A highly curated look at recent literature regarding the epidemiology and prevention of Barrett’s esophagus and esophageal adenocarcinoma.
Dr. Jessica Petrick and colleagues at NCI and in Denmark report on the relationship between childhood obesity and subsequent risk of esophageal and gastric cancer using record linkage and follow up of over 60,000 young Danish men. This is one of the first studies that indicate that reduction in obesity between childhood and adulthood may reduce subsequent risk.
Obesity (Silver Spring). 2019 Aug 5. doi: 10.1002/oby.22570. [Epub ahead of print]
Overweight Patterns Between Childhood and Early Adulthood and Esophageal and Gastric Cardia Adenocarcinoma Risk.
Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are among the most rapidly increasing cancers in Western countries. Elevated BMI in adulthood is a known risk factor, but associations in early life are unclear.
This study assessed weight change between childhood and early adulthood in relation to EA/GCA. Measured weights and heights during childhood (7-13 years) and early adulthood (17-26 years) were available for 64,695 young men from the Copenhagen School Health Records Register and the Danish Conscription Database. Individuals were categorized as having normal weight or overweight. Linkage with the Danish Cancer Registry identified 275 EA/GCA cases. Hazard ratios (HR) and 95% CI were estimated using Cox proportional hazards regression.
The risk of EA/GCA was 2.5 times higher in men who were first classified as having overweight at age 7 (HR = 2.49; 95% CI: 1.50-4.14) compared with men who were never classified as having overweight. Men who had persistent overweight at ages 7 and 13 and in early adulthood had an EA/GCA risk that was 3.2 times higher (HR = 3.18; 95% CI: 1.57-6.44). However, there was little evidence of increased EA/GCA risk for men with overweight during childhood and subsequent remittance by early adulthood.
Persistent overweight in early life is associated with increased EA/GCA risk, which declines if body weight is reduced.
J Surg Oncol. 2019 Aug 1. doi: 10.1002/jso.25656. [Epub ahead of print]
Screening high-risk populations for esophageal and gastric cancer.
Cancers of the esophagus and stomach remain important causes of mortality worldwide, in large part because they are most often diagnosed at advanced stages. Thus, it is imperative that we identify and treat these cancers in earlier stages. Due to significant heterogeneity in incidence and risk factors for these cancers, it has been challenging to develop standardized screening recommendations. This review summarizes the current recommendations for screening populations at high risk of developing esophagogastric cancers.
Michelle Hill and colleagues from the QIMR Berghofer in Queensland, AU, take a close look at non-invasive methods for collecting cells from the esophageal lining, and the role of blood-based biomarkers in risk stratification.
Transl Gastroenterol Hepatol. 2019 May 15;4:31. doi: 10.21037/tgh.2019.04.08. eCollection 2019.
To BE or not to BE: non-invasive screening for Barrett’s esophagus, dysplasia and adenocarcinoma.
In conclusion, recent studies report promising results in molecular markers for non-invasive diagnosis of BE,
and/or EAC. Due to the overall low incidence rate of dysplasia diagnosis and progression to EAC, multi-site
collaborative studies are needed to fully evaluate the clinical utility of these markers. Critical evaluation of the clinical pathways should be conducted, to ensure the trials address actionable clinical needs and not lead to overdiagnosis and overtreatment. If an appropriate point-of-care tool could be standardized to detect at-risk BE patients, subsequently an intensive surveillance protocol for this risk group with enhanced imaging guided endoscopy (22) could be applied to detect dysplasia and treat these patients using ablative modalities. With development and implementation of non-invasive tests and risk prediction algorithms, the ideal scenario for EAC prevention through screening (Figure 1) may become a future reality.
This provocative study, while based on a chart review, suggests that persons with obstructive sleep apnea have a three-fold increased risk of BE even after controlling for obesity and reflux symptoms.
J Gastroenterol Hepatol. 2019 Jul 10. doi: 10.1111/jgh.14779. [Epub ahead of print]
Independent association of obstructive sleep apnea with Barrett’s esophagus.
BACKGROUND AND AIM:
Current guidelines suggest screening at-risk groups of patients for Barrett’s esophagus (BE), a precursor to esophageal cancer. Although BE and obstructive sleep apnea (OSA) have common risk factors, including elevated body mass index and gastroesophageal reflux disease (GERD), the relationship between these two conditions has not been well established.
Retrospectively, all patients who had undergone a polysomnography and esophagogastroduodenoscopy at West Virginia University Hospital from 2013 to 2018 were identified and divided into groups on the basis of the presence or absence of OSA. Clinical course and procedure reports were reviewed to identify relevant variables.
One thousand ninety-one patients met inclusion criteria; 60.9% were female, and mean age of participants was 53.5 years. Univariate analysis revealed that male gender, age, diagnosis of OSA, severity of OSA, and a clinical diagnosis of GERD were associated with BE (P values < 0.05). Multiple logistic regression incorporating age, sex, clinical diagnosis of GERD, smoking history, body mass index, Helicobacter pylori status, and presence of hiatal hernia was utilized. Patients with OSA had an increased risk of BE than had those without OSA (P < 0.001, odds ratio 3.26 [1.72-6.85]). The risk increased with increasing severity of OSA, categorized in apnea-hypopnea index increments of 10.
Obstructive sleep apnea is associated with BE, a relationship that is independent of other known risk factors. Additionally, this risk increases with increasing severity of OSA. Future efforts should determine if patients with severe OSA need to be screened for BE due to its potential for causing esophageal cancer.
This paper describes the development of the IC-RISC™ calculator and provides examples of its application in the general population and among persons with Barrett’s esophagus. (See “What’s Your Risk” menu above for the actual calculator.)
BMC Gastroenterol. 2019 Jun 27;19(1):109. doi: 10.1186/s12876-019-1022-0.
Interactive decision support for esophageal adenocarcinoma screening and surveillance.
A 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.
U.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.
This 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.
This study is one of the first to suggest that, among patients with severe obesity, weight loss surgery might induce histologic regression of BE to normal lining.
Surg Endosc. 2018 Feb;32(2):930-936. doi: 10.1007/s00464-017-5768-6. Epub 2017 Aug 4.
Barrett’s esophagus before and after Roux-en-Y gastric bypass for severe obesity.
Barrett’s esophagus (BE) has been associated with obesity and metabolic syndrome. Laparoscopic Roux-en-Y gastric bypass (LRYGB) may represent a surgical approach which addresses both severe obesity and BE. LRYGB diverts bile away from the gastric pouch and esophagus due to the long Roux limb, and very little acid is produced in the cardia-based gastric pouch. Furthermore, surgically induced weight loss may diminish systemic inflammation, which may contribute to metaplastic changes in the esophagus. Moreover, improved compliance with proton-pump inhibitor therapy, as a consequence of enrolling in a bariatric program, will decrease acid production further. Decreased duodeno-gastro-esophageal reflux should lead to decreased BE. In this study we examine the effect of LRYGB on regression of BE.
METHODS AND PROCEDURES:
We performed a review of all patients with biopsy proven BE, who underwent LRYGB at our institution. A total of 19 patients were identified. A subset of those patients was identified who had at least 1 year of clinical, endoscopic, or histological data, comprising a total of 14 patients. Seven of these patients had symptoms of gastroesophageal reflux. All 19 patients had short-segment BE. One patient had low-grade dysplasia.
Post-LRYGB, 6 of 14 (42.9%) patients had histologic regression of BE to normal esophageal mucosa, with no evidence of ongoing BE. 13 of 14 patients (92.8%) reported compliance with continuing PPI therapy for at least the first year after surgery. Body mass index for the group of 14 patients improved from 46.6 to 30.3 kg/m2.
We recommend LRYGB as an effective combined bariatric and anti-reflux surgical procedure for patients with severe obesity and BE. In short-term follow-up, LRYGB achieved endoscopic and histologic regression to normal mucosa in a substantial number of the patients in our series. Long-term follow-up for patients with BE according to standard surveillance protocols is still recommended.
Some useful confirmatory data on the prevalence of BE according to status of various risk factors.
Gastrointest Endosc. 2019 May 29. pii: S0016-5107(19)31769-9. doi: 10.1016/j.gie.2019.05.030. [Epub ahead of print]
Systematic review and meta-analysis of prevalence and risk factors for Barrett’s esophagus.
BACKGROUND AND AIMS:
Although screening for Barrett’s esophagus (BE) is recommended in individuals with multiple risk factors, the type and number of risk factors necessary to trigger screening is unclear. In this systematic review and meta-analysis, we aimed to assess the relationship between number of risk factors and prevalence of BE.
Through October 17, 2018, we searched studies that described the prevalence of BE in the general population and based on presence of risk factors that included GERD, male gender, age >50 years, family history of BE and esophageal adenocarcinoma (EAC), and obesity (defined as body mass index >35). Risk of BE based on number of risk factors was assessed using meta-regression while controlling for potential confounders.
Of 2,741 studies, 49 were included in the analysis (307,273 individuals, 1,948 with biopsy-proven BE). Indications varied by study. The prevalence of BE for various populations was as follows: low-risk general population: 0.8% (95% CI, 0.6% – 1.1%); GERD: 3% (95% CI, 2.3% – 4%); GERD plus presence of any other risk factor: 12.2% (95% CI,10.2% – 14.6%); family history: 23.4% (95% CI,13.7% -37.2%); age > 50: 6.1% (95% CI, 4.6% – 8.1%); obesity: 1.9% (95% CI, 1.2% – 3%); and male sex: 6.8% (95% CI, 5.3% – 8.6%). Prevalence of BE varied significantly between Western and non-Western populations. In a meta-regression, controlling for the region of the study, age, and gender, there was a positive linear relationship between the number of risk factors and the prevalence of BE.
Results of this study provide estimates of BE prevalence based on the presence and the number of risk factors. These results add credence to current guidelines that suggest screening in the presence of multiple risk factors.
A thoughtful commentary on the strengths and weakness of the recent clinical trial of PPI and aspirin.
Nat Rev Clin Oncol. 2018 Dec;15(12):728-730. doi: 10.1038/s41571-018-0096-x.
Chemoprevention of Barrett’s oesophagus: a step closer with PPIs and aspirin.
Chemoprevention for patients with Barrett’s oesophagus remains a
controversial topic. Results of the first randomized trial of chemoprevention
using a proton pump inhibitor with or without aspirin were recently reported.
We highlight strengths and weaknesses in the design of the trial and discuss
the clinical implications of the findings.
In this cross-sectional study of patients seen at Mayo Clinic between 2002 and 2010, use of smokeless tobacco and cigars or pipes was found to be associated with risk of Barrett’s in persons with GERD. Confirmatory studies are needed.
Mayo Clin Proc. 2018 Sep;93(9):1282-1289. doi: 10.1016/j.mayocp.2018.04.022.
Smokeless Tobacco and Cigar and/or Pipe Are Risk Factors for Barrett Esophagus in Male Patients With Gastroesophageal Reflux Disease.
To investigate the effect of smokeless tobacco (ST), cigar and/or pipe smoking (CP) on the development of Barrett esophagus (BE) in white male patients with gastroesophageal reflux disease (GERD).
PATIENTS AND METHODS:
A total of 1015 records of white male adults with BE (cases; n=508) or GERD (controls, n=507) were reviewed for lifestyle factors. Logistic regression analyses were performed after adjusting for lifestyle factors to assess the effects of ST and CP on the risk of developing BE. Differences between patients with BE and those with GERD were compared using chi-square and t tests.
Patients with BE were significantly older than patients with GERD (mean age, 66±12 years for patients with BE and 55±15 years for patients with GERD; P<.001). The odds of developing BE in patients who used CS were 1.7 times higher than that in patients who never smoked cigarettes (odds ratio [OR], 1.7; 95% CI, 1.3-2.2). It was observed that when CS use was combined with either ST or CP use, the odds of having BE significantly increased (OR, 2.5; 95% CI, 1.2-5.2; P=.01 and OR, 1.9; 95% CI, 1.03-3.58; P=.04) in comparison to CS alone. There were no significant differences in body mass index and alcohol consumption between BE and GERD groups.
This study suggests that there is indeed an association between CS and BE. We believe that this is the first time that ST and CP were associated with an even higher odds of developing BE. Further studies are needed to investigate whether the use of ST and CP is also associated with an increased risk of developing BE-associated adenocarcinoma.
Dr. Michael Cook and colleagues at the Division of Cancer Epidemiology and Genetics at the NCI report that certain markers of inflammation in blood are associated with esophageal adenocarcinoma, and conclude that systemic inflammation may underlie some of the increased risk with obesity and cigarette smoking.
Gut. 2019 Jun;68(6):960-968. doi: 10.1136/gutjnl-2018-316678. Epub 2018 Aug 18.
Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma: a study within the National Cancer Institute Cohort Consortium.
Cook MB1, Barnett MJ2, Bock CH3, Cross AJ4, Goodman PJ5, Goodman GE2,6, Haiman CA7, Khaw KT8, McCullough ML9, Newton CC9, Boutron-Ruault MC10,11, Lund E12, Rutegård M13, Thornquist MD2, Spriggs M14, Giffen C14, Freedman ND1, Kemp T15, Kroenke CH16, Le Marchand L17, Park JY18, Simon M3, Wilkens LR16, Pinto L14, Hildesheim A1, Campbell PT9.
Cross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk.
This nested case-control study included 296 oesophageal adenocarcinoma cases and 296 incidence density matched controls from seven prospective cohort studies. We quantitated 69 circulating inflammation markers using Luminex-based multiplex assays. Conditional logistic regression models estimated associations between inflammation markers and oesophageal adenocarcinoma, as well as direct and indirect effects of obesity and smoking on risk of malignancy.
Soluble tumour necrosis factor receptor 2 (sTNFR2) (ORsquartile 4 vs 1=2.67, 95% CI 1.52 to 4.68) was significantly associated with oesophageal adenocarcinoma. Additional markers close to the adjusted significance threshold included C reactive protein, serum amyloid A, lipocalin-2, resistin, interleukin (IL) 3, IL17A, soluble IL-6 receptor and soluble vascular endothelial growth factor receptor 3. Adjustment for body mass index, waist circumference or smoking status slightly attenuated biomarker-cancer associations. Mediation analysis indicated that sTNFR2 may account for 33% (p=0.005) of the effect of waist circumference on oesophageal adenocarcinoma risk. Resistin, plasminogen activator inhibitor 1, C reactive protein and serum amyloid A were also identified as potential mediators of obesity-oesophageal adenocarcinoma associations. For smoking status, only plasminogen activator inhibitor 1 was a nominally statistically significant (p<0.05) mediator of cancer risk.
This prospective study provides evidence of a link between systemic inflammation and oesophageal adenocarcinoma risk. In addition, this study provides the first evidence that indirect effects of excess adiposity and cigarette smoking, via systemic inflammation, increase the risk of oesophageal adenocarcinoma.