Diseases of the Esophagus (2013) 26, 451456

DOI: 10.1111/j.1442-2050.2012.01372.x

Original article

dote_1372

451..456

Increase of lower esophageal sphincter pressure after osteopathic intervention

on the diaphragm in patients with gastroesophageal reflux
R. C. V. da Silva,1 C. C. de S,3 . O. Pascual-Vaca,1,2 L. H. de Souza Fontes,3
F. A. M. Herbella Fernandes,4 R. A. Dib,3 C. R. Blanco,1,2 R. A. Queiroz,1 T. Navarro-Rodriguez3
Escuela de Osteopatia de Madrid, Madrid, and 2Department of Physiotherapy, University of Seville, Seville,
Spain; and 3Department of Gastroenterology, University of So Paulo, and 4Department of Surgery, Escola
Paulista de Medicina, Federal University of So Paulo, So Paulo, Brazil

SUMMARY. The treatment of gastroesophageal reflux disease may be clinical or surgical. The clinical
consists basically of the use of drugs; however, there are new techniques to complement this treatment,
osteopathic intervention in the diaphragmatic muscle is one these. The objective of the study is to compare
pressure values in the examination of esophageal manometry of the lower esophageal sphincter (LES) before
and immediately after osteopathic intervention in the diaphragm muscle. Thirty-eight patients with gastroesophageal reflux disease 16 submitted to sham technique and 22 submitted osteopathic technique were
randomly selected. The average respiratory pressure (ARP) and the maximum expiratory pressure (MEP) of the
LES were measured by manometry before and after osteopathic technique at the point of highest pressure.
Statistical analysis was performed using the Students t-test and MannWhitney, and magnitude of the
technique proposed was measured using the Cohens index. Statistically significant difference in the osteopathic technique was found in three out of four in relation to the group of patients who performed the sham
technique for the following measures of LES pressure: ARP with P = 0.027. The MEP had no statistical
difference (P = 0.146). The values of Cohen d for the same measures were: ARP with d = 0.80 and MEP
d = 0.52. Osteopathic manipulative technique produces a positive increment in the LES region soon after
its performance.
KEY WORDS: gastroesophageal reflux, lower esophageal sphincter, osteopathic manipulation, treatment.

Address correspondence to: Dr Tomas Navarro-Rodriguez,

MD, PhD, Department of Gastroenterology Clinical
Gastroenterology, University of So Paulo School of
Medicine, Avenue Dr Eneas Carvalho de Aguiar, 255 ICHC,
9th floor, office 9159, So Paulo 05403-000, Brazil.
Email: tnavarro@usp.br
Conflict of Interest: Guarantor of the article: Tomas
Navarro-Rodriguez, MD, PhD
Specific author contributions: Study conductance, database
development, data analysis, and manuscript writing: Rafael
Corra Vieira da Silva; Study conductance and database
development: Cludia Cristina de S; Protocol development,
study conductance, database development, and data analysis:
Luiz Henrique de Souza Fontes, Fernando Augusto Mardiros
Herbella Fernandes, and Ricardo Anuar Dib; Data
interpretation and manuscript writing: ngel Oliva
Pascual-Vaca, Cleofs Rodriguez Blanco, and Rogerio Augusto
Queiroz; Protocol development, technology development,
supervision of study conductance, data interpretation, and
manuscript writing: Tomas Navarro-Rodriguez
Financial support: Nonfinancial
Potential competing interests: None

INTRODUCTION
Gastroesophageal reflux disease (GERD), although
not considered a severe illness,1 is one of the most
common disorders of the gastrointestinal system.2
It has a great medical-social importance, with a high
and growing prevalence. It is the cause of various
esophageal symptoms37 and extraesophageal symptoms,8,9 having a negative impact on quality of life10,11
with reflex on the economy of the society.12,13
The LES and the crural diaphragm represent the
intrinsic and extrinsic sphincters, respectively. They
are anatomically overlaid and anchored one to the
other through the phrenoesophageal ligament.14
During contraction of the crural diaphragm, an
increase of the LES pressure occurs,15 contributing to
a three- to four-fold growth of the pressure in the

2012 Copyright the Authors

Journal compilation 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus

451

452

Diseases of the Esophagus

gastroesophageal junction (GEJ) region.16 In addition, both the LES and the diaphragm relax during a
short period of time to allow passage of the food
bolus during esophageal peristalsis.17
Investigation using high-resolution manometry
reviewed the diaphragmatic function in patients with
and without gastroesophageal reflux (GER) and evidenced a diaphragmatic deficient function in patients
with GER, as shown by the reduced increase of the
inspiratory pressure of the GEJ.18
Nevertheless, the inspiratory muscles, including
the diaphragm, are morphologically and functionally
skeleton muscles and therefore should respond to
training just like the gait muscles, if submitted to an
appropriate stimulus. It has already been demonstrated that the diaphragm increases its thickness
when a resistance is applied against it during weightlifting training.17 Downey et al. reported an 812%
increase in the diaphragm thickness during contraction after muscular inspiratory post-training for
4 weeks.19
Within this background and considering other
studies that have shown good results with the osteopathic manipulative treatment in visceral dysfunctions,2022 the study of this kind of therapeutic
approach has shown to be important to be added to
the GERD conservative treatments and maybe, avoid
surgery.
Many authors have shown the fundamental
importance of the diaphragm within the GEJ structures, with an important role in the sphincter mechanism against reflux.16,18,2325 Therefore, we shall use
the lower esophageal sphincter (LES) manometric
study to review the immediate repercussion of the
diaphragmatic stretching technique widely used by
osteopathicians to obtain equilibrium of the diaphragm functions in the mechanism against GER
compared with the placebo technique.

MATERIALS AND METHODS

Patients
All patients above 18 years old, regardless of gender,
referred to the Laboratory of Digestive Motility
Investigation of the Gastroenterology Service of Hospital das Clinicas of the University of So Paulo
School of Medicine to undergo an esophageal manometric examination, who were released with a GERD
diagnostic, were randomly screened and invited to
participate in the study.

Studied groups
Patients were randomly allocated to two groups:
group O (osteopathy) undergoing the diaphragm
stretching technique, which included 22 individuals,

and group P (placebo control) who went through

the placebo technique and included 16 patients.
Diaphragm stretching technique

The diaphragm stretching technique has been performed by only one of the investigators, who was not
in charge of data collection nor interpretation of the
manometry measurements. The protocol includes the
technique suggested by Coster and Pollaris26 modified
as follows: the position of the patient laying back
(supine) with the legs bent and the feet against the
bed. A total of eight deep respiratory maneuvers were
performed in two steps: first step four deep respirations, in which the inspiration and expiration movements are exacerbated by the investigator through
manual contact on the lower rim of the last ribs;
second step: four deep respirations, in which, during
the expiratory phase, the investigator will sustain the
ribs grid using the same contact to avoid the descent
of the thoracic cage during the expiratory phase.
During the performance of the technique, the investigator would encourage and coordinate deep breathing of the patients through voice command.
Sham technique

The sham technique was performed by the same

investigator who performed the diaphragm stretching
techniques. Patient lying back with the legs bent and
feet against the bed. The investigator maintained one
hand in contact on the patients sternum and the
other hand on the abdomen, next to the gastric
region. The patient had to produce the same eight
deep breathings, during which the same voice commands of the diaphragm technique were given;
however, the investigators hands only maintain a
physical contact with the patient without exerting any
pressure, or putting any incentive or restriction to the
movements of the thoracic cage.
Esophageal manometry

The esophageal manometry exam was performed by

a specialized physician using the device Alacer Multiplex BP 108 (Alacer Biomedica, So Paulo, Brazil).
The manometric exam was performed normally by
the dedicated physician who, after reaching the
gastric cavity, coordinated so that the probe was
pulled each 0.5 cm throughout the extension of the
LES. The objective was to obtain a more faithful
characterization of all its extension and pressure
characteristics. After the end of the esophageal body
manometric exam, the probe was reintroduced in the
patients stomach, and the technique was performed
by the osteopathologist in charge. After 20 seconds,
the probe was pulled again each 0.5 cm throughout
the extension of the LES, and the data were immediately recorded after performing the diaphragm
stretch or sham techniques.

2012 Copyright the Authors

Journal compilation 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus

Sphincter after osteopathic intervention

Table 1

Selection of the points studied

After the end of the exam, the physician measured the
average respiratory pressure (ARP) and maximum
expiratory pressure (MEP)27 and chose the highest
point (HP) and the mean between all points before
and immediately after the osteopathic intervention
or application of the placebo technique. In case of
dispute as to which would be the best method to
measure the LES, excluding the diaphragm pressure
force.
Statistical analysis
Before analyzing the data was performed transformations of each variable in order to facilitate calculations and understanding of the problem. We chose to
change based on differences in values as follows: The
variables ARP from the HP pre-intervention and
postintervention of the group O gave rise to the variable Difference (pr-ps) of ARP (HP) of the group
O, the variables ARP from the HP pre-intervention,
and postintervention of the group P gave rise to the
variable Difference (pr-ps) of ARP (HP) of the
group P, and so on. Then, analyze the data to find
possible differences between the responses of two
groups are summarized in comparing these new
variables and determine whether they are statistically
different.
The next step was to analyze the distribution of
each group of new variables to correctly define which
the best test to use is. For this, it took several
Quantile-Quantile (QQ) plots more specifically,
normal QQ plots. Non-parametric tests (Mann
Whitney) were adopted for those variables that did
not comply with the homogeneity criteria of the
variance and/or normal distribution. For all other
variables, the Students t-test was except for the
comparison of the proportion of men and women in
each group, for which an exact Fisher test with 95%
significance level was used. In addition to the inferential analysis, as a way to quantify the magnitude of
the difference observed among two groups, the magnitude of the effect was determined (effect size:
Cohen d), a rate that measures the magnitude of the

453

Gender, age, and body mass index variation

Variable

Placebo group

Osteopathy group

Number
Women/men
Mean body mass index*
Mean age (years)*

16
09/07
23.52
50.5 16.21

22
16/06
25.72
49.4 15.01

*P > 0.21.

effect of the proposed technique.28 The d values for

small, medium, and large magnitude effects are 0.2,
0.5, and 0.8, respectively, and the medium and large
values are considered as having clinical importance.28

RESULTS
A total of 38 patients were assessed, of which 25 were
of the female gender (65.7%). The mean age, weight,
height, and body mass index (BMI) of the group O
(osteopathy) was 49.5 years of age, 67.3 kg, 1.61 m,
and BMI 25.72, respectively. And that of the placebo
group (group P) was 50.5 years of age, 61.8 kg,
1.62 m, and BMI 23.52. The two groups were not
different as far as age, weight, BMI, and height are
concerned (tests t P > 0.21), as well as with regard to
the gender distribution (Table 1).
Variables of the LES pressure
In Table 2, we analyzed variables of the LES
pressure in each group before and after the
procedures. All P-values were greater than 0.05;
however, the null hypothesis cannot be rejected.
In other words, all LES pressure variables may
be seen as normally distributed and parametric
(t-Student) being the tests suited to the task of group
comparison.
ARP and MEP mean values
A summary of the mean values of ARP and MEP is
shown in Table 3.

Table 2 Variables of the LES pressure: at the point of maximum pressure (ARP and MEP pre-intervention and postintervention)
ARP pre

ARP post

MEP pre

MEP post

Statistical analysis

Osteopathy
group

Placebo
group

Osteopathy
group

Placebo
group

Osteopathy
group

Placebo
group

Osteopathy
group

Placebo
group

Mean
Standard deviation
KolmogorovSmirnov Z
P-value

20.04
8.07
0.622
0.834

25.74
15.29
0.913
0.376

21.87
9.70
0.655
0.784

22.14
18.25
0.927
0.357

12.03
5.76
0.831
0.495

16.88
12.90
0.923
0.362

14.57
8.13
0.860
0.451

15.51
18.03
1.188
0.119

ARP, average respiratory pressure; LES, lower esophageal sphincter; MEP, maximum expiratory pressure; post, postintervention;
pre, pre-intervention.
2012 Copyright the Authors
Journal compilation 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus

454

Diseases of the Esophagus

Table 3 ARP and MEP values pre-intervention and postintervention in the groups placebo and osteopathic for the mean values
Variable
Number
Average respiratory pressure (mmHg)
Maximum expiratory pressure (mmHg)

Pre
Post
Pre
Post

Placebo group
16

Osteopathy group
22

25.74 15.28 SD
22.13 18.24 SD
16.87 12.89 SD
15.51 18.03 SD

20.03 8.07 SD
21.87 9.70 SD
12.03 5.76 SD
14.56 8.12 SD

Cohen values (d)

0.80
0.52

ARP, average respiratory pressure; MEP, maximum expiratory pressure; post, postintervention; pre, pre-intervention; SD, standard
deviation.

The values of d for small, medium, and large magnitude are, respectively, 0.2, 0.5, and 0.8, and the
medium and large values are considered as having
clinical relevance.28 The values of Cohen d for these
measurements were: ARP - d = 0.80 and MEP - d =
0.52. This demonstrates that the difference of the
measurement of ARP between the groups is of high
magnitude, considered clinically relevant by Cohen28
(Table 3).
Difference (prepost) of ARP (HP) between groups
O and P
Both variables arise from normal distributions. In
this case, the Students t-test was used to compare
the two groups with regard to this variable. The
mean difference of the ARP (HP) in the group O
was 1.84 + 5.20 standard deviation (SD) and the
mean of the difference of ARP (HP) in the group P
was -3.61 + 8.05 SD (P = 0.027). In reviewing each
group mean and considering that these are variables
related to the difference between two other values
(prepost), it may be stated that in the group O, the
value of ARP postintervention is generally greater
than the ARP value postintervention in the group P
(Table 4).
Difference (prepost) of ARP (mean between all
points) between groups O and P
The MannWhitney test was used to compare the
two groups regard to this variable. The median difference of ARP (mean between all points) in group O
was 3.70, and the median difference of ARP (mean

between all points) in group P was -1.85 (P = 0.0066).

In reviewing each group median, it may be stated that
in the group O, the value of ARP postintervention is
generally greater than the ARP value postintervention in the group P (Table 4).
Difference (prepost) of MEP (HP) between groups
O and P
Both variables arise from normal distributions. In
this case, the Students t-test was used to compare the
two groups with regard to this variable. The mean
of the difference of MEP (HP) in the group O was
2.53 4.75 SD and of group P -1.36 9.48 SD
(P = 0.146). Given the high value of P (>0.05), we
cannot say that the groups differed in terms of variable MEP (HP). Although the means are very different, the high SD value in group P also implies a large
variation, which may be why no differences were
found between the groups in this analysis (Table 4).
Difference (prepost) of MEP (mean between all
points) between groups O and P
The MannWhitney test was used to compare the
two groups with regard to this variable. The median
difference of MEP (Mean between all points) in
group O was 2.69, and the median difference of MEP
(mean between all points) in group P was -0.82 (P =
0.0493). Analyzing the value of P (<0.05), we can say
that the differences in groups are statistically significant between them. Looking again, their median can
be seen that group O has higher values than group P
after the intervention (Table 4).

Table 4 Difference (prepost) of ARP and difference (prepost) of MEP values for mean and median values in the placebo and
osteopathic groups
Variable
Difference (prepost) of ARP (mmHg)
Difference (prepost) of MEP (mmHg)

Mean
Median
Mean
Median

Placebo group (n = 16)

Osteopathy group (n = 22)

-3.61 8.05 SD
-1.85
-1.36 9.48 SD
-0.82

1.84 5.20 SD
3.70
2.53 4.75 SD
2.69

0.027
0.0066
0.146
0.0493

ARP, average respiratory pressure; MEP, maximum expiratory pressure; post, postintervention; pre, pre-intervention; SD, standard
deviation.
2012 Copyright the Authors
Journal compilation 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus

Sphincter after osteopathic intervention

DISCUSSION
The assumption of this study was that the diaphragm stretching maneuver largely used by osteopathicians to obtain the functional equilibrium of
this muscle fosters increase of the LES pressure
immediately after performing the maneuver, as a
consequence of an increased strengthening of the
diaphragm muscle. Among the major findings is
the observed LES increased pressure in patients
who underwent the osteopathic technique when
compared with the placebo technique for all the
measurements investigated.
Another interesting outcome was the response
with regard to the effect size that demonstrated the
clinical relevance in connection with the majority of
the variables reviewed.
Our results demonstrated that there was an
increase of 927% of the LES pressure in patients
who performed the osteopathic maneuvers, while in
the group of patients who did not perform the
maneuvers, a reduction of that pressure was observed
(Table 5). These results are quite close to those of
other investigators, who indicated that during the
contraction of the crural diaphragm, an increase of
the LES pressure occurs,15 contributing for a three- to
four-fold increase in the pressure in the GEJ region,16
as well as an increase from 8% to 12% in the diaphragm thickness during muscular inspiratory posttraining contraction for 4 weeks;19 this is different
from our study that showed an increase of the LES
pressure.
Our data are of extreme clinical importance and of
high practical relevance because in the assessment by
the LES esophageal manometry, we assessed the
regions of the LES having greater pressure either by
ARP or MEP, and not the average of all the sphincter
assessment. In addition to supporting the beliefs of
the osteopathic community and what they observe
clinically, nevertheless, we cannot say that a complete
osteopathic treatment has been conducted for the
diaphragm or even for the GEJ; this characterizes our
investigation only as an osteopathic technique study
and not as a complete osteopathic manipulative treatment study. However, the fact that the use of only
one single technique for one of the main GEJ struc-

Table 5 Difference between the values ARP (HP) and MEP (HP)
postintervention in relation to pre-intervention values in the
groups placebo and osteopathic (%)

Variable
ARP (mmHg)
MEP (mmHg)

post/pre
post/pre

Placebo group
(n = 16)

Osteopathy group
(n = 22)

14.02% reduction
8.06% reduction

9.18% increase
21.03% increase

ARP, average respiratory pressure; HP, highest point; MEP,

maximum expiratory pressure; post, postintervention; pre,
pre-intervention.

455

tures had a positive influence on the increase of the

LES pressure was seen with great enthusiasm by all
the investigators involved.
No other similar study was found in the literature
and our findings appear important in connection with
the potential clinical applications of the osteopathic
treatment for GERD and consequently its benefit as
co-adjuvant in the clinical or surgical treatment or
maybe even in the future as a single therapy for some
kinds of specific patients. It is still not possible to say
if these changes are durable, which requires continuation of the research in other centers and with a larger
number of patients.
However, the despite we not analyzed if there
were changes in symptoms after application of the
technique, subjects treated with this osteopathic diaphragm stretching technique often report an improvement in areas such as heartburn and reflux, which
corresponds with the values of large and medium
clinical effect (according to Cohens statistic) achieved
in the study variables.

CONCLUSION
The osteopathic manipulative technique used to
produce the diaphragm functional equilibrium causes
a positive increment, statistically significant, in the
LES region soon after it is performed.
Acknowledgments
We wish to thank the Gastroenterology Discipline
of University of So Paulo School of Medicine and
the Escuela de Osteopatia de Madrid for the support
and encouragement of the study conducted.
References
1 Ducrott P, Liker H R. How do people with gastrooesophageal reflux disease perceive their disease? Results of a
multinational survey. Curr Med Res Opin 2007; 23: 285765.
2 Cibor D, Ciecko-Michalska I, Szulewski P et al. Etiopathogenetic factors of esophagitis in patients with gastroesophageal
reflux disease. Przegl Lek 2007; 64: 14.
3 Chen C L, Robert J J, Orr W C. Sleep symptoms and gastroesophageal reflux. J Clin Gastroenterol 2008; 42: 137.
4 Corsi P R, Gagliardi D, Horn M et al. Presena de refluxo em
pacientes com sintomas tpicos de doena do refluxo gastroesofgico. Rev Assoc Med Bras 2007; 53: 1527.
5 Fass R, Navarro-Rodriguez T. Noncardiac chest pain. J Clin
Gastroenterol 2008; 42: 63646.
6 Voutilainen M, Sipponen P, Mecklin J P et al. Gastroesophagel
reflux disease: prevalence, clinical, endoscopic and histopathological findings in 1.128 consecutive patients referred for endoscopy due to dyspeptic and reflux symptoms. Digestion 2000;
61: 613.
7 Wong R K, Hanson D G, Waring P J et al. ENT manifestations of gastroesophageal reflux. Am J Gastroenterol 2000; 95:
S1522.
8 Struch F, Schwahn C, Wallaschofski H et al. Self-reported
halitosis and gastro-esophageal reflux disease in the general
population. J Gen Intern Med 2008; 23: 2606.

2012 Copyright the Authors

Journal compilation 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus

456

Diseases of the Esophagus

9 Moraes-Filho J P P, Navarro-Rodriguez T, Barbuti R et al.

Guidelines for the diagnosis and management of gastroesophageal reflux disease: an evidence-based consensus. Arq
Gastroenterol 2010; 47: 99115.
10 Irvine E J. Quality of life assessment in gastro-oesophageal
reflux disease. Gut 2004; 53 (Suppl 4): 359.
11 Quigley E M, Hungin A P. Review article: quality-of-life issues
in gastro-oesophageal reflux disease. Aliment Pharmacol Ther
2005; 22: 417.
12 Joish V N, Donaldson G, Stockdale W et al. The economic
impact of GERD and PUD: examination of direct and indirect
costs using a large integrated employer claims database. Curr
Med Res Opin 2005; 21: 53544.
13 Leodolter A, Nocon M, Kulig M et al. Gastro esophageal
reflux disease is associated with absence from work: results
from a prospective cohort study. World J Gastroenterol 2005;
11: 714851.
14 Sidhu A S, Triadafilopoulos G. Neuro-regulation of lower
esophageal sphincter function as treatment for gastroesophageal reflux disease. World J Gastroeterol 2008; 14: 98590.
15 Dantas R O, Lbo C J N. Contribuio da contrao diafragmtica na presso do esfncter inferior do esfago de pacientes
com doena de Chagas. Arq Gastroenterol 1994; 31: 147.
16 Sun X H, Ke M Y, Wang Z F et al. Roles of diaphragmatic
crural barrier and esophageal body clearance in patients with
gastroesophageal reflux disease. Zhongguo Yi Xue Ke Xue
Yuan Xue Bao 2002; 24: 28993.
17 Enright S J, Unnithan V B, Heward C et al. Effect of highintensity inspiratory muscle training on lung volumes, diaphragm thickness and exercise capacity in subjects who are
healthy. Phys Ther 2006; 86: 34554.
18 Pandolfino J E, Kim H, Ghosh S K et al. High-resolution
manometry of the EGJ: an analysis of crural diaphragm

19
20

21

22
23
24
25

26
27
28

function in GERD. Am J Gastroenterol 2007; 102: 1056

63.
Downey A E, Chenoweth L M, Townsend D K et al. Effects of
inspiratory muscle training on exercise responses in normoxia
and hypoxia. Respir Physiol Neurobiol 2007; 156: 13746.
Radjieski J M, Lumley M A, Cantieri M S. Effect of osteopathic manipulative treatment of length of stay for pancreatitis:
a randomized pilot study. J Am Osteopath Assoc 1998; 98:
26472.
Hundscheid H W, Pepels M J, Engels L G et al. Treatment of
irritable bowel syndrome with osteopathy: results of a randomized controlled pilot study. J Gastroenterol Hepatol 2007; 22:
13948.
Noll D R, Shores J H, Gamber R G et al. Benefits of osteopathic manipulative treatment for hospitalized elderly patients
with pneumonia. J Am Osteopath Assoc 2000; 100: 77682.
Miller L, Vegesna A, Kalra A et al. New observations on the
gastroesophageal antireflux barrier. Gastroenterol Clin North
Am 2007; 36: 60117.
Shafik A, Shafik I, El Sibai O et al. The effect of esophageal and
gastric distension on the crural diaphragm. World J Surg 2006;
30: 199204.
Shaker R, Bardan E, Gu C et al. Effect of lower esophageal
sphincter tone and crural diaphragm contraction on distensibility of the gastroesophageal junction in humans. Am J
Physiol Gastrointest Liver Physiol 2004; 287: G81521.
Coster M, Pollaris A. Osteopata Visceral, 1st edn. Barcelona:
Paidotribo, 2001.
Boyle J T, Altschuler S M, Nixon T E et al. Role of the diaphragm in the genesis of lower esophageal sphincter pressure in
the cat. Gastroenterology 1985; 88: 72330.
Cohen J. Statistical Power Analysis for the Behavioral Sciences,
2nd edn. Hillsdale, NJ: Lawrence Earlbaum Associates, 1988.

2012 Copyright the Authors

Journal compilation 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus