Current management of Barrett esophagus and esophageal adenocarcinoma

Article Type

Article

Changed

Fri, 11/01/2019 - 16:59

Display Headline

Current management of Barrett esophagus and esophageal adenocarcinoma

Author(s)

Tavankit Singh, MD

Vedha Sanghi, MD

Prashanthi N. Thota, MD, FACG

All cases of esophageal adenocarcinoma are thought to arise from Barrett esophagus.¹ But most cases of Barrett esophagus go undiagnosed. And Barrett esophagus is seen in 5% to 15% of patients with gastroesophageal reflux disease.² These facts clearly emphasize the need for screening. Here, we review the rationale and recommendations for screening and surveillance, as well as the range of treatment options.

SCOPE OF THE PROBLEM

The American Cancer Society estimated there were 17,290 new cases of esophageal cancer and 15,850 deaths from it in the United States in 2018.³ Of the 2 main histologic types of esophageal cancer, adenocarcinoma and squamous cell cancer, adenocarcinoma is more common in the United States.

The precursor lesion is Barrett esophagus, defined as an extension of salmon-colored mucosa at least 1 cm into the tubular esophagus proximal to the gastroesophageal junction, with biopsy confirmation of intestinal metaplasia.⁴

The natural course of progression to dysplasia and cancer in Barrett esophagus is unknown but is thought to be stepwise, from no dysplasia to low-grade dysplasia to high-grade dysplasia and cancer, and the cancer risk depends on the degree of dysplasia: the annual risk is 0.33% if there is no dysplasia, 0.54% with low-grade dysplasia, and 7% with high-grade dysplasia.⁴

Although all cases of esophageal adenocarcinoma are thought to arise from Barrett esophagus,¹ more than 90% of patients with newly diagnosed esophageal adenocarcinoma do not have a prior diagnosis of Barrett esophagus.⁵ Therefore, there is a substantial unmet need to expand screening for Barrett esophagus in people at risk.

GASTROESOPHAGEAL REFLUX DISEASE IS A RISK FACTOR FOR CANCER

The rationale behind screening is that detecting Barrett esophagus early and intervening in a timely manner in patients at higher risk of developing adenocarcinoma will decrease mortality.

Chronic gastroesophageal reflux disease is a strong risk factor for esophageal adenocarcinoma (odds ratio [OR] 7.7, 95% confidence interval [CI] 5.3–11.4), and the risk increases when symptoms are long-standing (> 20 years) or severe (OR 43.5, 95% CI 18.3–103.5) or occur daily (OR 5.5, 95% CI 3.2–9.3).⁶

Reflux symptoms are scored as follows:

Heartburn only, 1 point
Regurgitation only, 1 point
Heartburn with regurgitation, 1.5 points
Nightly symptoms (2 points if yes, 0 if no)
Symptoms once a week, 0 points; 2 to 6 times a week, 1 point; 7 to 15 times a week, 2 points; more than 15 times a week, 3 points.⁶

A score of 4.5 or higher indicates severe reflux disease. However, it is worth noting that the annual incidence of esophageal adenocarcinoma in patients with long-term gastroesophageal reflux disease is less than 0.001%.⁷

RISK FACTORS FOR BARRETT ESOPHAGUS

Risk factors for Barrett esophagus include:

Male sex. Barrett esophagus is more prevalent in men than in women, at a ratio of 2 to 1; but in individuals under age 50, the ratio is 4 to 1.⁸

Age 50 or older. Barrett esophagus is usually diagnosed in the sixth to seventh decade of life, and the prevalence increases from 2.1% in the third decade to 9.3% in the sixth decade.⁹

White race. It is more prevalent in whites than in blacks (5.0% vs 1.5%, P < .0001).¹⁰

Central obesity. Waist circumference is an independent risk factor: every 5-cm increase carries an OR of 1.14 (95% CI 1.03–1.27, P = .02).¹¹

Cigarette smoking increases the risk of Barrett esophagus (OR 1.42; 95% CI 1.15–1.76).¹²

A family history of Barrett esophagus or esophageal adenocarcinoma is a strong risk factor (OR 12, 95% CI 3.3–44.8). In 1 study, the risk in first- and second-degree relatives of patients with Barrett esophagus was 24%, compared with 5% in a control population (P < .005).¹³

SCREENING GUIDELINES AND DRAWBACKS

Figure 1. Four-quadrant biopsies are taken every 2 cm, plus at any mucosal irregularities in salmon-colored mucosa above the gastroesophageal junction.

American College of Gastroenterology guidelines recommend screening for Barrett esophagus in men who have chronic reflux disease (> 5 years) or frequent symptoms (weekly or more often), and 2 or more risk factors.⁴ In women, screening is recommended only in the presence of multiple risk factors.⁴

The standard screening method is esophagogastroduodenoscopy with sedation, with careful visual inspection and 4-quadrant biopsies every 2 cm using the Seattle protocol, ie, including biopsy of any mucosal irregularities in salmon-colored mucosa above the gastroesophageal junction (Figure 1).⁴

Endoscopic screening is cost-effective, costing $10,440 per quality-adjusted life-year saved, which is well below the accepted threshold of less than $100,000.¹⁴ However, it is still expensive, invasive, and not ideal for screening large populations.

Less-invasive methods under study

Less-invasive, less-expensive methods being tested for mass screening include:

Unsedated transnasal endoscopy. Done with only topical anesthesia, it has high diagnostic accuracy and is quicker and more cost-effective than standard esophagogastroduodenoscopy, with fewer adverse effects. However, the procedure has not yet gained widespread acceptance for regular use by gastroenterologists.¹⁵

A swallowable sponge. Another promising test is cell collection using the Cytosponge Cell Collection Device (Medtronic, Minneapolis, MN). An encapsulated compressed sponge with a string attached is swallowed; in the stomach, the capsule dissolves, and the sponge expands and is then withdrawn using the attached string. The obtained cytology sample from the lower esophagus is then tested for trefoil factor 3, a protein biomarker for Barrett esophagus.¹⁶

A retractable balloon. The EsoCheck Cell Collection Device is a retractable balloon attached to a string. When swallowed, it gathers distal esophageal cells for detecting methylated DNA markers for Barrett esophagus.¹⁷

Esophageal capsule endoscopy uses a camera to visualize the esophagus, but lacks the ability to obtain biopsy samples.

Other screening methods are being tested, although data are limited. Liquid biopsy uses a blood sample to detect microRNAs that are dysregulated in cancer. The “electronic nose” is a device that detects exhaled volatile organic compounds altered in Barrett esophagus. Another test involves taking an oral wash sample to study the oral microbiome for a pattern associated with adenocarcinoma.^18–21

SURVEILLANCE: WHAT’S INVOLVED, WHAT’S AVAILABLE

Surveillance in Barrett esophagus aims to detect premalignant changes or early-stage adenocarcinoma to provide longer survival and lower cancer-related mortality. Recent evidence suggests that patients with esophageal adenocarcinoma that is diagnosed in a Barrett esophagus surveillance program have an earlier stage of disease and therefore a survival benefit.²²

Patient education is essential

Before enrolling a patient in a surveillance program, the clinician should explain the risks, benefits, and limitations, the importance of periodic endoscopy, and the possible eventual need for endoscopic therapy or surgery.

The endoscopic procedure

Table 1. Surveillance guidelines for Barrett esophagus

Surveillance involves examination by high-definition white-light endoscopy, with random 4-quadrant biopsies every 2 cm (or every 1 cm in patients with a history of dysplasia) and biopsy of any mucosal irregularity (nodule, ulcer, or other visible lesion). The degree of dysplasia determines the frequency of follow-up surveillance intervals and the need for endoscopic eradication therapy, as presented in professional society guidelines (Table 1).^4,23,24

Advanced methods for detecting dysplasia

Newer endoscopic surveillance techniques include dye-based chromoendoscopy, narrow-band imaging, confocal laser endomicroscopy, volumetric laser endomicroscopy, and wide-area transepithelial sampling with computer-assisted 3-dimensional analysis. All these techniques are used to increase the detection of dysplasia. Of these, dye-based chromoendoscopy, narrow-band imaging, and confocal laser endomicroscopy meet current criteria of the American Society for Gastrointestinal Endoscopy for preservation and incorporation of valuable endoscopic innovations.²³

MANAGEMENT OF NONDYSPLASTIC BARRETT ESOPHAGUS

A proton pump inhibitor (PPI) is recommended to control reflux symptoms in patients with nondysplastic Barrett esophagus. But it is important to counsel patients on additional ways to protect against esophageal adenocarcinoma, such as:

Low to moderate alcohol consumption
Regular physical activity
Increased dietary intake of fruits, vegetables, folate, fiber, beta-carotene, and vitamin C
Weight control
Smoking cessation.²⁵

Surveillance endoscopy with 4-quadrant biopsies at 2-cm intervals is recommended every 3 to 5 years (Table 1).

DOES CHEMOPREVENTION HAVE A ROLE?

Chemoprevention is an exciting area of research in preventing progression to adenocarcinoma in patients with Barrett esophagus. Various drugs such as aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), PPIs, metformin, and statins have been studied.

Aspirin

Aspirin has been shown to prevent development of Barrett esophagus in patients with reflux disease,²⁶ but more studies are needed to validate those findings.

PPIs

Gastroesophageal reflux disease is a primary risk factor for esophageal adenocarcinoma, and gastric acid suppression with PPIs reduces cancer risk. PPI therapy is associated with a 71% decrease in the risk of high-grade dysplasia and adenocarcinoma in patients with Barrett esophagus (OR 0.29, 95% CI 0.12–0.79).²⁷ Long-term therapy (> 2 to 3 years) has a higher protective effect (adjusted OR 0.45, 95% CI 0.19–1.06) than short-term therapy (< 2 to 3 years) (adjusted OR 1.09, 95% CI 0.47–2.56).²⁷

NSAIDs

NSAIDs, including aspirin, have been associated with decreased risk of colon, stomach, lung, breast, and esophageal cancer due to their potential to inhibit cyclooxygenase 2 (COX-2) enzymes.

A meta-analysis demonstrated that aspirin and NSAIDs led to a 32% reduction in the risk of adenocarcinoma (OR 0.68, 95% CI 0.56–0.83). The benefit was even greater if the drug was taken daily or more frequently (OR 0.56, 95% CI 0.43–0.73, P < .001) or was taken for 10 or more years (OR 0.63, 95% CI 0.45–0.90, P = .04).²⁸

PPI plus aspirin

The best evidence for the role of PPIs and aspirin in reducing the risk of dysplasia comes from the Aspirin and Esomeprazole Chemoprevention in Barrett’s Metaplasia Trial.²⁹ This randomized, controlled trial compared 4 regimens consisting of esomeprazole (a PPI) in either a high dose (40 mg twice daily) or a low dose (20 mg once daily) plus either aspirin (300 or 320 mg per day) or no aspirin in 2,557 patients with Barrett esophagus. The composite end point was the time to all-cause mortality, adenocarcinoma, or high-grade dysplasia.

At a median follow-up of 8.9 years, the combination of high-dose esomeprazole plus aspirin had the strongest effect compared with low-dose esomeprazole without aspirin (time ratio 1.59, 95% CI 1.14–2.23, P = .0068). The number needed to treat was 34 for esomeprazole and 43 for aspirin.²⁹

Based on these data, we can conclude that aspirin and PPIs can prevent dysplasia and all-cause mortality in Barrett esophagus.

Metformin: No evidence of benefit

Metformin was studied as a protective agent against obesity-associated cancers including esophageal adenocarcinoma, as it reduces insulin levels.

In a randomized controlled trial³⁰ in 74 patients with Barrett esophagus, metformin (starting at 500 mg daily, increasing to 2,000 mg/day by week 4) was compared with placebo. At 12 weeks, the percent change in esophageal levels of the biomarker pS6K1—an intracellular mediator of insulin and insulin-like growth factor activation in Barrett epithelium—did not differ significantly between the 2 groups (1.4% with metformin vs −14.7% with placebo; 1-sided P = .80). This suggested that metformin did not significantly alter proliferation or apoptosis in Barrett epithelium, despite reducing serum insulin levels and insulin resistance. Thus, metformin did not demonstrate a chemoprotective effect in preventing the progression of Barrett esophagus to adenocarcinoma.

Vitamin D: No evidence of benefit

Vitamin D affects genes regulating proliferation, apoptosis, and differentiation, and has therefore been studied as a potential antineoplastic agent. Its deficiency has also been associated with increased risk of esophageal adenocarcinoma. However, its efficacy in chemoprevention is unclear.³¹

One study found no association between serum 25-hydroxyvitamin D levels and prevalence of dysplasia in Barrett esophagus (P = .90). An increase in vitamin D levels had no effect on progression to dysplasia or cancer (for every 5-nmol/L increase from baseline, hazard ratio 0.98, P = .62).³²

In another study, supplementation with vitamin D₃ (cholecalciferol 50,000 IU weekly) plus a PPI for 12 weeks significantly improved the serum 25-hydroxyvitamin D levels without significant changes in gene expression from Barrett epithelium.³³ These findings were confirmed in a meta-analysis that showed no consistent association between vitamin D exposure and risk of esophageal neoplasm.³⁴

Thus, there is currently no evidence to support vitamin D for chemoprevention in Barrett esophagus or esophageal adenocarcinoma.

Statins

In addition to lowering cholesterol, statins have antiproliferative, pro-apoptotic, anti-angiogenic, and immunomodulatory effects that prevent cancer, leading to a 41% reduction in the risk of adenocarcinoma in patients with Barrett esophagus in one study (adjusted OR 0.59, 95% CI 0.45–0.78); the number needed to treat with statins to prevent 1 case of adenocarcinoma was 389.³⁵

A meta-analysis also showed that statin use was associated with a lower risk of progression of Barrett esophagus (OR 0.48, 95% CI 0.31–0.73).³⁶

In general, statins appear promising for chemoprevention, but more study is needed.

When is chemoprevention appropriate?

Chemoprevention is not recommended for all patients with Barrett esophagus, given that the condition affects 1% to 2% of the US adult population, and very few patients have progression to esophageal adenocarcinoma. Rather, chemoprevention may be considered in patients with Barrett esophagus and multiple risk factors for adenocarcinoma.

INDEFINITE DYSPLASIA

In Barrett esophagus with indefinite dysplasia, either the epithelial abnormalities are insufficient for a diagnosis of dysplasia, or the nature of the epithelial abnormalities is uncertain due to inflammation or technical difficulties with specimen processing. The risk of high-grade dysplasia or cancer within 1 year of the diagnosis of indefinite dysplasia varies between 1.9% and 15%.³⁷ The recommendation for management is to optimize acid-suppressive therapy for 3 to 6 months and then to repeat esophagogastroduodenoscopy. If indefinite dysplasia is noted again, repeat endoscopy in 12 months is recommended.²

ENDOSCOPIC ERADICATION: AN OVERVIEW

Because dysplasia in Barrett esophagus carries a high risk of progression to cancer, the standard of care is endoscopic mucosal resection of visible lesions, followed by ablation of the flat mucosa, with the aim of achieving complete eradication of intestinal metaplasia.^4,38 The initial endoscopic treatment is followed by outpatient sessions every 8 to 10 weeks until the dysplasia is eradicated. A key part of treatment during this time is maximal acid suppression with a PPI twice daily and a histamine-2 blocker at night. In rare cases, fundoplication is required to control reflux refractory to medical therapy.

After eradication is confirmed, continued surveillance is necessary, as recurrences have been reported at a rate of 4.8% per year for intestinal metaplasia, and 2% per year for dysplasia.³⁹

Current endoscopic resection techniques

Figure 2. A: Endoscopic picture of Barrett esophagus with arrow pointing to nodule. B: After endoscopic mucosal resection of nodule. C: Barrett esophagus before radiofrequency ablation. D: Barrett esophagus after ablation.

Endoscopic resection techniques include mucosal resection, submucosal dissection, radiofrequency ablation, cryotherapy, argon plasma coagulation, and photodynamic therapy (Figure 2).

In mucosal resection, the lesion is either suctioned into a band ligator, after which a band is placed around the lesion, or suctioned into a cap fitted at the end of the endoscope, after which the lesion is removed using a snare.

In submucosal dissection, a liquid is injected into the submucosa to lift the lesion, making it easier to remove. The procedure is technically complex and requires additional training.

In radiofrequency ablation, a special catheter is passed through the endoscope to ablate the affected epithelium by thermal injury. Argon plasma coagulation works in a similar way, but uses ionized argon gas to induce thermal coagulation of metaplastic epithelium.

Cryotherapy produces cellular injury by rapid freezing and thawing of tissue using a cryogen such as liquid nitrogen or nitrous oxide.

In photodynamic therapy, a photosensitizer (porfimer sodium) is administered and taken up preferentially by metaplastic epithelium; it is then activated by transmission of red light using the endoscope, leading to destruction of the metaplastic epithelium.

Of the different techniques, radiofrequency ablation has the most evidence for efficacy and hence is the most commonly used.

All of these procedures are generally well tolerated and have favorable side-effect profiles. After radiofrequency ablation with or without mucosal resection, esophageal strictures are noted in 5.6% of patients, and bleeding and perforation occur rarely (1% and 0.6% of patients, respectively).⁴⁰ Submucosal dissection is associated with a higher rate of complications such as stricture formation (11% of patients) and bleeding or perforation (1.5% of patients).⁴¹

LOW-GRADE DYSPLASIA: RECOMMENDED MANAGEMENT

Most patients with low-grade dysplasia (73%) are down-staged to nondysplastic Barrett esophagus or to indefinite for dysplasia after review by expert pathologists.⁴² Patients with confirmed and persistent low-grade dysplasia are at higher risk of progression.⁴³

Once low-grade dysplasia is confirmed by a second gastrointestinal pathologist, the patient should undergo endoscopic ablation. A landmark study by Shaheen et al⁴⁴ demonstrated the benefit of radiofrequency ablation in achieving complete eradication of dysplasia (90.5% vs 22.7% for a sham procedure) and complete eradication of intestinal metaplasia (77.4% vs 2.3% for a sham procedure). In another trial of 136 patients with low-grade dysplasia followed for 3 years, Phoa et al⁴⁵ demonstrated that radiofrequency ablation reduced the rate of progression to high-grade dysplasia by 25% and to adenocarcinoma by 7.4% compared with endoscopic surveillance.

Patients with confirmed low-grade dysplasia who do not undergo eradication therapy should have surveillance endoscopy every 6 to 12 months (Table 1).

HIGH-GRADE DYSPLASIA: RECOMMENDED MANAGEMENT

As with low-grade dysplasia, the diagnosis of high-grade dysplasia needs to be confirmed by a second pathologist with gastrointestinal expertise. In the past, the treatment was esophagectomy, but due to lower morbidity and equivalent efficacy of radiofrequency ablation,⁴⁶ the current treatment of choice is endoscopic mucosal resection of raised lesions, followed by radiofrequency ablation of the entire affected segment.

In the study by Shaheen et al,⁴⁴ 42 patients with high-grade dysplasia were randomized to radiofrequency ablation and 21 to a sham procedure, and 81% of ablation patients achieved complete eradication of dysplasia vs 19% with the sham procedure. Eradication of intestinal metaplasia was achieved in 77% of ablation patients vs 2% of patients with the sham therapy. Results of 3-year follow-up from the same cohort showed complete eradication of dysplasia in 98% and of intestinal metaplasia in 91%.⁴⁷

Endoscopic eradication therapy is recommended for all patients with Barrett esophagus and high-grade dysplasia without a life-limiting comorbidity. Alternatively, surveillance every 3 months is an option if the patient does not wish to undergo eradication therapy. Radiofrequency ablation is more cost-effective than esophagectomy or endoscopic surveillance followed by treatment once patients develop adenocarcinoma.^48,49

EARLY ESOPHAGEAL ADENOCARCINOMA: RECOMMENDED MANAGEMENT

Adenocarcinoma limited to the mucosa and without evidence of nodal involvement can be resected endoscopically. In patients with localized cancer, mucosal resection is done not only for therapeutic purposes but also for staging. Ideal management is multidisciplinary, including a gastroenterologist, thoracic surgeon, oncologist, pathologist, and radiation oncologist.

If lesions have features suggesting submucosal invasion or are greater than 1.5 cm in size, or if it is difficult to separate (ie, lift) the mucosa from the submucosal layer with injection of saline, then submucosal dissection is recommended.⁵⁰ Because of the risk of metachronous lesions, ablation of the remaining Barrett esophagus mucosa is recommended after resection of cancer.

Endoscopic eradication is highly effective and durable for the treatment of intramucosal esophageal adenocarcinoma. In a study of 1,000 patients, 963 patients (96.3%) had achieved a complete response; 12 patients (3.7%) underwent surgery after eradication failed during a follow-up of almost 5 years.⁵¹ Metachronous lesions or recurrence of cancer developed during the follow-up period in 140 patients (14.5%) but were successfully treated endoscopically in 115, resulting in a long-term complete remission rate of 93.8%.

POSTABLATION MANAGEMENT

Because of the risk of recurrence of dysplasia after ablation, long-term PPI therapy and surveillance are recommended.

Surveillance endoscopy involves 4-quadrant biopsies taken every 1 cm from the entire length of segment where Barrett esophagus had been seen before ablation.

The timing of surveillance intervals depends on the preablation grade of dysplasia. For low-grade dysplasia, the recommendation is every 6 months for the first year after ablation and, if there is no recurrence of dysplasia, annually after that.² After treatment of high-grade dysplasia or intramucosal adenocarcinoma, the recommendation is every 3 months for the first year, every 6 months in the second year, and then annually.²

References

Mendes de Almeida JC, Chaves P, Pereira AD, Altorki NK. Is Barrett’s esophagus the precursor of most adenocarcinomas of the esophagus and cardia? A biochemical study. Ann Surg 1997; 226(6):725–733. pmid:9409571
Westhoff B, Brotze S, Weston A, et al. The frequency of Barrett’s esophagus in high-risk patients with chronic GERD. Gastrointest Endosc 2005; 61(2):226–231. pmid:15729230
National Cancer Institute. Cancer stat facts: esophageal cancer. https://seer.cancer.gov/statfacts/html/esoph.html. Accessed August 6, 2019.
Shaheen NJ, Falk GW, Iyer PG, Gerson LB; American College of Gastroenterology. ACG clinical guideline: diagnosis and management of Barrett’s esophagus. Am J Gastroenterol 2016; 111(1):30–50. doi:10.1038/ajg.2015.322
Dulai GS, Guha S, Kahn KL, Gornbein J, Weinstein WM. Preoperative prevalence of Barrett’s esophagus in esophageal adenocarcinoma: a systematic review. Gastroenterology 2002; 122(1):26–33. pmid:11781277
Lagergren J, Bergström R, Lindgren A, Nyrén O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999; 340(11):825–831. doi:10.1056/NEJM199903183401101
Shaheen N, Ransohoff DF. Gastroesophageal reflux, Barrett esophagus, and esophageal cancer: scientific review. JAMA 2002; 287(15):1972–1981. pmid:11960540
van Blankenstein M, Looman CW, Johnston BJ, Caygill CP. Age and sex distribution of the prevalence of Barrett’s esophagus found in a primary referral endoscopy center. Am J Gastroenterol 2005; 100(3):568–576.
Rubenstein JH, Mattek N, Eisen G. Age- and sex-specific yield of Barrett’s esophagus by endoscopy indication. Gastrointest Endosc 2010; 71(1):21–27. doi:10.1016/j.gie.2009.06.035
Wang A, Mattek NC, Holub JL, Lieberman DA, Eisen GM. Prevalence of complicated gastroesophageal reflux disease and Barrett’s esophagus among racial groups in a multi-center consortium. Dig Dis Sci 2009; 54(5):964–971. doi:10.1007/s10620-009-0742-3
Kubo A, Cook MB, Shaheen NJ, et al. Sex-specific associations between body mass index, waist circumference and the risk of Barrett’s esophagus: a pooled analysis from the international BEACON consortium. Gut 2013; 62(12):1684–1691. doi:10.1136/gutjnl-2012-303753
Andrici J, Cox MR, Eslick GD. Cigarette smoking and the risk of Barrett’s esophagus: a systematic review and meta-analysis. J Gastroenterol Hepatol 2013; 28(8):1258–1273. doi:10.1111/jgh.12230
Chak A, Lee T, Kinnard MF, et al. Familial aggregation of Barrett’s esophagus, esophageal adenocarcinoma, and esophagogastric junctional adenocarcinoma in Caucasian adults. Gut 2002; 51(3):323–328. pmid:12171951
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. pmid:12558356
Jobe BA, Hunter JG, Chang EY, et al. Office-based unsedated small-caliber endoscopy is equivalent to conventional sedated endoscopy in screening and surveillance for Barrett’s esophagus: a randomized and blinded comparison. Am J Gastroenterol 2006; 101(12):2693–2703.
Ross-Innes CS, Chettouh H, Achilleos A, et al; BEST2 study group. Risk stratification of Barrett’s esophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study. Lancet Gastroenterol Hepatol 2017; 2(1):23–31. doi:10.1016/S2468-1253(16)30118-2
Moinova HR, LaFramboise T, Lutterbaugh JD, et al. Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett’s esophagus. Sci Transl Med 2018; 10(424). pii:eaao5848. doi:10.1126/scitranslmed.aao5848
Chan DK, Zakko L, Visrodia KH, et al. Breath testing for Barrett’s esophagus using exhaled volatile organic compound profiling with an electronic nose device. Gastroenterology 2017; 152(1):24–26. doi:10.1053/j.gastro.2016.11.001
Kumar S, Huang J, Abbassi-Ghadi N, et al. Mass spectrometric analysis of exhaled breath for the identification of volatile organic compound biomarkers in esophageal and gastric adenocarcinoma. Ann Surg 2015; 262(6):981–990. doi:10.1097/SLA.0000000000001101
Peters BA, Wu J, Pei Z, et al. Oral microbiome composition reflects prospective risk for esophageal cancers. Cancer Res 2017; 77(23):6777–6787. doi:10.1158/0008-5472.CAN-17-1296
Mallick R, Patnaik SK, Wani S, Bansal A. A systematic review of esophageal microrna markers for diagnosis and monitoring of Barrett’s esophagus. Dig Dis Sci 2016; 61(4):1039–1050. doi:10.1007/s10620-015-3959-3
Codipilly DC, Chandar AK, Singh S, et al. The effect of endoscopic surveillance in patients with Barrett’s esophagus: a systematic review and meta-analysis. Gastroenterology 2018; 154(8):2068–2086.e5. doi:10.1053/j.gastro.2018.02.022
ASGE Technology Committee; Thosani N, Abu Dayyeh BK, Sharma P, et al. ASGE Technology Committee systematic review and meta-analysis assessing the ASGE preservation and incorporation of valuable endoscopic innovations thresholds for adopting real-time imaging-assisted endoscopic targeted biopsy during endoscopic surveillance of Barrett’s esophagus. Gastrointest Endosc 2016; 83(4):684–698.e7. doi:10.1016/j.gie.2016.01.007
Spechler SJ, Sharma P, Souza RF, Inadomi JM, Shaheen NJ; American Gastroenterological Association. American Gastroenterological Association technical review on the management of Barrett’s esophagus. Gastroenterology 2011; 140(3):e18–e52. doi:10.1053/j.gastro.2011.01.031
Castro C, Peleteiro B, Lunet N. Modifiable factors and esophageal cancer: a systematic review of published meta-analyses. J Gastroenterol 2018; 53(1):37–51. doi:10.1007/s00535-017-1375-5
Omer ZB, Ananthakrishnan AN, Nattinger KJ, et al. Aspirin protects against Barrett’s esophagus in a multivariate logistic regression analysis. Clin Gastroenterol Hepatol 2012; 10(7):722–727. doi:10.1016/j.cgh.2012.02.031
Singh S, Garg SK, Singh PP, Iyer PG, El-Serag HB. Acid-suppressive medications and risk of esophageal adenocarcinoma in patients with Barrett’s esophagus: a systematic review and meta-analysis. Gut 2014; 63(8):1229–1237. doi:10.1136/gutjnl-2013-305997
Liao LM, Vaughan TL, Corley DA, et al. Nonsteroidal anti-inflammatory drug use reduces risk of adenocarcinomas of the esophagus and esophagogastric junction in a pooled analysis. Gastroenterology 2012; 142(3):442–452.e5. doi:10.1053/j.gastro.2011.11.019
Jankowski JAZ, de Caestecker J, Love SB, et al; AspECT Trial Team. Esomeprazole and aspirin in Barrett’s esophagus (AspECT): a randomised factorial trial. Lancet 2018; 392(10145):400–408. doi:10.1016/S0140-6736(18)31388-6
Chak A, Buttar NS, Foster NR, et al; Cancer Prevention Network. Metformin does not reduce markers of cell proliferation in esophageal tissues of patients with Barrett’s esophagus. Clin Gastroenterol Hepatol 2015; 13(4):665–672.e1–e4. doi:10.1016/j.cgh.2014.08.040
Rouphael C, Kamal A, Sanaka MR, Thota PN. Vitamin D in esophageal cancer: is there a role for chemoprevention? World J Gastrointest Oncol 2018; 10(1):23–30. doi:10.4251/wjgo.v10.i1.23
Thota PN, Kistangari G, Singh P, et al. Serum 25-hydroxyvitamin D levels and the risk of dysplasia and esophageal adenocarcinoma in patients with Barrett’s esophagus. Dig Dis Sci 2016; 61(1):247–254. doi:10.1007/s10620-015-3823-5
Cummings LC, Thota PN, Willis JE, et al. A nonrandomized trial of vitamin D supplementation for Barrett’s esophagus. PLoS One 2017;1 2(9):e0184928. doi:10.1371/journal.pone.0184928
Zgaga L, O’Sullivan F, Cantwell MM, Murray LJ, Thota PN, Coleman HG. Markers of vitamin D exposure and esophageal cancer risk: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2016; 25(6):877–886. doi:10.1158/1055-9965.EPI-15-1162
Singh S, Singh AG, Singh PP, Murad MH, Iyer PG. Statins are associated with reduced risk of esophageal cancer, particularly in patients with Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2013; 11(6):620–629. doi:10.1016/j.cgh.2012.12.036
Krishnamoorthi R, Singh S, Ragunathan K, et al. Factors associated with progression of Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2018; 6(7):1046–1055.e8. doi:10.1016/j.cgh.2017.11.044
Thota PN, Kistangari G, Esnakula AK, Gonzalo DH, Liu XL. Clinical significance and management of Barrett’s esophagus with epithelial changes indefinite for dysplasia. World J Gastrointest Pharmacol Ther 2016; 7(3):406–411. doi:10.4292/wjgpt.v7.i3.406
Bennett C, Vakil N, Bergman J, et al. Consensus statements for management of Barrett’s dysplasia and early-stage esophageal adenocarcinoma, based on a Delphi process. Gastroenterology 2012; 143(2):336–346. doi:10.1053/j.gastro.2012.04.032
Desai M, Saligram S, Gupta N, et al. Efficacy and safety outcomes of multimodal endoscopic eradication therapy in Barrett’s esophagus-related neoplasia: a systematic review and pooled analysis. Gastrointest Endosc 2017; 85(3):482–495.e4. doi:10.1016/j.gie.2016.09.022
Qumseya BJ, Wani S, Desai M, et al. Adverse events after radiofrequency ablation in patients with Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2016; 14(8):1086–1095.e6. doi:10.1016/j.cgh.2016.04.001
Yang D, Zou F, Xiong S, Forde JJ, Wang Y, Draganov PV. Endoscopic submucosal dissection for early Barrett’s neoplasia: a meta-analysis. Gastrointest Endosc 2018; 87(6):1383–1393. doi:10.1016/j.gie.2017.09.038
Duits LC, Phoa KN, Curvers WL, et al. Barrett’s esophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel. Gut 2015; 64(5):700–706. doi:10.1136/gutjnl-2014-307278
Duits LC, van der Wel MJ, Cotton CC, et al. Patients with Barrett’s esophagus and confirmed persistent low-grade dysplasia are at increased risk for progression to neoplasia. Gastroenterology 2017; 152(5):993–1001.e1. doi:10.1053/j.gastro.2016.12.008
Shaheen NJ, Sharma P, Overholt BF, et al. Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med 2009; 360(22):2277–2288. doi:10.1056/NEJMoa0808145
Phoa KN, van Vilsteren FG, Weusten BL, et al. Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia: a randomized clinical trial. JAMA 2014; 311(12):1209–1217. doi:10.1001/jama.2014.2511
Hu Y, Puri V, Shami VM, Stukenborg GJ, Kozower BD. Comparative effectiveness of esophagectomy versus endoscopic treatment for esophageal high-grade dysplasia. Ann Surg 2016; 263(4):719–726. doi:10.1097/SLA.0000000000001387
Shaheen NJ, Overholt BF, Sampliner RE, et al. Durability of radiofrequency ablation in Barrett’s esophagus with dysplasia. Gastroenterology 2011; 141(2):460–468. doi:10.1053/j.gastro.2011.04.061
Hur C, Choi SE, Rubenstein JH, et al. The cost effectiveness of radiofrequency ablation for Barrett’s esophagus. Gastroenterology 2012; 143(3):567–575. doi:10.1053/j.gastro.2012.05.010
Boger PC, Turner D, Roderick P, Patel P. A UK-based cost-utility analysis of radiofrequency ablation or oesophagectomy for the management of high-grade dysplasia in Barrett’s esophagus. Aliment Pharmacol Ther 2010; 32(11-12):1332–1342. doi:10.1111/j.1365-2036.2010.04450.x
Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T, et al. Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 2015; 47(9):829–854. doi:10.1055/s-0034-1392882
Pech O, May A, Manner H, et al. Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus. Gastroenterology 2014; 146(3):652–660.e1. doi:10.1053/j.gastro.2013.11.006

Article PDF

724.pdf

Author and Disclosure Information

Tavankit Singh, MD
Department of Gastroenterology and Hepatology, Cleveland Clinic

Vedha Sanghi, MD
Department of Internal Medicine, Cleveland Clinic; Clinical Instructor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Prashanthi N. Thota, MD, FACG
Medical Director, Esophageal Center, Digestive Disease and Surgery Institute, Cleveland Clinic; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Address: Prashanthi N. Thota, MD, FACG, Esophageal Center, Digestive Disease and Surgery Institute, A31, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; thotap@ccf.org

Issue

Cleveland Clinic Journal of Medicine - 86(11)

Publications

Cleveland Clinic Journal of Medicine

Topics

Gastroenterology

Oncology

Preventive Care

Page Number

724-732

Legacy Keywords

Barrett esophagus, Barrett’s esophagus, esophageal adenocarcinoma, cancer of the esophagus, endoscopy, screening, gastroesophageal reflux disease, GERD, dysplasia, cancer precursor, proton pump inhibitor, PPI, aspirin, chemoprevention, mucosal resection, ablation, cryotherapy, Tavankit Singh, Vedha Sanghi, Prashanthi Thota

Sections

Author(s)

Prashanthi N. Thota, MD, FACG

Author(s)

Tavankit Singh, MD

Vedha Sanghi, MD

Prashanthi N. Thota, MD, FACG

Author and Disclosure Information

Tavankit Singh, MD
Department of Gastroenterology and Hepatology, Cleveland Clinic

Vedha Sanghi, MD
Department of Internal Medicine, Cleveland Clinic; Clinical Instructor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Prashanthi N. Thota, MD, FACG
Medical Director, Esophageal Center, Digestive Disease and Surgery Institute, Cleveland Clinic; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Address: Prashanthi N. Thota, MD, FACG, Esophageal Center, Digestive Disease and Surgery Institute, A31, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; thotap@ccf.org

Author and Disclosure Information

Tavankit Singh, MD
Department of Gastroenterology and Hepatology, Cleveland Clinic

Vedha Sanghi, MD
Department of Internal Medicine, Cleveland Clinic; Clinical Instructor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Prashanthi N. Thota, MD, FACG
Medical Director, Esophageal Center, Digestive Disease and Surgery Institute, Cleveland Clinic; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Address: Prashanthi N. Thota, MD, FACG, Esophageal Center, Digestive Disease and Surgery Institute, A31, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; thotap@ccf.org

Article PDF

724.pdf

Article PDF

724.pdf

All cases of esophageal adenocarcinoma are thought to arise from Barrett esophagus.¹ But most cases of Barrett esophagus go undiagnosed. And Barrett esophagus is seen in 5% to 15% of patients with gastroesophageal reflux disease.² These facts clearly emphasize the need for screening. Here, we review the rationale and recommendations for screening and surveillance, as well as the range of treatment options.