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Ass. Lecturer Tropical MedicineAss. Lecturer Tropical Medicine
Cairo UniversityCairo University
( 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
B. Endoscopic
1. Endocinch 1995
2. Stretta 1997
3. Enteryx 1999
4. Gate keeper 2002
(III) Barrett(III) Barrett’’s screening & surveillances screening & surveillance
“ 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
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
Bravo Wireless capsuleBravo Wireless capsule
New SensorNew Sensor
Vantrappen et al, have developed a new acid
exposure sensor
Cheap, disposable, easily applicable, and does not require the pCheap, disposable, easily applicable, and does not require the patient toatient to
carry recording equipment during the study.carry recording equipment during the study.
consists of a screena screen--printed, polymerprinted, polymer--based matrix that undergoesbased matrix that undergoes
pHpH-- and timeand time--dependent decomposition resulting in the release ofdependent decomposition resulting in the release of
electrically conductive material embedded in the polymer layer,electrically conductive material embedded in the polymer layer, whichwhich
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 theresponse) that can be measured after its removal from the esophagusesophagus..
This is a development that potentially bringsthat potentially brings esophagealesophageal acidacid
monitoring to the primary care level.monitoring to the primary care level.
Major disadvantages
1. Sensor response is a cumulative measurement and does not allo1. Sensor response is a cumulative measurement and does not alloww
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 bet2. It does not provide information on a temporal association betweenween
reflux events and symptoms.reflux events and symptoms.
MultichannelMultichannel IntraluminalIntraluminal
ImpedanceImpedance
(MII)(MII)
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.
Therapeutic advancesTherapeutic advances
MedicalMedical
TLESR
GABA agonists
Baclofen, a GABA- agonist, has been shown to
reduce triggering of TLESRs in normal subjects
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.
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.
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).
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
Combined therapy for NocturnalCombined therapy for Nocturnal
Acid BreakthroughAcid Breakthrough
• Known tolerance that develops to H2RAs.
• Useful adjunct on an intermittent basis.
Fackler et al., 2003
Are allAre all PPIPPI’’ss the same?the same?
pH>4 With Different PPIs
Long Term ManagementLong Term Management
strategiesstrategies
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
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
• 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
EndoscopicEndoscopic
EndocinchEndocinch 19951995
StrettaStretta 19971997
EnteryxEnteryx 19991999
GatekkeperGatekkeper 20022002
EndoCinch
““Single plication distal to OGJ, significantlySingle plication distal to OGJ, significantly
improved GERD symptomsimproved 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.
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%.
A balloon catheter, nickel titanium electrodes which supply radiA balloon catheter, nickel titanium electrodes which supply radiofrequencyofrequency
energy in a series of small thermal injuries applied to the sphienergy in a series of small thermal injuries applied to the sphincterncter
muscle, have been shown to reduce transient LES relaxations andmuscle, have been shown to reduce transient LES relaxations and perhapsperhaps
alter the dynamics by which reflux takes place.alter the dynamics by which reflux takes place.
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.
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.
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
Gate keeper 42 %
Enteryx 37 %
Stretta 21 %
Which One is Best ?
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
Barrett'sBarrett's screeningscreening
&&
SurveillanceSurveillance
HOW?HOW?
WHO?WHO?
WHEN?WHEN?
How?How?
• Chromoendoscopy
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
Gerd presentation

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Gerd presentation

  • 1. Review byReview by Ass. Lecturer Tropical MedicineAss. Lecturer Tropical Medicine Cairo UniversityCairo University
  • 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 B. Endoscopic 1. Endocinch 1995 2. Stretta 1997 3. Enteryx 1999 4. Gate keeper 2002 (III) Barrett(III) Barrett’’s screening & surveillances screening & surveillance
  • 3. “ 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
  • 4. 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
  • 5.
  • 6.
  • 7. Bravo Wireless capsuleBravo Wireless capsule
  • 8.
  • 9.
  • 10.
  • 12. Vantrappen et al, have developed a new acid exposure sensor Cheap, disposable, easily applicable, and does not require the pCheap, disposable, easily applicable, and does not require the patient toatient to carry recording equipment during the study.carry recording equipment during the study. consists of a screena screen--printed, polymerprinted, polymer--based matrix that undergoesbased matrix that undergoes pHpH-- and timeand time--dependent decomposition resulting in the release ofdependent decomposition resulting in the release of electrically conductive material embedded in the polymer layer,electrically conductive material embedded in the polymer layer, whichwhich 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 theresponse) that can be measured after its removal from the esophagusesophagus..
  • 13. This is a development that potentially bringsthat potentially brings esophagealesophageal acidacid monitoring to the primary care level.monitoring to the primary care level. Major disadvantages 1. Sensor response is a cumulative measurement and does not allo1. Sensor response is a cumulative measurement and does not alloww 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 bet2. It does not provide information on a temporal association betweenween reflux events and symptoms.reflux events and symptoms.
  • 15.
  • 16.
  • 17.
  • 18. 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.
  • 19.
  • 20.
  • 21.
  • 22.
  • 24. TLESR
  • 25. GABA agonists Baclofen, a GABA- agonist, has been shown to reduce triggering of TLESRs in normal subjects
  • 26. 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.
  • 27.
  • 28. 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.
  • 29. 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).
  • 30. 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
  • 31. Combined therapy for NocturnalCombined therapy for Nocturnal Acid BreakthroughAcid Breakthrough
  • 32.
  • 33.
  • 34. • Known tolerance that develops to H2RAs. • Useful adjunct on an intermittent basis. Fackler et al., 2003
  • 35. Are allAre all PPIPPI’’ss the same?the same? pH>4 With Different PPIs
  • 36. Long Term ManagementLong Term Management strategiesstrategies
  • 37. 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
  • 38. 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
  • 39. • 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
  • 43.
  • 44.
  • 45.
  • 46. ““Single plication distal to OGJ, significantlySingle plication distal to OGJ, significantly improved GERD symptomsimproved 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.
  • 47. 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%.
  • 48. A balloon catheter, nickel titanium electrodes which supply radiA balloon catheter, nickel titanium electrodes which supply radiofrequencyofrequency energy in a series of small thermal injuries applied to the sphienergy in a series of small thermal injuries applied to the sphincterncter muscle, have been shown to reduce transient LES relaxations andmuscle, have been shown to reduce transient LES relaxations and perhapsperhaps alter the dynamics by which reflux takes place.alter the dynamics by which reflux takes place.
  • 49.
  • 50.
  • 51.
  • 52.
  • 53. 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.
  • 54.
  • 55. 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.
  • 56.
  • 57.
  • 58. 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
  • 59.
  • 60. Gate keeper 42 % Enteryx 37 % Stretta 21 % Which One is Best ?
  • 61. 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
  • 65. 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