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.
An analogy is to think of squamous cells as dominoes lying on a table. Columnar cells are like dominoes standing on end with a smaller surface exposed to attack. Meanwhile the nerves centred within the cells are further moved from the attack so these cells are effectively less sensitive and the misery of heartburn may diminish. These cells resemble those that line the stomach or intestines and may be described as gastric or intestinal metaplasia.
The term "metaplasia" may mislead which infers they are changed squamous cells, whereas we now know they are actually new cells produced from stem cells as this paper from April 2022 reveals Research Finds BE Is Caused By Stomach–Intestinal Cell Hybrid
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)
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.
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.
(Just under 8000 people die each year from Oesophageal Cancer out of 64 million in UK, making the chances one in 8000. If there are 3 million with non-dysplasic Barrett's*, their risk is one in 400.)
Britain tops the world for incidence of oesophageal cancer where it is the fourth greatest cancer killer of men, claiming the life of one person an hour on average in the UK. [c-ii]
If it is going to occur, the progression is usually slow initially but by the time cancerous cells develop, it's frequently too late to treat with life expectancy measured in weeks rather than years.
This paper from 2017 "Barrett’s esophagus: Cancer risk is highest in first year after diagnosis" suggests risk of mutation to cancer from Barrett's decreases the longer you've had it.
* A paper published in 2014 [c-iii] suggests one in 20 have Barrett's. Applying that to the UK population implies there may be 3 million people with Barrett's though fewer than 150,000 know it. If the others can be identified, it may be possible to prevent this large number of deaths.
Barrett's cells protect against pain
Another metaphore for Acid Reflux oesophagitis and Barrett's.
Prague classification.
The size and extent of an observed area of Barrett's may be described using the Prague criteria using the letters c for circumferential ring and m for maximum length of any tongues. Thus c2m3 would mean a ring of Barrett's 2 cm wide with protrusions to a maximum of 3 cm.
The image shown would be described as c2m5
Image thanks to American College of Gastroenterology
Page updated 2 July 2023