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Gastroenterol Hepatol. 2011;34(Supl 1):28-34

Gastroenterologa y Hepatologa

Volumen 34, Extrao rdinario 1

Enero 2011

Jornada de Actualizacin
en Gastroenterologa
Aplicada

www.elsevier.es/gastroenterologia

ARTICLE ORIGINAL

Gastroesophageal reflux disease and Barrett's esophagus:

epidemiology, diagnosis and treatment
Xavier Calvet
Unitat de Malalties Digestives, Hospital de Sabadell, Institut Universitari Parc Taul, Sabadell, Departament de
Medicina, Universitat Autnoma de Barcelona, Barcelona, Espaa
Centro de Investigacin Biomdica en Red de Enfermedades Hepticas y Digestivas
KEYWORDS
Gastroesophageal
reflux disease;
Diagnostic;
Treatment;
Barret esophagu

Abstract
The advances presented in Digestive Disease Week 2010 on gastroesophageal reflux
disease are of special practical importance. The 5-year results of a randomized,
multicenter trial the LOTUS trial show that proton pump inhibitors are superior to
surgery in the treatment of patients with reflux. In addition, new studies have rescued
hygienic-dietary measures from oblivion in the treatment of reflux, showing that weight
loss and smoking cessation spectacularly improve symptoms. In Barretts esophagus, the
short-term efficacy of radiofrequency in patients with dysplasia has been confirmed and
highly encouraging data on the long-term efficacy of this treatment modality have
begun to appear.
2010 Elsevier Espaa, S.L. All rights reserved.

PALABRAS
CLAVE Reflujo
gastroesofgico;
Diagnstico;
Tratamiento;
Esfago de
Barrett

Enfermedad por reujo gastroesofgico y esfago de Barrett: epidemiologa,

diagnstico y tratamiento
Resumen
Las novedades presentadas en la semana de enfermedades digestivas de este ao sobre
reflujo gastroesofgico tienen especial relevancia prctica. Los resultados a 5 aos de
un estudio aleatorizado multicntrico el estudio LOTUS demuestran que los
inhibidores de la bomba de protones son superiores a la ciruga en el tratamiento de los
pacientes con reflujo. Por otro lado, nuevos estudios rescatan del olvido las medidas
higienicodie- tticas en el tratamiento del reflujo, demostrando que la prdida de
peso y dejar de fumar mejoran los sntomas del reflujo de manera espectacular.
Respecto al esfago de Barrett, se confirma no slo la eficacia a corto plazo del
tratamiento con radiofrecuencia en pacientes con displasia, sino que empiezan a
aparecer datos muy favorables sobre su eficacia a largo plazo.
2010 Elsevier
reservados.

Espaa,

S.L.

Correo electrnico: xcalvet@cspt.es

0210-5705/$ - see front matter 2010 Elsevier Espaa, S.L. Todos los derechos reservados

Todos

los

derechos

Porcentaje de pacientes en remisin

Enfermedad por reflujo gastroesofgico y esfago de Barrett: epidemiologa, diagnstico y tratamiento

29

100

Introduction
Digestive Disease Week (DDW) American always offers
interesting news. In the field of reflux, this year include
some for its practical importance. Among them, the role of
weight loss as a potential treatment of reflux symptoms
and confirmation that medical treatment is more effective
and safe surgery to treat reflux.

Reflux disease: diagnosis

Regarding diagnosis of gastroesophageal reflux disease
(GERD), Savarino et al 1 presented a study comparing the
usefulness of Rome III criteria for differentiating between
patients with functional dyspepsia and disease non-erosive
reflux. For this they evaluated 219 patients with suspected
non-erosive reflux disease by impedance - pH monitoring.
The in- correlation between both methods was acceptable
to the overall diagnosis (kappa = 0.67), but poor for
diagnosing or functional hypersensitive esophagus reflux
(kappa = 0.46). The authors conclude that the Rome III
criteria overestimate the proportion of patients with
functional esophagus.

Treatment of gastroesophageal reflux disease

Medical treatment is superior to surgical
The most relevant in the field of GERD in the DDW study
this year was presented by Galmiche et al 2 in plenary
session. This is the 5-year results of the LOTUS study, a
randomized, multicenter trial, Euro- pean in which medical
treatment was compared (esomeprazole
20 mg / 24 h, increasing the dose to 40 mg / 24 h when
necessary) versus laparoscopic antireflux surgery via ca 554
patients. After 5 years of treatment, the percentage of
patients without treatment failure was higher in patients
treated with esomeprazole (92%) compared to
85% in patients treated with surgery (p> 0.05) (Fig. 1). In
addition, an upper significantly supplied prevalence of
bloating, inability to belch or vomit, and dysphagia in
surgically treated was observed. Although no differences in
rates of adverse effects're long term between 2 groups 3
were observed. Therefore, the study clearly demonstrates
that the surgical treatment of reflux should be avoided
because it is less effective and causes more adverse effects
than treatment with proton-pump inhibitor (PPI).

Lose weight and stop smoking: Keys to treat reflux

Given the lack of evidence of the utility of the classic
address health measures ( . . For example , raising the
head of the bed) , there have been highly convincing
results ado- that there is a highly effective measure to
control the reflux : weight loss . Thus, Singh et al 4
evaluated the evolution of reflux symptoms in 179 patients
enrolled in a program of exercise and diet to lose weight
(101 kg initial average weight, BMI 31). The prevalence of
GERD was 38% before and after 17% weight loss. 66% of
patients with reflux symptoms at the beginning was in
remission at 6 months.

92%
85%

80
p = 0,0476
60
40
Esomeprazol

20

Ciruga

Aos

Graphic 1 Percentage of patients in remission at 5 years

after randomization to medical treatment (esomeprazole)
or laparoscopic surgery.

Thus, the weight loss of more than 5% and reducing

abdominal girth related to the disappearance of the
symptoms of GERD.
Crowell et al 5 showed very similar results in another set of
198 obese patients treated with caloric restriction and
exercise. The prevalence of reflux symptoms decreased
from 59 to 30% at 3 years and a correlation between the
magnitude of weight loss and improvement in reflux
symptoms was observed.
An ingenious Blondeau et al study in 6 healthy volunteers
suggests that increasing intra-abdominal pressure in obese
is probably the main factor in the occurrence of reflux and
determines its severity. The participants received a food
reflujognica and subsequently you were explored for 2 h
with
impedance
and
simultaneous
high-resolution
manometry. A large inflatable cuff placed around the
abdomen deflated inflatable ba and every 30 min. It was
noted that the intragastric inflate the cuff pressure
increased 40%; this increase correlated with a greater
number and, above all, a longer duration of reflux episodes,
confirming the key role of intra-abdominal pressure
increase in the occurrence of gastroesophageal reflux.
Another measure that has proved effective is to stop
smoking. So, Nakajima et al, in 33 patients who
participated in a program for addiction, assessed the
symptoms of reflux and dyspepsia and quality of life by
validated questionnaires. After smoking cessation a
significant decrease in both dyspeptic symptoms as reflux
and the improvement in quality of life was observed.

New pharmacological treatments.

Inhibitors paper relaxations transient lower
esophageal sphincter
A subgroup of patients with GERD symptoms despite
treatment with high doses of PPIs. Drugs that inhibit the
transient relaxations of the lower esophageal sphincter

30
logical (TLESR) may be useful as adjunctive therapy in
these patients with persistent symptoms despite high doses
of PPIs. The best-known drug in this therapeutic group is
baclofen, an agonist of the receptor of gamma-aminobutyric acid. Xenodemetropoulos et al 6 showed a
systematic review of the usefulness of this drug in patients
with GERD. 5 randomized clinical trials were identified.
Three studies evaluated the effect of a single dose of
baclofen 40 mg, showing a modest but significant reduction
in both reflux episodes as time esophageal pH below 4. Two
studies evaluated maintenance treatment with baclofen
and they observed similar results. However, none of the
studies a significant reduction of the symptoms of reflux in
the group receiving baclofen was observed. In addition,
patients receiving baclofen, a higher incidence of ad- verse
effects, particularly drowsiness, nausea and dizziness. The
authors suggest that the efficacy of baclofen is scarce, but
drugs of the same family with longer and better safety
profile half-life may be useful in the treatment of reflux.
Within this group of inhibitors described TLESR 3 new
drugs, AZD3355 (lesogaberan), AZD9343 and ADX10059.
Bruley of Varannes et al 7 and rum Zerbib et al 8 evaluated
the efficacy of ADX10059, a rich alost- negative modulator
of metabotropic glutamate receptor 5. In a double blind
assay in- randomized placebo, 103 patients received 120
mg reflux or placebo every 12 h for 3 weeks. ADX10059
induced a moderate, but significant vo, decrease reflux
symptoms and the number of reflux episodes. The most
common side effects were drowsiness feeling of instability
and, in mild general. The authors evaluated the drug as
potentially effective and suggest that it may be used as
adjunctive therapy in patients with symptoms despite PPI
treatment.

Reduced effectiveness of the proton-pump

inhibitor for the treatment of asthma
Regarding the atypical symptoms of GERD, Chan et al 9
eva- ated in a meta-analysis of 10 studies including 1,411
patients, the evidence on the efficacy of PPIs in patients
with asthma. Although a slight improvement of respiratory
function parameters was observed, specifically in peak
expiratory flow, no significant differences in scores of
clinical symptoms were observed. In addition, studies that
require a previous diagnosis of reflux tended to get better
results with IBP. The study concluded that the therapeutic
effect of PPIs in asthma is less and, probably, limited to
patients with concomitant GERD.

Barrett's esophagus
Entities that are not Barrett's esophagus
Remains a matter of debate and confusion if the co lumnar
esophagus esophagus Barrett's esophagus should be
considered, if intestinal metaplasia is detected. Therefore,
Bansal et al, 10 in a multicenter study in pathological data
bases, reviewed endoscopic biopsies of the distal esophagus
between 1999 and 2010. 253 were identified with columnar
esophagus without intestinal metaplasia. 763 patients a
database Barrett that- phage were used as controls. The
proportion of biopsies with dysplasia was 1.5% (confidence
interval [CI] 95%, 0.2 to 5.3%) in the group without
intestinal metaplasia and 25.4% (95% CI,18.3 to 33.6%) in
the group with intestinal metaplasia (relative risk [RR] 17.0
[4.1 to

X. Calvet
70.8]; p <0.001).The results were even more evident when
low-grade dysplasia was excluded. The percentage of
patients with high-grade dysplasia or cancer was 0% (95% CI,
0-2.7%) and 6% (95% CI, 2.6 to 11.4%), respectively ( RR
infinite; p <0.005). The study confirms that the presence of
intestinal metaplasia is essential for the diagnosis of
Barrett's esophagus element.
On the other hand, Jung et al 11 evaluated if limited to the
detection of intestinal metaplasia gastroesophageal
junction or not pathological significance. Using data from
the Rochester Epidemiology Project, 81 patients with this
condition, which were followed for eight years were
detected. During follow-up no patient developed Barrett
esophagus or esophageal adenocarcinoma. The authors
conclude that the presence of intestinal metaplasia limited
to the gastroesophageal junction gives probably not significance pathological and endoscopic monitoring is not
necessary peak.

Barrett. Epidemiology
On the prevalence and risk factors that- phage Barrett and
esophageal adenocarcinoma, rum presented two interesting
studies. In the first, Den Hoed et al 12 evaluated the prevalence
of esophagitis and Barrett's esophagus in 383 patients undergoing
colonoscopy. After completing a questionnaire on gastrointestinal
symptoms, upper gastrointestinal endoscopy prior to
colonoscopy. The mean age of patients was 53 years. 20% of
patients were treated with PPI, 14% showed signs of esophagitis
and Barrett's esophagus 14%, 20% with low-grade dysplasia. The
prevalence of esophageal rrett Bacon was the same in patients
with and without dyspepsia, being more common in obese
patients and in over 60 years. Therefore, Barrett's esophagus is
extremely common (20%), and obesity and age the main risk
factors.
On the other hand, Bjrn et al 13 analyzed the relationship
between metabolic syndrome and esophageal adenocarcinoma in
the Metabolic Syndrome and Cancer Project. In this study, a
group of 577,000 individuals in Austria, Norway and Sweden was
assessed by determining smoking, body mass index, cholesterol,
glucose and triglyceride levels. Cancer cases were detected using
national registries
On the other hand, Bjrn et al 13 analyzed the
relationship between metabolic syndrome and esophageal
adenocarcinoma in the Metabolic Syndrome and Cancer
Project. In this study, a group of 577,000 individuals in
Austria, Norway and Sweden was assessed by determining
smoking, body mass index, cholesterol, glucose and
triglyceride levels. Cancer cases were detected using
national registries espective. 114 cases of esophageal
adenocarcinoma were detected. The only metabolic factor
associated with an increased risk of esophageal
adenocarcinoma was the body mass index (RR, 7.34 [95%
CI, 2.88 to 18.68] rior upper front lower quintiles).
Furthermore,
2
spacious
and
well-designed
epidemiological studies confirm that the risk of
adenocarcinoma in Barrett's esophagus has been greatly
overestimated. So, Yousef et al 14 evaluated the incidence
of esophageal adenocarcinoma in a population registry of
patients with Barrett phage that- in Northern Ireland
between 1993 and 2005, in- cluding 7,585 patients
followed

Enfermedad por reflujo gastroesofgico y esfago de Barrett: epidemiologa, diagnstico y tratamiento

31
esophagus. For this they assessed 301 patients in whom the
For
five
years.
The
incidence
of
esophageal
NBI mucosal lesions detected: the rum blind biopsies
adenocarcinoma was 0.18 per 100 patients per year, and
detected high-grade dysplasia in 18% of cases and
the combined incidence of high-grade dysplasia and
adenocarcinoma esophageal carcinoma in 0.7%. They
adenocarcinoma was 0.41 per 100 patients per year.
conclude, therefore, that the negativity of exploration NBI
does not exclude significant lesions and can not substitute
Risk factors for adenocarcinoma were male gender, length
for routine esophageal biopsies.
of Barrett's esophagus, the presence of a hiatal hernia and
Cuvers et al 18 evaluated the usefulness of the
the presence of low-grade dysplasia. Meanwhile, Wani et al
combination of high resolution endoscopy, NBI and
15 evaluated the risk of esophageal adenocarcinoma in a
autofluorescence (in- trimodal endoscopy) for the diagnosis
large multi-centric cohort including 1,204 patients
of dysplasia in patients with Barrett's esophagus compared
followed for an average of
with conventional endoscope pia and systematic biopsy in
5 years. The risk of esophageal adenocarcinoma was 0.27
a randomized study which included 88 patients. Dysplasia,
per 100 patients per year, and the combined risk of highhigh grade dysplasia or in situ neoplasia in 61 patients
grade dysplasia and adenocarcinoma of 0.63 per 100
(69%) was detected. The sensitivity of the trimodal
patients per year. Figure 2 shows the marked decrease in
endoscopy for the detection of dysplasia was superior to
the prevalence of neoplasia observed over time, which is
probably attributable to a significant selection bias in the
conventional endoscopy, although the difference was not
initial studies.
significant (85 fren- you 79%; p = 0.53). Among the imaging
techniques, autofluorescence was the most useful for
Little use of screening in Barrett's esophagus to
detecting injuries Plasic device not detected by endoscopy
reduce mortality
high resolution. Furthermore, as in the previously
discussed study, the NBI showed a high rate of false
New data continue to question the usefulness of
negative results.
endoscopic screening for Barrett's esophagus appear. So
Gaddam et al 19 evaluated the risk factors for highCorley et al 16 evaluated the effect of screening on
grade dysplasia and cancer in a cohort of 1,496 patients
mortality. The cases were 36 patients diagnosed with
with Barrett's esophagus. 185 cases of high-grade dysplasia
Barrett's esophagus and esophageal adenocarcinoma killed
or adenocarcinoma were detected. he main risk factors
at least six months later. They were matched by age, sex,
were age, previous smoking, the length of Barrett's
race, hospital, date of diagnosis of Barrett's esophagus and
esophagus and the presence of visible mucosal lesions. On
time tracking with 136 controls. Rates previously
the other hand, previous use of acetylsalicylic acid or
endoscopic follow diagnosis were similar in cases and
NSAIDs had a protective effect. A score combining all these
controls, and no reduction in mortality associated with
factors showed an area under the ROC curve acceptable
endoscopic screening detected.
(0.78). However, even using the best cutoff point, the
score left undetected 10% of patients with severe injury, so
Barrett. New screening methods and strategies
it can not replace the endoscopic screening.
Okoro et al 17 evaluated the usefulness of narrow band
imaging (NBI) to detect dysplasia in patients with Barrett's

Barrett. Treatment

100 patients / year

2
1,75
1,5
1,25
1
0,75
0,5
0,25
0

Hameeteman
1998
(n = 50)

Streitzet
1998
(n = 149)

Bani Hani
2000
(n = 307)

Sharma
2006
(n = 618)

Yousef
2009
(n = 1.024)

Graphic 2 decreased risk of esophageal

adenocarcinoma in patients with Barrett's
esophagus without dysplasia in different
studies. It is noted that the most recent
and most extensive sampling studies show
significantly lower risk.

32
Pouw et al 20 presented preliminary results of a
multicenter European study evaluating the combination of
endoscopic mucosal resection and subsequent radiofrequency ablation in 118 patients with Barrett's esophagus
and high grade dysplasia or in situ neoplasia. We analyzed
55 who completed the study at the time of Tsar performed
the analysis. Eradication of the neoplasm or high-grade
dysplasia in 100% of patients and the eradication of
intestinal metaplasia in 96% of cases without significant
adverse effects register was achieved.
Deprez et al 21 compared endoscopic resection
mucosectomy with plastic cap and poly handle pectoma in
50 patients with Barrett's esophagus and neoplasia in situ
or high-grade dysplasia. Resection rates of neoplasia were
above 95% with both methods. Although mucosal resection
was associated with higher rates of en bloc resection, also
it presented a higher number of complications, especially
stenosis (44 versus 20%), so it is recommended resection in
fragments technique of choice.
Moss et al 22 evaluated the efficacy of resection of tumor
areas together with all the metaplastic mucosa by
repeated resections with plastic cap or resection in 53
patients with multiband. After an average of
2 sessions total resection was achieved taplsica least
mucosa. 15% of patients had a stricture requiring
endoscopic dilation.
Regarding the long-term efficacy, treatment with
radiofrequency seems lasting results. Thus, Shaheen et al
23 evaluated the recurrence of Barrett's esophagus after
radiofrequency ablation in a group of 65 patients with
Barrett's esophagus and dysplasia in which no intestinal
metaplasia was observed 1 year after treatment. In
addition, at 2 years of stopping treatment, 92% showed no
signs of recurrence. Of the 13 patients with follow-up to
three years, 100% remained free of intestinal metaplasia
end.
Fleischer et al 24 also assessed the rate of recurrence of
Barrett's esophagus after 5 years of follow-up in 50
patients with Barrett's esophagus without dysplasia treated
by radiofrequency ablation. After 5 years of follow-up
endoscopy and biopsy, both blind as any suggestive mucosa
area of Barrett's esophagus. 92% of patients had no
recurrence. 4 patients in whom intestinal metaplasia was
detected were treated again with radiofrequency and
biopsies at 2 months showed no intestinal metaplasia.
Instead, the long-term efficacy of other ablative
treatments appears much smaller than the radiofrequency.
So, Wani et al 25 also assessed the long-term
effectiveness of other techniques to eradicate esophageal
rrett Bacon, specifically the multipolar coagulation and
argon plasma coagulation in 42 patients. In contrast to
radiofrequency ablation, coagulation methods showed a
very high rate of recurrence. Thus, recurrence after a
mean follow-up was 2.7 years 50%, 41% in the case of
argon plasma coagulation and 68% in the case of the
multipolar coagulation. Since these methods also have a
higher risk of stenosis and perforation, they can not be
recommended for the treatment of Barrett's esophagus.

Endoscopic treatment
carcinoma located

of

esophageal

X. Calvet
squamous cell

Bergman et al 26 presented preliminary results

Two studies that assessed the efficacy of radiofrequency
ablation of high-grade dysplasia and neoplasia maas scale
in situ. In the first, a multicenter study conducted in China
in 29 patients after a single treatment with radiofrequency
completely eliminated neoplastic lesions in 86% of
patients. In the remaining 4 patients, segmental ablation
session eliminated the residual neoplastic tissue. Four of
the patients developed oped stenosis, which was treated
with dilation. In the second study combining scopic semi
endoscopic resection followed europeos27 radio frequency
in 12 patients were evaluated. The combination of
endoscopic resection and radiofrequency remove the "in
situ" neoplasia and / or high-grade dysplasia in all patients.
One patient developed a stenosis and perforation after
dilation, which was treated with antibiotic and a coated
prosthesis, with good response. Both studies suggest that
radiofrequency, with or without endoscopic resection, it is
also very effective and well tolerated in cases of
esophageal squamous neoplasia in situ.

Eosinophilic esophagitis
Molina-Infante et al 28 presented very interesting data
about eosinophilic esophagitis in our midst. Toma rum
esophageal biopsies of 712 adults undergoing endoscopy,
detecting 35 patients with a count of more than
15 intraepithelial eosinophils per high-power field. Most of
them had dysphagia or food impaction mentary as the
predominant symptom. PPI treatment resulted in clinical
improvement in 31 patients (89%) and histological
normalization in 26 (75%). Since one of the diagnostic
criteria for eosinophilic esophagitis is a lack of clinical
response to treatment with IBP29, these data supplied gest
that most of our patients with symptomatic dysphagia or
food impaction and esophageal eosinophilic infiltration
intraepithelial be considered as carried - res GERD and
treated with high doses of PPIs. Only the small percentage
who do not respond to treatment actually present
eosinophilic esophagitis.
Regarding treatment of eosinophilic esophagitis, Do- hil et
al30 compared oral budesonide for 3 months versus
placebo in 24 children with eosinophilic esophagitis.They
observed clinical response in 13 of the 15 children who
received budesonide (87%) ron vs 0% in the 9 who received
placebo. The number of intraepithelial lymphocytes
increased from
From 66.7 to 4.8 per high-power field in treated
patients. There was also a significant decrease in
symptoms and do not raise re- side effects were evident.
Straumann et al evaluated the long-term usefulness of
treatment with low doses of budesonide in eosinophilic
esophagitis in a randomized, placebo-controlled. Twentyeight patients who responded to treatment with
budesonide were randomized to budesonide 0.25 mg 2
times a day or placebo. Histological recurrence was
observed in 9 patients (64%) in the budesonide group and
in 100% of patients who received placebo. Also
symptomatic recurrence rate was lower and later in
patients receiving budesonide. The authors conclude that
low-dose budesonide is useful for maintenance treatment
in patients with eosinophilic esophagitis.

Enfermedad por reflujo gastroesofgico y esfago de Barrett: epidemiologa, diagnstico y tratamiento

One of the most common complications of eosinophilic
esophagitis is tis esophageal stricture requiring dilation.
Jung et al 31 presented a retrospective analysis of a series
expansions 293 in 161 patients with eosinophilic
esophagitis. Dilations were performed by Savary dilators or
balloon. The most frequent complications were the
appearance of a deep fissure (9.2%), hemorrhage (0.3%) or
perforation (n = 3, 1%). Of the 3 patients with perforation,
2 had been treated by dilation with Savary probe and the 3
evolved properly with medical treatment. Predictors of
complication were the presence of a stenosis in the middle
or upper third, the presence of a non-severe stenosis
franquea- ble with the endoscope and the use of probes
Savary.

Conclusions
The results of many of the studies presented at the
American Digestive Disease Week this year have great
practical utility. These include the demonstration that
medical treatment is superior to rrgico Qui for
uncomplicated reflux disease, and weight loss and smoking
cessation are extreme ly effective measures for the
treatment of gastroesophageal reflux .

Conflict of interests
The author declares no conflict of interest.

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