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Pocket Guide to
Gastro Esophageal Reflux
Disorder (GERD)
Priti Chugh
...
Anejo Health Communications
// 3
© Anejo Health Communications
E-mail: [email protected]
www.anejo.eu
First edition February 2014
All rights reserved
Printed in February 2014
Although the information about medication given in this book has
been carefully checked, the author and publisher accept no liability for
the accuracy of this information.
In every individual case the user must check such information by consulting
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This work is subject to copyright. All rights are reserved, whether the
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Table of Contents
Useful Web Resources
11
GERD- Definition and Prevalence
13
GERD- Clinical Features
. Pathophysiology of GERD
. Functional Abnormalities at the Esophagogastric Junction
. Clearance of Refluxate
. Nature of Refluxate
17
18
18
20
21
GERD- Diagnosis
. Response to PPI Therapy (Proton Pump Inhibitors)
. Esophageal pH-Monitoring
. Esophageal Impedance Monitoring and High-Resolution
Manometry (HRM)
. Radiological Findings
- Barium Swallow Radiograph
- Endoscopy
23
25
25
Treatment of GERD
. Lifestyle Modifications
. Antisecretory Drugs
-H2-Receptor Blockers
-Proton Pump Inhibitors (PPIs)
29
29
30
30
32
26
27
27
27
// 9
. Novel Pharmaceutical Approaches
-Stereoisomers
-Extended-Release PPIs
-Newer PPIs
-Potassium-Competitive Acid Blockers (PCABs)
-Combinations of PPI with Other Agents
-Agents in Pipeline
. Alternative Treatments
. Surgical Management
-Surgical Technique
-Restoration of Intra-Abdominal Esophagus
-Reconstruction of Extrinsic Sphincter
-Reinforcement of Intrinsic Sphincter
-Special Precaution After the Surgery
-Endoscopic Therapy
34
34
35
35
36
36
40
41
43
44
44
45
45
46
46
Complications of GERD
. Benign Esophageal Stricture
. Barrett’s Esophagus
- Diagnosis of BE
- Medical Management of BE
- Endoscopic Treatment of BE
. Extra Esophageal Syndromes
49
49
50
50
52
53
54
References
57
GERDDefinition and Prevalence
Gastro esophageal reflux disorder (GERD) is a commonly occurring
disorder in the modern world. It is primarily defined as "a condition that
develops when the reflux of stomach contents causes troublesome
symptoms and/or complications." The Montreal definition of the disorder
was developed by an international consensus group of experts and family
physicians over a period of 2 years. A series of statements was drafted
based on evidence from systematic reviews of the literature in 3 databases
(EMBASE, Cochrane Central Register of Controlled Trials, and
MEDLINE). The group went through multiple sessions of voting to
modify and approve the statements in order to incorporate all possible
complications and broaden the definition of GERD. Gastro esophageal
reflux occurring frequently (more than once a week) is designated
gastrointestinal reflux disease and affects the quality of life significantly.(1)
The main symptom of GERD in adults is frequent heartburn, also called
acid indigestion—burning-type pain in the lower part of the mid-chest,
behind the breast bone, and in the mid-abdomen. Most children under 12
years with GERD, and some adults, have GERD without heartburn.
Instead, they may experience a dry cough, asthma symptoms, or trouble
swallowing. Complications of GERD include erosive esophagitis,
hemorrhage, ulcerative esophagitis, and esophageal strictures. GERD is a
known risk factor for development of Barrett's esophagus (BE) and
esophageal adenocarcinoma, the most rapidly rising incidence of cancer
in the western world. GERD is described in subcategories for ease in
// 13
diagnosis, non-erosive esophageal reflux disease NERD and additional
pathologies that follow as result of GERD.(2)
In a recent study of GI disorders in the United States, abdominal pain
was the most common GI symptom that prompted a clinic visit (15.9
million visits). Gastro esophageal reflux was the most common GI
diagnosis (8.9 million visits). About seven percent of US population
is known to suffer from heartburn on a daily basis, of these about 2040% people are expected to be suffering from GERD. Reflux disease
is associated with a huge economic burden in the western countries
and significantly decreases the quality of life. It happens to be the most
common diagnosis in gastrointestinal-related complaints during office
visits and accounts for direct medical costs of over 10 billion dollars
per year in the United States alone and the indirect costs amounting
to additional burden of 75 billion dollars per year as a result of
decreased work productivity.
Reflux symptoms also account for the most common indication for
upper endoscopy. Barrett's esophagus accounted for almost a half
million visits in 2009. About 3.3 million Americans have been
diagnosed with Barrett's esophagus. A large number of patients (90%)
with Barrett's esophagus condition have non dysplastic disease.
According to the guidelines the patients with non-dysplastic disease
undergo endoscopic surveillance every 3 to 5 years. Given the large
number of subjects with Barrett's, these examinations represent a
substantial commitment of resources.(2,3,4)
Earlier GERD was recognized mostly in the western world and was
thought to be less prevalent in the developing countries. In a recent
systematic review, 10-20% prevalence of GERD (at least weekly
heartburn and/or regurgitation) was described in the western
countries; while less than 5% incidence was noted in Asia. However
there is an increasing trend in the prevalence of GERD over the last
two decades in Asian countries and is more common than was
previously recognized. Europe has an overall lower prevalence than
North America, however there are studies reporting an overall increase
in prevalence of GERD with time. Highest prevalence rates have been
described for North America.(3)
GERDClinical Features
GERD can cause a variety of symptoms. Typical symptoms are heartburn,
acid regurgitation, and dysphagia, which frequently occur in the absence
of endoscopic change (nonerosive GERD) or histopathologic change;
atypical symptoms reflect upper airway consequences of reflux (eg,
nonproductive cough, belching, wheezing) and noncardiac chest pain.
Heartburn the most common symptom is described as a burning sensation
in the retrosternal area. Heartburn is produced by the contact of the
refluxed material with inflamed esophageal mucosa. Regurgitation is defined
as the perception of flow of refluxed gastric contents into the mouth or
hypo pharynx. This aspiration of gastric juices into the esophagus can lead
to chronic cough, recurrent pneumonitis, dental erosion or idiopathic
pulmonary fibrosis. Epidemiological data suggests that 34-89% of
asthmatics have GERD. GERD is also commonly associated with sleep
disturbances and can also manifest as angina like radiating pain, hyper
salivation, globus sensation, nausea, or dysphagia in some patients.
Persistent dysphagia suggests development of peptic stricture; most
patients with peptic stricture have a history of heartburn for several years
preceding dysphagia. About one third of patients present with dysphagia
as their first symptom. Sometimes rapidly progressive dysphagia and weight
loss may indicate development of complications like adenocarcinoma in
Barret’s esophagus. Bleeding could also occur due to erosion of mucosa
or Barret’s ulcer. Laryngopharyngeal reflux is caused by reflux of gastric
contents into the laryngopharynx and may result in coughing, choking, and
hoarseness as a result of vocal cord edema or even ulceration. Patients may
// 17
describe throat-clearing and globus pharyngeus more frequently than
heartburn. Frequently occurring pulmonary aspiration could cause
aspiration pneumonia, pulmonary fibrosis or chronic asthma. Some patients
can remain asymptomatic over long periods of time.
Histopathologic changes in erosive GERD can result in epithelial
erosion, ulceration, and inflammation. Severe disease can cause severe
epithelial injury or even mucosal destruction; mild disease can cause
thickening of the basal zone and lengthening of the papillae.
Esophageal pathology and severity of symptoms do not always
correlate well: The majority of patients with symptoms of GERD
have either no or only very minor histopathologic changes, and not all
patients with histopathologic changes of GERD have symptoms.
Healing of esophageal ulceration may sometimes result in strictures
and scars. Barrett’s esophagus is a histopathologic consequence of
chronic GERD in which normal esophageal epithelium is replaced by
columnar epithelium; the presence of intestinal goblet cells is a marker
for an increased risk for adenocarcinoma.(2,6,8)
Pathophysiology of GERD
GE reflux is a normal physiological phenomenon and several
mechanisms exist to safeguard the esophageal mucosa from prolonged
acid exposure. Anti- reflux barrier at the esophagogastric junction forms
the first line of defense against acid reflux. Anomalous functioning of
the junction components lead to flow of stomach contents into the
esophagus. Caustic nature of refluxate and esophageal clearance
mechanisms also play a role in GERD pathophysiology.(2,6)
Functional Abnormalities
at the Esophagogastric Junction
Gastro esophageal reflux is expected to occur when the lower esophageal
sphincter (LES) opens spontaneously for varying periods of time, or does
not close properly and as a consequence the stomach contents rise up
into the esophagus. The esophageal environment is normally maintained
at a higher pH level than the stomach lining. When subjected to persistent
// Gastro Esophageal Reflux Disorder (GERD)
low pH acid, the esophageal lining is destroyed over long periods of time.
Multiple mechanisms exist at the LES that support its action as a barrier
to the acid reflux from the stomach. The sphincter is a physiological valve
ranging 3 to 7 cm in length. It is controlled by coordination of various
closing and opening mechanisms that contribute towards the proper
function of the LES. The crux of the diaphragm creates a pinch cork
action and functions to increase the pressure and the intra-abdominal
portion of the esophagus is important as the anti-reflux barrier. The
length of this portion is very important as it determines the functional
valve-like effect. The angle between the stomach and the esophagus (the
angle of His) is also of consequence in preventing reflux. Increased intraabdominal pressure arising from abnormalities like abdominal tumors,
coughing, and constipation also increase the intra-gastric pressure and
thus increases the risk of GERD.(5,6)
Esophageal
epithelium
Epithelium of
the stomach in
esophageal area
// 19
GERDDiagnosis
Gastro esophageal reflux disease (GERD) can be diagnosed based
on symptoms alone without additional diagnostic testing. The
Montreal definition of GERD describes a symptom-based, patientcentered approach to diagnosis of GERD. (GERD review) Newer
techniques for esophageal functional testing such as wireless pH
capsule monitoring, duodeno-gastroesophageal (also referred to as
alkaline or bile reflux) reflux detection, and esophageal impedance
testing have been introduced over the past decade and are utilized
in clinical practice when needed.(9)
Clinical Presentation- According to the Montreal definition
GERD can be diagnosed in primary care settings on the basis
careful analysis of symptoms presented by the patient without
additional diagnostic testing. This approach is appropriate for most
patients and does not require additional resources. This approach
to diagnosis relies on patient’s information regarding the effect of
symptoms on their everyday lives. In cases where patients present
with typical symptoms of heartburn, regurgitation and dysphagia
without any complications the diagnosis of GERD is usually
straightforward. However in the absence of classic symptoms, it
requires more thorough examination of patients in order to
eliminate other underlying illness. Among the atypical symptoms
that may be caused by GERD are chest pain, hoarseness, nausea,
cough, odynopia and asthma. In cases of chest pain it becomes
// 23
important to rule out cardiac issues similarly in cases of dysphagia,
odynophagia and weight loss it is important to rule out esophageal
stricture or cancer. More extensive investigation is done before the
diagnosis of GERD can be established. Different diagnostic tests
are used when the diagnosis is complicated or less obvious.
In infants suffering from GER, Orenstein’s infant GER
questionnaire (i-GERQ) may help in distinguishing GER from
GERD. Similarly, Rome III criteria can also be used to help
diagnosing GER in infants. Orenstein, et al. have developed a
symptom-based 11 points questionnaire (I-GERQ GERD) with
maximum score of 25 to differentiate GER from GERD and have
shown that a score of >7 has 74% sensitivity and 94% specificity
in diagnosing GERD in infants.(12)
pH
monitoring
catheter
Reflux
Meal
B
Monitoring
device
records pH
in esophagus
Supine
8
6
pH
4
2
10 AM
C
8
2 AM
6 AM
Meal
Heartburn (H)
10 AM
Supine
H
H
2 AM
6 AM
10 AM
Post Pain
6
pH
4
2
10 AM
2 AM
6 AM
10 AM
2 AM
6 AM
10 AM
// Gastro Esophageal Reflux Disorder (GERD)
Response to PPI Therapy (Proton Pump Inhibitors)
The role of proton pump inhibitor, omeprazole (Prilosec) in the
diagnosis of GERD has been investigated and is widely
recommended. It was found that the response to omeprazole (a
dosage of 40 mg per day for 14 days) had similar accuracy and
sensitivity to the results of 24-hour pH monitoring in context of
GERD. Failure in relieving reflux symptoms subsequent to
omeprazole intake often indicates a more detailed investigation of
other possible causes for a patient's symptoms.(11)
Esophageal pH-Monitoring
Documentation and quantification of reflux becomes necessary
when the reflux symptoms are complex. This can be accomplished
by ambulatory 24 hr esophageal pH recording. 24 hours ambulatory
pH-metry helps to establish the presence of acidic reflux (pH < 4)
in a patient who does not have GER symptoms and it also helps
to assess the efficacy of medical therapy. Esophageal pH
monitoring is especially beneficial for measuring GER in patients
not responding to anti reflux treatment and also in research.
Esophageal pH-monitoring has several advantages; it can be done
in any age (neonates to adults), it is relatively non-invasive, however
the main disadvantage is that it does not measure non-acid or
weakly acidic reflux (pH ≥4). PH monitoring has evolved to
wireless pH capsule technology that has improved patient
tolerability and allowed for prolonged recordings that allow for
both detection of acid reflux and response to therapy. The
sensitivity of pH monitoring might be enhanced by pH capsule
positioning closer to the SCJ, but further validation is needed
because of concerns for diminished diagnostic specificity.
Ambulatory impedance-pH, catheter pH, or wireless pH
monitoring (with PPI therapy withheld for 7 days) is suggested for
evaluation of patients with a suspected esophageal GERD
syndrome who have not responded to an empirical trial of PPI
therapy, have normal findings on endoscopy, and have no major
abnormality on manometry. Wireless pH monitoring has shown
// 25
Treatment of GERD
Interventions and Practices for initial treatment include lifestyle
modifications and use of Antisecretory drugs such as proton pump
inhibitors (PPIs), histamine receptor antagonists (H2RAs),
metoclopramide. In complicated cases that are refractory to PPI therapy,
diagnostic testing with Endoscopy
(with or without biopsy), esophageal
manometry, ambulatory
impedance pH, catheter pH,
or wireless pH monitoring
is recommended.
Chronic (long-term)
management includes
maintenance therapy with
PPIs or H2RAs, endoscopy
with or without mucosal biopsy,
antireflux surgery in severe cases.(14,17)
Lifestyle Modifications
Lifestyle modifications are recommended for management of GERD
and may include one or more of the following:
• Raising the head of the bed is recommended for patients with
nocturnal GERD, or erosive or complicated esophagitis, but is
usually not helpful for patients suffering from daytime upright reflux.
• Dietary changes could also be beneficial, lower intake of fatty foods,
smaller portions instead of large meals or not lying down within
approximately 3 hours after a meal.
• Avoidance of food triggers that may precipitate attacks (eg,
chocolate, caffeine, peppermint, spices, onions); these triggers need
to identified for the individual patient.
// 29
• Weight loss is recommended for GERD patients who have had recent
weight gain or are overweight. Obesity is a risk factor for GERD.
• Smoking is considered as one of the aggravating factors and should
be avoided.
• Avoiding clothing that is tight or constrictive around the abdomen
or lower chest
• Avoiding or reducing alcohol intake is also indicated in certain cases.
A quasi-systematic review of 16 clinical trials evaluated the effect of
lifestyle measures on changes in GERD symptoms, esophageal pH
variables, and lower esophageal pressure. Although alcohol, tobacco,
chocolate, and high-fat foods decrease lower esophageal pressure, no
evidence was found to support efficacy of dietary measures. Similarly,
stopping tobacco or alcohol led to improvement in esophageal pH
profiles or symptoms, although elevating the head of the bed and lying
on the left side improved the time that esophageal pH was less than
4.0. Weight loss improved pH and symptoms. These findings suggest
that weight loss and raising the head of the bed may be effective
modalities in treating GERD.(24)
Antisecretory Drugs
H2-Receptor Blockers
H2-receptor blockers were the first agents of choice for treating reflux
symptoms and healing esophagitis. Reflux treatment was
revolutionized with the introduction of cimetidine (Tagamet) in mid
1970s. Cimetidine is of the first blockbuster drugs. They remain the
mainstay of pharmacologic treatment. H2-receptor blockers act by
inhibiting histamine stimulation of the gastric parietal cell, thereby
suppressing gastric acid secretion. These agents are weak inhibitors of
meal-stimulated acid secretion since they minimally inhibit parietal cell
stimulation by gastrin and acetylcholine. They are known to effectively
suppress the nocturnal acid secretion. They can be used to treat peptic
ulcer disease in addition to relieving the symptoms of mild to
moderate GERD. H2-receptor blockers are very successful in healing
esophagitis because they are not able to inhibit acid secretion
Complications of GERD
Benign Esophageal Stricture
Chronic reflux of acidic gastric contents can lead to ulceration,
inflammation, and eventually stricture of the esophagus. An esophageal
stricture is defined as any loss of lumen area within the esophagus. The
normal esophagus measures 20 mm in diameter. The predominant
clinical symptom of strictures is dysphagia, which is usually most
prevalent when the luminal diameter is less than 15 mm. Even less
severe strictures can cause intermittent dysphagia to large food pieces
such as meat and bread. There are multiple intrinsic and extrinsic causes
for esophageal strictures. Intrinsic strictures are most common, with
acid or peptic causes accounting for the majority of cases (60% to
70%). Peptic strictures have become a less common due to the
widespread use of PPIs. Dilation techniques with either through-thescope balloon or Savary-type dilators are effective in treating peptic
stricture and relieving the associated dysphagia. In rare instances, peptic
strictures can be refractory to simple dilation and are treated with
endoscopic steroid injection, implanted stents, or anti-reflux surgery.
Surgery may be necessary if medical treatment and dilatations are
inadequate. There are two types of surgical repair, both of which are
usually approached via a left thoracoabdominal incision. Gastroplasty
after esophageal dilatation interposes the fundus of the stomach
between esophageal mucosa and the acidic milieu of the stomach. The
// 49
remaining fundus may be sewn to the lower esophagus to create a
valve-like effect. The second type of repair is resection of the stricture
and the creation of a thoracic end-to-side esophagogastrostomy.
Vagotomy and antrectomy are performed to eliminate stomach acidity,
and a Roux-en-Y gastric drainage procedure is performed to prevent
alkaline intestinal reflux.(34)
Barrett's Esophagus
Abnormal Cells
Normal Cells
Gastric Reflux
Stomach
Barrett's esophagus results from development of an abnormal
columnar epithelium that replaces the stratified squamous epithelium
that normally lines the distal esophagus. An Australian surgeon named
// Gastro Esophageal Reflux Disorder (GERD)
for Norman Barrett, drew attention to the columnar-lined esophagus
in 1950. Development of Barrett's esophagus is a risk factor for
esophageal adenocarcinoma. Barrett's esophagus is a consequence of
chronic gastroesophageal reflux disease (GERD). Metaplastic
columnar epithelium, also known as intestinal metaplasia (IM) develops
during healing of erosive esophagitis with continued acid reflux since
columnar epithelium is more resistant to acid and pepsin damage than
squamous epithelium. The metaplastic epithelium is a mosaic of
different epithelial types including goblet cells and columnar cells that
have features of both secretory and absorptive (incomplete or type 3
metaplasia). Barret’s epithelium progresses through a dyplastic stage
before developing into adenocarcinoma. The columnar-lined
esophagus causes no obvious symptoms; however the condition has
clinical importance because it is a risk factor for esophageal
adenocarcinoma, a tumor whose frequency has increased more than
six-fold over the past several decades. The risk of developing
esophageal cancer in BE patients is about 30 to 125 times the risk of
general population. Conservative estimates suggest that 3% to 12%
of patients with GERD will have BE, and this prevalence increases
with age, with up to 25% of people older than 50 years with some
degree of BE.(35,34)
Diagnosis of BE
Diagnosis of Barret’s esophagus can be made by endoscopic
examination that fulfills the following two criteria. First, the
examination should ascertain that columnar-appearing epithelium lines
the distal esophagus. The second evidence is gathered by biopsy of
the specimens and should show evidence of metaplasia (a change from
one adult cell type to another). Endoscopically, columnar epithelium
has a reddish color and velvet-like texture that can be distinguished
readily from normal esophageal squamous epithelium, which is pale
and glossy. There is a strong and probably causal relation between
symptomatic prolonged and untreated GERD, Barrett’s esophagus,
and esophageal adenocarcinoma. GI referral for upper endoscopy is
needed when there are concerns about associated peptic ulcer disease,
Barrett’s esophagus, or esophageal cancer. Patients with Barrett’s
esophagus are recommended to undergo surveillance endoscopy with
mucosal biopsy every 2 yr or less because the risk of developing
adenocarcinoma of esophagus is at least 30 times greater than that of
// 51
// Gastro Esophageal Reflux Disorder (GERD)
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