Rod (00:39):
Gabe, do you want to maybe wait till one or two minutes after? Just see if we can get a couple more people?
Speaker 2 (00:46):
Actually, I think three is a good start. If everyone else is comfortable with that. I think that's pretty good.
Rod (00:51):
Want to start on time? Okay.
Speaker 2 (01:04):
Yeah.
(01:04):
We're right at the top of that hour. I'm going to let the three participants in, have a great discussion today.
Rod (01:08):
Okay, great. Thank you.
(01:34):
Okay, looks like we've got a few people still connecting. So I'd like to welcome everyone to this Medscape, peer-to-peer discussion.
This is Challenges in Gastroesophageal Reflux Disease, Assessment and Management. We're just about to get started. We have
Dr. Pandolfino waiting to present. My name is Rod Smith. I'm a medical director with Medscape, and I'm just going to spend
a minute or two going over a couple of things regarding Zoom settings and today's program, and then we can get started. So
for those of you who have just joined, if you take a look at the slide that's up there right now, you want to go to the top
of your Zoom screen and click view. And if you're in full screen, you want to exit and go to side by side gallery. So you
should be seeing, when you click that, you should be seeing the slides on the left and then the cameras with the different
participants on the right.
(02:33):
And then at the bottom, if you're familiar with Zoom, you'll see that there's a chat feature. And if you open that up, you
can ask questions, you can provide comments. So we are going to be monitoring the chat feature during the program, so feel
free to use that. And then down at the bottom left, if you go to video settings, you want to go to hide non-video participants,
and check that box, if it's not already checked. So you should just see the active cameras. So this is meant to be, as the
name implies, a very kind of collegiate, collegial, conversational type of program. Therefore, we really would encourage you
to turn on your cameras, if you're comfortable doing that. We'd like to kind of see what everyone looks like and have your
participation. We welcome you to ask questions. So Dr. Pandolfino is going to present some slides, but there's going to be
some room for discussion as well.
(03:39):
So if we want to go to the next slide. So this is just some best practices for virtual learning. You're all probably familiar
with a lot of this stuff by now, if you've done other webinars during the last couple of years. So we would ask that if you're
not speaking, you would mute your microphone. Of course, if you're in a quiet environment at home, you're certainly welcome
to leave it on. But if you're in a public place or there's some background noise, we would ask you to mute just so there's
no distractions while Dr. Pandolfino is presenting. And again, we would like you to keep your webcam on if you're comfortable
doing that. It just makes for a more kind of intimate conversation. As I mentioned, you can use chat for questions and comments.
If you want to use reactions, hopefully a thumbs up, you can do that.
(04:27):
We are going to have some polling questions and some opportunities for discussion. So you will have opportunities to answer
some polling questions. And again, we will have some breaks where we can have some peer-to-peer discussion. Dr. Pan Pandolfino
is going to present the case, so there're going to be some opportunities for discussion around that. Just a reminder, it is
a CME event. So if you do decide to participate, we just ask you try to refrain from using any brand names of drugs and devices.
It's not the end of the world, but we try to use generic names only. And if you're going to talk about any cases, we would
just ask that you not disclose any information that could violate any privacy rules or anything like that. Just try to leave
personal details out of the discussion. So that's pretty much it. Again, I'd like to welcome you. This is Challenges in a
Gastroesophageal Reflux Disease, Assessment and Management. We're very fortunate today to have Dr. John Pandolfino. He's the
chair of the Department of Gastroenterology and Hepatology at Northwestern Feinberg School of Medicine in Chicago. So with
that, I'd like to welcome Dr. Pandolfino to the program.
Dr. Pandolfino (05:47):
Well, thank you very much. It's my pleasure to be here tonight talking about a topic that is near and dear to my heart. Gastroesophageal
reflux disease, and in particular a pretty vexing problem, really looking at these patients who are refractory to PPI therapy.
(06:06):
So before we start, we are going to start with a quick polling question. So how confident are you now in your ability to individualize
treatment for patients with refractory GERD? Are you not confident, slightly confident, moderately confident, mostly confident
or very confident? Please answer.
(06:37):
So it looks like we have a little work to do. We see most people are slightly confident or moderately confident. So certainly,
hopefully by the end of this we'll be mostly in the mostly confident, the very confident range is my goal.
(06:50):
So when you start to think about these particular patients and think about how to address them, I always think it's most important
to start with a case. And this is a typical case that I will see in my clinic. In fact, it is modeled after one of my patients,
a 42 year old man with heartburn and chest discomfort for about six months. He was originally seen by his PCP, he was referred
for an exercise stress test, an echocardiogram and a cardiac CT. Both were negative, and I think it's always an important
thing, especially when people are at a specific age and they're having chest pain to keep in the back of your mind that this
still could be cardiac. And if you're thinking that at all, you really need to rule that out. He was in with a Holter monitor
and that was also negative. At that point, he was also noting about a 15 pound weight gain and he wasn't really experiencing
any warning signs, like trouble swallowing, any evidence of GI bleeding or any early satiety.
(07:50):
So in terms of the management, when he was seeing his PCP, the first thing that happened was he was obviously started on PPI
and he was started on omeprazole 20 milligrams and he had a mild response. He was then increased to 20 milligrams twice daily,
20% better. He was then tried on Pantoprazole 40 milligrams twice a day, but there really was no change. And then he was eventually
switched to Dexlansoprazole 60 milligrams twice a day, and was really feeling about 20% better than he was when he started
his particular regimen. So what do people think? And let's be a little bit interactive here. What do people think about this
PPI management protocol, or this selection of PPIs that people have thought about here in terms of how this happened or how
this transpired? Any thoughts?
(08:45):
Well, I can tell you that in my mind when you see these particular patients, PPIs are pretty effective. But there are some
nuances that we'll talk about as we go through the presentation. But certainly I think that this kind of round robin, or merry-go-round
where we continue to try different types of PPIs, and expecting a much different response is kind of like insanity, right?
You're doing the same thing over and over and expecting a different outcome. Well, that's kind of the definition there, and
I think that's what we're kind of seeing here. So in terms of follow up, six months later after this PPI escapade, he was
finally referred to a gastroenterologist. Seven months later his endos was negative, and then at eight months he was finally
sent for reflux testing. So you can see that this patient has really been dealing with this problem for quite a while now,
and has gone almost eight months without having a definitive diagnosis. And I do think that's a problem.
(09:47):
Now, you would be remiss if you didn't start out any talk or any discussion about Gastroesophageal Reflux Disease and not
at least talk about this kind of Montreal consensus definition, where GERD is a condition that develops when the reflux of
stomach content causes troublesome symptoms or complications. And we try to break reflux up into two basic categories, especially
when we're dealing with typical esophageal complaints. Like these are non, not extra esophageal, but these are the typical
complaints. And these are either erosive GERD where they have endoscopic findings like esophagitis, stricture, Barrett, hopefully
not adenocarcinoma. These patients are typically quite sick coming in with pretty significant dysphagia and warning signs.
And then of course the majority of the patients though have non erosive reflux disease. They have symptomatic syndromes, non
erosive findings, and really no objective pathologic evidence of GERD on that endoscopy. But if we're going to call someone
non erosive reflux disease, they have to have objective pathologic GERD. And we'll see based on what we'll talk about in terms
of function testing and reflux testing, what the definition of that is. So that's really a classic distinction. People with
a positive endoscopy and people with a negative endoscopy. As I mentioned, there are people who have extra esophageal symptoms
and we'll keep those on the side for now as we address the patient who comes in with the typical symptoms of heartburn, maybe
chest pain and regurgitation.
(11:21):
Now, when you are scoping the patient, we try to be standardized in how we define esophagitis. And the reason for that is
that if you look at the Los Angeles grading scheme, we know that if you're diagnosed with Los Angeles grade A in the upper
left corner, this is a very mild esophagitis that you can actually see in asymptomatic controls. So when we're seeing a patient
and we document Los Angeles A esophagitis, this is not a pathognomonic diagnosis for reflux. Your suspicion is a little bit
higher than if it was negative, but certainly you would not hang your hat on this as objective evidence of Gastroesophageal
Reflux Disease. Now in contrast, you can see going to Los Angeles, B, C, and D, the erosions become much more dominant. In
fact, in this patient, they're extending way beyond the five millimeter cutoff. You can clearly see in the top right-hand
corner in the Los Angeles grade B, this patient even has a little bit of stricturing. And then of course in Los Angeles C
and D, you see these deep confluent erosions that are starting to take over much of the circumference of the end of the esophagus.
And those are very severe levels of esophagitis C and D. So when you see a Los Angeles B, C, and D, you can be confident that
that is objective evidence of Gastroesophageal Reflux Disease.
(12:45):
Now when you're seeing patients and you're evaluating these patients, with either erosive esophagitis or non erosive reflux
disease. The typical pattern is to look at these patients in terms of their response to PPI. Now you can look at response
to PPI as a symptomatic response, but to be honest, you can also look at it as an incomplete response to healing of esophagitis.
Now that being said, when we're dealing with patients who we're going to think about getting objective evidence of reflux
when they have non erosive reflux disease, we are really going to focus on doing reflux testing. And that's really the gist
of this particular slide. So we tend to take patients off of a PPI for about seven to 14 days. We document that there's absence
of erosive esophagitis, and then if that's absent, in order to rule in or rule out reflux disease, we will do ambulatory reflux
monitoring to assess for esophageal acid burden, our most important physio marker of objective evidence of Gastroesophageal
Reflux Disease.
(13:50):
Now, in the meantime, you know would be remiss if you did not, during this time at least bring up lifestyle modification and
diet changes in GERD, that could help this patient as you're trying to figure out what's going on. Because obviously many
of the lifestyle modifications and diet modifications are very simple to do. They're very low risk. So while you're working
these patients up, it really is important for you to recommend smoking cessation, weight reduction, avoiding alcohol consumption,
especially if it triggers symptoms. Avoid eating three hours before bed, especially if patients are having nocturnal symptoms.
Head of the bed elevation is also a very good idea, when you're thinking about patients who have nocturnal symptoms. And then
certainly for patients with postprandial symptoms, you might want them to eat smaller meals, not necessarily more frequent,
but not eating until they're full to avoid some of these postprandial symptoms. So once again, these lifestyle modifications
should be implemented as soon as you start seeing patients who you suspect may have Gastroesophageal Reflux Disease.
(14:59):
Now, this was the 2022, AGA clinical practice update kind of guidelines in terms of how we use PPI therapy, and how we're
supposed to monitor these patients. And really the gist of this is that we typically trial in a course of FDA approved single
dose PPI for about four to eight weeks. And these patients should be noticing a response within that four week period. When
they get to that four week period, usually most people are starting to notice that the medicine's starting to work, and there's
really no reason to extend that to 12 weeks or 16 weeks. Now, if patients have a partial or no response to symptoms, you want
to assess compliance escalate that PPI therapy to twice a day, which is not FDA approved than off-label or switch them to
a more effective acid suppressant.
(15:50):
So as I mentioned before, there are some nuances between the PPIs, and some PPIs are stronger than the other. Now, if they
have sustained resolution of symptoms, the most important thing at that particular point is to monitor them for a little bit,
but then to try to wean them to the lowest effective dose. And we really want to continue them at the lowest effective dose,
because even though PPIs are very safe, if someone's taking it twice a day, their lifestyle and their quality of life will
be much better if they only have to worry about taking it once a day. So once again, getting it to the lowest effective dose
is extremely important for the patient.
(16:29):
Now, in terms of our established safety and efficacy of PPI therapy, we know that many patients, especially patients with
erosive esophagitis, can get complete symptom relief with PPIs, up to 70 to 80%. However, when we start to see patients with
non erosive reflux disease, that response tends to go down. And the reason for that is, probably there is this overlap of
some of these functional complaints that may be at play. As I mentioned, we want to use the lowest effective dose. So if you
do get symptom relief, complete symptom relief, you can trial a PPI withdrawal where you start to cut the dose down in half
for a week to two weeks at a time and see how the patient does. Now in terms of this, there are a large number of patients,
and if you think about it, there are a large number of patients with reflux, but if 30% of patients with GERD don't experience
full or partial symptom response, that's a big problem.
(17:27):
That's a huge number of patients. Now, remembering though that compliance issues, and improper timing of medication, may be
a compromising component of the PPI therapy, but once again, most patients, when you counsel them and you bring them back,
it's very few that actually you get a major improvement with that real important timing when you've gone through this. But
once again, important to do. Now I will tell you the other thing too that many people want is many people don't want to have
the reliance on a chronic PPI and are looking for some alternatives like endoscopic or surgical intervention. But it's important
to realize that many of these patients do wind up back. I do think the number of 50% may be an overestimation of that, but
still you cannot guarantee that the patient will be off PPI therapy if they undergo some of these interventions, like the
endoscopic ones that we'll discuss in the surgical ones.
(18:29):
Now, there are medicines that are available in terms of acid suppression within the construct of H. pylori eradication. Some
of the PCABs are now coming into play in the United States awaiting FDA approval. But certainly these medications may have
an impact in some of these patients who have difficult to treat acid Gastroesophageal Reflux Disease. But once again, remember,
these are not FDA approved for the management of reflux currently, and we're still awaiting for that approval process to be
completed.
(19:01):
Now that being said, you've heard me talk a lot about PPIs and putting people on chronic PPI therapy, and a lot of the question
comes into play, are these medicine safe? Is there a risk of cancer, infection, issues with absorption, effects on other drugs,
and some other adverse effects? Well, I will tell you that certainly when people start a PPI, they definitely have this side
effect of headache and a change in their bowel habits, typically diarrhea. But occasionally they can get constipation. And
that's really just because you have something interrupting the normal bacterial flora and the pH of the GI system, which is
very sensitive to those things and can cause a little bit of change in bowel habits. Now, most of those side effects like
the headache and the change in bowel habits do get better as time goes along. What about these other risks?
(19:54):
Well, in terms of risk of cancer, gastric cancer after H. pylori treatment, there's really not great evidence. We do know
that if people have H. pylori on chronic PPI therapy, they can have a high propensity to develop pre malignant changes, but
really haven't seen a big signature. But it's probably not unreasonable to test and treat for H. pylori, in many people who
are actually going to be on chronic PPI therapy, there's not great data to support that, but I don't think it's unreasonable.
There can be some risks of infections once you change the pH in the GI tract. Certainly some bacteria will proliferate and
some will go away. And we certainly do know that people may be predisposed to some enteric infections, not so much pneumonia.
The data for that is pretty weak. But certainly C difficile, we do see a little bit of a uptick.
(20:46):
And then SPP and cirrhotics, certainly now we really think that the issue of covid has really been overblown, really not a
very good study in terms of proving cause and effect with that. And I think there's a lot of debate, but certainly I don't
think I would stop a PPI because I'm worried about covid. If you change the pH once again in the stomach, you may change some
absorption of vitamins and minerals. But once again, in terms of long serve cause and effect, there's really no reason to
stop a PPI because you're worried about bone fractures. There are some effects on other drugs like Clopidogrel, but this really
hasn't borne out into a major outcome. And then of course there are a whole host of miscellaneous adverse effects. So a really
important slide that I've spent a lot of time on.
(21:34):
But in the end, I think when people start to ask you about these side effects, we tell them that most identified side effects
or complications that are presumed to be related to PPI are not really true, because they're really weak associations and
observational studies that cannot establish cause and effect. However, that being said, we do know that we do need high quality
studies to look at these. And certainly I think that there is a slight uptick in enteric infections, and I think it's reasonable
to tell your patients about that risk, and also allow them to know that maybe when they travel to be careful if they're especially
in third world countries with bottled water and making sure their food is cooked. And then of course, any adverse effect related
to decreased acid production and gastric level will also likely pertain to PCABs. So although PCABs are a new medicine that
are available outside of the United States, not FDA approved, we [inaudible 00:22:40] think that if we switch the PCABs once
an FDA approval is obtained, if it is obtained, we'll change the risk profile of that.
(22:50):
So as we've now gone through a little bit of the beginning of this particular talk, I want to stop for a second here and ask
the audience, how many people in the audience would've gone to endoscopy before we went through this whole PPI cascade? Would
people have gone maybe after the first or second treatment course? What do people in the audience think? Any thoughts? How
about reflux testing? How comfortable is everybody here thinking about ordering reflux testing in people who are not responding
to PPIs? Well, it looks like we have a little bit of a shy group tonight, but I certainly will tell you that I would've probably
erred on getting endoscopy a lot sooner than that, and probably looked at getting reflux monitoring also a lot sooner than
getting to that eight month time period where this patient had to suffer. I always think it's important to realize that when
we're doing this, when we don't give someone an answer and they're sitting there at home thinking about their symptoms, worrying
about cancer, worrying that this could be something severe, that is definitely a detriment in their quality of life.
(24:09):
And I do think we need to be a lot more aggressive in not only treating these patients and giving them medicines, but also
figuring out what the idea is in terms of what could be possible here. So now going forward, this is the best way to work
up patients with typical GERD symptoms. So once they've gone through this particular process and have gotten through the PPI
response, and we're thinking about this, the real next step is to really look at this in the context of getting people to
reflux testing, that is really the most important thing that we can do at this particular point. So in your practice, do you
use wireless pH testing in terms of evaluating your patients? If this is a simple one, question is yes or no, please vote.
(25:18):
All right, we don't see the answers coming up yet. There we go. All right, so it looks like very few people are using wireless
pH testing in their practice right now, so hopefully I can convince you that maybe that should be done a little bit more.
So the next question is, if not, why are you not using reflux testing? So as I said in the audience, it seemed like most people
were not. So is it because you don't have access to it? Is it you don't think it has clinical value? Maybe you're not familiar
with it and the technique? Potentially maybe there are problems with insurance reimbursement, and maybe you need to refer
patients to a specialized center, and that can be an impediment. So what do you think the major reason you're not using wireless
reflux testing is?
(26:14):
All right, so none access, not familiar with it and need to refer patients to specialize. So I think those are all very reasonable
reasons not to advocate for doing that right away. And I think the next step would be obviously to talk a little bit about
the technology, and why it has value. So this is the wireless pH monitoring system. This is essentially a system that can
be done over 96 hours. The beautiful thing about this particular approach, is that when you are doing this, you can not only
assess whether or not the patient actually has significant reflux, but you could also look at the timing when it occurs overnight.
So this particular tracing is a 96 hour tracing, where the patient is being studied over four days, and the bars on top are
actually when the patient's sleeping. That red dot right in the middle of the tracing is showing when the pH level is four,
and how many times the pH tracing is dipping below that.
(27:21):
And really what you find here is that you have a very nice ability to assess these particular patients, and get a great sense
as to not only what their overall acid burden is, but the timing, and what type of reflux pattern they have. So whether that
pattern is associated with nocturnal reflux when they're sleeping, whether it's postprandial after they eat, very soon after
they eat. So really a lot of important information is gleaned from this. Now, when we actually looked at this, we have shown
that it is a very easy test to perform. It actually is able to, in most patients, at least 89% of the patients can get a study
for at least 36 hours, and about 70 to 80% of the patients can actually get a study for longer than that. So almost getting
three to four days. Now, this was a more recent study that we just published in the Journal of Gastroenterology with [inaudible
00:28:25] where we studied a hundred patients with refractory GERD who underwent four day wireless pH testing.
(28:31):
And what we found was that when we actually looked at these patients with a structured PPI withdrawal, we could actually see
that we could predict which patients would be best able to stop PPI therapy. So if you had zero days positive, most of the
patients could stop PPI therapy, they can discontinue PPI therapy in contra. In contrast to that, if you look at the patients
who have two or more days positive, most of these patients actually had to go back on their PPI. So this was a very nice way
to show that this has clinical utility. You can actually predict which patients need to go back on a PPI, and which patients
can need or can stop the PPI. And if you're going to relegate someone to chronic maintenance therapy for the rest of their
life, it's probably not a bad idea to have this kind of data, where you can convincingly tell your patients you're going to
need chronic maintenance therapy. Similarly, if you're going to send someone for surgery or an endoscopic procedure, you certainly
want to be confident that they have significant Gastroesophageal Reflux Disease.
(29:41):
Now, when we actually looked at these patients, we could clearly see that the patients with objective evidence of GERD were
able to resume their PPI, whereas the patients who had no evidence of GERD, so really very little evidence of GERD and they
were able to discontinue their PPI. So once again, you know this idea that you can use this tool to not only gauge the severity
of disease, but also make therapeutic decisions is extremely important. So if you have objective evidence of GERD, you're
more likely to resume your PPI. If you do not have objective evidence of GERD, you're probably going to be able to discontinue
your PPI.
(30:23):
Now, we do have other tests like 24 hour pH impedance, which can give you a little bit more information in terms of giving
you a reflux profile. So we tend to use 24 hour pH impedance when we're evaluating patients who have documented reflux. So
we've shown that they have objective esophagitis and not responding, or they have evidence of abnormal acid on the wireless
ambulatory pH testing. And when we actually see these particular patients and we want to figure out why the PPI's not working,
if someone who has objective evidence of GERD, the 24 hour pH impedance study can be done. And what's nice about this is that
we can actually look at the pattern of reflux. Is it a belch pattern? Is it a liquid pattern? How far proximal does it extend?
Is it associated with changes in the mucosa, that lead to increased permeability where the acid is getting deeper into the
layers and stimulating nerves in the esophagus?
(31:29):
Now, we've also extended some of our high resolution manometry with impedance, to study people after they eat to see what
their reflux mechanism is. This is actually an episode of a transient lower esophageal shrinker relaxation, the TLESR, which
is a very fancy terminology for belch. And what you're seeing here in the purple color, that's the liquid going up the esophagus,
on the top band, that's the upper esophageal sphincter. And on the lower band where you see the LES relaxation and the curl
inhibition, that's the esophagal gastric junction, the anti-reflux barrier. So what you're seeing here is this purple color
go up into the throat and the patient actually swallow it, some peristalsis and another reflux event. This is, as I mentioned,
akin to a belch and a belch reflux mediated mechanism.
(32:22):
So in terms of our emphasis now, and we're going to shift gears a little bit, the question really comes into play is, how
do we pick the right therapy for the right patient? How do we focus on the abnormality in their pathogenesis so that we can
provide the patient with a personalized approach? And you can clearly see from this particular slide that there are opportunities
to use a lot of different therapeutics. Now that being said, sometimes when you have too many choices, it becomes a little
bit more complex, and many of these treatments can be ineffective if you don't understand the mechanistic profile. So certainly
you wouldn't use a specific type of product that's going to coat the esophagus when most of the disease mechanisms are related
to volume reflux. So certainly you have to kind of think about the mechanism when you're making these choices.
(33:18):
And that gets to our medical management reflux, especially if it's refractory. Now, what are the medications that we can use
as reflux inhibitors and pro motility agents? Well, if you see that someone has a belch mediated reflux mechanism, they're
belching air, they're having a lot of postprandial reflux, Baclofen, which is not FDA approved, it's obviously a muscle relaxant,
but it can block the transient lower al skin or relaxation reflex, which is essentially a belch reflex. The problem with Baclofen
though is that it's poor tolerability. It gives people a lot of sedation and lightheadedness. In terms of motility agents,
none of these are FDA approved for the treatment of refractory reflux, but certainly they can help with poor gastric emptying.
And if you do document that someone has refractory reflux and poor gastric emptying with a gastric emptying study, then certainly
one of these agents like metoclopramide, domperidone and [inaudible 00:34:20] could be affected for those particular instances.
(34:25):
Now, what other options do we have? Well, you heard me allude to endoscopic and surgical interventions. This was a really
beautiful study done by Stu Spechler in the VA system where they looked at the effect of medical versus surgical treatment
in PPI refractory GERD patients in the VA. And this is a really difficult study to do, to randomize patients between surgery
and medicine is extremely hard. And although this study didn't reach its complete enrollment, we were able to glean some important
information here, which I think we all expected. And the one thing that you see from this particular slide here, is that surgery
is much more effective than active medical therapy or controlled medical therapy with continued PPI and a mix of potentially
Desipramine or Baclofen, depending on whether or not you were thinking this was hypersensitivity or a reflux mediated belch
type of pattern, it really didn't matter.
(35:22):
Surgery was much more beneficial in this PPI refractory population. Now, as I mentioned, there were some limitations to this
particular trial, and I think maybe the medical therapy group would've done a lot better if they targeted the baclofen towards
the belching patients and targeted the TCA to desipramine towards the patients who had more of a functional heartburn or a
reflux hypersensitivity. In addition, I probably would've used rabeprazole, or dexlansoprazole because those are much more
potent acid suppressive medicines to see if we not only provided some other active medications but escalated the acid suppressant
capabilities of the PPI, maybe that would've had a much more important or impressive effect in terms of the medication arms.
(36:14):
Now, in terms of other potential options, there are some ways to do a surgical procedure like a fundoplication, and do that
trans orally doing an endoscopic approach. And that's the TIF 2.0 procedure, which essentially is transoral fundoplication
and these TIF type procedures. There are many of them that are out there, different kinds, but this transoral or TIF approach
has been shown to be somewhat effective. And you can see in this particular study, the TEMPO trial at the one, three, and
five year follow up, these patients are doing quite well in terms of their overall GERD, HRQL and their regurgitation symptoms.
So symptomatically in terms of heartburn and quality of life and regurgitations, these patients are doing quite well at three
and five years.
(37:09):
Now, that being said, there are some other opportunities to make the surgical approach a little bit more standardized and
a little bit easier, and certainly one of those is the magnetic sphincter augmentation device. This is actually a small magnetic
ring that is placed around the end of the esophagus to provide some restriction at the EGJ during a reflux end. So what that
allows for is a reduction in the overall volume of flow of reflux into the esophagus. And this was a very nice study. There
was once again, a randomized study that looked at a PPI challenge. So this particular approach compared magnetic sphincter
augmentation versus PPI escalation in patients who had predominant moderate to severe regurgitation. And what you can clearly
see is that the escalation of PPI to BID from Q [inaudible 00:38:08] provided very little improvement in terms of their overall
ability to be satisfied with their treatment. And you can clearly see that magnetic center augmentation had a much better
effect in terms of its overall effect of improving regurgitation. So in the context of regurgitation, the magnetic sphincter
augmentation approach seems to be a much more effective approach.
(38:35):
Well, what about antidepressants for functional esophageal disorders? Well, what if your wireless pH monitoring showed four
days that were negative and you stopped the patient's PPI? Well, what are your other opportunities? Well, some of those are
to use antidepressants. And once again, these are all off-label and not FDA approved. But these medicines can do something
that's very important. They can modulate the neural transmission and sensitivity of that particular signaling. And with that,
you can see an improvement in symptoms. And these are some of the medicines that have been touted to use for these various
esophageal pain syndromes like functional chest pain, hypersensitive esophagus, refractory GERD, that's not related to reflux.
And then of course, globus, which is a lump in the throat.
(39:24):
So in the end, let's get back to our patient. He's a 42 year old man with heartburn and chest discomfort for six months. We've
gotten to the point where eight months later he finally had reflux testing and it was negative. Nine months later, he had
a manometry that was normal. So here you now have a patient nine months later, that is sitting here who'd been treated for
reflux disease despite the fact that no evidence here supports a diagnosis of Gastroesophageal Reflux Disease. So this patient
had refractory heartburn symptoms, not refractory reflux disease, and this person's refractory heartburn symptoms are likely
functional in immunology.
(40:09):
So in the end, it's extremely important to think about how we approach these patients. It's important to think about getting
the endoscopy sooner rather than later. We shouldn't wait three to six months to get an endoscopy on these patients. We really
should start thinking about getting an endoscopy sooner than that, and actually taking the patient off PPI therapy, especially
if they don't have erosive esophagitis or a history of objective evidence of reflux disease, and stratifying their risk based
on the wireless pH reflux testing. So if they have a negative study, all days are negative, they don't have GERD, they likely
have a functional disorder or potentially motility disorder. And if they do have some days that are positive, you can stratify
the severity based on the number of days positive and personalize their approach based on those numbers.
(41:02):
So in the end, we spent about 35 minutes talking about reflux and the management of reflux. Hopefully now you're a little
bit better off, but I wonder how confident you are right now in your ability to individualize treatment for patients with
refractory GERD. Are you still not confident? Are you maybe slightly confident, moderately confident, mostly confident, or
hopefully very confident? Please vote.
(41:39):
All right. Sorry, we're still waiting for the results.
(41:48):
All right, so we moved some people across to the mostly confident, very confident. I see somebody still slightly confident,
then someone who's still around moderate. So maybe we can use the QA session to hopefully get everybody up to that very confident
level. So any questions from the audience, anything especially for the people who are maybe not so confident in terms of how
to manage these particular patients? Well with that, I think the majority of the GERD patients can be effectively managed
in the community practice using endoscopy, wireless pH testing and PPIs based on degree of acid suppression.
(42:37):
Patients who have inadequate response or may be intolerant to PPI, they get headaches, their bowel symptoms don't change.
These are patients that probably need more sophisticated testing and a referral to a center of excellence. I do think that
patients can be phenotype very detailed. If you're using high resolution [inaudible 00:42:56] pH impedance, you can actually
nail it down to the actual mechanism of reflux, and then you can tailor your therapy and personalize your therapy based on
that particular patient's input and predictors of outcome. But once again, remember, anatomy is still extremely important.
Someone who has a large hernia is probably going to need surgery. Body mass index if someone is overweight, even mild weight
loss of 10 to 15 pounds can really help patients. And then of course, keep in mind the pattern type of reflux mechanism because
if people don't respond to PPI, you may be able to target that mechanism and make your patient feel much better.
(43:34):
So one more opportunity for questions from the audience. I can ask a question maybe. Do you think that PPIs are all the same?
Do you think that any PPI may be better than another PPI in terms of overall efficacy? Well, I just saw a question about thoughts
on PCABs. Well, as I mentioned, PCABs are not FDA available for the treatment of reflux disease. They are part of a treatment
protocol for H. pylori. They are a very novel approach to acid suppression, in terms of their ability to work very quickly,
and to work in a much more sustained fashion so they don't have to be tied to meals. So there were some advantages of the
PCABs. They're once again, faster acting. You get higher levels of acid suppression quicker, and you're not really tied to
this idea that you need to take it temporarily with food like you need to do with PPI.
(44:42):
So with those two effects, certainly you may be able to get better bang for your buck in terms of acid suppression in treating
these refractory patients. Got another question. Should patients with refractory Barrett's and symptoms always be sent for
surgical evaluation? No, I don't think they necessarily always need to be sent for surgical evaluation. I think if you can
manage these patients, and optimize their medication and get them to be symptom free, then you don't have to send them. But
if you've exploited all of your medical therapies, you put them on double dose proton pump inhibitor, which once again is
off-label, you know they're compliant, you've shown on 24 hour pH impedance that they've broken through that PPI and they're
continuing to have significant acid exposure, then of course those patients would need a surgical referral. Barrett's is very
interesting because Barrett's in and of itself is not an indication for surgical referral.
(45:41):
But certainly if you have someone who has significant Barrett's and they have evidence of low grade or high grade dysplasia,
you send for ablation therapy and they're having a lot of trouble getting a full response, the reason for that may be that
they still continue to have underlying reflux. And that reflux may not just be acid, it could be non-acid reflux. And in those
particular patients, you may need to send them for a surgical or endoscopic correction. Right now we're erring on the side
of surgical correction so that you can actually get rid of that acid and reflux, completely obliterate reflux and give that
person the best opportunity to have a good response and a complete response in terms of ablation therapy and variance.
(46:25):
So a quick discussion on PPI, efficacy and effectiveness. So one of the things that's really important, there was a beautiful
study from David Graham that was published where he looked at the PPI equivalent doses of medicine, and he took a page from
our pain specialist who used morphine equivalents, and he used omeprazole 20 milligrams as kind of that morphine equivalent.
And then what he did was he stratified the the acid suppression ability or effectiveness of PPIs based on a comparison of
omeprazole 20. And what he found was that pantoprazole was quite weak. In fact, 20 milligrams of pantoprazole was only equal
to five milligrams of omeprazole. So pantoprazole was a pretty low effect in terms of potency of acid suppression. So in my
particular practice, I like to use pantoprazole for people who have very mild disease and who are maybe having some side effects
like dyspepsia a little bit of headache and some changes in their bowel habit. Now, what he also found was rabeprazole was
probably the most potent PPI, in fact, 20 milligrams of rabeprazole was equivalent to about 36 milligrams of omeprazole in
that particular study. So there is a hierarchy in terms of asset suppression that you might want to keep in the back of your
mind when you're optimizing these patients medical management.
(47:58):
I don't think I see any more questions here, but I will say that when you're starting to think about these particular patients,
just keep in the back of your mind that there's a good portion of people who present with heartburn, chest pain, even regurgitation
that may not have reflux disease. And it's really imperative and incumbent upon us to make an important diagnosis for these
patients because that diagnosis could actually change their management. In fact, if we escalate the process and do endoscopy
and wireless testing sooner, we can stop a lot of people from getting inappropriate PPI therapy. In addition, we could also
send the right patients for an escalation of therapy, whether that's endoscopic or surgical therapy. So really important to
work these patients up with a good endoscopy, wireless pH testing if you're not sure they have reflux disease. And then to
use those tests to stratify severity, and also whether or not they even have reflux. And that's an important first step for
you to learn. And hopefully that's the message that I got across tonight. I saw one more question. How does [inaudible 00:49:17]
esomeprazole, so esomeprazole just real quick, is probably equivalent to the same thing in terms of rabeprazole, it's stronger
than omeprazole, just a little bit weaker than rabeprazole. So definitely on the higher end spectrum of PPI effectiveness,
but not the top.
Rod (49:45):
Any other questions for Dr. Pandolfino? Looks like you've answered everything.
Dr. Pandolfino (49:59):
Alright. Looks good.
Rod (50:00):
Well, I really appreciate it. That was a really interesting talk and I'd like to thank the audience for joining us tonight.
And we're going to put up a slide where you can, I believe we put a URL in the chat where you can go and get your credit for
this program. I think Pavana is going to do that. Yeah, so if you look in the chat, there's a credit link there, and you should
also be getting an email from Medscape with this information as well, so you can check your inbox. But if you want, you can
copy that credit, that link that's in the chat, and you can follow that to the instructions to get your credit for this program.
So yeah, Dr. Pandolfino, I'd like to really thank you again for your wisdom on this topic and your excellent presentation.
(50:55):
I'd like to thank the audience and we hope to see you again soon for another Medscape program. And just a reminder, medscape.org,
regardless of whether you're general internal medicine or you're a specialist, we have lots of CME programs that are up on
our website available for credit, and we have new ones coming up all the time. So please, if you're not a Medscape member,
I'm assuming most of you are, but it's free to join and there's a lot of interesting programs that are constantly being updated
and put up on the site. So thanks again.
Dr. Pandolfino (51:34):
Thank you very much.
