Lecture 16 GERD

GASTRO-ESOPHAGEAL GASTRO-ESOPHAGEAL REFLUX DISEASESREFLUX DISEASES(G E R D) (G E R D)

By:By:PROF. DR Dr I DEWA NYOMAN WIBAWA SpPD-KGEHPROF. DR Dr I DEWA NYOMAN WIBAWA SpPD-KGEH

Gastroenterology-hepatology Div., Gastroenterology-hepatology Div., Dept.of Internal Med./Sanglah Dept.of Internal Med./Sanglah

Hospital.Hospital.

Talley et al., BMJ 2001; 323: 1294–7.de Caestecker, BMJ 2001; 323: 736–9.Nathoo, Int J Clin Pract 2001; 55: 465–9.Quigley, Eur J Gastroenterol Hepatol 2001; 13(Suppl 1): S13–18.

Gastro-esophageal reflux disease (GERD):Gastro-esophageal reflux disease (GERD):– Pathological reflux ranges from simple to Pathological reflux ranges from simple to

erosive to Barrett’serosive to Barrett’s

Non-erosive reflux disease (NERD):Non-erosive reflux disease (NERD):– Reflux disease in which erosion does not Reflux disease in which erosion does not

occuroccur

Reflux Esophagitis: Reflux Esophagitis: - Symptoms or mucosal damage - Symptoms or mucosal damage

(esophagitis) (esophagitis) due to exposure of due to exposure of distal esophagus to reflux distal esophagus to reflux gastric gastric contentcontent

DefinitionsDefinitionsDefinitionsDefinitions

“GERD is a condition which develops when the refluxof gastric content causes troublesome symptoms

or complications”

Esophageal Syndromes

Extra-esophageal Syndromes

Symptomatic SyndromesTypical Reflux SyndromeReflux Chest Pain Syndrome

Syndromes with Esophageal InjuryReflux Esophagitis Reflux StrictureBarrett’s Esophagus Adenocarcinoma

Established AssociationsReflux Cough SyndrReflux LaryngitisReflux Asthma Reflux Dental Eros.

Proposed AssociationsPharyngitisSinusitis Idiopathic

Pulmonary FibrosisRecurrent Otitis Media

Vakil N et al. Am J Gastroenterol 2006

THE MONTREAL DEFINITION & CLASSIFICATION OF GERD

“GERD is a condition which develops when the refluxof gastric content causes troublesome symptoms

or complications”

GGastroastroEEsophageal sophageal RReflux eflux DDiseaseisease

Esophagitis

Barrett’s Metaplasiaand

Adenocarcinoma

BleedingStricture

Nonerosive GERD(EGD negative)

Impairs Qualityof Life

ExtraesophagealGERD

Dental

Asthma

ENT

EGD = esophagogastroduodenoscopy; ENT = ear, nose, and throat.

Typical symptoms(Heartburn/regurgitation)

Atypical symptoms Complications

With oesophagitis

Without oesophagitis

Chest pain(visceral

hyperalgesia)

Asthma, chronic cough,

wheezing

Hoarseness(‘reflux

laryngitis’)

Oesophageal erosions

and/or ulcers

Stricture

Barrett’s oesophagus

Oesophageal adenocarcinomaDental erosions

Nathoo, Int J Clin Pract 2001; 55: 465–9.

Range of presentations of GRange of presentations of GEERDRDRange of presentations of GRange of presentations of GEERDRD

(NERD=Non ErosiveReflux Diseases)

PATHOGENESIS & PATHOPHYSIOLOGY

GATRO-ESOPHAGEAL REFLUX DISEASES GATRO-ESOPHAGEAL REFLUX DISEASES

• Disturbance in esophageal clearanceDisturbance in esophageal clearance• TRLES (Transient Relaxation of LES) TRLES (Transient Relaxation of LES) • LES dysfunctionLES dysfunction• Delayed gastric emptiyingDelayed gastric emptiying HeartburnHeartburn main symptom! main symptom! GERD is not an acid hypersecretion problem!GERD is not an acid hypersecretion problem!

PathogenesisPathogenesis

Impaired mucosal defence

de Caestecker, BMJ 2001; 323:736–9.Johanson, Am J Med 2000; 108(Suppl 4A): S99–103.

salivary HCO3

Hiatus hernia

Impaired LOS (smoking, fat, alcohol)

– transient LOS relaxations

– basal toneH+

PepsinBile and

pancreatic enzymes

oesophageal clearance of acid (lying flat, alcohol, coffee)

acid output (smoking, coffee)

intragastric pressure (obesity, lying flat)

bile reflux gastric emptying (fat)

Pathophysiology of GERDPathophysiology of GERDPathophysiology of GERDPathophysiology of GERD

Gastric acid refluxate and pepsin Gastric acid refluxate and pepsin destroy esophageal mucosa and destroy esophageal mucosa and produces symptoms.produces symptoms.

““The dominant mechanism of symptom The dominant mechanism of symptom production in reflux disease is by contact of production in reflux disease is by contact of the esophageal mucosa with acid and pepsin”the esophageal mucosa with acid and pepsin”

Dent et al 1999

Genval statement 4, accepted completelyGenval statement 4, accepted completely

Genval statement 3, accepted completelyGenval statement 3, accepted completely

““In the majority of people with reflux In the majority of people with reflux disease there is abnormally prolonged disease there is abnormally prolonged exposure of the distal esophagus to exposure of the distal esophagus to acid and pepsin”acid and pepsin”

SymptomsSymptoms

Symptom Predominance (%)

Heartburn 80

Regurgitation 54

Abdominal Pain 29

Cough 27

Dysphagia for solids 23

Hoarseness 21

Belching 15

Aspiration 14

Wheezing 7

Globus 4

1.1. Based on typical GERD symptomsBased on typical GERD symptoms - useful in primary health care / to all practitioners- useful in primary health care / to all practitioners - Use GERD questioner : all patients can be diagnosed- Use GERD questioner : all patients can be diagnosed

2.2. Therapeutic trial (Therapeutic trial (PPI test=Empiric treatmentPPI test=Empiric treatment)) - helpful for confirmed Diagnosis of GERD and NCCP- helpful for confirmed Diagnosis of GERD and NCCP

3. Gastroscopy3. Gastroscopy - patient with ‘warning signs’: vomiting, dysphagia, - patient with ‘warning signs’: vomiting, dysphagia, odynophagia, GI bleeding, weight loss, Fe def anemiaodynophagia, GI bleeding, weight loss, Fe def anemia

- to diagnose of GERD complication- to diagnose of GERD complication

4. Other testings4. Other testings ((reflux monitoring, manometry)reflux monitoring, manometry) - to confirm diagnosis, prior to anti-reflux surgery - to confirm diagnosis, prior to anti-reflux surgery

Diagnosis of GERD Diagnosis of GERD

EGDEGD

Allows examination of the esophageal Allows examination of the esophageal mucosamucosa

Identifies presence of esophagitis and Identifies presence of esophagitis and grading of severitygrading of severity

Can identify other pathology, such as Can identify other pathology, such as diverticula, hiatal hernia, webs, rings, diverticula, hiatal hernia, webs, rings, or stricturesor strictures

Tissue biopsies to screen for Barrett’s Tissue biopsies to screen for Barrett’s esophagusesophagus

Odynophagia

Dysphagia

Vomiting

Bleeding

Weight loss

Alarm features


Alarm features for GERDAlarm features for GERD

Symptom-baseddiagnosis

Riskassessment

Non-erosive reflux disease

Reflux esophagitis

~35%

Complicated reflux disease

~5%

~60%

Endoscopy

Alarmsymptoms

Empiricaltherapy

1DeVault KR, Castell DO. Am J Gastroenterol 2005;100:190–200; Rao G. J Fam Pract 2005;54 (12 Suppl):3–8.

Adapted from Labenz J et al. World J Gastroenterol

2005;11:4291-99.

Following a symptom-based diagnosis, almost all patients can be managed in primary care

Following a symptom-based diagnosis, almost all patients can be managed in primary care

Treatment failure

~95% of patients

inprimary

care1

Grade A:Grade A:

The LA Classification system for theThe LA Classification system for theendoscopic assessment of reflux esophagitisendoscopic assessment of reflux esophagitis

Published with permission from Professor G Tytgat and Professor J Dent

One or more mucosal breaks no longer than 5 mm, none of which extends between the tops of themucosal folds

Grade B:Grade B: One or more mucosal breaks more than 5 mm long, none of which extends between the tops of two mucosal folds



Grade C:Grade C: Mucosal breaks that are continuous between the tops of two or more mucosal folds, but which involve less than 75% of the esophageal circumference



Grade D:Grade D: Mucosal breaks which involve at least 75% of the esophageal circumference



24-hour pH test24-hour pH test

Gold Standard for Gold Standard for presence of presence of pathologic refluxpathologic reflux

Parameters Parameters measured include: measured include: – Total of reflux episodes, Total of reflux episodes, – duration of longest duration of longest

reflux episode, reflux episode, – percentage of time pH percentage of time pH

is less than 4is less than 4

Ambulatory pH testing – Ambulatory pH testing – Recent AdvancesRecent Advances

Combined Combined impedance and impedance and acid testingacid testing– Allows for the Allows for the

measurement of measurement of both acid and both acid and nonacid (volume) nonacid (volume) reflux.reflux.

– Important in pt with Important in pt with persistent persistent symptoms despite symptoms despite an adequate an adequate medical trialmedical trial

Ambulatory pH testing – Ambulatory pH testing – Recent AdvancesRecent Advances

Tubeless method– Tubeless method– Bravo SystemBravo System– Allows a radiotelemetry Allows a radiotelemetry

capsule to be attached capsule to be attached to the esophageal to the esophageal mucosamucosa

– Decreases patient Decreases patient discomfort, allows for discomfort, allows for longer (48h) monitoring, longer (48h) monitoring, and may improve and may improve accuracy by allowing the accuracy by allowing the patient to carry out their patient to carry out their usual activitiesusual activities

Esophageal Manometry Esophageal Manometry

Lower Esophageal Lower Esophageal Sphincter (LES)Sphincter (LES)– Mean resting pressureMean resting pressure– Total lengthTotal length

Esophageal BodyEsophageal Body– To determine To determine

effectiveness of effectiveness of peristalsisperistalsis

– Amplitude of Amplitude of esophageal waveesophageal wave

EsophagramEsophagram

Useful when Useful when operation is plannedoperation is planned—shows anatomy of —shows anatomy of esophagus and esophagus and proximal stomachproximal stomach

Demonstrates Demonstrates presence and size of presence and size of hiatal hernia if hiatal hernia if presentpresent

PPI testPPI test

PPI test for symptomatic GERD:PPI test for symptomatic GERD:1.1.

– PPI high dose 2 x/ day, 7-14 daysPPI high dose 2 x/ day, 7-14 days– Specificity 75-85%, sensitivity 55-73%Specificity 75-85%, sensitivity 55-73%

– Positive response GERDPositive response GERD PPI test for NCCP (Meta-analysis):PPI test for NCCP (Meta-analysis):2.2.

– Sensitivity 80%, specificity 74%, compared with Sensitivity 80%, specificity 74%, compared with placebo 19%placebo 19%

– Indicative NCCP due to GERD: a Indicative NCCP due to GERD: a reduction > 50% of chest pain reduction > 50% of chest pain during PPI therapyduring PPI therapy

1. Bautista J, et al. Aliment Pharmacol Ther, 2004;19:1123-301. Bautista J, et al. Aliment Pharmacol Ther, 2004;19:1123-30

2. Wang, WH et al. Arch Intern Med 2005;165:1222–8.2. Wang, WH et al. Arch Intern Med 2005;165:1222–8.

Hiatus herniaHiatus hernia

Oesophageal strictureOesophageal stricture

Oesophageal cancerOesophageal cancer

Chest pain of cardiac Chest pain of cardiac origin origin

Functional dyspepsiaFunctional dyspepsia


Differential diagnosis of GERDDifferential diagnosis of GERDDifferential diagnosis of GERDDifferential diagnosis of GERD

Treatment options in GERD

Goals of TreatmentGoals of Treatment

relief of pain and symptomsrelief of pain and symptoms decrease frequency and duration of refluxdecrease frequency and duration of reflux promote healingpromote healing avoid complications (Barret's esophagus, avoid complications (Barret's esophagus,

cancer)cancer) prevent recurrenceprevent recurrence

Pharmacologic tx:PPIs, H2RAs,

Antacids, Prokinetic

motility agents

Endoscopic antirefluxproced

ure

Lifestyle modifications

Surgery

Hatlebakk & Berstad, Clin Pharmacokinet 1996; 31: 386–406.

Approaches

GERD treatment optionsGERD treatment optionsGERD treatment optionsGERD treatment options

Tx of complication

1.1. Lifestyle modificationLifestyle modification - Al- Almost always Recommended most always Recommended (although mostly weak of evidence)(although mostly weak of evidence)

2. Pharmacologic treatment2. Pharmacologic treatment - - Step-down strategy is better than Step-up strategy Step-down strategy is better than Step-up strategy - Effective drugs: H- Effective drugs: H22RA, Prokinetic, and PPI RA, Prokinetic, and PPI

2.A. Empirical / Initial therapy2.A. Empirical / Initial therapy 2.B. Maintenance therapy2.B. Maintenance therapy

- On-demand vs Continuous vs intermitten- On-demand vs Continuous vs intermitten

3. Anti-reflux surgery3. Anti-reflux surgery - very selective cases only- very selective cases only

Treatment of GERD Treatment of GERD

INITIAL THERAPYINITIAL THERAPY

? x2 daily PPI + H2RA

x2 daily PPI

x1 daily PPI

x1 daily ½ PPI

Prokinetic + H2RA

Prokinetic*

Antacids + lifestyle

Antacids

Lifestyle

H2RA*OR

*no clear dose-response established*no clear dose-response established

Highest efficacyHighest efficacy

Lowest efficacyLowest efficacy

RecommendedRecommended

Should beShould beabandonedabandoned

CurrentCurrent

guidelinesguidelines

Mainstream options for therapy of Mainstream options for therapy of GERDGERD

after Dent et al 2002after Dent et al 2002

I. Lifestyle modificationsI. Lifestyle modifications

1.1. Avoidance of foods that may precipitate reflux.Avoidance of foods that may precipitate reflux. - e.g. coffee, alcohol, chocolate, fatty foods- e.g. coffee, alcohol, chocolate, fatty foods

2.2. Avoidance of acidic foods that may precipitate Avoidance of acidic foods that may precipitate heartburn. heartburn. – e.g. citrus, carbonated drinks, spicy foods – e.g. citrus, carbonated drinks, spicy foods 3.3. Adoption of behaviors that may reduce esophageal Adoption of behaviors that may reduce esophageal

acid exposure. acid exposure. – – e.g. reduced body weight, stop smoking, e.g. reduced body weight, stop smoking, - raising the head of the bed, - raising the head of the bed,

- avoiding recumbency less than 3 hours after meals- avoiding recumbency less than 3 hours after meals

4. Good Practice: advice should be tailored to the 4. Good Practice: advice should be tailored to the specific-related symptom of patient specific-related symptom of patient

AGA Institute. Gastroenterology 2008;135:1392–1413

Drug therapy Drug therapy

Symptomatic reliefSymptomatic relief of GERD by: of GERD by: 1.1.

– Placebo 27%, HPlacebo 27%, H22RA 60%, and RA 60%, and PPI 83% PPI 83% Esophagitis healed by: Esophagitis healed by: 11..

– Placebo 24%, HPlacebo 24%, H22RA 50%, and RA 50%, and PPI 78%PPI 78% Relative Risk (RR) relief from heartburn increased Relative Risk (RR) relief from heartburn increased

with greater degrees of acid suppression: with greater degrees of acid suppression: 2.2.

– Prokinetic : RR 0.86 (95% CI 0.73-1.01)Prokinetic : RR 0.86 (95% CI 0.73-1.01)– HH22RA RA : RR 0.77 (95% CI 0.60-0.99) : RR 0.77 (95% CI 0.60-0.99)– PPIPPI : RR 0.37 (95% CI 0.32-0.44) : RR 0.37 (95% CI 0.32-0.44)

1.1. De Vault & Castell, Am J Gastroenterol 2005;100:190-200De Vault & Castell, Am J Gastroenterol 2005;100:190-2002.2. Van Pinxteren et al. Cochrane Database Syst Rev 2004;(4):CD002095Van Pinxteren et al. Cochrane Database Syst Rev 2004;(4):CD002095

Effectiveness of Medical Therapies for Effectiveness of Medical Therapies for GERDGERD

TreatmentTreatment ResponseResponse

Lifestyle modifications/antacidsLifestyle modifications/antacids 20 %20 %

HH22-receptor antagonists-receptor antagonists 50 %50 %

Single-dose PPI Single-dose PPI 80 %80 %

Increased-dose PPIIncreased-dose PPI up to 100 %up to 100 %

Step up or Step down treatment for GERD

Long-term treatment of

GERD

GERD is a Chronic Relapsing ConditionGERD is a Chronic Relapsing Condition

Esophagitis relapses quickly Esophagitis relapses quickly after cessation of therapyafter cessation of therapy– > 50 % relapse within 2 months> 50 % relapse within 2 months– > 80 % relapse within 6 months> 80 % relapse within 6 months

Effective maintenance therapy is Effective maintenance therapy is imperativeimperative

Treatment Modifications for Persistent Treatment Modifications for Persistent SymptomsSymptoms

Improve complianceImprove compliance

Optimize pharmacokineticsOptimize pharmacokinetics

– Adjust timing of medication to 15 – 30 Adjust timing of medication to 15 – 30 minutes before meals (as opposed to minutes before meals (as opposed to bedtime)bedtime)

– Allows for high blood level to interact with Allows for high blood level to interact with parietal cell proton pump activated by the parietal cell proton pump activated by the mealmeal

Consider switching to a different PPI Consider switching to a different PPI

PPI’s are effective and safe for short-term/ initial PPI’s are effective and safe for short-term/ initial therapy (8-12 weeks) and long-term therapy of GERD therapy (8-12 weeks) and long-term therapy of GERD patients (erosive esophagitis/ EE and non-erosive / patients (erosive esophagitis/ EE and non-erosive / NERD).NERD).

Subset of GERD patients may still need maintenance Subset of GERD patients may still need maintenance therapy to control the disease. therapy to control the disease.

Two strategies of maintenance therapy: ‘continuous Two strategies of maintenance therapy: ‘continuous PPI’ or “on-demand PPI”PPI’ or “on-demand PPI”

Trials result showed that ‘on-demand’ therapy Trials result showed that ‘on-demand’ therapy are as effective as ‘continuous’ therapy are as effective as ‘continuous’ therapy

Maintenance Therapy in Maintenance Therapy in GERDGERD

‘‘On-demand PPI’ vs ‘Continuous On-demand PPI’ vs ‘Continuous PPI’PPI’

Pace F, Porro GB Current Treat. Opt. in Gastroenterology 2008, 11:35–42

Maintenance Treatment Maintenance Treatment Strategy OptionsStrategy Options

s = symptom recurrence

Continuousmaintenance

Intermittent

“On Demand” (Step in)

0 26 weeks

S S

S S S S S S

26 w

8 w 8 w

Lecture 16 GERD

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Transcript of Lecture 16 GERD