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.

Breast density and risk of breast cancer.

Early studies reported a 4- to 6-fold risk of breast cancer between women with extremely dense and fatty breasts. As most early studies were case-control studies, we took advantage of a population-based screening program to study density and breast cancer incidence in a cohort design. In the Capital Region, Denmark, women aged 50 to 69 are invited to screening biennially. Women screened November 2012 to December 2017 were included, and classified by BI-RADS density code, version 4, at first screen after recruitment. Women were followed up for incident breast cancer, including ductal carcinoma in situ (DCIS), to 2020 in nationwide pathology data. Rate ratios (RRs) and 95% confidence intervals (CI) were compared across density groups using Poisson-regression. We included 189 609 women; 1 067 282 person-years; and 4110 incident breast cancers/DCIS. Thirty-three percent of women had BI-RADS density code 1; 38% code 2; 24% code 3; 4.7% code 4; and missing 0.3%. Using women with BI-RADS density code 1 as baseline; women with code 2 had RR 1.69 (95% CI 1.56-1.84); women with code 3, RR 2.06 (95% CI 1.89-2.25); and women with code 4, RR 2.37 (95% CI 1.05-2.74). Results differed between observations accumulated during screening and above screening age. Our results indicated less difference in breast cancer risk across level of breast density than normally stated. Translated into absolute risk of breast cancer after age 50, we found a 6.2% risk for the one-third of women with lowest density, and 14.7% for the 5% of women with highest density.

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.

Assessing Breast Cancer Risk by Combining AI for Lesion Detection and Mammographic Texture.

Background Recent mammography-based risk models can estimate short-term or long-term breast cancer risk, but whether risk assessment may improve by combining these models has not been evaluated. Purpose To determine whether breast cancer risk assessment improves when combining a diagnostic artificial intelligence (AI) system for lesion detection and a mammographic texture model. Materials and Methods This retrospective study included Danish women consecutively screened for breast cancer at mammography from November 2012 to December 2015 who had at least 5 years of follow-up data. Examinations were evaluated for short-term risk using a commercially available diagnostic AI system for lesion detection, which produced a score to indicate the probability of cancer. A mammographic texture model, trained on a separate data set, assessed textures associated with long-term cancer risk. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate both the individual and combined performance of the AI and texture models for the prediction of future cancers in women with a negative screening mammogram, including those with interval cancers diagnosed within 2 years of screening and long-term cancers diagnosed 2 years or more after screening. AUCs were compared using the DeLong test. Results The Danish screening cohort included 119 650 women (median age, 59 years [IQR, 53-64 years]), of whom 320 developed interval cancers and 1401 developed long-term cancers. The combination model achieved a higher AUC for interval and long-term cancers grouped together than either the diagnostic AI (AUC, 0.73 vs 0.70; P < .001) or the texture risk (AUC, 0.73 vs 0.66; P < .001) models. The 10% of women with the highest combined risk identified by the combination model accounted for 44.1% (141 of 320) of interval cancers and 33.7% (472 of 1401) of long-term cancers. Conclusion Combining a diagnostic AI system and mammographic texture model resulted in improved risk assessment for interval cancers and long-term cancers and enabled identification of women at high risk. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Poynton and Slanetz in this issue.

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

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

Risk Factors for 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.

An Artificial Intelligence-based Mammography Screening Protocol for Breast Cancer: Outcome and Radiologist Workload.

Background Developments in artificial intelligence (AI) systems to assist radiologists in reading mammograms could improve breast cancer screening efficiency. Purpose To investigate whether an AI system could detect normal, moderate-risk, and suspicious mammograms in a screening sample to safely reduce radiologist workload and evaluate across Breast Imaging Reporting and Data System (BI-RADS) densities. Materials and Methods This retrospective simulation study analyzed mammographic examination data consecutively collected from January 2014 to December 2015 in the Danish Capital Region breast cancer screening program. All mammograms were scored from 0 to 10, representing the risk of malignancy, using an AI tool. During simulation, normal mammograms (score < 5) would be excluded from radiologist reading and suspicious mammograms (score > recall threshold [RT]) would be recalled. Two radiologists read the remaining mammograms. The RT was fitted using another independent cohort (same institution) by matching to the radiologist sensitivity. This protocol was further applied to each BI-RADS density. Screening outcomes were measured using the sensitivity, specificity, workload, and false-positive rate. The AI-based screening was tested for noninferiority sensitivity compared with radiologist screening using the Farrington-Manning test. Specificities were compared using the McNemar test. Results The study sample comprised 114 421 screenings for breast cancer in 114 421 women, resulting in 791 screen-detected, 327 interval, and 1473 long-term cancers and 2107 false-positive screenings. The mean age of the women was 59 years ± 6 (SD). The AI-based screening sensitivity was 69.7% (779 of 1118; 95% CI: 66.9, 72.4) and was noninferior (P = .02) to the radiologist screening sensitivity of 70.8% (791 of 1118; 95% CI: 68.0, 73.5). The AI-based screening specificity was 98.6% (111 725 of 113 303; 95% CI: 98.5, 98.7), which was higher (P < .001) than the radiologist specificity of 98.1% (111 196 of 113 303; 95% CI: 98.1, 98.2). The radiologist workload was reduced by 62.6% (71 585 of 114 421), and 25.1% (529 of 2107) of false-positive screenings were avoided. Screening results were consistent across BI-RADS densities, although not significantly so for sensitivity. Conclusion Artificial intelligence (AI)-based screening could detect normal, moderate-risk, and suspicious mammograms in a breast cancer screening program, which may reduce the radiologist workload. AI-based screening performed consistently across breast densities. © RSNA, 2022 Online supplemental material is available for this article.

Esophageal Adenocarcinoma After Antireflux Surgery in a Cohort Study From the 5 Nordic Countries.

OBJECTIVE: We aimed to clarify the long-term risk development of EAC after antireflux surgery. SUMMARY OF BACKGROUND DATA: Gastroesophageal reflux disease (GERD) increases EAC risk, but whether antireflux surgery prevents EAC is uncertain. METHODS: Multinational, population-based cohort study including individuals with GERD from all 5 Nordic countries in 1964-2014. First, EAC risk after antireflux surgery in the cohort was compared with the corresponding background population by calculating standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs). Second, multivariable Cox proportional hazards regression, providing hazard ratios (HRs) with 95% CIs, compared EAC risk in GERD patients with antireflux surgery with those with nonsurgical treatment. RESULTS: Among 942,071 GERD patients, 48,863 underwent surgery and 893,208 did not. Compared to the corresponding background population, EAC risk did not decrease after antireflux surgery [SIR 4.90 (95% CI 3.62-6.47) 1-<5 years and SIR 4.57 (95% CI 3.44-5.95) ≥15 years after surgery]. Similarly, no decrease was found for patients with severe GERD (esophagitis or Barrett esophagus) after surgery [SIR 6.09 (95% CI 4.39-8.23) 1-<5 years and SIR = 5.27 (95% CI 3.73-7.23) ≥15 years]. The HRs of EAC were stable comparing the surgery group with the nonsurgery group with GERD [HR 1.71 (95% CI 1.26-2.33) 1-<5 years and HR 1.69 (95% CI 1.24-2.30) ≥15 years after treatment], or for severe GERD [HR 1.56 (95% CI 1.11-2.20) 1-<5 years and HR 1.57 (95% CI 1.08-2.26) ≥15 years after treatment]. CONCLUSIONS: Surgical treatment of GERD does not seem to reduce EAC risk.

Hospital Volume of Antireflux Surgery in Relation to Endoscopic and Surgical Re-interventions.

OBJECTIVE: To test the hypothesis that higher hospital volume decreases endoscopic and surgical re-intervention rates after antireflux surgery. BACKGROUND: Antireflux surgery for gastro-esophageal reflux disease is followed by varying rates of re-interventions. Whether hospital volume influences re-intervention rates is uncertain. METHODS: This population-based cohort study used nationwide data from Denmark, Finland, and Sweden for patients having undergone primary antireflux surgery. Hospitals were divided into tertiles based upon annual volume, that is, 3 equal-sized groups. The outcomes were 30-day surgical re-intervention, endoscopic re-intervention, and secondary antireflux surgery. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) for risk of the first outcome occurrence. Incidence rate ratios were calculated to count all outcome occurrences. All risk estimates were adjusted for age, sex, comorbidity, type of antireflux surgery, year of surgery, and country. RESULTS: Among 33,060 patients and a median follow-up of 12 years after antireflux surgery, the frequencies of 30-day re-intervention, endoscopic re-intervention, and secondary antireflux surgery were 1.2%, 4.6%, and 7.0%, respectively. When comparing the highest with the lowest tertiles, higher hospital volume did not decrease HRs of 30-day re-intervention (adjusted HR = 1.14, 95% CI 0.73-1.77), endoscopic re-intervention (HR = 1.21, 95% CI 0.96-1.51), or secondary antireflux surgery (HR = 1.28, 95% CI 1.05-1.54), but rather increased point estimates. The incidence rate ratios showed similar patterns. CONCLUSIONS: Higher hospital volume of primary antireflux surgery may not decrease risk of endoscopic or surgical re-intervention, suggesting that centralization will not decrease rates of postoperative complications or recurrence of gastro-esophageal reflux disease.

Outdoor light at night and breast cancer incidence in the Danish Nurse Cohort.

BACKGROUND: Knowledge of the role of melatonin, xenograft experiments, and epidemiological studies suggests that exposure to light at night (LAN) may disturb circadian rhythms, possibly increasing the risk of developing breast cancer. OBJECTIVES: We examined the association between residential outdoor LAN and the incidence of breast cancer: overall and subtypes classified by estrogen (ER) and progesterone (PR) receptor status. METHODS: We used data on 16,941 nurses from the Danish Nurse Cohort who were followed-up from the cohort baseline in 1993 or 1999 through 2012 in the Danish Cancer Registry for breast cancer incidence and the Danish Breast Cancer Cooperative Group for breast cancer ER and PR status. LAN exposure data were obtained from the U.S. Defense Meteorological Satellite Program (DMSP) available for 1996, 1999, 2000, 2003, 2004, 2006, and 2010 in nW/cm2/sr unit, and assigned to the study participants' residence addresses during the follow-up. Time-varying Cox regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LAN and breast cancer, adjusting for individual characteristics, road traffic noise, and air pollution. RESULTS: Of 16,941 nurses, 745 developed breast cancer in total during 320,289 person-years of follow-up. We found no association between exposure to LAN and overall breast cancer. In the fully adjusted models, HRs for the highest (65.8-446.4 nW/cm2/sr) and medium (22.0-65.7 nW/cm2/sr) LAN tertiles were 0.97 (95% CI: 0.77, 1.23) and 1.09 (95% CI: 0.90, 1.31), respectively, compared to the lowest tertile of LAN exposure (0-21.9 nW/cm2/sr). We found a suggestive association between LAN and ER-breast cancer. CONCLUSION: This large cohort study of Danish female nurses suggests weak evidence of the association between LAN and breast cancer incidence.

Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study.

Obesity is a risk factor for colorectal cancer. Yet, some research indicates that weight-reducing bariatric surgery also increases colorectal cancer risk. Our study was undertaken because current evidence examining bariatric surgery and risk of colorectal cancer is limited and inconsistent. This population-based cohort study included adults with a documented obesity diagnosis in Denmark, Finland, Iceland, Norway or Sweden in 1980-2015. The incidence of colorectal cancer in participants with obesity who had and had not undergone bariatric surgery was compared to the incidence in the corresponding background population by calculating standardized incidence ratios (SIR) with 95% confidence intervals (CI). Additionally, operated and nonoperated participants with obesity were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs adjusted for confounders. Among 502,772 cohort participants with an obesity diagnosis, 49,931(9.9%) underwent bariatric surgery. The overall SIR of colon cancer was increased after bariatric surgery (SIR 1.56; 95% CI 1.28-1.88), with higher SIRs ≥10 years postsurgery. The overall HR of colon cancer in operated compared to nonoperated participants was 1.13 (95% CI 0.92-1.39) and 1.55 (95% CI 1.04-2.31) 10-14 years after bariatric surgery. Bariatric surgery did not significantly increase the risk of rectal cancer (SIR 1.14, 95% CI 0.83-1.52; HR 1.08, 95% CI 0.79-1.49), but the risk estimates increased with longer follow-up periods. Our study suggests that bariatric surgery is associated with an increased risk of colon cancer, while the support for an increased risk of rectal cancer was weaker.

Effects of Obesity Surgery on Overall and Disease-Specific Mortality in a 5-Country Population-Based Study.

BACKGROUND & AIMS: Bariatric surgery might reduce overall mortality from obesity. We investigated whether the survival times of patients who have had bariatric surgery are similar to those of the general population and are longer than of obese individuals who did not receive surgery. METHODS: We performed a population-based cohort study of persons with a diagnosis of obesity listed in nationwide registries from Nordic countries from 1980 through 2012. Bariatric surgery was analyzed in relation to all-cause mortality and the obesity-related morbidities cardiovascular disease, diabetes, cancer, and suicide. Poisson models provided standardized mortality ratios (SMRs) with 95% confidence intervals (CIs). Multivariable Cox regression provided hazard ratios (HRs) for mortality in participants who did and did not have surgery. RESULTS: Among 505,258 participants, 49,977 had bariatric surgery. Overall all-cause SMR was increased after surgery (1.94; 95% CI, 1.83-2.05) and increased with longer follow-up, to 2.28 (95% CI, 2.07-2.51) at ≥15 years after surgery. SMRs were increased for cardiovascular disease (2.39; 95% CI, 2.17-2.63), diabetes (3.67; 95% CI, 2.85-4.72), and suicide (2.39; 95% CI, 1.96-2.92) but not for cancer (1.05; 95% CI, 0.95-1.17); SMRs increased with time. In obese participants who did not have surgery, all-cause SMR was 2.15 (95% CI, 2.11-2.20), which remained stable during follow-up. Compared with obese participants who did not have surgery, patients who had bariatric surgery had decreased overall mortality from all causes (HR, 0.63; 95% CI, 0.60-0.66), cardiovascular disease (HR, 0.57; 95% CI, 0.52-0.63), and diabetes (HR, 0.38; 95% CI, 0.29-0.49) but increased mortality from suicide (HR, 1.68; 95% CI, 1.32-2.14). Cancer mortality was decreased overall (HR, 0.84; 95% CI, 0.76-0.93) but increased at ≥15 years of follow-up (HR, 1.20; 95% CI, 1.02-1.42). CONCLUSIONS: In a study of persons with a diagnosis of obesity listed in nationwide registries of Nordic countries, we found that obese patients who have bariatric surgery have longer survival times than obese individuals who did not have bariatric surgery, but their mortality is higher than that of the general population and increases with time. Obesity-related morbidities could account for these findings.

Breast cancer mortality and overdiagnosis after implementation of population-based screening in Denmark.

INTRODUCTION: Service breast cancer screening is difficult to evaluate because there is no unscreened control group. Due to a natural experiment, where 20% of women were offered screening in two regions up to 17 years before other women, Denmark is in a unique position. We utilized this opportunity to assess outcome of service screening. MATERIALS AND METHODS: Screening was offered in Copenhagen from 1991 and Funen from 1993 to women aged 50-69 years. We used difference-in-differences methodology with a study group offered screening; a historical control group; a regional control group; and a regional-historical control group, comparing breast cancer mortality and incidence, including ductal carcinoma in situ, between study and historical control group adjusted for changes in other regions, and calculating ratios of rate ratios (RRR) with 95% confidence intervals (CI). Data came from Central Population Register; mammography screening databases; Cause of Death Register; and Danish Cancer Register. RESULTS: For breast cancer mortality, the study group accumulated 1,551,465 person-years and 911 deaths. Long-term breast cancer mortality in Copenhagen was 20% below expected in absence of screening; RRR 0.80 (95% CI 0.71-0.90), and in Funen 22% below; RRR 0.78 (95% CI 0.68-0.89). Combined, cumulative breast cancer incidence in women followed 8+ years post-screening was 2.3% above expected in absence of screening; RRR 1.023 (95% CI 0.97-1.08). DISCUSSION: Benefit-to-harm ratio of the two Danish screening programs was 2.6 saved breast cancer deaths per overdiagnosed case. Screening can affect only breast cancers diagnosed in screening age. Due to high breast cancer incidence after age 70, only one-third of breast cancer deaths after age 50 could potentially be affected by screening. Increasing upper age limit could be considered, but might affect benefit-to-harm ratio negatively.

Sensitivity of screening mammography by density and texture: a cohort study from a population-based screening program in Denmark.

BACKGROUND: Screening mammography works better in fatty than in dense breast tissue. Computerized assessment of parenchymal texture is a non-subjective method to obtain a refined description of breast tissue, potentially valuable in addition to breast density scoring for the identification of women in need of supplementary imaging. We studied the sensitivity of screening mammography by a combination of radiologist-assessed Breast Imaging Reporting and Data System (BI-RADS) density score and computer-assessed parenchymal texture marker, mammography texture resemblance (MTR), in a population-based screening program. METHODS: Breast density was coded according to the fourth edition of the BI-RADS density code, and MTR marker was divided into quartiles from 1 to 4. Screening data were followed up for the identification of screen-detected and interval cancers. We calculated sensitivity and specificity with 95% confidence intervals (CI) by BI-RADS density score, MTR marker, and combination hereof. RESULTS: Density and texture were strongly correlated, but the combination led to the identification of subgroups with different sensitivity. Sensitivity was high, about 80%, in women with BI-RADS density score 1 and MTR markers 1 or 2. Sensitivity was low, 67%, in women with BI-RADS density score 2 and MTR marker 4. For women with BI-RADS density scores 3 and 4, the already low sensitivity was further decreased for women with MTR marker 4. Specificity was 97-99% in all subgroups. CONCLUSION: Our study showed that women with low density constituted a heterogenous group. Classifying women for extra imaging based on density only might be a too crude approach. Screening sensitivity was systematically high in women with fatty and homogenous breast tissue.

Long-term risk of screen-detected and interval breast cancer after false-positive results at mammography screening: joint analysis of three national cohorts.

BACKGROUND: We assessed the long-term risk of screen-detected and interval breast cancer in women with a first or second false-positive screening result. METHODS: Joint analysis had been performed using individual-level data from three population-based screening programs in Europe (Copenhagen in Denmark, Norway, and Spain). Overall, 75,513 screened women aged 50-69 years from Denmark (1991-2010), 556,640 from Norway (1996-2008), and 517,314 from Spain (1994-2010) were included. We used partly conditional Cox hazards models to assess the association between false-positive results and the risk of subsequent screen-detected and interval cancer. RESULTS: During follow-up, 1,149,467 women underwent 3,510,450 screening exams, and 10,623 screen-detected and 5700 interval cancers were diagnosed. Compared to women with negative tests, those with false-positive results had a two-fold risk of screen-detected (HR = 2.04, 95% CI: 1.93-2.16) and interval cancer (HR = 2.18, 95% CI: 2.02-2.34). Women with a second false-positive result had over a four-fold risk of screen-detected and interval cancer (HR = 4.71, 95% CI: 3.81-5.83 and HR = 4.22, 95% CI: 3.27-5.46, respectively). Women remained at an elevated risk for 12 years after the false-positive result. CONCLUSIONS: Women with prior false-positive results had an increased risk of screen-detected and interval cancer for over a decade. This information should be considered to design personalised screening strategies based on individual risk.

Regular physical activity and mammographic density: a cohort study.

PURPOSE: Physical activity is a modifiable lifestyle risk factor in prevention of breast cancer. Mammographic density (MD) is a strong risk factor for breast cancer. We investigate the association of regular physical activity with MD. METHODS: For 5,703 women who participated in the Danish Diet, Cancer and Health cohort (1993-1997) and attended mammographic screening in Copenhagen (1993-2001), MD was assessed at the first screening after cohort entry. MD was defined as a binary measure equivalent to Breast Imaging Report and Data System (BI-RADS) to either mixed/dense or fatty. Participation and duration in physical activities (hours/week) and confounders were assessed by questionnaire at cohort baseline. Logistic regression was used to estimate associations [odds ratios (OR), 95% confidence intervals (CI)] between physical activities and MD. RESULTS: 56.3% of women had mixed/dense MD and 47.6% participated in sports. We found a significant positive association between participation in sports (OR 1.15; 95% CI 1.03-1.28) and do-it-yourself work (1.17; 1.05-1.31) and odds of having mixed/dense MD, which attenuated (1.08; 0.96-1.22 and 1.11; 0.98-1.25, respectively) in a fully adjusted model. No associations were found for time spent on physical activities or total metabolic equivalent of task scores with MD, in fully adjusted models. There was no effect modification of association between any physical activities and MD by obesity (BMI ≥ 30 kg/m2) and menopause status. CONCLUSIONS: Physical activity is not a determinant of MD.