Managing oesophagogastric cancer in general practice
Welcome everybody to this group session and thanks everyone for attending. I would like to begin by acknowledging the traditional owners of the land we are now meeting, I am here today, and pay my respects to the eldest past and present. This webinar is proudly supported by the Cancer Council Victoria, The University of Melbourne and Victorian Government. I would first like to introduce our two presenters of tonight’s webinar, Prof Jon Emery and Prof Alex Boussioutas. Prof Jon Emery is a Herman Professor of Primary Care Cancer Research at The University of Melbourne and the primary care research and education lead at the Victorian Comprehensive Cancer Centre. He is an NHMRC Practitioner Fellow, Director of the Cancer Australia Primary Care Collaborative Cancer Trials Group and a visiting research fellow at the Department of Public Health and Primary Care, University of Cambridge. He was previously professor of general practice and a head of the school of primary aboriginal and rural health care at The University of Western Australia. He has worked with Cancer Council Victoria on implementation of the optimal cancer care pathways in Victoria, so welcome. Prof Boussioutas is a tenured academic clinician at the University of Melbourne in the Department of Medicine at The Royal Melbourne Hospital. He is currently the associate dean of graduate research in the faculty of medicine, dentistry and health sciences. His current clinical positions are Deputy Director of Gastroenterology at The Royal Melbourne Hospital, gastroenterologist at Peter MacCallum Cancer Centre and Epworth Healthcare. He also leads the GI Risk Management Clinic at the Peter MacCallum Cancer Centre Familial Cancer Service where his interests include hereditary colorectal cancer and hereditary diffuse gastric cancer. Thanks Prof Boussioutas. I am going to turn off the video of you guys now so I will get straight into it and I will handover to you.
So, I presume that most of you are familiar with using this webinar software. I don’t know whether you want to add any more?
Yeah maybe if anyone has any questions throughout the session today, feel free to send through questions, you will find them in the panel on the right-hand side of your screen. Through our tonight’s webinar we will also be doing some polling questions, so answer them as swiftly as you can and we will endeavour to show you the results as quickly as possible. We usually leave them up for about 30 seconds to give everyone an opportunity. You are all on mute at the moment so there are no verbal questions; however, I will be taking written questions throughout the whole entire presentation. I will filter those, and I will pass those on to Alex and Jon throughout the presentation and we will answer those that come through that I think are relevant and worthy of being answered on the spot. Anything that is not we will endeavour to get back to you if we feel that it is necessary.
Okay, so these are the areas that we plan to cover in this evenings webinar so we are going be discussing some of the evidence related to prevention and early detection of oesophagogastric cancer and considering some of the initial investigations and referral pathways for people with suspected OG cancer. We will discuss the evidence around surveillance for Barrett’s oesophagus and then present some evidence-based chores around assessing risk of somebody who presents with symptoms and then what the local referral pathways and diagnostic pathways for people with suspected OG cancer look like. So, to begin with, this is our first polling question and I will explain why we are asking this in a moment, so please if you could answer this first question around your awareness of the current optimal care pathways in cancer.
Third good, third fair and third poor.
Okay that does not surprise me particularly that is the cause partly why we are here today, so this webinar is actually supported through the Victorian Government as part of their implantation of optimal care pathways which are now a national program which are really aimed at describing current best evidence and practice for the 15 commonest tumour types covering the whole continue of care from prevention, early detection, treatment for and palliative care and so they are really about defining what a standard of care should look like for the whole of Australia, for patients with these cancer types. They are slowly being implemented across all the states and there are some key aspects from a primary care point of view which relate to having clear pathways of diagnosis and an intubated pathway of care and particularly highlighting the importance of communication between the different health care sectors and key transition points along the diagnostic and treatment pathways with the aim to inform quality improvement projects which are beginning to be implemented in various states as part of this national program for optimal care pathways. So, we hope that you gradually become more familiar with this as you start to see some of these programs being implemented to improve the sort of quality of cancer care.
So, we are going to focus this session specifically on oesophageal and gastric cancer
I am going to begin with just some background around current Australian statistics; so, beginning with gastric cancer so these are the numbers of the estimated cases that will be diagnosed this year, so just over 2300. It is the 15th commonest cancer in Australia and actually the 50th commonest cause of cancer deaths in Australia, which is not terribly common and just over a 1000 people will die of the condition and you will see obviously that it is more common in men and current five-year survival for gastric cancer is 29%.
These are just to show that gastric cancer both the incidence and mortality have been falling really over the last 30 years and Alex might want to comment later on as to some of the reasons why that may be. Well, you might want to chip in now actually.
So certainly one of the things that has been noticed, and I will just backup one slide, talk about this reduction in prevalence of gastric cancer, this is a global phenomenon that has been happening and it is probably related to refrigeration, less pickling, less salting in food and nutritional improvements in certainly developed nations and this is what we are seeing across the board in developed nations. The highest incidence and prevalence are in East Asia and Eastern Europe and South America have got very high prevalence as well, but this phenomenon is also happening with them but probably less so. What is a bit of a concern that has been raised now in certainly gastrointestinal circle is being the slight plateauing that you are actually starting to see that towards 2010 to 2015 and this certainly is a phenomenon that again is being seen across the board that it may actually be plateauing out now and not reducing much further.
So age is probably a most important risk factor and just to highlight obviously again that it is more common in men but the incidences really only starts to rise in the sort of early to mid-50s and I will point out why that is relevant later on when we start to think about assessment of patients with symptoms and taking age into account as you determine risk of an undiagnosed gastric or oesophageal cancer.
So risk starts to increase from the age of 50 that is more common in men. Family history is a risk factor and there are specific familial gastric cancer syndromes that are relatively rare but with known genetic mutations underlying them. H pylori infection is an important risk factor and we will come on to that later on when we start to discuss H pylori eradication and then the other risk factors smoking, Asian descent and again that is probably partly dietary but also may be genetic as well. And then specific conditions pernicious anaemia and more historically really, partial gastrectomy for ulcer disease though obviously that is a much less common treatment these days.
If we then just think about oesophageal cancer slightly less common than gastric cancer so just over 16,000 people will be diagnosed this year again more common in men, it is the 19th commonest cancer in Australia but the 12th commonest cause of the cancer deaths and say nearly 1500 people would die of the condition this year and as you all see the five-year survival is somewhat less and is of gastric cancer and again some of this relates to late stage at presentation and again why early detection is an important part of the ability to try and improve survival rates both for oesophageal and gastric cancer.
So the incidence of oesophageal cancer is slightly confusing because there are two types of oesophageal cancer and while squamous cell carcinoma rates have been falling this has been occurring at the time when adenocarcinoma rates are rising and so you see this sort of relatively flat overall pattern of incidence and a slight reduction in mortality but not huge but we will come onto that discussion a bit later in the context of Barrett’s oesophagus as well. Again age is an important risk factor and again you do not really see rates beginning to rise until early 50s and again I will flag why this is important later on in the context of assessment of people with symptoms, so again male sex is again an important risk factor along with smoking, but again slightly different other risk factors so obesity and associated cause with that is gastro-oesophageal reflux. Alcohol again is an important risk factor so there are some preventative approaches to be considered particularly for oesophageal cancer in terms of smoking and alcohol reduction and then specific conditions achalasia and Barrett's oesophagus.
So, we have another polling question before we go on to a more detailed discussion around Barrett's.
It is about 75% of people and it is pretty evenly spread between the two, let us say.
Because that is 20% on either.
Right, so I am going to handover to Alex to discuss Barrett’s oesophagus in more detail.
Thanks Jon, so I have got a few detailed slides here, but I will just take you through them because I think there are some important aspects here. There are a couple of difficulties that gastroenterologist actually face, gastroenterologist and pathologist for that matter and one of them is defining what Barrett's actually is. The strict definition of it is that it requires the squamous epithelium of the oesophagus to be replaced with a condition called the intestinal metaplasia. Metaplasia is just that change of tissue from somewhere that it should not be and that does not normally grow in that place or have any development in that place. It often is referred to as a columnar epithelium but increasingly we’re requiring specialised intestinalisation which is what this diagram actually shows here, so hopefully this projects well but this is squamous epithelium which is stratified and basically what skin would look like as well and that is what the oesophagus should look like. When you get these glandular changes here which are very atypical and you get a single cell layer over here, this particular area you can see between these glands is quite inflamed and is pretty typical of an inflamed segment of Barrett's oesophagus. Intestinal metaplasia is where you actually get some specialisation of this epithelium with the existence of goblet cells and there is some here that you can actually see within the glandular structure but that is not an absolute necessity to diagnose this condition although increasingly it is being used to assess whether someone’s risk of developing adenocarcinoma is there so the importance of this is that it is a definite premalignant condition. The risk is actually of oesophageal adenocarcinoma not squamous, so this is a particular risk factor for the adenocarcinoma, which is the one that has got increasing rates. In Australia, the detection rates and this is sort of from a study that was published out of Queensland has shown an increase in patients, now this is a bit of a biased sample but this is effectively what we can try and sample and these are people having endoscopies back in 1990, 0.3% of these had Barrett's oesophagus whereas in 2002 some 10 or 12 years later it went up to almost 2%. This is sort of a graph that I think Jon was alluding to and you will see this sort of graph with oesophageal adenocarcinoma where with increasing timeframe we see an increase in the amounts of diagnoses of oesophageal adenocarcinoma but this is actually referring to Barrett's oesophagus and the Barrett's oesophagus diagnosis is that clock there, so you can actually see almost an exponential rise.
So again in terms of definition, it requires two people an endoscopist and a pathologist so an endoscopist alone might be able to say I can see Barrett's oesophagus but one of the difficulties there is where this line which is called the Z line or squamocolumnar junction actually occurs. Part of it is related to posture to eructation and to potentially a hiatus hernia that could actually make it look like this over here and so from an endoscopic view on their own you could get a false positive but effectively this is what happens when you get Barrett's oesophagus you get approximation of columnar epithelium which you see here and the true gastro-oesophageal junction is further down. This again is an image of a fairly classical intestinal metaplasia of Barrett’s with lots of goblet cells as you actually see there.
Now, what is the problem with it, why are we concerned about it and it is because as Jon alluded to, it is a premalignant condition with fairly clear progression to adenocarcinoma. I will take you through this slide but one of the critical things that we have been thinking about in this space is really this section on the left of the slide here which is basically the progression through normal squamous mucosa. Because of gastro-oesophageal reflux disease, you do develop an inflammatory insult that then requires at the metaplastic epithelium to establish or glandular epithelium and then you can actually get progression through these grades of dysplasia where the cells become more and more confused if you like and eventually to adenocarcinoma and the rights of progression which have really changed over the years and changed to a lower number are really something close to this and it is anywhere between 0.125% and 0.25% over one year developing into low-grade dysplasia. Once you have got low-grade dysplasia the number start to kick off but the range is still quite broad and there are lots of reasons for this and one of them is what truly is low-grade dysplasia and pathologists argue about this all the time, I am not going to get into it now but basically there is how much higher rate once you have got a dysplastic epithelium to actually progress down this cascade into high-grade. Once there is high grade, some people actually used to believe that if you have got high-grade dysplasia present you probably just miss the intramucosal or some sort of malignancy nearby anyway and so up to 60% of people might actually have adenocarcinoma in the same sort of segment but very high rates within the next five years of doing an adenocarcinoma so something has to be done about this. I put this in because I think this is a really fascinating story about of how evolution and genetics actually play a role and a guy called Carl O'Maley actually put this together some years ago and if you imagine this being a Barrett's segments so this is a picture of an oesophagus down at the bottom and this is a Barrett's segment over here with some squamous epithelium here and normal stomach on this side over here and this is the Barrett segment so just imagine somewhat this diagrammatically being represented in this white square here what you can see an overtime is the development of these mutations that occur in particular cells and in particular genes and these are particular genes that have been selected and some of which you might have heard like P53 CDKN2A, what they mean does it matter, effectively what this whole picture means is that you develop a clone which then divides and takes over most of the epithelium that you see and then you develop another clone that also takes over what has been happening here and you slowly accumulate these clones overtime to eventually result in a cancer and this is what has been thought to be happening throughout this cascade here so in the earlier phases you are getting much less of these sort of changes until you get to critical phases down here which might occur in high-grade dysplasia and there is good evidence now that says that P53 is happening in that region in that time to actually result in a cancer referring.
The other thing that, as endoscopists, we always get worked up about is actually diagnosing it endoscopically so this is a picture that we typically see here on the left where you have got gastric folds or the gastric palisades over here and you have got this sort of salmon coloured pink tissue and the white which is normal squamous oesophagus, now where do we start to measure whether Barrett’s is actually present, do we start here down the bottom, do we start at B over here or do we start at A, which is over here and this has been perplexing us for many many years but the best estimate has actually been published and looks like it is the top of these folds here are the best but this is a very static image. In reality, this is moving like a little snake all the time and making life very challenging for us as endoscopists but this becomes important because we measure the degree of Barrett's we have got because that is an important factor in terms of risk of progression of this disease. So ‘how long is my Barrett's’ becomes a very important question and we do measure it from what I said a gastro-oesophageal junction which is actually from those gastric folds but as you can see in this case, we cannot really see the gastric folds very easily so understanding anatomy becomes very important, but it is basically here that we start to measure it and we measure two things the circumferential length of Barrett's which is if you look at this diagram over here this is the distance from the gastro-oesophageal junction so this will be the level of circumferential Barrett's and that would be termed C2 and then the mucosal limit of Barrett's which is here at M5 so this would actually according to Prague criteria and there is a group of gastroenterologists at a _____ conference in Prague a few years ago and actually decided on this and Prateek Sharma is the first author of this, and he came up with the Prague criteria which actually gave the value of circumferential Barrett's and M and mucosal Barrett's, so this segment would be C2M5 and in our language that means that it is a reasonable extent of Barrett's oesophagus. Basically, anything more than C3, we start getting more excited about.
Alex, can I just ask you a question.
So, when you have diagnosed Barrett’s would you keep that level of information in a letter back to the GP?
Yes, so this is something about I would expect, so this sort of level of criteria I do routinely on my reports and I would expect that anyone that does good Barrett's mapping and does Seattle protocol biopsies, which I will go into in a sec, should be actually giving you this criteria because this is what we basically gauge to determine risk of whether this person is likely to actually have an adenocarcinoma in the future. So, I think it is important information to put in our report.
Just a couple of other questions from the audience, can oral drugs increase the risk of Barrett's.
There are no real drugs that will increase the risk of Barrett’s. There are drugs that can worsen reflux so you can actually get symptomatic issues with that so it is anything that actually interferes with smooth muscle that is at the lower oesophageal sphincter so if you have lessened the contractions of the lower oesophageal sphincter you will get more reflux and that theoretically could create Barrett's but there is not a specific association between certain drugs.
What about alcohol.
Yeah, alcohol is certainly there as Jon put in the risk factors for this condition alcohol is one of the factors that worsens reflux and in fact in lifestyle discussions that we have on managing reflux alcohol, fatty foods, chocolate, caffeine are all things that actually worsen reflux and sometimes it might be enough for some people with very mild reflux that do not need particular medication.
Thank you and does the severity of somebody's reflux symptoms affect their risk of Barrett's.
It is also a good question. I actually had another slide that I could not put on here, that actually basically outlined that about 50% of people with Barrett's oesophagus have no symptoms and if you think about it, Barrett’s is actually a survival mechanism or a coping mechanism if you like, of the oesophagus that has been constantly insulted by acid reflux or alkaline reflux for that matter that also can happen but predominantly acid reflux that causes damage and by changing to glandular mucosa that damages not as hurtful so theoretically you might have even less people once they have got Barrett's actually having symptoms. So symptoms are not right and actually picking Barrett’s. So in terms of summarising this section the Barrett's is defined endoscopically and with pathology we do rely on a very good pathology to actually find those goblet cells for us and sometimes it is hard. It is increasing in prevalence and it remains increasing in prevalence oesophageal adenocarcinoma also and that is certainly increasing in prevalence exponentially and Jon's slide had both squamous and oesophageal so they almost cancel each other out because one is going down, one is going up but the one that is going down we do not focus on too much but the one that is going up is oesophageal adenocarcinoma. We have covered that it is a premalignant condition and the risk of progression is associated with length, the presence and degree of dysplasia as I have shown and to some degree the degree of molecular changes that actually can be found in that.
So, Jon I do not know whether you wanted to talk to this, or I can as well _____ so endoscopically once we determine that someone has Barrett's of a certain length, then we decide whether we are going to enrol someone into a surveillance program and what is required for that is obviously an endoscopy with this thing here called Seattle protocol biopsies. What that means is that biopsies for a particular segment of Barrett's are quadrantic, so they are basically taken at 12 o'clock, 6 o'clock, 3 o'clock and 9 o'clock and they have taken every 2cm of the segment of nondysplastic Barrett's. On those biopsies that is where we get the diagnosis of whether there is intestinal metaplasia or not, and if there is intestinal metaplasia then you go down a Barrett's protocol down here. If there is not then you go down this pathway to the right but if there is without dysplasia then that person, depending on the maximal length and this again emphasises the length of Barrett's being important, so this is maximal length if it is less than 3cm, then a repeat endoscopy in 3 to 5 years would be in order and I would say that the caveat here is that the oesophagus that actually has quite a lot of inflammation, we often do another endoscopy at six months that is not unusual because when you have got a lot of inflammation it may influence the degree of dysplasia that is there because pathologists actually find dysplasia very difficult to diagnose so that is actually seen here in the second section which is indefinite for dysplasia. This repeat endoscopy often happens because we need to actually see it in the noninflamed environment so that the pathologist can very clearly say that the changes they see in the cells are truly dysplastic and not due to inflammation itself. So, I will go back to the Barrett’s without dysplasia over here, if the Barratt’s length is greater than 3cm, then a repeat endoscopy in about two or three years, I usually do it in two years in that context but I am sort of guided by again the Prague level of length of Barrett's that we have got in terms of how frequently I will do it then. Now moving onto low-grade dysplasia, that again we will repeat in six months’ time if we did see low-grade dysplasia because of that pathological issue I mentioned. I would refer to more expert centres to actually have this then looked at and the reason for that is low-grade dysplasia is becoming more and more treatable these days with some of the ablative techniques which I will talk about in a second. High-grade dysplasia, as I have implied before, is of a concern that there might be, if you have taken a biopsy sample just next door to it you might have actually got the adenocarcinoma, so could this high-grade dysplasia be just adjacent to an adenocarcinoma that is already present but it certainly has high rates of progression so that we certainly would refer to an expert centre that has a multidisciplinary team that actually discusses these sorts of cases and often they go for some sort of definitive treatment. If there is adenocarcinoma often its surgery, if it is high-grade dysplasia, we usually use either resection techniques endoscopically or ablative techniques with resection if we can actually see it.
A referral to the expert centre is that something that the endoscopist would usually do?
Not always I must admit, sometimes I think they would and it depends on the practice and as we all know there are open access endoscopies around and they might often send back the patient to a general practitioner and it might be up to them to actually refer him to a practice
And so how would a GP know where the local experts have to be?
Well that is a good question. I think what was the definition of expert centre, I would say that people that actually could comfortably deal with endoscopically high-grade dysplasia have an available MDM or multidisciplinary meeting or team that would approach these sorts of problems that they have definitions of an expert centre also we have said that over here that you would need integration of endoscopy imaging surgery and histopathology and that again defines really an MDM in that sort of context and that is where I would say an expert centre would be, having said that, there are expert practitioners that deal with these sorts of conditions all the time and it really depends on the practice that initially had the referral and like I said the open access endoscopy centres may not deal with that but they may just as easily do.
So, moving on in terms of guidelines internationally these are the ones that are probably the closest two hours, I would say almost identical, these are taken from the British Society of Gastroenterology Guidelines that were published and updated just earlier this year. The update for this year was really trying to clarify that indefinite for dysplasia and low-grade dysplasia but effectively the same advice is given here and rather reassuringly they say the same thing so for non-dysplastic Barrett's over here on two endoscopies they do want two endoscopies to actually define these and if it is a large segment of Barrett's two to three years less than 3cm segment Barrett's three to five years as we have said if there is dysplasia that is confirmed by an expert pathologist on two endoscopies again and you have these characteristics here, we do treat with high-dose PPI and re-scope and I should say that our current guidelines which are the once before say the same thing, so this is to try and reduce that level of inflammation that I was talking about before and if they have low-grade dysplasia, they endoscope every six months and this is what an expert may do here because the low-grade dysplastic one cases are not advocated all the time for ablative or resection. If there is an obvious nodule, will be resected but ablation techniques are only now coming to the fore to actually treat this condition. We are much more comfortable treating this condition with ablative techniques which is the high-grade dysplasia but again MDM or MDT discussion and a therapeutic intervention which could be endoscopic or could be surgical.
Just a quick question, a few questions coming in about PPI use. Can it revert Barret’s?
There is unfortunately no evidence of reversion of Barrett’s with PPI. This is an interesting discussion about the value of PPI at reducing the progression rate. There is no randomised controlled data that is currently available that suggests that there has been any sort of progression or avoidance of cancer. There is a recent study that was published in the Lancet in July this year which was the aspect study. This is a quite a complex design study using PPI and aspirin in combination and solo to actually look at whether high-dose PPI could avoid the progression we saw. Now the outcomes that they measured all caused mortality rather than progression so when they subgroup the data to look at progression of the cancer of the oesophageal to oesophageal adenocarcinoma it was empowered to actually see that difference. There was a suggestion that it would improve that, but it was empowered to actually do that, so the evidence is not quite there. There was some observational data that suggested that PPI use may actually reduce the rate of progression but certainly not regression of Barrett's.
What about spicy foods? Would they increase a risk?
No correlation although you will often hear patients that say they had something spicy and something has happened, that is fine but that spicy foods is not one of the risk factors that we often see in terms of changing behaviour, changing reflux. Now in terms of developments and detection, there has been quite a lot and I am not going to spend too much time here but just to tell you that we just do not use what is called white light endoscopy which is just the images that I have shown you so far, we do use a chromoendoscopy where we spray things on the surface of the mucosa so we can actually see these glandular structures, which are very nicely pointing out this is what the villi would look like which obviously should not be in the oesophagus, but we can see that quite clearly. That is using sprays, there are technologies with certain instruments that use a filtration of wavelengths of light so that we can only see blue light and this is an example of one endoscopy company’s version of this where this is the white light image of the Barrett's oesophagus segment and this is what NBI looks like and again you can see these almost villous-type structures here and this is what high-grade dysplasia can look like, I mean even in white light endoscopy this is magnified of course, we do not actually routinely use this but in suspicious areas we can and we can see these squiggly lines that look very very irregular and these are very clearly delineated with NBI and so I guess the point of this is that there are new technologies that can actually help us identify Barrett's oesophagus and even diagnose sort of more complex lesions like dysplasia but you need a good eye, so you need a good endoscopist that can use these technologies and actually critically takes the time to do this because this does take time. In terms of therapy, what do you do about Barrett's once you actually have it? There are a whole bunch of thermal technologies including now cryotherapies that can be used as well to destroy the Barrett's once you have actually seen it and I am not going to go through these in detail but I will so spend a little bit of time showing radiofrequency ablation because this is used quite substantially in these expert centres around town. Mucosal resection increasingly has been used so this is a technique called endoscopic mucosal resection or endoscopic submucosal dissection which is more extensive type of resection that quite expert endoscopists actually do around town. One of the complications of ablations when you actually do ablate the epithelium that contains the Barrett's you can stricture, you get chest pain, you can get dysphagia usually because of those strictures, you certainly can get odynophagia so those people that use photodynamic therapy can get photosensitivity but we do not really use this in Australia anyway and you get this condition called sub-squamous Barrett's which is basically depicted here, so this is overgrowth of squamous mucosa that has buried the Barrett's underneath. When you look at this endoscopically from up above here you actually cannot see the Barrett's so it is only when you biopsy this quite deeply that you would actually find that there is still Barrett's that still harbours a progression rate but the exact amount of progression rate is not really known. So this is the HALO device that is actually used. This is basically a radiofrequency ablator, so this gets pumped up into someone's oesophagus.I have just got a diagram, so this is a length of Barrett's here. We put the catheter in, we expand it and we actually burn the oesophagus and that is actually as simple as it gets and this is one case that has actually had a 4cm segment of the intestinal metaplasia extending all the way up here. This was at the time of ablation, so we actually completely denuded all this squamous epithelium and all the mucosa actually sloughed off. And then this is what it was before, and this is what it is like after ablation after a month of it. So, you can get rid of it and there is certainly ______ that actually says that radiofrequency ablation in Barrett's oesophagus with dysplasia is a good thing. Back in 2009 this was a landmark paper out of the US that actually showed very good effect of eradication of dysplastic lesion and the primary endpoint for this was eradication of dysplasia with a secondary one that was really eradication of metaplasia _____ this was the data 12 months after this so this was randomised controlled. It was controlled with the _____ procedure and the control is in the light blue here and the ablation is here and this is basically the proportion of people that had no intestinal metaplasia at the end of 12 months and it is about close to 80% of intestinal metaplasia whereas all these people still almost all of them still have their intestinal metaplasia. This is for low-grade dysplasia and high-grade dysplasia.
There is long-term data that actually suggesting this is a recent paper this year that looked at high-grade and low-grade dysplasia in both a UK and US population same population as you saw in the previous study but many many more since then and this is accumulated data over about an eight-year period and you actually see very few high-grade dysplastic actually recurring over a five-year period here and very few low-grade dysplastics over that period of time as well. So pretty good durability of response. And the other thing that is reasonably new although a lot of expertise is occurring with endoscopic resection and this is just a diagram of an endoscope with a cap in it that you inject under the submucosa over here, you raise bleb and this is the lesion that you want to cut out over here, you suck _____, you then can transect this with a snare and you are left with a defect here and this is what it looks like, this is actually an oesophageal segment, you can see those gastric folds over here so all these are Barrett’s and then there is a nodule that is here, you will have to believe me for it because it is very difficult to see on this view and this was resected by an EMR technique taking off all the mucosa very successfully over here and that grows over very nicely, it can stricture so we are careful about using the high-dose PPIs to actually prevent more damage occurring in this particular exposed area. So, the take homes I have from this section are really Barrett’s is a premalignant condition. Screening to find Barrett's oesophagus I have not really talked about that there is evidence that it is not really cost-effective but may have some value; the UK populations have sort of done some study in this space where it might be valuable in very high risk people. Surveillance programs have been altered to reflect local incidence rates and that is why there is 3 to 5 and 2 to 3 year intervals. There is a lot of active research in endoscopic imaging and therapeutics as well.
So I will just move over to the next polling question, I might handover to Jon if there are any final questions that are coming through. The only real questions that came through was more of the risks of doing the radiofrequency ablation.
Okay so they are quite small, there have been perforations, but they are quite rare. The most common side effects or adverse events from the ablation are chest pain that is not uncommon because you are actually heating the oesophageal mucosa and you often get chest pain but this is relieved with high-dose PPI and we often use Carafate which is a mucosal adhesive if you like and it basically protects the mucosa. Post-ablation stricturing is another problem that certainly can occur but that is fairly easily managed endoscopically. Often with HALO, I showed a very nice diagram that it all was completely disappeared of course but often it requires more than one go at completely eradicating it and some people can have up to about 4 to 5 goes.
Can it worsen _____
Not usually, we are very careful to not ablate the gastro-oesophageal junction too much although you can, but it usually does not worsen reflux. The functional part of reflux has nothing to do with the squamous mucosa, it has actually got more to do with the lower oesophageal sphincter, and this basically does not affect that that much.
There are a lot of aggressions coming in and out PPI use, how long you can use PPIs for, I kind of feel like we need to do another session on PPI.
Look, I think Jon and I were speaking about this earlier and I thought that might be the case, I mean there has been a lot of bad press about PPIs over the last few years and I would say use it when you need it, you use it certainly for symptomatic patients. For people that have got gastroesophageal reflux disease that are certainly erosive and so me as an endoscopist if I am endoscoping someone and I actually see erosive oesophagitis I treat them with PPI at a reasonable dose and that is 40mg of you select your best one and 40mg for about 1 to 2 months and I tell them to have that daily and then stop it and the recommendation is stop it and see what their sort of rates of symptoms come back and then you basically evaluate the frequency of reflux that they get over the week so if it is daily reflux they are going to need regular PPI. If it is infrequent reflux, they might not need it and might have prn type PPI.
And one last one, H Pylori.
I will say one thing here because people might read about the paradox of H Pylori and oesophageal adenocarcinoma because there has been this link on one of the risks of oesophageal adenocarcinoma, is actually eradication of Helicobacter pylori and the reasoning behind that, or I should say past pylori infection, and the reason for that was H pylori may cause atrophic gastritis which causes hypochlorhydria which is low acid output rather than antral-type gastritis which causes hyperacidity and that might worsen your reflux and if you eradicate the former, which is basically when you have got gastritis that causes atrophic change and low acid then your acid comes back and your reflux can get worse.
Okay thanks Alex, so we are going to move on now to issues of symptomatic diagnosis and start with the next polling question.
Let everyone read that because I do not have it up there at the moment so have a read of this question and I will put the question up in a second.
There were not enough characters available for me to put the full question in, sorry.
Thank you. Now we will see the question.
This is about an even split of 5 and 15%.
Yeah, right, pretty much.
There are a few of 2% and a few of 33%.
There is a pretty even split between 5 and 15.
Okay. I will come onto what the actual answer is as we go through this.
So, obviously when we think about trying to detect cancers in general earlier in primary care, we try and think about what are the red flag symptoms and in this particular case what are the red flag symptoms of oesophageal gastric cancer.
The problem that we have in primary care is there is probably only one single red flag that is reasonably predictive of oesophageal cancer and that is dysphagia.
But, it is a difficult diagnosis to make, and so this is based on data from a large survey of patients treated at the Victorian Comprehensive Cancer Centre and one of the questions that was looked at in this survey was about the number of attendances to a GP before they were referred on for a suspected diagnosis, and this was done across multiple cancers. What we found was that oesophageal gastric cancer was one of the cancers associated with a much higher frequency of multiple GP visits before a referral, which we think is reflective of the challenges of recognising this symptomatically early on and relates to what we talk about as the symptom signature of cancers. Some cancers have much clearer precise symptom signatures like breast cancer and melanoma, but things like oesophageal gastric cancer and pancreatic cancer as well have much weaker symptom signatures and we think that's the explanation for why patients often have multiple visits to their GP before it becomes clearer that a GP should be considering this as a possible diagnosis.
This of course is a challenge for many cancers in primary care because the symptoms of cancer as they present in primary care, they are often very common symptoms in the community and they often have much more common benign explanations. The chart I'm showing is really a reflection of that. These numbers are the positive predictive value of individual symptoms or in some cases abnormal test results, and in this top line this is thinking about single symptoms and the likelihood of somebody aged over 50 who presents in primary care with one of these symptoms of having OG cancer, and you'll see here this is what it said, dysphagia is the only true flag with a probability of just under 5%. That still means 19/20 people who present with dysphagia won’t have oesophageal cancer, but it is truly the only single red flag symptom in primary care. There are of course some other common symptoms that you need to think about where you note nausea and vomiting, dyspepsia, epigastric pain, reflux, these are such common symptoms on their own in primary care that they're very weak predictors. And if you then start to look at the rest of the chart this is how combinations of symptoms or abnormal test results can start to give you a bit more information. So, for example, here if we look at the combination of nausea and vomiting and reflux then that starts to increase your risk slightly so to 2.3%. Weight loss in the context of nausea and vomiting or dyspepsia or epigastric pain again starts to raise your probability of an OG cancer, but again not very high. As I said, only dysphagia is the really true one and only in combinations do you really start to get even moderately high prediction of symptoms. This is why diagnosing OG cancer in primary care is challenging and that even in a population as I said who are aged over 55 when their risk of OG cancer starts to rise.
So, in Victoria Alex and I have both been involved in development of these new guidelines that are aimed primarily for use in endoscopy units to support the triage of patients referred for an upper GI endoscopy, but they're very much based on this type of evidence from mainly primary care populations where you start to think about how combinations of symptoms and age and abnormal test results can be applied to identify people who require more urgent gastroscopy and those who might actually not require an endoscopy at all and those who can afford you can probably safely leave them on the waiting list because they are very unlikely to have an undiagnosed cancer there, they may still require an endoscopy to make a diagnosis and to inform treatment, but you are unlikely to be leaving him on the waiting list with an undiagnosed cancer. So, I am going to talk through some of the particular symptoms and symptom combinations that are from this guideline.
So, if we think about urgent upper GI endoscopy there are really only sort of two very strong predictors, one as I said is dysphagia and dysphagia at any age in an adult is a significant enough symptom to warrant referral for a very prompt endoscopy. The other one that wasn't in that chart that I showed you and mainly because this is usually an emergency presentation, is haematemesis and melaena, but I am sure there are many GPs on the line who have experienced patients who have come and seen them about two or three days later saying ‘Oh, I vomited the other day and noticed some blood in my vomit’. They still require an endoscopy and of course we are assuming in this context that there is this delayed presentation and that they're haemodynamically stable and not requiring immediate admission, but there will be patients in general practice who certainly present like this and assuming that they don't require immediate admission they still do require an urgent upper GI endoscopy.
Jon, can I have a …. So, in terms of the dysphagia I think one of the other clues that can be very helpful here that might discriminate, and that doesn’t always work, but it's actually really worthwhile, is the term progressive dysphagia, and that’s something we all got taught in med school and it really reflects the change of dysphagia from solids to liquids. So, solids are the first things that get affected and then eventually you can't have liquids. That progression is very very suggestive of a mechanical obstruction and a growth and that certainly I would almost put an extra red, double red.
Yeah. Thanks. So, we have another polling question.
How quickly should you refer someone?
Yeah. In the optimal care pathways the recommendation is for these types of presentation ideally they should be scoped within two weeks.
That’s a real challenge. In the public system that's a real challenge. And you know you’d see the categorisation guidelines say less than a month.
Because effectively from a scheduling perspective that's effectively probably the closest that you are going to get. Mainly because many public hospitals don't necessarily have open access, so you may need to go through a clinic to actually get that. Now some have hybrid models where you can actually have a slightly open access for some of the more urgent ones where you get an immediate triage by either a head of a unit or an advanced trainee or someone like that who reads the referrals, then certainly if they see a referral from a general practitioner that says progressive dysphagia I can tell you that that’s going to be the next list or very soon after.
If a patient just turns up and says I have some trouble swallowing my food last night, or food got stuck in my throat, that would warrant it ?
Not always I would say, but I mean a lot of them actually… the food getting stuck we see in the emergency anyway. So, often they will get one anyway if it’s truly stuck.
If it passes and they had trouble swallowing….
That’s certainly what you would flag.
So, we have our next polling question.
Should we read this out?
Do we need to read this out?
May be read it out.
Okay. So, Mary, she is 57, and she has come to see you after being found to be anaemic when she went to donate blood. She is asymptomatic. Her last period was five years ago. She is a non-smoker, drinks 10 units a week and is vegetarian. Hb is 111g/L and MCV 78. Her serum ferritin is low and total iron binding capacity is increased and I'm asking you what will be your next step.
The poll is up.
70%. So, about 60% of people say refer for colonoscopy or gastroscopy and then 23% say order some tests. Okay. A few would prescribe iron supplements and repeat the iron studies. Just a small number.
So, this is an algorithm that, those actually are originally published by the British Society of Gastroenterology a number of years ago. It’s been adopted internationally and again it is incorporated in Australian guidelines now as well, which is really a flowchart for anaemia or particularly microcytic anaemia and/or iron deficiency. And interestingly the first test they recommend rather than going straight into endoscopy is actually checking for coeliac serology. So, because of course malabsorption from coeliac disease is an important potential cause even in an older woman like this, and therefore actually if you have positive coeliac serology then you would be doing a slightly different form of endoscopic investigation. You would be able to rule out the need for colonoscopy as well, and so that’s why this first suggestion is to do coeliac serology and if it is positive then you would confirm coeliac disease with an OGD and a small bowel biopsy. Now, you will notice in the options I gave before, the suggestion that as well as doing this there you might add in an immunochemical FOBT test. Because, the usefulness of an iFOBT is actually if that were positive it points to the source of blood loss as being colonic, and therefore you could potentially rule out the need for an upper GI endoscopy at that point. So while this is not officially in the guidelines I think there is growing recognition that FOBT tests have a role in the assessment of symptomatic patients as well or anaemia. Would you agree with that Alex?
Yeah, I think that’s not unreasonable. Here, I notice that a lot of people wanted the _____, I think you know that is very reasonable to actually do it. I think the coeliac serology can give you a fairly quick answer and by the time you're waiting for those procedures, which you may need to do anyway. I must admit that if we have a referral as an endoscopist for iron deficiency anaemia we do and do both gastroscopy and colonoscopy at the same sitting, we always do small bowel biopsies irrespective because even if we don't have coeliac serology at hand, they are incredibly sensitive and very specific, so, a good test to have. One of the other possibilities there although it may not fit into this algorithm and it’s probably why it’s not included in is HLA testing both DQ2 and DQ8, which can exclude people from a coeliac diagnosis if they do not have DQ2 or DQ8 because it is very unlikely if they don't have the genetic susceptibility.
Regardless of their coeliac serology.
Yes. I mean coeliac serology could be completely negative because they might be she is vegetarian, she might not be having gluten in her diet and so, you know, the TTG might actually be low-titre because it’s like a well-controlled coeliac and the like. So, at that particular time it might be a negative and it might be a false negative.
So, we would like to just carry on while we talk through. So, assuming that the coeliac serology is negative, if it was a premenopausal women then you want to review their symptomatology. If they have upper GI symptoms and no family history of colorectal cancer then the suggestion is that you would just go straight to an AGD to begin with and only if that was normal then you might consider going onto colonoscopy. If in postmenopausal women or all men then the suggestion here is potentially doing an upper and/or lower endoscopy, but you might, as I said, potentially think about the role of FOBT.
When you do an FOBT is it always necessary to do three examples?
So, interestingly in the National Bowel Cancer Screening, that is a two-sample test, and that is sufficient.
Yep. Obviously the more samples you force people to have, the poorer compliance.
So, that’s iron deficiency anaemia.
When we talk now a bit more about reflux, and again this comes from those Victorian guidelines where we are starting to think about combinations of symptoms, age and test results to help define urgency for investigation. So, these are the features where you want a more urgent endoscopy. So, somebody with reflux is aged over 55 with any additional symptom as listed below, say dyspepsia, upper abdominal pain, persistent nausea and vomiting or weight loss, and again if you think back to that symptom risk tool, that is where these combinations of symptoms particularly in people over 55 where the risk of an undiagnosed OG cancer goes up, but also importantly, even if they only have a single symptom, this is where additional blood tests can be useful. It is unlikely that you'd be ordering imaging, but just that occasionally there may be imaging ordered as well and if it is an abnormal imaging too, but then you would be unlikely to see that, but we have talked about markers of anaemia, but raised platelets are also increasingly being recognised as an additional useful piece of information to identify people at high risk of cancer.
This is a recent meta-analysis of studies that have looked at, how useful a raised platelet count is ordered in general practice at predicting the risk of an diagnosed cancer in primary care and that you will see actually put all of these different cancers that you are at a high risk of an undiagnosed cancer with a raised platelet count. The risks are higher for certain cancers, although bearing in mind some of these confidence _____ a bit wider, but the particularly important ones are lung, oesophagogastric and colorectal, possibly ovarian too. So, it is just worth recognising that a high platelet count is certainly worth repeating because actually there are separate studies that are reported in here, which show two raised platelet counts further adds to the predictiveness of an underlies an diagnosed cancer and is certainly worth going back to take a good history to see if there are potentially important symptoms to make you think about investigation for potential cancer and that's why going back to these guidelines we’ve added in raised platelet count as an additional abnormal blood test to think about in the context of upper GI symptoms.
Now, we are moving onto dyspepsia. Again, these are three categories of urgency. The most urgent to gain are people with dyspepsia aged over 55 who have an additional symptom or again who have abnormal imaging or signs of either anaemia or a raised platelet count. But if they just have dyspepsia and this is where H. pylori treatment comes in and we will come onto that in a moment. If they are aged over 55 and non-responsive to a PPI and/or H. pylori therapy or they are H. pylori negative then they should be having a slightly less urgent endoscopy, usually within 60 days, or again if they are younger but have additional symptoms or additional abnormal blood tests then that would bump them up to slightly more urgent and only these groups would be on a very long waiting list for endoscopy, which moves us onto further discussion around H. pylori.
So, I just have a few slides here on Helicobacter pylori, some of the conditions that have been published related to it and of course, we would all recognise the Nobel Prize that was actually given to two Australians Warren and Marshall, who actually made the association between peptic ulcer disease and H pylori. Of course gastric cancer has since been associated and back in 1994 the WHO classed it as a class I carcinogen. It also is responsible for MALT lymphoma, which is mucosa associated lymphoid tissue lymphoma which occurs in the stomach as well. There are, however, some extra gastric associations that people may have read about. One that is probably lesser appreciated is iron deficiency anaemia and the mechanism of that is actually because of that atrophic change that I said before. You get low acid and you need acid to actually more efficiently absorb iron in your diet and so it does interfere with iron absorption, but also ITP and I have got numerous referrals from haematologists that have thrombocytopenia and wants these patients’ Helicobacter eradicated and in fact we've had some successes that I certainly share and there is good evidence for this as well across the literature.
So, who do you eradicate with Helicobacter? So, certainly peptic ulcer disease, I think we’ve got it, early gastric cancer, and these are uncommon in our community as our prognosis actually shows, but we still do get it and I must admit the Japanese do this extremely well where they can actually treat gastric cancer just endoscopically without any sort of adjuvant chemotherapy, no radiation, they actually just endoscopically remove these and obviously will have high rates of Helicobacter and they get certainly eradicated from the H pylori. There is a condition that is called gastric intestinal metaplasia, this is kind of a pet hobby of mine and I am not going to bore you guys with it, but in effect this is the Barrett’s of the stomach and in fact the risk profile of progression to gastric cancer is almost identical to what I showed before with Barrett's oesophagus progressing to oesophageal adenocarcinoma. The problem once you have this type of intestinal metaplasia is often it is related to Helicobacter pylori that might have been there many many years ago, but only a small proportion or about half or less than half actually regress once you get intestinal metaplasia. So, some of them still actually progress irrespective of getting rid of their Helicobacter pylori and this is thought to be the point of no return. Exactly when that occurs I'm still trying to find out with research at the moment, so I'll let you know in maybe 10 years, but probably more importantly is this premalignant stage called atrophic gastritis, which is basically the precursor to intestinal metaplasia and the evidence is that if you can treat the Helicobacter pylori at this stage you get much better regression or less progression rate to gastric carcinoma. Unexplained iron deficiency anaemia, now I put the qualifier of unexplained. If you obviously have a good reason for iron deficiency anaemia it’s probably not Helicobacter pylori, but if it is unexplained in any other way then eradicating H pylori may actually help. ITP as I mentioned. Vitamin B12 deficiency from usually an autoimmune gastritis that sometimes occurs with chronic Helicobacter infection can sometimes improve. MALT, and in fact some of the early MALT lymphomas can actually be effectively treated just with Helicobacter pylori eradication. There is also this dyspepsia with no alarm symptoms. I think this is really important. This is what John was referring to with those other abnormal symptoms. Alarm symptoms classically are weight loss, bleeding, so haematemesis and melaena, dysphagia obviously as shown in previous diagrams. There is this strategy that John might allude to in a few minutes called test and treat, are basically rather than endoscoping these people, you test them with a noninvasive strategy and then treat them on spec and I'll talk about some of the strategies in a sec. Also those patients that actually are going to have chronic nonsteroidal use and they are the osteoarthritics, rheumatoid arthritics or other conditions that might need aspirin or nonsteroidals where they are susceptible to getting peptic ulceration. For prophylaxis having Helicobacter as a cofactor will increase their chance of actually getting peptic ulcers. So, getting rid of the Helicobacter makes sense. This certainly comes from recommendations globally
So, how do you test it, what tests do you use. In terms of non-invasive testing I think one of the best is urea breath test and I think the simplest one is the Carbon-13, sensitivity and specificity is slightly different depending on which test kit you've actually got, but it is actually generally pretty high, and basically the methodology is this, the bug has got urease, you actually swallow something containing urea, the urea is broken down by the urease to release carbon dioxide, which is basically labelled with your marker of C-13 and ammonia. Carbon dioxide is very quickly absorbed in the bloodstream, gets to the lungs, you breathe it out and you can actually detect it on a mass spec. Stool antigen tests are getting better and better, that is quite a sensitive and specific test at the moment, there's been quite a lot of studies of this over the last few years. Serology is good, but don't forget it it's an IgG test so it actually will be positive for past infection. It doesn’t tell you anything about current infection. So, specificity and sensitivity are reasonable, but don't use this to actually test for eradication. In terms of invasive testing what I mean is someone having an endoscopy what do you do. There are really two types of tests to actually detect whether it is present. This uses that urease type tests, this is only one of multiple rapid urease test and you see basically a pH change over here and this is actually the ammonia component rather than the CO2 component that is actually doing it, so it normally starts as yellow turns to pink and that's positive for Helicobacter or positive for urease which means effectively Helicobacter. You can take biopsies for histology and you can actually stain up, there are now some very nice stains for Helicobacter pylori. The specificity is excellent for this, sensitivity is a little bit lower, and what I'm using, and I'll explain why in a couple of slides’ time, more and more these days is culturing of Helicobacter to look for sensitivity and this is sort of a culture, usually it’s a horse blood agar that we actually use. It is sometimes difficult to actually grow, but when you can it gives a useful information about what it is sensitive to and what it is specific to.
Sorry, a quick question.
If a family member has H pylori, do you test the other family members?
Yeah, it’s a good point and generally there is familial association of Helicobacter and that's because of this oral-oral spread. Yes is the short answer to that. I think it is not unreasonable.
Which of those tests are covered by Medicare for GPs.
I think the urea breath test is certainly covered.
Yep. And how long do you have to stop PPIs before you can do that test?
At least two to four weeks. I’d be safe and do it four, it should be okay with two, but you often do get false negatives and false positives. So, the next thing I just wanted to talk about was therapy for Helicobacter pylori. These are actually pools from up-to-date which some people might use and basically goes through what you would use for Helicobacter pylori eradication therapy as first-line therapy and then what you might use as second-line therapy and I will go through the summary. So, the reason for why there are complex matrices and why you just don't use Nexium Hp7 or some PPI with clarithromycin and amoxicillin is because of this previous exposure to macrolide antibiotics, which may influence the sensitivity and as well as this issue, which is clarithromycin resistance rates, which were previously very low and I will show you some fairly worrying data globally that have been published just this year, but generally if you don't have any problems with clarithromycin resistance you think that you are in a population that doesn't have it. You don't have a penicillin allergy you use the classic clarithromycin based triple therapy with amoxicillin. If you've got a penicillin allergy you use metronidazole instead of the amoxicillin and then if you had metronidazole used you go to bismuth quadruple therapy and I will talk about what that is a bit later.
So, in terms of second-line therapy and increasingly it would be interesting to see what you folks are finding in terms of the real-world practice, what you are finding in terms of the requirement for second-line therapy. Certainly, in my practice this is happening more and more, but I guess it's a very skewed population that I am seeing. But basically if you use clarithromycin based triple therapy as initial and you have a penicillin allergy, go to the bismuth. If you don't have a penicillin allergy you can go to levofloxacin triple therapy or bismuth or a high-dose dual therapy of these and you can use various combinations of these if you like. I won’t belabour the point.
This is a study that came out of the US earlier this year and it basically shows, and I am sorry that they are small figures, but basically this shows the resistance of clarithromycin in A, metronidazole in B and levofloxacin in C, and the colour code is less than, I think it is 10% in yellow, the next one up is 10 to 25% then 25 to 30%, 35% to 50% and then above 50% and you will see Australia both in clarithromycin and metronidazole rather worryingly. I knew about this with metronidazole that greater than 50% of our population are probably resistant, but this is a concern. So, more than 50% at least in this study, and this is only one study but probably needs further confirmation, have got primary clarithromycin resistance already in our community. Thankfully levofloxacin is rather low and so this is probably a reasonable second-line agent still, but we have got a question about whether we can use clarithromycin as first-line, and in fact anecdotally, in my practice, the problem patients that I've seen that haven’t eradicated with first-line therapy have all been clarithromycin resistant.
So, in terms of how to eradicate, you certainly can still use these PPI Amoxil clarithromycin for seven days for those people that have not got prior metronidazole use or clarithromycin used in the past. One of the questions I wonder whether we are going to have to address is the seven-day period here and I think increasingly, the data is showing that we are probably having to go back to the good old days of H2 receptor antagonists when we used to use it in triple and quadruple therapy where we used it for 14 days and you'll see that the second-line therapy are actually for prolonged periods and you could either use the bismuth-containing quadruple therapy. You can get bismuth in Australia, it is more difficult to get, but it is available, but certainly this is a much more amenable treatment using levofloxacin, a PPI and amoxicillin for those that are not allergic to penicillin. Now, third-line therapy you will read different things. Some people actually say, okay if you have used one of these second lines then go over to the alternative ones as third line. My practice and, again this is because I do endoscopy, is to actually endoscope these people, culture them and actually be a bit more informed using evidence to which one you can safely use or not.
So, may I just briefly just to highlight, part of the reason for _____ the H pylori stuff is also in the context of you say test and treat.
And the potential, particularly in younger people, so under 55, who just have dyspepsia, if you can use the test and treat strategy to safely avoid them requiring a gastroscopy.
I think that's the case John, that's certainly in eradication guidelines that we have suggested, that has certainly been put out there. Dyspepsia is difficult because it sometimes has a difficult meaning, but also on its own it is very difficult to know whether it is part of an irritable bowel spectrum or truly part of the process that Helicobacter pylori might be playing a role in. The data suggests that up to 50% might respond, but that's as good as we are going to get. So, basically up to 50% of the dyspeptic patients might get a response to Helicobacter pylori and therefore it is actually advocated as you suggest. So, with just dyspeptic no alarm symptoms, certainly you can do the test and treat where you would test with one of the sensitive measures that have been outlined before, the simple one would be urease breath testing and then treat and then of course not to forget to check eradication and that's one thing that people do forget to do and they sort of treat them and then assume they are better or if they do get better and then not check four weeks later or beyond off PPI and all the rest of it, off other antibiotics. You need to be off antibiotics for four weeks before you actually do these tests and I would be recommending doing a urease breath test as a check for eradication.
Thank you. I think you just answered all other questions that just came through. Can GPs prescribe levofloxacin?
I don't know. I am not sure if it’s an authority script only. I have not.
Yeah. That’s the only one that you will have to check ____ if that’s an authority script or not or whether it’s specialist only
Do you _____ patients on PPIs after you treat them or you stop them, wait four weeks, retest…
Yeah. I would stop them, so if you are just treating to eradicate you just stop it. So it is basically treated for the duration, you stop it afterwards. The time that I would be continuing PPI therapy is if there was a peptic ulcer that you have to heal, you have to cure and heal up. That takes about four weeks at least of PPI therapy.
We have had some advice come through; I don’t think it is PBS, listed now.
I don’t think it is.
I think you are right. I think it is a private script.
That’s it. I think that is, we’ve come to the end, so, thanks very much. There are a couple of resources through the Cancer Council website. Anyone who hasn't seen so far there's two handouts that are available for download for you now in your sidebar of the webinar. So, grab those now. I will be putting those up on the RACGP National Webinar Series website in the next couple of days. The recording will also be available in the next couple of days, but apart from that the survey will come up as soon as the webinar finishes. So, from the RACGP, thanks very much for coming along today John and Alex. Thanks again to Cancer Council Victoria, Melbourne University and Victorian Government as well. Thank you very much.