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 Eosinophilic Esophagitis
 Eosinophilic Esophagitis
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 Eosinophilic Esophagitis
 Eosinophilic Esophagitis
 Eosinophilic Esophagitis
 Eosinophilic Esophagitis
 Eosinophilic Esophagitis
 Eosinophilic Esophagitis
 Eosinophilic Esophagitis
 Eosinophilic Esophagitis
 Eosinophilic Esophagitis
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 Eosinophilic Esophagitis
 Eosinophilic Esophagitis
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Eosinophilic Esophagitis

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Eosinophilic Esophagitis …

Eosinophilic Esophagitis

Presented by Sadudee boonmee, MD.

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  • multiple biopsy specimens from the proximal and distal esophagus should be obtained and evaluated for a variety of pathologic features สิ่งที่ pathologist ควรรายงาน Peak eosinophil value (obtained from the area with the highest density of eosinophils), eosinophilic microabscesses, surface layering of eosinophils, extracellular eosinophil granules, basal cell hyperplasia, dilated intercellular spaces, and lamina propria fibrosis
  • Thus, in adult patients presenting with dysphagia, EoE should be strongly considered in the differential diagnosis.
  • Esophageal biopsy specimens should be taken to seek histologic evidence of EoE in patients with unexplained dysphagia, even if results of endoscopy appear normal or identify a potential cause of dysphagia other than EoE.
  • - นอกจาก symptom and endoscopic finding แล้ว Eo count in Esophageal tissue ก็ช่วย Dx EoE But not specific for EoE 100% becoz many other condition can result in signinicant Eo eg. Severe GERD
  • Extracellular Eo granule : major basic protein deposition, Eosinophil peroxidase, eosinophil derived neurotoxin This eosinophilic degranulation likely plays a role in the development of subepithelial esophageal fibrosis, a long-term complication of EoE, and itself acting as a marker that, if present, also suggests a diagnosis of EoE over GERD
  • Standardized of the unit of Eo enumeration validated of histologic feature may help to compare btw study and help to distinguish EoE from non EoE
  • Retrospective analysis 234 children (mean age 7.3 y, median age 7.0 y, and age range 0.2 to 19.5 y)
  • Tree and grass pollen levels can directly correlate with the numbers of patients given a diagnosis of EoE
  • 1.Distinguishing eosinophilic esophagitis in pediatric patients: clinical, endoscopic, and histologic features of an emerging disorder 2 3 Atopic Characteristics of Adult Patients With Eosinophilic Esophagitis
  • cross-sectional study of 53 pediatric patients with EE relevant history was obtained by questionnaire, and patch testing to foods Food and inhalant sensitivities were also assessed using skin prick testing and serum specific IgE measurement
  • Effective, but difficult to adhere, requirement large volumes to meet caloric needs
  • No randomized, prospective trials yet exist comparing the two elimination methods
  • SFED treatment associated with clinical and histologic improvement in EE in an observational study. It offers advantages of better acceptance, cost, and compliance than ELED and should be considered as an option in the initial management of children with EE
  • 1. cysteinyl leukotrienes are known eosinophil chemoattractants, One early study reported that montelukast at a dosage of 20 to 40 mg daily resolved symptoms in 6 out of 8 adult patients with EoE, but tissue eosinophilia remained 2. cysteinyl leukotriene levels not to be increased in patients with EoE
  • Transcript

    • 1. Eosinophilic Esophagitis : Diagnosis and Management Sadudee Boonmee Klakayan, MD
    • 2. Outline <ul><li>Prevalence </li></ul><ul><li>Diagnosis </li></ul><ul><li>Clinical presentation </li></ul><ul><li>Endoscopic and Histologic finding </li></ul><ul><li>Allergic evaluation </li></ul><ul><li>Treatment </li></ul><ul><li>- Dietary </li></ul><ul><li>- Pharmacotherapy </li></ul><ul><li>- Esophageal dilatation </li></ul>
    • 3. Prevalence <ul><li>Atopic male (male/female ratio 2:1 to 3:1) presents in childhood or during the third or fourth decades of life </li></ul><ul><li>White, non-Hispanic </li></ul><ul><li>Prevalence is increasing with rate 6-30 cases/100,000 </li></ul><ul><li>EoE in the United States 52/100,000 </li></ul>LIACOURAS ET AL, J Allergy Clin Immunol 2011;128:3-20.
    • 4. Pathogenesis Current Opinion in Allergy and Clinical Immunology 2010, 10:231–237
    • 5. Definition <ul><li>A chronic, immune/ antigen-mediated esophageal disease characterized clinically by - symptoms related to esophageal dysfunction </li></ul><ul><li>- histologically by eosinophil-predominant inflammation </li></ul>LIACOURAS ET AL, J Allergy Clin Immunol 2011;128:3-20.
    • 6. Diagnosis <ul><li>1. Symptoms related to esophageal dysfunction </li></ul><ul><li>2. One or more esophageal biopsy specimens show 15 Eo/hpf (peak value) </li></ul><ul><li>(minimum threshold for a diagnosis of EoE) </li></ul><ul><li>3. Disease is isolated to the esophagus (other causes of esophageal eosinophilia should be excluded ) </li></ul><ul><li>4. Disease remit with treatments of dietary exclusion, topical corticosteroids, or both </li></ul>
    • 7. Eosinophil associated Esophagitis ( Rothenberg, J Allergy Clin Immunol 2004;113:11-28.)
    • 8. LIACOURAS ET AL J Allergy Clin Immunol 2011;128:3-20.
    • 9. Most common clinical manifestration Mirna Chehade and Seema S. Aceves Current Opinion in Allergy and Clinical Immunology 2010, 10:231–237 Age Clinical presentation Infant and Toddlers feeding difficulties,feeding refusal or intolerance, irritability, vomiting, failure to thrive School-aged children Abdominal pain, vomiting, GERD-like symptoms, difficulty swallowing, food aversion/self-limited diet, failure to thrive Adolescents Dysphagia, esophageal food impactions, nausea, GERD-like symptoms, self-limited diet Adult Dysphagia, esophageal food impactions
    • 10. Clinical Manifestration <ul><li>Adult : Steriotypical symptom </li></ul><ul><li>- Dysphagia </li></ul><ul><li>- Chest pain </li></ul><ul><li>- Food impaction </li></ul><ul><li>- Upper abdominal pain </li></ul>LIACOURAS ET AL J Allergy Clin Immunol 2011;128:3-20.
    • 11. <ul><li>Patients presenting with dysphagia in endoscopy units, EoE has prevalence up to 12% to 15% </li></ul><ul><li>Food impaction is common in patients with histologic evidence consistent with EoE high as 40% at a median follow-up of 15 years </li></ul><ul><li>Food impaction necessitating endoscopic bolus removal occurs in 33% to 54% of adults with EoE </li></ul>Am J Gastroenterol 2007;102(12):2627–32. J Allergy Clin Immunol 2011;128:132-8. Gastrointest Endosc 2005;61:795-801
    • 12. <ul><li>Any pt with symptom suggestive of EoE should undergo careful history focus on eating and swallowing habits </li></ul><ul><li>Children and adult with EoE often rapidly adapt eating habits to manage their impaired esophageal function </li></ul>LIACOURAS ET AL J Allergy Clin Immunol 2011;128:3-20.
    • 13. EoE vs GERD ( Rothenberg, J Allergy Clin Immunol 2004;113:11-28.)
    • 14. LIACOURAS ET AL J Allergy Clin Immunol 2011;128:3-20. LIACOURAS ET AL J Allergy Clin Immunol 2011;128:3-20.
    • 15. Endoscopic Finding <ul><li>Esophageal endoscopy with biopsy  reliable diagnostic test for EoE </li></ul><ul><li>Appropriate clinical setting + any endoscopic finding supports but not establish the Dx of EoE </li></ul><ul><li>2 to 4 mucosal specimens of the proximal and distal esophagus should be obtain </li></ul>
    • 16. Endoscopic Finding <ul><li>Fixed esophageal rings (corrugated rings or </li></ul><ul><li>trachealization) </li></ul><ul><li>Transient esophageal rings (feline folds or felinization), </li></ul><ul><li>Whitish exudates </li></ul><ul><li>Longitudinal furrows </li></ul><ul><li>Edema </li></ul><ul><li>Diffuse esophageal narrowing </li></ul><ul><li>Narrow-caliber esophagus </li></ul><ul><li>Esophageal lacerations by passage of the endoscope </li></ul>Can be predictive but not pathognomonic for EoE
    • 17. Normal Esophagous Esophageal furrowing White mucosal plaques
    • 18. Esophageal ring trachealization Small-caliber esophagus with mucosal tearing after endoscopy
    • 19. Radiography <ul><li>Not a recommended routinely </li></ul><ul><li>Helpful in selected cases </li></ul><ul><li>anatomic abnormalities difficult to endoscope </li></ul><ul><li>esophageal strictures (length and diameter) </li></ul>LIACOURAS ET AL J Allergy Clin Immunol 2011;128:3-20.
    • 20. Histologic Finding <ul><li>At least 15 Eo/HPF in the maximally affected esophageal tissue </li></ul><ul><li>Histopathologic features of esophageal mucosal biopsy must be interpreted in with the patient’s clinical information </li></ul>LIACOURAS ET AL J Allergy Clin Immunol 2011;128:3-20.
    • 21. Typical finding associated with EoE > GERD Histologic Finding <ul><ul><li>Mucosal eosinophilia </li></ul></ul><ul><ul><li>Eosinophil microabscess formation </li></ul></ul><ul><ul><li>Superficial layering of eosinophils </li></ul></ul><ul><ul><li>Extracellular eosinophil granules </li></ul></ul><ul><ul><li>Epithelial desquamation </li></ul></ul><ul><ul><li>Basal zone hyperplasia </li></ul></ul><ul><ul><li>Rete peg elongation </li></ul></ul><ul><ul><li>Dilated intercellular spaces </li></ul></ul><ul><ul><li>Subepithelial fibrosis/sclerosis–lamina propria fibrosis </li></ul></ul><ul><ul><li>Mastocytosis and mast cell degranulation </li></ul></ul><ul><ul><li>CD8+ lymphocytes and B cells </li></ul></ul>
    • 22. Normal esophagous EoE Superficial layering of surface Eo Microabcess
    • 23. Distinguishing Eosinophilic Esophagitis in Pediatric Patients <ul><li>Retrospective case-control study </li></ul><ul><li>Children with esophageal eosinophilic inflammation who underwent esophageal biopsy ( EoE and non EoE) </li></ul>J Clin Gastroenterol Volume 41, Number 3, March 2007 Eo > 20/hpf
    • 24. Histologic Finding <ul><li>EoE might be focal and not be present in all biopsy specimens </li></ul><ul><li>Peak number vs average number of Eo/hpf </li></ul><ul><li>Site and number of biopsy </li></ul><ul><li> Affect Eo count </li></ul>LIACOURAS ET AL J Allergy Clin Immunol 2011;128:3-20.
    • 25. <ul><li>Esophageal pH monitoring (and pH impedance ) useful diagnostic test to evaluate for GERD in patients with esophageal eosinophilia </li></ul><ul><li>Peripheral eosinophil counts: patients EoE, 40% to 50% having increased numbers of circulating eosinophils (>300-350 per mm3) </li></ul><ul><li>Total IgE : inadequate data to support the measuring the total IgE level as a surrogate disease in patients with EoE. </li></ul>
    • 26. Allergic evaluation <ul><li>EoE is an antigen-driven allergic condition </li></ul><ul><li>EoE patient </li></ul><ul><li>- 28% to 86% of adults </li></ul><ul><li>- 42% to 93% of pediatric </li></ul><ul><li>50% to 60% of patients with EoE have a prior history of atopy </li></ul><ul><li>Major of patients have sensitization to food allergens, aeroallergens, or both (SPT or Specific IgE ) </li></ul>Have another allergic disease LIACOURAS ET AL J Allergy Clin Immunol 2011;128:3-20.
    • 27. nejm 2004 351(9) 940-941
    • 28. Evaluation of aeroallergen sensitization <ul><li>Aeroallergen-specific IgE </li></ul><ul><li>44% to 86% of patients have serum IgE to outdoor, indoor, or both aeroallergens </li></ul><ul><li>SPT to aeroallergen (pediatric and adult) </li></ul><ul><li>- outdoor aeroallergens (grass, weeds, trees, and molds) 64% to 93% </li></ul><ul><li>- indoor aeroallergens (dog, cat, cockroach, and dust mites) 16% to 69% </li></ul>LIACOURAS ET AL J Allergy Clin Immunol 2011;128:3-20.
    • 29. Studies Atopic disease Evidence of IgE to Aeroallergen Evidence of IgE to Food Aceves et al, J Clin Gastroenterol Vol 41, No 3, March 2007 Asthma 47% AR 40 % Eczema 4% + aeroallergen RAST 44% + food RAST 60% Collins et al, Clin Gastro and Hepato Vol. 6, No. 6 Asthma 52% AR 68 % Eczema 44% AC 56 % + SPT aeroallergen 71% + SPT food 76% ROY–GHANTA et al, Clin Gastro and Hepato Vol. 6, No. 5 Asthma 26% AR 78% AD 4% Specific IgE aeroallergen 86% ( Birch pollen ,Timothy ryegrass pollen Ragweed pollen , dust mite Pet dander ) Specific IgE for food 83%
    • 30. Is There a Seasonal Variation in the Incidence or Intensity of Allergic Eosinophilic Esophagitis in Newly Diagnosed Children? Winter had significantly fewer newly diagnosed patients with AEE when compared with Spring, Summer, and Fall individually (P=0.0008, P=0.0001, P=0.0118,respectively) Flint Y. J Clin Gastroenterol 2007;41:451–453
    • 31. Seasonal Distribution in Newly Diagnosed Cases of Eosinophilic Esophagitis in Adults signifi cant increase of EoE cases in spring and summer months ( n = 28) when compared with the fall and winter months ( n = 13) ( P = 0.019) Am J Gastroenterol 2009; 104:828 – 833;
    • 32. <ul><li>Complete evaluation of patients with EoE for aeroallergen sensitization might alter clinical management. </li></ul>LIACOURAS ET AL J Allergy Clin Immunol 2011;128:3-20.
    • 33. Evaluation of Food sensitization <ul><li>Food - specific IgE </li></ul><ul><li>- 50% of adult with EoE had positive at least 1 food, most common peanut 38%, egg 27%, and soy 23% </li></ul>Penfiel JD et al , J Clin Gastroenterol 2010; 44:22-7
    • 34. Atopic disease Aeroallergen Specific IgE Food specific IgE Aceves et al J Clin Gastroenterol Vol 41, No 3, March 2007 Asthma 47% AR 40 % Eczema 4% + aeroallergen RAST 44% + food RAST 60% COLLINS ET AL Clin Gastro and Hepato Vol. 6, No. 6 Asthma 52% AR 68 % Eczema 44% AC 56 % + SPT aeroallergen 71% + SPT food 76% ROY–GHANTA ET AL Clin Gastro and Hepato Vol. 6, No. 5 Asthma 26% AR 78% AD 4% Specific IgE aeroallergen 86% ( Birch pollen ,Timothy ryegrass pollen Ragweed pollen , dust mite Pet dander ) Specific IgE for food 83%
    • 35. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2008;6:531–535
    • 36. Serum IgE measurement and detection of food allergy in pediatric patients with eosinophilic esophagitis <ul><li>serum IgE measurement detected more positive results than did skin prick testing. Specific IgE to milk was most common (43%) </li></ul><ul><li>low-titer IgE antibody may be useful in identifying relevant food sensitivities making a more directed approach to food avoidance possib l e </li></ul>Ann Allergy Asthma Immunol. 2010;104:496 –502.
    • 37. SPT vs APT <ul><li>mix of immunoglobulin E (IgE)-mediated and non-IgE (cell mediated) hypersensitivity responses </li></ul><ul><li>Results from skin prick testing (SPT) and atopy patch testing (APT) may help to identify foods that contribute to the disease process, and removal of identified foods can be an effective treatment, </li></ul>
    • 38. <ul><li>High rates of food allergies in pt with EoE serum IgE and skin prick testing is warranted to identify comorbid food-induced allergic disease in patients with EoE </li></ul><ul><li>SPTs, serum IgE, and food patch tests can use to identify foods that associated with EoE, but not sufficient to make the diagnosis of food allergy–driven EoE </li></ul>SPT vs APT
    • 39. Treatment <ul><li>Diet therapy </li></ul><ul><li>Elemental diet : complete elimination of dietary antigen and use amino acid formula </li></ul>
    • 40. Patient Intervention Outcome Markowitz et al. Am J Gastroenterol Vol. 98, No. 4, 2003 51 with Dx EoE (age 3 - 16 yr mean 8.3 yr ) <ul><li>elemental diet (Neocate ) for 1 month </li></ul><ul><li>allowed to take water and one fruit (grape or apple) </li></ul><ul><li>improve in vomiting, abd pain, & dysphagia </li></ul><ul><li>Esoeos/hpf </li></ul><ul><li>33.7  1.0 after the </li></ul><ul><li>diet ( p 0.01). </li></ul>Chris A. Liacouras et al. Clin Gastroentrol Hepato 2005;3:1198–1206 10 yr study of 381 patients (66% male, age 9.1 + - 3.1 yr) Dx with EoE <ul><li>dietary restriction </li></ul><ul><li>(if SPT of APT to food + ) </li></ul><ul><li>complete </li></ul><ul><li>dietary elimination </li></ul><ul><li>(if can’t identified food allergy ) </li></ul><ul><li>Neocate, Neocate EO28, Neocate 1, Elecare </li></ul>
    • 41. esophageal eosinophils & No. of patients complaining of clinical symptoms before & 1 month after the initiation of dietary therapy Chris A. Liacouras et al. Clin Gastroentrol Hepato 2005;3:1198–1206
    • 42. Treatment <ul><li>Elimination diet </li></ul><ul><li>elimination of certain food allergens </li></ul>Restrict most common food allergens VS Restrict proteins based on allergy testing
    • 43. Effect of Six-Food Elimination Diet on Clinical and Histologic Outcomes in Eosinophilic Esophagitis <ul><li>Retrospective observational study of children and adolescence were Dx EoE in 2 cohort study </li></ul><ul><li>35 pt with SFED * 6 wk </li></ul><ul><li>(SFED : CM,egg,soy,wheat,peanut/treenut,fish) </li></ul><ul><li>25 pt with elemental diet (aminoacid formula * 6 wk ) </li></ul>CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2006;4:1097–1102
    • 44. Effect of Six-Food Elimination Diet on Clinical and Histologic Outcomes in Eosinophilic Esophagitis <ul><li>SFED treatment associated with clinical & histologic improvement </li></ul><ul><li>offers advantages of better acceptance, cost, and compliance than ELED and should be considered as an option in the initial management of children with EE </li></ul>CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2006;4:1097–1102
    • 45. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis Jonathan M. Sperge, Letters to Editor Jaci.2006.11.016
    • 46. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis Jonathan M. Sperge, Letters to Editor Jaci.2006.11.016
    • 47. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis <ul><li>The combination of the 2 testing methods had an excellent NPV (88% to 100%) for all foods except milk, which was very low at 41% </li></ul><ul><li>Combination of SPT and APT in designing a diet plan has a high success rate for food elimination or food reintroduction in EE with the exception of milk. </li></ul>Jonathan M. Sperge, Letters to Editor Jaci.2006.11.016
    • 48. Treatment <ul><li>Phamacological </li></ul><ul><li>Oral corticosteroid </li></ul><ul><li>- improve esophageal eosinophilia and </li></ul><ul><li>symptoms in patients with EoE </li></ul><ul><li>- disease relapse within less than 6 mo after cessation & adverse effects of long-term treatment </li></ul><ul><li>- used in severe cases,recommended dose </li></ul><ul><li> 1-2 mg/kg of prednisone equivalent </li></ul>
    • 49. Treatment <ul><li>Topical corticosteroid </li></ul>
    • 50. Study Design & No. of Pt Medication and Dosage Outcome Konikoff et al, 2006 RDBPC N = 36 Fluticasone propionate 2 puffs twice daily : All subjects received 220 mcg/puff( total 880mcg/d) * 3 mo (Ages 3–16 y) 1 o outcome : Prox EsoEo 65.9 + - 25.3 vs 1.4 + -1.1 eos/hpf [P =0.03] : Dist EsoEo 84.6 + -19.7 vs 19.6 + - 12.9 eos/hpf [P=0.04 ] 2 o outcome : Resolution of vomiting FP vs placebo  67% vs 27%; [ P =0 .04] :Improve endocopic finding (Furrow) [P=0.047] : reduce epithelial hyperplasia [ P= 0.01] :FP decreased the number of CD8 & mast cells in proximal and distal esophagus ( P=0 .05)
    • 51. Study Design & No. of Pt Medication and Dosage Outcome Dohil et al,2010 RDBPC N = 24 Oral viscous budesonide * 3 mo Subjects <5 ft tall : 1 mg daily Subjects >5 ft tall : 2 mg daily (Age 1–17 y mean 7.8 yr) 1 o outcome In OVB gr 87.6%  responder Reduce peak EsoEo all esophageal Levels proximal (P=0.0024), mid (P =0 .0001), and distal (P=0 .0001) when compared to baseline 2 o outcome :Upper gastrointestinal endoscopy score reduced 4.6  1.5 [P=0.0005] :Symptom score decrease from 3.5  1.2 [p=0.0007] : Epithelial &Lamina propria Eosinophilia&Fibrosis reduced [P=0.0035]
    • 52. Eosinophilic esophagitis: Updated consensus recommendations for children and adults (J Allergy Clin Immunol 2011;128:3-20.)
    • 53. <ul><li>After induction of clinicopathologic remission, topical corticosteroid therapy might need to be maintained </li></ul><ul><li>long-term therapy must be individualized for </li></ul><ul><li>each patient </li></ul><ul><li>When topical steroids used chronically : side effects, growth should be carefully monitored </li></ul><ul><li>in children </li></ul>(J Allergy Clin Immunol 2011;128:3-20.)
    • 54. Treatment <ul><li>11 adult patients were randomized to mepolizumab (n = 5) or placebo (n = 6) </li></ul><ul><li>Mepolizumab gr. decrease mean Eso Eo 54% vs placebo 5 % </li></ul><ul><li>But no complete resolution in any suject, no significant in symptom improvement </li></ul>Anti-interleukin-5 antibody treatment(mepolizumab) in active eosinophilic oesophagitis: a randomised, placebocontrolled, double-blind trial Gut 2010 ;59(1):21-30
    • 55. Treatment <ul><li>Treatment of EoE with cromolyn sodium, leukotriene receptor antagonists, and immunosuppressive agents (azathioprine or 6- MP) is not recommended </li></ul><ul><li>Anti–tumor necrosis factor (TNF) : one case report </li></ul><ul><li>Anti-IgE therapy (omalizumab) : no publish study, one case report </li></ul>
    • 56. Treatment <ul><li>Esophageal Dilation </li></ul><ul><li>- effective treatment of dysphagia, caused by strictures </li></ul><ul><li>- significant symptomatic relief in up to 83% of patients for 20 month  can be recurrence </li></ul><ul><li>- chest pain, deep muscle tear, rare perforation </li></ul>
    • 57. Summary <ul><li>Diagnosis of EoE should be made when symptoms of esophageal dysmotility + evidence of esophageal eosinophilia despite adequate acid suppression (adequate PPI Rx trial or normal esophageal pH). </li></ul>
    • 58.  
    • 59.  
    • 60.  
    • 61. Why 15 Eos/HPF ? GASTROENTEROLOGY 2007;133:1342–1363 10 studies 15 eos/HPF based on peak count or mean number of fields 8 studies 20 eos/HPF based on Peak or mean number 2 studies 24 eos/HPF based on peak count or mean number 1 study 30 eos/HPF peak count
    • 62. Elemental Diet Is an Effective Treatment for Eosinophilic Esophagitis in Children and Adolescents THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 98, No. 4, 2003

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