Progress in adult care for OA/TOF patients in the Netherlands

Chantel ten Kate

Good afternoon, everybody.

I would really like to thank the TOFS organisation for inviting me here today and to talk with you about my work. In 2022, I defended my PhD thesis. And during my thesis, I investigated the optimisation of health care throughout life for patients born with oesophageal atresia.

And as you can see in this figure, which is also part of the discussion of my thesis, I tried to study the whole circle of life. We start with the development of oesophageal atresia. I studied the formation of anastomotic strictures in the first year of life, comorbidities and the quality of life during childhood.

And finally also the transition to adult health care and the problems that adults can encounter during that time and during adult life.

For this presentation, I was asked to discuss with you this last part, the transition to adult health care. I will talk with you about gastrointestinal problems, pulmonary problems, endoscopic surveillance, and a little bit about genetics. In this figure, I’ve shown the paediatric follow up for oesophageal atresia patients in the Netherlands. And as you can see, it is very well organised.

For almost 25 years now, patients come into the hospital at standardised time points, starting at 4 months old and the last one at 17 years old. I will not go into detail because we’re going to talk about the adults. But as you can see, it’s really a multi-disciplinary program.

A psychologist is involved, a physiotherapist is involved, a pulmonologist is involved. But the last visit is at 17 years old. So what happens when you turn 18 for a long time? This is where it ended. The last visit was at 17 years old, and nothing was known about follow up in adulthood. And it was also not known that follow up in adulthood was even required. Like I said, for a long time, also in the Netherlands, also in Rotterdam, there was no adult follow up. But in 2013, we started the screening and surveillance program.

I will come back to this later, because first of all, I want to talk with you about the healthcare needs of adults. A common saying in medicine is that children are not small adults. But the same thing also applies the other way around. The problems that adults born with oesophageal atresia encounter during life are not the same as the problems that children face in daily life. Therefore, we started by investigating these healthcare needs. What is it? What are the problems that adults born with oesophageal atresia face? And most importantly, what do they think about those problems? And what is important to those adults.

And we did so by organising two focus group interviews, one with the adult patients and one with the family members of adult patients. A focus group is a small group of 10 to 15 people of the same population and is always led by a moderator, in our case a neuropsychologist. The moderator gives a topic to the focus group. The focus group is encouraged and stimulated to discuss this topic until saturation is reached. Saturation means that no new information is added to the discussion. The topics that we introduced to the focus groups are listed here on the slide, and they were set in advance by an expert panel. The expert panel consisted of a pulmonologist, a gastroenterologist, a dedicated researcher in the field of oesophageal atresia, a paediatrician, a psychologist. So also the expert panel was very multi-disciplinary with the goal to make it also cover all aspects of life.

These focus group interviews were literally transcribed and the text was coded and the codes were organised into themes. The whole goal of this process, which is called a thematic analysis, is to look for similarities.

This is quite a large table, and I don’t expect you to read it in detail, but this summarises the results of these focus groups. In this table we also use as a guide for physicians when they ask us what is important for adults born with oesophageal atresia, for example, general practitioners. Most importantly, a few things stand out that I want to discuss with you. The gastrointestinal and pulmonary problems are still experienced on a daily basis in some patients. Some patients have problems with dysphagia, reflux, coughing, frequent pulmonary infections. These are all the things we heard in the earlier presentation in childhood. But there are also adults who are still facing these problems frequently.

Mental health is also a large topic. Many adults experience emotional distress or anxiety for medical procedures due to experiences in their childhood.

Some adults have problems with how or even if they want to tell the people around them that they are born with oesophageal atresia. Some adults are having a hard time at work, for example, during lunch breaks or when they need to take a personal day to visit the hospital or are worried about not getting a promotion.

And last, and these are two very important things I think, is that the patients in the focus group really pointed out that it’s very important that there is one coordinating physician who coordinates their follow up, that they have one person coordinating their whole healthcare. And secondly, not very surprising, but that the general practitioner usually knows way too little about their condition to help them with this. So now we know what the most important health care needs of adults are.

But what are we going to do with that?

To address the gastrointestinal and the pulmonary problems, it is important to organise follow up possibilities with expert specialists. So follow up with a gastroenterologist and a pulmonologist are, are the basics for that. During these consults, it’s important to also pay attention to the emotional distress and other issues that influence the quality of life of these patients.

To this end, we have developed the SQEA questionnaire and SQEA stands for Specific Quality of life of Esophageal atresia Adults. The SQEA questionnaire is a tool that can be used preliminary to the consultation.

Currently it is implemented in the Netherlands in the Dutch healthcare. And patients are going to complete the questionnaire prior to the consultation with the goal to make the consultation in one way more efficient, but in another way also to open the door to discuss the other aspects of life.

For example, the psychological problems, anxiety. We feel that it’s more easy to check a box and then make it discussable with the doctor.

Instead of that you have to bring it up yourself. Also, this questionnaire is currently being translated and validated throughout Europe in the hope that we’re going to use it also in other countries. And we are also working on that here in the UK. And all of these aspects needs to be co-ordinated. All these aspects of the follow up needs to be co-ordinated by one person or one dedicated team.

So let’s start with the gastroenterologist. Why is follow up needed? First of all, of course, to discuss and wherever possible, treat the physical complaints that patients experience. But also another reason is the increased risk of Barrett’s Oesophagus. Barrett’s oesophagus is a condition in which the epithelium of the squamous cell, sorry, the squamous cells that are supposed to be in the oesophagus change into cylindrical cells, columnar epithelium that is supposed to be in the stomach.

Like you see here, the mucosa of the stomach is kind of shifting up into the oesophagus. Ten years ago, my colleague Flo Vergouwe already performed the literature research and found an increased reported prevalence of Barrett’s oesophagus and oesophageal carcinoma in patients born with oesophageal atresia compared to the general population. Also, these patients were at a much younger age than the general population and this has led to the start of our screening and surveillance program in 2013.

In this program, patients undergo a gastroscopy every three to five years depending on their age and potential outcomes of earlier endoscopies. During these endoscopies, biopsies are taken according to a standardised protocol and these biopsies are reviewed by a pathologist under the microscope.

In 2022 we have published the results of the first eight years of this surveillance program. During this period, almost 400 gastroscopies were performed in a total of 271 patients.

For the quick calculators among us, that means that over 100 of them also already had a second or third endoscopy and that means that we can also say something already about follow up results.

What did we find during these surveillance endoscopies in a period of eight years? Our patients ages ranged in this program from 15 to 68 years old. 19 of the 271 patients, so 7% of them had Barrett’s oesophagus at a median age of 32 years. Four of them developed Barrett’s oesophagus during follow up, meaning that the first endoscopy was clean and with their follow up endoscopy, the second endoscopy, Barrett’s oesophagus, was found.

At the time of the diagnosis of Barrett’s oesophagus, patients were median 32 years old. However, the youngest patient with a clinically relevant Barrett’s oesophagus fulfilling this international set of criteria and requiring more intense, more frequent follow up was 20 years old.  And last during this fine period. Unfortunately, two patients were detected with oesophageal carcinoma who were not under follow up and not under surveillance.

Based on these results, we have made some alterations to the surveillance program. First of all, we now start screening at 20 years old instead of 17 years old. This lowers the burden for young adolescents and is still proven to be safe. We have proven with our data from 8 years of surveillance that it is safe to start at 20 years.

Secondly, up to the age of 40 years, patients will be offered an endoscopy every 10 years and after the age of 40 every five years. This was respectively five and three years, with the cutoff at the age of 30. In the last two years, our cohort keeps expanding, both children becoming adults from our paediatric hospital, but also adults coming in from other hospitals or even sometimes other countries.

Of course, it is also interesting to wonder why patients born with oesophageal atresia develop Barrett’s oesophagus more often. Could this cause perhaps be genetic? Over the last 10, 15 years, several PhD theses have been devoted to discovering genetic defects causing oesophageal atresia. You hope to find one central gene that you know. When there is something wrong with this gene, then oesophageal atresia occurs. But this central gene has not been found so far. And we don’t really think that there is going to be one central gene to point out. However, multiple genetic variations and genetic syndromes have been associated with the development of oesophageal atresia. And this made us wonder whether these genetic variations could also be found associated with the more frequent development of Barrett oesophagus.

And to this end, we have compared the DNA of these patients. We took biopsies of patients born with oesophageal atresia who have developed Barrett’s oesophagus and patients who were born healthy and also had Barrett’s oesophagus. We extracted the DNA from the biopsies and compared the data. What we found was a higher genetic predisposition, meaning that genes associated with Barrett’s oesophagus were more frequently present in oesophageal atresia patients compared to the healthy adults. Also, we found that genes involved in inflammatory responses, stress responses and oncological processes were more frequently disturbed in oesophageal atresia patients compared to healthy born. 

Another thing that we wondered was if oesophageal atresia patients may also respond differently to reflux episodes. We know that reflux is more common in oesophageal atresia patients. But what if they are not only exposed more, but also respond more heavily to this exposure? 

To simulate this, we set up an experiment. We used fibroblasts of patients born with oesophageal atresia and of healthy controls. And fibroblasts are actually skin cells. And these skin cells can be compared to the squamous epithelium of the oesophagus. And the reason that we did this with fibroblast instead of the biopsies is of course that it’s not ethical to just take biopsies with a gastroscopy from healthy controls. So therefore, we chose the next best thing and we chose for the fibroblast. The fibroblasts were grown in a petri dish, either in a normal medium with a normal ph. or exposed to acid for 30 minutes. And after the cells were fully grown, we extracted DNA from the fibroblast and we compared the results. We found similar results in this experiment as in the previous.

So again, we found disturbances in genes involved in the inflammatory stress response and oncological processes, and there was an overlap between the results of the biopsies and those of the fibroblasts. Altogether, these results contribute to the puzzle, but again no central gene could be detected and similar to the development of oesophageal atresia itself, it seems to be a multifactorial cause. 

For the last part, I would like to tell you a little bit about the pulmonary follow up.

In 2019 the Center for Congenital and Perinatal Pulmonary Diseases was founded. In this center they treat multiple conditions next to oesophageal atresia. At this moment, 277 patients born with oesophageal atresia have visited the center for follow up. During the intake, which ideally takes place at 17 years old, patients undergo a lung function test, a CT scan and consult the pulmonologist. 

The results of the first 180 patients have been analysed and will be published very soon by my colleague Stephanie Wintos, who is a new PhD student in our department. 

To conclude, it is important for healthcare professionals to realise that many adults still experience gastrointestinal and pulmonary problems on a daily basis. A multidisciplinary follow up program is necessary, but with one coordinating physician. In practice that is most likely the gastroenterologist, which but could also be the pulmonologist or is discussable in every hospital for itself. 

This follow up program should not only pay attention to these physical problems, but also to the mental health, socioeconomic problems in daily life, of course, the gastrointestinal and the pulmonary complaints. Endoscopic surveillance to detect Barrett’s oesophagus at an early stage is important and of course, the involvement of the pulmonologist. 

If you have any additional questions after this presentation, I’m happy to of course answer them now, but this is the email address of the national email address for follow up in the Netherlands, and though it is for the Dutch patients, we are always happy to also answer your questions wherever possible or refer you to in the right direction for the right type of follow up. And with this I would like to close my presentation and I’m happy to answer any questions.