Gastro issues and EOE (Eosinophilic Oesophagitis) in patients with OA/TOF

I’m very happy to present and introduce one of the consultant gastroenterology colleagued and a friend Dr. Osvaldo Borrelli he’s the clinical lead of gastroenterology here at GOSH and he has specific interest on the oesophagus and we’ll talk today about gastro issues and eosinophilic oesophagitis – I made it. I pronounced it right – in oesophageal atresia and TOF patients.

Thanks Paulo.

Good morning for everyone. I want just to say I’m very happy to be this morning with you. I think is the most complicated talk I used to give. We usually speak to other professional experts and talking to the family given me a completely different perspective I have learned already. A few years ago I had a fantastic session where a number of questions that would never happen in clinic. So sometimes you hear from the family something that you never think in clinic and was absolutely know a fantastic moment.

Of course you know very well what we are talking about. There are different type of oesophageal atresia with associated tracheo-oesophageal fistula which can occur perhaps in 90% of the case. The prevalence is quite high in the most common oesophageal abnormalities of oesophageal atresia. I think it is great because now the surgical and the care after the surgery has significantly improved so the survival rate of the patient is absolutely very high. So it’s up to 90%.

And of course what is left. So there is a significant morbidity associated with OA/TOF and there is significant impact on quality of life and of course this challenging for us but is more challenging for yourself.

I think some of you know very well what we are talking about. So we have children, mainly in the in the first year of life, with feeding difficulties, difficulty in swallowing – dysphagia – food gets stuck in the chest in the pharynx. Then we have the presence of oesophagitis, reflux, problems with airway with the respiratory tract, recurrent wheezing, infection, chronic cough. And of course then we have long-term issue that can come with time mainly in adult, development of metaplasia or oesophageal cancer.

So there are a number of difficulties that patients with OA/TOF experience throughout the journey. Now I won’t start with the feeding difficulties because everyone is concentrating on reflux. Everyone is concentrating on this dysphagia. But I think everyone knows how difficult is at least the first year, first months, first year of life to feed a child with the oesophageal atresia. So the dysphagia difficulty swallowing 38% up to 85%. We have reports from the parents that they have difficulty in eating. Likely you know the majority of these children are breastfed during the first part of life which can help. It’s quite common to see patient that they really dislike some texture and is very commonly reported in clinic that the problem of food getting stuck in the throat is very common. In the chest is absolutely common.

Then we will talk about that. Again these are symptoms that require the support in almost 3/4 of children with OA/TOF require support from dietician. The cause of this feeding difficulties are dysmotility, we will discuss later I will mention you have the problem related to stricture, the presence of inflammation in the oesophagus. One aspect is important that you know I will show you later that children with OA/TOF also have problems with the dysmotility of the oesophagus.

I’m mentioning the most common cause of dysphagia. So of course the anastomotic stricture. Everyone is worried about after the surgery is stricture and I think a number of you, a number of children have received a number of dilatation – mainly in the first months of life. And the number of dilatation sometimes are so high in the first year of life because the oesophagus tends to stricture all the time. There are also other causes and we go through other causes. We can have congenital stricture in patient with OA/TOF. We can have problem with dysphagia related to ant-reflux surgery. Vascular abnormalities. Other abnormalities. But in the absence of any cause, the oesophageal dysmotility remains the most accepted explanation.

And this is the reason why I’m trying to show you now in these slides Virtually all the patients with the oesophageal atresia have affected motility of the oesophagus.

So if you can see here in the upper left this picture this is a normal motility of the oesophagus when we swallow. In the upper part we have relaxation of the pharynx . Then we have nice contraction that move down. And this contraction usually just behind the food. Just pushing everything down. And then you have the opening of the barrier between the oesophagus and the stomach. The lower oesophagus sphincter which lets everything go through the stop.

And this is a normal peristalsis. This is a normal activity. We have this fantastic complex motor activity in there to help everything move down. If you see in the other picture you can see there is no motor activity. This is the typical pattern of patient with OA/TOF. You can have complete absence of activity. You can have, in some patients, the oesophagus does not have this propulsion moving down but squeezes at the same time and some other patient have just in the distal part of the oesophagus some contraction. They are just progressing normally. So virtually all patient with OA/TOF have motility disorder. So I’m telling you already now that the majority of patient with OA/TOF the food goes down based on gravity. And this is the reason we quite commonly suggest not to lie down after eating because this system of helping everything to move down is absent.

Now the motility of the oesophagus is also important for other aspects. So everyone has got reflux acid. Everyone. Okay. So when it’s above a certain limit then we begin pathology. One of the main mechanisms to clear the oesophagus from the acid coming up of the gastric contents is the motility of the oesophagus. So when we have something coming up the oesophagus start moving down. Pushing down everything and clearing the surface. As you can imagine this system of clearance in the oesophagus is a fact because there is no motility at all which means that every time any gastric contents goes in the oesophagus, it stays there for much longer compared to the norm. And there is consequence to that.

So now which are the causes. I’m showing a lot of slides that maybe are complicated but I’m just talking you through. Okay. First, we know that children with oesophageal atresia have an abnormalities in the cells or in the nerves in the oesophagus. And this has been shown in a number of studies showing that how the neurotransmitters – all the molecules – help the nerves to work are completely ignored. And second and this is not of course a criticism against the surgeons. there is problem with some damage with the vagal nerves which is very difficult not to do during the surgery because the surgery is always complicated. Usually, and this is quite long time ago, these are guidelines published in 2016. I’m telling you already now that in 2026 2027 should come out the new guidelines from European society and North American society of paediatric gastroenterology in the management of children with oesophageal atresia. But essentially, when any child has got any symptoms we know that the first, and this is the reason, the first investigation that we suggest is a contrast study. And that the contrast studies is done just because we need to rule out physical abnormalities. If there is again stricture, if congenital stenosis, if there is again persistence of fistula, if there is an external compression then you know if it’s completely normal then we proceed to the further investigation. Which essentially are an endoscopy. In in the states for instance they do always also bronchoscopy in patient with OA/TOF and laryngoscopy and then we assess whether there is an oesophagitis or not based on that. Then we decide to do a test for assessing the presence of reflux. In general this is how we move through. And essentially these are, I’m not going through the investigation, I will mention just new a new tool that we have available but essentially also our speech and language therapist and Miss Stewart will talk about dysphagia later on. Go through the difficulty swallowing in the upper part and she will go through heavily. But essentially, we can have dysphagia which is related essentially to the pharynx and then we have a video fluoroscopy of oesophageal manometry which pressure tests the oesophagus.

Otherwise we can assess the oesophagus and again amongst the number of investigation that we have essentially we have the presence of or not pH-Impedance and then I will talk briefly about EndoFLIP. I don’t think we ever heard about. EndoFLIP, which is a new tool that is very useful.

Now of course everyone is worried about an anastomotic stricture and everyone is always worried that the oesophagus is going to stricture again and that needs another dilatation. Essentially, this is the pathway that is used for patient with a suspected anastomotic stricture. So you do a contrast study and then essentially you do an oesophageal dilatation. For a refractory stricture sometimes what we do combine with … and we can dilate endoscopically then we inject some steroids in the lesion. In the most difficult case then or we need to resection. Of course, oesophageal replacement is the most complicated situation that we are experiencing.

Now I want just to mention one study because some maybe some of you have heard that in some patients after the addition we use viscous budesonide which is a topical steroid. This topical steroid need to be swallowed. And after then, because I thin the dilatation can cause an inflammatory process and this inflammatory process can cause again restriction of the oesophagus. There is some data showing that not using these steroids after the dilatation can delay significantly. Okay. So as you can see and know the super segment here we have a need of dilation quite soon where the dilation are less frequent. And again the dysphagia is much better.

So there is possibility and we are start using much more the use of some medication just to delay the requirement or to stop the requirement of dilatation.

Another aspect is gastro reflux. I think you know better than me that it’s very common. And everyone knows that we need to treat gastro reflux because with the time there is a risk of developing a stricture There is a risk of developing severe oesophagitis. Then there is a risk of pulmonary complication. But most important in adult is Barrett’s oesophagus or oesophageal cancer.

But this has been shown in in other… a long time ago where the risk of Barrett’s which is pre-cancer is almost four times higher than the normal population. Now this is the whole guidelines and know essentially we have a patient is asymptomatic. he does have surgical correction. Everything is fine. He has PPI treatment for at least one year and then you perform a pH dense test just to see whether the reflux is there or not. If there is no reflux then you can consider to stop otherwise you carry on the treatment and you do further investigation. The problem when I go through the literature every time I go through the literature I have more question than answer unfortunately. This is the reality of the complexity of patient with oesophageal atresia.

First, if you go through the study that they have report the presence of gastro reflux as you can see. There is a study or clinical science clinical school not assessed. You have quite high prevalence but essentially has not been objective documented reflux again go through. Okay so again they are just important things. So the true prevalence of reflux is very difficult to know at the moment. However, it’s very common. And because of that it is difficult to decide how long a treatment with PPIs should be done.

This is from ERNICA and Professor de Coppi is part of. In it they discuss how they do not reach the consensus about how long PPIs should be administered. Of course my comment would be in this there are too many surgeons. We love surgeons but there are too many surgeons maybe.

From a gastroenterology point of view we have a different view but actually this study was done by my colleagues and they essentially report there is insufficient variation in the duration of PPI and at the moment there is no clear data. A lack of evidence in how long we should do PPI. Of course we follow the symptoms. But not always the symptoms that a child is reporting means that the child has got gastro oesophageal reflux. So this is the complexity.

And more again in this study just published a few years ago where they did an pH impedance monitoring with recommended test one year and the majority of patient actually they had no acid reflux. They do not have any acid. So they had episodes of reflux but we are talking about non acid reflux. So, if use anti-acid medication of course we are not treating the reflux in this case.

Also it’s interesting that despite the treatment with PPI of 50% of the children they still had complication from the reflux despite the treatment and the worst is that actually the PPI treatment seems do not prevent the formation of anastomotic stricture. So I’m completely confusing the word. I know, I know but it’s confusing for us as well.

Just to share with you how complicated a case the decision of treating a patient. And sometimes we request investigation. I know the parents are quite upset after so many surgeries. So many, It’s been a hell of journey during the first year of life and then you see doctors suggesting, let’s do some tests because we are not completely sure what we are looking at. We need to tailor the treatment on a specific patient. And again the oesophagitis maybe is not the only cause and there can be multifactorial problems. Again we were talking about before the abnormal motility of the oesophagus. So even if you try to treat with PPI is not going to improve because the motility is still affected.

I want just to mention one aspect is anti-reflux surgery. Because sometimes I say we have reflex let’s do another reflux surgery. Essentially this is the statement. The statement of the previous guidelines. They say we need to be sure that we are doing the antiflux surgery in the correct patient. And if we have a patient with poor control gastroesophageal reflux, so long-term dependency of trans-pyloric feeding option not expelled. Maybe an anti-reflux surgery can be effective.

I’m going back on an important concept here that we touch junction between oesophagus and stomach. One way we have touched that junction is very complicated. And this is very complex surgery and the complication from surgery are quite common. Okay. So when we alter this anatomy then it is quite humbling. Now as I explained to you before the oesophagus does not have the ability to push down what the patient eat. If we create high pressure zone okay just below the oesophagus, maybe the oesophagus is not able to clean itself. So instead of making better the patient we make worse.

So they complain much more of dysphagia. Which is very common in children with oesophageal atresia. Again before we decide on any treatment it is very important to define the characteristic of the patient because otherwise instead of making the patient better, we make the patient worse.

So this is the importance of understanding the patient with a specific test. Then I’m going the endoscopy of course that endoscopy is very important. Endoscopy is important for a number of reason. It’s quite common in children with atresia that unfortunately the symptoms do not parallel what we find in endoscopy.

So children with oesophageal atresia because they have, as I told you before, they have nerves do work optimally. And we are not talking about nerves or neurons, they are responsible for moving the bolus but also neurons are responsible for the sensation, it’s quite common that the symptoms that do not feel any pain but actually there is the presence of significant oesophagitis.

So the endoscopy has a role, a key role in assessing regular the patient with oesophageal atresia. In completely asymptomatic patient we know that they should have at least you at least three endoscopy. One year after they stop PPI. One year around the age of 10 and one year before transition.

This is absolutely normal. Of course then if the patient is symptomatic then we need to perform anyway an endoscopy.

As you know, reflux oesophagitis – this is just endoscope image that you can see ulcers but Paulo was mentioning is eosinophilic oesophagitis. Which I think is a new word for patient with the oesophageal atresia. I’m trying to do very quick. You know, this is just elephant in the room. Okay. So I’m going to be very quite… So eosinophilic oesophagitis (EOE) is a chronic immune / antigen-mediated oesophageal disease. It’s characterised, by I’m not talking about just children with oesophageal atresia but with EOE. They have dysphagia, food impaction. And this can be normal out can have some abnormality. In this endoscopy you have the increase of these specific cells. There needs to be above a specific number to make the diagnosis.

In the last few years we had a significant increase in the diagnosis. We have almost 34 cases per 100,000 children. Maybe it’s due to an increase in number of biopsy we do but there is definitely an increase in the diagnosis.

There are a number of slides just to show that essentially we have a patient with a predisposition to atopy. Genetic susceptibility. Then we have exposure to food activation of inflammatory cells. This is TH2 type of reaction. So the allergic reaction you have inflammation that can affect the mucosa and there is recruitment of these specific cells. Now what is going to happen. Which are the same sorry I’m okay. If you do not treat eosinophilic oesophagitis because of a inflammation. Fibrosis of the oesophagus which narrowed down became quite rich in the oesophagus and the motility of the oesophagus significantly affected. Now the symptoms are essentially symptoms that you have feeding problem, weight gain, regurgitation, abdominal pain, swallowing problem, food gets stuck. So I think all the symptoms that you know very well okay because they are quite common in children with oesophageal atresia. So there is significant overlap and again all these children have also this compensatory eating which is quite common in children with oesophageal atresia. What is happening? Okay, then we have treatment. We have treatment drugs essentially. We have as treatment PPI topical steroids. And you can have biologicals, you can have diet and you can have dilatation.

It seems you know the story.

Now what is happening. The first EoE case report was in 2002. We have case serious. then we have the first hypothesis of gene of association between oesophageal atresia and eosinophilic oesophagitis. There is a gene which is related. And of course I’m not going into the genetics but is related to oesophageal anatomical malformation in the gastric tract. But this gene is also responsible to eotaxin 3 Which is responsible for the recruitment of the eosinophils, these inflammatory cells, in the oesophagus.

So there is this combination. And the prevalence actually of eosinophilic oesophagitis now in oesophageal atresia is quite high range. Between 10% and 20%. And the prevalence is almost 20 times more than in the normal population.

So children with eosinophilic with oesophageal atresia are at risk of developing at some point eosinophilic oesophagitis. So there are a number of risks. Excess delivery and use of PPI. So the strong use of PPI seems to be responsible to make susceptible the patient to develop atopy. And we know in the general population they can develop allergies and then they can develop EoE.

So now, of course, your question is going to be yes but they start having PPI since four. So yes and PPI can be unfortunately one of the risk to developing EoE in the future. You see it’s very complicated. It’s interesting this study showing that there is genetic similarity between oesophageal atresia and eosinophilic oesophagitis.

Now patients have more reflux symptoms. They have more hypoxic spells, more dysphagia, more pulmonary problems. Then they have more surgery before diagnosis of EoE. The number of eosinophils – this is a study that we published a few years ago – showing that the number of eosinophils in the oesophagus in patient – they are predictive factor for stricture formation.

And we know that some patient once they have diagnosed eosinophilic oesophagitis and you treat eosinophilic oesophagitis, they do not have stricture anymore.

Almost getting there. Again I think this is management of PPI to steroids and elimination diet and management of such. We are lucky in GOSH. We have a multi-disciplinary clinic with fantastic CMS working with us. We have an allergist. We have the addition in our clinic. At GOSH we have almost 21/22 patient that we’re looking after. And there are a number of patient on PPI manage topical steroids and the diet restriction .

I think it’s very important that the eosinophilic oesophagitis is diagnosed and is managed properly. We are very happy because the surgeons now they are very, very careful about making diagnosis that always refer to our clinic. So we are absolutely set.

And the last the last output that we have. Okay, this is quite fascinating too.

This is called EndoFLIP. Maybe you have heard of it. It gives the possibility for us to assess the motility of the oesophagus but also to assess the resistance of a stricture. So every time we do an endoscopy now we are FLIPping everyone because this is done under anaesthesia. And we can assess if the stricture can be dilated. We can also make a diagnosis of congenial stricture and we can assess also if the mobility and the pressure of the lower eosinophilic is fine. So that do not need further investigation. Adding the FLIP is definitely the future for having much more results also in terms for research. Thank you for your attention.