The Kalixanda Study. Upper GI pathology in the general population

Transcription

1 The Kalixanda Study Upper GI pathology in the general population

2 The Kalixanda Study The project group Lars Agréus, PhD, GP, project leader Pertti Aro, GP Jukka Ronkainen, GP Tom Storskrubb, gastroenterologist Michael Vieth, PhD, pathologist Manfred Stolte, PhD, professor, pathologist Lars Engstrand, PhD, professor, microbiologist Elisabeth Bolling-Sternevald, PhD, scientist Tore Lind, PhD, GI surgeon Nicholas J. Talley, PhD, professor, gastroenterologist

3 Helicobacter pylori infection in non-patients (Dr. Storskrubb) The Kalixanda Study Three main research lines The epidemiology of upper GI symptoms and diseases in an unselected population (Dr. Aro) The epidemiology and natural history of lower esophageal macroscopic and microscopic findings on endoscopy (Dr. Ronkainen)

4 The Kalixanda Study Purpose of the study to study: 1.epidemiology 2.patophysiology 3.symptomatology of the disorders of the upper G.I tract in an unselected population

5 Why in Haparanda Kalix? Population register which covers all the inhabitants in the area Capacity to endoscope also in primary care Sole cover of the population Experienced endoscopists known to the population

6

7 The Kalixanda Study Randomization Mailed ASQ-questionnaire EGD invitation by phone All adults in Kalix&Haparanda age 18-80, n= in 1998 Random sample n= 3000 ASQ responders n= 2122 EGD responders n= 1001

8 The Kalixanda Study Stratified sample (every 7th) from the National Population Register All adults in Kalix&Haparanda age 18-80, n= in 1998 Population sample Randomized ID Spring -99 ASQ postal questionnaire n=600 ID Responders invited by phone to EGD in ID order 200 EGD s in ID order

9 The Kalixanda Study Stratified sample (every 7th) from the National Population Register All adults in Kalix&Haparanda age 18-80, n= in 1998 Population sample Randomized ID Spring -99 Autumn -99 Spring -00 Autumn -00 Spring -01 ASQ postal questionnaire n=600 ID ASQ Postal postal questionnaire n=600, ID ID Responders invited by phone to EGD in ID order ASQ postal questionnaire n=600 ID ASQ postal questionnaire n=600 ID ASQ postal questionnaire n=600 ID EGD s in ID order 196 EGD s in ID order 192 EGD s in ID order 193 EGD s in ID order 220 EGD s in ID order In total 1001 EGDs

10 Randomization Every 7th The Kalixanda Study Target population All adults in Kalix&Haparanda age 18-80, n= in 1998 Original study population n= 3000, male 52.0%, mean age 50.4 Non-response study Key questions by phone + H.p. Serology every 4th on both levels Mailed ASQ EGD invitation by phone n=1563 Eligible study population n=2860 ASQ responders (74%) n= 2122, male 50.5%, mean age 51.8 EGD responders (73%) n= 1001, male 48.8%, mean age 53.5 Non-responders n=738 (25.8%) Invited not eligible for EGD Total n=562 (36.0%) Excluded n=198 (12.7%) Denied n=364(23.3%) Aro et al. Scand J Gastroenterol (12):1280-8

11 Response to the Kalixanda study Response to the mailed ASQ 74.2% Response to the EGD study 73.3% Response to non-response study (non-responders to ASQ) 77.3%

12 Kalixanda; Demographic data Eligible study population (n=2,860) Studied at college/university Mean age 50.4 year versus 50.0 in Swedish population Males 51.8 % versus 49.7 % in Swedish population - Haparanda 15 % - Kalix 21 % and Swedish average 23%

13 Kalixanda; Demographic data Responders to ASQ (n=2,122) Mean age 51.8 versus 50.0 in Swedish population Males 50.5 versus 49.7 in Swedish population Studied at college/university 18% and Swedish average 23%

14 Kalixanda; Demographic data Endoscopy study sample (EGD) (n=1,001) Mean age 54.1 versus 50.0 year in Swedish population Males 48.8% versus 49.7% in Swedish population Studied at college/university 18% and Swedish average 23%

15 Questionnaire I Postal symptom questionnaire Abdominal symptom questionnaire (ASQ) - Validated both in Finnish and Swedish - Reliable - Reproducible - 27 general gastrointestinal symptoms - Troublesome symptoms past 3 months - 8 additional questions to meet Rome II criteria

16 The Kalixanda Study Exclusion for endoscopy: Myocardial infarction < 6 months Angina pectoris Cardiac failure Respiratory failure Esophageal varices Pregnancy Anticoagulant treatment Psychotics

17 Upper endoscopy (EGD) 3 endoscopists - 2 GPs in Haparanda (PA, JR) - 1 gastroenterologist in Kalix (TS) Experienced (2,500 6,000 endoscopies prior to the study) 2 consensus meetings for validation of findings Predefined form for findings Endoscopists not aware of the symptoms Medical history after the EGD registration

18 Biopsies Biopsies (X 2) obtained from 2cm above Z line, Z line, cardia, corpus, incisura (IDs 601-3,000), antrum, bulb of duodenum (1. segment of the duodenum), descendent duodenum (2. segment of the duodenum) Additional biopsies if lesions seen

19 Discussion

20 High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symtoms.. Scand J Gastroenterology 2005 Mar;40(3): GERD has been reported to be a common burden, but its manifestations are unclear To estimate prevalence of and to identify risk factors for GERS and EE 3000 ASQ 1000 EGD

21 High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symtoms.. Scand J Gastroenterology 2005 Mar;40(3): ,0 % GERS 15,5 % EE GERS+ ; 24,5 % EE+ EE+ ; 36,8 % GERS- Obesity and hernia sign risk factors (OR up to 14) Hp+ ; higher risk of GERS without EE (OR 1,71)

22 Gastro-oesophageal reflux symptoms and health related qol Aliment Pharmacol Ther 2006 Jun 15;23(12): The impact of GERD on health related qol is poorly characterized To identify the frequency of GERD symtoms with impaired qol 1001 EGD Short Form -36 Health Survey

23 Gastro-oesophageal reflux symptoms and health related qol Aliment Pharmacol Ther 2006 Jun 15;23(12): Spt: Heartburn and/or regurgitation 6 % daily, 14 % weekly, 20 % less than weekly P < 0,05 daily/weekly qol NS esofagitis qol

24 Prevalence of Barrets esophagus Gastroenterology 2005 Dec;129(6): BE ass with esophageal adenocarcinoma (dramatic increase in incidence) The prevalence of BE is uncertain To determine prevalence and risk factors 3000 ASQ 1000 EGD

25 Prevalence of Barrets esophagus Gastroenterology 2005 Dec;129(6): Overall prevalence 1,6 % BE+ ; GERS 40 % EE 15 % GERS+ ;2,3 % GERS- ;1,2 % (NS) Identical for EE Alcohol (p=0,04) and smoking (p=0,047) independent risk factors

26 Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults Gut 2007 May;56(5): Eosinophilic oesophagitis may be increasing but the prevalence remains unknown 1000 EGD Biopsies 2 at z-line and 2 cm above Eosinophils present; Definite (>20 X40), probable (15-19), possible (5-14)

27 Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults Gut 2007 May;56(5): Total 5 % eosinophils present 1 % definite or probable Erosive oesophagitis, absence of dyspepsia, Hp infection independent predictors Ass with dysphagia and narrowing of the eosophageal lumen (p=0.005)

28 Peptic ulcer disease in a general adult population Am J Epidemiol 2006 Jun 1;163(11): To explore prevalence, symptomatology and risk factors 3000 ASQ 1000 EGD

29 Peptic ulcer disease in a general adult population Am J Epidemiol 2006 Jun 1;163(11): ,1 % PUD (20 gastric, 21 duodenal) GU; Loss of weight OR 5,10 GU; Dysphagia OR 3,35 GU; Nausea OR 4,49 DU; Urgency at night OR 3,53 6 GU, 2 DU asymptomatic DU; 38 % NO evidence of current Hp 25 % GU, 19 % DU idiopathic Smoking, ASA, obesity GU Smoking, low dose ASA, Hp DU PUD often coexists with atypical symptoms or no symptoms. Idiopathic DU may be more common than anticipated

30 Do gastrointestinal symptoms fluctuate in the short-term perspective? Dig Dis 2008;26(3): Short term fluctuation of GI symptoms is largely unknown 3000 ASQ 1000 ASQ #2 after 2,5 months

31 Do gastrointestinal symptoms fluctuate in the short-term perspective? Dig Dis 2008;26(3): % initially symptomfree or could not be classified 39 % GERS 40 % dyspeptic symptoms 30 % IBS 75 % still complaints at second visit GI symptoms were common, symptom fluctuation occured in the shorter term, but troublesome GI complaints remained in appr 90 % of subjects over a 1-6 month period

32 GERS > 1/vecka påverkar QOL mätbart Eosinofil esofagit förekommer och kan vara en orsak till dysfagia eller stenos 40 % GERS, 15 % EE, hiatus hernia och fetma ökar risken 25 % GU, 19 % DU idiopatiska, 38 % av DU saknar bevis för Hp AB resistens hos Hp lägre än väntat, simuleringar visar att test-and-treat ändrar AB kons marginellt 90 % har symtom 4,1 % har magsår, många har ospecifika eller oväntade symtom 5,4 % har celiaki, biopsi och serologi stämmer överens Ångest men inte depression är relaterat till dyspeptiska symtom men inte till smärta 1,6 % har BE Alkohol och rökning ökar risken 33 % pågående Hp, 10 % gammal Hp, neg serology utesluter premaligna tillstånd Rökning vs PUD OR 2,32 Eosinofil duodenit förekommer och kan ligga bakom enstaka pat med dyspepsi

33 14:45