Gastroesophageal Gastroesophageal Reflux DiseaseReflux Disease

Rajeev Jain, MDRajeev Jain, MD

November 27, 2006November 27, 2006

GERD

OutlineOutline

DefinitionDefinition EpidemiologyEpidemiology PathophysiologyPathophysiology DiagnosisDiagnosis TreatmentTreatment ManagementManagement

GERD

Vakil N, et al. Am J Gastroenterol 101(8):1900-20.2006.

DefinitionDefinition

No gold standardNo gold standard Montreal DefinitionMontreal Definition

– “ “a condition which develops when a condition which develops when the reflux of stomach contents the reflux of stomach contents causes troublesome symptoms causes troublesome symptoms and/or complications”and/or complications”

GERD

ClassificationClassification

EndoscopyEndoscopy– Erosive esophagitisErosive esophagitis

Los Angeles classificationLos Angeles classification

– Non-erosive reflux disease (NERD) or Non-erosive reflux disease (NERD) or endoscopy negative reflux disease (ENRD)endoscopy negative reflux disease (ENRD)

SymptomsSymptoms– EsophagealEsophageal– Extra-esophagealExtra-esophageal

GERD

LA ClassificationLA ClassificationLA

Gra

de A

LA G

rade

B

LA G

rade

C

LA G

rade

D

GERD

EpidemiologyEpidemiology

PrevalencePrevalence– Symptoms in western populationsSymptoms in western populations

25% monthly25% monthly 12% weekly12% weekly 5% daily5% daily

IncidenceIncidence– 1.5 – 3% develop weekly GERD per yr1.5 – 3% develop weekly GERD per yr

Moayyedi P, Axon ATR. Aliment Pharmacol Ther 22(S1):11-9.2005.

GERD

Risk FactorsRisk Factors

DemographicDemographic– Age & gender not a major differenceAge & gender not a major difference

Lifestyle & EnvironmentalLifestyle & Environmental– Obesity, EtOH, & tobacco have weak Obesity, EtOH, & tobacco have weak

associations (OR 1.5 – 2.5) associations (OR 1.5 – 2.5) 11

– H. pyloriH. pylori has no impact has no impact 22

GeneticGenetic– Higher concordance in mono- than Higher concordance in mono- than

dizygotic twins dizygotic twins 11

1. Moayyedi P & Talley NJ. Lancet 367:2086-100.2006.

2. Raghunath AS, et al. Aliment Pharmacol Ther 20:733-44.2004.

GERD

PathophysiologyPathophysiology

Primary mechanism – impaired function Primary mechanism – impaired function of the lower esophageal sphincter (LES)of the lower esophageal sphincter (LES)

In most patients with GERD, exposure In most patients with GERD, exposure of the esophagus to refluxate is greater of the esophagus to refluxate is greater than normalthan normal

In a minority of patients, exposure is In a minority of patients, exposure is within normal limits; in these patients, within normal limits; in these patients, GERD may be due to decreased GERD may be due to decreased mucosal resistance to refluxate mucosal resistance to refluxate

GERD

Mechanisms of Acid Mechanisms of Acid RefluxReflux

GERD

Ineffective Ineffective peristalsisperistalsis

Reduced salivary Reduced salivary secretionsecretion

Reduced secretion Reduced secretion from esophageal from esophageal submucosal glandssubmucosal glands

Defective Esophageal Defective Esophageal ClearanceClearance

GERD

Inappropriate Inappropriate and prolonged and prolonged transient transient relaxationsrelaxations

Reduction in Reduction in basal LES basal LES pressure/tonepressure/tone

LES ‘dysfunction’LES ‘dysfunction’

GERD

Substances that Substances that Decrease LES PressureDecrease LES Pressure

HormonesHormones– SecretinSecretin– CholecystokininCholecystokinin– GlucagonGlucagon– SomatostatinSomatostatin– ProgesteroneProgesterone

FoodsFoods– FatFat– ChocolateChocolate– EthanolEthanol– PeppermintPeppermint

MedicationsMedications

GERD

-adrenergic -adrenergic agonistsagonists

TheophyllineTheophylline AnticholinergicsAnticholinergics Tricyclic Tricyclic

antidepressantsantidepressants

-adrenergic -adrenergic antagonistsantagonists

DiazepamDiazepam Calcium channel Calcium channel

blockersblockers

Medications that Medications that Decrease LES PressureDecrease LES Pressure

GERD

May trap a May trap a reservoir of reservoir of gastric contents gastric contents above the above the diaphragm, diaphragm, increasing refluxincreasing reflux

May compromise May compromise LES functionLES function

Hiatal HerniaHiatal Hernia

GERD

PregnancyPregnancy ObesityObesity BendingBending StrainingStraining CoughingCoughing Tight clothesTight clothes

Increased Increased Intra-abdominalIntra-abdominal PressurePressure

GERD

May result in an May result in an increase in the increase in the volume of gastric volume of gastric contents available contents available for reflux into the for reflux into the esophagusesophagus

Exact role in GERD Exact role in GERD remains to be remains to be clarifiedclarified

Delayed Gastric Delayed Gastric EmptyingEmptying

GERD

Diagnostic MethodsDiagnostic Methods

HistoryHistory EndoscopyEndoscopy Empiric therapyEmpiric therapy pH monitoring pH monitoring RadiologyRadiology

GERD

HistoryHistory

History taking is the primary diagnostic History taking is the primary diagnostic ‘tool’ for GERD‘tool’ for GERD– Heartburn – sensation of discomfort or Heartburn – sensation of discomfort or

burning behind the sternum rising up to the burning behind the sternum rising up to the neckneck

– Regurgitation – effortless return of gastric Regurgitation – effortless return of gastric contents into the pharynxcontents into the pharynx

Accuracy of symptoms when compared Accuracy of symptoms when compared to endoscopy as gold standard to endoscopy as gold standard – Sensitivity 30-76%Sensitivity 30-76%– Specificity 45-68%Specificity 45-68%

Moayyedi P, et al. JAMA 295:1566-76.2006.

GERD

Allows direct visualization Allows direct visualization of the esophageal mucosa of the esophageal mucosa and biopsy if necessaryand biopsy if necessary

Presence and severity of Presence and severity of erosive esophagitiserosive esophagitis

Detection of complications Detection of complications such as stricture or such as stricture or Barrett’s esophagusBarrett’s esophagus

DeVault et al. Am J Gastroenterol 1999

EndoscopyEndoscopy

GERD

Advances in Advances in EndoscopyEndoscopy

Ultra-thin endoscopesUltra-thin endoscopes– Transnasal or oralTransnasal or oral– No sedationNo sedation

Magnification endoscopyMagnification endoscopy Capsule endoscopyCapsule endoscopy

GERD

Referral for EndoscopyReferral for Endoscopy

Chronic symptoms requiring Chronic symptoms requiring continuous acid-suppression therapycontinuous acid-suppression therapy

Persistent suspected GERD symptoms Persistent suspected GERD symptoms that fail to respond to acid suppressionthat fail to respond to acid suppression

Any new GERD patient over the age of Any new GERD patient over the age of 4040

Warning signs:Warning signs:– Weight lossWeight loss– Anemia or BleedingAnemia or Bleeding– DysphagiaDysphagia

GERD

Empiric TherapyEmpiric TherapyPPI TestPPI Test

Logical as GERD is an acid-related Logical as GERD is an acid-related disorderdisorder

Normal or high-dose PPI for 1-4 Normal or high-dose PPI for 1-4 wks in the diagnosis of GERD wks in the diagnosis of GERD (gold (gold standard was 24 hr ambulatory pH study)standard was 24 hr ambulatory pH study)

–Sensitivity 78% (95% CI 66-86%)Sensitivity 78% (95% CI 66-86%)–Specificity 54% (95% CI 44-65%)Specificity 54% (95% CI 44-65%)

Numans ME, et al. Ann Intern Med 140:518-27.2006.

GERD

Allows investigation of:Allows investigation of:– the amount and timing of refluxthe amount and timing of reflux– the correlation between reflux and the correlation between reflux and

symptomssymptoms– the effect of therapy on refluxthe effect of therapy on reflux

In general, most useful in:In general, most useful in:– endoscopy-negative patientsendoscopy-negative patients– patients with chest pain or patients with chest pain or

pulmonary/upper respiratory pulmonary/upper respiratory symptomssymptoms

– patients with refractory symptomspatients with refractory symptoms

pH MonitoringpH Monitoring

GERD

pH MonitoringpH Monitoring

24 hr pH 24 hr pH monitoringmonitoring– single best testsingle best test– 50-60% will 50-60% will

have have abnormalitiesabnormalities

– new device:new device: BRAVO probeBRAVO probe 48 hr monitoring48 hr monitoring

GERD

pH MonitoringpH Monitoring

GERD

1Dent et al. Gut 1999

Now considered to be of Now considered to be of very limited practical value very limited practical value in the diagnosis of GERDin the diagnosis of GERD11

May be helpful in the May be helpful in the detection of subtle detection of subtle strictures and hiatal hernias strictures and hiatal hernias in patients with dysphagiain patients with dysphagia

May be helpful in May be helpful in identifying pathologies identifying pathologies unrelated to GERDunrelated to GERD

Barium EsophagramBarium Esophagram

GERD

Richter. Am J Gastroenterol 2000

Misc

Asthma

ENT

Chest pain

Non-erosive reflux disease

Erosive esophagitis

Yes

No

Need to investigate role of acid

0%

100%

Prevalence of GERD

The Pyramid of Diseases The Pyramid of Diseases Associated with GERD Associated with GERD

GERD

EsophagealEsophageal–Barrett’s Barrett’s esophagusesophagus

–adenocarcinoadenocarcinomama

–stricturestricture–ulcerationulceration–bleedingbleeding

Extra-Extra-esophagealesophageal–asthmaasthma–reflux laryngitisreflux laryngitis–vocal cord ulcersvocal cord ulcers–subglottic subglottic stenosisstenosis

–tracheal stenosistracheal stenosis

Complications of GERD Complications of GERD

GERD

Esophageal strictureEsophageal stricture

GERD

Barrett’s EsophagusBarrett’s Esophagus

GERD

1Lagergren et al. New Engl J Med 1999

Barrett’s Esophagus Barrett’s Esophagus Clinical SignificanceClinical Significance

Premalignant lesion for Premalignant lesion for esophageal adenocarcinomaesophageal adenocarcinoma

Patients with Barrett’s esophagus Patients with Barrett’s esophagus may be 30–60 times more likely to may be 30–60 times more likely to develop this cancer than the develop this cancer than the general populationgeneral population11

The reported incidence of The reported incidence of Barrett’s esophagus is risingBarrett’s esophagus is rising

GERDThe Risk of Esophageal The Risk of Esophageal Adenocarcinoma Increases Adenocarcinoma Increases

with:with:

Frequency of Frequency of reflux symptomsreflux symptoms– OR 16.7 with > 3/wkOR 16.7 with > 3/wk

Duration of reflux Duration of reflux symptomssymptoms– OR 16.4 with greater OR 16.4 with greater

than 20 yrsthan 20 yrs

Severity of reflux Severity of reflux symptomssymptoms– OR 20 with most OR 20 with most

severe scoresevere score

Lagergren et al. N Engl J Med 1999

TreatmentTreatment

GERD

Treatment OptionsTreatment Options

Lifestyle measuresLifestyle measures

Pharmacological therapyPharmacological therapy– Initial therapyInitial therapy–Maintenance therapyMaintenance therapy

Antireflux surgeryAntireflux surgery

Endoscopic techniquesEndoscopic techniques

GERD

Lifestyle MeasuresLifestyle Measures

Raise the head of the bed, or lie on Raise the head of the bed, or lie on left sideleft side

Decrease fat intakeDecrease fat intake Avoid certain foodsAvoid certain foods Avoid lying down for 3 hours after Avoid lying down for 3 hours after

eatingeating Stop smokingStop smoking Lose weight if appropriateLose weight if appropriate

GERD

Aggravating Dietary Aggravating Dietary FactorsFactors

Caffeinated Caffeinated productsproducts

PeppermintPeppermint Fatty foodsFatty foods ChocolateChocolate

Spicy foodsSpicy foods Citrus fruits and Citrus fruits and

juicesjuices Tomato-based Tomato-based

productsproducts AlcoholAlcohol

GERD

Pharmacological TherapyPharmacological Therapy

AntacidsAntacids ProkineticsProkinetics Acid suppressionAcid suppression

–Histamine 2-receptor antagonists Histamine 2-receptor antagonists (H(H22RAs)RAs)

–Proton pump inhibitors (PPIs)Proton pump inhibitors (PPIs)

GERD

Acid SuppressionAcid SuppressionErosive Esophagitis – Initial TherapyErosive Esophagitis – Initial Therapy

HH22RA v placebo (4-8 wks of therapy)RA v placebo (4-8 wks of therapy)– 18 trials, 2134 patients18 trials, 2134 patients– NNT 5 (95% CI, 3-22)NNT 5 (95% CI, 3-22)

PPI v placeboPPI v placebo– 5 trials, 635 patients5 trials, 635 patients– NNT 2 (95% CI, 1.4-2.5)NNT 2 (95% CI, 1.4-2.5)

PPI v HPPI v H22RARA– 26 trials, 4064 patients26 trials, 4064 patients– NNT 3 (95% CI, 2.8-3.6)NNT 3 (95% CI, 2.8-3.6)

Khan M, et al. Cochrane Database Syst Rev.2006.

GERD

Acid SuppressionAcid SuppressionErosive Esophagitis – Maintenance Erosive Esophagitis – Maintenance

TherapyTherapy

80% relapse after 6-12 months off 80% relapse after 6-12 months off therapytherapy

PPI v HPPI v H22RARA– 10 trials, 1583 patients, 24-52 wks 10 trials, 1583 patients, 24-52 wks

of therapyof therapy– Relapse rateRelapse rate

22% in PPI group22% in PPI group 58% in H58% in H22RA groupRA group

– NNT 2.5 (95% CI, 2.0-3.4)NNT 2.5 (95% CI, 2.0-3.4)

Donnellan C, et al. Cochrane Database Syst Rev.4:2004.

GERD

Antireflux Surgery – Antireflux Surgery – ProceduresProcedures

GERD

1DeVault et al. Am J Gastroenterol 19992Dent et al. Gut 1999

Antireflux Surgery – Antireflux Surgery – use and efficacyuse and efficacy

Antireflux surgery is an option as Antireflux surgery is an option as maintenance therapy for patients with maintenance therapy for patients with well documented GERDwell documented GERD11

The efficacy of antireflux surgery is The efficacy of antireflux surgery is similar to that of chronic PPI therapysimilar to that of chronic PPI therapy22

The outcome of surgery is highly The outcome of surgery is highly dependent on the skill and experience dependent on the skill and experience of the surgeonof the surgeon22

GERD

Endoscopic TherapyEndoscopic Therapy

Three FDA approved techniquesThree FDA approved techniques–Stretta: radiofrequency therapy to Stretta: radiofrequency therapy to LESLES

–EndoCinch: endoscopic EndoCinch: endoscopic gastroplicationgastroplication

–Enteryx: 8% ethylene vinyl alcohol Enteryx: 8% ethylene vinyl alcohol copolymercopolymer

GERD

Endoscopic Endoscopic GastroplicationGastroplication

GERD

ManagementManagementGoalsGoals

Provide complete relief from Provide complete relief from heartburn and other symptomsheartburn and other symptoms

Heal underlying erosive esophagitisHeal underlying erosive esophagitis

Treat or prevent complicationsTreat or prevent complications

Prevent recurrencePrevent recurrence

GERD

ManagementManagement

Clinical diagnosisClinical diagnosis Endoscopy in pts with alarm Endoscopy in pts with alarm

symptomssymptoms PPI once daily taken 30 min before PPI once daily taken 30 min before

breakfast for 4-8 weeksbreakfast for 4-8 weeks If symptoms resolve, consider on-If symptoms resolve, consider on-

demand therapy or step downdemand therapy or step down Relapse is commonRelapse is common

GERD

ManagementManagement

If symptoms persist despite daily PPIIf symptoms persist despite daily PPI– NonadherenceNonadherence– Inadequate dosing or timingInadequate dosing or timing– Nocturnal acid breakthroughNocturnal acid breakthrough– RareRare

Zollinger-Ellison syndromeZollinger-Ellison syndrome Drug resistanceDrug resistance

Surgery – right patient and right Surgery – right patient and right surgeonsurgeon