David Forcione, MD, of the Massachusetts General Hospital Barrett’s Esophagus Treatment Center, answers questions about Barrett’s esophagus, its causes and diagnosis, and the link between the condition and esophageal cancer.
What is Barrett’s esophagus?
Barrett's esophagus is a condition affecting the lining of the esophagus, the swallowing tube that carries foods and liquids from the mouth to the stomach. The condition was first described in 1950 by Dr. Norman Barrett, a British thoracic surgeon. Since this original description, numerous advances have been made in our understanding of Barrett's esophagus.
Barrett’s esophagus is a change in the lining of the esophagus from a normal, white lining (known as squamous mucosa) to a pink/red lining (known as intestinal-type mucosa). This change occurs over many years and is the esophageal response to chronic exposure to harmful chemicals from the stomach, most notably reflux of acid and bile.
The intestinal-type mucosa of Barrett's esophagus is thought to be more resilient, and is less prone to inflammation. Unfortunately, intestinal-type mucosa also appears to be a more unstable lining. This lining is more likely to undergo cellular changes that may lead to cancer.
What causes Barrett's esophagus?
Chronic acid reflux, or gastroesophageal reflux disease (GERD), is the strongest risk factor for the development of Barrett’s esophagus.
Studies have shown that 10%–15% of patients with GERD will have Barrett's esophagus. However, some patients with Barrett’s esophagus may not have active reflux symptoms. One study showed 25% of patients over 50 years old without GERD symptoms had Barrett's esophagus.
Symptoms of GERD include:
- Heartburn (burning sensation in the chest)
- Acid or bitter taste in the mouth
- Pain or discomfort in the chest
- Difficulty swallowing (dysphagia)
- Nausea after eating
- Bad breath
- Sore throat
- Chronic cough
- Hoarseness (voice changes)
- Excessive clearing of the throat
GERD is associated with increased exposure of the lower esophagus to contents of the stomach and small intestine. Reflux occurs when the muscular valve between the esophagus and stomach (known as the “lower esophageal sphincter”) is not functioning properly. This valve normally opens after a person swallows food or liquid, allowing what they ate or drank to reach the stomach. The valve then closes to prevent backwash up into the esophagus.
When this valve opens too frequently or does not close properly, there is an increased chance the esophagus will be exposed to irritating contents from the stomach. These contents are harmful to the normal esophageal lining, and will lead to inflammation, known as “reflux esophagitis.” Chronic reflux esophagitis appears to lead to Barrett’s esophagus. Therefore, most patients with frequent or longstanding symptoms of GERD should be evaluated for the presence of Barrett’s esophagus with an endoscopy. Treatment of GERD, either with medications or surgically, may slow the development and progression of Barrett's esophagus.
Who gets Barrett's esophagus?
It has been estimated that Barrett’s esophagus affects 3.3 million adults over 50 years of age in the United States. Individuals with chronic GERD are at the highest risk for developing the condition. Studies have also found that certain populations appear to be at highest risk for developing Barrett’s esophagus. Caucasian (white) males, particularly over age 50, are at highest risk. Obesity and smoking may also increase one’s risk of developing Barrett’s esophagus.
Barrett’s esophagus is uncommon in children and is not considered to run in families or to have a significant genetic component at this time.
How is Barrett’s esophagus diagnosed?
Two criteria are most often used by gastroenterologists to make a diagnosis of Barrett’s esophagus: a salmon-pink colored lining of the esophagus, and cellular changes seen under the microscope of biopsies taken at endoscopy.
First, the esophageal lining must have a certain appearance on an upper endoscopy exam. The normal esophageal lining (squamous mucosa) is light pink or white. If the lining is salmon-pink in color, it is likely Barrett’s esophagus. If identified, the gastroenterologist performing the exam notes the length of Barrett’s esophagus and notes if he/she sees additional features such as small growths (known as nodules) or ulcers.
Barrett's esophagus can be classified as short segment (less than 3 cm of Barrett's mucosa), long segment (4-10 cm of Barrett’s mucosa) or very long segment (more than 10 cm of Barrett’s mucosa).
The second criterion comes from examination of tissue samples (known as biopsies) of the salmon-pink colored lining. These small pieces of tissue are examined under a microscope by a pathologist. Specific changes are required for a diagnosis of Barrett's esophagus, most notably the presence of Goblet cells. These cells are usually present with intestinal-type mucosa and are one of the hallmark findings of Barrett’s esophagus.
Pathologists are also looking for cellular changes known as dysplasia, a precancerous change in Barrett’s esophagus. The presence and severity of dysplasia are important factors when it comes to deciding which treatments may be needed.
There are currently no X-ray studies or blood tests that can accurately diagnose Barrett's esophagus. A combination of a comprehensive history, a careful upper gastrointestinal endoscopy and pathologic review of biopsies remains the gold standard approach to identifying this disease.
What is the link between Barrett’s esophagus and esophageal cancer?
Since the 1970s, the frequency of esophageal cancer in the U.S. has risen by six-fold, a rate greater than that of melanoma, breast cancer and prostate cancer. In 2012, an estimated 17,460 Americans were diagnosed with esophageal cancer. Unfortunately, despite advances in treatment, only one in five patients with esophageal cancer will survive beyond five years, and virtually all of these survivors were diagnosed at an early stage.
Esophageal cancer has two common forms: squamous and adenocarcinoma. In the U.S., squamous cancer is the less common type, affecting individuals with a history of alcohol and tobacco abuse. There is no relationship between squamous carcinoma and Barrett’s esophagus.
Adenocarcinoma is the most common variant in the U.S. Barrett’s esophagus is the most important risk factor for the development of adenocarcinoma of the esophagus. Patients with Barrett’s esophagus have a much higher risk of developing esophageal adenocarcinoma compared to those without Barrett’s esophagus. This risk has been estimated to be a 30-fold increase over the general population. Despite this, it is important to remember that an individual’s overall risk is quite low and that the vast majority of people with Barrett’s esophagus will never develop esophageal cancer. Every year, only one out of every 200 patients with Barrett’s esophagus will be diagnosed with esophageal cancer.
This increased risk of esophageal cancer is one of the important reasons why patients with Barrett’s esophagus need ongoing care by a gastroenterologist. In addition to managing symptoms of GERD (the main cause of Barrett’s esophagus), a gastroenterologist will recommend monitoring of the Barrett’s esophagus using endoscopy. This exam focuses on evaluating the lining of the esophagus for growths and allows for tissue sampling.
Pathologists examine these biopsies looking for any evidence of dysplasia. Based on this microscopic examination, a pathologist may classify Barrett’s esophagus into three types:
- Non-dysplastic (NDBE)
- Low-grade dysplasia (LGD)
- High-grade dysplasia (HGD)
- The higher the grade of Barrett’s esophagus, the more changes that are occurring at the cellular level and the greater the likelihood of developing cancer.
NDBE has the salmon-pink coloring of intestinal type mucosa, but no worrisome cellular changes. Dysplasia progresses, or gets worse, over time when genetic changes in the tissue add up.
It is important to note that any given patient may have one type or a mix of types found on these biopsies. For this reason, it is important to do multiple biopsies during the endoscopy exam and for these biopsies to be carefully reviewed by expert pathologists. The Massachusetts General Hospital Barrett’s Esophagus Treatment Center staff includes gastrointestinal pathologists with special expertise in the diagnosis and staging of Barrett’s esophagus.
LGD has features of mildly atypical cells (larger cells with some distortion). HGD cells are larger and tend to appear more disorganized. Therefore, has many worrisome features that are considered much more likely to develop into cancer.
Without treatment, patients with any form of dysplasia are at higher risk of being diagnosed with esophageal adenocarcinoma within five years. As many as 40% of patients with HGD will be diagnosed with adenocarcinoma within two years. Patients with HGD are advised to undergo treatment once diagnosed rather than surveillance alone.
How is Barrett's esophagus treated?
Individuals with GERD should be evaluated for appropriate therapy by a gastroenterologist. This may include medical therapy and/or surgical therapy (antireflux surgery). Individuals with chronic GERD symptoms (typically more than five years), and particularly those with significant risk factors, should undergo screening for Barrett’s esophagus with endoscopy every three to five years.
Recent guidelines have been published and have outlined the current expert opinion on the treatment of Barrett’s esophagus. These are summarized in the table below.
Non-dysplastic (NDBE): Most patients with Barrett’s esophagus will not have dysplasia found in the biopsy specimens. Guidelines recommend that these patients undergo surveillance endoscopy every two to three years to evaluate for signs of dysplasia. Some high-risk patients without dysplasia may be advised to consider more aggressive treatment options such as radiofrequency ablation or cryotherapy. Patients with very long segments of Barrett's esophagus and those with a family history of esophageal cancer may be considered high risk.
Low-grade dysplasia (LGD): Patients with LGD may be offered short interval surveillance endoscopy (i.e. every six months) to check if the dysplasia is progressing or going away. Some patients with LGD will improve to a state of no dysplasia, if adequate antacid medications are utilized. A minority of patients with LGD may advance to HGD over a period of months to years.
Treatment options for patients with LGD are individualized. GERD management is optimized in all patients. The pros and cons of short interval surveillance endoscopy and endoscopic ablation of the dysplasia are considered and discussed with the patient. Esophagectomy is not recommended for these patients, given the overall low risk of progression to cancer at this stage.
High-grade dysplasia (HGD): Patients with HGD (confirmed by an expert pathologist) require some form of therapy, as these patients are at a much higher risk for progression to cancer. Treatment options are discussed with the patient, including endoscopic options (removal of tissue and/or ablation), and surgical options (esophagectomy).
The best option depends on a variety of factors, including age and the presence of other medical conditions. Patients with HGD are best cared for under the expert guidance of surgeons and gastroenterologists who can work together to provide the optimal treatment plan. To learn more about Barrett's esophagus treatment options, visit the Mass General Barrett's Esophagus Treatment Center.
Management Options for Barrett's Esophagus
|Type of Barrett's Esophagus||Medical Treatment||Endoscopic Treatment Options||Surgical Treatment Options|
Endoscopy every two to three years or ablation in high risk groups2
|Consider anti-reflux surgery for GERD|
|Low-grade dysplasia||GERD Treatment1||Surveillance
Endoscopy every six months or consider ablation treatments3
|Consider anti-reflux surgery for GERD once dysplasia is completely treated|
|High-grade dysplasia||GERD Treatment1||Endoscopic resection and/or ablation3||Consider esophagectomy|
|Intramucosal carcinoma (adenocarcinoma)||GERD Treatment1||Endoscopic resection of tumor followed by endoscopic ablation3||Consider esophagectomy|
1. GERD treatment: Consists of using high-dose antacid oral medications, typically in the proton pump inhibitor family, such as omeprazole (Prilosec) or pantoprazole (Protonix). Histamine blockers such as ranitidine (Zantac) would be an alternative.
Lifestyle modifications are also strongly recommended for patients with Barrett’s esophagus. We recommend avoiding caffeine, alcohol, carbonated beverages and tobacco. In addition, avoiding lying flat within four hours of a meal and elevating the head of the bed will reduce the chances of reflux.
2. High-risk patients include those with very long segment of Barrett's esophagus (more than 10 cm) and those with a strong family history of esophageal cancer.
3. Ablation treatments include radiofrequency ablation (RFA) and/or cryotherapy.