Recent Trends in Gerd Management

1. Review byReview by

2. ( I ) Diagnostic Advances:( I ) Diagnostic Advances:
A. PPI Test
B. Bravo capsule
C. New sensor
D. Multichannel Intraluminal Impedance
E. GERD diagnostic algorythm
( II ) Therapeutic advances( II ) Therapeutic advances
A. Medical
1. TLESR
• GABA agonist, Baclofen
• Glutamate inhibitor, Riluzole
2. Combination therapy
3. Are all PPIs the same
4. Long-term management strategies
5. Prokinetics
A. Endoscopic
1. Endocinch 1995
2. Stretta 1997
3. Enteryx 1999
4. Gate keeper 2002
(III) Barrett(III) Barrett’s screening & surveillance’s screening & surveillance

3. DEFINITION
Individuals with any symptomatic
condition or histopathologic
alteration resultant from episodes
of gastro-esophageal reflux.
Kahrilas and Quigley, 1996
Gastro-esophageal reflux diseaseGastro-esophageal reflux disease

4. SYMPTOMS
TypicalTypical
– HeartburnHeartburn
– RegurgitationRegurgitation
AtypicalAtypical
– DysphagiaDysphagia
– DyspepsiaDyspepsia
– NauseaNausea
– Chest painChest pain
– ENT symptomsENT symptoms
– Pulmonary symptomsPulmonary symptoms
Gastro-esophageal reflux diseaseGastro-esophageal reflux disease

5. Gastro-esophageal reflux diseaseGastro-esophageal reflux disease
LESIONS

6. WidenedWidened
intercellularintercellular
spacespace
SymptomsSymptoms
Stimulation ofStimulation of
sensory nervesensory nerve
endingsendings
MucosalMucosal
damagedamage
Acid exposureAcid exposure
Gastro-esophageal reflux diseaseGastro-esophageal reflux disease
ACID REFLUX AND SYMPTOMS

7. ““The dominant mechanism of symptomThe dominant mechanism of symptom
production in reflux disease is by contact of theproduction in reflux disease is by contact of the
esophageal mucosa with acid and pepsin”esophageal mucosa with acid and pepsin”
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 diseaseIn the majority of people with reflux disease
there is abnormally prolonged exposure of thethere is abnormally prolonged exposure of the
distal esophagus to acid and pepsin”distal esophagus to acid and pepsin”
Effective control of gastric acid is
central to the management of GERD
Genval GERD Guidelines, Dent et al 1999

8. TLESR

12. “ This is what happens in the community. Most
patients have a trial of PPI therapy. So I think
we have to accept that as being the standard
approach today. If it's successful you basically
have confirmed your diagnosis. ”
(Donald O Castle, MD, 2003).
PPI Test

13. PPI Test
• Lanzor 30mg 2 weeks
• Convenient
• Cost-effective
• Immediate diagnostic certainty
• Sensitivity 81%
• Specificity 85%
• Negative predictive value 91%
Saxena et al., Gut 1999.
Fondrick Am J Gastroentero, 2002

16. Bravo Wireless capsuleBravo Wireless capsule

20. New SensorNew Sensor

21. Vantrappen et al, have developed a new acid
exposure sensor
Cheap, disposable, easily applicable, and does not require the patient toCheap, disposable, easily applicable, and does not require the patient to
carry recording equipment during the study.carry recording equipment during the study.
consists of a screen-printed, polymer-based matrix that undergoesa screen-printed, polymer-based matrix that undergoes
pH- and time-dependent decomposition resulting in the release ofpH- and time-dependent decomposition resulting in the release of
electrically conductive material embedded in the polymer layer, whichelectrically conductive material embedded in the polymer layer, which
causes a change of electrical conductivity of the sensor (sensorcauses a change of electrical conductivity of the sensor (sensor
response) that can be measured after its removal from the esophagus.response) that can be measured after its removal from the esophagus.

22. This is a development that potentially brings esophageal acidthat potentially brings esophageal acid
monitoring to the primary care level.monitoring to the primary care level.
Major disadvantages
1. Sensor response is a cumulative measurement and does not allow1. Sensor response is a cumulative measurement and does not allow
upright, supine, and postprandial reflux to be distinguished.upright, supine, and postprandial reflux to be distinguished.
2. It does not provide information on a temporal association between2. It does not provide information on a temporal association between
reflux events and symptoms.reflux events and symptoms.

23. Multichannel IntraluminalMultichannel Intraluminal
ImpedanceImpedance
(MII)(MII)

27. That's non-acid reflux identified
by impedance. You would not
know it was happening if you
merely did a pH study as most
of us today.
This is an acid reflux episodeThis is an acid reflux episode
Because the pH dropped belowBecause the pH dropped below
4. pH electrode merely to tell4. pH electrode merely to tell
what type of reflux thewhat type of reflux the
impedance has identified.impedance has identified.

32. Therapeutic advancesTherapeutic advances
MedicalMedical

33. TLESR

34. GABA agonists
Baclofen, a GABA- agonist, has been shown to
reduce triggering of TLESRs in normal subjects

35. Zhang et al.,2003 reported a 40% reduction of postprandial
TLESR and reflux episodes after 40 mg baclofen orally.
Van-Herwaarden et al.,2003 who found not only a similar
reduction in TLESR and reflux episodes but also a 35% to
46% reduction in esophageal acid exposure time.
Cange et al.,2003 reported a significant reduction in
ambulatory esophageal acid exposure after a single "stat"
dose of baclofen 40 mg.

37. Significant reduction in the number of reflux episodes and also a
significant reduction in the time pH was less than 4 in patients on
baclofen compared with placebo, where there was no effect.

38. These findings suggest that the approach of
controlling reflux by controlling triggering of TLESRs
is feasible, but further studies and new agents are
required to establish the usefulness of GABA-
agonists in management of GERD.
(Donald O Castle, MD, 2003).

39. Glutamate Inhibitor
Riluzole an inhibitor of glutamate release,
significantly reduced the rate of TLESR during gastric
distension but had no effect on the amplitude or the
velocity of persistalsis, basal LES pressure, or LES
relaxation after water swallowing. These findings
suggested that glutamate may be involved in the
neurocircuitry of TLESR but its contribution appeared
to be small.
Hirsch et al., 2003Hirsch et al., 2003

40. Combined therapy for NocturnalCombined therapy for Nocturnal
Acid BreakthroughAcid Breakthrough

43. • Known tolerance that develops to H2RAs.
• Useful adjunct on an intermittent basis.
Fackler et al., 2003

44. Are all PPIAre all PPI’s the same?’s the same?
pH>4 With Different PPIs

45. Long Term ManagementLong Term Management
strategiesstrategies

46. 2
Continuous
maintenance
Intermittent
“on-demand”
s = symptom recurrence
0 6 months
S S
S S S S S S
26 w
2–4w
Long- term management strategies for GERDLong- term management strategies for GERD
Resolution of
symptoms
with
initial therapy
2–4w 2–4w 2–4w
S S

47. 8
• Patients using Nexiam
®
on demand take only
one dose approximately
every 3 days.
• As a result, this
management approach
has the potential to be
highly cost-effective.
Drug usage with Nexiam®
on-demand therapyDrug usage with Nexiam®
on-demand therapy
Nexiam®
, 20 mg,
once daily, on demand
Mean number of doses
Study 1 One dose every 3 days
(n=167)
Study 2 One dose every 3 days
(n=251)
Talley et al 2000; Talley et al 2001

48. • Role in management of GERD has been re-examined.
• Motilin receptor agonist ABT-229 at doses of 5 mg and
10 mg twice daily for 7 days, significantly reduced the
mean esophageal acid exposure time but had no effect
on esophageal motility or gastric half-emptying time
Netzer et al., 2003.
• Similar dosing treatment extended to 28 days, no
significant improvement in the Composite Reflux Severity
Score Chen et al., 2003.
ProkineticsProkinetics

49. EndoscopicEndoscopic

50. EndocinchEndocinch 19951995
StrettaStretta 19971997
EnteryxEnteryx 19991999
Gatekkeper 2002Gatekkeper 2002

51. EndoCinch

55. ““Single plication distal to OGJ, significantlySingle plication distal to OGJ, significantly
improved GERD symptoms”improved GERD symptoms”
• Multicenter study
• 64 patients, 6 months
• 74% off PPI
• 67% improvement in HRQLS (p <.001)
• 29% PH < 4 (p,.008)
• 30% PH normalized
• No manometry changes
• 1 perforation (managed conservatively)
D. Pleskow, Gastrointestinal Endoscopy, 2004.

56. StrettaStretta
The Stretta procedure (Curon Medical, Inc.) entails
delivery of radiofrequency energy to the
gastroesophageal junction and gastric cardia.
Trials reported an improvement in heartburn score and
GERD quality of life score after 6 to 12 months. PPI
requirement fell from 88% to 30% with significant
reduction in esophageal acid exposure time. The
procedure was well tolerated by patients, with self-
limited complications of 8.6%.

57. A balloon catheter, nickel titanium electrodes which supply radiofrequencyA balloon catheter, nickel titanium electrodes which supply radiofrequency
energy in a series of small thermal injuries applied to the sphincterenergy in a series of small thermal injuries applied to the sphincter
muscle, have been shown to reduce transient LES relaxations and perhapsmuscle, have been shown to reduce transient LES relaxations and perhaps
alter the dynamics by which reflux takes place.alter the dynamics by which reflux takes place.

62. These data suggest that the thermal energy applied, does
something to ablate both sensory nerves and perhaps
nerves that carry afferent signal for transient LES
relaxations, and this might be the mechanism by which
symptoms improve.
This could be a good treatment for patients with non-
erosive reflux disease, or
In fact, be something to be concerned about, because
patients no longer worry about symptoms since they don't
have any and continue to have acid in the lower
esophagus.

64. Enteryx
Deviere et al.,2003 reported the effects of the
injection of ethylene vinyl alcohol polymer (Enteryx,
Boston Scientific Corp.) into the muscular layer of the
LES to increase its bulk.
The procedure increased the LES pressure and
led to a sustained reduction in heartburn score in
most patients at 6 months.
More than two thirds of patients were able to
discontinue their acid suppression therapy.

67. Gate KeeperGate Keeper
• Gate keeper reflux repair system
• Hydrogel prothesis implanted in submucosa
• Pilot study showed safety (no prothesis migration)
• One definite advantage over other procedures ..
reversible
• No data available to compare it with medical therapy
∀ ∴ considered , so far , experimental
P. Fockens, 2003

69. Gate keeper 42 %
Enteryx 37 %
Stretta 21 %
Which One is Best ?

70. PPI, Surgery or Endoscopic
therapy ?
• Long term PPI
– Safe & effective, Large RCT’s, all grades of GERD.
– No mortality or morbidity.
• Surgery
– Can not guarantee cure, several RCT’s, all grades of GERD
– Measurable mortality/morbidity.
• Endoscopic therapy
– Evolving & not adequately studied
– Measurable morbidity
Nord H. J. 2003

71. Barrett'sBarrett's screeningscreening
&&
SurveillanceSurveillance

72. HOW?HOW?
WHO?WHO?
WHEN?WHEN?

73. How?How?
• Chromoendoscopy

74. Who? & When?Who? & When?
• Still No prospective controlled trials to answer those
questions.
• Retrospective studies provides data justifying
surveillance.
• “a decision based more on the art of medicine rather
than the science of medicine.”
Kearney DJ, et al. Gastrointestinal Endoscopy. 2003

76. • World J Gastroenterol. Mar 21, 2011; 17(11): 1480–
1487.
• Published online Mar 21, 2011. doi:
10.3748/wjg.v17.i11.1480
• PMCID: PMC3070023
• Proton pump inhibitor step-down therapy for GERD:
A multi-center study in Japan
• Takao Tsuzuki, Hiroyuki Okada, Yoshiro Kawahara,
Ryuta Takenaka, Junichiro Nasu, Hidehiko Ishioka,
Akiko Fujiwara, Fumiya Yoshinaga, and Kazuhide
Yamamoto