Gastroesophageal Reflux Disease

Gastroesophageal Gastroesophageal Reflux DiseaseReflux Disease

Gastroesophageal Gastroesophageal Reflux DiseaseReflux Disease

Professor of MedicineProfessor of MedicineCleveland Clinic Lerner College of Medicine of Cleveland Clinic Lerner College of Medicine of

Case Western Reserve UniversityCase Western Reserve UniversityDepartment of Gastroenterology & HepatologyDepartment of Gastroenterology & Hepatology

Taussig Cancer CenterTaussig Cancer CenterUSAUSA

Gary W. Falk, M.D., M.S.Gary W. Falk, M.D., M.S.

DisclosuresDisclosures

• Grant supportGrant support• NIDDKNIDDK

• NCINCI

• Astra ZenecaAstra Zeneca

• TakedaTakeda

• Given imagingGiven imaging

• ConsultantConsultant• Astra ZenecaAstra Zeneca

• NycomedNycomed

• OlympusOlympus

• EthiconEthicon

Gastroesophageal Reflux Gastroesophageal Reflux DiseaseDisease

• What are current working What are current working definitions?definitions?

• What is pathophysiology of GERDWhat is pathophysiology of GERD

• What is the current diagnostic What is the current diagnostic strategy?strategy?

• What is a rational treatment strategy?What is a rational treatment strategy?

GERD: Montreal Definition GERD: Montreal Definition

• A condition which develops when the A condition which develops when the reflux of stomach contents causes reflux of stomach contents causes troublesome symptoms and/or troublesome symptoms and/or complicationscomplications• >> 2 heartburn episodes/week 2 heartburn episodes/week

• Adversely affect an individual’s well Adversely affect an individual’s well beingbeing

From Vakil N et al. Am J Gastroenterol 2006;101:1900-20. From Vakil N et al. Am J Gastroenterol 2006;101:1900-20.

Montreal Classification of GERDMontreal Classification of GERD

From Vakil N et al. Am J Gastroenterol 2006;101:1900-20.From Vakil N et al. Am J Gastroenterol 2006;101:1900-20.

Montreal GERD Consensus Montreal GERD Consensus Conference: Atypical SymptomsConference: Atypical Symptoms

• GERD & extraesophageal symptoms are GERD & extraesophageal symptoms are associatedassociated

• Extraesophageal symptoms Extraesophageal symptoms rarely occur rarely occur in absence of typical GERD symptomsin absence of typical GERD symptoms

• Extraesophageal symptoms typically Extraesophageal symptoms typically multifactorialmultifactorial

• Data substantiating beneficial effect of Data substantiating beneficial effect of treatment weak treatment weak

From Vakil N et al. Am J Gastroenterol 2006;101:1900-20.From Vakil N et al. Am J Gastroenterol 2006;101:1900-20.

Pathogenesis of GERDPathogenesis of GERD

Impaired Esophageal ClearanceImpaired Esophageal Clearance

Decreased SalivationDecreased Salivation

Impaired Tissue ResistanceImpaired Tissue Resistance

Decreased LES Resting ToneDecreased LES Resting Tone

Delayed Gastric EmptyingDelayed Gastric Emptying

Bile RefluxBile Reflux

Hiatal HerniaHiatal Hernia

LESLES

DuodenumDuodenum

Different Reflux Mechanisms Different Reflux Mechanisms With Hiatal HerniaWith Hiatal Hernia

*PP<0.001.<0.001.††PP0.005.0.005.From van Herwaarden et al. From van Herwaarden et al. GastroenterologyGastroenterology. 2000;119:1439-1446.. 2000;119:1439-1446.

*

*†

Patients Without Hiatal Hernia (n = 10)Patients Without Hiatal Hernia (n = 10)

Patients With Hiatal Hernia (n = 12)Patients With Hiatal Hernia (n = 12)

TLESRsTLESRs Low LESPLow LESP Strain + Low LESPStrain + Low LESP

0

20

40

60

80

100

Ref

lux

Ep

iso

des

(%

)R

eflu

x E

pis

od

es (

%)

Relationship Between BMI & TLESrRelationship Between BMI & TLESr

From Wu JC et al. Gastroenterology 2007;132:883-9.From Wu JC et al. Gastroenterology 2007;132:883-9.

Gastroesophageal Pressure Gradients & Gastroesophageal Pressure Gradients & GERDGERD

From de Vries DR et al. Am J Gastroenterol 2008;103:1349-54.From de Vries DR et al. Am J Gastroenterol 2008;103:1349-54.

13

Duration of Esophageal Acid and Bile Duration of Esophageal Acid and Bile Exposure Affects GERD SeverityExposure Affects GERD Severity

1.57

15.4 14.7

22.8

0.43.2

14.6

23.0

46.0

0

10

20

30

40

50

60

70

Controls No Esophagitis Esophagitis UncomplicatedBarrett's

ComplicatedBarrett's

To

tal T

ime

pH

<4

an

d B

ilir

ub

in

0.1

4 (

%)

AcidBilirubin*

*Indirect measure of bile reflux.Indirect measure of bile reflux.From Vaezi and Richter. From Vaezi and Richter. Gastroenterology.Gastroenterology. 1996;111:1192-1199 1996;111:1192-1199.

GERD DiagnosisGERD Diagnosis

• There is no single There is no single diagnostic gold standard diagnostic gold standard for GERDfor GERD

GERD Diagnosis: MenuGERD Diagnosis: Menu

• Empiric trialEmpiric trial

• Barium esophagramBarium esophagram

• EndoscopyEndoscopy

• ManometryManometry

• pH testingpH testing

• ImpedanceImpedance

Clarifying Patient Symptoms: Clarifying Patient Symptoms: HeartburnHeartburn

Carlsson et al. Carlsson et al. Scand J Gastroenterol.Scand J Gastroenterol. 1998;33:1023-1029. 1998;33:1023-1029.

• Patients do not reliably Patients do not reliably interpret the word interpret the word “heartburn”“heartburn”

• For symptom evaluation, “a For symptom evaluation, “a burning feeling rising from burning feeling rising from the stomach or lower chest the stomach or lower chest up toward the neck” is more up toward the neck” is more reliable than “heartburn”reliable than “heartburn”

Alternative Diagnosis in GERDAlternative Diagnosis in GERD

• Coronary artery diseaseCoronary artery disease

• GallstonesGallstones

• Gastric /esophageal cancerGastric /esophageal cancer

• Peptic ulcer diseasePeptic ulcer disease

• Esophageal motility disordersEsophageal motility disorders

• Pill induced esophagitisPill induced esophagitis

• Eosinophilic esophagitisEosinophilic esophagitisFrom Kahrilas PJ. N Engl J Med 2008;359:1700-7.From Kahrilas PJ. N Engl J Med 2008;359:1700-7.

GERD DiagnosisGERD Diagnosis• Empiric trialEmpiric trial






GERD Diagnostic Approach GERD Diagnostic Approach ACG GuidelinesACG Guidelines

• If history typical for uncomplicated If history typical for uncomplicated GERD, initial trial of empiric GERD, initial trial of empiric therapy (including lifestyle therapy (including lifestyle modification) appropriate modification) appropriate

From DeVault KD et al. Am J Gastroenterol 2005;100:190-200.

Meta-Analysis of PPI Trials as a Meta-Analysis of PPI Trials as a Diagnostic Test for GERDDiagnostic Test for GERD

ComparatorComparator Sensitivity Sensitivity

(95% CI)(95% CI)

SpecificitySpecificity

(95% CI)(95% CI)

24-hr pH24-hr pH 0.78 0.78

(0.66-0.86)(0.66-0.86)

0.540.54

(0.44-0.65)(0.44-0.65)

EGDEGD 0.680.68

(0.56-0.79)(0.56-0.79)

0.460.46

(0.34-0.59)(0.34-0.59)

From Numans ME et al. Ann Intern Med 2004;140:518-27.From Numans ME et al. Ann Intern Med 2004;140:518-27.

Diagnostic Testing in GERDDiagnostic Testing in GERD

• Avert misdiagnosisAvert misdiagnosis

• Identify complicationsIdentify complications

• Evaluate treatment failuresEvaluate treatment failures

From Kahrilas PJ. N Engl J Med 2008;359:1700-7.From Kahrilas PJ. N Engl J Med 2008;359:1700-7.

Barium EsophagramBarium Esophagram• Especially sensitive in evaluating dysphagiaEspecially sensitive in evaluating dysphagia

• In pre- and postoperative evaluations, In pre- and postoperative evaluations, identifies:identifies:

• Normal or impaired esophageal emptyingNormal or impaired esophageal emptying

• Normal or impaired motilityNormal or impaired motility

• Presence and type of hiatal herniaPresence and type of hiatal hernia

• Distal stricture or mucosal ringDistal stricture or mucosal ring

• Presence of gastroesophageal refluxPresence of gastroesophageal reflux

• Main deficiency is insensitivity for erosive Main deficiency is insensitivity for erosive esophagitis & Barrett’s esophagusesophagitis & Barrett’s esophagus

GERD DiagnosisGERD Diagnosis

• Empiric trialEmpiric trial






Role of Endoscopy in Management Role of Endoscopy in Management of GERD: ASGE Guidelines of GERD: ASGE Guidelines

• GERD despite therapyGERD despite therapy

• Dysphagia Dysphagia

• OdynophagiaOdynophagia

• GI bleeding/anemiaGI bleeding/anemia

• Mass, stricture or ulcer on imaging studyMass, stricture or ulcer on imaging study

• Recurrent symptoms after antireflux Recurrent symptoms after antireflux surgerysurgery

From Gastrointest Endosc 2007;66:219-24.From Gastrointest Endosc 2007;66:219-24.

Role of Endoscopy in Management Role of Endoscopy in Management of GERD: ASGE Guidelines of GERD: ASGE Guidelines

• Screening for Barrett’s in selected Screening for Barrett’s in selected

patientspatients• Persistent vomitingPersistent vomiting• Suspected extraesophageal GERDSuspected extraesophageal GERD

From Gastrointest Endosc 2007;66:219-24.From Gastrointest Endosc 2007;66:219-24.

Spectrum of Esophageal Injury in Spectrum of Esophageal Injury in GERDGERD

From Kahrilas PJ. N Engl J Med 2008;359:1700-7.From Kahrilas PJ. N Engl J Med 2008;359:1700-7.

http://0-content.nejm.org.library.ccf.org/content/vol359/issue16/images/large/09f1.jpeg

Nonerosive Reflux Nonerosive Reflux Disease: NERDDisease: NERD

Reflux symptoms/mucosal breaks not visible in standard video endoscopyReflux symptoms/mucosal breaks not visible in standard video endoscopy

Symptoms Do Not Predict the Symptoms Do Not Predict the Presence of Erosive EsophagitisPresence of Erosive Esophagitis

From Venables et al. From Venables et al. Scand J Gastroenterol. Scand J Gastroenterol. 1997;32:965-973.1997;32:965-973.

MildMildModerateModerateSevereSevere

Heartburn GradeHeartburn Grade

68%68%NERDNERD(n = 677)n = 677)

32%32%EEEE

(n = 316)(n = 316)

Prevalence of Erosive EsophagitisPrevalence of Erosive Esophagitis

LA Classification of EsophagitisLA Classification of Esophagitis

From Nayar DS et al. Gastrointest Endosc 2004;60:253-7.From Nayar DS et al. Gastrointest Endosc 2004;60:253-7.

Screening for Barrett’s Screening for Barrett’s Esophagus: GuidelinesEsophagus: Guidelines

ACGACG

20082008

AGAAGA

20052005

BSGBSG

20052005

GERD GERD symptomssymptoms

IndividualizeIndividualize MaybeMaybe NoNo

No GERD No GERD symptomssymptoms

NoNo NoNo NoNo

Prevalence of Barrett’s Esophagus Prevalence of Barrett’s Esophagus in VA GERD Patients at Initial EGDin VA GERD Patients at Initial EGD

• 378 GERD patients378 GERD patients

• Barrett’s esophagus in Barrett’s esophagus in 13.2%13.2%

• LSBE-36%LSBE-36%

• SSBE-64%SSBE-64%

From Westhoff B et al. Gastrointest Endosc 2005;61:226-31.From Westhoff B et al. Gastrointest Endosc 2005;61:226-31.

Barrett’s Esophagus On Repeat Barrett’s Esophagus On Repeat Endoscopy Within 5 Years According Endoscopy Within 5 Years According To Finding At Baseline: CORI ProjectTo Finding At Baseline: CORI Project

From Rodriguez S et al. Am J Gastroenterol 2008;103:1892-7.From Rodriguez S et al. Am J Gastroenterol 2008;103:1892-7.

Symptomatic GERD As A Risk Factor For Esophageal Adenocarcinoma

0

20

40

60

80

100

Controls EsophagealAdenoca

Cardia Ca EsophagealSquamous

Cell Ca

From Lagergren J et al. NEJM 1999;340:825-31. From Lagergren J et al. NEJM 1999;340:825-31.

AbsenceAbsence of heartburn, regurgitation or both of heartburn, regurgitation or both >> once weekly once weekly

%%

Prevalence of Barrett’s Esophagus Prevalence of Barrett’s Esophagus in General Population of Swedenin General Population of Sweden

From Ronikainen J et al. Gastroenterology 2005;129:1825-31From Ronikainen J et al. Gastroenterology 2005;129:1825-31..

BEBE LSBELSBE

((>> 2cm) 2cm)

SSBESSBE

(< 2cm)(< 2cm)

No BENo BE

CasesCases

(%)(%)

16 16

(1.6%)(1.6%)

5 5

(0.5%)(0.5%)

1111

(1.1%)(1.1%)

984984

(98.4%)(98.4%)

% with % with GERD GERD symptomssymptoms

56.3%56.3% 80.0%80.0% 45.5%45.5% 39.7%39.7%

% with % with esophagitisesophagitis

25.0%25.0% 60.0%60.0% 9.1%9.1% 15.4%15.4%

Screening for Barrett’s Screening for Barrett’s Esophagus: ProblemsEsophagus: Problems

• Relatively few cases of esophageal adenocarcinoma

• High prevalence of GERD

• No prior GERD symptomsNo prior GERD symptoms in 40% of in 40% of adenocarcinoma patients adenocarcinoma patients

• EGD & pathology diagnostic inconsistencies

Screening for Barrett’s Screening for Barrett’s Esophagus: ProblemsEsophagus: Problems

• Cost/risk of endoscopy

• Lack of noninvasive alternatives

• Lack of predictors to increase yield

of screening

• Unproven

Screening Of Barrett’s Screening Of Barrett’s Esophagus: ProblemsEsophagus: Problems

• Risks of screening:Risks of screening:

• False positivesFalse positives

• Patient anxietyPatient anxiety

• Unnecessary follow-up examsUnnecessary follow-up exams

• Life insurance premiumsLife insurance premiums

From Sharma P et al. Am J Gastroenterol 2008;103:525-32.From Sharma P et al. Am J Gastroenterol 2008;103:525-32.

Esophageal Capsule Endoscopy for The Esophageal Capsule Endoscopy for The Diagnosis of Barrett’s EsophagusDiagnosis of Barrett’s Esophagus

Esophageal Capsule Endoscopy for Esophageal Capsule Endoscopy for The Diagnosis of Barrett’s EsophagusThe Diagnosis of Barrett’s Esophagus

From Sharma P et al. Am J Gastroenterol 2008;103:525-32.From Sharma P et al. Am J Gastroenterol 2008;103:525-32.

Capsule Endoscopy for Barrett’s Capsule Endoscopy for Barrett’s Esophagus ScreeningEsophagus Screening

• Currently not cost effective based on Currently not cost effective based on modeling studiesmodeling studies

• Broad adoption as screening technology Broad adoption as screening technology questionablequestionable

• Unclear benefits compared to Unclear benefits compared to conventional EGDconventional EGD

• Significant improvements in technology Significant improvements in technology needed to alter assessmentsneeded to alter assessments

From Hur C. Clin Gastroenterol Hepatol 2007;5:307-9.From Hur C. Clin Gastroenterol Hepatol 2007;5:307-9.

AGA Esophageal GERD Practice AGA Esophageal GERD Practice Guidelines: ManometryGuidelines: Manometry

• GERD despite therapyGERD despite therapy• Negative endoscopyNegative endoscopy• Goals:Goals:

• LES locationLES location• Peristaltic function preoperativelyPeristaltic function preoperatively• Detection of subtle motility abnormalitiesDetection of subtle motility abnormalities

• High resolution manometry superior to High resolution manometry superior to conventional manometry for achalasia conventional manometry for achalasia variants & distal esophageal spasmvariants & distal esophageal spasm

From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.

GI Motility onlineGI Motility online (May 2006) | doi:10.1038/gimo22 (May 2006) | doi:10.1038/gimo22

Contour Plot Topographic Analysis of Contour Plot Topographic Analysis of Esophageal Motility in Achalasia.Esophageal Motility in Achalasia.

AGA Esophageal GERD Practice AGA Esophageal GERD Practice Guidelines: Reflux MonitoringGuidelines: Reflux Monitoring

• Failure to respond to PPIFailure to respond to PPI

• Negative EGDNegative EGD

• No major manometric abnormalityNo major manometric abnormality

• Wireless pH studies superior for Wireless pH studies superior for detection of abnormal acid exposuredetection of abnormal acid exposure

• Studies should be done off therapyStudies should be done off therapy


24-Hour Esophageal pH Monitoring24-Hour Esophageal pH Monitoring

• Most accurate test for measuring Most accurate test for measuring pattern, frequency, and duration of pattern, frequency, and duration of reflux episodes reflux episodes

• Documents correlation between Documents correlation between reflux episodes and symptomsreflux episodes and symptoms

• Sensitivity (77-100%) Sensitivity (77-100%)

• Normal in 25% of esophagitis!Normal in 25% of esophagitis!

• Specificity 85-100%Specificity 85-100%

• Most useful when diagnosis still Most useful when diagnosis still unclearunclear

Dent et al. Dent et al. GutGut. 1999;44(suppl 2):S1-S16.. 1999;44(suppl 2):S1-S16.

Impedance pH CatheterImpedance pH Catheter

From Smout A. Aliment Pharmacol Ther 2007;26(Suppl2):7-12.From Smout A. Aliment Pharmacol Ther 2007;26(Suppl2):7-12.

Gastroesophageal Reflux Gastroesophageal Reflux Monitoring: The Porto ConferenceMonitoring: The Porto Conference

• Combined pH and impedance:Combined pH and impedance:

• Best detection of all reflux eventsBest detection of all reflux events

• Best evaluation of antireflux barrierBest evaluation of antireflux barrier

• Consider impedance pH for Consider impedance pH for persistent symptoms despite therapypersistent symptoms despite therapy

From Sifrim D et al. Gut 2004;53:1024-31.From Sifrim D et al. Gut 2004;53:1024-31.

AGA GERD Practice Guidelines: AGA GERD Practice Guidelines: Diagnostic Testing SequenceDiagnostic Testing Sequence

1.1. EndoscopyEndoscopy

2.2. ManometryManometry

3.3. pH testingpH testing


AGA GERD Practice Guidelines: AGA GERD Practice Guidelines: Lifestyle ModificationsLifestyle Modifications

• Weight loss should be recommended in Weight loss should be recommended in all patients (B)all patients (B)

• Lifestyle modificatons should be tailored Lifestyle modificatons should be tailored to individual circumstances (B)to individual circumstances (B)• Elevate HOB if nocturnal symptomsElevate HOB if nocturnal symptoms• Avoid precipitating foodsAvoid precipitating foods

• Broad lifestyle changes for all (vs. Broad lifestyle changes for all (vs. selected) not recommendedselected) not recommended


Systematic Review of Effect of Lifestyle Systematic Review of Effect of Lifestyle Intervention on GERD ParametersIntervention on GERD Parameters

From Kaltenbach T et al. Arch Intern Med 2006;166:965-71.From Kaltenbach T et al. Arch Intern Med 2006;166:965-71.

Weight Loss & GERDWeight Loss & GERD

““Our current treatment goals Our current treatment goals should move away from should move away from allowing our patients to eat allowing our patients to eat through their PPI therapy….”through their PPI therapy….”

From Pandolfino J. Am J Gastroenterol 2008;103:1355-7.From Pandolfino J. Am J Gastroenterol 2008;103:1355-7.

Short Term (1-12 Week) Treatment of GERD Short Term (1-12 Week) Treatment of GERD Symptoms Or Endoscopy Negative GERDSymptoms Or Endoscopy Negative GERDTreatment Treatment Heartburn Heartburn

Remission Remission RRRR

95% CI95% CI

Empiric Therapy GroupEmpiric Therapy Group

PPI vs. placeboPPI vs. placebo 0.370.37 0.32-0.440.32-0.44

H2RA vs. placeboH2RA vs. placebo 0.770.77 0.60-0.990.60-0.99

PPI vs. H2RAPPI vs. H2RA 0.660.66 0.60-0.730.60-0.73

Endoscopy Negative Reflux GroupEndoscopy Negative Reflux Group

PPI vs. placeboPPI vs. placebo 0.690.69 0.62-0.780.62-0.78

H2RA vs. placeboH2RA vs. placebo 0.840.84 0.74-0.950.74-0.95

PPI vs. H2RAPPI vs. H2RA 0.780.78 0.62-0.970.62-0.97From Van Pinxteren B et al. Cochrane Database of Systematic Reviews 2006:3:CD002095.From Van Pinxteren B et al. Cochrane Database of Systematic Reviews 2006:3:CD002095.

Esomeprazole Vs Other PPIs: Erosive Esomeprazole Vs Other PPIs: Erosive Esophagitis Healing @ 8 WeeksEsophagitis Healing @ 8 Weeks

From Gralnek I et al. Clin Gastroenterol Hepatol 2006;4:1452-8.From Gralnek I et al. Clin Gastroenterol Hepatol 2006;4:1452-8.

Esomeprazole Vs Other PPIs: GERD Esomeprazole Vs Other PPIs: GERD Symptom Relief @ 4 WeeksSymptom Relief @ 4 Weeks


Esomeprazole Vs Other PPIs: NNT Esomeprazole Vs Other PPIs: NNT For LA Grade EsophagitisFor LA Grade Esophagitis


Pat

ien

ts i

n s

ymp

tom

atic

rem

issi

on

(%

)P

atie

nts

in

sym

pto

mat

ic r

emis

sio

n (

%)

100

80

60

40

20

00 1 2 3 4 5 6

Time after cessation of therapy (monthsTime after cessation of therapy (months)

No mucosal breaksNo mucosal breaks

LA Grade ALA Grade A

LA Grade BLA Grade B

LA Grade CLA Grade C

GERD Is a Chronic Condition GERD Is a Chronic Condition Likely to RelapseLikely to Relapse

From Lundell LR, et al. From Lundell LR, et al. Gut.Gut. 1999; 1999;45:172-18045:172-180.

Step Down Management of GERD in Step Down Management of GERD in a Primary Care Settinga Primary Care Setting

From Inadomi JM et al. Gastroenterology 2001;121:1095-1100.From Inadomi JM et al. Gastroenterology 2001;121:1095-1100.

Adverse Events With Up to 1 YearAdverse Events With Up to 1 Year of of Esomeprazole TreatmentEsomeprazole Treatment

Adverse EventAdverse Event % Patients (N=807)% Patients (N=807)

HeadacheHeadache 10.310.3

DiarrheaDiarrhea 9.49.4

Abdominal painAbdominal pain 9.39.3

NauseaNausea 6.16.1

Back painBack pain 5.95.9

From Maton PN et al. Drug Safety 2001;24:625-35From Maton PN et al. Drug Safety 2001;24:625-35

Safety Profile of PPIsSafety Profile of PPIs

• Recent epidemiologic associationsRecent epidemiologic associations

• C. difficileC. difficile

• Aspiration pneumoniaAspiration pneumonia

• Hip fractureHip fracture

• Fundic gland polypsFundic gland polyps

Long-term Acid SuppressionLong-term Acid Suppressionand Risk of Hip Fractureand Risk of Hip Fracture

Adjusted OR > 1 year on acid suppression.Adjusted OR > 1 year on acid suppression.Yang Y-X, et al. Yang Y-X, et al. JAMA.JAMA. 296;2947-2953 296;2947-2953.

0 1 2 3 4

< 1.75< 1.75

> 1.75> 1.75

< 1.75< 1.75

> 1.75> 1.75

Average Average Daily doseDaily dose

PPIPPI

HH22RARA

Adjusted Odds RatioAdjusted Odds Ratio

Study cohort included 79% women, mean age 77 yo, with high baseline risk Study cohort included 79% women, mean age 77 yo, with high baseline risk for hip fracture for hip fracture

AGA GERD Practice Guidelines: AGA GERD Practice Guidelines: PPI SafetyPPI Safety

• Inadequate evidence to mandate:Inadequate evidence to mandate:• Bone density studiesBone density studies

• Calcium supplementationCalcium supplementation

• H. pylori H. pylori screeningscreening

• Good medical practice to screen & Good medical practice to screen & treat the elderly for osteoporosistreat the elderly for osteoporosis


Pharmacologic Therapy of Pharmacologic Therapy of GERD: Not RecommendedGERD: Not Recommended

• Nocturnal H2 blockerNocturnal H2 blocker• Not supported by clinical endpointsNot supported by clinical endpoints

• Rapid tachyphylaxisRapid tachyphylaxis

• Metoclopramide monotherapy or Metoclopramide monotherapy or adjunctive therapyadjunctive therapy

From Kahrilas PJ. Gastroenterology 2008;135:1383-91.From Kahrilas PJ. Gastroenterology 2008;135:1383-91.

Possible Causes For Failure of PPI Possible Causes For Failure of PPI Therapy Therapy

• ComplianceCompliance• Improper dosing timeImproper dosing time• Weakly acidic refluxWeakly acidic reflux• Visceral hypersensitivityVisceral hypersensitivity• Psychologic comorbiditiesPsychologic comorbidities• Concomitant functional bowel diseaseConcomitant functional bowel disease• Delayed gastric emptyingDelayed gastric emptying• Eosinophilic esophagitisEosinophilic esophagitis

From Fass R. Clin Gastroenterol Hepatol 2008;6:393-400.From Fass R. Clin Gastroenterol Hepatol 2008;6:393-400.

PPI Instructions By Primary PPI Instructions By Primary Care PhysiciansCare Physicians

From Chey WD et al. Am J Gastroenterol 2005;100:1237-42.From Chey WD et al. Am J Gastroenterol 2005;100:1237-42.

Eosinophilic Esophagitis: Endoscopy

From Gonsalves N et al. Gastrointest Endosc 2006;64:313-9.From Gonsalves N et al. Gastrointest Endosc 2006;64:313-9.


Histologic Features of Eosinophilic Histologic Features of Eosinophilic EsophagitisEsophagitis

Prevalence & Predictive Factors of Prevalence & Predictive Factors of Eosinophilic Esophagitis in AdultsEosinophilic Esophagitis in Adults

• 33/222 (15%) with midesophageal biopsies had EoE

• 10/102 (9.8%) with normal EGD had EoE

• 8/21 (38%) with endoscopic features of EoE had EoE!

From Prasad GA et al. Am J Gastroenterol 2007;102:2627-32.From Prasad GA et al. Am J Gastroenterol 2007;102:2627-32.

Eosinophilic Esophagitis: Number of Eosinophilic Esophagitis: Number of Biopsies Needed for Diagnosis With Biopsies Needed for Diagnosis With

Different Diagnostic CriteriaDifferent Diagnostic Criteria


Copyright ©2008 BMJ Publishing Group Ltd.

From Lundell L et al. Gut 2008;57:1207-1213.From Lundell L et al. Gut 2008;57:1207-1213.

RCT of Laparoscopic Antireflux Surgery RCT of Laparoscopic Antireflux Surgery Vs. Esomeprazole for GERDVs. Esomeprazole for GERD

Why Patients Choose SurgeryWhy Patients Choose SurgeryReason*Reason* Patients (%)Patients (%)

Medications did not workMedications did not work

Physician recommended itPhysician recommended it

Thought it would cure the diseaseThought it would cure the disease

Did not wish to take medications for long termDid not wish to take medications for long term

High cost of medications High cost of medications

To prevent cancerTo prevent cancer

4646

4545

2727

1515

44

33

N = 80.N = 80.*Some patients reported more than 1 reason.*Some patients reported more than 1 reason.Vakil et al. Vakil et al. Am J MedAm J Med. 2003;114:1-5.. 2003;114:1-5.

Risks of Antireflux SurgeryRisks of Antireflux Surgery

From Vakil N. Aliment Pharmacol Ther 2007;25:1365-72.From Vakil N. Aliment Pharmacol Ther 2007;25:1365-72.

Annual Number of Antireflux Annual Number of Antireflux Operations Performed in USAOperations Performed in USA

From Finks JF et al. Surg Endosc 2006;20:1698-1701.From Finks JF et al. Surg Endosc 2006;20:1698-1701.

Systematic Review of Surgical Vs. Systematic Review of Surgical Vs. Medical Therapy of Barrett’s Medical Therapy of Barrett’s

Esophagus: Cancer Incidence Esophagus: Cancer Incidence

From Chang EY et al. Ann Surg 2007;246:11-21.From Chang EY et al. Ann Surg 2007;246:11-21.

AGA GERD Practice Guidelines: AGA GERD Practice Guidelines: SurgerySurgery

• Patients with esophagitis who are well Patients with esophagitis who are well maintained on medical therapy have maintained on medical therapy have nothing to gain from surgerynothing to gain from surgery• Incur added riskIncur added risk• Should be advised against surgeryShould be advised against surgery

• Patients likely to benefit from surgery:Patients likely to benefit from surgery:• PPI intolerancePPI intolerance• Persistent symptoms especially regurgitationPersistent symptoms especially regurgitation


Indications for Antireflux Surgery: A Indications for Antireflux Surgery: A Systematic ReviewSystematic Review

• Requirements for surgeryRequirements for surgery• Experienced surgeonExperienced surgeon• Fit patientFit patient• Prior response to PPIPrior response to PPI

From Moayyedi P et al. Lancet 2006;367:2086-2100.From Moayyedi P et al. Lancet 2006;367:2086-2100.

SummarySummary• GERD currently classified by GERD currently classified by

Montreal systemMontreal system• EsophagealEsophageal

• ExtraesophagealExtraesophageal

• Diagnostic testing Diagnostic testing • Avert misdiagnosisAvert misdiagnosis

• Identify complicationsIdentify complications

• Evaluate treatment failuresEvaluate treatment failures

SummarySummary

• Diagnostic sequence:Diagnostic sequence:• EndoscopyEndoscopy


• pH studiespH studies

• Role of screening for Barrett’s Role of screening for Barrett’s esophagus remains controversialesophagus remains controversial

SummarySummary• PPIs are cornerstone of therapyPPIs are cornerstone of therapy

• Avoid metoclopramide and nocturnal H2RAsAvoid metoclopramide and nocturnal H2RAs

• Goal of therapy: lowest dose to control Goal of therapy: lowest dose to control symptomssymptoms

• Lifestyle changes should be used Lifestyle changes should be used selectivelyselectively

• Antireflux surgery reserved for nocturnal Antireflux surgery reserved for nocturnal regurgitation & PPI intoleranceregurgitation & PPI intolerance

Gastroesophageal Reflux Disease

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Transcript of Gastroesophageal Reflux Disease