Jukka Ronkainen

High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: A Kalixanda study report

Objective. Gastroesophageal reflux disease has been reported to be a common burden on health-care resources in the Western world, but its manifestations in the general population are as yet unclear. The aim of this study was to estimate the prevalence of, and to identify the risk factors for gastroesophageal reflux symptoms (GERS) and erosive esophagitis (EE) in the adult population of two Swedish municipalities. Material and methods. A random sample (n=3000) of the adult population (20–81 years of age) of two Swedish municipalities (n=21,610) was surveyed using a validated postal questionnaire assessing gastrointestinal symptoms. The response rate was 74%. A subsample (n=1000) of the responders was subsequently invited, in random order, for esophago-gastro-duodenoscopy with evaluation of GERS, risk factors and tests for Helicobacter pylori. Results. GERS were reported by 40.0% and EE was found in 15.5% of the population that had undergone endoscopy. Of those with GERS, 24.5% had EE while 36.8% of those with EE reported no GERS. Hiatus hernia and obesity remained significant risk factors for GERS and/or EE, with or without symptoms in a main effect model (OR up to 14 at EE). Those with active H. pylori infection had a higher risk of GERS without EE than those without H. pylori infection (OR=1.71 (1.23–2.38)). Conclusions. GERS and EE (of which one-third is asymptomatic) are highly prevalent in the Swedish adult population. H. pylori infection seems to play a role in the manifestations of gastroesophageal reflux.

Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: The population-based Kalixanda study

Background: Eosinophilic oesophagitis may be increasing but the prevalence in the general population remains unknown. Our aim was to assess this and the presence of eosinophils in the distal oesophageal epithelium in the community. Methods: Oesophagogastroduodenoscopy was performed in a random sample (n = 1000) of the adult Swedish population (mean age 54 years, 49% men). Oesophageal biopsy samples were obtained from 2 cm above, and at, the Z-line. Any eosinophil infiltration of the epithelium was defined as “eosinophils present”. Definite eosinophilic oesophagitis was defined as ⩾20, probable as 15–19, and possible as 5–14 eosinophils/high-power field (HPF, at magnification ×40) in oesophageal biopsy specimens. Results: Eosinophils were present in 48 subjects (4.8%, 95% CI 3.5 to 6.1%, mean age 54 years, 63% men), in 54% without troublesome reflux symptoms. Definite eosinophilic oesophagitis was present in four subjects (0.4%, 95% CI 0.01 to 0.8%, mean age 51 years, 75% men) and probable eosinophilic oesophagitis in seven subjects (0.7%, 95% CI 0.2 to 1.2%, mean age 58 years, 43% men). Erosive oesophagitis (OR = 2.99, 95% CI 1.58 to 5.66) and absence of dyspepsia (OR = 0.23, 95% CI 0.07 to 0.75) and Helicobacter pylori infection (OR = 0.41, 95% CI 0.19 to 0.92) were independent predictors for “eosinophils present”. Definite eosinophilic oesophagitis was associated with dysphagia (2/66 vs 2/926, p = 0.025), and probable eosinophilic oesophagitis with narrowing of the oesophageal lumen (2/15 vs 5/978, p = 0.005). Conclusions: Oesophageal eosinophils were present in nearly 5% of the general population; approximately 1% had definite or probable eosinophilic oesophagitis. Oesophageal eosinophils may be a manifestation of reflux disease in adults, but the condition is as likely to be asymptomatic and go unrecognised.

Detection of Celiac Disease and Lymphocytic Enteropathy by Parallel Serology and Histopathology in a Population-Based Study

BACKGROUND & AIMS Although serologic analysis is used in diagnosis of celiac disease, histopathology is considered most reliable. We performed a prospective study to determine the clinical, pathologic, and serologic spectrum of celiac disease in a general population (Kalixanda study). METHODS A random sample of an adult general population (n = 1000) was analyzed by upper endoscopy, duodenal biopsy, and serologic analysis of tissue transglutaminase (tTg) levels; endomysial antibody (EMA) levels were analyzed in samples that were tTg+. The cut off values for diagnosis of celiac disease were villous atrophy with 40 intraepithelial lymphocytes (IELs)/100 enterocytes (ECs). RESULTS Samples from 33 subjects were tTg+, and 16 were EMA+. Histologic analysis identified 7 of 1000 subjects (0.7%) with celiac disease; all were tTg+, and 6 of 7 were EMA+. Another 26 subjects were tTg+ (7/26 EMA+). This was addressed by a second quantitative pathology study (nested case control design) using a threshold of 25 IELS/100 ECs. In this analysis, all 13 samples that were tTg+ and EMA+ had > or =25 IELs/100 ECs. In total, 16 subjects (1.6%) had serologic and histologic evidence of gluten-sensitive enteropathy. IELs were quantified in duodenal biopsy samples from seronegative individuals (n = 500); 19 (3.8%) had >25 IELs and lymphocytic duodenosis. CONCLUSIONS Measurement of > or =25 IELs/100 ECs correlated with serologic indicators of celiac disease; a higher IEL threshold could miss 50% of cases. Quantification of tTg is a sensitive test for celiac disease; diagnosis can be confirmed by observation of > or =25 IELs/100ECs in duodenal biopsy specimens. Lymphocytic enteropathy (celiac disease and lymphocytic duodenosis) is common in the population (5.4%).

Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia

Background  Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional disorders without defined pathology. Mast cells and eosinophils interact with T lymphocytes and may alter enteric nerve and smooth muscle function.

Anxiety Is Associated With Uninvestigated and Functional Dyspepsia (Rome III Criteria) in a Swedish Population-Based Study

BACKGROUND & AIMS The Rome III criteria for functional dyspepsia have been changed to include 2 distinct syndromes: postprandial distress syndrome and epigastric pain syndrome. We investigated risk factors for functional dyspepsia among the functional dyspepsia subgroups defined by the Rome III criteria. METHODS We performed a cross-sectional population-based study in a primary care setting (the Kalixanda study). A random sample (n = 2860) of the adult population from 2 northern Swedish municipalities (n = 21,610) was surveyed using a validated postal questionnaire to assess gastrointestinal symptoms (response rate, 74.2%; n = 2122). A randomly selected subgroup (n = 1001) of responders was invited to undergo an esophagogastroduodenoscopy (participation rate, 73.3%) including biopsy specimen collection, Helicobacter pylori culture and serology, and symptom assessments. RESULTS Of the 1001 subjects examined by endoscopy, 202 (20.2%; 95% confidence interval [CI], 17.7-22.7) were classified as having uninvestigated dyspepsia and 157 (15.7%; 95% CI, 13.4-18.0) as having functional dyspepsia. Major anxiety (Hospital Anxiety and Depression Scale score > or = 11) was associated with uninvestigated dyspepsia (odds ratio [OR], 3.01; 95% CI, 1.39-6.54), as was obesity (body mass index > or = 30 kg/m(2)) (OR, 1.86; 95% CI, 1.15-3.01). Major anxiety was associated with functional dyspepsia and postprandial distress syndrome (OR of 2.56 [95% CI, 1.06-6.19] and 4.35 [95% CI, 1.81-10.46], respectively), as was use of nonsteroidal anti-inflammatory drugs (OR, 2.49 [95% CI, 1.29-4.78] and 2.75 [95% CI, 1.38-5.50], respectively). Depression was not associated with any dyspepsia group. CONCLUSIONS Anxiety but not depression is linked to uninvestigated dyspepsia, functional dyspepsia, and postprandial distress syndrome but not to epigastric pain syndrome.

Gastro-oesophageal reflux symptoms and health-related quality of life in the adult general population--the Kalixanda study.

The impact of gastro‐oesophageal reflux symptoms on health‐related quality of life in the general population is poorly characterized.

Serum biomarkers provide an accurate method for diagnosis of atrophic gastritis in a general population: The Kalixanda study

Objective. Serological biomarkers can be used for non-invasive diagnosis of gastritis and atrophic gastritis. The aim of this study was to compare the validity of serum levels of pepsinogen I (PGI) and II (PGII), gastrin-17 (G-17) and Helicobacter pylori antibodies (Hpab) with that of the gold standard histology for diagnosis of atrophic gastritis in a population sample from Northern Sweden. Material and methods. In all, 1000 subjects underwent endoscopies with biopsies. Serum biomarkers were available in 976 subjects for independent diagnosis of gastric mucosal status using a predetermined diagnostic algorithm. Results. Overall agreement between histology and serological biomarkers in diagnosing corpus atrophy was 96% (CI 95%: 95–97%). Sensitivity and specificity of markers for atrophic gastritis were 71% (CI 68–74%) and 98% (CI 97–99%) respectively, corresponding to 69% (CI 95%: 66–72%) and 98% (95% CI 97–99%) positive and negative predictive values. The positive likelihood ratio was 35.5 (95% CI: 35.0–36.0%). In subgroups with normal stomachs, H. pylori non-atrophic gastritis and H. pylori-negative gastritis by histology, the prevalence of corpus atrophy diagnosed with the biomarkers was 0.8% and 4.9%, respectively. In total, 6.6% of subjects in the study population had corpus atrophy according to the serological biomarkers. Conclusions. Serological biomarkers show a high degree of accuracy as a non-invasive method to diagnose corpus atrophy, which is common in the general population.

Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers

Abstract Background and aims. Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers. Methods. The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice. Results. In AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria. Conclusions. Stomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach.

Body mass index and chronic unexplained gastrointestinal symptoms: an adult endoscopic population-based study

Background: We aimed to determine whether obese subjects experience more gastro-oesophageal reflux (GORS) symptoms than normal subjects, and further to determine if this association was explained by oesophagitis or medications that lower oesophageal sphincter pressure. Methods: In a representative Swedish population, a random sample (n = 1001, mean age 53.5 years, 51% women) had upper endoscopy. GORS was defined as any bothersome heartburn or acid regurgitation. Results: The prevalence of obesity (body mass index ⩾30) was 16%; oesophagitis was significantly more prevalent in obesity (26.5%) than in normal subjects (9.3%). There were associations between obesity and GORS (odds ratio (OR) 2.05 (95% confidence interval (CI) 1.39, 3.01)), epigastric pain (OR 1.63 (95% CI 1.05, 2.55)), irritable bowel symptoms (OR 1.58 (95% CI 1.05, 2.38)), any abdominal pain (OR 1.59 (95% CI 1.08, 2.35)), vomiting (OR 3.11 (95% CI 1.18, 8.20)), retching (OR 1.74 (95% CI 1.1.3, 2.67)), diarrhoea (OR 2.2 (95% CI 1.38, 3.46)), any stool urgency (OR 1.60 (95% CI 1.04, 2.47)), nocturnal urgency (OR 2.57 (95% CI 1.33, 4.98)), and incomplete rectal evacuation (OR 1.64 (95% CI 1.09, 2.47)), adjusting for age, sex, and education. When subjects with oesophagitis and peptic ulcer were excluded, only diarrhoea, incomplete evacuation, and vomiting were significantly associated with obesity. The association between GORS and obesity remained significant adjusting for medication use (OR 1.9 (95% CI 1.3, 3.0)). Conclusions: GORS is associated with obesity; this appears to be explained by increased upper endoscopy findings in obesity.

A negative Helicobacter pylori serology test is more reliable for exclusion of premalignant gastric conditions than a negative test for current H. pylori infection: a report on histology and H. pylori detection in the general adult population.

Objective. Corpus-dominant gastritis, gastric mucosal atrophy and intestinal metaplasia (IM) associated with Helicobacter pylori infection are all known potential risk markers for the development of gastric cancer. As the accuracy for finding cases at risk in the general population is unknown, we aimed to determine the prevalence of current and/or past H. pylori infection and associated gastric mucosal findings by means of histological survey of a random adult population. Material and methods. A random Swedish sample (n=3000, age 20–81 years) was surveyed using a validated gastrointestinal symptom questionnaire with 74% response rate. One-third of the responders were selected at random for esophago-gastro-duodenoscopy with biopsies and H. pylori serology. Results. Of those endoscoped (n=1000, mean age 53.5, 51% women), 43.0% were H. pylori+ by serology (seropositive), 33.9% had signs of current infection on either histology or culture (gold standard+), and 9.3% were seropositive, but gold standard negative. Corpus atrophy was found in 10% and IM in 13% when gold standard positive, and in a significantly higher number (17% and 21%, respectively) of those with only a serological sign of past infection. Among those who were seronegative, values were 1% and 2%, respectively. Corpus-dominant gastritis was found in 4.1%, all seropositive. Conclusion. One-third had an ongoing H. pylori infection, and a further 10% had signs of past infection. Corpus-dominant gastritis was found mostly among the former, while detection of those with corpus atrophy and IM also required a test for past infection. Seronegativity almost excludes precancerous conditions in a screening situation.