Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

Conditional survival and annual hazard of death in older patients with esophageal cancer receiving definitive chemoradiotherapy.

BACKGROUND: Definitive chemoradiotherapy is one of the primary treatment modalities for older patients with esophageal cancer (EC). However, the evolution of prognosis over time and the factors affected non-EC deaths remain inadequately studied. We examined the conditional survival and annual hazard of death in older patients with EC after chemoradiotherapy. METHODS: We collected data from patients aged 65 or older with EC registered in the Surveillance, Epidemiology, and End Results database during 2000-2019. Conditional survival was defined as the probability of survival given a specific time survived. Annual hazard of death was defined the yearly event rate. Restricted cubic spline (RCS) analysis identified the association of age at diagnosis with mortality. RESULTS: Among 3739 patients, the 3-year conditional overall survival increased annually by 7-10%. Non-EC causes accounted for 18.8% of deaths, predominantly due to cardio-cerebrovascular diseases. The hazard of death decreased from 40 to 10% in the first 6 years and then gradually increased to 20% in the tenth year. Non-EC causes surpassed EC causes in hazard starting 5 years post-treatment. RCS indicated a consistent increase in death hazard with advancing age, following a linear relationship. The overall cohort was divided into two groups: 65-74 and ≥ 75 years old, with the ≥ 75-year-old group showing poorer survival and earlier onset of non-EC deaths (HR = 1.36, 95% CI: 1.15-1.62, P < 0.001). Patients with early-stage disease (I-II) had higher risks of death from non-EC causes (HR = 0.82, 95% CI: 0.68-0.98, P = 0.035). Tumor histology had no significant impact on non-EC death risk (HR = 1.17, 95% CI: 0.98-1.39, P = 0.081). CONCLUSIONS: Survival probability increases with time for older patients with EC treated with chemoradiotherapy. Clinicians and patients should prioritize managing and preventing age-related comorbidities, especially in older cohorts and those with early-stage disease.

Optimal lymph node yield in oesophagectomy for oesophageal cancer: a nationwide population-based study.

OBJECTIVES: The desirable lymph node count was determined to maximize the survival time expectancy according to the lymph node count among patients who have undergone oesophagectomy for oesophageal cancer. METHODS: The data of national Finnish population-based cohort including all patients who have undergone oesophagectomy due to oesophageal cancer during 2002-2016 were used. Restricted mean survival time (RMST) estimates were determined by lymph node count, and the desirable count was determined using locally estimated scatterplot smoothing regression. RESULTS: A total of 883 patients with the median follow-up time of 3.73 (interquartile range 1.43-7.50) years were included. The lymph node count of 27 (95% confidence interval 25-28) was associated with the highest RMST estimates. Sensitivity analyses indicated that in pN0 patients, the highest RMST estimates was observed at 26 (95% confidence interval 24-28) lymph nodes and in pN+ patients, the RMST estimates peaked at 28 (95% confidence interval 25-33) lymph nodes. CONCLUSIONS: According to the findings of this study, at least 24 examined lymph nodes is the recommended target for the lymph node count after oesophagectomy for oesophageal cancer. The beneficial effect of this count on survival may be achieved regardless of nodal metastases.

Effects of physical and psychological symptoms on cancer-related fatigue among esophageal cancer patients.

BACKGROUND: Cancer-related fatigue (CRF) is considered one of the most prevalent and distressing symptoms among cancer patients and may vary among patients with different cancer types. However, few studies have explored the influence of physical and psychological symptoms on CRF among esophageal cancer (EC) patients without esophagectomy. Therefore, this study aimed to examine the effects of physical and psychological symptoms on CRF among EC patients without esophagectomy. METHODS: In the present study, a cross-sectional study was conducted from February 2021 to March 2022 in Liaoning Province, China. Among the 112 included participants, 97 completed our investigation. The questionnaires used consisted of the Brief Fatigue Inventory (BFI), the MD Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI), the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7), and demographic and clinical information. Multivariate linear regression was conducted to test the relationships between physical and psychological symptoms and CRF. RESULTS: Of the 97 EC patients, 60.8% reported CRF (BFI ≥ 4). The mean age of the participants was 64.92 years (SD = 8.67). According to the regression model, all the variables explained 74.5% of the variance in CRF. Regression analysis indicated that physical symptoms, including constipation, diarrhoea, and difficulty swallowing, contributed to CRF. On the other hand, depressive symptoms increased the level of CRF among EC patients without esophagectomy. CONCLUSIONS: Given the high prevalence of CRF among EC patients without esophagectomy, it is urgent to emphasize the importance of fatigue management interventions based on physical and psychological symptoms to alleviate CRF in EC patients.

Risk of Esophageal Adenocarcinoma After Bariatric Surgery: A Meta-Analysis of Retrospective Studies.

PURPOSE: This study aims to systematically review and meta-analyze the evidence on the risk of esophageal adenocarcinoma (EAC) following metabolic and bariatric surgery (MBS). MATERIALS AND METHODS: A systematic literature search was conducted on the China National Knowledge Infrastructure (CNKI), Wanfang, EMBASE, MEDLINE, Web of Science, The Cochrane Library, and PubMed databases. Meta-analysis utilized odds ratios (ORs) and 95% confidence intervals (CIs) to analyze the correlation between MBS and the risk of EAC. Meta-analysis was performed using STATA software (version 12.0). RESULTS: Fourteen studies involving patients with obesity undergoing bariatric surgery and control groups receiving conventional treatment were included. The meta-analysis indicated a reduction in the overall incidence of esophageal cancer after bariatric surgery (OR = 0.69, 95% CI: 0.51-0.95, P = 0.022). Subgroup analysis results demonstrated a decreased risk of EAC in European patients with obesity undergoing MBS treatment (OR: 0.60, 95% CI: 0.38-0.95, P = 0.028). In studies with a sample size greater than or equal to 100,000 patients, the risk of EAC in patients with obesity undergoing MBS was significantly lower than the non-surgery group (OR: 0.59, 95% CI: 0.42-0.83, P = 0.003). Articles published before 2020 and those published in 2020 or earlier showed a significant difference in the incidence of EAC between the surgery and non-surgery groups (OR: 0.57, 95% CI: 0.43-0.75, P < 0.001). The risk of EAC in patients with obesity with a follow-up time of less than 5 years was statistically significant (OR: 0.46, 95% CI: 0.25-0.82, P = 0.009). CONCLUSION: Our meta-analysis results suggest a reduced risk of esophageal cancer in patients with obesity after bariatric surgery. PROSPERO REGISTRATION: CRD 42024505177.

Global burden of esophageal cancer attributable to high BMI in 204 countries and territories: 1990-2019.

BACKGROUND: Esophageal cancer (EC), a common and fatal disease, includes two histological subtypes; esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (ECA). To aid policymakers in the allocation of resources for the prevention and treatment of EC, updated data on EC deaths and disability-adjusted life years (DALYs) attributable to high body mass index (BMI) are necessary. The objective of this study was to identify trends in EC associated with high BMI between 1990 and 2019 using 2019 Global Burden of Disease data. METHODS: In this observational population-based study, epidemiological data on the association between high BMI and EC were obtained from GBD 2019. The age-standardized mortality rate (ASMRs) and disability-adjusted life year rate (ASDRs) attributable to high BMI-related EC were stratified by year, age, country, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends of the ASMRs and ASDRs between 1990 and 2019. RESULTS: In 2019, the proportion of EC deaths and DALYs attributed to high BMI was 18.1% and 18.9%, respectively, resulting in 89 904 (95% confidence interval [CI]: 27 879-171 255) deaths and 2 202 314 (95% CI: 681 901-4 173 080) DALYs. High BMI-related deaths and DALYs showed a strong upward trend, increasing by more than two-fold since 1990. East Asia and Western Europe showed the highest risk of EC mortality and DALYs attributable to high BMI; China and the USA bear the greatest burden. The ASMR and ASDR increased in five SDI regions. CONCLUSIONS: The incidence of EC is increasing, particularly in developing nations, which may be attributed to the prevalence of high BMI. To mitigate the impact of high BMI on the incidence of EC, it is important to increase awareness of its deleterious effects, which may alleviate the burden of this disease.

Discrepant effect of high-density lipoprotein cholesterol on esophageal and gastric cancer risk in a nationwide cohort.

BACKGROUND: The relationship between high-density lipoprotein cholesterol (HDL-C) and gastroesophageal cancer is not constant. METHODS: In this population-based cohort study, 4.518 million cancer-free individuals among those who underwent national cancer screening in 2010 were enrolled and followed up until December 2017. HDL-C level was classified into eight groups at 10 mg/dL intervals. The risk of gastroesophageal cancers by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: During 8 years of follow-up, 38,362 gastric and 3022 esophageal cancers developed. Low HDL-C level was associated with an increased risk of gastric cancer; aHR was 1.19 (95% CI 1.09-1.30) for HDL-C < 30 mg/dL, 1.07 (95% CI 1.03-1.12) for HDL-C of 30-39 mg/dL, and 1.07 (95% CI 1.03-1.12) for HDL-C of 40-49 mg/dL comparing to HDL-C of 60-69 mg/dL. HDL-C was positively associated with esophageal cancer risk; aHR was 1.30 (1.12-1.51) for HDL-C of 70-79 mg/dL, 1.84 (1.53-2.22) for HDL-C of 80-89 mg/dL, 2.10 (1.67-2.61) for HDL-C ≥ 90 mg/dL. These site-specific effects of HDL-C were robust in sensitivity analyses. The range of HDL-C for the lowest cancer risk was different by sex and site. The hazardous effect of low HDL-C on gastric cancer was prominent in never and past smokers, and extremely high HDL-C increased gastric cancer risk (aHR 1.19; 95% CI 1.04-1.36) only in current smokers. Unfavorable effect of high HDL-C on gastroesophageal cancer risk was remarkable in smokers. CONCLUSIONS: Low HDL-C increased the risk of gastric cancer, wherein high HDL-C was associated with esophageal cancer risk with discrepancies by sex and smoking status.

Adherence to prescription proton pump inhibitor therapy amongst individuals diagnosed with Barrett's esophagus.

INTRODUCTION: In the United States, clinical guidelines recommend daily use of proton pump inhibitors (PPIs) amongst individuals diagnosed with Barrett's esophagus to decrease the risk of progression to dysplasia and neoplasia. Prior studies documenting adherence to PPIs in this population have not characterized heterogeneity in adherence patterns. Factors that may relate to adherence are incompletely described. METHODS: We used administrative claims data from the Merative MarketScan Commercial Claims and Encounters database to conduct a retrospective study of adherence to prescription PPIs. A cohort of individuals diagnosed with incident Barrett's esophagus between 2010 and 2019 was identified. Group-based trajectory models were generated to detect longitudinal adherence subgroups. RESULTS: 79 701 individuals with a new diagnosis of Barrett's esophagus were identified. The best fitting model detected five distinct adherence trajectory groups: consistently high (44% of the population), moderate decline (18%), slow decline (12%), rapid decline (10%), and decline-then-increase (16%). Compared to individuals starting PPIs, those already using PPIs were less likely to have a declining adherence pattern. Other factors associated with membership in a declining adherence group included (but were not limited to): female sex, having a past diagnosis of anxiety or depression, and having one or more emergency department visits in the past year. DISCUSSION: Using an exploratory method, we detected heterogeneity in adherence to prescription PPIs. Less than half of individuals were classified into the consistently high adherence group, suggesting that many individuals with Barrett's esophagus receive inadequate pharmacologic therapy.

Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people.

An East Asian-specific variant on aldehyde dehydrogenase 2 (ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci (GCKR, KLB, and ADH1B) in wild-type homozygotes and six (GCKR, ADH1B, ALDH1B1, ALDH1A1, ALDH2, and GOT2) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four (GCKR, ADH1B, ALDH1A1, and ALDH2) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.

Burdens of stomach and esophageal cancer from 1990 to 2019 and projection to 2030 in China: Findings from the 2019 Global Burden of Disease Study.

Background: Stomach and esophageal cancer exhibit high morbidity and mortality rate in China, resulting in substantial disease burdens. It is imperative to identify the temporal trends of stomach and esophageal cancer from 1990 to 2019 and project future trends until 2030, which can provide valuable information for planning effective management and prevention strategies. Methods: We collected and analysed data from the Global Burden of Disease (GBD) between 1990 and 2019, including incidence, mortality, disability-adjusted life years (DALYs), age-standardised incidence rate (ASIR), mortality rate (ASMR) and DALYs rate. We also calculated and reported the proportion of mortality and DALYs attributable to risk factors by sex in China and different regions. The Bayesian age-period-cohort model was applied to project future trends until 2030. Results: The new cases, deaths and DALYs of stomach and esophageal cancer increased from 1990 to 2019. However, the ASIR, ASMR and age-standardised DALYs rates for stomach and esophageal cancer all decreased during the same period. These changes may be related to risks, such as smoking and diet. Furthermore, we utilised the projection model to estimate that the ASIR and ASMR of stomach and esophageal cancer among females will likely follow steady downward trends, while the ASMR of stomach cancer among males is expected to exhibit a significant decline. However, the ASIR of stomach and esophageal cancer and the ASMR of esophageal cancer among males are projected to display slight upward trends until 2030. Conclusions: The analysis of stomach and esophageal cancer trends in China from 1990 to 2030 reveals a general decline. However, it is crucial to acknowledge the persistent high burden of both cancers in the country. Adopting healthy lifestyle practices, including the reduction of tobacco and alcohol intake, avoidance of moldy foods and increased consumption of fresh fruits and vegetables can contribute to mitigating the risk of stomach and esophageal cancer. Significantly, the formulation and implementation of well-founded and efficacious public health policies are imperative for alleviating the disease burden in China.

Correlation between sarcopenia and esophageal cancer: a narrative review.

BACKGROUND: In recent years, the research on the relationship between sarcopenia before and after the treatment of esophageal cancer, as well as its impact on prognosis of esophageal cancer, has increased rapidly, which has aroused people's attention to the disease of patients with esophageal cancer complicated with sarcopenia. This review examines the prevalence of sarcopenia in patients with esophageal cancer, as well as the relationship between sarcopenia (before and after surgery or chemotherapy) and prognosis in patients with esophageal cancer. Moreover, we summarized the potential pathogenesis of sarcopenia and pharmacologic and non-pharmacologic therapies. METHODS: A narrative review was performed in PubMed and Web of Science using the keywords ("esophageal cancer" or "esophageal neoplasm" or "neoplasm, esophageal" or "esophagus neoplasm" or "esophagus neoplasms" or "neoplasm, esophagus" or "neoplasms, esophagus" or "neoplasms, esophageal" or "cancer of esophagus" or "cancer of the esophagus" or "esophagus cancer" or "cancer, esophagus" or "cancers, esophagus" or "esophagus cancers" or "esophageal cancer" or "cancer, esophageal" or "cancers, esophageal" or "esophageal cancers") and ("sarcopenia" or "muscular atrophy" or "aging" or "senescence" or "biological aging" or "aging, biological" or "atrophies, muscular" or "atrophy, muscular" or "muscular atrophies" or "atrophy, muscle" or "atrophies, muscle" or "muscle atrophies"). Studies reporting relationship between sarcopenia and esophageal cancer were analyzed. RESULTS: The results of the review suggest that the average prevalence of sarcopenia in esophageal cancer was 46.3% ± 19.6% ranging from 14.4 to 81% and sarcopenia can be an important predictor of poor prognosis in patients with esophageal cancer. Patients with esophageal cancer can suffer from sarcopenia due to their nutritional deficiencies, reduced physical activity, chemotherapy, and the effects of certain inflammatory factors and pathways. When classic diagnostic values for sarcopenia such as skeletal muscle index (SMI) are not available clinically, it is also feasible to predict esophageal cancer prognosis using simpler metrics, such as calf circumference (CC), five-count sit-up test (5-CST), and six-minute walk distance (6MWD). CONCLUSIONS: Identifying the potential mechanism of sarcopenia in patients with esophageal cancer and implementing appropriate interventions may hold the key to improving the prognosis of these patients.

Age-period-cohort analysis of incidence, mortality and disability-adjusted life years of esophageal cancer in global, regional and national regions from 1990 to 2019.

OBJECTIVE: In view of the high incidence and mortality of esophageal cancer, the latest statistical data on the disease burden of esophageal cancer can provide strategies for cancer screening, early detection and treatment, and help to rationally allocate health resources. This study provides an analysis of the global disease burden and risk factors of esophageal cancer from 1990 to 2019. METHODS: Using the 2019 Global Burden of Disease, Injury and Risk Factor (GBD) data, we present the incidence, mortality and disability-adjusted life years (DALY) of esophageal cancer in 21 regions and 204 countries and different sociodemographic index (SDI) regions from 1990 to 2019. The age-period-cohort model was used to estimate the age, period, and cohort trend of esophageal cancer in different SDI regions. The estimated proportion of DALY attributable to each risk factor from 1990 to 2019. RESULTS: From 1990 to 2019, the number of new cases of esophageal cancer, the number of deaths and DALY increased by 67.07%, 55.97% and 42.13%, respectively, but age standardized incidence rate (ASIR), age standardized mortality rate (ASMR) and age standardized DALY rate (ASDR) decreased by 19.28%, 25.32% and 88.22%, respectively. Overall, the results of the age-period-cohort model showed that the incidence, mortality, and DALY rates in countries and regions with higher SDI levels showed a downward trend over time and with the passage of time. Conversely, there were no significant changes in incidence and mortality in countries and regions with low SDI levels. In the past 30 years, the incidence and death of esophageal cancer in the world has gradually changed to people over 80 years old, but the population aged 60-79 still accounts for the largest proportion. The global DALY in esophageal cancer is mainly attributable to smoking, followed by alcohol consumption and occupational exposure. CONCLUSIONS: Although ASIR, ASMR and ASDR have decreased significantly, esophageal cancer is still the main factor causing the disease burden worldwide. Public health administrators in low SDI and low-middle SDI countries are high-risk areas for esophageal cancer, and preventive control measures should be implemented to raise awareness, screening, and treatment of esophageal cancer in these areas. Tobacco and alcohol control and reduction of occupational hazards are key steps in reducing the burden of esophageal cancer.

Poor oral health and the risk of esophageal squamous cell carcinoma in Malawi.

Esophageal squamous cell carcinoma (ESCC) is the second most common cancer in Malawi. Risk factors for this cancer in Malawi are poorly understood. Poor oral health has previously been linked to increased ESCC risk in other high-incidence regions, including parts of Eastern and Southern Africa. We assessed the relationship between oral health and ESCC risk in a sex, age and location frequency-matched case-control study based at two hospitals in Lilongwe, Malawi from 2017 to 2020. Trained interviewers used a structured questionnaire and direct observation to collect data on demographics; behaviors; oral hygiene habits; the sum of decayed, missing or filled teeth (DMFT score); oral mucosa status; lip depigmentation and dental fluorosis via a visual scale. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI), adjusted for known and suspected ESCC risk factors. During the study period, 300 cases and 300 controls were enrolled. Subjects in the highest tertile of DMFT score (≥7) had an increased risk of ESCC with an adjusted OR of 1.96 (95% CI: 1.16-3.36) compared to those with a DMFT score of 0. Severe dental fluorosis was associated with a statistically nonsignificant increased risk of ESCC (adjusted OR = 2.24, 95% CI: 0.97-5.49) compared to individuals with no fluorosis. Associations with oral mucosa status, lip depigmentation and toothbrushing method and frequency were mostly null or uncertain. Poor oral health, indicated by a higher DMFT score, was associated with increased ESCC risk in Malawi. Dental fluorosis is another possible risk factor in this population, but further evaluation is necessary to clarify any effects of fluorosis on ESCC risk.

Prevalence and Predictors of Barrett's Esophagus After Negative Initial Endoscopy: Analysis From Two National Databases.

BACKGROUND & AIMS: Guidelines suggest a single screening esophagogastroduodenoscopy (EGD) in patients with multiple risk factors for Barrett's esophagus (BE). We aimed to determine BE prevalence and predictors on repeat EGD after a negative initial EGD, using 2 large national databases (GI Quality Improvement Consortium [GIQuIC] and TriNetX). METHODS: Patients who underwent at least 2 EGDs were included and those with BE or esophageal adenocarcinoma detected at initial EGD were excluded. Patient demographics and prevalence of BE on repeat EGD were collected. Multivariate logistic regression was performed to assess for independent risk factors for BE detected on the repeat EGD. RESULTS: In 214,318 and 153,445 patients undergoing at least 2 EGDs over a median follow-up of 28-35 months, the prevalence of BE on repeat EGD was 1.7% in GIQuIC and 3.4% in TriNetX, respectively (26%-45% of baseline BE prevalence). Most (89%) patients had nondysplastic BE. The prevalence of BE remained stable over time (from 1 to >5 years from negative initial EGD) but increased with increasing number of risk factors. BE prevalence in a high-risk population (gastroesophageal reflux disease plus ≥1 risk factor for BE) was 3%-4%. CONCLUSIONS: In this study of >350,000 patients, rates of BE on repeat EGD ranged from 1.7%-3.4%, and were higher in those with multiple risk factors. Most were likely missed at initial evaluation, underscoring the importance of a high-quality initial endoscopic examination. Although routine repeat endoscopic BE screening after a negative initial examination is not recommended, repeat screening may be considered in carefully selected patients with gastroesophageal reflux disease and ≥2 risk factors for BE, potentially using nonendoscopic tools.

Population Based Time Trends in the Epidemiology and Mortality of Gastroesophageal Junction and Esophageal Adenocarcinoma.

BACKGROUND: Limited data are available on the epidemiology of gastroesophageal junction adenocarcinoma (GEJAC), particularly in comparison to esophageal adenocarcinoma (EAC). With the advent of molecular non-endoscopic Barrett's esophagus (BE) detection tests which sample the esophagus and gastroesophageal junction, early detection of EAC and GEJAC has become a possibility and their epidemiology has gained importance. AIMS: We sought to evaluate time trends in the epidemiology and survival of patients with EAC and GEJAC in a population-based cohort. METHODS: EAC and GEJAC patients from 1976 to 2019 were identified using ICD 9 and 10 diagnostic codes from the Rochester Epidemiology Project (REP). Clinical data and survival status were abstracted. Poisson regression was used to calculate incidence rate ratios (IRR). Survival analysis and Cox proportional models were used to assess predictors of survival. RESULTS: We included 443 patients (287 EAC,156 GEJAC). The incidence of EAC and GEJAC during 1976-2019 was 1.40 (CI 1.1-1.74) and 0.83 (CI 0.61-1.11) per 100,000 people, respectively. There was an increase in the incidence of EAC (IRR = 2.45, p = 0.011) and GEJAC (IRR = 3.17, p = 0.08) from 2000 to 2004 compared to 1995-1999, plateauing in later time periods. Most patients had associated BE and presented at advanced stages, leading to high 5-year mortality rates (66% in EAC and 59% in GEJAC). Age and stage at diagnosis were predictors of mortality. CONCLUSION: The rising incidence of EAC/GEJAC appears to have plateaued somewhat in the last decade. However, both cancers present at advanced stages with persistently poor survival, underscoring the need for early detection.

Causal relationships between coffee intake, apolipoprotein B and gastric, colorectal, and esophageal cancers: univariable and multivariable Mendelian randomization.

PURPOSE: Coffee intake and apolipoprotein B levels have been linked to gastric, colorectal, and esophageal cancers in numerous recent studies. However, whether these associations are all causal remains unestablished. This study aimed to assess the potential causal associations of apolipoprotein B and coffee intake with the risk of gastric, colorectal, and esophageal cancers using Mendelian randomization analysis. METHODS: In this study, we utilized a two-sample Mendelian randomization analysis to access the causal effects of coffee intake and apolipoprotein B on gastric, colorectal, and esophageal cancers. The summary statistics of coffee intake (n = 428,860) and apolipoprotein B (n = 439,214) were obtained from the UK Biobank. In addition, the summary statistics of gastric cancer, colorectal cancer, and esophageal cancer were obtained from the FinnGen biobank (n = 218,792). Inverse variance weighted, MR-Egger, weighted median, and weighted mode were applied to examine the causal relationship between coffee intake, apolipoprotein B and gastric, colorectal, and esophageal cancers. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. Steiger filtering and bidirectional mendelian randomization analysis were performed to evaluate the possible reverse causality. RESULTS: The result of the inverse variance weighted method indicated that apolipoprotein B levels were significantly associated with a higher risk of gastric cancer (OR = 1.392, 95% CI 1.027-1.889, P = 0.0333) and colorectal cancer (OR = 1.188, 95% CI 1.001-1.411, P = 0.0491). Furthermore, multivariable Mendelian randomization analysis also revealed a positive association between apolipoprotein B levels and colorectal cancer risk, but the effect of apolipoprotein B on gastric cancer risk disappeared after adjustment of coffee intake, body mass index or lipid-related traits. However, we did not discover any conclusive evidence linking coffee intake to gastric, colorectal, or esophageal cancers. CONCLUSIONS: This study suggested a causal association between genetically increased apolipoprotein B levels and higher risk of colorectal cancer. No causal relationship was observed between coffee intake and gastric, colorectal, or esophageal cancers.