Gastro-Esophageal Reflux Disease

GERD

Gastro-esophageal reflux disease

Epidemiology

GERD is one of the most frequent

GI complaints 35% US population - symptoms 1x / month 7% US population - symptoms daily reflux esophagitis is the most frequent finding in UGI endoscopy (~ 20%) complications are present in ~ 20% of patients with esophagitis

Gastro-esophageal reflux disease

Epidemiology

disease of the developed world

more frequently - US, EU less frequently - Africa, Asia more frequently in men more frequently in elderly esophagitis - peak incidence ~ 60 - 70 y more frequently in obese and smokers markedly decreased quality of life

Gastro-esophageal reflux disease

Definitions
Occurrence of typical symptoms and/or inflammatory changes of esophageal mucosa caused by repeated episodes of gastro-esophageal reflux

Gastro-esophageal reflux disease (GERD)

Gastro-esophageal reflux disease

Definitions

The presence of inflammatory changes (mucosal breaks erosions / ulcerations) in the esophageal mucosa confirmed macroscopically (endoscopy) Reflux esophagitis (RE) Erosive GERD (E-GERD)

Gastro-esophageal reflux disease

Definitions
At least 2 episodes of heartburn of moderate to severe intensity during 7 consecutive days with no endoscopic changes (mucosal breaks or Barretts esophagus) relieved after trial PPI therapy.

Non-erosive reflux disease (NERD) Endoscopy-negative reflux disease (ENRD) Symptomatic GERD (S-GERD)

Gastro-esophageal reflux disease

Pathology: TLESRs

most important pathogenic factor of GERD 10 - 60 s relaxation of LES (swallowing: 6 - 8 s) neural reflex form brain stem
through the vagal nerve caused by: - CCK - stomach distension - meal - stimulation of pharyngeal mucosa receptors

Gastro-esophageal reflux disease

Pathology: hiatal hernia

sliding hernia change of angle of His (loss of flap-valve) loss of intra-abdominal part of the esophagus widening of the esophageal hiatus separation of both parts of sphincter acid reservoir in the hernial sac - easier reflux during TLESRs decreased esophageal clearance hernia is present in about 3/4 cases of GERD

Gastro-esophageal reflux disease

Symptoms

esophageal extra-esophageal

Symptoms may not correlate with the severity of esophagitis.

Esophagitis may be totally asymptomatic.

Gastro-esophageal reflux disease

Symptoms

typical:

heartburn belching acid regurgitation odynophagia

nausea and vomiting dyspepsia

atypical: retrosternal chest pain alarm symptoms - complications

Gastro-esophageal reflux disease

Heartburn

heartburn (burning, retrosternal pain)

is the most typical, pathognomonic symptom of GERD

heartburn usually occurs with

decrease of lower esophageal pH < 4.0

Gastro-esophageal reflux disease

Extra-esophageal symptoms of GERD

pulmonary:

chronic cough dyspnea asthma and bronchitis recurrent infections

throat pain

laryngo-pharyngeal: hoarseness stomatological: hematological:

dental erosions anemia

Gastro-esophageal reflux disease

Alarm symptoms

dysphagia bleeding anemia weight loss

severe chest pain

Gastro-esophageal reflux disease

Risk factors for severe GERD

male sex
advanced age (> 50-60 yrs ?)

long-lasting symptoms (> 5-10 yrs ?)

obesity smoking & alcohol

Gastro-esophageal reflux disease

Diagnostic tests

endoscopy trial therapy with PPI esophageal impedance testing

24-hour ambulatory pH-monitoring

esophageal manometry

bilitec
other (scintigraphy, provocative tests)

Gastro-esophageal reflux disease

Upper GI endoscopy (EGD)

diagnosis of esophagitis staging complications (Barretts esophagus, strictures) differential diagnosis (neoplasms, other etiologies of esophagitis)
Endoscopy should be the first (basic) diagnostic test in GERD !

Gastro-esophageal reflux disease

Los-Angeles system
A B One or more mucosal breaks, < 5 mm long One or more mucosal breaks > 5 mm, affecting one or more folds, non-continuous between the tops of two folds One or more mucosal breaks, continuous between the tops of at least two folds, but not circumferential (< ) Circumferential (> ) mucosal break

Gastro-esophageal reflux disease

Los-Angeles system

RE Los Angeles system

Grade 0 (no esophagitis, normal)

FE Silverstein, GNJ Tytgat Gastrointestinal Endoscopy, Mosby-Wolfe 1997

RE Los Angeles system

Grade A

LA: A
SM: I

RE Los Angeles system

Grade A

LA: A
SM: I

RE Los Angeles system

Grade B

LA: B
SM: II

RE Los Angeles system

Grade B

LA: B
SM: II

RE Los Angeles system

Grade C

LA: C
SM: II

RE Los Angeles system

Grade C

LA: C
SM: II

RE Los Angeles system

Grade D

LA: D
SM: IV a/b?

Gastro-esophageal reflux disease

Trial therapy with PPIs

PPI: 2 weeks, standard dose BID may be used as a first diagnostic tests
in patients with low-risk of esophagitis (young, female, short history of symptoms)

Gastro-esophageal reflux disease

Ambulatory 24-hour pH-monitoring

Gastro-esophageal reflux disease

Ambulatory 24-hour pH-monitoring
No drug pH < 4: 34% DM score: 130 (n: < 18)
On PPI pH < 4: 6.6% DM score: 29
KGA AM 2001

Multichannel intraluminal impedance

Intraluminal ions allow for electrical current flow

Current generator

no bolus = few ions = high impedance

bolus present = many ions = low impedance

Multichannel intraluminal impedance

Bolus in
Impedance Bolus present

Bolus out

Time

Impedance measurement electrodes

Multichannel intraluminal impedance

GI Motility online (May 2006) | doi:10.1038/gimo31

Multichannel intraluminal impedance

Antegrade Retrograde

17 cm
15 cm 9 cm 7 cm 5 cm 3 cm

Gastro-esophageal reflux disease

Diagnostic scheme
GERD symptoms EGD Trial therapy with PPI pH / impedance Manometry, bilitec, scintigraphy, etc. test positive

test negative

End of diagnostic process

Gastro-esophageal reflux disease

Treatment

lifestyle modifications pharmacotherapy surgery / Tx endoscopy

Gastro-esophageal reflux disease

Lifestyle modifications

diet restrictions (fat, coffee, etc) change of number, volume and timing of meals reduction of weight head of the bed elevation cessation of smoking, avoiding alcohol avoiding / change of certain drugs (if possible)

Gastro-esophageal reflux disease

Pharmacotherapy

antacids (alginic acid) sucralfate prokinetics anti-secretory agents - H2 receptor antagonists - proton pump inhibitors combined therapy

Gastro-esophageal reflux disease

Pharmacotherapy: H2-receptor antagonists (H2RA)

cimetidine (Altramet, Tagamet) ranitidine (Zantac, Ranigast) famotidine (Pepcid, Ulfamid, Famogast) nizatidine (Axid) roxatidine (Roxit, Roxane)

Gastro-esophageal reflux disease

Pharmacotherapy: proton pump inhibitors (PPI)

omeprazole (Losec, Antra, Prilosec, Mopral) lansoprazole (Prevacid, Lanzul) pantoprazole (Controloc, Pantozol, Protonix) rabeprazole (Pariet) esomeprazole (Nexium)

tenatoprazole

Gastro-esophageal reflux disease

Pharmacotherapy: standard doses of PPIs (OD)

omeprazole rabeprazole lansoprazole pantoprazole esomeprazole

20 mg / d 20 mg / d 30 mg / d 40 mg / d 40 mg / d

Gastro-esophageal reflux disease

Pharmacotherapy: step-down vs. step-up
Double dose PPI (BID) + H2RA Double dose PPI (BID) Standard (full) dose PPI (OD)

Step-down

Step-up

Half dose PPI (OD) Full dose H2RA

Standard dose PPI (e 2nd d) Full dose prokinetic

On demand treatment (antacids)

Off treatment (life-style measures)

Gastro-esophageal reflux disease

Pharmacotherapy of an acute episode

Inadomi JM, Medscape Gastroenterology 2006

Gastro-esophageal reflux disease

Pharmacotherapy of an acute episode

Inadomi JM, Medscape Gastroenterology 2006

Gastro-esophageal reflux disease

Pharmacotherapy of an acute episode

Inadomi JM, Medscape Gastroenterology 2006

Gastro-esophageal reflux disease

Maintenance pharmacotherapy

on demand
- relapse treatment

intermittent treatment
- week-end (Fri to Sun) - every second day

continuous treatement
- prokinetics - H2RA - H2RA + prokinetics - PPI (the lowest effective dose) - PPI + prokinetics

Gastro-esophageal reflux disease

Maintenance pharmacotherapy
continuous

intermittent

on demand
recurrence of symptoms

Gastro-esophageal reflux disease

Pharmacotherapy: nocturnal acid breakthrough

no good effect of PPI BID no inhibition of nocturnal

basal acid secretion proposed scheme: PPI OD + H2RA at bedtime PPI BID+ H2RA at bedtime

Gastro-esophageal reflux disease

Surgical procedures

Hill

Belsey

Nissen

Gastro-esophageal reflux disease

Laparoscopic fundoplication

Gastro-esophageal reflux disease

Surgical treatment

technique: laparoscopic
total fundoplication (360) or partial fundoplication (180-270)
- lower risk of dysphagia

indications:

complications of GERD (local, pulmonary) young age (< 40) failure of pharmacotherapy
(after minimum 6 months of treatment)

Gastro-esophageal reflux disease

Laparoscopic fundoplication

complications 4 - 26% conversion ~ 10% mortality < 1% transient dysphagia ~ 35% re-operation 2 - 14% good long term result ~ 85% late (3 yr) dysphagia < 5% treatment cheaper than pharmacotherapy with expected survival ~ 6 - 7 years (USA)

Gastro-esophageal reflux disease

Laparoscopic fundoplication

only 50% improvement in extra-esophageal

symptoms of GERD symptoms should not be the only indication for surgery extensive diagnostic workup (EGD, impedance, manometry, trial PPI therapy) is mandatory before surgery experience of surgeon extremely important

Gastro-esophageal reflux disease

Endoscopic treatment
injection
- collagen - poly-tetrafluoroethylen (Polytef, PTFE) - polymethylmethacrylate microspheres (Artecol) - hydrogel polyacrylonitril prostheses (Gatekeeper) - ethylene-vinyl alcohol polymer (Enteryx) suturing - EndoCinch (BARD) - Endoscopic Suturing Device (Wilson-Cook) endo-plication - stapler (NDO Surgical Plicator) radio-frequency application (Stretta)

Enteryx

Boston Scientific Corp., Nattick, Ma

Enteryx

Boston Scientific Corp., Nattick, Ma

Gatekeeper

Torquati, ASGE 2004; Fockens et al., Endoscopy 2004

EndoCinch

CR Bard. Inc., Billerica, Ma

Full-Thickness Plicator
ePTFE Pledgets & Pre -tied Suture Endoscopic Tissue Retractor

Scope Channel Retractor handle

Leak Test Port

Instrument controls

Scope Exit

Low Profile (<= 6mm) Gastroscope

Single -Use Cartridge & Implant

NDO Surgical, Inc., Mansfield, Ma

Full-Thickness Plicator

NDO Surgical, Inc., Mansfield, Ma

EsophyX 2

EndoGastric Solutions, Redwood City, Ca

MediGus SRS

Medigus Ltd, Omer , Israel

Stretta

Curon Medical, Inc., Fremont, Ca

Stretta

Curon Medical, Inc., Fremont, Ca

Gastro-esophageal reflux disease

Endoscopic treatment

short-term results encouraging injection dangerous withdrawn long-term results not yet fully available efficiency decreasing over time (especially for suturing techniques) should not be recommended as standard treatment (as yet) probably optional treatment for selected subgroup of patients in future

Gastro-esophageal reflux disease

Summary

diagnosis based on symptoms GERD and especially its complications

may be asymptomatic EGD should be done before treatment, but may be not necessary in younger patients with short duration of symptoms multichannel impedance + pH-metry is gold Dx standard in doubtful cases

Gastro-esophageal reflux disease

Summary

PPIs are the mainstay of pharmacotherapy sugrery (laparoscopic fundoplication)

when pharmacotherapy fails no indications for endoscopic tretament at present future: - drugs inihibitng TLESRs - full-thickness fundoplications