Gastroesophageal Reflux Disease: Diagnosis and Investigations

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Gastroesophageal Reflux DiseaseDiagnosis and
Investigations

• Dr. Abdulmalik Altaf

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Epidemiology

• Western populations
• GERD is a very common condition
• One third of population experience symptoms of
  GERD at least once a month,
• Four to 7 experience symptoms daily
• The prevalence and severity of GERD reflux are
  likely increasing
• The diagnosis of a columnar cell-lined esophagus
  is also increasing at a rapid rate

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Symptoms of GERD

• Three categories of symptoms
• Typical symptoms
• Regurgitation and Heartburn
• Worse in a recumbent position or when bending
• Frequent in tense and overweight pts
• Age of onset and duration possible markers of
  increased risks for Barrett's esophagus
• These two symptoms were the only valid ones that
  indicate a difference between patients who have
  normal and pathologic pH-metry when heartburn is
  present
• Specificity is considered adequate, but
  sensitivity is low

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Symptoms of GERD

• Symptoms related to complications of GERD
• Dysphagia and odynophagia
• Associated with mechanical or functional
  obstructions that may cause reflux damage
• Hematemesis and melena
• Rarer complications
• Related to bleeding esophagitis,
• Indicate extensive mucosal damage and suggest the
  possibility of columnar-lined mucosa

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Symptoms of GERD

• Atypical reflux symptoms
• Oropharyngeal dysphagia and aspiration
• Episodes of asthma
• Noncardiac chest pain
• Hoarseness and pharyngitis
• Stress, psychologic traits, and chronic anxiety
  may have an effect on reflux symptoms

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Symptoms of GERD

• Usually, regurgitation and heartburn seen in
  uncomplicated GERD
• In 22 of patients, typical heartburn result from
  stomach or duodenal abnormalities
• Even in cases in which the esophagus is the
  source of symptoms, they are not necessarily
  caused by reflux
• Heartburn may be absent in severe reflux
  esophagitis

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Symptoms of GERD

• 25 of patients with columnar-lined esophagus
  have no symptoms that suggest reflux
• Overall, symptoms are not good predictors of the
  presence and severity of esophagitis and its
  complications
• Because of this unspecificity and poor
  sensitivity, symptoms must not be used as a guide
  to therapy but rather to investigate and document
  the condition

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Diagnostic Tests

• Empiric Trial of Acid Suppression
• Endoscopy
• Esophageal Biopsy
• Esophageal pH Monitoring
• Barium Esophagram
• Esophageal Manometry

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Empiric Trial of Acid Suppression

• The simplest and most definitive method for
  diagnosing GERD and assessing its relationship to
  symptoms
• Assures a cause-and-effect relationship between
  GERD and symptoms
• Became the first test used in patients with
  classic or atypical reflux symptoms without alarm
  complaints
• Approach was aided by the introduction PPIs
• Symptoms usually respond to a PPI trial in 7 to
  14 days

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Empiric Trial of Acid Suppression

• GERD may be assumed if symptoms disappear with
  therapy and then return when the medication is
  stopped
• Reported empiric trials with heartburn
• The initial dose of PPI was high (eg, 4080
  mg/day omeprazole) and given for not less than 14
  days.
• A positive response was defined as at least 50
  improvement in heartburn
• Sensitivity of 68 to 83

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Empiric Trial of Acid Suppression

• Fass et al,1998
• In noncardiac chest pain, a 7-day trial of 40 mg
  of omeprazole in the morning and 20 mg in the
  evening
• Sensitivity of 78 and specificity of 86 for
  predicting GERD, compared with traditional tests
• Ours et al, 1999
• 40 mg omeprazole twice daily for 2 weeks a very
  reliable method for identifying acid-related
  cough
• Patients with suspected asthma and ENT symptoms
• Two to 4-month regimen of twice-daily PPIs

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Empiric Trial of Acid Suppression

• Advantages
• Office-based, easily performed, relatively
  inexpensive, available to all physicians, and
  avoids many needless procedures
• Disadvantages
• Placebo response and uncertain symptomatic
  endpoint if symptoms do not totally resolve with
  extended treatment

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Upper GI Endoscopy

• The standard for documenting the type and extent
  of mucosal injury to the esophagus
• Identifies the presence of esophagitis
• Excludes other causes of the patients complaints
• Only 40 to 60 of patients with abnormal
  esophageal reflux by pH testing have endoscopic
  evidence of esophagitis
• Sensitivity is 60 at best
• Specificity 90 to 95

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Upper GI Endoscopy

• Endoscopic signs of acid reflux
• Edema and erythema
• Earliest signs but neither is specific for GERD
• Very dependent upon the quality of endoscopic
  visual images
• Friability, granularity, and red streaks
• More reliable
• Erosions
• Develop with progressive acid injury
• May also be caused by NSAIDs use, heavy smoking,
  and infectious esophagitis

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Upper GI Endoscopy

• Ulcers
• Reflect more severe esophageal damage
• They have depth into the mucosa, tend to have
  either a white or yellow discolored base
• May be seen either isolated along a fold or
  surrounding the EG junction
• Other signs
• Schatzki ring
• A thin, pearly white tissue structure located at
  the squamocolumnar junction
• Recent debate suggests that it is a complication
  of GERD

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Upper GI Endoscopy

• Peptic strictures
• Narrowing of the distal esophagus because of
  long-term chronic acid-induced inflammation
• Shortened, thick, noncompliant region of scarring
• Like rings, peptic strictures tend to occur
  distally at the EG junction
• Typically short and less than 1 cm in length
• If they are longer, other causes, should be
  sought.
• Further evidence of esophagitis is often seen
  proximal to the stricture

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Upper GI Endoscopy

• Barrett esophagus
• Appears as a salmon- or pink-colored mucosa in
  the tubular esophagus
• Mucosal biopsies are always necessary to confirm
  the presence of specialized intestinal metaplasia

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Upper GI Endoscopy

• Endoscopic grading of GERD
• Depends upon the endoscopists interpretation of
  visual images
• There is no standard classification scheme for
  endoscopic findings
• Several grading systems are available, but none
  is completely satisfactory
• Savary-Miller classification
• Most popular scheme in Europe
• Based on degree of mucosal erosions
• Hetzel and Los Angeles systems
• Most popular in the United States
• Hetzel the area of mucosal injury
• Los Angeles system the number, length, and
  location of mucosal breaks

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Upper GI Endoscopy
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Upper GI Endoscopy

• What is the role of endoscopy?
• Initially, endoscopy was used to characterize
  patients into mild erosive and severe erosive
  disease and to better direct their management.
• Because PPIs treat both groups equally well,
  early endoscopy has less impact on the choice of
  therapy

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Upper GI Endoscopy

• When to do endoscopy?
• Patients experiencing alarm symptoms
  dysphagia, odynophagia, weight loss, and GI
  bleeding
• To rule out other entities such as infections,
  ulcers, cancer, or varices
• Currently, the most important reason for
  performing endoscopy in GERD patients is to
  identify reflux complications
• Using this rationale, most patients with chronic
  GERD need only one endoscopy while on therapy

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Esophageal Biopsy

• Microscopic changes may occur even when the
  mucosa appears normal endoscopically
• Biopsy helps to..
• identify reflux injury
• exclude other esophageal diseases
• confirm complications, especially Barrett
  esophagus
• In classic esophagitis, biopsies are not taken
  unless needed to exclude other diagnoses
• When Barrett esophagus is suspected
• biopsies are mandatory
• best done when esophagitis is healed

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Esophageal Biopsy

• Where to biopsy?
• If lesions are present
• from the base of the lesion to demonstrate the
  depth of injury as well as reparative process
• If no lesions are noted
• at least 3 cm above the EG junction (Z-line) to
  look for reactive changes caused by reflux
• Multiple biopsies are gathered because of the
  sporadic nature of the histological changes
• Tissue closer to the Z-line is not sampled
  because of the decreased specificity for
  diagnosing GERD
• Diagnostic yield
• Depends on the sample size, biopsy location,
  tissue orientation, and the expertise of the
  pathologist

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Esophageal Biopsy

• Histopathology
• The most sensitive markers are reactive
  epithelial changes
• An increase in the basal cell layer greater than
  15 of the epithelium thickness or papillae
  elongation into the upper third of the epithelium
• Papillae height increases because of loss of
  surface cells from acid injury
• Basal cell hyperplasia is indicative of mucosal
  repair
• These changes are also noted in up to 50 of
  healthy persons
• Sensitive markers for GERD but have poor
  specificity
• Short-term inflammation characterized by the
  presence of neutrophils and eosinophils

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Esophageal pH Monitoring

• Ambulatory intraesophageal pH monitoring is now
  the standard for establishing pathologic reflux
• Technique
• The test is performed with a pH probe passed
  nasally and positioned 5 cm above the
  manometrically determined lower esophageal
  sphincter (LES)
• The probe is connected to a battery-powered data
  logger capable of collecting pH values every 4 to
  6 seconds
• An event marker is activated by the subject in
  response to symptoms, meals, and body position
  changes
• Patients are encouraged to eat normally and have
  regular daily activities
• Monitoring is carried out usually for 18 to 24
  hours
• Reflux episodes are detected by a drop in pH to
  below 4

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Esophageal pH Monitoring

• Commonly measured parameters
• percentage of total time at pH lt 4
• percentage of time upright and supine at pH lt 4
• total number of reflux episodes
• duration of longest reflux episode
• number of episodes greater than 5 minutes
• Total percentage of time at pH lt 4
• The most reproducible measurement for GERD
• Reported upper limits of normal values ranging
  from 4 to 5.5

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Esophageal pH Monitoring

• Problems with esophageal pH monitoring
• No absolute threshold value that reliably
  identifies pathologic GER
• Validation studies comparing the presence of
  esophagitis with abnormal pH tests
• Sensitivities ranging from 77 to 100
• Specificities from 85 to 100.
• False-negative studies caused by dietary or
  activity limitations from poor tolerability of
  the nasal probe

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Esophageal pH Monitoring

• Advantages of ambulatory esophageal pH monitoring
  
• Ability to record and correlate symptoms with
  reflux episodes over extended periods
• Replaced the shorter acid perfusion (Bernstein)
  test, the standard acid reflux (Tuttle) test and
  radionuclide scintigraphy

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Esophageal pH Monitoring

• Clinical applications for ambulatory pH
  monitoring
• Patients with a normal endoscopy and suspected
  reflux symptoms
• Before fundoplication, pH testing should be
  performed in patients with normal endoscopy to
  identify the presence of pathological reflux
• Persistent or recurrent symptoms after antireflux
  surgery
• Evaluation of patients with reflux symptoms
  resistant to treatment with normal or equivocal
  endoscopic findings
• pH testing may help in defining patients with
  extraesophageal manifestations of GERD

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Barium Esophagram

• Most useful in demonstrating structural narrowing
  of the esophagus
• Consuming a 13-mm radiopaque pill along with the
  barium liquid is the most sensitive test
• Sensitivity 95-100
• Shows subtle findings usually missed by endoscopy
  
• Schatzki rings, webs, or minimally narrowed
  peptic strictures
• Allows good assessment of peristalsis
• By giving the patient swallows of barium in the
  prone oblique position
• Helpful preoperatively in identifying a weak
  esophageal pump

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Barium Esophagram

• Identifies GER when contrast moves in a
  retrograde fashion from the stomach into the
  esophagus
• Only has a sensitivity of about 40 for defining
  GERD.
• Provocative maneuvers can be used to elicit
  stress reflux but might also decrease its
  specificity
• Primarily used in evaluating the GERD patient
  with new-onset dysphagia because it can define
  subtle strictures and rings as well as assess
  motility
• The ability to detect esophagitis varies
• Also falls short when addressing the presence of
  a Barrett esophagus

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Esophageal Manometry

• Provides information on the functional ability of
  the esophageal muscles
• Quantifies the contractile activities of the
  esophageal sphincters and body during swallowing
• Records
• Resting pressures of the lower and upper
  esophageal sphincters
• The timing and completeness of the relaxation
• In the esophageal body, peristalsis is evaluated
• The presence, propagation, velocity, amplitude,
  and duration of contraction waves in response to
  wet swallows
• Measurement of LES pressures logically should be
  associated with the severity of GERD because of
  its importance as a major barrier to reflux

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Esophageal Manometry

• Generally not indicated in the evaluation of the
  uncomplicated GERD patient
• The vast majority of have a normal resting LES
  pressure, and transient LES relaxation is the
  primary mechanism by which their reflux occurs
• Esophageal manometry is an essential test in the
  preoperative evaluation of patients before
  antireflux surgery
• A normal LES pressure does not preclude surgery
• Occasionally. an alternative diagnosis is made,
  which may change the clinical approach
• Most importantly, the presence of ineffective
  peristalsis suggests a weak esophageal pump. A
  loose 360 fundoplication or an incomplete
  fundoplication will minimize the risk of
  postoperative dysphagia.

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References

• Richter, Joel E. Diagnostic tests for
  gastroesophageal reflux disease. Am J Med Sci.
  2003 Nov326(5)300-8.
• Greenfield, LA et al. Surgery scientific
  principles and practice, 3rd ed. Lippincott
  Williams Wilkins, Philadelphia, 2001.
• Duranceau A, Ferraro P, Jamieson GG.
  Evidence-based investigation for reflux disease.
  Chest Surg Clin N Am. 2001 Aug11(3)495-506, vi.

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