Barrett's oesophagus

Barrett's Oesophagus

Barrett’s is a condition characterised by changes in the cells lining the lower oesophagus.  It is thought to be due to severe, longstanding, gastroesophageal reflux disease (GORD). However only a small proportion of people effected by GORD develop Barrett’s. Nevertheless, the presence of Barrett’s oesophagus is an important observation since those who develop it are at greater than normal risk of developing Oesophageal cancer.

Anatomy

Normally, the oesophageal lining (the epithelium) consists of flat, layered cells similar to those in the skin. This squamous epithelium stops abruptly at the junction of the oesophagus with the stomach, near the lower end of the lower oesophageal sphincter. The epithelium of the rest of the gut, down to the anus, consists of a single layer of side-by-side rectangular cells, which is called columnar epithelium. In some people, the transition from squamous to columnar epithelium occurs higher within the oesophagus than normal. There may also be islands of columnar epithelium above the normal junction of the stomach and oesophagus. Barrett’s columnar epithelial cells may resemble those of the colon, small bowel, or stomach. One oesophagus may contain several types. The process of cell change from flat, layered squamous to tall columnar epithelium is an example of metaplastic change.

Columnar cells are thought to be more resistant to acid and pepsin and the metaplasia may be a defence against refluxed acid. In Barrett’s, the cells are usually of a type referred to as specialized columnar epithelium (a distinctive type of intestinal metaplasia). They include mucus cells, and have a tendency to resemble cells found in the small intestine.

Diagnosis

Barrett’s oesophagus can only be seen through an endoscope (a thin, flexible, device used to look inside the body) but always requires tissue specimens (biopsies) to confirm the diagnosis. Normally, the point where the red tissue that lines the stomach (gastric mucosa) ends and the paler pink squamous oesophageal mucosa begins sharply demarcates the junction between the stomach and the oesophagus. In Barrett’s oesophagus, the separation is above its normal position. It may reach upwards in tongue-like projections of gastric tissue into the oesophagus, as islands of gastric mucosa amongst the (oesophageal) squamous, or may involve the whole circumference of the oesophagus to a certain level. This abnormal columnar tissue may extend to any level within the oesophagus, even as high as the upper oesophageal sphincter. The doctor, through endoscopy, can normally recognize the abnormal (metaplastic) tissue, but an overlying inflammation due to reflux may obscure it. Peptic ulcers [sores or erosions] sometimes occur in Barrett’s epithelium and can be large.

Oesophageal cancer

The importance of Barrett’s oesophagus is its significantly increased risk of oesophageal cancer, though the incidence of this cancer remains low. The exact figure is difficult to obtain because an unbiased estimate of the prevalence of Barrett’s oesophagus is unavailable. However, a 2011 study in the general population suggested a rate of 0.12% annually. The risk is real and is further increased by factors such as tobacco and alcohol use. Also, the risk is greatest if the metaplastic epithelium is of the specialized columnar type and if the area of metaplasia is large. Changes can be detected in the Barrett’s tissue of those more likely to develop cancer. Called dysplasia, these changes are an indication for repeated endoscopy and biopsy. Dysplasia is an abnormal condition in which cells may have altered shape or may divide in a manner that alters the appearance of the tissue or organ. The degree of change ranges from minor to significant changes (low-grade), to serious or very abnormal changes (high-grade) dysplasia. The presence of inflammation of the Barrett's tissue may be confused with dysplasia, but resolves with treatment (proton pump inhibitors -PPI). Failure of dysplasia to regress with treatment should prompt close surveillance (repeated endoscopy).

There are two types of oesopahgeal cancer;  squamous cell carcinoma that develops in the normal squamous cell lining of the oesophagus. This cancer may be treated by radiotherapy or surgery. The other form of cancer that can develop in the columnar cells of Barrett’s epithelium is called an adenocarcinoma, and resembles stomach cancer. The incidence of this cancer is increasing in North America & Europe especially in white males. Adenocarcinomas do not respond well to radiation treatment.


Treatment of Barrett’s oesophagus

The management of newly discovered Barrett’s oesophagus has three objectives:

  • The treatment of any associated inflammation -oesophagitis.
  • Management of  dysplasia in patients with Barrett’s
  • The early detection or prevention of cancer through a surveillance programme.


Medical Treatment – Oesophagitis is commonly treated with medications to control acid production or secretion (Proton pump inhibitors PPI's). PPIs are recognized as the most powerful and effective drugs used to inhibit acid secretion and allow healing of tissue damage in the oesophagus.

Management of  dysplasia in patients with Barrett’s

Low-Grade Dysplasia; High dose PPI treatment for 6-8 weeks is recommended  to look for any histological improvement. Endoscopic examination should continue every 6 months for one year if there is no improvement.

High-Grade Dysplasia; Expert confirmation (second opinion). Depending on individual factors doctor may recommend selective resection (surgical removal of the oesophagus) or ablation therapy (endoscopic therapies that remove or destroy the Barrett’s tissue). There is no doubt that modern endoscopic techniques including endoscopic mucosal resection are highly effective in the management of high grade dysplasia. They greatly enhance the histological assessment by providing a larger specimen which can prove curative without the need for surgery.


Elimination of Barrett's tissue – Recently, several tools that can eliminate (ablate) Barrett's tissue have been introduced. They include freezing (cryo) or burning (radiofrequency) the Barrett's tissue. Careful post-treatment surveillance is still required with these treatments. Small areas of Barrett's oesophagus may be buried beneath newly formed squamous tissue in the oesophagus. Continued research is needed.

Early detection or prevention – How can we prevent cancer from occurring in Barrett’s oesophagus? Early detection and prevention of cancer are difficult. Since Barrett’s oesophagus is believed to result from chronic GORD, vigorous treatment of that condition has been tried. However, while proton pump inhibitors improve the esophagitis and heartburn, they fail to reverse the Barrett’s metaplasia. Anti-reflux surgery has also failed to reverse Barrett's tissue. Ablation (elimination) of Barrett's tissue is presently indicated only in those with dysplasia.


Risk Factors and Protective Factors

Anything that increases a person’s chance of developing a disease is called a risk factor; anything that decreases a person’s chance of developing a disease is called a protective factor. Some risk factors can be avoided (e.g., diet or lifestyle), but some cannot (e.g., genetics). Avoiding risk factors and increasing protective factors that can be controlled may decrease chances of developing a disease. Studies have suggested that risk of oesophageal cancer is amplified by factors that either increase reflux (e.g., tobacco, alcohol, high dietary fat, chocolate, caffeine, obesity, certain medications); or are genotoxic, which means capable of damaging DNA (e.g., a diet low in vegetables and fruits, tobacco use, dietary nitrosamines found in cured meat).

Measures that may be protective include lifestyle modifications emphasizing controlling reflux, tobacco cessation, improvements in diet (e.g., less fat, more fruits and vegetables), and weight loss if you are overweight.

Surgical removal of the abnormal tissue would remove the cancer risk. However, most people with Barrett’s oesophagus never develop oesophageal cancer, and such major surgery cannot be justified unless cancer is proven to be imminent. The challenge is the timely discovery of those with Barrett’s oesophagus that are at risk.

Cancer detection programs employ periodic endoscopic examination of the oesophagus and the procurement of tiny tissue samples (biopsies) for the pathologist to examine. For this discussion, Barrett’s oesophagus is defined as a junction of squamous and columnar epithelium that is three or more centimetres above the normal anatomical junction of the oesophagus with the stomach, or the presence of specialized columnar epithelium at any level of the oesophagus.

In newly detected cases the abnormal segment is systematically biopsied (in four quadrants at 2-cm intervals within the metaplastic oesophagus). If there is doubt about the pathologist’s interpretation of the biopsies, they should be promptly repeated. Severe dysplasia seen at multiple sites in a young person may prompt the physician to suggest surgical removal of the lower oesophagus (oesophagectomy). For those individuals for whom surgery is considered too risky, close observation at three-month intervals may be a safer alternative.

If low-grade dysplasia persists after adequate treatment of the esophagitis, the patient should be followed yearly with endoscopy and biopsy. Otherwise, all affected persons should be endoscoped and have the affected area biopsied at 18 to 24 month intervals.

Not all the experts subscribe to such an aggressive and expensive program, nor has it yet been shown to save lives or improve quality of life. However, few question the ominous implications of severe or “high-grade” dysplasia. Patients with Barrett’s oesophagus should not have the condition ignored, so a surveillance protocol is indicated for those who have the condition. The most appropriate method of evaluating whether surveillance reduces oesophageal adenocarcinoma and overall mortality is through a randomised controlled study. This is now underway as the Barrett’s Oesophagus Surveillance Study (BOSS)>


Summary

Barrett’s oesophagus consists of a change in the normally squamous lining of the lower oesophagus to columnar epithelium (metaplasia). Unless there is severe esophagitis, this change can be recognized during an endoscopy. Because there is an increased risk of oesophageal cancer in people with Barrett’s oesophagus, most physicians recommend regular endoscopy and biopsy of the altered tissue to detect pre-cancerous changes (dysplasia). If these changes persist and are severe (high-grade dysplasia), aggressive treatment is necessary to prevent development of adenocarcinoma.

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