2014-04-24 18:57:38 UTC

Who Needs Endoscopic Therapy for Barrett’s Esophagus?

May 1, 2014


Nicholas J. Shaheen, MD, MPH

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill

You have been to the national meetings, have seen the training videos and have convinced your hospital to make the investment in equipment to do endoscopic ablative therapy. Now comes the hard question: who do you treat?

In reality, this is a question that you should have asked yourself before you obtained the equipment. When contemplating any endoscopic service, you need to ensure that you will have adequate volume to stay proficient in the technique. If you are in a solo or small practice which sees few patients in need of endoscopic therapy, it may be better to refer those patients to someone doing higher volumes, since that endoscopist is likely to be better at the procedure than you are. On the other hand, if you are in a large practice, or will receive referrals from other practitioners in your community to do endoscopic therapy, then it makes sense to move forward.

The next hurdle you face is how to get trained. It is difficult in the U.S. for the working clinician to get training in new procedures, and it is difficult for hospitals to decide what experience is necessary to credential a practitioner in advanced procedures. Our professional organizations have moved to address these shortcomings with hands-on courses, training centers and visiting-clinician programs. However, even with these venues, the vital, proctored, hands-on experience necessary for competence is often lacking. Pragmatically, for this procedure, I would suggest that the practitioner at minimum undergo a formal didactic session on the procedure (available at many societal venues), and then perform multiple procedures proctored by a physician experienced in the procedure. How many is enough? Ideally, our yardstick for competence would be criterion-based, and not number-based (i.e., have they mastered the skill?). But from training many fellows, I would suggest that, for radiofrequency ablation, at least five balloon-based and five focal procedures are necessary at minimum to become familiar with the equipment.

Who you choose to treat should reflect an understanding of the risks of the procedure, the efficacy of the procedure and the risk of cancer in the patient if left untreated. While some of these variables are still somewhat unclear, recent literature sheds light on these questions. The only current risk stratifier, degree of dysplasia, strongly predicts cancer risk. Patients with Barrett’s esophagus (BE) and high-grade dysplasia (HGD) have an annual risk of progression to cancer of 6 to 19 percent; conversely, annual progression rates for those with BE and no dysplasia are 0.2 to 0.6 percent.1 The risks of the procedure, however, are relatively static regardless of the degree of dysplasia, and vary in most series between 3 to 10 percent overall, with stricture being predominant. With respect to the efficacy of endoscopic therapy, while there is some variability in the literature, a relative risk reduction of 70 to 90 percent seems achievable.

In light of these numbers, who with BE to treat with endoscopic therapy becomes clearer. Patients with intramucosal cancer and patients with HGD have an aggressive natural history. Further, both of these lesions have a morbid competing management strategy, esophagectomy. Additionally, in the case of HGD, level-one evidence demonstrates that radiofrequency ablation results in a high rate of reversion to neosquamous epithelium and a low rate of progression to cancer.2 Therefore, endoscopic ablative therapy is the strategy of choice in these patients.

For patients with BE and low-grade dysplasia (LGD), rates of progression to cancer are lower (1 percent or so in meta-analyses). However, recent level-one data demonstrate a marked decrease in the risk of progression to HGD and cancer in subjects with LGD undergoing ablative therapy, compared to controls undergoing endoscopic surveillance.3 Given the large relative risk reduction associated with endoscopic therapy, the risk of progression in the untreated patient, and the good safety profile of the intervention (at least as demonstrated with radiofrequency ablation), BE with LGD confirmed by a second pathologist is appropriate for consideration of ablative therapy. This is especially true in the younger patient with few co-morbidities, who presumably has a large number of life-years at stake.

Is ablative therapy appropriate for patients with non-dysplastic BE? Unlike the case for BE with HGD or LGD, no level-one evidence demonstrates a protective effect of ablative therapy in such subjects. The number of patients needed to be enrolled in such a study makes it a prohibitive undertaking. Our inability to stratify risk in the large number of non-dysplastic BE patients makes it difficult to target therapy. Indeed, for every 20 such patients treated with endoscopic therapy, 19 or more would likely accrue no benefit, because they were never destined to develop cancer in the first place. All 20 patients would, however, assume the risks and costs of the procedure.

Who you choose to treat should reflect an understanding of the risks of the procedure, the efficacy of the procedure and the risk of cancer in the patient if left untreated.

In the case of subjects with non-dysplastic BE, this calculus might be changed if we could use additional risk factors to identify a subgroup of patients at higher risk for progression. Few such predictors are available in common clinical practice. The length of the BE segment appears to be such a risk factor,4 although its strength as a stratifier of risk is not clear. Similarly, age appears in some studies to be a predictor of cancer risk. Unfortunately age may also predict risk of complications of endoscopic therapy. Family history of BE or esophageal adenocarcinoma in multiple first- and second-degree relatives may identify a subgroup of patients with a different risk profile as well.

As long as the risk-benefit calculus of ablative therapy in subjects with non-dysplastic BE remains unsettled, it is premature of offer ablative therapy to all such subjects in your practice. In my practice, I have offered ablative therapy to non-dysplastic BE patients with a family history of esophageal neoplasia, as well as patients with substantial long-segment BE (greater than 5 to 6 cm) at a young age; these subjects represent less than 5 percent of the total population treated with ablative therapies at our center. Further work will tell whether these applications of ablative therapy in the non-dysplastic population are appropriate.

For the remainder of patients with non-dysplastic BE sent for consideration of endoscopic therapy, we continue to recommend periodic endoscopic surveillance at three-to-five year intervals. We also acknowledge that the value of endoscopic surveillance is unknown, and this strategy may not be protective against death from cancer.5 In addition, we re-emphasize to them their low risk of progression. We also tell them that both technology and our knowledge base about BE will continue to march forward. Even a five-year delay in endoscopic therapy is likely to bring substantial improvements in technique and outcomes — consider the evolution of these technologies in the previous decade! The additional data we collect while a non-dysplastic BE patient undergoes a cycle or two of endoscopic surveillance might clarify who with non-dysplastic BE should be selected for more aggressive therapy. Whether it is a biomarker panel, a cumulative risk score or other clinical indicators which predict risk, such data will eventually allow us to pick those BE patients most likely to progress to cancer, and to focus our efforts and attention on them.

Dr. Shaheen receives research funding from CSA Medical, Covidien Medical, NeoGenomics, Takeda Pharmaceuticals and Oncoscope. He is a consultant for Oncoscope.


1. Sikkema M, de Jonge PJ, Steyerberg EW, Kuipers EJ. Risk of esophageal adenocarcinoma and mortality in patients with Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2010;8(3):235-244.

2. 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.

3. Phoa KYN, van Vilsteren FG, Pouw RE et al. Radiofrequency Ablation in Barrett’s Esophagus With Confirmed Low-Grade Dysplasia: Interim Results of a European Multicenter Randomized Controlled Trial (SURF). Gastroenterology 2013;144(5):S187.

4. Anaparthy R, Gaddam S, Kanakadandi V et al. Association between length of Barrett’s esophagus and risk of high-grade dysplasia or adenocarcinoma in patients without dysplasia. Clin Gastroenterol Hepatol 2013;11(11):1430-1436.

5. Corley DA, Mehtani K, Quesenberry C, Zhao W, de BJ, Weiss NS. Impact of endoscopic surveillance on mortality from Barrett’s esophagus-associated esophageal adenocarcinomas. Gastroenterology 2013;145(2):312-319.

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