Post on 20-Jul-2019
Pathogenesis and current treatment
of gastroesophageal reflux disease
Georgios P. Karamanolis
Assistant Professor in Gastroenterology
Aretaieion Hospital
GERD - definitionGERD is a condition which develops when the reflux of stomach content causes troublesome symptoms
and / or complications
Symptomatic Syndromes
Typical reflux syndrome
Reflux chest pain syndrome
Syndromes with Esophageal Injury
Reflux esophagitis
Reflux stricture
Barrett's esophagus
Adenocarcinoma
Esophageal Syndromes
Established Association
Reflux cough
Reflux laryngitis
Reflux asthma
Reflux dental erosions
Proposed Association
Sinusitis
Pulmonary fibrosis
Pharyngitis
Recurrent otitis media
Extra-esophageal Syndromes
Vakil et al. Am J Gastroenterol 2006
pathophysiology
impaired clearance
hiatal herniaTLESRs
hypotensive sphincterdelayed gastric
emptying
anti-reflux barrier
CD LES
failure
l low basal LESP
l transient LES relaxations
l hiatal hernia
LES pressure
*
(98)
**
0
10
20
30
40
50
60
70
80
NormalVolunteers GERD
Mildesoph
Severeesoph
PatientControls
LESPressure(mmHg)
Kahrilas et al., 1986
swallow
LES
stomach
7
1
20
40
40
40
40
20
3
7
11
15
pH
mm Hg
Manometry
cm
ab
ove
LE
S
20
transient LES relaxations
pathways mediating
Inhibitory
Motor Neuron
--
-
NO
+ +
InterneuronVagal
efferent
CNS
Vagal
afferent
Fundic
mechanoreceptors
transient LES relaxations
TLESRs
No. / h5
10
15
0
80
100
Controls GERD
60
40
20
%TLESRswith
acid reflux
Controls GERD
Sifrim et al., 2001
transient LES relaxations
Transient LESrelaxation
Swallow-induced LES
relaxation
LES pressuredrift
Absent basalLES pressure
pHPharynx
LOS
Stomach
100
80
60
40
20
0
%Reflux
episodes
reflux mechamisms in GERD
– ambulatory study
Penagini et al., 1996
hiatal hernia
lower threshold for
triggering TLESRs
retention in hernia
with re-reflux
low LESPsusceptible to intra-
abdominal pressure rises
Sivri and Mittal, 1991
Kahrilas et al., 2000
Van Herwaarden et al., 2000
initialmanagement
long-term management
GERD: clinical management
non-erosive reflux disease (NERD) : 60-70%
reflux esophagitis (RE): 30-40%
GERD phenotypes
reflux symptoms
normal endoscopy
reflux symptoms
endoscopic criteria
Lundell et al. Gut 1999
LA Grade C
1 mucosal
breaks bridging
the tops of folds
but involving
<75% of the
circumference
LA Grade D
1 mucosal
breaks bridging
the tops of folds
and involving
>75% of the
circumference
LA classification
1 isolated
mucosal breaks
>5 mm long
LA Grade B1 isolated
mucosal breaks
5 mm long
LA Grade A
? 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
highest efficacy
lowest efficacy
Recommended
Should beabandoned
Current
guidelines
mainstream options for therapy of
GERD
Dent et al. Gut 1999 (Suppl 2)
hours / day
gastric pH > 4
lifestyle advices
stop smoking
reduce alcohol intake
weight loss in obese patients
elevation of the head of the bed
eat 3-4 hrs before sleeping
4 weeks PPIs
Dent et al. Gut 1999 (Suppl 2)
non-erosive reflux disease (NERD)
PPIs vs. placebo
NERD - cochrane 2006
NERD - cochrane 2006
PPIs vs. H2RAs
Α/Β LA
Dent et al. Gut 1999 (Suppl 2)
C/D LA
4 weeks PPIs 8 weeks PPIs
90-95% 5-10%
reflux esophagitis (RE)
esophagitis - cochrane 2007
PPIs vs. placebo
4 weeks
PPIs vs. H2RAs
8 weeks
esophagitis - cochrane 2007
0
20
40
60
80
100
0 1 2 3 4 5 6
patients without esophagitis
patients with esophagitis
25%
10%
monthstime since treatment cessation
Carlsson et al 1998
repalse of symptomsp
atients
in s
ym
pto
ma
tic r
em
issio
n %
maintenance therapy
sustain satisfactory symptom control
maintain endoscopic remission
prevention of complications
MAINTENANCE THERAPY
medical therapy
surgical therapy
endoscopic therapy
Medical therapy
initial
therapy
successful
step down
to the lowest PPIs
efficient dose
Dent & Talley. Aliment Pharmacol Ther 2003 ( Suppl 1)Dent et al. Gut 2004 (Suppl 4)
MAINTENANCE THERAPY
continuous long-term PPIs therapy
Dent et al. Gut 1999 (Suppl 2)
MAINTENANCE THERAPY
C / D LA esophagitis
s = symptom recurrence
continuous (months)
intermittent (weeks)
S S
“on demand” (days)
S S S S S S
NERD and A / B LA esophagitis
on demand vs. continuous
maintenance therapy
Bour et al. APT 2005
NSP=0.065
on demand continuous
18
12
% failures
75 86
% symptom free
0.31
0.96
Nb units / day
drawbacks of PPIs
daily administration
incomplete symptom relief
need to chronically consume drugs
not address the pathophysiology of GERD
baclofen (GABA agonist) in GERD
Van Herwaarden et al., 2002
** ** *
0
5
10
15
20
25
30
35
N TLESRs N acid reflux events % time pH < 4
Nu
mb
er
Placebo
Baclofen
surgical therapy
indications for surgical
treatment of GERD
reflux patients who need long-term medical
treatment with standard or increased
dose of PPIs
candidates for surgical treatment
good response to PPIs
predicts good response
to surgical therapy
SO JB, et al. Surgery 1998
nissen fundoplication
long-term outcomes of
laparoscopic Nissen
No of pts f/p (yrs) efficacy (%) revised (%)
Lafullarde et al 178 5-8 87 13
Booth et al 175 2-8 90 6
Bammer et al 171 5-8 94 nr
Dallemange et al 86 10 90 5
limitations of surgical therapy
surgical expertise
hospitalization / post-operative recovery
efficacy may wane over time
up to 50% of patients require acid antisecretory therapy to control symptoms
new symptoms following the procedure
dysphagia 35%
inability to belch 20%
flatulence 41%
dyspepsia 30%
Freston & Triantafilopoulos. APT 2004
dysphagia after Nissen
0
5
10
15
20
25
30
Early dysphagia Late dysphagia Dilation
Nu
mb
er
of
pa
tie
nts
(%
)
Perdikis, et al.Surg Laparosc Endosc 1997
meta-analysis in 2453 patients
with laparoscopic Nissen
endoscopic therapy
10
implantation
radiofrequency endoscopic suturing
deviceinjection of bulking agents
endoscopic fundoplication
esophyx
conclusions
multifactorial disease
TLERs are the most predominant mechanism
chronic disease with relapses
PPIs are the corn stone medical treatment
antireflux surgery is an effective alternative treatment
ΚΑΛΗ ΕΠΙΤΥΧΙΑ ΣΤΟ Κ.Ε.Ε.Λ