Incidence Of Esophageal Adenocarcinoma Research Articles

We previously identified associations of esophageal adenocarcinoma risk with four inflammation-related candidate biomarkers: TNF receptor 2 (TNFR2), IL17A, VEGFR3, and resistin. We aimed to replicate these candidates and discover novel associations with additional proteins. We conducted a nested case-control study of men with prediagnostic biospecimens stored at the US Department of Defense Serum Repository, including 203 incident esophageal adenocarcinoma cases. Controls were matched to cases in a ∼2:1 ratio by date of birth, race, service branch, and blood draw date. Multiplex immunoassays (Olink/Proseek panels) measured 254 proteins detected in ≥10% of all samples. Multivariable-adjusted conditional logistic regression models calculated associations between biomarker quantiles and esophageal adenocarcinoma. P values (<0.05) were used to indicate the statistical significance of candidates, and FDR was applied to the additional proteins. ORs from the current analysis and those from previous studies were combined for the candidate markers using fixed-effects meta-analysis. Among the four candidates, the highest category of TNFR2 was associated with significantly increased esophageal adenocarcinoma risk (ORQ4 vs. Q1 = 1.87; 95% confidence interval: 1.02-3.42). In the meta-analysis, associations with esophageal adenocarcinoma were positive for TNFR2 (meta-analyzed ORhighest-vs.-lowest = 2.04; 1.12-2.95) and inverse for IL17A (meta-analyzed ORhighest-vs.-lowest = 0.53; 0.26-0.80). Of the additional 250 proteins, 45 were associated with esophageal adenocarcinoma risk and 6 (monocyte chemotactic protein 3, IL6, TNFR1, hepatocyte growth factor, TFF3, and FURIN) remained significant after FDR correction. We confirmed associations of TNFR2 and IL17A with esophageal adenocarcinoma risk. Additionally, our study expands the range of proteins associated with esophageal adenocarcinoma development. This is the largest assessment to discover novel associations of inflammation-related proteins with esophageal adenocarcinoma to date.

Esophageal cancer (EC) consists of two main histological subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), each with distinct epidemiological patterns. Historically, ESCC has been the dominant subtype worldwide, especially in Asian countries. However, in recent decades, the incidence of EAC has been rising rapidly, particularly in European and American countries, reflecting significant shifts in global EC epidemiology. This study presents a comprehensive analysis of 25 years of high-quality continuous data on ESCC and EAC incidence trends across 25 countries. It highlights declining ESCC rates in most regions, rising EAC rates in Western nations, pronounced sex differences, and narrowing ESCC-to-EAC ratios. These diverse trends reveal the need to investigate region-specific risk factors and their contributions to the shifting burden of EC globally. The distinct trends of ESCC and EAC call for tailored public health strategies based on regional and histological patterns. Countries experiencing a rising burden of EAC or ESCC can implement targeted risk factor prevention and control measures to address the increasing trends. In clinical practice, a stronger focus on EAC in high-income countries and ESCC in regions, where it remains dominant, can improve early detection and treatment outcomes. Understanding these evolving patterns will aid in designing evidence-based interventions and optimizing resource allocation to reduce the global esophageal cancer burden effectively.

The incidence of oesophageal adenocarcinoma (OAC) is increasing at a rapid rate in Western countries. Early oesophageal cancer is often asymptomatic and metastatic disease is common at presentation leading to poor prognosis and survival rates. Cell migration is tightly controlled in the healthy cell but can become dysregulated in diseases such as OAC where increased cell motility and migration can contribute to metastasis. We investigated the role of an actin-based molecular motor, non-muscle myosin heavy chain IIA (NMHCIIA) in the migratory capacity of oesophageal adenocarcinoma cells. Immunofluorescence microscopy and ratiometric imaging demonstrated that NMHCIIA co-localises with F-actin at the leading edge and retracting rear of migrating FLO-1 OAC cells. siRNA-mediated depletion of NMHCIIA from FLO-1 cells altered cell morphology, gave rise to an increased number of stress fibre like structures and reduced FLO-1 cell migration. These findings suggest that NMHCIIA influences FLO-1 cell migration by regulating F-actin dynamics and the actin cytoskeleton, providing insight into the mechanisms of migration employed by OAC cells and identifying NMHCIIA as a potential therapeutic target for this disease.

BackgroundThe incidence of early-onset esophageal adenocarcinoma (EAC) in adults aged <50 years is rising, yet remains under-investigated. This study compared demographic, clinical and socioeconomic predictors of early- vs. late-onset EAC using national hospitalization data.MethodsWe analyzed adult patients diagnosed with EAC from the National Inpatient Sample (2016-2020). Cases were stratified into early-onset (age <50 years) and late-onset (≥50 years), and further categorized by tumor location (upper, middle, lower esophagus). ICD-10-CM codes were used to identify diagnoses. Demographics, comorbidities and socioeconomic variables were compared using Rao-Scott chi-square tests.ResultsAmong 105,228 EAC admissions, early-onset cases comprised 5.89%. Lower esophagus involvement was most common (74.6%). Compared to late-onset patients, early-onset cases had a lower proportion of Caucasians (71.5% vs. 79.8%, P<0.001) and higher proportions of Black (13.9% vs. 9.6%) and Hispanic individuals (7.0% vs. 5.4%). Smoking (25.1% vs. 17.9%), obesity (11.4% vs. 8.4%), and drug use (28.9% vs. 19.7%) were more prevalent in early-onset patients (P<0.001). In contrast, late-onset patients had higher rates of hypertension (47.1% vs. 26.7%), diabetes, chronic obstructive pulmonary disease and gastroesophageal reflex disease (P<0.001). Early-onset patients were less likely to be insured with Medicare (6.8% vs. 57.9%), and more likely with Medicaid (35.0% vs. 10.6%) or to be self-payers (3.9% vs. 1.8%).ConclusionsEarly-onset EAC presents with distinct racial, socioeconomic and clinical profiles compared to late-onset disease. These findings underscore the need for tailored screening strategies and further research to address disparities and risk factors in younger populations.

Introduction: Diet has been recognized as the most pivotal modifiable lifestyle factor in the development of Gastroesophageal Reflux Disease (GERD), Barrett's Esophagus (BE) and Esophageal Adenocarcinoma (EA). However, the associations between dietary ingredients, patterns, and diet-gene interactions with the risk of GERD, BE and EA remain unclear. Methods: The prospective cohort study included 502 412 participants from the UK Biobank. Dietary ingredients, patterns, and the associations with the incidence of GERD, BE and EA were investigated using Cox proportional hazard models. Additionally, we calculated a healthy dietary score based on eight primary dietary factors. Furthermore, polygenic risk scores were developed to explore potential diet-gene interactions. Results: Over an average follow-up of 12.5 years, we identified 29 564 incident cases of GERD, 4081 cases of BE and 539 cases of EA. Frequent tea intake was consistently associated with an increased risk of GERD (HR = 1.04, CI: 1.03, 1.05), BE (HR = 1.08, CI: 1.06, 1.11) and EA (HR = 1.07, CI: 1.01, 1.14), while higher dietary fiber consumption was inversely associated with the risks (HR = 0.92 for GERD, CI: 0.90, 0.94; HR = 0.78 for BE, CI: 0.73, 0.84; HR = 0.81 for EA, CI: 0.68, 0.97). In the dietary pattern analysis, the prudent pattern was linked to a lower risk of GERD, BE and EA (HR = 0.95 for GERD, CI: 0.91, 0.98; HR = 0.84 for BE, CI: 0.76, 0.92; HR = 0.70 for EA, CI: 0.53, 0.93). Significant additive and multiplicative interactions were observed between diet and genetic risk for BE (RERI = 0.32, CI: 0.11, 0.52; Pmultiplicative interaction = 0.039) and EA (RERI = 0.84, CI: 0.34, 1.33; Pmultiplicative interaction = 0.038). Discussion: Our study highlights the role of dietary exposure in the etiology of GERD, BE and EA. Healthy dietary interventions may be beneficial, especially for populations with high genetic risk.

Disparities in Gastrointestinal Cancer Incidence in Asian American, Native Hawaiian, and Other Pacific Islander Groups.

The incidence of oesophageal adenocarcinoma (OAC) has risen six-fold in western countries over the last forty years but survival rates have only marginally improved. Hyperactivation of the PI3K-AKT-mTOR pathway is a common occurrence in OAC, driving cell survival, proliferation and resistance to chemotherapeutic agents. Inhibition of AKT has been explored as a treatment strategy with limited success and current inhibitors have failed to progress through clinical trials. Our study, describes a novel allosteric AKT inhibitor, ALM301, and demonstrates an enhancement of the efficacy of conventional chemotherapy when combined with ALM301 in OAC. Reduced sensitivity to ALM301 is associated with high expression of the Inhibitor of Apoptosis (IAP) family of proteins, particularly XIAP. Combined AKT and IAP inhibition synergistically enhanced OAC cell death and successfully re-sensitized ALM301 and chemotherapy resistant cell lines. A high degree of synergism was also observed in patient-derived OAC organoids indicating the potential clinical relevance of the combination. This study demonstrates the role for dual AKT/IAP inhibition in OAC and provides a strong rationale for the further investigation of this highly efficacious combination strategy.

Esophageal cancer (EC)is identified as a predominant health threat worldwide, with its highest incidence and mortality rates reported in China. The complex molecular mechanisms underlying EC, coupled with the differential incidence of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) across various regions, highlight the necessity for in-depth research targeting molecular pathogenesis and innovative treatment strategies. Despite recent progress in targeted therapy and immunotherapy, challenges such as drug resistance and the lack of effective biomarkers for patient selection persist, impeding the optimization of therapeutic outcomes. Our review delves into the molecular pathology of EC, emphasizing genetic and epigenetic alterations, aberrant signaling pathways, tumor microenvironment factors, and the mechanisms of metastasis and immune evasion. We further scrutinize the current landscape of targeted therapies, including the roles of EGFR, HER2, and VEGFR, alongside the transformative impact of ICIs. The discussion extends to evaluating combination therapies, spotlighting the synergy between targeted and immune-mediated treatments, and introduces the burgeoning domain of antibody-drug conjugates, bispecific antibodies, and multitarget-directed ligands. This review lies in its holistic synthesis of EC's molecular underpinnings and therapeutic interventions, fused with an outlook on future directions including overcoming resistance mechanisms, biomarker discovery, and the potential of novel drug formulations.

Trends in incidence, treatment modalities and prognosis of esophageal adenocarcinoma in the US population

Abstract Background Barrett’s esophagus is the precursor to esophageal adenocarcinoma (EAC). EAC detected from endoscopic surveillance programs accounts for &amp;lt;10% of all EAC, suggesting a large number of patients with Barrett’s esophagus are likely unaccounted for. Several studies have estimated the observed prevalence of Barrett’s esophagus to be approximately 1%, but this may be an underestimate. The aim of this study is to use population incidence of EAC and rate of progression from Barrett’s esophagus from large cohort studies to estimate a realistic prevalence of Barrett’s esophagus. Methods A simple tree cohort model was created for progression to EAC from birth to death (100 years) for American and Australian population. Lifetime risk of esophageal cancer and adenocarcinoma were endpoints. This was then used to back-calculate age-specific and overall prevalence of Barrett’s esophagus using an optimisation algorithm. Results Lifetime risk of esophageal cancer and adenocarcinoma in US Whites is 0.56% and 0.36% respectively, while in Australian population is slightly higher at 0.81% and 0.61% (range 0.57% - 0.65%). Estimated overall prevalence of Barrett’s esophagus is ~3% (±0.3%) and ~5.4% (±0.6%) in US White and Australian populations, while in males is 5.3% (±0.6%) and 7.4% (±0.3%), respectively. Female cohorts were seen to have lower chance of developing esophageal cancer, adenocarcinoma, and Barrett’s esophagus. Conclusion Cohort studies of Barrett’s esophagus are likely to underestimate its prevalence of this silent disease. Computational models based on progression from Barrett’s esophagus to EAC accounting for undetected disease reveal higher estimates, which can help in future screening options.

The incidence of esophageal adenocarcinoma has recently increased in Asia, including Japan. A system to identify individuals at high risk for Barrett's esophagus (BE), a pre-cancerous condition of esophageal adenocarcinoma, among the general population is needed to perform endoscopic surveillance appropriately. We therefore developed risk prediction scores for BE at health checkups in Japan. 4128 consecutive health checkup examinees were retrospectively enrolled from October 2021 to March 2022. A prediction score for BE was developed based on the linear transformation of β-regression coefficients in a multivariable regression model incorporating BE predictors. Internal validation was performed by evaluating discrimination and calibration of the prediction model. Three prediction scores corresponding to BE based on its length were developed: all lengths, ≥ 1cm, ≥ 2cm. All scores were internally validated, and the model calibration was excellent. The performance of the prediction models was better for longer BE, with a c-statistic of 0.70 for BE ≥ 2cm, than for shorter values. The prediction score for BE ≥ 2cm yielded sensitivity and specificity of 52.9% and 78.6% in high-risk subjects and 91.2% and 29.3% in intermediate- or high-risk subjects, respectively. This prediction score can potentially increase the endoscopic detection of BE by identifying potentially high-risk individuals from the general population. This is the first report on developing a prediction score for BE that may suit the Japanese population.

The cancer risk for each length of Barrett's esophagus (BE) in Japanese is unknown. This nationwide, multi-institutional study aims to clarify the cancer risk by length of BE in the general Japanese population. Consecutive subjects who underwent upper endoscopic screening at 17 centers between 2013 and 2017 and had at least one follow-up endoscopy by December 2022 were included. The presence/absence of BE and, if present, its length were retrospectively assessed using the retrieved endoscopic images recorded at baseline. Information on the subsequent occurrence of esophageal adenocarcinoma and other upper gastrointestinal cancers was also collected. Cancer incidence was calculated and expressed as %/year. A total of 33,478 subjects were enrolled, and 17,884 (53.4%), 10,641 (31.8%), 4889 (14.6%), and 64 (0.2%) were diagnosed as absent BE, BE < 1cm, 1-3cm, and ≥ 3cm, respectively. During a median follow-up of 80months, 11 cases of esophageal adenocarcinoma developed. The annual incidence of esophageal adenocarcinoma is 0%/year for absent BE, 0.0032 (0.00066-0.013)%/year for BE < 1cm, 0.026 (0.011-0.054)%/year for 1-3cm, and 0.58 (0.042-2.11)%/year for ≥ 3cm, respectively. Meanwhile, the incidence of esophageal squamous cell carcinoma and gastric cancer were 0.039 (0.031-0.049)%/year and 0.16 (0.14-0.18)%/year, respectively. By enrolling a large number of subjects with long-term follow-up, this study demonstrated that the risk of cancer increased steadily with increasing length of BE in the Japanese population. Therefore, it is important to consider the length of BE when determining the management strategy for BE.

Esophageal adenocarcinoma incidence is increasing in Western nations. There has been a shift toward minimally invasive approaches for transhiatal esophagectomy (THE). This study compares the outcomes of robotic THE for esophageal adenocarcinoma resection at our institution with the predicted metrics from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). With Institutional Review Board (IRB) approval, we prospectively followed 83 patients who underwent robotic THE from 2012 to 2023. Predicted outcomes were determined using the ACS NSQIP Surgical Risk Calculator. Our outcomes were compared with these predicted outcomes and with general outcomes for transhiatal esophagectomy reported in ACS NSQIP, which includes a mix of surgical approaches. The median age of patients was 70years, with a body mass index (BMI) of 26.4kg/m2 and a male prevalence of 82%. The median length of stay was 7days. The rates of any complications and in-hospital mortality were 16% and 5%, respectively. Seven patients (8%) were readmitted within a 30-day postoperative window. The median survival is anticipated to surpass 95months. Our outcomes were generally aligned with or surpassed the predicted ACS NSQIP metrics. The extended median survival of over 95months highlights the potential effectiveness of robotic THE in the resection of esophageal adenocarcinoma. Further exploration into its long-term survival benefits and outcomes is warranted, along with studies that provide a more direct comparison between robotic and other surgical approaches.

Background:Barrett’s esophagus (BE) is a diagnosis of esophageal intestinal metaplasia, which can progress to esophageal adenocarcinoma (EAC), and guidelines recommend endoscopic surveillance for early detection and treatment of EAC. However, current practices have limited effectiveness in risk-stratifying patients with BE.Aim:This study aimed to evaluate use of the TSP-9 test in risk-stratifying clinically relevant subsets of patients with BE in clinical practice.Methods:TSP-9 results for tests ordered by 891 physicians for 8080 patients with BE with clinicopathologic data were evaluated. Orders were from nonacademic (94.3%) and academic (5.7%) settings for nondysplastic BE (NDBE; n=7586; 93.9%), indefinite for dysplasia (IND, n=312, 3.9%), and low-grade dysplasia (LGD, n=182, 2.3%).Results:The TSP-9 test scored 83.2% of patients with low risk, 10.6% intermediate risk, and 6.2% high risk, respectively, for progression to HGD/EAC within 5 years. TSP-9 provided significant risk-stratification independently of clinicopathologic features, within NDBE, IND, and LGD subsets, male and female, and short- and long-segment subsets of patients. TSP-9 identified 15.3% of patients with NDBE as intermediate/high-risk for progression, which was 6.4 times more than patients with a pathology diagnosis of LGD. Patients with NDBE who scored intermediate or high risk had a predicted 5-year progression risk of 8.1% and 15.3%, respectively, which are similar to and higher than published progression rates in patients with BE with confirmed LGD.Conclusions:The TSP-9 test identified a high-risk subset of patients with NDBE who were predicted to progress at a higher rate than confirmed LGD, enabling early detection of patients requiring management escalation to reduce the incidence of EAC. TSP-9 scored the majority of patients with NDBE as low risk, providing support to adhere to 3- to 5-year surveillance per guidelines.

The incidence of Barrett's esophageal adenocarcinoma (BEA) is increasing, and endoscopic submucosal dissection (ESD) has been frequently performed for its treatment. However, the differences between the characteristics and ESD outcomes between short- and long-segment BEA (SSBEA and LSBEA, respectively) are unclear. We compared the clinicopathological characteristics and short- and long-term outcomes of ESD between both groups. We retrospectively reviewed 155 superficial BEAs (106 SSBEAs and 49 LSBEAs) treated with ESD in 139 patients and examined their clinicopathological features and ESD outcomes. SSBEA and LSBEA were classified based on whether the maximum length of the background mucosa of BEA was < 3cm or ≥ 3cm, respectively. Compared with SSBEA, LSBEA showed significantly higher proportions of cases with the macroscopically flat type (36.7% vs. 5.7%, p < 0.001), left wall location (38.8% vs. 11.3%, p < 0.001), over half of the tumor circumference (20.4% vs. 1.9%, p < 0.001), and synchronous lesions (17.6% vs. 0%, p < 0.001). Compared with SSBEA, regarding ESD outcomes, LSBEA showed significantly longer resection duration (91.0min vs. 60.5min, p < 0.001); a lower proportion of submucosal invasion (14.3% vs. 29.2%, p = 0.047), horizontal margin negativity (79.6% vs. 94.3%, p = 0.0089), and R0 resection (69.4% vs. 86.8%, p = 0.024); and a higher proportion of post-procedural stenosis cases (10.9% vs. 1.9%, p = 0.027). The 5-year cumulative incidence of metachronous cancer in patients without additional treatment was significantly higher for LSBEA than for SSBEA (25.0% vs. 0%, p < 0.001). The clinicopathological features of LSBEA and SSBEA and their treatment outcomes differed in many aspects. As LSBEAs are difficult to diagnose and treat and show a high risk of metachronous cancer development, careful ESD and follow-up or eradication of the remaining BE may be required.

Introduction: Gastro-esophageal junction (GEJ) is subjected to controversy due to limited knowledge of its anatomy and histology. We conducted a study to determine the origins of the glandular mucosa at GEJ. Methods: Three groups were used, groups A and B, with grossly normal GEJs and Group C with endoscopic evidence of reflux damage. Group A comprised 23 esophago-gastrectomies, group B, 112 dyspeptic patients with normal GEJ and group C, 46 dyspeptic patients with reflux damaged GEJs. Origins of cardiac mucosa (CM), intestinal metaplasia (IM), and oxyntocardiac mucosa (OCM) were determined by studying their associations with esophageal markers (EM): esophageal glands and ducts, multilayered epithelium and squamous islands highlighted with immunohistochemistry. The histological gap between esophageal squamous and gastric oxyntic mucosa containing CM/IM/OCM was considered as squamo-oxyntic (SO) gap. Results: In Group A and B, a microscopic SO gap was detected in 58.1% and the prevalence of CM was 43% and IM 4.4% and CM 89.7%; 100% IM were associated with EM. Prevalence of CM and IM, in group C was 56.5% and 15.2% respectively and EM were present in 85.7% IM and 88.5% CM. When only OCM is present, 41.2% were proven to be metaplastic. Conclusions: Even when GEJ is grossly normal, microscopic columnar lined esophagus was common at the GEJ and with increased sampling and using several EM almost all CM and IM at the GEJ could be proven to be metaplastic in origin.

This study aims to systematically review and meta-analyze the evidence on the risk of esophageal adenocarcinoma (EAC) following metabolic and bariatric surgery (MBS). 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). 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 5years was statistically significant (OR: 0.46, 95% CI: 0.25-0.82, P = 0.009). Our meta-analysis results suggest a reduced risk of esophageal cancer in patients with obesity after bariatric surgery. CRD 42024505177.

Esophageal cancer (EC) poses a significant challenge to the healthcare system due to its profound impact on cancer-related morbidity and mortality worldwide. This malignancy ranks among the most arduous conditions confronting the surgeon. EC arises from a complex interplay of genetic predispositions and environmental factors. While the incidence of esophageal adenocarcinoma (EAC) is on the rise in the West, esophageal squamous cell carcinoma (ESCC) remains prevalent in the East. Chronic inflammation plays a pivotal role in the initiation and progression of EC. Accordingly, serum inflammatory markers, growth factors, and cytokines have been shown to be clinically useful. Thus, evaluating serum cytokine levels for EC prediction is a safe and feasible screening method. Given the aggressive nature and poor prognosis of the disease, innovative approaches to diagnosis, prognosis, and management of EC are indispensable. This review discusses the major risk factors and the current landscape of EC, with a specific focus on the potential contributions of new inflammatory markers to enhance disease management and improve patient outcomes.

Unlike most cancer types, the incidence of esophageal adenocarcinoma (EAC) has rapidly escalated in the western world over recent decades. Using whole genome bisulfite sequencing (WGBS), we identify the transcription factor (TF) FOXM1 as an important epigenetic regulator of EAC. FOXM1 plays a critical role in cellular proliferation and tumor growth in EAC patient-derived organoids and cell line models. We identify ERBB2 as an upstream regulator of the expression and transcriptional activity of FOXM1. Unexpectedly, gene set enrichment analysis (GSEA) unbiased screen reveals a prominent anti-correlation between FOXM1 and immune response pathways. Indeed, syngeneic mouse models show that FOXM1 inhibits the infiltration of CD8+ T cells into the tumor microenvironment. Consistently, FOXM1 suppresses CD8+ T cell chemotaxis in vitro and antigen-dependent CD8+ T cell killing. This study characterizes FOXM1 as a significant EAC-promoting TF and elucidates its novel function in regulating anti-tumor immune response.

It is important to note that although the current treatment for advanced esophageal cancer (EC) has made great technological advances, patients' 5-year survival rates do not appear to be encouraging. Therefore, understanding the clinicopathological features and metastasis patterns of the patients with stage IV EC, combined with the prognosis of these patients, can aid in choosing the optimal treatment plan. It is well known that esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two most common pathological types. The aim of this study is to examine and compare the clinicopathological features and metastatic modes of stage IV ESCC and EAC, as well as their prognosis and survival. Based on the Surveillance, Epidemiology, and End Results (SEER) database, we assessed the characteristics of ESCCs and EACs associated with prognosis using the Kaplan-Meier survival analysis, and the Cox regression model. Furthermore, the clinical data of 217 patients with stage IV ESCC and EAC in the Department of Gastroenterology of the Second Affiliated Hospital of Nantong University between 2014 and 2016 were reviewed. A total of 3,707 cases treated between 2010 and 2016 were included. The incidence of EAC in the United States is much higher than that of ESCC. Common metastasis patterns were lungs only, liver only, bones only, and lung & liver. The multivariate Cox analysis showed that treatment mode and metastasis patterns were independent risk factors affecting the overall survival (OS) time of patients (stage IV ESCC & EAC). EAC patients with only lung metastases may have a longer survival if chose treatment options that included surgery. In the external cohort, a total of 217 cases were included. The prevalence of ESCC is much higher than that of EAC, and the common metastasis patterns are liver only, lung only, and liver & lung. The multivariate Cox analysis showed that treatment mode was independent risk factor affecting the OS time of patients (stage IV ESCC & EAC). EAC patients treated with surgery combined with chemoradiotherapy may have a better prognosis. In general, the prognosis of patients with stage IV ESCC and EAC are poor. However, surgery was found to significantly improve the OS time of patients with stage IV EAC in this study.