Upload
patrick89
View
429
Download
1
Tags:
Embed Size (px)
Citation preview
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?
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.
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?
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.
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 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
• Barium esophagramBarium esophagram
• EndoscopyEndoscopy
• ManometryManometry
• pH testingpH testing
• ImpedanceImpedance
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.
GERD DiagnosisGERD Diagnosis• Empiric trialEmpiric trial
• Barium esophagramBarium esophagram
• EndoscopyEndoscopy
• ManometryManometry
• pH testingpH testing
• ImpedanceImpedance
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
• Barium esophagramBarium esophagram
• EndoscopyEndoscopy
• ManometryManometry
• pH testingpH testing
• ImpedanceImpedance
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.
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.
GERD DiagnosisGERD Diagnosis• Empiric trialEmpiric trial
• Barium esophagramBarium esophagram
• EndoscopyEndoscopy
• ManometryManometry
• pH testingpH testing
• ImpedanceImpedance
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.
GERD DiagnosisGERD Diagnosis• Empiric trialEmpiric trial
• Barium esophagramBarium esophagram
• EndoscopyEndoscopy
• ManometryManometry
• pH testingpH testing
• ImpedanceImpedance
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
From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.
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
From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.
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?
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
From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.
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
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: NNT Esomeprazole Vs Other PPIs: NNT For LA Grade EsophagitisFor LA Grade Esophagitis
From Gralnek I et al. Clin Gastroenterol Hepatol 2006;4:1452-8.From Gralnek I et al. Clin Gastroenterol Hepatol 2006;4:1452-8.
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
From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.
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.
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
From Gonsalves N et al. Gastrointest Endosc 2006;64:313-9.From Gonsalves N et al. Gastrointest Endosc 2006;64:313-9.
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
From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.
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
• ManometryManometry
• 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