1. Gastroesophageal Reflux Disease: Diagnosis and Investigations
Dr. Abdulmalik Altaf

2. 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

3. Symptoms of GERD Typical symptoms Three categories of 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

4. 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

5. 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

6. 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

7. 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

8. Diagnostic Tests Empiric Trial of Acid Suppression Endoscopy
Esophageal Biopsy
Esophageal pH Monitoring
Barium Esophagram
Esophageal Manometry

9. 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

10. 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, 40–80 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%

11. 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

12. 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

13. 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 patient’s 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%

14. 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

15. Upper GI Endoscopy Ulcers Other signs Schatzki ring
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

16. 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

17. 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

18. Upper GI Endoscopy Endoscopic grading of GERD
Depends upon the endoscopist’s 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

19. Upper GI Endoscopy

20. 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

21. 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

22. 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

23. Esophageal Biopsy Where to biopsy? Diagnostic yield
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

24. 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

25. 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

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

27. 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

28. 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

29. 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

30. 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: %
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

31. 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

32. 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

33. 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.

34. References
Richter, Joel E. Diagnostic tests for gastroesophageal reflux disease. Am J Med Sci Nov;326(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 Aug;11(3): , vi.

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