GERD
Gastroesophageal reflux is a normal physiologic phenomenon
experienced intermittently by most people, particularly after a meal.
Gastroesophageal reflux disease (GERD) occurs when the amount of gastric juice
that refluxes into the esophagus exceeds the normal limit, causing symptoms
with or without associated esophageal mucosal injury (i.e., esophagitis)
Most commonly manifested clinically by pyrosis (heartburn), at least once a month.
In most persons with GERD, endogenous defense mechanisms either
limit the amount of noxious material that is introduced into the esophagus or
rapidly clear the material from the esophagus so that symptoms and esophageal
mucosal irritation are minimized. Examples of the defense mechanisms include actions of the lower esophageal sphincter
(LES) and normal esophageal motility. When the defense mechanisms are
defective or become overwhelmed so that the esophagus is bathed in acid or bile
and acid-containing fluid for prolonged periods, GERD can be said to exist.
Patients with GERD can exhibit various symptoms, both typical and
atypical. Typical symptoms include heartburn,
regurgitation, and dysphagia. Atypical symptoms include
noncardiac chest pain, asthma, pneumonia, hoarseness, and aspiration.[3, 4] Patients
typically have numerous daily episodes of symptomatic reflux, including
pyrosis, water brash or sour taste in the mouth, nighttime coughing or
aspiration, pneumonia or pneumonitis, bronchospasm, and laryngitis and voice
changes, including hoarseness. In addition, objective evidence of esophageal
damage can be seen on esophagogastroduodenoscopy as manifested by the
incremental grades of esophagitis discussed below. (See Clinical Presentation.)
Laboratory tests are seldom useful in establishing a diagnosis of
GERD. Esophageal manometry and pH monitoring are considered essential before
performing an antireflux operation. Endoscopy reveals that 50% of patients do
not have esophagitis. The only way to determine if abnormal reflux is present
and if symptoms are actually caused by gastroesophageal reflux is through pH
monitoring. Achalasia can present with heartburn. Only esophageal manometry and
pH monitoring can be used to distinguish achalasia from GERD. Therapy is
completely different for the 2 conditions.
GERD is treated via a stepwise approach that is based on lifestyle
modification and control of gastric secretion by means of medical or surgical
treatment.
GI disorders are some of the most frequent complaints during
pregnancy, and gastroesophageal reflux is among these complaints. Some women
have certain GI disorders that are unique to pregnancy, and others have chronic
GI disorders that require special consideration during pregnancy. Understanding
the presentation and prevalence of various GI disorders is necessary in order
to optimize care for these patients.
Anatomy
The anatomy of the
esophagus, stomach, and esophagogastric junction is critical in the
understanding of the pathogenesis of reflux.
The esophagus is divided
into 3 parts: cervical, thoracic, and abdominal. The body of the esophagus is
made up of inner circular and outer longitudinal muscular layers. The proximal
third of the esophagus is striated muscle, which transitions to smooth muscle
in the distal two thirds. The proximal esophagus contains the upper esophageal
sphincter (UES), which comprises the cricopharyngeus and thyropharyngeus
muscles.
The distal thoracic
esophagus is located to the left side of midline. As the thoracic esophagus
enters the abdomen through the esophageal hiatus in the diaphragm, it becomes
the abdominal esophagus. The hiatus is formed by the right crus of the
diaphragm, which forms a sling around the esophagus with the right and left
pillars, so that the esophagus narrows when the diaphragm contracts.[11, 12, 13] The actual contribution the diaphragm provides
in maintaining an adequate length of intra-abdominal esophagus is not clearly
understood; however, careful identification and approximation of the pillars
during surgical treatment is crucial for preventing recurrence of reflux
disease.
At this level, the phrenoesophageal
ligament or membrane (see the image below), which is the reflection of the
subdiaphragmatic fascia onto the transversalis fascia of the anterior abdominal
wall, also encircles the esophagus. A prominent fat pad located on the anterior
surface of the esophagus marks the lower limit of the phrenoesophageal
ligament, which corresponds to the esophagogastric junction. This junction lies
in the abdomen and forms the angle of His. The acute angle and the length of
abdominal esophagus both contribute to the normal closure of the esophagus when
intragastric and intra-abdominal pressures are high.
The lower esophageal
sphincter—or, more accurately, the distal esophageal high-pressure zone
(HPZ)—is the distal most segment of the esophagus (3-5 cm in adults) and can be
anywhere from 2-5 cm in length. Maintenance of an adequate intra-abdominal HPZ
is crucial in preventing GERD. This HPZ does not correspond to any visible
anatomic structure. It is a zone created by a complex architecture of smooth
muscle fibers, and it is typically identified during manometry.
Usually, GERD is caused
by a malfunction of one or more of these anatomic features. Proper surgical
treatment requires complete preoperative and intraoperative evaluation and
correction of all defective features.
Blood supply of esophagus and stomach
The blood supply of the
esophagus is segmental (see the image below). The inferior thyroid artery
supplies the cervical esophagus. Branches of the bronchial arteries and
branches directly off of the aorta supply the proximal and distal thoracic
esophagus, respectively. Finally, branches of the left gastric and inferior
phrenic artery supply the abdominal esophagus. A relatively constant branch
connects the left gastric and inferior phrenic arteries, called the Belsey artery.
The blood supply of the
stomach is rich, with overlap among the vessels. The lesser curve is supplied
by the left and right gastric arteries, branches of the celiac trunk and proper
hepatic artery, respectively. The greater curve is supplied by the right
gastroepiploic artery arising from the gastroduodenal artery and the left
gastroepiploic artery and the short gastric arteries originating from the
splenic artery. This excellent collateral blood supply of the stomach allows
the surgeon to ligate much of the arterial supply (i.e., the short gastric
arteries during fundoplication) without risk of ischemia (see the image above).
Pathophysiology
Schematically, the
esophagus, lower esophageal sphincter (LES), and stomach can be envisioned as a
simple plumbing circuit as described by Stein and coworkers.[14] The esophagus functions as an antegrade pump,
the LES as a valve, and the stomach as a reservoir. The abnormalities that
contribute to GERD can stem from any component of the system. Poor esophageal
motility decreases clearance of acidic material. A dysfunctional LES allows
reflux of large amounts of gastric juice. Delayed gastric emptying can increase
volume and pressure in the reservoir until the valve mechanism is defeated,
leading to GERD. From a medical or surgical standpoint, it is extremely
important to identify which of these components is defective so that effective
therapy can be applied.
Esophageal defense mechanisms
Esophageal defense
mechanisms can be broken down into 2 categories (i.e., esophageal clearance and
mucosal resistance). Proper esophageal clearance is an extremely important
factor in preventing mucosal injury. Esophageal clearance must be able to
neutralize the acid refluxed through the lower esophageal sphincter.
(Mechanical clearance is achieved with esophageal peristalsis; chemical
clearance is achieved with saliva.) Normal clearance limits the amount of time
the esophagus is exposed to refluxed acid or bile and gastric acid mixtures.
Abnormal peristalsis can cause inefficient and delayed acid clearance.
Whether peristaltic
dysfunction is secondary to esophageal exposure to acids or a primary defect is
not understood clearly. In a review by Kahrilas et al, peristaltic dysfunction
was progressively more common in patients with greater degrees of esophagitis.[15] Abnormal peristalsis was identified in 25% of
patients with mild esophagitis and 48% of patients with severe esophagitis.
Buttar and associates
described the importance of esophageal mucosal resistance as a protective
mechanism.[16] They classified the factors into pre-epithelial,
epithelial, and postepithelial defenses. When the defenses fail, esophagitis
and other complications of reflux disease arise.
Dysfunction of the lower esophageal sphincter
The lower esophageal
sphincter (LES) is defined by manometry as a zone of elevated intraluminal
pressure at the esophagogastric junction. For proper LES function, this
junction must be located in the abdomen so that the diaphragmatic crura can
assist the action of the LES, thus functioning as an extrinsic sphincter. In
addition, the LES must have a normal length and pressure and a normal number of
episodes of transient relaxation (relaxation in the absence of swallowing).
LES dysfunction occurs
via one of several mechanisms: transient relaxation of the LES (most common
mechanism), permanent LES relaxation, and transient increase of intra-abdominal
pressure that overcomes the LES pressure.
Delayed gastric emptying
The postulated mechanism
by which delayed gastric emptying may cause GERD is an increase in gastric
contents resulting in increased intragastric pressure and, ultimately,
increased pressure against the lower esophageal sphincter. This pressure
eventually defeats the LES and leads to reflux. However, objective studies have
produced conflicting data regarding the role of delayed gastric emptying in the
pathogenesis of GERD.
Hiatal hernia
When discussing
mechanisms for GERD, the issue of hiatal hernia must be addressed. Hiatal
hernias can be encountered frequently in patients with reflux disease; however,
it has been well proven that not all patients with hiatal hernias have
symptomatic reflux.
Buttar and coworkers
state that a hiatal hernia may contribute to reflux via a variety of
mechanisms.[16] (See image below). The lower esophageal
sphincter may migrate proximally into the chest and lose its abdominal
high-pressure zone (HPZ), or the length of the HPZ may decrease. The
diaphragmatic hiatus may be widened by a large hernia, which impairs the
ability of the crura to function as an external sphincter. Finally, gastric
contents may be trapped in the hernial sac and reflux proximally into the
esophagus during relaxation of the LES. Reduction of the hernias and crural
closure is key to restoring an adequate intra-abdominal length of esophagus and
recreating the HPZ.
Obesity as contributing factor
Some studies have shown
that GERD is highly prevalent in patients who are morbidly obese and that a
high body mass index (BMI) is a risk factor for the development of this
condition.[17, 18, 19, 20, 21, 22] The hypothesis that obesity increases esophageal
acid exposure is supported by the documentation of a dose-response relationship
between increased BMI and increased prevalence of GERD and its complications.
Therefore, the pathophysiology of GERD in patients who are morbidly obese might
differ from that of patients who are not obese. The therapeutic implication of
such a premise is that the correction of reflux in patients who are morbidly
obese might be better achieved with a procedure that first controls obesity.
The mechanism by which a
high BMI increases esophageal acid exposure is not completely understood.
Increased intragastric pressure and gastroesophageal pressure gradient,
incompetence of the lower esophageal sphincter (LES), and increased frequency
of transient LES relaxations may all play a role in the pathophysiology of GERD
in patients who are morbidly obese.
Etiology
Excessive retrograde movement of acid-containing gastric
secretions or bile and acid-containing secretions from the duodenum and stomach
into the esophagus is the etiologic effector of GERD. From a therapeutic point
of view, informing patients that gastric refluxate is made up not only of acid
but also of duodenal contents (e.g., bile, pancreatic secretions) is important.
A functional (frequent transient LES relaxation) or mechanical
(hypotensive LES) problem of the LES is the most common cause of GERD.
Transient relaxation of the LES can be caused by foods (coffee, alcohol,
chocolate, fatty meals), medications (beta-agonists,[23] nitrates, calcium channel
blockers, anticholinergics), hormones (e.g., progesterone), and nicotine.
Epidemiology
Western dietary habits have made GERD a common disease. Because
many individuals control symptoms with over-the-counter (OTC) medications and
without consulting a medical professional, the actual number of individuals
with GERD is probably higher.
No sexual predilection exists: GERD is as common in men as in
women. However, the male-to-female incidence ratio for esophagitis is 2:1-3:1. The male-to-female incidence ratio for Barrett esophagus is 10:1. White
males are at a greater risk for Barrett esophagus and adenocarcinoma than other
populations.
GERD occurs in all age groups. The prevalence of GERD increases in
people older than 40 years.
Prognosis
Most patients with GERD do well with medications, although a
relapse after cessation of medical therapy is common and indicates the need for
long-term maintenance therapy.
Identifying the subgroup of patients who may develop the most
serious complications of GERD and treating them aggressively is important.
Surgery at an early stage is most likely indicated in these patients. After a
laparoscopic Nissen fundoplication, symptoms resolve in
approximately 92% of patients.
Most cases of gastroesophageal reflux in infants and very young
children are benign and respond to conservative nonpharmacologic treatment
(developmental disabilities represent an important diagnostic exception); 80%
resolve by age 18 months (55% resolve by age 10 mo). Some patients require a
"step-up" to acid-reducing medications, and only a very small
minority requires surgery. Because symptomatic gastroesophageal reflux after
age 18 months likely represents a chronic condition, long-term risks are
increased. For patients whose gastroesophageal reflux persists into later childhood,
long-term therapy with antisecretory agents is often required.
In refractory cases or when complications related to reflux
disease are identified (e.g., stricture,
aspiration, airway disease, Barrett
esophagus), surgical treatment (fundoplication)
is typically necessary. The prognosis with surgery is considered excellent. The
surgical morbidity and mortality is higher in patients who have complex medical
problems in addition to gastroesophageal reflux.
History
Gastroesophageal reflux disease (GERD) is associated with a set of
typical (esophageal) symptoms, including heartburn,
regurgitation, and dysphagia. (However, a diagnosis of
GERD based on the presence of typical symptoms is correct in only 70% of
patients.) In addition to these typical symptoms, abnormal reflux can cause
atypical (extraesophageal) symptoms, such as coughing, chest pain, and wheezing.
The American College of Gastroenterology (ACG) published updated
guidelines for the diagnosis and treatment of GERD in 2005. According to the
guidelines, for patients with symptoms and history consistent with
uncomplicated GERD, the diagnosis of GERD may be assumed and empirical therapy
begun. Patients who show signs of GERD complications or other illness or who do
not respond to therapy should be considered for further diagnostic testing.[24]
A history of nausea, vomiting, or regurgitation should alert the physician to evaluate for delayed
gastric emptying.
Patients with GERD may also experience significant complications
associated with the disease, such as esophagitis,
stricture, and Barrett esophagus.
Approximately 50% of patients with gastric reflux develop esophagitis
Physical Examination
Typical esophageal symptoms
Heartburn is
the most common typical symptom of GERD. It is felt as a retrosternal sensation
of burning or discomfort that usually occurs after eating or when lying supine
or bending over.
Regurgitation is
an effortless return of gastric and/or esophageal contents into the pharynx.
Regurgitation can induce respiratory complications if gastric contents spill
into the tracheobronchial tree.
Dysphagia
occurs in approximately one third of patients. Patients with dysphagia
experience a sensation that food is stuck, particularly in the retrosternal
area. Dysphagia can be an advanced symptom and can be due to a primary
underlying esophageal motility disorder, a motility disorder secondary to
esophagitis, or stricture formation.
Atypical extraesophageal symptoms
Coughing and/or wheezing are respiratory symptoms
resulting from the aspiration of gastric contents into the tracheobronchial
tree or from the vagal reflex arc producing bronchoconstriction. Approximately 50% of patients who have
GERD-induced asthma do not experience heartburn.
Hoarseness
results from irritation of the vocal cords by gastric refluxate and is often
experienced by patients in the morning.
Reflux is the most
common cause of noncardiac chest pain, accounting for approximately 50%
of cases. Patients can present to the emergency department with pain resembling
a myocardial infarction. Reflux should be ruled out (using esophageal manometry
and 24-hour pH testing if necessary; see the image below) once a cardiac cause
for the chest pain has been excluded. Alternatively, a therapeutic trial of a
high-dose proton pump inhibitor (PPI) can be tried.
Additional atypical
symptoms from abnormal reflux include damage to the lungs (e.g., pneumonia,
asthma, idiopathic pulmonary fibrosis), vocal cords (e.g., laryngitis, cancer),
ear (e.g., otitis media), and teeth (e.g., enamel decay).
Complications of
Disease
Esophagitis
Esophagitis (esophageal
mucosal damage) is the most common complication of GERD; occurring in
approximately 50% of patients.
Esophagitis may be
diagnosed using endoscopy, although it cannot always be appreciated on
endoscopy. As many as 50% of symptomatic patients with GERD demonstrate no
evidence of esophagitis on endoscopy. Still, documentation of this complication
is important in diagnosing GERD. Degrees of esophagitis are described by the Savary-Miller classification as
follows.
·
Grade I – Erythema
·
Grade II – Linear
nonconfluent erosions
·
Grade III – Circular
confluent erosions
·
Grade IV – Stricture or
Barrett esophagus.
Stricture
Strictures are advanced
forms of esophagitis and are caused by circumferential fibrosis due to chronic
deep injury. Strictures can result in dysphagia and a short esophagus.
Gastroesophageal reflux strictures typically occur in the mid-to-distal
esophagus and can be visualized on upper GI tract studies and endoscopy.
Presence of a stricture with a history of reflux can also help diagnose GERD.
Patients present with dysphagia to solid meals and vomiting of nondigested
foods.
As a rule, the presence
of any esophageal stricture is an indication that the patient needs surgical
consultation and treatment (usually surgical fundoplication). When patients
present with dysphagia, barium esophagography is indicated to evaluate for
possible stricture formation. In these cases, especially when associated with
food impaction, eosinophilic esophagitis must be ruled out prior to attempting
any mechanical dilatation of the narrowed esophageal region.
Barrett esophagus
The most serious
complication of long-standing or severe GERD is the development of Barrett esophagus. Barrett esophagus is present in 8-15% of patients with
GERD. Barrett esophagus is thought to be caused by the chronic reflux of
gastric juice into the esophagus. It is defined by metaplastic conversion of
the normal distal squamous esophageal epithelium to columnar epithelium (see
the image below). Histologic examination of esophageal biopsy specimens is
required to make the diagnosis. Varying degrees of dysplasia may be found on
histologic examination.
Barrett esophagus with
intestinal type metaplasia has malignant potential and is a risk factor for the
development of esophageal adenocarcinoma, increasing the risk of adenocarcinoma
30-40 times. The incidence of adenocarcinoma of the esophagus is increasing
steadily in Western society. Currently, adenocarcinoma accounts for more than
50% of esophageal cancers in Western industrialized nations.As with esophageal
stricture, the presence of Barrett esophagus indicates the need for surgical
consultation and treatment (usually surgical fundoplication).
Diagnostic
Considerations
Gastroesophageal reflux
may be classified into 3 categories as follows:
·
Physiologic
(or functional) gastroesophageal reflux: These patients have no underlying predisposing
factors or conditions; growth and development are normal; and pharmacologic
treatment is typically not necessary, though it may be needed to relieve
symptoms if lifestyle changes are unsuccessful.[24]
·
Pathologic
gastroesophageal reflux or GERD: Patients frequently experience complications noted above,
requiring careful evaluation and treatment[25]
·
Secondary
gastroesophageal reflux: This refers to a case in which an underlying condition may
predispose to gastroesophageal reflux, with examples including asthma (a
condition that may also be, in part, caused by or exacerbated by reflux) and
gastric outlet obstruction
The diagnosis of GERD in
patients with atypical symptoms can be difficult. When patients present with
atypical complaints, the diagnosis of GERD must be kept in mind. Patients with
recurrent aspiration can have asthma, history of pneumonias, and progressive
pulmonary fibrosis. Additionally, hoarseness can be present due to chronic
laryngeal irritation. Chest pain is another presenting symptom that can be
difficult to evaluate. In these patients, excluding cardiac etiology is
important prior to labeling the pain as noncardiac chest pain secondary to
GERD.
The clinical
presentation of GERD in pregnant women is similar to that for the general
population. Heartburn and regurgitation are the cardinal symptoms. The
diagnostic evaluation consists of a thorough history and physical examination.
Differential Diagnoses
·
Antral Web
Cholelithiasis
Approach Considerations
Mandatory studies include upper GI endoscopy and manometry.
Endoscopy can help confirm the diagnosis of reflux by demonstrating
complications of reflux (esophagitis, strictures, Barrett esophagus) and can
help in evaluating the anatomy (e.g., hiatal hernia, masses, strictures).
Manometry helps surgical planning by determining the lower esophageal sphincter
(LES) pressure and identifying any esophageal motility disorders. Esophageal
amplitudes and propagation of esophageal swallows are also evaluated.
Optional studies include 24-hour pH probe test and upper GI
series. Use of 24-hour pH testing helps confirm the diagnosis in patients in
whom the history is not clear, atypical symptoms dominate the clinical picture,
or endoscopy shows no complications of reflux disease. Upper GI series can be
ordered to further delineate the anatomy. Hiatal hernias can be evaluated
(size) and reflux can be demonstrated. In addition, gastric emptying can be
evaluated to a limited. If a question exists regarding inadequate gastric
emptying or if the patient has a history of nausea and vomiting, a nuclear
medicine gastric emptying study can be obtained.
At the authors' institution, endoscopy, manometry, and 24-hour pH
studies are obtained routinely. Upper GI series and nuclear medicine gastric
emptying studies are ordered only if clinically indicated. Currently, no role
exists for CT, MRI, or ultrasonography in the routine evaluation of patients
with reflux disease.
Upper Gastrointestinal
Endoscopy
Esophagogastroduodenoscopy
(EGD) demonstrates anatomy and identifies the possible presence and severity of
complications of reflux disease (esophagitis, Barrett esophagus, strictures)
(see the image below). Using the patient's history and pathologic analysis of
biopsy specimens obtained during endoscopy, the diagnosis of GERD can be made.
EGD also excludes the presence of other diseases (e.g., peptic ulcer) that can
present similarly to GERD.
Although EGD is
frequently performed to help diagnose GERD, it is not the most cost-effective
diagnostic study, because esophagitis is present in only 50% of patients with
GERD.
Esophageal Manometry
Esophageal manometry
defines the function of the LES and the esophageal body (peristalsis).
Esophageal manometry is essential for correctly positioning the probe for the
24-hour pH monitoring.
Indications for
esophageal manometry and prolonged pH monitoring include the following:
·
Persistence of symptoms while
taking adequate antisecretory therapy, such as PPI therapy
·
Recurrence of symptoms
after discontinuation of acid-reducing medications
·
Investigation of
atypical symptoms, such as chest pain or asthma, in patients without
esophagitis
·
Confirmation of the
diagnosis in preparation for antireflux surgery
Ambulatory 24-Hour pH Monitoring
Ambulatory 24-hour pH monitoring is the criterion standard in
establishing a diagnosis of GERD, with a sensitivity of 96% and a specificity
of 95%. It quantifies the gastroesophageal reflux and allows a correlation
between the symptoms of reflux and the episodes of reflux.
Patients with endoscopically confirmed esophagitis do not need pH
monitoring to establish a diagnosis of GERD.
Imaging in Gastroesophageal Reflux Disease
Plain radiographic findings are not useful in evaluating patients
for GERD, but they are helpful in evaluating pulmonary status and basic
anatomy. Chest images may demonstrate a large hiatal hernia, but small hernias
can be easily missed. Upper GI contrast-enhanced studies are the initial
radiologic procedure of choice in the workup of the patient in whom GERD is
suggested. Esophageal inflammatory and neoplastic diseases are better detected
with double-contrast techniques. Conversely, single-contrast techniques are
more sensitive for structural defects such as hiatal hernias and strictures or
esophageal rings.[26]
Although delayed gastric emptying is present in as many as 60% of
patients with GERD, this emptying is usually a minor factor in the pathogenesis
of the disease in most patients (except in patients with advanced diabetes
mellitus or connective tissue disorders). Patients with delayed gastric
emptying typically experience postprandial bloating and fullness in addition to
other symptoms. Gastric-emptying studies may be worthwhile in the evaluation of
patients in whom delayed gastric emptying is believed to contribute to the
manifestation of GERD symptoms.
Nuclear Medicine Gastric Emptying Study
Gastroesophageal reflux scintigraphy can be performed with
acidified orange juice labeled with technetium-99m sulfur colloid. Compared
with fluoroscopy, this allows for a longer time of evaluation, a decreased
radiation dose, and the ability to semiquantitate the amount of reflux.
However, gastroesophageal reflux scintigraphy has little role in the adult
patient due to limited sensitivity and the availability of other methods of
evaluation.
Gastroesophageal reflux scintigraphy is much more commonly used in
infants and children due to the noninvasive nature of the study and relatively
low radiation dose. In infants and children the study is often performed with
labeled milk. In addition to evaluating the degree of reflux, pulmonary
aspiration can be detected by imaging over the lungs.
Intraluminal
Esophageal Electrical Impedance
Intraluminal esophageal
electrical impedance (EEI), a newer test, is useful for detecting both acid
reflux and nonacid reflux by measuring retrograde flow in the esophagus.
Gastroesophageal reflux episodes as brief as 15 seconds may be measured (see
the image below).
The image is a representation of concomitant
intraesophageal pH and esophageal electrical impedance measurements. The
vertical solid arrow indicates commencement of a nonacid gastroesophageal
reflux (GER) episode (diagonal arrow). The vertical dashed arrow indicates the
onset of a normal swallow.
In adult studies,
impedance measurements have been used in conjunction with 24-hour intraesophageal
pH monitoring in order to provide a more complete picture of bolus movement in
the esophagus. EEI has not been thoroughly validated, and normal values have
not been determined in the pediatric age group.
Approach Considerations
Treatment of GERD involves a stepwise approach. The goals are to
control symptoms, to heal esophagitis, and to prevent recurrent esophagitis or
other complications. The treatment is based on (1) lifestyle modification and
(2) control of gastric acid secretion through medical therapy with antacids or
PPIs or surgical treatment with corrective antireflux surgery.[5, 6,
7, 8, 9, 10]
Approximately 80% of patients have a recurrent but nonprogressive
form of GERD that is controlled with medications. Identifying the 20% of
patients who have a progressive form of the disease is important, because they
may develop severe complications, such as strictures or Barrett esophagus. For
patients who develop complications, surgical treatment should be considered at
an earlier stage to avoid the sequelae of the disease that can have serious
consequences.Use of a patient management tool such as the self-administered
GERD Questionnaire (GerdQ) to stratify patients may improve the management of
GERD patients in primary care settings.[27]
Lifestyle
Modifications
Lifestyle modifications
include the following:
·
Losing weight (if
overweight)
·
Avoiding alcohol,
chocolate, citrus juice, and tomato-based products (The ACG 2005 guidelines
also suggest avoiding peppermint, coffee, and possibly the onion family as
well.[24] )
·
Avoiding large meals
·
Waiting 3 hours after a
meal before lying down
·
Elevating the head of
the bed 8 inches
According to the ACG
2005 guidelines, studies have shown decreased distal esophageal acid exposure
after these changes is made, but little data are available to confirm these
findings.[24]
Lifestyle modifications
are the first line of management in pregnant women with GERD. Advise patients
to elevate the head of the bed; avoid bending or stooping positions; eat small,
frequent meals; and refrain from ingesting food (except liquids) within 3 hours
of bedtime.
Pharmacologic Therapy
Antacids
Antacids were the standard treatment in the 1970s and are still
effective in controlling mild symptoms of GERD. Antacids should be taken after
each meal and at bedtime.
H2 receptor antagonists and H2 blocker therapy
H2 receptor antagonists are the first-line agents for patients
with mild to moderate symptoms and grades I-II esophagitis. Options include
ranitidine (Zantac), cimetidine (Tagamet), famotidine (Pepcid), and nizatidine
(Axid).
H2 receptor antagonists are effective for healing only mild
esophagitis in 70-80% of patients with GERD and for providing maintenance
therapy to prevent relapse. Tachyphylaxis has been observed, suggesting that
pharmacologic tolerance can reduce the long-term efficacy of these drugs.
Additional H2 blocker therapy has been reported to be useful in
patients with severe disease (particularly those with Barrett esophagus) who
have nocturnal acid breakthrough.
Proton pump inhibitors
PPIs are the most powerful medications available for treating
GERD. These agents should be used only when this condition has been objectively
documented. They have few adverse effects and are well tolerated for long-term
use. However, data have shown that PPIs can interfere with calcium homeostasis and aggravate cardiac conduction defects. These agents have also been responsible
for hip fracture in postmenopausal women.[28] Options
include omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex),
and esomeprazole (Nexium). A research review by the Agency for Healthcare
Research and Quality (AHRQ) concluded, on the basis of grade A evidence, that
PPIs were superior to H2 receptor antagonists for the resolution of GERD
symptoms at 4 weeks and healing of esophagitis at 8 weeks.[29]
In addition, the AHRQ found no difference between individual PPIs
(omeprazole, lansoprazole, pantoprazole, and rabeprazole) for relief of
symptoms at 8 weeks. For symptom relief at 4 weeks, esomeprazole 20 mg was
equivalent, but esomeprazole 40 mg superior, to omeprazole 20 mg.[29]
The LOTUS trial, a 5-year exploratory randomized, open,
parallel-group trial demonstrated that with antireflux therapy for GERD, either
using drug-induced acid suppression with esomeprazole or laparoscopic
antireflux surgery, most patients achieve and remain in remission at 5 years.[30]
Prokinetic medications and reflux inhibitors
Prokinetic agents are somewhat effective but only in patients with
mild symptoms; other patients usually require additional acid-suppressing
medications, such as PPIs. The usual regimen in adults is metoclopramide, 10
mg/day orally. Long-term use of prokinetic agents may have serious, even
potentially fatal, complications and should be discouraged.
Indications for Surgical
Treatment
As in many other fields,
surgical therapy for gastroesophageal reflux has evolved a great deal. A few
historical procedures of note include the Allison
crural repair, the Boerema anterior
gastropexy, and the Angelchik
prosthesis. Both the Allison and the Boerema repairs have high failure
rates and are rarely, if ever, used.[31, 32] The Angelchik prosthesis is a silicone ring that
is positioned at the gastroesophageal junction and prevents reflux. The
Angelchik prosthesis was rarely used in children and has been largely abandoned
because of a high rate of complications.[33]
Today, both
transthoracic and transabdominal fundoplications are performed, including
partial (anterior or posterior) and circumferential wraps. The most commonly
performed operation today in both children and adults is the Nissen fundoplication, which is a 360°
transabdominal fundoplication (see the image below).[34, 35] First reported in 1991, laparoscopic
fundoplication is well studied in adult populations. Laparoscopic
fundoplication has also quickly gained acceptance for use in children.[36, 37, 38, 39, 40, 41]
Indications for
fundoplication include the following:
·
Patients with symptoms
that are not completely controlled by PPI therapy can be considered for surgery;
surgery can also be considered in patients with well-controlled GERD who desire
definitive, one-time treatment
·
The presence of Barrett
esophagus is an indication for surgery (whether acid suppression improves the
outcome or prevents the progression of Barrett esophagus remains unknown, but
most authorities recommend complete acid suppression in patients with
histologically proven Barrett esophagus)
·
The presence of
extraesophageal manifestations of GERD may indicate the need for surgery; these
include the following: (1) respiratory manifestations (e.g., cough, wheezing,
aspiration); (2) ear, nose, and throat manifestations (e.g., hoarseness, sore
throat, otitis media); and (3) dental manifestations (e.g., enamel erosion)
·
Young patients
·
Poor patient compliance
with regard to medications
·
Postmenopausal women
with osteoporosis
·
Patients with cardiac
conduction defects
·
Cost of medical therapy
Several randomized
clinical trials have challenged the benefits of surgery in controlling GERD.
Lundell followed up his cohort of patients for 5 years and did not find surgery
to be superior to PPI therapy.[42] Spechler found that, at 10 years after surgery,
62% of patients were back on antireflux medications.[43] A very rigorous, randomized study by Anvari et
al reestablished surgery as the criterion standard in treating GERD.[44] The investigators showed that, at 1 year, the
outcome and the symptom control in the surgical group was better than that in
the medical group.[44]
Laparoscopic fundoplication
Laparoscopic
fundoplication is performed under general endotracheal anesthesia. Five small
(5-mm to 10-mm) incisions are used (see image below). The fundus of the stomach
is wrapped around the esophagus to create a new valve at the level of the
esophagogastric junction.
The essential elements
of the operation are as follows:
·
Complete mobilization of
the fundus of the stomach with division of the short gastric vessels
·
Reduction of the hiatal
hernia
·
Narrowing of the
esophageal hiatus
·
Creation of a 360° fundoplication
over a large intraesophageal dilator (Nissen fundoplication)
Laparoscopic
fundoplication lasts 2-2.5 hours. The hospital stay is approximately 2 days.
Patients resume regular activities within 2-3 weeks. Approximately 92% of
patients obtain resolution of symptoms after undergoing laparoscopic
fundoplication.
The AHRQ found, on the
basis of limited evidence, that laparoscopic fundoplication was as effective as
open fundoplication for relieving heartburn and regurgitation, improving
quality of life, and decreasing use of antisecretory medications.[29]
Although a prospective,
randomized trial has never been performed to compare PPIs to laparoscopic
fundoplication, the authors believe fundoplication is preferable for the
following reasons:
·
PPIs, although effective
in controlling the acid component of the refluxate, do not eliminate the reflux
of bile, which some believe to be a major contributor to the pathogenesis of
Barrett epithelium
·
Patients with Barrett
esophagus tend to have lower LES pressure and worse esophageal peristalsis than
patients without Barrett esophagus; patients with Barrett esophagus are also
exposed to a larger amount of reflux
·
A fundoplication offers
the only possibility of stopping any kind of reflux by creating a competent
LES; however, until the definitive answer is known, the authors recommend that
patients with Barrett esophagus continue to undergo periodic endoscopic
surveillance even after laparoscopic fundoplication
Devices
The US Food and Drug
Administration approved the LINX Reflux Management System in March 2012. This
device is designed to augment the lower esophageal sphincter. The system is a
small flexible band that is placed laparoscopically around the esophagus just
above the stomach to create a natural barrier to reflux. The band consists of
interlinked titanium beads with magnetic cores. The act of swallowing
temporarily breaks the magnetic bond, allowing food and liquid to pass
normally.[47]
H2-Receptor
Antagonists
Class Summary
H2 receptor antagonists
are the first-line agents for patients with mild to moderate symptoms and
grades I-II esophagitis. Options include ranitidine (Zantac), cimetidine (Tagamet),
famotidine (Pepcid), and nizatidine (Axid).
The H2 receptor
antagonists are reversible competitive blockers of histamine at the H2
receptors, particularly those in the gastric parietal cells, where they inhibit
acid secretion. They are highly selective, do not affect the H1 receptors, and
are not anticholinergic agents. Although IV administration of H2 blockers may
be used to treat acute complications (e.g., gastrointestinal bleeding), the
benefits are not yet proven.
These agents are
effective for healing only mild esophagitis in 70-80% of patients with GERD and
for providing maintenance therapy to prevent relapse. Tachyphylaxis has been
observed, suggesting that pharmacologic tolerance can reduce the long-term
efficacy of these drugs.
Additional H2 blocker
therapy has been reported to be useful in patients with severe disease
(particularly those with Barrett esophagus) who have nocturnal acid
breakthrough.
Ranitidine inhibits
histamine stimulation of the H2 receptor in gastric parietal cells, which, in
turn, reduces gastric acid secretion, gastric volume, and hydrogen
concentrations.
Cimetidine inhibits
histamine at H2 receptors of gastric parietal cells, which results in reduced
gastric acid secretion, gastric volume, and hydrogen concentrations.
Famotidine competitively
inhibits histamine at H2 receptor of gastric parietal cells, resulting in
reduced gastric acid secretion, gastric volume, and hydrogen concentrations.
Nizatidine competitively
inhibits histamine at the H2 receptor of the gastric parietal cells, resulting
in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.
Proton Pump Inhibitors
Class Summary
Proton pump inhibitors
(PPIs) inhibit gastric acid secretion by inhibition of the H+/K+ ATPase
enzyme system in the gastric parietal cells. These agents are used in cases of
severe esophagitis and in patients whose conditions do not respond to H2
receptor antagonist therapy. Options include omeprazole (Prilosec),
lansoprazole (Prevacid), rabeprazole (Aciphex), and esomeprazole (Nexium).
PPIs are the most
powerful medications available for treating GERD. These agents should be used
only when this condition has been objectively documented. They have few adverse
effects and are well tolerated for long-term use. However, data have shown that
PPIs can interfere with calcium homeostasis and aggravate cardiac conduction
defects. These agents have also been responsible for hip fracture in
postmenopausal women.[28]
Omeprazole is used for
up to 4 weeks to treat and relieve the symptoms of active duodenal ulcers. I
may be used for up to 8 weeks to treat all grades of erosive esophagitis.
Lansoprazole inhibits
gastric acid secretion. It is used for up to 8 weeks to treat all grades of
erosive esophagitis.
Rabeprazole is for
short-term (4- to 8-wk) treatment and relief of symptomatic erosive or
ulcerative GERD. In patients who are not healed after 8 weeks, consider an
additional 8-wk course.
Esomeprazole is an
S-isomer of omeprazole. It inhibits gastric acid secretion by inhibiting the
H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells.
Pantoprazole suppresses
gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme
system at the secretory surface of gastric parietal cells. Use of the
intravenous preparation has only been studied for short-term use (ie, 7-10 d).
Prokinetics
Class Summary
Prokinetic agents, such
as metoclopramide (Reglan), improve the motility of the esophagus and stomach
and increase the lower esophageal sphincter (LES) pressure to help reduce
reflux of gastric contents. They also accelerate gastric emptying.
Prokinetic agents are
somewhat effective but only in patients with mild symptoms; other patients
usually require additional acid-suppressing medications, such as PPIs.
Long-term use of prokinetic agents may have serious, even potentially fatal,
complications and should be discouraged.
Metoclopramide is a GI
prokinetic agent that increases GI motility, increases resting esophageal
sphincter tone, and relaxes the pyloric sphincter.
Antacid
Class Summary
Antacids were the
standard treatment in the 1970s and are still effective in controlling mild
symptoms of GERD. Antacids should be taken after each meal and at bedtime.
These agents are used as diagnostic tools to provide symptomatic relief in
infants. Associated benefits include symptomatic alleviation of constipation
(aluminum antacids, such as ALternaGEL and Amphojel) or loose stools (magnesium
antacids, such as Phillips Milk of Magnesia).
Aluminum hydroxide
increases gastric pH to greater than 4 and inhibits proteolytic activity of
pepsin, reducing acid indigestion. Antacids can initially be used in mild
cases. They have no effect on the frequency of reflux, but they decrease its
acidity.
Magnesium hydroxide is
used as antacid to relieve indigestion. It also causes osmotic retention of
fluid, which distends the colon and increases peristaltic activity that
provides laxative effect. In vivo, forms magnesium chloride after reacting with
stomach hydrochloric acid.
Overview
Excessive retrograde
movement of acid-containing gastric secretions or bile and acid-containing
secretions from the duodenum and stomach into the esophagus is the etiologic
effector of gastroesophageal reflux disease (GERD).
Barium esophagogram demonstrating gastroesophageal reflux with
the patient in the upright position.
Gastroesophageal reflux at the level of the thoracic inlet is
demonstrated on this barium esophagogram.
In most of these people,
endogenous defense mechanisms either limit the amount of noxious material that
is introduced into the esophagus or rapidly clear the material from the
esophagus so that symptoms and esophageal mucosal irritation are minimized.
Examples of the defense mechanisms include actions of the lower esophageal
sphincter (LES) and normal esophageal motility.
When the defense
mechanisms are defective or become overwhelmed so that the esophagus is bathed
in acid or bile and acid-containing fluid for prolonged periods, GERD can be
said to exist. Patients typically have numerous daily episodes of symptomatic
reflux, including pyrosis, water brash or sour taste in the mouth, nighttime
coughing or aspiration, pneumonia or pneumonitis, bronchospasm, and laryngitis
and voice changes including hoarseness. In addition, objective evidence of
esophageal damage can be seen on esophagogastroduodenoscopy.
Preferred examination
Among imaging studies,
barium esophagogram findings can demonstrate anatomy and possible complications
of reflux disease (strictures). Reflux and inadequate gastric emptying may also
be demonstrated.
Nuclear medicine gastric
emptying studies are sensitive in evaluating for incomplete gastric emptying.
Presently, no role
exists for computed tomography (CT) scanning, magnetic resonance imaging (MRI),
or ultrasonography in the routine evaluation of patients with reflux disease.
Limitations of techniques
A conclusive diagnosis
of reflux disease cannot be made by using barium esophagography. This technique
is not sensitive for the detection of motility disorders. Nuclear medicine
gastric-emptying study does not help in assessing anatomy and cannot help in
the diagnosis of reflux disease.
Radiography
Plain radiographic
findings are not useful in evaluating patients for GERD, but they are helpful
in evaluating pulmonary status and basic anatomy. Chest images may demonstrate a
large hiatal hernia, but small hernias can be missed easily. (See the image
below.)
In patients with
pulmonary symptoms, an infiltrate due to aspiration pneumonia may be seen. The
standard radiologic workup of a patient with reflux disease does not require
chest radiography.
Upper GI series
Upper GI
contrast-enhanced studies are the initial radiologic procedure of choice in the
workup of the patient in whom GERD is suggested.
The primary use of an
upper GI in suspected reflux is to evaluate anatomy and not to detect reflux,
as sensitivity is limited in patients with known esophagitis and normal
controls can have visualized reflux. Drinking 15-30 mL of iced water can
improve the sensitivity and specificity for reflux.
Barium esophagograms or
swallows are helpful for identifying structural abnormalities of the esophagus
and esophageal hiatus, which include esophageal rings, strictures and ulcers,
and hiatal hernias. (Barium esophagograms are presented below.)
Barium esophagogram demonstrating gastroesophageal reflux with
the patient in the upright position.
Barium esophagogram demonstrating gastroesophageal reflux with
the patient in the supine position.
Reflux esophagitis is demonstrated on barium esophagogram.
Gastroesophageal reflux at the level of the thoracic inlet is
demonstrated on this barium esophagogram.
Various techniques are
used, and each has relative strengths and weaknesses in the ability to detect
specific abnormalities or disease processes.
A typical barium
esophagogram is performed in multiple steps or phases. A high-density barium
suspension is administered, and double-contrast views are used for images taken
with the patient in the upright position. Prone-positioned images are typically
obtained with single contrast and a lower-density barium suspension. Mucosal
relief images can be made to complement these techniques.
Esophageal inflammatory
and neoplastic diseases are better detected with double-contrast techniques.
Conversely, single-contrast techniques are more sensitive for structural
defects such as hiatal hernias and strictures or esophageal rings.[4]
The presence of Barrett
esophagus occasionally is detected as a reticular mucosal pattern. As may be
expected, the more advanced the esophageal disease, the more sensitive is
barium swallow at detecting it.
Early esophagitis is not
well demonstrated and decreases the overall sensitivity of barium swallows,
especially compared to tests such as 24-hour pH monitoring. This is why many
clinicians reserve barium swallow for the evaluation of patients with GERD and
symptoms that include dysphagia.
Barium swallow is not
sensitive in the detection of actual reflux, except in the occasional patient
who has a wide-open LES and free reflux.
Barium swallow is a very
important study in the investigation and detection of postoperative
complications following fundoplication. Recurrent hiatal hernia, disruption or
slippage of the fundoplication, and other structural abnormalities can be
identified.[5, 6, 7]
Late postoperative
dysphagia can be investigated by a combination of manometry and esophageal
fluoroscopic examination. Increases in esophagogastric transit time of liquid
barium and solid boluses correlate positively with the presence of
postoperative dysphagia.[8]
Degree of confidence
The degree of confidence
offered by plain films for the diagnosis of GERD is low. A suggested diagnosis
of GERD must always be confirmed by other, more sensitive and specific tests.
No well-described,
normal variants of GERD can be detected by using CT scans.
Computed Tomography
CT scanning, similar to chest radiography, is not a part of the
standard radiologic workup of patients with GERD. CT scans can provide
information regarding the anatomy (ie, presence and size of a hiatal hernia)
but do not provide information regarding the presence or absence of reflux. CT
does not need to be performed in most of patients with reflux disease. No
well-described, normal variants of GERD can be detected by using CT scans.
Nuclear Imaging
Gastric-emptying studies may be worthwhile in the evaluation of
patients in whom delayed gastric emptying is believed to contribute to the
manifestation of GERD symptoms.
Gastroesophageal reflux scintigraphy can be performed with
acidified orange juice labeled with technetium-99m (99m Tc) sulfur colloid. Compared with fluoroscopy, this allows for a
longer time of evaluation, a decreased radiation dose, and the ability to
semiquantitate the amount of reflux. However, gastroesophageal reflux
scintigraphy has little role in the adult patient due to limited sensitivity
and the availability of other methods of evaluation.
Gastroesophageal reflux scintigraphy is much more commonly used in
infants and children due to the noninvasive nature of the study and relatively
low radiation dose. In infants and children the study is often performed with
labeled milk. In addition to evaluating the degree of reflux, pulmonary
aspiration can be detected by imaging over the lungs.
No normal scintigraphic variants for GERD have been described.
Degree of confidence
Scintigraphic studies are neither sensitive nor specific for the
diagnosis of GERD. The results should always be confirmed with another study,
preferably upper GI endoscopy or 24-hour pH monitoring.
