Glen A' Lehman, M'D'

1
Managing GERD Lifestyle Changes, Medications,
Endoscopy, Surgery, Testing

• Glen A. Lehman, M.D.
• Professor of Medicine and Radiology
• Indiana University School of Medicine

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What is Gastroesophageal Reflux Disease (GERD)?

• It is a condition in which the gastric contents
  regurgitate (reflux) into the esophagus causing
  harm to upstream structures

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PATHOGENESIS OF GERD Primary Factors
-5 mmHg
5 mmHg
4
GERD Manifestations and Complications
Esophageal manifestations
Extraesophageal manifestations
(Heartburn / Regurgitation)
ENT
Pulmonary
Cardiac
Others

• Laryngitis
• Sinusitis
• Otitis
• Ulcers
• Granuloma
• Polyps

• Asthma
• Chronic cough
• Pneumonia
• Bronchitis
• Interstitial fibrosis

• Chest pain
• Sinus arrhythmia

• Dental erosions
• Halitosis

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GERD symptoms
Yes
Alarm symptoms
Early endoscopy to R/O cancer
No
Empiric therapy Life style modification Antacids O
TC H2RA
Unsuccessful
Maintain therapy for 3 months and then discontinue
H2RA BID
Successful
Relapse within 6 months
No relapse
PPI QD

• Endoscopy..R/O Barretts and
• detect/eradicate H-pylori
• Re-treat

PPI BID
Refractory GERD
Unsuccessful
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Refractory GERD Definition

• Persistent GERD symptoms/esophagitis despite
  double dose PPI x 30-60 days

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Causes of Refractory GERD
Therapy Related Factors
Patient Related Factors

• Compliance
• Motility Disorder
• Eosinophilic Esophagitis
• Hypersensitive Esophagitis
• Non-Acidic Reflux
• Psychological Comorbidity

• Eradification of Helicobacter
• Pylori infection
• Nocturnal Acid Breakthrough
• (NAB)
• Resistance to PPI
• Rapid Metabolism of PPIs

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Motility Disorders

• Esophageal dysmotility
• Delayed gastric emptying
• Duodeno-gastroesophageal reflux

• Spasm
• Hypomotility

• 50 frequency

• frequency??

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Eosinophilic Esophagitis

• When to suspect?
• Long standing esophageal symptoms such as
  dysphagia with or without food impaction.
• Refractory heartburn on PPIs
• Allergic history
• Peripheral Eosinophilia
• Elevated IgE

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Eosinophilic Esophagitis
Esophageal biopsygt1520 eosinophils/HPF
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Eosinophilic EsophagitisHigh risk of mucosal
tears/perforations
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Hypersensitive Esophagus(Neuropathy)

• Typical HB with meal/food association
• burning tongue/mouth
• No/little PPI response
• pH probe (48 hr) no/minimal esophageal
• acid reflux
• No evidence of bile/nonacidic reflux
• Endoscopy usually normal. Consider biopsy for
  eosinophilic esophagitis

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Non-Acidic Reflux

• Definition The reflux of gastric contents
• into the esophagus with pH gt4
• Multichannel Intraluminal Impedance
• (detects any fluid in lumen)

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Causes of Refractory GERD
Therapy related factors
Patient Related factors

• Compliance
• Motility Disorder
• Eosinophilic Esophagitis
• Hypersensitive Esophagitis
• Non-Acidic Reflux
• Psychological Comorbidity

• Eradification of Helicobacter
• Pylori infection
• Nocturnal Acid Breakthrough
• (NAB)
• Resistance to PPI
• Rapid Metabolism of PPIs

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Nocturnal Acid Breakthrough (NAB)

• Gastric pH lt4 for at least 1 hour during the
  night.

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Omeprazole/NaHCO3 (ZEGERID)

• NaHCO3 raises gastric pH and protects Omeprazole
  from acid degradation.
• Immediate-release formulation with peak plasma
  levels being reached in 30 minutes
• Maintain gastric pH gt 4 for 55 (median) of the
  10pm to 6am period vs 27 for a delayed-release
  oral PPI

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Acid Suppression with PPIs

• Esomeprazole 40 mg b.i.d. 70
• Esomeprazole 40 mg q.d. 50
• Lansoprazole 30 mg b.i.d. 61
• Lansoprazole 30 mg q.d. 48

Mean Percent Time Gastric pH gt4
DA Johnson, et al. European DDW 2004
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Long-term (Possible) Side Effects of Acid
Suppression with PPIs

• Achlorhydria
• Pneumonia risk
• Laheij et al, JAMA
  20042921955-1960
• Risk of hip fracture
• Yang et al, JAMA, 20062962947-2953
• C-difficile infection
• Cunningham et al, J Hosp infection,
  200354243-245
• Mucosal hyperplasia.

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Hyperplastic gastric polyps after chronic PPI
use
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Current Tools to Prove GERD

• Endoscopy endoscopic picture, histology
• pH probeabnormal pH lt4 gt4.2 of time
• Others Barium swallow, Scintigraphy, PPI trial
  therapy

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pH Probes

• Standard transnasal catheter
• - Single probe
• - Dual probe
• Capsule (tubeless) (Bravo capsule)
• Intra-nasopharyngeal (Restech)
• Impedance-pH probe (Multichannel Intraluminal
  Impedance)

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pH Probes
Tubeless pH probe (Bravo)
Restech
Traditional transnasal pH probe or Impedence probe
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Are the Symptoms Reported by the Patient During
pH Monitoring Associated with Gastroesophageal
Reflux?

• Symptom index

Number of Times Symptom Occurred when pH lt4
100
x
Total Number of Times Symptom Reported
Positive SI gt 50
Wiener G et al Am J Gastroenterol 83623, 1988
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pH Probes

• Standard transnasal catheter
• - Single probe
• - Dual probe
• Capsule (tubeless) (Bravo capsule)
• Intra-nasopharyngeal (Restech)
• Impedance-pH probe (Multichannel Intraluminal
  Impedance)

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(Reference ranges undefined)
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pH Probes

• Standard transnasal catheter
• - Single probe
• - Dual probe
• Capsule (Tubeless) 48 hr (Bravo capsule)
• Intra-nasopharyngeal (Restech)
• Impedance-pH probe (Multichannel Intraluminal
  Impedance)

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Tubeless pH probe (Bravo)

• More data 48 hours
• Better patient tolerability
• Less restriction in daily activity

Advantages
Fajardo et a, GIE 200663184-185
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48-hour pH Monitoring gtSensitivity in Detecting
Abnormal Esophageal Acid Exposure (AEAE)
190 patients underwent Bravo capsule study
ve study in 115 (61) patients
ve study in 54/115 (56) patients for both days
ve study in 51/115 (44) patients in a single day

• Forty-eight-hour pH testing may increase
  detection
• accuracy and sensitivity for AEAE by as much as
  22.

Tseng et al., J Gastrointest Surg. 2005
Nov9(8)1043-51
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Tubeless pH probe (Bravo)

• Difficult nasal passageEndoscopy is needed
• Early capsule detachment 5Replacement, manual
  
• inspection of the tracing
• Late capsule persistent attachmentEndoscopic
  removal
• Perforation?..Case report

Disadvantages
Fajardo et al, GIE 200663184-185
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Restech

• Oropharyngeal aerosolized pH probe detecting
  aerosolized and liquid reflux in the airway in
  real-time
• System has a miniature 1.5mm probe that is
  inserted trans-nasally, with a resting position
  posterior to the uvula
• All data is transmitted wirelessly
• Mainly for detecting laryngopharyngeal reflux
  (LPR)
• Very limited studies with ill-defined cut-offs
• Does not provide data regarding the total reflux
  time

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pH Probes

• Standard transnasal catheter
• - Single probe
• - Dual probe
• Capsule (tubeless) 48 hr (Bravo capsule)
• Intra-nasopharyngeal (Restech)
• Impedance-pH probe (Multichannel Intraluminal
  Impedance)

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(No Transcript)
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WHY DOES IMPEDANCE CHANGE?

• No bolus few ions high impedance

Bolus present many ions low impedance
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Rationale for Impedance-pH Monitoring

• Impedance allows detection of bolus movement in
  the esophagus
• Reflux is detected by impedance when retrograde
  bolus movement episodes occur
• Acidity of reflux episodes is categorized with a
  standard pH sensor
• Impedance-pH detects all types of reflux
• Acid reflux
• Nonacid reflux

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PPI Therapy Does Not Change Number of Reflux
Episodes
Non-acid
acid
(Blonski et al DDW,2007)
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MII-pH in Patients with Symptoms on PPI BID
200 patients
Symptoms 172 (86)
No symptoms 28 (14)
Symptoms not associated with reflux 98 (57)
Non-acid reflux 61 (35)
Acid reflux 13 (8)
(Mainie et al GUT, 2006 55 1398)
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pH Probes
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Approach to Refractory GERD
Possible GERD symptoms
Trial of PPI Rx (Acid Reduction)
Success (Confirm Dx)
Persistent symptoms
MII-pH monitoring on Rx
No GER with Symptoms (_at_55)
Acid GER with symptoms (_at_10)
Non-acid GER with symptoms
(_at_35)
(Reflux Reduction Rx)
(Pursue other Dx)
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Endoscopic Treatment of GERD
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Reasons for Limited Use of Endoscopic Therapy of
Refractory GERD

• Efficacy
• 50-70 symptom improvement rate/short-term
• Little long-term data
• pH normalization in 30
• Safety
• Reimbursement
• Availability

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Multiple other endscopic GERD therapies under
development
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EsophyX (FDA approved)
After 4 weeks
Pre-op Post-op
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Medigus (not FDA approved)
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Laparoscopic Anti-Reflux Surgery
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Laparoscopic Anti-Reflux SurgeryNissen and
Toupet Fundoplication
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Seven-year follow-up of a randomized clinical
trial comparing proton-pump inhibition with
surgical therapy for reflux esophagitis.
Cumulative proportion of patients staying in
remission over the 7 years after randomization to
antireflux surgery or continuous omeprazole
therapy. Patients maintained on 20 mg omeprazole
Lundell et al, Br J Surg. 2007 Feb94(2)198-203
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Seven-year follow-up of a randomized clinical
trial comparing proton-pump inhibition with
surgical therapy for reflux esophagitis.
Cumulative proportion of patients staying in
remission over the 7 years after randomization to
antireflux surgery or continuous omeprazole
therapy. Inclusion of patients who relapsed on
the initial dose and had a dose adjustment to 40
or 60 mg omeprazole.
Lundell et al, Br J Surg. 2007 Feb94(2)198-203
48
Medical vs Surgical Therapyin pH probe negative
patients with refractory GERD symptoms
10
7
Symptoms improvement after fundoplication
compared with continued PPI therapy in refractory
GERD patients presented with laryngopharyngeal
reflux symptoms and with -ve pH probe studies
Swoger et al, Clin Gastroenterol Hepatol
20064433-441