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.

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

BACKGROUND & 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.

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.

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.

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.

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.

Incidence and Mortality in Upper Gastrointestinal Cancer After Negative Endoscopy for Gastroesophageal Reflux Disease.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is associated with an increased risk of cancer of the upper gastrointestinal tract. This study aimed to assess whether and to what extent a negative upper endoscopy in patients with GERD is associated with decreased incidence and mortality in upper gastrointestinal cancer (ie, esophageal, gastric, or duodenal cancer). METHODS: We conducted a population-based cohort study of all patients with newly diagnosed GERD between July 1, 1979 and December 31, 2018 in Denmark, Finland, Norway, and Sweden. The exposure, negative upper endoscopy, was examined as a time-varying exposure, where participants contributed unexposed person-time from GERD diagnosis until screened and exposed person-time from the negative upper endoscopy. The incidence and mortality in upper gastrointestinal cancer were assessed using parametric flexible models, providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among 1,062,740 patients with GERD (median age 58 years; 52% were women) followed for a mean of 7.0 person-years, 5324 (0.5%) developed upper gastrointestinal cancer and 4465 (0.4%) died from such cancer. Patients who had a negative upper endoscopy had a 55% decreased risk of upper gastrointestinal cancer compared with those who did not undergo endoscopy (HR, 0.45; 95% CI, 0.43-0.48), a decrease that was more pronounced during more recent years (HR, 0.34; 95% CI, 0.30-0.38 from 2008 onward), and was otherwise stable across sex and age groups. The corresponding reduction in upper gastrointestinal mortality among patients with upper endoscopy was 61% (adjusted HR, 0.39; 95% CI, 0.37-0.42). The risk reduction after a negative upper endoscopy in incidence and mortality lasted for 5 and at least 10 years, respectively. CONCLUSIONS: Negative upper endoscopy is associated with strong and long-lasting decreases in incidence and mortality in upper gastrointestinal cancer in patients with GERD.

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.

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.

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.

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.

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.

Laryngeal and Pharyngeal Squamous Cell Carcinoma After Antireflux Surgery in the 5 Nordic Countries.

OBJECTIVE: The aim of this study was to clarify whether antireflux surgery prevents laryngeal and pharyngeal squamous cell carcinoma. SUMMARY BACKGROUND DATA: Gastroesophageal reflux disease (GERD) seems to increase the risk of laryngeal and pharyngeal squamous cell carcinoma. METHODS: All-Nordic (Denmark, Finland, Iceland, Norway, and Sweden) population-based cohort study of adults with documented GERD in 1980 to 2014. First, cancer risk after antireflux surgery was compared to the expected risk in the corresponding background population by calculating standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). Second, cancer risk among antireflux surgery patients was compared to nonoperated GERD patients using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs, adjusted for sex, age, calendar period, and diagnoses related to tobacco smoking, obesity, and alcohol overconsumption. RESULTS: Among 814,230 GERD patients, 47,016 (5.8%) underwent antireflux surgery. The overall SIRs and HRs of the combined outcome laryngeal or pharyngeal squamous cell carcinoma (n=39) were decreased after antireflux surgery [SIR=0.62 (95% CI 0.44-0.85) and HR=0.55 (95% CI 0.38-0.80)]. The point estimates were further decreased >10 years after antireflux surgery [SIR=0.48 (95% CI 0.26-0.80) and HR=0.47 (95% CI 0.26-0.85)]. The risk estimates of laryngeal squamous cell carcinoma were particularly decreased >10 years after antireflux surgery [SIR=0.28 (95% CI 0.08-0.72) and HR=0.23 (95% CI 0.08-0.69)], whereas no such decrease over time after surgery was found for pharyngeal squamous cell carcinoma. Analyses of patients with severe GERD (reflux esophagitis or Barrett esophagus) showed similar results. CONCLUSION: Antireflux surgery may decrease the risk of laryngeal squamous cell carcinoma and possibly also of pharyngeal squamous cell carcinoma.

Risk Factors for Suicide After Bariatric Surgery in a Population-based Nationwide Study in Five Nordic Countries.

OBJECTIVE: To identify risk factors for suicide after bariatric surgery. SUMMARY BACKGROUND DATA: Bariatric surgery reduces obesity-related mortality. However, it is for unclear reasons is associated with an increased risk of suicide. METHODS: This population-based cohort study included patients having undergone bariatric surgery in 1982 to 2012 in any of the 5 Nordic countries, with follow-up through 2012. Eleven potential risk factors of suicide (sex, age, comorbidity, surgery type, surgical approach, calendar year of surgery, history of depression or anxiety, psychosis, schizophrenia, mania, or bipolar disorder, personality disorder, substance use, and number of previously documented psychiatric diagnoses) were analyzed using Cox regression. RESULTS: Of 49,977 bariatric surgery patients, 98 (0.2%) committed suicide during follow-up. Women had a decreased risk of suicide compared to men (hazard ratio [HR] = 0.48, 95% confidence interval [CI] 0.33-0.77), although age and comorbidity did not influence this risk. Compared to gastric bypass, other types of bariatric surgery had lower risk of suicide (HR = 0.44, 95%CI 0.27-0.99). There was no difference in suicide risk between laparoscopic and open surgical approach. A history of depression or anxiety (HR = 6.87, 95%CI 3.97-11.90); mania, bipolar disorder, psychosis, or schizophrenia (HR = 2.70, 95%CI 1.14-6.37); and substance use (HR = 2.28, 95%CI 1.08-4.80), increased the risk of suicide. More of the above psychiatric diagnoses increased the risk of suicide (HR = 22.59, 95%CI 12.96-39.38 for ≥2 compared to 0 diagnoses). CONCLUSIONS: Although the risk of suicide is low, psychiatric disorders, male sex, and gastric bypass procedure seem to increase the risk of suicide after bariatric surgery, indicating a role for tailored preoperative psychiatric evaluation and postoperative surveillance.

Mortality, Reoperation, and Hospital Stay Within 90 Days of Primary and Secondary Antireflux Surgery in a Population-Based Multinational Study.

BACKGROUND & AIMS: Absolute rates and risk factors of short-term outcomes after antireflux surgery remain largely unknown. We aimed to clarify absolute risks and risk factors for poor 90-day outcomes of primary laparoscopic and secondary antireflux surgery. METHODS: This population-based cohort study included patients who had primary laparoscopic or secondary antireflux surgery in the 5 Nordic countries in 2000-2018. In addition to absolute rates, we analyzed age, sex, comorbidity, hospital volume, and calendar period in relation to all-cause 90-day mortality (main outcome), 90-day reoperation, and prolonged hospital stay (≥2 days over median stay). Multivariable logistic regression provided odds ratios (ORs) with 95% confidence intervals (95% CI), adjusted for confounders. RESULTS: Among 26,193 patients who underwent primary laparoscopic antireflux surgery, postoperative 90-day mortality and 90-day reoperation rates were 0.13% (n = 35) and 3.0% (n = 750), respectively. The corresponding rates after secondary antireflux surgery (n = 1 618) were 0.19% (n = 3) and 6.2% (n = 94). Higher age (56-80 years vs 18-42 years: OR, 2.66; 95% CI 1.03-6.85) and comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 6.25; 95% CI 2.42-16.14) increased risk of 90-day mortality after primary surgery, and higher hospital volume suggested a decreased risk (highest vs lowest tertile: OR, 0.58; 95% CI, 0.22-1.57). Comorbidity increased the risk of 90-day reoperation. Higher age and comorbidity increased risk of prolonged hospital stay after both primary and secondary surgery. Higher annual hospital volume decreased the risk of prolonged hospital stay after primary surgery (highest vs lowest tertile: OR, 0.74; 95% CI, 0.67-0.80). CONCLUSION: These findings suggest that laparoscopic antireflux surgery has an overall favorable safety profile in the treatment of gastroesophageal reflux disease, particularly in younger patients without severe comorbidity who undergo surgery at high-volume centers.

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.

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.

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.

Prediagnostic circulating levels of sex hormones and survival in esophageal adenocarcinoma.

Sex hormonal differences may contribute to the strong male predominance in esophageal adenocarcinoma (EAC), but whether sex hormone levels influence survival in EAC is unstudied. Our study aimed to assess associations between prediagnostic sex hormone levels and survival in EAC. In a population-based cohort study, 244 male EAC patients from the Janus Serum Bank Cohort in Norway were followed up through 2018. Associations between prediagnostic serum levels of 12 sex hormone measures and disease-specific mortality were assessed using multivariable Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, body mass index, tobacco smoking, physical activity and surgical resection. Higher levels of sex hormone-binding globulin (SHBG) indicated decreased disease-specific mortality (HR 0.68, 95% CI 0.44-1.07, highest vs lowest tertile). In stratified analyses by surgery, such associations remained in nonoperated patients (HR 0.58, 95% CI 0.35-0.96, highest vs lowest tertile), but not in operated patients. Higher levels of follicle-stimulating hormone (FSH) were associated with increased disease-specific mortality in an exposure-response pattern; HRs for the middle and highest tertiles vs the lowest tertile were 1.35 (95% CI 0.89-2.05) and 1.61 (95% CI 1.06-2.43), respectively. No clear associations were observed with serum levels of dehydroepiandrosterone sulfate, luteinizing hormone, prolactin, testosterone, 17-OH-progesterone, progesterone, estradiol, androstenedione, testosterone:estradiol ratio or free testosterone index. These findings suggest that higher endogenous levels of SHBG and lower levels of FSH may increase the survival in EAC. The other 10 examined sex hormone measures may not influence the survival.