Download Clinical presentation, diagnosis, and management of

Clinical presentation, diagnosis,
and
management of gastroesophageal
reflux disease
Mitchell S. Cappell, MD, PhD, FACG
Med Clin N Am 89 (2005) 243–291
胃腸內科 陳青富 醫師
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Terminology
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GERD refers to the pathologic reflux of gastric fluid into
the esophagus through the gastroesophageal junction.
Belching, which is reflux of air from the stomach to the
esophagus and beyond.
Vomiting, which is reflux of digested foods (primarily a
semisolid solution).
Reflux esophagitis have evident esophageal
abnormalities at esophagogastroduodenoscopy (EGD)
or at pathologic analysis of endoscopic biopsies.
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Terminology
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Nonerosive reflux disease have reflux symptoms and
abnormal acid exposure with no evident esophageal
abnormalities at EGD or at pathologic evaluation of
endoscopic biopsies.
Although gastroesophageal reflux has been defined as
reflux of acid (pH<4), gastroesophageal reflux may
incorporate reflux (regurgitation) of nonacid (neutral or
alkaline) fluids.
GERD is also used as an all-inclusive term for any
extraesophageal clinical consequences, symptomatic or
anatomic, from reflux.
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Pathogenesis
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Pathogenesis
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Epidemiology
Incidence
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About 40% of US adults complain of monthly heartburn,
about 20% complain of weekly heartburn, and about 7%
complain of daily heartburn.
The prevalence of erosive esophagitis is, however, less,
with estimates of 2% to 7% as determined by EGD.
About 0.25% of adults in the United States develop BE
as a complication of GERD.
The prevalence of gastroesophageal reflux seems to
have increased during the last 30 years.
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Epidemiology
Risk factors
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Epidemiology
Risk factors
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Epidemiology
Risk factors
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Epidemiology
Risk factors
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Epidemiology
Risk factors
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Epidemiology
Risk factors
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Clinical presentation
Symptoms
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Pyrosis is the cardinal symptom. Typically, a burning
pain arises from the epigastrium and radiates
retrosternally to the throat and neck;
exacerbated by meals, by recumbency, by bending over,
and by ingesting acidic drinks; and is relieved by
ingestion of antacids, milk, or other alkaline foods and
by standing up.
Regurgitation: Patients may complain of bitter or acidic
fluid in the oropharynx from regurgitation.
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Clinical presentation
Symptoms
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Nausea and vomiting is rare in GERD and suggests other
diseases. Patients occasionally complain of atypical chest
pain. Globus is an uncommon symptom that is usually
caused by GERD.
Dysphagia suggests luminal obstruction from a refluxinduced peptic stricture or from esophageal
adenocarcinoma complicating BE, sometimes
uncomplicated erosive esophagitis.
Involuntary weight loss with chronic reflux symptoms
suggests possible esophageal adenocarcinoma,
particularly when the patient is elderly and has
dysphagia of recent origin.
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Clinical presentation
Symptoms
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Severe erosive esophagitis can occasionally cause
odynophagia.
Ulcerative reflux esophagitis may present with acute
gastrointestinal bleeding manifesting as hematemesis
or melena.
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Clinical presentation
Signs
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GERD without esophageal complications and without
extraesophageal symptoms rarely produces signs.
Signs may occur with esophageal complications or
with extraesophageal disease.
Hemorrhagic esophagitis may produce pallor from
acute GI bleeding, whereas esophageal ulcerations or
adenocarcinoma may produce fecal occult blood with
chronic GI bleeding.
Esophageal adenocarcinoma from BE may cause
cancer cachexia.
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Clinical presentation
Laboratory tests
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Routine blood tests are characteristically normal with
uncomplicated GERD.
Complicated GERD can cause abnormal blood tests.
Hemorrhagic reflux esophagitis may cause anemia.
Patients with esophageal adenocarcinoma may have
hypoalbuminemia from malnutrition.
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Differential diagnosis
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The D/D of epigastric pain includes cholelithiasis,
choledocholithiasis, acute viral hepatitis, alcoholic
hepatitis, acute pancreatitis, PUD, gastritis,
pyelonephritis, nephrolithiasis, shingles, and
mesenteric ischemia.
The D/D of atypical chest pain includes angina,
myocardial infarction, and diffuse esophageal spasm.
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Differential diagnosis
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Dysphagia may be caused by esophageal obstruction
from esophageal s.c.c, large polyps, webs, radiationinduced stricture, foreign body ingestion, or lye
ingestion; extrinsic compression, or paraesophageal
hernia.
Odynophagia suggests infectious esophagitis caused
by Candida, herpes simplex, cytomegalovirus, or
primary HIV infection; pill esophagitis or radiationinduced esophageal injury.
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Diagnosis
Trial of empiric therapy
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A 6-week trial of empiric acid-suppressive (PPI) therapy,
without performing EGD, for patients who present with
uncomplicated pyrosis or epigastric pain caused by
suspected GERD.
Symptom resolution with therapy initiation and
recurrence with therapy cessation provides presumptive
evidence of GERD.
Sensitivity: 75% and specificity : 80% for GERD,
using a 50% improvement in pyrosis as the therapeutic
end point.
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Diagnosis
Esophagram
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Barium studies are used to evaluate a patient with
suspected GERD to document the reflux; detect refluxinduced mucosal injury; identify an associated sliding
hiatal hernia; exclude complications, such as BE, peptic
stricture, or adenocarcinoma.
the sensitivity : 60% for single-contrast
90% for double-contrast studies
for moderate to severe reflux esophagitis.
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Diagnosis
Esophagogastroduodenoscopy
with endoscopic biopsies
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EGD is the standard clinical test for GERD, evaluates the
severity and extent of mucosal injury, and detects the
presence of complications from GERD.
Severity of esophagitis is endoscopically graded
according to one of three systems. ( the Los Angeles,
Savary-Miller grading system or the Hetzel classification )
In the Los Angeles grading system, esophagitis is graded
from A, where mucosal breaks are confined to folds and
no longer than 5 mm, to D, where mucosal breaks are
circumferential.
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Grade A, LA classification
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Grade B, LA classification
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Grade C, LA classification
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Grade D, LA classification
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Diagnosis
Esophagogastroduodenoscopy
with endoscopic biopsies
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EGD cannot detect abnormal acid reflux without mucosal
injury (nonerosive reflux disease).
It misses about 40% of acid reflux determined by pH
monitoring, but such reflux tends to be mild and
uncomplicated.
EGD often fails to diagnose clinically significant
extraesophageal manifestations of GERD, which often
occur without esophagitis.
When extraesophageal manifestations of GERD are
suspected, normal findings at EGD should prompt 24hour ambulatory pH monitoring.
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Diagnosis
Esophagogastroduodenoscopy
with endoscopic biopsies
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GERD is associated with a sliding hiatal hernia.
EGD reveals a small pouch between the tubular
esophagus and the baggy stomach; the pouch is lined by
gastric mucosa and covered by gastric rugae that extend
several centimeters above the diaphragmatic hiatus.
A stricture associated with reflux esophagitis may be
benign from peptic injury, or malignant from
adenocarcinoma, should be extensively biopsied.
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Hiatal hernia
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Esophageal Peptic Strictures
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Esophageal Cancer
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Diagnosis
Ambulatory pH monitoring
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24-hour ambulatory pH monitoring is the most
sensitive test, but cannot detect reflux of nonacidic
fluids and cannot assess mucosal damage from the
refluxate.
Indicated for pts with typical reflux symptoms
refractory to conventional therapy who have
nonerosive reflux disease; for pts presenting with
extraesophageal symptoms of undetermined etiology
and before antireflux surgery.
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Diagnosis
Ambulatory pH monitoring
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The acid exposure time is defined as the percentage of
time that the esophageal pH is less than 4. ( normal
upper limit : 6.3% in the supine and 1.2% in the upright
position).
Gastroesophageal reflux is most simply defined as an
abnormally high acid exposure time.
An abnormal result at ambulatory 24-hour pH monitoring
highly correlates with the diagnosis of reflux esophagitis
at EGD.
Between 84% and 96% of patients with reflux
esophagitis at EGD have abnormal esophageal acid
exposure times.
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Medical therapy
Lifestyle and dietary modifications
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Factors that promote or exacerbate gastroesophageal
reflux should be avoided.
Obese patients should lose weight and avoid heavy or
fatty meals.
Patients should avoid late night snacks and recumbency
soon after eating.
The head of the bed should be elevated.
Patients should avoid midabdominal tight-fitting clothes
or belts.
Patients should eliminate smoking and restrict alcohol
intake.
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Medical therapy
Lifestyle and dietary modifications
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Foods that exacerbate symptoms should be avoided;
these foods often include citrus drinks, spicy foods,
coffee, tea, cola beverages, and chocolate.
Medications known to lower the LES pressure, such as
calcium channel blockers or nitrates, and that can
exacerbate esophageal injury, such as NSAIDs, should
be avoided if possible.
Avoidance of psychologic stress at home and work is
advisable.
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Medical therapy
Medications
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Medical therapy
γ-Aminobutyric acid agonists
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A major current focus of research is to develop tLESR
inhibitors that may effectively prevent GERD with
minimal side effects.
γ -Aminobutyric acid is a powerful CNS inhibitory
neurotransmitter. Baclofen is a γ-aminobutyric acidB
receptor agonist blocks tLESR relaxation in laboratory
animals and in humans.
Baclofen reduced the frequency of reflux episodes and of
tLESRs by 40- 60% as compared with placebo.
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Endoscopic therapy
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Surgical therapy
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The two most common antireflux operations are the
Nissen and Toupet fundoplications.
Both procedures are most commonly performed
laparoscopically.
Common indications include failed medical therapy
despite adequate acid suppression; intolerance or
noncompliance to PPI therapy in young patients with
moderate to severe GERD; persistent extraesophageal
symptoms; and reflux-induced regurgitation, aspiration,
asthma, or bronchiectasis not responding to PPI therapy.
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Surgical therapy
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Antireflux surgery is relatively contraindicated in elderly
patients or in patients with significant comorbidity
unrelated to GERD.
Both procedures are successful in more than 90% of
patients, with relief of symptoms and prevention of
recurrent strictures when performed by experienced
surgeons at high-volume referral centers.
Postoperative complications include esophageal
hemorrhage, esophageal perforation, crural disruption,
paraesophageal herniation, and gastric volvulus.
The mortality of the Nissen fundoplication is
approximately 0.2%.
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Special situations
Extraesophageal manifestations of GERD
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Pulmonary manifestations of GERD may becaused by
microaspiration of acid and pepsin into the
tracheobronchial tree, or a bronchoconstrictive vagal
reflex triggered by esophageal irritation.
Asthma is frequently associated with GERD.
The asthma is typically nocturnal because of the
promotion of gastroesophageal reflux with recumbency,
and the absence of food to buffer refluxed acid during
overnight fasting.
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Special situations
Extraesophageal manifestations of GERD
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GERD-associated asthma should be considered in
patients who present with asthma in adulthood, lack a
personal and family history of allergy, have heartburn,
and respond poorly to traditional bronchodilator or
steroid therapy.
Currently treated with PPI therapy. High dose, twicedaily, and long-term therapy is generally recommended.
Symptoms improved in 69% of patients receiving
antireflux medications.
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Special situations
Extraesophageal manifestations of GERD
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Reflux laryngitis is caused by microaspiration of acid.
The most common symptom is hoarseness. Others
include globus sensation, frequent throat clearing,
halitosis, sore throats, and chronic cough.
10% to 40% of patients with chronic cough have GERD.
Only a minority of patients have heartburn, and
endoscopic evidence of esophagitis.
Esophageal pH monitoring is the best available
diagnostic test, but is only moderately sensitive( 54%),
and specific.
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Special situations
Extraesophageal manifestations of GERD
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PPIs are the generally recommended therapy, with
from 63% to 100% of patients experiencing significant
improvement in laryngeal symptoms and laryngoscopic
findings with therapy.
GERD is an important cause of nonbacterial dental
erosions, in a prospective study, 47.5% of 181
patients with dental erosions had GERD, whereas only
12.5% of 72 healthy subjects had GERD.
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Special situations
GERD and Helicobacter pylori infection
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An association between the decreasing prevalence of H
pylori infection, caused by antibacterial therapy, and the
increasing incidence of GERD and esophageal
adenocarcinoma in Western countries.
A recent meta-analysis of 14 case-controlled studies
reported that H pylori–negative status was significantly
associated with GERD, and of 10 therapeutic clinical
trials reported that anti–H pylori therapy was
significantly associated with GERD.
Anti–H pylori therapy should not be withheld, when
otherwise indicated, because of the quantitatively small
increased risk of esophageal adenocarcinoma after H
pylori eradication.
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Complications
Barrett’s esophagus and esophageal
adenocarcinoma
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BE is defined as replacement of normal stratified
squamous epithelium by metaplastic, specialized,
intestinal epithelium that contains goblet cells.
BE is a premalignant lesion.
From 1/3-2/3 of esophageal adenocarcinoma contain
foci of Barrett’s metaplasia.
About 10% of pts have esophageal adenocarcinoma at
the time of diagnosis of BE.
The annual incidence of esophageal adenocarcinoma in
pts with established BE is about 1 in 200.
The risk of developing esophageal adenocarcinoma is
increased about 100-fold in patients with BE.
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Complications
Barrett’s esophagus and esophageal
adenocarcinoma
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Demographic risk factors include male sex, older age,
white race, lower socioeconomic status. and probably
smoking tobacco.
Obesity is an important risk factor.
Patients with a hiatal hernia are more likely to have
severe reflux esophagitis, BE, and esophageal cancer.
At EGD numerous biopsies should be taken to confirm
the diagnosis of BE histologically and to exclude
dysplasia or adenocarcinoma.
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Complications
Barrett’s esophagus and esophageal
adenocarcinoma
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The surveillance interval for BE depends on the degree
of dysplasia. BE without dysplasia :every 3 years; with
mild dysplasia :every 6 months; with severe dysplasia,
generally require esophagectomy.
PPIs are the mainstay of medical therapy for GERD
complicated by BE.
Although intense PPI therapy usually effectively reverses
severe erosive esophagitis, evidence for its effect on
reversing Barrett’s metaplasia and on reducing the risk
of esophageal adenocarcinoma is indirect and
inconclusive.
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Complications
Hemorrhagic esophagitis
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About 7% of patients with GERD have clinically
significant acute hemorrhage.
Only about 40% of these patients report a history of
heartburn.
Other risk factors for hemorrhagic reflux esophagitis
include cirrhosis, coagulopathy, and anticoagulant
therapy.
Focal lesions with stigmata of recent hemorrhage should
receive endoscopic therapy at the time of endoscopic
diagnosis.
Hemorrhagic reflux esophagitis is generally managed
medically with intense PPI therapy.
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Complications
Peptic stricture
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Risk factors include old age, a long history of GERD, a
hypotensive LES, abnormalities in esophageal peristalsis,
and a hiatal hernia.
Characteristically presents with progressive dysphagia,
typically to solids and often with antecedent pyrosis.
Weight loss associated with an esophageal stricture
suggests possible malignancy.
Barium esophagrams reliably detect peptic esophageal
strictures.
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Complications
Peptic stricture
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EGD is usually the choice to evaluate a suspected peptic
stricture because of high sensitivity; high specificity; and
the ability to perform endoscopic therapy.
Multiple biopsies are taken at EGD to exclude BE,
esophageal adenocarcinoma, or other lesions.
Peptic strictures are usually treated with mechanical
dilatation, especially strictures that are tight, severely
symptomatic, or refractory to medical therapy.
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Complications
Peptic stricture
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Patients with a peptic stricture should receive intense
PPI therapy to reduce the mucosal inflammation from
acid-induced injury.
Maintenance PPI therapy greatly decreases the need
for repeated stricture dilatations.
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