Barrett’s Esophagus: Today’s Mistakes and Tomorrow’s Wisdom

Barrett’s esophagus is a disease that has been extensively studied since the phenomenon of columnar epithelium in the distal esophagus was first described in the fifties [1]. In the 1970s, its relationship with gastroesophageal reflux disease became apparent [2], and in the late 1980s, the association with development of esophageal adenocarcinoma was established [3].

Given the dismal prognosis of patients with esophageal adenocarcinoma, patients with known Barrett’s esophagus undergo endoscopic surveillance. Back in the days, surveillance was aimed at detecting esophageal adenocarcinoma at a stage in which curative surgical treatment was still an option. Nowadays, however, endoscopic surveillance is aimed at detecting early cancer at a stage in which endoscopic treatment can be used to cure the patient, as a less invasive alternative to esophagectomy [4]. Furthermore, surveillance may lead to detection of precursor lesions for cancer, such as high-grade or low-grade dysplasia, in which case, prophylactic treatment using ablation can be offered to patients [4].

Management of Barrett’s esophagus has become less invasive, more efficient, and more personalized. And still novel improvements and innovations are changing the way we survey and treat patients with Barrett’s esophagus and Barrett’s related neoplasia and cancer.

Despite all the progress in the treatment of esophageal adenocarcinoma, the majority of patients are still diagnosed at a symptomatic stage when curative treatment is no longer an option. The majority of these patients were not known with Barrett’s esophagus and did not benefit from endoscopic surveillance. Therefore, identifying more patients with Barrett’s esophagus may be the true key to improving mortality of esophageal adenocarcinoma. In Chapter 1, Di Pietro et al. [5] discuss how new research using epidemiological and clinical data has allowed the creation of risk prediction algorithms to identify patients at risk for Barrett’s esophagus. The chapter also describes new, minimally invasive devices to screen for Barrett’s esophagus, such as transnasal endoscopy, cytosponge, volumetric laser endomicroscopy, and volatile organic compounds. Furthermore, the authors discuss how chemopreventive strategies in patients with Barrett’s esophagus may provide an opportunity to reduce the risk of malignant progression.

Once patients are diagnosed with Barrett’s esophagus, they are offered endoscopic surveillance to detect neoplasia in a curable stage. However, the overall efficacy and cost-effectiveness of surveillance are questioned. Novel techniques, such as artificial intelligence use during endoscopic and histological assessment, and more personalized surveillance intervals, may help to overcome the current drawbacks of endoscopic surveillance. In Chapter 2, Zellenrath et al. [6] provide an overview of current Barrett’s esophagus surveillance strategies, its pitfalls, and potential future directions to optimize Barrett’s surveillance. They discuss where there is room for improvement in Barrett’s surveillance, and how better risk stratification may reduce both patient and healthcare burden.

Currently, a histological diagnosis of dysplasia is the best predictor of progression in Barrett’s esophagus. However, as Frei et al. [7] describe in Chapter 3, progression of nondysplastic Barrett’s esophagus to esophageal adenocarcinoma is heterogenous and can accelerate via genome doubling and genome catastrophes, resulting in different ways of progression. The use of biomarkers may therefore lead to more accurate risk stratification of Barrett’s patients into low or high risk for progression. In Chapter 3, the authors discuss the development and validation of biomarker panels, and how such biomarker panels may be implemented in clinical practice.

A lot of relevant innovations that have improved the detection of early neoplasia during Barrett’s esophagus surveillance have taken place in the field of endoscopic imaging. In Chapter 4, van Heijst et al. [8] discuss advancements in endoscopic imaging techniques, such as optical chromoendoscopy, fluorescence molecular endoscopy, and the use of computer-aided detection algorithms. Next to the technical innovations, this chapter also describes the importance of appropriate mucosal cleansing, sufficient inspection time, and competence of the performing gastroenterologist in the detection of esophageal adenocarcinoma.

Once a patient is diagnosed with early neoplasia in a Barrett’s esophagus, endoscopic treatment is nowadays the treatment of choice in case of low-grade dysplasia, high-grade dysplasia, and cancer limited to the mucosal layer. Endoscopic treatment is very safe and effective, if performed by trained endoscopists. In Chapter 5, Barret [9] gives an overview of endoscopic treatment techniques and discusses pitfalls in endoscopic treatment and he discusses the controversy around the use of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett’s neoplasia.

As discussed in Chapter 5, mucosal (T1a) adenocarcinoma is an indication for endoscopic treatment, whereas T1b adenocarcinoma has long been an indication for surgical treatment. However, novel insights have demonstrated that also in selected cases of T1b adenocarcinoma, endoscopic management may be a justified alternative to surgery, given a lower risk of lymph node metastases than previously assumed. Chan et al. [10] discuss these novel insights in the management of T1b esophageal adenocarcinoma in Chapter 7.

In more advanced stages of esophageal adenocarcinoma, where endoscopic treatment is not an option, the standard of care is multimodal therapy including esophagectomy. In Chapter 8, Garbarino et al. [11] discuss current indications for surgery, different operative techniques, and future expectations regarding indications for resection, neoadjuvant or perioperative therapy, type of surgery, and postoperative follow-up for Barrett’s adenocarcinoma.

Although esophageal adenocarcinoma is still a disease with a dismal prognosis, a lot of improvement has already been made in the detection of early neoplastic lesions and optimizing endoscopic and surgical treatment and more innovations are ahead. Furthermore, minimally invasive screening and accurate, objective risk stratification will allow for earlier detection of patients at risk of esophageal adenocarcinoma, allowing for early intervention and thereby hopefully in a decrease of esophageal cancer-related mortality.

Conflict of Interest Statement

R.E. Pouw received a speaker fee from Medtronic and does consultancy for MicroTech. O. Pech received speaker fees from Medtronic, Fujifilm, Olympus, Boston Scientific and Aohua

Funding Sources

The authors received no funding for this editorial.

Author Contributions

Both authors contributed equally.

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