Dr Ahmad, a consultant gastroenterologist and interventional endoscopist at University College Hospital London, recently gave a talk at our London Barrett’s Support Group about the endoscopic treatment of Barrett’s dysplasia and early cancer. Here we share a transcript of his talk.
Barrett’s Diagnosis – What Next?
Many of you will already know that when it comes to Barrett’s a lot of the focus has been on identifying patients, so there’s a lot of patients out there who probably have Barrett’s but don’t know about it, and a lot of national and charity work has been done to try and raise awareness and try and get patients diagnosed.
Once the diagnosis is made the real question is what next. And really the main reason why we try and diagnose Barrett’s is because we want to try and interrupt or prevent progression to cancer.
Progression from Barrett’s to Cancer
Barrett’s oesophagus can increase your risk of cancer of the oesophagus, although the risk is still small. Many people with Barrett’s oesophagus do not develop cancer.
Between 3 and 13 people out of 100 (between 3 and 13%) with Barrett’s oesophagus in the UK will develop oesophageal adenocarcinoma in their lifetime. And each year, less than 1 in 100 people with Barrett’s (less than 1%) develop oesophageal adenocarcinoma.
But there’s a very important subgroup of patients where there is a risk of progression along a sequence of changes from low grade dysplasia to high grade dysplasia and then early cancer. It’s very important to recognise that early so that we can intervene endoscopically and that’s really the key when it comes to these sorts of discussions between doctors and patients.
Quality of Endoscopy and Missed Cancers
It’s great that we’re diagnosing Barrett’s, but a lot of work still remains to be done nationally. And if you look at the quality of endoscopy it can be very variable.
The UK has actually led the way internationally through the British Society of Gastroenterology. There has been a lot of work trying on quality assurance and attempting to reduce the risk of post endoscopy upper GI cancers – PEUGIC – and PEUGIC is defined as a
cancer being found within three years of an endoscopy which in many causes could have been avoidable and it should trigger a root cause analysis to see what went wrong.
If you look at some of the published data – and Nigel Trudgill’s group has done a lot of work on this – you’ll find that the PEUGIC rate was higher in those with Barrett’s oesophagus. The likely reason is that the dysplasia or early cancer is often very subtle, and could be easily missed within a segment of Barrett’s, especially if surveillance is not performed on a dedicated expert list.
The quality of upper GI and Barrett’s oesophagus surveillance endoscopy is improving but a lot of people are still very reliant on biopsy protocols (Seattle Protocol) – you take four quadrant biopsies every two centimetres, you sample about 3.5% of the mucosa, which is only really a safety net and cannot replace a high quality endoscopic assessment and inspection.
AI and Detection of Dysplasia
There is extensive research ongoing to develop AI tools to help detect Barrett’s dysplasia and early cancer changes during endoscopic procedures. In fact, some are now commercially available. During my PhD research at UCL in conjunction with a university spin-out called Odin Vision and subsequently Olympus, we were able to produce an AI algorithm that works in real-time to spot subtle abnormalities during Barrett’s surveillance procedures.
This is available at UCLH and I use this in my clinical practice, having demonstrated the technology during live endoscopy courses to help highlight subtle lesions referred to our practice. It would be important to evaluate this further in clinical trials but so far the technology seems very promising and in particular could help non expert endoscopists.
Importance of Depth Assessment
One of the points I wanted to bring out in particular is the importance of depth assessment. When you think about cancer it’s important not just to think about the mucosal layer but also the submucosal layer.
If a cancer spreads into the submucosa then there is a risk that it can access lymphatic channels and blood vessels.
And so, it’s really important to try and assess the depth of invasion when determining treatment options to know if it is likely to offer a curative resection.
Treatment Guidelines and Resection of Visible Lesions
We follow the European Society of Gastrointestinal Endoscopy (ESGE) guidelines for Barrett’s oesophagus. Generally, it is critical to perform a high-quality endoscopic assessment to identify any visible lesions and resect (remove) them wherever possible this in particular allows for histopathological staging i.e. the pathologist can tell you the depth of invasion and if there are any high risk features.
Endoscopic Resection Techniques: EMR and ESD
There are different ways of removing lesions.
For Barrett’s oesophagus with dysplasia or early cancer, both EMR (Endoscopic Mucosal Resection) and ESD (Endoscopic Submucosal Dissection) are used to remove abnormal tissue. EMR is simpler and faster, suitable for smaller lesions, while ESD allows for en-bloc removal of larger lesions, potentially reducing recurrence risk,
ESD however is more technically demanding, potentially takes a longer time so has more associated costs depending on the operator and carries a high risk of complications.
However, we have gained considerable experience now in the West, including at UCLH, of performing ESD with good outcomes.
There’s some evidence emerging via systematic review, meta-analysis where they pooled studies and found that the endoscopic submucosal dissection (ESD) actually does have some better outcomes, including a higher rate of complete removal in one piece and no significant increased risk of complications, bleeding, perforation causing a tear or strictures, narrowing in the oesophagus compared to piecemeal EMR (multiple EMR pieces) for these large Barrett’s lesions.
We generally follow the ESGE guidelines again for when to chose ESD, and discuss the cases in a specialist multidisciplinary meeting along with patient discussions about preference. ESD can be preferred in cases where there might be concerns about superficial invasion into the submucosa, if the lesion (growth) is particularly bulky, has some depression, is larger than 2cm or we are concerned about fibrosis/scarring often because of prior treatment attempts.
It is possible that some of the lesion (growths) removed by endoscopic resection such as ESD can have some high risk features for lymph node metastases. There is some evolving research risk stratifying patients who have undergone endoscopic resection of early oesophageal adenocarcinoma (T1) with high risk features, as some more recent endoscopic studies have suggested that the risk of lymph node metastases may be lower than previously thought. In selected cases it might be possible to offer strict high-quality surveillance rather than referring all patients for oesophagectomy if there has been complete (radical) endoscopic resection. We need to see more data from this international study led by a Dutch group, before we can really inform clinical practice. Ideally, we could then offer more personalised treatment options for patients with more accurate risk prediction after endoscopic resection of early high risk cancers.
