Editorials: Controversies in Family Medicine
Should We Screen Patients for Barrett's Esophagus? Yes: Men with Long-standing Reflux Symptoms Should Be Screened with Endoscopy
Am Fam Physician. 2011 May 15;83(10):1140-1143.
This is one in a series of pro/con editorials discussing controversial issues in family medicine.
Reflux is a common and challenging problem among primary care patients. This condition deserves particular attention given its association with esophageal adenocarcinoma, a disease that is rising in incidence1 and kills approximately 6,000 persons annually.2 Esophageal adenocarcinoma can occur when acid exposure to the esophageal epithelium leads to chronic esophagitis. Subsequently, metaplasia may occur, progressing to dysplasia and ultimately carcinoma. Barrett's esophagus is a precursor lesion for these cancers and can be diagnosed easily by endoscopic visualization of columnar mucosa in the distal esophageal epithelium, and can be confirmed by biopsy demonstrating intestinal metaplasia.3 A strong argument can be made for Barrett's esophagus screening to prevent esophageal adenocarcinoma because excellent screening and treatment options are available.
Despite increasing evidence supporting prevention of esophageal adenocarcinoma through endoscopic screening and surveillance for Barrett's esophagus, the effectiveness of this approach has been questioned.3 Even the most recent American College of Gastroenterology guidelines stop short of recommending endoscopic screening.4 However, screening patients at high risk of developing Barrett's esophagus and esophageal adenocarcinoma is supported by solid evidence on risk factors for Barrett's esophagus, effectiveness of chemoprevention, rates of progression from Barrett's esophagus to esophageal adenocarcinoma, and the cost-effectiveness of screening programs.
It has been estimated that endoscopic screening of all patients older than 50 years with weekly reflux symptoms would include at least 10 million patients, and that this is not cost-effective based on low rates of progression from reflux to esophageal adenocarcinoma.3 However, new data on risk stratification favor selective screening. Patients can be stratified based on known risk factors for Barrett's esophagus, including smoking, obesity (body mass index greater than 30 kg per m2), longer duration of gastroesophageal reflux disease symptoms, and other factors described in Table 1.5–10 These data are strengthened by a recent nationwide retrospective cohort study conducted in the Netherlands confirming that male sex, older age, and low-grade dysplasia at initial diagnosis are independent predictors of malignant progression in Barrett's esophagus.11 Patients with high-grade dysplasia on diagnosis of Barrett's esophagus have a 6 to 7 percent higher rate of malignant transformation per year according to a meta-analysis performed in 2008.12
Table 1: Risk Factors for Barrett's Esophagus in Persons with Reflux Symptoms
Risk Factors for Barrett's Esophagus in Persons with Reflux Symptoms
|Risk factor||Odds ratio|
Smoking and self-reported acid reflux5 *
Obesity (body mass index > 30 kg per m2) and self-reported acid reflux5 *
Self-reported weekly acid reflux5 *
GERD for more than 10 years6 †
GERD for five to 10 years6 †
Age older than 40 years7 ‡
Hiatal hernia9 ∥
Male sex10 ¶
GERD for one to five years6 †
Smoking (former or current)5 *
GERD less than one year6 †
GERD = gastroesophageal reflux disease.
*—Case-control study with 428 patients identified through two Australian pathology laboratories in a metropolitan area.
†—Prospective observational study with 662 patients from U.S. community-based gastrointestinal practices.
‡—Case-control study with 211 patients at U.S. Veteran's Medical Center.
§—Case-control study with 129 patients at U.S. Veteran's Medical Center.
∥—Multicenter, case-control study with 600 patients from eight Italian Departments of Gastroenterology.
¶—Prospective observational study with 517 patients from U.S. Veteran's Medical Center.
In patients with Barrett's esophagus and/or dysplasia, prevention efforts have advanced dramatically. Chemoprevention remains a mainstay in treatment, with growing evidence for newer endoscopic techniques and survival data supporting surveillance in patients with Barrett's esophagus. All patients with Barrett's esophagus and no dysplasia should be treated with proton pump inhibitors because there is a 37 percent absolute risk reduction for developing dysplasia (number needed to treat = 2.7) based on a 20-year prospective cohort.13 Support for endoscopic therapies includes a recent retrospective comparison study of patients with high-grade dysplasia that found no significant difference in five-year mortality between photodynamic therapy (8.5 percent) and esophagectomy (9 percent).14 Additionally, a Cochrane review that included 16 studies and 1,074 patients found good evidence that photodynamic therapy, argon plasma coagulation, and radiofrequency ablation all induced regression of Barrett's esophagus and dysplasia. Results favored radiofrequency ablation compared with photodynamic therapy because of fewer complications and effective eradication of Barrett's esophagus (82 percent) and dysplasia (94 percent).15 With surgery, operative mortality for esophagectomy can be improved by limiting this procedure to hospitals that perform at least 20 procedures annually.16
Endoscopic surveillance in patients with Barrett's esophagus is supported by multiple retrospective studies demonstrating statistically significant survival advantage in patients with cancers detected by endoscopic surveillance based on an average absolute risk reduction of 58 percent across all studies (number needed to treat = 1.7).4 According to the American College of Gastroenterology's Practice Guidelines, patients diagnosed with Barrett's esophagus (without dysplasia) should receive two upper endoscopies within one year and then every three years thereafter. More frequent intervals are recommended if dysplasia is present.4
One-time screening with targeted surveillance in white men 50 years of age with gastroesophageal reflux disease is cost-effective according to a recent cost-utility analysis.17 The model yielded an incremental cost-effectiveness ratio of $10,440 per quality-adjusted life-year saved as long as subsequent surveillance was limited to patients with Barrett's esophagus and dysplasia.17 This estimate was sensitive to the rate of progression to esophageal adenocarcinoma, but would hold true based on the annual risk of progression to esophageal adenocarcinoma of 0.4 percent and rates of malignant transformation in high-grade dysplasia found in the Danish cohort study described above.11 In addition, newer ultrathin endoscopy, which can be performed in physicians' offices without sedation, has the potential to significantly decrease the cost of screening and is well tolerated by patients.18
Although screening and surveillance for Barrett's esophagus is controversial, the latest evidence supports this approach to decrease morbidity and mortality. Carefully evaluating patients with reflux symptoms and stratifying them based on known risk factors (Table 15–10) has the potential to result in decreased cases of fatal esophageal adenocarcinoma in the United States.
1. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005;97(2):142–146.
2. Gerson LB, Triadafilopoulos G. Screening for esophageal adenocarcinoma: an evidence-based approach. Am J Med. 2002;113(6):499–505.
3. Shaheen N, Ransohoff DF. Gastroesophageal reflux, barrett esophagus, and esophageal cancer: scientific review. JAMA. 2002;287(15):1972–1981.
4. Wang KK, Sampliner RE; Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus. Am J Gastroenterol. 2008;103(3):788–797.
5. Smith KJ, O'Brien SM, Smithers BM, et al. Interactions among smoking, obesity, and symptoms of acid reflux in Barrett's esophagus. Cancer Epidemiol Biomarkers Prev. 2005;14(11 pt 1):2481–2486.
6. Lieberman DA, Oehlke M, Helfand M; Gastroenterology Outcomes Research Group in Endoscopy. Risk factors for Barrett's esophagus in community-based practice. GORGE consortium. Am J Gastroenterol. 1997;92(8):1293–1297.
7. Eloubeidi MA, Provenzale D. Clinical and demographic predictors of Barrett's esophagus among patients with gastroesophageal reflux disease: a multivariable analysis in veterans. J Clin Gastroenterol. 2001;33(4):306–309.
8. El-Serag HB, Kvapil P, Hacken-Bitar J, Kramer JR. Abdominal obesity and the risk of Barrett's esophagus. Am J Gastroenterol. 2005;100(10):2151–2156.
9. Conio M, Filiberti R, Blanchi S, et al.; Gruppo Operativo per lo Studio delle Precancerosi Esofagee (GOSPE). Risk factors for Barrett's esophagus: a case-control study. Int J Cancer. 2002;97(2):225–229.
10. Gerson LB, Edson R, Lavori PW, Triadafilopoulos G. Use of a simple symptom questionnaire to predict Barrett's esophagus in patients with symptoms of gastroesophageal reflux. Am J Gastroenterol. 2001;96(7):2005–2012.
11. de Jonge PJ, van Blankenstein M, Looman CW, Casparie MK, Meijer GA, Kuipers EJ. Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study. Gut. 2010;59(8):1030–1036.
12. Rastogi A, Puli S, El-Serag HB, Bansal A, Wani S, Sharma P. Incidence of esophageal adenocarcinoma in patients with Barrett's esophagus and high-grade dysplasia: a meta-analysis. Gastrointest Endosc. 2008;67(3):394–398.
13. El-Serag HB, Aguirre TV, Davis S, Kuebeler M, Bhattacharyya A, Sampliner RE. Proton pump inhibitors are associated with reduced incidence of dysplasia in Barrett's esophagus. Am J Gastroenterol. 2004;99(10):1877–1883.
14. Prasad GA, Wang KK, Buttar NS, et al. Long-term survival following endoscopic and surgical treatment of high-grade dysplasia in Barrett's esophagus. Gastroenterology. 2007;132(4):1226–1233.
15. Rees JR, Lao-Sirieix P, Wong A, Fitzgerald RC. Treatment for Barrett's oesophagus. Cochrane Database Syst Rev. 2010;(1):CD004060.
16. Birkmeyer JD, Siewers AE, Finlayson EV, et al. Hospital volume and surgical mortality in the United States. N Engl J Med. 2002;346(15):1128–1137.
17. Inadomi JM, Sampliner R, Lagergren J, Lieberman D, Fendrick AM, Vakil N. Screening and surveillance for Barrett esophagus in high-risk groups: a cost-utility analysis. Ann Intern Med. 2003;138(3):176–186.
18. Wilkins T, Gillies RA. Office-based unsedated ultrathin esophagoscopy in a primary care setting. Ann Fam Med. 2005;3(2):126–130.
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