strongyloides stercoralis ( Ss ) is commonly clinically asymptomatic that is often accompanied by peripheral eosinophilia. Granulocytes are activated during helminth infection and can act as immune effector cells. Plasma levels of eosinophil and neutrophil granular proteins convey an indirect measure of granulocyte degranulation and are prominently augmented in numerous helminth-infected patients. In this study, we sought to examine the levels of eosinophil, neutrophil, and mast cell activation-associated granule proteins in asymptomatic Ss infection and to understand their kinetics following anthelmintic therapy. To this end, we measured the plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, neutrophil elastase, myeloperoxidase, neutrophil proteinase-3, mast cell tryptase, leukotriene C4, and mast cell carboxypeptidase-A3 in individuals with asymptomatic Ss infection or without Ss infection [uninfected (UN)]. We also estimated the levels of all of these analytes in infected individuals following definitive treatment of Ss infection. We demonstrated that those infected individuals have significantly enhanced plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, elastase, myeloperoxidase, mast cell tryptase, leukotriene C4, and carboxypeptidase-A3 compared to UN individuals. Following the treatment of Ss infection, each of these granulocyte-associated proteins drops significantly. Our data suggest that eosinophil, neutrophil, and mast cell activation may play a role in the response to Ss infection.

Suppressive effects of primed eosinophils on single epicutaneous sensitization through regulation of dermal dendritic cells.

PubMed

Lin, Jing-Yi; Ta, Yng-Cun; Liu, I-Lin; Chen, Hsi-Wen; Wang, Li-Fang

2016-07-01

Eosinophils are multifunctional innate immune cells involved in many aspects of innate and adaptive immunity. Epicutaneous sensitization with protein allergen is an important sensitization route for atopic dermatitis. In this study, using a murine single protein-patch model, we show that eosinophils of a primed status accumulate in draining lymph nodes following single epicutaneous sensitization. Further, depletion of eosinophils results in enhancement of the induced Th1/Th2 immune responses, whereas IL-5-induced hypereosinophilia suppresses these responses. Mechanistically, primed eosinophils cause a reduction in the numbers and activation status of dermal dendritic cells in draining lymph nodes. Collectively, these results demonstrate that primed eosinophils exert suppressive effects on single epicutaneous sensitization through regulation of dermal dendritic cells. Thus, these findings highlight the critical roles of eosinophils in the pathogenesis of atopic dermatitis with important clinical implications for the prevention of allergen sensitization. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intestinal macrophage/epithelial cell-derived CCL11/eotaxin-1 mediates eosinophil recruitment and function in pediatric ulcerative colitis.

PubMed

Ahrens, Richard; Waddell, Amanda; Seidu, Luqman; Blanchard, Carine; Carey, Rebecca; Forbes, Elizabeth; Lampinen, Maria; Wilson, Tara; Cohen, Elizabeth; Stringer, Keith; Ballard, Edgar; Munitz, Ariel; Xu, Huan; Lee, Nancy; Lee, James J; Rothenberg, Marc E; Denson, Lee; Hogan, Simon P

2008-11-15

Clinical studies have demonstrated a link between the eosinophil-selective chemokines, eotaxins (eotaxin-1/CCL11 and eotaxin-2/CCL24), eosinophils, and the inflammatory bowel diseases, Crohn's disease and ulcerative colitis (UC). However, the cellular source and individual contribution of the eotaxins to colonic eosinophilic accumulation in inflammatory bowel diseases remain unclear. In this study we demonstrate, by gene array and quantitative PCR, elevated levels of eotaxin-1 mRNA in the rectosigmoid colon of pediatric UC patients. We show that elevated levels of eotaxin-1 mRNA positively correlated with rectosigmoid eosinophil numbers. Further, colonic eosinophils appeared to be degranulating, and the levels positively correlated with disease severity. Using the dextran sodium sulfate (DSS)-induced intestinal epithelial injury model, we show that DSS treatment of mice strongly induced colonic eotaxin-1 and eotaxin-2 expression and eosinophil levels. Analysis of eosinophil-deficient mice defined an effector role for eosinophils in disease pathology. DSS treatment of eotaxin-2(-/-) and eotaxin-1/2(-/-) mice demonstrated that eosinophil recruitment was dependent on eotaxin-1. In situ and immunofluorescence analysis-identified eotaxin-1 expression was restricted to intestinal F4/80(+)CD11b(+) macrophages in DSS-induced epithelial injury and to CD68(+) intestinal macrophages and the basolateral compartment of intestinal epithelial cells in pediatric UC. These data demonstrate that intestinal macrophage and epithelial cell-derived eotaxin-1 plays a critical role in the regulation of eosinophil recruitment in colonic eosinophilic disease such as pediatric UC and provides a basis for targeting the eosinophil/eotaxin-1 axis in UC.

The Eosinophil Count Tends to Be Negatively Associated with Levels of Serum Glucose in Patients with Adrenal Cushing Syndrome.

PubMed

Lee, Younghak; Yi, Hyon Seung; Kim, Hae Ri; Joung, Kyong Hye; Kang, Yea Eun; Lee, Ju Hee; Kim, Koon Soon; Kim, Hyun Jin; Ku, Bon Jeong; Shong, Minho

2017-09-01

Cushing syndrome is characterized by glucose intolerance, cardiovascular disease, and an enhanced systemic inflammatory response caused by chronic exposure to excess cortisol. Eosinopenia is frequently observed in patients with adrenal Cushing syndrome, but the relationship between the eosinophil count in peripheral blood and indicators of glucose level in patients with adrenal Cushing syndrome has not been determined. A retrospective study was undertaken of the clinical and laboratory findings of 40 patients diagnosed with adrenal Cushing syndrome at Chungnam National University Hospital from January 2006 to December 2016. Clinical characteristics, complete blood cell counts with white blood cell differential, measures of their endocrine function, description of imaging studies, and pathologic findings were obtained from their medical records. Eosinophil composition and count were restored by surgical treatment of all of the patients with adrenal Cushing disease. The eosinophil count was inversely correlated with serum and urine cortisol, glycated hemoglobin, and inflammatory markers in the patients with adrenal Cushing syndrome. Smaller eosinophil populations in patients with adrenal Cushing syndrome tend to be correlated with higher levels of blood sugar and glycated hemoglobin. This study suggests that peripheral blood eosinophil composition or count may be associated with serum glucose levels in patients with adrenal Cushing syndrome. Copyright © 2017 Korean Endocrine Society

The Eosinophil Count Tends to Be Negatively Associated with Levels of Serum Glucose in Patients with Adrenal Cushing Syndrome

PubMed Central

Lee, Younghak; Kim, Hae Ri; Joung, Kyong Hye; Kang, Yea Eun; Lee, Ju Hee; Kim, Koon Soon; Kim, Hyun Jin; Ku, Bon Jeong; Shong, Minho

2017-01-01

Background Cushing syndrome is characterized by glucose intolerance, cardiovascular disease, and an enhanced systemic inflammatory response caused by chronic exposure to excess cortisol. Eosinopenia is frequently observed in patients with adrenal Cushing syndrome, but the relationship between the eosinophil count in peripheral blood and indicators of glucose level in patients with adrenal Cushing syndrome has not been determined. Methods A retrospective study was undertaken of the clinical and laboratory findings of 40 patients diagnosed with adrenal Cushing syndrome at Chungnam National University Hospital from January 2006 to December 2016. Clinical characteristics, complete blood cell counts with white blood cell differential, measures of their endocrine function, description of imaging studies, and pathologic findings were obtained from their medical records. Results Eosinophil composition and count were restored by surgical treatment of all of the patients with adrenal Cushing disease. The eosinophil count was inversely correlated with serum and urine cortisol, glycated hemoglobin, and inflammatory markers in the patients with adrenal Cushing syndrome. Conclusion Smaller eosinophil populations in patients with adrenal Cushing syndrome tend to be correlated with higher levels of blood sugar and glycated hemoglobin. This study suggests that peripheral blood eosinophil composition or count may be associated with serum glucose levels in patients with adrenal Cushing syndrome. PMID:28956365

A rare case of Ibuprofen-induced eosinophilic meningitis in a 13-year-old girl.

PubMed

Bansal, Sharad; Gupta, Mukesh; Sharma, Deepak; Bansal, Shweta

2014-01-01

Eosinophilic meningoencephalitis is based on clinical manifestations and microscopic identification of eosinophils present in cerebrospinal fluid (CSF). It is caused by a variety of helminthic infections with most common being angiostrongyliasis, gnathostomiasis, toxocariasis, cysticercosis, schistosomiasis, baylisascariasis, and paragonimiasis. Many case reports are there in which parasites have been found responsible, but there are rare reports of CSF eosinophilia associated with the use of drugs. We report a case of drug-induced (ibuprofen) eosinophilic meningitis in a healthy female who presented to us with severe headache and improved dramatically after drug withdrawal.

SU-E-T-575: To Analyze the Clinical Impact of Esophageal Sparing on Treatment Plans for Patients with Grade 3 Esophagitis.

PubMed

Niedzielski, J; Bluett, J; Williamson, R; Liao, Z; Gomez, D; Court, L

2012-06-01

To analyze the clinical impact of esophageal sparing on treatment plans for patients with grade 3 esophagitis. The treatment plans of 8 patients (project total: 20 patients) who were treated with IMRT and exhibited stage 3 esophagitis were re-planned to give a simulated clinical plan with dose distribution that mirrored our current clinical practice (74Gy to the target, and 5mm margins), and a plan that emphasized esophageal sparing. Doses to the esophagus, heart, cord, lung and PTV were compared. Comparing the esophageal sparing plan to the simulated clinical plan, the mean reduction in esophageal volume receiving 50, 55, 60, 65, and 70Gy were 2.0, 3.2, 5.0, 7.2, and 10.9 cm 3 , respectively. The mean reduction in the continuous length of esophagus receiving 50, 55, 60, 65, and 70Gy were 12, 24, 38, 40, and 47mm, respectively. The associated reduction in dose to 90% and 95% of the PTV was 2.2 and 3.8Gy, respectively. Of the 8 patients examined, 2 showed a significant decrease in PTV coverage (4.6Gy, 12.3Gy for 90% of PTV), 4 showed decreases under 1.1Gy, but 2 showed an increase of 1.4Gy and 0.5Gy for 90% PTV. Cord dose was maintained below 50Gy, and there was a slight increase in mean heart dose and mean lung dose of 2.4Gy, and 2.7Gy, respectively. Data will also be presented comparing these plans with the actual treated plans (for which the patients had grade 3 esophagitis) and plans that emphasize PTV coverage. Treatment planning to emphasize esophageal sparing can reduce the volume and continuous length of the esophagus which receives high doses. There is some associated modest reduction in PTV coverage. In summary, in many cases esophageal sparing can be accomplished for lung cancer cases while maintaining adequate PTV coverage, although there is variability between patients. © 2012 American Association of Physicists in Medicine.

Eosinophilic Pleural Effusion: A Rare Manifestation of Hypereosinophilic Syndrome

PubMed Central

Okafor, Ndubuisi C.; Oso, Ayodeji A.; Oranu, Amanke C.; Wolff, Steven M.; Murray, John J.

2009-01-01

Several causes of eosinophilic pleural effusions have been described with malignancy being the commonest cause. Hypereosinophilic syndrome (HES) is a rare disease and very few cases have been reported of HES presenting as eosinophilic pleural effusion (EPE). We report a case of a 26-year-old male who presented with shortness of breath. He had bilateral pleural effusions, generalized lymphadenopathy, splenomegaly, and leukocytosis with marked peripheral blood eosinophilia. The pleural fluid was exudative, with 25%–30% eosinophilis, and absence of neoplastic cells. Hypereosinophilic syndrome was diagnosed after other causes of eosinophilia were excluded. He continued to be dyspneic with persistent accumulation of eosinophilic pleural fluid, even after his peripheral eosinophil count had normalized in response to treatment. This patient represents a very unusual presentation of HES with dyspnea and pleural effusions and demonstrates that treatment based on response of peripheral eosinophil counts, as is currently recommended, may not always be clinically adequate. PMID:20111739

Eosinophilic pleural effusion: a rare manifestation of hypereosinophilic syndrome.

PubMed

Okafor, Ndubuisi C; Oso, Ayodeji A; Oranu, Amanke C; Wolff, Steven M; Murray, John J

2009-01-01

Several causes of eosinophilic pleural effusions have been described with malignancy being the commonest cause. Hypereosinophilic syndrome (HES) is a rare disease and very few cases have been reported of HES presenting as eosinophilic pleural effusion (EPE). We report a case of a 26-year-old male who presented with shortness of breath. He had bilateral pleural effusions, generalized lymphadenopathy, splenomegaly, and leukocytosis with marked peripheral blood eosinophilia. The pleural fluid was exudative, with 25%-30% eosinophilis, and absence of neoplastic cells. Hypereosinophilic syndrome was diagnosed after other causes of eosinophilia were excluded. He continued to be dyspneic with persistent accumulation of eosinophilic pleural fluid, even after his peripheral eosinophil count had normalized in response to treatment. This patient represents a very unusual presentation of HES with dyspnea and pleural effusions and demonstrates that treatment based on response of peripheral eosinophil counts, as is currently recommended, may not always be clinically adequate.

Increasing Comorbidities Suggest that Atopic Dermatitis Is a Systemic Disorder.

PubMed

Brunner, Patrick M; Silverberg, Jonathan I; Guttman-Yassky, Emma; Paller, Amy S; Kabashima, Kenji; Amagai, Masayuki; Luger, Thomas A; Deleuran, Mette; Werfel, Thomas; Eyerich, Kilian; Stingl, Georg

2017-01-01

Atopic dermatitis comorbidities extend well beyond the march to allergic conditions (food allergy, asthma, allergic rhinitis, allergic conjunctivitis, and eosinophilic esophagitis), suggesting both cutaneous and systemic immune activation. In reviewing atopic dermatitis comorbidities, Councilors of the International Eczema Council found a strong pattern of immune activation in peripheral blood and the propensity to both skin and systemic infections. Associations with cardiovascular, neuropsychiatric, and malignant diseases were increasingly reported, but confirmation of their link with atopic dermatitis requires longitudinal studies. Given the possibility of atopic dermatitis-related systemic immune activation, future investigations of new interventions should concurrently examine the impact on these comorbidities. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer: frequency and prediction.

PubMed

Atsumi, Kazushige; Shioyama, Yoshiyuki; Arimura, Hidetaka; Terashima, Kotaro; Matsuki, Takaomi; Ohga, Saiji; Yoshitake, Tadamasa; Nonoshita, Takeshi; Tsurumaru, Daisuke; Ohnishi, Kayoko; Asai, Kaori; Matsumoto, Keiji; Nakamura, Katsumasa; Honda, Hiroshi

2012-04-01

To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Impact of esophageal flexion level on the surgical outcome in patients with sigmoid esophageal achalasia.

PubMed

Tsuboi, Kazuto; Omura, Nobuo; Yano, Fumiaki; Hoshino, Masato; Yamamoto, Se-Ryung; Akimoto, Shunsuke; Masuda, Takahiro; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2017-11-01

Esophageal achalasia can be roughly divided into non-sigmoid and sigmoid types. Laparoscopic surgery has been reported to be less than optimally effective for sigmoid type. The aim of this study was to examine the impact of the esophageal flexion level on the clinical condition and surgical outcomes of patients with sigmoid esophageal achalasia. The subjects were 36 patients with sigmoid esophageal achalasia who had been observed for >1 year after surgery. The subjects were divided into sigmoid type (Sg) and advanced sigmoid type (aSg) groups based on the flexion level of the lower esophagus to compare their clinical parameters and surgical outcomes. The Sg and aSg groups included 26 (72%) and 10 subjects, respectively. There were no marked differences in the clinical parameters or surgical outcomes between the two groups. However, the clearance rate calculated using the timed barium esophagogram was lower in the aSg group than in the Sg group. No differences were found in the postoperative symptom scores between the two groups, and both reported a high level of satisfaction. Although laparoscopic surgery for symptoms of sigmoid esophageal achalasia was highly successful regardless of the flexion level, the improvement in esophageal clearance was lower when the flexion level was higher.

Eosinophil count, allergies, and rejection in pediatric heart transplant recipients.

PubMed

Arbon, Kate S; Albers, Erin; Kemna, Mariska; Law, Sabrina; Law, Yuk

2015-08-01

Allograft rejection and long-term immunosuppression remain significant challenges in pediatric heart transplantation. Pediatric recipients are known to have fewer rejection episodes and to develop more allergic conditions than adults. A T-helper 2 cell dominant phenotype, manifested clinically by allergies and an elevated eosinophil count, may be associated with immunologic quiescence in transplant recipients. This study assessed whether the longitudinal eosinophil count and an allergic phenotype were associated with freedom from rejection. This single-center, longitudinal, observational study included 86 heart transplant patients monitored from 1994 to 2011. Post-transplant biannual complete blood counts, allergic conditions, and clinical characteristics related to rejection risk were examined. At least 1 episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody-mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were diagnosed with an allergic condition. Patients with ACR or AMR had a lower eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022, respectively). In the multivariable regression analysis, the presence of panel reactive antibodies to human leukocyte antigen I (p = 0.014) and the median eosinophil count (p = 0.011) were the only independent covariates associated with AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent risk factors for ACR. Allergic conditions or young age at transplant were not protective from rejection. This study demonstrates a novel association between a high eosinophil count and freedom from rejection. Identifying a biomarker for low rejection risk may allow a reduction in immunosuppression. Further investigation into the role of the T-helper 2 cell phenotype and eosinophils in rejection quiescence is warranted. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): a systematic review and meta-analysis.

PubMed

Petsky, Helen L; Cates, Chris J; Kew, Kayleigh M; Chang, Anne B

2018-06-01

Asthma guidelines guide health practitioners to adjust treatments to the minimum level required for asthma control. As many people with asthma have an eosinophilic endotype, tailoring asthma medications based on airway eosinophilic levels (sputum eosinophils or exhaled nitric oxide, FeNO) may improve asthma outcomes. To synthesise the evidence from our updated Cochrane systematic reviews, for tailoring asthma medication based on eosinophilic inflammatory markers (sputum analysis and FeNO) for improving asthma-related outcomes in children and adults. Cochrane reviews with standardised searches up to February 2017. The Cochrane reviews included randomised controlled comparisons of tailoring asthma medications based on sputum analysis or FeNO compared with controls (primarily clinical symptoms and/or spirometry/peak flow). The 16 included studies of FeNO-based management (seven in adults) and 6 of sputum-based management (five in adults) were clinically heterogeneous. On follow-up, participants randomised to the sputum eosinophils strategy (compared with controls) were significantly less likely to have exacerbations (62 vs 82/100 participants with ≥1 exacerbation; OR 0.36, 95% CI 0.21 to 0.62). For the FeNO strategy, the respective numbers were adults OR 0.60 (95% CI 0.43 to 0.84) and children 0.58 (95% CI 0.45 to 0.75). However, there were no significant group differences for either strategy on daily inhaled corticosteroids dose (at end of study), asthma control or lung function. Adjusting treatment based on airway eosinophilic markers reduced the likelihood of asthma exacerbations but had no significant impact on asthma control or lung function. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Widespread eosinophilic pustular folliculitis in a nonimmunocompromised patient.

PubMed

Almodovar-Real, Ana; Molina-Leyva, Alejandro; Espiñeira-Carmona, María Jose; Ríos-Pelegrina, Rosa; Naranjo-Sintes, Ramón; Husein El-Ahmed, Husein

2014-01-01

We present a case of eosinophilic pustular folliculitis, a rare dermatosis which is often associated with HIV infection or internal malignancies. We report the case of a 66-year-old man with a medical history of hypertension. Histopathological examination showed a dense follicular inflammatory infiltrate with abundant eosinophils. The clinical response to indomethacin was excellent with no recurrence during the follow-up. The patient responded well to indomethacin treatment. © 2014 S. Karger AG, Basel.

Intestinal Macrophage/Epithelial Cell-Derived CCL11/Eotaxin-1 Mediates Eosinophil Recruitment and Function in Pediatric Ulcerative Colitis1

PubMed Central

Ahrens, Richard; Waddell, Amanda; Seidu, Luqman; Blanchard, Carine; Carey, Rebecca; Forbes, Elizabeth; Lampinen, Maria; Wilson, Tara; Cohen, Elizabeth; Stringer, Keith; Ballard, Edgar; Munitz, Ariel; Xu, Huan; Lee, Nancy; Lee, James J.; Rothenberg, Marc E.; Denson, Lee; Hogan, Simon P.

2009-01-01

Clinical studies have demonstrated a link between the eosinophil-selective chemokines, eotaxins (eotaxin-1/CCL11 and eotaxin-2/CCL24), eosinophils, and the inflammatory bowel diseases, Crohn’s disease and ulcerative colitis (UC). However, the cellular source and individual contribution of the eotaxins to colonic eosinophilic accumulation in inflammatory bowel diseases remain unclear. In this study we demonstrate, by gene array and quantitative PCR, elevated levels of eotaxin-1 mRNA in the rectosigmoid colon of pediatric UC patients. We show that elevated levels of eotaxin-1 mRNA positively correlated with rectosigmoid eosinophil numbers. Further, colonic eosinophils appeared to be degranulating, and the levels positively correlated with disease severity. Using the dextran sodium sulfate (DSS)-induced intestinal epithelial injury model, we show that DSS treatment of mice strongly induced colonic eotaxin-1 and eotaxin-2 expression and eosinophil levels. Analysis of eosinophil-deficient mice defined an effector role for eosinophils in disease pathology. DSS treatment of eotaxin-2−/− and eotaxin-1/2−/− mice demonstrated that eosinophil recruitment was dependent on eotaxin-1. In situ and immunofluorescence analysis-identified eotaxin-1 expression was restricted to intestinal F4/80+CD11b+ macrophages in DSS-induced epithelial injury and to CD68+ intestinal macrophages and the basolateral compartment of intestinal epithelial cells in pediatric UC. These data demonstrate that intestinal macrophage and epithelial cell-derived eotaxin-1 plays a critical role in the regulation of eosinophil recruitment in colonic eosinophilic disease such as pediatric UC and provides a basis for targeting the eosinophil/eotaxin-1 axis in UC. PMID:18981162

From blood to breath: New horizons for esophageal cancer biomarkers.

PubMed

Yazbeck, Roger; Jaenisch, Simone E; Watson, David I

2016-12-14

Esophageal cancer is a lethal cancer encompassing adenocarcinoma and squamous cell carcinoma sub-types. The global incidence of esophageal cancer is increasing world-wide, associated with the increased prevalence of associated risk factors. The asymptomatic nature of disease often leads to late diagnosis and five-year survival rates of less than 15%. Current diagnostic tools are restricted to invasive and costly endoscopy and biopsy for histopathology. Minimally and non-invasive biomarkers of esophageal cancer are needed to facilitate earlier detection and better clinical management of patients. This paper summarises recent insights into the development and clinical validation of esophageal cancer biomarkers, focussing on circulating markers in the blood, and the emerging area of breath and odorant biomarkers.

Churg-Strauss syndrome with coexistence of eosinophilic vasculitis, granulomatous phlebitis and granulomatous dermatitis in bullous pemphigoid-like blisters.

PubMed

Ishibashi, Masafumi; Kudo, Saori; Yamamoto, Kyoko; Shimai, Nobuko; Chen, Ko-Ron

2011-03-01

The main histopathological features in the cutaneous lesions of Churg-Strauss syndrome (CSS) are dermal leukocytoclastic vasculitis with a variable eosinophilic infiltrate and non-vasculitic tissue eosinophilia with granuloma formation. This wide histopathological spectrum may account for the various skin manifestations of CSS. However, the unique histopathological combination of dermal eosinophilic vasculitis and subcutaneous granulomatous phlebitis accompanied by bulla formation has not been previously described. We report an unusual CSS case showing dermal necrotizing eosinophilic vasculitis and granulomatous phlebitis in purpuric lesions coupled with subepidermal blistering. The blisters showed dermal granulomatous dermatitis and eosinophilia without evidence of vasculitis. Dermal necrotizing eosinophilic vasculitis was characterized by fibrinoid alteration of the vessel wall, a prominent perivascular eosinophilic infiltrate, a few infiltrating histiocytes along the affected vessel wall, and the absence of neutrophilic infiltration. The underlying subcutaneous granulomatous phlebitis was characterized by an angiocentric histiocytic infiltrate surrounded by marked eosinophilic infiltrate. Deposition of cytotoxic proteins and radicals derived from eosinophils in the vessel walls and papillary dermis followed by a secondary granulomatous response may account for the unique clinical and histopathological features in this case. Copyright © 2010 John Wiley & Sons A/S.

Platelet–Eosinophil Interactions As a Potential Therapeutic Target in Allergic Inflammation and Asthma

PubMed Central

Shah, Sajeel A.; Page, Clive P.; Pitchford, Simon C.

2017-01-01

The importance of platelet activation during hemostasis is well understood. An understanding of these mechanisms has led to the use of several classes of anti-platelet drugs to inhibit aggregation for the prevention of thrombi during cardiovascular disease. It is now also recognized that platelets can function very differently during inflammation, as part of their role in the innate immune response against pathogens. This dichotomy in platelet function occurs through distinct physiological processes and alternative signaling pathways compared to that of hemostasis (leading to platelet aggregation) and is manifested as increased rheological interactions with leukocytes, the ability to undergo chemotaxis, communication with antigen-presenting cells, and direct anti-pathogen responses. Mounting evidence suggests platelets are also critical in the pathogenesis of allergic diseases such as asthma, where they have been associated with antigen presentation, bronchoconstriction, bronchial hyperresponsiveness, airway inflammation, and airway remodeling in both clinical and experimental studies. In particular, platelets have been reported bound to eosinophils in the blood of patients with asthma and the incidence of these events increases after both spontaneous asthma attacks in a biphasic manner, or after allergen challenge in the clinic. Platelet depletion in animal models of allergic airway inflammation causes a profound reduction in eosinophil recruitment to the lung, suggesting that the association of platelets with eosinophils is indeed an important event during eosinophil activation. Furthermore, in cases of severe asthma, and in animal models of allergic airways inflammation, platelet–eosinophil complexes move into the lung through a platelet P-selectin-mediated, eosinophil β1-integrin activation-dependent process, while platelets increase adherence of eosinophils to the vascular endothelium in vitro, demonstrating a clear interaction between these cell types in allergic inflammatory diseases. This review will explore non-thrombotic platelet activation in the context of allergy and the association of platelets with eosinophils, to reveal how these phenomena may lead to the discovery of novel therapeutic targets. PMID:28848732

The Greater Cincinnati Pediatric Clinic Repository: A Novel Framework for Childhood Asthma and Allergy Research

PubMed Central

Butsch Kovacic, Melinda; Biagini Myers, Jocelyn M.; Lindsey, Mark; Patterson, Tia; Sauter, Sharon; Ericksen, Mark B.; Ryan, Patrick; Assa'ad, Amal; Lierl, Michelle; Fischer, Thomas; Kercsmar, Carolyn; McDowell, Karen; Lucky, Anne W.; Sheth, Anita P.; Hershey, Andrew D.; Ruddy, Richard M.; Rothenberg, Marc E.

2012-01-01

Background Allergic disorders, including asthma, allergic rhinitis, atopic dermatitis, eosinophilic esophagitis, and food allergy, are a major global health burden. The study and management of allergic disorders is complicated by the considerable heterogeneity in both the presentation and natural history of these disorders. Biorepositories serve as an excellent source of data and biospecimens for delineating subphenotypes of allergic disorders, but such resources are lacking. Methods In order to define subphenotypes of allergic disease accurately, we established an infrastructure to link and efficiently utilize clinical and epidemiologic data with biospecimens into a single biorepository called the Greater Cincinnati Pediatric Clinic Repository (GCPCR). Children with allergic disorders as well as healthy controls are followed longitudinally at hospital clinic, emergency department, and inpatient visits. Subjects' asthma, allergy, and skin symptoms; past medical, family, social, diet, and environmental histories; physical activity; medication adherence; perceived quality of life; and demographics are ascertained. DNA is collected from all participants, and other biospecimens such as blood, hair, and nasal epithelial cells are collected on a subset. Results To date, the GCPCR has 6,317 predominantly Caucasian and African American participants, and 93% have banked DNA. This large sample size supports adequately powered genetic, epidemiologic, environmental, and health disparities studies of childhood allergic diseases. Conclusions The GCPCR is a unique biorepository that is continuously evaluated and refined to achieve and maintain rigorous clinical phenotype and biological data. Development of similar disease-specific repositories using common data elements is necessary to enable studies across multiple populations of comprehensively phenotyped patients. PMID:22768387

Eosinophils from Physiology to Disease: A Comprehensive Review

PubMed Central

Yacoub, Mona-Rita; Ripa, Marco; Mannina, Daniele; Cariddi, Adriana; Saporiti, Nicoletta; Ciceri, Fabio; Castagna, Antonella; Dagna, Lorenzo

2018-01-01

Despite being the second least represented granulocyte subpopulation in the circulating blood, eosinophils are receiving a growing interest from the scientific community, due to their complex pathophysiological role in a broad range of local and systemic inflammatory diseases as well as in cancer and thrombosis. Eosinophils are crucial for the control of parasitic infections, but increasing evidence suggests that they are also involved in vital defensive tasks against bacterial and viral pathogens including HIV. On the other side of the coin, eosinophil potential to provide a strong defensive response against invading microbes through the release of a large array of compounds can prove toxic to the host tissues and dysregulate haemostasis. Increasing knowledge of eosinophil biological behaviour is leading to major changes in established paradigms for the classification and diagnosis of several allergic and autoimmune diseases and has paved the way to a “golden age” of eosinophil-targeted agents. In this review, we provide a comprehensive update on the pathophysiological role of eosinophils in host defence, inflammation, and cancer and discuss potential clinical implications in light of recent therapeutic advances. PMID:29619379

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atsumi, Kazushige; Shioyama, Yoshiyuki, E-mail: shioyama@radiol.med.kyushu-u.ac.jp; Arimura, Hidetaka

Purpose: To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Methods and Materials: The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors andmore » therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Results: Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Conclusion: Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer.« less

When Should Infants with Cow's Milk Protein Allergy Use an Amino Acid Formula? A Practical Guide.

PubMed

Meyer, Rosan; Groetch, Marion; Venter, Carina

Cow's milk protein allergy (CMPA) is the most common food allergy in childhood and its prevalence ranges between 1.9% and 4.9%. Most children present with CMPA at age less than 1 year and therefore may require a hypoallergenic formula in the absence of breast milk. Hypoallergenic formulas include both extensively hydrolyzed formula (EHF) and amino acid formula (AAF). For most children with a CMPA, an EHF will be sufficient for symptom resolution, as reflected in current guidelines, but there is a subset of children with CMPA where an AAF may be indicated. The appropriate use of an AAF is a highly debated topic, because there is a significant fiscal burden to either the health care system or the parents. From the literature, the following themes were identified as possible reasons for choosing an AAF: (1) symptoms not fully resolved on EHF, (2) faltering growth/failure to thrive, (3) multiple food eliminations, (4) severe complex gastrointestinal food allergies, (5) eosinophilic esophagitis, (6) food protein-induced enterocolitis syndrome, (7) severe eczema, and (8) symptoms while breast-feeding. Each of these themes was critically reviewed using all available published data and found that using an AAF in height growth faltering may be indicated. In addition, patients who end up on an AAF often present with multisystem involvement, requiring multiple food eliminations and fall within the more severe spectrum of gastrointestinal allergies. In eosinophilic esophagitis, all current recommendations support the use of an AAF as first-line approach, and in children with anaphylaxis, despite limited evidence an AAF is recommended because of the potential risk for a severe reaction. The use of an AAF in children who are breast-fed remains a highly controversial topic and at all times breast-feeding should be supported in children with CMPA. This article provides a practical guide that is evidence based for health care professionals to the use of AAF. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Population-based familial aggregation of eosinophilic esophagitis suggests a genetic contribution.

PubMed

Allen-Brady, Kristina; Firszt, Rafael; Fang, John C; Wong, Jathine; Smith, Ken R; Peterson, Kathryn A

2017-10-01

Prior familial clustering studies have observed an increased risk of eosinophilic esophagitis (EoE) mostly among first-degree relatives, suggesting a genetic contribution to EoE, and twin studies have suggested a powerful contribution from environmental factors. This study sought to clarify the contribution of genetic factors to EoE through estimation of familial aggregation and risk of EoE in extended relatives. The Utah Population Database, a population-based genealogy resource linked to electronic medical records for health care systems across the state of Utah, was used to identify EoE cases and age, sex, and birthplace-matched controls at a 5:1 ratio. Logistic regression was used to determine the odds of EoE among relatives of EoE probands compared with the odds of EoE among relatives of controls. There were 4,423 EoE cases and 24,322 controls. The population-attributable risk of EoE was 31% (95% CI, 28% to 34%), suggesting a relatively strong genetic contribution. Risks of EoE were significantly increased among first-degree relatives (odds ratio [OR], 7.19; 95% CI, 5.65-9.14), particularly first-degree relatives of EoE cases diagnosed <18 years of age (OR, 16.3; 95% CI, 9.4-28.3); second-degree relatives (OR, 1.99; 95% CI, 1.49-2.65); and first cousins (OR, 1.35; 95% CI, 1.03-1.77), providing evidence of a genetic contribution. However, spouses of EoE probands were observed to be at increased risk of EoE (OR, 2.86; 95% CI, 1.31-6.25), suggesting either positive assortative mating or a shared environmental contribution to EoE. This study supports a significant genetic contribution to EoE as evidenced by increased risk of EoE in distant relatives. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

New Insights into Eosinophilic Otitis Media.

PubMed

Kanazawa, Hiromi; Yoshida, Naohiro; Iino, Yukiko

2015-12-01

Eosinophilic otitis media (EOM) is a type of intractable otitis media that occurs mainly in patients with bronchial asthma (BA). In 2011, the diagnostic criteria for EOM were established. EOM is characterized by the presence of a highly viscous yellowish effusion containing eosinophils and immunoglobulin E (IgE), eosinophil chemoattractants, such as eosinophil cationic protein, interleukin-5, and eotaxin. Local sensitization against foreign agents such as fungi or bacteria (e.g., Staphylococcus aureus) may result in local IgE production in the middle ear and may be responsible for the severity of EOM. The clinical features of EOM closely resemble localized eosinophilic granulomatosis polyangiitis, therefore it is necessary to be vigilant to the symptoms of mononeuritis, polyneuritis, and skin purpura during diagnosis. Standard treatment for EOM is the instillation of triamcinolone acetonide into the mesotympanum. However, severe cases exhibiting strong inflammation and otorrhea are not easily controlled with antibiotics and/or corticosteroids. We proposed the introduction of a severity score to evaluate the severity of EOM. This score correlated with local IgE levels in middle ear effusion. Clinically, the risk factors associated with this severity score were body mass index, and the duration of bronchial asthma (from the onset of BA to the age of the first consultation of otitis media to our hospital). We emphasize that early diagnosis and adequate treatment are vital in preventing progressive and sudden hearing loss resulting from EOM.

Real-time assessment of inflammation and treatment response in a mouse model of allergic airway inflammation

PubMed Central

Cortez-Retamozo, Virna; Swirski, Filip K.; Waterman, Peter; Yuan, Hushan; Figueiredo, Jose Luiz; Newton, Andita P.; Upadhyay, Rabi; Vinegoni, Claudio; Kohler, Rainer; Blois, Joseph; Smith, Adam; Nahrendorf, Matthias; Josephson, Lee; Weissleder, Ralph; Pittet, Mikael J.

2008-01-01

Eosinophils are multifunctional leukocytes that degrade and remodel tissue extracellular matrix through production of proteolytic enzymes, release of proinflammatory factors to initiate and propagate inflammatory responses, and direct activation of mucus secretion and smooth muscle cell constriction. Thus, eosinophils are central effector cells during allergic airway inflammation and an important clinical therapeutic target. Here we describe the use of an injectable MMP-targeted optical sensor that specifically and quantitatively resolves eosinophil activity in the lungs of mice with experimental allergic airway inflammation. Through the use of real-time molecular imaging methods, we report the visualization of eosinophil responses in vivo and at different scales. Eosinophil responses were seen at single-cell resolution in conducting airways using near-infrared fluorescence fiberoptic bronchoscopy, in lung parenchyma using intravital microscopy, and in the whole body using fluorescence-mediated molecular tomography. Using these real-time imaging methods, we confirmed the immunosuppressive effects of the glucocorticoid drug dexamethasone in the mouse model of allergic airway inflammation and identified a viridin-derived prodrug that potently inhibited the accumulation and enzyme activity of eosinophils in the lungs. The combination of sensitive enzyme-targeted sensors with noninvasive molecular imaging approaches permitted evaluation of airway inflammation severity and was used as a model to rapidly screen for new drug effects. Both fluorescence-mediated tomography and fiberoptic bronchoscopy techniques have the potential to be translated into the clinic. PMID:19033674

[Determination of hyperregeneratory esophagopathy in dogs with clinical signs attributable to esophageal disease].

PubMed

Münster, M; Kook, P; Araujo, R; Hörauf, A; Vieth, M

2015-01-01

It was hypothesized that typical characteristics of hyperregeneratory esophagopathy (HRE) in humans such as basal cell hyperplasia and elongation of stromal papillae are also histologically detectable in canine esophageal epithelium, and that these changes are associated with clinical signs and endoscopic findings suggesting gastroesophageal reflux (GER). Sixty-five adult dogs with clinical signs attributable to esophageal disease underwent esophagoscopy and biopsy. Clinical signs suggesting GER (regurgitation, ptyalism, painful discomfort) were prospectively evaluated through a questionnaire. Endoscopic mucosal alterations suggesting GER such as minimal endoscopic changes and obvious mucosal defects were assessed via video endoscopy. Biopsy specimens obtained from the esophageal squamous epithelium were evaluated histologically. The squamous epithelium's substructures of esophageal biopsies were quantitatively assessed through microscopic morphometry. Esophageal squamous epithelium was considered normal in 48 dogs, and HRE was detected histologically in 17 dogs; both pathognomonic changes (basal cell hyperplasia, elongation of stromal papillae) were consistently present. Morphometrically assessed stromal papillary length and basal cell layer thickness was significantly (each, p < 0.0001) higher in the 17 dogs with HRE than in the 48 dogs without HRE, respectively. Overall, clinical signs suggesting GER were significantly (p = 0.02) more frequently encountered and regurgitation was significantly (p = 0.009) more common in the 17 dogs with HRE than in the 48 dogs without HRE. Similarly, endoscopic changes were significantly (p = 0.002) more frequently observed and minimal endoscopic changes suggesting GER were significantly (p = 0.004) more common in 17 dogs with HRE than in the 48 dogs without HRE. Typical characteristics of hyperregeneratory esophagopathy in humans are also histologically detectable in canine esophageal epithelium. Histological changes are associated with clinical signs and endoscopic findings suggesting GER.

Anti-IL-5 attenuates activation and surface density of β2-integrins on circulating eosinophils after segmental antigen challenge

PubMed Central

Johansson, Mats W.; Gunderson, Kristin A.; Kelly, Elizabeth A. B.; Denlinger, Loren C.; Jarjour, Nizar N.; Mosher, Deane F.

2013-01-01

Background IL-5 activates αMβ2 integrin on blood eosinophils in vitro. Eosinophils in bronchoalveolar lavage (BAL) following segmental antigen challenge have activated β2-integrins. Objective To identify roles for IL-5 in regulating human eosinophil integrins in vivo. Methods Blood and BAL eosinophils were analyzed by flow cytometry in ten subjects with allergic asthma who underwent a segmental antigen challenge protocol before and after anti-IL-5 administration. Results Blood eosinophil reactivity with monoclonal antibody (mAb) KIM-127, which recognizes partially activated β2-integrins, was decreased after anti-IL-5. Before anti-IL-5, surface densities of blood eosinophil β2, αM, and αL integrin subunits increased modestly post-challenge. After anti-IL-5, such increases did not occur. Before or after anti-IL-5, surface densities of β2,αM, αL, and αD and reactivity with KIM-127 and mAb CBRM1/5, which recognizes high-activity αMβ2, were similarly high on BAL eosinophils 48 h post-challenge. Density and activation state of β1-integrins on blood and BAL eosinophils were not impacted by anti-IL-5, even though anti-IL-5 ablated a modest post-challenge increase on blood or BAL eosinophils of P-selectin glycoprotein ligand-1 (PSGL-1), a receptor for P-selectin that causes activation of β1-integrins. Forward scatter of blood eosinophils post-challenge was less heterogeneous and on the average decreased after anti-IL-5; however, anti-IL-5 had no effect on the decreased forward scatter of eosinophils in post-challenge BAL compared to eosinophils in blood. Blood eosinophil KIM-127 reactivity at the time of challenge correlated with the percentage of eosinophils in BAL post-challenge. Conclusion and Clinical Relevance IL-5 supports a heterogeneous population of circulating eosinophils with partially activated β2-integrins and is responsible for upregulation of β2-integrins and PSGL-1 on circulating eosinophils following segmental antigen challenge but has minimal effects on properties of eosinophils in BAL. Dampening of β2-integrin function of eosinophils in transit to inflamed airway may contribute to the decrease in lung inflammation caused by anti-IL-5. PMID:23414537

From blood to breath: New horizons for esophageal cancer biomarkers

PubMed Central

Yazbeck, Roger; Jaenisch, Simone E; Watson, David I

2016-01-01

Esophageal cancer is a lethal cancer encompassing adenocarcinoma and squamous cell carcinoma sub-types. The global incidence of esophageal cancer is increasing world-wide, associated with the increased prevalence of associated risk factors. The asymptomatic nature of disease often leads to late diagnosis and five-year survival rates of less than 15%. Current diagnostic tools are restricted to invasive and costly endoscopy and biopsy for histopathology. Minimally and non-invasive biomarkers of esophageal cancer are needed to facilitate earlier detection and better clinical management of patients. This paper summarises recent insights into the development and clinical validation of esophageal cancer biomarkers, focussing on circulating markers in the blood, and the emerging area of breath and odorant biomarkers. PMID:28028355

Functional and phenotypic evaluation of eosinophils from patients with the acute form of paracoccidioidomycosis.

PubMed

Braga, Fernanda Gambogi; Ruas, Luciana Pereira; Pereira, Ricardo Mendes; Lima, Xinaida Taligare; Antunes, Edson; Mamoni, Ronei Luciano; Blotta, Maria Heloisa Souza Lima

2017-05-01

Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This clinical form is characterized by depressed cellular immune response and production of Th2 cytokines. Moreover, it has been shown that the increased number of eosinophils in peripheral blood of patients returns to normal values after antifungal treatment. However, the role of eosinophils in PCM has never been evaluated. This study aimed to assess the phenotypic and functional characteristics of eosinophils in PCM. In 15 patients with the acute form of the disease, we detected expression of MBP, CCL5 (RANTES) and CCL11 (eotaxin) in biopsies of lymph nodes and liver. In addition, there were higher levels of chemokines and granule proteins in the peripheral blood of patients compared to controls. Isolation of eosinophils from blood revealed a higher frequency of CD69+ and TLR2+ eosinophils in patients compared to controls, and a lower population of CD80+ cells. We also evaluated the fungicidal capacity of eosinophils in vitro. Our results revealed that eosinophils from PCM patients and controls exhibit similar ability to kill P. brasiliensis yeast cells, although eosinophils of patients were less responsive to IL-5 stimulation than controls. In conclusion, we suggest that eosinophils might play a role in the host response to fungi and in the pathophysiology of PCM by inducing an intense and systemic inflammatory response in the initial phase of the infection.

Preoperative endoscopic titanium clip placement facilitates intraoperative localization of early-stage esophageal cancer or severe dysplasia.

PubMed

Tan, Lei; Feng, Juan; Zhao, Qin; Chen, Ping; Yang, Guotao

2017-08-02

Accurate intraoperative localization of esophageal lesions is essential for successful surgical resection. We tested whether preoperative endoscopic placement of titanium clips could facilitate intraoperative localization of early-stage esophageal cancer or severe dysplasia. A prospective randomized clinical trial was performed between May 2012 and July 2014. All enrolled patients received preoperative endoscopy and esophageal endoscopic ultrasound, as well as pathological study on the biopsy specimen, to confirm early stage esophageal cancer or severe dysplasia. One day before the surgical operation, patients in the experimental group received the preoperative endoscopic titanium labeling of esophageal lesions. Then, during the surgical operation, palpitation of titanium clips was used to localize the lesions in these patients. In patients in the control group, palpitation of nodules or esophageal wall mucosal thickening, together with the consideration of the results from preoperative endoscopic and ultrasound studies, was applied to estimate the location of the esophageal lesions. Study outcomes included the proportions of patients having successful intraoperative pre-resection lesion localization, post-esophagectomy lesion visualization, negative upper surgical margin, change of surgical approaches, and positive postoperative pathological diagnosis. A total of 27 patients were enrolled into the study, with 14 in the experimental group and 13 in the control group. Compared to the patients in the control group, a higher proportion of patients in the experimental group had statistically significant successful intraoperative esophageal lesion localization (100 versus 15.3% in the experimental versus control group). Preoperative endoscopic titanium clip placement could facilitate intraoperative localization of early-stage esophageal cancer or severe dysplasia. Current study was registered in Chinese Clinical Trial Registry and World Health Organization International Clinical Trials Registry Platform, ChiCTR-INR-17010949 . Registered 22 March 2017, retrospectively registered.

[Advances in the research of scar stricture after esophageal burn].

PubMed

Zhao, Shi-lei; Gu, Chun-dong

2013-10-01

Caustic esophageal burn is a common ailment in clinical practice. In some patients, scar stricture was formed in the late stage of injury, and it seriously undermined quality of life of the patients. We adopted various clinical interventions at an early stage in order to relieve and alleviate the formation and development of corrosive esophageal stricture as a result of chemical injury as well as to avoid invasive operations to make it more acceptable for the patients. This article summarized the progress in etiology, pathological changes, identification, early prevention, and surgical management of corrosive esophageal stricture.

Diagnosis and treatment of esophageal foreign body or stricture in three ferrets (Mustela putorius furo).

PubMed

Webb, Joanna; Graham, Jennifer; Fordham, Margaret; DeCubellis, Julie; Buckley, Faith; Hobbs, Joshua; Berent, Allyson; Weisse, Chick

2017-08-15

CASE DESCRIPTION 3 ferrets (Mustela putorius furo), aged 1 to 2 years, were referred for evaluation of a 4-day to 2-week history of gastrointestinal signs, including anorexia, regurgitation, and vomiting. CLINICAL FINDINGS All 3 ferrets had clinical signs suggestive of dysphagia or esophagitis on initial examination. Esophagoscopy, barium-contrast esophagography, or both revealed foreign bodies with mucosal inflammation in 1 patient and an esophageal foreign body with stricture in 2 patients. One of the latter ferrets had a recent history of gastrotomy to remove a foreign body. TREATMENT AND OUTCOME 1 ferret was treated with endoscopic retrieval of the foreign bodies. Esophageal stricture was treated in 2 ferrets by means of endoscopic balloon dilation accompanied by placement of an esophageal stent in 1 ferret. After resolution of clinical signs and completion of all prescribed treatments, 2 of 3 ferrets successfully transitioned to a regular hard kibble diet; 1 ferret remained on a soft diet for 2 years. All owners were satisfied with the outcome of treatment. CLINICAL RELEVANCE Ferrets are prone to foreign body ingestion. Results of this small series of cases suggested that minimally invasive techniques may be useful for the management of esophageal disease in this species.

Esophageal Lichen Planus: Clinical and Radiographic Findings in Eight Patients.

PubMed

Rauschecker, Andreas M; Levine, Marc S; Whitson, Matthew J; Tondon, Rashmi; Rubesin, Stephen E; Furth, Emma E; Metz, David C

2017-01-01

The purpose of this study is to present the clinical and radiographic findings of esophageal lichen planus. A search of computerized medical records identified 15 patients with pathologic findings of esophageal lichen planus on endoscopic biopsy specimens. Three other patients had presumed esophageal lichen planus, although no biopsy specimens were obtained. Twelve of these 18 patients (67%) had double-contrast esophagography performed at our institution; for eight of the 12 patients (67%), the studies revealed abnormalities in the esophagus. These eight patients constituted our study group. The barium esophagrams and medical records of these eight patients were reviewed to determine the clinical, radiographic, and endoscopic findings of esophageal lichen planus as well as the treatment and patient outcome. All eight patients were women (median age, 66.5 years), and all eight presented with dysphagia (mean duration, 3.2 years). Four patients had previous lichen planus that involved the skin (n = 1), the oral cavity (n = 2), or both (n = 1), and one patient later had lichen planus that involved the vagina. Five patients had a small-caliber esophagus with diffuse esophageal narrowing. The remaining three patients had segmental strictures in the cervical (n = 1), upper thoracic (n = 1), and distal thoracic (n = 1) esophagus. Esophageal lichen planus typically occurs in older women with longstanding dysphagia and often develops in the absence of extraesophageal disease. Barium esophagrams may reveal a small-caliber esophagus or, less commonly, segmental esophageal strictures. Greater awareness of the radiographic findings of esophageal lichen planus hopefully will lead to earlier diagnosis and better management of this condition.

Retrospective Analyses of Esophageal Bypass Surgery for Patients with Esophagorespiratory Fistulas Caused by Esophageal Carcinomas.

PubMed

Nakajima, Yasuaki; Kawada, Kenro; Tokairin, Yutaka; Miyawaki, Yutaka; Okada, Takuya; Miyake, Satoshi; Kawano, Tatsuyuki

2016-05-01

Esophagorespiratory fistula (ERF) caused by esophageal carcinoma is a fatal complication. In our institution, esophageal bypass surgery has been indicated when possible. We herein retrospectively describe the clinical results of esophageal bypass surgery for ERF. Between April 2001 and March 2015, 20 patients with ERF underwent esophageal bypass surgery. For these patients, the clinical safety, validity, and effectiveness of esophageal bypass surgery were examined and compared with the results of bypass surgery without ERF. Eight patients developed ERF at the initial diagnosis, while 10 patients developed ERF during and after chemoradiotherapy. Postoperative complications such as pneumonia, surgical site infection, and anastomotic leakage developed in 12, 5, and 1 patient, respectively. All the patients could eat solid foods at a median of 9 postoperative days. Two patients died within 30 days after the operation and 1 patient developed in-hospital death. Fourteen patients received chemo(radio)therapy after the operation. The median overall survival was 244 days and the one-year and three-year overall survival rates were 45.7 and 15.3 %, respectively. There was no significant difference in terms of the intraoperative findings, postoperative morbidities, and short-term and long-term clinical results between the two groups. Esophageal bypass surgery for ERF is not considered to be highly invasive or risky compared with bypass surgery without ERF. After the operation, respiratory symptoms caused by ERF may improve and oral intake can be achieved. Esophageal bypass surgery should therefore be aggressively performed for patients with a tolerable performance status.

Severe eosinophilic colitis caused by neuropathic agents in a patient with chronic fatigue syndrome and functional abdominal pain: case report and review of the literature.

PubMed

Fragkos, Konstantinos C; Barragry, John; Fernando, Charisma Shahi; Novelli, Marco; Begent, Joanna; Zárate-Lopez, Natalia

2018-06-01

Eosinophilic colitis is a rare clinical condition that belongs to the group of eosinophilic gastrointestinal disorders. Its occurrence can be primary or secondary to infection, medications, or autoimmune/hematological conditions. We present a case of a young female adult with severe chronic fatigue syndrome, widespread chronic pain, including functional abdominal pain, who developed severe eosinophilic colitis following successive treatments with gabapentin and pregabalin. On both occasions, symptoms manifested as abdominal pain, diarrhea, and eosinophilia and improved upon discontinuation of the medications. Magnetic resonance imaging of the small bowel demonstrated an ascending colon colitis, and endoscopic investigations confirmed florid colitis mainly in the ascending colon with biopsies demonstrating a dense eosinophilic infiltrate with micro-abscesses. Serum eosinophil counts correlated well with the timing of the agents' administration. There was no other organ involvement. Symptoms improved upon discontinuation of the drugs and steroid administration. Eosinophilic colitis is an exceptionally rare entity and its mechanism of action is still unclear. Suspicion of eosinophilic colitis should be raised if a patient presents with abdominal pain, diarrhea, and peripheral eosinophilia following treatment with pregabalin or gabapentin. © Georg Thieme Verlag KG Stuttgart · New York.

Eosinophils are rare in biopsy specimens of psoriasis vulgaris.

PubMed

Rosa, Gabriela; Fernandez, Anthony P; Schneider, Sarah; Billings, Steven D

2017-12-01

Histological features of lesional biopsies can be helpful in distinguishing psoriasis subtypes from disease mimickers. However, occasionally, classic histological features are not sufficient for distinction, and additional clues would be useful. There is a common belief that the presence of eosinophils in skin biopsies argues against psoriasis, but actual literature is scant. Skin biopsies with a diagnosis of psoriasis from 2013 to 2016 were reviewed. For inclusion, both histological and clinical features were required to be consistent with psoriasis. For biopsies meeting inclusion criteria, a detailed evaluation for typical histological parameters of psoriasis, as well as presence of dermal eosinophils, was performed. Of 85 cases meeting inclusion criteria, all had either individual or grouped intracorneal neutrophils and dilated papillary blood vessels. Diminished or complete loss of the granular cell layer was seen in 83 cases (98%), and parakeratosis was seen in 84 cases (99%). Alternatively, dermal eosinophils were seen in only 15 cases (18%). Of cases with eosinophils, none had more than 3 eosinophils upon examination of the entire dermis. Active treatment did not appear to impact presence/absence or numbers of eosinophils. Eosinophils are uncommon in psoriasis biopsies, and when present, they are found in small numbers. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eosinophilic folliculitis: an important differential diagnosis after allogeneic bone-marrow transplant.

PubMed

Fraser, S J; Benton, E C; Roddie, P H; Krajewski, A S; Goodlad, J R

2009-04-01

Eosinophilic folliculitis (EF) is a descriptive histopathological term applied to a heterogeneous group of disorders. In EF, the characteristic histopathological features are eosinophilic spongiosis and pustulosis involving the infundibular region of the hair follicle. EF may be seen in association with bacterial and fungal infection, drug reactions and haematological disorders. However, in those conditions, the histopathological changes are rarely restricted to the infundibula but in most cases include a moderate to dense perifollicular or even diffuse dermal infiltrate of lymphocytes, or eosinophilic or neutrophilic granulocytes. We present two cases of EF after mini-allogeneic bone-marrow transplantation (BMT) in order to highlight this rare and perhaps under-recognized clinical association.

Functional restoration of the esophagus after peroral endoscopic myotomy for achalasia.

PubMed

Huh, Cheal Wung; Youn, Young Hoon; Chung, Hyunsoo; Lee, Yong Chan; Park, Hyojin

2017-01-01

Peroral endoscopic myotomy (POEM) is a new efficacious treatment option for achalasia. We propose to define "esophageal remodeling" as the functional restoration of the esophagus that involves decreased lower esophageal sphincter (LES) pressure, recovery of esophageal body peristalsis, and reduction of luminal diameter. The aim of this study was to investigate "esophageal remodeling" after POEM for achalasia. We analyzed data from a prospectively collected database of POEM subjects, which included preoperative and 2-month postoperative Eckardt symptom scores, and results from esophageal high resolution manometry (HRM) and barium esophagogram (BE). We recruited 23 patients (13 male; mean age: 53.9 years) whose preoperative and postoperative HRM and BE results were available, from among 30 patients with achalasia who underwent POEM at two institutions between July 2013 and December 2015. All patients achieved clinical treatment success (Eckardt score≤3). Partial recovery of esophageal body peristalsis was noted in 1/5 patients with type I (20%), 6/11 with type II (54.5%), and 7/7 with type III (100%) achalasia after POEM. Pan-esophageal pressurization disappeared after POEM in 10/11 type II achalasia patients. The average diameter of the esophageal body after POEM was significantly decreased in all types of achalasia. POEM provided excellent clinical symptomatic relief and esophageal remodeling in terms of restoration of peristalsis and reduction in diameter of the esophageal body, especially in patients with type III achalasia.

Novel disposable transnasal endoscopy for assessment of esophageal motor function.

PubMed

Lim, Chul-Hyun; Choi, Myung-Gyu; Baeg, Myong-Ki; Moon, Sung Jin; Kim, Jin Su; Cho, Yu Kyung; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Kyu Yong

2014-01-01

A novel disposable transnasal endoscopy (DTE) with a portable system has been developed to provide unsedated esophagoscopy by modifying capsule endoscopy. The aim of this study was to assess the feasibility of DTE to evaluate esophageal motor function. Patients with or suspected esophageal motility disorders and healthy volunteers were enrolled. Participants underwent esophageal high-resolution manometry and DTE in random order on different days. Motility was observed with DTE at 1, 8, and 16 cm above the gastroesophageal junction. Twenty healthy volunteers and 20 symptomatic subjects participated (8 achalasia, 5 scleroderma, 3 diffuse esophageal spasm, 1 hypertensive peristalsis, 1 peristaltic dysfunction, and 22 normal esophageal function). The normal findings on DTE were as follows. As the subject swallowed water, swallow-induced relaxation with elevation of the lower esophageal sphincter caused the endoscope to cross the Z-line into the gastric lumen. After the passage of water and air, complete closure of the lower esophageal sphincter occurred, with the return of the endoscope to its previous position. During the resting stage of the esophageal body, an air bubble could be seen in the center of the radially wrinkled and occluded lumen. The endoscopic diagnosis was in agreement with the clinical diagnosis in all but 2. Most of the participants reported acceptable discomfort during DTE and 62.5% of the subjects preferred DTE to manometry. DTE can accurately characterize normal esophageal motor function, allowing the diagnosis of esophageal motility disorders. DTE has potential widespread applications, especially in outpatient clinics.

Eosinophilic/T-cell Chorionic Vasculitis: Histological and Clinical Correlations.

PubMed

Cheek, Bradley; Heinrich, Stephen; Ward, Kenneth; Craver, Randall

2015-04-01

Eosinophilic T-cell chorionic vasculitis (E/TCV) is composed of eosinophils and T-lymphocytes originating within chorionic vessels, radiating toward the intervillous space and away from the amnion in a fashion different from the fetal vascular response seen in amnionitis. Clinical significance and risk factors are not well established. We report four pregnancies (five infants, one triplet was spared) with E/TCV, gestational ranging from 23 weeks to term. All had concurrent acute chorioamnionitis, three had the typical acute fetal inflammatory response. One had placental fetal obstructive vasculopathy and an upper extremity reduction defect (radio-ulnar synostosis), the mother had pre-eclampsia. A second case involved 2 of 3 23 week previable triplets. Our third case had a metatarsus varus resistant to casting, the mother had gestational diabetes. The last case was a normal infant. We review the literature, discuss the clinical findings and present the histologic characteristics of this infrequently recognized lesion.

Clinical aspects of eosinophilic meningitis and meningoencephalitis caused by Angiostrongylus cantonensis, the rat lungworm.

PubMed

Murphy, Gerald S; Johnson, Stuart

2013-06-01

Angiostrongylus Eosinophilic Meningitis is caused by human infection with larvae of the rat lungworm, Angiostrongylus cantonensis. The clinical presentation includes a spectrum of disease, from meningitis through radiculitis, cranial nerve abnormalities, ataxia, encephalitis, coma, and rarely death. The condition is diagnosed by recognizing the triad of: the clinical syndrome, eosinophils in the cerebrospinal fluid or blood, and exposure history. A history of eating raw or poorly cooked snails is classic, but ingestion of other intermediate hosts or unwashed produce (such as lettuce) harboring hosts is not uncommon. Several serologic tests exist but none has yet been fully validated. There is good evidence that a 2 week course of high dose corticosteroids shortens the duration and severity of symptoms. There is somewhat weaker evidence that albendazole reduces symptoms. The combination of prednisolone and albendazole is being used more commonly for treatment. Some suggestions for future research are given.

Eosinophils enhance WNT-5a and TGF-β1 genes expression in airway smooth muscle cells and promote their proliferation by increased extracellular matrix proteins production in asthma.

PubMed

Januskevicius, Andrius; Vaitkiene, Simona; Gosens, Reinoud; Janulaityte, Ieva; Hoppenot, Deimante; Sakalauskas, Raimundas; Malakauskas, Kestutis

2016-06-13

Recent studies have suggested that eosinophils may have a direct effect on airway smooth muscle cells (ASMC), causing their proliferation in patients with asthma, but the precise mechanism of the interaction between these cells remains unknown. We propose that changes in Wnt signaling activity and extracellular matrix (ECM) production may help explain these findings. Therefore, the aim of this study was to investigate the effect of eosinophils from asthmatic and non-asthmatic subjects on Wnt-5a, transforming growth factor β1 (TGF-β1), and ECM protein (fibronectin and collagen) gene expression and ASMC proliferation. A total of 18 subjects were involved in the study: 8 steroid-free asthma patients and 10 healthy subjects. Peripheral blood eosinophils were isolated using centrifugation and magnetic separation. An individual co-culture of eosinophils with human ASMC was prepared for each study subject. Adhesion of eosinophils to ASMC (evaluated by assaying eosinophil peroxidase activity) was determined following various incubation periods (30, 45, 60, 120, and 240 min). The expression of Wnt-5a, TGF-β1, and ECM protein genes in ASMC was measured using quantitative real-time polymerase chain reaction (PCR) after 24 h of co-culture. Proliferation of ASMC was measured using the Alamar blue method after 48 h and 72 h of co-culture with eosinophils. Eosinophils from asthmatic subjects demonstrated increased adhesion to ASMC compared with eosinophils from healthy subjects (p < 0.05) in vitro. The expression of Wnt-5a, TGF-β1, collagen, and fibronectin genes in ASMC was significantly higher after 24 h of co-culture with eosinophils from asthmatic subjects, while co-culture of ASMC with eosinophils from healthy subjects increased only TGF-β1 and fibronectin gene expression. ASMC proliferation was augmented after co-culture with eosinophils from asthma patients compared with co-culture with eosinophils from healthy subjects (p < 0.05). Eosinophils enhance Wnt-5a, TGF-β1, fibronectin, and collagen gene expression in ASMC and promote proliferation of these cells in asthma. ClinicalTrials.gov Identifier: NCT02648074 .

Esophageal Cancer Screening

MedlinePlus

... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... stage . There is no standard or routine screening test for esophageal cancer. Screening for esophageal cancer is under study with screening clinical trials taking place in many ...

Immunohistological analysis of eotaxin and RANTES in the model animal of eosinophilic otitis media.

PubMed

Kudo, Naomi; Matsubara, Atsushi; Nishizawa, Hisanori; Miura, Tomoya

2017-05-01

The most crucial clinical problem of Eosinophilic Otitis Media (EOM) is sensorineural hearing loss. A previous report revealed that repeated antigen stimulation of middle ear causes eosinophilic inflammation not only in the middle ear but also in the inner ear. The purpose of the present study was to elucidate the mechanism of eosinophil infiltration to the inner ear in the animal model of EOM. Continuous OVA stimulation to the middle ear of guinea pigs was performed for 7 days, 14 days, and 28 days. Histological observation was made for eosinophil infiltration and morphological change of the inner ear. Immunostaining for eotaxin and RANTES was performed to study immunoreactivity of those chemokines. In the 7-day stimulation side, a few eosinophils were found in the scala tympani, without obvious morphological damage of the inner ear. Moreover, immunoreactivity of both eotaxin and RANTES was significantly higher in the OVA stimulation sides than control sides. For both eotaxin and RANTES, the number of immunopositive cells was significantly increased in the 14-day stimulation side over the 7-day stimulation side. Eotaxin and RANTES seem to play some important roles for the eosinophil infiltration in the middle and inner ear of model animal of EOM.

Esophageal perforation due to blunt chest trauma: Difficult diagnosis because of coexisting severe disturbance of consciousness.

PubMed

Mezuki, Satomi; Shono, Yuji; Akahoshi, Tomohiko; Hisanaga, Kana; Saeki, Hiroshi; Nakashima, Yuichiro; Momii, Kenta; Maki, Jun; Tokuda, Kentaro; Maehara, Yoshihiko

2017-11-01

Esophageal perforation due to blunt trauma is a rare clinical condition, and the diagnosis is often difficult because patients have few specific symptoms. Delayed diagnosis may result in a fatal clinical course due to mediastinitis and subsequent sepsis. In this article, we describe a 26-year-old man with esophageal perforation due to blunt chest trauma resulting from a motor vehicle accident. Because a severe disturbance of consciousness masked the patient's trauma-induced thoracic symptoms, we required 11h to diagnose the esophageal perforation. Therefore, the patient developed septic shock due to mediastinitis. However, his subsequent clinical course was good because of prompt combined therapy involving surgical repair and medical treatment after the diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical spectrum of food allergies: a comprehensive review.

PubMed

Ho, Marco H-K; Wong, Wilfred H-S; Chang, Christopher

2014-06-01

Food allergy is defined as an adverse immune response towards food proteins or as a form of a food intolerance associated with a hypersensitive immune response. It should also be reproducible by a double-blind placebo-controlled food challenge. Many reported that food reactions are not allergic but are intolerances. Food allergy often presents to clinicians as a symptom complex. This review focuses on the clinical spectrum and manifestations of various forms of food allergies. According to clinical presentations and allergy testing, there are three types of food allergy: IgE mediated, mixed (IgE/Non-IgE), and non-IgE mediated (cellular, delayed type hypersensitivity). Recent advances in food allergy in early childhood have highlighted increasing recognition of a spectrum of delayed-onset non-IgE-mediated manifestation of food allergy. Common presentations of food allergy in infancy including atopic eczema, infantile colic, and gastroesophageal reflux. These clinical observations are frequently associated with food hypersensitivity and respond to dietary elimination. Non-IgE-mediated food allergy includes a wide range of diseases, from atopic dermatitis to food protein-induced enterocolitis and from eosinophilic esophagitis to celiac disease. The most common food allergies in children include milk, egg, soy, wheat, peanut, treenut, fish, and shellfish. Milk and egg allergies are usually outgrown, but peanut and treenut allergy tends to persist. The prevalence of food allergy in infancy is increasing and may affect up to 15-20 % of infants. The alarming rate of increase calls for a public health approach in the prevention and treatment of food allergy in children.

Functional and phenotypic evaluation of eosinophils from patients with the acute form of paracoccidioidomycosis

PubMed Central

Braga, Fernanda Gambogi; Ruas, Luciana Pereira; Pereira, Ricardo Mendes; Lima, Xinaida Taligare; Antunes, Edson; Mamoni, Ronei Luciano

2017-01-01

Background Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This clinical form is characterized by depressed cellular immune response and production of Th2 cytokines. Moreover, it has been shown that the increased number of eosinophils in peripheral blood of patients returns to normal values after antifungal treatment. However, the role of eosinophils in PCM has never been evaluated. This study aimed to assess the phenotypic and functional characteristics of eosinophils in PCM. Methods/Principal findings In 15 patients with the acute form of the disease, we detected expression of MBP, CCL5 (RANTES) and CCL11 (eotaxin) in biopsies of lymph nodes and liver. In addition, there were higher levels of chemokines and granule proteins in the peripheral blood of patients compared to controls. Isolation of eosinophils from blood revealed a higher frequency of CD69+ and TLR2+ eosinophils in patients compared to controls, and a lower population of CD80+ cells. We also evaluated the fungicidal capacity of eosinophils in vitro. Our results revealed that eosinophils from PCM patients and controls exhibit similar ability to kill P. brasiliensis yeast cells, although eosinophils of patients were less responsive to IL-5 stimulation than controls. Conclusion/Principal findings In conclusion, we suggest that eosinophils might play a role in the host response to fungi and in the pathophysiology of PCM by inducing an intense and systemic inflammatory response in the initial phase of the infection. PMID:28489854

Eosinophilic gastroenteritis in a domestic ferret.

PubMed Central

Fazakas, S

2000-01-01

Eosinophilic gastroenteritis without peripheral eosinophilia was diagnosed histologically in a 5-year-old neutered male ferret showing acute signs of projectile vomiting, dark mucoid diarrhea, and chronic weight loss for 2 mo. The ferret was clinically normal after 4 days of treatment with parenteral fluids, antibiotics, and corticosteroids. PMID:10992990

Advances in the Evaluation and Management of Esophageal Disease of Systemic Sclerosis

PubMed Central

Carlson, Dustin A.; Hinchcliff, Monique; Pandolfino, John E.

2015-01-01

Symptoms of heartburn and dysphagia, as well as objective findings of abnormal esophageal acid exposure and esophageal dysmotility are common in patients with systemic sclerosis (SSc). Treatments for SSc esophageal disease are generally limited to gastroesophageal reflux disease (GERD) treatment with proton pump inhibitors. Progresses made in esophageal diagnostic testing offer the potential for improved clinical characterization of esophageal disease in SSc that may help direct management decisions. In addition to reviewing GERD management in patients with SSc, present and potential uses of endoscopy, reflux monitoring, manometry, impedance planimetry, and endoscopic ultrasound are discussed. PMID:25475597

Esophageal stenosis with sloughing esophagitis: A curious manifestation of graft-vs-host disease.

PubMed

Trabulo, Daniel; Ferreira, Sara; Lage, Pedro; Rego, Rafaela Lima; Teixeira, Gilda; Pereira, A Dias

2015-08-14

We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years, complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease (GVHD). Balloon dilation, corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease, ulceration, esophageal webs, casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context.

Risks of Esophageal Cancer Screening

MedlinePlus

... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... stage . There is no standard or routine screening test for esophageal cancer. Screening for esophageal cancer is under study with screening clinical trials taking place in many ...

Gastroesophageal reflux disease after peroral endoscopic myotomy: Analysis of clinical, procedural and functional factors, associated with gastroesophageal reflux disease and esophagitis.

PubMed

Familiari, Pietro; Greco, Santi; Gigante, Giovanni; Calì, Anna; Boškoski, Ivo; Onder, Graziano; Perri, Vincenzo; Costamagna, Guido

2016-01-01

Peroral endoscopic myotomy (POEM) does not include any antireflux procedure, resulting in a certain risk of iatrogenic gastroesophageal reflux disease (GERD). The aim of the present study was to evaluate the incidence of iatrogenic GERD after POEM and identify preoperative, perioperative and postoperative factors associated with GERD. All patients treated at a single center who had a complete GERD evaluation after POEM were included in the study. Demographics, preoperative and follow-up data, results of functional studies and procedural data were collected and analyzed. A total of 103 patients (mean age 46.6 years, 47 males) were included. Postoperative altered esophageal acid exposure was attested in 52 patients (50.5%). A total of 19 patients (18.4%) had heartburn and 21 had esophagitis (20.4%). Overall, a clinically relevant GERD (altered esophageal acid exposure, associated with heartburn and/or esophagitis) was diagnosed in 30 patients (29.1%). Correlation between the severity of esophageal acid exposure with heartburn and esophagitis after POEM was found. Patients with heartburn had a lower postoperative 4-second integrated relaxation pressure compared to patients without symptoms (7.6 ± 3.8 mmHg vs 10.01 ± 4.4 mmHg, p<0.05). No correlations were identified with patient sex, age, postoperative body mass index, esophageal shape (sigmoid vs non sigmoid), lower esophageal sphincter pressure, length of myotomy, previous therapies and type of achalasia at high-resolution manometry. Preoperative, perioperative or postoperative factors minimally correlated with GERD after POEM. Clinically relevant GERD was identified in less than one-third of patients, but all patients were well controlled with medical therapy. © 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.

The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression.

PubMed

Chen, Miao-Fen; Chen, Ping-Tsung; Chen, Wen-Cheng; Lu, Ming-Shian; Lin, Paul-Yang; Lee, Kuan Der

2016-02-16

The aim of this study was to assess the significance of programmed cell death 1 ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) and its association with IL-6 and radiation response. Weretrospectively enrolled 162 patients with ESCC, and examined the correlation between PD-L1 levels and clinical outcomes in esophageal cancer patients. Furthermore, the human esophageal SCC cell line CE81T and TE2 were selected for cellular experiments to investigate the role of PD-L1 in T cell functions and radiation response. Here we demonstrated that PD-L1 expression was significantly higher in esophageal cancer specimens than in non-malignant epithelium. In clinical outcome analysis, this staining of PD-L1 was positively linked to the clinical T4 stage (p=0.004), development of LN metastasis (p=0.012) and higher loco-regional failure rate (p=0.0001). In addition, the frequency of PD-L1 immunoreactivity was significantly higher in IL-6-positive esophageal cancer specimens. When IL-6 signaling was inhibited in vitro, the level of PD-L1 is significantly down-regulated. PD-L1 is a significant predictor for poor treatment response and shorter survival.As demonstrated through in vitro experiments, Irradiation increased PD-L1 expression in human esophageal cancer cells. The inhibition of T cell functions including proliferation and cytotoxicity against tumor cells might be the mechanisms responsible to the role of PD-L1 in radiation response. In conclusion, PD-L1 is important in determining the radiation response and could predict the prognosis of patients with esophageal SCC. Therefore, we suggest inhibition of PD-L1 as a potential strategy for the treatment of esophageal SCC.

Does the Use of Pacifier Affect Gastro-Esophageal Reflux in Preterm Infants?

PubMed

Corvaglia, Luigi; Martini, Silvia; Corrado, Maria Francesca; Mariani, Elisa; Legnani, Elena; Bosi, Isabella; Faldella, Giacomo; Aceti, Arianna

2016-05-01

This crossover study showed that non-nutritive sucking, provided with a pacifier in 30 preterm infants, had no effect on acid and nonacid gastro-esophageal reflux evaluated by esophageal pH-impedance, and thus may be reasonably used in preterm neonates with symptoms of gastro-esophageal reflux. ClinicalTrials.gov: NCT02023216. Copyright © 2016 Elsevier Inc. All rights reserved.

Dysphagia: Thinking outside the box

PubMed Central

Philpott, Hamish; Garg, Mayur; Tomic, Dunya; Balasubramanian, Smrithya; Sweis, Rami

2017-01-01

Dysphagia is a common symptom that is important to recognise and appropriately manage, given that causes include life threatening oesophageal neoplasia, oropharyngeal dysfunction, the risk of aspiration, as well as chronic disabling gastroesophageal reflux (GORD). The predominant causes of dysphagia varies between cohorts depending on the interplay between genetic predisposition and environmental risk factors, and is changing with time. Currently in white Caucasian societies adopting a western lifestyle, obesity is common and thus associated gastroesophageal reflux disease is increasingly diagnosed. Similarly, food allergies are increasing in the west, and eosinophilic oesophagitis is increasingly found as a cause. Other regions where cigarette smoking is still prevalent, or where access to medical care and antisecretory agents such as proton pump inhibitors are less available, benign oesophageal peptic strictures, Barrett’s oesophagus, adeno- as well as squamous cell carcinoma are endemic. The evaluation should consider the severity of symptoms, as well as the pre-test probability of a given condition. In young white Caucasian males who are atopic or describe heartburn, eosinophilic esophagitis and gastroesophageal reflux disease will predominate and a proton pump inhibitor could be commenced prior to further investigation. Upper gastrointestinal endoscopy remains a valid first line investigation for patients with suspected oesophageal dysphagia. Barium swallow is particularly useful for oropharyngeal dysphagia, and oesophageal manometry mandatory to diagnose motility disorders. PMID:29097867

Eosinophilic fasciitis associated with hypereosinophilia, abnormal bone-marrow karyotype and inversion of chromosome 5.

PubMed

Ferguson, J S; Bosworth, J; Min, T; Mercieca, J; Holden, C A

2014-03-01

We report the case of a male patient presenting with eosinophilia, pulmonary oedema and eosinophilic fasciitis (EF). He had the classic clinical appearance and magnetic resonance imaging of EF. Cytogenetic analysis of the bone marrow revealed a previously undescribed pericentric inversion of chromosome 5. Overall, the presentation was consistent with a diagnosis of chronic eosinophilic leukaemia, not otherwise specified (CEL-NOS). Dermatologists should consult a haematologist in cases of EF, in order to rule out possible haematological malignancies. © 2013 British Association of Dermatologists.

Shall We Focus on the Eosinophil to Guide Treatment with Systemic Corticosteroids during Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)? CON.

PubMed

Marcos, Pedro J; López-Campos, José Luis

2018-06-08

The employment of systemic corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) has been shown to improve airway limitation, decrease treatment failure and risk of relapse, and may improve symptoms in addition to decreasing the length of hospital stay. Nowadays, all clinical guidelines recommend systemic corticosteroids to treat moderate or severe COPD exacerbations. However, their use is associated with potential side effects, mainly hyperglycemia. In the era of precision medicine, the possibility of employing blood eosinophil count has emerged as a potential way of optimizing therapy. Issues regarding the intra-individual variability of blood eosinophil count determination, a lack of clear data regarding the real prevalence of eosinophilic acute exacerbations, the fact that previously published studies have demonstrated the benefit of systemic corticosteroids irrespective of eosinophil levels, and especially the fact that there is only one well-designed study justifying this approach have led us to think that we are not ready to use eosinophil count to guide treatment with systemic corticosteroids during acute exacerbations of COPD.

Functional restoration of the esophagus after peroral endoscopic myotomy for achalasia

PubMed Central

Huh, Cheal Wung; Youn, Young Hoon; Chung, Hyunsoo; Lee, Yong Chan; Park, Hyojin

2017-01-01

Purpose Peroral endoscopic myotomy (POEM) is a new efficacious treatment option for achalasia. We propose to define “esophageal remodeling” as the functional restoration of the esophagus that involves decreased lower esophageal sphincter (LES) pressure, recovery of esophageal body peristalsis, and reduction of luminal diameter. The aim of this study was to investigate “esophageal remodeling” after POEM for achalasia. Materials and methods We analyzed data from a prospectively collected database of POEM subjects, which included preoperative and 2-month postoperative Eckardt symptom scores, and results from esophageal high resolution manometry (HRM) and barium esophagogram (BE). We recruited 23 patients (13 male; mean age: 53.9 years) whose preoperative and postoperative HRM and BE results were available, from among 30 patients with achalasia who underwent POEM at two institutions between July 2013 and December 2015. Results All patients achieved clinical treatment success (Eckardt score≤3). Partial recovery of esophageal body peristalsis was noted in 1/5 patients with type I (20%), 6/11 with type II (54.5%), and 7/7 with type III (100%) achalasia after POEM. Pan-esophageal pressurization disappeared after POEM in 10/11 type II achalasia patients. The average diameter of the esophageal body after POEM was significantly decreased in all types of achalasia. Conclusion POEM provided excellent clinical symptomatic relief and esophageal remodeling in terms of restoration of peristalsis and reduction in diameter of the esophageal body, especially in patients with type III achalasia. PMID:28542509

Recent advances in intensity modulated radiotherapy and proton therapy for esophageal cancer.

PubMed

Xi, Mian; Lin, Steven H

2017-07-01

Radiotherapy is an important component of the standard of care for esophageal cancer. In the past decades, significant improvements in the planning and delivery of radiation techniques have led to better dose conformity to the target volume and improved normal tissue sparing. Areas covered: This review focuses on the advances in radiotherapy techniques and summarizes the availably dosimetric and clinical outcomes of intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy, proton therapy, and four-dimensional radiotherapy for esophageal cancer, and discusses the challenges and future development of proton therapy. Expert commentary: Although three-dimensional conformal radiotherapy is the standard radiotherapy technique in esophageal cancer, the retrospectively comparative studies strongly suggest that the dosimetric advantage of IMRT over three-dimensional conformal radiotherapy can translate into improved clinical outcomes, despite the lack of prospective randomized evidence. As a novel form of conventional IMRT technique, volumetric modulated arc therapy can produce equivalent or superior dosimetric quality with significantly higher treatment efficiency in esophageal cancer. Compared with photon therapy, proton therapy has the potential to achieve further clinical improvement due to their physical properties; however, prospective clinical data, long-term results, and cost-effectiveness are needed.

The low IGFBP-3 level is associated with esophageal cancer patients: a meta-analysis.

PubMed

Song, Guiqin; Liu, Kang; Zhu, Xiaoyan; Yang, Xiaolin; Shen, Yuewu; Wang, Wan; Shi, Guidong; Li, Qing; Duan, Yi; Zhao, Yunxia; Feng, Gang

2016-12-15

Esophageal cancer was a vital cause of cancer-related mortality worldwide, and the insulin-like growth factor-binding proteins (IGFBPs) has been proved to be an important factor of multiple types of tumors. There is a controversy that whether the IGFBP-3 level is associated with the clinical pathological characteristics and overall survival of esophageal cancer patients. Herein, we aimed to comprehensively assess the association between the low IGFBP-3 level and the risk, overall survival and clinical pathological characteristics of esophageal cancer. We conducted a meta-analysis using seven eligible studies. The overall odds ratios (OR)/relative risk (RR) and their corresponding 95% confidence interval (CI) were calculated for each parameter. For the risk of esophageal cancer, the OR was 2.342 (p = 0.000), indicating that individuals with lower IGFBP-3 level were more likely to suffer from esophageal cancer, compared to those with relatively high IGFBP-3 level. With respect to the 3-year survival rate, the RR was 2.163 (p = 0.027), which demonstrated that esophageal cancer patients with low IGFBP-3 level had significantly lower 3-year survival rate; in terms of clinical pathological characteristics, significantly lower IGFBP-3 level was found for patients in all categories; for survival status, patients in low IGFBP-3 level are more likely to be in the dead survival status (OR = 4.480, p = 0.000). Our meta-analysis suggests that for esophageal cancer, the low IGFBP-3 level is associated with high cancer risk, poor prognosis, and unfavorable tumor stage and metastasis.

Clinical significance of preoperative and postoperative cytokeratin 19 messenger RNA level in peripheral blood of esophageal cancer patients.

PubMed

Qiao, Y-F; Chen, C-G; Yue, J; Ma, Z; Yu, Z-T

2016-11-01

The purpose of this study is to analyze the correlation between preoperative/postoperative Cytokeratin 19 (CK19) messenger RNA (mRNA) level in peripheral blood (PB) and the clinical significance in esophageal cancer patients with different clinicopathological factors. We detected the preoperative and postoperative CK19 mRNA level in the PB of 139 esophageal cancer patients who underwent complete resection and evaluated its clinical significance. We found that both the preoperative and postoperative CK19 mRNA level increased in the esophageal cancer patients with lymph node metastasis, relapse or distant metastasis compared with that in cancers without lymph node metastasis, relapse or distant metastasis. High postoperative CK19 mRNA levels indicate a short disease-free survival (DFS) for the whole cohort esophageal cancer patients, whereas the high preoperative CK19 mRNA levels only indicate a short DFS for the esophageal cancer patients with squamous cell carcinoma, TNM III stage, and lymph node metastasis. The dynamic change of CK19 mRNA levels could indicate the prognosis of esophageal cancer patients. The patients with decreasing CK19 mRNA level after surgery had good prognosis, and the patients with changeless CK19 mRNA level had poor prognosis. Taken together, CK19 mRNA levels could be a promising marker in assessing prognosis or assigning treatment for the esophageal cancer patients according to different clinicopathological factors. © 2015 International Society for Diseases of the Esophagus.

Congenital esophageal stenosis: the differential diagnosis and management.

PubMed

Jones, Douglas W; Kunisaki, Shaun M; Teitelbaum, Daniel H; Spigland, Nitsana A; Coran, Arnold G

2010-05-01

Congenital esophageal stenosis (CES) is a rare congenital abnormality that is difficult to diagnose and often masquerades as other types of structural esophageal disease. We report three cases of CES with different presenting symptoms. We advocate for balloon dilation as the preferred first approach to therapeutic intervention. CES is an important clinical entity in the evaluation of pediatric esophageal disorders and should be suspected in young infants with dysphagia.

cDNA microarray analysis of esophageal cancer: discoveries and prospects.

PubMed

Shimada, Yutaka; Sato, Fumiaki; Shimizu, Kazuharu; Tsujimoto, Gozoh; Tsukada, Kazuhiro

2009-07-01

Recent progress in molecular biology has revealed many genetic and epigenetic alterations that are involved in the development and progression of esophageal cancer. Microarray analysis has also revealed several genetic networks that are involved in esophageal cancer. However, clinical application of microarray techniques and use of microarray data have not yet occurred. In this review, we focus on the recent developments and problems with microarray analysis of esophageal cancer.

Malignant esophageal-tracheobronchial strictures: parallel placement of covered retrievable expandable nitinol stents.

PubMed

Nam, D H; Shin, J H; Song, H Y; Jung, G S; Han, Y M

2006-02-01

To assess the safety and clinical effectiveness of the parallel placement of covered retrievable expandable metallic stents in the palliative treatment of malignant esophageal and tracheobronchial strictures. Under fluoroscopic guidance, parallel stents were placed in 12 symptomatic patients with both malignant esophageal and tracheobronchial strictures. Seven of these 12 patients also had an esophagorespiratory fistula (ERF) and one patient had an esophagocutaneous fistula. Technical success, clinical improvement, complications, and survival rates were evaluated. A total of 28 esophageal and airway stents were successfully placed. The grade of dysphagia and dyspnea score significantly decreased after stent placement (P=0.002 and 0.003, respectively). ERF and esophagocutaneous fistula were sealed off in all eight patients after esophageal stent placement; however, the esophagocutaneous fistula reopened 1 month later. Complications included stent migration or expectoration (n=3), tracheal compression by the esophageal stent (n=3), new fistula development due to covering membrane degradation of the esophageal stent (n=1), and symptomatic sputum retention (n=1). Stent removal was easily performed for two stents; one migrated stent and the other with covering membrane degradation. All 12 patients died within the mean survival period of 72.50 days (range 7-375 days). Parallel placement of covered retrievable expandable metallic stents is safe and effective for the palliative treatment of malignant esophageal and tracheobronchial strictures.

Biodegradable esophageal stent placement does not prevent high-grade stricture formation after circumferential mucosal resection in a porcine model.

PubMed

Pauli, Eric M; Schomisch, Steve J; Furlan, Joseph P; Marks, Andrea S; Chak, Amitabh; Lash, Richard H; Ponsky, Jeffrey L; Marks, Jeffrey M

2012-12-01

Advanced esophageal dysplasia and early cancers have been treated traditionally with esophagectomy. Endoscopic esophageal mucosectomy (EEM) offers less-invasive therapy, but high-degree stricture formation limits its applicability. We hypothesized that placement of a biodegradable stent (BD-stent) immediately after circumferential EEM would prevent stricturing. Ten pigs (five unstented controls, five BD-stent) were utilized. Under anesthesia, a flexible endoscope with a band ligator and snare was used to incise the mucosa approximately 20 cm proximal to the lower esophageal sphincter. A 10-cm, circumferential, mucosal segment was dissected and excised by using snare electrocautery. In the stented group, an 18-×120-mm, self-expanding, woven polydioxanone stent (ELLA-CS, Hradec-Kralove) was deployed. Weekly esophagograms evaluated for percent reduction in esophageal diameter, stricture length, and proximal esophageal dilation. Animals were euthanized when the stricture exceeded 80% and were unable to gain weight (despite high-calorie liquid diet) or at 14 weeks. The control group rapidly developed esophageal strictures; no animal survived beyond the third week of evaluation. At 2 weeks post-EEM, the BD-stent group had a significant reduction in esophageal diameter (77.7 vs. 26.6%, p < 0.001) and degree of proximal dilation (175 vs. 131%, p = 0.04) compared with controls. Survival in the BD-stent group was significantly longer than in the control group (9.2 vs. 2.4 weeks, p = 0.01). However, all BD-stent animals ultimately developed clinically significant strictures (range, 4-14 weeks). Comparison between the maximum reduction in esophageal diameter and stricture length (immediately before euthanasia) demonstrated no differences between the groups. Circumferential EEM results in severe stricture formation and clinical deterioration within 3 weeks. BD-stent placement significantly delays the time of clinical deterioration from 2.4 to 9.2 weeks, but does not affect the maximum reduction in esophageal diameter or proximal esophageal dilatation. The timing of stricture formation in the BD-stent group correlated with the loss radial force and stent disintegration.

Development of a Multicomponent Prediction Model for Acute Esophagitis in Lung Cancer Patients Receiving Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Ruyck, Kim, E-mail: kim.deruyck@UGent.be; Sabbe, Nick; Oberije, Cary

2011-10-01

Purpose: To construct a model for the prediction of acute esophagitis in lung cancer patients receiving chemoradiotherapy by combining clinical data, treatment parameters, and genotyping profile. Patients and Methods: Data were available for 273 lung cancer patients treated with curative chemoradiotherapy. Clinical data included gender, age, World Health Organization performance score, nicotine use, diabetes, chronic disease, tumor type, tumor stage, lymph node stage, tumor location, and medical center. Treatment parameters included chemotherapy, surgery, radiotherapy technique, tumor dose, mean fractionation size, mean and maximal esophageal dose, and overall treatment time. A total of 332 genetic polymorphisms were considered in 112 candidatemore » genes. The predicting model was achieved by lasso logistic regression for predictor selection, followed by classic logistic regression for unbiased estimation of the coefficients. Performance of the model was expressed as the area under the curve of the receiver operating characteristic and as the false-negative rate in the optimal point on the receiver operating characteristic curve. Results: A total of 110 patients (40%) developed acute esophagitis Grade {>=}2 (Common Terminology Criteria for Adverse Events v3.0). The final model contained chemotherapy treatment, lymph node stage, mean esophageal dose, gender, overall treatment time, radiotherapy technique, rs2302535 (EGFR), rs16930129 (ENG), rs1131877 (TRAF3), and rs2230528 (ITGB2). The area under the curve was 0.87, and the false-negative rate was 16%. Conclusion: Prediction of acute esophagitis can be improved by combining clinical, treatment, and genetic factors. A multicomponent prediction model for acute esophagitis with a sensitivity of 84% was constructed with two clinical parameters, four treatment parameters, and four genetic polymorphisms.« less

Phase I/II study of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma.

PubMed

Song, Y-P; Ma, J-B; Hu, L-K; Zhou, W; Chen, E-C; Zhang, W

2011-02-01

Compared to conventional fractionated-dose radiotherapy, high hypofractionated-dose radiotherapy could yield tumoricidal effects. However, few clinical trials of hypofractionated radiotherapy in loco-regionally advanced incurable esophageal cancer at present have yet been performed. The purpose of the current study was to evaluate the efficacy and toxicity of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma. From September 2003 to December 2005, 45 patients with locally advanced esophageal carcinoma were grouped and received three-dimensional conformal hypofractioned radiotherapy (3D-CRT) whose fractionated dose was gradually increase per group. Radiotherapy was administered to a total dose of from 50 to 54 Gy (fractionated dose of from 3.0 to 6.0 Gy, 3 times weekly), over a 3-4 week period. And patients received 4 cycles chemotherapy. The median follow-up period for survivors was 38 months. Treatment tolerance rate was 78.8% with daily dose of from 3 to 5 Gy. There are 21.2% patients occurring Grade ≥ 3 acute toxicities. But patients couldn't tolerate daily dose of 6 Gy (55.6%). The 1-year, 2-year and 3-year local control rates were 62%, 49% and 39% respectively. And the 1-year, 2-year and 3-year overall survival rates were 34%, 21% and 9% respectively. The median overall survival time was 17 months. At the time of following up, 13 patients (31.0%) had occurred esophageal late complications, with mainly esophageal perforation, hemorrhage or stenosis, including initial stenosis aggravation. Therefore hypofractionated irradiation was thought to be feasible for clinical T3-4N0-1M0 stage esophageal carcinoma. And daily dose of ≤5 Gy was comparatively suitable in hypofractionated irradiation for esophageal carcinoma, and the patients tolerated well. But further research was in need also.

Esophageal dysfunction in four alpaca crias and a llama cria with vascular ring anomalies.

PubMed

McKenzie, Erica C; Seguin, Bernard; Cebra, Christopher K; Margiocco, Marco L; Anderson, David E; Löhr, Christiane V

2010-08-01

3 alpaca crias and cadavers of an alpaca cria and a llama cria were evaluated for evidence of esophageal dysfunction. All 5 crias were between 3 and 5 months of age when clinical signs developed, and all had a thin body condition when examined. Clinical signs included coughing, regurgitation, and grossly visible esophageal peristaltic waves. A barium esophagram was used to diagnose esophageal obstruction, megaesophagus, and a vascular ring anomaly (VRA). Fluoroscopy was used to evaluate deglutition, esophageal peristalsis, and the extent of esophageal dilation in 1 alpaca cria. A persistent right aortic arch was identified in 1 alpaca cria, and a left aortic arch with right ductus arteriosus or ligamentum arteriosum and an aberrant right subclavian artery were identified in the 4 remaining crias. Surgical correction of the VRA was attempted in the 3 live alpaca crias. It was complicated by the conformation and location of each VRA and inaccurate anatomic diagnosis of the VRAs before surgery. Treatment was universally unsuccessful because of intraoperative complications and the persistence of clinical signs after surgery. Megaesophagus is typically an idiopathic condition in camelids. However, these findings suggested that camelids with esophageal dysfunction during the neonatal period may have a VRA. The prognosis is grave for camelids with VRA, and accurate anatomic diagnosis of the VRA via the use of advanced imaging techniques (eg, angiography, computed tomography, or magnetic resonance imaging) may improve the success of surgical intervention.

Chicago Classification Criteria of Esophageal Motility Disorders Defined in High Resolution Esophageal Pressure Topography (EPT)†

PubMed Central

Bredenoord, Albert J; Fox, Mark; Kahrilas, Peter J; Pandolfino, John E; Schwizer, Werner; Smout, AJPM; Conklin, Jeffrey L; Cook, Ian J; Gyawali, Prakash; Hebbard, Geoffrey; Holloway, Richard H; Ke, Meiyun; Keller, Jutta; Mittal, Ravinder K; Peters, Jeff; Richter, Joel; Roman, Sabine; Rommel, Nathalie; Sifrim, Daniel; Tutuian, Radu; Valdovinos, Miguel; Vela, Marcelo F; Zerbib, Frank

2011-01-01

Background The Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high resolution esophageal pressure topography (EPT) studies, concurrent with the widespread adoption of this technology into clinical practice. The Chicago Classification has been, and will continue to be, an evolutionary process, molded first by published evidence pertinent to the clinical interpretation of high resolution manometry (HRM) studies and secondarily by group experience when suitable evidence is lacking. Methods This publication summarizes the state of our knowledge as of the most recent meeting of the International High Resolution Manometry Working Group in Ascona, Switzerland in April 2011. The prior iteration of the Chicago Classification was updated through a process of literature analysis and discussion. Key Results The major changes in this document from the prior iteration are largely attributable to research studies published since the prior iteration, in many cases research conducted in response to prior deliberations of the International High Resolution Manometry Working Group. The classification now includes criteria for subtyping achalasia, EGJ outflow obstruction, motility disorders not observed in normal subjects (Distal esophageal spasm, Hypercontractile esophagus, and Absent peristalsis), and statistically defined peristaltic abnormalities (Weak peristalsis, Frequent failed peristalsis, Rapid contractions with normal latency, and Hypertensive peristalsis). Conclusions & Inferences The Chicago Classification is an algorithmic scheme for diagnosis of esophageal motility disorders from clinical EPT studies. Moving forward, we anticipate continuing this process with increased emphasis placed on natural history studies and outcome data based on the classification. PMID:22248109

Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography.

PubMed

Bredenoord, A J; Fox, M; Kahrilas, P J; Pandolfino, J E; Schwizer, W; Smout, A J P M

2012-03-01

The Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high resolution esophageal pressure topography (EPT) studies, concurrent with the widespread adoption of this technology into clinical practice. The Chicago Classification has been an evolutionary process, molded first by published evidence pertinent to the clinical interpretation of high resolution manometry (HRM) studies and secondarily by group experience when suitable evidence is lacking. This publication summarizes the state of our knowledge as of the most recent meeting of the International High Resolution Manometry Working Group in Ascona, Switzerland in April 2011. The prior iteration of the Chicago Classification was updated through a process of literature analysis and discussion. The major changes in this document from the prior iteration are largely attributable to research studies published since the prior iteration, in many cases research conducted in response to prior deliberations of the International High Resolution Manometry Working Group. The classification now includes criteria for subtyping achalasia, EGJ outflow obstruction, motility disorders not observed in normal subjects (Distal esophageal spasm, Hypercontractile esophagus, and Absent peristalsis), and statistically defined peristaltic abnormalities (Weak peristalsis, Frequent failed peristalsis, Rapid contractions with normal latency, and Hypertensive peristalsis). The Chicago Classification is an algorithmic scheme for diagnosis of esophageal motility disorders from clinical EPT studies. Moving forward, we anticipate continuing this process with increased emphasis placed on natural history studies and outcome data based on the classification. © 2012 Blackwell Publishing Ltd.

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuong, Michael D.; Hallemeier, Christopher L.; Jabbour, Salma K.

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with protonmore » beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.« less

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.

PubMed

Chuong, Michael D; Hallemeier, Christopher L; Jabbour, Salma K; Yu, Jen; Badiyan, Shahed; Merrell, Kenneth W; Mishra, Mark V; Li, Heng; Verma, Vivek; Lin, Steven H

2016-05-01

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT. Copyright © 2016 Elsevier Inc. All rights reserved.

Early diagnosis based on clinical history and BALF for successful management of smoking-induced acute eosinophilic pneumonia without unnecessary antibiotic usage: a case report.

PubMed

Song, Jee In; Kim, Yang-Ki; Hwang, Jung Hwa; Yang, Hyeon-Jong

2016-01-01

Acute eosinophilic pneumonia (AEP) is a rapid onset and severe respiratory illness characterized by acute febrile respiratory insufficiency, eosinophilic infiltration in the lungs and unique findings on chest imaging. Difficulty in differentiating from other respiratory distress caused by community-acquired pneumonia may result in a delayed diagnosis or treatment with empirical antibiotics. Sixteen-year-old boy who developed AEP with marked eosinophilia in bronchoalveolar lavage fluid (BALF, 36.6%), decreased diffusion capacity of the lung for carbon monoxide (62%) and unique radiological findings. Although he initially denied tobacco use, on repeated thorough clinical history questioning, he eventually admitted beginning smoking 19 days before the onset of symptoms with gradually increasing frequency. His symptoms resolved quickly without use of antibiotics after cessation of tobacco and treatment with corticosteroids. Careful clinical history taking regarding tobacco use combined with early examination of BALF and recognition of unique radiological findings are critical for proper management of AEP.

Association of interleukin 1 receptor-like 1 gene polymorphisms with eosinophilic phenotype in Japanese adults with asthma.

PubMed

Inoue, Hideki; Ito, Isao; Niimi, Akio; Matsumoto, Hisako; Oguma, Tsuyoshi; Tajiri, Tomoko; Iwata, Toshiyuki; Nagasaki, Tadao; Kanemitsu, Yoshihiro; Morishima, Toshitaka; Hirota, Tomomitsu; Tamari, Mayumi; Wenzel, Sally E; Mishima, Michiaki

2017-11-01

IL1RL1 (ST2) is involved in Th2 inflammation including eosinophil activation. Single nucleotide polymorphisms (SNPs) of the IL1RL1 gene are associated with asthma development and increased peripheral blood eosinophil counts. However, the association between IL1RL1 SNPs and eosinophilic phenotype among adults with asthma remains unexplored. In a primary cohort of 110 adult Japanese patients with stable asthma, we examined the associations between IL1RL1 SNPs and clinical measurements including forced expiratory volume (FEV 1 ), airway reversibility of FEV 1 , exhaled nitric oxide (FeNO), serum soluble-ST2 (sST2) levels, peripheral blood eosinophil differentials and serum total IgE level. The findings in the primary cohort were confirmed in a validation cohort of 126 adult Japanese patients with stable asthma. Patients with minor alleles in 3 SNPs (rs17026974, rs1420101, and rs1921622) had high FeNO, blood eosinophil differentials, and reversibility of FEV 1 , but low levels of serum sST2 and FEV 1 . Minor alleles of rs1041973 were associated with low serum sST2 levels alone. In the validation cohort, minor alleles of rs1420101 were associated with high FeNO and blood eosinophil differentials, whereas minor alleles of rs17026974 and rs1921622 were associated with high blood eosinophil differentials and FeNO, respectively. Multivariate analyses revealed that the minor allele of rs1420101 additively contributed to the FeNO, blood eosinophil differentials, and reversibility of FEV 1 . The minor alleles of IL1RL1 SNPs were associated with high FeNO and peripheral blood eosinophilia among adult Japanese patients with stable asthma. IL1RL1 SNPs may characterize the eosinophilic phenotype with greater eosinophilic inflammation in the Japanese asthma cohort. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Human parasitic meningitis caused by Angiostrongylus cantonensis infection in Taiwan.

PubMed

Tsai, Hung-Chin; Chen, Yao-Shen; Yen, Chuan-Min

2013-06-01

The major cause of eosinophilic meningitis in Taiwan is Angiostrongylus cantonensis. Humans are infected by ingesting terrestrial and freshwater snails and slugs. In 1998 and 1999, two outbreaks of eosinophilic meningitis caused by A. cantonensis infection were reported among 17 adult male immigrant Thai laborers who had eaten raw golden apple snails (Pomacea canaliculata). Another outbreak associated with consuming a health drink consisting of raw vegetable juice was reported in 2001. These adult cases differed from reports in the 1970s and 1980s, in which most of the cases were in children. With improvements in public health and education of foreign laborers, there have since been only sporadic cases in Taiwan. Review of clinical research indicates inconsistent association of Magnetic Resonance Imaging (MRI) results with clinical features of eosinophilic meningitis. MRI features were nonspecific but there was an association between the presence of high brain MRI signal intensities and severity of peripheral and cerebrospinal fluid (CSF) eosinophilia. Inflammatory markers have been identified in the CSF of patients with eosinophilic meningitis caused by A. cantonensis infection, and vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and the matrix metalloproteinase system may be associated with blood-brain barrier disruption. Eosinophilic meningitis caused by A. cantonensis infection is not a reportable disease in Taiwan. It is important that a public advisory and education program be developed to reduce future accidental infection.

A pediatric case of Fascioliasis with eosinophilic pneumonia.

PubMed

Bayhan, Gülsüm İclal; Batur, Abdulsamet; Taylan-Özkan, Ayşegül; Demirören, Kaan; Beyhan, Yunus Emre

2016-01-01

Fasciolia spp. are common trematode infestations worldwide. Fasciolia spp. may lead to hepatic diseases in the acute phase and may cause biliary diseases in the chronic phase. In addition, Fasciolia spp. may rarely cause extrahepatic signs and symptoms. The clinical manifestations of fascioliasis are divided into three groups: typical, atypical, and ectopic. Eosinophilic pneumonia is an atypical presentation of acute fascioliasis and it has been reported very rarely. Herein, we report a boy with marked blood eosinophilia and eosinophilic pneumonia who was diagnosed with fascioliasis by serologic tests and abdominal USG. The patient recovered completely following triclabendazole treatment.

Eosinophilic pustular folliculitis in infancy: report of a new case.

PubMed

Alonso-Castro, L; Pérez-García, B; González-García, C; Jaén-Olasolo, P

2012-10-15

We report a new case of eosinophilic pustular folliculitis in a 23-month-old boy. He presented with a seven-month history of recurrent episodes of pustular lesions on the scalp after having been treated with oral antifungal and topic antibiotics without response. The diagnosis was based on the clinical course and typical histopathological findings. Eosinophilic pustular folliculitis in infancy is an idiopathic and rare inflammatory disease characterized by recurrent crops of sterile pustules involving mainly the scalp. Because it is a benign, self-limiting condition an accurate diagnosis is essential to avoid unnecessary therapies.

Congenital esophageal stenosis associated with esophageal atresia/tracheoesophageal fistula: clinical and radiologic features.

PubMed

Yoo, Hye Jin; Kim, Woo Sun; Cheon, Jung-Eun; Yoo, So-Young; Park, Kwi-Won; Jung, Sung-Eun; Shin, Su-Mi; Kim, In-One; Yeon, Kyung Mo

2010-08-01

Congenital esophageal stenosis (CES) can be associated with esophageal atresia/tracheoesophageal fistula (EA/TEF). Because there are a variety of degrees of obstruction and symptoms of CES, it is frequently difficult to make a pre- and post-operative diagnosis of the distal CES associated with EA/TEF. To evaluate the clinical and radiologic features of congenital esophageal stenosis associated with esophageal atresia/tracheoesophageal fistula. We retrospectively reviewed postoperative esophagograms and medical records of 187 children (107 boys, 80 girls) who had primary repair of EA/TEF from 1992 to 2009 at our institution. We evaluated the incidence of CES, clinical findings, radiologic features and management of CES in these children. CES was diagnosed in 22 of 187 EA/TEF children (12%); one child had double CES lesions, for a total of 23 lesions. Ten of those 22 children (45%) had presented with significant symptoms of esophageal obstruction. The diagnosis of CES was delayed in 10 children (45%) until 1-10 years of age. On esophagogram, CES (n = 23) was located in the distal esophagus (n = 20, 87%) or mid-esophagus (n = 3, 13%). The degree of stenosis was severe (n = 6, 26%), moderate (n = 10, 43%), or mild (n = 7, 30%). Eight children, including two with unsuccessful esophageal balloon dilatation of CES, were treated surgically. Histologic examination revealed tracheobronchial remnant (n = 7) or fibromuscular hyperplasia (n = 1). One child with surgically treated CES developed achalasia at the age of 3 years 9 months. Esophagography after EA/TEF repair should be performed with a high index of suspicion for the presence of distal CES, because the diagnosis and adequate management of CES can often be delayed.

Preoperative chemoradiation with paclitaxel-carboplatin or with fluorouracil-oxaliplatin-folinic acid (FOLFOX) for resectable esophageal and junctional cancer: the PROTECT-1402, randomized phase 2 trial.

PubMed

Messager, Mathieu; Mirabel, Xavier; Tresch, Emmanuelle; Paumier, Amaury; Vendrely, Véronique; Dahan, Laetitia; Glehen, Olivier; Vasseur, Frederique; Lacornerie, Thomas; Piessen, Guillaume; El Hajbi, Farid; Robb, William B; Clisant, Stéphanie; Kramar, Andrew; Mariette, Christophe; Adenis, Antoine

2016-05-18

Often curative treatment for locally advanced resectable esophageal or gastro-esophageal junctional cancer consists of concurrent neoadjuvant radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy regimens in this setting is a combination of a fluoropyrimidin and of a platinum analogue. Due to the promising results of the recent CROSS trial, another regimen combining paclitaxel and carboplatin is also widely used by European and American centers. No clinical study has shown the superiority of one treatment over the other. The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments. Our aim is to evaluate, in operable esophageal and gastro-esophageal junctional cancer, the complete resection rate and severe postoperative morbidity rate associated with these two neoadjuvant chemotherapeutic regimens (carboplatin-paclitaxel or fluorouracil-oxaliplatin-folinic acid) when each is combined with the radiation regime utilized in the CROSS trial. PROTECT is a prospective, randomized, multicenter, open arms, phase II trial. Eligible patients will have a histologically confirmed adenocarcinoma or squamous cell carcinoma and be treated with neoadjuvant radiochemotherapy followed by surgery for stage IIB or stage III resectable esophageal cancer. A total of 106 patients will be randomized to receive either 3 cycles of FOLFOX combined to concurrent radiotherapy (41.4 Grays) or carboplatin and paclitaxel with the same radiation regimen, using a 1:1 allocation ratio. This ongoing trial offers the unique opportunity to compare two standards of chemotherapy delivered with a common regimen of preoperative radiation, in the setting of operable locally advanced esophageal or gastro-esophageal junctional tumors. NCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014-000649-62 (registration date: 10 FEB 2014).

Dysphagia among adult patients who underwent surgery for esophageal atresia at birth.

PubMed

Huynh Trudeau, Valérie; Maynard, Stéphanie; Terzic, Tatjana; Soucy, Geneviève; Bouin, Mickeal

2015-03-01

Clinical experiences of adults who underwent surgery for esophageal atresia at birth is limited. There is some evidence that suggests considerable long-term morbidity, partly because of dysphagia, which has been reported in up to 85% of adult patients who undergo surgery for esophageal atresia. The authors hypothesized that dysphagia in this population is caused by dysmotility and⁄or anatomical anomalies. To determine the motor and anatomical causes of dysphagia. A total of 41 adults, followed at the Esophageal Atresia Clinic at Hôpital Saint-Luc (Montreal, Quebec), were approached to particpate in the present prospective study. Evaluation was completed using upper endoscopy, manometry and barium swallow for the participants who consented. The medical charts of respondents were systematically reviewed from the neonatal period to 18 years of age to assess medical and surgical history. All 41 patients followed at the clinic consented and were included in the study. Dysphagia was present in 73% of patients. Esophagogastroduodenoscopy was performed in 32 patients: hiatal hernia was present in 62% (n=20); esophageal diverticulum in 13% (n=4); macroscopic Barrett esophagus in 31% (n=10); and esophagitis in 19% (n=6). Histological esophagitis was present in 20% and intestinal metaplasia in 10%. There were no cases of dysplagia or adenocarcinoma. Esophageal manometry was performed on 56% of the patients (n=23). Manometry revealed hypomotility in 100% of patients and included an insufficient number of peristaltic waves in 96%, nonpropagating peristalsis in 78% and low-wave amplitude in 95%. Complete aperistalsis was present in 78%. The lower esophageal sphincter was abnormal in 12 (52%) patients, with incomplete relaxation the most common anomaly. Of the 41 patients, 29 (71%) consented to a barium swallow, which was abnormal in 13 (45%). The anomalies found were short esophageal dilation in 28%, delay in esophageal emptying in 14%, diverticula in 14% and stenosis in 7% of patients. There was more than one anomaly in 14% of patients. Dysphagia was a highly prevalent symptom in adults who underwent surgery for esophageal atresia. The present study is the first to demonstrate that motor and anatomical abnormalities may be implicated in causes of dysphagia in this population. Furthermore, these anomalies may be demonstrated with simple investigations such as endoscopy, manometry and barium swallow.

Dysphagia among adult patients who underwent surgery for esophageal atresia at birth

PubMed Central

Huynh-Trudeau, Valérie; Maynard, Stéphanie; Terzic, Tatjana; Soucy, Geneviève; Bouin, Mickael

2015-01-01

BACKGROUND: Clinical experiences of adults who underwent surgery for esophageal atresia at birth is limited. There is some evidence that suggests considerable long-term morbidity, partly because of dysphagia, which has been reported in up to 85% of adult patients who undergo surgery for esophageal atresia. The authors hypothesized that dysphagia in this population is caused by dysmotility and/or anatomical anomalies. OBJECTIVE: To determine the motor and anatomical causes of dysphagia. METHODS: A total of 41 adults, followed at the Esophageal Atresia Clinic at Hôpital Saint-Luc (Montreal, Quebec), were approached to particpate in the present prospective study. Evaluation was completed using upper endoscopy, manometry and barium swallow for the participants who consented. The medical charts of respondents were systematically reviewed from the neonatal period to 18 years of age to assess medical and surgical history. RESULTS: All 41 patients followed at the clinic consented and were included in the study. Dysphagia was present in 73% of patients. Esophagogastroduodenoscopy was performed in 32 patients: hiatal hernia was present in 62% (n=20); esophageal diverticulum in 13% (n=4); macroscopic Barrett esophagus in 31% (n=10); and esophagitis in 19% (n=6). Histological esophagitis was present in 20% and intestinal metaplasia in 10%. There were no cases of dysplagia or adenocarcinoma. Esophageal manometry was performed on 56% of the patients (n=23). Manometry revealed hypomotility in 100% of patients and included an insufficient number of peristaltic waves in 96%, non-propagating peristalsis in 78% and low-wave amplitude in 95%. Complete aperistalsis was present in 78%. The lower esophageal sphincter was abnormal in 12 (52%) patients, with incomplete relaxation the most common anomaly. Of the 41 patients, 29 (71%) consented to a barium swallow, which was abnormal in 13 (45%). The anomalies found were short esophageal dilation in 28%, delay in esophageal emptying in 14%, diverticula in 14% and stenosis in 7% of patients. There was more than one anomaly in 14% of patients. CONCLUSION: Dysphagia was a highly prevalent symptom in adults who underwent surgery for esophageal atresia. The present study is the first to demonstrate that motor and anatomical abnormalities may be implicated in causes of dysphagia in this population. Furthermore, these anomalies may be demonstrated with simple investigations such as endoscopy, manometry and barium swallow. PMID:25803019

Esophageal Achalasia: Pathophysiology, Clinical Presentation, and Diagnostic Evaluation.

PubMed

Schlottmann, Francisco; Neto, Rafael M L; Herbella, Fernando A M; Patti, Marco G

2018-04-01

Esophageal achalasia is a primary esophageal motility disorder characterized by the absence of esophageal peristalsis and failure of the lower esophageal sphincter to relax in response to swallowing. These abnormalities lead to impaired emptying of food from the esophagus into the stomach with resulting food stasis. Most patients experience severe dysphagia, and regurgitation can lead to aspiration and respiratory problems. Consequently, the quality of life of patients affected by achalasia is severely impacted. A thorough evaluation with upper endoscopy, barium swallow, and esophageal manometry is mandatory to establish the diagnosis and plan the optimal treatment. In selected patients, an ambulatory pH monitoring is recommended to distinguish between gastroesophageal reflux disease and achalasia.

Current and future treatment options for esophageal cancer in the elderly.

PubMed

Bollschweiler, Elfriede; Plum, Patrick; Mönig, Stefan P; Hölscher, Arnulf H

2017-07-01

Esophageal cancer is the eighth most common cancer globally and has the sixth worst prognosis because of its aggressiveness and poor survival. Data regarding cancer treatment in older patients is limited because the elderly have been under-represented in clinical trials. Therefore, we reviewed the existing literature regarding treatment results for elderly patients (70+ years). Areas covered: We used pubmed to analyze the actual literature according to elderly esophageal cancer patients with subheading of incidence, esophagectomy, chemoradiation or chemotherapy. The main points of interest were treatment options for patients with Barrett's esophagus or early carcinoma, advanced tumor stages, and inoperable cancer. Expert opinion: The incidence of esophageal cancer has been increasing over the past thirty years, with a rapid increase of esophageal adenocarcinoma in Western industrialized nations. Patients aged over 60 years have been particularly affected. In this review, we have shown that elderly patients with esophageal cancer have various alternatives for adequate treatment. Clinical evaluation of comorbidity is necessary to make treatment decisions. Therapeutic options for early carcinomas are endoscopic or surgical resection. For elderly patients with advanced carcinomas, preoperative chemoradiation or chemotherapy should be discussed.

Esophageal tissue engineering: Current status and perspectives.

PubMed

Poghosyan, T; Catry, J; Luong-Nguyen, M; Bruneval, P; Domet, T; Arakelian, L; Sfeir, R; Michaud, L; Vanneaux, V; Gottrand, F; Larghero, J; Cattan, P

2016-02-01

Tissue engineering, which consists of the combination and in vivo implantation of elements required for tissue remodeling toward a specific organ phenotype, could be an alternative for classical techniques of esophageal replacement. The current hybrid approach entails creation of an esophageal substitute composed of an acellular matrix and autologous epithelial and muscle cells provides the most successful results. Current research is based on the use of mesenchymal stem cells, whose potential for differentiation and proangioogenic, immune-modulator and anti-inflammatory properties are important assets. In the near future, esophageal substitutes could be constructed from acellular "intelligent matrices" that contain the molecules necessary for tissue regeneration; this should allow circumvention of the implantation step and still obtain standardized in vivo biological responses. At present, tissue engineering applications to esophageal replacement are limited to enlargement plasties with absorbable, non-cellular matrices. Nevertheless, the application of existing clinical techniques for replacement of other organs by tissue engineering in combination with a multiplication of translational research protocols for esophageal replacement in large animals should soon pave the way for health agencies to authorize clinical trials. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Clinicopathological findings of primary esophageal malignant melanoma: report of six cases and review of literature.

PubMed

Zheng, Jinfeng; Mo, Haiying; Ma, Shufang; Wang, Zhenzheng

2014-01-01

We studied images and histopathological features of primary esophageal malignant melanoma to explore the clinical pathological features, diagnosis, differential diagnoses, and treatment. Immunolabelling was conducted on six cases of esophageal malignant melanoma using histological and immunohistochemical techniques. Combined with the related literature, the clinical manifestations, imaging, histopathological and immunohistochemical features, treatment, and prognosis of primary esophageal malignant melanoma were observed and analyzed. The six patients with primary esophageal malignant melanoma were all male with an average age of 63.4 years. Poor food intake was observed in all patients, and the symptoms showed progressive aggravation. Endoscopic feed tube revealed dark brown and black nodular and polypoid lesions, 1/4-1/2 loop cavity. Tumor histopathology revealed the following characteristics: tumor cells arranged in nests, sheets and cords, round or polygonal, abundant and red-stained cytoplasm, melanin granules in the cytoplasm, heterogeneous nucleus sizes, centered or deviated nuclei, clearly identifiable nucleoli, and apparent pathological mitosis. The immune phenotype was as follows: tumor cells had diffuse expression of HMB45, Melan A, and S100. The cells were CK negative, and the Ki67-positive cell number was 40%-45%. Primary esophageal malignant melanoma is rare with high malignancy and poor prognosis. Immunohistochemical staining is helpful for diagnosing this tumor. The differential diagnosis includes low differentiated carcinoma, primitive neuroectodermal tumor, esophageal sarcomatoid carcinoma, esophageal lymphoma, and other tumors.

Pruritic papular eruption and eosinophilic folliculitis associated with human immunodeficiency virus (HIV) infection: a histopathological and immunohistochemical comparative study.

PubMed

Afonso, João Paulo Junqueira Magalhães; Tomimori, Jane; Michalany, Nilceo Schwery; Nonogaki, Suely; Porro, Adriana Maria

2012-08-01

Among the papular-pruriginous dermatoses related to human immunodeficiency (HIV) infection, two entities remain poorly differentiated leading to confusion in their diagnosis: HIV-related pruritic papular eruption (HIV-PPE or prurigo) and eosinophilic folliculitis (HIV-EF). To establish histopathological and immunohistochemical parameters to differentiate between two conditions associated with HIV infection, the pruritic papular eruption (HIV-PPE) and eosinophilic folliculitis (HIV-EF). Clinically typical HIV-PPE (18 cases) and HIV-EF (10 cases) cases were compared with each other in terms of the following topics: clinical and laboratory features (gender, age, CD4+ cell and eosinophil count), histopathological features (hematoxylin-eosin and toluidine blue staining) and immunohistochemical features (anti-CD1a, anti-CD4, anti-CD7, anti-CD8, anti-CD15, anti-CD20, anti-CD30, anti-CD68/macrophage and anti-S-100 reactions). Among the HIV-EF patients, we found an intense perivascular and diffuse inflammatory infiltration compared with those patients with HIV-PPE. The tissue mast cell count by toluidine staining was higher in the HIV-EF patients, who also presented higher expression levels of CD15 (for eosinophils), CD4 (T helper), and CD7 (pan-T lymphocytes) than the HIV-PPE patients. Only quantitative differences and not qualitative differences were found. These data indicate that HIV-related PPE and EF could possibly be differentiated by histopathological and immunohistochemical findings in addition to clinical characteristics. In fact, these two inflammatory manifestations could be within the spectrum of the same disease because only quantitative, and not qualitative, differences were found. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Exploratory Research on Latent Esophageal Motility Disorders in Dysphagia Patients.

PubMed

Kawaguchi, Shinpei; Takeuchi, Toshihisa; Inoue, Yousuke; Takahashi, Yoshiaki; Ozaki, Haruhiko; Ota, Kazuhiro; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Yamashita, Hiroshi; Fukuchi, Takumi; Ashida, Kiyoshi; Higuchi, Kazuhide

2017-01-01

High-resolution manometry (HRM) has been applied to assess esophageal motility disorders. However, the frequency and types of motility disorders in patients with dysphagia, which are frequently seen in clinical practice, are not clear. We evaluated latent esophageal motility disorders associated with dysphagia. The study included patients without erosive esophageal mucosal damage and with dysphagia symptoms refractory to at least 8 weeks of standard-dose proton pump inhibitors. After enrolment, HRM was used to evaluate for esophageal motility disorder based on the Chicago classification. Esophageal motility disorder was found in 58 of 100 patients and was classified based on the causes: achalasia (13%), esophagogastric junction outflow obstruction (16%), distal esophageal spasms (3%), weak peristalsis (14%), frequently failed peristalsis (5%), and hypertensive peristalsis (7%). Primary esophageal motility disorder was found in approximately 50% of cases in dysphagia patients. Therefore, esophageal motility disorder is not an uncommon condition and should be sought for in order to elucidate precisely the cause of dysphagia. © 2017 S. Karger AG, Basel.

Human immunodeficiency virus-associated eosinophilic folliculitis. A unique dermatosis associated with advanced human immunodeficiency virus infection.

PubMed

Rosenthal, D; LeBoit, P E; Klumpp, L; Berger, T G

1991-02-01

We studied 13 patients with human immunodeficiency virus (HIV) infection and a chronic pruritic folliculitis that was unresponsive to systemic treatment with bactericidal anti-staphylococcal antibiotics. The skin eruption was characterized by multiple urticarial follicular papules scattered on the trunk (100%), the head and neck (85%), and the proximal aspect of the extremities (62%). Absolute peripheral eosinophil counts were increased in six of 13 patients; a relative peripheral eosinophilia was present in 10 of 13 patients. Serum IgE levels were elevated in all seven patients tested (range, 88 to 9050 IU). Histopathologic features included a folliculitis with eosinophils. Pathogenic bacteria were not consistently found by routine bacterial skin cultures, cultures of skin biopsy specimens, or histopathologic evaluation. CD4 counts were decreased in all of the 12 patients tested (less than 300 cells per cubic millimeter) and were below 250 cells per cubic millimeter in 10 patients. A clinical response was noted to astemizole, to ultraviolet light in the B range, and to topical clobetasol propionate. These observations demonstrate that HIV-associated eosinophilic folliculitis is a unique HIV-related cutaneous disorder that is characterized by a culture-negative, chronic, pruritic folliculitis and a characteristic histopathologic picture. Of special importance, because it is associated with CD4 counts of less than 250 to 300 cells per cubic millimeter, eosinophilic folliculitis appears to be an important clinical marker of HIV infection and, particularly, of patients at increased risk of developing opportunistic infections. We suggest that the term eosinophilic pustular folliculitis (Ofuji's disease), previously used to describe this dermatosis in HIV-infected patients, should be discarded.

Eosinophilic Dermatosis of Hematologic Malignancy.

PubMed

Lucas-Truyols, S; Rodrigo-Nicolás, B; Lloret-Ruiz, C; Quecedo-Estébanez, E

Dermatosis characterized by tissue eosinophilia arising in the context of hematologic disease is known as eosinophilic dermatosis of hematologic malignancy. The most commonly associated malignancy is chronic lymphocytic leukemia. Eosinophilic dermatosis of hematologic malignancy is a rare condition with a wide variety of clinical presentations, ranging from papules, erythematous nodules, or blisters that simulate arthropod bites, to the formation of true plaques of differing sizes. Histology reveals the presence of abundant eosinophils. We present 4 new cases seen in Hospital Arnau de Vilanova, Valencia, during the past 7 years. Three of these cases were associated with chronic lymphocytic leukemia and 1 with mycosis fungoides. It is important to recognize this dermatosis as it can indicate progression of the underlying disease, as was the case in 3 of our patients. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

[Eosinophilic spongiosis and ICS antibodies in a child with strophulus-like dermatosis].

PubMed

Klein, G F; Hintner, H; Fristch, P O

1984-01-01

Eosinophilic spongiosis associated with in vivo-bound antibodies to the epidermal intercellular space (ICS) were consistently observed in a recurrent strophulus-like eruption in an 11-year-old boy, thus suggesting pemphigus. The clinical course, however, ruled this diagnosis out since neither acantholysis nor the clinical picture of pemphigus developed in a period of 2.5 years. Since in vivo-bound ICS-antibodies have been described in several case reports of bullous impetigo we speculate that immune reactions to bacterial antigens may be involved in producing eruptions mimicking pemphigus vulgaris.

The Potential Benefits of Applying Recent Advances in Esophageal Motility Testing in Patients with Esophageal Atresia

PubMed Central

Rommel, Nathalie; Rayyan, Maissa; Scheerens, Charlotte; Omari, Taher

2017-01-01

Infants and children with esophageal atresia commonly present with swallowing dysfunction or dysphagia. Dysphagia can lead to a range of significant consequences such as aspiration pneumonia, malnutrition, dehydration, and food impaction. To improve oral intake, the clinical diagnosis of dysphagia in patients with esophageal atresia should focus on both the pharynx and the esophagus. To characterize the complex interactions of bolus flow and motor function between mouth, pharynx, and esophagus, a detailed understanding of normal and abnormal deglutition is required through the use of adequate and objective assessment techniques. As clinical symptoms do not correlate well with conventional assessment methods of motor function such as radiology or manometry but do correlate with bolus flow, the current state-of-the-art diagnosis involves high-resolution manometry combined with impedance measurements to characterize the interplay between esophageal motor function and bolus clearance. Using a novel pressure flow analysis (PFA) method as an integrated analysis method of manometric and impedance measurements, differentiation of patients with impaired esophago-gastric junction relaxation from patients with bolus outflow disorders is clinically relevant. In this, pressure flow matrix categorizing the quantitative PFA measures may be used to make rational therapeutic decisions in patients with esophageal atresia. Through more advanced diagnostics, improved understanding of pathophysiology may improve our patient care by directly targeting the failed biomechanics of both the pharynx and the esophagus. PMID:28680874

The Potential Benefits of Applying Recent Advances in Esophageal Motility Testing in Patients with Esophageal Atresia.

PubMed

Rommel, Nathalie; Rayyan, Maissa; Scheerens, Charlotte; Omari, Taher

2017-01-01

Infants and children with esophageal atresia commonly present with swallowing dysfunction or dysphagia. Dysphagia can lead to a range of significant consequences such as aspiration pneumonia, malnutrition, dehydration, and food impaction. To improve oral intake, the clinical diagnosis of dysphagia in patients with esophageal atresia should focus on both the pharynx and the esophagus. To characterize the complex interactions of bolus flow and motor function between mouth, pharynx, and esophagus, a detailed understanding of normal and abnormal deglutition is required through the use of adequate and objective assessment techniques. As clinical symptoms do not correlate well with conventional assessment methods of motor function such as radiology or manometry but do correlate with bolus flow, the current state-of-the-art diagnosis involves high-resolution manometry combined with impedance measurements to characterize the interplay between esophageal motor function and bolus clearance. Using a novel pressure flow analysis (PFA) method as an integrated analysis method of manometric and impedance measurements, differentiation of patients with impaired esophago-gastric junction relaxation from patients with bolus outflow disorders is clinically relevant. In this, pressure flow matrix categorizing the quantitative PFA measures may be used to make rational therapeutic decisions in patients with esophageal atresia. Through more advanced diagnostics, improved understanding of pathophysiology may improve our patient care by directly targeting the failed biomechanics of both the pharynx and the esophagus.

Specific IgG4 antibodies to cow's milk proteins in pediatric patients with eosinophilic esophagitis.

PubMed

Schuyler, Alexander J; Wilson, Jeffrey M; Tripathi, Anubha; Commins, Scott P; Ogbogu, Princess U; Kruzsewski, Patrice G; Barnes, Barrett H; McGowan, Emily C; Workman, Lisa J; Lidholm, Jonas; Rifas-Shiman, Sheryl L; Oken, Emily; Gold, Diane R; Platts-Mills, Thomas A E; Erwin, Elizabeth A

2018-04-18

Allergen-specific IgG 4 (sIgG 4 ) antibodies are often associated with tolerance, but sIgG 4 antibodies to causally relevant foods have been reported recently in adults with eosinophilic esophagitis (EoE). Prevalence and levels of food sIgG 4 are not well established in the general pediatric population. We sought to investigate serum food sIgG 4 with component diagnostics in children with EoE and children from an unselected birth cohort and to explore the effects of sex, age, and milk consumption on sIgG 4 levels. Sera from 71 pediatric patients with EoE and 210 early adolescent children from an unselected birth cohort (Project Viva) were assayed for sIgG 4 and specific IgE (sIgE) to major cow's milk (CM) proteins (α-lactalbumin, β-lactoglobulin, and caseins) and to wheat, soy, egg, and peanut proteins. In the EoE cohort high-titer sIgG 4 (≥10 μg/mL) to CM proteins was more common than in control sera and achieved odds ratios for EoE ranging from 5.5 to 8.4. sIgE levels to CM proteins were mostly 4 IU/mL or less in patients with EoE, such that sIgG 4 /sIgE ratios were often 10,000 or greater. When adjusted for age and milk consumption, high-titer sIgG 4 to CM proteins was strongly associated with EoE, with an odds ratio of greater than 20 to all 3 CM proteins in boys. sIgG 4 to CM proteins are common and high titer in children with EoE. Although it is not clear that this response is pathogenic, sIgG 4 levels imply that these antibodies are an important feature of the local immune response that gives rise to EoE. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Fluoroscopically guided large balloon dilatation for treating congenital esophageal stenosis in children.

PubMed

Hu, Hong-Tao; Shin, Ji Hoon; Kim, Jin-Hyoung; Jang, Jong Keon; Park, Jung-Hoon; Kim, Tae-Hyung; Nam, Deok Ho; Song, Ho-Young

2015-07-01

We aimed to evaluate the safety and clinical effectiveness of fluoroscopically guided large balloon dilatation for treating congenital esophageal stenosis in children. Our study included seven children (mean age 4.0 years) who underwent a total of ten balloon dilatation sessions. The initial balloon diameters were 10-15 mm. The technical success, clinical success (improved food intake and reduced dysphagia within 1 month following the first balloon dilatation), dysphagia recurrence, and complications were retrospectively evaluated. Technical and clinical success rates were 100 %. During the mean 38-month follow-up period after the first balloon dilatation, 3 (43 %) patients underwent only one additional balloon dilatation 4-5 months after the first balloon dilatation for dysphagia recurrence. Two of them showed improvement without further recurrence, while the remaining one underwent partial esophagectomy. Well-contained transmural esophageal rupture (type 2) occurred in two (29 %, 2/7) patients and during two (20 %, 2/10) balloon dilatation sessions. All ruptures were successfully treated conservatively. Our study showed that fluoroscopically guided large balloon dilatation seems to be a simple and effective primary treatment technique for congenital esophageal stenosis in children. Esophageal ruptures were not uncommon although they were not fatal.

Severe Prolonged Cough as Presenting Manifestation of FIP1L1-PDGFRA+ Chronic Eosinophilic Leukaemia: A Widely Ignored Association.

PubMed

Roufosse, Florence; Heimann, Pierre; Lambert, Frédéric; Sidon, Pierre; Bron, Dominique; Cottin, Vincent; Cordier, Jean-François

2016-01-01

Chronic eosinophilic leukaemia associated with the FIP1L1-PDGFRA fusion gene (F/P+ CEL) is a rare cause of marked persistent hypereosinophilia, arising almost exclusively in male patients. Clinical presentations are heterogeneous with a higher incidence of eosinophil-mediated cardiomyopathy than in other hypereosinophilic syndrome variants. Features of chronic myeloproliferative disease are often present, including splenomegaly and elevated serum vitamin B12 levels. The diagnosis is made by fluorescence in situ hybridization (FISH) showing the deletion of the CHIC2 locus and/or RT-PCR showing the FIP1L1-PDGFRA fusion transcript. Treatment with imatinib mesylate, a tyrosine kinase inhibitor, results in rapid and complete resolution of hypereosinophilia and associated symptoms, except for those related to sub-endocardial fibrosis that may be irreversible. We report the case of a male patient in whom isolated intractable cough remained the only clinical manifestation of F/P+ CEL for 4 years. Furthermore, eosinophil autofluorescence, an as yet unreported artefact in this setting, precluded the detection of the CHIC2 deletion and further delayed diagnosis, underlining that both FISH and RT-PCR should be performed when this disease is suspected. © 2016 S. Karger AG, Basel.

Eosinophilic oesophagitis: Current evidence-based diagnosis and treatment.

PubMed

Lucendo, Alfredo J; Molina-Infante, Javier

2018-04-01

Eosinophilic oesophagitis (EoE) is a disease caused by an immune response to food antigens in contact with the oesophageal mucosa. Its diagnosis is defined by the combination of oesophageal dysfunction symptoms and inflammation of the oesophageal mucosa predominantly by eosinophils. Its chronic course and frequent progression to subepithelial fibrosis and oesophageal strictures indicate the need for treatment. The information provided by recent clinical trials and systematic reviews has led to the development of new clinical guidelines, endorsed by several European scientific societies. This review includes the most relevant aspects of the new guidelines, updates the EoE concept and reports its epidemiology and risk factors, associated conditions and its natural history in children and adults. Diagnostic criteria are provided, and tests for EoE diagnosis and monitoring and therapeutic options are analysed based on the best scientific evidence and consensus opinion of experts. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders.

PubMed

Farmer, Adam D; Ruffle, James K; Aziz, Qasim

2017-02-01

The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.

Long Esophageal Stricture in a Brittle Diabetic

PubMed Central

Darr, Umar; Alastal, Yaseen; Yoon, Youngsook

2017-01-01

Aim: We report a case of atypical esophageal stricture in a young diabetic woman. Background: Diabetes mellitus and gastroesophageal reflux disease (GERD) are two common disorders in modern society. Case report: A young diabetic woman developed a 6-cm-long esophageal stricture. This stricture was refractory to multiple esophageal dilation procedures. She underwent subtotal esophagectomy and had excellent treatment outcome. Conclusion: Gastroesophageal reflux disease can cause severe long esophageal stricture in a brittle diabetic. Clinical significance: Improving the awareness of their association between diabetes and GERD would greatly benefit the day-to-day practice of medicine. How to cite this article: Pak SC, Darr U, Alastal Y, Yoon Y. Long Esophageal Stricture in a Brittle Diabetic. Euroasian J Hepato-Gastroenterol 2017;7(2):191-192. PMID:29201809

A gastroplasty for short esophagus and reflux esophagitis: experimental and clinical studies.

PubMed Central

Demos, N J; Smith, N; Williams, D

1975-01-01

A safe, simple, effective gastroplasty for short esophagus with reflux esophagitis is described. It has been evaluated in dogs for up to three years with flexible fiberesophagoscopy, esophagrams and intraluminal pressure studies. Successful clinical experience has been encouraging. Images Fig. 2. Fig. 3. Fig. 5. Fig. 6. Fig. 7. PMID:1089392

[Laparoscopic Heller myotomy for esophageal achalasia].

PubMed

Ibáñez, Luis; Butte, Jean Michel; Pimentel, Fernando; Escalona, Alex; Pérez, Gustavo; Crovari, Fernando; Guzmán, Sergio; Llanos, Osvaldo

2007-04-01

Achalasia is characterized by an incomplete relaxation of the lower esophageal sphincter. The best treatment is surgical and the laparoscopic approach may have good results. To assess the results of laparoscopic Heller myotomy among patients with achalasia. Prospective study of patients subjected to a laparoscopic Heller myotomy between 1995 and 2004. Clinical features, early and late operative results were assessed. Twenty seven patients aged 12 to 74 years (12 females) were operated. All had disphagia lasting for a mean of 32 months. Mean lower esophageal sphincter pressure ranged from 18 to 85 mmHg. Eight patients received other treatments prior to surgery but symptoms persisted or reappeared. The preoperative clinical score was 7. No patient died and no procedure had to be converted to open surgery. In a follow up of 21 to 131 months, all patients are satisfied with the surgical results and the postoperative clinical score is 1. Only one patient with a mega esophagus maintained a clinical score of six. In this series of patients, laparoscopic Heller myotomy was an effective and safe treatment for esophageal achalasia.

Androgens and esophageal cancer: What do we know?

PubMed

Sukocheva, Olga A; Li, Bin; Due, Steven L; Hussey, Damian J; Watson, David I

2015-05-28

Significant disparities exist between genders for the development and progression of several gastro-intestinal (GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors (AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome - poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer.

Esophageal dysmotility in scleroderma: a prospective study of 183 cases.

PubMed

Lahcene, M; Oumnia, N; Matougui, N; Boudjella, M; Tebaibia, A; Touchene, B

2009-01-01

The goal of the study was to evaluate the prevalence and risk factors of esophageal motor disorders in systemic sclerosis. In 183 consecutive cases of scleroderma, as diagnosed by American College of Rheumatology criteria (1980). Patients' mean age was 40.6+/-13.3 years, the gender ratio was 0.13 and the average duration of disease was 6.8+/-7.5 years. A localized, cutaneous form was observed in 148 patients (81%) and a diffuse form in 35 (19%). All patients underwent upper gastrointestinal endoscopy and standard esophageal manometry. Esophageal symptoms and reflux esophagitis were found in 108 (59%) and 68 (37%) of patients, respectively. Esophageal motor disorders were present in 148 patients (81%), and were associated with a hypotensive lower esophageal sphincter in 114 (62%). The presence of these motor abnormalities was not related to age, gender, skin extension or duration of disease. Esophageal motor disorders were present in almost all patients with esophageal symptoms or esophagitis, and were also found in 48 (64%) of the asymptomatic patients. Esophageal motor disorders are frequently seen in scleroderma, especially in cases with clinical symptoms, but are not associated with a specific form of the disease.

Current advances in esophageal cancer proteomics.

PubMed

Uemura, Norihisa; Kondo, Tadashi

2015-06-01

We review the current status of proteomics for esophageal cancer (EC) from a clinician's viewpoint. The ultimate goal of cancer proteomics is the improvement of clinical outcome. The proteome as a functional translation of the genome is a straightforward representation of genomic mechanisms that trigger carcinogenesis. Cancer proteomics has identified the mechanisms of carcinogenesis and tumor progression, detected biomarker candidates for early diagnosis, and provided novel therapeutic targets for personalized treatments. Our review focuses on three major topics in EC proteomics: diagnostics, treatment, and molecular mechanisms. We discuss the major histological differences between EC types, i.e., esophageal squamous cell carcinoma and adenocarcinoma, and evaluate the clinical significance of published proteomics studies, including promising diagnostic biomarkers and novel therapeutic targets, which should be further validated prior to launching clinical trials. Multi-disciplinary collaborations between basic scientists, clinicians, and pathologists should be established for inter-institutional validation. In conclusion, EC proteomics has provided significant results, which after thorough validation, should lead to the development of novel clinical tools and improvement of the clinical outcome for esophageal cancer patients. This article is part of a Special Issue entitled: Medical Proteomics. Copyright © 2014 Elsevier B.V. All rights reserved.

Eosinophil Resistance to Glucocorticoid-Induced Apoptosis is Mediated by the Transcription Factor NFIL3

PubMed Central

Pazdrak, Konrad; Moon, Young; Straub, Christof; Stafford, Susan; Kurosky, Alexander

2016-01-01

The mainstay of asthma therapy, glucocorticoids (GCs) exert their therapeutic effects through the inhibition of inflammatory signaling and induction of eosinophil apoptosis. However, laboratory and clinical observations of GC-resistant asthma suggest that GCs' effects on eosinophil viability may depend on the state of eosinophil activation. In the present study we demonstrate that eosinophils stimulated with IL-5 show impaired prop-aptoptotic response to GCs. We sought to determine the contribution of GC-mediated transactivating (TA) and transrepressing (TR) pathways in modulation of activated eosinophils' response to GC by comparing their response to the selective GC receptor (GR) agonist Compound A (CpdA) devoid of TA activity to that upon treatment with Dexamethasone (Dex). IL-5-activated eosinophils showed contrasting responses to CpdA and Dex, as IL-5-treated eosinophils showed no increase in apoptosis compared to cells treated with Dex alone, while CpdA elicited an apoptotic response regardless of IL-5 stimulation. Proteomic analysis revealed that both Nuclear Factor IL-3 (NFIL3) and Map Kinase Phosphatase 1 (MKP1) were inducible by IL-5 and enhanced by Dex; however, CpdA had no effect on NFIL3 and MKP1 expression. We found that inhibiting NFIL3 with specific siRNA or by blocking the IL-5-inducible Pim-1 kinase abrogated the protective effect of IL-5 on Dex-induced apoptosis, indicating crosstalk between IL-5 anti-apoptotic pathways and GR-mediated TA signaling occurring via the NFIL3 molecule. Collectively, these results indicate that 1) GCs' TA pathway may support eosinophil viability in IL-5-stimulated cells through synergistic upregulation of NFIL3; and 2) functional inhibition of IL-5 signaling (anti-Pim1) or the use of selective GR agonists that don't upregulate NFIL3 may be effective strategies for the restoring pro-apoptotic effect of GCs on IL-5-activated eosinophils. PMID:26880402

Clinical Outcomes, Efficacy, and Adverse Events in Patients Undergoing Esophageal Stent Placement for Benign Indications: A Large Multicenter Study.

PubMed

Suzuki, Takayuki; Siddiqui, Ali; Taylor, Linda J; Cox, Kristen; Hasan, Raza A; Laique, Sobia N; Mathew, Arun; Wrobel, Piotr; Adler, Douglas G

2016-01-01

Esophageal stents are commonly used to treat benign esophageal conditions including refractory benign esophageal strictures, anastomotic strictures, fistulae, perforations and anastomotic leaks. Data on outcomes in these settings remain limited. We performed a retrospective multicenter study of patients who underwent fully or partially covered self-expandable stent placement for benign esophageal diseases. Esophageal stent placements were performed for the following indications: (1) benign refractory esophageal strictures, (2) surgical anastomotic strictures, (3) esophageal perforations, (4) esophageal fistulae, and (5) surgical anastomotic leaks. A total of 70 patients underwent esophageal stent placement for benign esophageal conditions. A total of 114 separate procedures were performed. The most common indication for esophageal stent placement was refractory benign esophageal stricture (48.2%). Global treatment success rate was 55.7%. Treatment success rate was 33.3% in refractory benign strictures, 23.1% in anastomotic strictures, 100% in perforations, 71.4% in fistulae, and 80% in anastomotic leaks. Stent migration was noted in 28 of 70 patients (40%), most commonly seen in refractory benign strictures. This is one of the largest studies to date of esophageal stents to treat benign esophageal diseases. Success rates are lowest in benign esophageal strictures. These patients have few other options beyond chronic dilations, feeding tubes, and surgery, and fully covered self-expandable metallic stent give patients a chance to have their problem fixed endoscopically and still eat by mouth. Perforations, fistulas, and leaks respond very well to esophageal stenting, and stenting should be considered as a first-line therapy in these settings.

Regenerative Medicine Strategies for Esophageal Repair

PubMed Central

Londono, Ricardo

2015-01-01

Pathologies that involve the structure and/or function of the esophagus can be life-threatening. The esophagus is a complex organ comprising nonredundant tissue that does not have the ability to regenerate. Currently available interventions for esophageal pathology have limited success and are typically associated with significant morbidity. Hence, there is currently an unmet clinical need for effective methods of esophageal repair. The present article presents a review of esophageal disease along with the anatomic and functional consequences of each pathologic process, the shortcomings associated with currently available therapies, and the latest advancements in the field of regenerative medicine with respect to strategies for esophageal repair from benchtop to bedside. PMID:25813694

Targeted therapy in esophageal cancer.

PubMed

Zhang, Lei; Ma, Jiaojiao; Han, Yu; Liu, Jinqiang; Zhou, Wei; Hong, Liu; Fan, Daiming

2016-01-01

An increasing number of patients are diagnosed with esophageal cancer at an advanced stages, and only a small group of them can benefit from the traditional chemotherapy and radiotherapy. So far, multiple monoclonal antibodies and tyrosine kinase inhibitors have been developed, alone or in combination with traditional therapy, to improve the prognosis of patients with advanced esophageal cancer. This review summarizes the recent advances of targeted therapies against EGFR, HER2, VEGFR and c-MET in esophageal cancer. More clinical trials should be performed to evaluate the efficacy and safety of various targeted therapy regimens. Future basic research should focus on investigating the molecular mechanisms of therapeutic targets in esophageal cancer.

[Interpretation of update on The AJCC Esophageal Cancer Staging System, Eighth Edition].

PubMed

Yuan, Y; Chen, L Q

2017-02-01

The recently published AJCC Esophageal Cancer Staging System, 8(th) Edition will be implemented on Januray 1, 2018, which was developed by Worldwide Esophageal Cancer Collaboration based on 22 654 esophageal cancer patients from 33 worldwide centers. The definition of T, N, M, G stage and regional lymph nodes were optimized in the 8(th) edition. And the new "2 cm" principle has simplified the definition for the cancer of esophagogastric junction. In addition to pathologic staging, the 8(th) edition also provided clinical staging and pathologic staging after neoadjuvant therapy, making the new esophageal cancer staging system more practicable and reasonable.

Esophageal replacement.

PubMed

Kunisaki, Shaun M; Coran, Arnold G

2017-04-01

This article focuses on esophageal replacement as a surgical option for pediatric patients with end-stage esophageal disease. While it is obvious that the patient׳s own esophagus is the best esophagus, persisting with attempts to retain a native esophagus with no function and at all costs are futile and usually detrimental to the overall well-being of the child. In such cases, the esophagus should be abandoned, and the appropriate esophageal replacement is chosen for definitive reconstruction. We review the various types of conduits used for esophageal replacement and discuss the unique advantages and disadvantages that are relevant for clinical decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

High TRAF6 Expression Is Associated With Esophageal Carcinoma Recurrence and Prompts Cancer Cell Invasion.

PubMed

Liu, Xinyang; Wang, Zhichao; Zhang, Guoliang; Zhu, Qikun; Zeng, Hui; Wang, Tao; Gao, Feng; Qi, Zhan; Zhang, Jinwen; Wang, Rui

2017-04-14

Esophageal cancer is one of the most common types of cancer, and it has a poor prognosis. The molecular mechanisms of esophageal cancer progression remain largely unknown. In this study, we aimed to investigate the clinical significance and biological function of tumor necrosis factor receptor-associated factor 6 (TRAF6) in esophageal cancer. Expression of TRAF6 in esophageal cancer was examined, and its correlation with clinicopathological factors and patient prognosis was analyzed. A series of functional and mechanism assays were performed to further investigate the function and underlying mechanisms in esophageal cancer. Expression of TRAF6 was highly elevated in esophageal cancer tissues, and patients with high TRAF6 expression have a significantly shorter survival time than those with low TRAF6 expression. Furthermore, loss-of-function experiments showed that knockdown of TRAF6 significantly reduced the migration and invasion abilities of esophageal cancer cells. Moreover, the pro-oncogenic effects of TRAF6 in esophageal cancer were mediated by the upregulation of AEP and MMP2. Altogether, our data suggest that high expression of TRAF6 is significant for esophageal cancer progression, and TRAF6 indicates poor prognosis in esophageal cancer patients, which might be a novel prognostic biomarker or potential therapeutic target in esophageal cancer.

Witnessed and unwitnessed esophageal foreign bodies in children.

PubMed

Louie, Jeffrey P; Alpern, Elizabeth R; Windreich, Randy M

2005-09-01

The purpose of this study was to describe the clinical presentation of children with either an unwitnessed or witnessed esophageal foreign body. Retrospective chart review was performed. Patients were identified using ICD-9 code for esophageal foreign body. Clinical data and management techniques, along with complications were abstracted. For the 5-year period of review, 255 patients were identified with an esophageal foreign body. 214 children had a witnessed ingestion. The mean age of the unwitnessed ingestion group was 2.3 years, compared to 4.6 years for a witnessed ingestion. In both groups, males and females were distributed equally and the most common ingested object was a coin. Bivariate, unadjusted analysis revealed that history of wheeze (OR, 4.35) and fever (OR, 11.15) had the largest association with patients who had an unwitnessed ingestion. Multivariate analysis indicated that any physical findings of wheeze, rhonchi, stridor, or retractions were associated significantly with a diagnosis of an unwitnessed foreign body. Children less than 2 years of age and with a documented fever are also predictive of an unwitnessed ingestion. Eleven children (4.3%) with esophageal abnormalities were also noted to have foreign bodies. Children who present to the emergency department two years old and younger, who have a documented fever and with respiratory findings should be considered at risk for having a retained esophageal foreign body. Children with esophageal abnormalities may also be at risk for retained esophageal foreign bodies.

Facial and extrafacial eosinophilic pustular folliculitis: a clinical and histopathological comparative study.

PubMed

Lee, W J; Won, K H; Won, C H; Chang, S E; Choi, J H; Moon, K C; Lee, M W

2014-05-01

Although more than 300 cases of eosinophilic pustular folliculitis (EPF) have been reported to date, differences in clinicohistopathological findings among affected sites have not yet been evaluated. To evaluate differences in the clinical and histopathological features of facial and extrafacial EPF. Forty-six patients diagnosed with EPF were classified into those with facial and extrafacial disease according to the affected site. Clinical and histopathological characteristics were retrospectively compared, using all data available in the patient medical records. There were no significant between-group differences in subject ages at presentation, but a male predominance was observed in the extrafacial group. In addition, immunosuppression-associated type EPF was more common in the extrafacial group. Eruptions of plaques with an annular appearance were more common in the facial group. Histologically, perifollicular infiltration of eosinophils occurred more frequently in the facial group, whereas perivascular patterns occurred more frequently in the extrafacial group. Follicular mucinosis and exocytosis of inflammatory cells in the hair follicles were strongly associated with facial EPF. The clinical and histopathological characteristics of patients with facial and extrafacial EPF differ, suggesting the involvement of different pathogenic processes in the development of EPF at different sites. © 2013 British Association of Dermatologists.

Wells syndrome and its relationship to Churg-Strauss syndrome.

PubMed

Ratzinger, Gudrun; Zankl, Julia; Zelger, Bernhard

2013-08-01

  Wells syndrome has been described as an inflammatory disorder based on typical clinical appearance combined with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Churg-Strauss syndrome, on the other hand, is primarily a diffuse, necrotizing vasculitis but is also typically displaying eosinophils and flame figures. Despite several parallels, the present understanding of these two diseases excludes any pathogenetic relationship.   We describe the clinical course and histopathological appearance of three patients who had initially been diagnosed with Wells syndrome that developed into Churg-Strauss syndrome during the course of their disease.   The clinical presentation of all three patients led to the diagnosis of Wells syndrome by independent specialists. Histopathology showed an eosinophilic infiltrate and flame figures next to features of leukocytoclastic vasculitis. Detailed examination revealed asthma bronchiale and additional symptoms indicating Churg-Strauss syndrome. The initial diagnosis of Wells syndrome had to be revised to Churg-Strauss syndrome.   We conclude that Wells syndrome could be the starting point of a pathogenetic process that might reach its maximum in Churg-Strauss syndrome. As a clinical consequence, patients with Wells syndrome should be evaluated and followed for Churg-Strauss syndrome. © 2013 The International Society of Dermatology.

Miniaturised optical fiber pH sensor for gastro-esophageal applications

NASA Astrophysics Data System (ADS)

Baldini, F.; Chiavaioli, F.; Cosi, F.; Giannetti, A.; Tombelli, S.; Trono, C.

2013-05-01

Monitoring pH for long periods, usually 24 h, in the stomach and in the esophagus may be essential in the diagnosis of gastro-esophageal diseases. The clinical range of interest is quite extended, between 1 to 8 pH units. Methyl red, after its covalent immobilization on controlled pore glass (CPG), is characterized by a working range which fits well with the clinical one. A novel probe, suitable for gastro-esophageal applications, was designed in order to optimize the performances of the colored CPG. This leads to a very simple probe configuration characterized by a very fast response.

Scintigraphic scoring system for grading severity of gastro-esophageal reflux on 99mTc sulfur colloid gastro-esophageal reflux scintigraphy: A prospective study of 39 cases with pre and post treatment assessment.

PubMed

Puranik, Ameya D; Nair, Gopinathan; Aggarwal, Rajiv; Bandyopadhyay, Abhijit; Shinto, Ajit; Zade, Anand

2013-04-01

The study aimed at developing a scoring system for scintigraphic grading of gastro-esophageal reflux (GER), on gastro-esophageal reflux scintigraphy (GERS) and comparison of clinical and scintigraphic scores, pre- and post-treatment. A total of 39 cases with clinically symptomatic GER underwent 99mTc sulfur colloid GERS; scores were assigned based on the clinical and scintigraphic parameters. Post domperidone GERS was performed after completion of treatment. Follow up GERS was performed and clinical and scintigraphic parameters were compared with baseline parameters. Paired t-test on pre and post domperidone treatment clinical scores showed that the decline in post-treatment scores was highly significant, with P value < 0.001. The scintigraphic scoring system had a sensitivity of 93.9% in assessing treatment response to domperidone, specificity of 83.3% i.e., 83.3% of children with no decline in scintigraphic scores show no clinical response to Domperidone. The scintigraphic scoring system had a positive predictive value of 96.9% and a negative predictive value of 71.4%. GERS with its quantitative parameters is a good investigation for assessing the severity of reflux and also for following children post-treatment.

Intramural esophageal bleeding in a hemodialysis patient

PubMed Central

Lien, J. W. K.; Dufresne, L. R.; Daly, D. S.

1974-01-01

A case of intramural esophageal hemorrhage in a hemodialysis patient is described. The hemorrhage followed an episode of vomiting and violent retching. Spontaneous resolution occurred with conservative management. The clinical course resembled that of previous case reports of intramural esophageal hemorrhage, whether or not associated with chronic renal failure and intermittent hemodialysis. ImagesFIG. 1FIG. 2FIG. 3 PMID:4434294

Gastric-tube versus whole-stomach esophagectomy for esophageal cancer: A systematic review and meta-analysis.

PubMed

Zhang, Wenxiong; Yu, Dongliang; Peng, Jinhua; Xu, Jianjun; Wei, Yiping

2017-01-01

To conduct a systematic review and meta-analysis of studies comparing the gastric-tube vs. whole-stomach for esophageal cancer in order to determine the optimal surgical technique of esophagectomy. A comprehensive literature search was performed using PubMed, EMBASE, ScienceDirect, Ovid MEDLINE, Cochrane Library, Web of Science, Google Scholar, and Scopus. Clinical trials that compared the gastric-tube versus whole-stomach for esophageal cancer were selected. The clinical endpoints included anastomotic leakage, anastomotic stenosis, reflux esophagitis, pneumonia, delayed gastric emptying, and thoracic stomach syndrome. A total of 6 articles (1571 patients) were included. Compared to the whole-stomach approach, the gastric-tube approach was associated with a lower incidence of reflux esophagitis (95% confidence interval [CI]: 0.16 to 0.81, p = 0.01) and thoracic stomach syndrome (95% CI: 0.17 to 0.55, p < 0.0001). The rates of anastomotic leakage, anastomotic stenosis, pneumonia, and delayed gastric emptying did not significantly differ between the two groups. The gastric-tube esophagectomy is superior to the whole-stomach approach, as it is associated with a lower incidence of postoperative reflux esophagitis and thoracic stomach syndrome. Our findings must be validated in large-scale randomized controlled trials.

Pulmonary eosinophilia.

PubMed

Campos, Luiz Eduardo Mendes; Pereira, Luiz Fernando Ferreira

2009-06-01

Pulmonary eosinophilia comprises a heterogeneous group of diseases defined by eosinophilia in pulmonary infiltrates (bronchoalveolar lavage fluid) or in tissue (lung biopsy specimens). Although the inflammatory infiltrate is composed of macrophages, lymphocytes, neutrophils and eosinophils, eosinophilia is an important marker for the diagnosis and treatment. Clinical and radiological presentations can include simple pulmonary eosinophilia, chronic eosinophilic pneumonia, acute eosinophilic pneumonia, allergic bronchopulmonary aspergillosis and pulmonary eosinophilia associated with a systemic disease, such as in Churg-Strauss syndrome and hypereosinophilic syndrome. Asthma is frequently concomitant and can be a prerequisite, as in allergic bronchopulmonary aspergillosis and Churg-Strauss syndrome. In diseases with systemic involvement, the skin, the heart and the nervous system are the most affected organs. The radiological presentation can be typical, or at least suggestive, of one of three types of pulmonary eosinophilia: chronic eosinophilic pneumonia, acute eosinophilic pneumonia and allergic bronchopulmonary aspergillosis. The etiology of pulmonary eosinophilia can be either primary (idiopathic) or secondary, due to known causes, such as drugs, parasites, fungal infection, mycobacterial infection, irradiation and toxins. Pulmonary eosinophilia can be also associated with diffuse lung diseases, connective tissue diseases and neoplasia.

Usefulness of induced sputum eosinophil count to assess severity and treatment outcome in asthma patients

PubMed Central

Bandyopadhyay, Ankan; Roy, Partha P.; Saha, Kaushik; Chakraborty, Semanti; Jash, Debraj; Saha, Debabrata

2013-01-01

Context: Currently treatment decisions in asthma are governed by clinical assessment and spirometry. Sputum eosinophil, being a marker of airway inflammation, can serve as a tool for assessing severity and response to treatment in asthma patients. Aims: To establish correlation between change in sputum eosinophil count and forced expiratory volume in one second (FEV1)% predicted value of asthma patients in response to treatment. In this study, we also predicted prognosis and treatment outcome of asthma patients from baseline sputum eosinophil count. Settings and Design: A longitudinal study was conducted to determine the treatment outcome among newly diagnosed asthma patients who were classified into A (n = 80) and B (n = 80) groups on the basis of initial sputum eosinophil count (A ≥ 3% and B < 3%). Materials and Methods: After starting treatment according to Global Initiative for Asthma Guideline, both A and B groups were evaluated every 15 days interval for the 1st month and monthly thereafter for a total duration of 12 months. In each follow-up visit detailed history, induced sputum eosinophil count and spirometry were done to evaluate severity and treatment outcome. Results: FEV1% predicted of group A asthma patients gradually increased and sputum eosinophil count gradually decreased on treatment. Longer time was required to achieve satisfactory improvement (FEV1% predicted) in asthma patients with sputum eosinophil count ≥3%. There was statistically significant negative correlation between FEV1% predicted and sputum eosinophil count (%) in of group A patients in each follow-up visit, with most significant negative correlation found in 8th visit (r = −0.9237 and P = < 0.001). Change in mean FEV1% (predicted) from baseline showed strong positive correlation (r = 0.976) with change in reduction of mean sputum eosinophil count at each follow-up visits in group A patients. Conclusions: Sputum eosinophil count, being an excellent biomarker of airway inflammation, can serve as a useful marker to assess disease severity, treatment outcome, and prognosis in asthma patients. PMID:23741092

Use of the blue cotton screen method with endoscopy to detect occult esophageal foreign bodies

PubMed Central

Xia, Yan; Zhang, Fan; Xu, Weiran

2017-01-01

More than 20,000 cases of upper gastrointestinal foreign bodies (FBs) have been reported in the last 5 years in China. Early detection and treatment is vital in these patients. Differential diagnosis of esophageal injury and occult esophageal foreign bodies is challenging, particularly in the case of non-radio-opaque foreign bodies. A diagnostic technique with high accuracy and low risk is needed for clinical practice. We describe successful use of the “blue cotton screen method” to detect esophageal foreign bodies in 2 patients. The advantages and disadvantages of various diagnostic modalities in the management of patients with foreign body ingestion are presented. This technique is safer and more effective than traditional methods for foreign body impaction in the esophageal cavity. It could be applied for screening and in the differential diagnosis of esophageal injury and FBs in the esophageal lumen. PMID:29362659

Can involved-field irradiation replace elective nodal irradiation in chemoradiotherapy for esophageal cancer? A systematic review and meta-analysis.

PubMed

Wang, Xiaoyue; Miao, Chuanwang; Chen, Zhen; Li, Wanhu; Yuan, Shuanghu; Yu, Jinming; Hu, Xudong

2017-01-01

Chemoradiotherapy is the most common treatment for inoperable esophageal cancer. However, there is no consensus on the delineation of the clinical target volume. Elective nodal irradiation (ENI) is recommended for inoperable esophageal cancer. A few studies have reported a decrease in the incidence of radiation-related toxicity of involved-field irradiation (IFI) for esophageal cancer. A systematic review and pooled analysis were performed to determine whether IFI in definitive chemoradiotherapy was more beneficial than ENI for esophageal cancer. The results showed no significant differences in the overall survival and local control rates between the IFI and ENI arms. Meanwhile, the incidences of esophageal and lung toxicities were significantly decreased in the IFI arm. These results suggest that IFI is a feasible treatment option for locally advanced esophageal cancer, especially to minimize irradiation-related toxicity.

Can involved-field irradiation replace elective nodal irradiation in chemoradiotherapy for esophageal cancer? A systematic review and meta-analysis

PubMed Central

Wang, Xiaoyue; Miao, Chuanwang; Chen, Zhen; Li, Wanhu; Yuan, Shuanghu; Yu, Jinming; Hu, Xudong

2017-01-01

Chemoradiotherapy is the most common treatment for inoperable esophageal cancer. However, there is no consensus on the delineation of the clinical target volume. Elective nodal irradiation (ENI) is recommended for inoperable esophageal cancer. A few studies have reported a decrease in the incidence of radiation-related toxicity of involved-field irradiation (IFI) for esophageal cancer. A systematic review and pooled analysis were performed to determine whether IFI in definitive chemoradiotherapy was more beneficial than ENI for esophageal cancer. The results showed no significant differences in the overall survival and local control rates between the IFI and ENI arms. Meanwhile, the incidences of esophageal and lung toxicities were significantly decreased in the IFI arm. These results suggest that IFI is a feasible treatment option for locally advanced esophageal cancer, especially to minimize irradiation-related toxicity. PMID:28442917

Relationship between transmembrane serine protease expression and prognosis of esophageal squamous cell carcinoma.

PubMed

Liu, G T; Shen, C; Ren, X H; Yang, L; Yu, Y M; Xiu, Y X; Li, R H; Jiang, L; Zhang, C L; Li, Y W

2017-01-01

Esophageal squamous cell carcinoma is the most common type of esophageal cancer in Eastern Europe and Asia, being the 6th most common cause of cancer deaths worldwide. The aim of this study was to analyze the expression of transmembrane serine protein in esophageal squamous cell carcinoma, and to correlate it with the clinical biological features of esophageal cancer. The expression of transmembrane protease serine 4 (TMPRSS4) mRNA and protein in carcinoma tissues and corresponding adjacent tissues and non-tumorous esophageal tissues was determined using PCR (qRT-PCR). The results show that both TMPRSS4 mRNA and protein expression were remarkably lower in adjacent normal tissues than in tumorous tissues. TMPRSS4 protein expression in esophageal carcinoma was correlated with patient demographic characteristics, tumor type, high TNM stages and overall survival (OS). Based on the experimental results, we conclude that TMPRSS4 is closely related to the occurrence, development and metastasis of esophageal squamous cell carcinoma.

A Case of Eosinophilic Gastroenteritis Forming a Rigid Chamber Mimicking Giant Duodenal Ulcer on Computed Tomography Imaging.

PubMed

Shimamoto, Yoko; Harima, Yohei

2016-04-18

The clinical manifestations of eosinophilic gastroenteritis are nonspecific and vary depending on which layer of the gastrointestinal tract is involved. Computed tomography (CT) is valuable for detecting and characterizing gastrointestinal wall abnormalities. We report a case of eosinophilic gastroenteritis that formed a chamber in the rigid duodenal wall of a 67-year-old woman. Abdominal CT showed symmetrical wall thickening of the gastric antrum and duodenal bulb, and the bowel walls consisted of 2 continuous, symmetrically stratified layers. There was a chamber mimicking a giant ulcer at the orifice of the descending duodenum. Eosinophilic inflammation was present through this rigid wall of the descending duodenum, accompanied by perienteric inflammation, which infiltrated the anterior pararenal space, gall bladder, and right colic flexure. Gastrointestinal endoscopy showed spotty erosions and reddish mucosa, with the edematous gastric antrum and duodenal bulb narrowed at their lumens. Just beyond the supraduodenal angle at the orifice of the descending duodenum, there was a chamber with only minor mucosal changes, and it was not a duodenal ulcer. Endoscopic biopsy of the duodenum showed intramucosal eosinophilic infiltration. Treatment with prednisolone resulted in normalization of radiologic and endoscopic abnormalities. We present a case of eosinophilic gastroenteritis with both mucosal and muscular involvement. CT imaging and endoscopic examination confirmed the diagnosis.

Chronic eosinophilic pneumonia.

PubMed Central

Fox, B; Seed, W A

1980-01-01

We described three cases of eosinophilic pneumonia of unknown aetiology investigated clinically and by lung biopsy. The illnesses lasted between six and 20 weeks and consisted of cough, dyspnoea, malaise, and in two cases prolonged pyrexia. All had blood eosinophilia and chest radiographs showing widespread bilateral shadowing; in two cases this had a characteristic peripheral distribution. One patient recovered spontaneously and the other two responded to steroids, with disappearance of pyrexia within 12 hours and radiological clearing within 14 days. Lung function tests during the acute illness showed volume restriction or gas transfer defects or both in two cases. After remission all three showed abnormalities if small airways function. Lung biopsies performed during the acute illness were examined histologically and by transmission electron microscopy, and in two cases by immunofluorescence. There was both intra-alveolar and interstitial eosinophilic pneumonia with bronchiolitis obliterans, microgranulomata, and a vasculitis. Electron microscopy showed numerous eosinophils, many degranulated, and macrophages with phagocytosed eosinophilic granules and intracytoplasmic inclusions. In one case IgM, IgG, and IgA were demonstrated in the bronchial walls and interstitium. No IgE or complement was present. We believe that eosinophil granules are responsible for the tissue damage and fever and suggest mechanisms for this and for the response to steroid therapy. Images PMID:7003796

Successful treatment of recalcitrant necrotizing eosinophilic folliculitis using indomethacin and cephalexin.

PubMed

Fallah, Haady; Dunlop, Kate; Kossard, Steven

2006-11-01

A 56-year-old man presented with a 4-month history of a painful and pruritic eruption consisting of crusted plaques and blisters on his face, scalp and chest. The patient suffered from headaches and malaise but was afebrile. Two skin biopsies revealed an epidermis which was eroded and covered by locules of serum and neutrophils. In the underlying dermis, there was a marked mixed inflammatory reaction including lymphocytes, neutrophils and numerous eosinophils. There was exocytosis of eosinophils into several follicles with areas of follicular mucinosis. A diagnosis of necrotizing eosinophilic folliculitis was made based upon the clinical and histopathological findings. The diagnosis was supported by the rapid response to a combination of indomethacin and cephalexin. The patient has taken continuous indomethacin (with rabeprazole and misoprostol cover) and cephalexin for 2 years. If treatment is withdrawn he experiences a flare of his disease within 2 weeks. This case highlights the potentially chronic nature of this disease.

Serum periostin: a novel biomarker for asthma management.

PubMed

Matsumoto, Hisako

2014-06-01

Chronic airway inflammation and remodeling are fundamental features of asthma. Even with adequate inhaled corticosteroid (ICS) treatment, there are still patients who exhibit Th2/eosinophilic inflammation and develop airflow limitation, a functional consequence of airway remodeling. There are few biomarkers that are applicable in the clinical setting that reflect refractory Th2/eosinophilic inflammation and remodeling of the asthmatic airways. Therefore, establishing such biomarkers is essential for managing patients who suffer from these conditions. This review addresses the importance of serum periostin measurements by describing observations made in a KiHAC multicenter cohort with periostin used as a marker of pulmonary function decline and refractory Th2/eosinophilic inflammation in patients with asthma receiving long-term ICS treatment. Furthermore, serum periostin could be a companion diagnostic for targeted therapy against refractory Th2/eosinophilic inflammation. Finally, the distinct characteristics of serum periostin as compared to conventional biomarkers are addressed.

Adding Targeted Therapy to Treatment for Esophageal Cancer

Cancer.gov

In this phase III clinical trial, people with confirmed HER2-positive locally advanced esophageal cancer will be randomly assigned to receive preoperative radiation therapy and chemotherapy, with or without trastuzumab.

Frequency of motor alterations detected through manometry in patients with esophageal symptoms and scleroderma.

PubMed

Pérez Y López, N; Lugo-Zamudio, G; Barbosa-Cobos, R E; Wong-Lam, A; Torres-López, E

Scleroderma can present with esophageal involvement causing important morbidity. To describe the manometric findings and clinical characteristics of patients with scleroderma and esophageal symptoms. Patients with scleroderma and esophageal symptoms were evaluated through esophageal manometry within the time frame of one year. Descriptive statistics were carried out and the continuous variables were expressed as means and standard deviation. Frequencies were expressed as percentages. The study included 24 female patients with a mean age of 53.5 years and mean disease progression of 7.84 years. The most frequent findings were short and hypotonic lower esophageal sphincter (mean length 1.58cm and mean tone 9.49mmHg) and ineffective esophageal motility (mean non-transmitted waves 92.91%, mean effective primary peristalsis 40.05%, and mean amplitude 13.11mmHg). The most frequent symptom was dysphagia. Scleroderma is associated with lower esophageal sphincter alterations and symptomatic ineffective esophageal motility. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Clinical study of esophageal foreign bodies attributable to PTP material.

PubMed

Sakakura, A; Yamamoto, Y; Terada, M; Takenaka, H; Ueda, N; Furuya, T

1997-10-01

Retrospective survey of patients with esophageal foreign bodies who were treated in the Osaka Medical College over the past 21 years, and the patients with esophageal foreign bodies attributed to press through package (PTP) who were treated at the Osaka Central Emergency Clinic, a representative holiday emergency institution in Japan, was carried out. The incidence of foreign bodies attributed to PTP material tends to increase throughout the period reviewed. The patients over 60 years of age accounted for 25/28 (89%) of all PTP patients in Osaka Medical College and 27/32 (84%) in Osaka Central Emergency Clinic, strongly suggesting that PTP dysphagia is most common in elderly patients. Diagnostic methods and preventive measures against PTP foreign bodies were discussed.

Management and endoscopic techniques for digestive foreign body and food bolus impaction.

PubMed

Chauvin, Armelle; Viala, Jerome; Marteau, Philippe; Hermann, Philippe; Dray, Xavier

2013-07-01

Ingested foreign bodies, food bolus impaction, migration or retention of medical devices are frequent, in children as well as in adults. Most of these foreign bodies will naturally pass through the gastro-intestinal tract. Complications are rare but sometimes severe (oesophageal perforations are the most frequent and most feared). We aimed to review the literature on therapeutic management of digestive foreign bodies and food bolus impaction, with special focus on endoscopic indications, material, timing and techniques for removal. The role of the gastroenterologist is to recognise specific situations and to plan endoscopic removal in a timely manner with the most adequate conditions and extraction tools. Risk factors and underlying pathology, for example eosinophilic esophagitis, must be investigated and if necessary treated. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Emerging enhanced imaging technologies of the esophagus: spectroscopy, confocal laser endomicroscopy, and optical coherence tomography.

PubMed

Robles, Lourdes Y; Singh, Satish; Fisichella, Piero Marco

2015-05-15

Despite advances in diagnoses and therapy, esophageal adenocarcinoma remains a highly lethal neoplasm. Hence, a great interest has been placed in detecting early lesions and in the detection of Barrett esophagus (BE). Advanced imaging technologies of the esophagus have then been developed with the aim of improving biopsy sensitivity and detection of preplastic and neoplastic cells. The purpose of this article was to review emerging imaging technologies for esophageal pathology, spectroscopy, confocal laser endomicroscopy (CLE), and optical coherence tomography (OCT). We conducted a PubMed search using the search string "esophagus or esophageal or oesophageal or oesophagus" and "Barrett or esophageal neoplasm" and "spectroscopy or optical spectroscopy" and "confocal laser endomicroscopy" and "confocal microscopy" and "optical coherence tomography." The first and senior author separately reviewed all articles. Our search identified: 19 in vivo studies with spectroscopy that accounted for 1021 patients and 4 ex vivo studies; 14 clinical CLE in vivo studies that accounted for 941 patients and 1 ex vivo study with 13 patients; and 17 clinical OCT in vivo studies that accounted for 773 patients and 2 ex vivo studies. Human studies using spectroscopy had a very high sensitivity and specificity for the detection of BE. CLE showed a high interobserver agreement in diagnosing esophageal pathology and an accuracy of predicting neoplasia. We also found several clinical studies that reported excellent diagnostic sensitivity and specificity for the detection of BE using OCT. Advanced imaging technology for the detection of esophageal lesions is a promising field that aims to improve the detection of early esophageal lesions. Although advancing imaging techniques improve diagnostic sensitivities and specificities, their integration into diagnostic protocols has yet to be perfected. Copyright © 2015 Elsevier Inc. All rights reserved.

Expert Consensus Contouring Guidelines for Intensity Modulated Radiation Therapy in Esophageal and Gastroesophageal Junction Cancer.

PubMed

Wu, Abraham J; Bosch, Walter R; Chang, Daniel T; Hong, Theodore S; Jabbour, Salma K; Kleinberg, Lawrence R; Mamon, Harvey J; Thomas, Charles R; Goodman, Karyn A

2015-07-15

Current guidelines for esophageal cancer contouring are derived from traditional 2-dimensional fields based on bony landmarks, and they do not provide sufficient anatomic detail to ensure consistent contouring for more conformal radiation therapy techniques such as intensity modulated radiation therapy (IMRT). Therefore, we convened an expert panel with the specific aim to derive contouring guidelines and generate an atlas for the clinical target volume (CTV) in esophageal or gastroesophageal junction (GEJ) cancer. Eight expert academically based gastrointestinal radiation oncologists participated. Three sample cases were chosen: a GEJ cancer, a distal esophageal cancer, and a mid-upper esophageal cancer. Uniform computed tomographic (CT) simulation datasets and accompanying diagnostic positron emission tomographic/CT images were distributed to each expert, and the expert was instructed to generate gross tumor volume (GTV) and CTV contours for each case. All contours were aggregated and subjected to quantitative analysis to assess the degree of concordance between experts and to generate draft consensus contours. The panel then refined these contours to generate the contouring atlas. The κ statistics indicated substantial agreement between panelists for each of the 3 test cases. A consensus CTV atlas was generated for the 3 test cases, each representing common anatomic presentations of esophageal cancer. The panel agreed on guidelines and principles to facilitate the generalizability of the atlas to individual cases. This expert panel successfully reached agreement on contouring guidelines for esophageal and GEJ IMRT and generated a reference CTV atlas. This atlas will serve as a reference for IMRT contours for clinical practice and prospective trial design. Subsequent patterns of failure analyses of clinical datasets using these guidelines may require modification in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

Expert consensus contouring guidelines for IMRT in esophageal and gastroesophageal junction cancer

PubMed Central

Wu, Abraham J.; Bosch, Walter R.; Chang, Daniel T.; Hong, Theodore S.; Jabbour, Salma K.; Kleinberg, Lawrence R.; Mamon, Harvey J.; Thomas, Charles R.; Goodman, Karyn A.

2015-01-01

Purpose/Objective(s) Current guidelines for esophageal cancer contouring are derived from traditional two-dimensional fields based on bony landmarks, and do not provide sufficient anatomical detail to ensure consistent contouring for more conformal radiotherapy techniques such as intensity-modulated radiation therapy (IMRT). Therefore, we convened an expert panel with the specific aim to derive contouring guidelines and generate an atlas for the clinical target volume (CTV) in esophageal or gastroesophageal junction (GEJ) cancer. Methods and Materials Eight expert academically-based gastrointestinal radiation oncologists participated. Three sample cases were chosen: a GEJ cancer, a distal esophageal cancer, and a mid-upper esophageal cancer. Uniform CT simulation datasets and an accompanying diagnostic PET-CT were distributed to each expert, and he/she was instructed to generate gross tumor volume (GTV) and CTV contours for each case. All contours were aggregated and subjected to quantitative analysis to assess the degree of concordance between experts and generate draft consensus contours. The panel then refined these contours to generate the contouring atlas. Results Kappa statistics indicated substantial agreement between panelists for each of the three test cases. A consensus CTV atlas was generated for the three test cases, each representing common anatomic presentations of esophageal cancer. The panel agreed on guidelines and principles to facilitate the generalizability of the atlas to individual cases. Conclusions This expert panel successfully reached agreement on contouring guidelines for esophageal and GEJ IMRT and generated a reference CTV atlas. This atlas will serve as a reference for IMRT contours for clinical practice and prospective trial design. Subsequent patterns of failure analyses of clinical datasets utilizing these guidelines may require modification in the future. PMID:26104943

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) presenting as diffuse myositis.

PubMed

Parent, Marc-Etienne; Larue, Sandrine; Ellezam, Benjamin

2014-11-21

Eosinophilic granulomatosis with polyangiitis is a complex multisystemic syndrome with heterogeneous presentation. Most often, there is a clinical history of asthma or other atopic conditions, and current presentation generally includes signs of cutaneous or pulmonary involvement. Very few reports described myalgia or weakness as the chief complaint. Of these, only a few included muscle biopsy evaluation and none showed convincing evidence of primary myositis. We believe this report is the first to demonstrate true myositis in the setting of early eosinophilic granulomatosis with polyangiitis. This report describes a 74 year old Caucasian man, with no known allergies, presenting severe myalgia, muscle weakness, jaw claudication, and fever. Blood work showed marked eosinophilia and high creatine kinase levels. Biceps brachialis muscle biopsy revealed eosinophilic necrotizing vasculitis and true myositis with myophagocytosis of non-necrotic fibers and strong sarcolemmal MHC-1 overexpression by immunohistochemistry. This patient was successfully treated with prednisone and azathioprine. Our finding of true myositis in a case of eosinophilic granulomatosis with polyangiitis suggests that primary auto-immunity against muscle fibers, distinct from the secondary effects of vasculitis, can occur in this entity and may represent an overlap syndrome. Early recognition of eosinophilic granulomatosis with polyangiitis in patients presenting with myositis may provide an opportunity to treat the vasculitis before onset of severe multisystemic disease. We recommend the use of muscle biopsy with immunohistochemistry for MHC-1 to confirm the diagnosis of myositis in the setting of eosinophilic granulomatosis with polyangiitis.

Updates on esophageal and gastric cancers.

PubMed

Gallo, Amy; Cha, Charles

2006-05-28

Esophageal and gastric cancers are both common and deadly. Patients present most often after disease progression and survival is therefore poor. Due to demographic variability and recent changes in disease incidence, much emphasis has been placed on studying risk factors for both esophageal and gastric cancers. However, with increasing understanding of these diseases, low survival rates persist and continued intensive studies are necessary to optimize treatment plans. This review article discusses updates in the evolving epidemiology, clinical presentation, risk factors, and diagnostic and treatment modalities of esophageal and gastric cancers.

Choice of radiotherapy planning modality influences toxicity in the treatment of locally advanced esophageal cancer.

PubMed

Mackley, Heath B; Adelstein, Jonathan S; Reddy, Chandana A; Adelstein, David J; Rice, Thomas W; Saxton, Jerrold P; Videtic, Gregory M M

2008-01-01

Three-dimensional computed tomography-based radiotherapy planning (3DCTP) is increasingly employed in the treatment of esophageal cancer. It is unknown whether a 3DCTP approach influences outcomes compared to two-dimensional planning (2DP). This study compares clinical outcomes for homogeneously treated patient cohorts stratified by planning modality. A retrospective chart review was conducted on patients with T3/4 and/or node-positive esophageal carcinoma treated at the Cleveland Clinic between July 1, 2003 and May 31, 2006 who were managed with an institutional regimen consisting of preoperative radiotherapy, whether 3DCTP or 2DP [30 Gy/20 fractions/1.5 Gy twice daily over 2 weeks], with concurrent cisplatin and 5-fluorouracil the first week. Following definitive resection, an identical postoperative course of concurrent chemoradiotherapy (CRT) was delivered. One hundred and forty-one patients completed preoperative CRT and were available for review. The median follow-up of living patients is 21.7 months. Fifty-five percent underwent 3DCTP and 45% had 2DP. The treatment groups were similar, with the exception of clinical stage group, with 2DP having more stage II and fewer stage III patients than 3DCTP (p = 0.02). 3DCTP plans had significantly smaller field sizes by area (p < 0.0001). Pathologic response, locoregional control, distant control, and overall survival were equivalent between the two planning modalities. Esophagitis was significantly less common with a 3D approach compared to 2D planning (49% vs. 71%, p = 0.0096), with other toxicities equivalent between the groups. 3DCTP reduces acute esophagitis in patients receiving multimodality therapy for esophageal cancer without compromising clinical outcomes.

Clinical and biological significance of stem-like CD133(+)CXCR4(+) cells in esophageal squamous cell carcinoma.

PubMed

Lu, Chunlai; Xu, Fengkai; Gu, Jie; Yuan, Yunfeng; Zhao, Guangyin; Yu, Xiaofang; Ge, Di

2015-08-01

Esophageal squamous cell carcinoma is one of the most frequent malignant tumors. Cancer stem cells are considered to be responsible for tumor growth, metastasis, and recurrence. Cluster of differentiation 133 (CD133) and C-X-C chemokine receptor type 4 (CXCR4) are frequently applied markers for the identification and isolation of cancer stem cells. However, few studies have investigated the coexpression of CD133 and CXCR4 in esophageal squamous cell carcinoma. This study aims to explore the clinical and biological role of stem-like CD133(+)CXCR4(+) cells in esophageal squamous cell carcinoma. Immunohistochemical staining was performed to detect the expression of CD133 and CXCR4 in esophageal squamous cell carcinoma tissues of patients. Flow cytometry and fluorescence-activated cell sorting were applied to analyze and isolate each subgroup in esophageal squamous cell carcinoma cell line TE-1. The characteristic differences between each subgroup were assayed in vitro. The association between CD133/CXCR4 expression and patients' prognosis was analyzed by Kaplan-Meier and Cox regression. Among 154 patient tissues, concomitant high CD133-CXCR4 expression accounts for 20.78% (32/154). In vitro, CXCR4(+) cells (CD133(+)CXCR4(+) and CD133(-)CXCR4(+)) showed high invasive potential and CD133(+)CXCR4(+) cells showed high proliferative capacity. Clinically, patients with concomitant high CD133-CXCR4 expression had decreased disease-free survival and overall survival (P < .01). Esophageal squamous cell carcinoma cells coexpressing CD133 and CXCR4 possess the characteristics of cancer stem cells. The concomitant high CD133-CXCR4 expression might be a novel marker for predicting the poor prognosis of patients with esophageal squamous cell carcinoma, and CD133 and CXCR4 may serve as potential therapeutic targets. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

[Clinical analysis of diagnosis and treatment on retro-esophageal space abscess].

PubMed

Chen, Ze; Zhong, Zhaotang; Liang, Minzhi

2014-12-01

To explore the clinical manifestations and treatments of retro-esophageal space abscess. The clinical data of 27 cases with retro-esophageal space abscess were analyzed retrospectively. Twenty-one cases (77. 78%) were secondary to acute injury of esophageal meatus caused by foreign bodies. 2 cases (7. 41%)were secondary to old foreign body infection in retro-esophageal space, 3 cases (11. 11%) after secondary to pharyngeal abscess, and 1 case (3. 70%) was unknown to etiology. All patients were confirmed by sectional medicalimageology. Six cases(Conservation group, C group) were treated conservatively and 6 cases (Oropharyngeal incision group, OI group) were performed with oropharyngeal incision drainage. 15 cases(Extra-neck incision group, ENI group)were performed with extra-neck incision and vacuum sealing drainage. In C group, 6 cases were cured with conservative therapy and the average hospital stay was 15. 6 days. In OI group, 5 cases were healed with oropharyngeal drainage but aspiration pneumonia complicated with septic shock occurred in 2 cases, and 1 case dead from septic shock secondary to mediastinum and lung abscess. The average hospital stay was 18. 8 days. In ENI group, 15 patients were cured with extra-neck drainage without complication and the average hospital stay was 9. 5 days. The main causes of retro-esophageal space abscess are foreign body injury of upper esophagus and remnant of retro-esophageal space. Sectional medicalimageology can be of important value of diagnosis and treatment for displaying the retro-esophageal space abscess and other deep cervical fascia space sufficiently. Incision and vacuum sealing drainage via extra-neck is an effective therapy while oropharyngeal drainage is less effective and is not advocated as a primary treatment because of aspiration pneumonia complication . Conservative cure is a choice for patients without dyspnoea and background diseases, and it is necessary to recognize and treat severe complications early.

Predictors of large esophageal varices in patients with cirrhosis.

PubMed

Chalasani, N; Imperiale, T F; Ismail, A; Sood, G; Carey, M; Wilcox, C M; Madichetty, H; Kwo, P Y; Boyer, T D

1999-11-01

Recent guidelines recommend that all cirrhotics undergo screening upper endoscopy to identify those patients at risk for bleeding from varices. However, this practice may not be cost effective as large esophageal varices are seen only in 9-36% of these patients. The aim of this study was to determine whether clinical variables were predictive of the presence of large esophageal varices. This is a retrospective analysis of cirrhotics who had a screening upper endoscopy during an evaluation for liver transplantation at three different centers and who had not previously bled from varices. A multivariate model was derived on the combined cohort using logistic regression. Three hundred forty-six patients were eligible for the study. The prevalence of large esophageal varices was 20%. On multivariate analysis, splenomegaly detected by computed tomographic scan (odds ratio: 4.3; 95% confidence interval: 1.6-11.5) or by physical examination (odds ratio: 2.0; 95% confidence interval: 1.1-3.8), and low platelet count were independent predictors of large esophageal varices. On the basis of these variables, cirrhotics were stratified into high- and low-risk groups for the presence of large esophageal varices. Patients with a platelet count of > or = 88,000/mm3 (median value) and no splenomegaly by physical examination had a risk of large esophageal varices of 7.2%. Those with splenomegaly or platelet count < 88,000/mm3 had a risk of large esophageal varices of 28% (p < 0.0001). Our data show that clinical predictors could be used to stratify cirrhotic patients for the risk of large esophageal varices and such stratification could be used to improve the cost effectiveness of screening endoscopy.

Esophageal bypass operation prior to definitive chemoradiotherapy in advanced esophageal cancer with tracheobronchial invasion.

PubMed

Hihara, Jun; Hamai, Yoichi; Emi, Manabu; Aoki, Yoshiro; Taomoto, Junya; Miyata, Yoshihiro; Okada, Morihito

2014-01-01

In T4 esophageal cancer with tracheobronchial invasion, an esophagorespiratory fistula (ERF) often occurs during or after chemoradiotherapy. We have performed esophageal bypass operations prior to definitive chemoradiotherapy for these patients to increase the chemoradiotherapy completion rate by minimizing the potential effect of an ERF. The aim of this study was to examine the clinical outcome of esophageal bypass surgery prior to chemoradiotherapy. Between 1997 and 2010, 17 patients underwent esophageal bypass surgery followed by definitive chemoradiotherapy for esophageal cancer with tracheobronchial invasion (bypass group). Ten patients in the same circumstances were treated with chemoradiotherapy alone (control group). Overall survival, the clinical effect of chemoradiotherapy, the ERF incidence rate, and the safety of esophageal bypass surgery were assessed. The overall response rate to chemoradiotherapy was 64.7% in the bypass group and 90.0% in the control group. Except for 2 patients with ERF at initial diagnosis, 4 (26.7%) of the 15 patients developed ERF in the bypass group, and 3 (30.0%) of the 10 patients developed ERF in the control group during or after chemoradiotherapy. The 2-year and 3-year overall survival rates were 17.6% and 17.6% in the bypass group and 20.0% and 0% in the control group, respectively (p = 0.924); long-term survival of more than 3 years was seen only in the bypass group. Esophageal bypass surgery prior to definitive chemoradiotherapy could be performed safely, and this strategy contributed to long-term survival in the patients who achieved a good response to chemoradiotherapy but developed an ERF. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Utility of silicone esophageal bypass stents in the management of delayed complex esophageal disruptions.

PubMed

Kim, Anthony W; Liptay, Michael J; Snow, Norman; Donahue, Philip; Warren, William H

2008-06-01

The objective of this study was to review the clinical experience of temporarily placing an endoesophageal silicone salivary bypass stent and its value in managing patients with life-threatening esophageal disruptions. Clinical records of patients undergoing placement of silicone Montgomery salivary bypass stents from June 1998 to September 2007 were reviewed. Seventeen patients had a proven esophageal disruption in the absence of malignancy and with life-threatening sepsis refractory to conventional management. Underlying conditions were iatrogenic trauma from prior pulmonary surgery (4 patients), significant anastomotic leaks after an esophagogastrectomy (4 patients), delayed presentation (> 24 hours) of a perforated esophagus (4 patients), leak after esophageal surgery (3 patients), and esophagobronchial fistula secondary to inflammation and infection (2 patients). Stents were placed without securing, were sutured in place to the esophageal wall at the time of thoracotomy, or were secured by bringing holding sutures through the nostrils and tied over the bridge of the nose. In all cases, placement of the esophageal stent led to prompt improvement of the leak and, within a week, improvement of the sepsis. Supportive measures were continued after placement of the stent. Sixteen patients overcame the sepsis with ultimate healing of the esophageal disruption (13 patients) or maturation of the perforation into a chronic fistula (3 patients). Endoscopic stent removal was performed 2 to 16 weeks after placement. No patient had a stricture develop at the disruption site. One patient died of ruptured thoracic aorta. Silicone salivary bypass stents serve as an effective way of diverting and excluding the oral-alimentary stream, thereby providing optimal conditions for sepsis control. They are a useful adjunct in the management of complex esophageal conditions.

Preliminary clinical data on a new photodynamic therapy photosensitizer: 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) for treatment of obstructive esophageal cancer

NASA Astrophysics Data System (ADS)

Dougherty, Thomas J.; Pandey, R. K.; Nava, Hector R.; Smith, Judy L.; Douglass, Harold O.; Edge, Stephen B.; Bellnier, David A.; O'Malley, Linda; Cooper, Michele

2000-03-01

The hexyl ether derivative or HPPH, has been identified as an optimal active in vivo photosensitizer in pre-clinical studies and has been evaluated clinically in obstructive esophageal cancer in five patients to date. The photosensitizer appears to have no systemic toxicity and be effective at low drug and light doses. Further, cutaneous photosensitivity appears to persist only 5-7 days.

[Management of the esophageal candidiasis by the primary care physician].

PubMed

Behrens, Garance; Bocherens, Astrid; Senn, Nicolas

2014-05-14

Esophageal candidiasis is one of the most common opportunistic infections in patients infected by human immunodeficiency virus (HIV). This pathology is also found in patients without overt immunodeficiency. Other risk factors are known to be associated with this disease like inhaled or systemic corticosteroid treatment or proton-pump inhibitors and H2 receptor antagonists. In the absence of identified risk factors, a primary immune deficiency should be sought. Prevention of esophageal candidiasis is based primarily on the identification of risk factors, and a better control of them. This article presents a review of the physiopathology, clinical presentation and management of esophageal candidiasis by primary care physicians. We will also discuss ways of preventing esophageal candidiasis when necessary.

Esophageal Motor Abnormalities in Patients With Scleroderma: Heterogeneity, Risk Factors, and Effects on Quality of Life.

PubMed

Crowell, Michael D; Umar, Sarah B; Griffing, W Leroy; DiBaise, John K; Lacy, Brian E; Vela, Marcelo F

2017-02-01

Systemic scleroderma (SSc) is associated with esophageal aperistalsis and hypotensive esophagogastric junction pressure, although there could be a gradation in esophageal motor dysfunction. We characterized esophageal motor function by high-resolution esophageal manometry (HRM) and assessed associations between SSc severity, health-related quality of life (HRQOL), and HRM findings in patients. We performed a prospective study of 200 patients with SSc and 102 patients without SSc (controls) who underwent HRM at Mayo Clinic Arizona from May 2006 through January 2015. We used data on integrated relaxation pressure, distal contractile integral, and distal latency to classify esophageal motility disorders according to the Chicago Classification v 3.0. A subset of subjects (n = 122) completed SSc-specific gastrointestinal symptom and HRQOL questionnaires. HRM findings, symptoms, and HRQOL data were compared among diffuse SSc, limited SSc, and control subjects. Categorical variables were compared by using the χ 2 or Fisher exact test; continuous variables were compared by using Mann-Whitney or Kruskal-Wallis test. Multivariable logistic regression was used to assess the association between severity of esophageal dysmotility and baseline clinical factors. Among patients with SSc, 83 had diffuse SSc (42%), and 117 had limited SSc (58%). Absent contractility was more frequent in patients with SSc than in controls (56% vs 13%; P < .001). HRM findings varied among the patients; absent contractility (56%) was the most frequent diagnosis, followed by normal motility (26%) and ineffective esophageal motility (10%). Classic scleroderma esophagus (esophagogastric junction pressure with absent contractility) was only observed in 33% of patients (34% with diffuse SSc vs 32% limited SSc) (P = .880). Severe esophageal dysmotility was associated with disease duration, interstitial lung disease, and higher gastrointestinal symptom scores (P < .001). HRQOL was decreased in patients with SSc and severe esophageal dysmotility. Although severe dysmotility is more common in patients with SSc than in controls, we observed the so-called scleroderma esophagus in only one-third of patients with SSc. Esophageal motor function appears to be heterogeneous in SSc. Esophageal dysmotility reduces HRQOL in patients with SSc. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Relationship of Inhaled Corticosteroid Adherence to Asthma Exacerbations in Patients with Moderate-to-Severe Asthma.

PubMed

Papi, Alberto; Ryan, Dermot; Soriano, Joan B; Chrystyn, Henry; Bjermer, Leif; Rodríguez-Roisin, Roberto; Dolovich, Myrna B; Harris, Mark; Wood, Lucy; Batsiou, Maria; Thornhill, Susannah I; Price, David B

2018-04-05

Patients with asthma and elevated blood eosinophils are at increased risk of severe exacerbations. Management of these patients should consider nonadherence to inhaled corticosteroid (ICS) therapy as a factor for increased exacerbation risk. The objective of this study was to investigate whether poor adherence to ICS therapy explains the occurrence of asthma exacerbations in patients with elevated blood eosinophil levels. This historical cohort study identified patients within the Optimum Patient Care Research Database, aged 18 years or more, at Global Initiative for Asthma step 3 or 4, with 2 or more ICS prescriptions during the year before the clinical review. Patient characteristics and adherence (based on prescription refills and patient self-report) for ICS therapy were analyzed for those with elevated (>400 cells/μL) or normal (≤400 cells/μL) blood eosinophils. We studied 7195 patients (66% female, mean age 60 years) with median eosinophil count of 200 cells/μL and found 81% to be not fully adherent to ICS therapy. A total of 1031 patients (14%) had elevated blood eosinophil counts (58% female, mean age 60 years), 83% of whom were not fully adherent to ICS. An increased proportion of adherent patients in the elevated blood eosinophil group had 2 or more exacerbations (14.0% vs 7.2%; P = .003) and uncontrolled asthma (73% vs 60.8%; P = .004) as compared with non-fully adherent patients. Approximately 1 in 7 patients had elevated eosinophils. Adherence to ICS therapy was not associated with decreased exacerbations for these patients. Additional therapy should be considered for these patients, such as biologics, which have been previously shown to improve control in severe uncontrolled eosinophilic asthma. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Eosinophils, pruritus and psoriasis: effects of treatment with etretinate or cyclosporin-A.

PubMed

Schopf, R E; Hultsch, T; Lotz, J; Bräutigam, M

1998-11-01

The antipsoriatic drugs cyclosporin A (CyA) and etretinate have been found to influence proinflammatory eosinophilic leukocytes and pruritus. We compared the number of blood eosinophils, concentration of serum eosinophil cationic protein (ECP), and pruritus in patients with psoriasis treated with either CyA or etretinate. Patients with psoriasis vulgaris were randomly assigned to treatment for 10 weeks with either CyA (n = 21) or etretinate (n = 10). The psoriasis area-and-severity index (PASI-score) and pruritus (according to a 0-3 scale) served as clinical parameters, the blood esosinophil counts (Coulter Counter) and the serum ECP (RIA, Pharmacia) as laboratory parameters. After CyA treatment the PASI-score amounted to 24 +/- 4%, after etretinate to 56 +/- 6% of the initial values (mean +/- SEM). One week after CyA treatment, esosinophils dropped from 190 +/- 21 to 137 +/- 16/microliter (P = 0.038, Wilcoxon test), after 10 weeks to 127 +/- 18/microliter (P = 0.006). By contrast, under etretinate blood eosinophil counts only changed marginally. Before treatment, ECP concentrations of 15.71 +/- 1.30 (CyA) and 15.3 +/- 5.53 micrograms/l (etretinate) were measured (normal range 3-16 micrograms/l), ECP remained constant under both CyA and etretinate or tended to increase after 10 weeks; about 50% of the patients exhibited elevated ECP concentrations. Pruritus diminished more with CyA than etretinate therapy. PASI-scores and pruritus were directly proportional. We conclude that treatment of psoriasis with CyA leads to a rapid drop of blood eosinophils and that the activation state of eosinophils does not decrease after antipsoriatic treatment. Pruritus in psoriasis is coupled to disease severity. The underlying antipsoriatic mechanisms of CyA may be linked to lowering the number of blood eosinophils.

Stability of Blood Eosinophil Count in Patients with COPD in the UK Clinical Practice Research Datalink.

PubMed

Landis, Sarah H; Suruki, Robert; Hilton, Emma; Compton, Chris; Galwey, Nicholas W

2017-08-01

Blood eosinophil counts may be predictive of corticosteroid response in chronic obstructive pulmonary disease (COPD) patients. However, little is known about measurement stability, which is important for understanding the utility of blood eosinophil counts as a potential biomarker. We evaluated the stability of blood eosinophil counts over 1 year in a population-based cohort of patients with COPD in primary care. Patients were aged ≥ 40 years with forced expiratory volume in 1 second/forced vital capacity < 0.7 and ≥ 1 blood eosinophil measurement taken during a period of stable disease within 6 months of a COPD diagnosis code recorded between January 1, 2010 and December 31, 2012. Generalized linear mixed models were fitted to log-transformed data to estimate the between-(s 2 between ) and within-patient (s 2 within ) variance in eosinophil count; an intra-class correlation coefficient R i was calculated (s 2 between /[s 2 between + s 2 within ]). A sensitivity analysis was performed from which patients who were prescribed systemic corticosteroids or antibiotics at any time during follow-up were excluded. All models were adjusted for age, gender, smoking status, and asthma history. Overall, 27,557 patients were included in the full cohort (51.5% male, mean age [standard deviation] 71.1 [10.6] years) and 54% of patients had ≥ 2 eosinophil measurements (median 2 [interquartile range 1]) during follow-up. For the full cohort, R i = 0.64, and in the sensitivity analysis subgroup, R i = 0.70, mainly due to a decrease in s 2 within . For patients with COPD in primary care, eosinophil measurements demonstrated reasonable repeatability over 1 year, which increased after exclusion of patients who were prescribed systemic corticosteroids or antibiotics.

Blood Count of Eosinophil Polymorphonuclear Leucocytes and Bronchial Hyperreactivity in Chronic Obstructive Pulmonary Disease

PubMed Central

Cukic, Vesna

2017-01-01

Introduction: Polymorphonuclear eosinophil leucocytes (eosinophils) are found in increased numbers in the circulation and sputum in asthma patients, usually in relation to the severity of asthma but it is the question whether they have a significant role in the development and level of bronchial hyperreactivity in patients with chronic obstructive pulmonary disease (COPD). Objective: to show the role of the eosinophils in the development and level of BHR in patients with COPD and so in the severity of illness. Material and methods: We observed 240 patients with COPD treated in Clinic for Pulmonary Diseases and TB «Podhrastovi» Sarajevo during five years: from 2012 to 2016. They were divided into groups and subgroups according to the first registration of BHR in the course of illness and to the number of exacerbations of the disease in one year. The number of blood eosinophils was measured at the onset of exacerbation of the disease before switching on any therapy, at the beginning and at the end of the research. Results: we did not find any significant difference in the eosinophil blood count between the COPD patients with and without BHR, nor according to the time of the first registration of BHR in the course of illness nor according to the number of exacerbations of illness per one year. There was not statistically significant difference in eosinophil count (increase-drop) within any of the groups or subgroups, or between the groups and subgroups between the first and last test. Conclusion: There is not significant correlation between the eosinophil blood count and the level of BHR, number of exacerbations and the severity of COPD. PMID:29284904

Incidences of esophageal injury during esophageal temperature monitoring: a comparative study of a multi-thermocouple temperature probe and a deflectable temperature probe in atrial fibrillation ablation.

PubMed

Kuwahara, Taishi; Takahashi, Atsushi; Takahashi, Yoshihide; Okubo, Kenji; Takagi, Katsumasa; Fujino, Tadashi; Kusa, Shigeki; Takigawa, Masateru; Watari, Yuji; Yamao, Kazuya; Nakashima, Emiko; Kawaguchi, Naohiko; Hikita, Hiroyuki; Sato, Akira; Aonuma, Kazutaka

2014-04-01

The study aim was to compare the incidence of esophageal injuries between different temperature probes in the monitoring of esophageal temperature during atrial fibrillation (AF) ablation. One hundred patients with drug-resistant AF were prospectively and randomly assigned into two groups according to the esophageal temperature probe used: the multi-thermocouple probe group (n = 50) and the deflectable temperature probe group (n = 50). Extensive pulmonary vein (PV) isolation was performed with a 3.5-mm open irrigated tip ablation catheter by using a radiofrequency (RF) power of 25-30 W. In both groups, the esophageal temperature thermocouple was placed on the area of the esophagus adjacent to the ablation site. When the esophageal temperature reached 42 °C, the RF energy delivery was stopped. Esophageal endoscopy was performed 1 day after the catheter ablation. No differences existed between the two groups in terms of clinical background and various parameters related to the catheter ablation, including RF delivery time and number of RF deliveries at an esophageal temperature of >42 °C. Esophageal lesions, such as esophagitis and esophageal ulcers, occurred in 10/50 (20 %) and 15/50 (30 %) patients in the multi-thermocouple and deflectable temperature probe groups, respectively (P = 0.25). Most lesions were mild to moderate injuries, and all were cured using conservative treatment. The incidence of esophageal injury was almost equal between the multi-thermocouple temperature probe and the deflectable temperature probe during esophageal temperature monitoring. Most of the esophageal lesions that developed during esophageal temperature monitoring were mild to moderate and reversible.

Cardiac tamponade leading to the diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a case report and review of the literature.

PubMed

Yano, Toshiyuki; Ishimura, Shutaro; Furukawa, Tetsuaki; Koyama, Masayuki; Tanaka, Marenao; Shimoshige, Shinya; Hashimoto, Akiyoshi; Miura, Tetsuji

2015-11-01

Eosinophilic granulomatosis with polyangiitis (EGPA), which was previously called Churg-Strauss syndrome, is a necrotizing systemic vasculitis of unknown cause accompanied by prominent eosinophilia. Cardiovascular complications, including eosinophilic myocarditis, are a major cause of mortality in this disorder. Acute pericarditis with slight pericardial effusion is a typical manifestation in EGPA, though hemodynamically significant pericardial effusion has been reported in a few cases. We report a case that initially presented with isolated cardiac tamponade, which was followed by systemic manifestations of EGPA over 3 weeks. Including the present case, previous EGPA cases with cardiac tamponade are reviewed to delineate its clinical characteristics.

Transdermal nicotine patches for eosinophilic pustular folliculitis.

PubMed

Yoshifuku, Asuka; Higashi, Yuko; Matsushita, Shigeto; Kawai, Kazuhiro; Kanekura, Takuro

2013-09-01

We previously reported the clinical effectiveness of transdermal nicotine patches for the treatment of skin disorders with eosinophilic infiltration such as Kimura's disease, erythema nodosum and eosinophilic pustular folliculitis (EPF). We assessed the efficacy and safety of transdermal nicotine patches for EPF. We treated eight patients with EPF with transdermal nicotine patches and evaluated the treatment response by performing overall lesional assessment. Excellent 77and good responses were obtained in five and one patient(s), respectively. In the other two patients, the lesions remained unchanged. No severe adverse effects were observed. Our results suggest that transdermal nicotine patches may be useful and safe in the treatment of EPF. © 2013 Japanese Dermatological Association.

Chemoprevention of esophageal squamous cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoner, Gary D.; Wang Lishu; Chen Tong

2007-11-01

Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, andmore » to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC.« less

Dysphagia in the elderly.

PubMed

Khan, Abraham; Carmona, Richard; Traube, Morris

2014-02-01

Dysphagia, or difficulty swallowing, is a common problem in the elderly. Based on the initial clinical history and physical examination, the dysphagia is assessed as either primarily oropharyngeal or esophageal in origin. Most oropharyngeal dysphagia is of neurologic origin, and management is coordinated with a clinical swallow specialist in conjunction with an ear, nose, and throat (ENT) physician if warning signs imply malignancy. Several structural and functional esophageal disorders can cause dysphagia. If a patient has likely esophageal dysphagia, a video barium esophagram is a good initial test, and referral to a gastroenterologist is generally warranted leading to appropriate treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical and Economic Burden of Elevated Blood Eosinophils in Patients With and Without Uncontrolled Asthma.

PubMed

Casciano, Julian; Krishnan, Jerry; Dotiwala, Zenobia; Li, Chenghui; Sun, Shawn X

2017-01-01

The European Respiratory Society and American Thoracic Society (ERS/ATS) published guidelines in 2014 for the evaluation and treatment of asthma. These guidelines draw attention to management of patients with asthma that remains uncontrolled despite therapy. One phenotypic characteristic of therapy-resistant asthma is eosinophil elevation. It is important to better understand the burden of care gaps in this patient subgroup in order to support improved treatment strategies in the future. To quantify the economic burden of asthma patients with and without peripheral blood eosinophil elevation. A retrospective cohort study was conducted using data from patients aged 12 years or older with a diagnosis of asthma using electronic health records of over 2 million patients between 2004-2010. Patients with a diagnosis of chronic obstructive pulmonary disease, Churg Strauss syndrome/Wegener's granulomatosis, eosinophilia, cystic/pulmonary fibrosis, allergic bronchopulmonary aspergillosis, or lung cancer in the 12-month period before the date of asthma diagnosis were excluded. Patients with asthma were followed for 12 months after their initial asthma diagnosis to identify those with controlled versus uncontrolled asthma based on ERS/ATS criteria. Patients with at least 1 peripheral blood eosinophil test result of ≥ 400 cells/µL were classified as those with elevated eosinophils. Total annual paid-claim cost was compared by eosinophil levels within the controlled and uncontrolled asthma subgroups. Costs were adjusted to 2015 U.S. dollars. Patients were stratified by control level, and generalized linear modeling regressions were used to assess the magnitude of increase in cost of the elevated eosinophil group. A total of 2,701 patients were included in the study, of which 17% had uncontrolled asthma and 21% had elevated eosinophils. The mean total annual cost of patients with uncontrolled asthma was more than 2 times the cost of those with controlled asthma ($18,341 vs. $8,670, P < 0.001). Patients with uncontrolled asthma in the elevated eosinophil group had almost double the total cost ($28,644 vs. $14,188, P = 0.008) compared with those with blood eosinophil levels in a normal range. Similarly, patients classified as those with controlled asthma in the elevated eosinophil group had almost twice the average costs as those without elevated eosinophils ($14,754 vs. $7,203, P < 0.001). Uncontrolled asthma with elevated eosinophils had 4 times greater hospital admissions and over 4 times higher total costs than controlled asthma without elevated eosinophils. Among patients with uncontrolled asthma, patients with elevated eosinophils had a 53% increase in mean cost ($17,723 vs. $11,581, P < 0.001) compared with patients without elevated eosinophils. Among patients with controlled asthma, patients with elevated eosinophils had a 62% increase in mean cost ($8,897 vs. $5,486, P < 0.001) compared with patients without elevated eosinophils. Elevated peripheral blood eosinophil level is associated with higher cost irrespective of disease control status. This study was funded by Teva Pharmaceuticals. Dotiwala and Casciano report consulting and writing fees from Teva Pharmaceuticals for work on this study. Sun is an employee and stockholder of Teva Pharmaceuticals. Li reports consulting fees from eMAX Health. All authors contributed to study design. Dotiwala took the lead in data collection, along with the other authors, and data interpretation was performed primarily by Krishnan, Sun, and Li, along with Casciano and Dotiwala. The manuscript was written by Casciano, Dotiwala, and Li, along with Sun and Krishnan, and revised by Casciano, Dotiwala, Sun, and Li, with assistance from Krishnan.

Current and future treatment of chest pain of presumed esophageal origin.

PubMed

Schmulson, Max J; Valdovinos, Miguel Angel

2004-03-01

Patients with chest pain of presumed esophageal origin should be reassured and should undergo an esophageal manometry study. In patients with spastic esophageal disorders, a trial with calcium channel blockers or low-dose antidepressants used as visceral analgesics is the best approach. Inpatients with non GERD-related, nonspastic esophageal motility disorder, low-dose antidepressants seem reasonable. Anxiolytics are useful in patients with panic disorders, and psychological interventions (eg, cognitive-behavioral therapy) are also valuable, mainly in patients in whom reassurance is not sufficient to avoid the misinterpretation of their symptoms. In the future, visceral sensitivity modifying agents such as serotoninergic agonists or antagonists may become the cornerstone of therapy in patients with chest pain of presumed esophageal origin. Combinations of different approaches, such as proton pump inhibitors and psychotropic or antinociceptive agents, should also be evaluated in clinical trials.

Gastro-Esophageal Reflux in Children.

PubMed

Rybak, Anna; Pesce, Marcella; Thapar, Nikhil; Borrelli, Osvaldo

2017-08-01

Gastro-esophageal reflux (GER) is common in infants and children and has a varied clinical presentation: from infants with innocent regurgitation to infants and children with severe esophageal and extra-esophageal complications that define pathological gastro-esophageal reflux disease (GERD). Although the pathophysiology is similar to that of adults, symptoms of GERD in infants and children are often distinct from classic ones such as heartburn. The passage of gastric contents into the esophagus is a normal phenomenon occurring many times a day both in adults and children, but, in infants, several factors contribute to exacerbate this phenomenon, including a liquid milk-based diet, recumbent position and both structural and functional immaturity of the gastro-esophageal junction. This article focuses on the presentation, diagnosis and treatment of GERD that occurs in infants and children, based on available and current guidelines.

Gastro-Esophageal Reflux in Children

PubMed Central

Pesce, Marcella; Thapar, Nikhil; Borrelli, Osvaldo

2017-01-01

Gastro-esophageal reflux (GER) is common in infants and children and has a varied clinical presentation: from infants with innocent regurgitation to infants and children with severe esophageal and extra-esophageal complications that define pathological gastro-esophageal reflux disease (GERD). Although the pathophysiology is similar to that of adults, symptoms of GERD in infants and children are often distinct from classic ones such as heartburn. The passage of gastric contents into the esophagus is a normal phenomenon occurring many times a day both in adults and children, but, in infants, several factors contribute to exacerbate this phenomenon, including a liquid milk-based diet, recumbent position and both structural and functional immaturity of the gastro-esophageal junction. This article focuses on the presentation, diagnosis and treatment of GERD that occurs in infants and children, based on available and current guidelines. PMID:28763023

Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

PubMed Central

2009-01-01

Background HIWI, the human homologue of Piwi family, is present in CD34+ hematopoietic stem cells and germ cells, but not in well-differentiated cell populations, indicating that HIWI may play an impotent role in determining or maintaining stemness of these cells. That HIWI expression has been detected in several type tumours may suggest its association with clinical outcome in cancer patients. Methods With the methods of real-time PCR, western blot, immunocytochemistry and immunohistochemistry, the expression of HIWI in three esophageal squamous cancer cell lines KYSE70, KYSE140 and KYSE450 has been characterized. Then, we investigated HIWI expression in a series of 153 esophageal squamous cell carcinomas using immunohistochemistry and explored its association with clinicopathological features. Results The expression of HIWI was observed in tumour cell nuclei or/and cytoplasm in 137 (89.5%) cases, 16 (10.5%) cases were negative in both nuclei and cytoplasm. 86 (56.2%) were strongly positive in cytoplasm, while 49 (32.0%) were strongly positive in nuclei. The expression level of HIWI in cytoplasm of esophageal cancer cells was significantly associated with histological grade (P = 0.011), T stage (P = 0.035), and clinic outcome (P < 0.001), while there was no correlation between the nuclear HIWI expression and clinicopathological features. Conclusion The expression of HIWI in the cytoplasm of esophageal cancer cells is significantly associated with higher histological grade, clinical stage and poorer clinical outcome, indicating its possible involvement in cancer development. PMID:19995427

Emerging immunotherapy for the treatment of esophageal cancer.

PubMed

Jackie Oh, SeungJu; Han, Songhee; Lee, Wooin; Lockhart, A Craig

2016-06-01

Esophageal cancer is the third most common cancer of the gastrointestinal tract. Despite new therapies, the prognosis for patients with these cancers remains poor with 5-year survival rates lower than 15%. Recently, immunotherapy has increasingly gained attention as a novel treatment strategy for advanced esophageal cancer. Recent success of immunotherapy in treating other solid tumors has shed light on the utility of these approaches for esophageal cancers. Here, the authors focus on antibody-based, adoptive-cell-therapy-based, and vaccine-based immunotherapies, and briefly address their rationale, clinical data, and implications. Immunotherapy is now established to be a key treatment modality that can improve the outcomes of many cancer patients and appears to be ushering in a new era in cancer treatment. Checkpoint inhibitor drugs have shown preliminary favorable results in esophageal cancer treatment. Adoptive cell therapy and vaccine studies have also shown some promise in various clinical studies. Future endeavors will need to focus on identifying patients who are likely to benefit from immunotherapy, monitoring and managing immune responses and designing optimal combination strategies where immunotherapy agents are combined with other traditional treatment modalities.

Current status of predictive biomarkers for neoadjuvant therapy in esophageal cancer

PubMed Central

Uemura, Norihisa; Kondo, Tadashi

2014-01-01

Neoadjuvant therapy has been proven to be extremely valuable and is widely used for advanced esophageal cancer. However, a significant proportion of treated patients (60%-70%) does not respond well to neoadjuvant treatments and develop severe adverse effects. Therefore, predictive markers for individualization of multimodality treatments are urgently needed in esophageal cancer. Recently, molecular biomarkers that predict the response to neoadjuvant therapy have been explored in multimodal approaches in esophageal cancer and successful examples of biomarker identification have been reported. In this review, promising candidates for predictive molecular biomarkers developed by using multiple molecular approaches are reviewed. Moreover, treatment strategies based on the status of predicted biomarkers are discussed, while considering the international differences in the clinical background. However, in the absence of adequate treatment options related to the results of the biomarker test, the usefulness of these diagnostic tools is limited and new effective therapies for biomarker-identified nonresponders to cancer treatment should be concurrent with the progress of predictive technologies. Further improvement in the prognosis of esophageal cancer patients can be achieved through the introduction of novel therapeutic approaches in clinical practice. PMID:25133032

Predictors of radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with three-dimensional conformal radiotherapy.

PubMed

Singh, Anurag K; Lockett, Mary Ann; Bradley, Jeffrey D

2003-02-01

To evaluate the incidence and clinical/dosimetric predictors of acute and late Radiation Therapy Oncology Group Grade 3-5 esophageal toxicity in patients with non-small-cell lung cancer (NSCLC) treated with definitive three-dimensional conformal radiotherapy (3D-CRT). We retrospectively reviewed the charts of 207 consecutive patients with NSCLC who were treated with high-dose, definitive 3D-CRT between March 1991 and December 1998. This population consisted of 107 men and 100 women. The median age was 67 years (range 31-90). The following patient and treatment parameters were studied: age, gender, race, performance status, sequential chemotherapy, concurrent chemotherapy, presence of subcarinal nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy. All doses are reported without heterogeneity corrections. The median prescription dose to the isocenter in this population was 70 Gy (range 60-74) delivered in 2-Gy daily fractions. All patients were treated once daily. Acute and late esophageal toxicities were graded by Radiation Therapy Oncology Group criteria. Patient and clinical/dosimetric factors were coded and correlated with acute and late Grade 3-5 esophageal toxicity using univariate and multivariate regression analyses. Of 207 patients, 16 (8%) developed acute (10 patients) or late (13 patients) Grade 3-5 esophageal toxicity. Seven patients had both acute and late Grade 3-5 esophageal toxicity. One patient died (Grade 5 esophageal toxicity) of late esophageal perforation. Concurrent chemotherapy, maximal point dose to the esophagus >58 Gy, and a mean dose to the entire esophagus >34 Gy were significantly associated with a risk of Grade 3-5 esophageal toxicity on univariate analysis. Concurrent chemotherapy and maximal point dose to the esophagus >58 Gy retained significance on multivariate analysis. Of 207 patients, 53 (26%) received concurrent chemotherapy. Fourteen (88%) of the 16 patients who developed Grade 3-5 esophageal toxicity had received concurrent chemotherapy (p = 0.0001, Pearson's chi-square test). No case of Grade 3-5 esophageal toxicity occurred in patients who received a maximal point dose to the esophagus of <58 Gy (p = 0.0001, Fisher's exact test, two-tail). Only 2 patients developed Grade 3-5 esophageal toxicity in the absence of concurrent chemotherapy; both received a maximal esophageal point dose >69 Gy. All assessable patients who developed Grade 3-5 esophageal toxicity had a mean dose to the entire esophagus >34 Gy (p = 0.0351, Pearson's chi-square test). However, the mean dose was not predictive on multivariate analysis. Concurrent chemotherapy and the maximal esophageal point dose were significantly associated with a risk of Grade 3-5 esophageal toxicity in patients with NSCLC treated with high-dose 3D-CRT. In patients who received concurrent chemotherapy, the threshold maximal esophageal point dose for Grade 3-5 esophageal toxicity was 58 Gy. An insufficient number of patients developed Grade 3-5 esophageal toxicity in the absence of chemotherapy to allow a valid statistical analysis of the relationship between the maximal esophageal point dose and esophagitis.

Black esophagus syndrome associated with diabetic ketoacidosis

PubMed Central

Rigolon, Riccardo; Fossà, Irene; Rodella, Luca; Targher, Giovanni

2016-01-01

Acute esophageal necrosis, also known as “black esophagus syndrome”, is a rare acute esophageal disease that is often associated with vomiting and upper gastrointestinal haemorrhage. At present, little is known regarding the pathogenesis of this disease. We present the case of a 50-year-old white male patient with diabetic ketoacidosis suffering from acute esophageal necrosis with nausea and vomiting but without any clinical signs of upper gastrointestinal bleeding. PMID:26881192

Strategy aimed at reduction of sputum eosinophils decreases exacerbation rate in patients with asthma.

PubMed

Chlumský, J; Striz, I; Terl, M; Vondracek, J

2006-01-01

Under Global Initiative for Asthma guidelines, the clinical control of disease activity and the adjustment of treatment in patients with asthma are based on symptoms, use of rescue medication, lung function and peak expiratory flow measurement (standard strategy). We investigated whether a strategy to reduce the number of sputum eosinophils (EOS strategy) gives better clinical control and a lower exacerbation rate compared with the standard strategy. Fifty-five patients with moderate to severe asthma entered this open, randomized, parallel-group study and visited the out-patient department every 3 months for 18 months. The dose of corticosteroids was adjusted according to the standard strategy or the percentage of sputum eosinophils (EOS strategy). During the study period, the EOS strategy led to a significantly lower incidence of asthma exacerbations compared with the standard strategy group (0.22 and 0.78 exacerbations per year per patient, respectively). There were significant differences between the strategies in time to first exacerbation.

PPMP, a novel tubulin-depolymerizing agent against esophageal cancer in patient-derived tumor xenografts.

PubMed

Sheng, Yuqiao; Liu, Kangdong; Wu, Qiong; Oi, Naomi; Chen, Hanyong; Reddy, Kanamata; Jiang, Yanan; Yao, Ke; Li, Haitao; Li, Wei; Zhang, Yi; Saleem, Mohammad; Ma, Wei-Ya; Bode, Ann M; Dong, Ziming; Dong, Zigang

2016-05-24

Esophageal cancer is one of the least studied and deadliest cancers worldwide with a poor prognosis due to limited options for treatment. Chemotherapy agents such as the microtubule-targeting compounds are the mainstay of palliation for advanced esophageal cancer treatment. However, the toxicity and side effects of tubulin-binding agents (TBAs) have promoted the development of novel, more potent but less toxic TBAs. Herein, we identified 2-[4-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrazol-5-yl]-5-[(2-methylprop-2-en-1-yl)oxy] phenol (PPMP) as a novel TBA for esophageal cancer treatment. PPMP markedly inhibited tubulin polymerization, and decreased viability and anchorage-independent growth of esophageal cancer cell lines, effects that were accompanied by G2/M arrest and apoptosis. Importantly, we produced patient-derived esophageal cancer xenografts to evaluate the therapeutic effect of PPMP in a setting that best mimics the clinical context in patients with esophageal cancer. Overall, we identified PPMP as a novel microtubule-destabilizing compound and as a new therapeutic agent against esophageal carcinoma.

Esophageal xanthoma--report of two new cases and review of the literature.

PubMed

Becheanu, Gabriel; Dumbrava, Mona; Arbanas, Tudor; Diculescu, Mircea; Hoyeau-Idrissi, Nadia; Fléjou, Jean-François

2011-12-01

Esophageal xanthoma is a very rare lesion which can be incidentally discovered during endoscopy. Only eleven cases have been reported, including ours. We present two new cases of esophageal xanthoma localized in the lower esophagus in a 56-year-old woman and a 62-year-old man. Endoscopically, esophageal xanthoma appears as yellowish granular spots or a slightly elevated lesion. Microscopically, it consists of fat accumulation in foamy histiocytes beneath the squamous epithelium. The clinical and pathological importance of these lesions and what they mean in patients is discussed, along with a review of the literature.

Influence of experimental esophageal acidification on sleep bruxism: a randomized trial.

PubMed

Ohmure, H; Oikawa, K; Kanematsu, K; Saito, Y; Yamamoto, T; Nagahama, H; Tsubouchi, H; Miyawaki, S

2011-05-01

The aim of this cross-over, randomized, single-blinded trial was to examine whether intra-esophageal acidification induces sleep bruxism (SB). Polysomnography with electromyogram (EMG) of masseter muscle, audio-video recording, and esophageal pH monitoring were performed in a sleep laboratory. Twelve healthy adult males without SB participated. Intra-esophageal infusions of 5-mL acidic solution (0.1 N HCl) or saline were administered. The frequencies of EMG bursts, rhythmic masticatory muscle activity (RMMA) episodes, grinding noise, and the RMMA/microarousal ratio were significantly higher in the 20-minute period after acidic infusion than after saline infusion. RMMA episodes including SB were induced by esophageal acidification. This trial is registered with the UMIN Clinical Trials Registry, UMIN000002923. ASDA, American Sleep Disorders Association; EMG, electromyogram; GER, gastroesophageal reflux; LES, lower esophageal sphincter; NREM, non-rapid eye movement; REM, rapid eye movement; RMMA, rhythmic masticatory muscle activity; SB, sleep bruxism; SD, standard deviation; UES, upper esophageal sphincter.

Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease.

PubMed

Cicala, Michele; Emerenziani, Sara; Guarino, Michele Pier Luca; Ribolsi, Mentore

2013-10-21

Gastro-esophageal reflux disease (GERD) is one of the most prevalent chronic diseases. Although proton pump inhibitors (PPIs) represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief, several studies have shown that up to 40% of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily. Several mechanisms have been proposed as involved in PPIs resistance, including ineffective control of gastric acid secretion, esophageal hypersensitivity, ultrastructural and functional changes in the esophageal epithelium. The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation, upper endoscopy, esophageal manometry and ambulatory pH-impedance monitoring, which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn. Treatment has been primarily based on doubling the PPI dose or switching to another PPI. Patients with proven disease, not responding to PPI twice daily, are eligible for anti-reflux surgery.

Removable self-expanding metal stents insertion for the treatment of perforations and postoperative leaks of the esophagus.

PubMed

Nasa, Mukesh; Sharma, Zubin Dev; Choudhary, Narendra S; Puri, Rajesh; Sud, Randhir

2016-03-01

Esophageal rupture, spontaneous or iatrogenic, is associated with significant morbidity and mortality. The current study aims at highlighting the various clinical scenarios, where esophageal fully covered self-expanding removable metal stents (FCSEMS) can be used in esophageal rupture. In patients who underwent insertion of FCSEMS between January 2013 and June 2014, all data regarding demographics, indications, insertion, removal, and outcomes were studied retrospectively. Seven patients underwent the placement of esophageal covered SEMS. Two patients had Boerhaave syndrome, two had leak following the repair of aortic aneurysm, one had extensive esophageal injury following transesophageal echocardiography, one had carcinoma esophagus with tracheaesophageal fistula, and one had dehiscence of esophagogastric anastomosis. Stent insertion was successful in all the patients; one had stent migration which was managed endoscopically. Two patients died due to underlying illness; the rest had successful removal of stents after 8-10 weeks and good outcomes. Esophageal FCSEMS placement is safe and effective modality in management of patients with esophageal rupture.

Preoperative determinants of an esophageal lengthening procedure in laparoscopic antireflux surgery.

PubMed

Urbach, D R; Khajanchee, Y S; Glasgow, R E; Hansen, P D; Swanstrom, L L

2001-12-01

In a minority of patients undergoing antireflux surgery, an esophageal lengthening procedure is required to reduce the gastroesophageal junction (GEJ) below the esophageal hiatus. We evaluated risk factors associated with an irreducible GEJ to identify clinical features that were predictive of the need for a Collis gastroplasty in patients undergoing laparoscopic antireflux surgery. Patients who required a Collis gastroplasty during a laparoscopic antireflux procedure (defined as the inability to reduce the GEJ > 2.5 cm below the esophageal hiatus despite extensive mobilization of the mediastinal esophagus) were compared to a random sample of patients who did not have a Collis gastroplasty. Predictors of the need for an esophageal lengthening procedure were identified using logistic regression modeling. Risks were expressed as odds ratios (OR) and 95% confidence intervals (CI). Twenty patients who had a Collis gastroplasty were compared to 133 patients who had adequate esophageal length. The presence of a stricture (OR 3.0; 95% CI 1.0, 9.7), paraesophageal hernia (OR 3.5; 95% CI 1.3, 9.6), Barrett's esophagus (OR 3.7, 95% CI 1.3, 10.7), and re-do antireflux surgery (OR 6.4; 95% CI 2.0, 20.7) were associated with the need for gastroplasty. Patients with none of these factors were extremely unlikely to require a gastroplasty (OR 0.08; 95% CI 0.02, 0.34). Patients undergoing laparoscopic antireflux surgery who are at high risk of needing an esophageal lengthening procedure can be easily identified preoperatively using simple clinical characteristics.

Preoperative Chemotherapy, Radiation Improve Survival in Esophageal Cancer (Updated)

Cancer.gov

Patients with esophageal cancer who received chemotherapy and radiation before surgery survived, on average, nearly twice as long as patients treated with surgery alone, according to results of a randomized clinical trial published May 31, 2012, in NEJM.

[Expression and significance of immunosuppressive acidic protein (IAP) in human esophageal squamous cell carcinoma].

PubMed

Guo, S Z; Shen, Q; Zhang, H B

1994-03-01

The expression of IAP in the esophageal tissues of 74 patients with esophageal squamous cell carcinoma and 12 normal controls were determined by using MI2, and anti-IAP monoclonal antibody, and ABC immunohistochemical staining. The results showed that there was no expression of IAP in normal esophageal epithelium of all control subjects, and the positive rate in specimens of the esophageal carcinomas was 90.3% (P < 0.001). The staining intensity of IAP was increasing with the decrease in degrees of cell differentiation of the tumors (P < 0.05). The expression of IAP in long survivors without lymph node metastasis were lower than that in cases with metastasis (P < 0.005) and short survivors (P < 0.001). The results suggest that IAP may play an important role in tumor cell differentiation, clinical course and prognosis of esophageal carcinoma, and may be used as a tumor marker for the diagnosis of this malignancy.

Risk Factors for Esophageal Fistula Associated With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Cancer

PubMed Central

Tsushima, Takahiro; Mizusawa, Junki; Sudo, Kazuki; Honma, Yoshitaka; Kato, Ken; Igaki, Hiroyasu; Tsubosa, Yasuhiro; Shinoda, Masayuki; Nakamura, Kenichi; Fukuda, Haruhiko; Kitagawa, Yuko

2016-01-01

Abstract Esophageal fistula is a critical adverse event in patients treated with chemoradiotherapy (CRT) for locally advanced esophageal cancer. However, risk factors associated with esophageal fistula formation in patients receiving CRT have not yet been elucidated. We retrospectively analyzed data obtained from 140 patients who were enrolled in a phase II/III trial comparing low-dose cisplatin with standard-dose cisplatin administered in combination with 5-flurouracil and concomitant radiotherapy. Inclusion criteria were performance status (PS) 0 to 2 and histologically proven thoracic esophageal cancer clinically diagnosed as T4 and/or unresectable lymph node metastasis for which definitive CRT was applicable. Risk factors for esophageal fistula were examined with univariate analysis using Fisher exact test and multivariate analysis using logistic regression models. Esophageal fistula was observed in 31 patients (22%). Of these, 6 patients developed fistula during CRT. Median time interval between the date of CRT initiation and that of fistula diagnosis was 100 days (inter quartile range, 45–171). Esophageal stenosis was the only significant risk factor for esophageal fistula formation both in univariate (P = 0.026) and in multivariate analyses (odds ratio, 2.59; 95% confidence interval, 1.13–5.92, P = 0.025). Other clinicopathological factors, namely treatment arm, age, sex, PS, primary tumor location, T stage, lymph node invasion to adjacent organs, blood cell count, albumin level, and body mass index, were not risk factors fistula formation. Esophageal stenosis was a significant risk factor for esophageal fistula formation in patients treated with CRT for unresectable locally advanced thoracic esophageal squamous cell carcinoma. PMID:27196482

Clinical lesson: eosinophilic oesophagitis, a new diagnosis to swallow.

PubMed

Lamb, C A; Kanakala, V; Stirling, R W; Attwood, S E A

2010-04-01

Eosinophilic oesophagitis (EoE) is a recently described condition that has gained increasing recognition over the past 5 years. Despite this, many clinicians remain unaware of EoE, often leading to diagnostic delay and therefore significant morbidity. The diagnosis of EoE should be considered in any patient with a history of intermittent or continuous dysphagia, or oesophageal food impaction. It should be strongly suspected in young patients, particularly men, presenting with dysphagia and a history of atopy. Here, three patients are presented that highlight common features of EoE. In addition, a clinical review of the worldwide literature is provided to heighten physician awareness and understanding of the condition.

Successful treatment with alectinib after crizotinib-induced esophageal ulceration.

PubMed

Yoneshima, Yasuto; Okamoto, Isamu; Takano, Tomotsugu; Enokizu, Aimi; Iwama, Eiji; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi

2015-06-01

Crizotinib was the first clinically available inhibitor of the tyrosine kinase ALK, and next-generation ALK inhibitors, such as alectinib, are now under development. Although crizotinib is generally well tolerated, severe esophageal injury has been reported as a rare but serious adverse event of crizotinib therapy. We now describe the successful treatment with alectinib of a patient who developed crizotinib-induced esophageal ulceration. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation of urgent esophagectomy in esophageal perforation

PubMed Central

de AQUINO, José Luis Braga; de CAMARGO, José Gonzaga Teixeira; CECCHINO, Gustavo Nardini; PEREIRA, Douglas Alexandre Rizzanti; BENTO, Caroline Agnelli; LEANDRO-MERHI, Vânia Aparecida

2014-01-01

Background Esophageal trauma is considered one of the most severe lesions of the digestive tract. There is still much controversy in choosing the best treatment for cases of esophageal perforation since that decision involves many variables. The readiness of medical care, the patient's clinical status, the local conditions of the perforated segment, and the severity of the associated injuries must be considered for the most adequate therapeutic choice. Aim To demonstrate and to analyze the results of urgent esophagectomy in a series of patients with esophageal perforation. Methods A retrospective study of 31 patients with confirmed esophageal perforation. Most injuries were due to endoscopic dilatation of benign esophageal disorders, which had evolved with stenosis. The diagnosis of perforation was based on clinical parameters, laboratory tests, and endoscopic images. ‪The main surgical technique used was transmediastinal esophagectomy followed by reconstruction of the digestive tract in a second surgical procedure. Patients were evaluated for the development of systemic and local complications, especially for the dehiscence or stricture of the anastomosis of the cervical esophagus with either the stomach or the transposed colon. Results Early postoperative evaluation showed a survival rate of 77.1% in relation to the proposed surgery, and 45% of these patients presented no further complications. The other patients had one or more complications, being pulmonary infection and anastomotic fistula the most frequent. The seven patients (22.9%) who underwent esophageal resection 48 hours after the diagnosis died of sepsis. At medium and long-term assessments, most patients reported a good quality of life and full satisfaction regarding the surgery outcomes. Conclusions Despite the morbidity, emergency esophagectomy has its validity, especially in well indicated cases of esophageal perforation subsequent to endoscopic dilation for benign strictures. PMID:25626932

Effects of acotiamide on esophageal motor function and gastroesophageal reflux in healthy volunteers.

PubMed

Ishimura, Norihisa; Mori, Mami; Mikami, Hironobu; Shimura, Shino; Uno, Goichi; Aimi, Masahito; Oshima, Naoki; Ishihara, Shunji; Kinoshita, Yoshikazu

2015-09-11

The prevalence of gastroesophageal reflux disease (GERD) has been increasing worldwide, with proton pump inhibitor (PPI) administration the current mainstay therapy for affected individuals. However, PPI efficacy is insufficient especially for non-erosive reflux disease. Although it has been reported that prokinetic drugs improve GERD, their effects on esophageal function remain to be clearly investigated. In the present study, we evaluated the direct effects of acotiamide, a novel prokinetic agent for the treatment of functional dyspepsia, on esophageal motor function and gastroesophageal reflux. Ten adult healthy volunteers (average age 24 years, range 20-36 years; 7 males, 3 females) were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure with and without acotiamide administration were recorded using high resolution manometry using a cross-over protocol. Total and acidic reflux levels for 24 h and during the postprandial period were also recorded using a multichannel intraluminal impedance and pH monitoring system. Data were analyzed blind by one observer. Acotiamide at a standard dose of 300 mg/day did not significantly stimulate esophageal motor function. Although the frequency of swallows with weak contraction tended to decrease with acotiamide administration, the difference as compared to no administration was not statistically significant. In addition, the drug neither decreased total or postprandial gastroesophageal acid/non-acid reflux events nor accelerated esophageal clearance time. Acotiamide, a novel gastrointestinal motility modulator, at a standard dose did not significantly affect esophageal motor functions or gastroesophageal reflux in healthy adults. Additional investigations with GERD patients are necessary to elucidate its clinical significance. This study was registered on 1st August 2013 with the University Hospital Medical Information Network (UMIN) clinical trials registry, as number: UMIN000011260.

N-acetylcysteine for the prevention of stricture after circumferential endoscopic submucosal dissection of the esophagus: a randomized trial in a porcine model.

PubMed

Barret, Maximilien; Batteux, Frédéric; Beuvon, Frédéric; Mangialavori, Luigi; Chryssostalis, Ariane; Pratico, Carlos; Chaussade, Stanislas; Prat, Frédéric

2012-05-28

Circumferential endoscopic submucosal dissection (CESD) of the esophagus would allow for both the eradication of Barrett's esophagus and its related complications, such as advanced neoplasia. However, such procedures generally induce inflammatory repair resulting in a fibrotic stricture. N-acetylcysteine (NAC) is an antioxidant that has shown some efficacy against pulmonary and hepatic fibrosis. The aim of our study was to evaluate the benefit of NAC in the prevention of esophageal cicatricial stricture after CESD in a swine model. Two groups of six pigs each were subjected to general anesthesia and CESD: after randomization, a first group received an oral NAC treatment regimen of 100 mg/kg/day, initiated one week before the procedure, whereas a second group was followed without any prophylactic treatment. Follow-up endoscopies took place seven, fourteen, twenty-one, and twenty-eight days after CESD. Necropsy, histological assessment of esophageal inflammation, and fibrosis were performed on day 28. The median esophageal lumen diameter on day 21 (main judgment criterion) was 4 mm (range 2 to 5) in group 1 and 3 mm (range 1 to 7) in group 2 (P = 0.95). No significant difference was observed between the two groups regarding clinical evaluation (time before onset of clinically significant esophageal obstruction), number of dilations, esophageal inflammation and fibrosis, or oxidative stress damage on immunohistochemistry. Despite its antioxidant effect, systemic administration of NAC did not show significant benefit on esophageal fibrosis in our animal model of esophageal wound healing within the experimental conditions of this study. Since the administered doses were relatively high, it seems unlikely that NAC might be a valuable option for the prevention of post-endoscopic esophageal stricture.

N-acetylcysteine for the prevention of stricture after circumferential endoscopic submucosal dissection of the esophagus: a randomized trial in a porcine model

PubMed Central

2012-01-01

Background Circumferential endoscopic submucosal dissection (CESD) of the esophagus would allow for both the eradication of Barrett’s esophagus and its related complications, such as advanced neoplasia. However, such procedures generally induce inflammatory repair resulting in a fibrotic stricture. N-acetylcysteine (NAC) is an antioxidant that has shown some efficacy against pulmonary and hepatic fibrosis. The aim of our study was to evaluate the benefit of NAC in the prevention of esophageal cicatricial stricture after CESD in a swine model. Animals and methods Two groups of six pigs each were subjected to general anesthesia and CESD: after randomization, a first group received an oral NAC treatment regimen of 100 mg/kg/day, initiated one week before the procedure, whereas a second group was followed without any prophylactic treatment. Follow-up endoscopies took place seven, fourteen, twenty-one, and twenty-eight days after CESD. Necropsy, histological assessment of esophageal inflammation, and fibrosis were performed on day 28. Results The median esophageal lumen diameter on day 21 (main judgment criterion) was 4 mm (range 2 to 5) in group 1 and 3 mm (range 1 to 7) in group 2 (P = 0.95). No significant difference was observed between the two groups regarding clinical evaluation (time before onset of clinically significant esophageal obstruction), number of dilations, esophageal inflammation and fibrosis, or oxidative stress damage on immunohistochemistry. Conclusions Despite its antioxidant effect, systemic administration of NAC did not show significant benefit on esophageal fibrosis in our animal model of esophageal wound healing within the experimental conditions of this study. Since the administered doses were relatively high, it seems unlikely that NAC might be a valuable option for the prevention of post-endoscopic esophageal stricture. PMID:22640979

[Membrane-covered self-expanding stents in the treatment of high-positioned esophageal stenosis or fistula].

PubMed

Liu, Jing-zheng; Zhong, Yun-shi; Xu, Mei-dong; Chen, Wei-feng; Zhou, Ping-hong; Yao, Li-qing

2013-12-01

To investigate the efficacy and safety of membrane-covered self-expanding metal stent in the treatment of high-positioned esophageal diseases, including esophageal stenosis, esophagotracheal fistula and anastomotic stricture. Clinical data of 84 patients who underwent stenting in our center from May 2005 to July 2013 were retrospectively analyzed. Of 84 patients, 31 were diagnosed as esophageal malignant stenosis, 2 compression stenosis, 10 radiation stenosis, 4 recurrent malignant stenosis, 27 anastomotic stricture, 1 esophageal stenosis after endoscopic submucosal dissection (ESD), 7 esophageal-tracheal fistula, 1 esophageal-mediastinal fistula, and 1 remnant stomach fistula. Distance from stenosis or fistula to central incisor was 15-20 cm in 48 cases, and more than 20 cm in 36 cases. All the patients were treated by 16 mm membrane-covered self-expanding metal stents. Main clinical manifestations and complications were evaluated. A total of 100 stents were placed in 84 patients,with a success rate of 100%. There were no complications such as perforation and bleeding during operation. Dysphagia and cough were improved quickly with a success rate of 100%. After the placement of stents, the incidence of complication was 6.0% (5/84), of which 2 cases were severe retrosternal pain, 1 was tracheal collapse, and 2 were stent displacement. Seventy-six patients (90.5%) received complete follow-up of 1 to 36 months (mean 15 months). Re-stenosis occurred in 4 cases, new esophageal-tracheal fistula in 2 cases. Among these 6 cases, 5 cases underwent successfully stent placement once again, and another one case received Savary bougie and Argon-ion coagulation with good efficacy. Endoscopic membrane-covered self-expanding metal stent placement is effective and safe for the relieve of dysphagia symptoms and the sealing of esophagotracheal fistula.

[Evaluation of stents in treating childhood benign esophageal strictures].

PubMed

Reinshagen, K; Kähler, G; Manegold, B C; Waag, K-L

2009-01-01

Esophageal stenting is a popular of treatment of esophageal strictures in adults. It has also been described for children with benign strictures who did not respond to standard dilatation therapy. The aim of the study was to evaluate weather esophageal stents could be used safely and effectively in the treatment of benign esophageal strictures in children. From 1993 to 2005 stenting therapy was performed in 12 children with complicated esophageal strictures. Etiologies of the strictures were caustic burns in 9 patients, postoperative strictures due to complicated esophageal atresia in 2 patients and iatrogenic esophageal injury in 1 patient. Esophageal silicon tubi, covered retrievable expandable nitinol and plastic stents were placed endoscopically. The clinical course and the long term follow up were evaluated retrospectively The stents and tubi were placed in all patients without complications and were later removed successfully. 6 patients were treated with a self expanding plastic stent. The plastic stents showed a distinct tendency to migrate but in 5/6 patients esophageal stricture was treated successfully. 3 patients were treated by a covered self expanding nitinol stent. No migration occurred. One patient was asymptomatic after therapy, one required further dilatation therapy and the third had esophageal resection. 3 patients were treated by esophageal tubi. 2 patients required surgery in the follow up, one patient is asymptomatic. The use of stenting devices in children to treat benign esophageal strictures is safe and efficient. The self expanding plastic stents had the best long term results but required high compliance of parents and children due to the tendency of stent migration. Self expanding nitinol stents are more traumatic at the extraction procedure and are useful in patients with low compliance. Recurrence of strictures occurred most often after esophageal tubi possibly due to the lack of radial expansion.

Acute esophageal necrosis and low-flow state

PubMed Central

Burtally, Ahmad; Gregoire, Philippe

2007-01-01

Acute esophageal necrosis (AEN), also called black esophagus, is quite exceptional. Endoscopic findings show circumferential black discolouration of the esophagus with or without exudates. The etiology of AEN is presently unknown and is assumed to be multifactorial. Distal esophageal involvement with proximal extension ending sharply at the gastroesophageal junction is the most common presentation. The present case report describes the clinical and endoscopic evolution of black esophagus observed in a patient with significant peripheral vascular disease, who was presented to the intensive care unit at the Hopital Saint-Francois d’Assise (Quebec City, Quebec). Through an extensive review of the literature, common underlying clinical conditions of patients diagnosed with AEN have been identified. PMID:17431514

Genetics Home Reference: PDGFRA-associated chronic eosinophilic leukemia

MedlinePlus

... area? Other Names for This Condition PDGFRA-associated myeloproliferative neoplasm Related Information How are genetic conditions and genes ... Disorders Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasia, MD Anderson Cancer Center ... ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific ...

Self-expandable metal stents for malignant esophageal obstruction: a comparative study between extrinsic and intrinsic compression.

PubMed

Rhee, K; Kim, J-H; Jung, D H; Han, J W; Lee, Y C; Lee, S K; Shin, S K; Park, J C; Chung, H S; Park, J J; Youn, Y H; Park, H

2016-04-01

Self-expandable metal stents (SEMSs) are effective for malignant esophageal obstruction, but usefulness of SEMSs in extrinsic lesions is yet to be elucidated. This study is aimed at evaluating the clinical usefulness of SEMSs in the extrinsic compression compared with intrinsic. A retrospective review was conducted for 105 patients (intrinsic, 85; extrinsic, 20) with malignant esophageal obstruction who underwent endoscopic SEMSs placement. Technical and clinical success rates were evaluated and clinical outcomes were compared between extrinsic and intrinsic group. Extrinsic group was mostly pulmonary origin. Overall technical and clinical success rate was 100% and 91%, respectively, without immediate complications. Extrinsic and intrinsic group did not differ significantly in clinical success rate. The median stent patency time was 131.3 ± 85.8 days in intrinsic group while that of extrinsic was 54.6 ± 45.1 due to shorter survival after stent insertion. The 4-, 8-, and 12-week patency rates were 90.5%, 78.8%, and 64.9% respectively in intrinsic group, while stents of extrinsic group remained patent until death. Uncovered, fully covered, and double-layered stent were used evenly and the types did not influence patency in both groups. In conclusion, esophageal SEMSs can safely and effectively be used for malignant extrinsic compression as well as intrinsic. © 2015 International Society for Diseases of the Esophagus.

Clinical and manometric characteristics of patients with Parkinson's disease and esophageal symptoms.

PubMed

Su, A; Gandhy, R; Barlow, C; Triadafilopoulos, G

2017-04-01

Dysphagia is a common problem in patients with Parkinson's disease (PD); its etiology is multifactorial and its management is challenging. In this retrospective cohort analysis using prospectively collected data, we aimed to objectively characterize dysphagia and/or other esophageal symptoms in patients with PD, assess the prevalence of outflow obstruction as well as major or minor disorders of esophageal peristalsis leading to impaired esophageal clearance and highlight objective parameters that can help in the current management algorithm. Thirty-three consecutive patients with PD presenting with dysphagia, odynophagia, heartburn, regurgitation, chest pain, and weight loss underwent clinical and functional evaluation by high-resolution manometry (HRM). Esophagogastric junction (EGJ) outflow obstruction and major as well as minor disorders of peristalsis were then assessed using the Chicago classification (v3). Thirty-three PD patients with esophageal symptoms were enrolled in the study; 12 of them reported weight loss that was considered as potentially reflecting underlying esophageal dysfunction. The median age of the patients was 70 years (range: 53-89 years), 24 (75%) were men. The majority (62%) experienced dysphagia, likely contributing to weight loss in 41% of patients. Odynophagia was rare (6%) while GER symptoms, such as heartburn, regurgitation, and chest pain were noted in 37%, 31%, and 28% of patients, respectively. Using the hierarchy of the Chicago classification, 12 patients (39%) exhibited EGJ outflow obstruction, 16 (48%) diffuse esophageal spasm (DES), 18 (55%), ineffective esophageal peristalsis (IEM), 16 (48%) fragmented peristalsis, and only 2 patients (6%) had normal HRM tracings. There were no patients with HRM features of achalasia. Dysphagia is common in patients with PD and is associated with a high prevalence of underlying motility disturbances as identified by HRM. The exact impact of these motility abnormalities on symptom induction and their role in influencing clinical management are unclear and will require further study. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Reversal of lower esophageal sphincter hypotension and esophageal aperistalsis after treatment for hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eastwood, G.L.; Braverman, L.E.; White, E.M.

1982-08-01

A 65-year-old woman suffered from both chronic gastroesophageal reflux, which was complicated by columnar metaplasia (Barrett's epithelium), and profound hypothyroidism. An esophageal motility tracing showed absence of peristalsis in the lower esophagus and the lower esophageal sphincter (LES) could not be identified. Thyroid replacement therapy, in conjunction with antacid and cimetidine treatment, was associated not only with improvement in the gastroesophageal reflux symptoms, but also with a return of esophageal peristalsis and LES pressure to normal. To support our clinical observations, we rendered four cats hypothyroid with /sup 131/I and documented a fall in LES pressure. We propose that abnormalmore » smooth-muscle function of the esophagus may be another manifestation of the gastrointestinal motility disturbances which are associated with hypothyroidism.« less

Clinical features and treatment of patients with esophageal cancer and a history of gastrectomy: a multicenter, questionnaire survey in Kyushu, Japan

PubMed Central

Mori, N.; Tanaka, T.; Morita, M.; Toh, Y.; Saeki, H.; Maehara, Y.; Nakamura, K.; Honda, H.; Yoshida, N.; Baba, H.; Natsugoe, S.

2015-01-01

Summary It is still controversial whether patients with a history of gastrectomy have high risk of esophageal carcinogenesis. On the other hand, the treatment strategy for esophageal cancer patients after gastrectomy is complicated. The association between histories of gastrectomy and esophageal carcinogenesis was retrospectively analyzed, and the treatment of esophageal cancer patients after gastrectomy was evaluated based on questionnaire data collected from multiple centers in Kyushu, Japan. The initial subject population comprised 205 esophageal cancer patients after gastrectomy. Among them, 108 patients underwent curative surgical treatment, and 70 patients underwent chemoradiation therapy (CRT). The time between gastrectomy and esophageal cancer development was longer in peptic ulcer patients (28.3 years) than in gastric cancer patients (9.6 years). There were no differences in the location of esophageal cancer according to the gastrectomy reconstruction method. There were no significant differences in the clinical background characteristics between patients with and without a history of gastrectomy. Among the 108 patients in the surgery group, the 5‐year overall survival rates for stages I (n = 30), II (n = 18), and III (n = 60) were 68.2%, 62.9%, and 32.1%, respectively. In the CRT group, the 5‐year overall survival rate of stage I (n = 29) was 82.6%, but there were no 5‐year survivors in other stages. The 5‐year overall survival rate of patients with CR (n = 33) or salvage surgery (n = 10) was 61.2% or 36%, respectively. For the treatment of gastrectomized esophageal cancer patients, surgery or CRT is recommended for stage I, and surgery with or without adjuvant therapy is the main central treatment in advanced stages, with surgery for stage II, neoadjuvant therapy + surgery for stage III, and CRT + salvage surgery for any stage, if the patient's condition permits. PMID:26542524

Clinical features and treatment of patients with esophageal cancer and a history of gastrectomy: a multicenter, questionnaire survey in Kyushu, Japan.

PubMed

Okumura, H; Mori, N; Tanaka, T; Morita, M; Toh, Y; Saeki, H; Maehara, Y; Nakamura, K; Honda, H; Yoshida, N; Baba, H; Natsugoe, S

2016-11-01

It is still controversial whether patients with a history of gastrectomy have high risk of esophageal carcinogenesis. On the other hand, the treatment strategy for esophageal cancer patients after gastrectomy is complicated. The association between histories of gastrectomy and esophageal carcinogenesis was retrospectively analyzed, and the treatment of esophageal cancer patients after gastrectomy was evaluated based on questionnaire data collected from multiple centers in Kyushu, Japan. The initial subject population comprised 205 esophageal cancer patients after gastrectomy. Among them, 108 patients underwent curative surgical treatment, and 70 patients underwent chemoradiation therapy (CRT). The time between gastrectomy and esophageal cancer development was longer in peptic ulcer patients (28.3 years) than in gastric cancer patients (9.6 years). There were no differences in the location of esophageal cancer according to the gastrectomy reconstruction method. There were no significant differences in the clinical background characteristics between patients with and without a history of gastrectomy. Among the 108 patients in the surgery group, the 5-year overall survival rates for stages I (n = 30), II (n = 18), and III (n = 60) were 68.2%, 62.9%, and 32.1%, respectively. In the CRT group, the 5-year overall survival rate of stage I (n = 29) was 82.6%, but there were no 5-year survivors in other stages. The 5-year overall survival rate of patients with CR (n = 33) or salvage surgery (n = 10) was 61.2% or 36%, respectively. For the treatment of gastrectomized esophageal cancer patients, surgery or CRT is recommended for stage I, and surgery with or without adjuvant therapy is the main central treatment in advanced stages, with surgery for stage II, neoadjuvant therapy + surgery for stage III, and CRT + salvage surgery for any stage, if the patient's condition permits. © 2015 The Authors. Diseases of the Esophagus published by Wiley Periodicals, Inc. on behalf of International Society for Diseases of the Esophagus.

Fully covered self-expandable metal stents (SEMS), partially covered SEMS and self-expandable plastic stents for the treatment of benign esophageal ruptures and anastomotic leaks.

PubMed

van Boeckel, Petra G A; Dua, Kulwinder S; Weusten, Bas L A M; Schmits, Ruben J H; Surapaneni, Naveen; Timmer, Robin; Vleggaar, Frank P; Siersema, Peter D

2012-02-29

Benign esophageal ruptures and anastomotic leaks are life-threatening conditions that are often treated surgically. Recently, placement of partially and fully covered metal or plastic stents has emerged as a minimally invasive treatment option. We aimed to determine the clinical effectiveness of covered stent placement for the treatment of esophageal ruptures and anastomotic leaks with special emphasis on different stent designs. Consecutive patients who underwent placement of a fully covered self-expandable metal stent (FSEMS), a partially covered SEMS (PSEMS) or a self-expanding plastic stent (SEPS) for a benign esophageal rupture or anastomotic leak after upper gastrointestinal surgery in the period 2007-2010 were included. Data on patient demographics, type of lesion, stent placement and removal, clinical success and complications were collected A total of 52 patients received 83 esophageal stents (61 PSEMS, 15 FSEMS, 7 SEPS) for an anastomotic leak (n=32), iatrogenic rupture (n=13), Boerhaave's syndrome (n=4) or other cause (n=3). Endoscopic stent removal was successful in all but eight patients treated with a PSEMS due to tissue ingrowth. Clinical success was achieved in 34 (76%, intention-to-treat: 65%) patients (PSEMS: 73%, FSEMS: 83%, SEPS: 83%) after a median of 1 (range 1-5) stent and a median stenting time of 39 (range 7-120) days. In total, 33 complications in 24 (46%) patients occurred (tissue in- or overgrowth (n=8), stent migration (n=10), ruptured stent cover (all Ultraflex; n=6), food obstruction (n=3), severe pain (n=2), esophageal rupture (n=2), hemorrhage (n=2)). One (2%) patient died of a stent-related cause. Covered stents placed for a period of 5-6 weeks may well be an alternative to surgery for treating benign esophageal ruptures or anastomotic leaks. As efficacy between PSEMS, FSEMS and SEPS is not different, stent choice should depend on expected risks of stent migration (SEPS and FSEMS) and tissue in- or overgrowth (PSEMS).

A randomized, double blind, controlled, multi center study of Ilaparazole in the treatment of reflux esophagitis-Phase III clinical trial.

PubMed

Xue, Yan; Qin, Xianghong; Zhou, Liya; Lin, Sanren; Wang, Ling; Hu, Haitang; Xia, Jielai

2018-05-01

Proton pump inhibitors (PPIs) are the main drugs for the treatment of reflux esophagitis. Phase II clinical trials showed that, compared with Esomeprazole, the new PPI Ilaparazole is great in terms of efficacy for reflux symptoms relief and curling for esophagitis. The aim of this study was to confirm suitable dose of Ilaparazole in the treatment of reflux esophagitis. This study used a randomized, double-blind, parallel positive drug control, multi-center design. A total of 537patients diagnosed as reflux esophagitis by gastroscopy were randomly divided into Ilaparazole group (n = 322, Ilaparazole 10 mg QD) and esomeprazole group (n = 215, Esomeprazole 40 mg QD). The patients in the two groups were treated for 8 weeks. Heartburn and reflux symptoms prior to treatment, and 2, 4 and 8 weeks after the treatment were assessed. Gastroscopy was performed after 4 weeks of treatment. Unhealed patients within 4 weeks underwent gastroscopy again at the end of 8 weeks. A total of 471 cases completed the treatment. In Esomeprazole and Ilaparazole groups. After 8 weeks treatment, the healing rate in Esomeprazole group and Ilaparazole group were 82.79% (94.94%) and 83.54% (92.50%), respectively. The corresponding rate difference [Ilaparazole-esomeprazole] was 0.75% (-2.44%) and the two-sided 95% CI was -5.72 to 7.22 (-6.90 to 2.01). The symptom disappearance rates for FAS (PPS) were 75.81% (82.02%) and 76.71% (80.36%) P = 0.8223 (0.7742). Adverse reactions related to the drugs were: 10.70% and 11.80%, (P = 0.7817). The efficacy and safety of Ilaparazole (10 mg/day) in treating reflux esophagitis was similar to esomeprazole (40 mg/day). Ilaparazole (10 mg/day) can be used in the treatment of esophagitis. The clinical trial registration number of the study is NCT 02860624. Copyright © 2018. Published by Elsevier Inc.

Eosinophilic pneumonia caused by daptomycin: Six cases from two institutions and a review of the literature.

PubMed

Hirai, Jun; Hagihara, Mao; Haranaga, Shusaku; Kinjo, Takeshi; Hashioka, Hiroe; Kato, Hideo; Sakanashi, Daisuke; Yamagishi, Yuka; Mikamo, Hiroshige; Fujita, Jiro

2017-04-01

Here we report six cases of daptomycin (DAP)-induced eosinophilic pneumonia (DIEP) encountered at two medical centers and present a review of 43 DIEP patients from 26 studies to compare the clinical characteristics and radiographic findings of acute and chronic eosinophilic pneumonia (AEP; CEP). Four of the six patients did not exhibit respiratory symptoms, and one patient with only fever was misdiagnosed with DAP-induced fever. According to our literature review and the present findings, male sex and old age were dominant risk factors for DIEP. Fever and fine crackles were the most common clinical manifestations. The DAP dose and duration of administration were not significant risk factors for DIEP, and we also could not find any association between allergic predisposition and DIEP. Among the reviewed patients, 51.8% did not show more than 25% eosinophils in bronchoalveolar lavage, which is a criterion for the diagnosis of drug-induced eosinophilic pneumonia. Chest images of all patients showed CEP patterns such as multiple reticulonodular infiltrates in the subpleural region and diffuse bilateral pulmonary infiltrates with ground-glass opacities. However, 66.7% of patients also exhibited pleural effusion, a feature specific to AEP. All patients showed prompt recovery after DAP withdrawal. Our results suggest that clinicians should consider DIEP as a differential diagnosis when patients receiving DAP therapy, particularly men and elderly patients, present with fever, even in the absence of respiratory symptoms. Furthermore, they should be aware that the occurrence of DIEP is independent of the DAP dose and administration duration, and allergic reaction. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Practice guidelines on the use of esophageal manometry - A GISMAD-SIGE-AIGO medical position statement.

PubMed

Savarino, Edoardo; de Bortoli, Nicola; Bellini, Massimo; Galeazzi, Francesca; Ribolsi, Mentore; Salvador, Renato; Savarino, Vincenzo; Penagini, Roberto

2016-10-01

Patients with esophageal symptoms potentially associated to esophageal motor disorders such as dysphagia, chest pain, heartburn and regurgitation, represent one of the most frequent reasons for referral to gastroenterological evaluation. The utility of esophageal manometry in clinical practice is: (1) to accurately define esophageal motor function, (2) to identify abnormal motor function, and (3) to establish a treatment plan based on motor abnormalities. With this in mind, in the last decade, investigations and technical advances, with the introduction of high-resolution esophageal manometry, have enhanced our understanding and management of esophageal motility disorders. The following recommendations were developed to assist physicians in the appropriate use of esophageal manometry in modern patient care. They were discussed and approved after a comprehensive review of the medical literature pertaining to manometric techniques and their recent application. This position statement created under the auspices of the Gruppo Italiano di Studio per la Motilità dell'Apparato Digerente (GISMAD), Società Italiana di Gastroenterologia ed Endoscopia Digestiva (SIGE) and Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) is intended to help clinicians in applying manometric studies in the most fruitful manner within the context of their patients with esophageal symptoms. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Review of esophageal injuries and stenosis: Lessons learn and current concepts of management.

PubMed

Ramareddy, Raghu Sampalli; Alladi, Anand

2016-01-01

To review the patients with esophageal injuries and stenosis with respect to their etiology, clinical course, management, and the lessons learnt from these. Retrospective descriptive observation review of children with esophageal injuries and stenosis admitted between January 2009 and April 2015. Eighteen children with esophageal injuries of varied etiology were managed and included, seven with corrosive injury, five with perforation due to various causes, three with mucosal erosion, two with trachea esophageal fistula (TEF), and one wall erosion. The five children who had perforation were due to poststricture dilatation in a child with esophageal atresia and secondary to foreign body impaction or its attempted retrieval in four. Alkaline button cell had caused TEF in two. Three congenital esophageal stenosis (CES) had presented with dysphagia and respiratory tract infection. Six corrosive stricture and two CES responded to dilatation alone and one each of them required surgery. Four of the children with esophageal perforation were detected early and required drainage procedure (1), diversion (1), and medical management (2). Pseudo diverticulum was managed expectantly. Among TEF, one had spontaneous closure and other one was lost to follow-up. All the remaining nineteen children have recovered well except one CES had mortality. Esophageal injuries though rare can be potentially devastating and life-threatening.

Allergic colitis in infants related to cow's milk: clinical characteristics, pathologic changes, and immunologic findings.

PubMed

Yu, Man-Chun; Tsai, Chia-Lun; Yang, Yao-Jong; Yang, Sing-San; Wang, Li-Hui; Lee, Chung-Ta; Jan, Ren-Long; Wang, Jiu-Yao

2013-02-01

Allergic colitis (AC) is an inflammatory condition characterized by eosinophils infiltrating the colonic wall. It can be a benign and/or severe illness among gastrointestinal diseases in infants. We report five infants who, since January 2009, in whom AC under fibrotic endoscopic examinations has been diagnosed. The criterion for histopathologic diagnosis of AC in this study was five or more eosinophils per high-power field. Patients' clinical symptoms, pathologic findings, and immunologic studies, such as specific antibodies against component of cow's milk protein, were compared with those of allergic children without AC and those of nonatopic control children. Histopathologic examinations of biopsy specimens revealed acute inflammation with characteristic eosinophilic infiltration of lamina propria (5-15 eosinophils per high-power field) in all five patients. They all had strongly positive skin prick tests against milk protein, which were not correlated with in vitro allergen-specific immunoglobulin (Ig) E levels. In contrast, there were significantly higher levels of IgE antibodies, and lower specific IgG4 and IgA levels to components and whole milk proteins in AC, as compared to control children without AC. Endoscopic biopsy specimens of intestine confirm the diagnosis of AC. However, allergen skin prick test and IgE antibody to milk protein components also provide helpful diagnostic tools for this rare disease in children. Copyright © 2012. Published by Elsevier B.V.

Predictors of Progression to High-Grade Dysplasia or Adenocarcinoma in Barrett’s Esophagus

PubMed Central

Whitson, Matthew J.; Falk, Gary W.

2015-01-01

Article Synopsis The prevalence of esophageal adenocarcinoma is increasing dramatically. Barrett’s esophagus remains the most well established risk factor for the development of esophageal adenocarcinoma. There are multiple clinical, endoscopic, and pathologic factors that increase the risk of neoplastic progression to high-grade dysplasia or esophageal adenocarcinoma in Barrett’s esophagus. This article will review both risk and protective factors for neoplastic progression in patients with Barrett’s esophagus. PMID:26021196

Evaluation of esophageal function in patients with esophageal motor abnormalities using multichannel intraluminal impedance esophageal manometry.

PubMed

Cho, Yu Kyung; Choi, Myung-Gyu; Park, Jae Myung; Oh, Jung Hwan; Paik, Chang Nyol; Lee, Joon Wook; Lee, In Seok; Kim, Sang Woo; Chung, In-Sik

2006-10-21

To evaluate the functional aspect of esophageal motility in healthy subjects and in patients who were referred for esophageal function testing using multichannel intraluminal impedance-esophageal manometry (MII-EM), and to assess the clinical utility of MII-EM. From September 2003 to January 2004, we performed the MII-EM on healthy volunteers and all the patients who were referred for esophageal function testing. Each patient received 10 liquid and 10 viscous swallows. We analyzed the results, the impedance and the manometric findings. Some of the subjects had additional ambulatory 24-h pH study performed to diagnose gastroesophageal reflux disease (GERD). Among 89 studied subjects, the MII-EM findings showed normal esophageal motility in 50 (56.17%), ineffective esophageal motility (IEM) in 17 (19.10%), nutcracker esophagus in 7 (7.86%), achalasia in 4 (4.49%), and scleroderma esophagus in 11 (12.35%) cases. The completeness and the speed of bolus transit were in the order of nutcracker esophagus, normal manometry and IEM. Some of the swallows showing normal manometry and IEM had incomplete transit. In the achalasia and scleroderma esophagus, almost all the swallows had incomplete transit. The body amplitudes were higher for the swallows with complete transit than for the swallows with incomplete transit. There was not a significant difference in the manometric and impedance findings between the subjects with and without GERD. MII-EM is a useful tool in assessing the esophageal function in the patients having esophageal motility abnormality. The primary factors influencing the bolus transit are the amplitude of the esophageal body and normal peristalsis.

Stem cell autocrine CXCL12/CXCR4 stimulates invasion and metastasis of esophageal cancer.

PubMed

Wang, Xingwei; Cao, Yan; Zhang, Shirong; Chen, Zhihui; Fan, Ling; Shen, Xiaochun; Zhou, Shiwen; Chen, Dongfeng

2017-05-30

Esophageal cancer is one of the most common malignant tumors of the digestive tract. The greatest obstacle to the curing of esophageal cancer is its propensity to spread and metastasize. Esophageal cancer stem cells are considered the source for recurrence and metastasis of the tumors. While clinical evidence suggested that continuous up-regulation of CXCL12/CXCR4 was significantly associated with poor prognosis in patients with esophageal cancer, but the role and mechanism of CXCL12/CXCR4 in the invasion and metastasis of esophageal cancer has not been reported by far. This study found that esophageal cancer stem cells not only autocrine a great amount of CXCL12, but also high expression of its corresponding receptor CXCR4. Most importantly, the ability of esophageal cancer stem cells to spread and metastasize could be inhibited by blockage of CXCR4 with inhibitors or shRNA approaches both in vivo and in vitro studies. The important role of CXCL12 in the invasion and metastasis of esophageal cancer stem cells was also confirmed by loss-of-function and gain-of-function strategies. Mechanistically, we demonstrated that CXCL12/CXCR4 activated the ERK1/2 pathway and thereby ultimately maintained the characteristics of high-level invasion and metastasis of esophageal cancer stem cells. Taken together, our findings suggested that autocrine CXCL12/CXCR4 was one of the major mechanisms underlying the metastatic property of esophageal cancer stem cells through ERK1/2 signaling pathway, and might serve as a therapeutic target for esophageal cancer patients.

Esophageal cancer stem cells and implications for future therapeutics.

PubMed

Qian, Xia; Tan, Cheng; Wang, Feng; Yang, Baixia; Ge, Yangyang; Guan, Zhifeng; Cai, Jing

2016-01-01

Esophageal carcinoma (EC) is a lethal disease with high morbidity and mortality worldwide, and the incidence has been increasing in recent years. Although the diagnosis and treatment of EC have improved considerably, EC has rapidly progressed in the clinical setting and has a poor prognosis for its metastasis and recurrence. The general idea of cancer stem cells (CSCs) is primarily based on clinical and experimental observations, indicating the existence of a subpopulation of cells that can self-renew and differentiate. The EC stem cells, which can be isolated from normal pluripotent stem cells by applying similar biomarkers, may participate in promoting esophageal tumorigenesis through renewal and repair. In this review, major emphasis is given to CSC markers, altered CSC-specific pathways, and molecular targeting agents currently available to target CSCs of esophageal cancer. The roles of numerous markers (CD44, aldehyde dehydrogenase, CD133, and ATP-binding cassette subfamily G member 2) and developmental signaling pathways (Wnt/β-catenin, Notch, hedgehog, and Hippo) in isolating esophageal CSCs are discussed in detail. Targeting CSCs can be a logical strategy to treat EC, as these cells are responsible for carcinoma recurrence and chemoradiation resistance.

RNA editing is induced by type I interferon in esophageal squamous cell carcinoma.

PubMed

Zhang, Jinyao; Chen, Zhaoli; Tang, Zefang; Huang, Jianbing; Hu, Xueda; He, Jie

2017-07-01

In recent years, abnormal RNA editing has been shown to play an important role in the development of esophageal squamous cell carcinoma, as such abnormal editing is catalyzed by ADAR (adenosine deaminases acting on RNA). However, the regulatory mechanism of ADAR1 in esophageal squamous cell carcinomas remains largely unknown. In this study, we investigated ADAR1 expression and its association with RNA editing in esophageal squamous cell carcinomas. RNA sequencing applied to esophageal squamous cell carcinoma clinical samples showed that ADAR1 expression was correlated with the expression of STAT1, STAT2, and IRF9. In vitro experiments showed that the abundance of ADAR1 protein was associated with the induced activation of the JAK/STAT pathway by type I interferon. RNA sequencing results showed that treatment with type I interferon caused an increase in the number and degree of RNA editing in esophageal squamous cell carcinoma cell lines. In conclusion, the activation of the JAK/STAT pathway is a regulatory mechanism of ADAR1 expression and causes abnormal RNA editing profile in esophageal squamous cell carcinoma. This mechanism may serve as a new target for esophageal squamous cell carcinoma therapy.

The association between reflux esophagitis and airway hyper-reactivity in patients with gastro-esophageal reflux.

PubMed

Karbasi, Ashraf; Ardestani, Mohammad Emami; Ghanei, Mostafa; Harandi, Ali Amini

2013-06-01

The association of gastro-esophageal reflux (GER) with a wide variety of pulmonary disorders was recognized. We aimed to evaluate the effect of GER-induced esophagitis on airway hyper-reactivity (AHR) in patients and the response to treatment. In this cohort study, 30 patients attending the gastrointestinal clinic of a university hospital with acid reflux symptoms were included. All patients were evaluated endoscopically and divided into case group with esophagitis and control group without any evidence of esophagitis. Spirometry and methacholine test were done in all patients before and after treatment of GER with pantoprazole 40 mg daily for six months. There was a significant difference in the rate of positive methacholine test between the cases (40%) and the controls (6.7%) prior to anti-acid therapy (P < 0.0001). After six months of treatment, the frequency of positive methacholine test diminished from 40 to 13.3% in the case group (P < 0.05) but did not change in the controls (P = 0.15). The presence of esophagitis due to GER would increase the AHR and treatment with pantoperazole would decrease AHR in patients with proved esophagitis and no previous history of asthma after six months.

Manometric evaluation of the esophagus in patients with Behçet's disease.

PubMed

Bektas, Mehmet; Altan, Mehmet; Alkan, Murat; Ormeci, Necati; Soykan, Irfan

2007-01-01

Gastrointestinal (GI) involvement in Behçet's disease (BD) mainly appears in mucosa and affects 5-40% of patients, however the effects of the disease on lower esophageal sphincter (LES) pressure and esophageal contractions are not well known. The aims of this study were to evaluate esophageal motor function and to identify whether there was any specific motility pattern for patients with BD who had upper GI symptoms without endoscopic abnormality. 25 patients with BD, with a mean age of 43.1 (range 20-66) years, were admitted to our clinic whose main complaints were dyspeptic such as reflux, epigastric pain, vomiting and bloating. 25 healthy and age-matched individuals were also included in the study as controls. After one night fasting, LES pressure and esophageal contractions were measured. Esophageal motor abnormalities were detected in 16% (4/25) of these patients with manometric studies (non-specific esophageal motor disorder in 1, esophageal hypomotility in 2, and LES hypotension in 1 patient); 16% (4/25) of these patients had endoscopic findings and overall 32% (8/25) of the cases showed esophageal pathology. All cases with esophageal motor abnormalities were suffering from reflux and endoscopy showed grade B esophagitis in 2 of these cases. Median LES pressure and LES relaxation were significantly lower in patients with BD compared to the control group (16.8 +/- 10.5 vs. 20.4 +/- 6.1, p = 0.02, and 92.1 +/- 10.1 vs. 96.4 +/- 4.5, p = 0.03 respectively). Esophageal involvement in BD is significantly high. We propose manometric studies are necessary to evaluate esophageal manifestations in BD patients with esophageal symptoms even without endoscopic findings.

Fully covered stents versus partially covered stents for palliative treatment of esophageal cancer: Is there a difference?

PubMed

Alonso Lárraga, J O; Flores Carmona, D Y; Hernández Guerrero, A; Ramírez Solís, M E; de la Mora Levy, J G; Sánchez Del Monte, J C

2018-02-26

Malignant dysphagia is difficulty swallowing resulting from esophageal obstruction due to cancer. The goal of palliative treatment is to reduce the dysphagia and improve oral dietary intake. Self-expandable metallic stents are the current treatment of choice, given that they enable the immediate restoration of oral intake. The aim of the present study was to describe the results of using totally covered and partially covered esophageal stents for palliating esophageal cancer. A retrospective study was conducted on patients with inoperable esophageal cancer treated with self-expandable metallic stents. The 2 groups formed were: group A, which consisted of patients with a fully covered self-expandable stent (SX-ELLA ® ), and group B, which was made up of patients with a partially covered self-expandable stent (Ultraflex ® ). Of the 69-patient total, 50 were included in the study. Group A had 19 men and 2 women and their mean age was 63.6 years (range 41-84). Technical success was achieved in 100% (n=21) of the cases and clinical success in 90.4% (n=19). Group B had 24 men and 5 women and their mean age was 67.5 years (range 43-92). Technical success was achieved in 100% (n=29) of the cases and clinical success in 89.6% (n=26). Complications were similar in both groups (33.3 vs. 51.7%). There was no difference between the 2 types of stent for the palliative treatment of esophageal cancer with respect to technical success, clinical success, or complications. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Expert Consensus Contouring Guidelines for Intensity Modulated Radiation Therapy in Esophageal and Gastroesophageal Junction Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Abraham J., E-mail: wua@mskcc.org; Bosch, Walter R.; Chang, Daniel T.

Purpose/Objective(s): Current guidelines for esophageal cancer contouring are derived from traditional 2-dimensional fields based on bony landmarks, and they do not provide sufficient anatomic detail to ensure consistent contouring for more conformal radiation therapy techniques such as intensity modulated radiation therapy (IMRT). Therefore, we convened an expert panel with the specific aim to derive contouring guidelines and generate an atlas for the clinical target volume (CTV) in esophageal or gastroesophageal junction (GEJ) cancer. Methods and Materials: Eight expert academically based gastrointestinal radiation oncologists participated. Three sample cases were chosen: a GEJ cancer, a distal esophageal cancer, and a mid-upper esophagealmore » cancer. Uniform computed tomographic (CT) simulation datasets and accompanying diagnostic positron emission tomographic/CT images were distributed to each expert, and the expert was instructed to generate gross tumor volume (GTV) and CTV contours for each case. All contours were aggregated and subjected to quantitative analysis to assess the degree of concordance between experts and to generate draft consensus contours. The panel then refined these contours to generate the contouring atlas. Results: The κ statistics indicated substantial agreement between panelists for each of the 3 test cases. A consensus CTV atlas was generated for the 3 test cases, each representing common anatomic presentations of esophageal cancer. The panel agreed on guidelines and principles to facilitate the generalizability of the atlas to individual cases. Conclusions: This expert panel successfully reached agreement on contouring guidelines for esophageal and GEJ IMRT and generated a reference CTV atlas. This atlas will serve as a reference for IMRT contours for clinical practice and prospective trial design. Subsequent patterns of failure analyses of clinical datasets using these guidelines may require modification in the future.« less

Anti-Inflammatory Activities of Pentaherbs Formula, Berberine, Gallic Acid and Chlorogenic Acid in Atopic Dermatitis-Like Skin Inflammation.

PubMed

Tsang, Miranda S M; Jiao, Delong; Chan, Ben C L; Hon, Kam-Lun; Leung, Ping C; Lau, Clara B S; Wong, Eric C W; Cheng, Ling; Chan, Carmen K M; Lam, Christopher W K; Wong, Chun K

2016-04-20

Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD. In this study, an in vivo murine model with oxazolone (OXA)-mediated dermatitis was used to elucidate the efficacy of PHF. Active ingredients of PHF water extract were also identified and quantified, and their in vitro anti-inflammatory activities on pruritogenic cytokine IL-31- and alarmin IL-33-activated human eosinophils and dermal fibroblasts were evaluated. Ear swelling, epidermis thickening and eosinophils infiltration in epidermal and dermal layers, and the release of serum IL-12 of the murine OXA-mediated dermatitis were significantly reduced upon oral or topical treatment with PHF (all p < 0.05). Gallic acid, chlorogenic acid and berberine contents (w/w) in PHF were found to be 0.479%, 1.201% and 0.022%, respectively. Gallic acid and chlorogenic acid could suppress the release of pro-inflammatory cytokine IL-6 and chemokine CCL7 and CXCL8, respectively, in IL-31- and IL-33-treated eosinophils-dermal fibroblasts co-culture; while berberine could suppress the release of IL-6, CXCL8, CCL2 and CCL7 in the eosinophil culture and eosinophils-dermal fibroblasts co-culture (all p < 0.05). These findings suggest that PHF can ameliorate allergic inflammation and attenuate the activation of eosinophils.

Safety and benefit of curative surgical resection for esophageal squamous cell cancer associated with multiple primary cancers.

PubMed

Otowa, Y; Nakamura, T; Takiguchi, G; Yamamoto, M; Kanaji, S; Imanishi, T; Oshikiri, T; Suzuki, S; Tanaka, K; Kakeji, Y

2016-03-01

Enhancements in surgical techniques have led to improved outcomes for esophageal cancer. Recent findings have showed that esophageal cancer is frequently associated with multiple primary cancers, and surgical resection is usually complicated in such cases. The aim of this study was to clarify the clinical significance of surgery for patients with esophageal squamous cell cancer associated with multiple primary cancers. The clinical outcomes of surgical resection for esophageal cancer were compared among 79 patients with antecedent and/or synchronous cancers (Multiple cancer group) and 194 patients without antecedent and/or synchronous cancers (Single cancer group). The most common site of multiple primary cancers was the pharynx (36 patients; 29.7%), followed by the stomach (24 patients; 19.8%). The reconstruction method was more complicated in the Multiple cancer group as a result of the prolonged surgery time and increased blood loss. However, postoperative morbidity and overall survival (OS) did not differ between the two groups. After esophagectomy, metachronous cancers were observed in 26 patients, with 30 regions in total, and 93.1% were found to be curable. Sex was the only independent risk factors for developing metachronous cancer after esophagectomy. The presence of antecedent and synchronous cancers complicates the surgical resection of esophageal cancer; however, no differences were found in the OS and postoperative morbidity between the two groups. Therefore, surgical intervention should be selected as a first-line treatment. Because second primary cancers are often observed in esophageal cancer, we recommend a close follow-up using esophagogastroduodenoscopy and contrast-enhanced computed tomography. Copyright © 2015 Elsevier Ltd. All rights reserved.

Obesity's effect on asthma extends to diagnostic criteria.

PubMed

Lugogo, Njira; Green, Cynthia L; Agada, Noah; Zhang, Siyi; Meghdadpour, Susanne; Zhou, Run; Yang, Siyun; Anstrom, Kevin J; Israel, Elliot; Martin, Richard; Lemanske, Robert F; Boushey, Homer; Lazarus, Stephen C; Wasserman, Stephen I; Castro, Mario; Calhoun, William; Peters, Stephen P; DiMango, Emily; Chinchilli, Vernon; Kunselman, Susan; King, Tonya S; Icitovic, Nikolina; Kraft, Monica

2018-03-01

The use of inflammatory biomarkers to delineate the type of lung inflammation present in asthmatic subjects is increasingly common. However, the effect of obesity on these markers is unknown. We aimed to determine the effect of obesity on conventional markers of inflammation in asthmatic subjects. We performed secondary analysis of data from 652 subjects previously enrolled in 2 Asthma Clinical Research Network trials. We performed linear correlations between biomarkers and logistic regression analysis to determine the predictive value of IgE levels, blood eosinophil counts, and fraction of exhaled nitric oxide values in relationship to sputum eosinophil counts (>2%), as well as to determine whether cut points existed that would maximize the sensitivity and specificity for predicting sputum eosinophilia in the 3 weight groups. Overall, statistically significant but relatively weak correlations were observed among all 4 markers of inflammation. Within obese subjects, the only significant correlation found was between IgE levels and blood eosinophil counts (r = 0.33, P < .001); furthermore, all other correlations between inflammatory markers were approximately 0, including correlations with sputum eosinophil counts. In addition, the predictive value of each biomarker alone or in combination was poor in obese subjects. In fact, in obese subjects none of the biomarkers of inflammation significantly predicted the presence of high sputum eosinophil counts. Obese asthmatic subjects have lower cut points for IgE levels (268 IU), fraction of exhaled nitric oxide values (14.5 ppb), and blood eosinophil counts (96 cells/μL) than all other groups. In obese asthmatic subjects conventional biomarkers of inflammation are poorly predictive of eosinophilic airway inflammation. As such, biomarkers currently used to delineate eosinophilic inflammation in asthmatic subjects should be approached with caution in these subjects. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Eosinophil-rich trichoblastic carcinoma with aggressive clinical course in a young man.

PubMed

Toberer, Ferdinand; Rütten, Arno; Requena, Luis; Kazakov, Dmitry V; Enk, Alexander; Hartschuh, Wolfgang; Haenssle, Holger A

2017-11-01

We present the case of a 35-year-old man who developed a follicular differentiated cutaneous carcinoma with an eosinophil-rich infiltrate and an aggressive clinical behavior. After an in-depth histopathological investigation the diagnosis of trichoblastic carcinoma was made. Over the course of the disease the patient developed a cutaneous in-transit metastasis as well as an axillary lymph node metastasis 18 months after the excision of the primary tumor on his back. Based on a literature review we discuss the different concepts behind the term "trichoblastic carcinoma" and we summarize the clinical and histological details of previously reported cases. Furthermore, we focus on the phenomenon of tumor-associated eosinophilia. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The role of macrophages and eosinophils in reactive lesions of the oral cavity.

PubMed

Aghbali, Amir Ala; Akbarzadeh, Ayshin; Kouhsoltani, Maryam

2018-01-01

Many studies have reported that macrophages and eosinophils are involved in the pathogenesis of several diseases. To the best of our knowledge, this is the first study comparing macrophages and eosinophils in oral reactive lesions. In this study, we aimed to determine the contribution of macrophages and eosinophils to the pathogenesis of oral reactive lesions and the relationships between these biomarkers and the diverse histopathologic features. Seventy-five paraffin-embedded tissue samples were assessed in this study. Five categories (15 cases for each group), including peripheral ossifying fibroma, pyogenic granuloma, fibroma, inflammatory fibrous hyperplasia, and peripheral giant-cell granuloma, were considered. Anti-CD68 immunohistochemical and hematoxylin-eosin staining was carried out. We found that macrophages, but not eosinophils, were a significant internal component of oral reactive lesions. Macrophages were observed in high densities in all studied groups and diffusely distributed or clustered throughout these lesions. The number of macrophages was increased in peripheral giant-cell granuloma compared with other groups. Our findings suggest that macrophages are involved in the pathogenesis and the variation of microscopic features of oral reactive lesions. However, further clinical studies should be conducted to identify the biological process behind macrophages and the molecular interactions of these cells, with the ultimate aim of suggesting a new potential therapeutic target for these lesions. We found that eosinophils were not involved in the fibrotic process and the variation of microscopic features in oral reactive lesions. Our results showed that peripheral giant-cell granulomas highly demonstrated histiocytic characteristics.

Eosinophilic colitis in infants.

PubMed

Lozinsky, Adriana Chebar; Morais, Mauro Batista de

2014-01-01

To review the literature for clinical data on infants with allergic or eosinophilic colitis. MEDLINE search of all indexes was performed using the words "colitis or proctocolitis and eosinophilic" or "colitis or proctocolitis and allergic" between 1966 and February of 2013. All articles that described patients' characteristics were selected. A total of 770 articles were identified, of which 32 met the inclusion criteria. The 32 articles included a total of 314 infants. According to the available information, 61.6% of infants were male and 78.6% were younger than 6 months. Of the 314 patients, 49.0% were fed exclusively breast milk, 44.2% received cow's milk protein, and 6.8% received soy protein. Diarrheal stools were described in 28.3% of patients. Eosinophilia was found in 43.8% (115/263) of infants. Colonic or rectal biopsy showed infiltration by eosinophils (between 5 and 25 per high-power field) in 89.3% (236/264) of patients. Most patients showed improvement with the removal of the protein in cow's milk from their diet or the mother's diet. Allergy challenge tests with cow's milk protein were cited by 12 of the 32 articles (66 patients). Eosinophilic colitis occurs predominantly in the first six months of life and in males. Allergy to cow's milk was considered the main cause of eosinophilic colitis. Exclusion of cow's milk from the diet of the lactating mother or from the infant's diet is generally an effective therapeutic measure. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Acute secondary effects in the esophagus in patients undergoing radiotherapy for carcinoma of the lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mascarenhas, F.; Silvestre, M.E.; Sa da Costa, M.

1989-02-01

The incidence and nature of acute secondary irradiation esophagitis was studied in a series of 38 patients undergoing 60Co teletherapy for carcinoma of the lung. Thirty-four patients were male and four female, with ages ranging from 38 to 78 years. The mediastinum being irradiated in the process, all the patients underwent endoscopy for signs of esophagitis and/or gastritis after a dose of 30-40 Gy was delivered to the esophagus. Eighteen patients complained of dysphagia, but only in 12 of them did endoscopy show esophagitis. Of the remaining patients without complaints five had endoscopic signs of esophagitis. Gastritis was found inmore » 18 cases and confirmed histologically in 14. In 17 cases, esophagitis and/or gastritis were confirmed histologically. It is believed that there is a fairly close correlation among clinical, endoscopic, and histological findings to support the claim that esophagitis in these patients is radiation induced. However, the cause of gastritis is not well understood. Data in the literature suggest that nonsteroid anti-inflammatory agents can act as prophylactic means of preventing radiation esophagitis.« less

The pathogenesis of pseudoachalasia: a clinicopathologic study of 13 cases of a rare entity.

PubMed

Liu, Wendy; Fackler, William; Rice, Thomas W; Richter, Joel E; Achkar, Edgar; Goldblum, John R

2002-06-01

Pseudoachalasia is an esophageal motor disorder usually associated with malignancy that has clinical, radiographic, and manometric findings that are often indistinguishable from primary achalasia. There are few reports examining the histologic features of the associated neoplasms and their relationship with the esophageal myenteric plexus. We studied the clinical and pathologic features of 13 cases of pseudoachalasia seen at our institution between 1979 and 1999. Detailed clinical and radiographic data were obtained from medical records. In all cases available histologic material was reviewed to confirm the presence and type of associated neoplasm. When possible, the relationship of the neoplasm to the esophageal myenteric plexus was examined. In selected cases immunohistochemical stains were performed to further evaluate this relationship. All patients had clinical, radiographic, and manometric features similar to primary achalasia. The cohort included seven men and six women, age range 24-79 years (median 61 years). Associated neoplasms included esophageal adenocarcinoma arising in Barrett's esophagus (n = 1), adenocarcinoma of the esophagogastric junction (n = 7), metastatic renal cell carcinoma to the esophagogastric junction (n = 1), breast adenocarcinoma (n = 1), pulmonary small cell carcinoma (n = 1), pleural malignant mesothelioma (n = 1), and mediastinal fibrosis (n = 1). The mechanism of pseudoachalasia was consistent with neoplastic infiltration of the esophageal myenteric plexus in 11 cases. Neoplastic cells surrounded myenteric ganglion cells, which appeared normal in number and morphology. In the patient with pulmonary small cell carcinoma, there was no evidence of neoplastic infiltration of the esophagogastric junction, and anti-ANNA-1 antibody was detected, suggesting a paraneoplastic syndrome. Tissue obtained at the time of esophagomyotomy revealed lymphocytic myenteric inflammation and marked depletion of ganglion cells identical to that seen in primary achalasia. The mechanism pseudoachalasia in the patient with breast adenocarcinoma is uncertain, as there was no evidence of direct involvement of the esophagogastric junction. In summary, we describe 13 cases of pseudoachalasia resulting in a clinical syndrome indistinguishable from primary achalasia. The most common mechanism is direct involvement of the esophageal myenteric plexus by neoplastic cells. Rarely, a distant neoplasm may cause this syndrome as a paraneoplastic process.

Diagnostic value of eosinophils in pleural effusion: a prospective study of 26 cases.

PubMed

Matthai, Smita Mary; Kini, Usha

2003-02-01

Eosinophilic pleural effusions (EPFs), defined as the presence of 10% or more eosinophils in the pleural fluid, are relatively rare. Their diagnostic and prognostic significance, however, remains controversial, as most of the studies are based almost entirely on retrospective case studies. This prospective study examines 26 eosinophilic pleural effusions from among 444 consecutive pleural effusions investigated at this tertiary health care center from October 1999 to April 2002. This study was attempted to unravel the diagnostic and prognostic significance of these eosinophilic effusions and assess their clinical implications, if any. Koss and Light's criteria were applied in the analysis, which comprised macroscopic, biochemical, cytological, and microbiological examinations. Of the 26 EPFs studied, five were associated with tuberculosis and three with metastatic disease. Nineteen patients had significant associated lymphocytosis. Twenty-four patients have been followed up and are in good health to date and have had no recurrence of effusion. Thus, EPF could be associated with inflammatory, benign, and malignant conditions. Hence, a closer search for a definite etiological agent is warranted in the setting of such an effusion, especially in populations endemic for tuberculosis, as in a developing country like India and in populations with a high prevalence of malignancy. Copyright 2003 Wiley-Liss, Inc.

Impact on Health-Related Quality of Life in Adults with Eosinophilic Gastritis and Gastroenteritis: A Qualitative Assessment.

PubMed

Bedell, Alyse; Taft, Tiffany; Craven, Meredith R; Guadagnoli, Livia; Hirano, Ikuo; Gonsalves, Nirmala

2018-05-01

Eosinophilic gastritis (EG) and eosinophilic gastroenteritis (EGE) are chronic immune-mediated conditions of the digestive tract, which affect the stomach only, or the stomach and small intestines, respectively. Though these disorders are uncommon, they are being increasingly recognized and diagnosed. While health-related quality of life (HRQOL) has been evaluated in other eosinophilic gastrointestinal diseases, this study is the first to describe HRQOL impacts unique to EG/EGE. This study aims to qualitatively describe experiences of adults diagnosed with EG and EGE. We aim to identify impacts on HRQOL in this population in order to inform clinical care and assessment. Seven patients diagnosed with EG or EGE participated in semi-structured interviews assessing common domains of HRQOL. Four distinct themes emerged from qualitative analyses, which represent impacts to HRQOL: the psychological impact of the diagnosis, impact on social relationships, financial impact, and impact on the body. These generally improved over time and with effective treatment. This study demonstrated that patients with EG/EGE experience impacts to HRQOL, some of which differ from HRQOL of other eosinophilic gastrointestinal diseases. These results support the development of a disease-specific measure, or adaptation of an existing measure, to assess HRQOL in EG/EGE.

Clinical Characteristics and Treatment Response of Peripheral Neuropathy in the Presence of Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Experience at a Single Tertiary Center.

PubMed

Cho, Hye Jin; Yune, Sehyo; Seok, Jin Myoung; Cho, Eun Bin; Min, Ju Hong; Seo, Yeon Lim; Lee, Byung Jae; Kim, Byoung Joon; Choi, Dong Chull

2017-01-01

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic small-vessel vasculitis accompanied by asthma, eosinophilia, and eosinophilic inflammation of various tissues including the peripheral nerves. This study investigated the clinical course and long-term outcomes of peripheral neuropathy in patients with EGPA. Seventy-one patients with physician-diagnosed EGPA were identified at Samsung Medical Center between January 1995 and April 2014. Sixty-one of these patients were followed-up for more than 1 year and received corticosteroid therapy with or without intravenous cyclophosphamide pulse therapy for 6 to 18 months. Medical records of the 61 patients including demographic data, clinical features, laboratory and pathological findings, treatments, and outcomes were reviewed. Peripheral neuropathy as a manifestation of EGPA was present in 46 (75%) of the 61 patients. The mean follow-up duration of the patients with neuropathy was 6.4 years (range 1.2-18.8 years). The scores on the neurological functional disability scale before and after the combination treatment with corticosteroid and cyclophosphamide were 2.43±0.86 and 0.54±0.95 (mean±SD; p<0.001), respectively. The peripheral neuropathy relapsed in one patient. The long-term clinical outcome of peripheral neuropathy in patients with EGPA receiving initial corticosteroid and cyclophosphamide combination therapy was favorable with a very low relapse rate.

Clinical lesson: eosinophilic oesophagitis, a new diagnosis to swallow

PubMed Central

Lamb, C A; Kanakala, V; Stirling, R W; Attwood, S E A

2010-01-01

Eosinophilic oesophagitis (EoE) is a recently described condition that has gained increasing recognition over the past 5 years. Despite this, many clinicians remain unaware of EoE, often leading to diagnostic delay and therefore significant morbidity. The diagnosis of EoE should be considered in any patient with a history of intermittent or continuous dysphagia, or oesophageal food impaction. It should be strongly suspected in young patients, particularly men, presenting with dysphagia and a history of atopy. Here, three patients are presented that highlight common features of EoE. In addition, a clinical review of the worldwide literature is provided to heighten physician awareness and understanding of the condition. PMID:28839538

HIV seronegative eosinophilic pustular folliculitis successfully treated with doxicycline.

PubMed

Brazzelli, V; Barbagallo, T; Prestinari, F; Ciocca, O; Vassallo, C; Borroni, G

2004-07-01

Eosinophilic pustular folliculitis (EPF) is an unusual disease, first described in adult East Asians in 1970 by Ofuji. It is characterized by follicular papules and pustules tending to coalesce and form plaques involving the trunk, face and extremities. In recent years, it has been often associated with human immunodeficiency virus (HIV) infection or with immunosuppressed and/or oncohaematological patients. EPF has been described in immunocompetent adult caucasian patients only occasionally. The diagnosis requires clinical and microbiological features such as sterile folliculitis and histopathological findings characterized by folliculitis and perifolliculitis with eosinophilic infiltrate. We describe an HIV seronegative caucasian male with EPF, allergic to non-steroidal anti-inflammatory drugs and indomethacin, treated with oral doxicycline. The treatment led to the complete remission of the lesions within 2 months.

Clinical evaluation of radiotherapy for advanced esophageal cancer after metallic stent placement

PubMed Central

Yu, You-Tao; Yang, Guang; Liu, Yan; Shen, Bao-Zhong

2004-01-01

AIM: To evaluate the therapeutic effect of radiotherapy for esophageal cancer after expandable metallic stent placement. METHODS: Ten cases of advanced esophageal cancer were evaluated, 7 having complete obstruction and 3 with digestive-respiratory fistula. Ten nitinol stents were placed at the site of stenosis. Patients were treated with a total dose of 1200 cGy divided into 3 fractions of 400 cGy 4-7 d after stents placement. RESULTS: All the 10 stents were placed successfully at one time. After radiotherapy for advanced esophageal cancer, the survival period of the cases ranged from 14 to 22 mo, with a mean survival of 17 mo. No re-stenosis occurred among all the 10 cases. CONCLUSION: Stent placement combined with radiotherapy for esophageal cancer is helpful to prolong patients’ survival and reduce occurrence of re-stenosis. PMID:15237455

Differential diagnosis of CNS angiostrongyliasis: a short review.

PubMed

Senthong, Vichai; Chindaprasirt, Jarin; Sawanyawisuth, Kittisak

2013-06-01

The diagnostic criterion for eosinophilic meningitis (EOM) is the identification of an absolute count of 10 eosinophils per ml or more than 10% of the total white blood cells in the cerebrospinal fluid (CSF) in the proper clinical context. The most common cause of EOM is Angiostrongylus cantonensis infection, termed meningitic angiostrongyliasis (MA). Neurognathostomiasis (NG) is the main parasitic disease in the differential diagnosis of meningitic angiostrongyliasis. This short review is based on articles published on Medline between 2000 and 2012 related to EOM. There are three main approaches that can be used to differentiate between MA and NG, involving clinical factors, history of larval exposure, and serological tests. MA patients presented with acute severe headache but without neurological deficit, combined with a history of eating uncooked snails or slugs. NG patients always presented with motor weakness, migratory swelling, radicular pain and had history of eating uncooked poultry or fish. Specific antigenic bands in immunoblot tests are helpful tools to differentiate the two diseases. Other causes of eosinophilic meningitis are neurocysticercosis, cerebral paragonimiasis, Toxoplasma canis, Baylisascaris, tuberculous meningitis, and cryptococcal meningitis.

Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications.

PubMed

Baba, Yoshifumi; Iwatsuki, Masaaki; Yoshida, Naoya; Watanabe, Masayuki; Baba, Hideo

2017-06-01

Esophageal cancer ranks among the most aggressive malignant diseases. The limited improvements in treatment outcomes provided by conventional therapies have prompted us to seek innovative strategies for treating this cancer. More than 100 trillion microorganisms inhabit the human intestinal tract and play a crucial role in health and disease conditions, including cancer. The human intestinal microbiome is thought to influence tumor development and progression in the gastrointestinal tract by various mechanisms. For example, Fusobacterium nucleatum , which primarily inhabits the oral cavity and causes periodontal disease, might contribute to aggressive tumor behavior through activation of chemokines such as CCL20 in esophageal cancer tissue. Composition of the intestinal microbiota is influenced by diet, lifestyle, antibiotics, and pro- and prebiotics. Therefore, by better understanding how the bacterial microbiota contributes to esophageal carcinogenesis, we might develop novel cancer prevention and treatment strategies through targeting the gastrointestinal microflora. This review discusses the current knowledge, available data and information on the relationship of microbiota with esophagitis, Barrett's esophagus, esophageal adenocarcinoma and squamous cell carcinoma.

Clinical value of integrated-signature miRNAs in esophageal cancer.

PubMed

Zhang, Heng-Chao; Tang, Kai-Fu

2017-08-01

MicroRNAs (miRNAs) are crucial regulators of gene expression in tumorigenesis and are of great interest to researchers, but miRNA profiles are often inconsistent between studies. The aim of this study was to confirm candidate miRNA biomarkers for esophageal cancer from integrated-miRNA expression profiling data and TCGA (The Cancer Genome Atlas) data in tissues. Here, we identify five significant miRNAs by a comprehensive analysis in esophageal cancer, and two of them (hsa-miR-100-5p and hsa-miR-133b) show better prognoses with significant difference for both 3-year and 5-year survival. Additionally, they participate in esophageal cancer occurrence and development according to KEGG and Panther enrichment analyses. Therefore, these five miRNAs may serve as miRNA biomarkers in esophageal cancer. Analysis of differential expression for target genes of these miRNAs may also provide new therapeutic alternatives in esophageal cancer. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

SATB1 plays an oncogenic role in esophageal cancer by up-regulation of FN1 and PDGFRB.

PubMed

Song, Guiqin; Liu, Kang; Yang, Xiaolin; Mu, Bo; Yang, Junbao; He, Lang; Hu, Xin; Li, Qiujiang; Zhao, Yunxia; Cai, Xiaoming; Feng, Gang

2017-03-14

Esophageal cancer is a highly aggressive malignancy with very poor overall prognosis. Given the strong clinical relevance of SATB1 in esophagus cancer and other cancers suggested by previous studies, the exact function of SATB1 in esophagus cancer development is still unknown. Here we showed that the knockdown of SATB1 in esophageal cancer cell lines diminished the cell proliferation, survival and invasion. Whole genome transcriptome analysis of SATB1 knockdown cells revealed the different gene expression profiles between TE-1 cells and MDA-MB-231 cells. Network analysis and functional experiments further identified FN1 and PDGFRB to be key downstream genes regulated by SATB1 in esophageal cancer cells. Importantly, FN1 and PDGFRB were found to be highly expressed in human esophageal cancer. In summary, we provided the first molecular evidence that SATB1 played an oncogenic role in esophageal cancer by up-regulation of FN1 and PDGFRB.