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30 Diagnostic Tests forGastroesophageal Reux Disease
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Table 30.1 (continued)
Test Indication Common Findings
pH
monitoring
Esophageal manometry Preoperative planning
24 h or 48
h pH
monitoring
Impedance
1. Failure of
medical therapy
2. Preoperative
Evaluation
3. Atypical
symptoms
4. Symptoms
without
endoscopic
evidence of
esophagitis
5. Recurrence of
symptoms
following
anti-reux
surgery
1. Refractory
symptoms
2. Atypical or
extraesophageal
symptoms
for anti-reux (i.e.,
fundoplication)
surgery
Abnormal score based
on
• Frequency of
reux episodes
• Duration of longest
reux episode
• Number of
episodes longer
than 5min
• Total time pH less
than 4.0in supine
and standing
position
Normal impedance
values include
• total reux events
≤73
• acid reux events
≤55
• weakly acid reux
events ≤26
• weakly alkaline
reux ≤1
• Normal or
abnormal
esophageal
function
• If low DCI (<500
mmHg/s/cm),
consideration for
partial
fundoplication
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H. T. Jackson and I. N. Haskins
Barium Esophagram
Barium esophagram is a key study in the workup of GERD; however, it should not be performed with the goal of establishing the
diagnosis of GERD. In contrast to a 24 or 48-h pH study, an
esophagram only allows for evaluation of reux during a 10-min
time period. The esophagram has a relatively low diagnostic sensitivity and specicity for GERD (40% and 85%, respectively)
[3]. Even when reux is demonstrated, the short duration of the
study does not allow a differentiation between physiologic and
abnormal reux. Esophageal motility can be assessed with an
esophagram; however, manometry will provide a more in-depth
and descriptive analysis of esophageal motility. We believe the
value of the esophagram lies in providing information about the
length and diameter of the esophagus, the presence and morphology of a hiatal hernia, and the presence of a peptic stricture or
Schatzki ring.
Esophagogastroduodenoscopy (EGD)
Esophagogastroduodenoscopy (EGD) is the standard modality
used in the evaluation of the esophageal mucosa in patients with
GERD symptoms [1]. For patients with typical GERD symptoms,
which include heartburn and/or regurgitation, a trial of medical
therapy with an antacid, histamine-receptor blocker, or proton
pump inhibitor medication is typically the rst intervention [1, 2].
Evaluation of the esophagus and stomach in a patient with typical
GERD symptoms is not recommended as rst-line treatment due
to the high specicity of heartburn (89%) and regurgitation (97%)
with GERD [1]. Nevertheless, it is important to remember that a
small subset of patients may have endoscopic evidence of GERD
in the absence of any GERD symptoms [1].
In general, the recommendations for EGD in a patient with
GERD symptoms are:
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1. A patient with typical GERD symptoms refractory to medical
therapy.
2. A patient with atypical or alarming GERD symptoms, such as
dysphagia, odynophagia, anemia or acute blood loss, and
unintentional weight loss [1, 4].
3. Suspicion for mass, stricture, or ulcer as seen on other imaging
studies, including barium esophagram or computed tomography scan.
4. As an adjunct for proper placement of pH probe as part of a
preoperative workup for fundoplication or other surgical management of GERD.
When performing an EGD in a patient with GERD symptoms,
in addition to evaluation of the esophageal and gastric mucosa, it
is important to perform random biopsies of both the esophagus
(near the Z-line) and the stomach (near the antrum) to evaluate for
esophagitis, Barrett’s esophagus, and associated dysplasia, gastritis, and Helicobacter pylori. Further, it is important to note any
anatomical abnormalities found on EGD, including hiatal hernia,
peptic stricture, gastric mass, etc., which may be contributing to
the patient’s symptoms. Finally, it is important to remember that
most patients with typical GERD symptoms have no abnormalities on EGD and that a normal EGD does not rule out GERD [1,
2, 4].
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Esophageal Manometry
The performance of esophageal manometry is not part of the routine workup for GERD unless a patient is being considered for
anti-reux surgery [1]. In the case of preoperative surgical evaluation, esophageal manometry is used to evaluate the overall function of the esophagus, to rule out severe motility disorders,
including achalasia and scleroderma, which are contraindications to fundoplication, and to assist with placement of transnasal
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pH probes [1]. There is no pathognomonic manometry tracing
for GERD.When reviewing manometry, the important values to
review are the location and length of the lower esophageal
sphincter (LES), the resting and residual LES pressures, the percent peristalsis of wet swallows, and the distal contractile integral (DCI).
H. T. Jackson and I. N. Haskins
pH Monitoring
pH monitoring is the gold standard for the diagnosis of GERD. 24or 48-h pH monitoring objectively establishes the presence of
pathologic reux and allows for correlation between the symptoms
reported by the patient and episodes of reux. pH monitoring provides information on the frequency of reux episodes, duration of
the longest episode of reux, the number of episodes longer than 5
min, and the total time the pH is less than 4.0in the supine and
standing position. These components make up the composite score
(DeMeester score) that denes normal and abnormal reux (greater
than 14.7 indicates pathologic reux) [5]. An abnormal score is also
an important predictive factor in the success of anti-reux surgery.
A multivariate analysis by Campos etal. of patients who received a
laparoscopic nissen fundoplication found that the 24-h pH monitoring score was the greatest predictor of a good or excellent outcome
[6]. The study similarly showed that 25% of patients with normal
pH scores who had typical symptoms and responsiveness to medication had only a fair or poor outcome following surgery [ 6].
Forty-eight hours wireless esophageal pH monitoring (BRAVO
probe) can avoid the discomfort, embarrassment, and changes in
daily activity and diet that patients may experience with the 24-h
nasal probe [7]. Limitations of the BRAVO study include that it
only records the pH of the lower esophagus; in contrast to the 24
h probe, early detachment of the probe into the stomach can lead
to false positive results (Fig.30.1).
Impedance pH Monitoring is another helpful study that can be
used in the workup for patients with GERD.The study measures
the ow of liquid and gas across the gastroesophageal junction
independently of the pH of the reux contents. It provides details
30 Diagnostic Tests forGastroesophageal Reux Disease
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Fig. 30.1 BRAVO study tracing demonstrating reux, early detachment
of the probe from the esophagus into the stomach that can lead to false
positive results, and the typical subsequent tracing as the probe travels into
the duodenum
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regarding the characteristics of the reuxate (gas, liquid, mixed),
the pH (acid, weakly acid, alkaline) [8]. This study is typically
recommended in patients with symptoms refractory to proton
pump inhibitors or atypical symptoms such as cough. Mainie etal.
showed that patients with refractory symptoms can have successful outcomes following anti reux surgery when impedance- pH
monitoring shows a correlation between symptoms and reux episodes regardless of pH [9]. Normal impedance values include:
total reux events ≤73, acid reux events ≤55, weakly acid reux
events ≤26, and weakly alkaline reux ≤1 [10].
Summary
Accurately establishing a diagnosis of GERD is of paramount
importance prior to offering surgical management. Diagnostic
studies in the workup of GERD serve to establish abnormal
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H. T. Jackson and I. N. Haskins
esophageal exposure, identify anatomical and functional abnormalities, and to correlate symptoms to reux events. Table30.1
provides an overview of the diagnostic test indications and common ndings.
References
1. Badillo R, Francis D.Diagnosis and treatment of gastroesophageal reux
disease. World J Gastrointest Pharmacol Ther. 2014;5(3):105–12.
2. Muthusamy VR, Lightdale JR, Acosta RD, Chandrasekhara V, Chathadi
KV, Eloubeidi MA, et al. The role of endoscopy in the management of
GERD.Gastrointest Endosc. 2015;81(6):1305–10.
3. Streets CG, DeMeester TR.Ambulatory 24-hour esophageal pH monitoring: why, when, and what to do. J Clin Gastroenterol. 2003;37(1):14–22.
4. Smith L. Updated ACG guidelines for diagnosis and treatment of
GERD.Am Fam Physician. 2005;71(12):2376–82.
5. Jamieson JR, Stein HJ, DeMeester TR, Bonavina L, Schwizer W, Hinder
RA, Albertucci M.Ambulatory 24-h esophageal pH monitoring: normal
values, optimal thresholds, specicity, sensitivity, and reproducibility.
Am J Gastroenterol. 1992;87:1102.
6. Campos GM, Peters JH, DeMeester TR, Öberg S, Crookes PF, Tan S,
DeMeester SR, Hagen JA, Bremner CG.Multivariate analysis of factors
predicting outcome after laparoscopic Nissen fundoplication. J
Gastrointest Surg. 1999;3(3):292–300.
7. Håkanson BS, Berggren P, Granqvist S, Ljungqvist O, Thorell
A.Comparison of wireless 48-h (Bravo) versus traditional ambulatory
24-h esophageal pH monitoring. Scand J Gastroenterol. 2009;44(3):276–
83.
8. Blonski W, Vela MF, Castell DO.Comparison of reux frequency during
prolonged multichannel intraluminal impedance and pH monitoring on
and off acid suppression therapy. J Clin Gastroenterol. 2009;43(9):816–
20.
9. Mainie I, Tutuian R, Agrawal A, Adams D, Castell DO.Combined multichannel intraluminal impedance–pH monitoring to select patients with
persistent gastro-oesophageal reux for laparoscopic Nissen fundoplication. Br J Surg. 2006;93(12):1483–7.
10. Cho YK. How to interpret esophageal impedance pH monitoring. J
Neurogastroenterol Motil. 2010;16(3):327.
Laryngopharyngeal Reux
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31
CharlesHill, StephanieDoggett,
andFrancisP.Buckley III
Introduction
Gastroesophageal reux disease (GERD) develops when gastric
reuxate causes troublesome symptoms or complications [1].
This denes a diagnosis of GERD as one founded on patient
symptoms and includes both liquid and gaseous reuxate which
can be acidic, weakly acidic, or weakly alkaline. The typical
GERD symptoms include heartburn and regurgitation and can
result in esophageal injury. Additional extraesophageal symptoms, including chronic cough, hoarseness, asthma, throat clearing, globus sensation, and post nasal drip, fall under the broad
category of laryngopharyngeal reux (LPR). These reux-related
symptoms occur throughout the day and are associated with an
upright posture. While there is a clear association between LPR
and GERD, the symptoms of LPR can occur independently and
proving a causative relationship is difcult [2]. For this chapter,
we will focus on the presentation, diagnosis, and management of
LPR as an extraesophageal manifestation of underlying
GERD. The Montreal Denition of LPR refers to established
C. Hill (*) · S. Doggett · F. P. Buckley III
Dell Medical School, University of Texas at Austin, Austin, TX, USA
e-mail: Charles.hill2@ascension.org
© Society of American Gastrointestinal and Endoscopic Surgeons
(SAGES) 2023
A. D. Patel et al. (eds.), The SAGES Manual of Physiologic
Evaluation of Foregut Diseases,
https://doi.org/10.1007/978-3-031-39199-6_31
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associations of reux cough, laryngitis, and asthma which require
careful investigation to eliminate the numerous multifactorial
aggravating cofactors before the treatment can begin.
C. Hill et al.
Epidemiology
The true incidence of LPR is difcult to establish due to the lack
of gold standard diagnostics and complex patient presentations.
The CDC estimates that cough, throat symptoms, and asthma
encompass over 12% of chief complaints for primary care visits
each year. A hidden prevalence likely exists within this estimate in
patients presenting with isolated LPR, but because LPR is also
found in up to 70% of patients with GERD, the true effect has yet
to be determined [3, 4]. Because many of the primary symptoms
are nonspecic, the subsequent workup can involve multiple specialty consults, procedures, diagnostic tests, and medication prescriptions. Annual healthcare costs attributed to GERD
management have been estimated to be $9–12 billion [5, 6]. A
recent cost analysis of Medicare patients undergoing LPR management found an average per patient cost of over $5,000/year,
which is 5.6 times than that of GERD [7]. By this estimation, the
healthcare burden of LPR would be over $50 billion annually.
Additionally, 86% of the per patient cost was related to medication purchases, of which 61% was directly attributed to protonpump inhibitor (PPI) usage.
Pathophysiology
There are multiple physiologic barriers to reux that can be disrupted by independent patient factors. The lower esophageal
sphincter (LES), located at the gastroesophageal junction roughly
40cm from the incisors, functions to prevent stomach acid and
food from owing retrograde into the esophagus during gastric
peristalsis with a resting pressure of 10–45 mmHg. The upper
esophageal sphincter’s (UES) baseline tonic contraction of 30–50
mmHg prevents air from entering the esophagus during respira-
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tion as well as reux into the pharynx during swallowing. The
UES is augmented by increased esophageal pressure during swallowing, but both physiologic sphincters can be compromised by
excessive intra-abdominal pressure, incompetent resting tone, and
anatomic distortions such as a hiatal hernia [8]. Inherent reexes
of glottis closure, coughing, and swallowing also aid in preventing airway exposure to harmful gastroesophageal reux.
Direct exposure, and indirect neurogenic interactions have proposed mechanisms for upper airway injury during LPR. The
reux theory proposes that the inherent reux barriers are overwhelmed causing a direct tissue exposure of the upper airway tissues to gastric acid, reuxate, pepsin, and bile acids. The laryngeal
mucosa lacks the protective alkaline mucous secreting cells of the
stomach that buffer the acidic uid, leading to injury with exposure to the caustic secretions. The mucosal injury causes swelling,
mucous hypersecretion, and an inammatory reaction. Pepsin, the
primary enzyme for protein degradation which can be present in
the gastric reuxate, is most active at a pH <2 and generally inactive at a pH >6.5. Although the minimum acid exposure duration
needed to produce symptoms is unknown, esophageal and laryngeal damage due to reuxed pepsin can be seen at any pH below
8.6. Regarding indirect neurogenic interactions, the reex theory
proposes a vagally-mediated mechanism of bronchoconstriction
in response to esophageal-bronchial neural cough reex. This
neurogenic inammation of the lung mimics the response of the
tracheobronchial tree to micro-aspirations of gastric contents,
releasing inammatory mediators and disrupting normal tissue
[9].
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Diagnosis
As the constellation of symptoms associated with LPR is nonspecic, several other differential diagnoses must rst be considered
and evaluated before proceeding with treatment. In all patients, a
history and physical should be performed with special attention to
alarm symptoms such as stridor, recent surgery, recent intubation,
a history of head and neck radiation, or history of smoking. Any
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C. Hill et al.
of these would prompt a more urgent specialist evaluation to rule
out malignancy. For patients presenting with a chronic cough for
more than 8 weeks, the American College of Chest Physicians
recommends an empiric PPI therapy only after excluding the
more frequent causes like smoking, post-nasal drip, asthma,
bronchitis, and acetylcholinesterase inhibitor usage [10]. Another
common primary complaint is hoarseness, frequently explained
by excessive voice usage, throat clearing, allergies, infection, and
smoking history. The American Academy of Otolaryngology recommends that these possible etiologies be ruled out, followed by
the conrmation of LPR by the combination of a validated patient
reported symptom index and laryngoscopic ndings of injury
prior to initiating empiric PPI therapy [11]. Adult onset asthma is
frequently implicated as LPR, especially in those with concomitant GERD.An expert panel report for the management of asthma
supports an empiric PPI trial in all asthma patients with GERD
and in those with poorly controlled asthma despite maximum
medical therapy [12].
An empiric trial of double-dose PPIs has been favored as a
diagnostic and therapeutic approach for LPR and is based on the
assumption that LPR is caused by GERD. Furthermore, it is
believed to be less expensive and less time-consuming than invasive testing, although the economic impact on long-term PPI
usage is not insignicant. Multiple RCT comparing PPIs to placebo however has only shown a modest (<50%) improvement in
LPR symptoms, with little to no impact on endoscopic esophageal
or laryngeal injury [9, 13–15]. As a diagnostic tool for LPR, the
patient-reported symptoms alone have a sensitivity and specicity
of 49% and 79%, respectively, and there is no improvement in the
diagnostic yield when considering the response to PPI therapy
[14, 16]. When symptoms of LPR remain despite full PPI therapy,
subsequent workup is recommended to rule out GERD and identify other possible etiologies.
Lacking a gold standard diagnostic test, patient symptoms
have become a necessary diagnostic tool. Patient reported outcome (PRO) measures are designed to evaluate disease-specic
symptom severity and their impact on quality of life. The laryngopharyngeal reux symptom index (RSI) is the most commonly
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