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Barrett’s esophagus (BE) is the only identifiable premalignant condition for esophageal adenocarcinoma (EAC),1 an aggressive malignancy for which the median overall survival at 5 years only reaches 19%.2 Despite a low annual risk of patients with BE developing EAC,3 current guidelines recommend that surveillance and endoscopic eradication may be appropriate as cancer risk varies based on presence and grade of dysplasia.1 BE is believed to develop due to reflux-induced esophageal damage,1 which creates the potential for a significant patient population for GI clinicians and fellows to treat.4 Thus, it is important for GIs to recognize which patients with reflux-causing conditions may benefit from surveillance or require endoscopic eradication to stem cancer risk.

“There is considerable anxiety among patients about premalignant conditions like BE, but the guidelines do not support endoscopic eradication in every BE patient,” explained Srinadh Komanduri, MD, professor of medicine and surgery at Northwestern University Feinberg School of Medicine, in Chicago, Illinois. It is typical that if BE progresses to low- (LGD) or high-grade dysplasia (HGD) that endoscopic mucosal resection (EMR), radiofrequency ablation (RFA), or cryotherapy are employed to remove BE lesions,5 following the confirmation of the diagnosis by an expert pathologist or a panel of pathologists.5 “A confirmed diagnosis of LGD is evidence of a substantially increased risk of cancer relative to nondysplastic BE, but we always obtain a second opinion from an expert BE pathologist prior to proceeding with ablation,” said Anthony Infantolino, MD, director of the Barrett’s Esophagus Treatment Center at Thomas Jefferson University Hospital in Philadelphia, Pennsylvania.

The data documenting the risk for progression have been accumulating along with evidence of the efficacy and safety of endoscopic eradication therapy. Because BE is associated with acid-related injury from chronic gastroesophageal reflux disease, the intestinal-type metaplastic columnar epithelium is already a risk factor for progression to cancer.6 Among patients with BE, risk for progression to cancer has been variably estimated,7 but a large cohort study estimated the annual risk is approximately 0.4%.8

According to Dr Komanduri, all modes of endoscopic eradication therapy have value, but of the ablative methods, RFA has become the standard of care for the majority of cases. Other modalities are effective particularly in the uncommon circumstances when RFA does not achieve complete eradication. “We consider other modalities, such as cryoablation or argon plasma coagulation, if there is persistent BE after several sessions with RFA, but we have a large body of data associating RFA with both efficacy and safety, which is why it is generally considered the standard of care,” said Vladimir Kushnir, MD, director of endoscopic research at Washington University School of Medicine in St. Louis, Missouri.

RFA is sufficiently safe and effective so that many experts, including Dr Kushnir, discuss RFA in a selected group of high-risk patients with BE who have not yet developed dysplasia. Patients with a family history of EAC are at the top of this list, but some clinicians use risk-scoring systems that consider clinical characteristics, such as long-segment BE.6,9 “Risk scoring can be useful when speaking with patients with nondysplastic BE who wonder why their premalignant condition is not being treated,” Dr Infantolino said. “When there is a low risk score, it is easier to explain why surveillance is the more appropriate approach. When the risk score is high, a conversation about the risks and benefits of endoscopic eradication becomes more reasonable.”

By itself, anxiety about cancer is not a sufficient justification for endoscopic eradication in nondysplastic BE epithelium, according to Dr Kushnir. The potential for serious complications from current strategies of ablation is low, but not zero.10 Dr Kushnir considers ablation of nondysplastic BE epithelium in patients with a family history, but he does not routinely use risk-scoring systems. He explained that he exercises a conservative approach. However, he does advocate complete ablation of BE epithelium when intervention is warranted. “Once treatment is initiated, the goal is a normal-looking esophagus. This is spelled out in the guidelines. The quality metric is complete eradication of intestinal metaplasia [CEIM], because this provides the best protection against subsequent recurrence,” Dr Kushnir said.

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Srinadh Komanduri, MD

“Anytime we embark on endoscopic eradication, the goal is complete eradication of BE,” Dr Komanduri agreed. American Society for Gastrointestinal Endoscopy (ASGE) guidelines also recommend endoscopic eradication therapy in those with LGD unless patients prefer surveillance.5 In patients with visible lesions, such as areas of depression, mucosal discoloration, nodularity, plaques, or ulceration, EMR is recommended.5 “If the lesion is large, it is essential to perform endoscopic ultrasound to confirm there has been no invasion into or through the muscularis propria,” Dr Infantolino said. In the event of this degree of invasion, identified as a T2 or more advanced adenocarcinoma, patients are candidates for esophagectomy. Although Dr Infantolino believes all noninvasive lesions should be removed with EMR if possible, he noted that higher stage lesions “are best served with multimodality therapy,” including RFA.

Although endoscopic eradication therapy is very effective at removing BE-related neoplasia,5 there is still a chance for future recurrence; as such, endoscopic surveillance is essential. According to data in the ASGE guidelines, the incidence of any recurrence from pooled studies is 7.5% per 100 patient-years,5 but this risk is likely to be variable according to patient features and the adequacy of the eradication treatment. The ASGE guidelines recommend initial endoscopic surveillance 3 to 6 months after treatment, but acknowledge that the optimal surveillance interval remains unclear.5 “The current guidelines establish a reasonable approach to managing the risk of BE, but there are important unanswered questions and I think we can step up our game,” Dr Infantolino said. Several groups are working on developing evidence-based quality indicators aimed to increase detection of dysplasia and ensure complete eradication, he noted.

Newer technologies and strategies for detecting dysplasia also are reaching advanced stages of clinical testing, according to Dr Komanduri. Some of these technologies have the potential to permit surveillance without the need for endoscopy, but their most important contribution may be allowing for more consistent detection of dysplasia earlier and providing more complete eradication to reduce potential recurrence risk. Such technologies may become important tools for newly practicing GIs or fellows seeking an interventional endoscopy subspecialty.

“There is no question that we have a lot of room for improvement, but we can also do better even now by adhering strictly to established protocols,” Dr Kushnir said. “I think we are going to see quality indicators increasingly emphasized in the management of BE like we have seen with colonoscopy in managing adenomatous polyps in the colon.” Steps, such as spending at least 30 seconds evaluating each 1 cm of BE epithelium, are already emerging as measures of quality care. Although all of the experts commenting on current practice in the management of BE anticipate evolving practice with newer techniques, they also uniformly emphasized that this form of interventional endoscopy is already playing a critical role to reduce a key risk for esophageal malignancies.

References

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  2. National Cancer Institute. https://seer.cancer.gov/ statfacts/ html/ esoph.html. Accessed August 30, 2018.
  3. Hvid-Jensen F, Pedersen L, Drewes AM, et al. N Engl J Med. 2011;365(15): 1375-1383.
  4. Boeckxstaens G, El-Serag HB, Smout AJ, et al. Gut. 2014;63(7):1185-1193.
  5. Wani S, Qumseya B, Sultan S, et al. Gastrointest Endosc. 2018;87(4):907-931.e9.
  6. Shaheen NJ, Falk GW, Iyer PG, et al. Am J Gastroenterol. 2016;111(1):30-50.
  7. Singh S, Manickam P, Amin AV, et al. Gastrointest Endosc. 2014;79(6):897-909.
  8. de Jonge PJF, van Blankenstein M, Looman CW, et al. Gut. 2010;59(8):1030-1036.
  9. Parasa S, Vennalaganti S, Gaddam S, et al. Gastroenterology. 2018;154(5):1282-1289.e2.
  10. Qumseya BJ, Wani S, Desai M, et al. Clin Gastroenterol Hepatol. 2016;14(8):1086-1095.e6.