Barrett's Oesophagus

A perceived possible progression

Acid Reflux -> Oesophagitis -> Barrett's Oesophagus -> Oesophageal cancer

Acid refluxing into the oesophagus may wash aside the mucous lining and attack the squamous cells beneath - in the same way as pouring acid on your hand would burn and scar. This may be felt as heartburn and continued erosion can result in oesophagitis.

If bile refluxes onto the inflamed area, it could permit the acid to start digesting the exposed lining in the same way as it would break down ingested animal products. As a protection, the squamous cells can be replaced by columnar cells.

This is the condition known as Barrett's Oesophagus and it is a permanent change. Sometimes Barrett's appears to go away but if it's not seen, it may be hidden in the corrugations of the epithelium or a second mucosal layer may have grown over it. The burning sensations may reduce or disappear adding to the illusion that the Barrett's has gone but Barrett's itself is asymptomatic and the cells being less sensitive are protecting against the pain.

However, these cells are unregulated and in a small minority of cases can mutate. In our analogy, it's like some of the dominoes toppling. This is called Low Grade Dysplasia (LGD).

If a large mass of these dominoes topples into a disorganised heap, it's known as High Grade Dysplasia (HGD).

Further mutations may now occur which can cause a proliferation of mutated cells which is Oesophageal Adenocarcinoma - that's cancer!

The different "stages" of Barrett's Oesophagus are:

1. Non-Dysplastic Barrett's Oesophagus (NDBO/NDBE)

1a. Indefinite for Dysplasia (IND)*

2. Low Grade Dysplasia (LGD)

3. High Grade Dysplasia (HGD)

4. Neoplasia - initial stage of adenocarcinoma. (OAC/EAC)

• The phrase "Indefinite for Dysplasia" is often used if there is uncertainty whether it's NDBO or LGD. It requires close follow up to ascertain whether it is dysplasia or not.

In an article in Gastroenterology & Endoscopy News in October 2024, on follow up endoscopy, of 223 patients diagnosed IND, 22 (10%) were found to have dysplasia.

The researchers concluded that rates of prevalent dysplasia in Barrett’s esophagus patients are high in the first half-year after an IND diagnosis. They noted that Barrett’s esophagus patients are likely to need follow-ups with their providers within the first year of receiving an IND diagnosis. “IND carries substantial risk for progression to dysplasia, including HGD/EAC, especially in the first year after IND diagnosis,” they wrote. “Close follow-up within the first year is critical to exclude prevalent dysplasia.” 

• The term "Stage" may be misleading: it must be stressed there is no inevitability of any "progression" of Barrett's Oesophagus to Oesophageal cancer are very low and it is treatable.

The above progression model is really a bit simplistic.

Acdi reflux can indeed cause oesophagitis but that does not necessarily mean the body will create Barrett's cells as there are many other factors required..

We know that Barrett's oesophagus is formed from gastric stem cells, described in this paper: Research Finds BE Is Caused By Stomach–Intestinal Cell Hybrid.

But Acid refluxing isn't the only factor to trigger the production of Barrett's cells. Bile needs to reflux along with the acid, as this paper showed, Bile acid at low pH reduces squamous differentiation.

There have also been a number of genes identified which may be implicated: "Somatic mutations in several different genes have been found in esophageal cancer tissue. These genes include TP53), CDKN2A, DEC1, DCC, DLEC1, TGFBR2, LZTS1, RNF6, WWOX, APC, and RUNX3"

All cells of the human body have the ability to mutate to cancer. Barrett's cells are alien to that part of the body so may not be recognised by the body's immune system which may explain why those cells are more likely to mutate.

Although Oesophageal AdenoCarcinoma (OAC) is now known to be invariably preceded by Barrett's, it is wrong to say Barrett's progresses to cancer. There is noinevitability of that happening and for the vast majority of those with Barrett's, it will never happen.

A description of how Barrett's cells may mutate to cancer may be found in the chapter on oesophageal cancer.

In 2023, there were more than 11,000 members of the Facebook group Barrett's Esophagus Awareness. In 2014 it was around 2,000: a mean of 6,500. If 2/3rds have Barrett's that provides a mean of 4,400 members with nearly 40,000 patient years of data of patients taking daily medication (PPIs) and regular surveillance every few years. During the 9 years, there have only been 3 deaths to OAC, giving an annual risk of Barrett's mutating to cancer of about 0.007%.

For those who know they have Barrett's, following the recommended management protocol, reduces the risk of mutation to cancer to practically zero.

The chapter "Put Simply" describes how Barrett's can occur.

Page updated 24 October 2024