BRITISH BROADCASTING CORPORATION
RADIO SCIENCE UNIT CASE NOTES Programme no. 2 - Barrett's Oesophagus
RADIO 4 TX DATE: PRESENTER: TUESDAY 28TH JULY 2009 2100-2130 MARK PORTER
CONTRIBUTORS: REBECCA FITZGERALD RICHARD LOGAN ELIZABETH EVANS PAM GODDARD RICHARD HARDWICK IRENE DEBRAM
NOT CHECKED AS BROADCAST
PORTER Hello. Today's programme focuses on the link between indigestion or heartburn and cancer of the oesophagus. It's the ninth most common cancer in the UK, and very difficult to treat if caught late. There are nearly 8,000 cases a year in the UK, two thirds of whom will be dead within just 12 months of diagnosis. The link with heartburn centres on a condition called Barrett's Ooesophagus - a change in the lining of the gullet known to increase the odds of cancer. Stomach acid is almost as strong as car battery acid and while the stomach has a layer of slime to protect itself, the lower part of the oesophagus or gullet does not. If acid travels back into the gullet - a condition known as reflux - it can burn the delicate lining causing heartburn and, in some people, the pre-cancerous changes associated with Barrett's. At least three million people in the UK have reflux and heartburn due to a weak valve at the top of their stomach - a problem that is particularly common in pregnancy and in anyone over the age of 35. One in 10 people with reflux will develop Barrett's - and one in 10 of them will go on to develop cancer of the oesophagus. But how can doctors identify those who have something to worry about, and reassure the millions of reflux sufferers who do not? Later on I'll be trying out a new screening test developed by the Medical Research Cancer Cell Unit at Addenbrooke's Hospital in Cambridge. Rebecca Fitzgerald is leading the research and is a consultant gastroenterologist at the hospital. FITZGERALD So most people with reflux of acid and bile do get symptoms, not everyone. So some people can have acid and bile coming up and just not be aware of it, their oesophagus is just quite insensitive. So it's possible to have it without knowing. But most people have symptoms and the typical symptoms are a burning sensation which occurs in your chest, the reason it's called heartburn is because you feel it in your chest near your heart but it's nothing at all of course to do with your heart. So the burning sensation can go high, all the way up towards the back of your throat. You may get an acid or a bitter taste in your mouth. Often it's worse when you bend over or when you lie down at night because then you haven't got gravity to help the acid stay down. LOGAN Yes, so Richard Logan. It was heartburn when I laid down in bed at night and I had a monitor put down me which was basically a reel to reel tape recorder strapped on the side of you which monitored the acid level and they found out I was getting reflux during the night. FITZGERALD Well for most people it's just a nuisance, the symptoms are a nuisance, and it can affect your quality of life. But for a proportion of people, about 10% of people with reflux, it can lead on to more serious consequences and in particular damage to the lining called Barrett's Oesophagus and that potentially can lead to cancer. So for most people it's harmless, a nuisance, the symptoms just need to be dealt with but there are
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a minority of people in whom it can be serious and those are the people we need to know about and check out. PORTER And what actually happens in Barrett's, I mean where does the name Barrett's come from? FITZGERALD So Barrett's Oesophagus is the name of the surgeon that first described it. He was a surgeon who worked in St. Thomas' in the 1950s called Norman Barrett and he described this phenomenon, it was named after him. So what he noticed was that in some people with heartburn and reflux symptoms the bottom end of the oesophagus, the lining, had changed. So instead of being the type of lining which is quite like the skin, it's turned to a lining where it resembles the stomach or the intestine. And the idea is that maybe if you keep having acid and bile burning your lower oesophagus then the cells kind of change to try and protect themselves, to become more like the lining of the stomach or the intestine that's used to having acid and bile but it's like a kind of protective, adaptive, mechanism. But unfortunately it's not purely a good adaptation, it can sometimes go wrong. PORTER So some of those people who've got these changes will go on to develop cancer at some stage, do we know what the timeline is? FITZGERALD It's slow, it's a process that takes years, so that's good because it can be monitored. So roughly speaking about 10% of people will have Barrett's and between 2 and 10% of those will go on to get cancer. So about one in every 200 patients we see per year with Barrett's will get cancer. PORTER Over what sort of period, I mean say many years - are we talking two or three or 10 or 20? FITZGERALD Probably 10 or 20. The trouble is we don't always catch people when they've very first got their Barrett's, so we may not know quite where we are in that 20 year timeline. PORTER Because I'm sitting here as a GP thinking I've got lots of people on these medicines for their heartburn, how do I know which of those one in 10 may have Barrett's, first of all, I mean presumably the one way is to do an endoscopy? FITZGERALD Yeah, I mean that's the big question and that's something which researchers like me are very interested to try and better understand because we don't want to be putting every single person in the UK through an endoscopy that's got heartburn ... PORTER
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Well you wouldn't be able to. FITZGERALD We wouldn't be able to, exactly, it would be completely impractical. So we've got to find smarter ways of picking up the people with Barrett's. But at the moment the only real way that's sort of proven to diagnose Barrett's is an endoscopy and taking a biopsy. So it means if you've got a patient who's had reflux for a number of years and the symptoms are quite bad they have to be permanently on proton pump inhibitors, then those are the sorts of people that need an endoscopy. PORTER People like Elizabeth Evans. EVANS Well anything I ate that was spicy or milk or dairy products then they had to come back, they didn't stay down. PORTER You mean come back you're actually sick? EVANS Yeah, sick, really sick. PORTER And did you have discomfort as well? EVANS Yeah, not so much the heartburn but really bad indigestion, real bad pains and deep down indigestion. PORTER You said you had it four years so what did you do about it, were you treating yourself or had you been to your doctor? EVANS I'd been to the doctor and I'd been given different pills - Gaviscon and pills and different things. FITZGERALD Some people have belching, some people rather than a burning they feel more of a pain in the top of their - just under their breastbone and that's perhaps what people more classically describe as indigestion rather than heartburn. PORTER And presumably by the time patients come and see you many of them have been selfmedicating for a while, I mean is it normal for them to have had these symptoms for long periods and they've been treating themselves? FITZGERALD
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Yeah, I mean often patients will say oh I've had this for years and I've always had Rennies in my pocket, that kind of thing. So we - you can get some medication very easily over the counter, you don't have to go and see your GP and medicines that before you had to go and get a prescription for, like omeprazole or losec, the class of drugs called proton pump inhibitors which are very effective indigestion and heartburn remedies, you can now just buy for yourself without a prescription. PORTER Indeed, I mean the PPIs I mean they're one of the most widely prescribed drugs in general practice, they're incredibly effective at relieving symptoms. We often go on the story alone, I mean a lot of our patients come in with the classic story of reflux, we'll put them on [indistinct words], they'll get better but how are the drugs actually working - they're switching off acid production are they? FITZGERALD Yeah, so they do exactly what the name suggests really, so you're making - acid production is by pumping out protons and these block those pumps, so they just switch them off, so you no longer produce acid. PORTER Does that matter? FITZGERALD For most people the heartburn is such a nuisance that they're much better on the medication and they may have very little or nothing in the way of side effects. However, patients might be more prone to getting tummy upsets, for example, just because you haven't got that defence mechanism there. Like all drugs there are potential side effects - some people get a bit of diarrhoea - but for most people they tolerate them very, very well and they're happy to take them. PORTER The vast majority of people with heartburn and acid reflux will never develop Barrett's, and nine out of 10 of those that do, will never develop cancer. But if you have Barrett's the odds are still high enough to make regular monitoring advisable. And the only way to do that - at the moment - is by having by an endoscopy - a camera down your throat - every two years or so. FITZGERALD So the endoscope we're using for this procedure is a long tube, about one and a half metres in length, which is about the size of my little finger. It's very flexible, so you can move it side to side and up and down and you can control that - you use two hands, one to introduce the instrument and the other to control whether you're bending it or not with your right hand on the controls. You can blow a bit of air down the instrument, so that helps to open up - the oesophagus is normally collapsed if you're not eating, so if I puff in a bit of air you can distend it, so you can really see what's going on. PORTER
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I remember going to my first endoscopy that you know you'd actually look down the instrument and that's all changed - we're standing here in front of a big video screen which must make it much easier. FITZGERALD Much, much easier. And the quality of the pictures too are much better, so they used to be fibre optic scopes and if one of the fibres blew you'd have a little black dot on your picture but now we've got this very nice high resolution video image. PORTER This gentleman's been sedated, what's the normal procedure for it? FITZGERALD So we normally give patients a choice between being sedated or just having the throat numbed. For Barrett's we're often taking a number of biopsies so patients tend to opt for sedation but not always. There are pros and cons, the sedation's a valium type of drug, it wipes out your memory of the procedure afterwards and he'll go home later today, he'll stay - if he's been sedated we'll let him rest after the procedure for about 20 minutes and have a sleep, he probably won't remember anything about it at all, we'll then give him a cup of tea, explain what we found and he'll go home about an hour after the procedure. So we're going into the oesophagus now. You can see that this is the normal light pink appearance of the oesophagus. PORTER The colour of a raw sausage. FITZGERALD Yeah, that's right exactly, that very light pink. That looks nice and normal. And then that black hole down the bottom of the screen is going into the stomach but what you can see is that there's much deeper red sort of salmon colour lining coming up into the oesophagus and that appearance you shouldn't see until you get into the stomach. So if you like you've got a stomach kind of appearing lining further up in the oesophagus. PORTER So looking at this what sort of length - how long is that strip that we're looking at, give me some idea of the scales? FITZGERALD It's about four centimetres. PORTER A couple of inches or just under. FITZGERALD Yeah and the complete oesophageal length is about 20 centimetres, so it's just a very lower bit of the oesophagus. PORTER
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Now so this is the area ... FITZGERALD That's looking at the Barrett's now, so we're just going to measure it, we've got markings - centimetre markings - on the endoscope, so we can just measure how long it is and compare how long it is this time compared with last time. PORTER So surveillance involves, what two things - measuring whether it's actually got any bigger and whether there's been any change within that tissue itself? FITZGERALD We do always measure it, although to be honest it rarely changes in length, once you've got your length, whatever it is - four centimetres, 10 centimetres - it tends to stay that long. But there are two main parts to the surveillance really, one is really looking carefully to see if there's anything that looks - doesn't look smooth, any little nodules or ulcers, those are things which give you a warning sign that there may be cancerous changes. So we always look very carefully for that. And then taking biopsies which are looked at under the microscope. So we take biopsies of area even that look normal in the Barrett's, as well as any little nodular things we can see. This man's got a hiatus hernia, it's what we're looking at here, so this is where the stomach, the top of the stomach, has just moved above the diaphragm. PORTER And that will compromise his valve at the top of the stomach, which may be one of the reasons why he's got this in the first place. FITZGERALD Yeah, so that will make his reflux worse. PORTER So by looking at - I mean it all looks pretty uniformly red here, but you can tell just by looking at areas that are perhaps more suspicious than others. FITZGERALD You can get an idea and there are newer techniques coming on board which enable you to look with more detail that we're not using here today but sometimes if you look at the fluorescent properties of the oesophagus, for example, that can tell you that a particular area might be changing, so then we can biopsy that. But this all looks quite normal does it Beth, it looks nice and smooth, nothing that makes us worried. So what we're now starting to do now is to take biopsies and what we do is for a four centimetre segment we take two levels, so we tend to take biopsies every two centimetres and we take them in four positions - 12 o'clock, three o'clock, six o'clock and nine o'clock - so we take four biopsies every two centimetres. You can see the little tiny spike on the end of the biopsy forcep, that just helps us get a nice bite. The piece we get though it might sound as if it's going to be huge, it's only two or three millimetres. LOGAN
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Having had the monitoring they then sent me for an endoscopy which found Barrett's Oesophagus, which otherwise you don't know anything about. So I was then monitored for quite a few years, I think I started back in about 2003. PORTER But how did they explain Barrett's to you, I mean they use this term, what did they say it was? LOGAN It was really damage to the oesophagus caused by stomach acid coming back up. I too had the hernia of the stomach. PORTER Hiatus hernia, weakening of the valve, which weakens the valves. LOGAN Yes, but the trouble is you - a lot of people don't even know they've got it, this is the problem. I was very lucky that they found it and they then monitored it because they did explain to me that it could turn cancerous, should the cells change. So I had regular endoscopies, about every year or two years. It then started to get more frequent, so they obviously were picking up some change in the cells. At the same time Dr Fitzgerald runs a Barrett's Oesophagus club, for want of a better word, which I went to one or two of their meetings and things were explained in far more detail there, not only of the ways of treatment but of new techniques coming in from the States and Europe which I was fortunate enough to have the option to take. FITZGERALD Well the good thing is that if you detect cancer very early in Barrett's you can cure it. And over the last few years it's now become possible to cure it not with an operation but with simple endoscopy treatments. So this is a relatively new treatment, it's called radio frequency oblation. So it uses radio frequency energy to burn off the lining of the oesophagus. So we simply do an endoscopy procedure, sedate the patient, use a balloon to size up the lower oesophagus and then apply this energy and it can usually be done in one or two treatment sessions and it just literally burns off the lining. It's still quite early days for this treatment, so NICE are considering whether to approve it or not. The first big study's just been published in the New England Journal, it looks to be very successful. LOGAN The first option is to do nothing of course which could be disastrous. The second option was to go for radio frequency oblation treatment, which is a new treatment, relatively new treatment or to have complete invasion of the chest and removal of the relative bit of tubing. I opted, because of the recovery period really for that, I opted for the radio frequency oblation because it was non-invasive and I was off work for about two days. PORTER So it was done by an endoscope rather than surgeon's knife? LOGAN
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Yes exactly, exactly, so you came out of it really no worse than a normal endoscopy, other than a bit of a sore throat. And you were then on a limited diet for about 10 days - a liquid diet. PORTER And what's happened since? LOGAN I've been fine. I've been back - I had two treatments because the average I think is one and half treatments, so I was one of the double treatments. They then monitor they now monitor me, I'm on a heavy, sort of every three months, monitoring course because my operation was in November last year. So we now monitor it to see how it goes. But I have no problem whatsoever but I'm still on medication. PORTER Yes because while they stripped away, if you like, the bad lining they've not affected the fundamental problem which is that you've got acid coming to the wrong place. So you're still on anti-acid medication? LOGAN Yes, yes but it's been totally successful and what I really appreciate is the lack of intrusion - invasion in your systems really and long recovery periods. And possible changes of lifestyle - you know your eating habits have to change. PORTER You've not had to make any changes? LOGAN I've not had to make any changes at all. PORTER Pam Goddard was not so lucky - by the time her Barrett's was picked up it was already progressing towards early cancer, and more radical treatment was required. GODDARD It was one Christmas I found I couldn't swallow, which was what kicked off me actually going to the doctor's. PORTER When you say you couldn't swallow, what did you ....? GODDARD It was trying to eat food, it would not go down. You'd sort of sometimes have to bring it back up, you'd have to really chew it up small and it wouldn't go through the oesophagus. PORTER So you went to your GP and what did he or she do? GODDARD
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She referred me for an endoscope and that's when they found I'd got Barrett's Oesophagus and they put me on some pills and then about a month later you see your specialist and he said - because they take biopsies at the time - that he couldn't believe that I'd got a negative result from how bad the oesophagus was. PORTER So it looked bad ... GODDARD It looked bad and he couldn't believe that I'd got a clear result back from the test. So he sent me for another one. And that was when they found I'd got nodules and it had changed. So then you hit the ground running. And then came back to see Mr Safranek and that was when he told me what the options were really. PORTER And those options were? GODDARD Well to remove it. So I didn't have any other choice really, it's have it removed or not live for very long. PORTER Richard Hardwick is consultant upper gastro-intestinal surgeon at Addenbrooke's. HARDWICK You know the great difficulty Mark is that the gullet couldn't be further from the outside world if it tried, it sits right in the middle behind the heart and between the lungs and getting at it is the big problem. And traditionally that's always involved a big operation, either with one single cut in the upper abdomen or more usually an abdominal incision plus a big cut in the chest to be able to get to the gullet because you have to deflate one of the lungs and it's big surgery, it takes a lot out of the patients. As techniques have developed we've been able to start using keyhole surgery to get at the gullet but that in itself is not straightforward. PORTER And presumably you're doing exactly the same procedure, it's just smaller scars on the outside which sounds like it makes your job more difficult. HARDWICK Yes, I mean there are specific technical challenges and one of my colleagues, Peter Safranek, who has introduced the technique here in Cambridge and is bringing this forward, he has to use lots of different instruments with tiny little holes and cameras and actually once all the equipment's in place you get a fantastic view. But you know these keyhole operations do generate their own technical difficulties but for the patient, if we do it safely, the advantage is that it's much less painful because you avoid the big incisions and their recovery back to normal health is definitely quicker. PORTER
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And what's actually being removed, when you - obviously if you remove the gullet that leaves you with no collection from the top end of the gullet to the stomach, so how do you reconnect the plumbing? HARDWICK So what we've got to do basically is use another part of the gut to make up the difference. And actually the stomach is an amazing organ and it can be cut into a long thin tube to replace the gullet and that's what we usually do. PORTER So you're drawing part of the stomach up into the chest effectively. HARDWICK That's right and depending on how much of the gullet we take out obviously the tube will have to be of varying lengths and be attached at various heights within the chest but we usually take most of the gullet out. PORTER What will the patient notice afterwards in terms of their ability to eat and drink, once they're fully recovered? HARDWICK The big issues they have are the amount of food that they can eat, the volume of food, and that is their biggest challenge is that they have to eat little and often. And with time - and we're talking about probably a year to 18 months - they do get back to eating pretty good amounts of food but it's never quite the same. They've lost the normal valves that regulate things going down and back up again and that clearly is an issue, so they need to be careful they don't lie down, for instance, too soon after eating otherwise the food tends to come back and we have usually interfered with the major nerves, the vagus nerves, that run next to the gullet in taking it out and that can cause a condition called dumping with abdominal tummy cramps and feeling strange after you've eaten. So there are some longer term problems that patients who've had their oesophagus removed need to grapple with. Most of them cope with it in time but it's never the same as having your own gullet. GODDARD Well it's been a long road, it's hard work, you've had to learn - I eat little and often now. You get upset stomachs, you learn what you can eat and what you can't. PORTER So you've lost the lower part of your gullet and the top part of your stomach effectively. GODDARD Yes that's right but I had keyhole surgery so that was less invasive. I've got a scar in my neck, and little nicks you know. PORTER Small scars on the outside but still a fairly big operation, how long did it take?
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GODDARD Well I was off work for nine months. PORTER And how long was the procedure itself? GODDARD It was an eight hour op. PORTER But at the time I mean to commit to an operation of that size you must have realised that the condition you had was potentially ... GODDARD Oh yeah, yeah, oh yeah. PORTER ... very serious, I mean did someone spell it out - if we don't go in now? GODDARD Oh yeah. PORTER Well what did they say to you? GODDARD He said really they thought this was the only option, you couldn't leave it there it had got to come out, you couldn't leave it in. PORTER Because this is curable at this stage but if we leave it, it might not be. GODDARD Exactly, but if we leave it you don't know and I do know several other people that were diagnosed at the same time as me, maybe they were a little bit worse but they haven't survived. I want to live. PORTER Pam was fortunate but ideally the sinister changes in her gullet would have been picked up even earlier. And they might be if Rebecca Fitzgerald gets her way. Rebecca and her team at Addenbrooke's have come up with a simple screening test that can be used to identify which people with reflux have Barrett's. And it can be used in a GP surgery. FITZGERALD So what we've come up with is a we call it a capsule test and then the test has two parts, a little device which is very easy, you can swallow at the GP's surgery, and a molecular test. So it's a capsule like a pill on a string and you swallow that down and you hold on to the string, which is quite important, so it doesn't disappear off. You swallow this little capsule down and it wiggles down on the string, down your
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oesophagus, and it just sits in the top part of your stomach. And the capsule dissolves over just two or three minutes and when the capsule's dissolved it gives you a little sponge ball, it's a bit like a sort of brillo mesh, and that opens up and it's about the same diameter as your oesophagus, so then when we pull it back we collect a cell specimen on the sponge. So that comes out, we put it in to some preservative fluid and we've developed a molecular test using a couple of proteins that we know are only present in Barrett's and not present in normal oesophagus and we then test for those with the idea that we can then see who's got Barrett's without doing an endoscopy. PORTER And how accurate has your early work showed that test to be compared to the conventional endoscopy and biopsy? FITZGERALD So, so far we've given it to about 400 people and we seem to be able to detect about 82% and we get it right 94% of the time. PORTER That's pretty good for a screening test. FITZGERALD So we're pretty happy with that. PORTER Well I, as you know, have had reflux for a number of years and in fact I take a proton pump inhibitor everyday, so I suppose I should avail myself of your new technology. FITZGERALD We'd be delighted. PORTER Time to meet Irene Debram, who's the senior research nurse on the Barrett's Oesophagus Screening Trial - or BEST for short. DEBRAM So that's the sponge you're going to swallow, it's a capsule on a string. What we tend to do is to bunch the string up, so it makes it easier for you to swallow it all in one go and we want you to put it as far back to the back of your throat as possible. Nice big gulp of water and then just keep drinking till the capsule goes down. A bit of cardboard stays on the outside so we can pull it back. PORTER I wasn't going to swallow that as well don't worry. It's bad enough the capsule, it's about one and a half times the size of an antibiotic capsule, so it's not too bad. Good idea you put an apron on I think. So Irene how many people have - you've given this to hundreds of people presumably, is it you that's doing all the giving? DEBRAM
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Well it was in the hospital we've ran - this is the pilot study. The patients we've recruited for Barrett's Oesophagus we've done about a 100. PORTER And most people manage to swallow it without any problem? DEBRAM Most people. And with the other study now we're doing there is a number of people in the community who are suffering with long term reflux we've recruited over 400 individuals and we do this test on the patients out there and then they come in at least seven days later to have an endoscopy. Are you right handed? PORTER Yeah. DEBRAM Take it into your right hand, holding the string, glass in hand. All the way back to the back of your throat and keep drinking, I want as much - don't stop drinking, keep drinking. If you stop for a moment, let's have a look. Oh perfect. Well done. So we leave it down for about five minutes. If you want to drink more you can. Is it irritating the back of your throat at all? Just breathe through your nose and out through your mouth, it tends to settle everything. PORTER It's going to be a long five minutes. And it was - though nowhere near as bad as anticipated. I will spare you the sounds of the sponge being pulled out - suffice to say that the subsequent analysis showed that I do not have Barrett's. But what if I had - other than the regular follow up, what could I do to minimise my risk of developing cancer? FITZGERALD At the moment the standard clinical advice we give to patients is that they should have treatment to control their heartburn symptoms, so that might mean losing a little bit of weight, it might mean elevating the head of their bed, that just helps the acid and bile keep down and not come up and often taking acid suppressant tablets and proton pump inhibitors are the most effective, sometimes in high doses. Whether that will actually prevent you progressing to cancer we don't really fully understand but there is some early laboratory evidence suggesting it might and there is a trial going on in the UK looking at whether suppressing acid and having an aspirin to reduce inflammation might reduce risk of progression to cancer. PORTER Elizabeth Evans' s Barretts was picked up when she was screened as part of the BEST trial. EVANS They've increased my medication and I've got to stay on that for always and I have an endoscopy every one to two years to make sure that it doesn't go further.
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PORTER But in terms of symptoms on the high dose medication do you get any heartburn, do you get any problems? EVANS Still a bit on occasions but I watch the things that give me it, I don't eat spicy food, well not very spicy food. I think what they've done is magic really because I know I'll be watched and I'm on medication and if there's any changes I've only got to pick up the phone. PORTER It's nice being looked after isn't it. EVANS Yes it is yeah.
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