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used questionnaire, which was validated by Belfasky et al. in
patients with esophageal double pH probe conrmed LPR [17].
This nine-question survey uses a ve-point severity scale for common LPR symptoms with a cutoff of >13 considered to be diagnostic. The RSI score can be followed overtime to monitor
treatment outcomes and direct clinical decision-making [18].
Conventionally, the diagnosis of LPR has been dened by a positive RSI combined with specic ndings on laryngoscopy.
Laryngoscopy is used by Otolaryngologists to evaluate the
upper respiratory tract for signs of injury and malignancy and can
be performed in an ofce setting. Common ndings of laryngeal
irritation include edema or hyperemia of larynx, cobblestoning of
posterior pharynx, contact ulcers, polyps, interarytenoid changes,
granulomas, and subglottic stenosis. In an effort to standardize
ndings that support a diagnosis of LPR, the Reux Finding
Score (RFS) was developed by Belafsky etal. [19]. Although the
validation study for the eight item rating scale reported excellent
inter-relator reliability, the subsequent studies have failed to support this correlation. Laryngeal irritation has been identied in
80–90% of normal healthy volunteers without symptoms, and the
rating scale is highly subjective [9, 20]. Evaluation of the posterior larynx especially, traditionally thought to be a primary site of
injury, is consistently the most difcult to rate and assess with
poor inter-rater correlation [21]. Given its low specicity for LPR,
the focus of laryngoscopy has shifted instead towards ruling out
malignancy and has been supplanted by instruments that direct
measure esophageal and pharyngeal pH and pressures.
Distal esophageal pH measurements reported as a cumulative
DeMeester score have long been the gold standard for diagnosis
of GERD, but studies have shown poor correlation between PPI
responders and distal esophageal acid exposure [22]. To measure
oropharyngeal pH changes, a single oropharyngeal probe was
designed to be placed proximal to the UES.Unfortunately, clinical trials determined up to 43% of healthy volunteers may have
abnormal hypopharyngeal pH, and these instruments failed to
clearly differentiate between healthy volunteers and those with
LPR and GERD [9, 23, 24]. Pharyngeal pH measurements also
fail to measure nonacid events which likely contributes to the
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poor diagnostic yield. Multichannel intraluminal impedance
(MII) probes are placed in the esophagus to measure the physiologic reux events by detecting changes in the intraluminal pressure. Combined with a distal and proximal pH probes (MII/pH),
these instruments are able to differentiate between composition
(liquid, gas, or mixed) and acid content of reuxate. Subsequent
studies have shown that MII/pH can detect LPR episodes, but the
cutoff values for reuxate pH and exposure times, and proximal
probe position in relation to the UES varies greatly between studies [13, 15, 25]. In an effort to establish correlation of distal
esophageal reux events with LPR, several studies have compared the ndings from oropharyngeal pH probes to MII/pH
probes in select patients. Results were inconclusive, as oropharyngeal pH probes detected only acidic events and MII/pH
detected both acid and nonacid events, but 90% of the oropharyngeal ndings were independent of MII/pH events without any
obvious correlation found [2]. The use of MII/pH probes in LPR
patients lacking common GERD symptoms provides a diagnostic
yield of 40–50% for detecting associated GERD and improves
patient selection for surgery [13]. Currently, these instruments
provide the most complete picture of the reux burden in LPR,
but their clinical utility for determining the treatment response is
limited to those patients with objective conrmation of GERD.
Another area of research involves the detection of upper airway pepsin exposure. Techniques for the specimen collection
vary, with some studies performing laryngeal/pharyngeal biopsies
and others using salivary samples to run rapid monoclonal antibody tests or quantitative ELISA PCR studies [26–28]. Pepsin
levels vary depending on time of day, as higher levels are found
on waking and directly after reux events. Oropharyngeal pepsin
can be found in healthy controls, but the concentration is noticeably lower compared to GERD and LPR patients, thus favoring a
quantitative study for a diagnostic value. Studies have shown that
pepsin at pathologic levels in the upper airway can be considered
a marker for LPR but have failed to differentiate between GERDrelated and non-GERD-related LPR.A recent systematic review
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concluded that current evidence lacks appropriate standardization
of specimen collection location, collection timing, and cutoff values, thus limiting its utility as a tool to identify potential treatment
responders [29].
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Treatment
As in the treatment of GERD, lifestyle and dietary modications
can have a meaningful impact on disease burden for patients with
LPR. The recommendations are similar, with lifestyle changes
such as weight loss, cessation of smoking and alcohol usage, and
refraining from supine positioning directly following a meal.
Dietary changes incorporate a low fat (<45 g/day) diet, small meal
size, and the elimination of coffee, tea, carbonated, and caffeinated soft drinks, chocolate, and citrus [3, 8]. A systematic review
of the RCT of medical therapy for LPR treatment showed that the
dietary changes were associated with a signicant improvement
of symptoms in both PPI responders and nonresponders [15].
The initial medical therapy for LPR has also mirrored GERD
with the empirical usage of PPIs, although a mounting evidence
shows a poor response rate compared to placebo. Although these
studies are primarily RCT comparing PPI usage to placebo, the
limitations are signicant and due in large part to the poor diagnostic criteria for LPR as well as failure to standardized reported
outcomes. In studies reporting a benet from PPI usage over placebo, the studied cohort included patients with LPR who either
had common GERD symptoms or objective evidence of GERD
[9, 30, 31]. Of these studies, some responders reported an
improvement in mean RSI scores, but investigators found no
objective improvement by laryngoscopy or endoscopy [11]. The
inconsistent therapeutic rate of empiric PPIs is likely multifactorial, as non-responders may have non-acid reuxate episodes or
may not even have GERD.Overall, the current literature indicates
that a positive response to the empiric therapy is the best indicator
for eventual symptom resolution, but failure to continue the main-
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tenance therapy carries a high risk of symptom recurrence [32,
33]. Analyses supporting anti-reux interventions have promising
long-term results but rely greatly on the appropriate workup with
MII/pH identifying underlying GERD.
Endoluminal anti-reux interventions have garnered recent
attention with successful outcomes comparable to surgery. The
transoral incisionless fundoplication (TIF) is performed
endoscopically and creates and 270° anterior fundoplication
secured with H-shaped fasteners. Cessation of daily PPI usage is
reported in 70–80% of patients and was more likely in patients
with poor symptom control despite maximum PPI therapy and in
those with objective evidence of GERD on MII/pH or endoscopy
[34–36]. Additionally, up to 60% of patients report resolution of
LPR symptoms postoperatively. Recent meta-analysis show
decreased efcacy with time; however, raising concern for the
durability of the endoscopically reinforced LES [37]. Relatively
well tolerated with a low adverse event prole, TIF is a reasonable
treatment modality for the extraesophageal manifestations of
GERD and should be considered in patients unable or unwilling
to undergo surgery.
Anti-reux surgery (ARS) is a highly successful treatment
with excellent long-term outcomes in select patients with GERD,
but predicting success in patients with concomitant and/or pure
LPRD has been difcult. ARS is performed laparoscopically in
the majority of cases and involves hiatal dissection, cruroplasty,
and fundoplication for static reinforcement of the LES. Recent
comparisons of patients undergoing ARS vs PPI therapy revealed
a higher rate of symptom improvement by mean RSI (84% vs
50%), a higher proportion of patient satisfaction (63% vs 44%),
and higher percentage of patients able to discontinue PPI therapy
(44% vs 7%) at long-term follow-up [38, 39]. Patients with conrmed reux asthma report a decrease in asthma symptoms and
medication usage following ARS [40]. An alternative to fundoplication, magnetic sphincter augmentation (MSA) using the LINX
device (Torax Medical, Shoreview, MN) provides a dynamic augmentation to the LES.Outcomes of ARS with MSA are compa-
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437
rable to standard fundoplication, with up to 85% of patients
reporting discontinuation of PPIs and resolution of LPR symptoms [39, 41–43]. Interestingly, the frequency or severity of proximal reux events on pharyngeal pH or MII/pH have not been
shown to be predictive of therapy response. Although these outcomes are promising, the preoperative evaluation for LPR patients
should include extensive counseling explaining that resolution of
extraesophageal symptoms is less reliable than the response rate
of typical symptoms.
Conclusion
LPR represents a signicant healthcare burden as a result of complex diagnostic criteria lacking gold standard testing and poor
treatment response in a signicant number of patients. Further
study is needed to establish the best diagnostic test for LPR,
which is complicated by the lack of standardization in reporting
both preoperative ndings and postoperative outcomes. Treatment
efcacy is thereby difcult to establish, although subjective symptom resolution may be the most important measurable outcome to
patients. Using symptom resolution and cessation of PPIs as measures of treatment success, endoscopic and surgical treatments
appear to have better short- and long-term results compared to
medical therapy alone. However, predicting treatment responses
remains a challenge, and extensive preoperative counseling is
necessary prior to any intervention.
Acknowledgements None.
Conicts of Interest There are no conicts of interest to disclose and no
funding for this study.
Author Contributions Literature review: CH.
Writing: CH, SD, FPB.
Critical revision: CH, SD, FPB.
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C. Hill et al.
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FedericoSerrot
Introduction
Gastroesophageal reux disease (GERD) is a chronic and highly
prevalent disorder. A recent systematic review showed that the
prevalence of GERD is 18.1–27.8% in North America, 8.8–25.9%
in Europe, 2.5–7.8% in East Asia, 8.7–33.1% in the Middle East,
11.6% in Australia, and 23.0% in South America [1].
According to the published practice guidelines of the American
College of Gastroenterology, a presumptive diagnosis of GERD
can be made on the basis of typical symptoms, such as heartburn,
regurgitation, epigastric pain, and sleep disturbance. An improvement of reux symptoms on empiric medical therapy with a proton pump inhibitor (PPI) ideally conrms this symptom- based
diagnosis (so-called PPI test). Upper gastrointestinal endoscopy is
only recommended in the presence of lack of improvement of
symptoms as well as screening of patients at high risk for complications [2, 3].
F. Serrot (*)
Department of Surgery, Emory University, Atlanta, GA, USA
© 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_32
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