Gastroesophageal Reflux Disease: Diagnosis and Investigations Dr. Abdulmalik Altaf

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

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

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

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

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

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

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

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

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%

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

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

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%

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

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

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

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

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

Upper GI Endoscopy

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

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

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

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

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

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

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%

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

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

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

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

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

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

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.

References Richter, Joel E. Diagnostic tests for gastroesophageal reflux disease. Am J Med Sci. 2003 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. 2001 Aug;11(3):495-506, vi.

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