Risk Of Esophageal Adenocarcinoma Research Articles

1719 Esophageal Adenocarcinoma Arising From <1 cm of Intestinal Metaplasia at the Gastroesophageal Junction: Is <1 cm Actually Low Risk?

INTRODUCTION: Barrett’s esophagus (BE) is defined by length, which has been shown to correlate with the risk for esophageal adenocarcinoma (EAC). Although long-segment (>3 cm) and short-segment (between 1 and 3 cm) BE are well-established definitions, current ACG practice guidelines recommend against defining columnar goblet-cell metaplasia in the distal esophagus <1 cm as BE. This specific variation of metaplasia disease has been officially defined as “specialized IM of the esophagogastric junction” (SIM-EGJ) over alternatives such as ultra-short segment BE. Given the relatively low incidence of EAC in this group and the high degree of inter-observer variability in defining metaplasia of this length, current guidelines recommend against biopsy in this setting. Individual cases in practice however have demonstrated reasons to question this paradigm. CASE DESCRIPTION/METHODS: A 42 year old white man with obesity and 10 years of reflux symptoms was diagnosed with a GE junction nodule on index endoscopy. Cold forceps biopsy of the nodule revealed high grade dysplasia, prompting referral to the BE Treatment Center at Thomas Jefferson University Hospital (TJUH). His repeat EGD revealed salmon-colored mucosa suggestive of intestinal metaplasia in an area less than 1 cm in length (Z-line at 39 cm). An 8 mm nodule was identified in the area of abnormal mucosa and removed by endoscopic mucosal resection. Pathology of the nodule revealed a T1a moderately differentiated intramucosal adenocarcinoma arising in BE. All margins were negative for invasive carcinoma, dysplasia, and intestinal metaplasia. The patient patients underwent endoscopic eradication therapy (EET) with radiofrequency ablation at the GE junction and in subsequent endoscopy achieved complete eradication of intestinal metaplasia (CE-IM) and dysplasia (CE-D). DISCUSSION: Although current guidelines advise against biopsying <1 cm of variability in Z line given its status as a relatively low risk lesion, data used to generate many of these risk predictions for EAC exclude visible lesions in their studies. Therefore in practice there may be under-evaluation of SIM-EGJ, potentially missing advanced dysplastic or cancerous disease. This case illustrates that the consideration BE risk factors and all endoscopic findings, such as nodules, need to be taken together when assessing abnormal mucosa at the GE junction, even with <1 cm variability of the Z line.

915 A Comparison of Endoscopic Submucosal Resection (EMR) vs. Endoscopic Submucosal Dissection (ESD) on Histologic Margins and Pathologic Evaluation for Endoscopically Managed Early Esophageal Adenocarcinoma

INTRODUCTION: Accurate histologic determination is important to determine the completeness of endoscopic resection for esophageal adenocarcinoma (EAC) and gauge risk of recurrence. EMR and ESD are both endoscopic resection techniques used for the treatment of early EAC. ESD advocates believe ESD specimens allow for more precise histopathologic analysis than EMR, but this has never been proven. We aim to determine the effect of EMR vs ESD techniques on histologic analysis in endoscopically treated early EAC. METHODS: This is a retrospective, single center study of EMR and ESD resection specimens with pathologic confirmation of HGD or T1 EAC between 1/15-12/18. Lesions with suspected invasion into the muscularis mucosa or beyond (T2 carcinoma or higher) were excluded. Endoscopic and histologic characteristics were collected. Pathology slides were re-analyzed by a blinded GI pathologist for typical pathologic features. RESULTS: 52 patients with early EAC were analyzed (23 ESD;29 EMR) [Table 1]. ESD-resected tumors were larger compared to those resected by EMR (20 mm [20.0, 28.0] vs 11 mm [9.0, 13.0], P < 0.001) [Table 2]. As per Table 3, EMR specimens were more likely to have positive lateral margins compared to ESD (38% vs 13%, P < 0.005) and have lower confidence in determining lateral margins. Reasons for lower confidence in the EMR group included cautery artifact (37.9%) and difficulty in orientation (20.7%). When accounting for differences in specimen thickness, EMR had a higher percentage of cauterized tissue per total tissue thickness (11.8% vs 3.9%, P < 0.001). EMR specimens had cautery effect abutting the lesion while ESD did not (0 μm vs 2259 μm distance of lesion from nearest cautery, P = 0.001). Cautery effect was more likely to interfere with margin evaluation in EMR (38% vs 13%, P = 0.04). ESD specimens were well-oriented compared to EMR (P = 0.011). EMR and ESD had no difference in positive vertical margins (7% vs 9%, P = 0.33), lymphovascular invasion (P = 0.11), or submucosal invasion (P = 0.62). CONCLUSION: Cautery effect and the inability to orient the specimens appropriately play a role in limiting the evaluation of EMR specimens. EMR and ESD had similar rates of positive vertical margins but rates of positive lateral margins were significantly higher in EMR, despite a smaller lesion size resected with EMR. We postulate that this is a limitation of EMR technique and there is a certain lateral size that is unsuitable for EMR as it may not be able to resect enough of a “normal” margin to the tumor compared to ESD.

1712 Detection of Sub-Surface High-Grade Dysplasia Following Radiofrequency Ablation (RFA) of Barrett’s Esophagus

INTRODUCTION: Barrett's esophagus (BE) occurs when intestinal epithelium replaces squamous epithelium normally lining the distal esophagus. BE is associated with an increased risk of esophageal adenocarcinoma (EAC). While traditionally associated with Caucasian males, prevalence of BE and EAC in Asian populations is projected to rise, associated with increasing prevalence of gastroesophageal reflux disease (GERD), which is associated with obesity and hiatal hernia. Radiofrequency ablation (RFA) is an endoscopic treatment modality shown to be safe and effective in inducing reversion to squamous epithelium, with a treatment depth of 500-1000 microns. We present a case of BE with high-grade dysplasia identified on random forceps biopsy after RFA for BE with low grade dysplasia, after which significant sub-surface disease was detected by volumetric laser endomicroscopy (VLE). CASE DESCRIPTION/METHODS: A 72 yo Chinese male was diagnosed with short-segment BE containing low grade dysplasia, and was treated with 2 sessions of focal RFA 5 months apart. He was lost to follow up and re-established care two years later. At presentation, the patient denied any heartburn, dysphagia or weight loss. Surveillance endoscopy with white light and narrow band imaging (Figure 1) revealed short tongues of salmon-colored mucosa suspicious for residual BE. Forceps biopsy confirmed BE with high grade dysplasia at the 12:00 position. Repeat endoscopy using VLE demonstrated suspicious-appearing glands, primarily sub-surface, which were laser marked and resected with band ligation and snare instead of forceps biopsy (Figure 2). Pathology results confirmed high-grade dysplasia within BE (Figure 3). Due to the presence of dysplasia deeper into the epithelium, in the setting of prior RFA, the patient was referred for liquid nitrogen spray cryotherapy. DISCUSSION: Residual or recurrent BE following RFA is a relatively common finding, but it is uncommon to see disease with a higher dysplasia grade than what was found pre-treatment. In this case, the use of VLE to evaluate these findings identified deeper disease that may not have been amenable to initial RFA treatment, with the lesion becoming “buried” after incomplete ablation. VLE, which visualizes the esophageal wall to a depth of 3 mm, should be considered as part of the evaluation of residual BE, especially when dysplasia is present. Its use may improve patient outcomes by leading to an alternate approach to both tissue sampling and further treatment selection.

Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases

Gastroesophageal reflux disease (GERD) is caused by gastric acid entering the esophagus. GERD has high prevalence and is the major risk factor for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EA). We conduct a large GERD GWAS meta-analysis (80,265 cases, 305,011 controls), identifying 25 independent genome-wide significant loci for GERD. Several of the implicated genes are existing or putative drug targets. Loci discovery is greatest with a broad GERD definition (including cases defined by self-report or medication data). Further, 91% of the GERD risk-increasing alleles also increase BE and/or EA risk, greatly expanding gene discovery for these traits. Our results map genes for GERD and related traits and uncover potential new drug targets for these conditions.

Diabetes in relation to Barrett's esophagus and adenocarcinomas of the esophagus: A pooled study from the International Barrett's and Esophageal Adenocarcinoma Consortium.

Diabetes is positively associated with various cancers, but its relationship with tumors of the esophagus/esophagogastric junction remains unclear. Data were harmonized across 13 studies in the International Barrett's and Esophageal Adenocarcinoma Consortium, comprising 2309 esophageal adenocarcinoma (EA) cases, 1938 esophagogastric junction adenocarcinoma (EGJA) cases, 1728 Barrett's esophagus (BE) cases, and 16,354 controls. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% CIs for self-reported diabetes in association with EA, EGJA, and BE. Adjusted ORs were then combined using random-effects meta-analysis. Diabetes was associated with a 34% increased risk of EA (OR, 1.34; 95% CI, 1.00-1.80; I2 =48.8% [where 0% indicates no heterogeneity, and larger values indicate increasing heterogeneity between studies]), 27% for EGJA (OR, 1.27; 95% CI, 1.05-1.55; I2 =0.0%), and 30% for EA/EGJA combined (OR, 1.30; 95% CI, 1.06-1.58; I2 =34.9%). Regurgitation symptoms modified the diabetes-EA/EGJA association (P for interaction=.04) with a 63% increased risk among participants with regurgitation (OR, 1.63; 95% CI, 1.19-2.22), but not among those without regurgitation (OR, 1.03; 95% CI, 0.74-1.43). No consistent association was found between diabetes and BE. Diabetes was associated with increased EA and EGJA risk, which was confined to individuals with regurgitation symptoms. Lack of an association between diabetes and BE suggests that diabetes may influence progression of BE to cancer.

Helicobacter pylori infection, chronic atrophic gastritis and risk of stomach and esophagus cancer: Results from the prospective population-based ESTHER cohort study.

Helicobacter pylori (H. pylori) infection is considered as principal cause of gastric cancer. It is further associated with a reduced risk of esophageal adenocarcinomas. In a large prospective population-based cohort study including 9,949 subjects with average observation time of 13.8 years, we assessed the risk of invasive gastric and esophageal cancer according to H. pylori infection and presence of chronic atrophic gastritis (CAG). Incidence rates and hazard ratios (HR) derived by Cox proportional hazards models and adjusted for relevant confounders were derived by seroprevalence of H. pylori and cytotoxin-associated gene A (CagA) antibodies and presence of CAG based on serological markers at baseline, respectively. During follow-up, 30 cases of noncardia gastric cancer and 33 cases of esophageal cancer were observed. Infection by H. pylori without and with expression of CagA was associated with a 5.2-fold (95% confidence interval 1.00-27.1) and an 18.2-fold (4.3-77.4) increase of noncardia gastric cancer incidence. A 0.65-fold decreased risk of esophageal adenocarcinomas (HR 0.35, 0.12-0.97) was observed among H. pylori-infected individuals. In participants infected with CagA expressed H. pylori, the presence of mild/moderate and severe CAG was associated with a 6.4-fold (1.3-31.0) and an 11.8-fold (3.1-45.4) increase of gastric cancer incidence, respectively. The results of this prospective population-based cohort study may contribute relevant evidence to the ongoing research of H. pylori-related cancers. The results may furthermore enhance the empirical basis for risk stratification among H. pylori-infected people and for recommendations regarding H. pylori screening and treatment among older adults in a Western population.

Persistent confirmed low-grade dysplasia in Barrett's esophagus is a risk factor for progression to high-grade dysplasia and adenocarcinoma in a US Veterans cohort.

Patients with Barrett's esophagus (BE) and low-grade dysplasia (LGD) are at increased risk of esophageal adenocarcinoma (EAC), although many regress to nondysplastic BE. This has significant clinical importance for patients being considered for endoscopic eradication therapy. Our aim is to determine the risk for progression in patients with confirmed persistent LGD. We performed a single-center retrospective cohort study of patients with BE and confirmed LGD between 2006 and 2016. Confirmed LGD was defined as LGD diagnosed by consensus conference with an expert GI pathologist or review by an expert GI pathologist and persistence as LGD present on subsequent endoscopic biopsy. The primary outcome was the incidence rate of HGD (high-grade dysplasia)/EAC. Secondary outcomes included risk factors for dysplastic progression. Risk factors for progression were assessed using univariate and multivariate analysis with logistic regression. Of 69 patients (mean age 65.2 years) with confirmed LGD were included. In total, 16 of 69 patients (23.2%) with LGD developed HGD/EAC during a median follow-up of 3.74 years (IQR, 1.24-5.45). For persistent confirmed LGD, the rate was 6.44 (95% confidence interval (CI), 2.61-13.40) compared to 2.61 cases per 100 patient-years (95% CI, 0.83-6.30) for nonpersistent LGD. Persistent LGD was found in only 29% of patients. Persistent LGD was an independent risk factor for the development of HGD/EAC (OR 4.18; [95% CI, 1.03-17.1]). Persistent confirmed LGD, present in only 1/3 of patients, was an independent risk factor for the development of HGD/EAC. Persistence LGD may be useful in decision making regarding the management of BE.

Red and processed meat consumption and esophageal cancer risk: a systematic review and meta-analysis.

The associations between red and processed meat consumption and esophageal cancer risk remain inconclusive. We performed a systematic review and meta-analysis to analyze these associations. We searched PubMed and EMBASE to identify studies published between the databases' dates of inception and May 2019. We ultimately selected 33 eligible studies for analysis. We found that the summary relative risks for the associations between meat consumption and esophageal cancer risk were positive for the case-control studies (P < 0.05), but negative for the cohort studies included in the analysis (P > 0.05). Subtype analysis indicated that red and processed meat consumption was not associated with the risks of esophageal adenocarcinoma (P > 0.05) and esophageal squamous cell carcinoma (P > 0.05) in the cohort studies. We found case-control but not cohort studies to associate consumption of red and processed meat with the risk of esophageal cancer. Further large prospective studies are needed to validate these findings.

Abstract 1588: Germline variation in DNA repair genes and risk of Barrett's esophagus and esophageal adenocarcinoma

Abstract Incidence of esophageal adenocarcinoma (EA) has risen substantially in Western countries over recent decades. Established risk factors for EA and its precursor lesion, Barrett’s esophagus (BE), include reflux, obesity, and tobacco smoking. Inherited genetic variation also influences disease risk, although only a limited number of susceptibility loci have been identified. Genomic analyses of EA tumors have revealed a distinctive mutational signature, high mutational burden, and extensive somatic chromosome alterations, features also observed in high-risk BE tissue. To explore whether germline variation in DNA repair-related genes may be associated with altered disease susceptibility, we analyzed data from a recent meta-analysis of genome-wide association studies (GWAS) encompassing 4,112 EA cases, 6,167 BE cases, and 17,159 controls, representing the largest sample size assembled for these conditions. Using a gene-based testing approach (VEGAS2), we assessed 263 DNA repair-related genes and found that variation in NEIL2, a mediator of base excision repair (BER), was significantly associated with risk of BE (P=1.4×10-5, q&amp;lt;0.05). No other gene-level associations with BE or EA survived correction for multiple comparisons. SNP-level analysis of 239 polymorphisms at the NEIL2 locus revealed six variants strongly associated with altered risk of BE (P&amp;lt;5×10-5, q&amp;lt;0.01), with the index SNP classified as an intronic eQTL for NEIL2 in esophageal tissue. Four of these SNPs were also associated with risk of EA (P&amp;lt;0.05), with odds ratios in the same direction and of similar magnitude. Our results provide evidence that germline genetic variation in a DNA glycosylase enzyme (NEIL2) may influence risk of BE/EA, and suggest a potential novel biological role for altered BER in BE/EA pathogenesis. Citation Format: Matthew F. Buas, Li Yan, Xuan Peng, Qianya Qi, Jianhong Chen, Aaron Thrift, Qianchuan He, Lynn Onstad, Puya Gharahkhani, Stuart MacGregor, Thomas L. Vaughan, Margaret M. Madeleine. Germline variation in DNA repair genes and risk of Barrett's esophagus and esophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1588.

Abstract 2416: Vitamin D concentration and the risks of Barrett’s esophagus and esophageal adenocarcinoma: A Mendelian randomization study

Abstract Background Epidemiological studies on circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risks of esophageal adenocarcinoma (EAC) have shown conflicting results. Here we conducted a Mendelian randomization (MR) study to determine the associations between circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risks of EAC and its precursor, Barrett’s esophagus (BE). Methods We conducted a MR study using a two-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs) (rs3755967, rs10741657, rs12785878, rs10745742, rs8018720 and rs17216707) associated with circulating 25(OH)D concentrations were used as instrumental variables. Data from 6,167 BE patients, 4,112 EAC patients and 17,159 control participants were from studies participating in the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON), as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC. Results Overall, we found no evidence for an association between genetically estimated 25(OH)D concentrations and the risk of BE or EAC. The odds ratio (OR) per standard deviation unit increase in genetically estimated 25(OH)D concentrations for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% confidence interval, CI, 0.77-1.92; P = 0.41). The OR for EAC risk estimated by combining the individual SNP association using inverse variance weighting was 0.68 (95% CI, 0.39-1.19; P = 0.18). Conclusions This Mendelian randomization study found that genetically estimated low 25(OH)D concentrations were not associated with increased risks of BE or EAC. Citation Format: Jing Dong, Aaron Thrift. Vitamin D concentration and the risks of Barrett’s esophagus and esophageal adenocarcinoma: A Mendelian randomization study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2416.

Risk and Predictors of Esophageal and Stomach Cancers in HIV-Infected Veterans: A Matched Cohort Study.

To evaluate the risks of esophageal and stomach carcinomas in people living with HIV (PLWH) compared with the general population and risk factors for these cancers in PLWH. Retrospective cohort study in the Veterans Health Administration. We compared incidence rates for esophageal and stomach cancers in 44,075 HIV-infected male veterans with those in a matched HIV-uninfected cohort (N = 157,705; 4:1 matched on age and HIV-index date). We used Cox regression models to estimate Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with HIV infection and for cancer risk factors in PLWH. In unadjusted models, HIV infection was associated with increased risks of esophageal squamous cell carcinoma (ESCC; HR, 2.21; 95% CI: 1.47 to 3.13) and gastric cardia cancer (HR, 1.69; 95% CI: 1.00 to 2.85) but associated with lower risk of esophageal adenocarcinoma (EAC; HR, 0.48; 95% CI: 0.31 to 0.74). After adjusting for age, race/ethnicity, smoking and alcohol use, HIV infection remained statistically significantly associated with elevated risk for ESCC [adjusted hazard ratio (aHR), 1.58; 95% CI: 1.02 to 2.47], especially among HIV-infected patients with CD4 count ≤200 (aHR, 2.20; 95% CI: 1.35 to 3.60). HIV infection was not associated with risks of EAC (aHR, 0.82; 95% CI: 0.53 to 1.26), gastric cardia (aHR, 0.80; 95% CI: 0.33 to 1.94), or noncardia (aHR, 1.06; 95% CI: 0.61 to 1.84) cancers. Risk factors for these cancers in HIV-infected patients were otherwise similar to those in general population (eg, Helicobacter pylori for gastric noncardia cancer). HIV-infected individuals with low CD4 count are at highest risk for ESCC, but HIV infection was not independently associated with EAC or gastric cancer after adjusting for confounders.

Interactive decision support for esophageal adenocarcinoma screening and surveillance

BackgroundA key barrier to controlling esophageal adenocarcinoma (EAC) is identifying those most likely to benefit from screening and surveillance. We aimed to develop an online educational tool, termed IC-RISC™, for providers and patients to estimate more precisely their absolute risk of developing EAC, interpret this estimate in the context of risk of dying from other causes, and aid in decision-making.ResultsU.S. incidence and mortality data and published relative risk estimates from observational studies and clinical trials were used to calculate absolute risk of EAC over 10 years adjusting for competing risks. These input parameters varied depending on presence of the key precursor, Barrett’s esophagus. The open source application works across common devices to gather risk factor data and graphically illustrate estimated risk on a single page. Changes to input data are immediately reflected in the colored graphs. We used the calculator to compare the risk distribution between EAC cases and controls from six population-based studies to gain insight into the discrimination metrics of current practice guidelines for screening, observing that current guidelines sacrifice a significant amount of specificity to identify 78–86% of eventual cases in the US population.ConclusionsThis educational tool provides a simple and rapid means to graphically communicate risk of EAC in the context of other health risks, facilitates “what-if” scenarios regarding potential preventative actions, and can inform discussions regarding screening, surveillance and treatment options. Its generic architecture lends itself to being easily extended to other cancers with distinct pathways and/or intermediate stages, such as hepatocellular cancer. IC-RISC™ extends current qualitative clinical practice guidelines into a quantitative assessment, which brings the possibility of preventative actions being offered to persons not currently targeted for screening and, conversely, reducing unnecessary procedures in those at low risk. Prospective validation and application to existing well-characterized cohort studies are needed.

Association between blood pressure and risk of cancer development: a systematic review and meta-analysis of observational studies

With the exception of renal cell carcinoma, studies assessing the association between hypertension and other cancers are inconsistent. We conducted a meta-analysis to assess this evidence. We included observational studies investigating the association between any definition of hypertension or systolic and diastolic blood pressure and risk of any cancer, after searching PubMed until November 2017. We calculated summary relative risks (RR) and 95% confidence intervals (CI) using inverse-variance weighted random effects methods. A total of 148 eligible publications were identified out of 39,891 initially screened citations. Considering only evidence from 85 prospective studies, positive associations were observed between hypertension and kidney, colorectal and breast cancer. Positive associations between hypertension and risk of oesophageal adenocarcinoma and squamous cell carcinoma, liver and endometrial cancer were also observed, but the majority of studies did not perform comprehensive multivariable adjustments. Systolic and diastolic blood pressure were positively associated with risk of kidney cancer but not with other cancers. In addition to the previously well-described association between hypertension and risk of kidney cancer, the current meta-analysis suggested that hypertensive individuals may also be at higher risk of colorectal and breast cancer. However, careful interpretation is required as most meta-analyses included relatively small number of studies, several relative risks had weak or moderate magnitude and maybe affected by residual confounding.

Mo1217 ENDOSCOPIC SUBMUCOSAL DISSECTION IS ASSOCIATED WITH LESS PATHOLOGIC UNCERTAINTY THAN ENDOSCOPIC MUCOSAL RESECTION IN DIAGNOSING AND STAGING BARRET'S RELATED NEOPLASIA

Secondary to the rising incidence and poor prognosis of advanced esophageal adenocarcinoma, a concerted effort to identify those at risk for esophageal adenocarcinoma by screening for its precursor lesion, Barret’s Esophagus (BE) and Barret’s associated neoplasia (BN), has been suggested by multiple societal guidelines.

Physical Activity in Cancer Prevention and Survival: A Systematic Review.

This article reviews and updates the evidence on the associations between physical activity and risk for cancer, and for mortality in persons with cancer, as presented in the 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Systematic reviews of meta-analyses, systematic reviews, and pooled analyses were conducted through December 2016. An updated systematic review of such reports plus original research through February 2018 was conducted. This article also identifies future research needs. In reviewing 45 reports comprising hundreds of epidemiologic studies with several million study participants, the report found strong evidence for an association between highest versus lowest physical activity levels and reduced risks of bladder, breast, colon, endometrial, esophageal adenocarcinoma, renal, and gastric cancers. Relative risk reductions ranged from approximately 10% to 20%. Based on 18 systematic reviews and meta-analyses, the report also found moderate or limited associations between greater amounts of physical activity and decreased all-cause and cancer-specific mortality in individuals with a diagnosis of breast, colorectal, or prostate cancer, with relative risk reductions ranging almost up to 40% to 50%. The updated search, with five meta-analyses and 25 source articles reviewed, confirmed these findings. Levels of physical activity recommended in the 2018 Guidelines are associated with reduced risk and improved survival for several cancers. More research is needed to determine the associations between physical activity and incidence for less common cancers and associations with survival for other cancers. Future studies of cancer incidence and mortality should consider these associations for population subgroups, to determine dose-response relationships between physical activity and cancer risk and prognosis, and to establish mechanisms to explain these associations.

Oesophageal Adenocarcinoma after Surgery and Medication Against Gastro-Oesophageal Reflux Disease in a Nordic Cohort Study

Background: Gastro-oesophageal reflux disease (GORD) increases risk of oesophageal adenocarcinoma (OAC), but whether antireflux therapy prevents OAC is uncertain. We aimed to clarify this issue and assess potential differences after surgical and medical treatment. Methods: Multinational, population-based cohort study including individuals with GORD from the five Nordic countries in 1964-2014. The exposure was antireflux surgery or medication and the outcome was OAC. First, OAC risk after antireflux surgery and medication in the cohort was compared with the respective corresponding background population by calculating standardised incidence ratios (SIRs) with 95% confidence intervals (95%CIs). Second, multivariable Cox proportional hazards regression, providing hazard ratios (HRs) with 95%CIs, was used to compare antireflux surgery with medication in relation to OAC risk. Findings: Among 942,071 GORD patients, 48,863 underwent surgery and 893,208 received medication. Compared to the background population, OAC risk did not decrease following surgery (SIR=4.90 [95%CI 3.62-6.47] 1-<5 years and SIR=4.57 [95%CI 3.44-5.95] ≥15 years after surgery) or medication (SIR=2.37 [95%CI 2.17-2.59] 1-<5 years and SIR=3.07 [95%CI 2.65-3.54] ≥15 years after medication). Similarly, no decrease was found for patients with severe GORD over time after surgical (SIR=6.09 [95%CI 4.39-8.23] 1-<5 years and SIR=5.27 [95%CI 3.73-7.23] ≥15 years) or medical (SIR=3.61 [95%CI 3.19-4.07] 1-<5 years and SIR=3.82 [95%CI (3.19-4.55] ≥15 years) antireflux therapy. The HRs of OAC were stable over time over time after surgery compared with medication (HR=1.71 [95%CI 1.26-2.33] 1-<5 years and HR=1.69 [95%CI 1.24-2.30] ≥15 years after treatment), and remained stable over time after treatment in participants with severe GORD (HR=1.56 [95%CI 1.11-2.20] 1-<5 years and HR=1.57 [95%CI 1.08-2.26] ≥15 years after treatment). Interpretation: Medical and surgical treatment of GORD does not seem to reduce OAC risk. Funding: Nordic Cancer Union, Swedish Cancer Society and Swedish Research Council. Declaration of Interest: None. Ethical Approval: All required ethical and data permissions were retrieved from the relevant authorities within each country (The Danish Data Protection Agency; Population Register Centre, National Institute for Health and Welfare, Statistics Finland; The Icelandic Data Protection Authority, The National Bioethics Committee; Regional Ethics Committee, Norway; and Regional Ethics Committee, Sweden).

Sa1164 – Men with Esophageal Adenocarcinoma Risk Factors are Less Likely Than Women to Undergo Upper Endoscopy

Sa1164 – Men with Esophageal Adenocarcinoma Risk Factors are Less Likely Than Women to Undergo Upper Endoscopy

Genetic variants in Barrett's esophagus and esophageal adenocarcinoma: a literature review

Surveillance of Barrett's esophagus (BE) is a clinical challenge; metaplasia of the distal esophagus increases a patient's risk of esophageal adenocarcinoma (EAC) significantly but the actual percentage of patients who progress is low. The current screening recommendations require frequent endoscopy and biopsy, which has inherent risk, high cost, and operator variation. Identifying BE patients genetically who are at high risk of progressing could deemphasize the role of endoscopic screening and create an opportunity for early therapeutic intervention. Genetic alterations in germline DNA have been identified in other disease processes and allow for early intervention or surveillance well before disease develops. The genetic component of BE remains mostly unknown and only a few genome-wide association studies exist on this topic. This review summarizes the current literature available that examines genetic alterations in BE and EAC with a particular emphasis on clinical implications.

Esophageal adenocarcinoma in a first-degree relative increases risk for esophageal adenocarcinoma in patients with Barrett's esophagus.

The significance of a family history of esophageal adenocarcinoma in the progression to esophageal adenocarcinoma in patients with Barrett's esophagus has not been thoroughly evaluated. The purpose of this study is to evaluate the presence of esophageal adenocarcinoma in a first-degree relative in patients with Barrett's esophagus. A retrospective cohort study was conducted of patients with Barrett's esophagus at a tertiary care center undergoing radiofrequency ablation. Family history, demographics, and pathology and endoscopy reports were assessed in all patients. Three hundred and one patients with Barrett's esophagus were assessed. Nineteen patients who had a diagnosis of esophageal adenocarcinoma on index endoscopy were excluded. Nineteen (6.7%) patients had a first-degree relative with esophageal adenocarcinoma. Four (21.1%) of these patients progressed to esophageal adenocarcinoma. Of patients without first-degree relative with esophageal adenocarcinoma 22/263 (8.7%) progressed to esophageal adenocarcinoma. In a logistic regression model adjusted for sex and the number of radiofrequency ablation treatments, we found that family history of esophageal adenocarcinoma was a significant independent predictor of progression to esophageal adenocarcinoma (odds ratio = 5.55, 95% confidence interval: 1.47-20.0). Our study indicates that Barrett's esophagus patients with a first-degree family member with esophageal adenocarcinoma are at 5.5-fold higher risk for disease progression to esophageal adenocarcinoma. Family history of esophageal adenocarcinoma in Barrett's esophagus patients should be considered in patient surveillance and radiofrequency ablation treatment, beyond recommended guidelines.

Mediterranean diet adherence and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

BackgroundMediterranean diet (MD) adherence has been associated with reduced risks of esophageal and gastric cancer (subtypes) in a limited number of studies. We prospectively investigated associations between MD adherence and risks of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA) in a Dutch cohort.MethodsAnalyses were conducted using data from the 120852 participants of the Netherlands Cohort Study (NLCS), who were aged between 55 and 69 years at enrollment. Various MD scores, with and without alcohol, were calculated to estimate MD adherence. Using 20.3 years of follow-up, 133 ESCC, 200 EAC, 191 GCA, and 586 GNCA cases could be included in multivariable Cox regression analyses.ResultsOf the investigated scores, the alternate Mediterranean diet score without alcohol (aMEDr) performed best. aMEDr was inversely associated with risks of GCA and GNCA in men and women. However, statistical significance was only reached in men [ptrend: 0.019 (GCA), 0.016 (GNCA)]. Furthermore, higher aMEDr values were significantly associated with a reduced ESCC risk in men [HRper two−point increment (95% CI) = 0.57 (0.41–0.80), ptrend = 0.013], but not in women (pheterogeneity = 0.008). There was no evidence of an association between aMEDr and EAC risk. Educational level was a significant effect modifier for the association between aMEDr and GNCA risk (pheterogeneity = 0.0073).ConclusionsHigher MD adherence was associated with reduced risks of ESCC, GCA, and GNCA in the NLCS. However, the decreased ESCC risk might be limited to men.