The importance of optimizing reflux control to improve outcomes after endoscopic eradication therapy for Barrett’s neoplasia

Endoscopic eradication therapy (EET) with a combined approach of resection and ablation is safe and effective. The evolution of endoscopic mucosal resection (EMR) for visible lesions followed by radiofrequency ablation (RFA) has become the gold standard for Barrett’s associated neoplasia. Despite the effectiveness of EET, recurrence of intestinal metaplasia (IM) after achieving complete eradication (CE-IM) can occur anywhere from 5 to 20 percent.1 Recurrence of IM or dysplasia after achieving CE-IM is one major reason surveillance endoscopy remains essential. Ideally, if the rate of recurrence could be mitigated and surveillance intervals extended or eliminated, the impact of EET would be significantly greater.

Predictors of recurrence are not fully understood, but it is clear uncontrolled reflux plays a critical role. Gastroesophageal reflux disease (GERD) is often silent in patients with Barrett’s esophagus. After successful EET, the neosquamous epithelium can be very sensitive to an uncontrolled reflux burden resulting in visible esophagitis or symptomatic GERD. This can perpetuate the metaplastic-dysplastic pathway and result in recurrence of disease. We have previously demonstrated that a vigorous antireflux protocol with early physiologic testing and optimization results in reduced rates of recurrence.1 Such a protocol involves ensuring compliance and adherence to proton pump inhibitor (PPI) therapy, recognition of uncontrolled reflux despite not having symptoms, and consideration of an antireflux procedure if PPI therapy is suboptimal. The majority of reported recurrences of IM detected appear to occur in the first three years and subsequently plateau. This further supports the likelihood that this predominantly due to uncontrolled reflux burden.

Optimization of reflux burden has been demonstrated to minimize the number of treatment sessions of EET. Strategies may range from increasing PPI dosage to antireflux surgery. Across multiple national and international registries, the mean number of sessions to achieve CE-IM has been around three.2,3 The most significant predictor of incomplete response by three sessions is uncontrolled reflux. This ranges from persistent acid reflux, weakly acid reflux and bile reflux.4 As such, it is essential to consider physiologic testing on therapy for patients not achieving a significant response to EET after three sessions. This is ideally a 24-hour pH impedance test to ensure we capture all measures of reflux burden. Other objective tests of reflux are more appropriately performed when confirming the presence or absence of GERD which is not needed in patients with Barrett’s. It is equally important to recognize endoscopic predictors of poor reflux control such as erosive esophagitis which can occur after starting therapy. There is nothing more enticing for uncontrolled reflux then normalized mucosa after ablation. We have also previously demonstrated that antireflux surgery allows for achieving CE-IM in patients with prior incomplete response within one to two additional sessions.1


Predictors of recurrence are not fully understood, but it is clear uncontrolled reflux plays a critical role.


Patient adherence and compliance with PPI therapy is often overlooked and can be the simplest solution to optimize reflux control. Compliance refers to the patient taking his/her medication every day while adherence is defined by taking the medication as directed (e.g., twice daily, 30 minutes before meals). It is important to reconcile the patient’s antireflux regimen at each visit to ensure compliance and adherence. In addition, de-escalation or cessation of medicine as a result of an insurance request or the patient themselves who misinterprets EET as a therapy for GERD must also be reconciled.

It is not surprising that uncontrolled reflux has been implicated as a major risk factor for recurrence of IM after successfully EET. After all, this very reflux is the underlying cause for the development of Barrett’s esophagus from the start. The success of EET has also allowed for us to further validate the inflammatory-metaplasia-dysplasia pathway which will ultimately restart once neosquamous epithelium is present and reflux is not optimally controlled. It is essential that physicians performing EET for Barrett’s understand this relationship and ensure adequate antireflux measures are in place before, during, and after EET. A successful program in EET requires a multidisciplinary approach involving esophagologists, advanced endoscopists, and surgeons. It is critical that we approach our patients with GERD and Barrett’s as we would with any other patient with chronic disease and not simply ablation to achieve CE-IM. This is truly a continuum of care in medicine from GERD to esophageal cancer.

References

1. Komanduri S., Kahrilas P.J., Krishnan K, McGorisk T., et al. Recurrence of Barrett’s esophagus is rare following endoscopic eradication therapy coupled with effective reflux control. Am J Gastroenterol. 2017;112(4):556-566.

2. Pasricha S., Bulsiewicz W.J., Hathorn K.E., Komanduri S., et al. Durability and predictors of successful radiofrequency ablation for Barrett’s esophagus. Clin Gastroenterol Hepatol. 2014;12(11):1840-1847.

3. Haidry R.J., Lipman G., Banks M.R., Butt M.A., et al. Comparing outcome of radiofrequency ablation in Barrett’s with high grade dysplasia and intramucosal carcinoma: A prospective multicenter U.K. registry. Endoscopy. 2015;47(11):980-987.

4. Krishnan K., Pandolfino J.E., Kahrilas P.J., Keefer L., et al. Increased risk for persistent intestinal metaplasia in patients with Barrett’s esophagus and uncontrolled reflux exposure before radiofrequency ablation. Gasterenterology. 2012;143(3):576-581.

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