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.

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.

Neoadjuvant chemotherapy in relation to long-term mortality in individuals cured of gastric adenocarcinoma.

BACKGROUND: Late effects of chemotherapy could affect mortality amongst cancer survivors. This study aimed to clarify if neoadjuvant chemotherapy for gastric adenocarcinoma influences the long-term survival in individuals cured of this tumour. METHODS: This was a nationwide and population-based cohort study that included all individuals who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 and survived for ≥ 5 years after surgery. The cohort was followed up until death or end of study period (31 December 2020). Multivariable Cox proportional hazards regression was used to provide hazard ratios (HR) with 95% confidence intervals (CI). The HR were adjusted for age, sex, comorbidity, education, calendar year, tumour sub-location, in-hospital complications, and splenectomy. Data came from medical records and nationwide registers. RESULTS: Amongst 613 gastric adenocarcinoma survivors, neoadjuvant chemotherapy (used in 269 patients; 43.9%) was associated with a decreased crude mortality rate (HR 0.66, 95% CI 0.46-0.96). However, the association attenuated and became statistically non-significant after adjustment for all confounders (HR 0.83, 95% CI 0.56-1.23) and after adjustments solely for age and comorbidity (HR 0.82, 95% CI 0.56-1.20). Stratified analyses did not reveal any statistically significant associations between neoadjuvant chemotherapy and long-term mortality in categories of age, sex, comorbidity, calendar year and tumour sub-location. CONCLUSION: Neoadjuvant chemotherapy did not decrease the long-term survival amongst gastric adenocarcinoma survivors. Patients who received neoadjuvant chemotherapy were a selected group characterised by younger age and fewer severe comorbidities and therefore with better chances of long-term survival.

Survival among patients cured from gastric adenocarcinoma compared to the background population.

BACKGROUND: It is unknown if gastric adenocarcinoma survivors have longer, shorter, or similar survival compared to the background population. This knowledge could contribute to evidence-based monitoring strategies, healthcare recommendations, and information for patients and families. METHODS: This population-based cohort study included all patients who underwent gastrectomy for gastric adenocarcinoma between 2006-2015 in Sweden and survived ≥ 5 years after surgery. They were followed up until death, postoperative year 10, or end of study period (31 December, 2020). Division of the observed by the expected survival yielded relative survival rates with 95% confidence intervals (CIs) using the life table method. The expected survival was derived from the entire Swedish population of the corresponding age, sex, and calendar year. Data came from medical records and nationwide registers. RESULTS: The survival among all 767 gastric adenocarcinoma survivors was shorter than the expected. The reduction in relative survival increased for each follow-up year, from 97.3% (95% CI 95.4-99.1%) year 6 to 86.6% (95% CI 82.3-90.9%) year 10. The decline in relative survival was more pronounced among patients who had gastrectomy in earlier calendar years (82.9% [95% CI 77.4-88.4%] year 10 for years 2011-2015), shorter education (85.2% [95% CI 77.4-93.0%] year 10 for education ≤ 9 years), more comorbidities (78.0% [95% CI 63.9-92.0%] year 10 for Charlson comorbidity score ≥ 2), and no neoadjuvant therapy (83.2% [95% CI 77.4-89.0%] year 10). CONCLUSION: Gastric adenocarcinoma survivors seem to have poorer survival than the corresponding background population, particularly in certain subgroups.

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.

Risk of Myocardial Infarction, Ischemic Stroke, and Mortality in Patients Who Undergo Gastric Bypass for Obesity Compared With Nonoperated Obese Patients and Population Controls.

OBJECTIVE: The aim of this study was to estimate risks of myocardial infarction, ischemic stroke, and cardiovascular-related and all-cause mortality after Roux-en-Y gastric bypass (RYGB) for obesity compared with nonop-erated obese patients and matched nonobese population controls. BACKGROUND: Few studies have assessed the influence of RYGB on fatal and non-fatal myocardial infarction and ischemic stroke, and the results vary between studies. METHOD: All patients aged 20 to 65 years with obesity diagnosis in the nationwide Swedish Patient Registry in 2001 to 2013 were included. These participants were divided into those who underwent RYGB within 2 years of obesity diagnosis (n = 28,204) and nonoperated (n = 40,827), and were matched for age, sex, and region with 2 nonobese population controls. Participants were followed until onset of outcome disease, death, or end of follow-up. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (95% CI). RESULTS: Compared with nonoperated patients with obesity, RYGB patients had a reduced risk of myocardial infarction [HR = 0.44 (95% CI 0.28-0.63)], similar risk of ischemic stroke [HR = 0.79 (95% CI 0.54-1.14)], and decreased risks of cardiovascular-related [HR = 0.47 (95% CI 0.35-0.65)] and all-cause mortality [HR = 0.66 (95% CI 0.54-0.81)] within the first 3 years of follow-up, but not later. Compared with nonobese population controls, RYGB patients had excess risks of ischemic stroke [HR = 1.57 (95% CI 1.08-2.29)], cardiovascular-related mortality [HR = 1.82 (95% CI 1.29-2.60)], and all-cause mortality [HR = 1.42 (95% CI 1.16-1.74)], but not of myocardial infarction [HR = 1.02 (95% CI 0.72-1.46)]. CONCLUSION: RYGB for obesity might not decrease the risk of ischemic stroke, but seems to decrease the risk of myocardial infarction back to population levels.

Extent of Lymphadenectomy and Long-term Survival in Esophageal Cancer.

OBJECTIVE: To examine the hypothesis that survival in esophageal cancer increases with more removed lymph nodes during esophagectomy up to a plateau, after which it levels out or even decreases with further lymphadenec-tomy. SUMMARY OF BACKGROUND DATA: There is uncertainty regarding the ideal extent of lymphadenectomy during esophagectomy to optimize long-term survival in esophageal cancer. METHODS: This population-based cohort study included almost every patient who underwent esophagectomy for esophageal cancer in Sweden or Finland in 2000-2016 with follow-up through 2019. Degree of lymphadenectomy, divided into deciles, was analyzed in relation to all-cause 5-year mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for all established prognostic factors. RESULTS: Among 2306 patients, the second (4-8 nodes), seventh (21-24 nodes) and eighth decile (25-30 nodes) of lymphadenectomy showed the lowest all-cause 5-year mortality compared to the first decile [hazard ratio (HR) = 0.77, 95% CI 0.61-0.97, HR = 0.76, 95% CI 0.59-0.99, and HR = 0.73, 95% CI 0.57-0.93, respectively]. In stratified analyses, the survival benefit was greatest in decile 7 for patients with pathological T-stage T3/T4 (HR = 0.56, 95% CI0.40-0.78), although it was statistically improved in all deciles except decile 10. For patients without neoadjuvant chemotherapy, survival was greatest in decile 7 (HR = 0.60, 95% CI 0.41-0.86), although survival was also statistically significantly improved in deciles 2, 6, and 8. CONCLUSION: Survival in esophageal cancer was not improved by extensive lymphadenectomy, but resection of a moderate number (20-30) of nodes was prognostically beneficial for patients with advanced T-stages (T3/T4) and those not receiving neoadjuvant therapy.

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.

Impact of Age on the Treatment and Survival in Esophagogastric Cancer.

BACKGROUND: The age-specific risks of mortality for patients with esophagogastric cancer and their probability of surgical treatment are not well-known. METHODS: This population-based, nationwide cohort study included all patients with esophageal or gastric (esophagogastric) cancer in Sweden between 1990 and 2013, with follow-up evaluation throughout 2018. Age at diagnosis (exposure) was categorized into nine 5-year groups. The main outcome was 5-year all-cause mortality. The secondary outcomes were 90-day all-cause mortality, 5-year disease-specific mortality, 5-year disease-specific mortality excluding 90-day all-cause mortality, and non-operation. For mortality outcomes, Cox regression provided hazard ratios (HRs) with 95% confidence intervals (95% CIs) adjusted for confounders. For non-operation, logistic regression provided odds ratios (ORs) with 95% CIs. RESULTS: Among 28,725 patients, 11,207 (39.0%) underwent surgery. For those who underwent surgery, the HRs of 5-year all-cause mortality were stable before the ages of 65 to 69 years. After that, it gradually increased for patients 65 to 69 years old (HR, 1.13; 95% CI, 1.01-1.26), patients 75 to 79 years old (HR, 1.29; 95% CI, 1.56-1.44), and patients older than 85 years (HR, 1.84; 95% CI, 1.60-2.11) compared with those younger than 50 years. Analyses of age as a continuous variable, other mortality outcomes and stratification by comorbidity and tumor type showed similar results. The odds of non-operation increased for patients 75 to 79 years old (OR, 2.09 [95% CI, 1.84-2.94] for patients 80 to 84 years old and OR, 5.00 [95% CI, 4.31-5.78] for patients ≥85 years old or older), compared with those younger than 50 years. CONCLUSION: Older age, starting from 65 years, is associated with worse survival after surgery for esophagogastric cancer, and from 75 years with lower odds of surgical treatment.

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.

Metabolic tumour and nodal response to neoadjuvant chemotherapy on FDG PET-CT as a predictor of pathological response and survival in patients with oesophageal adenocarcinoma.

OBJECTIVES: 2-deoxy-2[18F]Fluoro-D-glucose (FDG) PET-CT has an emerging role in assessing response to neoadjuvant therapy in oesophageal cancer. This study evaluated FDG PET-CT in predicting pathological tumour response (pTR), pathological nodal response (pNR) and survival. METHODS: Cohort study of 75 patients with oesophageal or oesophago-gastric junction (GOJ) adenocarcinoma treated with neoadjuvant chemotherapy then surgery at Guy's and St Thomas' NHS Foundation Trust, London (2017-2020). Standardised uptake value (SUV) metrics on pre- and post-treatment FDG PET-CT in the primary tumour (mTR) and loco-regional lymph nodes (mNR) were derived. Optimum SUVmax thresholds for predicting pathological response were identified using receiver operating characteristic analysis. Predictive accuracy was compared to PERCIST (30% SUVmax reduction) and MUNICON (35%) criteria. Survival was assessed using Cox regression. RESULTS: Optimum tumour SUVmax decrease for predicting pTR was 51.2%. A 50% cut-off predicted pTR with 73.5% sensitivity, 69.2% specificity and greater accuracy than PERCIST or MUNICON (area under the curve [AUC] 0.714, PERCIST 0.631, MUNICON 0.659). Using a 30% SUVmax threshold, mNR predicted pNR with high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p = 0.010). pTR, mTR, pNR and mNR were independent predictive factors for survival (pTR hazard ratio [HR] 0.10 95% confidence interval [CI] 0.03-0.34; mTR HR 0.17 95% CI 0.06-0.48; pNR HR 0.17 95% CI 0.06-0.54; mNR HR 0.13 95% CI 0.02-0.66). CONCLUSIONS: Metabolic tumour and nodal response predicted pTR and pNR, respectively, in patients with oesophageal or GOJ adenocarcinoma. However, currently utilised response criteria may not be optimal. pTR, mTR, pNR and mNR were independent predictors of survival. KEY POINTS: • FDG PET-CT has an emerging role in evaluating response to neoadjuvant therapy in patients with oesophageal cancer. • Prospective cohort study demonstrated that metabolic response in the primary tumour and lymph nodes was predictive of pathological response in a cohort of patients with adenocarcinoma of the oesophagus or oesophago-gastric junction treated with neoadjuvant chemotherapy followed by surgical resection. • Patients who demonstrated a response to neoadjuvant chemotherapy in the primary tumour or lymph nodes on FDG PET-CT demonstrated better survival and reduced rates of tumour recurrence.

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.

Use of 5α-reductase inhibitors and survival of oesophageal and gastric cancer in a nationwide Swedish cohort study.

BACKGROUND: We hypothesised that the use of the anti-androgenic drug 5α-reductase inhibitors (5-ARIs) improves survival in patients with oesophago-gastric cancer. METHODS: This nationwide Swedish population-based cohort study included men who underwent surgery for oesophageal or gastric cancer between 2006-2015, with follow-up until the end of 2020. Multivariable Cox regression estimated hazard ratios (HR) for associations between 5-ARIs use and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome). The HR was adjusted for age, comorbidity, education, calendar year, neoadjuvant chemo(radio)therapy, tumour stage, and resection margin status. RESULTS: Among 1769 patients with oesophago-gastric cancer, 64 (3.6%) were users of 5-ARIs. Compared to non-users, users of 5-ARIs were not at any decreased risk of 5-year all-cause mortality (adjusted HR 1.13, 95% CI 0.79-1.63) or 5-year disease-specific mortality (adjusted HR 1.10, 95% CI 0.79-1.52). Use of 5-ARIs was not associated with any decreased risk of 5-year all-cause mortality in subgroup analyses stratified by categories of age, comorbidity, tumour stage, or tumour subtype (oesophageal or cardia adenocarcinoma, non-cardia gastric adenocarcinoma, or oesophageal squamous cell carcinoma). CONCLUSION: This study did not support the hypothesis of improved survival among users of 5-ARIs after curatively intended treatment for oesophago-gastric cancer.

Menopausal hormone therapy and risk of oesophageal adenocarcinoma in a population-based cohort study.

BACKGROUND: Oesophageal adenocarcinoma is characterised by a strong male predominance. We aimed to test the hypothesis that menopausal hormonal therapy decreases the risk of oesophageal adenocarcinoma. METHODS: This population-based cohort study included all women who used systemic menopausal hormonal therapy (exposed) in Sweden between 2005 and 2018. For each exposed participant, five randomly selected female age-matched non-users of menopausal hormonal therapy (unexposed) were included. Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, smoking-related diagnoses, Helicobacter pylori eradication, use of non-steroidal anti-inflammatory drugs/aspirin, use of statins and hysterectomy. RESULTS: The study included 296,964 users of menopausal hormonal therapy and 1,484,820 non-users. Ever-users of menopausal hormonal therapy had an overall decreased risk of oesophageal adenocarcinoma (HR 0.78, 95% CI 0.63-0.97), which remained unchanged after further adjustment for gastro-oesophageal reflux disease (HR 0.78, 95% CI 0.63-0.97) and obesity/diabetes (HR 0.79, 95% CI 0.63-0.98). Decreased HRs were indicated both in users of oestrogen only (HR 0.82, 95% CI 0.60-1.12) and oestrogen combined with progestogen (HR 0.75, 95% CI 0.56-1.00). The risk reduction was more pronounced in users younger than 60 years (HR 0.57, 95% CI 0.38-0.86). CONCLUSIONS: Menopausal hormone therapy in women may decrease the risk of oesophageal adenocarcinoma.

Haemoglobin A1c and serum glucose levels and risk of gastric cancer: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis examined associations between serum levels of haemoglobin A1c (HbA1c) and glucose and the risk of gastric cancer. METHODS: MEDLINE, Embase, and Cochrane Library were searched for studies examining associations between serum levels of HbA1c or glucose and the risk of gastric cancer. Inclusion of studies, quality assessment, and data extraction were conducted independently by two authors. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were synthesised using random-effects models. Cochran's Q test and I2 statistic were used to assess heterogeneity. RESULTS: Among 3473 identified studies, 12 were included. Of these, 5 studies examined HbA1c levels and 7 studies examined serum glucose levels. Serum HbA1c levels >6% were associated with an increased risk of gastric cancer (HR 1.36, 95% CI 1.06-1.74). When compared with the lowest glucose categories, the highest glucose categories were associated with a borderline increased risk of gastric cancer (HR 1.11, 95% CI 0.98-1.26). In subgroup analyses, studies that adjusted for Helicobacter pylori infection indicated stronger associations between elevated HbA1c levels and gastric cancer (HR 2.08, 95% CI 1.46-2.98) than those without such adjustment (HR 1.10, 95% CI 0.91-1.32). CONCLUSIONS: Long-standing poor glycaemic control may increase the risk of gastric cancer. REGISTRATION NUMBER: PROSPERO CRD42020157453.

Use of anti-androgenic 5α-reductase inhibitors and risk of oesophageal and gastric cancer by histological type and anatomical sub-site.

BACKGROUND: To investigate if anti-androgenic medications 5α-reductase inhibitors (5-ARIs) decrease the risk of developing oesophageal and gastric tumours, analysed by histological type and anatomical sub-site. METHODS: A Swedish population-based cohort study between 2005 and 2018 where men using 5-ARIs were considered exposed. For each exposed participant, ten male age-matched non-users of 5-ARIs (non-exposed) were included. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, smoking, non-steroidal anti-inflammatory drugs/aspirin use, and statins use. Further adjustments were made depending on the tumour analysed. RESULTS: The cohort included 191,156 users of 5-ARIs and 1,911,560 non-users. Overall, the use of 5-ARIs was not associated with any statistically significantly reduced risk of oesophageal or cardia adenocarcinoma (adjusted HR 0.92, 95% CI 0.82-1.02) or gastric non-cardia adenocarcinoma (adjusted HR 0.90, 95% CI 0.80-1.02). However, the use of 5-ARIs indicated a decreased risk of oesophageal or cardia adenocarcinoma among obese or diabetic participants (adjusted HR 0.55, 95% CI 0.39-0.80) and a reduced risk of oesophageal squamous cell carcinoma (adjusted HR 0.49, 95% CI 0.37-0.65). CONCLUSION: Users of 5-ARIs may have a decreased risk of developing oesophageal or cardia adenocarcinoma among those obese or diabetic, and a decreased risk of oesophageal squamous cell carcinoma.