Barrett’s Esophagus

Speaker 1: Welcome to Bench to Bedside, a weekly series of live conversations about recent advances in cancer from the research bench to treatment at the patient’s bedside. And now, your host and the director of The University at Kansas Cancer Center, Dr. Roy Jensen.

Dr. Roy Jensen: Cancer of the esophagus is 1 of the fastest growing cancer diagnoses in the United States. In the last 40 years, esophageal adenocarcinoma, a type of esophageal cancer has increased in individuals younger than 50. The 5-year survival rate for esophageal cancer over all is about 19%, which believe it or not, is an improvement over the last several decades. But we can do better. Researchers at The University of Kansas Cancer Center are looking into new ways to better prevent, treat and diagnose esophageal cancer.

Good morning, I'm Dr. Roy Jensen, director of The University of Kansas Cancer Center. And joining me this morning is Dr. Prateek Sharma, a gastroenterologist with The University of Kansas Cancer Center and an internationally renowned expert in esophageal cancer and Barrett's esophagus, a precursor to esophageal cancer. Also, joining us via Skype is, Megan Peters, to take your questions. Well welcome, Dr. Sharma. Could you tell us why esophageal cancer is on the rise, particularly adenocarcinoma in the United States?

Dr. Prateek Sharma: Okay. Thanks, Dr. Roy. Good to be here. First, esophageal adenocarcinoma, this is the type of cancer which occurs in the lower part of the esophagus. The upper part of the esophagus, the cancer, which happens is squamous cell cancer, which is on the decline and adenocarcinoma, which is the lower part is on the increase as you mentioned. And something which is unique to this is it's linked with a very common condition of gastroesophageal reflux disease, or acid reflux as it’s commonly known. That's to be a risk factor for esophageal adenocarcinoma and reflux is on the rise in this country. There was a recent survey done looking at close to 70,000 subjects of the adult U.S. population, and anywhere from 20-40% of those participants suffered from gastroesophageal reflux disease. That's increasing and that's probably increasing because of our diet. We've got fast food joints, McDonald's, Burger King right around the corner, increased fat in our diet. I think that's contributing to it. And that's leading to obesity, specifically central obesity. And that's also one of the reasons why esophageal adenocarcinoma is increasing in incidents. The precursor that you mentioned, Barrett's esophagus, that also appears to be on the rise and that also is related to reflux disease.

Dr. Jensen: What are the symptoms of esophageal cancer?

Dr. Sharma: Unfortunately, by the time you get symptoms, it's a late stage cancer. And that's part of the reason of those dismal numbers that you discussed, Roy, about 15-20%, 5-year survival. Early cancer may just have either no symptoms or mild symptoms of reflux disease, long standing reflux, obesity, smoking, a diet, which is low in fiber, cereals and green vegetables. Those are related to that. But once the cancer goes to the point where it's blocking the lumen of the esophagus and causes it to get narrowed, then you get symptoms like dysphagia, which is difficulty swallowing, and you may start throwing up blood. You may start losing weight. You may start seeing dark colored stools, which is a sign of blood in the stools. Once you have, or anyone has those symptoms, those are alarm symptoms. You definitely, definitely need to go and see your doctor, if you start developing any of those symptoms.

Dr. Jensen: Mm-hmm (affirmative) You correctly point out there, esophageal cancer tends to be diagnosed at a much later stage. What do you think about our efforts to try to shift the curve there and diagnose esophageal cancer in a much earlier state?

Dr. Sharma: Right. That goes to the screening part of the disease. And we've made some advances about the risks factors and trying to risk stratify the population. We are not to a point where we can justify screening the general population. For example, for colon cancer, we say that at age 50 you start screening for colon cancer, so there are different options available for screening, including endoscopy, including stool test, et cetera. For esophageal cancer, we've tried to come up with some risk scores in trying to look at certain risk factors. Age is important, age 50 or 55 or greater. It tends to impact whites more than African Americans or the Hispanic race. Smoking again, increasing obesity, chronic reflux symptoms or acid reflux for 5 years or longer. A family history of reflux in your family or esophageal adenocarcinoma.

Those patients are considered to be high risk, and you can screen those patients. Right now, screening those patients involves an endoscopy test. And there is some research being done that we are also doing about trying to look at noninvasive methods such as dropping a capsule down into the esophagus, a brush or a sponge, and then scraping the lining of the esophagus. Those are some of the cutting-edge research that we are doing at the cancer center.

Dr. Jensen: Mm-hmm (affirmative). Let's talk a little bit more about Barrett's esophagus, a condition which will put folks at a little bit of an increased risk for esophageal cancer. Tell us exactly what it is, what are the symptoms and what is causing this increase in Barrett's esophagus?

Dr. Sharma: Okay. Good question. Barrett's is a change in the lining of the tissue of the esophagus. Normally, the esophagus is lined with squamous mucosa, which is white, pearly colored mucosa. When that lining changes to a columnar type of mucosa, which is a type of mucosa which normally lines the stomach or the small intestines. That's called a metaplastic change. When that happens, it's called Barrett's esophagus. Now this condition was diagnosed way back in the 1950s, actually, by a surgeon when they were operating on patients with acid reflux, they found this red color in the esophagus, and they actually thought that this was the stomach, which is migrated up into the esophagus, but that was in the situation. It was a change in the lining.

This change in the lining, the metaplastic condition, is called Barrett's esophagus, and it's a pre-cancerous condition. The good news is that the absolute risk of somebody with Barrett's going on into cancer is still quite low. But if once a diagnosis has been made, we can have these patients enrolled in surveillance programs, which means that we bring these patients back every 3, 4, 5 years to do regular checkups on them, to make sure that the Barrett's is not progressing towards cancer. That surveillance can help diagnose is all esophageal adenocarcinoma at an early stage when it is still can be treated for a cure rather than waiting for late stage cancer.

Dr. Jensen: Mm-hmm (affirmative). One of the things I really want to impress upon our audience is you are truly a world expert in Barrett's esophagus, and your work and contributions to the field have really significantly impacted how we diagnose this disease, how we think about this disease. And I think it's fair to say that a physician treating a patient with Barrett's esophagus in any part of the world is likely to have been impacted by the work of you and your team. Maybe, could you share with us a little bit about some of the tools and techniques that you have developed to diagnose this disease and to treat it?

Dr. Sharma: Sure. Thanks. First is just the diagnosis. I mean, once our team started doing some of this research, we found that patients were being misdiagnosed. There's always the issue about correct diagnosis, but there's always this issue about over-diagnosis. Because if you over call this disease as well, that's not good for a patient because now you've labeled them with the diagnosis of a pre-cancerous condition and more than them getting the cancer, it's the anxiety, which I think really impacts patients’ lives. And I think that was our initial reason to start looking critically at the diagnosis. Our team here in Kansas City have come up with very strict criteria as to how this diagnosis should be made. We've made some changes in how the endoscopic landmarks should be recognized, how the extent of Barrett's esophagus should be measured. And we've proposed some criteria which are called the Prague criteria.

And it's just a way of globalizing – as well as standardizing – a validated tool for making a diagnosis, so that when a patient is given this diagnosis, there is a standardized diagnosis which goes with them. Even if the patient moves from town from Kansas City to Wichita, Omaha, the physicians can look at the report and know exactly what we are talking about. It is a standardized language. We have also then looked at different endoscopic tools with different color wavelengths of lights. And what we've found is when we use light of a shorter wavelength, and again, it may sound or sounds very fancy, but it happens with the switch on the tip of an endoscope. A physician or an endoscopist or a gastroenterologist can easily do that is you start seeing different pit patterns or mucosal surface patterns of the esophageal aligning. And that points towards areas of pre-cancer, cancer, early cancer.

We've tried to improve this diagnosis of making esophageal cancer an early diagnosis. Subsequently, with that, we've also introduced techniques of treating these early cancerous changes through the endoscope. What we do is we prevent surgery, which is a major surgery, esophagectomy, or removal of part of your esophagus so you can resect abnormal areas of the Barrett's and try to remove it endoscopically and treated endoscopically. And there's now good 5-year survival data on patients with early cancer of esophagus and Barrett's in which we show that the 5 year survival data is close to 96-97%.

Dr. Jensen: Beats the heck out of 19%. That's what we [crosstalk 00:13:51].

Dr. Sharma: Yeah. Absolutely.

Dr. Jensen: If you're just joining us, we're here with Dr. Prateek Sharma, talking about advances in the treatment of esophageal cancer and Barrett's esophagus. And Megan Peters, is here via Skype taking your questions. Remember to share this link with people you think might benefit from our discussion. Use the hashtag, #BenchToBedside. And Megan, I understand that we have a couple of questions.

Megan Peters: Yes, we do. The 1st question is what is the prognosis for stage 2 esophageal cancer?

Dr. Sharma: Yes. A good question. Just like other cancers as the stage of the cancer increases, unfortunately, the survival decreases. For stage 1 cancer, we've shared numbers, the 5-year survival is 95% plus or is in the 90s. It's excellent survival. On the other hand, stage 4 cancer, which is at the other extreme, it's very poor, it's 5% or less. Those are the 2 extremes. Stage 2 cancer and stage 3 cancer fall somewhere in between. I would say that for stage 2 cancer, it's probably close to about 60-70% and that would require neoadjuvant chemotherapy, plus surgery after that. And the problem with that also, and the reason we try to avoid those is not just the morbidity and the mortality of the procedure, but some of the side effects that patients have to live with after an esophagectomy. Which again, can be done. Great. We've got excellent thoracic surgeons here, the multidisciplinary aspect. The goals should still be to try to recognize this cancer when it's stage 1 and early on in the disease. Otherwise, there will be a gradual decline in the survival.

Dr. Jensen: Just to make sure that folks understand the concept of stage; basically, staging refers to where a tumor is in its natural history. A stage 1 tumor presumably is confined to very superficial layer of the esophagus.

Dr. Sharma: Right.

Dr. Jensen: And then stage 2 and 3 means it's basically grown further into the esophagus.

Dr. Sharma: Right.

Dr. Jensen: And then stage 4, obviously, [crosstalk 00:16:18] is when it's gone everywhere.

Dr. Sharma: Yeah. Absolutely.

Dr. Jensen: That's why there's such a difference in the survival between stage 4 and stage 1. And our next question, Megan.

Megan Peters: The question is, I have Barrett's and get tested every 3 years. My brother died from cancer of the esophagus. Are there any other treatments for Barrett's besides diet and proton pump inhibitors?

Dr. Sharma: Right. Excellent question. This gets into the realm of what we call chemo prevention. And chemo prevention in simple terms is, can you take therapies or apply therapies to prevent the progression to cancer? And it's a very valid question because it's really necessary for precancerous conditions, such as Barrett's esophagus. A couple of things which have been tested in randomized trials, which is the best quality of evidence that you get are aspirin and statins. Aspirin has been shown to delay the progression from Barrett's esophagus into the high-grade dysplasia, which dysplasia means that it's another step towards cancer, not yet cancer. High grade dysplasia is almost cancer, but not yet cancer. I apologize for these terminologies, but it's important to recognize, especially if you or someone in your family does have Barrett's esophagus. That's another goal.

Aspirin, something which can be tried in conjunction with proton pump inhibitors and has not been shown to prevent it, but delay the progression. Again, check with your doctor about maybe other risk factors that you may have, or the risks of taking aspirin, i.e., such as a bleed. For example, the risk of taking aspirin is a hemorrhagic stroke, which we definitely don't want. I'd weigh the risks and benefits given your entire situation. That's 1 aspect that you look at. Weight reduction, control of your reflux symptoms, and again, better eating on nutrition such as increasing the fiber in your diet and reducing the amount of red meat consumption.

I think those are all simple, but yet difficult, to do things which will go a long way as impacting somebody who is at a high risk for that. And this, again, the person asking this question, especially the risk factors you have is not just Barrett's esophagus, but also family history of esophageal cancer. I'd be very religiously following your gastroenterologist and endoscopist’s recommendation of the surveillance and make sure that you do comply with that, because that will be a very important way to catch your dysplasia or cancer during the surveillance endoscopy.

Dr. Jensen: You mentioned that 1 of the contributions of your group is being able to measure and assess the amount of Barrett's. Why is that important in term of cancer risk? And what implications does it have to have an extensive Barrett's versus early, early stage of it [inaudible 00:19:40]?

Dr. Sharma: Right. One of the things we found early on during our research programs was that we found a differential progression rates amongst individuals who had Barrett's esophagus. And we were trying to figure out that, why do some patients progress either faster or progress at all, versus others progress either slowly or don't progress at all to cancer? And 1 of the things we found out to our interests was the extent of the metaplastic tissue. In a way, it's measuring the extent and intuitively, it makes sense that if you have a smaller area of a pre-cancerous condition, your risk for progression is probably low. If you have a larger surface area, which is abnormal, perhaps your risk of aggression is higher. And that's what we were able to show here in Kansas City, is this differential.

Our recommendation based on that is having differential surveillance intervals. If you have very short extent of the Barrett's esophagus, perhaps the surveillance can be extended to up to 5 years. If you have a larger surface area of the Barrett's esophagus, which may put you at a higher risk, your extent of surveillance interval may be shorter down to 3 years. And if you have additional risk factors such as smoking, such as obesity, of family history, or you have what we call low grade dysplasia – not the high-grade dysplasia – then again, those surveillance intervals may change. And what we are working on is personalized medicine. Barrett's esophagus in our societies say, okay, survey everyone with Barrett's 3-5 years. Our philosophy is, can we designate and personalize that intervention? And that's what we are working on, is a scoring system. What we have called it, the PIB score or the Progression in Barrett's, PIB score in which we can assign the risk. And so we can personalize treatment to patients with Barrett's esophagus.

Dr. Jensen: Yeah. I suspect no one enjoys swallowing an endoscope. Yeah. Recently, you were named chair of the Artificial Intelligence Taskforce for the American Society for Gastrointestinal Endoscopy. Could you tell us a little about what's the goal of that task force and what are you trying to accomplish?

Dr. Sharma: Yes. Personally, I think that artificial intelligence or AI will dramatically impact how we practice, not just endoscopy or gastroenterology what I do, but all of medicine. A simple example I give my patients, because we are actively doing trials in artificial intelligence now, is our smartphones or Amazon or Google. When you go to Amazon and you buy a shirt, and you've put in certain features that I'm looking for with this brand or this size, and this price range, 2 days later or a week later when you go back, it will automatically repopulate for you. And it will show you that buy this shirt, here's a sale for this, right?

Dr. Jensen: Mm-hmm (affirmative).

Dr. Sharma: That's in artificial intelligence. It's the computer that is now recognized to know your habits, which may be creepy in a way, but still it's true. I mean, that's how we are working. Artificial intelligence in gastroenterology and endoscopy is having that same intelligence built into our endoscopes, in a way to say. Our endoscopes are connected to a monitor and to a processor, and we build in artificial intelligence in there. What these endoscopes will do, or smart endoscopes, is that they will highlight for you when we are performing the procedure. Any small abnormalities would show up because some of these, as we were talking about early adenocarcinoma, sometimes I hate to say it, but the early adenocarcinoma may be so subtle that it may not be very clear to the naked eye. And that's what you go by is a human or individual's perception of seeing that abnormality. I think we'll become much smarter by using these kinds of endoscopes. This is just a small, I'd say, the tip of the iceberg example that I'm giving in endoscopy and in gastroenterology.

I was obviously very thrilled when our GI society asked me to lead this effort. We are trying to lead the field in terms of education, both for patients, as well as for physicians. We are trying to lead research in this field. We've started off with detection of colon polyps, which are, again, precursors for colon cancer. We will be shortly doing studies in Barrett's esophagus to see if we can pick up on these smaller, subtle lesions. Then the general community endoscopist can also get the benefit of some of these research tools and do that. I think it's exciting times, and I think our main goal will be to impact patient outcomes and impact healthcare.

Dr. Jensen: Mm-hmm (affirmative). What are the advantages of an individual seeking care at an NCI-designated cancer center, like The University of Kansas Cancer Center in terms of having access to a full range of services that can help with their condition?

Dr. Sharma: Right. Hopefully, some of this has been clear as we've been discussing this. You've heard a lot about the research, which has been conducted at the cancer center, not just for esophageal cancer, but other cancers. And so you get access to cutting-edge research. You get access to physicians who are conducting that research. You get access to clinical trials, which may not be available elsewhere. I feel that, that's a huge advantage. The other is just this multidisciplinary approach. For example, if you have somebody with early esophageal adenocarcinoma, we discuss those patients in a multidisciplinary tumor board, and that includes having our expert thoracic surgeons there, our medical oncologists there, radiation oncologists, pathologists, because that's something near and dear to you is that they are very critical in telling us whether it's advanced cancer or it's just superficial cancer. Our radiologist to look at the CAT scans, the PET scans, look at lymph nodes, et cetera. It is a more of a holistic approach towards the patient, rather than me making just a decision right off the cuff and saying, "Okay, let's just do this." Right?

Dr. Jensen: Mm-hmm (affirmative).

Dr. Sharma: It's putting all brains together and then coming up with a comprehensive treatment plan.

Dr. Jensen: Patients like to have as much control over their health as possible. What lifestyle changes can someone with Barrett's esophagus – or hopes to prevent Barrett's esophagus – do to put themselves in a better position to do that?

Dr. Sharma: Right. Many of the things, Roy, are very generic, I think, to other diseases as well. And I'll emphasize to my patients that what I'm going to tell you is not just going to help you with your acid reflux, with your Barrett's esophagus, but other more common conditions too, such as heart disease, such as diabetes, high cholesterol. If you keep in mind that approach, you will be more likely to follow some of these lifestyle changes, weight reduction, exercise, eating healthy. I think, you would say that, well, why is this specific to reflux disease or Barrett's? But as I mentioned, it isn't. This is all part of the thing. These promote acid reflux, which promotes Barrett's esophagus, which is a risk factor for esophageal adenocarcinoma. Having a healthy diet, which is low in red meats, which is high in fiber, cereals, green vegetables, I think, that has been shown to be negatively associated with esophageal adenocarcinoma.

Hiatial hernia, which we didn't discuss in detail, but that is a factor which promotes reflux disease. And 1 of the ways that you can reduce the reflux in those situations is by reducing that pressure on the hernia. And that's by weight reduction, specifically the weight or the fat around your belly, which is very difficult to do. Exercise or setting up an exercise routine, I think is an important thing for you. And then reducing the amount of fat and the caloric content that you have. Medication, if you have reflux, talk to your doctor, see if the proton pump inhibitors or the acid medicines are right for you or not, do you need aspirin or not? And then, of course, your gastroenterologist and endoscopist to figure out, whether you are in a regular surveillance program for your disease or not.

Dr. Jensen: Megan, I understand that we have a number of questions. Could you go ahead and start reading those off please?

Megan Peters: Sure. The 1^st question says, I've had an esophagectomy in 2013, how do I deal with pyloric stenosis?

Dr. Sharma: Okay. Esophagectomy, again, just for other folks joining in, esophagectomy means in which part of your esophagus is cut and removed. And what that entails is removing the distal part of your esophagus and part of your stomach, the early part of your stomach. And then the surgeon will hook up or anastomose or join whatever esophagus is left to part of the stomach. It's pulling up the stomach, basically, into your chest and doing the anastomosis. It appears that this individual asking this question has, unfortunately, had that procedure done. Pyloric stenosis on the other hand, is stenosis means a narrowing. The pylorus is the opening, which goes from your stomach into your small intestine. I'm guessing what you mean is a narrowing of the anastomosis rather than the stenosis.

But if you have the pyloric stenosis too, the same thing will apply for that is endoscopically, that can be stretched out. And the way we do it is during the endoscopy procedure, we can advance a balloon through the channel of the endoscope. Then we go in and we will inflate the balloon. If this is the lumen, which is narrowed, the balloon goes in there, it expands, and it stretches this opening. It sounds like that you have a narrowing there, which could be stretched. Again, not knowing your full history, I'm not saying that, that definitely can be done. But that definitely, as a gastroenterologist to me, is an option, which I think you should explore.

Dr. Jensen: All right. Megan, next question.

Megan Peters: Yes. We have several individuals that have asked if Barrett's can be reversed.

Dr. Sharma: Okay. Excellent question. And again, Roy, that was something I didn't mention during our conversation is about the reversal of Barrett's esophagus. And what we have shown is that Barrett's can be reversed by endoscopic ablation. And by ablation. I mean, in which we cauterize the lining of the esophagus of the Barrett's, which as I told you, is the columnar type mucosa. And we reverted back to what we call is the new squamous mucosa, which is not the original mucosa, but it's new because we are applying some therapy. Endoscopic ablation can do the reversal and endoscopic ablation includes EMR, which is endoscopic mucosal resection, which is cutting the lining of the esophagus. It can be done with RFA or radio frequency ablation in which we cauterize the lining. Another area is called APC or Argon Plasma Coagulation, which can also reverse the lining of esophagus.

These are all ways to reverse the Barrett's esophagus. Now, just like anything else in medicine, every time you do a procedure, it carries some risks with it. Just because you have Barrett's does not mean that you automatically should get these procedures done or that you qualify for it. Your gastroenterologist and endoscopist will weigh the risks and benefit. If you have dysplasia, I would say that that's much more, you are likely a candidate to get that. If you don't have dysplasia, you probably should not get into one of these reversal procedures because the risks may outweigh the benefits. But again, I talked about personalized medicine, so this is just a global gestalt and then opinion I have about this, but please confer and talk about it. But in general, if you don't have any dysplasia, you don't need any one of those ablation procedures.

Dr. Jensen: Just to clarify for our audience, could you give us some data around, what is risk for developing esophageal adenocarcinoma in a setting of early Barrett's where there's no dysplasia, versus advanced or extensive Barrett's where you have clear cut dysplasia?

Dr. Sharma: Right. Excellent question. And again, one of those things that a lot of the data quoted comes from Kansas City in terms of the risk of progression, and the way we define it is in annual risk of progression, which again, to our audience means, what is your risk of getting cancer every year if you had Barrett's esophagus? When we first, or when I started first doing research in this field, the risk was quoted to be 1 in 100. Okay? That 1 out of every 100 patients with Barrett's esophagus in the given year will get esophageal adenocarcinoma, which to some folks may sound low. But it actually is a very high risk, which means that if there were 100 patients in this room right now, 1 unlucky person would get cancer. And the reason this cancer is bad is because of your opening remark, Roy, that it's a very poor survival, and plus the surgery for this is very extensive.

Over the years, what we've done is we've downgraded that risk of cancer, and that's not by any magic, but by recruiting more patients for studies, really, enrolling and following the natural history of the disease. And we've got downgraded it to a point where we think that the risk in some individuals with that very short Barrett's, maybe as low as 1 in 1,000. We've gone from 1 in 100 to 1 in 1,000. You can see what that risk is. In individuals who have a bigger extent or low-grade dysplasia that risk may increase from 1 in 1,000 to maybe about 5 in 1,000. Okay. It goes up by 5-fold, but still the absolute. Meaning, if you look at it in these terms, I think it's still less 5 in a 1,000.

Dr. Jensen: Mm-hmm (affirmative).

Dr. Sharma: Once you start getting to high grade dysplasia, which is when I told you earlier is very close to cancer, that's when your risk is about 1 in 20. You can see the major jump which that happens. Another take home message is all of you who are listening here is that Barrett's is a low risk disease. And I tell my patients that, again, it is important to diagnose it, but I don't want folks who are listening patients who have this to really start getting very nervous about it, because if you put it in this perspective, the absolute risk is quite low. I tell patients is that all those preventative measures that I've told you is probably going to help you prevent a heart attack first before it's going to impact your esophageal adenocarcinoma. Doesn't mean that esophageal cancer isn't important, it's extremely important, but just the absolute risk is quite low.

Dr. Jensen: Yeah. Additional questions, Megan.

Megan Peters: Yes. We have quite a few more. The 1^st one is what are the risks of recurrence of cancer after an esophagectomy?

Dr. Sharma: Okay, great. The recurrence rate of cancer after esophagectomy is very, very low. In studies which have been published, it's about, I'd say 5%. And it's mainly not the recurrence of cancer, but it's the recurrence of Barrett's, which is more common rather than the recurrence of cancer. Recurrence of cancer may happen if all the cancer cells were not removed during the esophagectomy or the resection or removal of esophagus. That's why esophagectomy should remove all the bad cells. And recurrence of cancer is highly unlikely or uncommon. What can recur is the Barrett's rather than the cancer coming back. In the same breath, recurrence can happen even after doing the endoscopic therapy, which again, as we are doing more and more of it, we are sending fewer and fewer patients to the surgeons for esophagectomy. And so we do keep you in surveillance or regular endoscopic checks, even after the surgery or the endoscopic resection has been done to make sure that we pick up any recurrence early on.

Dr. Jensen: I also will suspect that, that recurrence level depends upon the stage of the disease at the diagnosis [crosstalk 00:39:01] as well.

Dr. Sharma: Right. Absolutely. Yes.

Dr. Jensen: Stage 3 disease much higher than stage 1 disease?

Dr. Sharma: Right. And stage 3 disease, as you rightly mentioned earlier on, Roy, talks about not just the depth of how deep the cancer is going, but also if it has spread to the lymph nodes and stuff. For many of these patients, the recurrence and the individual asking the question is absolutely right. The recurrence may not just happen locally at where the surgery was done, but it could come back in the lymph nodes. And that is a much more common place of having the recurrence in an advanced cancer, rather than at the site of the anastomosis.

Dr. Jensen: Next question, Megan.

Megan Peters: Yes. We have several folks asking about research studies for Barrett's esophagus and esophageal cancer. And if we have any current studies happening at KU and how people can get involved or become parts of those studies?

Dr. Sharma: Right. Good question. There are always studies ongoing for patients with Barrett's esophagus, and I'd urge rather than me spelling all of those out and perhaps missing some of them, right from diagnosis to endoscopic treatment, as well as all our gastroenterologist and endoscopist here who are experts in providing care for this, I'd urge you to visit the cancer center website and try and get information from there. If you're unable to get that, you can reach out to us via email, as well through the cancer center. And we can address a number of your specific questions that you may have based on the condition and the disease you have.

Dr. Jensen: This might be an opportunity to plug our clinical trials app as well.

Dr. Sharma: Right.

Dr. Jensen: I don't know if all of those trials are in the clinical trials app, but hopefully, at least part of them are, and you can actually download our KUCC clinical trials app from either the Apple or Google websites. Next question, Megan.

Megan Peters: Yes. Now that the criteria is better defined, is anyone ever rediagnosed as not having Barrett's esophagus?

Dr. Sharma: Yeah. Great question. And part of the reason for that was exactly what this individual or group of individuals are asking is it's always difficult to get the horse back in the barn, so as to say. And I personally do, do it and at several national international meetings, people will ask me that same questions and I'm all for it because I do think that it's equally important not to give a wrong diagnosis to a patient. And I will have several patients come back in, in which biopsies were taken somewhere in the lower part of the esophagus around the stomach. And that's an area where you can get a wrong or an erroneous diagnosis of Barrett's esophagus.

Yes, what I'll do is I'll, first of all, sit down with the patient, explain to them what was done. It's not that somebody made that error on purpose, but they were probably following the older criteria and that's when the diagnosis was made. We followed these individuals long enough now in our research studies to show that the risk is so minuscule that it's not worth giving the diagnosis. And also remember that at some point, the risk of treatment may outweigh the risk of the diagnosis or that individual getting anything bad happening to them. Yeah, definitely that can be done. Please confer with your gastroenterologist and at your next endoscopy, they can look at these criteria critically and see, whether you meet the criteria or not. Great question.

Dr. Jensen: Next question, Megan.

Megan Peters: How common is esophageal cancer in patients who have never had gastroesophageal reflux disease?

Dr. Sharma: Okay. Another excellent question. Although we are talking about reflux or gastroesophageal reflux disease being a risk factor for esophageal adenocarcinoma, the first study, which brought this to our attention was a large or a huge population based study from Scandinavia. As you know, Roy, they've got the centralized database in which all their patients in those small countries, the size of Kansas get entered into that. And that study showed this clear-cut relationship between reflux and cancer. But the other interesting part that they also showed was that in close to 30- 40% of their esophageal adenocarcinoma patients, there was no reflux.

Reflux being the major risk factor is not a unique risk factor. You could have, or you could be at risk for esophageal adenocarcinoma despite having reflux symptoms. And that's, I think, where a lot of research is being done to identify what are additional risk factors beyond that. And that's why now our society guidelines don't say that, "Hey, if you have reflux, you need to be screened," because we recognize that there may be additional risk factors for that. And that's why we list 6 or 7 different risk factors, which we’ve gone over multiple times, that if you have any 2 or 3 of those risk factors, you may be at a risk for esophageal adenocarcinoma and not just acid reflux.

Dr. Jensen: Next question, Megan.

Megan Peters: Yes. Why is the acid reflux so much worse after an esophagectomy?

Dr. Sharma: Right. The way we prevent acid reflux or individuals don't get acid reflux is at the junction between your esophagus and stomach, right here between that junction, is a sphincter muscle, which is called the lower esophageal sphincter or the LES. The sphincter muscle, once you've eaten food, prevents it from coming back up into the esophagus. In a way, it acts as a 1 way valve, which it truly isn't purely a 1 way valve because it still relaxes sometimes in order for you to belch or burp or get some of those gasses out. That's the sphincter muscle which prevents acid reflux. Now imagine that part being removed during the esophagectomy.

As I mentioned earlier, esophageal adenocarcinoma occurs in the lower part of esophagus, close to the sphincter muscle. And once you have that esophagectomy virtually 100% or 99% of the times, that sphincter muscle gets removed during that surgery. Unfortunately, it has to be removed. Now you can imagine that you have that hookup between your esophagus and the stomach without the sphincter muscle. Anything that you eat, especially if you lay flat or recumbent, things can flow backwards into your esophagus, and that's why you get bad reflux from that. It's an unfortunate side effect of the surgery, which has to be performed sometimes.

Dr. Jensen:Nearly, a lot of folks who have reflux or Barrett's take protein or proton pump inhibitors. And recently, there's been some issues with proton pump inhibitors in contamination with known carcinogens. Could you tell us a little bit about that and how folks can avoid that issue?

Dr. Sharma: Right. No great question. I think everyone listening on is well aware, you walk into a CVS, Walgreens, the aisles are full of anti-acids, medicines, et cetera. It, again, speaks to how common and gastroesophageal reflux disease is, but also that we have the availability of these medications now over the counter. There are 2 separate things. One is that contaminant that you're talking about, that from my knowledge was more on the H2 blocker side in Zantac or Ranitidine. And the FDA had those warnings, those got pulled out, et cetera. Right now, when patients come – or sometimes even friends and family – they're asking about having some heartburn after eating pizza or a big meal, et cetera, you use famotidine, for example, and that's with the trade names goes by Pepcid. That's something which can be used, and there's no black box warning against that right now.

On the other hand, proton pump inhibitors are like Prilosec, Prevacid, Nexium, these are the medications which are available, Protonix, and these don't have that warning on there. But they also have been linked in different studies to infections, for example. One thing that people have suggested that maybe they reduce the stomach acid so much that other bacteria proliferate and cause that. Sometimes travelers’ diarrhea, ICU based infections, they have been related to it. Rarely kidney damage age has been reported.

There are certain risk factors for it, but they're again, very good medications. If those of you who are taking it over the counter, but taking it for prolonged time periods, again, please confer with your physician because as, Roy, mentioned, all of these, although very safe medications, may have some certain side effects. Not that you shouldn't be taking them, but you should just be aware of some of those potential side effects.

Dr. Jensen: Last thing is, 1 of your mentors was a true KUMC icon, and that's, Dr. Greenberger. Could you tell us a little bit about him and your relationship with him?

Dr. Sharma: Right. Norton, unfortunately – as you know – passed away recently. And so this is about, Norton Greenberger. And I'm sure several of you listening in probably, either may have seen them at some point at KU, or may have heard of him. Truly one of the icons in gastroenterology. And I have to say that he was instrumental in bringing me to Kansas City when I was right fresh out of my fellowship from the University of Arizona in Tucson. And Norton, was the Chief of Department of Gastroenterology and also chairman of the Department of Internal Medicine, and really passionate about clinical research, education, mentoring and had a major impact on what I'm doing right now. I mean, initially when I moved here, I thought I'd be here just for a couple of years, but because of Norton and several people, we are here for several years now. Norton, and his family are always in our thoughts and a true icon for KU, but also for gastroenterology in general.

Dr. Jensen: And I'd say even American medicine.

Dr. Sharma: Yeah, exactly.

Dr. Jensen:Yeah. We're approaching the end of our episode. What would you say are some of the key takeaways you want to get out there for our audience?

Dr. Sharma: Right. Number 1 is that if you have Barrett's esophagus or you've been diagnosed with esophageal adenocarcinoma, again, make sure that you're seeing the expert in the field; make sure that your gastroenterologists or your treating physician is well aware of the cutting edge research which is going on in this field, the different clinical trials which are available. If you were diagnosed with Barrett's esophagus several decades ago, just make sure that you do discuss with your gastroenterologists about the criteria for the diagnosis. You are enrolled in a surveillance program, and you're not getting too frequent surveillance because getting too frequent surveillance is not good either. And last and not the least, is that if it's only Barrett's without any dysplasia, your absolute risk for cancer is quite low. I hope that's a little bit of reassuring news to all of you who have Barrett's esophagus. For those who don't have it, but have a gastroesophageal reflux disease, again, just because you have acid reflux does not mean you will get Barrett's esophagus or that you will get esophageal adenocarcinoma. It's a very common condition. Again, confer with your physician, talk to them about that. And again, if you have any questions, feel free to reach us at the cancer center. And thank you for having me, Roy.

Dr. Jensen: Well, thank you, Dr. Sharma, for a really outstanding episode and for being part of this week's Bench to Bedside. To learn more about esophageal cancer, visit kucancercenter.org/EsophagealCancer. That's it for today. Join us next week at 10 a.m. for Bench to Bedside. Thanks for watching.