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.

Magnitude and Time-Trends of Post-Endoscopy Esophageal Adenocarcinoma and Post-Endoscopy Esophageal Neoplasia in a Population-Based Cohort Study: The Nordic Barrett's Esophagus Study.

BACKGROUND & AIMS: Post-endoscopy esophageal adenocarcinoma (PEEC) and post-endoscopy esophageal neoplasia (PEEN) undermine early cancer detection in Barrett's esophagus (BE). We aimed to assess the magnitude and conduct time-trend analysis of PEEC and PEEN among patients with newly diagnosed BE. METHODS: This population-based cohort study was conducted in Denmark, Finland, and Sweden between 2006 and 2020 and included 20,588 patients with newly diagnosed BE. PEEC and PEEN were defined as esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD)/EAC, respectively, diagnosed 30-365 days from BE diagnosis (index endoscopy). HGD/EAC diagnosed from 0-29 days and HGD/EAC diagnosed >365 days from BE diagnosis (incident HGD/EAC) were assessed. Patients were followed up until HGD/EAC, death, or end of study period. Incidence rates (IR) per 100,000 person-years with 95% confidence interval (95% CI) were calculated using Poisson regression. RESULTS: Among 293 patients diagnosed with EAC, 69 (23.5%) were categorized as PEEC, 43 (14.7%) as index EAC, and 181 (61.8%) as incident EAC. The IRs/100,000 person-years for PEEC and incident EAC were 392 (95% CI, 309-496), and 208 (95% CI, 180-241), respectively. Among 279 patients diagnosed with HGD/EAC (Sweden only), 17.2% were categorized as PEEN, 14.6% as index HGD/EAC, and 68.1% as incident HGD/EAC. IRs/100,000 person-years for PEEN, and incident HGD/EAC were 421 (95% CI, 317-558), and 285 (95% CI, 247-328), respectively. Sensitivity analyses that varied time interval for occurrence of PEEC/PEEN demonstrated similar results. A time-trend analysis for IRs demonstrated rising incidence rates of PEEC/PEEN. CONCLUSIONS: Almost a quarter of all EACs are detected within a year after an ostensibly negative upper endoscopy in patients with newly diagnosed BE. Interventions to improve detection may reduce PEEC/PEEN rates.

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.

Statin use in relation to long-term survival after gastrectomy for gastric adenocarcinoma: a Swedish population-based cohort study.

BACKGROUND: Studies have suggested that medication with statins improves survival in patients with gastric cancer, but methodological issues have limited the interpretability and prohibited conclusive results. We aimed to provide valid evidence as to whether statin use improves survival of gastric adenocarcinoma. METHODS: This nationwide and population-based cohort study included virtually all patients who underwent curatively intended surgery (gastrectomy) for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2019 for disease-specific mortality and 2020 for all-cause mortality. Data came from medical records and national healthcare registries. The exposure was statin use during the year prior to gastrectomy which was compared to no such use during the same period. The outcomes were 5-year disease-specific mortality (main) and 5-year all-cause mortality (secondary). Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, low-dose aspirin use, tumour sublocation, pathological tumour stage, neoadjuvant chemotherapy, annual surgeon volume, and surgical radicality. RESULTS: Among 1515 participating patients, the mean age was 69 years and 58.4% were men. Statin use, identified in 399 (26.3%) patients, was not associated with any statistically significantly decreased 5-year disease-specific mortality (HR 0.99, 95% CI 0.82-1.21) or 5-year all-cause mortality (HR 0.94, 95% CI 0.79-1.12). No risk reductions were found across subgroups of age, sex, aspirin user status, or tumour stage, or in patients with long-term preoperative of postoperative use of statins, all with point estimates close to 1. CONCLUSIONS: Perioperative use of statins does not seem to improve the 5-year survival in patients who undergo gastrectomy with curative intent for gastric adenocarcinoma in Sweden.

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.

Bariatric surgery volume by hospital and long-term survival: population-based NordOSCo data.

BACKGROUND: It is unclear whether annual hospital volume of bariatric surgery influences the long-term survival of individuals who undergo surgery for severe obesity. The hypothesis that higher annual hospital volume of bariatric surgery is associated with better long-term survival was evaluated. METHODS: This retrospective population-based study included patients who underwent bariatric surgery in Sweden and Finland between 1989 and 2020. Annual hospital volume was analysed for risk of all-cause mortality. Multivariable Cox regression provided HRs with 95 per cent confidence intervals adjusted for age, sex, co-morbidity, country, and type of bariatric procedure. RESULTS: Weight loss surgery was performed in 77 870 patients with a 0.5 per cent risk of postoperative death (mortality rate (MR) per 100 000 people 592.7, 95 per cent c.i. 575.0 to 610.9). Higher annual hospital volume of bariatric surgery was associated with a lower risk of all-cause mortality. The adjusted HRs were slightly more reduced for each quartile of annual hospital volume compared with the lowest quartile (MR per 100 000 people for lowest quartile 815.1, 95 per cent c.i. 781.7 to 849.9; for quartile II: HR 0.88, 95 per cent c.i. 0.81 to 0.96 (MR per 100 000 people 545.0, 512.0 to 580.1); for quartile III: HR 0.87, 0.78 to 0.97 (MR per 100 000 people 428.8, 395.5 to 465.0); for quartile IV: HR 0.82, 0.73 to 0.93 (MR per 100 000 people 356.0, 324.1 to 391.1)). In analyses restricted to laparoscopic surgery, volume and mortality were related only in the crude model (HR 0.86, 0.75 to 0.98), but not in the multivariable model (HR 0.97, 0.84 to 1.13) that compared highest and lowest quartiles. CONCLUSION: If there was a survival benefit associated with hospital volume, it may have been due to a faster uptake of laparoscopic surgery in the busier hospitals.

Aspirin or statin use in relation to survival after surgery for esophageal cancer: a population-based cohort study.

BACKGROUND: Adjuvant postoperative treatment with aspirin and statins may improve survival in several solid tumors. This study aimed to assess whether these medications improve the survival after curatively intended treatment (including esophagectomy) for esophageal cancer in an unselected setting. METHODS: This nationwide cohort study included nearly all patients who underwent esophagectomy for esophageal cancer in Sweden from 2006 to 2015, with complete follow-up throughout 2019. Risk of 5-year disease-specific mortality in users compared to non-users of aspirin and statins was analyzed using Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI). The HRs were adjusted for age, sex, education, calendar year, comorbidity, aspirin/statin use (mutual adjustment), tumor histology, pathological tumor stage, and neoadjuvant chemo(radio)therapy. RESULTS: The cohort included 838 patients who survived at least 1 year after esophagectomy for esophageal cancer. Of these, 165 (19.7%) used aspirin and 187 (22.3%) used statins during the first postoperative year. Neither aspirin use (HR 0.92, 95% CI 0.67-1.28) nor statin use (HR 0.88, 95% CI 0.64-1.23) were associated with any statistically significant decreased 5-year disease-specific mortality. Analyses stratified by subgroups of age, sex, tumor stage, and tumor histology did not reveal any associations between aspirin or statin use and 5-year disease-specific mortality. Three years of preoperative use of aspirin (HR 1.26, 95% CI 0.98-1.65) or statins (HR 0.99, 95% CI 0.67-1.45) did not decrease the 5-year disease-specific mortality. CONCLUSIONS: Use of aspirin or statins might not improve the 5-year survival in surgically treated esophageal cancer patients.

Aspirin use in relation to long-term survival after gastrectomy for gastric adenocarcinoma.

BACKGROUND: Low-dose aspirin use may reduce cancer incidence and mortality, but its influence on gastric adenocarcinoma survival is unclear. This study aimed to assess whether aspirin use improves long-term survival following gastrectomy for gastric adenocarcinoma. METHODS: This population-based cohort study included almost all patients who underwent gastrectomy for gastric adenocarcinoma in Sweden from 2006 to 2015, with follow-up throughout 2020. Preoperative exposure to a daily low-dose (75-160 mg) aspirin for 1 (main exposure), 2 and 3 years and for 1 year after gastrectomy was examined in relation to 5-year all-cause mortality (primary outcome) and disease-specific mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, statin use, tumour location, tumour stage, neoadjuvant chemotherapy, surgeon volume of gastrectomy and surgical radicality. RESULTS: Among 2025 patients, 545 (26.9%) used aspirin at the date of gastrectomy. Aspirin use within 1 year before surgery did not decrease the adjusted risk of 5-year all-cause mortality (HR = 0.98, 95% CI 0.85-1.13) or disease-specific mortality (HR = 1.00, 95% CI 0.86-1.17). Preoperative aspirin use for 2 years (HR = 0.98, 95% CI 0.84-1.15) or 3 years (HR = 0.94, 95% CI 0.79-1.12) did not decrease the risk of 5-year all-cause mortality. Patients remaining on aspirin during the first year after gastrectomy had a similar 5-year all-cause mortality as non-users of aspirin (HR = 1.01, 95% CI 0.82-1.25). CONCLUSIONS: Low-dose aspirin use might not improve long-term survival after gastrectomy for gastric adenocarcinoma and may thus not be a target for adjuvant therapy in this group of patients.

Endoscopy for gastroesophageal reflux disease and survival in esophageal adenocarcinoma.

Gastroesophageal reflux disease (GERD) is a risk factor of esophageal adenocarcinoma (EAC) and the most common indication for upper gastrointestinal endoscopy. Yet, whether GERD or endoscopy practice influence survival in EAC is largely unknown and was assessed in our study.This nationwide cohort study included all Swedish residents diagnosed with EAC in 1997-2013 with follow-up to 2018. Exposures were history of GERD and endoscopies prior to EAC. The main outcome was EAC-specific 5-year mortality. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for potential confounders. Among 6,600 EAC patients (79.3% males, median age 70 years) followed for 9,138 person-years, 440 (6.7%) had GERD and 592 (9.0%) had ≥1 endoscopy before EAC diagnosis. GERD was associated with a decreased risk of mortality (adjusted HR 0.71, 95% CI 0.64-0.80), which was only slightly attenuated by adjustment for prior endoscopies (HR 0.79, 95% CI 0.70-0.90), and further adjustments also for tumor stage and surgical resection (HR 0.74, 95% CI 0.62-0.89). Compared to EAC patients without prior endoscopy, mortality was unchanged in GERD patients having undergone 1 or 2 endoscopies before EAC diagnosis (HR 1.02, 95% CI 0.80-1.31, for 1 endoscopy; HR 0.90, 95% CI 0.63-1.30, for 2 endoscopies), while the mortality was decreased in patients with ≥3 endoscopies (HR 0.55, 95% CI 0.36-0.85). Our study indicates that GERD may be associated with a better prognosis in the event of EAC; however, the use of endoscopy screening has a limited impact on survival unless performed very frequently.

Adherence to clinical guidelines for Barrett's esophagus.

Background and aim: Clinical guidelines recommend endoscopy surveillance at given intervals or endoscopic therapy for Barrett's esophagus with low-grade dysplasia (LGD) and high-grade dysplasia (HGD). Whether these guidelines are followed in clinical practice is unknown and was assessed in this study. Methods: This nationwide Swedish cohort study included patients with Barrett's esophagus with histologically verified LGD or HGD from 50 centers in 2006-2013. These patients were followed up using nationwide registers. Adherence to clinical guidelines was explored. Eight potential risk factors for deviation from guidelines were assessed using multivariable logistic regression, providing adjusted odds ratios (OR) with 95% confidence intervals (95%CI). Results: Among 211 patients with Barrett's esophagus (mean age 67.0 years, standard deviation 9.7 years, 81% male), 71% had LGD and 29% had HGD. During median 3.9 years of follow-up, 84% underwent a follow-up endoscopy, 17% received endoscopic therapy and 8% underwent esophagectomy. The clinical management deviated from guidelines in 60% of all patients (69% in LGD and 39% in HGD), which was mainly due to under-surveillance (86%). Risk factors for deviation from guidelines were LGD compared to HGD (OR 3.4, 95%CI 1.7-6.8), longer Barrett's segment length (OR 2.0, 95%CI 1.0-3.9, comparing ≥3 cm with <3 cm), and treatment at gastroenterology compared to surgery departments (OR 2.3, 95%CI 1.2-4.4). Age, sex, calendar period and university hospital status were not associated with deviation from surveillance guidelines. Conclusions: Adherence to guidelines for dysplastic Barrett's esophagus is poor, particularly for LGD. Efforts to implement clinical guideline recommendations are needed.

Clinical prediction model for tumor progression in Barrett's esophagus.

BACKGROUND: Individuals with Barrett's esophagus (BE) are at increased risk of high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC), but the cost-effectiveness of general surveillance of BE is low. This study aimed to identify a risk prediction model for tumor progression in individuals with BE based on age, sex, and risk factors found at upper endoscopy, enabling tailored surveillance. METHODS: This nested case-control study originated from a cohort of 8171 adults diagnosed with BE in 2006-2013 in the Swedish Patient Registry. Cases had EAC/HGD (n = 279) as identified from the Swedish Cancer Registry, whereas controls had no EAC/HGD (n = 1089). Findings from endoscopy and histopathology reports were extracted from medical records at 71 Swedish hospitals and from the Swedish Patient Registry. Multivariable logistic regression provided odds ratios (OR) with 95% confidence intervals (CIs). RESULTS: Older age (OR 1.02 [95% CI 1.01-1.03] per year), male sex (OR 2.8 [95% CI 1.9-4.1]), and increasing maximum BE length (OR 2.3 [95% CI 1.4-3.9] for segments 3-8 cm and OR 4.3 [95% CI 2.5-7.2] for segments ≥ 8 cm) increased the risk of EAC/HGD, while the circumferential extent of the BE, hiatal hernia or reflux esophagitis did not. A model based on age, sex, and maximum BE length predicted 71% of all EAC/HGD cases. CONCLUSIONS: A simple combination of the variables age, sex and maximum BE length showed fairly good accuracy for predicting tumor progression in BE. This clinical risk prediction model may help to tailor future surveillance programs.

Cerebrospinal fluid kynurenine and kynurenic acid concentrations are associated with coma duration and long-term neurocognitive impairment in Ugandan children with cerebral malaria.

BACKGROUND: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated. METHODS: Cerebrospinal fluid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed. CSF kynurenine and KYNA were compared to CSF cytokine levels, acute and long-term neurologic complications, and long-term cognitive impairments. CSF kynurenine and KYNA from eight Swedish children without neurological or infectious disease admitted to Astrid Lindgren's Children's Hospital were quantified and used for comparison. RESULTS: Children with CM had significantly higher CSF concentration of kynurenine and KYNA than Swedish children (P < 0.0001 for both), and CSF kynurenine and KYNA were positively correlated. In children with CM, CSF kynurenine and KYNA concentrations were associated with coma duration in children of all ages (P = 0.003 and 0.04, respectively), and CSF kynurenine concentrations were associated with worse overall cognition (P = 0.056) and attention (P = 0.003) at 12-month follow-up in children ≥5 years old. CONCLUSIONS: CSF KYNA and kynurenine are elevated in children with CM, indicating an inhibition of glutamatergic and cholinergic signaling. This inhibition may lead acutely to prolonged coma and long-term to impairment of attention and cognition.

Temporal Changes in Obesity-Related Medication After Bariatric Surgery vs No Surgery for Obesity.

Importance: Bariatric surgery can resolve hyperlipidemia, cardiovascular disease, and diabetes, but the long-term postoperative trajectories of medications for these conditions are unknown. Objective: To clarify the long-term use of lipid-lowering, cardiovascular, and antidiabetic medication after bariatric surgery compared with no surgery for morbid obesity. Design, Setting, and Participants: This population-based cohort study took place in Sweden (2005-2020) and Finland (1995-2018) and included individuals diagnosed with obesity. Analysis took place between July 2021 and January 2022. Exposures: Bariatric surgery (gastric bypass or sleeve gastrectomy) patients using lipid-lowering, cardiovascular, or antidiabetic medication were compared with 5 times as many control patients with an obesity diagnosis treated with no surgery, matched for country, age, sex, calendar year, and medication use. Main Outcomes and Measures: Proportions with 95% CIs of lipid-lowering, cardiovascular, or antidiabetic medication. Results: A total of 26 396 patients underwent bariatric surgery (with gastric bypass or sleeve gastrectomy) (17 521 [66.4%] women; median [IQR] age, 50 [43-56] years) and 131 980 matched control patients (87 605 [66.4%%] women; median [IQR] age, 50 [43-56] years) were included. The proportion of lipid-lowering medication after bariatric surgery decreased from 20.3% (95% CI, 20.2%-20.5%) at baseline to 12.9% (95% CI, 12.7%-13.0%) after 2 years and 17.6% (95% CI, 13.3%-21.8%) after 15 years, while it increased in the no surgery group from 21.0% (95% CI, 20.9%-21.1%) at baseline to 44.6% (95% CI, 41.7%-47.5%) after 15 years. Cardiovascular medications were used by 60.2% (95% CI, 60.0%-60.5%) of bariatric surgery patients at baseline, decreased to 43.2% (95% CI, 42.9%-43.4%) after 2 years, and increased to 74.6% (95% CI, 65.8%-83.4%) after 15 years, while it increased in the no surgery group from 54.4% (95% CI, 54.3%-54.5%) at baseline to 83.3% (95% CI, 79.3%-87.3%) after 15 years. Antidiabetic medications were used by 27.7% (95% CI, 27.6%-27.9%) in the bariatric surgery group at baseline, decreased to 10.0% (95% CI, 9.9%-10.2%) after 2 years, and increased to 23.5% (95% CI, 18.5%-28.5%) after 15 years, while it increased in the no surgery group from 27.7% (95% CI, 27.6%-27.7%) at baseline to 54.2% (95% CI, 51.0%-57.5%) after 15 years. Conclusions and Relevance: In this study, undergoing bariatric surgery was associated with a substantial and long-lasting reduction in the use of lipid-lowering and antidiabetic medications compared with no surgery for obesity, while for cardiovascular medications this reduction was only transient.

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.

The association between bariatric surgery and cataract: a propensity score-matched cohort study.

BACKGROUND: Obesity is considered a risk factor for cataracts. The association between weight loss and a cataract among patients with obesity has not been assessed to date. OBJECTIVES: To assess the association between weight loss following bariatric surgery and cataracts. SETTING: Nationwide Swedish healthcare registries between 2006 and 2019. METHODS: We performed a population-based cohort study. Patients aged 40-79 years who underwent bariatric surgery were matched on their propensity score (PS) to up to 2 patients with obesity ("unexposed patients"). Cox proportional hazard regression analyses calculated hazard ratios (HRs) and 95% confidence intervals (CIs) of developing cataracts following bariatric surgery, compared with unexposed patients. Subgroup analyses by age, sex, bariatric surgery type, and duration of follow-up were conducted. RESULTS: In total, 22,560 bariatric surgery patients were PS-matched to 35,523 unexposed patients. The risk of cataracts was decreased in bariatric surgery patients compared with unexposed patients (HR .71, 95% CI .66-.76). We observed the lowest risk of cataracts among bariatric surgery patients aged 40-49 years (HR .52, 95% CI .44-.75) but a null result for patients aged ≥60 years. Gastric bypass or duodenal switch were associated with decreased risks of cataracts, whereas sleeve gastrectomy yielded a null result. Subgroups of sex and duration of follow-up showed no evidence of effect modification (hazards were proportional throughout follow-up). CONCLUSION: Our results suggest that substantial weight loss following bariatric surgery is associated with a decreased risk of cataracts, especially if bariatric surgery was performed before age 60.

Long-term Survival After Sleeve Gastrectomy Versus Gastric Bypass in a Binational Cohort Study.

OBJECTIVE: Bariatric surgery prolongs life expectancy in severely obese individuals, but it is uncertain which of the two dominating bariatric procedures, sleeve gastrectomy or gastric bypass, offers the best long-term survival. RESEARCH DESIGN AND METHODS: This was a population-based cohort study of primary laparoscopic sleeve gastrectomy compared with gastric bypass for obesity in Sweden and Finland between 1 January 2007 and 31 December 2020. The risk of all-cause mortality was calculated using multivariable Cox regression, providing hazard ratios (HRs) with 95% CIs adjusted for age, sex, hypertension, diabetes, Charlson comorbidity index, country, and calendar year. RESULTS: Among 61,503 patients (median age 42 years; 75.4% women), who contributed 415,712 person-years at risk (mean 6.8 person-years), 1,571 (2.6%) died during follow-up. Compared with patients who underwent gastric bypass (n = 51,891 [84.4%]), the sleeve gastrectomy group (n = 9,612 [15.6%]) had similar all-cause mortality during the entire study period (HR 0.98, 95% CI 0.81-1.20), but decreased all-cause mortality in more recent years (HR 0.72, 95% CI 0.54-0.97, from 2014 onward). Diabetes interacted statistically significantly with the type of bariatric surgery, with higher all-cause mortality after sleeve gastrectomy than after gastric bypass (HR 1.54, 95% CI 1.06-2.24). CONCLUSIONS: The overall survival following sleeve gastrectomy seems to compare well with gastric bypass and may even be better during recent years. A tailored surgical approach in relation to patients' diabetes status may optimize survival in patients selected for bariatric surgery (i.e., sleeve gastrectomy for patients without diabetes and gastric bypass for patients with diabetes).

The association of bariatric surgery and Dupuytren's disease: a propensity score-matched cohort study.

We aimed to assess the association between bariatric surgery and incident Dupuytren's disease (DD) using propensity score-matched cohort studies among Swedish nationwide healthcare registries. Patients aged 30-79 years who underwent bariatric surgery 2006-2019 were matched on their propensity scores, up to two obese bariatric surgery-free (unexposed) patients. We applied Cox proportional hazard regression to calculate hazard ratios (HR) with 95% confidence intervals (CI) for the risk of DD overall, in subgroups of age, sex, bariatric surgery type and duration of follow-up. Among 34,959 bariatric surgery patients and 54,769 propensity score-matched obese patients, the risk of DD was increased in bariatric surgery patients compared with obese unexposed patients (HR 1.30, 95% CI 1.02-1.65), among women (HR 1.36; 1.00-1.84); those undergoing gastric bypass (HR 1.33; 1.04-1.71) and those with >5 years follow-up (HR 1.63; 1.14-2.34). Our results suggest that substantial weight loss is associated with an increased risk of DD in an obese population.Level of evidence: III.

The associations between bariatric surgery and hip or knee arthroplasty, and hip or knee osteoarthritis: Propensity score-matched cohort studies.

Objective: To investigate the associations between bariatric surgery and hip or knee arthroplasty, and secondary care hip or knee osteoarthritis (OA). Methods: We performed cohort studies using data from Swedish nationwide healthcare registries. Patients aged 18-79 years who underwent bariatric surgery between 2006 and 2019 were matched on their propensity score (PS) to up to 2 obese patients ("unexposed episodes") in risk-set sampling. After a 1-year run-in period, episodes were followed in an "as-treated" approach. Using Cox proportional hazard regression, we calculated hazard ratios (HR) with 95% confidence intervals (CIs) of hip or knee arthroplasty overall and in subgroups of age, sex, joint location, arthroplasty type, bariatric surgery type, and by duration of follow-up if proportional hazard assumptions were violated. In a secondary cohort, we assessed the outcome incident secondary care hip or knee osteoarthritis (OA). Results: Among 39'392 bariatric surgery episodes when compared to 61'085 â€‹PS-matched unexposed episodes (47'594 unique patients), the risk of hip or knee arthroplasty was strongest increased within the first three years of follow-up (HR 1.79, 95% CI 1.56-2.07), decreased thereafter, but remained elevated throughout follow-up. In a secondary cohort of 37'929 exposed when compared to 58'600 â€‹PS-matched unexposed episodes, the risk of hip or knee osteoarthritis was decreased (HR 0.84, 95% CI 0.79-0.90). Conclusion: Bariatric surgery is associated with increased risks of hip or knee arthroplasty, but also with decreased risks of secondary care OA. This contradiction supports the hypothesis that bariatric surgery may act as an enabler for hip or knee arthroplasty.