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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: 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: 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.)

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.)

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.

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.)

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.)

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).)

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.)

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: Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability., Methods: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression., Results: Although the standard approach did not identify significant signals, the eQTL set-based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1)., Conclusions: This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set-based genetic association approach., Impact: This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set-based genetic association approach as an alternative method for TWAS analysis., (©2022 American Association for Cancer Research.)

Background: Recent research indicates long-term survival benefits of minimally invasive esophagectomy (MIE) compared with open esophagectomy (OE) for patients with esophageal and gastroesophageal junction (GEJ) cancers, but there is a need for more population-based studies., Methods: We conducted a prospective population-based nationwide cohort study including all patients in Sweden diagnosed with esophageal or junctional cancer who underwent a transthoracic esophagectomy with intrathoracic anastomosis. Data were collected from the Swedish National Register for Esophageal and Gastric Cancer in 2006-2019. Patients were grouped into OE and MIE including hybrid MIE (HMIE) and totally MIE (TMIE). Overall survival and short-term postoperative outcomes were compared using Cox regression and logistic regression models, respectively. All models were adjusted for age, sex, American Society of Anesthesiologists (ASA) score, clinical T and N stage, neoadjuvant therapy, year of surgery, and hospital volume., Results: Among 1404 patients, 998 (71.1%) underwent OE and 406 (28.9%) underwent MIE. Compared with OE, overall survival was better following MIE (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.55-0.94), TMIE (HR 0.67, 95% CI 0.47-0.94), and possibly also after HMIE (HR 0.76, 95% CI 0.56-1.02). MIE was associated with shorter operation time, less intraoperative bleeding, higher number of resected lymph nodes, and shorter hospital stay compared with OE. MIE was also associated with fewer overall complications (odds ratio [OR] 0.70, 95% CI 0.47-1.03) as well as non-surgical complications (OR 0.64, 95% CI 0.40-1.00)., Conclusions: MIE seems to offer better survival and similar or improved short-term postoperative outcomes in esophageal and GEJ cancers compared with OE in this unselected population-based cohort., (© 2022. Society of Surgical Oncology.)

Background: To investigate if anti-androgenic medications 5α-reductase inhibitors (5-ARIs) decrease the risk of developing oesophageal and gastric tumours, analysed by histological type and anatomical sub-site., Methods: A Swedish population-based cohort study between 2005 and 2018 where men using 5-ARIs were considered exposed. For each exposed participant, ten male age-matched non-users of 5-ARIs (non-exposed) were included. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, smoking, non-steroidal anti-inflammatory drugs/aspirin use, and statins use. Further adjustments were made depending on the tumour analysed., Results: The cohort included 191,156 users of 5-ARIs and 1,911,560 non-users. Overall, the use of 5-ARIs was not associated with any statistically significantly reduced risk of oesophageal or cardia adenocarcinoma (adjusted HR 0.92, 95% CI 0.82-1.02) or gastric non-cardia adenocarcinoma (adjusted HR 0.90, 95% CI 0.80-1.02). However, the use of 5-ARIs indicated a decreased risk of oesophageal or cardia adenocarcinoma among obese or diabetic participants (adjusted HR 0.55, 95% CI 0.39-0.80) and a reduced risk of oesophageal squamous cell carcinoma (adjusted HR 0.49, 95% CI 0.37-0.65)., Conclusion: Users of 5-ARIs may have a decreased risk of developing oesophageal or cardia adenocarcinoma among those obese or diabetic, and a decreased risk of oesophageal squamous cell carcinoma., (© 2022. The Author(s).)

Purpose: Long-lasting symptoms and reductions in quality of life are common after oesophago-gastric surgery. Post-operative follow-up has traditionally focussed on tumour recurrence and survival, but there is a growing need to also identify and treat functional sequelae to improve patients' recovery., Methods: An electronic survey was circulated via a British national charity for patients undergoing oesophago-gastric surgery and their families. Patients were asked about post-operative symptoms they deemed important to their quality of life, as well as satisfaction and preferences for post-operative follow-up. Differences between satisfied and dissatisfied patients with reference to follow-up were assessed., Results: Among 362 respondents with a median follow-up of 58 months since surgery (range 3-412), 36 different symptoms were reported as being important to recovery and quality of life after surgery, with a median of 13 symptoms per patient. Most (84%) respondents indicated satisfaction with follow-up. Satisfied patients were more likely to have received longer follow-up (5-year or longer follow-up 60% among satisfied patients vs 27% among unsatisfied, p < 0.001). These were also less likely to have seen a dietitian as part of routine follow-up (37% vs 58%, p = 0.005)., Conclusion: This patient survey highlights preferences regarding follow-up after oesophago-gastrectomy. Longer follow-up and dietician involvement improved patient satisfaction. Patients reported being concerned by a large number of gastrointestinal and non-gastrointestinal symptoms, highlighting the need for multidisciplinary input and a consensus on how to manage the poly-symptomatic patient., (© 2022. The Author(s).)

It is unknown whether the survival of patients cured of esophageal cancer differs from that of the corresponding background population. This nationwide and population-based cohort study included all patients who survived for at least 5 years after surgery for esophageal cancer in Sweden between 1987 and 2015, with follow-up throughout 2020. Relative survival rates with 95% confidence intervals (95% CI) were calculated by dividing the observed with the expected survival. The expected survival was assessed from the entire Swedish population of the corresponding age, sex, and calendar year. Yearly relative survival rates were calculated between 6 and 10 years postoperatively. Among all 762 participants, the relative survival was initially similar to the background population (96.1%, 95% CI 94.3-97.9%), but decreased each following postoperative year to 83.5% (95% CI 79.5-87.6%) by year 10. The drop in relative survival between 6 and 10 years was more pronounced in participants with a history of squamous cell carcinoma [from 94.5% (95% CI 91.2-97.8%) to 70.8% (95% CI 64.0-77.6%)] than in those with adenocarcinoma [from 96.9% (95% CI 94.8-99.0%) to 91.5% (95% CI 86.6-96.3%)], and in men [from 96.0% (95% CI 93.8-98.1%) to 81.8% (95% CI 76.8-86.8%)] than in women [from 96.4% (95% CI 93.4-99.5%) to 88.1% (95% CI 81.5-94.8%)]. No major differences were found between age groups. In conclusion, esophageal cancer survivors had a decline in survival between 6 and 10 years after surgery compared with the corresponding general population, particularly those with a history of squamous cell carcinoma of the esophagus and male sex., (© 2022. The Author(s).)

Background: There is increasing evidence for the use of exercise in cancer patients and data supporting enhanced tumour volume reduction following chemotherapy in animal models. To date, there is no reported histopathological evidence of a similar oncological benefit in oesophageal cancer., Methods: A prospective non-randomised trial compared a structured prehabilitation exercise intervention during neoadjuvant chemotherapy and surgery versus conventional best-practice for oesophageal cancer patients. Biochemical and body composition analyses were performed at multiple time points. Outcome measures included radiological and pathological markers of disease regression. Logistic regression calculated ORs with 95% CI for the likelihood of pathological response adjusting for chemotherapy regimen and chemotherapy delivery., Results: Comparison of the Intervention (n=21) and Control (n=19) groups indicated the Intervention group had higher rates of tumour regression (Mandard TRG 1-3 Intervention n=15/20 (75%) vs Control n=7/19 (36.8%) p=0.025) including adjusted analyses (OR 6.57; 95% CI 1.52 to 28.30). Combined tumour and node downstaging (Intervention n=9 (42.9%) vs Control n=3 (15.8%) p=0.089) and Fat Free Mass index were also improved (Intervention 17.8 vs 18.7 kg/m 2 ; Control 16.3 vs 14.7 kg/m 2 , p=0.026). Differences in markers of immunity (CD-3 and CD-8) and inflammation (IL-6, VEGF, INF-y, TNFa, MCP-1 and EGF) were observed., Conclusion: The results suggest improved tumour regression and downstaging in the exercise intervention group and should prompt larger studies on this topic., Trial Registration Number: NCT03626610., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To assess the outcomes of patients with early esophageal cancer and high-grade dysplasia comparing esophagectomy, the historical treatment of choice, to endoscopic eradication therapy (EET)., Methods: Retrospective cohort study of consecutive patients with early esophageal cancer/high-grade dysplasia, treated between 2000 and 2018 at a tertiary center. Primary outcomes were all-cause and disease-specific mortality assessed by multivariable Cox regression and a propensity score matching sub analysis, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, tumor grade (G1/2 vs. G3), tumor stage, and lymphovascular invasion. Secondary outcomes included complications, hospital stay, and overall costs., Results: Among 269 patients, 133 underwent esophagectomy and 136 received EET. Adjusted survival analysis showed no difference between groups regarding all-cause mortality (HR 1.85, 95% CI 0.73, 4.72) and disease-specific mortality (HR 1.10, 95% CI 0.26, 4.65). In-hospital and 30-day mortality was 0% in both groups. The surgical group had a significantly higher rate of complications (Clavien-Dindo ≥3 26.3% vs. endoscopic therapy 0.74%), longer in-patient stay (median 14 vs. 0 days endoscopic therapy) and higher hospital costs(£16 360 vs. £8786 per patient)., Conclusion: This series of patients treated during a transition period from surgery to EET, demonstrates a primary endoscopic approach does not compromise oncological outcomes with the benefit of fewer complications, shorter hospital stays, and lower costs compared to surgery. It should be available as the gold standard treatment for patients with early esophageal cancer. Those with adverse prognostic features may still benefit from esophagectomy., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Peri-operative chemotherapy improves survival in patients with locally advanced oesophago-gastric adenocarcinoma. Two regimens with proven survival benefits are epirubicin, cisplatin plus capecitabine or fluorouracil (Medical Research Council Adjuvant Gastric Infusional Chemotherapy, MAGIC) and fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). This study aimed to compare the effect of these regimens on survival (primary aim) and pathological response, surgical complications, adverse events and chemotherapy completion rates., Methods: Cohort study including 946 patients treated with FLOT (n = 257) or MAGIC (n = 689) who underwent surgical resection for oesophageal (n = 743) or gastric (n = 203) adenocarcinoma between 2002 and 2021 at St Thomas' Hospital or The Royal Marsden Hospital, London, UK. Survival analysis was performed using multivariable Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, clinical T-stage, clinical N-stage, tumour grade and presence of signet ring cells., Results: Patients treated with FLOT had better overall survival (HR = 0.69, 95% CI 0.50-0.94) and disease-free survival (HR = 0.75, 95% CI 0.58-0.98) than MAGIC. Patients treated with FLOT were more likely to have a complete pathological response (9.5% FLOT versus 5.5% MAGIC, p = 0.027) and were less likely to have a positive resection margin (19.1% FLOT versus 32.2% MAGIC, p < 0.001). The stratified analysis revealed similar results for oesophageal and gastric tumours. Rates of surgical complications, chemotherapy-associated adverse events and completion were similarly distributed between treatment groups., Conclusions: Patients with oesophageal or gastric adenocarcinoma treated with peri-operative FLOT had better survival and pathological response than those treated with peri-operative MAGIC. Rates of surgical complications, adverse events and chemotherapy completion were comparable., Competing Interests: Conflict of interest statement 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 article., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Oesophageal adenocarcinoma is characterised by a strong male predominance. We aimed to test the hypothesis that menopausal hormonal therapy decreases the risk of oesophageal adenocarcinoma., Methods: This population-based cohort study included all women who used systemic menopausal hormonal therapy (exposed) in Sweden between 2005 and 2018. For each exposed participant, five randomly selected female age-matched non-users of menopausal hormonal therapy (unexposed) were included. Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, smoking-related diagnoses, Helicobacter pylori eradication, use of non-steroidal anti-inflammatory drugs/aspirin, use of statins and hysterectomy., Results: The study included 296,964 users of menopausal hormonal therapy and 1,484,820 non-users. Ever-users of menopausal hormonal therapy had an overall decreased risk of oesophageal adenocarcinoma (HR 0.78, 95% CI 0.63-0.97), which remained unchanged after further adjustment for gastro-oesophageal reflux disease (HR 0.78, 95% CI 0.63-0.97) and obesity/diabetes (HR 0.79, 95% CI 0.63-0.98). Decreased HRs were indicated both in users of oestrogen only (HR 0.82, 95% CI 0.60-1.12) and oestrogen combined with progestogen (HR 0.75, 95% CI 0.56-1.00). The risk reduction was more pronounced in users younger than 60 years (HR 0.57, 95% CI 0.38-0.86)., Conclusions: Menopausal hormone therapy in women may decrease the risk of oesophageal adenocarcinoma., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Neoadjuvant chemotherapy is often used prior to surgical resection for oesophageal adenocarcinoma but remains ineffective in a high proportion of patients. The histological Mandard tumour regression grade is used to determine chemoresponse but is not available at the time of treatment decision-making. The aim of this cohort study was to identify factors that predict chemotherapy response prior to surgery., Methods: A prospectively collected database of patients undergoing surgical resection for oesophageal adenocarcinoma from a high-volume UK institution was used. Patients were subcategorised using pathological tumour response into 'responders' (Mandard grade 1-3) and 'non-responders' (Mandard grade 4 and 5). Multivariable logistic regression analysis was performed to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for responder status adjusting for a variety of parameters. Receiver operating characteristic (ROC) curves were calculated., Results: Among 315 patients included, 102 (32%) were responders and 213 (68%) non-responders. A decrease in radiological tumour volume (OR 1.92 95%CI 1.02-3.62; p  = 0.05), a 'partial response' RECIST score (OR 7.16 95%CI 1.49-34.36; p  = 0.01), a clinically improved dysphagia score (OR 2.79 95%CI 1.05-7.04; p  = 0.04) and lymphovascular invasion (OR 0.06 95%CI 0.02-0.13; p  = 0.000) influenced responder status. ROC curve analysis for responder status utilising all available parameters had an area under the curve (AUC) of 0.86., Conclusion: This study has highlighted the potential for using pre-defined factors to identify those patients who have responded to neoadjuvant chemotherapy, prior to surgical resection, potentially facilitating a more individualised therapeutic approach.

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Most patients presenting with oesophageal cancer do so with advanced disease not suitable for surgery. However, there are examples of encouraging survival following surgery in highly selected patients who respond well to chemotherapy., Methods: This was a retrospective cohort study of patients who presented with advanced but nonvisceral metastatic oesophageal cancer. Consecutive patients on a prolonged primary chemotherapy pathway who underwent surgical resection following a favourable response to chemotherapy were included. Survival and recurrence rates were analysed using Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: A total of 57 patients included in the cohort operated between 2007 and 2015, the overall median survival was 44 months and the 5-year survival was 42%. Prechemotherapy cN0/cN1 (HR: 0.27, 95% CI: 0.12-0.62) conferred an independent survival advantage compared to cN2 and cN3 disease. Poor differentiation (HR: 2.46, 95% CI: 1.11-5.42), R1 resection (HR: 2.43, 95% CI: 1.14-5.19) and advanced nodal status (HR: 3.28, 95% CI: 1.44-7.47) predicted worse survival on univariable analysis. Poor differentiation (HR: 3.93, 95% CI: 1.62-9.56) was independently associated with poor survival when adjusted for other variables., Conclusion: Patients who present with advanced inoperable oesophageal cancer who have a favourable response to chemotherapy represent a limited group of patients who may benefit from surgery., (© 2021 Wiley Periodicals LLC.)

Objective: This population-based study aimed to compare presentation, treatment allocation and survival of potentially curable esophageal cancer patients between Sweden and the Netherlands., Summary of Background Data: Identification of inter-country differences in treatment allocation and survival may be used for targeted esophageal cancer care improvement., Methods: Nationwide datasets were acquired from a Swedish cohort study and the Netherlands Cancer Registry. Patients with potentially curable (cT1-T4a/Tx, cN0/+, cM0/x) esophageal adenocarcinoma or squamous cell carcinoma (SCC) diagnosed in 2011-2015 were included. Multivariable logistic regression provided odds ratios (OR) for treatment allocation, and multivariable Cox model provided hazard ratios (HR) for overall survival, all with 95% confidence intervals (CI), adjusted for age, sex, year, tumor sub-location and stage., Results: Among 1980 Swedish and 7829 Dutch esophageal cancer patients, Swedish patients were older (71 vs 69 years, P <0.001) and had higher cT-stage (cT3: 49% vs 46%, P <0.001). After adjustment for confounders, Swedish patients were less frequently allocated to curative treatment (adenocarcinoma: OR=0.31, 95%CI 0.26-0.36; SCC: OR=0.28, 95%CI 0.22-0.36). Overall survival was lower in Swedish patients (adenocarcinoma: HR=1.36, 95%CI 1.27-1.46; SCC: HR=1.38, 95%CI 1.24-1.53), also when allocated to curative treatment (adenocarcinoma: HR=1.12, 95%CI 1.01-1.24; SCC: HR=1.34, 95%CI 1.14-1.59)., Conclusion: Swedish patients with potentially curable esophageal cancer were less frequently allocated to curative treatment, and showed lower survival compared to Dutch patients. The less pronounced inter-country survival difference after curative treatment suggests that the overall survival difference could at least partly be due to relative undertreatment of Swedish patients. Shared curative treatment thresholds across Europe may help improve survival of esophageal cancer patients., Competing Interests: Van Laarhoven has served as a consultant for BMS, Celgene, Lilly, Merck, Nordic, and Servier and has received unrestricted research funding from Bayer, BMS, Celgene, Lilly, Merck Serono, MSD, Nordic, Philips, Roche and Servier. Van Berge Henegouwen reports research grants from Olympus and Stryker, in addition to consulting fees from Medtronic, Mylan, Alesi Surgical and Johnson and Johnson. Verhoeven has received unrestricted research grants from BMS and Roche. The remaining authors have no conflict of interest to report. No funding was received for this study., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The aim of this study was to explore the male predominance in esophageal and gastric adenocarcinoma by evaluating the preventive potential of androgen deprivation therapy (ADT). This matched cohort study was based on a national Swedish database of prostate cancer patients in 2006-2013. Prostate cancer patients receiving ADT were the exposed group. Prostate cancer-free men from the general population were randomly selected and matched to the index case by birth year and county of residence, forming the unexposed control group. The participants were followed until a diagnosis of esophageal or gastric cancer, death, emigration, or end of the study period. The risk of esophageal adenocarcinoma, cardia gastric adenocarcinoma, non-cardia gastric adenocarcinoma, and esophageal squamous-cell carcinoma among ADT-exposed compared to unexposed was calculated by multivariable Cox proportional hazard regression. The hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted for confounders. There was a risk reduction of non-cardia gastric adenocarcinoma among ADT-users compared to non-users (HR 0.49 [95% CI 0.24-0.98]). No such decreased risk was found for esophageal adenocarcinoma (HR 1.17 [95% CI 0.60-2.32]), cardia gastric adenocarcinoma (HR 0.99 [95% CI 0.40-2.46]), or esophageal squamous cell carcinoma (HR 0.99 [95% CI 0.31-3.13]). This study indicates that androgen deprivation therapy decreases the risk of non-cardia gastric adenocarcinoma, while no decreased risk was found for esophageal adenocarcinoma, cardia gastric adenocarcinoma, or esophageal squamous-cell carcinoma.

Objective: We aimed to develop prediction models for estimating the long-term survival in patients who have undergone surgery for esophageal cancer., Background: Few prediction models have been developed for the long-term survival in esophageal cancer patients., Methods: This nationwide Swedish population-based cohort study included 1542 patients who survived for ≥90 days after esophageal cancer surgery between 1987 and 2010, with follow-up until 2016. Risk prediction models for 1-, 3-, and 5-year all-cause mortality and 3- and 5-year disease-specific mortality were developed using logistic regression. Candidate predictors were established and readily identifiable prognostic factors. The performance of the models was assessed by the area under receiver-operating characteristic curve (AUC) with interquartile range (IQR) using bootstrap cross-validation and risk calibration., Results: Predictors included in all models were age, sex, pathological tumor stage, tumor histology, and resection margin status. The models also included various additional predictors depending on the outcome, that is, education level, neoadjuvant therapy, reoperation (within 30 d of primary surgery) and comorbidity (Charlson comorbidity index). The AUC statistics after cross-validation were 0.71 (IQR 0.69-0.74) for 1-year, 0.77 (IQR 0.75-0.80) for 3-year, and 0.78 (IQR 0.76-0.81) for 5-year all-cause mortality. The corresponding values were 0.76 (IQR 0.74-0.79) for 3-year and 0.77 (IQR 0.71-0.83) for 5-year disease-specific mortality. All models showed good agreement between the observed and predicted risks., Conclusions: These models showed good performance for predicting long-term survival after esophageal cancer surgery and may thus be useful for patients in planning their lives and to guide the postoperative treatment and follow-up., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Esophageal squamous cell carcinoma (ESCC) carries a poor prognosis, but earlier tumor detection would improve survival. We aimed to develop and externally validate a risk prediction model based on exposure to readily available risk factors to identify high-risk individuals of ESCC., Methods: Competing risk regression modeling was used to develop a risk prediction model. Individuals' absolute risk of ESCC during follow-up was computed with the cumulative incidence function. We used prospectively collected data from the Nord-Trøndelag Health Study (HUNT) for model derivation and the UK Biobank cohort for validation. Candidate predictors were age, sex, tobacco smoking, alcohol consumption, body mass index (BMI), education, cohabitation, physical exercise, and employment. Model performance was validated internally and externally by evaluating model discrimination using the area under the receiver-operating characteristic curve (AUC) and model calibration., Results: The developed risk prediction model included age, sex, smoking, alcohol, and BMI. The AUC for 5-year risk of ESCC was 0.76 (95% confidence interval [CI], 0.58-0.93) in the derivation cohort and 0.70 (95% CI, 0.64-0.75) in the validation cohort. The calibration showed close agreement between the predicted cumulative risk and observed probabilities of developing ESCC. Higher net benefit was observed when applying the risk prediction model than considering all participants as being at high risk, indicating good clinical usefulness. A web tool for risk calculation was developed: https://sites.google.com/view/escc-ugis-ki., Discussion: This ESCC risk prediction model showed good discrimination and calibration and validated well in an independent cohort. This readily available model can help select high-risk individuals for preventive interventions.

Sex hormonal differences may contribute to the strong male predominance in esophageal adenocarcinoma (EAC), but whether sex hormone levels influence survival in EAC is unstudied. Our study aimed to assess associations between prediagnostic sex hormone levels and survival in EAC. In a population-based cohort study, 244 male EAC patients from the Janus Serum Bank Cohort in Norway were followed up through 2018. Associations between prediagnostic serum levels of 12 sex hormone measures and disease-specific mortality were assessed using multivariable Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, body mass index, tobacco smoking, physical activity and surgical resection. Higher levels of sex hormone-binding globulin (SHBG) indicated decreased disease-specific mortality (HR 0.68, 95% CI 0.44-1.07, highest vs lowest tertile). In stratified analyses by surgery, such associations remained in nonoperated patients (HR 0.58, 95% CI 0.35-0.96, highest vs lowest tertile), but not in operated patients. Higher levels of follicle-stimulating hormone (FSH) were associated with increased disease-specific mortality in an exposure-response pattern; HRs for the middle and highest tertiles vs the lowest tertile were 1.35 (95% CI 0.89-2.05) and 1.61 (95% CI 1.06-2.43), respectively. No clear associations were observed with serum levels of dehydroepiandrosterone sulfate, luteinizing hormone, prolactin, testosterone, 17-OH-progesterone, progesterone, estradiol, androstenedione, testosterone:estradiol ratio or free testosterone index. These findings suggest that higher endogenous levels of SHBG and lower levels of FSH may increase the survival in EAC. The other 10 examined sex hormone measures may not influence the survival., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

No previous study has sought to identify the effect of hospital volume of esophagectomy on anti-reflux surgery outcomes. The hypothesis under investigation was hospitals performing esophagectomies, particularly those of higher annual volume, have better outcomes from primary anti-reflux surgery. This population-based cohort study included adult individuals (≥18 years) in Sweden receiving primary anti-reflux surgery for a recorded gastro-esophageal reflux disease in 1997-2010, with follow-up until 2013 The 'exposure' was hospital volume of esophagectomy, with hospitals conducting esophagectomies divided into 0, >0-1, >1-3 and ≥ 4 based on annual volume, and hospitals not conducting esophagectomies were the reference category. The outcomes were 30-day re-intervention and surgical re-intervention during the entire follow-up after anti-reflux surgery. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for age, sex, comorbidity, type of anti-reflux surgery, and year of anti-reflux surgery. Among 10,959 participants having undergone primary anti-reflux surgery, the 30-day re-intervention rate was 1.1%, and the rate of surgical re-intervention during the entire follow-up was 6.8%. Compared with hospitals not performing esophagectomy, hospitals in the highest volume group of esophagectomy showed no decreased risks of 30-day re-intervention (HR = 1.46, 95% CI 0.89-2.39) or surgical re-intervention (HR = 1.21, 95%CI 0.91-1.60) during follow-up. Similarly, the intermediate hospital volume categories of esophageal cancer surgery had no decreased risk of surgical re-interventions after anti-reflux surgery. This study provides no evidence for centralization of primary anti-reflux surgery to centers for esophageal cancer surgery., (© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Background: Esophagectomy for esophageal cancer is associated with a substantial risk of life-threatening complications and a limited long-term survival. This study aimed to clarify the controversial questions of how age influences short-term and long-term survival., Methods: This population-based cohort study included almost all patients who underwent curatively intended esophagectomy for esophageal cancer in Sweden in 1987-2010, with follow-up through 2016. The exposure was age, analyzed both as a continuous and categorical variable. The probability of mortality was computed using a novel flexible parametric model approach. The reported probabilities are proper measures of the risk of dying, and the related odds ratios (OR) are therefore more suitable measures of association than hazard ratios. The outcomes were 90-day all-cause mortality, 5-year all-cause mortality, and 5-year disease-specific mortality. A novel flexible parametric model was used to derive the instantaneous probability of dying and the related OR along with 95% confidence intervals (CIs), adjusted for sex, education, comorbidity, tumor histology, pathological tumor stage, and resection margin status., Results: Among 1737 included patients, the median age was 65.6 years. When analyzed as a continuous variable, older age was associated with slightly higher odds of 90-day all-cause mortality (OR 1.05, 95% CI 1.02-1.07), 5-year all-cause mortality (OR 1.02, 95% CI 1.01-1.03), and 5-year disease-specific mortality (OR 1.01, 95% CI 1.01-1.02). Compared with patients aged < 70 years, those aged 70-74 years had no increased risk of any mortality outcome, while patients aged ≥ 75 years had higher odds of 90-day mortality (OR 2.85, 95% CI 1.68-4.84), 5-year all-cause mortality (OR 1.56, 95% CI 1.27-1.92), and 5-year disease-specific mortality (OR 1.38, 95% CI 1.09-1.76)., Conclusions: Patient age 75 years or older at esophagectomy for esophageal cancer appears to be an independent risk factor for higher short-term mortality and lower long-term survival.

Background & Aims: Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored., Methods: Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits., Results: We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, P BONF  = .039) that was statistically significantly associated with BE/EA risk in male individuals only, and 1 variant at chromosome 8p23.1 (rs13259457, PRSS55-RP1L1, P BONF  = 0.057) associated, at borderline significance, with BE/EA risk in female individuals only. We also observed strong genetic correlations of BE/EA with gastroesophageal reflux disease in male individuals and obesity in female individuals., Conclusions: The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance., (Copyright © 2020 AGA Institute. All rights reserved.)

Associations between circulating levels of obesity-related biomarkers and risk of esophageal adenocarcinoma and Barrett esophagus have been reported, but the results are inconsistent. A literature search until October 2018 in MEDLINE and EMBASE was performed. Pooled ORs with 95% confidence intervals (CI) were estimated for associations between 13 obesity-related inflammatory and metabolic biomarkers and risk of esophageal adenocarcinoma or Barrett esophagus using random effect meta-analyses. Among 7,641 studies, 19 were eligible for inclusion (12 cross-sectional, two nested case-control, and five cohort studies). Comparing the highest versus lowest categories of circulating biomarker levels, the pooled ORs were increased for leptin (OR, 1.68; 95% CI, 0.95-2.97 for Barrett esophagus), glucose (OR, 1.12; 95% CI, 1.03-1.22 for esophageal adenocarcinoma), insulin (OR, 1.47; 95% CI, 1.06-2.00 for Barrett esophagus), C-reactive protein (CRP; OR, 2.06; 95% CI, 1.28-3.31 for esophageal adenocarcinoma), IL6 (OR, 1.50; 95% CI, 1.03-2.19 for esophageal adenocarcinoma), and soluble TNF receptor 2 (sTNFR-2; OR, 3.16; 95% CI, 1.76-5.65 for esophageal adenocarcinoma). No associations were identified for adiponectin, ghrelin, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, triglycerides, IL8, or TNFα. Higher circulating levels of leptin, glucose, insulin, CRP, IL6, and sTNFR-2 may be associated with an increased risk of esophageal adenocarcinoma or Barrett esophagus. More prospective studies are required to identify biomarkers that can help select high-risk individuals for targeted prevention and early detection., (©2020 American Association for Cancer Research.)

Background & Aims: Esophageal adenocarcinoma (EAC) occurs most frequently in men. We performed a Mendelian randomization analysis to investigate whether genetic factors that regulate levels of sex hormones are associated with risk of EAC or Barrett's esophagus (BE)., Methods: We conducted a Mendelian randomization analysis using data from patients with EAC (n = 2488) or BE (n = 3247) and control participants (n = 2127), included in international consortia of genome-wide association studies in Australia, Europe, and North America. Genetic risk scores or single-nucleotide variants were used as instrumental variables for 9 specific sex hormones. Logistic regression provided odds ratios (ORs) with 95% CIs., Results: Higher genetically predicted levels of follicle-stimulating hormones were associated with increased risks of EAC and/or BE in men (OR, 1.14 per allele increase; 95% CI, 1.01-1.27) and in women (OR, 1.28; 95% CI, 1.03-1.59). Higher predicted levels of luteinizing hormone were associated with a decreased risk of EAC in men (OR, 0.92 per SD increase; 95% CI, 0.87-0.99) and in women (OR, 0.93; 95% CI, 0.79-1.09), and decreased risks of BE (OR, 0.88; 95% CI, 0.77-0.99) and EAC and/or BE (OR, 0.89; 95% CI, 0.79-1.00) in women. We found no clear associations for other hormones studied, including sex hormone-binding globulin, dehydroepiandrosterone sulfate, testosterone, dihydrotestosterone, estradiol, progesterone, or free androgen index., Conclusions: In a Mendelian randomization analysis of data from patients with EAC or BE, we found an association between genetically predicted levels of follicle-stimulating and luteinizing hormones and risk of BE and EAC., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: The public health disorder gastro-oesophageal reflux disease (GORD) is linked with several comorbidities, including oesophageal adenocarcinoma (OAC), but whether life expectancy is reduced by GORD is uncertain. This study assessed all-cause and cancer-specific mortality in GORD after controlling for confounding by heredity and other factors., Design: Population-based cohort study from 1998 to 2015., Setting: Swedish nationwide study., Participants: Twins (n=40 961) born in 1958 or earlier in Sweden., Exposure: GORD symptoms reported in structured computer-assisted telephone interviews., Outcomes: The primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality among twins with GORD and twins without GORD. HRs and 95% CIs were analysed using parametric survival models, both in individual twin analyses and co-twin pair analyses, with adjustment for body mass index, smoking, education and comorbidity., Results: Among 40 961 individual twins, 5812 (14.2%) had GORD at baseline and 8062 (19.7%) died during follow-up of up to 16 years. The risks of all-cause mortality (HR=1.00, 95% CI: 0.94-1.07) and cancer-specific mortality (HR=0.99, 95% CI: 0.89-1.10) were not increased in individual twins with GORD compared with individual twins without GORD. Similarly, there were no differences in mortality outcomes in within-pair analyses. The OAC-specific mortality rate was 0.45 (95% CI: 0.32-0.66) per 1000 person-years in individual twins with GORD and 0.22 (95% CI: 0.18-0.27) per 1000 person-years without GORD, rendering an adjusted HR of 2.01 (95% CI: 1.35-2.98)., Conclusions: GORD did not increase all-cause or cancer-specific mortality when taking heredity and other confounders into account. The increased relative risk of mortality in OAC was low in absolute numbers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: Esophageal cancer surgery reduces patients' health-related quality of life (HRQoL). This study examined whether comorbidities influence HRQoL in these patients., Methods: This prospective cohort study included esophageal cancer patients having undergone curatively intended esophagectomy at St Thomas' Hospital London in 2011-2015. Clinical data were collected from patient reports and medical records. Well-validated cancer-specific and esophageal cancer-specific questionnaires (EORTC QLQ-C30 and QLQ-OG25) were used to assess HRQoL before and 6 months after esophagectomy. Number of comorbidities, American Society of Anesthesiologists physical status classification (ASA), and specific comorbidities were analyzed in relation to HRQoL aspects using multivariable linear regression models. Mean score differences with 95% confidence intervals were adjusted for potential confounders., Results: Among 136 patients, those with three or more comorbidities at the time of surgery had poorer global quality of life and physical function and more fatigue compared with those with no comorbidity. Patients with ASA III-IV reported more problems with the above HRQoL aspects and worse social function and pain compared with those with ASA I-II. Cardiac comorbidity was associated with worse global quality of life and dyspnea, while pulmonary comorbidities were related to coughing. Patients assessed both before and 6 months after surgery (n = 80) deteriorated in most HRQoL aspects regardless of comorbidity status, but patients with several comorbidities had worse physical function and fatigue and more trouble with coughing compared with those with fewer comorbidities., Conclusion: Comorbidity appears to negatively influence HRQoL before esophagectomy, but appears not to severely impact 6-month recovery of HRQoL.

Gastroesophageal reflux disease (GERD) is a risk factor of esophageal adenocarcinoma (EAC) and the most common indication for upper gastrointestinal endoscopy. Yet, whether GERD or endoscopy practice influence survival in EAC is largely unknown and was assessed in our study.This nationwide cohort study included all Swedish residents diagnosed with EAC in 1997-2013 with follow-up to 2018. Exposures were history of GERD and endoscopies prior to EAC. The main outcome was EAC-specific 5-year mortality. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for potential confounders. Among 6,600 EAC patients (79.3% males, median age 70 years) followed for 9,138 person-years, 440 (6.7%) had GERD and 592 (9.0%) had ≥1 endoscopy before EAC diagnosis. GERD was associated with a decreased risk of mortality (adjusted HR 0.71, 95% CI 0.64-0.80), which was only slightly attenuated by adjustment for prior endoscopies (HR 0.79, 95% CI 0.70-0.90), and further adjustments also for tumor stage and surgical resection (HR 0.74, 95% CI 0.62-0.89). Compared to EAC patients without prior endoscopy, mortality was unchanged in GERD patients having undergone 1 or 2 endoscopies before EAC diagnosis (HR 1.02, 95% CI 0.80-1.31, for 1 endoscopy; HR 0.90, 95% CI 0.63-1.30, for 2 endoscopies), while the mortality was decreased in patients with ≥3 endoscopies (HR 0.55, 95% CI 0.36-0.85). Our study indicates that GERD may be associated with a better prognosis in the event of EAC; however, the use of endoscopy screening has a limited impact on survival unless performed very frequently., (© 2019 UICC.)