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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., (© 2024. The Author(s).)

Background: Blood transfusion has been associated with decreased long-term survival in cancer patients, possibly due to various immunological factors. We aimed to evaluate if perioperative transfusions decrease survival in patients who undergo resection for esophageal or gastric cancer and to identify factors associated with such events., Methods: A population-based cohort study was conducted based on the Swedish National Registry for Esophageal and Gastric Cancer, which prospectively collects clinical data of patients with these tumors. Almost all patients (96 %) resected for esophageal or gastric cancer in Sweden between 2017 and 2022 were included. Survival data were acquired from the Swedish Cause of Death Registry. Multivariable Cox regression was used to calculate hazard ratios (HR) with 95 % confidence intervals (CI), adjusted for age, fitness, neoadjuvant therapy, surgical access, and pathological TNM stage., Results: Of all 1365 patients, 227 (17 %) received perioperative transfusions. Transfusion was associated with an increased risk of all-cause mortality within 3 years of surgery (adjusted HR 1.50, 95 % CI 1.17-1.91). To exclude the influence of surgery-related postoperative complications, a sensitivity analysis was performed excluding patients who died within 30 days of resection and the negative impact of transfusions on 3-year mortality remained (adjusted HR 1.30, 95 % CI 1.01-1.68). Increasing age, open surgery, esophagectomy, perioperative bleeding, and nodal tumor involvement were all associated with an increased likelihood of receiving transfusions., Conclusion: Perioperative blood transfusions might have a negative impact on 3-year survival in patients who undergo surgery for esophageal or gastric cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Jakob hedberg reports financial support was provided by Swedish Cancer Society. Jesper Lagergren reports financial support was provided by Swedish Cancer Society. Jesper Lagergren reports financial support was provided by Swedish Research Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2024. The Author(s).)

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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

Background: The presence of distinct long-term disease-specific HRQL trajectories after curative treatment for esophageal cancer and factors associated with such trajectories are unclear., Materials and Methods: This population-based and longitudinal cohort study included 425 esophageal cancer patients who underwent curative treatment, including esophagectomy, in Sweden in 2001-2005 and were followed up until 2020, that is, 15-year follow-up. The outcomes were 10 disease-specific HRQL symptoms, measured by the well-validated EORTC QLQ-OES18 questionnaire at 6 months (n = 402 patients), and 3 (n = 178), 5 (n = 141), 10 (n = 92), and 15 years (n = 52) after treatment. HRQL symptoms were examined for distinct trajectories by growth mixture models. Weighted logistic regression models provided odds ratios (OR) with 95% confidence intervals (95% CI) for nine factors in relation to HRQL trajectories: age, sex, education, proxy baseline HRQL, comorbidity, tumor histology, chemo(radio)therapy, pathological tumor stage, and postoperative complications., Results: Distinct HRQL trajectories were identified for each of the 10 disease-specific symptoms. HRQL trajectories with more symptoms tended to persist or alleviate over time, while trajectories with fewer symptoms were more stable. Eating difficulty had three trajectories: persistently less, persistently moderate, and persistently more symptoms. The OR of having a persistently more eating difficulty trajectory was decreased for adenocarcinoma histology (OR = 0.44, 95% CI 0.21-0.95), and increased for pathological tumor stage III-IV (OR = 2.19, 95% CI 0.99-4.82) and 30-day postoperative complications (OR = 2.54, 95% CI 1.26-5.12)., Conclusion: Distinct trajectories with long-term persistent or deteriorating disease-specific HRQL symptoms were identified after esophageal cancer treatment. Tumor histology, tumor stage, and postoperative complications may facilitate detection of high-risk patients for unwanted trajectories., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

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., (© 2024. The Author(s).)

It is unclear how increasing body mass index (BMI) influences risk of cancer in young women. We used data from the Medical Birth, Patient and Cause of Death registers collected between 1982 and 2014 to determine the risk of obesity-related cancer types, breast cancer, all cancer and cancer-related death in relation to BMI in 1,386,725 women, aged between 18 and 45 years, in Sweden. During a median follow-up of 16.3 years (IQR 7.7-23.5), 9808 women developed cancer. The hazard ratio (HR) of endometrial and ovarian cancer increased with higher BMI from 1.08 (95% CI 0.93-1.24) and 1.08 (95% CI 0.96-1.21) among women with BMI 22.5-< 25 to 2.33 (95% CI 1.92-2.83) and 1.48 (95% CI 1.24-1.77), respectively, among women with BMI ≥ 30. There were linear and positive associations between BMI and incident cancer in the ovary, colon, endometrium, pancreas, rectum, gallbladder, esophageal cancer and renal cell carcinoma, as well as death from obesity-related cancer forms. In conclusion, we found that elevated BMI in young women linearly associated with several obesity-related cancer forms, including death from these cancers., (© 2024. The Author(s).)

Background: Increasing surgeon age may influence patient outcomes after complex procedures due to gained experience but also decreased technical and cognitive abilities. This study aimed to clarify whether surgeon age influences patients' long-term survival after gastrectomy for gastric adenocarcinoma., Methods: Population-based cohort study including all patients who underwent open and curatively intended gastrectomy for gastric adenocarcinoma between 2006 and 2015 in Sweden, with follow-up throughout 2020. Surgeon age, categorized into three equal-sized groups (tertiles), was assessed in relation to 5-year all-cause mortality rate (main outcome) and 5-year disease-specific death (secondary outcome) using multivariable Cox regression adjusted for patient age, sex, education, co-morbidity, pathological tumour stage, tumour sublocation and neoadjuvant therapy. Lymph node yield, resection margin status, in-hospital complications and annual surgeon volume of gastrectomy were considered potential mediators., Results: Among 1647 patients, the 5-year all-cause mortality rate was increased for surgeon age ≥55 years (adjusted HR 1.21, 95% c.i. 1.04 to 1.41) and borderline elevated for age 47-54 years (HR 1.16, 95% c.i. 0.99 to 1.36), compared with age ≤46 years. Five-year disease-specific death was increased for surgeon age ≥55 years (HR 1.25, 95% c.i. 1.06 to 1.48) and 47-54 years (HR 1.22, 95% c.i. 1.02 to 1.44), compared with age ≤46 years. The associations attenuated and became statistically non-significant after adjustment for lymph node yield, resection margin status and complications., Conclusion: Surgeon age ≥47 years might be associated with worse long-term survival in patients who undergo gastrectomy for gastric adenocarcinoma, possibly mediated in part by differences in lymph node yield, resection margin status and complications., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background: The differentiation of specific, long-term health-related quality of life (HRQL) trajectories among esophageal cancer survivors remains unclear. The authors aimed to identify potentially distinctly different HRQL-trajectories and uncover the underlying factors of such trajectories in patients having undergone surgery (esophagectomy) for esophageal cancer., Materials and Methods: This nationwide, prospective, and longitudinal cohort study included 420 patients who underwent curative treatment for esophageal cancer, including esophageal cancer surgery, in Sweden from 2001to 2005. The main outcome was HRQL summary score trajectories, measured by the well-validated EORTC QLQ-C30 questionnaire at 6 months, 3, 5, 10, and 15 years after esophagectomy, and analyzed using growth mixture models. Potentially underlying factors for these trajectories (age, sex, education, proxy baseline HRQL, comorbidity, tumor histology, chemo(radio)therapy, pathological tumor stage, and postoperative complications) were analyzed using weighted logistic regression providing odds ratios (OR) with 95% CI., Results: Four distinct HRQL summary score trajectories were identified: Persistently good, improving, deteriorating, and persistently poor. The odds of belonging to a persistently poor trajectory were decreased by longer education (>12 years versus <9 years: OR 0.18, 95% CI: 0.05-0.66) and adenocarcinoma histology (adenocarcinoma versus squamous cell carcinoma: OR 0.37, 95% CI: 0.16-0.85), and increased by more advanced pathological tumor stage (III-IV versus 0-I: OR 2.82, 95% CI: 1.08-7.41) and postoperative complications (OR 2.94, 95% CI: 1.36-6.36)., Conclusion: Distinct trajectories with persistently poor or deteriorating HRQL were identified after curative treatment for esophageal cancer. Education, tumor histology, pathological tumor stage, and postoperative complications might influence HRQL trajectories. The results may contribute to a more tailored follow-up with timely and targeted interventions. Future research remains to confirm these findings., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: To assess the long-term risk of developing type 2 diabetes in patients with obesity who have undergone gastric bypass surgery compared to non-operated patients with obesity and the general population., Methods: This study included 71,495 patients aged 20-65 years with a principal diagnosis of obesity in the Swedish Patient Register in 2001-2013. Of these, 23,099 had undergone gastric bypass and 32,435 had not. Each patient was matched by age, sex and geographic region with two controls from the general population without obesity diagnosis, i.e., 44,735 controls for the gastric bypass cohort and 62,522 controls for the non-operated cohort with obesity. Operated and non-operated patients with obesity were also directly compared using Cox regression analysis, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, education, and sex., Results: During a median follow-up of 4.3 years (interquartile range [IQR] 2.4, 7.0 years), 3792 (11.7%) non-operated patients with obesity developed type 2 diabetes (incidence rate 22.8/1000 person-years, 95% CI 22.1-23.6) compared to 394 (1.7%) among gastric bypass patients (incidence rate 4.0/1000 person-years, 95% CI 3.6-4.5). The latter incidence was comparable to population controls (3.5/1000 person-years, 95% CI 3.2-3.8). Gastric bypass patients had 85% lower risk of diabetes compared to non-operated patients with obesity during the first six years of follow-up (HR 0.15; 95% CI 0.13-0.17)., Conclusion: Gastric bypass surgery for obesity seems to reduce the risk of developing type 2 diabetes to levels similar to that of the general population during the first six years of follow-up but not thereafter., Competing Interests: Declaration of Competing Interest None of the authors has any conflicts of interest to declare with respect to the present study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose: There is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma., Methods: Multicenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS)-LNRS 1, complete response; 2, <10% residual tumor; 3, 10%-50% residual tumor; 4, >50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index., Results: In total, 17,930 LNs from 763 patients were examined. LN response classified as complete LN response (LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%), partial LN response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%), poor/no LN response (LNRS 4-5; n = 303, 39.7%), or LN negative (no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio [HR], 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%)., Conclusion: Pathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.

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., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent research indicates that use of proton pump inhibitors (PPIs) is associated with pneumonia, but existing evidence is inconclusive because of methodological issues. This study aimed to answer whether PPI-use increases risk of pneumonia while taking the methodological concerns of previous research into account., Methods: This population-based and nationwide Swedish study conducted in 2005-2019 used a self-controlled case series design. Data came from national registries for medications, diagnoses, and mortality. Conditional fixed-effect Poisson regression provided incidence rate ratios (IRR) with 95% confidence intervals (CI) for pneumonia comparing PPI-exposed periods with unexposed periods in the same individuals, thus controlling for confounding. Analyses were stratified by PPI-treatment duration, sex, age, and smoking-related diseases. Use of histamine type-2 receptor antagonists (used for the same indications as PPIs) and risk of pneumonia was analysed for assessing the validity and specificity of the results for PPI-therapy and pneumonia., Results: Among 519,152 patients with at least one pneumonia episode during the study period, 307,709 periods of PPI-treatment occurred. PPI-use was followed by an overall 73% increased risk of pneumonia (IRR 1.73, 95% CI 1.71-1.75). The IRRs were increased across strata of PPI-treatment duration, sex, age, and smoking-related disease status. No such strong association was found between histamine type-2 receptor antagonist use and risk of pneumonia (IRR 1.08, 95% CI 1.02-1.14)., Conclusions: PPI-use seems to be associated with an increased risk of pneumonia. This finding highlights a need for caution in using PPIs in individuals with a history of pneumonia., (© 2023. The Author(s).)

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.

Background: Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent., Methods: We systematically searched MEDLINE and Embase databases to identify prospective studies examining associations between prediagnostic circulating levels of sex hormones and risk of five gastrointestinal cancers: esophageal, gastric, liver, pancreatic, and colorectal cancer. Pooled ORs and 95% confidence intervals (95% CI) were calculated using random-effects models., Results: Among 16,879 identified studies, 29 were included (11 cohort, 15 nested case-control, and three case-cohort studies). Comparing the highest versus lowest tertiles, levels of most sex hormones were not associated with the studied tumors. Higher levels of sex hormone binding globulin (SHBG) were associated with increased risk of gastric cancer (OR = 1.35; 95% CI, 1.06-1.72), but such associations were restricted in men only (OR = 1.43; 95% CI, 1.10-1.85) when stratified by sex. Higher SHBG levels were associated with increased risk of liver cancer (OR = 2.07; 95% CI, 1.40-3.06). Higher testosterone levels were associated with increased risk of liver cancer overall (OR = 2.10; 95% CI, 1.48-2.96), particularly in men (OR = 2.63; 95% CI, 1.65-4.18), Asian populations (OR = 3.27; 95% CI, 1.57-6.83), and in hepatitis B surface antigen-positive individuals (OR = 3.90; 95% CI, 1.43-10.64). Higher levels of SHBG and testosterone were associated with decreased risk of colorectal cancer in men (OR = 0.89; 95% CI, 0.80-0.98 and OR = 0.88; 95% CI, 0.80-0.97, respectively) but not in women., Conclusions: Circulating levels of SHBG and testosterone may influence the risk of gastric, liver, and colorectal cancer., Impact: Further clarifying the role of sex hormones in the development of gastrointestinal cancer may unravel future novel targets for prevention and treatment., (©2023 American Association for Cancer Research.)

Background: It is unclear how diabetes and metformin use is associated with survival of esophageal cancer., Methods: This population-based cohort study included new cases of esophageal cancer reported in Sweden from 2006 to 2018 with follow-up through 2019. Diabetes status and metformin use were analyzed in relation to all-cause and disease-specific mortality using multivariable Cox regression. The hazard ratios (HRs) with 95% confidence intervals (CIs) were adjusted for age, sex, calendar year, obesity, comorbidity, and use of nonsteroidal anti-inflammatory drugs or statins. For comparison reasons, 3 other antidiabetic medications were also analyzed (ie, sulfonylureas, insulin, and thiazolidinedione)., Results: Among 4851 esophageal cancer patients (8404 person-years), 4072 (84%) died during follow-up. Compared with esophageal cancer patients with diabetes but not using metformin, decreased all-cause mortality was indicated among nondiabetic patients (without metformin) (HR = 0.86, 95% CI = 0.77 to 0.96) and diabetic patients who used metformin (HR = 0.86, 95% CI = 0.75 to 1.00). The hazard ratios of all-cause mortality decreased with a higher daily dose of metformin (Ptrend = .04). The corresponding hazard ratios for disease-specific mortality were similar but slightly attenuated. The results were also similar in separate analyses of esophageal cancer patients with adenocarcinoma or squamous cell carcinoma, with tumor stage I-II or III-IV, and in those who had or had not undergone surgery. No associations with mortality outcomes were found for use of sulfonylureas, insulin, or thiazolidinedione., Conclusions: Diabetes was associated with an increased all-cause mortality, whereas metformin use was associated with decreased all-cause mortality among esophageal cancer patients. More research is needed to determine if metformin affects survival in esophageal cancer., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: Quality of surgery is essential for survival in gastric adenocarcinoma, but studies examining surgeons' proficiency gain of gastrectomies are scarce. This study aimed to reveal potential proficiency gain curves for surgeons operating patients with gastric cancer., Methods: Population-based cohort study of patients who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2020. Data were retrieved from national registries and medical records. Risk prediction models were used to calculate outcome probabilities, and risk-adjusted cumulative sum curves were plotted to assess differences (change points) between observed and expected outcomes. The main outcome was long-term (>3-5 years) all-cause mortality after surgery. Secondary outcomes were all-cause mortality within 30 days, 31-90 days, 91 days to 1 year and>1-3 years of surgery, resection margin status, and lymph node yield., Results: The study included 261 surgeons and 1636 patients. The>3- to 5-year mortality was improved after 20 cases, and decreased from 12.4% before to 8.6% after this change point (p = 0.027). Change points were suggested, but not statistically significant, after 22 cases for 30-day mortality, 28 cases for 31- to 90-day mortality, 9 cases for 91-day to 1-year mortality, and 10 cases for>1- to 3-year all-cause mortality. There were statistically significant improvements in tumour-free resection margins after 28 cases (p < 0.005) and greater lymph node yield after 13 cases (p < 0.001)., Conclusions: This study reveals proficiency gain curves regarding long-term survival, resection margin status, and lymph node yield in gastrectomy for gastric adenocarcinoma, and that at least 20 gastrectomies should be conducted with experienced support before doing these operations independently., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Early-onset adenocarcinomas of different sites are increasing in high-income countries, data on esophagogastric adenocarcinoma are sparse., Methods: We performed a Swedish population-based cohort study over 1993 to 2019 to delineate differences in incidence and survival in early-onset (age 20-54 years) compared with later-onset (55-99 years) esophageal, cardia, and noncardia gastric adenocarcinoma. Temporal incidence trends were quantified as annual percentage changes (APC) and survival differences as excess mortality rate ratios (EMRR) using Poisson regression and including 95% confidence intervals (CI)., Results: Among 27,854 patients with esophagogastric adenocarcinoma, 2,576 were early-onset whereof 470 were esophageal, 645 were cardia, and 1,461 were noncardia gastric. Except noncardia gastric, the male predominance was larger in early-onset compared with later-onset disease. Advanced stage and signet ring cell morphology were more common among early-onset patients. Early-onset and later-onset APC estimates were comparable and esophageal adenocarcinoma incidence increased, cardia remained stable, and noncardia gastric decreased. Early-onset patients had better survival than later-onset, which was amplified when adjusting for prognostic factors including stage [adjusted EMRR 0.73 (95% CI, 0.63-0.85) in esophageal, 0.75 (95% CI, 0.65-0.86) in cardia, and 0.67 (95% CI, 0.61-0.74) in noncardia gastric adenocarcinoma]. The early-onset survival advantage was more pronounced in localized stages 0 to II (all sites) and women (esophageal and noncardia gastric)., Conclusions: We found no major differences in incidence trends comparing early-onset and later-onset esophagogastric adenocarcinoma. Despite unfavorable prognostic features, early-onset esophagogastric adenocarcinoma survival was better than later-onset, particularly in localized stages and women., Impact: Our findings suggest delayed diagnosis in younger individuals and especially men., (©2023 American Association for Cancer Research.)

Incidence and mortality are default measures to describe cancer trends. Mortality compounds incidence and survival but not age at death. We calculated years of life lost (YLL) due to 1 of the 10 solid tumors causing most deaths (lung, colorectal, prostate, pancreatic, breast, hepatobiliary, urinary, central nervous system, gastric, melanoma) using Swedish National Cancer and Cause of Death Registers. Comparing YLL with mortality in 2019, lung (43 152 YLL) and colorectal (32 340 YLL) cancer remained at the top, pancreatic cancer was upranked fourth to third (22 592 YLL) and breast cancer fifth to fourth (21 810 YLL), while prostate cancer was downranked third to fifth (17 380 YLL). Assessing YLL over 2010-2019, women lost consistently more life years because of lung and pancreatic cancer. A downward colorectal cancer mortality trend was reflected as a YLL decline only in women. YLL is simple to calculate, is intuitive to interpret, and expands the understanding of the cancer burden on society., (© The Author(s) 2023. Published by Oxford University Press.)

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.

Background: The authors aimed to produce a prediction model for survival at any given date after surgery for esophageal cancer (conditional survival), which has not been done previously., Materials and Methods: Using joint density functions, the authors developed and validated a prediction model for all-cause and disease-specific mortality after surgery with esophagectomy, for esophageal cancer, conditional on postsurgery survival time. The model performance was assessed by the area under the receiver operating characteristic curve (AUC) and risk calibration, with internal cross-validation. The derivation cohort was a nationwide Swedish population-based cohort of 1027 patients treated in 1987-2010, with follow-up throughout 2016. This validation cohort was another Swedish population-based cohort of 558 patients treated in 2011-2013, with follow-up throughout 2018., Results: The model predictors were age, sex, education, tumor histology, chemo(radio)therapy, tumor stage, resection margin status, and reoperation. The medians of AUC after internal cross-validation in the derivation cohort were 0.74 (95% CI: 0.69-0.78) for 3-year all-cause mortality, 0.76 (95% CI: 0.72-0.79) for 5-year all-cause mortality, 0.74 (95% CI: 0.70-0.78) for 3-year disease-specific mortality, and 0.75 (95% CI: 0.72-0.79) for 5-year disease-specific mortality. The corresponding AUC values in the validation cohort ranged from 0.71 to 0.73. The model showed good agreement between observed and predicted risks. Complete results for conditional survival any given date between 1 and 5 years of surgery are available from an interactive web-tool: https://sites.google.com/view/pcsec/home ., Conclusion: This novel prediction model provided accurate estimates of conditional survival any time after esophageal cancer surgery. The web-tool may help guide postoperative treatment and follow-up., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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.

Objectives: 2-deoxy-2[ 18 F]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 SUV max thresholds for predicting pathological response were identified using receiver operating characteristic analysis. Predictive accuracy was compared to PERCIST (30% SUV max reduction) and MUNICON (35%) criteria. Survival was assessed using Cox regression., Results: Optimum tumour SUV max 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% SUV max 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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

Patients with pancreatic ductal adenocarcinoma (PDAC) commonly develop symptoms and signs in the 1-2 years before diagnosis that can result in changes to medications. We investigate recent medication changes and PDAC diagnosis in Nurses' Health Study (NHS; females) and Health Professionals Follow-up Study (HPFS; males), including up to 148,973 U.S. participants followed for 2,994,057 person-years and 991 incident PDAC cases. Here we show recent initiation of antidiabetic (NHS) or anticoagulant (NHS, HFS) medications and cessation of antihypertensive medications (NHS, HPFS) are associated with pancreatic cancer diagnosis in the next 2 years. Two-year PDAC risk increases as number of relevant medication changes increases (P-trend <1 × 10 -5 ), with participants who recently start antidiabetic and stop antihypertensive medications having multivariable-adjusted hazard ratio of 4.86 (95%CI, 1.74-13.6). These changes are not associated with diagnosis of other digestive system cancers. Recent medication changes should be considered as candidate features in multi-factor risk models for PDAC, though they are not causally implicated in development of PDAC., (© 2023. The Author(s).)

Previous studies indicate differences in short-term postoperative outcomes depending on the surgical starting time of the day, but long-term data are lacking. The aim of this study was to clarify if surgical starting time of the day influences long-term survival in gastric cancer patients. This cohort study consecutively included 2728 patients who underwent curatively intended gastrectomy for gastric cancer in 2011-2015 at a high-volume hospital in China, with follow-up until June 2019. Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) for 3-year all-cause mortality, adjusted for age, sex, health insurance, pathological tumor stage, surgical approach, neoadjuvant therapy, and weekday of surgery. Compared with patients with early starting time of gastrectomy (08:00-09:29), the point estimates for 3-year all-cause mortality were modestly increased in patients with a starting time in the middle of day (09:30-13:29; HR 1.15, 95% CI 0.97 to 1.37) and later (13:30-21:25; HR 1.10, 0.91 to 1.32). The corresponding HRs were increased particularly in patients who underwent laparoscopic gastrectomy (HR 1.54, 1.10 to 2.14 and HR 1.59, 1.12 to 2.25, respectively) and in those with stage II tumors (HR 1.74, 1.11 to 2.73 and HR 1.60, 1.00 to 2.58, respectively). Our study indicated that in patients who underwent laparoscopic gastrectomy and in those who with stage II tumors, starting surgery in the early morning might be associated with better long-term survival., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Cancer surgery conducted late during the working week might decrease long-term survival for some tumours. Studies on how weekday of gastrectomy influences long-term survival following gastric cancer are few and show conflicting results, which prompted the present investigation., Methods: This population-based cohort study included almost all patients who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015, with follow-up throughout 2020. Associations between weekday of gastrectomy and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome) were analysed using multivariable Cox regression. The hazard ratios (HR) with 95% confidence intervals (CI) were adjusted for age, sex, education, comorbidity, pathological tumour stage, tumour sub-location, neoadjuvant therapy, annual surgeon volume of gastrectomy, and calendar year., Results: Among 1678 patients, surgery on Thursday-Friday was not associated with any statistically significantly increased risk of 5-year all-cause mortality (HR 1.05, 95% CI 0.91-1.22) or 5-year disease-specific mortality (HR 1.04, 95% CI 0.89-1.23) compared to Monday-Wednesday. No associations were found when each weekday was analysed separately, with point estimates close to 1.00 (range 0.98-1.00) Monday-Thursday, but increased for Friday (HR 1.22, 95% CI 0.89-1.68) when fewer patients underwent surgery (4% of all). Stratified analyses by age, comorbidity, tumour stage, neoadjuvant therapy, surgeon volume, and tumour sub-location did not reveal any associations between weekday of surgery on Thursday-Friday compared with Monday-Wednesday and risk of 5-year all-cause mortality., Conclusions: Weekday of gastrectomy might not influence the 5-year survival in patients with gastric adenocarcinoma., Competing Interests: Declarations of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Due to shared hepatic metabolism, concomitant medication with a proton pump inhibitor (PPI) and clopidogrel might reduce the effectiveness of clopidogrel in the prevention of cardiovascular events after percutaneous coronary intervention (PCI). We aimed to examine the risk of major cardiovascular events after PCI comparing patients who used clopidogrel together with PPI with those who used clopidogrel alone., Methods: This Swedish nationwide cohort study included patients who received clopidogrel after primary PCI in 2005-2019. Patients were followed for up to 12 months after PCI. Data were retrieved from the Swedish Prescribed Drug Registry, Patient Registry, Cancer Registry, and Cause of Death Registry. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular events comparing PPI users (exposed) with non-users of PPI (non-exposed). The HRs were adjusted for sex, age, comorbidity, calendar period, obesity, diabetes, anti-diabetic medication, tobacco-related diseases, hypertension, and congestive heart failure., Results: The cohort included 99,836 patients who received clopidogrel after primary PCI. Among these, 35,772 (35.8%) received concomitant PPI. Compared to non-users, PPI users had increased adjusted HRs of all study outcomes, i.e., the main outcome myocardial infarction (HR = 1.23, 95% CI 1.15-1.32) and the secondary outcomes coronary heart disease (HR = 1.28, 95% CI 1.24-1.33), stroke (HR = 1.21, 95% CI 1.05-1.40), and death due to coronary heart disease (HR = 1.52, 95% CI 1.37-1.69). The results were similar in analyses including both primary and secondary PCIs., Conclusions: In patients who receive clopidogrel after PCI, concomitant use of PPI seems to increase the risk of major cardiovascular events., (© 2021. The Author(s).)

Background: Oesophago-gastric cancers have had sharply different and changing incidence patterns depending on subsite and histology, but incidence data for the last few years are missing. We aimed to provide updated incidence trends of oesophago-gastric tumours by subsite and histology in Sweden., Material and Methods: The Swedish Cancer Registry provided data for 74,303 patients with oesophago-gastric cancer aged ≥50 years in 1970-2020. The focus was on the last available 6-year period, i.e., from 2015 until 2020 inclusive. We calculated yearly age-standardized and sex-specific incidence rates per 100,000 person-years, with the age distribution (in 5-year age groups) of the Swedish population in year 2000 as reference., Results: For oesophageal squamous cell carcinoma, the incidence continued to decrease between 2015 and 2020 (from 6.46 to 5.53/100,000 person-years in men, and from 4.26 to 3.78/100,000 person-years in women). For oesophageal adenocarcinoma, the earlier increasing incidence rates rather slightly decreased in men between 2015 and 2020 (from 12.39 to 11.70/100,000 person-years) and increased marginally in women (from 2.49 to 2.85/100,000 person-years). The incidence rates of cardia adenocarcinoma were stable between 2015 and 2020 (from 9.83 to 10.13/100,000 person-years in men, and from 2.21 to 2.41/100,000 person-years in women). For gastric non-cardia adenocarcinoma, the incidence rates continued to decrease between 2015 and 2020 (from 14.67 to 13.29/100,000 person-years in men, and from 9.37 to 8.14/100,000 person-years in women). There were no major age-group differences in recent incidence trends., Conclusion: The 6-year period from 2015 to 2020 inclusive has witnessed stabilising incidence rates of oesophageal and cardia adenocarcinoma in Sweden, whereas the incidence rates of oesophageal squamous cell carcinoma and non-cardia gastric adenocarcinoma have continued to decrease.

Objective: To examine 5-year survival in esophageal cancer after MIE compared to OE., Summary Background Data: MIE is becoming an increasingly common approach in the surgical treatment of esophageal cancer. A recent meta-analysis suggested 18% lower 5-year all-cause mortality after MIE compared to OE, but the quality of the included studies was limited., Methods: Population-based cohort study including almost all patients who underwent elective esophagectomy for esophageal cancer in Sweden or Finland in 2010 to 2016, with follow-up until end of 2019. Cox regression was used to provide hazard ratios (HRs) with 95% confidence intervals (CIs) of all-cause 5-year mortality (main outcome) after MIE (hybrid or total) versus OE. Adjustments were made for age, sex, comorbidity, pathological tumor stage, histological tumor type, neoadjuvant chemo(radio)therapy, country, and annual hospital volume of esophagectomy., Results: Among all 1264 patients, 470 (37.2%) underwent MIE and 794 (62.8%) underwent OE. MIE was associated with an 18% decreased risk of all-cause 5-year mortality, compared to OE [adjusted HR 0.82, 95% CI 0.67- 1.00 ( P = 0.048)]. The HR of all-cause 5-year mortality was seemingly lower after total MIE compared to OE (adjusted HR 0.77, 95% CI 0.60-0.98) than after hybrid MIE compared to OE (adjusted HR 0.87, 95% CI 0.68-1.11)., Conclusions: This bi-national study indicates that MIE is associated with a higher 5-year survival than OE in patients with esophageal cancer, and that the survival benefit is greater after total MIE than hybrid MIE., Competing Interests: The study was funded by the Swedish Research Council (grant number 2019-00209) and Swedish Cancer Society (grant number 180684). The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There is uncertainty whether long-term use of proton-pump inhibitors can cause gastric adenocarcinoma (GAC) and oesophageal adenocarcinoma (OAC). This study aimed to determine how discontinuation of long-term PPI therapy influences the risk of GAC and OAC., Methods: This population-based cohort study included all long-term users of PPI therapy in Sweden in 2005-2018 was based on Swedish nationwide health registry data. The exposure was discontinuation of long-term PPI therapy, defined as no dispensation of PPI following inclusion and used as a time-varying variable, compared to remaining on PPI. Main outcomes were GAC and OAC, while oesophageal squamous cell carcinoma (OSCC) was included as a comparison outcome. Incidence rate ratios (IRR) with 95% CI adjusted for age, sex, comorbidity, obesity, diabetes, hyperlipidaemia, NSAIDs/aspirin, and statins were calculated with Poisson regression., Results: Among 730,176 long-term PPI users (mean age 65.6 years, 58.4% females) with 4,210,925 person-years at risk (median 5.5 person-years), 439,390 (60.2%) discontinued PPIs. In total, 495 developed GAC, 598 OAC, and 188 developed OSCC. PPI discontinuation was associated with decreased risk of GAC (IRR 0.81, 95% CI 0.67-0.98) and OAC (IRR 0.80, 95% CI 0.68-0.96), but not OSCC (IRR 1.10, 95% CI 0.82-1.49) compared to continued PPI use. Stratified analyses showed decreased point estimates across most age categories and both sexes for GAC and OAC risk among participants discontinuing PPI therapy., Conclusion: Discontinuation of long-term PPI therapy may decrease the risk of GAC and OAC, suggesting that physicians should consider ceasing prescribing long-term PPI in patients without continued indication for its use., (© 2022. The Author(s).)

Background: Studies on risk factors for severe COVID-19 in people of working age have generally not included non-working persons or established population attributable fractions (PAFs) for occupational and other factors., Objectives: We describe the effect of job-related, sociodemographic, and other exposures on the incidence, relative risks and PAFs of severe COVID-19 in individuals aged 18-64., Methods: We conducted a registry-based study in Swedish citizens aged 18-64 from 1 January 2020 to 1 February 2021 with respect to COVID-19-related hospitalizations and death., Results: Of 6,205,459 persons, 272,043 (7.5%) were registered as infected, 3399 (0.05%) needed intensive care, and 620 (0.01%) died, with an estimated case fatality rate of 0.06% over the last 4-month period when testing was adequate. Non-Nordic origin was associated with a RR for need of intensive care of 3·13, 95%CI 2·91-3·36, and a PAF of 32·2% after adjustment for age, sex, work, region and comorbidities. In a second model with occupation as main exposure, and adjusted for age, sex, region, comorbidities and origin, essential workers had an RR of 1·51, 95%CI, 1·35-1·6, blue-collar workers 1·18, 95%CI 1·06-1·31, school staff 1·21, 95%CI 1·01-1·46, and health and social care workers 1·89, 95%CI 1·67-2·135) compared with people able to work from home, with altogether about 13% of the PAF associated with these occupations. Essential workers and blue-collar workers, but no other job categories had higher risk of death, adjusted RRs of 1·79, 95%CI 1·34-2·38 and 1·37, 95%CI 1·04-1·81, with adjusted PAFs of altogether 9%., Conclusion: Among people of working age in Sweden, overall mortality and case fatality were low. Occupations that require physical presence at work were associated with elevated risk of needing intensive care for COVID-19, with 14% cases attributable to this factor, and 9% of deaths., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objective: This study aimed to determine the risk of atrial fibrillation in patients with objectively confirmed GERD., Methods: This was a nationwide population-based cohort study between 2005 and 2018, including the majority ( n = 8 421 115) of all Swedish adult residents (≥18 years). Within this cohort, the exposed group were all individuals with a diagnosis of esophagitis or Barrett's esophagus, and the unexposed group was made up of five times as many individuals without any GERD, matched by age, sex, and calendar year. The outcome was the first diagnosis of atrial fibrillation. Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for confounders., Results: Among 118 013 individuals with esophagitis or Barrett's esophagus and 590 065 without GERD, 7042 (6.0%) and 40 962 (6.9%) developed atrial fibrillation, respectively. The risk of atrial fibrillation among patients with GERD was 13% increased within the first year of diagnosis (HR, 1.13; 95% CI, 1.06-1.20), but was not increased after that. Among individuals aged less than 60 years, the HR of atrial fibrillation was 55% increased within the first year of diagnosis (HR, 1.55; 95% CI, 1.27-1.88), and this association remained increased after the first year (HR, 1.14; 95% CI, 1.06-1.22). No association was found in older participants (≥60 years). Results were similar in men and women., Conclusion: This large population-based cohort study indicates that objectively determined GERD increases the risk of atrial fibrillation shortly after diagnosis in men and women younger than 60 years., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)