CARE Initiative™ on

GI M
Motility
tilit Disorders
Di d
in Primary Care:
GERD

1
Course Director
ƒ Lawrence J. Brandt, MD, MACG, AGAF, FASGE,
FACP, FAACH
Emeritus Chief, Division of Gastroenterology
Montefiore Medical Center and
Albert Einstein College of Medicine
Professor of Medicine and Surgery
g y
Albert Einstein College of Medicine
New York, New York

2
Faculty
y
ƒ John Allen, MD, MBA, AGAF
Medical Director for Quality
Minnesota Gastroenterology
Chair, AGAI Clinical Practice and Quality Management Committee
Clinical Councillor, AGA Governing Board

ƒ Peter J. Kahrilas, MD, AGAF

Gilbert H. Marquardt Professor of Medicine
Northwestern University Feinberg School of Medicine
Lead author of AGA guidelines
ƒ Stuart Spechler,
p , MD,, AGAF
Chief, Division of Gastroenterology, Dallas VA Medical Center
Professor of Medicine, Berta M. and Cecil O. Patterson Chair in
Gastroenterologygy
University of Texas Southwestern Medical Center at Dallas
3
Accreditation and Funding
ƒ This activity has been planned and implemented in
accordance with the Essential Areas and Policies of
the Accreditation Council for Continuing Medical
Education (ACCME) through joint sponsorship of
Albert Einstein College of Medicine
Medicine, Gullapalli &
Associates LLC, Medikly®, and PeerView Academic
Network. Albert Einstein College of Medicine is
accredited by the ACCME to provide continuing
medical education for physicians.
ƒ This activity is funded through an educational grant
from Takeda Pharmaceuticals North America, Inc.

4
Sponsorship
p p
ƒ Co-sponsored by: Albert Einstein College of
Medicine The American Gastroenterological
Medicine,
Association, DIME, and PeerPoint Medical
Education Institute, LLC
ƒ Jointly sponsored by: Albert Einstein College of
Medicine, Montefiore Medical Center, Gullapalli
& Associates, LLC,
C Medikly, and PeerView
Academic Network

5
Conflict of Interest Statement
ƒ The “Conflict of Interest Disclosure Policy” of Albert Einstein
College
g of Medicine requires that faculty y participating
g in any
y
CME activity disclose to the audience any relationship(s) with
a pharmaceutical, product, or device company. Any
presenter whose disclosed relationships prove to create a
conflict of interest with regard to their contribution to the
activity will not be permitted to present.
ƒ The Albert Einstein College of Medicine also requires that
faculty participating in any CME activity disclose to the
audience when discussing any unlabeled or investigational
use o
of a
anyy co
commercial
e ca p product
oduc oor de
device
ce not
o ye
yet app
approved
o ed for
o
use in the United States. The Albert Einstein College of
Medicine CCME staff has no conflicts of interest with
commercial interests related directlyy or indirectlyy to this
educational activity.
6
Faculty
y Disclosures
John Allen, MD, MBA, AGAF
Sources of Funding for Research: None
Consulting Agreements: Medtronic, Inc.
Speakers’ Bureau/Honorarium Agreements: None
Financial Interests/Stock Ownership: None
Discussion of Off-Label, Investigational, or Experimental Drug Use: None

Lawrence J. Brandt, MD, MACG, AGAF, FASGE, FACP, FAACH

Sources of Funding for Research: None
Consulting Agreements: None
Speakers’
p Bureau/Honorarium Agreements:
g None
Financial Interests/Stock Ownership: None
Discussion of Off-Label, Investigational, or Experimental Drug Use: None

7
Faculty
y Disclosures (cont)
( )
Peter J. Kahrilas, MD, AGAF
Sources of Funding for Research: National Institutes of Health
Consulting Agreements: AstraZeneca Pharmaceuticals LP; Revalesio
Corporation; XenoPort, Inc.
Speakers’ Bureau/Honorarium Agreements: None
Financial Interests/Stock Ownership: None
Discussion of Off-Label, Investigational, or Experimental Drug Use: None

Stuart Spechler, MD, AGAF

Sources of Funding for Research: AstraZeneca Pharmaceuticals LP;
Takeda Pharmaceuticals; BARRX Medical, Inc.
Consulting Agreements: Procter & Gamble
Speakers’ Bureau/Honorarium Agreements: None
Financial Interests/Stock Ownership: None
Discussion of Off-Label, Investigational, or Experimental Drug Use: None
8
Planning
g Committee
Rosalee Blumer, MA
DIME Editor
Sources of Funding for Research: None
Consulting Agreements: None
Speakers’ Bureau/Honorarium Agreements: None
Financial Interests/Stock Ownership: None
Discussion of Off-Label, Investigational, or Experimental Drug Use: None

Steven Jay Feld

CCME of Albert Einstein College of Medicine
Sources of Funding for Research: None
Consultingg Agreements:
g Procter & Gamble
Speakers’ Bureau/Honorarium Agreements: None
Financial Interests/Stock Ownership: Bioheart, Inc.; Chelsea Therapeutics, Inc.;
Pharmacopeia, Inc.
Discussion of Off-Label, Investigational, or Experimental Drug Use: None
Planning
g Committee ((cont))
Bonny McClain, MS, DC
Gullapalli & Associates Editor
Sources of Funding for Research: None
Consulting Agreements: None
Speakers’ Bureau/Honorarium Agreements: None
Financial Interests/Stock Ownership: None
Discussion of Off-Label, Investigational, or Experimental Drug Use: None

Charles E
E. Willis
Willis, MBA
The AGA Institute
Sources of Funding for Research: None
Consultingg Agreements:
g Procter & Gamble
Speakers’ Bureau/Honorarium Agreements: None
Financial Interests/Stock Ownership: None
Discussion of Off-Label, Investigational,
g or Experimental
p Drug
g Use: None
The staff of CCME of Albert Einstein College of Medicine,
The American Gastroenterological Association,
Gullapalli & Associates, and DIME have no conflicts
of interests to report with commercial interests related
directly or indirectly to this educational activity
activity.
Continuing Education Credit
ƒ Albert Einstein College of Medicine designates this
educational activity for a maximum of 4.0 AMA PRA
Category 1 Credits™. Physicians should only claim
credit commensurate with the extent of their participation
y
in the activity.

ƒ Participants must complete and return the evaluation

form at the conclusion of this activity to receive credit.

ƒ Certificates will be available online. Please visit

www medikly com/gerd to complete the evaluation and
www.medikly.com/gerd
receive your certificate.

12
Primary Care Management of
GI Motility Disorders: GERD
ƒ Overview
– Multidisciplinary, multi-interventional educational
program that provides relevant and concise
information intended to measurably identify
identify,
validate, and address the gaps and barriers
related to gastroesophageal reflux disease
(GERD) care in the primary care setting
ƒ Multiple
p educational activities
– Educational outreach program; 3 regional
workshops; Performance Improvement activity;
e-monograph;h andd
websitewww.medikly.com/gerd 13
Learning Objectives
On completion
p of this activity,
y pparticipants
p should be
able to:
ƒ Identifyy risk factors for GERD
ƒ Demonstrate multidisciplinary management of
patients with GERD, highlighting appropriate
referral and surgical options
ƒ Select appropriate therapeutic interventions for the
management of patients at risk for or diagnosed
with GERD
14
Agenda
Welcome and Introduction

GERD Case Study 1: Carol

American Gastroenterological Association Institute (AGAI)

2008 Guideline Recommendations

GERD Case Study 2: Jim

Question and Answer Session

15
Audience Response System (ARS)
ƒ When instructed, press the number
button(s)
( ) that correspond
p with yyour selected
answer (you do not need to press Enter)
ƒ Individual responses
p will be displayed
p y in the
screen at the top of the keypad
ƒ If y
you want to change
g yyour answer,, press
p
the C key to clear; you may enter a new
answer as long as voting is open
ƒ Audience results will be displayed on your
main screen immediately after voting is
closed
Performance Improvement and
GERD

17
The Need for Performance Improvement
ƒ Performance Improvement (PI) is designed to measure
and demonstrate ppractice p
process changes
g that are
linked by evidence to improved patient outcomes
ƒ Selected activities will integrate
g a continuous p
process by
y
which a provider or a practice environment participates
in the following:
– Uses th
U the llatest
t t GERD guidelines
id li ffor iimprovedd patient
ti t care
– Improves provider–patient communication
– Assesses baseline knowledge g regarding
g g the GERD g guidelines
– Learns about specific performance measures
– Retrospectively assesses their clinical practice
– Applies performance improvement metrics prospectively over a
useful interval and re-evaluates performance
CARE Initiative on GI Motility Disorders in
Primary Care: GERD

ƒ Patient-related
P ti t l t d b barriers
i
ƒ From the p
patient’s p
perspective,
p , there are
challenges and barriers to meeting GERD
diagnosis and treatment needs:
– Lack of awareness about GERD
– The psychological impact of GERD
– Polypharmacy
– Poor adherence
CARE Initiative on GI Motility Disorders
in Primary Care: GERD (cont)
ƒ Provider-related barriers in the p
primary
y care of GERD
ƒ Although many providers are involved in the management of
GERD, they experience barriers to optimal care for their
GERD patients, including:
– Burden of care assigned to PCPs
– Poor adherence to guidelines for diagnosis and treatment in
primary care
– Patients’ psychological resistance to long-term treatment with
pharmaceuticals
– Difficulties in referral to gastroenterologists
– Financial challenges
 How Can I Improve
p Patient Outcomes?
• To begin
g evaluating
g and p
potentially
y improving
p g
patient care:
1. Go to www.medikly.com/gerd
2. Fill out a brief baseline self-assessment survey
3. Gather appropriate patient-level data (based on identified
performance
f measures)) retrospectively
t ti l or prospectively
ti l
on 10 GERD patients
4 Review tools and resources
4.

No HIPAA Concerns

HIPAA = Health Insurance Portability and Accountability Act

 Participant Support and Recognition
ƒ Live support will be available throughout the initiative
ƒ All communication will be confidential
ƒ To self
self-assess
assess your practice patterns
patterns, you will receive
a quantitative report of the data you submitted
ƒ Initiative findings will be described and discussed in
an article that will be submitted to a peer-reviewed
journal that focuses on improving patient care
nationally
ti ll
ƒ You will receive up
p to 20.0 AMA PRA Category
g y1
Credits™ for successful completion of the program
*Registrants must complete the entire program to receive the maximum available 
CME/CNE credit  
 How interested would you be to participate in a
Performance Improvement activity that would allow
you to do the following for your practice?:
ƒ Assess your practice performance against nationally recognized measures.
ƒ Compare your practice performance to your peers on a local, regional and
national level.
level
ƒ Compare your performance to other healthcare providers and specialists.
(Receive up to 20 CME/CE credits)

Very Interested, Not at all

interested tell me more interested
1 2 3 4 5 6 7

0 / 100 Label
Cross-Tab
Do you have additional questions?

Please speak
p to p
personnel on site
or call a PeerPoint
p
Performance Improvement
site coordinator:

800.777.5790
 Please turn off
cellphones and pagers while
participating in today’s activity.

Please refrain from photography

or recording.
recording

Thank you.
you
25
Your Presenters for Today
Peter J. Kahrilas, MD, AGAF
Gilbert H
H. Marquardt Professor of Medicine
Northwestern University Feinberg School of Medicine
Lead author of AGA guidelines

Stuart Spechler, MD, AGAF

Chief,, Division of Gastroenterology,
gy, Dallas VA Medical Center
Professor of Medicine, Berta M. and Cecil O. Patterson Chair
in Gastroenterology
University of Texas Southwestern Medical Center at Dallas
ARS Question ?
ƒ What is your specialty?
1. Internal medicine
2. Family practice
3. General practitioner
4. Physician assistant
5. Physical medicine
6. Gastroenterologist
g
7. Other
ARS Question ?
ƒ Which of the following best describes your
type of practice?
1. Private (individual)
2 Private
2. P i t (partnership
( t hi or group))
3. Hospital-based
4. HMO
5. VA
6. Other
GERD C
Case St
Study
d 11: C
Caroll

29
Case Study: Carol
ƒ Carol, a 37-year-old African American
woman presents to PCP with a complaint
woman,
of heartburn and occasional regurgitation
of food or fluids into her mouth
ƒ Ht 5’2”, W 148 lbs, BMI 27
ƒ Cor: Regular rhythm and normal rate
ƒ Labs: Normal, including hemoglobin 13
g/dL,, hemocrit
g/d e oc t 42%
%
ƒ Current meds: inhaler
ƒ Existing
E i ti conditions:
diti asthma,
th hi
hiatal
t lhhernia
i
30
ARS Question ?
ƒ On a scale of 1 to 5, with 1 being “not
confident at all,” and 5 being “extremely
confident,” how would you rate your
confidence
fid in
i treating
t ti Carol?
C l?
1. Not at all confident
2. Somewhat confident
3. Confident
4. Very confident
5
5. Extremely confident
31
ARS Question ?
ƒ When initially treating patients with symptoms
of heartburn and regurgitation, which approach
do you typically take?
1. Recommend lifestyle modifications
2 Step
2. Step-up
up approach
approach, ieie, start with histamine 2 receptor
antagonists [H2RAs] and move up to proton pump
inhibitors (PPIs) if symptoms persist
3. Step-down approach, ie, start with PPI therapy
4. None of the above
32
Clinical Practice Key Points

Participants perspectives on individual

Participants’
practice environment
 American Gastroenterological Association
I tit t (AGAI)—
Institute (AGAI)
2008 Guideline Recommendations
ƒ For patients with esophageal GERD syndromes, treatment
with antisecretory drugs is recommended for healing
esophagitis, symptomatic relief, and maintenance of
esophageal healing. In this setting, PPIs are more
effective than H2RAs,, which,, in turn,, are more effective
than placebo
– Grade A: strongly recommended based on good
e de ce
evidence

34
Kahrilas P et al. Gastroenterology. 2008; 135:1392-1413.
 American Gastroenterological
Association Institute (AGAI)—
2008 Guideline Recommendations

35
 AGAI 2008 Guidelines

36
Kahrilas P, Shaheen N, Vaezi M. American Gastroenterological Association Institute Technical Review on the
Management of Gastroesophageal Reflux Disease. Gastroenterology. 2008;135:1392-1413.
Standards of Care for Assessing Evidence
G id li
Guidelines ffor GERD
ƒ The U
U.S.
S does not have an agency to validate
guidelines, ie, the US does not put a priority on which
guidelines to use
ƒ This process is being refined and may be part of
healthcare reform, but we are not there yet
ƒ AGAI guidelines use US Preventive Services
Task Force (USPSTF) grades to assign strength of
evidence
id

37
 USPSTF Grades Used
in AGAI Guidelines
Grade A: strongly recommended based on good evidence that it
improves important health outcomes
Grade B: recommended with fair evidence that it improves
important outcomes
Grade C: balance of benefits and harm is too close to justify a
general recommendation
Grade D: recommend against; fair evidence that it is ineffective
or that harms outweigh benefits
Grade Insufficient: no recommendation; insufficient evidence to
recommend for or against

38

Kahrilas P, Shaheen N, Vaezi M. Gastroenterology. 2008;135:1392-1413.

The Difficulty of Defining GERD

39
Symptoms of Gastroesophageal
R fl Di
Reflux Disease (GERD)
ƒ Classic
Cl i symptoms
t
– Heartburn
– Regurgitation
ƒ Common symptoms
– Chest pain (noncardiac)
– Dysphagia

Source: US National Library of Medicine,

National Institutes of Health

40
 GERD: The Montreal Definition
GERD is a condition that develops when the reflux of stomach content
causes troublesome symptoms and/or complications

Esophageal syndromes Extra-esophageal syndromes

Symptomatic Syndromes With Established Proposed

Syndromes Esophageal Injury Association Association
• Typical reflux • Reflux esophagitis • Reflux cough • Sinusitis
syndrome • Reflux stricture • Reflux • Pulmonary
• Reflux chest • Barrett’s laryngitis fibrosis
pain syndrome esophagus • Reflux asthma • Pharyngitis
• Adenocarcinoma • Reflux dental • Recurrent otitis
erosions media

41
Adapted from Vakil N et al. Am J Gastroenterol. 2006;101:1900-1920.
 What is the Distinction Between
GERD and Episodic Heartburn?
ƒ In the absence of esophageal injury,
heartburn of sufficient intensityy to be
perceived as troublesome by the patient
(after assurance of its benign nature)
meetst the
th Montreal
M t l definition
d fi iti off a
symptomatic esophageal GERD syndrome

42
Kahrilas P et al. Gastroenterology. 2008; 135:1392-1413.
Vakil N et al. Am J Gastroenterol. 2006;101:1900-1920.
PCP Review of the Pathophsysiology of GERD
External factors Tissue resistance
• Diet • Stratified squamous epithelium
• Medication • Bicarbonate secretion
• Smoking
• Obesity
Esophageal clearance
• Motility (peristalsis)
• Body position (gravity)
Gastric emptying

Antireflux barriers
• LES
• Crural diaphragm
• Hiatal hernia

Gastric refluxate
• Acid
• Pepsin
• Bile Acids

43
ARS Question ?
ƒ What is/are your goal(s) when
treating a patient such as Carol
who has typical symptoms of
GERD?
1. Relieve the symptoms
2. Prevent relapse and complications
3. Heal the esophagus
4. All of the above
5 1 and 2
5.
44
Goals of Treatment: AGAI Guidelines
ƒ Relieve symptoms
y p
ƒ Prevent relapse and complications
ƒ Heal the esophagus in patients with
erosive esophagitis

45
ARS Question ?
ƒ What are the next steps in
diagnosing Carol?
1 Once-daily
1. O d il PPI ttrial
i l
2. Endoscopy
3. Manometry
4. p
pH monitoring
g
5. Refer to gastroenterologist
6 Other
6.
46
 Diagnosis of Uncomplicated GERD:
AGAI Guidelines
G id li
ƒ Current consensus: empirical
PPI therapy is appropriate for
patients with uncomplicated
p p
heartburn such as Carol’s
ƒ In uncomplicated GERD
GERD, no
need exists for endoscopy or
upper GI studies (this would
require immediate referral to
a specialist)
47

Kahrilas P et al. Gastroenterology. 2008;135:1392-1413.

Diagnosis of Uncomplicated GERD:
AGAI Guidelines (cont)
ƒ Although Carol has
coexisting
g conditions,, her
case qualifies as
uncomplicated GERD
because she has no
warning signs

48
ARS Question ?
ƒ Which of the following would be a warning
sign(s) that would warrant endoscopy
and/or immediate referral to a specialist?
1. Weight loss
g
2. GI bleeding
3. Loss of appetite
4 Chest pain
4.
5. Dysphagia
6. All of the above
49
Carol’s Risk Factors for GERD
ARS Question ?
ƒ Which of the following is/are
( ) for GERD?
risk factor(s)
1. Overweight
2 Asthma
2. A th
3. Hiatal hernia
4. None of the above
5. 1,, 2,, and 3
50
Clinical Practice Key Points

Participants’ perspectives on individual practice

environment
ARS Question: ?
Extraesophageal Syndromes
ƒ Carol has a history of asthma
asthma, which may be
classified as an extraesophageal syndrome, as
well as laryngitis. If Carol did present with adult-
onset asthma or laryngitis concomitant with any
common or uncommon symptoms of GERD,
should she be treated for GERD?
1. Yes
2 No
2.
3. Depends on physical examination
4. Not sure 52
 Treatment of Extraesophageal Reflux
Syndromes: AGAI Guideline
Recommendations

ƒ Acute or maintenance therapypy with once- or twice-daily

y
PPIs (or H2RAs) for patients with a suspected
extraesophageal GERD syndrome (laryngitis, asthma)
with a concomitant esophageal GERD syndrome
– Grade B: recommended with fair evidence that it
improves important outcomes

53

Kahrilas P et al. Gastroenterology. 2008;135:1392-1413.

 Treatment of Extraesophageal Reflux
S d
Syndromes: AGAI Guideline
G id li
Recommendations (cont)

ƒ Once- or twice-daily PPIs (or H2RAs) for acute

t
treatment
t t off patients
ti t with
ith potential
t ti l extraesophageal
t h l
GERD syndromes (laryngitis, asthma) in the absence
of a concomitant esophageal GERD syndrome
– Grade D: recommend against; fair evidence that it
is ineffective or that harm outweighs benefits

54

Kahrilas P et al. Gastroenterology. 2008;135:1392-1413.

 Treatment of Extraesophageal Reflux
S d
Syndromes: AGAI Guideline
G id li
Recommendations (cont)

ƒ Once- or twice-daily PPIs for patients with suspected

reflux
fl cough h syndrome
d
– Grade Insufficient: no recommendation; insufficient
evidence to recommend for or against

55

Kahrilas P et al. Gastroenterology. 2008;135:1392-1413.

ARS Q
Question
ti ?
ƒ Which of the following might help improve
Carol’s GERD symptoms?
1 Weight loss
1.
2. OTC antihistamines
3. Change in diet
4. All of the above
5. None of the above

56
Nonpharmacologic Approaches

57
 AGAI 2008 Guideline Recommendation

ƒ Weight loss is advised for patients who are overweight

or obese (or who have recently gained weight) and who
have esophageal GERD syndromes
– Grade B: recommended with fair evidence that it
improves important outcomes

58

Kahrilas P et al. Gastroenterology. 2008;135:1392-1413.

 BMI Associated With Symptoms of GERD in Normal
Weight and Overweight Women
Association Between BMI and GERD Symptoms in Women

35
3.5 Healthy Weight Overweight Ob
Obese
3
2.93 (2.24–3.85)
P<0.001
25
2.5
2.92 ((2.35–3.62))
Multi- 2.43 (1.96–3.01)
variate 2
2.20 (1.81–2.66)
Odds
Ratio 15
1.5

------------------------------------------- 1.38 (1.13–1.67)

---------------- ----------------------------------------------
1

05
0.5
0.67 (048–0.93)
0

<20.0 20.0–22.4 22.5–24.9 25.0–27.4 27.5–34.9 30.0–34.9 >35.0

Body Mass Index 59

Adapted from Jacobson BC et al. N Engl J Med. 2006;354:2340-2348.

 Study Findings
ƒ BMI is associated with symptoms of
GERD in both normal weight and
overweight
g women
ƒ Even moderate weight gain among
persons of normal weight may cause or
exacerbate symptoms of reflux

60

Jacobson BC et al. N Engl J Med. 2006;354:2340-2348.

Lifestyle Modifications
ƒ Avoid foods that may
precipitate reflux
– Coffee, alcohol, chocolate,
fatty foods
ƒ Avoid acidic foods that may
precipitate heartburn
– Red sauce,, tomatoes,, citrus,,
carbonated drinks, spicy foods

61
Lifestyle Modifications (cont)
ƒ Adopt behaviors that may reduce
esophageal exposure
– Avoid late-night
late night meals and bedtime snacks
– Raise the head of the bed
– Stop
p smoking g
– Weight loss

62
Lifestyle Modifications: AGAI Guideline
ƒ Except for weight loss, evidence for lifestyle
modifications
difi ti (including
(i l di smoking)
ki ) iis generally
ll
weak
ƒ H
However, modifications
difi ti tailored
t il d tto each
h patient’s
ti t’
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

63
 Contributing Conditions:
The Role of Hiatal Hernia in GERD

64
What is the Role of Hiatal Hernia in GERD?
ƒ Promotes reflux of stomach contents (via its direct
and indirect actions on the antireflux mechanism)
and thus is associated with GERD
ƒ In this way,
way hiatal hernia is associated with the
potential consequences of GERD: heartburn,
esophagitis, Barrett’s esophagitis, and esophageal
cancer
ƒ However, the role attributed to hiatal hernia is
variable and difficult to quantify

65
 Axial Hiatus Hernia is Commonly Associated
With GERD,
GERD E Especially
i ll Wh
When S
Severe

Type I hiatal hernia.

In this example, the
herniated gastric cardia is
evident at rest, after
completion of esophageal
emptying.

66
Kahrilas, PJ, Pandolfino JE. Hiatus hernia. In: Castell DO, Richter JE, eds. The Esophagus. 4th ed.
Philadelphia: Lippincott Williams & Wilkins, 2004:389-407.
Two-Sphincter Model of the
Esophagogastric Junction
LES relaxation Squamocolumnar junction
LES relaxation

CD incompetence?
CD relaxation

Right
crus

Normal Hi t l hernia
Hiatal h i

67
 Muscular Anatomy
y of the EGJ

Longitudinal m.
Spiral m.
Sling
g
fibers

Clasp
fibers

68
PJ Kahrilas 2004.
 The “Flap Valve” Concept of EGJ Disruption
Grade I Grade II Grade III Grade IV

Normal ridge of Ridge is slightly Ridge is effaced Hiatus is wide open at

tissue closely less well defined and the hiatus is all times and displaced
approximated to the andd opens with
ith patulous
t l
scope axially
respiration
69

Adapted from Hill LD et al. Gastrointest Endosc 1996;44:541-547.

 Radiographic Appearance of a Small Sliding
Hiatal
ata Hernia
e a During
u gS Swallowing
a o g
Tubular Esophageal
Esophagus Vestibule

Phrenic Ampulla
Sliding Hiatal
Hernia
“A” ring

“B” ring

Rugal Folds
Diaphragmatic Traversing Hiatus
impression
70

Kahrilas PJ and Pandolfino JE. GI Motility Online. 2006;doi:10.1038/gimo48.

 Type I (Sliding) and Type II (Paraesophageal)
Hiatus Hernia
Squamocolumnar
junction
Esophagus Esophagus
Phreno-
Phreno-
esophageal Herniated
Herniated
membrane gastric fundus
stomach

Herniated
parietal
p
peritoneum

Diaphragm Diaphragm
Squamocolumnar
junction (normal position)

71
Modified from Jaffee BM, Surgery of the esophagus. In Orlando RC Ed. Atlas of Esophageal
Diseases, Second Edition. pp 223–242.
Pharmacologic Treatments

72
ARS Question ?
ƒ According to AGAI guidelines, which one
of the following agents is never appropriate
in the treatment of GERD?
1. OTC PPIs
p
2. Metoclopramide
3. H2RAs
4 OTC antacids
4.
5. None of the above, they are all appropriate

73
 Available Treatments for GERD
ƒ Promotility agents
– Bethanechol
– Metoclopramide
M t l id (black
(bl k box
b warning;
i see following
f ll i slide
lid for
f AGAI
recommendation)
ƒ Histamine2 receptor antagonists (H2RAs)
– Cimetidine
Ci tidi
– Famotidine
– Nizatidine
– Ranitidine
ƒ Proton pump inhibitors (PPIs)
– Dexlansoprazole
– E
Esomeprazole
l
– Lansoprazole
– Omeprazole
– Pantoprazole
– Rabeprazole
74

Source: www.fda.gov. Accessed on August 20, 2009.

 Metoclopramide:
AGAI Guideline Recommendation
• Metoclopramide as monotherapy or adjunctive therapy
in patients with esophageal or suspected
extraesophageal GERD syndromes
– Grade D: recommend against; fair evidence that it is
ineffective or harms outweigh benefits

75

Kahrilas P et al. Gastroenterology. 2008;135:1392-1413.

Clinical Practice Key Points

Participants’ perspectives on individual practice

environment
 PPIs and H2RAs:
Comparing Efficacy

77
ARS Question ?
ƒ According g to AGAI gguidelines, which agent
g is most
effective for the treatment of patients with
esophageal GERD syndromes (healing esophagitis
and symptomatic relief)?
1. H2Ra
2 PPI
2.
3. OTC antacids
4. All are equally effective

78
 AGAI 2008
Guideline Recommendation
ƒ Antisecretory drugs for the treatment of patients with
esophageal GERD syndromes (healing esophagitis
and symptomatic relief)
ƒ In these uses, PPIs are more effective than H2RAs,
which are more effective than placebo
– Grade A: strongly recommended based on good
evidence

79

Kahrilas P et al. Gastroenterology. 2008;135:1392-1413.

ARS Question ?
ƒ Which
Whi h off the
th following
f ll i agentst h
has th
the
most rapid speed of healing?
1. H2RAs
2 OTC antacids
2.
3. PPIs
4 Onset
4. O t off action
ti isi about
b t the
th same for
f each
h

80
 Speed of Healing GERD: PPIs vs H2RAs
Speed of healing GERD expressed as the mean percentage of
healing per week for each drug class at evaluation time points

Placebo
35
30 PPI
Healed/week
H2RA
(%) 25

20

15

10
5
0
2 4 6 8 12
Weeks
ƒ With longer treatment
treatment, PPIs continue to heal GERD faster than H2RAs, RAs
but the speed of healing falls off as fewer patients are left to be healed81
Adapted from Chiba N et al. Gastroenterology. 1997;112:1798-1810.
ARS Question ?
ƒ According
A di tto th
the AGAI guidelines,
id li which
hi h
of the following agents heal(s) more
patients in the longer term?
1. PPIs
2. H2RAs
3. Promotility agents
4. A and B are equal

82
 Healing-time Curve: PPIs vs H2RAs vs Placebo
100
(3) (2)
(26)
PPI
80
% Total healed

(27)
(4)
(22)
60
(25)
H2RA
(25)
40 (23)
(9)
(2)
(5) Placebo
20 (5)
(8)

0
2 4 6 8 12
Time in weeks

ƒ By
y week 4, PPIs heal more ppatients than H2RAs and continue to do so
even after 12 weeks of treatment (number of studies is shown in
parentheses) 83

Adapted from Chiba N et al. Gastroenterology. 1997;112:1798-1810.

 Percentage of Symptom-Free Patients
for PPIs and H2RAs
40
PPI
Heartburn-
free/week 30 H2RA
(%)
20

10

1–2 3–4 6–8

Time in Weeks
With longer therapy, PPIs continue to relieve heartburn faster than
H2RAs,, but the speed
p of symptom
y p relief falls off as fewer patients
p
remain symptom-free
84

Adapted from Chiba N et al. Gastroenterology. 1997;112:1798-1810.

 Proton Pump Inhibitors
FDA-Approved
FDA Approved Indications for the Treatment of GERD
GERD Omeprazole Esomeprazole Lansoprazole Pantoprazole Rabeprazole Dexlansoprazole

Symptomatic
relief 20 mg daily 20 mg daily 15 mg daily 40 mg daily 20 mg daily 20 mg daily
X 4 weeks X 4 weeks X 8 weeks X 4–8 X 4–8 X 4–8 weeks
weeks
k weeks
k

Healing of
erosive of 40 mg daily 20 or 40 mg 30 mg daily 40 mg daily 20 mg daily 30 or 60 mg
ulcerative X 4–8 weeks daily X 4–8 X 8–16 X 8–16 X 4–8 daily X 4–8
esophagitis weeks weeks weeks weeks weeks

Maintenance
of healing or 20 mg daily 20 mg daily 15 mg daily 40 mg daily 20 mg daily 30 mg daily
erosive or
ulcerative
esophagitis
85 85

Source: www.fda.gov. Accessed on August 22, 2009.

 H2RAs
FDA A
FDA-Approved
d IIndications
di i for
f the
h Treatment
T off GERD

GERD Cimetidine Famotidine Nizatidine Ranitidine

Treatment of 800 mg at night, 20 mg bid for up 150 mg bid for

GERD or in divided to 6 weeks up to 12 weeks 150 mg bid
doses, for up to
12 weeks

Maintenance 800 mg at night, 20 or 40 mg bid 150 mg bid for 150 mg up to 4x

of healing or or in divided for up to 12 up to 12 weeks per day
erosive or doses,, for up
p to weeks
ulcerative 12 weeks
esophagitis

86 86

Source: www.fda.gov. Accessed on September 2, 2009.

Nocturnal Breakthrough Symptoms
of GERD

87
Case Study
y 1: Carol
ƒ After 4 weeks of once-daily
PPI therapy, Carol returns
to your office
ƒ Her symptoms have
improved somewhat,
especially during the day;
however, she wakes up
about
b t 2 nights
i ht a weekk with
ith
heartburn and regurgitation
88
ARS Question ?
ƒ How would you proceed with your
management of Carol’s symptoms?
1. Endoscopy
py
2. pH monitoring
3 Advise as-needed
3. as needed use of OTC antacid
4. Increase PPI to twice a day
5. Refer for surgical consultation
6. None of the above
89
Clinical Practice Key Points

Participants’ perspectives on individual practice

environment
 AGAI Guideline Recommendation

ƒ AGAI guidelines recommend endoscopy to evaluate

patients with a suspected esophageal GERD syndrome
who have not responded to an empirical trial of twice
twice-
daily PPI therapy
– Grade B: recommended with fair evidence that it
i
improves important
i t t outcomes
t

91

Kahrilas P et al. Gastroenterology. 2008;135:1392-1413.

 “Nocturnal
Nocturnal Acid Breakthrough”
Breakthrough
ƒ Defined as the presence of gastric pH
level <4 for at least 1 hour during sleep
–R
Refers
f to
t pH,
H nott symptoms,
t therefore
th f nott
useful for the management of symptoms

92
Katz PO et al. Curbside Consultation: 49 Clinical Questions. Thorofare, NJ: SLACK Inc., 2008.
 Nocturnal Breakthrough
g Symptoms:
y p AGAI
2008 Guideline Recommendation

ƒ There is no evidence of improved long-term efficacy by

adding a nocturnal dose of an H2RAs to twice-daily PPI
therapy
– Grade Insufficient: no recommendation; insufficient
evidence to recommend for or against

93

Kahrilas P et al. Gastroenterology. 2008;135:1392-1413.

 ARS Question ?
ƒ Carol’s symptoms are successfully
managed after 3 weeks on twice-daily
PPI therapy. How would you approach
maintenance therapy?
1 C
1. Continue
ti llong-term
t therapy
th att the
th same
dosage
g
2. Continue long-term therapy
py and titrate down
to the lowest effective dose on the basis of
symptom control
3 Titrate therapy for a few weeks and then
3.
discontinue until symptoms reappear
4. All of the above
5. None of the above 94
Multidisciplinary
M ltidi i li M
Managementt
of Patients With GERD:
Appropriate Referrals

95
Case Study:
y Jim
ƒ 63 years old
ƒ Comorbid conditions: CABG
stent, arthritis, GERD
ƒ Ht 5
5’7
7, Wt 192,
192 BMI 30 (obese)
ƒ Meds: clopidogrel, low-dose
aspirin beta blocker
aspirin,
ƒ Smoker, drinks a 6-pack of beer
2 to 3 times a week
ƒ Presenting symptoms: on twice-
daily
da y PPI but reports
epo ts pe
persistent
s ste t
heartburn 96
ARS Question ?
ƒ Because Jim’s presenting symptom is
persistent heartburn,
heartburn how would you
proceed?
1 Refer him to a gastroenterologist
1.
2. Perform diagnostic tests to rule out cardiac-
related conditions
3. Prescribe an antacid trial to see if it relieves
his symptoms
4. Refer him to a cardiologist

97
ARS Question ?
ƒ Which of the following
medication(s) should be
closely monitored if Jim is
prescribed PPI therapy?
p py
1. Clopidogrel
2 Beta
2. B t blockers
bl k
3. Low-dose aspirin
4. All of the above

98
Clinical Practice Key Points

Participants’ perspectives on individual practice

environment
 Are PPIs Contraindicated in Patients
T ki Clopidogrel?
Taking Cl id l?
ƒ Retrospective
p cohort study
y of 8205 p
patients with
acute coronary syndrome (ACS) taking clopidogrel
after discharge from 127 Veterans Affairs hospitals
between October 1, 1 2003 and January 3131, 2006
ƒ Conclusion: Concomitant use of clopidogrel and PPI
for ACS after hospital discharge was associated with
a higher risk of adverse outcomes than use of
clopidogrel without PPI, suggesting that use of PPI
may be
b associated
i t d with
ith attenuation
tt ti off benefits
b fit off
clopidogrel after ACS

100

Ho PM et al. JAMA. 2009;301:937-944.

 Cumulative Hazard for Death or ACS
0.60
Deaths or 
Recurrent ACS
0.40
ortion of D

0
R
Propo

0.20

None
Clop
PPI
Clop+PPI
0.00

0 90 180 270 360 450 540 630 720 810 900 990 1080

Days Since Discharge
Adapted from Ho PM et al. JAMA. 2009;301:937-944.
 PPIs,, Clopidogrel,
p g , and Cardiovascular
Events: Expert Consensus Statement
ƒ In 2008, the American College of Cardiology
Foundation, the American College of
Gastroenterology and the American Heart
Gastroenterology,
Association recommended that all patients who are
receiving NSAIDs, aspirin, dual antiplatelet therapy,
or concomitant
it t anticoagulant
ti l t therapy
th andd who
h are
at risk for gastrointestinal injury should receive
prophylactic
p p y treatment with a PPI to reduce the risk
of ulcer complications and GI bleeding

Bhatt D et al. J Am Coll Cardiol. 2008;52:1502-1517.

 Conflicting Results
ƒ Several recent publications have reported
conflicting results regarding the clinical
outcomes of patients concurrently taking
p g and a PPI vs clopidogrel
clopidogrel p g alone
ƒ Also, it is unclear if an interaction between
clopidogrel and PPIs would result in any
clinically meaningful adverse outcomes

Rude MK, Chey WD. Gastroenterology. 2009;137:1168-1171.

 Case Study: Jim (cont) ?
ƒ How would you proceed with
Jim’s treatment?
1. Consider surgery
2. Recommend endoscopy
3. Order impedance pH monitoring
4. Switch to a different PPI
5. First ensure that he is taking his
twice-daily PPI therapy at the
appropriate time

104
 AGAI 2008
G id li R
Guideline Recommendation
d ti
ƒ AGAI guidelines recommend endoscopy to evaluate
patients with a suspected esophageal GERD syndrome
who have not responded to an empirical trial of twice-
daily PPI therapy
ƒ Biopsies should target any area of suspected
metaplasia, dysplasia, or malignancy
– Grade B: recommended with fair evidence that it
improves important outcomes

105

Kahrilas P et al. Gastroenterology. 2008;135:1392-1413.

ƒ
ARS Question ?
Jim reports that he is taking his PPI
medication one-half hour before
breakfast and one-half hour before
dinner
ƒ How would you proceed?
1. Endoscopy with or without biopsy
2. Upper GI series
3. Esophageal manometry
4. Ambulatory pH monitoring
5. Impedance-pH monitoring
6. Other
106
Case Study: Jim (cont) ?
ƒ Which of the following
characteristics put Jim at
high risk for Barrett’s
esophagus?
h ?
1. Over 50 years of age
2. White man
3 Obese
3.
4. All of the above

107
Clinical Practice Key Points

Participants’ perspectives on individual practice

environment
 Barrett’s Esophagus:
p g Risk Factors
Group at Highest Risk
Age >50 years
White men
Obese
GERD symptoms
ƒ Early age of onset
ƒ Longer duration ( >5–10 years)

109

Adapted from Katz PO et al. Curbside Consultation: 49 Clinical Questions. Thorofare, NJ: SLACK Inc., 2008.
Ji ’ Di
Jim’s Diagnosis
i
ƒ Jim is sent for an
endoscopy
ƒ Results show Barrett’s
p g with high-
esophagus g
grade dysplasia

110
ARS Question ?
ƒ What are the treatment options for patients
with known Barrett's?
Barrett s?
1. Do nothing
2. Surveillance
3. Antireflux surgery
g y
4. Mucosal ablation
5 Depends
5. D d on existence
i t and
d llevell off d
dysplasia
l i
6. I do not know

111
Clinical Practice Key Points

Participants’ perspectives on individual practice

environment
ARS Question ?
ƒ What are the next steps
for Jim?
1. Referral to a
gastroenterologist if he
isn’t seeing one already
2 Surveillance
2.
3. Antireflux surgery
4. Mucosal ablation
5. Depends
p on existence
and level of dysplasia 113
Barrett’s Esophagus
p g

114
 Barrett’s Esophagus

115

Shaheen NJ. Gastroenterology. 2000;119:333..

 Adenocarcinoma Risk?

Patients with Barrett’s esophagus develop adenocarcinoma at the

rate of approximately 0.5% per year (1 per 200 patients/year). 116

Shaheen NJ. Gastroenterology. 2000;119:333.

 Barrett’s Esophagus and
Adenocarcinoma
ƒ Patients with Barrett's esophagus have an
increased risk of developing esophageal
adenocarcinoma
d i
ƒ The incidence of esophageal
adenocarcinoma is 0.3%–0.5% per patient
year
ƒ However, lifetime incidence in an
individual p
patient may
y be 10%–11%
117
Reid BL et al. Annu Rev Med. 1987;38:477-492.
Eisen GM. Gastrointest Endosc. 2003;58:760-769.
Frequency of Barrett’s Esophagus in
Colonoscopy
Co o oscopy Patients
at e ts With
t aand
d Without
t out Heartburn
ea tbu
9.0%
8.0%
7.0% 2.6% Long-Segment
Barrett’s
6.0%
5.0% 0.4%
4.0%
3.0%
5.2% 5.7% Short-Segment
2.0% Barrett’s
1.0%
0.0%
556 Without 384 With
Heartburn Heartburn 118

Adapted from Rex DK. Gastroenterology. 2003.

 Prevalence of Barrett’s
Barrett s Esophagus
in the General Population of Sweden
ƒ 1000 persons had endoscopy
ƒ 16 (1.6%)
(1 6%) had Barrett’s
Barrett s esophagus
ƒ 9 (56%) had symptoms of GERD

119

Ronkainen J. Gastroenterology. 2005;129:1825.

Metaplasia: Response to Chronic Inflammation
One adult cell type replaces another

GERD

Stratified Squamous Specialized Intestinal

Epithelium Metaplasia
(Normal Esophagus) (Barrett’s Esophagus)
120
Histological Features of Dysplasia
in Barrett’s
Barrett s Esophagus
Nuclei show
enlargement,
g
pleomorphism,
hyperchromatism,
stratification,
atypical mitoses

Villiform surfaces
and tubules show
crowding

121

No Dysplasia Dysplasia
Estimates of Annual Cancer Incidence for
Patients with Barrett’s
Barrett s Esophagus 2008
• All patients: 0.5%
0 5%
• Shaheen. Gastroenterology. 2000;119:333.

• Low-Grade Dysplasia: 0.6%

• Sharma. Clin Gastroenterol Hepatol. 2006;4:566.

• High-Grade
High Grade Dysplasia: 6%–7%
6% 7%
• Spechler. Am J Gastroenterol. 2005;100:927.
• Rastogi. Gastrointest Endosc. 2008;67:399.

122
Endoscopic Screening and Surveillance
for Barrett’s Esophagus: Pros
ƒ B
Barrett’s
tt’ with
ith cancer is
i iincreasing
i iin
frequency
ƒ Computer models suggest benefit
ƒ Most observational studies suggest benefit
ƒ No study shows physical harm

123
Endoscopic Screening and Surveillance
for Barrett’s Esophagus: Cons
ƒ Endoscopy is expensive
ƒ No proof that these procedures improve
survival
ƒ No
opproof
oo likely
e y in the
e near
ea future
uue

124
 ARS Question
ƒ
?
As previously noted, Jim has been
diagnosed with Barrett’s esophagus and
high-grade dysplasia
dysplasia. If
If, however
however, no
dysplasia is found on 2 endoscopies within
1 year, which would be the appropriate next
step?
t ?
1. Surveillance endoscopy every year
2. Surveillance endoscopy every 6 months
3. Surveillance endoscopy with biopsy
every 3 years
4. No future surveillance endoscopy
needed 125

Wang KK et al. ACG Practice Parameters Committee. Am J Gastroenterol. 2008;103:788.

 ARS Question ?
ƒ If Jim had low-grade dysplasia, how
would you proceed?
1. When dysplasia is first noted,
repeat endoscopy and biopsy
within 6 months
2 Have diagnosis confirmed by
2.
expert pathologist
3 Yearly endoscopy until no
3.
dysplasia is seen on 2
consecutive endoscopies
4. All of the above 126

Wang KK et al. ACG Practice Parameters Committee. Am J Gastroenterol. 2008;103:788.

ƒ
ARS Question ?
Which of the following would be
an appropriate step(s) in the
management of Jim’s
Jim s high-grade
dysplasia?
1 Have diagnosis confirmed by
1.
an expert pathologist
2 Repeat endoscopy within 3
2.
months
3. Consider options of intensive
surveillance (Q 3 months),
EMR, endoscopic ablation,
esophagectomy
127
4. All of the above
Clinical Practice Key Points

Participants’ perspectives on individual practice

environment
 Appropriate Management of High-Grade
Dysplasia in Barrett’s
Barrett s Esophagus
Have diagnosis confirmed by an expert pathologist

Repeat endoscopy within 3 months;

q
4-quadrant biopsies
p at 1-cm intervals;;
mucosal irregularity should have EMR

Consider
C id options
ti off iintensive
t i surveillance
ill (Q 3 months);
th )
EMR; endoscopic ablation; esophagectomy

Individualize treatment

129

Wang KK. ACG Practice Parameters Committee. Am J Gastroenterol. 2008;103:788.

ARS Question ?
ƒ Jim experiences hoarseness, which may
be an extraesophageal symptom of
GERD. Which of the following is not a
potential extraesophageal symptom of
GERD?
1 Globus sensation
1.
2. Neck pain
3. Chronic cough
4. Halitosis
130
Extraesophageal
p g Symptoms
y p of GERD

ƒ Globus sensation ƒ Bronchitis

ƒ Hoarseness ƒ Chronic cough
ƒ Laryngitis ƒ Dental erosions
ƒ Sinusitis ƒ Halitosis

131
Maintenance Therapy
py
ƒ Typical esophageal reflux syndrome
(with or without esophagitis)
ƒ Extraesophageal reflux syndromes
(asthma, laryngitis, cough)
ƒ Should antisecretory therapy be
decreased or discontinued?
– Associated risks

132
ARS Question ?
ƒ Under what condition(s) should antisecretory
therapy be decreased or discontinued?
1. Patient reports likely adverse effect (headache,
diarrhea) not experienced prior to taking PPIs
2. Patient has been taking PPIs for a prolonged
period (years) and is relatively symptom-free
3. It is unclear why the patient is taking PPIs
4. The patient was started on twice-daily PPI before
once-daily dosage was tried
5. All off the
h above
b
133
 AGAI Guideline Recommendation

• Once PPIs have proven to be clinically effective for the

treatment of patients with esophagitis, therapy should be
continued long
long-term
term and titrated down to the lowest
effective dose on the basis of symptom control
• Grade A: strongly recommended based on good evidence

134

Kahrilas P et al. Gastroenterology. 2008;135:1392-1413.

Clinical Consequences
q
of Long-term Acid Inhibition
ƒ Screening for potential adverse effects
– Bone density studies?
– Calcium supplementation?
– H. pylori screening?

135
 Clinical Consequences
q
of Long-term Acid Inhibition (cont)
ƒ Dependency?
– Recent study in Gastroenterology: treatment
with PPIs for 8 weeks may induce rebound
acid-related symptoms upon discontinuance
off the
th PPI

136

Reimer C et al. Gastroenterology. 2009;137:80-87.

ARS Question ?
Role of Endoscopy in the Long-term
g
Management of GERD
ƒ When should endoscopy be used as a tool for
evaluating treatment failure or risk management?
1. Every 5 years
2. When a patient reports occasional breakthrough
heartburn usually associated with eating late meals
heartburn,
3. When the patient reports the new sensation of food
sticking in his esophagus
4. Every 10 years
5. When the patient was begun on empiric PPI therapy and
h 80% resolution
has l ti off h
heartburn
tb after
ft 2 weeks
k off th
therapy
137
Case Study: Jim—Antireflux Surgery

ARS Question ?
ƒ Under what conditions should
antireflux surgery be recommended
for a patient like Jim?
1. Never
2. If Jim has worsening symptoms
3. After 2 years of PPI therapy,
because it is safer
4. If Jim cannot tolerate acid
suppressive
i th
therapy, even if it iis
effective 138
Clinical Practice Key Points

Participants’ perspectives on individual practice

environment
 Surgery vs Acid-Suppressive Therapy:
AGAI Guidelines
G id li
• Antireflux surgery should be recommended when a
patient with esophageal GERD syndrome cannot
tolerate acid-suppressive therapy, even if pharmacology
is effective
• When treatment with antireflux surgery or PPIs is
thought to be similarly effective in a patient with
esophageal GERD syndrome, PPI therapy is considered
safer and is therefore preferred as initial treatment
• Grade A: strongly
g y recommended based on g good
evidence

140

Kahrilas P et al. Gastroenterology. 2008; 135:1392-1413.

Question and Answer
S
Session
i

141