Care Initiative on Gerd Meeting Transcript

8/9/2019 Care Initiative on Gerd Meeting Transcript

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CARE Initiative on GI Motility Disorders

In Primary Care: GERD

Introduction

Bonny McClain

Bonny McClain: Good morning. Welcome to our CARE initiative

on GI motility disorders in primary care. The focus today

is on GERD. As a courtesy to your colleagues and our

faculty, please turn off your cellphones and pagers while

participating in todays activity. Feel free to set them to

buzz and take any calls that may happen out in the lobby

there. We appreciate that. And please refrain from

photography or recording because were doing that for you.

Were actually capturing video. So if you could use the

outer lanes for maneuvering in and out wed appreciate it

because the camera is right down the middle aisle there.

Our course director for the Initiative is

Dr. Lawrence Brandt. Our faculty Dr. John Allen, Dr. Peter

Kahrilas, Dr. Spechler. All this information is in your

will be on your thumb drive.

Accreditation and funding: this activity has

been planned and implemented in accordance with the ACCME

through the joint sponsorship of the Albert Einstein

College of Medicine, Gullapalli & Associates, Medikly

(which Ill give you a little more information on in a few

minutes), PeerView Academic Network and our accreditor is

Albert Einstein College of Medicine. And were funded

through a generous contribution from Takeda

Pharmaceuticals. Our sponsorship again, the AGA, Discovery

International Medical Education, PeerPoint Medical


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Education and co-sponsored with Albert Einstein College of

Medicine as well.

And conflicts of interest, youll see the

statements on the slides that follow and in your thumb

drive. Any conflict of interest would have had to have been

resolved prior to participation in the program. And the

faculty that participate in any of our programs have to

disclose to the audience when any unlabeled or

investigational use of any commercial product. So while we

welcome you know discussions that help clarify any

information, well have to declare if its something thats

not FDA approved.

Here are the faculty disclosures for our

selected faculty. This describes our planning committee. We

had a lot of contribution in putting this content together

with the faculty. Rosalee Blumer is our editor from DIME.

Steven Feld is the CCME representative of Albert Einstein

College of Medicine. Thats me, Im Bonny McClain. Im

actually a VP of curriculum and strategy for Gullapalli &

Associates, and Dr. Charles Willis Charles Willis. Hes

from the AGA Institute. And we have no conflicts of

interest to report.

And heres information on your credit. This

activity is approved for a maximum of 4.0 AMA PRA Category

credits. Please just claim credit for what youve earned

today. And please return the evals out to the registration

desk as you leave. And you can get your certificates online

at this web address: www.Medikly.com/gerd. This information

is also in the materials that youve received. Medikly is

moving forward our registration platform and this is also

where you will go to participate in participate in any of

the other interventions that weve provided, e-monograph,


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any other activities. The video of this event will be

posted there as well. And you can also download your

certificates here. And whats great about Medikly, this is

Facebook more or less for the medical profession. Its a

brand new social network where we have a lot of

participation by your colleagues. And its a good forum for

collaboration, sharing ideas, sharing presentations, a good

way to open up a dialogue about any medical issues you have

in a variety of therapeutic areas. So its a really good

tool and we will invite you to participate through your

email address that you provided at registration. So if you

could confirm that on your with the front desk there

well make sure that you get the enrollment information.

And here we are today. Our overview is to

focus on the multidisciplinary, multi-interventional

educational program. So theres more than one activity. You

can participate to receive credit and to extend your

learning. And the whole goal here is to measurably

identify, validate and address gaps and barriers related to

GERD care in the primary care setting. And as I mentioned

we have three regional workshops. We also have a

performance improvement activity which Ill describe

briefly in just a moment. We have an e-monograph and to

avail yourself of that and any credit associated you would

go to that Medikly website when its available.

Now performance improvement in GERD. The

trigger for developing this is a separate program from

this. Its one of the other interventions that I mentioned.

But the trigger for this was that the finding that GERD

has been the most common outpatient GI diagnosis since

2006. So clearly there is a need to help manage these

patients. And performance improvement is a nice forum for


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that. These few slides here, what they describe to you is

that it gives you a way to demonstrate your practice

process changes that are linked by evidence. So all the

suggestions that come from the program are evidence based

and rely on tools that are readily available for you to

utilize once you register for the program. Theyll be

posted on the website. And as you see here we have the GERD

guidelines, will be a very important resource. Theres

going to be information on how to improve provider-patient

communication which is so big in the GI arena, getting your

patients to talk and give you that information that you

need to reach a diagnosis. This allows you to assess

baseline knowledge about those guidelines and how youre

applying them to your patients, maybe how you can better

apply them to your patients, and creating an awareness. And

youll also learn about specific performance measures that

are standards in your field of care and what those measures

might be. We identify them. You apply them to a proportion

of your patient population and you get to measure how your

performance has improved.

Now also the patient theres patient

related barriers that Im sure many of you think about. But

from the patients perspective the challenges and barriers

to meeting those diagnosis and treatment needs, they dont

know about GERD. They think you know I have heartburn and

thats the end of story. So theres awareness that can come

from patient communication. Theres a psychologic impact of

GERD. Polypharmacy, theyll try anything to help to get

symptom relief because theres a lot of OTC stuff available

that may not be effective or appropriate for self-care.

Poor adherence and awareness of poor adherence.


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From the provider perspective, although many

of the providers are involved in managing these patients

with GERD, the burden seems to shift a lot to the primary

care doc. I mean theyre in your office. So poor adherence

to guidelines for diagnosis from the perspective, maybe

lack of awareness from a provider perspective. Maybe the

patient doesnt want to commit to a long term treatment.

You know so also working on the provider patient

communication. Trying to refer to a GI, to a

gastroenterologist, maybe you dont have a network where

you have a lot available. Maybe the wait times. And

financial challenges to managing these patients as well.

So to improve patient outcomes and

participate in a performance improvement activity to get

more information all you need to do is go to that website

that you have, Medikly.com/gerd. You fill out a brief

baseline assessment based on some of the practices that you

have in your current practice environment. You gather up

patient level data either from a chart review or just

understanding you know the process that you have in your

practice and you look at the tools and resources that we

provide and see what thats provided there might really be

able to be pulled into your practice and help improve care

of these patients. And there arent any HIPAA concerns

because any information you provide will be de-identified.

And theres live support for you, communication. Youll

always have access to someone that can help you and provide

you any coaching you might need or support. And the bolded

part there, the bright yellow part for you, is you can

receive up to 20 AMA PRA credits.

Now today we have the audience response

system. You see it right out there on your desk. We ask


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that they remain in the room. And the responses, they stay

you can change your response if you change your mind

later just by pressing the C key to clear. And as long as

the voting is open, which youll see as a count down,

youll have the option to change your vote and well

display your results on the main screen after we close your

voting. And just to try it out and see how its working, if

you could respond just to assess your interest in

participating in a performance improvement type CME

activity. We would be asking you to assess your practice

performance against those nationally recognized measures,

compare your performance to your peers. Youll be able to

see what your colleagues are doing, what the guidelines say

to do which arent always the same thing. And you compare

your performance to other healthcare providers and

specialists. So if you could start the vote. Okay. And if

you have any additional questions about participation the

results didnt show. Ill if youre interested in knowing

I can share that with you. You can speak to me if you have

any questions about the performance improvement and I can

point you to the right website. Or you can call that number

to talk to your site coordinator.

Your presenters for today are Dr. Peter

Kahrilas, MD. Hes the Gilbert Marquardt Professor of

Medicine, Northwestern University, Feinberg School of

Medicine and hes a lead author of the AGA guidelines that

were going to be looking at so extensively today. And Dr.

Stuart Spechler, MD. Hes the chief, Division of

Gastroenterology, Dallas VA Medical Center and Professor of

Medicine at Berta M. and Cecil O. Patterson Chair in

Gastroenterology and he comes to us from the University of


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Texas Southwestern Medical Center at Dallas. Id like you

to join me in welcoming Dr. Peter Kahrilas.

GERD Case Study 1: Carol

American Gastroenterological Association Institute (AGAI)

2008 Guideline Recommendations

Dr. Peter Kahrilas

Dr. Kahrilas: And Dr. Spechler. Good morning. So this is

the new evolution of medical teaching. Were going to web

based learning at this point. So in addition to Facebook we

now have Medikly. I think its been a very interesting

evolution as one looks at how medical teaching and

information transfer has evolved. When I was a student or

fellow we used to use textbooks and now when one is on

medical wards in the hospitals its very unusual actually

to see residents or students go beyond web based learning

things. And I think this is just the continuing of that

process where were looking at the whole system now of

getting CME credit as well as being a web-based exercise.

So I guess my own personal view on it is you can like or

you can not like it, but its almost certainly the future.

So our agenda, we just got through the

introduction. And the structure of the program is going to

be two cases. The first is the hard one, and thats the one

that Ill do. The second one is the easy one and thats the

one that Dr. Spechler will do.

A lot of this is based on a document, two

documents actually that the that were written for the

American Gastroenterological Association Institute or the

AGAI centered around reflux disease. The first was a

technical review where a series of management issues were


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presented to some selected authors of which I was the lead.

And then there was a medical position panel that met after

that that kind of distilled down the findings of the

technical review into a position statement. And youll see

this come out, Ill describe it more as I go along, into a

series of recommendations. Well last year the subject of

the technical review and medical position statement was

gastroesophageal reflux disease and after that was

completed they initiated another project which was the

actually the management of Barretts esophagus. And Dr.

Spechler is currently finalizing that. Of course hes been

finalizing it for about a year now but he is finalizing it.

So Case 1 is going to be Carol. The

objectives here are to identify risk factors for reflux

disease; to demonstrate a multi-disciplinary management of

patients with GERD, highlighting appropriate referral and

surgical options; and to select appropriate therapeutic

interventions for the management of patients at risk for

diagnosis or with GERD.

So to get a little background on you, we

have small ns here, but nonetheless what is your

specialist. We are going to show the results of these by

the way. Were not going to hide them from you. So well

find out what they are. So were going to have a count down

here and then let us know what your specialty is. Other.

Well there were 50% other and 50% primary care, internal

medicine or family practice. Thats challenging, what do

you think other is?

Dr. Spechler: Im not sure. Surgeons perhaps.

Dr. Kahrilas: So which of the following best describes

your type of practice? Private, private (partnership or


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group), hospital based, HMO, VA or other? Private practice

or hospital based. Very good.

Back to Carol. So heres our patient number

one. Carol is a 37 year old African American woman who

presents to one of 100% of you with a complaint of

heartburn and occasional regurgitation of food or fluids

into her mouth. She denies any significant dysphagia or

involuntary weight loss. Her height is 52, weight 148,

giving her a BMI of 27. That would be in the overweight

range between 25 and 30. Cardiac exam is normal. Her labs

are normal including a normal hemoglobin. She uses an

inhaler for asthma. Her existing conditions are asthma and

a hiatal hernia.

So presented with Carol, on a scale of one

to five one being not confident at all and five being

extremely confident, how would you rate your confidence in

treating Carol? And were from medium confidence to high

confidence, centered around four. Very good. So when

initially treating patients with symptoms of heartburn and

regurgitation which approach do you typically take?

Recommend lifestyle modifications; a step up approach which

is generally described as starting with an H2 receptor

antagonist and moving up to a proton pump inhibitor if

symptoms persist or are inadequately addressed; a step down

approach which would be to start with PPI therapy and then

withdraw or step down to H2RAs depending on the success of

the PPI; or none of the above. So 50% are recommending

lifestyle modifications as an initial approach and then we

have a split of 25-25 with step up or step down. Thats

interesting.

Dr. Spechler: Can I ask the people who wanted to recommend

lifestyle modifications, what kind of lifestyle


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modifications are you recommending at this point? Please

dont you know dont feel intimidated, just let us know.

Just curious. Lose weight. It sounds like a very good

lifestyle modification for this woman. I think that would

be a very good one. Okay. Anything else? Is anybody

recommending that they elevate the head of the bed on

blocks? All right, just curious to see whats still

happening. Good.

Dr. Kahrilas: And this was in fact one of the questions

that the AGAI guidelines was charged to address. So I want

to describe that process to you a little bit of how we went

about doing this and youll see these recommendations crop

up thereafter. This is the document itself, the technical

review that was published in Gastroenterologyjust about a

year ago. And the framework here again was that the AGA

Council framed a series of ten questions around the

management of reflux disease. And one of the questions was

the utility of lifestyle modifications. And then the

authors did an extensive literature review with the help of

the AGA staff around these topics, did a critical appraisal

of them and then generated recommendations.

The reason for doing this is that the United

States actually does not have an agency to validate

guidelines. The US does not put a priority on which

guidelines to use. So for the last decade or so youve seen

quite an array of these guidelines emanating from a variety

of organizations or even groups of practitioners in some

cases. And there was no there is no government agency

that validates them. This is sharply different than what

you see in Europe where there are government approved

organizations which look very critically at guidelines and

then accept them as the norms for practice of the entire


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country. And its a very formal process. So in lieu of that

what weve done here in the AGA is that weve tried to

substitute for that process. The process is being refined

and may be part of healthcare reform, but were not there

yet.

Now in assessing the literature the AGA

guidelines used the US Preventative Services Task Force

grades to assign strength of evidence. And the thats the

USPSTF, difficult initials to remember. But when we talk

about levels of evidence, grade A to grade B or

insufficient at the bottom there, this is what they mean.

And this is just the latest of a sequence of this type of

grading that has evolved. And this one I think is the most

practical that Ive seen yet, which is why I was happy to

use it. When something is described as having grade A

evidence, you can strongly recommend it based on good

evidence that it improves important health outcomes. Grade

B evidence can be recommended with fair evidence that it

improves important outcomes. Grade C, the balance of

benefits and harm is too close to justify a general

recommendation. Grade D you can actually recommend against

because there is fair evidence that it is ineffective or

that its harms outweigh the benefits. And when we say its

insufficient we really cant make any recommendation

because the evidence that exists is insufficient to judge.

Most of what we do in medicine youll find is not grade A.

Hopefully most of it is not grade B either. But we do shoot

for grade B and I think thats where youll see most of the

positive recommendations landing.

So getting back to this question, this was

grade A evidence. So there was strong evidence to recommend

this. For patients with esophageal GERD syndromes treatment


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with antisecretory drugs is recommended for healing

esophagitis, symptomatic relief, and maintenance of

esophagitis healing. In this setting PPIs are more

effective than H2RAs which in turn are more effective than

placebo. Not surprising that this is grade A, because if

one accesses the medical literature there is more written

about pharmacotherapy than about any other management

strategy in reflux disease. There are high quality studies

left and right comparing the efficacy of antisecretory

drugs, meaning H2 receptor antagonists, to placebo and then

another huge body of studies comparing proton pump

inhibitors to H2 receptor antagonists. So every single

study has consistently shown this ranking of efficacy. Its

very easy to make a grade A recommendation in that domain.

So having presented you with that Im going

to see if there is any reaction to that from the audience

where were basically saying that PPIs are better than

H2RAs which are better than placebo. Is there any push back

on this?

Dr. Spechler: Just to review a little bit of the history,

back in the 1980s before we had proton pump inhibitors, it

was very traditional to start with lifestyle modifications.

That was always the right answer to that question back at

least in the early 1980s. And then we would step things up.

But as far as the lifestyle modifications let me ask you

Peter, are you still using lifestyle modifications for your

patients?

Dr. Kahrilas: As an ancillary treatment but not as a part

of a step up process. Because it has never been my

expectation that it was going to be sufficient treatment at

the get go. It may be something that one could effectively

step down to after having instituted effective care. But


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very rarely are you going to subject somebody to say well

lose weight for the next year and then Ill treat you, I

mean because thats what it would amount to if one was

adopting say weight loss as a recommendation.

Dr. Spechler: And the recommendations, things like losing

weight and avoiding alcohol and cigarette smoking, those

are good general recommendations but whats the evidence

that theyre actually doing very much to help the reflux

disease?

Dr. Kahrilas: Well maybe you can look at it as a slant

thats occurred in the literature where we dont have very

many management trials. The only management trials we

really have pertain to pharmacotherapy. These have not been

systematically applied and studied. It would be very

difficult to do so. So the evidence is next to nil.

Dr. Spechler: And is anybody still telling their patients

to elevate the head of the bed up on blocks? Still doing

that? I dont see any hands. Do you still do that?

Dr. Kahrilas: I think theres a setting where that is an

appropriate thing and the setting is where a patient is

selectively complaining of nocturnal heartburn. So theyre

waking up after going to sleep because of heartburn or a

sense of regurgitation. If you look at those people

physiologically they tend to be individuals who have a

significant size hiatal hernia because theyre very prone

to regurgitation and nighttime heartburn.

Dr. Spechler: Interesting. Yeah you know when we used to

use these people would sometimes tell us about wearing silk

pajamas to bed and sliding out of bed. You know so that was

sort of a deterrent to using that. But yeah I think theres

still a role for some of these things even today and Id

certainly agree with you on that one.


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Dr. Kahrilas: The difficulty of defining reflux disease.

You know Bonny made the statement in the introduction that

GERD has become the most common outpatient diagnosis in GI

practices. And I find that a very interesting thing. There

are a number of ways of interpreting it. One would be that

its actually getting much more common than it used to be.

And another one pertains to definition and maybe that were

just defining it differently. Whats your perspective on

the answer to that one Dr. Spechler?

Dr. Spechler: Well I think an awful lot gets called GERD

that really is not GERD. Anybody who has a little bit of

funny sensation in the chest or even in the abdomen often

gets comes away with the diagnosis of GERD. But the real

substantiation of that diagnosis is often not there. And I

think if you want to really make a diagnosis of GERD the

patient should have classic heartburn. If you want to do

this without any kind of diagnostic testing, the patient

gives you a classic history of heartburn. Burning sensation

in the chest, often described with an open hand rather than

a closed fist. A burning sensation that kind of rolls up

the chest and that goes away when you put the patient on

antisecretory medications or when they take an antacid,

thats very strong evidence that yeah there is probably

reflux disease. But how often do we see patients who dont

have that classic history who have been told they have

reflux disease. What do you think?

Dr. Kahrilas: Well what do you make out of someone who has

heartburn once a month?

Dr. Spechler: Okay. Well now were going to get into the

difficulty this is the real difficulty in defining GERD.

Is that GERD because the patient has heartburn once a

month? Is that patient getting heartburn because theres a


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problem with the mechanism to prevent the reflux of acidic

contents? And if theyre getting it once a month is that

enough to call it a disease?

Dr. Kahrilas: Thats troublesome. I know that you tackled

that in the Montreal definition.

Dr. Spechler: Yes, and interestingly it was the word

troublesome that came up.

Dr. Kahrilas: Yes. Trying to establish what this threshold

is that differentiates occasional heartburn from

gastroesophageal reflux disease. It has to be the

assessment that the severity or the frequency of the

symptoms is such that it is impairing somebodys quality of

life to the point that it is troublesome to them. So there

is a distinction but its a bit different for different

people. Some individuals will look at the occasional

episode of heartburn as simply a nuisance. And others will

be very worried by it and it will be changing their daily

activities, even changing what they eat, and changing their

lives. And so it could be defined as reflux.

Dr. Spechler: So how troublesome is troublesome? You get

it once a month but its horrible on that one day out of

the month. Is that reflux disease?

Dr. Kahrilas: Well this introduces another distinction

that we had to make which is what you do in practice as

opposed to what you do in the process of conducting a

study. If youre conducting a study on the treatment of

symptomatic reflux disease you have to broadly apply a

definition of what that threshold is. And the threshold

that has widely been adopted is somewhere between two and

three episodes of moderate to severe heartburn a week. And

that would be the threshold when youre doing a study on

symptomatic reflux disease for saying thats our study


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population. However when you have Carol or whoever in the

office and they say they have two episodes of heartburn a

week but they take some antacids for it and theyre not

terribly troubled by it, that does not constitute

gastroesophageal reflux disease for that person. So there

is that distinction you have to draw between what you do in

practice and what you do when youre actually conducting a

study of pharmaceuticals.

Dr. Spechler: Is it possible that that patient who is not

bothered by the symptoms could have bad esophagitis if you

bothered to do an endoscopy?

Dr. Kahrilas: Well yes it is. There isnt always a very

good parallel. As a matter of fact the rule is that theres

a very poor parallel between the level of symptomatology

reported by the patient and what endoscopic findings you

might have. This pertains to the finding of esophagitis and

this pertains to the finding of Barretts metaplasia, as

Im sure well get into a little later on.

Dr. Spechler: So its really still a very subjective

definition that youre using.

Dr. Kahrilas: It is.

Dr. Spechler: The troublesome. And even non troublesome

symptoms could still be associated with some very severe

esophageal disease.

Dr. Kahrilas: And when we look at the difficulty here

another issue that commonly arises now as a referral doc is

a patient comes to me telling me that they have GERD. And I

ask them how they know that, and theyll say that they went

to their otolaryngologist and he did a laryngoscopy and

looked at their larynx and noticed some posterior erythema

and said oh you have GERD. And then promptly referred the


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patient to me. How do you react to that patient Dr.

Spechler?

Dr. Spechler: Yeah this is really one of the sore points

now in gastroenterology because the as Dr. Kahrilas said,

the ENT physicians have gone into this concept hook, line

and sinker. If you send a patient to an ENT specialist with

hoarseness, and hopefully theres no cancer there. But if

theres hoarseness and no obvious anything else, the

likelihood is that patient will come away with a diagnosis

of GERD. And the problem then becomes that you cant

convince either the patient or the ENT physician that the

diagnosis is not GERD. Theyve said this is it. Thats why

this patient is having the hoarseness. And even though they

havent responded to treatment theyre stuck on that

diagnosis of GERD. So this is a very difficult management

issue. I dont know how many of you are actually seeing

that in your practices when you send your patients with

hoarseness or chronic cough or burning tongue, having this

problem, coming back from the ENT physician, the diagnosis

is GERD? We see it. I know Dr. Kahrilas sees it.

Dr. Kahrilas: And just to highlight how this feeds back is

the GI physician more often than not will then code that

person as GERD.

Dr. Spechler: Thats true too.

Dr. Kahrilas: Which gets back to why its become the most

common outpatient diagnosis.

Dr. Spechler: Yes. Its been estimated that if you see an

ENT physician 10% of the diagnoses coming out of an ENT

office is reflux laryngitis. GERD induced laryngeal

problems.

Dr. Kahrilas: So to try to get at this issue of how to

diagnose reflux disease or what the definition should be,


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the classic symptoms are clearly heartburn and

regurgitation. And common symptoms that are also esophageal

are chest pain and dysphagia. Now a couple caveats on these

things. Heartburn I think Dr. Spechler clearly explained

what was meant, this burning sensation usually with an open

hand over the chest, not a clenched fist. And one can

sometimes describe that as chest pain but again as soon as

chest pain is mentioned as a symptom one has to really

explore it to make sure that the cardiac angle is covered

because one doesnt want to be in a position of treating

somebody with angina for reflux disease. With respect to

regurgitation theres actually variable interpretation of

what the word regurgitation means. Even among the group of

expert gastroenterologists from around the world that set

about creating this Montreal definition of reflux disease

there was a 50/50 split in what the meaning of

regurgitation was. Half of the individuals interpreted it

to mean the sense of acidic fluid coming into the

hypopharynx that could be tasted. So it was a bitter

regurgitant. The other half simply took regurgitation to

mean the sense of fluid returning into the chest without

ever getting above the upper sphincter into the

hypopharynx. So there is no taste element to it, just this

unpleasant sensation of fluid moving into the chest. So

regurgitation isnt as clear as one might want. And one can

make the same statement about dysphagia because there is

dysphagia and there is dysphagia. Some people describe

dysphagia as simply the sensation of food going down the

esophagus without any obstruction per se. Whereas other

individuals will clearly require that there be a sense of

obstruction with discomfort associated with that, sometimes

with frank pain. Of those two the more significant is the


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latter as that would be troublesome dysphagia, whereas the

sensation of food passing down the esophagus can simply be

a manifestation of some degree of inflammation or

irritation of the esophagus. And this is in fact the

Montreal definition that Ill describe to you a little

process and then Ill tell you how or why its structured

the way it is. First of all the reason its called the

Montreal definition is that it was a two year processing in

developing this. And as I mentioned, this was 50 world

renowned gastroenterologists from every continent except

Antarctica and I dont think they have any

gastroenterologists there. And it was Montreal because it

was finalized at the Montreal World Congress of

Gastroenterology. But the overarching definition is on top

here, which is that GERD is a condition that develops when

the reflux of stomach content causes troublesome symptoms

and/or complications. And immediately it branches into

esophageal syndromes and extra-esophageal syndromes,

recognizing that these two families have emerged. With

respect to esophageal syndromes there are those that are

defined by symptoms and it would be the typical reflux

syndrome which is heartburn regurgitation and 37% of these

people or 30% of these people say they have dysphagia as

well, or a reflux chest pain syndrome where the only

manifestation the individual is reporting really is of

troublesome chest pain. But then remaining on the

esophageal side there are syndromes that are defined by the

presence of esophageal injury. So theyre investigated by

definition because you wouldnt know they had this injury

if they werent. And that could be reflux esophagitis which

endoscopically is a distinct lesion and looks different

than other forms of esophagitis; reflux stricture which


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used to be a lot more common than it is, in the widespread

use of proton pump inhibitors in fact thats becoming a

relatively unusual problem; Barretts esophagus and

adenocarcinoma of the esophagus. Note that you can have

these without these. And you can have symptomatic syndromes

without any esophageal injury.

On the other side you have the extra

esophageal syndromes. Now note that the terminology here

immediately changes. Its no longer causal but now it says

established association or proposed association. So for

this family of disorders were no longer certain of the

etiology. Were not sure that its coming from reflux

disease. However epidemiological studies can tell you that

these things are associated. And what are they? Reflux

cough, reflux laryngitis, reflux asthma, and reflux dental

erosions. So all of these things can epidemiologically be

linked to reflux disease. Presumably in some instances

theyre causal. But a big challenge in managing them is to

establish in which instances theyre causal. And then you

have over here proposed association. And this list is

actually longer than is listed here. But it encompasses

things such as sinusitis, pulmonary fibrosis, pharyngitis,

recurrent otitis media, and as we discussed yesterday, even

halitosis. So theres a lot that has proposed association,

thats the weakest group of all. But this is the best

framework that we were able to devise in getting

capturing the entire umbrella of what gets called reflux

disease.

Back to this issue which I raised a little

earlier: what is the distinction between GERD and episodic

heartburn? From the Montreal definition this is the way the

group described it. In the absence of esophageal injury,


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heartburn of sufficient intensity to be perceived as

troublesome by the patient after assurance of its benign

nature meets the Montreal definition of symptomatic

esophageal GERD syndrome.

And now we have a little detour here to

review what the actual pathophysiology of reflux disease

is. Id say its brief, its one slide. Ive actually spent

many years looking at this. But Ill kind of synopsize it

as to where we are now. Obviously reflux disease involves

gastric refluxate. So you have fluid in the stomach and

its going to go up the esophagus. Whats in the fluid in

the stomach thats troublesome for the esophagus? Well its

the combination of acid, pepsin and to a lesser degree bile

acids. Acid is bad. It will injure the esophagus. The

esophagus is a squamous epithelium; its pretty tolerant of

acid, but not nearly as tolerant as the gastric epithelium

which of course lives in it all the time. However pepsin is

the major player here because pepsin is a digestive enzyme

that will digest tissue. It digests meat. Thats what it

does naturally and it will digest the esophagus. However

the Achilles heel of pepsin is that its a pH optimized

enzyme. So it works at a range of pHs that is usually

present in the esophagus -- in the stomach and rarely

present in the esophagus. So its reflux together of acid

and pepsin which proves to be very injurious. Bile acids

have less to do with esophagitis but probably more to do

with the development of Barretts metaplasia. And then key

to the disease is the anti-reflux barrier at the EG

junction over here. And that consists of the lower

esophageal sphincter which is part of the esophagus itself,

the surrounding pleural diaphragm which is sort of an

external sphincter. It crimps off the EG junction and of


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course that gets potentially compromised in the setting of

hiatus hernia where the two are physically separated and

perhaps less functional than normal. And then you have

defensive factors operational in the esophagus. If you do

have reflux it elicits peristalsis so you have secondary or

even primary peristalsis which will tend to sweep things

back down into the stomach, and the influence of body

position or gravity. This is the basis of the

recommendation of head of bed elevation because if you have

reflux while youre in a supine posture and say you have an

impairment in peristalsis or you have hiatus hernia such

that the natural processes of clearance are impaired, one

can, of course, employ gravity to help you out. And then

there is the fact that this is a stratified squamous

epithelium in the esophagus that is somewhat resistant to

injury. It actually has a small population of glands within

it which secrete bicarbonate and will neutralize small

amounts of acid that happen to get into the esophagus. And

then at the stomach end of things theres the process of

gastric emptying. And theres a longstanding controversy as

to how big a role impaired gastric emptying plays in reflux

disease. But taking the extreme case nobody argues with the

fact that if you have very impaired gastric emptying you

get a state of longstanding gastric distension and that

makes reflux a lot more common. Reflux is clearly accepted

as a secondary syndrome of gastroparesis or pyloric

stenosis, some profound problem of gastric emptying. And

then there are the external factors as well which we tend

to focus on a lot and well get into to some degree of

diet, medications which may be impairing either salivation

or the motor function of the esophagus, smoking which has

fairly diverse influences. It impairs salivation. It may


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have effects on the lower esophageal sphincter, and

obesity. Obesity is a big player here. Obesity both in

terms of the secondary side of it which is what diet leads

to obesity but also obesity changes the pressure dynamics

between the abdomen and the chest such that you have

increased intra-abdominal pressure and to some degree this

is a mechanical disease. If you have chronic increased

intra-abdominal pressure youre going to be developing

hiatal hernia with a greater frequency and youre also

going to be promoting reflux on strictly a mechanical

basis.

So back to Carol. In approaching her what

are the goals when treating her for typical symptoms of

reflux disease? Relieve the symptoms, prevent relapse and

complications, heal the esophagus, all of the above or just

items one and two? Well were all very well intended

physicians. This is good. We want to do all of the above.

What are your thoughts on that Stuart?

Dr. Spechler: I think thats great. I would like to do all

of the above also. The only problem is that you know how

can you argue with heal the esophagus? Or course you want

to heal the esophagus. But do we have any proof that by

healing the esophagus we do any of the one and two on this

list? And that we thats the problem. Do we really

prevent relapse and complications by healing the esophagus?

I understand what you say when you say we want to heal the

esophagus. How do you know youve healed the esophagus?

Really the only way to do that would be to do another

endoscopy. So do you really want to heal the esophagus? I

think yeah you do. Do you really want to do an endoscopy on

Carol here to make sure youve healed her esophagus? Thats

the tougher question.


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Dr. Kahrilas: What about preventing relapse and

complications?

Dr. Spechler: Yes well obviously thats a goal. I want to

prevent relapse and complications. But again its very

tough to tell that weve done any of these things with our

treatments. I mean most of the studies that we have are

focusing on the symptomatic relief or on the healing of

injury in the esophagus. But as far as actually preventing

the complications, very difficult to prove were doing

that. I think its hard to argue though that were

certainly seeing far fewer strictures in the esophagus than

we used to.

Dr. Kahrilas: Yes. I think thats the one case where we

have been successful in preventing a complication which is

peptic strictures. There is very good epidemiological

evidence at this point that the incidence of peptic

stricture of the esophagus has fallen dramatically since

the advent of proton pump inhibitors.

Dr. Spechler: Yes. And I think it certainly makes sense.

Its probably the PPIs. On the other hand we dont proof of

that either.

Dr. Kahrilas: No its epidemiological data but its new

strictures are not nearly as common a finding as they once

were and now when you do see them theyre almost invariably

related to eosinophilic esophagitis.

Dr. Spechler: Yes, absolutely. Thats an interesting new

disease too. Let me ask you though Peter, because this is

something that bothers me a bit. Before we had proton pump

inhibitors we would see people come in not only with

strictures but with the worst esophagitis imaginable. Huge

ulcerations, deep ulcerations and tight strictures. And

frankly we just dont see that very much anymore,


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occasionally but very infrequently. It used to be very

common. You really buy it that its just the PPIs that have

changed this?

Dr. Kahrilas: Well they are ubiquitous. I mean you now

have proton pump inhibitors that are generic, over the

counter, generic over the counter. One can argue that it

has so permeated the population that you may well change

it. I mean its it gets back to the issue of duodenal

ulcers. You know it doesnt take much to treat a duodenal

ulcer. And we dont see those at all anymore.

Dr. Spechler: No, thats for sure.

Dr. Kahrilas: It probably doesnt take much to prevent a

peptic stricture. It takes a lot to prevent symptoms but

you know you need a lot of ulceration and ongoing scar to

develop a stricture.

Dr. Spechler: Yes. No I think it certainly makes sense.

Im still just a little bit skeptical though because Im

just not seeing that kind of disease anymore just walking

in de novo.

Dr. Kahrilas: So what are the next steps in managing

Carol? Once daily PPI trial, endoscopy, manometry, pH

monitoring, refer to a gastroenterologist or other. I guess

we havent done anything for her yet. Weve talked about

her a lot but were going to do something now. So what is

it going to be?

Oh thats good. Yes, I think the notion here

is it appropriate to empirically treat? Were not giving

you treatment options here. So its treat versus diagnostic

testing or referral. And everybody is comfortable with the

notion of a once daily PPI as an initial intervention. And

were going to agree with that. And going back to the AGAI

guidelines there is a current consensus that the empirical


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PPI therapy is appropriate for patients with uncomplicated

heartburn such as Carols. There is no need for diagnostic

testing when the symptom profile strongly suggests GERD. In

uncomplicated GERD no need exists for endoscopy or upper GI

studies. This would require immediate referral to a

specialist or certainly endoscopy would. So were in

complete agreement with you there.

And although Carol has coexisting conditions

her case qualifies as uncomplicated GERD because she has no

particular warning signs. And the warning signs, what do we

mean when we talk about warning signs which might lead you

to an immediate referral? Which of the following warning

signs would warrant endoscopy and/or immediate referral to

a specialist? Weight loss, GI bleeding, loss of appetite,

chest pain, dysphagia or all of the above? All of the

above. And I think you know thats quite reasonable because

in different settings obviously one explores each of these

symptoms a little bit and its not 100% but in the broad

sense if somebody has involuntary weight loss, they havent

just enrolled in Jenny Craig, that becomes something of a

concerning symptom. GI bleeding in general other than the

obvious hemorrhoidal bleeding or whatever is something that

is always going to warrant investigation. Loss of appetite

suggests pathology of the stomach. Chest pain, theres

chest pain and theres chest pain but if theres any flavor

here of a cardiac etiology that should always be explored

because of the potential for cardiac disease to be fatal

whereas esophageal disease is rarely going to be fatal. And

dysphagia, again with the caveat that there is dysphagia

and there is dysphagia. You want to there is some that is

just over interpreted esophageal sensation whereas in other

instances its clearly an obstructive process.


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Dr. Spechler: And if I could just chime in because Ive

been given a soapbox and Im going to use it now. On the

chest pain thing you know there is certainly the tendency

that once a patient has a diagnosis of GERD to blame

everything on GERD. But be very careful about ascribing

chest pain to GERD. Not that its not common. It certainly

is. Atypical chest syndrome chest pain syndromes are

common in GERD but be absolutely certain that your patient

doesnt have heart disease because as Dr. Kahrilas says,

heart disease kills.

Dr. Kahrilas: So which of the following is or are risk

factors for reflux or for GERD? Overweight. Its a funny

word but she typically fits this overweight with a BMI

between 25 and 30. Asthma, hiatal hernia, female gender, or

items one, two and three? Didnt fool anybody there.

Dr. Spechler: We should sit down.

Dr. Kahrilas: Overweight clearly is a risk factor and

there is just a ton of studies exploring this association

lately. Asthma, yeah about -- as many as 80% of asthmatics

will have objective evidence of reflux disease depending on

what objective evidence you choose to accept. But if you do

pH monitoring studies on them youll show that that exists.

Its not saying that the reflux is causing the asthma as

some people interpret that to be, its just saying they

coexist in the same individual. Hiatal hernia, also an

interesting story but definitely associated. Female gender,

no. Its really 50/50 males and females. Males are more

likely to get esophagitis but not symptomatic reflux

disease.

Dr. Spechler: And with the asthma its interesting.

Theres rationales that could go both ways. As Dr. Kahrilas

said its very difficult to prove whether its cause and


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effect but asthma, reflux disease might cause asthma both

by the refluxate getting into the esophagus probably can

stimulate vagal nerves that cause bronchospasm. If the

material actually goes up into the larynx its possible to

get microaspiration of that stuff that could cause asthma.

And the other way around, asthma, its been said some of

the medications might predispose to reflux, the medications

that are used to treat asthma and the fact that the

diaphragms may be down a little bit in asthma and

increasing intra-abdominal pressure may actually favor

reflux. Still its an interesting association but very

difficult to establish cause and effect.

Dr. Kahrilas: Good. Any thoughts on that as to how this

impacts on patients in your experience? Have you treated

patients with asthma and put them on reflux medications and

seen that the asthma suddenly got much better?

Dr. Spechler: You see that. Have you seen that?

Dr. Kahrilas: Yes, but its a very select group and in

fact there was great interest in the pharmaceutical

industry to get this indication. So there was a large

placebo-controlled trial done with esomeprazole looking at

a group of asthmatics who had nighttime asthma episodes and

then they subdivided them as to whether or not they had

nighttime reflux episodes as well. And it was a placebo-

controlled trial of 40 b.i.d. of esomeprazole versus

placebo with the outcome measure being pulmonary function

in the morning. And they were able to show that one

subgroup and its not terribly surprising what subgroup it

was, one subgroup did get improvement in pulmonary

function. And it was the group that was experiencing both

nocturnal reflux symptoms and nocturnal asthma symptoms.

But they did stand to benefit from PPI therapy. The others


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you could show no benefit whatever. Meaning the ones who

didnt have nighttime reflux experiences, their pulmonary

function was unchanged.

Which brings us to a broad consideration of

the extra-esophageal syndromes here. Carol has a history of

asthma which may be classified as an extra-esophageal

syndrome as is laryngitis. If Carol did present with adult

onset asthma or laryngitis without esophageal symptoms or

GERD should she be treated for GERD? Yes? No? It depends on

the physical examination. Not sure. Some yes, some no and

some not sure. This is the issue that we raised a little

bit, especially when one invokes the laryngitis aspect and

theres a lot of that that goes yes, because theres a lot

of ENT literature that suggests that to be the case. But

50% here say no and then theres the uncertainty factor.

This was an issue that we carefully addressed with the AGAI

guidelines and this is the statement there are two

statements here that come out of this. Acute or maintenance

therapy with once or twice daily PPIs (or H2RAs) for

patients with a suspected extra-esophageal GERD syndrome

such as laryngitis or asthma with a concomitant GERD

syndrome so were saying that you should treat them with

a concomitant GERD syndrome with grade B evidence. So its

recommended with fair evidence that it improves important

outcomes. But thats not what we just asked you. What we

asked you was this. Once or twice daily PPIs or H2RAs for

acute treatment of patients with potential extra-esophageal

GERD syndromes in the absence of a concomitant esophageal

GERD syndrome. And there its grade D evidence which is

recommending against this with fair evidence that it is

ineffective or that the harm outweighs the benefit. Theres

not much harm to H2RA or PPI therapy. Theoretically you can


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say that if there is no benefit to something then any risk

is harm. But there is substantial evidence that its

ineffective leading to that recommendation. So with

laryngitis or asthma fine to treat them with PPIs or H2RAs

if theyve got the esophageal symptom profile to go along

with it but not otherwise.

The exception, and theres always an

exception to everything here is cough. Because the most

difficult reflux syndrome to deal with is the suspected

reflux cough. And the reason its so difficult is because

there are no data showing that anything really works other

than consistent anecdotal reports that anti-reflux surgery

can be effective in the ones who you really distill this

down to suspected reflux cough syndrome. PPIs have never

been shown to be effective in relieving that. But you get

this consistent flavor in the surgical and even in the

pulmonary literature that anti-reflux surgery can be.

However the strength of that evidence is so weak that you

really cant make a recommendation, you just have to at

least isolate it as a special case.

So which of the following might help improve

Carols symptoms? And this gets back to the utility of

recommendations beyond pharmacology. Weight loss, OTC

allergy medicines, change in diet, all of the above, just

one and three. Well take your votes. So all of the above

and one and three. Everybody is agreeing probably with

weight loss and a change in diet. Those two things are

somewhat related. OTC allergy medicines. Stuart?

Dr. Spechler: I think OTC allergy medicine is not

something I would expect to help improve her GERD symptoms.

On the other hand I could make up a scenario where perhaps

it might. So Im not entirely sure its 100% wrong. But I


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think probably the best answers are one and three, that the

patient should certainly be instructed to lose weight. That

would do that would have many good consequences for her.

And change in diet, I think there are things that can be

done to help her prevent reflux. I think the dietary

recommendations; its easy to remember what foods cause

reflux because its basically anything that tastes good.

Anything with a high fat content, chocolates, things like

that would certainly predispose her to reflux.

Dr. Kahrilas: So what did we end up concluding with the

AGAI guidelines? Well weight loss is the one that comes out

with grade B evidence. Weight loss is advised for patients

who are overweight or obese or who have recently gained

weight and who have esophageal GERD syndromes. Because in

fact the benefit of weight loss is even demonstrable in the

normal weight range, meaning BMI of 20 to 25. But certainly

in people who go into the overweight or obese range. Its

grade B evidence and like I say there are few instances

when anything other than these rigorous pharmacological

trials are going to come out as grade A evidence. So grade

B tends to be as good as you get. And this is the type of

evidence that exists. This is a fairly recent study that

came from the the Nurses Health Survey?

Dr. Spechler: Yeah out of Tufts.

Dr. Kahrilas: Where they looked at the current or the

likelihood of getting reflux symptoms as a function of BMI.

And as people go up and down this curve and clearly as they

go from normal BMI to obese out here, you can see the

occurrence of reflux symptoms being directly related to

BMI. So BMI is associated with symptoms of GERD in both

normal weight and overweight women. Even moderate weight

gain among persons of normal weight may cause or exacerbate


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symptoms of reflux. And this emphasizes the fact that a

certain part of this is clearly a mechanical disease where

youre talking about pressure gradients between the abdomen

and the chest.

As far as other lifestyle modifications,

avoid foods that may precipitate reflux. And in excess

these all fall under that category: coffee, alcohol,

chocolate or fatty foods. And then theres another group of

foods that may precipitate heartburn just because theyre

acidic and if you have a sensitive esophagus red sauce,

tomatoes, citrus, carbonation or spicy foods will all

irritate the esophagus. This whole group of recommendation

though need not be made to everybody and you should really

adopt behaviors that reduce Im sorry Im going to skip

ahead to the next slide in a second. But the continuation

of that is adopt behaviors that may reduce esophageal acid

exposure. So avoid late night meals and bedtime snacks. Of

all of the lifestyle recommendations that you can make

thats probably the one that is going to make the biggest

difference. Raise the head of the bed, stop smoking or

weight loss. And in the AGAI guidelines what we ended up

saying about this was that except for weight loss the

evidence for lifestyle modifications including smoking is

generally weak. However modifications tailored to each

patients individual circumstances may sometimes be

effective, elevating the head of the bed for selected

patients who are troubled with heartburn or regurgitation

when recumbent, other lifestyle modifications including but

not limited to avoiding late meals, specific foods or

specific activities. The emphasis here though is to be

selective. Because Stuart alluded to this when he was

saying that just tell them to do not to do everything


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they enjoy doing. And theres too much of that going on

with respect to the management of reflux disease. Not all

of these recommendations are sensible for everybody who has

heartburn. You have to be selective as to what might apply

to the individual in front of you.

Dr. Spechler: Absolutely. And you know when the PPIs came

along they took care symptoms in many patients such that

patients were totally unwilling to accept lifestyle

modifications. If you could take a pill rather than do

something rather than a lifestyle modification which is

very difficult they do prefer pills. On the other hand it

would be very nice to have your patient stop smoking and

for your overweight patients to lose weight. So certainly

not speaking out against the lifestyle modifications but

they are very difficult to implement effectively.

Dr. Kahrilas: Contributing conditions, the role of hiatus

hernia in reflux disease. Well this is a complex topic. But

I think what we can say about it is that it promotes the

reflux of gastric content by its direct and indirect

actions on the antireflux mechanism and thus is associated

with reflux disease. In this way hiatus hernia is

associated with the potential consequences of GERD,

heartburn, esophagitis, Barretts and even esophageal

cancer. However the role of hiatal hernia is variable and

somewhat difficult to quantify.

The type of hernia were talking about is

this, which is a type 1 or sliding hiatal hernia. This is a

fairly obvious one. This would be the diaphragmatic hiatus

over here and you see the cardia of the stomach clearly

protruding above. This is the area of the lower esophageal

sphincter here. And conceptually in a normal situation this

would be the anatomy where you have the pleural diaphragm


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surrounding the lower esophageal sphincter right at the

left of the squamocolumnar junction and you have two

sphincters in essence. You have the intrinsic one to the

esophagus and then you have the surrounding one. So when

you have relaxation in fact the sphincter doesnt open. It

doesnt because its still in the abdomen. Its

fundamentally different than the situation with a sliding

hiatal hernia where now you have the crual diaphragm which

is not only mispositioned, its further down than it was

before. But the aperture itself has become dilated and as a

sphincter its less effective. So now youve positioned the

lower esophageal sphincter in the chest and you have intra-

gastric pressure reflecting up to it. So when that

sphincter relaxes it tends to open. And as it opens youre

going to get flow of liquid into the esophagus when youre

in a supine posture just a function of laying down. That

doesnt happen in normal individuals. So there are a

multitude of ways that hiatus hernia gets involved in the

pathophysiology here. It promotes reflux in certain

circumstances and it impairs acid clearance.

Dr. Spechler: The history of hiatal hernia is actually

kind of fascinating. I at least find it fascinating. But

back in the late forties, early fifties surgeons were

working on this reflux problem, blamed the hiatal hernia

virtually for everything. I mean the hiatal hernia was the

culprit. That was the cause of all reflux disease. And if

you saw one of these surgeons during back then in the

forties and fifties the chances are that they were going to

recommend that you have your hiatal hernia fixed to improve

your reflux problem. And then in the early seventies there

was a study that came out in the New England Journal that

said hiatal hernia has nothing to do with GERD. It has


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nothing to do. Its all the lower esophageal sphincter. And

that study was as wrong as the surgeons had been about the

hiatal hernias, the sole cause of reflux disease. And weve

kind of come full circle on this. Dr. Kahrilas has been

very instrumental in showing how important the hiatal

hernia is in the pathogenesis of reflux disease. So it

clearly plays a role. But weve also learned that just

having the hiatal hernia doesnt mean it has to be fixed.

We can treat the reflux disease without necessarily doing

an operation to correct this problem.

Dr. Kahrilas: So according to AGAI guidelines which one of

the following agents is never appropriate in the treatment

of reflux disease? Turning this around, OTC PPIs,

metoclopramide, H2RAs, OTC antacids or none of the above,

they are all appropriate. Aha. Stuart.

Dr. Spechler: Well on this one actually there is a right

answer. And the right answer is two. Metoclopramide is

actually never appropriate as the sole treatment for GERD.

And thats this is another drug that has a very checkered

history, metoclopramide. You know in treating reflux

disease there are many people who have said reflux isnt an

acid problem; reflux is a motility problem. If the motility

were working correctly you wouldnt have to give an antacid

medication because the patient wouldnt get reflux. And

metoclopramide was one of the attempts to correct the

problem, the so-called prokinetic agent, an agent that

focused on the underlying kinetic problem. The problem with

metoclopramide is that its side effects are so bad, they so

frequently outweigh any therapeutic benefit of the drug

that its just not a good treatment for reflux disease. Now

having said that there are still do you still use the

drug ever in your patients with reflux disease?


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Dr. Kahrilas: Not when its just reflux disease. I think

the caveat is if someone has reflux thats secondary to

gastroparesis and in fact metoclopramide only recently got

that indication for reflux symptoms associated with

gastroparesis. But in the absence of gastroparesis, no. The

harm here clearly outweighs the good. And this gets down

to, this discussion here, what the available medications

for reflux disease are. And in terms of promotility agents

metoclopramide now in fact has a black box warning against

continued use. And the risk is of tardive dyskinesia which

is an irreversible neurologic disorder which is far more

common than previously recognized and now the subject of

quite a number of lawsuits including a class action suit.

So look out for that one. H2RAs, the four of them, proton

pump inhibitors, we now have quite a few of them with dex

lansoprazole, esomeprazole, lansoprazole, omeprazole both

as enteric and on enteric coated, pantoprazole and

rabeprazole. But of all of these this is the AGAI statement

and its the one of the relatively few grade D meaning

recommend against. Fair evidence that it is ineffective or

in this case the harms outweigh the benefit. And the

statement is that metoclopramide as monotherapy or

adjunctive therapy in patients with esophageal or suspected

esophageal GERD syndrome. So the recommendation is not to

do this. Any comments on that?

Speaker: inaudible remarks

Dr. Kahrilas: Well nausea and vomiting have a loose

relationship with reflux disease. They clearly can be

reflux related symptoms. You would use an antiemetic I

think if the vomiting is a difficult problem unto itself.

My experience with these is that usually if thats a reflux

related problem its associated with a fairly high level of


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esophagitis. So youre talking about basically ulcerative

esophagitis and thats the problem that really needs to be

addressed. Its not so much the gastric emptying side of

things. Im very I very rarely use metoclopramide and

never have really.

Dr. Spechler: I agree. I think there are things that

generally work better as emetics, antiemetic medications

and theyre just the side effects of the metoclopramide

are very, very worrisome. It goes with all the promotility

agents. You know the promotility agents have had a very

checkered history and most of them now have been taken away

for one reason or the other. I wouldnt be surprised if we

dont have metoclopramide available in the near future

either.

Dr. Kahrilas: Except that they just got that gastroparesis

approval.

Dr. Spechler: Yes, yes. But boy there are a lot of

lawsuits about this tardive dyskinesia. Whats that? Oh

something like Compazine, for an anti-emetic medication?

Yes something like Compazine.

Dr. Kahrilas: Compazine, Zofran, that sort of thing. Yes

sir.

Speaker: inaudible remarks

Dr. Kahrilas: You mean duration of therapy? Yes I think

youre in the four week range is what you should limit it

to.

Dr. Spechler: Yes, Id agree. Id agree.

Dr. Kahrilas: Comparing the efficacies of PPIs and H2RAs,

according to the AGAI guidelines which agent is most

effective for the treatment of patients with esophageal

GERD syndrome, meaning healing esophagitis and symptom

relief? H2RAs, PPI, OTC antacids, all are equally


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effective. Right. I think the answer to that is correct.

Its one of those circumstances where you get grade A

evidence because again there is this multitude of

pharmacological trials out there which directly compare

these in placebo controlled, double blind studies. And you

can say with great certainty that any secretory drugs for

the treatment of patients with esophageal GERD syndromes in

these uses, PPIs are more effective than H2RAs, which are

more effective than placebo.

Which of the following agents has been the

most rapid or has the most rapid speed of healing? The same

choices. H2RAs, OTC antacids, PPIs.

Dr. Spechler: And I think this is healing esophagitis

right?

Dr. Kahrilas: Right, speed of healing esophagitis. Go

ahead. PPIs again and again the same thing. I mean you can

show this from meta analyses such as this. This is the

speed of healing, two weeks and youre seeing PPIs being

significantly better than H2RAs and antacids really not

very effective at all.

Dr. Spechler: Now Peter this is esophagitis again.

Dr. Kahrilas: This is healing esophagitis.

Dr. Spechler: So what about your patient with the

troublesome heartburn once a month? The heartburn episode

and that patient is having a lot of difficulty with the

heartburn episode. Youll say pop a PPI?

Dr. Kahrilas: Well no because healing esophagitis is a

fundamentally different issue than resolving an episode of

heartburn. Healing esophagitis is a process set in motion

by changing the equilibrium between acid secretion and

reflux. Resolving heartburn is a matter of neutralizing the

esophageal mucosa which youre going to need something that


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pharmacologically acts quickly. So theoretically theres

actually nothing better than an antacid to accomplish that.

But H2RAs are going to be better than PPIs in that regard

because they work within 15 minutes or so whereas a PPI,

the onset of action you would predict for most of them is

more like four hours.

According to guidelines which of the

following agents heals more patients in the longer term?

PPIs, H2RAs, promotility agents, 1 and 2 are equal. Well

thats interesting that anybody thought H2RAs have a longer

term effect. If anything the issue of tachyphylaxis is

greater with H2RAs than with PPIs. You cant show

pharmacological tachyphylaxis with PPIs but theres been

considerable discussion about that with H2RAs. So the

answer here really should be one.

Dr. Spechler: Yes, long term H2RAs as Peter pointed out,

its just a very common problem that they lose their

antisecretory effect, and so they just become ineffective

after a while. Although I will say that as enamored as we

were of the PPIs when they came out because we finally had

agents that could heal these horrible ulcers that nothing

else would touch, Im surprised still at the number of

patients who remain symptomatic. They still have symptoms

on PPIs. What do you think about that?

Dr. Kahrilas: Well our expectations have grown. And you

know I mean we were looking for perfection. They were a

huge increment but they dont bring it to zero. So I think

part of that is a matter of expectation.

This is healing PPIs versus H2RAs versus

placebo. So placebo, H2RAs, PPIs, looking at time in weeks

and there really isnt any question in this meta analysis

of the relative efficacy of the agents nor of the speed at


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which you see change. So these are clearly of vastly

different potency. And one would predict that from their

pharmacological properties.

This is something different here. This is

looking at the percentage of symptom free patients for PPIs

versus H2RAs and you still see a significant difference and

its about this is now a smaller therapeutic gain here.

This is 15% therapeutic gain but the difference still

exists.

And this is actually a very interesting

slide. Theres a lot of material on here but its looking

at FDA approved indications for the treatment of GERD along

with the associated doses. Do you want to comment on that

to some degree Stuart as to what you see being done in the

in the medical community now versus what these

Dr. Spechler: I think its interesting to look at this

because this is what the FDA has approved. This is

generally not what we do in practice. It really is a

tremendous disconnect.

Dr. Kahrilas: I mean esomeprazole 20 mg daily for

symptomatic relief, healing 20 or 40, maintenance therapy

20. Ninety-five percent of prescriptions for esomeprazole

in the US are 40 mg.

Dr. Spechler: Forty milligrams. Yes. So Im not advocating

that we should do what weve been doing. Im just saying

that what is done in practice really doesnt conform to

these guidelines.

Dr. Kahrilas: Lansoprazole 15 mg for symptomatic relief

and for maintenance therapy.

Dr. Spechler: Has anybody ever prescribed 15 mg

lansoprazole? I dont see anybody who has used the 15 mg

dose.


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Dr. Kahrilas: Regarding lansoprazole just FYI, this is

going to be available as an OTC at that dose probably some

time before the end of the year. The other thing thats

developing with lansoprazole is that this dose actually

will be available as a generic I believe in about 20 days

and there will be instantly six companies marketing generic

lansoprazole at the same time 20 days from now. So one can

expect some impact on pricing as a result of that. Its

referred to in the pharmacological community as a jail

break when you get that many generics coming in all at the

same time. And this is for maintenance treatment of reflux

disease with the H2RAs, the available agents and again the

doses may not be what youre terribly familiar with but for

treatment of reflux disease or for maintenance of healing

of erosive or ulcerative esophagitis. And the H2RAs also

have those indications. Thats not to say theyre as

effective as PPIs because theyre not. We know that. But

they do have efficacy. One cant deny that either.

Nocturnal breakthrough symptoms. Back to our

case. After four weeks of once daily PPI therapy Carol

returns to your office. Her symptoms have improved somewhat

especially during the day. However she wakes up about two

nights a week with heartburn and regurgitation. How would

you proceed with your management of her symptoms? Now would

you investigate her with endoscopy, pH monitoring, advice

her to use OTC antacids, increase her PPI to twice daily,

refer for surgical consultation or none of the above? Well

we have a two-thirds, one-third. Thoughts?

Dr. Spechler: I think youre justified actually in either

one of these two. Now certainly what most people are doing

here I think is what is done most commonly in practice.

Many people would say this woman has no warning symptoms at


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all. What am I going to accomplish with my endoscopy in

this particular patient? And so Im just going to increase

the PPI to twice a day.

Dr. Kahrilas: Because thats what youre going to do after

the endoscopy.

Dr. Spechler: Yes, absolutely. On the other hand you would

be perfectly justified in recommending an endoscopy for

this woman because that is one of the guidelines that her

symptoms have not responded completely to the PPI therapy.

So I think that either one of those choices is okay.

Dr. Kahrilas: And I think thats fine. And this, you know

this is what we end up saying. But its the recognition

that here youre on thinner ice than you were before. And

of all the trials there are of PPIs, there are no trials

with b.i.d. therapy. There is no FDA indication for b.i.d.

therapy. This is something that has been adopted very

broadly by the practicing community including myself and

every other gastroenterologist I know because were

convinced that it works. And for a while people were just

referring everybody who failed once daily therapy to us for

endoscopy. We do the endoscopy. We see that it looks normal

and then we put them on twice daily. So its sort of just

skipping ahead with respect to that. And it led in fact to

this recommendation which to my knowledge is the first time

this has ever really been suggested by a professional

organization. Recommended with fair evidence that it

improves important outcomes. The fair evidence however is

the strength of the practicing community with virtually

everybody agreeing on it that we recommend endoscopy to

evaluate patients with suspected GERD syndromes who have

not responded to an empirical trial of twice daily PPIs. So


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the threshold then for referral really is not after once

but after twice daily.

Dr. Spechler: Would you still feel though that it would be

wrong to send the patient

Dr. Kahrilas: No. Its not wrong but I think youre going

to see difference in the gastroenterology community as to

whether or not they do endoscopy or whether or not they

first try upping the dose.

Dr. Spechler: Thats for sure.

Dr. Kahrilas: And it brings up this whole notion of

nocturnal acid breakthrough. I mean there is an official

definition of this which is defined as the presence of a

gastric pH of less than four for an hour during sleep. It

refers to the measurement of gastric pH though, not

symptoms, and its therefore not used for the management of

symptoms. There was a lot of literature about this

nocturnal acid breakthrough but its its really a

pharmacological observation more than something that

pertains to Carol in this case. And with respect to

nocturnal breakthrough symptoms again back to the position

statement here, there is no evidence of improved long term

efficacy by adding a nocturnal dose of H2RA to again its

twice daily PPI therapies. And the reason well we just

say there is just no evidence for that recommendation.

There are some pharmacological observations that co-therapy

may do something to suppress this nocturnal acid

breakthrough but there are no clinical data showing that it

ever made anybody feel better.

Dr. Spechler: You know I think another way to look at this

question of you know should you send this patient for

endoscopy to double the dose, and say what is the endoscopy

going to tell you that youre going to thats going to be


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helpful in managing this patient? Because the endoscopy can

only tell you a few things. The endoscopy could tell you if

there is reflux esophagitis. But the chance of finding that

in a woman like this who is already on a PPI is really

fairly low at this point. It can tell you if theres a

stricture. She has no reason to suspect that particularly.

It could tell you if theres Barretts esophagus but she is

would be very low risk for Barretts esophagus at this

point. And it could tell you the thing that we worry about,

is there some other disease in there? Is there cancer? Is

there eosinophilic esophagitis? But again the chances of

finding those things are really very small in this

situation so you know I think that its very reasonable to

just double the dose.

Dr. Kahrilas: And it works. Carols symptoms are

successfully managed after three weeks of twice daily PPI

therapy. How would you approach maintenance therapy?

Continued long term therapy at the same dosage? Continued

long term therapy and titrate down to the lowest effective

dose on the basis of symptom control? Titrate therapy for a

few weeks and then discontinue until symptoms reappear? All

of the above, none of the above. Yes, this is actually very

interesting. I mean because it gets to the basic issue of

do people go on PPIs forever? Or do you at some point try

and reduce dosage to the minimum that maintains symptom

control? No data out there. But there is no data out there

for using twice daily to begin with. So you know it is a

point where it just has to be a common sense approach to

the thing. And this is the high ground with respect to

common sense, which is youre going to continue long term

therapy here because unless some of the fundamentals change

this lady is going to continue to have reflux disease. But


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on the other hand you dont necessarily have to leave her

at the highest dose. Symptoms tend to wax and wane in

reflux disease. Shell get into a period of relative

remission. And always fighting the fight to get the dose

down to a minimal reasonable level is perfectly valid.

Dr. Spechler: Peter what do you think of the recent study

showing that the PPIs themselves can induce symptoms when

you stop them because of acid hypersecretion?

Dr. Kahrilas: Yes I the issue is whether or not by

treating somebody with a PPI you create a circumstance of

hypergastrinemia so that when you stop the PPI all this

gastrin stimulates more acid secretion and whether youve

not made somebody into a symptomatic reflux patient as a

result of treating them with a PPI. There is there was a

paper published a couple months ago to that effect. But if

one looks at the magnitude of change that they observed I

would grade it as a fairly trivial change. So I dont think

this is playing out in the clinical community. I think its

again in the family of observations that is true but on the

other hand probably not robust enough to explain a lot of

what we see.

So we agree with that one. We talked about

this a little bit before as far as the extra esophageal

symptoms when I was going through the Montreal definition.

Again these are those with established association and

these are with proposed association over here. And when it

comes to maintenance therapy for typical esophageal reflux

symptoms with or without esophagitis, extra esophageal

reflux syndromes (asthma, laryngitis, cough) should

antisecretory therapy be decreased or discontinued? And one

looks at the associated risks. Im not sure what this slide

is there. Nice slide. All right. But this question must


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pertain to it. Under what conditions should antisecretory

therapy be decreased or discontinued? Patients report

likely adverse effects, headache, diarrhea, not experienced

prior to taking PPIs. The patient has been taking PPIs for

a prolonged period, years, and is relatively symptom free.

It is unclear why the patient is taking PPIs. The patient

was started on twice daily PPI before once daily dosage was

tried. All of the above. So its decreased or discontinued.

Yes, I think these are all valid and theyre all commonly

encountered as well. Certainly these are the most likely

two side effects from PPI. Headache, diarrhea, you can

argue whether or not one PPI is more likely to cause one

than the other. The third I believe is abdominal pa

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