Rates Of Esophageal Adenocarcinoma Research Articles

Nonendoscopic Screening for Barrett's Esophagus and Esophageal Adenocarcinoma in At-Risk Veterans.

Although rates of esophageal adenocarcinoma (EAC) in the United States continue to rise, many patients at risk of disease are not screened. EsoCheck (EC), a nonendoscopic esophageal balloon sampling device coupled with EsoGuard (EG), a DNA-based screening assay, is an US Food and Drug Administration-approved minimally invasive alternative to the traditional screening method of upper endoscopy. The objective of this study was to prospectively determine the diagnostic accuracy, tolerance, and acceptability of the EC/EG test in a screening population. We recruited veterans who met the American College of Gastroenterology Guideline criteria for endoscopic Barrett's esophagus (BE) and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center. All study participants completed unsedated EC-guided distal esophageal sampling followed by a sedated esophagogastroduodenoscopy (EGD). Diagnostic yield of the EG assay and EGD was recorded and used in calculation of sensitivity and specificity of EC/EG in prospective screening. The abbreviated Spielberger State-Trait Anxiety Inventory questionnaire was administered before and after completion of EC. Overall tolerance of EC sampling was evaluated on a 10-point Likert scale. Esophageal cancer screening was accepted by 130 of 782 eligible veterans (16.6%), and we analyzed results of those who completed both screening tests (N = 124). Prevalence of BE/EAC among studied veterans was 12.9% (16/124), based on EGD. Sensitivity and specificity of EC/EG for EGD-detected BE/EAC were 92.9% (95% confidence interval [CI] 66.1-99.8) and 72.2% (95% CI 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI 18.6-49.1) and 98.6% (95% CI 92.4-100), respectively. Baseline Spielberger State-Trait Anxiety Inventory-6 scores were reflective of notable levels of anxiety among veterans in the periprocedural setting. The mean postprocedure acceptability score for the EC test was 7.23 (SD 2.45). Our data suggest excellent sensitivity and negative predictive value of EC/EG in a screening population of veterans, making this modality a powerful screening tool for BE and EAC.

The pluripotency factor NANOG contributes to mesenchymal plasticity and is predictive for outcome in esophageal adenocarcinoma

BackgroundDespite the advent of neoadjuvant chemoradiotherapy (CRT), overall survival rates of esophageal adenocarcinoma (EAC) remain low. A readily induced mesenchymal transition of EAC cells contributes to resistance to CRT.MethodsIn this study, we aimed to chart the heterogeneity in cell state transition after CRT and to identify its underpinnings. A panel of 12 esophageal cultures were treated with CRT and ranked by their relative epithelial-mesenchymal plasticity. RNA-sequencing was performed on 100 pre-treatment biopsies. After RNA-sequencing, Ridge regression analysis was applied to correlate gene expression to ranked plasticity, and models were developed to predict mesenchymal transitions in patients. Plasticity score predictions of the three highest significant predictive models were projected on the pre-treatment biopsies and related to clinical outcome data. Motif enrichment analysis of the genes associated with all three models was performed.ResultsThis study reveals NANOG as the key associated transcription factor predicting mesenchymal plasticity in EAC. Expression of NANOG in pre-treatment biopsies is highly associated with poor response to neoadjuvant chemoradiation, the occurrence of recurrences, and median overall survival difference in EAC patients (>48 months). Perturbation of NANOG reduces plasticity and resensitizes cell lines, organoid cultures, and patient-derived in vivo grafts.ConclusionsIn conclusion, NANOG is a key transcription factor in mesenchymal plasticity in EAC and a promising predictive marker for outcome.

Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma in three Nordic countries: population based cohort study

ObjectiveTo assess the incidence rate of oesophageal adenocarcinoma among patients with non-erosive gastro-oesophageal reflux disease compared with the general population.DesignPopulation based cohort study.SettingAll patients in hospital and specialised outpatient healthcare...

Missed opportunities for screening for Barrett's esophagus in the primary care setting of a large health system.

The rate of esophageal adenocarcinoma (EAC) is rising. This is partly due to the lack of identification of Barrett's esophagus (BE), the main risk factor for EAC. Identifying neoplastic BE can allow for endoscopic therapy to prevent EAC. Our aim was to determine how many eligible patients for screening are being screened for BE in the primary care setting of a large health system. A digital search algorithm was constructed using the established gastroenterology guidelines and Kunzmann model for screening for BE. The algorithm was then applied to the electronic medical record of all patients seen in the primary care setting of the health system. A manual review of charts of the identified patients was performed to confirm the high-risk status and determine if screening occurred. Of 936,371 primary care charts analyzed by the algorithm, 3535 patients (0.4%) were determined to be high-risk for BE. Of the 3535 patients, only 1077 (30%) were screened for BE in clinical practice with endoscopy. The algorithm identified 2,458 (70%) additional high-risk patients. Of the patients screened in clinical practice, 105 (10%) were found to have BE (10% with neoplasia). Numerous screening opportunities for Barrett's esophagus are missed in the primary care setting of a large health system. Collaboration between gastroenterology and primary care services is needed to improve the screening rate.

Esophageal cancer: the rise of adenocarcinoma over squamous cell carcinoma in the Asian belt.

Esophageal cancer is a common cancer worldwide with a high associated mortality rate. Amongst the two most frequent subsets of disease, squamous cell carcinoma (SCC) and adenocarcinoma (AC), there has been an epidemiologic shift towards adenocarcinoma over the last few decades. However, squamous cell carcinoma still predominates worldwide. Within Western countries, obesity has been associated with an increase in esophageal AC. A striking report from the World Health Organization (WHO) stated that worldwide obesity has tripled since 1975. In 2016, the WHO reported that greater than 1.9 billion adults are overweight and over 650 million were obese. In this review our goal is to analyze the esophageal cancer trends of China, which is the largest contributor among the esophageal cancer "Asian belt." Our intent is to evaluate whether there is a correlation between the rise in esophageal adenocarcinoma and obesity in this esophageal cancer "hotspot." With further analysis, the high-risk populations that are identified can be targeted to implement preventative strategies. This focus will aid in decreasing the burden of esophageal cancer at the global health level by addressing preventative strategies, such as screening endoscopy and lifestyle modifications. For example, WHO developed a global action plan on physical activity in response to the rise in obesity worldwide. Prevention is key to decreasing the rate of esophageal adenocarcinoma as majority of cases are diagnosed in the late stages leading to high mortality rates.

Geographical variations in the incidence of oesophageal cancer in Sweden

Background: Geographical variations in the incidence and tumour stage distribution of oesophageal cancer in Sweden are not well characterised.Methods: Using data from the Swedish Cancer Registry over 45 years (1972–2016), we compared the age-standardised incidence rates of oesophageal cancer by histological type across all seven national areas (in five-year periods) and 21 counties (in 15-year periods) in Sweden, and assessed the geographical distribution of tumour stage at diagnosis since 2004.Results: The incidence rate of oesophageal adenocarcinoma increased in all national areas and counties and in both sexes over time, while the rate of oesophageal squamous cell carcinoma decreased from the 1980s onwards. In the latest period (2012– 2016), the incidence rate of adenocarcinoma in men ranged from 3.5/100,000 person-years in West Sweden to 6.2/100,000 person-years in North Middle Sweden. At the county level, the rate of adenocarcinoma in men was lowest in Jämtland (2.7/100,000 person-years) and highest in Gotland (6.2/100 000 person-years) in 2002–2016. The incidence rates of both adenocarcinoma and squamous cell carcinoma in women were below 2/100,000 person-years in all national areas and counties in the latest calendar periods, i.e., 2012–2016 and 2002–2016, respectively. The proportion of patents with tumour stage IV ranged from 22% in Stockholm area to 31% in Middle Norrland, while at the healthcare region level it was lowest in Stockholm healthcare region (23%) and highest in North (30%) and Uppsala-Örebro (29%) healthcare regions.Conclusion: There are considerable geographical variations in the incidence and tumour stage distribution of oesophageal cancer in Sweden.

360 Gender and Racial Disparities in Incidence Rates of Esophageal Adenocarcinoma

INTRODUCTION: Adenocarcinoma is more common in the US than squamous cell cancer of the esophagus. The purpose of this study is to investigate the impact of gender, and race/ethnicity on the incidence of esophageal adenocarcinoma cancer from 2000-2016 using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients diagnosed with esophageal adenocarcinoma from 2000-2016 were identified from the SEER Registry. We retrospectively evaluated gender-specific, and race/ethnicity variations in age-adjusted annual percent changes in incidence rates during 2000-2016 for people above the age above 20. A secondary analysis was also done in regards to stage distribution for disease from 2007-2016. RESULTS: Based on the SEER 21 areas data sets, the annual percent change of incidence for esophageal adenocarcinoma was 2.3% from 2000-2007 and -0.8% from 2007-2016 for both males and females. The annual percent change for females was 2.0% from 2000-2008, -5.7% from 2008-2011, and 3.5% from 2011-2016. For males, the annual percent change was 2.3 from 2000-2007 and -1.1 from 2007-2016. There was an increase in the annual percent change incidence for females from 2011-2016. Annual percentage of incidence rates by race/ethnicity can be seen in Table 1. Percent of incidence of cases of esophageal adenocarcinoma from 2007-2016 by stage distribution was evaluated by gender. Males had the highest percent of incidence cases for distant spread at 39.4, and regional spread at 32.5. Females had the highest percent of incidence cases for localized spread at 23.8. Percent of incidence of cases of esophageal adenocarcinoma from 2007-2016 by stage distribution for race/ethnicity can be seen in Table 2. For distant spread, the highest percent of cases was seen with American Indian/Alaska Natives at 46.5. CONCLUSION: Esophageal adenocarcinoma can be prevented. Our study shows that there has been an increase in the annual percent change of incidence for females in the last decade. In addition, males had the highest incidence cases for distant spread and regional spread. This study shows that American Indian/Alaskan Native and Non-Hispanic White and White (including Hispanics) had the highest percentage of cases for distant and regional spread, respectively. This may support interventions to inform certain gender and race/ethnic populations about the importance of screening for esophageal adenocarcinoma.

2861 Importance of Barrett's Surveillance in the Senior Population

INTRODUCTION: It is estimated that 5.6% of adults in the United States have Barrett’s esophagus (1). The annual cancer incidence in patients with Barrett’s esophagus is 0.1-0.4% per year, with it being higher among men, older patients, and patients with long segment Barrett’s mucosa. In patients with Barrett’s esophagus with low grade dysplasia (LGD), the annual incidence rates of esophageal adenocarcinoma (EAC) is 0.54% and of high-grade dysplasia (HGD) and/or EAC is 1.73%. Although the benefit of surveillance endoscopy remains unclear, current guidelines recommend surveillance endoscopy to detect dysplasia or EAC early enough to provide effective treatment. Currently there is no consensus on the age limit for Barrett’s surveillance, nor is there a recommended duration of surveillance. This may lead to endoscopic surveillance being performed without clear benefit. (2,3) Our aim was to assess the role of Barrett’s surveillance in detecting dysplasia and malignancy in all age groups; and evaluate the incidence and progression of Barrett's dysplasia to determine an age or duration limit to endoscopic surveillance. METHODS: A retrospective single center, longitudinal study was done by Sierra Nevada Gastroenterology Medical Associates, Inc., a community based gastroenterology group in Grass Valley, California. All outpatient upper endoscopies for Barrett’s screening and surveillance were included in the study. 300 electronic medical records were randomly selected and reviewed from Jan 2005 to Oct 2018. Data was collected on age, gender, race, ASA class, procedure findings, complications, pathology, and dysplasia status. RESULTS: See attached tables. CONCLUSION: In this study LGD was found in 10%, HGD in 0.3% and EAC in 0.3% of patients. In the subgroup of patients with LGD: 27% were detected in patients over 80 years old, 87% detected in patients with short Barrett's, 97% regressed to no dysplasia, and 3% progressed to HGD requiring ablation therapy. 16% of patients over 80 years old maintained or had dysplasia progress. Overall, 1 patient presented with EAC at index endoscopy. 91% of our study population had short Barrett's. There was no dysplasia before age 50 and dysplasia incidence increased with age. There were no endoscopy related complications. In patients over 80 years old, the incidence and progression of dysplasia remains significant. When evaluating endoscopy in this population, risks and benefits need to be considered, but age alone should not exclude a patient from surveillance.

Barrett's Esophagus and Esophageal Carcinoma: Can Biomarkers Guide Clinical Practice?

Despite gastrointestinal societal recommendations for endoscopic screening and surveillance of Barrett's esophagus, the rates of esophageal adenocarcinoma continue to rise. Furthermore, this current practice is costly to patients and the medical system without clear evidence of reduction in cancer mortality. The use of biomarkers to guide screening, surveillance, and treatment strategies might alleviate some of these issues. Incredible advances in biomarker identification, biomarker assays, and minimally-invasive modalities to acquire biomarkers have shown promising results. We will highlight recently published, key studies demonstrating where we are with using biomarkers for screening and surveillance in clinical practice, and what is on the horizon regarding novel non-invasive and minimally invasive methods to acquire biomarkers. Proof-of principle studies using in silico models demonstrate that biomarker-guided screening, surveillance, and therapeutic intervention strategies can be cost-effective and can reduce cancer deaths in patients with Barrett's esophagus.

Clustering of esophageal cancer among white men in the United States.

Studies of the geographic distribution of esophageal cancer in the United States have been limited. We aimed to examine geographic clustering of esophageal cancer in the United States and assess whether that clustering is explained by the distribution of known risk factors for esophageal cancer. We conducted cluster analyses derived from county mortality rates of esophageal cancer, using publicly available datasets. State incidence rates of esophageal adenocarcinoma were from the National Program of Cancer Registries, and county esophageal-cancer mortality rates were from the Vital Statistics Cooperative Program. County prevalences of cigarette use, alcohol use, obesity, education, and income were published estimates derived from the Behavioral Risk Factor Surveillance System and the American Community Survey. The primary outcomes were clusters of high and low esophageal-cancer mortality rates among non-Hispanic white men, both unadjusted and adjusted for risk factors. Age-standardized county rates of esophageal-cancer mortality among non-Hispanic white men ranged from 4.8 to 21.2 per 100,000/year. There was a cluster of high mortality in the Great Lakes states and New England and a cluster of low mortality in the Southeastern United States. State incidence rates of esophageal adenocarcinoma were consistent with this pattern. Adjusting for risk factors did little to change the pattern of observed rates or the clusters derived from them. Among non-Hispanic white men, there are clusters of high and low mortality rates with esophageal cancer within the United States, likely representing esophageal adenocarcinoma; but those clusters were not explained by several known risk factors. Focusing future efforts in the high-cluster areas might improve the efficiency of cancer screening and control.

Lorenz Curves and Gini Coefficient Analyses Indicate Inefficiencies in Esophageal Adenocarcinoma Screening

Rates of esophageal adenocarcinoma (EAC) have increased rapidly in the United States and much of western Europe, and 5-year survival continues to be poor.1 Prevention and early detection efforts for EAC have focused on identifying persons with EAC precursor state, Barrett's esophagus, but the survival benefit has been disappointingly low.

Esophageal cancer in patients under 50: a SEER analysis

Concomitant with rising rates of esophageal adenocarcinoma, there has been a significant increase of diagnoses among relatively younger individuals. However, most studies that focus on esophageal cancer (EC) in younger patients have had small sample sizes of patients treated at a single institute. The aim of this study was to analyze the clinical characteristics, outcomes and independent prognostic factors for EC in patients under 50-year-old using a large, multi-center dataset. The national Surveillance, Epidemiology, and End Results (SEER) database was analyzed for EC reported from 2004 to 2013. Patients were divided into two groups, those under 50-year-old and those 50 years or older, and comparisons were made regarding demographics, histology, stage distribution, treatment, overall survival (OS), and esophageal cancer-specific survival (ECSS). Multivariate Cox proportional hazard regression analyses were also used to identify independent prognostic factors. Among the 16,544 eligible patients, 1,385 (8.37%) were under 50 and 15,159 (91.63%) were over 50. Compared with the older group, patients under 50 were characterized by a higher frequency of males, lower esophagus involvement, adenocarcinoma histology, stage III/IV disease, and receiving esophagectomy or radiation therapy. The stage-wise OS and ECSS were significantly better in the younger group (P<0.001). The multivariate analysis indicated that African-American heritage, grade III or IV, later stage, and not undergoing surgical or radiation therapy were independent negative prognostic factors of ECSS for patients under 50. EC patients under 50-year-old had distinctive clinicopathological characteristics compared with patients over 50-year-old. Despite more often presenting with stage III and IV disease, survival rates were better in the younger cohort. Prognostic factors for ECSS in patients under 50 differed from those in all age patients.

Quality of Life After Endoscopic Mucosal Resection of Early Stage Esophageal Adenocarcinoma: 2017 Presidential Poster Award

Incidence rates of esophageal adenocarcinoma (EA) arising from esophageal dysplasia have continued to increase over the last few decades. Historically patients with EA have had a poor prognosis, often due late stage of disease at time of diagnosis. Recent changes in National Comprehensive Cancer Network guidelines for the management of early EA now recommend endoscopic rather than surgical interventions for T1aN0M0 disease. Our goal was to assess the quality of life (QOL) for patients that have undergone endoscopic therapy for their early EA. All patients included in the study were previously diagnosed with T1aN0M0 EA, and underwent management with endoscopic mucosal resection (ER). Using the validated disease specific Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) instrument, we surveyed our cohort to assess for their current quality of life after therapeutic intervention. The mean time from procedure to survey completion for our cohort was 27 months. The response rate for our survey was one hundred percent (Table 1). All patients reported being on proton pump inhibitors at time of survey. The total scores ranged from zero to fourteen, with a mean score of 3.6, consistent with excellent symptom control. The heartburn scores ranged from zero to nine with a mean score of 1.8. The regurgitation scores ranged from zero to four with a mean score of 1.2. All five patients reported being satisfied with their present condition. On average all patients had well controlled symptoms at time of survey administration, nearly two years after initial intervention. Three of the five patients had a total score of zero, indicating no reported symptoms, while two of the five patients had perceived symptoms. Of those reporting presence of both heartburn and regurgitation, their survey scores were still below the threshold to be considered significant. The two patients that reported symptoms had more distal EA (37 cm - 43 cm from the incisors) near or including the lower esophageal sphincter (LES). These two patients also required more interventions to achieve disease clearance (cryoablations and balloon dilatations). We believe involvement of the LES and need for repeat interventions is the driving factors of ongoing mild symptoms in our patients. Our study demonstrates that patients treated with ER for early EA have an excellent quality of life, with minimal symptoms, which may occur more frequently with disease involving the LES.Table: Table. Results of GERD-HRQL for our cohort

Incidence trends in oesophageal cancer by histological type: An updated analysis in Sweden

BackgroundWe aimed to update incidence trends of oesophageal cancer by histological type in Sweden. MethodsUsing data from the Swedish Cancer Registry, we examined incidence trends of oesophageal cancer by histological types in individuals aged ≥50 years in 1970–2014 using log-linear joinpoint regressions. ResultsThe age-standardised incidence rate of oesophageal adenocarcinoma in men increased on average by 3.0% per year in 1970–1994, followed by a more rapid increase of 13.7% per year in 1994–2000, and a slower increase of 2.6% per year in 2010–2014. The rate of oesophageal adenocarcinoma in women increased on average by 4.2% per year during the entire period. The rate of squamous cell carcinoma generally decreased over the past 2–3 decades in both sexes. ConclusionsThe incidence of oesophageal adenocarcinoma continues to rise in Sweden, although the increase seems to have slowed down in men since 2000. The incidence of oesophageal squamous cell carcinoma is decreasing.

Risk of oesophageal adenocarcinoma in individuals with Barrett's oesophagus

IntroductionRecent studies have indicated a lower incidence rate of oesophageal adenocarcinoma (OAC) in individuals with Barrett's oesophagus (BO) than most earlier studies. Our objective was to assess the risk of OAC in a Swedish unselected cohort of individuals with BO. MethodsThis population-based cohort study included all Swedish residents diagnosed with BO in 2006–2013, identified through the Swedish Patient Registry. The cohort members were followed from the date of first BO diagnosis until the first occurrence of OAC, high-grade dysplasia (HGD), death, emigration or end of study period. The main outcome was incidence rates with 95% confidence intervals (CIs) of OAC. ResultsAmong 7932 participants with BO and 18,415 person-years of follow-up, the overall incidence of OAC was 1.47 (95% CI 0.91–2.02) per 1000 person-years. When stratified into follow-up periods after BO diagnosis, the incidence rate of OAC was 15.53 (4.77–26.29) from 7 to 30 d, 4.10 (0.82–7.38) from 31 to 100 d, 1.87 (0.00–3.99) from 101 d to 6 months, 1.44 (0.18–2.70) from >6 months to 1 year, 0.94 (0.36–1.53) from >1 year to 3 years and 2.17 (1.14–3.21) from >3 years to the end of follow-up. The median follow-up time was 2.13 person-years. ConclusionThis population-based study indicates that OAC is primarily diagnosed during the first months following an initial diagnosis of BO. This could justify a changed surveillance strategy of BO with a repeated thorough endoscopy shortly after initial BO diagnosis to identify prevalent early OAC or HGD.

Esophageal Cancer Clinical Presentation: Trends in the Last 3 Decades in a Large Italian Series.

The aim of this study was to investigate trends in patients' characteristics and comorbidities in esophageal cancer (EC) patients. Identifying changing pattern is essential to understand and predict further changes and to plan surgical procedures and resource allocation. Trends in patients' characteristics and comorbidities were evaluated in 4440 EC patients at the Center for Esophageal Diseases in Padova, Italy, during 1980 to 2011. Joinpoint regression analysis was performed to evaluate trends and to estimate annual percentage changes (APCs). During the study period, there has been a statistically significant increment of the rate of esophageal adenocarcinoma (APC 3.70). The rates of elderly and of asymptomatic patients increased over time (APCs 0.98 and 6.24), whereas the rates of malnutrition, alcoholic drinking, and gastric ulcer decreased (APCs -1.50, -1.72, and -5.20). Reflux rate increased until 1997 and decreased thereafter (APCs 6.96 and -4.48), whereas the rate of Barrett esophagus increased until 1992 (APC 35.84) and then leveled. The rates of patients with previous neoplasms increased over time (APCs 3.22 and 4.86). There have been significant changes in systemic comorbidities, with an increase of hypertension and cardiac disease (APCs 7.56 and 1.86) and a decrease of advanced liver disease and pulmonary disease (APCs -2.67 and -1.74). The current EC patient has more often an esophageal adenocarcinoma and is more frequently elderly, asymptomatic, a survivor of previous neoplasms, and a patient with hypertension and cardiac disease than 30 years ago. On the contrary, malnutrition, alcoholic drinking, gastric ulcer, pulmonary disease, and advanced liver disease decreased.

Is Barrett Esophagus Surveillance Effective in Prevention of Incident Cancer

Recent reports highlight the high rate of esophageal adenocarcinoma (EAC) that is found in patients with Barrett esophagus (BE) within a year after

Time trends in the incidence of oesophageal cancer in Asia: Variations across populations and histological types

ObjectiveWe aimed to assess temporal trends in incidence rates of oesophageal cancer in Asian countries. Materials and methodsUsing data from the Cancer Incidence in Five Continents series, we examined the temporal trends in incidence rates of oesophageal cancer by population and histological type in seven Asian countries in 1988–2007. Age-period-cohort analyses estimated the overall annual percentage changes (net drifts) and their 95% confidence intervals (CIs) in incidence rates. ResultsThe age-standardised incidence rate of oesophageal cancer declined in most Asian populations, but remained relatively unchanged in Japan and Israel. The rate of oesophageal squamous cell carcinoma decreased in Hong Kong, Singapore and Israel, but was stable in Japan. The net drifts were statistically significant in men in Hong Kong (−3.4%, 95% CI: −6.1%, −0.7%) and in women in Singapore (−10.1%, 95% CI: −14.4%, −5.5%). The age-standardised incidence rates of oesophageal adenocarcinoma were below 2 and 0.5 per 100 000 in men and women, respectively, across all periods in the all registers containing valid data on histological type. The age-standardised incidence rate of oesophageal adenocarcinoma slightly increased in Japan, Singapore, and Israel, although the net drift was statistically significant only in Israeli men (4.9%, 95% CI: 0.8%, 9.1%). ConclusionThe overall incidence rates of oesophageal cancer declined in most Asian countries, which is due to a decrease in oesophageal squamous cell carcinoma incidence. However, attention needs to be paid to a probable beginning of an increasing incidence of oesophageal adenocarcinoma in Asia.

Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas.

The current high mortality rate of esophageal adenocarcinoma (EAC) reflects frequent presentation at an advanced stage. Recent efforts utilizing fluorescent peptides have identified overexpressed cell surface targets for endoscopic detection of early stage Barrett's-derived EAC. Unfortunately, 30% of EAC patients present with gastroesophageal junction adenocarcinomas (GEJAC) and lack premalignant Barrett's metaplasia, limiting this early detection strategy. We compared mRNA profiles from 52 EACs (tubular EAC; tEAC) collected above the gastroesophageal junction with 70 GEJACs, 8 normal esophageal and 5 normal gastric mucosa samples. We also analyzed our previously published whole-exome sequencing data in a large cohort of these tumors. Principal component analysis, hierarchical clustering and survival-based analyses demonstrated that GEJAC and tEAC were highly similar, with only modest differences in expression and mutation profiles. The combined expression cohort allowed identification of 49 genes coding cell surface targets overexpressed in both GEJAC and tEAC. We confirmed that three of these candidates (CDH11, ICAM1 and CLDN3) were overexpressed in tumors when compared to normal esophagus, normal gastric and non-dysplastic Barrett's, and localized to the surface of tumor cells. Molecular profiling of tEAC and GEJAC tumors indicated extensive similarity and related molecular processes. Identified genes that encode cell surface proteins overexpressed in both Barrett's-derived EAC and those that arise without Barrett's metaplasia will allow simultaneous detection strategies.

Emerging therapeutic targets in esophageal adenocarcinoma.

The incidence of gastro-esophageal disease and associated rate of esophageal adenocarcinoma (EAC) is rising at an exponential rate in the United States. However, research targeting EAC is lagging behind, and much research is needed in the field to identify ways to diagnose EAC early as well as to improve the rate of pathologic complete response (pCR) to systemic therapies. Esophagectomy with subsequent reconstruction is known to be a morbid procedure that significantly impacts a patient's quality of life. If indeed the pCR rate of patients can be improved and those patients destined to be pCR can be identified ahead of time, they may be able to avoid this life-altering procedure. While cancer-specific biological pathways have been thoroughly investigated in other solid malignancies, much remains unexplored in EAC. In this review, we will highlight some of the latest research in the field in regards with EAC, along with new therapeutic targets that are currently being explored. After reviewing conventional treatment and current changes in medical therapy for EAC, we will focus on unchartered grounds such as cancer stem cells, genetics and epigenetics, immunotherapy, and chemoradio-resistant pathways as we simultaneously propose some investigational possibilities that could be applicable to EAC.