For this session on the esophagus, I have selected three conditions that are somewhat related, namely gastro esophageal reflux disease, which from

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Preston Barton
5 years ago
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2 For this session on the esophagus, I have selected three conditions that are somewhat related, namely gastro esophageal reflux disease, which from here on I would refer to as GERD, eosinophilic esophagitis, and motor disorders of the esophagus. Indeed they are related because even though their pathogenesis differs markedly, they have clinical overlap and each one of them figures in the differential diagnosis of the other two. Let s address first the medical management of GERD. Before we do so, let s ask the question what are we actually treating? As you well know, heartburn is a very common symptom. It s estimated that 38% of people in the US suffer of heartburn at some time. 11% have it daily, and 25% of women suffer of heartburn somewhere during their pregnancy. Now, we ought at the start to distinguish maybe GER from GERD and that is gastro esophageal reflux, which actually is a physiologic phenomenon, namely the entry of acid content or gastric content into the esophagus. And, this doesn t constitute a disease. What happens is that some people have more reflux than others, and they may start to feel it. This is, unfortunately, has also been called a disease and you will hear a term often used NERD, which refers to non erosive reflux disease. To me, GERD or disease means that there is an added complication such as esophagitis, there is mucosal damage, there may be metaplasia in the form of Barret s esophagus or eventually cancer. Nevertheless, for practical purposes, the term GERD has been so frequently used that we will use it as in practice to encompass all these problems. 2

3 So, the treatment of GERD is actually a dose of guilt to the patient and a dose of treatment from the physician. So, behavior and medication is an attempt to change patient s perceived bad habits. And then, we have acid neutralization, mucosal protection, acid suppression, and the creation of a mechanical barrier either surgically or endoscopically. I will not address the latter as this would be left to some other time, but I will brief you each one of those items separately. So, let s talk about behavior modification. Every patient that comes in see us for reflux, or even dyspepsia is given a sheet. This is used, not only by internists and gastroenterologists but increasingly by ENT surgeons and other subspecialists. 3

4 And, these items address raising the head of the bed, avoiding lying down after meals, avoiding bedtime snacks, eating smaller meals, limiting consumption of fatty foods, avoiding chocolate and peppermint, stop smoking, and avoiding coffee, tea and alcohol. So, the patient is given that list and sent on his or her way with the hope that they re going to suddenly improve their habits. 4

5 Now, let s look at at least some of these items and see if they are based on any evidence. Unfortunately, I don t have any recent literature on this, and any reference is going to be at least 20 to 25 years old 5

6 So, this is an old study showing the effect of position on lower esophageal sphincter pressure or LESP in normal subjects. So, these are some who are not suffering of heartburn, and whether they lie supine, right side, left side, or sit up really there is very little change in LES pressure and if there is a change, it is not significant. 6

7 On the other hand if you look at the effect of body position on reflux, measuring now acidity as defined by EPH of less than 4 on the GERD as shown here, you will see that patient that goes supine or prone or left or right position, there is a, the percent of time where acid is present in the esophagus increases and the worst one is the position on the right side. This has to do with the anatomy of the stomach, and patients will often tell you that lying on the right side at night is the worst for that heartburn. So, this seems to have some relevance in patients with reflux. 7

8 Well, what if you then reverse this and you ask patients to lie on a wedge or a bunch of old books, what happens? Well, the percentage of time that the ph is less than 4 improves when you use the wedge, but for some reason it doesn t work with old books. That may be, you know, not extremely important, and I tell patients to raise their bed with a bunch of old books or blocks because it s cheaper and easier to do. 8

9 So, we can conclude or summarize the effect of body position on gastro esophageal reflux by saying that the sense of evidence is kind of moderate, but that we know that eating and lying down after being in the supine position is probably detrimental. 9

10 Now, how about foods? You know, this is an old slide showing old, bad, things in life, and if you look at every one of those items, many patients like to eat those chocolate, fried food, onions, peppermint, fatty foods. It s a tall order for patients to avoid all these. Is there any evidence for that? And of course alcohol, caffeine and smoking are always considered bad. 10

11 This is, again, an old experiment where you measure the lower esophageal sphincter pressure change on the ordinate and you follow by minutes from zero to 60 minutes after you give the patient first a carbohydrate, then a protein, then a fatty meal. And, what happen is that with carbohydrate, much, much change occurs in the pressure of the LES, whereas with protein it actually increases a little bit so it can t be bad. And, fat indeed has a physiologic affect on the LES. So, this is where the recommendation to avoid fatty foods comes from. Now, what we have to realize, though, or keep in mind, is that changing the LES pressure presumably allows the entry of gastric content in the esophagus may not be clinically relevant. So, this is a physiologic effect, it makes sense, but there is really no proof that avoiding fat is going to make your patients any better. 11

12 Well, how about acid solutions? We always ban tomato juice and orange juice and acid solution because, gee, they cause acid. Well now, let s take a bunch of patients and look at how many are going to react when the solution becomes acid. So, on the X axis you have the ph, which starts at 4, and you have about 13 patients here. So, when the ph is reaches 4, one patient feels it. You re dripping acid solution through a catheter passed through the nose. The ph reaches 3, another patient says, Ouch. When you reach the ph 2, 4 of the patients now feel it, and when you reach the ph of 1, everybody feels it. So, we are all sensitive to acid. However, we don t eat acid; we re not having acid dripped around the esophagus. And, the old test of Bernstein test which actually is a clinical application of this experiment is not used anymore today because it does not correlate with clinical reality. 12

13 Now, the interesting part about this is you take now orange juice, a spicy drink, and coffee, all known to create discomfort in many patients. And, you buffer them to a ph of 7. So, you are taking the acid away, and what happens now? Is that the patients who were sensitive, you ve taken the patients who were sensitive on the previous test, now 8 of the 9 continue to say, Ouch when you drip ph 7 orange juice. And, 8 of 9 when you drip a spicy drink buffered to 7, and 7 of 9 coffee. So, it s not the acid, we don t know what causes heart burn in orange juice. I m not denying that it causes heart burn, but I m saying it s not because it s acid. It s something else, and frankly nobody knows what it is. 13

14 Now, how about tobacco? Again, a physiologic effect, very well known. You take, you measure the LES pressure in patients, and you give them a puff of smoke at 15 minutes as the slide shows, and immediately within minutes the LES pressure falls, stays down to about 30, 35 minutes and rises again. So yes, smoking is bad because it relieves LES, but again there is no evidence, well is there any evidence? 14

Let s see on the next slide if you will stop smoking, will you improve your GI reflux? And, this slide shows 8 male patients in whom 24 RPH is being measured on and off smoking.

15 Let s see on the next slide if you will stop smoking, will you improve your GI reflux? And, this slide shows 8 male patients in whom 24 RPH is being measured on and off smoking. And, measuring the mean number of reflux episode over 24 hours you see that in the column of smoking, as opposed to non smoking, the number of reflux episode falls significantly. The upright, in the upright position it falls significantly. But, frankly in the supine it doesn t change much. And, while the change is significant statistically, numerically it s not terribly impressive. So, again it s not right to advocate for smoking and I always have wives or husbands nudging me to tell the patient to stop smoking, and I will say I agree. You shouldn t smoke, it s bad for your health, but I honestly cannot say that it s going to make a big difference in reflux disease. 15

16 Well, how about coffee? You know, again, a bad guy who we should avoid completely. Here is a slide showing now, the pressure again of the LES compared to those of caffeine you give. And, interestingly in pink we have coffee, in yellow we have decaf, and in blue we have caffeine. So, when you give caffeine alone, what happens to the LES, nothing. No change. You give coffee, which is pink, and guess what? The LES pressure goes up. So, if anything, based on that actually physiologic effect coffee s actually good. And, the more interesting part is when you give decaf it has exactly the same effect. So, if you re going to tell patients not to drink coffee, you should really ask them to not drink decaf either. And, frankly it s not based on the fact that LES pressure goes down, but it s based on a common, or common perception that coffee is bad. And, what I tell patient is if coffee bothers you, don t drink it. But, you know what if it doesn t, God bless you drink as much coffee as you want. 16

17 So, to try to summarize these attempts at behavioral changes in GERD we can say that there is reasonable evidence that body position and meal size make a difference, that there is indeed a physiologic affect to coffee, which actually is in the wrong direction. To tobacco, which is in the negative effect, and some foods have been shown to actually decrease LES pressure like fatty foods. As for alcohol, acid juice and exercise, they are really anecdotal evidence, and there is no proof that one is better than the other. So, in summary when you are trying to invest in educating patients, you should insist really on avoiding late meals and lying down after meals. The rest is individual, and it can be dictated by the patient telling you what is worsening their symptoms 17

18 Let s move now to what the doctor does, we re done with educating the patient and making them feel guilty. Well, the first side of treatment is been around for years and years, and at that time that s actually all we had is give antacid to patient with reflux. Well, we know that they produce heartburn relief, patients will tell you, When I take an antacid, my heartburn improves. They, however, have no effect on healing of esophagitis, so if you have a patient with a complication such as esophagitis or ulcerations, then antacids are not good enough. But, for many patients who have occasional heartburn particularly after some foods, or if they go out, eat a large dinner and have a cigar, taking an antacid is perfectly reasonable. 18

19 How about mucosal protection, and namely here an agent sucralfate which got in some literature on healing ulcers and by extension was used in esophagitis. Well, it produces some symptom relief, but frankly it s rarely effective as a sole agent and I have not heard of anybody prescribing it lately, although I do see occasionally a patient with a prescription for sucralfate and I politely try to tell them to throw it away 19

20 Now, acid suppression is really the mainstay of reflux treatment. And we have two large categories, H2 receptor antagonists and proton pump inhibitors or PPI s 20

21 If we compare H2 receptor antagonists to PPI, there is no question that PPI s are much more potent acid suppressors than an H2 receptor antagonist. Symptom relief is markedly more significant with PPI s and the healing rates are certainly more impressive in the tune of 80 to 90% as compared to 27 to 45% 21

22 And, this is a slide showing the effect of placebo in green compared to H2 receptor antagonists in red, and PPI s in blue. And, as expected placebos do very little for healing of erosions whereas H2 receptor antagonists will heal about 50 55% of patients. But, the most effect is not surprisingly is obtained with PPI s. So, there is no question that PPI is your most potent acid suppression around today. 22

23 And, there is the list of genetic names of all the PPI s available on market today from Omeprazole to Lansoprazole, Pantoprazole to Rabeprazole, Esomeprazole and Dexlansoprazole. And, people are familiar with the brand names that go with each one of those. 23

24 Now, the question is is Omeprazole really better than Ranitidine? And, we ve shown that in the previous slide, but this is a better done slide study showing the effect of Ranitidine 150 mg BID in red compared to Omeprazole 20 mg taken just on weekend as needed, in yellow, and 20mg a day of Omeprazole every single day over 12 months. And, as you can see, gradually even with Ranitidine you start after a couple of weeks to see a drop in the percent of, an improvement in the patient field. Unfortunately, as time goes by only Omeprazole will maintain that healing in the 90% and for Ranitidine or Omeprazole even the initial effect gets lost after a year. So, for the maintenance of healing esophagitis, you are certainly better off with a PPI. So, if you are dealing with significant esophagitis or ulcerations or a stricture, you cannot start the patient on Omeprazole or another PPI and switch them later on to antacids or a placebo. You must maintain the dose that has been effective to heal the esophagitis initially. 24

25 Now, the next question is, Does it make a difference which one I use? And, there are several comparative studies, this is one of them, Lansoprazole in pink to Omeprazole in blue. And, initially as you can see, Lansoprazole has maybe a better benefit, but by the day 56 they re really equal. 25

26 And, this is another study showing Esomeprazole 20 vs. 40 vs. Omeprazole in yellow 20mg. And, again over four weeks or 28 days, you see that the blue, the 20mg everyday or the 40mg everyday rather has a more beneficial effect. But, the difference is numerically small. 26

So, when we look now at comparative healing rate of Esomeprazole against Omeprazole, these are here two studies showing again a slight advantage to

27 So, when we look now at comparative healing rate of Esomeprazole against Omeprazole, these are here two studies showing again a slight advantage to Esomeprazole over Omeprazole, 94 vs. 87, 94 vs. 84. And, another study comparing Esomeprazole 40 to Lansoprazole 30 shows again a slight advantage for the Esomeprazole. 27

28 So, the bottom line frankly for comparing PPI is that, PPI s, yes they provide different results. And, that Esomeprazole at least those studies shows a numerical advantage of 4 to 8%, but the subject response is variable, and frankly the choice of a PPI is not a major issue. But, cost is and I tell patient to choose the most effective cheapest dose, stick to the generic if they can or whatever their insurance company covers because beyond that really there is no evidence that one is superior to the other. 28

29 The other concept in treatment of reflux disease in the use of PPI is the so called Step Up and Step Down therapy. Now, Step Up means you start with the less potent and you go up, Step Down means you go with the highest dose and you try to come down. 29

30 Now, this is an interesting concept, but frankly patients often coming now they are already taking PPI. So, you are beyond that. Secondly, I think you should pick treatment based on severity of the disease, and not on step up and step down, and patients once they have started the most effective pill are going to be very reluctant to work down. And, the bottom line is the cost considerations is going to dictate what you do. 30

31 So, what about dose escalation? Now, patients don t get better with one dose, we immediately double the dose. I think doubling the dose should be reserved to patients who got partial relief with single dose and were indeed compliant, patients with Barrett s esophagus perhaps, and certainly patients with Barrett s with dysplasia. Other than that higher dosage which I often observe, tripling the dose, quadrupling the dose, make absolutely no sense to me. 31

32 How about the refractory patient, finally, the patient who is you have treated, told them to change their behavior, they ve done everything, they return and say, I m not any better. Well at this point doubling or tripling the dose I think one has to stop and reassess the history. Are we really dealing with GERD? Because, keep in mind not all chest pain is heart burn, not all heart burn is caused by acid, and beware of the chronic belcher because belching is actually bringing gastric contents in the esophagus. But, the horse is in front of the cart. The cause is not acid, the cause is belching, bringing up acid. And, at this point, if you look actually at most clinical studies, the patient that responds better to PPI are the patients who have heartburn alone. So, the symptom complex of GERD may not be related to acid alone. And, at that point, you really want then to obtain objective assessment by endoscopy or by ph monitoring. 32

33 And, this is a quick look at the modern way to monitor ph, you don t need to put the patient, a tube through a patient s nose. On the left here, you have the small capsule blown up, it s about 1 to 2cm in length, and on the right the recorder that the patient carries on their belt. 33

34 This is a close up of the capsule in its with a device that loads it, 34

35 you insert the scope, you position the scope 6 cm above the ileus and you release remotely the capsule. And, as you can see on the right it s being released here 35

36 and you take a picture of it as evidence that it has been implanted. This will fall off by itself in four to seven days. It s extremely well tolerated, although there is a small number of patients will complain of discomfort. 36

37 So, the indication for this test, however, is not indicated for every patient with reflux. It should be reserved for patient who responds do not respond to treatment, having a typical form of GERD or absolutely definitely for patient who are being considered for anti reflux surgery. 37

38 So, in conclusion, the take home message is acid suppression is really the mainstay of GERD treatment. Behavioral modification may be of some value; the difference among PPI s are real but small. And, finally, you have to evaluate your patient prior to intervention, and this is extremely important. Thank you. 38

It is Friday night. Pedro, Juan, and Fernando are grilling some steaks at Pedro s house. They are

A Publication of the National Center for Farmworker Health My Chest and Throat Are Burning! It is Friday night. Pedro, Juan, and Fernando are grilling some steaks at Pedro s house. They are celebrating