Barrett’s Esophagus: Pathophysiology and Clinical Information

Introduction

Barrett’s esophagus (BE) is “ a metaplastic change of the esophageal mucosa from squamous to columnar mucosa (Halland, Katzka & Iyer, 2015, p. 6480).” In the clinical setting, many patients have diagnosis’s that include gastroesophageal reflux disease (GERD). Overtime, chronic GERD irritation leads to a change in the esophageal lining and the progression to BE. BE further acts as the leading precursor for the development esophageal adenocarcinoma (EAC) (Halland, Katzka & Iyer, 2015). This chain of events highlights the importance of understanding the pathophysiology related to BE in order to promote proper identification, prevention and surveillance initiatives.

Pathophysiology of Barrett’s Esophagus

As discussed previously, BE forms when metaplasia changes the esophageal lining from squamous to columnar cells. BE is often initially identified in patients experiencing symptoms of GERD who undergo an exploratory endoscopy, where columnar cells are identified at the gastroesophageal junction (GEJ). Risk factors include males, advanced age, Caucasian race, obesity and obstructive sleep apnea (Halland, Katzka & Iyer, 2015, p. 6480).

Obesity, specifically central obesity, has been linked to BE independent of other risk factors. Although the exact molecular processes remain unclear, centralized fat distribution, as seen in central obesity, promotes metaplasia of injured squamous cells to transform into columnar cells. Recently, an association has also been observed between smoking and BE Halland, Katzka & Iyer, 2015, p. 6481).

Furthermore, several genetic polymorphisms have been identified in this disease process. Two genome connections have been linked to both 19p13 in CRTC1 and 9q22 in BARX1. The gene CRTC1, involving chromosome 19p13, is responsible for the activation of oncogenes, whereas BARX1, relating to chromosome 9q22, possesses a transcription factor within esophageal specification. Additional polymorphisms have been found in the genes that regulate esophageal development: TBX5 and GDF7 (Halland, Katzka & Iyer, 2015, p. 6482). Examining specific genomes associated with certain diseases processes, such as BE, is likely the future of medicine in the identification of high-risk individuals and implementation of early prevention programs to avoid further disease progression.

Applicability to Clinical Setting

A diagnosis of BE can take a toll on a patient both physically and emotionally. That is why it is imperative to correctly diagnosis BE prior to committing a patient to a lifelong surveillance program. In a recent study that focused on retraining gastroenterologists on proper GEJ identification and BE classification, 33% of patients were identified as being previously misdiagnosed and were re-classified, no longer meeting the diagnostic criteria for BE (Halland, Katzka & Iyer, 2015, p. 6480). With this sobering statistic, it is understandable why many patients have a mistrusting relationship with healthcare professionals. Moving forward, reeducation programs for advanced care providers performing diagnostic endoscopies should be considered.

Fortunately, there are several new screening tools on the rise that are far less invasive, more reasonably priced, and having higher specificity ratings compared to the current standard of endoscopic testing. The trans-nasal endoscopy is a promising alternative that uses a much smaller scope and does not require patients to undergo sedation or have down time. In a randomized control study, the trans-nasal endoscope was proven to be favorable and correctly diagnose 98% of participants (Halland, Katzka & Iyer, 2015, p. 6482).

Another diagnostic alternative is the Cytosponge: an ingestible sampling device taken by mouth. The Cytosponge is comprised of a gelatin capsule containing mesh adjoined to a string that allows brushings from the device to be used in diagnosing BE. An immunological assay identifies the trefoil factor 3 marker seen within the columnar mucosa.  This surveillance device is another cost-effective option and shown to correctly identify 94% of BE patients (Halland, Katzka & Iyer, 2015, p. 6482).

Influence on Patient Care

Being diagnosed with BE has previously meant a lifelong endoscopy requirement with the purpose of consistent surveillance for EAC. As further studies have been conducted, screening guidelines are now recommended based on the level of dysplasia. In individuals identified without dysplasia, current surveillance endoscopies are recommended every three to five years. However, recent research has indicated that non-dysplastic BE has such a low progression rate that providers may want to consider advocating for “exit rules” for patients meeting this criteria after testing negative on three to five consecutive occasions. In patients with low-grade dysplasia, surveillance is recommended every six to twelve months, whereas in patients with high-grade dysplasia, surgical intervention is advised (Halland, Katzka & Iyer, 2015, p. 6483).

Chemoprevention agents are also available to aid in the prevention of BE progression. Although non-steroidal anti-inflammatory agents have been researched, presently only metformin, statins, and proton pump inhibitors (PPI) have shown a link in the reduction of BE progression. Metformin, in vitro, has been shown to decrease esophageal cancer cell proliferation as measured by pS6K1 levels. Statins, often seen as a mechanism to treat cardiovascular disease, have shown a similar decrease in cell proliferation, as well as apoptosis among cancerous cells. PPI’s, usually initiated for symptom management and acid reduction in GERD, are similarly associated with this outcome (Halland, Katzka & Iyer, 2015, p. 6485). With these recent findings, chemoprevention agents could be a beneficial management tool in the treatment of BE patients.

Conclusion

By understanding the pathophysiology associated with this disease process, BE patients can gain insight into the treatment options available. Acknowledging the symptoms correlated with BE can help identify those at risk to act appropriately in preventing further progression. Caring for patients with this diagnosis can be improved through standardizing surveillance guidelines and incorporating evidence based research into the care being provided. When applying this information to clinical practice, patient will experience better care outcomes.

Reference

• Halland, M., Katzka, D., & Iyer, P. (2015). Recent developments in pathogenesis, diagnosis and               therapy of Barrett’s esophagus.
  
  World Journal of Gastroenterology
  
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  21
  
  (21), 6479–6490. doi: 10.3748/wjg.v21.i21.6479