Prevalence and risk factors of gastro-oesophageal reflux symptoms among adolescents, the HUNT study.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is recognized by symptoms of heartburn and acid regurgitation. These gastro-oesophageal reflux symptoms (GORS) are common in adults, but data from adolescents are sparse. This study aimed to assess the prevalence and risk factors of GORS among adolescents in a large and unselected population. METHODS: This study was based on the Trøndelag Health Study (HUNT), a longitudinal series of population-based health surveys conducted in Nord-Trøndelag County, Norway. This study included data from Young-HUNT4 performed in 2017-2019, where all inhabitants aged 13-19 years were invited and 8066 (76.0%) participated. The presence of GORS (any or frequent) during the past 12 months and tobacco smoking status were reported through self-administrated questionnaires, whereas body mass index (BMI) was objectively measured. RESULTS: Among 7620 participating adolescents reporting on the presence of GORS, the prevalence of any GORS and frequent GORS was 33.2% (95% confidence interval [CI] 32.2 - 34.3%) and 3.6% (95% CI 3.2 - 4.0%), respectively. The risk of frequent GORS was lower among boys compared to girls (OR 0.61; 95% CI 0.46 - 0.79), higher in current smokers compared to never smokers (OR 1.80; 95% CI 1.10 - 2.93) and higher among obese compared to underweight/normal weight adolescents (OR 2.50; 95% CI 1.70 - 3.66). CONCLUSION: A considerable proportion of adolescents had GORS in this population-based study, particularly girls, tobacco smokers, and individuals with obesity, but frequent GORS was relatively uncommon. Measures to avoid tobacco smoking and obesity in adolescents may prevent GORS.

The relationship between weight change and inflammatory bowel disease. A population-based cohort study, the HUNT study.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) is increasing. The prevalence of overweight and obesity is increasing in parallel with IBD and could contribute to IBD development. The aim of this study was to assess the relationship between weight change and the risk for IBD. METHODS: Data gathered from 55,896 adult participants in the three first population-based Trøndelag Health Studies (HUNT1-3), Norway, performed in 1984-2008 was used. The exposure was change in body mass index between two HUNT studies. The outcome was a new IBD diagnosis recorded during a ten-year follow-up period after the exposure assessment. The risk of IBD by weight change was assessed by Cox regression analyses reporting hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for sex, age, and smoking status. RESULTS: There were 334 new cases of ulcerative colitis (UC) and 54 of Crohn's disease (CD). Weight loss decreased the risk of a new UC diagnosis by 38% (adjusted HR 0.62, 95% CI 0.39-0.97) and seemed to double the risk of getting a new CD diagnosis (adjusted HR 2.01, 95% CI 0.91-4.46). Weight gain was not associated with a new diagnosis of neither UC (adjusted HR 1.00, 95% CI 0.78-1.26) nor CD (adjusted HR 1.08, 95% CI 0.56-2.08). CONCLUSION: In this study, weight loss was associated with decreased risk of UC. However, no associations were seen between weight gain and the risk of UC or CD, suggesting that the increasing weight in the general population cannot explain the increasing incidence of IBD.

External validation of the colorectal cancer risk score LiFeCRC using food frequency questions in the HUNT study.

PURPOSE: To mitigate the increasing colorectal cancer (CRC) incidence globally and prevent CRC at the individual level, individual lifestyle information needs to be easily translated into CRC risk assessment. Several CRC risk prediction models exist and their clinical usefulness depends on their ease of use. Our objectives were to assess and externally validate the LiFeCRC score in our independent, unselected population and to investigate the use of simpler food frequency measurements in the score. METHODS: Incidental colon and rectal cancer cases were compared to the general population among 78,580 individuals participating in a longitudinal health study in Norway (HUNT). Vegetable, dairy product, processed meat and sugar/confectionary consumption was scored based on food frequency. The LiFeCRC risk score was calculated for each individual. RESULTS: Over a median of 10 years following participation in HUNT, colon cancer was diagnosed in 1355 patients and rectal cancer was diagnosed in 473 patients. The LiFeCRC score using food frequencies demonstrated good discrimination in CRC overall (AUC 0.77) and in sex-specific models (AUC men 0.76 and women 0.77) in this population also including individuals ≥ 70 years and patients with diabetes. It performed somewhat better in colon (AUC 0.80) than in rectal cancer (AUC 0.72) and worked best for female colon cancer (AUC 0.81). CONCLUSION: Readily available clinical variables and food frequency questions in a modified LiFeCRC score can identify patients at risk of CRC and may improve primary prevention by motivating to lifestyle change or participation in the CRC screening programme.

Risk of Esophageal Adenocarcinoma After Helicobacter pylori Eradication Treatment in a Population-Based Multinational Cohort Study.

BACKGROUND AND AIMS: Helicobacter pylori infection is associated with a decreased risk of esophageal adenocarcinoma, and the decreasing prevalence of such infection might contribute to the increasing incidence of this tumor. We examined the hypothesis that eradication treatment of H pylori increases the risk of esophageal adenocarcinoma. METHODS: This population-based multinational cohort, entitled "Nordic Helicobacter Pylori Eradication Project (NordHePEP)," included all adults (≥18 years) receiving H pylori eradication treatment from 1995-2018 in any of the 5 Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) with follow-up throughout 2019. Data came from national registers. We calculated standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) by dividing the cancer incidence in the exposed cohort by that of the entire Nordic background populations of the corresponding age, sex, calendar period, and country. Analyses were stratified by factors associated with esophageal adenocarcinoma (ie, education, comorbidity, gastroesophageal reflux, and certain medications). RESULTS: Among 661,987 participants who contributed 5,495,552 person-years after eradication treatment (median follow-up, 7.8 years; range, 1-24 years), 550 cases of esophageal adenocarcinoma developed. The overall SIR of esophageal adenocarcinoma was not increased (SIR = 0.89; 95% CI, 0.82-0.97). The SIR did not increase over time after eradication treatment, but rather decreased and was 0.73 (95% CI, 0.61-0.86) at 11-24 years after treatment. There were no major differences in the stratified analyses. The overall SIR of esophageal squamous cell carcinoma, calculated for comparison, showed no association (SIR = 0.99; 95% CI, 0.89-1.11). CONCLUSIONS: This absence on an increased risk of esophageal adenocarcinoma after eradication treatment of H pylori suggests eradication is safe from a cancer perspective.

Coeliac disease in the Trøndelag Health Study (HUNT), Norway, a population-based cohort of coeliac disease patients.

PURPOSE: Coeliac disease (CD) is a common disorder and affects about 1% of the population worldwide. CD in the Trøndelag Health Study (HUNT) is a population-based cohort study which was established to provide new knowledge about CD that can improve the diagnostics and management, prevent the onset or progression and expand the knowledge about the role of genetics of the disease. PARTICIPANTS: The cohort is based on the fourth wave of the population-based HUNT study (HUNT4), Norway, performed during 2017-2019, also including linkage to hospital records and the Norwegian Patient Registry (NPR). A total of 54 541 HUNT4 participants with available sera were screened for CD by serology. All seropositive participants were invited to a clinical assessment, including endoscopy with duodenal biopsies, during 2019-2023. FINDINGS TO DATE: A total of 1107 HUNT4 participants (2%) were seropositive for CD and 1048 were eligible for clinical assessment, including biopsy. Of these, 724 participants attended the clinical assessment and 482 were identified with CD. In addition, 371 participants with CD were identified through the hospital records and NPR. In total, 853 participants in HUNT4 with biopsy-verified CD diagnosis were identified. FUTURE PLANS: All participants in the study will be invited to a follow-up assessment after at least 1 year, including repeated standard serological testing, endoscopy and tissue sampling. The collected data and material will be used to establish the true population-based prevalence of CD. The consequences of CD, including symptoms, deficiencies and comorbidity, will be investigated and possible triggers and predictors, will be studied. With access to serum samples from the previous HUNT surveys in HUNT Biobank, serological signs of CD in prediagnostic samples of seropositive individuals will be used. Genetic studies will identify new CD markers, assess genotype-phenotype links and explore gene-environment correlations. REGISTRATION: clinicaltrials.gov identifier: NCT04041622.

Antireflux Surgery Versus Antireflux Medication and Risk of Esophageal Adenocarcinoma in Patients With Barrett's Esophagus.

BACKGROUND & AIMS: Antireflux treatment is recommended to reduce esophageal adenocarcinoma in patients with Barrett's esophagus. Antireflux surgery (fundoplication) counteracts gastroesophageal reflux of all types of carcinogenic gastric content and reduces esophageal acid exposure to a greater extent than antireflux medication (eg, proton pump inhibitors). We examined the hypothesis that antireflux surgery prevents esophageal adenocarcinoma to a larger degree than antireflux medication in patients with Barrett's esophagus. METHODS: This multinational and population-based cohort study included all patients with a diagnosis of Barrett's esophagus in any of the national patient registries in Denmark (2012-2020), Finland (1987-1996 and 2010-2020), Norway (2008-2020), or Sweden (2006-2020). Patients who underwent antireflux surgery were compared with nonoperated patients using antireflux medication. The risk of esophageal adenocarcinoma was calculated using multivariable Cox regression, providing hazard ratios (HRs) and 95% CIs adjusted for age, sex, country, calendar year, and comorbidity. RESULTS: The cohort consisted of 33,939 patients with Barrett's esophagus. Of these, 542 (1.6%) had undergone antireflux surgery. During up to 32 years of follow-up, the overall HR was not decreased in patients having undergone antireflux surgery compared with nonoperated patients using antireflux medication, but rather increased (adjusted HR, 1.9; 95% CI, 1.1-3.5). In addition, HRs did not decrease with longer follow-up, but instead increased for each follow-up category, from 1.8 (95% CI, 0.6-5.0) within 1-4 years of follow-up to 4.4 (95% CI, 1.4-13.5) after 10-32 years of follow-up. CONCLUSIONS: Patients with Barrett's esophagus who undergo antireflux surgery do not seem to have a lower risk of esophageal adenocarcinoma than those using antireflux medication.

Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma in three Nordic countries: population based cohort study.

OBJECTIVE: To assess the incidence rate of oesophageal adenocarcinoma among patients with non-erosive gastro-oesophageal reflux disease compared with the general population. DESIGN: Population based cohort study. SETTING: All patients in hospital and specialised outpatient healthcare in Denmark, Finland, and Sweden from 1 January 1987 to 31 December 2019. PARTICIPANTS: 486 556 adults (>18 years) who underwent endoscopy were eligible for inclusion: 285 811 patients were included in the non-erosive gastro-oesophageal reflux disease cohort and 200 745 patients in the validation cohort with erosive gastro-oesophageal reflux disease. EXPOSURES: Non-erosive gastro-oesophageal reflux disease was defined by an absence of oesophagitis and any other oesophageal diagnosis at endoscopy. Erosive gastro-oesophageal reflux disease was examined for comparison reasons and was defined by the presence of oesophagitis at endoscopy. MAIN OUTCOME MEASURES: The incidence rate of oesophageal adenocarcinoma was assessed for up to 31 years of follow-up. Standardised incidence ratios with 95% confidence intervals were calculated by dividing the observed number of oesophageal adenocarcinomas in each of the gastro-oesophageal reflux disease cohorts by the expected number, derived from the general populations in Denmark, Finland, and Sweden of the corresponding age, sex, and calendar period. RESULTS: Among 285 811 patients with non-erosive gastro-oesophageal reflux disease, 228 developed oesophageal adenocarcinomas during 2 081 051 person-years of follow-up. The incidence rate of oesophageal adenocarcinoma in patients with non-erosive gastro-oesophageal reflux disease was 11.0/100 000 person-years. The incidence was similar to that of the general population (standardised incidence ratio 1.04 (95% confidence interval 0.91 to 1.18)), and did not increase with longer follow-up (1.07 (0.65 to 1.65) for 15-31 years of follow-up). For validity reasons, we also analysed people with erosive oesophagitis at endoscopy (200 745 patients, 1 750 249 person-years, and 542 oesophageal adenocarcinomas, corresponding to an incidence rate of 31.0/100 000 person-years) showing an increased overall standardised incidence ratio of oesophageal adenocarcinoma (2.36 (2.17 to 2.57)), which became more pronounced with longer follow-up. CONCLUSIONS: Patients with non-erosive gastro-oesophageal reflux disease seem to have a similar incidence of oesophageal adenocarcinoma as the general population. This finding suggests that endoscopically confirmed non-erosive gastro-oesophageal reflux disease does not require additional endoscopic monitoring for oesophageal adenocarcinoma.

Is empiric proton pump inhibition in patients with symptoms of extraesophageal gastroesophageal reflux justified?

BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) has had a marked increase in Western countries with a paralleling interest in extraesophageal (EE) manifestations of GERD, including laryngopharyngeal reflux (LPR). There are considerable differences in clinical practice between gastroenterologists, otolaryngologists and pulmonologists. METHODS: In this narrative review we address some of these controversies concerning EE manifestations of GERD and LPR. RESULTS: It is disputed whether there is causal relationship between reflux and the numerous symptoms and conditions suggested to be EE manifestations of GERD. Similarly, the pathophysiology is uncertain and there are disagreements concerning diagnostic criteria. Consequently, it is challenging to provide evidence-based treatment recommendations. A significant number of patients are given a trial course with a proton pump inhibitor (PPI) for several months before symptoms are evaluated. In randomized controlled trials (RCTs) and meta-analyses of RCTs PPI treatment does not seem to be advantageous over placebo, and the evidence supporting that patients without verified GERD have any benefit of PPI treatment is negligible. There is a large increase in both over the counter and prescribed PPI use in several countries and a significant proportion of this use is without any symptomatic benefit for the patients. Whereas short-term treatment has few side effects, there is concern about side-effects after long-term use. Although empiric PPI treatment for suspected EE manifestations of GERD instead of prior esophageal 24-hour pH and impedance monitoring is included in several guidelines by various societies, this practice contributes to overtreatment with PPI. CONCLUSION: We argue that the current knowledge suggests that diagnostic testing with pH and impedance monitoring rather than empiric PPI treatment should be chosen in a higher proportion of patients presenting with symptoms possibly attributable to EE reflux.

Decreased Risk of Esophageal Adenocarcinoma After Gastric Bypass Surgery in a Cohort Study From 3 Nordic Countries.

OBJECTIVE: The objective of this study was to test the hypothesis that bariatric surgery decreases the risk of esophageal and cardia adenocarcinoma. BACKGROUND: Obesity is strongly associated with esophageal adenocarcinoma and moderately with cardia adenocarcinoma, but whether weight loss prevents these tumors is unknown. METHODS: This population-based cohort study included patients with an obesity diagnosis in Sweden, Finland, or Denmark. Participants were divided into a bariatric surgery group and a nonoperated group. The incidence of esophageal and cardia adenocarcinoma (ECA) was first compared with the corresponding background population by calculating standardized incidence ratios (SIR) with 95% CIs. Second, the bariatric surgery group and the nonoperated group were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CI, adjusted for sex, age, comorbidity, calendar year, and country. RESULTS: Among 748,932 participants with an obesity diagnosis, 91,731 underwent bariatric surgery, predominantly gastric bypass (n=70,176; 76.5%). The SIRs of ECA decreased over time after gastric bypass, from SIR=2.2 (95% CI, 0.9-4.3) after 2 to 5 years to SIR=0.6 (95% CI, <0.1-3.6) after 10 to 40 years. Gastric bypass patients were also at a decreased risk of ECA compared with nonoperated patients with obesity [adjusted HR=0.6, 95% CI, 0.4-1.0 (0.98)], with decreasing point estimates over time. Gastric bypass was followed by a strongly decreased adjusted risk of esophageal adenocarcinoma (HR=0.3, 95% CI, 0.1-0.8) but not of cardia adenocarcinoma (HR=0.9, 95% CI, 0.5-1.6), when analyzed separately. There were no consistent associations between other bariatric procedures (mainly gastroplasty, gastric banding, sleeve gastrectomy, and biliopancreatic diversion) and ECA. CONCLUSIONS: Gastric bypass surgery may counteract the development of esophageal adenocarcinoma in morbidly obese individuals.

Trends in gastro-oesophageal reflux in a Norwegian general population: the Tromsø Study 1979-2016.

BACKGROUND: The prevalence of overweight and smoking has changed over time. However, whether the changes in the risk factors are reflected in the prevalence of gastro-oesophageal reflux disease (GORD) is unknown. The aims of this study were to assess the changes in prevalence of GORD and the associated risk factors over time in a general population. METHODS: This was a population-based study using repeated surveys of the Tromsø Study: Tromsø2 (1979-1980, n = 14,279), Tromsø6 (2007-2008, n = 11,460) and Tromsø7 (2015-2016, n = 20,664). Complaints of heartburn and acid regurgitation and common risk factors were reported, and height and weight were measured. The prevalence of GORD was calculated and the association with risk factors was assessed at each time point by odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression. RESULTS: The prevalence of GORD was 13% in 1979-1980, 6% in 2007-2008 and 11% in 2015-2016. In all three surveys, the risk of GORD was consistently increased with overweight and smoking. However, overweight was a weaker risk factor in the first (OR 1.58, 95% CI 1.42-1.76) compared to the last (OR 2.16, 95% CI 1.94-2.41) survey. Smoking was a stronger risk factor in the first (OR 1.45, 95% CI 1.31-1.60) than at the last (OR 1.14, 95% CI 1.01-2.29) survey. CONCLUSION: During four decades of follow-up of the same population, no clear change in prevalence of GORD was found. GORD was clearly and consistently associated with overweight and smoking. However, overweight has become a more important risk factor than smoking over time.

Cohort profile: Nordic Helicobacter Pylori eradication project (NordHePEP).

PURPOSE: This cohort description presents the Nordic Helicobacter Pylori Eradication Project (NordHePEP), a population-based cohort of patients having received eradication treatment for Helicobacter pylori (HP). The cohort is created with the main purpose of examining whether and to what extent HP eradication treatment influences the risk of gastrointestinal cancer. PARTICIPANTS: NordHePEP includes all adults (aged ≥18 years) having been prescribed and dispensed HP eradication treatment according to the nationwide complete drug registries in any of the five Nordic countries (Denmark, Finland, Iceland, Norway, or Sweden) between 1994 and 2020 (start and end year varies between countries). We have retrieved and merged individual-level data from multiple national registries, including drug, patient, cancer, population, and death registries. FINDINGS: The cohort includes 674,771 patients having received HP eradication treatment. During up to 23 years of follow-up, 59,292 (8.8%) participants were diagnosed with cancer (non-melanoma skin cancer excluded), whereof 15,496 (2.3%) in the gastrointestinal tract. FUTURE PLANS: We will analyse HP eradication treatment in relation to gastrointestinal cancer risk. Standardised incidence ratios will be calculated as the observed cancer incidence in the cohort divided by the expected cancer incidence, derived from the background population of the corresponding age, sex, and calendar year.

Risk factors for right colon, left colon and rectal cancers differ between men and women: the population-based HUNT study in Norway.

AIM: The aim of this study was to assess established risk factors for colorectal cancer (CRC) separately for right colon, left colon and rectal cancer in men and women. METHOD: This was a prospective cohort study comparing incidental CRC cases and the general population participating in a longitudinal health study in Norway (the HUNT study). RESULTS: Among 78 580 participants (36 825 men and 41 754 women), 1827 incidental CRCs were registered (931 men and 896 women). Among men, the risk of cancer at all locations increased with age [HR 1.46 (1.40-1.51), HR 1.32 (1.27-1.36), HR 1.30 (1.25-1.34) per 5 years for right colon, left colon and rectal cancer, respectively] and the risk of left colon cancer increased with higher body mass index [HR 1.28 (1.12-1.46) per 5 kg/m2 ]. The risk of right colon cancer (RCC) increased with smoking [HR 1.07 (1.04-1.10) per 5 pack years]. Among women, the risk of cancer at all locations increased with age [HR 1.38 (1.34-1.43), HR 1.23 (1.19-1.27), HR 1.20 (1.16-1.24) per 5 years] and smoking [HR 1.07 (1.02-1.12), HR 1.07 (1.02-1.12), HR 1.10 (1.05-1.17) per 5 pack years] for right colon, left colon and rectal cancer, respectively. The risk of RCC increased with night shift work [HR 1.93 (1.22-3.05)]. CONCLUSION: The risk factors for developing CRC differ by anatomical location and sex. The relationship between risk factors and CRC may be more nuanced than previously known.

Prevalence and risk factors of nonalcoholic fatty liver disease in a general population, the HUNT study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and the metabolic syndrome is the main risk factor. Alanine aminotransferase (ALT) is widely used to screen for NAFLD, and the aims of this study were to assess the prevalence and risk factors of NAFLD in a general population. METHODS: The study was based on the third population-based Trøndelag Health Study (HUNT3), Norway, performed 2006-2008. In HUNT3, ALT and lipids were analyzed, anthropometric measures done, and comorbidity and risk factors reported. Elevated ALT was used to define NAFLD and participants with other diagnosed liver diseases and excessive alcohol consumption were excluded. Multivariable logistic regression reporting odds ratio (OR) and 95% confidence interval (CI) was used to assess risk factors. RESULTS: In HUNT3, 2373 (4.7%) of 50,006 participants were diagnosed with NAFLD. The risk increased with obesity (OR 1.73, 95% CI 1.46-2.05) and very increased waist circumference (OR 1.97, 95% CI 1.65-2.35), and the risk increased dose-dependently (p for trend <0.001). Hypertension (OR 1.58, 95% CI 1.42-1.76), diabetes mellitus (OR 1.48, 95% CI 1.30-1.68), high triglycerides (OR 1.55, 95% CI 1.41-1.71), high total cholesterol (OR 1.52, 95% CI 1.29-1.81) and low high-density lipoproteins (OR 1.33, 95% CI 1.21-1.47) also increased the risk of NAFLD. The risk was lower in men (OR 0.71, 95% CI 0.64-0.79) and among current smokers (OR 0.79, 95% CI 0.70-0.89). CONCLUSION: NAFLD is a common condition in the general population. NAFLD should be suspected in individuals with abdominal obesity, hypertension, diabetes mellitus and dyslipidemias.

Risk of gastric and oesophageal adenocarcinoma following discontinuation of long-term proton-pump inhibitor therapy.

BACKGROUND: There is uncertainty whether long-term use of proton-pump inhibitors can cause gastric adenocarcinoma (GAC) and oesophageal adenocarcinoma (OAC). This study aimed to determine how discontinuation of long-term PPI therapy influences the risk of GAC and OAC. METHODS: This population-based cohort study included all long-term users of PPI therapy in Sweden in 2005-2018 was based on Swedish nationwide health registry data. The exposure was discontinuation of long-term PPI therapy, defined as no dispensation of PPI following inclusion and used as a time-varying variable, compared to remaining on PPI. Main outcomes were GAC and OAC, while oesophageal squamous cell carcinoma (OSCC) was included as a comparison outcome. Incidence rate ratios (IRR) with 95% CI adjusted for age, sex, comorbidity, obesity, diabetes, hyperlipidaemia, NSAIDs/aspirin, and statins were calculated with Poisson regression. RESULTS: Among 730,176 long-term PPI users (mean age 65.6 years, 58.4% females) with 4,210,925 person-years at risk (median 5.5 person-years), 439,390 (60.2%) discontinued PPIs. In total, 495 developed GAC, 598 OAC, and 188 developed OSCC. PPI discontinuation was associated with decreased risk of GAC (IRR 0.81, 95% CI 0.67-0.98) and OAC (IRR 0.80, 95% CI 0.68-0.96), but not OSCC (IRR 1.10, 95% CI 0.82-1.49) compared to continued PPI use. Stratified analyses showed decreased point estimates across most age categories and both sexes for GAC and OAC risk among participants discontinuing PPI therapy. CONCLUSION: Discontinuation of long-term PPI therapy may decrease the risk of GAC and OAC, suggesting that physicians should consider ceasing prescribing long-term PPI in patients without continued indication for its use.

The development and validation of a high-capacity serological assay for celiac disease.

BACKGROUND: The aim of the present study was to develop and clinically validate a high-throughput assay for serum IgA and IgG antibodies against transglutaminase-2 (TG2) and to determine appropriate assay cut-offs for large-scale population screening for celiac disease. METHOD: An automated method was developed using dual label time-resolved fluorometry on the AutoDELFIA platform. Individuals (n = 1920) from the general population were screened. Subjects with serum anti-TG2 concentrations above a preliminary cut-off (>0.3 mg*/L anti-TG2 IgA or >0.5 mg*/L anti-TG2 IgG) were offered endoscopic examination and biopsy. A diagnosis of celiac disease was given if villous atrophy (Marsh grade 3) was found. RESULTS: The assay had a limit of quantification of 0.25 mg*/L (anti-TG2 IgA) and 0.60 mg*/L (anti-TG2 IgG) with imprecision (CV) < 16% and <18% respectively. A total of 66 individuals were above the preliminary cut-off, and 56 underwent endoscopy. Of these, 26 were diagnosed with celiac disease. Sixty-eight percent of subjects with anti-TG2 IgA ≥ 0.7 mg*/L or anti-TG2 IgG ≥ 1.0 mg*/L had biopsy-proven celiac disease, and utilization of these higher cut-offs identified 96% of biopsy-positive patients. At the time of endoscopy, all individuals with anti-TG2 IgA > 2.0 mg*/L had celiac disease, and this cut-off identified 88% of newly diagnosed celiac patients. Eight percent (2/26) of the newly diagnosed patients had primarily anti-TG2 IgG. CONCLUSIONS: In this study we developed and clinically validated a robust and automated assay suitable for celiac disease screening in the general population.

Absolute Risk of Oropharyngeal Cancer After an HPV16-E6 Serology Test and Potential Implications for Screening: Results From the Human Papillomavirus Cancer Cohort Consortium.

PURPOSE: Seropositivity for the HPV16-E6 oncoprotein is a promising marker for early detection of oropharyngeal cancer (OPC), but the absolute risk of OPC after a positive or negative test is unknown. METHODS: We constructed an OPC risk prediction model that integrates (1) relative odds of OPC for HPV16-E6 serostatus and cigarette smoking from the human papillomavirus (HPV) Cancer Cohort Consortium (HPVC3), (2) US population risk factor data from the National Health Interview Survey, and (3) US sex-specific population rates of OPC and mortality. RESULTS: The nine HPVC3 cohorts included 365 participants with OPC with up to 10 years between blood draw and diagnosis and 5,794 controls. The estimated 10-year OPC risk for HPV16-E6 seropositive males at age 50 years was 17.4% (95% CI, 12.4 to 28.6) and at age 60 years was 27.1% (95% CI, 19.2 to 45.4). Corresponding 5-year risk estimates were 7.3% and 14.4%, respectively. For HPV16-E6 seropositive females, 10-year risk estimates were 3.6% (95% CI, 2.5 to 5.9) at age 50 years and 5.5% (95% CI, 3.8 to 9.2) at age 60 years and 5-year risk estimates were 1.5% and 2.7%, respectively. Over 30 years, after a seropositive result at age 50 years, an estimated 49.9% of males and 13.3% of females would develop OPC. By contrast, 10-year risks among HPV16-E6 seronegative people were very low, ranging from 0.01% to 0.25% depending on age, sex, and smoking status. CONCLUSION: We estimate that a substantial proportion of HPV16-E6 seropositive individuals will develop OPC, with 10-year risks of 17%-27% for males and 4%-6% for females age 50-60 years in the United States. This high level of risk may warrant periodic, minimally invasive surveillance after a positive HPV16-E6 serology test, particularly for males in high-incidence regions. However, an appropriate clinical protocol for surveillance remains to be established.

Epidemiology and prevention of oesophageal adenocarcinoma.

Oesophageal adenocarcinoma (OAC) develops from columnar metaplasia of the distal oesophagus, Barrett's oesophagus (BO), secondary to chronic gastro-oesophageal reflux disease (GORD). In the present review, the stepwise development of GORD, BO and OAC is presented and the evidence of OAC prevention, including treatment with proton pump inhibitors (PPIs). PPIs are the main treatment of GORD and BO, with some evidence of prevention of OAC in these patients. However, as about 40% of OAC patient do not report a history of GORD and fewer than 15% of OAC cases are detected in individuals during BO surveillance, prevention of OAC is limited by PPI use in GORD and BO patients.

The changes in prevalence and risk of irritable bowel syndrome over time in a population-based cohort, the HUNT study, Norway.

OBJECTIVE: To study the changes in prevalence of irritable bowel syndrome (IBS), the distribution between the sexes and age groups, and risk factors for the disease and its subtypes. MATERIAL AND METHODS: Every inhabitant of Nord-Trøndelag county, Norway, over 20 years of age was invited to participate in the Trøndelag Health Study (HUNT). In HUNT3 (2006-2008) and HUNT4 (2017-2019), IBS was assessed by a questionnaire. The standardized prevalence was calculated, and risk factors were assessed by multivariable logistic regression, reporting odds ratios (OR) and 95% confidence intervals (CI). RESULTS: In HUNT3 and HUNT4, 41,198 and 42,669 individuals were included, respectively. The prevalence of IBS was 7.5% in HUNT3 and 9.5% in HUNT4. Both surveys showed higher prevalence among women and among young adults. In HUNT4, the most prevalent subtype was mixed IBS (46.1%). Women had increased risk of IBS compared to men (OR 1.82, 95% CI 1.69-1.96). Age ≥40 years decreased the risk of IBS compared to age <40 years (OR 0.82, 95% CI 0.75-0.90). Being unmarried increased the risk for IBS compared to being married (OR 1.21, 95% CI 1.11-1.32). Both previous (OR 1.28, 95% CI 1.20-1.38) and current (OR 1.35, 95% CI 1.20-1.51) smokers had increased risk of IBS compared to never smokers. CONCLUSIONS: IBS is a prevalent disease, and the prevalence has increased between 2006-2008 and 2017-2019. Risk of IBS was increased among women, young adults, smokers and unmarried participants.

Intramural gastric abscess. / Intramural gastrisk abscess.

BACKGROUND: Fever and abdominal pain are common symptoms with many possible differential diagnoses. CASE PRESENTATION: An otherwise healthy man in his twenties was admitted to hospital with fever and epigastric pain. On admission he was febrile. The physical examination revealed nothing abnormal except epigastric tenderness. Laboratory data showed elevated white blood cell count and C-reactive protein level. Abdominal CT scan demonstrated a large mass in the gastric antrum. The patient underwent upper endoscopy revealing a submucosal tumour-like expansion. Puncture of the mass resulted in drainage of pus, and biopsies additionally confirmed the diagnosis of gastric wall abscess. Follow-up scans eight weeks after drainage showed complete resolution. INTERPRETATION: Gastric wall abscess is a rare but important differential diagnosis in patients presenting with fever and abdominal pain. As shown, the condition can also occur in younger patients without any known risk factors.

Hypergastrinemia and mortality in gastric adenocarcinoma: a population-based cohort study, the HUNT study.

Purpose: Hypergastrinemia increases the risk of developing proximal gastric adenocarcinoma. However, it is unclear if hypergastrinemia affects the survival in patients with gastric adenocarcinoma. This study aimed to examine the hypothesis that hypergastrinemia is associated with increased risk of mortality in patients with gastric adenocarcinoma.Materials and methods: This prospective population-based cohort study based on the Trøndelag Health Study (HUNT) included 78,962 adult individuals (≥20 years). During the baseline assessment period (1995-2008) of these participants, serum samples were collected and frozen. All participants with a newly diagnosed gastric adenocarcinoma in the cohort in 1995-2015 were identified and their gastrin levels were measured in the pre-diagnostic serum samples. Gastrin levels were analysed in relation to all-cause mortality until year 2020 using multivariable Cox regression providing hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for sex, age, body mass index (BMI), tobacco smoking, tumour stage, completeness of surgical resection, and peri-operative chemotherapy.Results: Among 172 patients with gastric adenocarcinoma, 81 (47%) had hypergastrinemia (serum gastrin >60 pmol/L) and 91 (53%) had normal gastrin level. The tumour location was proximal in 83 patients (43%) and distal in 78 (41%). Hypergastrinemia was not associated with any increased risk of all-cause mortality in all patients (adjusted HR 0.8, 95% CI 0.5-1.1), or in sub-groups of patients with proximal tumour location (HR 0.9, 95% CI 0.4-2.2) or distal tumour location (HR 0.9, 95% CI 0.5-1.7).Conclusion: This population-based cohort study indicates that hypergastrinemia may not increase the risk of mortality in patients with gastric adenocarcinoma.