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Hello, everyone and welcome to me education today. Um We have got uh John Whiting chatting to us about os esophageal cancer. That's the one I am. I think people that know and come and join these er, events know that I'm really rubbish at pronouncing things. Anyway, so we're gonna chat about that. We would love for you to pop some questions in the chat. Er John will answer them as we go along hopefully. Um just so that, you know, at the end of this event, there will be a feedback form in your inbox, please complete that um there is a question in there as well about other topics you would like within this subject. Please do fill those out and I can fill that feed feedback form out and I will pass that on to John. It's really helpful for, for us speakers to get feedback from yourselves. So please do offer them good solid feedback. Um, like I said, after you filled that out, you'll get your attendance certificate. Ok. If you want to see any of our catch up, you can find that on medal education and there are loads of events happening on medal that you are more than welcome to sign up to. Ok. So without any further ado I'm gonna pass you on to John. All right, thank you John. Ok, welcome everybody. So I can't see you all but I know you're out there. Um My name's John Whiting. I'm one of the upper G I surgeons at the Queens Hospital in Birmingham. I've been asked to talk to you about esophageal cancer. So I to try and do is to give you an overview of it, not focusing too much on surgery because that's one of the dangers of uh asking a surgeon to do that. So let's crack on any, if you've got any questions, put them through, I'll try and keep an eye out for the uh the chat and try and answer them as I go along. So the first thing to say about esophageal cancer is that there really are two different types. There's squamous cell cancer and adenocarcinoma and they are different diseases and you'll see why they're different diseases. Uh But fortunately, the treatment for them are, is, is pretty similar actually. And you can see here these are just endoscopic pictures of esophageal cancers. So it's the eight most eighth most common cancer in the world. Uh Nearly half a million new cases per and you can see the vast majority of them are squamous cell cancer. So nearly 400,000 squamous cancers and 50,000 adeno carcinomas. And if you look, you can see there's 456,000 cases per annum and 400,000 deaths per annum. A and if you add that up, it means that we're not very good at treating and curing it. So we're going to talk in this today about definitions, incidents, risk factors, symptoms, diagnosing, staging it, how you treat it. But actually, you know, if you're looking at worldwide surgery, the costs involved and, and actually where we can spend the money best. So as I said previously, there's two main types, there's squamous cell cancer, which is the commonest worldwide and adenocarcinoma, which is commonest in western countries. So this is a map, ok, which shows for adenocarcinomas at the top, the incidence rates and for squamous cell cancers at the bottom. And you can see immediately that for adenocarcinomas, you can see it's America Europe, Australia, New Zealand, parts of South America, ok? And, and parts of Central Asia here and, and you can see Britain is a hot spot. So it's nice to know that Britain can lead the world still in something. Um If it's only for instance of adenocarcinomas, if you look on the other hand, at squamous cell cancers, you can see that actually the distribution is very different. If you look at China, there's a huge instance there in Southeast Asia. And if you look at Africa across the east coast of Africa and Sub Saharan Africa, it's, it's got very high instances and much less incidence compared with adenocarcinomas in the West. Now, if you look at the instances here, the top rates uh 10.5 to 20. The next slide here is for females and you can see that the instance rates are much smaller, but again, it looks very similar. So, adenocarcinomas often in the western areas and squamous cell cancers in the areas we've mentioned previously. And again, if you look at it, so this is by comparison size. So adenocarcinoma is much smaller than squamous cell cancers. And if you look at the, the areas which are got large numbers, then you can say it's North Western Europe, North America, China because it's got such a big population and then we got Central and South America. Whereas for squamous cell cancers, China has over half the cases in the world, Southeast Asia, India, Central Asia and Sub Saharan Africa. And you can see that the West America Europe Australasia very, very poorly represented for squamous cell cancers. So if we then look at squamous cell cancers, these are essentially mid and upper third cancers and they originate from the squamous epithelium. So if you think about the esophagus, there's two linings of it. The majority of the lining in the esophagus is squamous. So this is the wear and tear as food goes down, it'll abrade the lining. So it's resistant to mechanical abrasion. Ok. Demographics, males, more than females, although very high risk areas, if you start looking at China and East Africa. The the instances become much closer between males and females and like most cancers, it's associated with poverty. If you look at the risk factors for squamous cell cancers, then there's a lot of commonality with oral squamous cell cancers, chronic irritation. So smoking, alcohol, spirits more than beers, hot drinks in some places, silicates in food. So all of these things damage the squamous epithelium and you get that damage repair cycle, which we think is very important for, for, for creating cancers in high risk areas. Then family history becomes a much, much more important thing. And although we haven't identified any specific genes, we know that in high risk areas, it's important. But in low risk areas, there doesn't seem to be that much of a family connection and protective factors. The main ones, fruit and vegetables. So your mother always told you eat your fruit and veg and she was right now, if you look at adenocarcinomas, then these are different. These are lower third cancers, these are junctional cancers. So these are cancers that occur at the lower part of the esophagus and around the gastric gastroesophageal junction. And these originate from the gastric intestinal type epithelium. Ok. Barrett's esophagus. So this is where you get change of the mucosa at the bottom of the esophagus to a more acid resistant one and again, age males more than females and associate it again with poverty. Ok? If you start looking at junctional cancers. Ok. Uh These are the adenocarcinomas, you can divide them into three types. There's see what classification, see, what was a German surgeon. Uh So if the bulk of them are in the esophagus, it's a type one. If it's really right in the middle of the gastroesophageal junction, it's type two and if most of it is in the stomach, it's type three and they originate from this. Barrett's esophagus. So Barrett originally said that this was a shortened esophagus, but it isn't, it's actually metaplasia. So if you get reflux, which is one of the main causes of it, what happens is that you get acid from the stomach going and burning the squamous cell epithelium, which although it is very good at resisting wear and tear and mechanical abrasion isn't very good at resisting acid. So the body is smart, the body changes. So the epithelium at the bottom of the esophagus to resist this acid changes from squamous to gastric type mucosa intestinal type mucosa, which is much more acid resistant. And as soon as you start getting that change, you then can start initiating a cycle of actually, the cells have almost got used to changing, they can change more and again, males, more than females common as you get older and associated with poverty. And so if you look at the risk factors, the big one here is reflux intestinal metaplasia, which I've spoken about, which is a result of reflux and then you get progression from intestinal metaplasia through to dysplasia, low grade dysplasia, high grade dysplasia, carcinoma in situ and then invasive cancer. So there is a, a sequence there. And if you look here, this is the map that I showed you earlier of adenocarcinomas. And this is a map of uh where the fattest people in the world are. And again, you can see some similarities mainly in America, Europe and Australia and New Zealand. So what are the global trends? Well, there's good news and bad news. Ok. So if you look in the last 30 years, the age standardized incidence has fallen by 22% and mortality has fallen by 29%. So we're doing better, but the total number of new cases has increased by 52% and the number of deaths has increased by 40%. And what this is saying is that there's an increasing population. So, although there's fewer cancers per population, if the population's got a lot bigger, we'll have more cancers. So it's, although the incidence is falling, the actual numbers of cases that we're having to deal with is going up. So, coming on to what are we, what are the symptoms that the main symptom of esophageal cancer? The current symptom which you can't afford to ignore is food sticking. Ok. Uh Sorry, someone said, can we see the previous slide? I've probably gone way beyond that now. So sorry. Uh the cardinal symptom is food sticking. Ok. And if you think about it, the reason for this is that there's a cancer in the esophagus, the esophagus can only stretch up so much. And as the cancer grows the space for the food to go down past the cancer gets smaller and smaller. So food sticks. And what we mean by progressive is it's getting worse. We all have moments of dysphagia. You eat something a bit too fast, you'll feel it sticking, have a glass of water, it'll go down and then you don't have it again. We don't have to worry about cancers like that. Ok. That's sorry, dysphagia like that. What we're talking about is dysphagia which starts off with chunky things, bread meat and then softer things like rice, vegetables until eventually you can only take liquids. Ok. Yeah. And we've all seen people, you know, when they're swallowing, you can see them in a bit of discomfort, indigestion or heartburn, discomfort in the chest area. People often describe it as being a bit of a pressure. If the cancer bleeds, they may become anemic and that the hallmark of that is iron deficiency anemia. And if it bleeds a lot, they may have vomiting. One thing if for the dependants around there is we all say, have you got any difficulty in swallowing? But that's not what dysphagia means. Dysphagia is food sticking. If you think about food swallowing, putting the food in the back of your mouth and initiating a swallow for it to go to the top of the esophagus. If there are problems with that, it's normally a problem with strokes, cranial nerves because that's a very mechanistic thing. So, systemic symptoms. Well, if you get any advanced cancer, you'll see people have weight loss, lethargy, tiredness and nausea and vomiting. But you've got to be careful because if somebody's lost a lot of weight, it may not be because the cancer has metastasized and has advanced. But just because they can't really eat and sometimes just getting a dietician to see them to explain what's going on. They need to eat soft and sloppy foods is often enough for them to actually stop losing weight while you're staging them and actually start to put some weight on. Ok. So diagnosis, if we're going to diagnose these, the two things really for diagnosis, the key one really is endoscopy and biopsy. So if you go down with a scope, you can see something like this, which looks obvious. The problem is it's easier to miss an early cancer. And here you can see an earlier cancer and these signs can be very subtle. And, and the, the takeaway message here is if you see something at all abnormal, don't ignore it. Take lots of biopsies so that you don't miss it. On contrast, swallows. It's easy to see an obvious cancer. Here. You can see the indentations here, but here you've got just little bits of granularity, some abnormalities. And again, it'd be very easy just to say, well, it's something, nothing but, but the early cancers are the ones you want to see because those are the ones that you actually have a chance of curing. So, staging, you know, why do we stage if we're going to cure a cancer, we have to take it all away. So, in the UK, and a lot of countries, we have these things called dandelions which grow in our lawns and, er, and if you want to get rid of them, you have to take them out, but they set seed and if they set seed, then whatever you do to the, to the, the main dandelion, you're not going to get rid of all the, all the little seedlings that will grow from the seeds. So if the cancer spread, we know we're not gonna be able to cure them. So to cure a cancer, we have to take it all away. There are two staging systems in use and this is common for a lot of cancers. Actually, there's the Union for International Cancer Control. I think it was originally Union, International Contra Cancer, which was French. But we've got a little bit more International English now and we're currently on the TM version eight. It's more descriptive. So if you talk about the T two N one M zero cancer, it's more descriptive than the stage. Ok. Uh And if you've got the TNM, you can always get the A JCC classification, the advantage of the A JCC classification. OK? Is that uh it's easier to see survival by stage. So if we look at the TNM staging the T stage for tumor, it goes from T zero to T four. So TX is a specialist thing that says tumor cannot be assessed. OK? And what that means is that you can't see the cancer. So for instance, if you had a CT scan and the CT scan was poor quality, you can't see the cancer. You can't say there isn't any cancer there. You just can't make a comment. That's TX. OK. T zero means that there's no evidence of primary cancer. So if you've got a good CT scan and you can't see a cancer, you'll call it T zero tis in situ is a very specialist thing which shows high grade dysplasia. Um And what that means is that this is a very early stage cancer and you may be able to treat it endoscopically. T one can divide it into T one A and B and I'll show you what that means in the slide. T two means it goes into the muscle of the esophagus. T three means it's gone outside of the esophagus and T four, it means that it's invaded something outside the esophagus. T four A pleura pericardium, diaphragm of peritoneum. These are things that we can potentially chop away with surgery So it doesn't mean we can't operate, might mean we shouldn't operate, which I've come on to. And T four B means it invades some things such as the aorta, the vertebral bodies or the Jaia, which we, we can't, we can't take out. OK. So moving on. So this is tis T one, T, two, T three, T four. And you can see as this T stage goes up, it gets bigger and bigger until you get T four which is invading the aorta. OK. So the end stage, sorry, someone said is there going to be a uh a catcher? So I'm just gonna turn my phone off because somebody keeps trying to call me. Sorry about that. Uh Is there going to be a catch up session? Yes. So looking at the end stage, so again, NX means that you can't make an assessment. N zero means no regional lymph nodes, N 11 or two lymph nodes, N 23 to 6 nodes, N 37 or more lymph nodes involved. OK. And mm zero. No distant metastases. M one distant metastases. And I've highlighted these in red because it really means that if you've got N three disease and you can show that or distant metastases, we're not going to be talking about curative treatments. So again, forgive me, this is, this is something which is a bit simplified uh because the A JCC also includes the grade of tumor. But what you can see here is, it goes from grade one to grade four. And you can see as the T stage goes up, then the grade goes up. But if you look here, you can have a T one tumor. Uh but N one, so as soon as you get a node, it puts you into a much worse category than if you just have the T one tumor. You can have quite advanced local T stage T three. But if you node negative, you stay in two V. Whereas here with T one and N two, you go up the stage. And the important thing here is the ones I've highlighted in red are the ones where really the chance of cure is very small if, if it exists at all. So if you look at T four A N two, well, we've already said we can chop out T four A, we can take those nodes away, we can potentially get it all out. But should we? So if you look at survival, you can see it's dismal. Yeah, once you get to stage four, these are the ones which I said we shouldn't be operating. You're looking at 5 to 6% 5 year survival rate. And most of these survivors are people who've had a very good response to chemotherapy. It's not surgery that's doing that. So for the patients that we can potentially cure, the vast majority of patients that we see are still in stage two or three, we only end up saving 26% after five years. Ok? And these are patients. So this is in the United States. These are patients who we have, you know, all the treatments that we can and we still only save 26% of them. So if you look at stage, you know, when we're staging, we're looking for N One disease, we're looking for obvious signs of metastases. If we can show that the cancer has gone to the liver or the lungs, then we know we're not going to cure it. So we're into palliation. OK. What I said about, can we take it all out and should we take it all out if you've got T four, N three disease, T four, N three, you're into stage four. And, and this is, this is a graph of survival after esophagectomy. And you can see that for stage four, the, the survival is pretty poor. You know, you're probably running at about six or 7% there. And, and actually, you can probably just get that with chemotherapy. So how do we stage these? Well, fortunately, the single most important test is the CT scan. I always try to say to patients that the staging we do is a series of barriers that you've got to jump over. And if you get over all the barriers, then we can talk about treatment and cure and the CT scan is the highest barrier. OK. So here you can see a CT scan on this side, you can see lung metastases. So this is m one incurable disease on this side, you can see there's a bulky tumor and you can see how it's very, very close to the aorta there. And in the old days we'd say that if, if it, if it attached to more than 90 oops, sorry, if it attached to more than 90 degrees of the aorta, it was probably invading it. And here we can see it bulging into trachea. So this is likely to be T four B disease. Now, if we wanted to know this, for sure, then in an ideal world, we get an endoscopic ultrasound because with an endoscopic ultrasound, it's real time, we can see whether or not the edge of the tumor moves as the aorta pulsates. And if it's sliding over each other, then it can't be attached. If they're rigidly attached, then we know it's T four A. Ok. More recently we started to use pet. Uh and this probably once we've got a clear ct scan will say no, the cancer spread in about another 10% of patients. Now. Pets. Fascinating because it's positron emission tomography, you have 18 fluorodeoxyglucos, which is basically a sugar. So it's taken up by, by cells that are actively metabolizing. So you can see here that the uh the brain is active, the kidneys are active, the heart's active. But cancers such as here are also more active. And here you can see metastatic disease. And the beauty of a pet is that, you know, it's very easy to see metastatic disease. Although the resolution is uh is not quite so great. Ok. So I talked briefly about laparoscopy. We tend to laparoscope patients who have adenocarcinomas. For squamous carcinomas, it's much less important because those are mainly in the chest. So you're not going to get spread from the, the top of the stomach into the abdomen. But for adenocarcinomas, it can be useful. And what we're looking for is is these little sheets of white peritoneal disease. And if we saw that we'd biopsy them, we'd also get cytology, we'd wash some fluid in, send it off for cytology. And again, if all those are positive, we know we've got metastatic disease. Endoscopic ultrasound, you can see a snapshot here. This is the wall of the esophagus. This is the uh ultrasound probe and they sort of blow it up with a balloon on the inside. And you can see there's a lymph node there, the aorta and you can see the layers of the esophagus quite clearly but not so much on this one. But you can also see here that if we thought that was a worrying lymph node that would be out of field, it's a long way from the primary cancer. It would be out of field. For radiotherapy field, they can stick a needle into it and tell us whether it's metastatic disease. So we're looking for essentially incurable disease. But at the other end, we're also potentially looking for disease that we can treat with the minimalist option with endoscopy. Because if we saw a lymph node, obviously, if we have an endoscopic mucosal resection, we're not going to cure the cancer. Uh so we can sample that lymph node. And if the lymph nodes negative, we can think about doing a, doing an er, so that's a another staging modality. We've also got to assess the patients. These are patients who in certainly in the West are often elderly, a lot of them have smoked, a lot of them haven't had very healthy lives. So fitness becomes very important. So we can assess that with things like the child and comorbidity score assa performance status. How fit are they? We can do lung function tests, we can do echoes, which gives us an idea. But the thing that I probably still rely on more than anything else is the end of the bed test. You look at a patient and you say wow, ok, you're very fit or actually you're not very fit. One warning about using the end of the bed test is that these patients can sometimes look a lot weaker because they're not getting nutrition in. And if you can change their nutrition, if you put an NJ tube in or a feeding jejunostomy, get the dieticians to see them if they can improve their nutrition. You can often see them two or three weeks later and they look completely different. So don't write somebody off just because you think I'm not, not sure they're fit enough, get their nutrition right. If they've got disease that's potentially treatable. See them again after two or three weeks and see how they're getting and, and a lot of the time you'll be pleasantly surprised at how, how much better patients get. So, if we come forward with treatment now, there are really four modalities now. Ok. Um And the, the fourth one is really very new but surgery, oldest, oldest modality. So surgery really only has a place if we're intending to try and cure somebody for esophageal surgery. There is no place for surgery and palliation. You would never do a palliative esophagectomy because it's just too big and too morbid an operation. Ok. You've got radiotherapy. So for squamous cell cancers with radical chemo radiation, you can have cure rates that are as good as surgery. There are advantages to radiotherapy, there are advantages to surgery for mid third Squam. One of the problems that we have with surgery is there's very little tissue between the esophagus and the trachea and the bronchi for instance. So if you've got any t three disease, you may well have local invasion of the trachea, which we just won't see when we're doing the operation, but it will be inc curative radiation treatment. Not only will treat the cancer, but it'll actually treat the trachea. So if there are any, any little bits of T four disease in the trachea, you still have a chance with a cure with radiotherapy. More recently. Uh We've got neoadjuvant chemo radiation, the so called cross regime, which has got people very excited and I'll talk about that a little bit later. And the other role for radiotherapy is control the bleeding if you have somebody um who's bleeding a lot esophageal cancer, but it also applies to other cancers giving radiation treatment. A short dose radiation can often control that because very often it's not big vessels that are bleeding. It's the whole surface is raw and one of the side effects of radiation, uh One of the side effects of radiation is that it causes small vessels to, to shrivel up. And that's exactly what you want to do with control of bleeding. So somebody's just asked is staging really important. The answer is yes. And I'll come on to that because if you've got staging, if, if you're trying to treat somebody, if you're going to do a big 56 hour operation on somebody which has serious risk to their life, you need to be able to tell them what are your chances of cure. Because if, if it's early stage and says we can put you through all this and we've got a 60% chance of curing you. The outlook is very different to saying, well, actually it's quite advanced. We've only got a 20% chance of curing you. So, so staging is important. The other thing which is even more important is to make sure that we don't operate on people where there is no chance of cure. So if we can look hard and find that the cancer has metastasized, we can see it in the lung or the liver. It means that we don't put somebody through a very, very big operation when there is no chance of curing them. So, staging, yes, very important. Which treatment there are risks and benefits. Why are we looking at the chance of cure? Now, with surgery, what I always explain it to patients. You know, the difference between surgery and radiation treatment is if you want to get down from the top of the cliff, you know, to the bottom surgery is jumping off, hold your nose and you'll get to the bottom pretty quick. The problem is, is once you've made that leap, you can't get halfway down and think this wasn't a great idea you're committed. Whereas with radiation treatment, you start climbing down and if it gets difficult, not always, but you've got a good chance that you'll be able to climb up again. So, although the overall mortality and morbidity between surgery and radiation treatment is probably similar, one advantage of radiotherapy is that it allows you to go down slowly. And so if somebody is a little bit less fit. You can see how they go and if they tolerate it well, they're fitter than you think you can put them through the treatment. Whereas with surgery you can't do that test. It's, it's jumping off a cliff, it's all or nothing. The other thing you have to look at is that what's available, not all countries will have radiation treatment available because the linear accelerators are big, they're expensive surgery. Uh, Although it's big surgery can often, often be done in normal operating theaters in normal hospitals. So sometimes surgery may be the only modality that you've got. Uh, in which case, that's what you'd go with. So what are the principles we'll talk about surgery? Well, it's what I said earlier. If we're going to cure somebody, we have to take away all the cancer. So if you've got t four disease to the uh pleura pericardium, you can take it all out. But actually your chances of curing that are going to be very small. What kind of surgery you do depends very much on where you think you're going to run into problems with the longitudinal margins. And I, I've got a slide that'll come on, show that in a moment. If you're going to do surgery, you should really be trying to take at least 20 lymph nodes. Uh And that means that you've got an accurate end stage which allows you to give you prognosis if you only take two lymph nodes and you've got one involved. Does that mean there is only one lymph node involved or if you took 20 would you find there were 10 involved if you take 20 lymph nodes and you've only got one involved, it gives you a lot more information. OK. So the type of surgery type of reconstruction. So there's lots of different types of operation. If a patient with stage four disease and was asked, showed regression after chemo or radiotherapy, can we go for surgical resection? That's something that's a good question actually. And it's one that we keep discussing at the end, the end, the answer to that is, it depends on the stage. If they've got overtly metastatic disease, liver mets or lung mets, I would say no, because what you're saying is the chemotherapy has got rid of all of the metastatic disease. So therefore, if you took out the primary, there's a chance of cure. But if it took out all of the metastatic disease, why hasn't it taken out all of the primary disease? And the answer is for patients with metastatic disease, it's very likely that they'll still be residual disease. Now, for patients where it's locally invasive T four A and you get a good response, then the answer is you'd have to talk to them very carefully and say the chance of cure is quite small. But for those patients, I would probably be prepared to operate on whether we're doing the right thing or not, I can't say. So, going back to surgery, longitudinal margins, shape the choice and also the type of surgery. So when we started doing minimally invasive esophagectomy, where previously we do a two stage, we went to do a three stage. So we could do the joint in the neck. We've moved on since then, we can now do the joints, uh thoraco ically in the chest. Ok. So this is essentially what we do. If you've got a cancer in the esophagus, we'll turn the stomach into a tube. Ok. Remove the area where the cancer is. And then we take the uh, the stump tube that we've made and join it up in the neck. And that's simplistically what we do with surgery. Now, we generally do this for an abdominal incision or laparoscopically these days and a thoraco a thoracotomy through the right side and we need to get the lung down. So we've got access to the esophagus. We generally would probably make an incision. That's only half that size these days. So I talked about what kind of operation we do if you have an esophagectomy. Ok. Say your cancers around the gastroesophageal junction. So this will be an adeno carcinoma and there's the cancer that you can see this little red, red, uh um cancer macroscopically. And then you've got this yellow cloud, which is where you might get microscopic spread. And you can see that if you do an esophagectomy. You can get close to this margin here. So we would worry about this margin because we're taking the esophagus so high, the proximal margin is always going to be fine. Ok. Here's one way you do a total gastrectomy. And again, here, because you're taking the hole of the stomach, the distal margin is absolutely fine. But here because you can only go so high up, you'll find that the proximal margin is the one that's important. And so for this reason, we have a rule in our unit that, you know, we will always rescope the patient ourselves. It's not that we don't trust the gastroenterologist. Actually, it is, we don't trust the gastroenterologist. But if they get their measurements wrong by a couple of centimeters, you know, and they say it's lower than it is or higher than it is, we could do completely the wrong operation. So if you're going to operate on these patients, you really need to either have a look at it yourself. So you can plan surgery or you have a colleague who you trust implicitly to have a look at it. Ok. But some of the biggest errors that that come about uh are when you, you take measurements done by somebody who you don't know at face value. So, should we operate? Yeah, that's a good question. You know, the operation. When we, we do it, it's a huge operation. It's the abdomen, it's the chest. If you look in the 19 seventies and eighties mortality was 30% was significantly better than that. But, you know, even here we say 30% of patients will get major complications. Uh, and if you don't survive a year, we've probably done you harm. If we operate on you, there's no doubt that we suppress your immune system and we'll talk about immunotherapy later on. But immunotherapy is the next great thing, you know, boosting the body's own immune system has, has proved miraculous for a lot of cancers. So if boosting it is great for cancer, then immunosuppression is probably equally bad. We also have to look at our own, our own fragility. You know, if we see patients who have complications as surgeons, we feel responsible for them. You know, there's this feeling if I was a better surgeon, this wouldn't have happened. It doesn't happen to medics or oncologists. If you give someone on chemotherapy and they get neutropenia and they become horribly toxic, it's the drug, it's not you. But for surgeons, we feel it's, it's our fault, it's personal. And I suspect that probably is a good thing because the surgeons who I've always worried about are the ones where complications are always somebody else's fault, not my fault. So we mentioned earlier that there are potentially alternatives, radiotherapy. Now, in squamous cell cancer, the cure rates for surgery or radiotherapy are the same. So going down a radiotherapy route is, is actually good. And for middle third sways when they're around the clockwork, which we can't take out the trachea, the bronchi, we would probably prefer to go down a radiotherapy route. Adenocarcinomas. We think that surgery, chemotherapy and surgery is better. But actually, there are areas including a very famous cancer surgery in the North England called the Christie where they would still treat adenocarcinomas with chemotherapy and radiation treatment. So that's another option. We've also got to look at the, the cost of the healthcare, you know, if we're going to do what's going to be a very expensive treatment. If we're going to give them a very expensive operation, then there's no country in the world where healthcare budgets are unlimited. That means that someone somewhere else doesn't get other treatments. And again, I'll touch on it later. But we also have to look at the cost to a country. You know, if, if we're spending money, huge amount of money trying to get someone to live a little bit longer, then that money isn't available for things like education. And one of the things I've always thought is that if you look at health, giving somebody a good education will mean that that person has more health, has more long term health than I will ever give them as a surgeon because it'll mean that they can get a job, they can get a, an income, they can afford to live somewhere. They can afford to, to actually live a healthy life. And that's something that we need to think about centralization of surgery. So, when we look at surgery, when we look at surgery around the world, we, we've in the UK, because we've got a lot of it and because we have, I suppose, a socialist healthcare system where, you know, patients don't pay for their own treatment and, and there isn't an incentive if I do 10 more esophagectomy, my salary doesn't go up at all. I get exactly the same amount of money we've been able to centralize services. So if you look in America, they'll define a high volume center there. Now, as one that does 12 esophagectomy, you know, per hospital in the UK, we originally said to be a high volume center, you have to have four or five surgeons, each surgeon doing 20 gastroesophageal resections that does include gastrectomy. So it's not quite there, but we're doing a lot more. And what we find is that as we do more, we get better at dealing with the complications. Our complication rates are probably just the same as the surgeons who do fewer. But what changes is our ability to deal with those complications to get patients through and get them back to having a good quality of life. Now, if you look, this is a slightly old slide but it's 2004. But what you can see here is when you talk about number of esophagectomy per year in a center this is not per surgeon. This is in a center. If they were doing them less than 5% they have an 18% mortality. Once you got to, more than 20 mortality rate went down to 4.9%. So that's something that says, the more you do, the better you get at it. Ok. In the UK minimum, 20 per year, our current rates are looking at 30 day mortality for esophagectomy. We're looking at 1.5% and 3.1% 90 day mortality. So we're pretty good. We've got to the stage now where we're much less worried about mortality. And we're saying, well, how can we reduce morbidity? How can we reduce length of stay because we've got mortality down to something that's reasonable. So we talked about surgery. Now, let's go on to radiotherapy. So most radiotherapy certainly in the West now is uh some form of IMRT conformal radiation treatment. And essentially I'm not a, I'm not an oncologist. So I'll be quite brief on this, but they basically get a ct scan map out where the cancer is. And with these new devices deliver radiation in, in lots of different collimator beams. So where they crisscross over where the cancer is, they can deliver much higher doses of radiation to the tumor, hopefully sparing the normal tissue outwards. Now, as a surgeon, we always like to think that surgery is best. But actually for squamous cell cancers, my own feeling is, is that if they're up a third, if it was me, I'd probably go for radiation treatment. And the reason for that is that if it works, if it cures the cancer and gets rid of the cancer, and this is the important thing, if it does that without creating a whole load of scarring, then you have a, a relatively normal esophagus afterwards. You can, you can eat, normally, you can have a normal life, which after surgery, yes, you can eat, you can eat normal foods. But there are so many compromises that you have to do because we've removed the stomach and created a, a gastric tube. The other thing is is that if radical radiation treatment doesn't work, we can still do an operation. People have been very frightened of salvage esophagectomy in the past because they said everything got very stuck and horrible. After radiotherapy, we, we've been doing quite a lot there. And again, it's the advantage of being in a high volume center where we're not frightened by the operation. And although some of them have been pretty horrible, most of them are ok. It's not as bad as people say. The disadvantage of radiotherapy is largely strictures. Ok. So you can get really horrible strictures, which can be incredibly difficult to deal with. The only reason that we've talked about with Radiotherapy now is cross, ok? And that's neoadjuvant chemo RT, which I'll come to. So if we talk about neo jut chemotherapy, then we should start with ne Arin chemotherapy because that's standard of care. Certainly in the UK, now for a adenocarcinomas and squamous cell cancers. And so this was a trial of CISplatin 55 fluorouracil compared with surgery alone. And this was chemotherapy given before surgery because all the trials said that chemotherapy after surgery didn't work. In actual fact, it was a trial of chemotherapy, followed by surgery, followed by more chemotherapy. But because of the time when this trial was run, surgery wasn't quite as good as it is. Now, most patients didn't have the chemotherapy after surgery. So we really think the benefit accrues from the chemotherapy that you give prior to surgery. And when it originally came out, you could see five year survival rates. It wasn't a massive improvement, but it was significant. So that became standard of care. And fortunately when you start going out to nine or 10 years, the, the survival benefit seems to, to be less. Ok. So we've moved on. Uh, that's all right. Despite chemotherapy, you can see the most important thing. This was surgery, taking it all out. If you took it all out, you had a good chance of cure. If you didn't take it all out, the chance of cure was really very small. So we then moved on to uh something called flo, uh which is fluorouracil, leucovorin, oxalin DOCEtaxel. And this is a slightly more aggressive chemotherapy regime. But you can see here that again, neo drink chemotherapy, chemotherapy before surgery, you can see, actually there's quite a big difference and, and this difference is maintained up to six years. So flo has now become our standard of care. So in the UK for adenocarcinomas, this is the treatment. Now, if you go to the continent for adenocarcinomas, they will give cross. OK. And cross is adjuvant radiotherapy. So this is 41 grays of radiotherapy. Curative for squamous cell cancers would be about 55 grays. So it's, it's sort of 70 80% of what you'd give to try and cure squamous cell cancer with these chemotherapeutic agents which are there to make the cells more sensitive to radiotherapy, to make the th the radiotherapy more effective rather than being chemotherapy to try and kill off little micro metastases. And you can see here at 10 years, there's a huge difference. 38% survival with cross compared with 25% survival with, with surgery alone. So everywhere on the continent went up to cross. But in the UK, we haven't why. Well, the reason that we're, we're still skeptical in the UK is because this was a trial that included squamous cell cancers and adenocarcinomas. And if you look at just the adenocarcinomas, which I've starred here. So this was cross for adenocarcinomas, followed by surgery and this was surgery alone, you can see the difference is actually smaller. And if you go back to flo this was the difference. You can see how they look similar. And if we put one on top of the other, you can see, actually there isn't much of a difference and giving eight weeks of chemotherapy four cycles of basically one day of chemotherapy is a lot easier for the patients than having to go Monday to Friday for radiation treatment for 4.5 weeks. So that's why we're not believers in cross in this country for adenocarcinomas, but for squamous cell cancers, yes, because the difference is, is, is, is huge. So, immunotherapy, I'm just gonna finally come to finish really with immunotherapy. And this is, this is if you like the new frontier in the next 10 or 20 years, I think all the massive advantages, advances we're going to see in the treatment probably of all cancers. I is going to be immunotherapy. And this was a trial called Checkmate 648 and it was advanced esophageal squamous cell cancer with nivolumab. OK. So 970 patients with basically advanced metastatic or untreated squamous cell cancer. And they looked at Nivolumab plus chemotherapy, nivolumab plus Ilia, I can't pronounce that properly and chemotherapy on their own. And how it works is that Nivolumab is an IgG four monoclonal antibody and it blocks PD one programmed cell death protein. One. And what that does is it within the cancer? You have a tumor cell and we've also got immuno uh T cells. So these are cytotoxic cells which will try to kill virus infected cells. It will try to kill cancer cells. But if you have, if the tumor cell has this programmed cell death len one or two that can attach to the PD one protein. And when they link up the tumor cell is turned off, the T cell, not the tumor cell, sorry, the T cell, the T the T cell immunocyte is turned off. So it doesn't kill the tumor cell. So the idea of the volume is it attaches to here. So you can't get that linkage. So the T cell is not turned off. OK. And it'll start killing the tumor cells. And what we found is these graphs show that actually, it does seem to work. If you've got a lot of expression, the cancer produces a lot of this PD L1, then you can see the difference is really quite big if it doesn't. So this was the overall population, the difference is smaller. Now being very cynical. If you look at the difference there, the patients who did have this high PD L1 expression, they're 100 and 50 in each arm overall, it was 300. So, so this was half of the patients. And if you go from 37 to 58 well, that's 21. If you go from 40 to 54 that's 10. So if half of this 24 was in this group of patients who have this PD one expression. Then my reading of this is that if you don't have that, then you probably don't get much benefit. But that's not how the trial was published. It was, these patients will benefit as well. And when you look at the cost of it, you know, you're talking about 250 mgs every two weeks until disease progression or for 24 months. And the cost of this is 3000 over dollars per dose, $84,000 per year. You can see potentially why they may have suggested that all patients will benefit. But realistically, my view is is that if your PDR one expression is low, the benefit is going to be pretty darn small. So what I'm going to finally finish on is the economics of this treatment of esophageal cancer is expensive. Yeah, we're looking. So I've got my pounds and dollars mixed up surgery in the UK is probably going to cost $25,000. Uh, by the time you've looked at what we'd normally get for an esophagectomy. Plus, if somebody stays in hospital in ICU for two months, we get paid for that as well. On average, it's probably about $25,000 in America. It can easily be 10 or 20 times that amount, radiotherapy. The machines are expensive. One of the things that people never look at is the cost of mass endoscopy. If we weren't worried about cancer, then we would do very few endoscopies because if somebody's got indigestion, they might have an ulcer, they might have reflux. Well, in this day and age, you would treat that with PPI S helicobacter eradication, but we don't do that because we're worried about cancer. So in the UK, the cost of an endoscopy is 400 lbs, about $500. And if you think the pick up rate 1 to 2% so it'll take 20 say 75 endoscopies to pick up one cancer. It's going to cost 30,000 lbs to pick up one cancer. And if the cure rate we have for the ones we operate is only 26% that means it's 100 and 20,000 lbs to diagnose one curable cancer. And that doesn't include the the cost of treatment. So when we look at the economics of dealing with gastroesophageal cancer, you have to say that the amount of money we spend can even a rich country afford it. Yeah, and I'm saying that as a gastroesophageal uh surgeon. So hopefully we've had a bit of a whistle stop. So that's the last slide. And so we've talked about, you know, the, the distribution over the world, uh how to diagnose it, how to, to stage it and what treatments are available did say I would talk to you about how to counsel patients. I I specifically avoided that because how you counsel a patient depends very much on what treatments are available to you. And also what the risks are. If you're in a, a low volume center in the states where your mortality rate is 15 16 17% you know how you counsel a patient is going to be very different to if you're in a low volume center where the mortality, the high volume center where the mortality is going to be one or 2%. So, you know, and, and one of the things that we, we never think about in medicine is, is costs. And as I say, unless you are an incredibly rich country and even then, you know, if you go to America, there are huge numbers of p patients who are not getting treated because they're not insured. Then you do have to look at, you know, how do you get the best bang for the buck? And actually within medicine, there are things that strike me as better value than others and outside of medicine, health care for, you know, in pregnancy education, those are things which probably in my view are probably more important than, than you know, this very expensive healthcare. Ok. So I'll open it to any questions. So I'll stop presenting now. Is that what I should do? That's perfect. Does anyone have any questions? That was a very good talk. Hala says it's the first time seeing a slid with economics. It, it's very basic economics, but it's one of the things that you have to start looking at, you know, and if you look at the health care in the UK, you're now getting into robotics, you know, which again make the operations more expensive for some operations, it'll make them better. So for instance, for prostate surgery, it means that they can do it as a day case, as opposed to a week in hospital with laparoscopic surgery. So the economics may stack up. But a lot of if you go to the States, people are using the robots purely and simply to say I'm using a robot, it must be better come to us. I actually do have a question. Um What is ok, this is gonna be a very basic question. OK. So you had mentioned radiotherapy. Um, obviously with radiotherapy, there does come, um things later on that may occur through having that radiotherapy. Uh my dad had prostate cancer, he had radiotherapy and now he has prostate cystitis. So, so with um your esophageal one, what implications are there down the line from having that radiotherapy? What like what are the downsides of having it even five years on? What are the downsides of the radiation? The problem with radiation treatment is that it damages normal tissue. So you mentioned it in your dad's case, they're zapping the prostate, but the prostate is right next to the bottom of the bladder. So when they're zapping the prostate, they zap the, the bladder and they damage the bladder which gives you that radiation uh cystitis, which can be quite distressing. So the newer, the newer machines are better at delivering the dose of radiation just to the prostate. Uh and the very latest machines, things like Cyberknife uh will, will deliver radiation really in a high dose. And, and they can almost draw a 3D model and say we can give the radiation, you know, give 90% of the radiation within that model. So you're having far fewer complications. So that's probably the future for radiation in the esophagus. It probably won't help that much because most of the stuff apart from the heart. Uh and we tend not to zap the heart, but the bronchus and the aorta are are relatively resistant to radiation treatment. The big problem with radiation treatment is it can cause scarring, it causes tissue damage. And if the body reacts to that by laying down a lot of fibrous tissue, uh you can get very, very rigid scar tissue, which means that people can't eat afterwards. So at one end, you can get no, you can get no scar tissue and you can have, yeah, you just look entirely normal and you can have a normal life. At the other end, you can get horrendous scarring, which means that you might be reliant on feed, feeding tubes for the rest of your life. But with surgery, you know, there are so many things that can go wrong. We, you can have anastomotic leaks, you can stay in ICU for, you know, occasionally months. Uh So, so there is a, there is a balance of risks and, and actually explaining that to a patient is quite difficult in the UK. We're lucky I can see somebody with squamous cell cancer and say you have two options and this is what I want to do America. I'm very cynical of the American health care service. But somebody once said to me that whether you have radiation treatment or surgery for your esophageal cancer, the biggest determining factor is whether you see a surgeon or oncologist when you first present, because if you do an operation, you can buy a new car. You know, for me, if I don't do an operation, I'll do four gallbladders on my list. There's no, you know, there's no, there's no financial incentive. Is there any benefit of robotic esophagectomy over a laparoscopic M I in terms of outcomes. The answer to that is we have no evidence. I I've been a consultant in the UK, 19 years when I started, basically, most people were doing open, open surgery. Uh we, we pushed and some of the, some of the leaders in doing laparoscopic surgery. So basically, everybody in my hospital now will do a laparoscopic abdomen. Um myself and one of the others will still do thoraco um surgery of the chest. Whether or not the thoraco bit makes a difference. I'm not sure the only trial that we've had of open versus hybrid, which was open, open versus hybrid showed no difference. Uh, that was a Romeo trial. But the problem is, is that, you know, I'm guilty as anybody else when you have a trial that doesn't show what you want it to, to show you tend to go. Oh, it was a rubbish trial. And we're going to ignore it for all these reasons. If on the other hand, it showed what you wanted to believe. We say it's a fantastic trial and this is what we should do. But I think Romeo, the reason I don't believe it is that it, it was actually in the fairly early stages of laparoscopic surgery. And if you look at how we started the first 10, 20 laparoscopic abdomens that we took, the actual abdominal part took us about five hours. Whereas now we can do it in two hours. So, you know, I have no doubt we're doing a lot better now than we were 15 years ago. Uh, robotics. I don't know, it should make the chest bit easier. I can see how it would make things easier. Uh, whether that translates into improved patient outcomes. It is difficult to, to, to see when we looked at our own data. Uh, we looked at there's no difference in mortality, morbidity, leak rates, length of stay for a hybrid. I think average length of stay was 50 not median average. And there's a big difference in esophageal surgery because in esophageal surgery, we have a few patients who stay in for a huge length of time. So the median which is, you know, will, will flatter you. But if you look at the average, uh you can see how many bed days are taken. And so for hybrid, it was 14 days, uh and for Mio it was 13 days. So not a huge difference. Perfect. Thank you very much. Does anyone else have any questions? See, I ask a question that's really basic so that it gives everyone else a chance to type in a question. The only thing I'd say is that there are no, there are no dumb questions. You know, the only, you know, I don't know, I don't know. You know, I'll tell you, I go to meetings, especially if they're management meetings and they're all talking and they'll use jargon and I'm the first person to put my hand up and go, sorry, you know, what does that mean? And, and you kind of think you're going to be dumb and then everyone looks at you and go, oh thank God, you asked that because I didn't know either. So, you know, don't, don't be frightened of asking questions. Perfect. Well, if no one else has any questions, we will wrap it up here. Like I said, there will be a feedback form. We'll pop this on, catch up as well. Um In the next couple of days you'll have it in catch up. Um And in the feedback, there are there is a question to say, what other topics would you like to learn? And maybe John will come back and give us another talk based on what it is you have popped in as an answer to that question. Ok, so we will say goodbye now and we will see you again soon. Thank you. Bye bye.