CLINICAL REVIEW

Effect of Increased Intra-abdominal Pressure

on the Esophagogastric Junction
A Systematic Review
Stefano Siboni, MD,* Luigi Bonavina, MD,* Benjamin D. Rogers, MD,†
Ciara Egan, BSc, MS,‡ Edoardo Savarino, MD,§ C. Prakash Gyawali, MD,†
and Tom R. DeMeester, MD∥

opened new perspectives by recognizing the contribution of

Abstract: With the advent of high-resolution esophageal man- both the LES as an intrinsic sphincter and the crural dia-
ometry, it is recognized that the antireflux barrier receives a phragm (CD) as an extrinsic sphincter (Fig. 1). About 20%
contribution from both the lower esophageal sphincter (intrinsic of the western population experience reflux symptoms at
sphincter) and the muscle of the crural diaphragm (extrinsic
least weekly.2 Consequently, the modern diagnosis and
sphincter). Further, an increased intra-abdominal pressure is a
major force responsible for an adaptive response of a competent treatment of GERD has become a priority for both gas-
sphincter or the disruption of the esophagogastric junction resulting troenterologists and surgeons.
in gastroesophageal reflux, especially in the presence of a hiatal It has been known that increased intra-abdominal
hernia. This review describes how the pressure dynamics in the pressure (IAP) can initiate GERD by equalizing gastric and
lower esophageal sphincter were discovered and measured over time esophageal pressure. This has stimulated studies by several
and how this has influenced the development of antireflux surgery. investigators on the effects of straight leg raising (SLR),
Key Words: intra-abdominal pressure, intragastric pressure, lower
Valsalva maneuver, and the abdominal binders as maneu-
esophageal sphincter, crural diaphragm, esophageal manometry,
vers to increase IAP and challenge the antireflux barrier.
high-resolution manometry, esophageal acid exposure, straight leg
Aim of the current study was to assess the response of
raise, gastroesophageal reflux disease
the LES to increased IAP. Our review showed that increased
IAP is the major force responsible for an adaptive response
(J Clin Gastroenterol 2022;56:821–830) of a competent LES. If the LES has been damaged, an
increase in abdominal pressure can disrupt the gastro-
esophageal junction and result in gastroesophageal reflux.
This is especially so in the presence of a hiatal hernia.

T he existence of the lower esophageal sphincter (LES)

was proven by Code who, in 1956, recorded a persistent
high-pressure zone in the distal esophagus which relaxed
Further, the review described how the pressure dynamics
were discovered, measured, maintained, and identified when
a surgical repair was needed.
with swallowing.1 The finding became the subject of intense Finally, this review looked at the past to gain a per-
in vivo and in vitro investigation. The precise physiological spective on the present. It also represents a tribute to the
role and clinical implications in patients with gastro- extraordinary work done by pioneers and mentors of
esophageal reflux disease (GERD) are still openly debated. esophageal pathophysiology in light of the current knowl-
Based solely on the LES tone, conventional manometric edge obtained by HRM.
readings of the LES pressure failed to reliably segregate
individuals with physiological reflux from those with
pathologic levels. High-resolution manometry (HRM) has METHODS
A systematic review was performed using the
From the *Division of General and Foregut Surgery, Department of Cochrane, Embase, and PubMed databases according to the
Biomedical Sciences for Health, University of Milan, IRCCS Poli- Preferred Reporting Items for Systematic Reviews and
clinico San Donato, San Donato Milanese; ‡Humanitas University,
Humanitas Research Hospital, Rozzano, Milan; §Gastroenterology
Meta-analyses (PRISMA) guidelines.3 Two authors (S.S.
Unit, Department of Surgery, Oncology, and Gastroenterology, and C.E.) independently queried the databases with the
University Hospital of Padova, Padova, Italy; †Division of Gas- following terms: “intra-abdominal pressure,” “esophageal
troenterology, St. Louis, MO; and ∥Emeritus, Keck School of manometry,” “provocative maneuvers,” “gastro-esophageal
Medicine, University of Southern California, Montague, MI.
S.S. and L.B. conceived the study and wrote the first draft of the
reflux disease,” “lower-esophageal sphincter,” “esoph-
manuscript. B.D.R., E.S., C.P.G., E.S., and T.R.D. revised the agogastric junction,” Abbreviations and synonyms were
manuscript for important intellectual content. also included. Boolean operators AND, OR, and NOT were
The authors declare that they have nothing to disclose. used. References from selected papers were analyzed to
Address correspondence to: Luigi Bonavina, MD, Piazza Edmondo
Malan, IRCCS Policlinico San Donato, San Donato Milanese,
identify additional full-text papers. All original full-text
Milan 20097, Italy (e-mail: [email protected]). English-written papers that included the relationship
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, between IAP and LES were incorporated into the study.
Inc. This is an open access article distributed under the Creative Papers not available in the full text were excluded. The
Commons Attribution License 4.0 (CCBY), which permits unre-
stricted use, distribution, and reproduction in any medium, provided
following topics were analyzed and categorized in thematic
the original work is properly cited. sections: methodology used to increase IAP, LES response
DOI: 10.1097/MCG.0000000000001756 to IAP, relationship between LES and CD, effect of

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Siboni et al J Clin Gastroenterol  Volume 56, Number 10, November/December 2022

FIGURE 1. A, Effect of IAP and inspiration on the LES and CD in normal subjects. B, Normal LES pressure tracing indicating thor-
acoabdominal gradient fluctuations during respiratory phases. CD indicates crural diaphragm; IAP, intra-abdominal pressure; IGP,
intragastric pressure; LESp, lower esophageal sphincter pressure; RIP, Respiratory Inversion Point.

increased IAP on hiatal hernia, effect of increased IAP of final review (Fig. 2). According to the specific pertinence,
esophageal acid exposure, use of IAP as a provocative each study was classified in 1 or more of the 7 thematic
maneuver, and the effect of increased IAP on the outcomes sections. The selected studies are chronologically summar-
of antireflux surgery. ized in Table 1.

Methodology Used to Increase IAP

RESULTS
Multiple methodologies have been evaluated for their
Computerized search using selected criteria identified ability to physiologically or artificially increase IAP. In the
366 studies. Of these, 198, consisting of abstracts, reviews, early stage of esophageal manometry, pneumatic cuffs and
letters, and editorials, were excluded. Further, there were 79 abdominal binders were studied extensively for their ability
duplicate publications and all were removed. The remaining to provide a controlled external pressure on the abdomen. In
89 publications were screened and 22 met the inclusion 1961, Nagler and Spiro4 described 3 asymptomatic volun-
criteria. The references of the eligible publications were then teers who underwent esophageal manometry during
reviewed, and 9 additional manuscripts met the inclusion abdominal compression with a pneumatic cuff. In 2 of the 3
criteria. A total number of 30 studies were included in the subjects, an increased pressure in the intra-abdominal seg-
ment of the LES was noted. A few years later, Cohen and
Harris10 studied 75 patients, with or without hiatal hernia,
during increased IAP from a Valsalva maneuver, an
abdominal binder, or leg raising. No significant LES pres-
sure differences were noted between the 3 modalities. Dodds
et al14 first evaluated the effect different modalities had on
IAP in a study of 20 normal volunteers and 35 patients with
esophagitis. Abdominal compression was achieved using a
pneumatic pressure cuff inflated to 50 and 100 mm Hg,
while Valsalva and SLR maneuvers were both sustained for
at least 20 seconds. Interestingly, while the gastric pressure
increment was similar between the 3 methods, the LES-
gastric pressure gradient was significantly higher during the
SLR maneuver. The authors hypothesized that “the mech-
anical intrahiatal compression of the LES could create LES
pressure changes that exceed those in gastric pressure.”
From this point forward, SLR has been used as an alter-
native to abdominal binders to increase IAP. Thus, even
though available data are scarce to draw robust conclusions,
SLR may be an effective modality to study the LES
response to increased IAP.

LES Response to IAP

Pressure Response
Some studies have artificially increased IAP as a
method to assess the physiological response of the LES in an
attempt to define competence and predict esophageal path-
FIGURE 2. The Preferred Reporting Items for Systematic Reviews ology. In 1966, Lind et al7 used an abdominal binder in a
and Meta-analyses (PRISMA) flow chart. cohort of patients without hiatal hernia and noted a pressure

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J Clin Gastroenterol  Volume 56, Number 10, November/December 2022 Effect of Increased IAP on EGJ

TABLE 1. Timeline of Key Scientific Contributions and Pathophysiological Studies Investigating the Effect of IAP on the EGJ Barrier
Year References Main Findings
1956 Code et al1 First manometric evidence of the LES
1961 Nagler and Spiro4 Increased IAP through a pneumatic cuff. Two of 3 volunteers had increased intra-abdominal LES
pressure
1964 Vanderstappen and Texter5 Differentiation from a crural (pinchcock) and a dome (IAP) action of the diagram
1965 Wankling et al6 LES pressure increase following IAP increase was seen in patients with normal LES pressure, regardless
the presence of hiatal hernia. They hypothesized that increase IAP might be a provocative maneuver
during esophageal manometry
1966 Lind et al7 Discovery of 2 high-pressure zones in patients with hiatal hernia. During abdominal compression, the
region between LES and CD reached intragastric pressure. They concluded that LES rather than CD
had the major role in competence
1968 Lind et al8 LES pressure did not differ in symptomatic, asymptomatic pregnant women, and controls
1968 Lind et al9 Decreased LES pressure during atropine infusion. Concluded that the intrinsic contraction of the LES
was due to vagal reflex
1971 Cohen and Harris10 In 75 patients with and without hiatal hernia, the increased IAP generated an increased LES pressure in
asymptomatic patients, regardless the presence of hiatal hernia
1972 Butterfield et al11 Introduction of the “common cavity test”. Increased esophageal pressure during IAP increase in
symptomatic patients
1973 Alday and Goldsmith12 Degree of fundoplication has a direct relationship with restoration of a pressure gradient across the EGJ
1974 DeMeester et al13 Nissen fundoplication provides a greater increase of LES pressure and intra-abdominal LES length than
Hill and Belsey operations. Abdominal compression by hand showed that the decrease of gastric
pressure transmitted to the esophagus was greatest with the Nissen operation
1975 Dodds et al14 Comparison between 20 volunteers and 35 esophagitis patients. LES response to increased IAP was not
affected by atropine infusion. Support of the main contribution of extrinsic factors to EGJ response to
increased IAP
1979 DeMeester et al15 Clinical and in vitro study. Intra-abdominal LES length played a major role in sphincter competency
1979 Muller et al16 During abdominal loading, the tonic activity of diaphragm increased proportionally to the amount of
the load
1980 Wernly et al17 Study combining IAP and 24-h pH monitoring. IAP increase became significant only in patients with
severe LES alterations
1981 DeMeester et al18 Importance of phrenoesophageal ligament insertion to provide competency during IAP increase
1982 Joelsson et al19 Abnormal esophageal acid exposure on 24-h pH monitoring correlated to either an anatomic or
functional LES dysfunction or a defective pump action of esophageal body
1986 Bonavina et al20 Mixed clinical and in vitro study. Higher prevalence of abnormal 24-h pH test in patients with defective
sphincter
1989 Mittal et al21 Introduction of the 2-sphincter hypothesis: LES and CD are distinct sphincters that operate in synergy
1990 Mittal et al22 Electromyography and atropine infusion in 15 healthy subjects showed diaphragmatic activation during
IAP increase
1993 Klein et al23 Demonstration of a high-pressure zone at the thoracoabdominal junction after esophagectomy
reflecting the pinchcock effect of the CD
2011 Kwiatek et al24 3-dimensional HRM study on CD contribution to competence of the EGJ
2013 Louie et al25 Hiatal closure contributes more to restore LES pressure
2015 Lee and McColl26 Obesity and waist belt contribute to reflux through disruption of EGJ and IAP increase
2017 Mitchell et al27 Impaired clearance might be induced or worsened by increased high IAP, especially after meals
2020 Rogers et al28 First use of straight leg raise maneuver with HRM, significant association between increased esophageal
pressure during leg raise and AET
2020 Stefanova et al29 Intraoperative EndoFLIP study in 100 patients who underwent Nissen, Toupet, or magnetic sphincter
augmentation. Diaphragmatic repair and LES intra-abdominal relocation have greater effect on
competency than sphincter augmentation
2021 Siboni et al30 Hiatoplasty contribution to EGJ barrier function after magnetic sphincter augmentation
2021 Gysen et al31 Introduction of gastrosphincteric pressure gradient to differentiate rumination from GERD patients
2021 Attaar et al32 Intraoperative EndoFLIP study in 97 patients. Hiatal repair provided a significant decrease in LES
distensibility
AET indicates acid exposure time; CD, crural diaphragm; EGJ, esophagogastric junction; EndoFLIP, endoluminal functional lumen imaging probe; GERD,
gastroesophageal reflux disease; HRM, high-resolution manometry; IAP, intra-abdominal pressure; LES, lower esophageal sphincter.

increase in the high-pressure zone corresponding to the CD- than the CD, plays a major role in maintaining the gastro-
LES complex. They hypothesized that this response might esophageal pressure gradient, supporting the hypothesis of
be due either to the compression of the abdominal portion an intrinsic LES contraction.
of the esophagus by the CD or by a contraction of the An additional study demonstrated that LES pressure
sphincter itself. To solve the dilemma, they added a sub- differed among symptomatic and asymptomatic pregnant
group of patients with hiatal hernia. In resting conditions, 2 women, regardless of the presence of a hiatal hernia.8
high-pressure zones corresponding to LES and CD were Further, an additional study was performed with the
recorded; conversely, during abdominal compression, the administration of atropine sulfate (0.025 mg/kg) in healthy
region between the high-pressure zones reached the intra- subjects. During resting conditions, there was a pressure
gastric pressure. The authors concluded that the LES, rather drop of 11.9 cm of water between the stomach and

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Siboni et al J Clin Gastroenterol  Volume 56, Number 10, November/December 2022

FIGURE 3. Decrease of lower esophageal sphincter pressure with atropine infusion during resting conditions and abdominal
compression.9

esophagus, but this difference increased to 20.1 cm of water diaphragmatic activation, which disappeared at the end of
during abdominal compression (Fig. 3). An interesting the maneuver. During atropine infusion, resting LES pres-
observation was that esophageal pressure increased during sure was diminished, whereas peak LES pressure during
abdominal compression in some subjects. Based on these SLR and Muller maneuver were not different from the
findings, the authors speculated that the intrinsic con- premedication period. Combining these findings, the
traction of the smooth muscle in response to abdominal authors concluded that the increase of LES pressure is
compression was related to a vagal reflex.9 mostly due to active diaphragmatic contraction during leg
A study by Cohen and Harris,10 in 1971, further dem- raise (Fig. 5).
onstrated that LES response to increased IAP is independent In summary, these studies demonstrate that during
from the presence of hiatal hernia in asymptomatic subjects. increased IAP, LES, and/or CD tone increases and con-
There were significant differences in LES pressure change in tributes to antireflux barrier competency. The differences
patients with GERD symptoms compared with asymptomatic between the studies may be related to patient selection or
patients (Fig. 4), suggesting that LES pressure dynamics in differing experimental protocols and measurement
response to abdominal strain might contribute to GERD. techniques.
However, a few years later Dodds et al14 refuted this hypothesis
showing that percent change and pressure profile of the LES Length Response
response to SLR after atropine infusion was similar to baseline DeMeester and colleagues15,17,20,33 proposed that the
response before atropine infusion. Instead, they demonstrated intra-abdominal LES length played a major role in pre-
that LES pressure increased significantly only during leg raise, venting IAP from being transmitted into the esophagus. In
rather than by abdominal compression or the Valsalva an in vitro study,15 they showed that competency of LES as
maneuver, indicating a mechanical barrier response rather than measured by amplitude of the distal high-pressure zone,
a smooth muscle response. without intrinsic tone, was related to its length. Under
In 1990, Mittal et al22 recorded diaphragm activation similar conditions, a longer abdominal esophageal length
through electromyography (EMG) and LES pressure was necessary to maintain competence when IAP was
response via esophageal manometry during atropine infu- increased. When artificially generated intrinsic tone was
sion, SLR, abdominal binder application, and the Muller applied to the LES, the interrelationship between these 2
maneuver on 15 healthy subjects. The results showed a slow factors further clarified that the intra-abdominal esophagus
(2 to 5 s) but significant increase of the LES pressure (from is paramount to maintain competence. In fact, with LES
25 to 85 mm Hg) at the onset of the SLR maneuver, with a length <1 cm, the intrinsic tone of the sphincter necessary to
rapid fall at the end. Further, EMG demonstrated prevent reflux became infinite (Fig. 6). These findings

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J Clin Gastroenterol  Volume 56, Number 10, November/December 2022 Effect of Increased IAP on EGJ

FIGURE 5. Modifications in esophageal (E) pressure, lower

esophageal sphincter (LES) pressure, gastric (S) pressure, and
diaphragm electromyogram (DEMG) during straight leg raise
FIGURE 4. Relationship between increased intragastric and lower maneuver.22
esophageal sphincter pressures in patients with gastroesophageal
reflux disease symptoms (A) compared with asymptomatic con- in muscular tone of the LES itself or external compression
trols (B).10 by the CD. Since a pressure rise within the intra-abdominal
LES segment caused by deep inspiration alone was unlikely,
emphasized the importance of adequate intra-abdominal they concluded that augmentation of the high-pressure zone
esophageal length to compensate for increases in IAP, and during deep inspiration might be caused by the peripheral
led to the conclusion that a sufficient amount of intra- (pinchcock) action of the diaphragm.
abdominal esophagus must be restored during antireflux Two years later, Lind et al7 evaluated 24 normal vol-
surgery for benefit to be obtained. Ten years later, a review unteers and 9 hiatal hernia patients and showed that, during
on this topic summarized the available evidence and reached abdominal compression, pressure between the 2 high-pres-
similar conclusions.33 Since IAP compresses both the sure zones (representing the LES and the CD) was com-
stomach and the intra-abdominal portion of the LES, an parable to intragastric pressure in the presence of a hiatus
increase in IAP mechanically helps the sphincter to maintain hernia, while esophageal pressure proximal to the LES
competence. However, if the sphincter is entirely intra- remained stable. The authors concluded that the gastro-
thoracic as in the presence of a hiatus hernia, this benefit is esophageal pressure gradient was maintained by the intrinsic
lost and the sphincter is unable to sustain increased IAP, tone of the LES, which was considered responsible for
thus increasing the likelihood of gastroesophageal reflux. competency.
Muller et al16 studied the muscular tone of the dia-
Relationship Between LES and CD: the “Two- phragm using EMG during abdominal compression and
sphincter” Theory added important insights into the function of the dia-
One of the most controversial issues is whether the phragm. Although the study cohort had only 3 subjects, the
effect of increased IAP on the high-pressure zone is imput- tonic activity of the diaphragm was increased during
able to the intrinsic LES tone or is an extrinsic (ie, dia- abdominal pressure loading, and was proportional to the
phragmatic) contribution. In 1964, Vanderstappen and amount of the load. Therefore, the authors hypothesized a
Texter5 differentiated for the first time the crural (pinch- “stretch reflex” of diaphragmatic muscle spindles contrib-
cock) from the dome (IAP) action of the diaphragm. Intra- uting to diaphragmatic tone, even if they could not exclude
abdominal pressure was increased by both external other mechanisms such as a vagal reflex.
abdominal compression and deep inspiration, resulting in a In 1990, Mittal et al22 added further knowledge to the
mean increase of fundic pressure of 12 and 15 mm Hg, role of the diaphragm by studying 15 healthy subjects with a
respectively. During deep inspiration, the gastroesophageal manometric catheter equipped with 2 platinum electrodes to
pressure gradient was 32 mm Hg, while during external detect diaphragmatic EMG activity. During the SLR
compression this gradient reached 20 mm Hg. The authors maneuver, gastric pressure reached a mean value of
postulated 2 potential mechanisms for these findings, a rise 30 mm Hg, while LES pressure increased up to 85 mm Hg.

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Siboni et al J Clin Gastroenterol  Volume 56, Number 10, November/December 2022

presence of hiatal hernia. The authors concluded that the

presence of a hiatus hernia was not essential for reflux to
occur, but the ability of the sphincter to maintain com-
petence even when displaced into the thorax determined
whether reflux occurred or not.
In 1971, Cohen and Harris,10 stratified 75 patients by
GERD symptoms and hiatal hernia. Again, increase in
gastric pressure exceeded the increase in LES pressure in
patients with symptoms but not in asymptomatic patients
with hiatal hernia, where the increase of LES pressure
exceeded the increase in gastric pressure during Valsalva
maneuver, SLR, or abdominal compression (Fig. 4). The
authors concluded that a sliding hiatus hernia does not
predispose to GERD, pressure surrounding the LES does
not affect competence, and increase in LES strength sec-
ondary to increase in gastric pressure is not influenced by
location of the LES in the abdomen or the chest.
In 1980, Wernly et al17 attempted to explain these
findings using simultaneous esophageal manometry,
24-hour pH monitoring, and increased IAP. They calculated
that there was a high number of increased IAP episodes
through the study day, but only 8% of them induced a reflux
episode. The key point of their discussion was that the distal
portion of the esophagus in the hernia sac was exposed to
abdominal pressure even in the presence of a hiatal hernia
(Fig. 7). Based on the observation that > 90% of episodes of
increased IAP did not generate reflux even in patients with
reflux, the authors concluded that only a severe mechanical
or functional alteration of the cardia (ie, pressure of the
sphincter <5 mm Hg and abdominal length <1 cm) resulted
in reflux with increased IAP.
An explanation for the equivocal results regarding the
role of the hiatus hernia was proposed by DeMeester et al.18
FIGURE 6. Relationship between lower esophageal sphincter This study demonstrated the importance of the phrenoeso-
pressure and length in providing lower esophageal sphincter
competence.15 DES indicates Distal Esophageal Pressure.
phageal ligament, where high insertion of this ligament
resulted in an adequate esophageal abdominal length likely
EMG showed an activation of the diaphragm during the because IAP is transmitted to the sphincter through the
maneuver, suggesting a significant contribution of the dia- hernia sac (Fig. 7). Furthermore, DeMeester33 showed in an
phragm to the pressure increase. in vitro model that stepwise increase of IAP caused a step-
Overall, these studies emphasize the importance of the wise increase in sphincter pressure only if the sphincter was
diaphragm in the barrier function of the esophagogastric placed in the abdominal cavity. In conclusion, isolated
junction (EGJ) during increased IAP. However, the lack of increase of IAP cannot predict reflux, even in the presence of
overlap of CD and LES in patients without hiatal hernia a hiatus hernia, and patients with intact LES tone may be
makes it difficult to assess, even with modern technology, able to sustain IAP challenges even when the sphincter is
which element contributes more to the barrier. Recent intrathoracic.
studies with 3-dimensional HRM have hypothesized that in Effect of Increased IAP on Esophageal Acid
patients with superimposed Lower Esophageal Sphincter
Exposure
and CD, the latter contributes with an asymmetric and
vigorous pressure.24 The first study to report a relationship between
increased IAP and esophageal acid exposure was published
by Vanderstappen and Texter5 in 1964. A simultaneous
Effect of Increased IAP in Patients With Hiatal recording of intraluminal pressure and pH showed that
Hernia acidification of the esophagus often occurred with an
The first study defining the effect of increased IAP in increased IAP. In normal subjects, reflux occurred only at
patients with a hiatus hernia was published by Wankling the time of sphincter relaxation during deglutition. These
et al.6 Twenty asymptomatic controls and 24 patients with findings emphasized the importance of the high-pressure
hiatal hernia were studied using abdominal compression via zone and its capacity to adapt to increased IAP. Despite
a pneumatic cuff (50 mm Hg). The study population was significant limitations (ie, low number of patients, rudi-
stratified by presence of hiatal hernia and resting LES mental technology, and absence of 24-h pH data), this study
pressure, thus dividing the population into normal or feeble helped to define the concept of LES and its correlation
sphincter. In the feeble sphincter group, abdominal com- with GERD.
pression increased esophageal pressure by 20 cm H2O, with Subsequently, Wernly et al17 focused on the relation-
a 5 cm decrease of pressure gradient between stomach and ship between IAP and 24-hour esophageal pH. IAP was
esophagus. These differences were not demonstrated in monitored with a guard-ring tocodynamometer and pH
patients with normal sphincter pressure, regardless of the with a standard pH probe. Only 8% of the IAP challenges

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J Clin Gastroenterol  Volume 56, Number 10, November/December 2022 Effect of Increased IAP on EGJ

increased IAP may be an initiator of GERD. Therefore,

challenging the EGJ with a provocative maneuver during
HRM could facilitate the identification of true GERD
patients.

Rising IAP to Improve the Diagnostic Yield

of Esophageal Manometry
The first study to validate the SLR maneuver as an
adjunctive “stress” test to prove the competency of the LES
was published by Wankling et al6 in 1965. An increase in
esophageal pressure was seen only when LES pressure did
not increase in response to the increased IAP, both in vol-
unteers and hiatal hernia patients. Although this study
involved only a few subjects, there was a significant corre-
lation with intraesophageal pressure increase in patients
with a feeble sphincter. On the contrary, no correlation was
found in patients with or without hiatal hernia. The authors
concluded that the addition of abdominal compression
allowed better assessment of the functional integrity of LES.
In 1972, Butterfield et al11 introduced the concept of a
“common cavity” test, where gradual abdominal com-
pression resulted in a higher increase in esophageal pressure
in symptomatic patients compared with asymptomatic
patients (34 vs. 9.9 mm Hg, P < 0.001). Interestingly, resting
LES pressure was similar in the 2 groups but increased
significantly in asymptomatic compared with symptomatic
FIGURE 7. Diagram showing the effect of hiatal hernia sac on patients during abdominal compression. Since esophageal
lower esophageal sphincter.17 pressure equalized gastric pressure during abdominal com-
pression, they called this the “common cavity” phenom-
enon, and proposed gradual abdominal compression as a
induced a reflux episode. This rate, however, increased to provocative test during esophageal manometry. However,
13% when only patients with defective LES were taken into the common cavity test was not widely adopted in clinical
account. The number of reflux episodes recorded during the practice, and only few studies have reported its utility to
study period was 2.7 per hour and only 38.7% of them were validate the effectiveness of antireflux surgery.34,35
caused by an increased IAP. The authors concluded that the In 1975, Dodds et al14 demonstrated the “common
role of IAP was important in the genesis of reflux only if the cavity” phenomenon in 6/35 patients with esophagitis dur-
LES was defective (pressure <5 mm Hg and intra-abdomi- ing a 100 mm Hg abdominal compression. Surprisingly,
nal length <1 cm). Further, in an in vitro and clinical study, they did not give much significance to this finding, stating
Bonavina et al20 showed a higher prevalence of abnormal that “abdominal compression did not separate most patients
24-hour pH test in patients with intra-abdominal LES with esophagitis from asymptomatic volunteers.” They also
length <1 cm and LES pressure <6 mm Hg. However, the suggested that abdominal compression provided further
fact that patients with normal parameters still might have diagnostic information only when a “common cavity”
reflux indicated that there were other factors responsible for phenomenon was present, thus minimizing the importance
competence of the cardia, such as the degree of gastric of the SLR as a possible provocative test during esophageal
dilatation. The authors concluded that individuals with manometry. Conversely, in all other studies, a positive
either low LES pressure or short intra-abdominal LES “common cavity” test was associated with symptoms. Given
length are unable to cope with the physiological increase of the lack of precise cutoffs and the relative low sample size,
IAP caused by normal activities such as straining or a Butterfield and colleagues’ study did not gain popularity,
change in body position, can result in gastroesophageal and the scientific community lost a promising provocative
reflux. maneuver that could have improved the accuracy of
In 1982, Joelsson et al19 explored a larger population of esophageal manometry.
GERD patients to characterize the pathogenesis of reflux.
They found that increased esophageal acid exposure resulted Increased IAP and Outcomes of Antireflux
from multiple mechanisms, including anatomic or func- Surgery
tional LES failure and a defective pump action of the There has been a mix of serendipity and pure science in
esophageal body. More recently, Mitchell et al27 showed the evolution of modern antireflux surgery. The surgical
that impaired esophageal clearance might be induced or community watched closely and often contributed to the
worsened by increased IAP, especially after meals. Further, understanding of esophageal pathophysiology with the aim
the application of a waist belt increased the rate of transient to improve surgical outcomes. Since the first description of
LES relaxations associated with reflux and impaired the hiatal hernia repair published in 1919 by Soresi,36 dia-
esophageal clearance of refluxed acid. Finally, Lee and phragmatic repair has represented the mainstay of treatment
McColl26 speculated that in patients with either central or to keep the stomach within the abdominal cavity. However,
waist belt obesity, an intrasphinteric reflux might also occur it was only in 1951 that Allison37 and Barrett38 found a
which may be associated with the current rise of adeno- physiological correlation between hiatal hernia and GERD,
carcinoma of the EGJ. These studies demonstrate that giving birth to the true antireflux surgery era. However,

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Siboni et al J Clin Gastroenterol  Volume 56, Number 10, November/December 2022

FIGURE 8. High-resolution manometry plot showing increased esophageal pressure during straight leg raising. LES indicates lower
esophageal sphincter; UES, upper esophageal sphincter.

there were important conceptual differences between the 2 represents a distinct barrier to reflux in addition to the
pioneers’ views. Allison believed in the pinchcock function intrinsic LES.
of the CD and therefore focused his operation on hiatal Louie et al23 confirmed that the crural plasty contrib-
repair and fixation of the phrenoesophageal ligament to the utes more to restore LES pressure than LES intra-abdominal
diaphragm. In contrast, Barrett thought that the most length, while fundoplication is more active in avoiding LES
effective physiological antireflux mechanism was the angle shortening and spontaneous LES relaxation. More recently,
of His, therefore its restoration became the target of anti- studies assessing the separate effect of hiatal repair and
reflux surgery. Later, Skinner and Belsey39 and Hill40 based fundoplication using the endoluminal functional lumen
their operation on this mechanistic hypothesis. In the imaging probe (EndoFLIP) suggested that hiatal repair and
meantime, Rudolf Nissen developed his technique of relocation of the LES into the abdomen are more important
360-degree fundoplication by focusing on restoration of the than fundoplication to restore competency to the EGJ.29,32
intra-abdominal esophageal segment and augmentation of All the above findings support the hypothesis that the LES
LES pressure. Interestingly, Nissen developed his technique and CD function as distinct sphincters and operate in
serendipitously, by realizing that use of the residual gastric synergy to prevent reflux; therefore, to be effective, antireflux
fundus to protect the esophagogastric anastomosis from surgery must restore competence of both sphincters.
leaks prevented postoperative symptomatic GERD.
In 1973, Alday and Goldsmith12 demonstrated in
experimental model a direct relation between the degree of DISCUSSION
fundoplication and its efficacy in maintaining competence This review shows that LES response to increased IAP
and a low esophageal pressure during progressive gastric has been a topic of interest for several decades. Integration
compression. At a minimum, a 270-degree wrap was nec- of experimental data into clinical practice has demonstrated
essary to maintain an effective pressure gradient across the that increasing IAP is a simple and effective method to
EGJ. Furthermore, in a prospective study comparing Nis- assess the LES. The information obtained may prove useful
sen, Hill, and Belsey operations, DeMeester et al13 demon- to augment diagnostic accuracy in patients with suspected
strated that Nissen fundoplication was superior in increasing GERD and to clarify the indications for antireflux surgery.
LES pressure and placing the sphincter in the positive A common finding throughout the studies was an
abdominal environment. The abdominal compression test increased LES pressure in response to increased IAP in
performed by hand clearly demonstrated that the amount of asymptomatic volunteers and patients with normal LES
gastric pressure transmitted to the esophagus was greatest pressure and length. In symptomatic GERD patients, the
with the 360-degree fundoplication. Therefore, the Nissen LES pressure increase was more unlikely and was inde-
operation rapidly became the gold standard in the surgical pendent of the presence of hiatal hernia.6,10 Assessment
treatment of GERD and hiatal hernia. Further evolution of of the separate contributions of LES and CD to competence
the technique led to shortening the fundoplication to 2 cm. of the EGJ was challenging, given the anatomic proximity
in length and calibrating its circumference with a 60 French of the 2 sphincters.5,7 Studies with atropine infusion, EMG,
bougie to prevent dysphagia.41 and 3-dimensional esophageal HRM seem to suggest that
In 1989, Mittal et al21 developed the “two-sphincter” the CD plays a crucial role in increasing the LES-CD
hypothesis and revisited the contribution of CD to the complex pressure.9,22,24 This is supported by more recent
competence of the EGJ. In 1993, Klein et al25 described a evidence that hiatal repair is an essential component of
sphincter-like high-pressure zone at the thoracoabdominal antireflux surgery,25,29,30,32 confirming the “two-sphincter
junction in patients who underwent esophagectomy and hypothesis” originally proposed by Mittal et al.21
gastric conduit replacement. This further supported the Increased IAP is certainly not the only determinant of
hypothesis that the pinchcock mechanism of the CD gastroesophageal reflux.33 Rather, increased IAP is part of a

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J Clin Gastroenterol  Volume 56, Number 10, November/December 2022 Effect of Increased IAP on EGJ

spectrum of pathophysiological mechanisms including 5. Vanderstappen G, Texter EC Jr. Response of the physiologic
transient LES relaxations, impairment of esophageal clear- gastroesophageal sphincter to increased intra-abdominal pres-
ance, increased thoracoabdominal pressure gradient,42 and sure. J Clin Invest. 1964;43:1856–1868.
6. Wankling WJ, Warrian WG, Lind JF. The gastroesophageal
the gastric acid pocket.43 This could explain why the out- sphincter in hiatus hernia. Can J Surg. 1965;8:61–67.
comes of current antireflux procedures, such as magnetic 7. Lind JF, Warrian WG, Wankling WJ. Responses of the
sphincter augmentation, are improved by routine media- gastroesophageal junctional zone to increases in abdominal
stinal dissection and posterior crural repair.30,44,45,46 Dis- pressure. Can J Surg. 1966;9:32–38.
ruption of the EGJ frequently occurs in patients with central 8. Lind JF, Smith AM, McIver DK, et al. Heartburn in
obesity which is associated with increased IAP.26 This could pregnancy: a manometric study. Can Med Assoc J.
1968;98:571–574.
also explain why Roux-en-Y gastric bypass is considered 9. Lind JF, Crispin JS, McIver DK. The effect of atropine on the
more effective than fundoplication in reducing GERD gastroesophageal sphincter. Can J Physiol Pharmacol. 1968;46:
symptoms and recurrence rates in morbid obese patients.47 233–238.
Last, HRM-impedance studies on patients with rumi- 10. Cohen S, Harris LD. Does hiatus hernia affect competence of
nation syndrome have emphasized the role of the gastro- the gastroesophageal sphincter? N Engl J Med. 1971;284:
sphincteric pressure gradient rather than the gastroesophageal 1053–1056.
pressure gradient as an independent factor of backward 11. Butterfield DG, Struthers JE Jr, Showalter JP. A test of
flow.31 This supports the bulk of evidence that increased IAP gastroesophageal sphincter competence. The common cavity test
Am J Dig Dis. 1972;17:415–421.
promotes reflux mainly in patients with disrupted EGJ.
12. Alday ES, Goldsmith HS. Efficacy of fundoplication in
Despite the important limitations due to heterogeneity preventing gastric reflux. Am J Surg. 1973;126:322–324.
of the experimental models and the fact that active or pas- 13. DeMeester TR, Johnson LF, Kent AH. Evaluation of current
sive IAP increase might activate different physiological operations for the prevention of gastroesophageal reflux. Ann
patterns,14 several studies demonstrate the utility of adding Surg. 1974;180:511–525.
a stress test as a provocative maneuver during esophageal 14. Dodds WJ, Hogan WJ, Miller WN, et al. Effect of increased
manometry. The reasons for this assumption are 2-fold. intraabdominal pressure on lower esophageal sphincter pres-
First, assessing LES response to increased IAP might help to sure. Am J Dig Dis. 1975;20:298–308.
better characterize sphincter function and its ability to 15. DeMeester TR, Wernly JA, Bryant GH, et al. Clinical and
in vitro analysis of determinants of gastroesophageal compe-
endure a pressure challenge.7 Second, the increase in
tence. A study of the principles of antireflux surgery. Am J
esophageal pressure (“common cavity” test) might help to Surg. 1979;137:39–46.
identify patients with a defective LES.11 Furthermore, the 16. Muller N, Volgyesi G, Becker L, et al. Diaphragmatic muscle
addition of a Muller maneuver might help to quantify the tone. J Appl Physiol Respir Environ Exerc Physiol. 1979;47:
single contribution of CD to competency. 279–284.
With the advent of HRM and the recognition that the 17. Wernly JA, DeMeester TR, Bryant GH, et al. Intra-abdominal
CD is a crucial component of the EGJ barrier, there has been pressure and manometric data of the distal esophageal
a better overall understanding of GERD pathophysiology. sphincter. Their relationship to gastroesophageal reflux. Arch
Rogers et al28 first demonstrated a significant association Surg. 1980;115:534–539.
18. DeMeester TR, Lafontaine E, Joelsson BE, et al. Relationship
between SLR and esophageal acid exposure time. However,
of a hiatal hernia to the function of the body of the esophagus
strong evidence in terms of thresholds and modalities to and the gastroesophageal junction. J Thorac Cardiovasc Surg.
establish a reproducible pressure increase is still lacking. A 1981;82:547–558.
multicenter study to determine the optimal cutoff of 19. Joelsson BE, DeMeester TR, Skinner DB, et al. The role of the
increased esophageal pressure during HRM with SLR is esophageal body in the antireflux mechanism. Surgery.
underway48 (Fig. 8). 1982;92:417–424.
20. Bonavina L, Evander A, DeMeester TR, et al. Length of the
distal esophageal sphincter and competency of the cardia. Am J
Surg. 1986;151:25–34.
CONCLUSIONS 21. Mittal RK, Rochester DF, McCallum RW. Sphincteric action
Increasing IAP during esophageal manometry is a of the diaphragm during a relaxed lower esophageal sphincter
useful and practical adjunctive provocative maneuver that in humans. Am J Physiol. 1989;256(pt 1):G139–G144.
might help to better characterize the GERD phenotype in 22. Mittal RK, Fisher M, McCallum RW, et al. Human lower
clinical practice. Further translational research and stand- esophageal sphincter pressure response to increased intra-
ardization of HRM protocols is needed to improve the abdominal pressure. Am J Physiol. 1990;258(pt 1):G624–G630.
23. Louie BE, Kapur S, Blitz M, et al. Length and pressure of the
diagnostic yield and to improve patient selection for anti-
reconstructed lower esophageal sphincter is determined by
reflux surgery. both crural closure and Nissen fundoplication. J Gastrointest
Surg. 2013;17:236–243.
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